2024-03-28T18:00:14Zhttps://repositori.udl.cat/server/oai/requestoai:repositori.udl.cat:10459.1/483732022-05-06T13:09:22Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_66064col_10459.1_314col_10459.1_59998col_10459.1_66068
00925njm 22002777a 4500
dc
Laplana Lafaja, Marina
author
Royo Sánchez-Palencia, José Luis
author
Aluja Fabregat, Antón
author
López Ortega, Ricard
author
Heine-Suñer, Damià
author
Fibla Palazón, Joan
author
2014
Autism spectrum disorder (ASD) is a highly heritable disease (∼0.9) with a complex genetic etiology. It is initially characterized by
altered cognitive ability which commonly includes impaired language and communication skills as well as fundamental deficits in
social interaction. Despite the large amount of studies described so far, the high clinical diversity affecting the autism phenotype
remains poorly explained. Recent studies suggest that rare genomic variations, in particular copy number variation (CNV), may
account for a significant proportion of the genetic basis of ASD. The use of disease-discordant monozygotic twins represents a
powerful strategy to identify de novo and inherited CNV in the disorder. Here we present the results of a comparative genome
hybridization (CGH) analysis with a pair of monozygotic twins affected of ASD with significant differences in their clinical
manifestations that specially affect speech language impairment and communication skills. Array CGH was performed in three
different tissues: blood, saliva, and hair follicle, in an attempt to identify germinal and somatic CNV regions that may explain these
differences. Our results argue against a role of large CNV rearrangements as a molecular etiology of the observed differences.This
forwards future research to explore de novo point mutation and epigenomic alterations as potential explanations of the observed
clinical differences.
https://doi.org/10.1155/2014/516529
021653
2090-6544
http://hdl.handle.net/10459.1/48373
Absence of substantial copy number differences in a pair of monozygotic twins discordant for features of autism spectrum disorder
oai:repositori.udl.cat:10459.1/3192020-07-14T08:39:35Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Vilaprinyo Terré, Ester
author
Alves, Rui
author
Sorribas Tello, Albert
author
2006
Background: Understanding the relationship between gene expression changes, enzyme activity shifts, and the corresponding physiological adaptive response of organisms to environmental cues is crucial in explaining how cells cope with stress. For example, adaptation of yeast to heat shock
involves a characteristic profile of changes to the expression levels of genes coding for enzymes of the glycolytic pathway and some of its branches. The experimental determination of changes in gene expression profiles provides a descriptive picture of the adaptive response to stress. However, it does not explain why a particular profile is selected for any given response.
Results: We used mathematical models and analysis of in silico gene expression profiles (GEPs) to understand how changes in gene expression correlate to an efficient response of yeast cells to heat shock. An exhaustive set of GEPs, matched with the corresponding set of enzyme activities, was
simulated and analyzed. The effectiveness of each profile in the response to heat shock was evaluated according to relevant physiological and functional criteria. The small subset of GEPs that lead to effective physiological responses after heat shock was identified as the result of the tuning
of several evolutionary criteria. The experimentally observed transcriptional changes in response to heat shock belong to this set and can be explained by quantitative design principles at the
physiological level that ultimately constrain changes in gene expression.
Conclusion: Our theoretical approach suggests a method for understanding the combined effect of changes in the expression of multiple genes on the activity of metabolic pathways, and consequently on the adaptation of cellular metabolism to heat shock. This method identifies quantitative design principles that facilitate understating the response of the cell to stress.
https://doi.org/10.1186%2F1471-2105-7-184
009118
1471-2105
http://hdl.handle.net/10459.1/319
Use of physiological constraints to identify quantitative design principles for gene expression in yeast adaptation to heat shock
oai:repositori.udl.cat:10459.1/832712022-05-13T00:08:21Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Sarlabous Uranga, Leonardo
author
Aquino Esperanza, Jose
author
Magrans, Rudys
author
de Haro, Candelaria
author
López-Aguilar, Josefina
author
Subirà, Carles
author
Batlle, Montserrat
author
Rué i Monné, Montserrat
author
Gomà Fernández, Gemma
author
Ochagavía, Ana
author
Fernández, Rafael
author
Blanch, Lluís
author
2020
Patient-ventilator asynchronies can be detected by close monitoring of ventilator screens by clinicians or through automated algorithms. However, detecting complex patient-ventilator interactions (CP-VI), consisting of changes in the respiratory rate and/or clusters of asynchronies, is a challenge. Sample Entropy (SE) of airway flow (SE-Flow) and airway pressure (SE-Paw) waveforms obtained from 27 critically ill patients was used to develop and validate an automated algorithm for detecting CP-VI. The algorithm’s performance was compared versus the gold standard (the ventilator’s waveform recordings for CP-VI were scored visually by three experts; Fleiss’ kappa = 0.90 (0.87–0.93)). A repeated holdout cross-validation procedure using the Matthews correlation coefficient (MCC) as a measure of effectiveness was used for optimization of different combinations of SE settings (embedding dimension, m, and tolerance value, r), derived SE features (mean and maximum values), and the thresholds of change (Th) from patient’s own baseline SE value. The most accurate results were obtained using the maximum values of SE-Flow (m = 2, r = 0.2, Th = 25%) and SE-Paw (m = 4, r = 0.2, Th = 30%) which report MCCs of 0.85 (0.78–0.86) and 0.78 (0.78–0.85), and accuracies of 0.93 (0.89–0.93) and 0.89 (0.89–0.93), respectively. This approach promises an improvement in the accurate detection of CP-VI, and future study of their clinical implications.
https://doi.org/10.1038/s41598-020-70814-4
030748
2045-2322
http://hdl.handle.net/10459.1/83271
Enginyeria biomèdica
Marcadors bioquímics
Bases de dades
Aprenentatge automàtic
Estadística
Biomedical engineering
Biochemical markers
Database
Machine learning
Statistics
Development and validation of a sample entropy-based method to identify complex patient-ventilator interactions during mechanical ventilation
oai:repositori.udl.cat:10459.1/494282021-08-30T15:04:33Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Royo Sánchez-Palencia, José Luis
author
Pascual Pons, Mariona
author
Lupiañez, Arantxa
author
Sanchez Lopez, Isabel
author
Fibla Palazón, Joan
author
2015
Copy number variant (CNV) regions have been proven to have a significant impact on gene expression. Some of them have been also found to be associated to different human diseases. CNV genotyping is often prone to error and cross-validation with independent methods is frequently required. The platform of choice depends on whether it is a genome-wide discovery screening or a candidate CNV study, the cohort size and the number of CNVs included in the assay and, finally, the budget available. Here we illustrate a affordable approach to determine the CNV genotype using matrix-assisted laser desorption/ ionization mass spectrometry (MALDI-MS) and based on the quantitative determination of single nucleotide duplicated mismatches (SNDM) mapping the CNV region and a paralogue genomic region that is used as a two-copy reference. We have genotyped nsv436327, a common CNV mapping SIRPB1 intron 1 that has been associated to human personality behavior. SIRP cluster region was subjected to several ancestral duplication events what makes SIRPB1 CNV genotyping technically challenging. We designed three sets of primer pairs that amplified paralogue regions inside and outside the CNV, containing three SNDMs. Post-PCR extension analyses of sequencing oligonucleotides mapping immediately upstream each SNDM allowed us to quantify using MALDI-MS the proportion of PCR products derived from the CNV region versus the external reference. In contrast to other approaches, setting up this genotyping method requires an affordable investment.
https://doi.org/10.1016/j.mcp.2015.07.009
023182
0890-8508
http://hdl.handle.net/10459.1/49428
SIRPB1
cnv
MALDI-TOF
genotyping-by-sequencing
Genotyping of common SIRPB1 copy number variant using Paralogue Ratio Test coupled to MALDI-MS quantification
oai:repositori.udl.cat:10459.1/570002021-08-30T15:04:33Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Puigpinós, R.
author
Borrell i Thió, Carme
author
Pasarín, M.I.
author
Montellà, N.
author
Pérez, G.
author
Plasència, A.
author
Rué i Monné, Montserrat
author
2000
Most of the studies of inequalities in mortality
carried out in Spain have been ecological, due
to the di culty of obtaining good quality socioeconomic
information at individual level. The objective
of this study was to describe inequalities in mortality
by social class, based on occupation, among men
residents of Barcelona in 1993. A representative
sample was obtained of men residents of Barcelona
who died during the year 1993, aged between 15 and
65 years. It was a retrospective interview given to
relatives of the deceased, or other closely related
persons. The variables analysed were: age, education
level, underlying cause of death, and social class
based on occupation (manual and non-manual
workers). Rates, relative risks (RRs) and their 95%
con®dence intervals (95% CIs) are presented by age
groups and cause of death. The main results show
that among young people, the excess of mortality due
to infectious diseases is notable (RR: 1.9; 95% CI:
1.6±2.2), and also due to external causes (RR: 2.1;
95% CI: 1.8±2.4) among manual workers with respect
to non-manual workers, mainly due to AIDS
and drug overdose. No signi®cant di erences were
found in mortality due to tumours. For respiratory
and cardiovascular causes, there is an increase in
mortality in the less favoured social classes, as also
occurs for mortality due to diseases of the digestive
system, particularly among young manual workers,
with an RR: 2.6 (95% CI: 1.5±3.6) compared to nonmanual
workers. This study shows that it is necessary
to continue exploring inequalities in health, but
above all it is necessary to implement e cient preventive
measures addressed mainly at young people
in situations of disadvantage, in order to avoid the
excess of avoidable mortality which is found.
https://doi.org/10.1023/A:1026706302783
009182
0393-2990
http://hdl.handle.net/10459.1/57000
Barcelona
Inequalities
Mortality
Retrospective survey
Inequalities in mortality by social class in men in Barcelona, Spain
oai:repositori.udl.cat:10459.1/571612021-08-30T15:04:28Zcom_10459.1_227com_10459.1_2com_10459.1_59159com_10459.1_47453col_10459.1_314col_10459.1_59160col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Sorolla Bardají, Maria Alba
author
Reverter Branchat, Gemma
author
Tamarit Sumalla, Jordi
author
Ferrer, Isidre
author
Ros Salvador, Joaquim
author
Cabiscol Català, Elisa
author
2008
Huntington disease (HD) is a neurodegenerative disorder caused by expansion of CAG repeats in exon 1 of the
huntingtin gene, affecting initially the striatum and progressively the cortex. This work reports a proteomic
analysis of human brain postmortem samples obtained from striatum and cortex of patients with HD
compared to samples of age- and sex-matched controls. Antioxidant defense proteins that were strongly
induced in striatum, but also detectable in cortex, were identified as peroxiredoxins 1, 2, and 6, as well as
glutathione peroxidases 1 and 6. The activities of other antioxidant enzymes such as mitochondrial
superoxide dismutase and catalase were also increased in HD. Aconitase, a protein involved in energy
metabolism, showed decreased activities in striatum of HD patients. Protein carbonyls, used as markers of
oxidative stress, were increased in HD, and glial fibrillary acidic protein, aconitase, γ-enolase, and creatine
kinase B were identified as the main targets. Taken together, these results indicate that oxidative stress and
damage to specific macromolecules would participate in the disease progression. Also, these data support the
rationale for therapeutic strategies that either potentiate antioxidant defenses or avoid oxidative stress
generation to delay disease progression.
https://doi.org/10.1016/j.freeradbiomed.2008.05.014
012451
0891-5849
http://hdl.handle.net/10459.1/57161
Huntington disease
Proteomic analysis
Oxidative stress
Protein carbonylation
Proteomic and oxidative stress analysis in human brain samples of Huntington disease
oai:repositori.udl.cat:10459.1/455882023-01-27T19:50:26Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Salvadó López, Baldiri
author
Vilaprinyo Terré, Ester
author
Karathia, Hiren
author
Sorribas Tello, Albert
author
Alves, Rui
author
2012
Signal transduction systems mediate the response and adaptation of organisms to environmental changes. In prokaryotes, this signal transduction is often done through Two Component Systems (TCS). These TCS are phosphotransfer protein cascades, and in their prototypical form they are composed by a kinase that senses the environmental signals (SK) and by a response regulator (RR) that regulates the cellular response. This basic motif can be modified by the addition of a third protein that interacts either with the SK or the RR in a way that could change the dynamic response of the TCS module. In this work we aim at understanding the effect of such an additional protein (which we call ‘‘third component’’) on the
functional properties of a prototypical TCS. To do so we build mathematical models of TCS with alternative designs for their
interaction with that third component. These mathematical models are analyzed in order to identify the differences in dynamic behavior inherent to each design, with respect to functionally relevant properties such as sensitivity to changes in either the parameter values or the molecular concentrations, temporal responsiveness, possibility of multiple steady states, or stochastic fluctuations in the system. The differences are then correlated to the physiological requirements that impinge on the functioning of the TCS. This analysis sheds light on both, the dynamic behavior of synthetically designed TCS, and the conditions under which natural selection might favor each of the designs. We find that a third component that
modulates SK activity increases the parameter space where a bistable response of the TCS module to signals is possible, if
SK is monofunctional, but decreases it when the SK is bifunctional. The presence of a third component that modulates RR activity decreases the parameter space where a bistable response of the TCS module to signals is possible.
https://doi.org/10.1371/journal.pone.0031095
020994
1932-6203
http://hdl.handle.net/10459.1/45588
Two component systems: physiological effect of a third component
oai:repositori.udl.cat:10459.1/570542021-08-30T15:04:34Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Igoshin, Oleg A.
author
Alves, Rui
author
Savageau, Michael A.
author
2008
Bacterial two-component systems (TCS) are key
signal transduction networks regulating global
responses to environmental change. Environmental
signals may modulate the phosphorylation state of
sensor kinases (SK). The phosphorylated SK trans-
fers the phosphate to its cognate response regulator
(RR), which causes physiological response to the
signal. Frequently, the SK is bifunctional and, when
unphosphorylated, it is also capable of dephosphory-
lating the RR. The phosphatase activity may also be
modulated by environmental signals. Using the EnvZ/
OmpR system as an example, we constructed math-
ematical models to examine the steady-state and
kinetic properties of the network. Mathematical
modelling reveals that the TCS can show bistable
behaviour for a given range of parameter values
if unphosphorylated SK and RR form a dead-end
complex that prevents SK autophosphorylation. Addi-
tionally, for bistability to exist the major dephospho-
rylation flux of the RR must not depend on the
unphosphorylated SK. Structural modelling and pub-
lished affinity studies suggest that the unphosphory-
lated SK EnvZ and the RR OmpR form a dead-end
complex. However, bistability is not possible because
the dephosphorylation of OmpR
~
P is mainly done by
unphosphorylated EnvZ. The implications of this
potential bistability in the design of the EnvZ/OmpR
network and other TCS are discussed.
https://doi.org/10.1111/j.1365-2958.2008.06221.x
011508
0950-382X
http://hdl.handle.net/10459.1/57054
Hysteretic and graded responses in bacterial two-component signal transduction
oai:repositori.udl.cat:10459.1/416672020-07-14T08:39:35Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Reveiz, Ludovic
author
Chan, An-Wen
author
Krleza-Jeric, Karmela
author
Granados, Carlos Eduardo
author
Pinart, Mariona
author
Etxeandia, Itziar
author
Rada, Diego
author
Martínez Alonso, Montserrat
author
Bonfill, Xavier
author
Cardona, Andrés Felipe
author
2010
Background: Although randomized clinical trials (RCTs) are considered the gold standard of evidence, their reporting is
often suboptimal. Trial registries have the potential to contribute important methodologic information for critical appraisal of study results.
Methods and Findings: The objective of the study was to evaluate the reporting of key methodologic study characteristics in trial registries. We identified a random sample (n = 265) of actively recruiting RCTs using the World Health Organization International Clinical Trials Registry Platform (ICTRP) search portal in 2008. We assessed the reporting of relevant domains from the Cochrane Collaboration’s ‘Risk of bias’ tool and other key methodological aspects. Our primary outcomes were the proportion of registry records with adequate reporting of random sequence generation, allocation concealment, blinding, and trial outcomes. Two reviewers independently assessed each record. Weighted overall proportions in the ICTRP search portal for adequate reporting of sequence generation, allocation concealment, blinding (including and excluding open label RCT) and primary outcomes were 5.7% (95% CI 3.0–8.4%), 1.4% (0–2.8%), 41% (35–47%), 8.4% (4.1–13%), and 66% (60–72%), respectively. The proportion of adequately reported RCTs was higher for registries that used specific methodological fields for describing methods of randomization and allocation concealment compared to registries that did not. Concerning other key methodological aspects, weighted overall proportions of RCTs with adequately reported items were as follows:
eligibility criteria (81%), secondary outcomes (46%), harm (5%) follow-up duration (62%), description of the interventions
(53%) and sample size calculation (1%).
Conclusions: Trial registries currently contain limited methodologic information about registered RCTs. In order to permit
adequate critical appraisal of trial results reported in journals and registries, trial registries should consider requesting details
on key RCT methods to complement journal publications. Full protocols remain the most comprehensive source of methodologic information and should be made publicly available.
https://doi.org/10.1371%2Fjournal.pone.0012484
016421
1932-6203
http://hdl.handle.net/10459.1/41667
Reporting of methodologic information on trial registries for quality assessment: a study of trial records retrieved from the WHO search portal
oai:repositori.udl.cat:10459.1/566622023-04-25T12:44:42Zcom_10459.1_227com_10459.1_2com_10459.1_463061com_10459.1_47453col_10459.1_314col_10459.1_463062col_10459.1_59998
00925njm 22002777a 4500
dc
Usié Chimenos, Anabel
author
Alves, Rui
author
Solsona Tehàs, Francesc
author
Vázquez, Miguel
author
Valéncia, Alfonso
author
2013
Motivation: Chemical named entity recognition is used to automatically
identify mentions to chemical compounds in text, and is the
basis for more elaborate information extraction. However, only a
small number of applications are freely available to identify such
mentions. Particularly challenging and useful is the identification of
IUPAC chemical compounds, which due to the complex morphology
of IUPAC names requires more advanced techniques than that of
brand names.
Results: We present CheNER, a tool for automated identification of
systematic IUPAC chemical mentions. We evaluated different systems
using an established literature corpus to show that CheNER
has a superior performance in identifying IUPAC names specifically,
and that it makes better use of computational resources.
Availability: http://metres.udl.cat/index.php/9-download/4-chener,
http://ubio.bioinfo.cnio.es/biotools/CheNER/
Supplementary information: Both web sites above include the
user manual for the software. Supplementary materials accompany
this publication.
https://doi.org/10.1093/bioinformatics/btt639
020206
1367-4803
http://hdl.handle.net/10459.1/56662
CheNER: Chemical Named Entity Recognizer
oai:repositori.udl.cat:10459.1/604282022-01-12T12:23:51Zcom_10459.1_227com_10459.1_2com_10459.1_237com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_354col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Granado Casas, Minerva
author
Martínez Alonso, Montserrat
author
Alcubierre Calvo, Núria
author
Ramírez-Morros, Anna
author
Hernández García, Marta
author
Castelblanco Echavarría, Esmeralda
author
Torres Puig-gros, Joan
author
Mauricio Puente, Dídac
author
2017-10-18
Objectives. Our main aim was to assess the quality of life (QoL) and treatment satisfaction (TS) of subjects with LADA (latent autoimmune diabetes of the adult) and compare these measures with those of patients with other diabetes types, i.e., type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Methods. This was a cross-sectional study with a total of 48 patients with LADA, 297 patients with T2DM and 124 with T1DM. The Audit of Diabetes-Dependent Quality of Life (ADDQoL-19) questionnaire and the Diabetes Treatment Satisfaction Questionnaire (DTSQ) were administered. Relevant clinical variables were also assessed. The data analysis included comparisons between groups and multivariate linear models. Results. The LADA patients presented lower diabetes-specific QoL (p D 0:045) and average weighted impact scores (p D 0:007) than the T2DM patients. The subgroup of LADA patients with diabetic retinopathy (DR) who were treated with insulin had a lowerADDQoLaverage weighted impact score than the other diabetic groups. Although the overall measure of TS was not different between the LADA and T2DM (pD0:389) and T1DM (pD0:091) groups, the patients with LADA showed a poorer hyperglycemic frequency perception than the T2DM patients (p<0:001) and an improved frequency of hypoglycemic perception compared with the T1DM patients (pD0:021). Conclusions. The current findings suggest a poorer quality of life, especially in terms of DRand insulin treatment, among patients with LADA compared with those withT1DM and T2DM. Hyperglycemia frequency perception was also poorer in the LADA patients than in the T1DM and T2DM patients. Further research with prospective studies and a large number of patients is necessary.
https://doi.org/10.7717/peerj.3928
026046
2167-8359
http://hdl.handle.net/10459.1/60428
Decreased quality of live and treatment satisfaction in patients with latent autoinmune diabetes of the adult
oai:repositori.udl.cat:10459.1/489932022-11-28T19:36:37Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Eritja Sánchez, Núria
author
Mirantes Barbeito, Cristina
author
Llobet Navàs, David
author
Masip Vilà, Gemma
author
Matias-Guiu, Xavier
author
Dolcet Roca, Xavier
author
2013
Most glandular tissues comprise polarized epithelial cells organized around a single central lumen. Although there is active research investigating the molecular networks involved in the regulation of lumenogenesis, little is known about the extracellular factors that influence lumen formation and maintenance. Using a three-dimensional culture system of epithelial endometrial cells, we have revealed a new role for pro-inflammatory cytokines such as TNF alpha and IL1 alpha in the formation and, more importantly, maintenance of a single central lumen. We also studied the mechanism by which glucocorticoids repress TNF alpha and IL1 alpha expression. Interestingly, regulation of pro-inflammatory cytokine expression and subsequent lumen formation is mediated by estrogen receptor alpha (ER alpha) but not by the glucocorticoid receptor. Finally, we investigated the signaling pathways involved in the regulation of lumen formation by pro-inflammatory cytokines. Our results demonstrate that activation of the ERK/MAPK signaling pathway, but not the PI3K/Akt signaling pathway, is important for the formation and maintenance of a single central lumen. In summary, our results suggest a novel role for ER alpha-regulated pro-inflammatory cytokine expression in lumen formation and maintenance.
017679
0021-9533
http://hdl.handle.net/10459.1/48993
Pro-inflammatory cytokines
Epithelial cell polarity
ER alpha
ER alpha-mediated repression of pro-inflammatory cytokine expression by glucocorticoids reveals a crucial role for TNF alpha and IL1 alpha in lumen formation and maintenance
oai:repositori.udl.cat:10459.1/648382021-10-29T12:13:54Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
García de la Fuente, María Reyes
author
Santacana Espasa, Maria
author
Valls Marsal, Joan
author
Vilardell, Felip
author
Fernández Armenteros, José Manuel
author
Pujol Vallverdú, Ramón M.
author
Garí Marsol, Eloi
author
Casanova i Seuma, Josep M. (Josep Manel)
author
2018
Basal cell carcinoma (BCC) seems to originate from
ultraviolet light-induced mutations involving the bulge or the outer
sheath of the hair follicle cells. However, the etiopathogenic
mechanisms involved in the development of these tumors in
nonphotoexposed and in hairless areas remain unclear. The cytokeratin
(CK) profile (including CK5/6, CK7, CK14, CK15, CK17, and
CK19) from a series of different BCC subtypes developing in
sun-exposed and non–sun-exposed areas, including hairless regions,
was evaluated. The authors have observed that CK7 expression in
BCC is associated with the anatomical localization of the tumor and
its sun-exposition, but not with other factors such as histological
subtype. The expression of this CK is higher in BCCs located in
non–sun-exposed and nonhairy areas, such as the vulvar semimucosa
and the nipple. Because CK7 is a marker of simple glandular
epithelia, the authors suggest a glandular origin for BCCs located
in hairless and nonphotoexposed areas.
https://doi.org/10.1097/DAD.0000000000001042
026993
0193-1091
http://hdl.handle.net/10459.1/64838
Basal cell carcinoma
Cytokeratins
Hair follicle
Sebaceous gland
Photoexposition
Cytokeratin profile of basal cell carcinomas according to the degree of sun exposure and to the anatomical localization
oai:repositori.udl.cat:10459.1/569442017-03-10T13:54:56Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Chiner, Eusebi
author
Llombart, Mónica
author
Valls Marsal, Joan
author
Pastor, Esther
author
Sancho-Chust, José
author
Luz Andreu, Ada
author
Sánchez de la Torre, Manuel
author
Barbé Illa, Ferran
author
2016
Background:
We hypothesized that obstructive sleep apnea (OSA) can predispose individuals to lower
airway infections and community-acquired pneumonia (CAP) due to upper airway microaspiration.
This study evaluated the association between OSA and CAP.
Methods:
We performed a case-control study that included 82 patients with CAP and 41 patients with
other infections (control group). The controls were matched according to age, sex and body
mass index (BMI). A respiratory polygraph (RP) was performed upon admission for patients
in both groups. The severity of pneumonia was assessed according to the Pneumonia
Severity Index (PSI). The associations between CAP and the Epworth Sleepiness Scale
(ESS), OSA, OSA severity and other sleep-related variables were evaluated using logistic
regression models. The associations between OSA, OSA severity with CAP severity were
evaluated with linear regression models and non-parametric tests.
Findings:
No significant differences were found between CAP and control patients regarding anthropometric
variables, toxic habits and risk factors for CAP. Patients with OSA, defined as individuals
with an Apnea-Hypopnea Index (AHI) 10, showed an increased risk of CAP (OR =
2 86, 95%CI 1 29–6 44, p = 0 01). Patients with severe OSA (AHI 30) also had a higher
risk of CAP (OR = 3 18, 95%CI 1 11–11 56, p = 0 047). In addition, OSA severity, defined
according to the AHI quartile, was also significantly associated with CAP (p = 0 007). Furthermore,
OSA was significantly associated with CAP severity (p = 0 0002), and OSA severity
was also associated with CAP severity (p = 0 0006).
Conclusions:
OSA and OSA severity are associated with CAP when compared to patients admitted to the
hospital for non-respiratory infections. In addition, OSA and OSA severity are associated with CAP severity. These results support the potential role of OSA in the pathogenesis of
CAP and could have clinical implications. This link between OSA and infection risk should
be explored to investigate the relationships among gastroesophageal reflux, silent aspiration,
laryngeal sensory dysfunction and CAP.
https://doi.org/10.1371/journal.pone.0152749
024336
1932-6203
http://hdl.handle.net/10459.1/56944
Association between Obstructive Sleep Apnea and Community-Acquired Pneumonia
oai:repositori.udl.cat:10459.1/694702020-09-09T00:19:35Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Alza, Lía
author
Visa Pretel, Anna
author
Herreros Danés, Judit
author
Cantí Nicolás, Carles
author
2020-04-07
Hyperactivation of the Mitogen Activated Protein Kinase (MAPK) pathway is prevalent in melanoma, principally due to mutations in the B-Raf and NRas genes. MAPK inhibitors are effective only shortterm, and recurrence occurs due to functional redundancies or intertwined pathways. The remodeling of Ca2+ signaling is also common in melanoma cells, partly through the increased expression of T-type channels (TTCCs). Here we summarize current knowledge about the prognostic value and molecular targeting of TTCCs. Furthermore, we discuss recent evidence pointing to TTCCs as molecular switches for melanoma chemoresistance, which set the grounds for novel combined therapies against the advanced disease.
https://doi.org/10.1016/j.bbcan.2020.188364
029978
0304-419X
http://hdl.handle.net/10459.1/69470
Melanoma
T-type channels
MAPK
RAF/RAS mutants
PTEN mutants
Macroautophagy
Chemotherapeutic resistance
The rise of T-type channels in melanoma progression and chemotherapeutic resistance
oai:repositori.udl.cat:10459.1/566842023-06-26T09:53:56Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Barbé Illa, Ferran
author
Durán-Cantolla, Joaquín
author
Sánchez de la Torre, Manuel
author
Martínez Alonso, Montserrat
author
Carmona, Carmen
author
Barceló Bennasar, Antònia
author
Chiner, Eusebi
author
Masa, Juan Fernando
author
González, Mónica
author
Marín, J. M.
author
García-Río, Francisco
author
Díaz de Atauri, María Josefa
author
Terán, Joaquin
author
Mayós Pérez, Mercè
author
Peña, Mónica de la
author
Monasterio, Carmen
author
Campo, Félix del
author
Montserrat i Capdevila, Josep
author
2013
Context Continuous positive airway pressure (CPAP) is the first-line treatment for patients
with symptomatic obstructive sleep apnea (OSA). However, its indication for all
patients with sleep-disordered breathing, regardless of daytime symptoms, is unclear.
Objective To evaluate the effect of CPAP treatment on the incidence of hypertension
or cardiovascular events in a cohort of nonsleepy patients with OSA.
Design, Setting, and Patients Multicenter, parallel-group, randomized controlled
trial in 14 teaching hospitals in Spain. Between May 2004 and May 2006, 725
consecutive patients were enrolled who had an apnea-hypopnea index of 20 h−1 or
greater and an Epworth Sleepiness Scale score of 10 or less (scores range from 0-24,
with values 10 suggesting no daytime sleepiness). Exclusion criteria were previous
cardiovascular event, physical or psychological incapacity, chronic disease, or drug or
alcohol addiction. Follow-up ended in May 2009.
Intervention Patients were allocated to receive CPAP treatment or no active intervention.
All participants received dietary counseling and sleep hygiene advice.
Main Outcome Measures Incidence of either systemic hypertension (taking antihypertensive
medication or blood pressure greater than 140/90 mm Hg) or cardiovascular
event (nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack,
hospitalization for unstable angina or arrhythmia, heart failure, or cardiovascular death).
Results Seven hundred twenty-three patients underwent follow-up for a median of 4
(interquartile range, 2.7-4.4) years (1 patient from each group did not receive allocated
treatment); 357 in the CPAP group and 366 in the control group were included in the
analysis. In the CPAP group there were 68 patients with new hypertension and 28 cardiovascular
events (17 unstable angina or arrhythmia, 3 nonfatal stroke, 3 heart failure,
2 nonfatal myocardial infarction, 2 transient ischemic attack, 1 cardiovascular death). In
the control group there were 79 patients with new hypertension and 31 cardiovascular
events (11 unstable angina or arrhythmia, 8 nonfatal myocardial infarction, 5 transient
ischemic attack, 5 heart failure, 2 nonfatal stroke). The hypertension or cardiovascular
event incidence density rate was 9.20 per 100 person-years (95% CI, 7.36-11.04) in
the CPAP group and 11.02 per 100 person-years (95% CI, 8.96-13.08) in the control
group. The incidence density ratio was 0.83 (95% CI, 0.63-1.1; P=.20).
Conclusions In patients with OSA without daytime sleepiness, the prescription of
CPAP compared with usual care did not result in a statistically significant reduction in
the incidence of hypertension or cardiovascular events. However, the study may have
had limited power to detect a significant difference.
https://doi.org/10.1001/jama.2012.4366
019356
0098-7484
http://hdl.handle.net/10459.1/56684
Effect of Continuous Positive Airway Pressure on the Incidence of Hypertension and Cardiovascular Eventsin Nonsleepy Patients With Obstructive Sleep Apnea
oai:repositori.udl.cat:10459.1/4639652023-09-14T03:00:22Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Batlle Garcia, Jordi de
author
Benítez, Iván
author
Moncusí Moix, Anna
author
Androutsos, Odysseas
author
Barbastro, Rosana Angles
author
Antonini, Alessio
author
Arana, Eunate
author
Cabrera-Umpierrez, Maria Fernanda
author
Cea, Gloria
author
Dafoulas, George Ε.
author
Folkvord, Frans
author
Fullaondo, Ane
author
Giuliani, Francesco
author
Huang, Hsiao-Ling
author
Innominato, Pasquale F.
author
Kardas, Przemyslaw
author
Lou, Vivian W.Q.
author
Manios, Yannis
author
Matsangidou, Maria
author
Mercalli, Franco
author
Mokhtari, Mounir
author
Pagliara, Silvio
author
Schellong, Julia
author
Stieler, Lisa
author
Votis, Konstantinos
author
Currás, Paula
author
Arredondo, Maria Teresa
author
Posada, Jorge
author
Guillén, Sergio
author
Pecchia, Leandro
author
Barbé Illa, Ferran
author
Torres, Gerard
author
Fico, Giuseppe
author
2023
Background: The World Health Organization’s strategy toward healthy aging fosters person-centered integrated care sustained by eHealth systems. However, there is a need for standardized frameworks or platforms accommodating and interconnecting multiple of these systems while ensuring secure, relevant, fair, trust-based data sharing and use. The H2020 project GATEKEEPER aims to implement and test an open-source, European, standard-based, interoperable, and secure framework serving broad populations of aging citizens with heterogeneous health needs.
Objective: We aim to describe the rationale for the selection of an optimal group of settings for the multinational large-scale piloting of the GATEKEEPER platform.
Methods: The selection of implementation sites and reference use cases (RUCs) was based on the adoption of a double stratification pyramid reflecting the overall health of target populations and the intensity of proposed interventions; the identification of a principles guiding implementation site selection; and the elaboration of guidelines for RUC selection, ensuring clinical relevance and scientific excellence while covering the whole spectrum of citizen complexities and intervention intensities.
Results: Seven European countries were selected, covering Europe’s geographical and socioeconomic heterogeneity: Cyprus, Germany, Greece, Italy, Poland, Spain, and the United Kingdom. These were complemented by the following 3 Asian pilots: Hong Kong, Singapore, and Taiwan. Implementation sites consisted of local ecosystems, including health care organizations and partners from industry, civil society, academia, and government, prioritizing the highly rated European Innovation Partnership on Active and Healthy Aging reference sites. RUCs covered the whole spectrum of chronic diseases, citizen complexities, and intervention intensities while privileging clinical relevance and scientific rigor. These included lifestyle-related early detection and interventions, using artificial intelligence–based digital coaches to promote healthy lifestyle and delay the onset or worsening of chronic diseases in healthy citizens; chronic obstructive pulmonary disease and heart failure decompensations management, proposing integrated care management based on advanced wearable monitoring and machine learning (ML) to predict decompensations; management of glycemic status in diabetes mellitus, based on beat to beat monitoring and short-term ML-based prediction of glycemic dynamics; treatment decision support systems for Parkinson disease, continuously monitoring motor and nonmotor complications to trigger enhanced treatment strategies; primary and secondary stroke prevention, using a coaching app and educational simulations with virtual and augmented reality; management of multimorbid older patients or patients with cancer, exploring novel chronic care models based on digital coaching, and advanced monitoring and ML; high blood pressure management, with ML-based predictions based on different intensities of monitoring through self-managed apps; and COVID-19 management, with integrated management tools limiting physical contact among actors.
Conclusions: This paper provides a methodology for selecting adequate settings for the large-scale piloting of eHealth frameworks and exemplifies with the decisions taken in GATEKEEPER the current views of the WHO and European Commission while moving forward toward a European Data Space.
https://doi.org/10.2196/42187
033428
1438-8871
https://repositori.udl.cat/handle/10459.1/463965
Big data
Chronic diseases
eHealth
Healthy aging
Integrated care
Large-scale pilots
GATEKEEPER's Strategy for the Multinational Large-Scale Piloting of an eHealth Platform: Tutorial on How to Identify Relevant Settings and Use Cases
oai:repositori.udl.cat:10459.1/658262022-05-26T13:07:13Zcom_10459.1_56965com_10459.1_2com_10459.1_227com_10459.1_241com_10459.1_244col_10459.1_57707col_10459.1_314col_10459.1_30324col_10459.1_363col_10459.1_44504
00925njm 22002777a 4500
dc
Granado-Serrano, Ana Belén
author
Martín Garí, Meritxell
author
Sánchez, Virginia
author
Riart Solans, Marissa
author
Berdún Hernández, Rebeca
author
Ludwig, Iziar A.
author
Rubió Piqué, Laura
author
Vilaprinyo Terré, Ester
author
Portero Otín, Manuel
author
Serrano Casasola, José Carlos Enrique
author
2019
Gut microbiota has been suggested to affect lipid metabolism. The objective of this study was to characterize the faecal microbiota signature and both short chain fatty acids (SCFAs) and bile acids (BA) profile of hypercholesterolemic subjects. Microbiota composition, SCFAs, BA and blood lipid profile from male volunteers with hypercholesterolemia (HC) and normocholesterolemia (NC) were determined by 16S rDNA sequencing, HPLC, GC and NMR, respectively. HC subjects were characterized by having lower relative abundance of Anaeroplasma (0.002% vs 0.219%, p-value = 0.026) and Haemophilus (0.041% vs 0.078%, p-value = 0.049), and higher of Odoribacter (0.51% vs 0.16%; p-value = 0.044). Correlation analysis revealed that Anaeroplasma and Haemophilus were associated to an unfavourable lipid profile: they correlated negatively to cholesterol and triglycerides related biomarkers and the ratio total to high density lipoprotein (HDL) cholesterol, and positively to HDL size. Odoribacter displayed an opposite behaviour. Faecal SCFAs profile revealed higher abundance of isobutyric (2.76% vs 0.82%, p-value = 0.049) and isovaleric acid (1.32% vs 0.06%, p-value = 0.016) in HC. Isobutyric acid correlated positively with Odoribacter and lipid parameters indicative of an unfavourable profile. BA profile did not show differences between groups. It was concluded that HC subjects showed a particular faecal bacterial signature and SCFAs profile associated with their lipid profile.
https://doi.org/10.1038/s41598-019-38874-3
028252
2045-2322
http://hdl.handle.net/10459.1/65826
Hypercholesterolemia
Faecal bacteria
short chain fatty acids
Branched short chain fatty acids
Bile acids
Faecal bacterial and short-chain fatty acids signature in hypercholesterolemia
oai:repositori.udl.cat:10459.1/832752023-06-02T09:33:16Zcom_10459.1_227com_10459.1_2com_10459.1_237com_10459.1_47453com_10459.1_241com_10459.1_240col_10459.1_314col_10459.1_354col_10459.1_59998col_10459.1_30324col_10459.1_333
00925njm 22002777a 4500
dc
Cambray Carner, Serafí
author
Ibarz Escuer, Mercedes
author
Bermúdez López, Marcelino
author
Martí Antonio, Manuel
author
Bozić Stanojević, Milica
author
Fernández i Giráldez, Elvira
author
Valdivielso Revilla, José Manuel
author
2020
Classical risk factors of atherosclerosis in the general population show paradoxical effects in chronic kidney disease (CKD) patients. Thus, low low-density lipoprotein (LDL) cholesterol levels have been associated with worse cardiovascular outcomes. Magnesium (Mg) is a divalent cation whose homeostasis is altered in CKD. Furthermore, Mg levels have been associated with cardiovascular health. The present study aims to understand the relationships of Mg and lipid parameters with atherosclerosis in CKD. In this analysis, 1754 participants from the Observatorio Nacional de Atherosclerosis en Nefrologia (NEFRONA) cohort were included. Carotid intima media thickness (cIMT) was determined in six arterial territories, and associated factors were investigated by linear regression. cIMT correlated positively with being male, Caucasian, a smoker, diabetic, hypertensive, dyslipidemic and with increased age, BMI, and triglyceride levels, and negatively with levels of HDL cholesterol. First-order interactions in linear regression analysis showed that Mg was an effect modifier on the influence of lipidic parameters. Thus, cIMT predicted values were higher when triglycerides or LDL levels were high and Mg levels were low. On the contrary, when Mg levels were high, this effect disappeared. In conclusion, Mg acts as an effect modifier between lipidic parameters and atherosclerotic cardiovascular disease. Therefore, Mg levels, together with lipidic parameters, should be taken into account when assessing atherosclerotic risk.
https://doi.org/10.3390/nu12092631
032814
2072-6643
http://hdl.handle.net/10459.1/83275
Atherosclerosis
Cardiovascular risk
Cholesterol
First-order interaction
Magnesium
Magnesium Levels Modify the Effect of Lipid Parameters on Carotid Intima Media Thickness
oai:repositori.udl.cat:10459.1/626812023-03-15T12:36:12Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_314col_10459.1_59998col_10459.1_30324
00925njm 22002777a 4500
dc
Maiques Carlos, Oscar
author
Barceló Gómez, Carla
author
Panosa, Anais
author
Pijuan Marquilles, Jordi
author
Orgaz, Jose L.
author
Rodríguez Hernández, Irene
author
Matas Nadal, Clara
author
Tell, Gemma
author
Vilella, Ramón
author
Fabra, Angels
author
Puig, Susana
author
Sanz Moreno, Victoria
author
Matias-Guiu, Xavier
author
Cantí Nicolás, Carles
author
Herreros Danés, Judit
author
Martí Laborda, Rosa Ma.
author
Macià Armengol, Anna
author
2018
Melanoma is a malignant tumor derived from melanocytes. Once disseminated, it is usually highly resistant to chemotherapy and is associated with poor prognosis. We have recently reported that T-type calcium channels (TTCCs) are overexpressed in melanoma cells and play an important role in melanoma progression. Importantly, TTCC pharmacological blockers reduce proliferation and deregulate autophagy leading to apoptosis. Here, we analyze the role of autophagy during migration/invasion of melanoma cells. TTCC Cav3.1 and LC3-II proteins are highly expressed in BRAFV600E compared with NRAS mutant melanomas, both in cell lines and biopsies. Chloroquine, pharmacological blockade, or gene silencing of TTCCs inhibit the autophagic flux and impair the migration and invasion capabilities, specifically in BRAFV600E melanoma cells. Snail1 plays an important role in motility and invasion of melanoma cells. We show that Snail1 is strongly expressed in BRAFV600E melanoma cells and patient biopsies, and its expression decreases when autophagy is blocked. These results demonstrate a role of Snail1 during BRAFV600E melanoma progression and strongly suggest that targeting macroautophagy and, particularly TTCCs, might be a good therapeutic strategy to inhibit metastasis of the most common melanoma type (BRAFV600E).
https://doi.org/10.1111/pcmr.12690
026992
1755-1471
http://hdl.handle.net/10459.1/62681
Melanoma
T-Type Calcium channels
Autophagy
Migration
Invasion
BRAFV600E
T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1
oai:repositori.udl.cat:10459.1/680252020-02-18T00:16:18Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Wang, Yufei
author
McKay, James D.
author
Rafnar, Thorunn
author
Wang, Zhaoming
author
Timofeeva, Maria N.
author
Broderick, Peter
author
Zong, Xuchen
author
Laplana Lafaja, Marina
author
Wei, Yongyue
author
Han, Younghun
author
Lloyd, Amy
author
Delahaye-Sourdeix, Manon
author
Chubb, Daniel
author
Gaborieau, Valerie
author
Wheeler, William
author
Chatterjee, Nilanjan
author
Thorleifsson, Gudmar
author
Sulem, Patrick
author
Liu, Geoffrey
author
Kaaks, Rudolf
author
Henrion, Marc
author
Kinnersley, Ben
author
Vallée, Maxime
author
LeCalvez-Kelm, Florence
author
Stevens, Victoria L.
author
Gapstur, Susan M.
author
Chen, Wei V.
author
Zaridze, David
author
Szeszenia-Dabrowska, Neonilia
author
Lissowska, Jolanta
author
Rudnai, Peter
author
Fabianova, Eleonora
author
Mates, Dana
author
Bencko, Vladimir
author
Foretova, Lenka
author
Janout, Vladimir
author
Krokan, Hans E.
author
Gabrielsen, Maiken Elvestad
author
Skorpen, Frank
author
Vatten, Lars
author
2014
We conducted imputation to the 1000 Genomes Project of four genome-wide association studies of lung cancer in populations of European ancestry (11,348 cases and 15,861 controls) and genotyped an additional 10,246 cases and 38,295 controls for follow-up. We identified large-effect genome-wide associations for squamous lung cancer with the rare variants BRCA2 p.Lys3326X (rs11571833, odds ratio (OR) = 2.47, P = 4.74 × 10−20) and CHEK2 p.Ile157Thr (rs17879961, OR = 0.38, P = 1.27 × 10−13). We also showed an association between common variation at 3q28 (TP63, rs13314271, OR = 1.13, P = 7.22 × 10−10) and lung adenocarcinoma that had been previously reported only in Asians. These findings provide further evidence for inherited genetic susceptibility to lung cancer and its biological basis. Additionally, our analysis demonstrates that imputation can identify rare disease-causing variants with substantive effects on cancer risk from preexisting genome-wide association study data.
https://doi.org/10.1038/ng.3002
020889
1061-4036
http://hdl.handle.net/10459.1/68025
Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer
oai:repositori.udl.cat:10459.1/574022021-06-28T08:55:43Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998col_10459.1_44504
00925njm 22002777a 4500
dc
Campoy, Irene
author
Lanau, Lucia
author
Altadill, Tatiana
author
Sequeiros, Tamara
author
Cabrera, Silvia
author
Cubo Abert, Montserrat
author
Pérez Benavente, Assumpción
author
Garcia, Angel
author
Borrós i Gómez, Salvador
author
Santamaria, Anna
author
Ponce, Jordi
author
Matias-Guiu, Xavier
author
Reventós, Jaume
author
Gil-Moreno, Antonio
author
Rigau, Marina
author
Colás, Eva
author
2016
Background: Uterine aspirates are used in the diagnostic process of endometrial disorders, yet further applications
could emerge if its complex milieu was simplified. Exosome-like vesicles isolated from uterine aspirates could become
an attractive source of biomarkers, but there is a need to standardize isolation protocols. The objective of the study
was to determine whether exosome-like vesicles exist in the fluid fraction of uterine aspirates and to compare protocols
for their isolation, characterization, and analysis.
Methods: We collected uterine aspirates from 39 pre-menopausal women suffering from benign gynecological diseases.
The fluid fraction of 27 of those aspirates were pooled and split into equal volumes to evaluate three differential
centrifugation-based procedures: (1) a standard protocol, (2) a filtration protocol, and (3) a sucrose cushion protocol.
Characterization of isolated vesicles was assessed by electron microscopy, nanoparticle tracking analysis and immunoblot.
Specifically for RNA material, we evaluate the effect of sonication and RNase A treatment at different steps of
the protocol. We finally confirmed the efficiency of the selected methods in non-pooled samples.
Results: All protocols were useful to isolate exosome-like vesicles. However, the Standard procedure was the best
performing protocol to isolate exosome-like vesicles from uterine aspirates: nanoparticle tracking analysis revealed
a higher concentration of vesicles with a mode of 135 ± 5 nm, and immunoblot showed a higher expression of
exosome-related markers (CD9, CD63, and CD81) thus verifying an enrichment in this type of vesicles. RNA contained
in exosome-like vesicles was successfully extracted with no sonication treatment and exogenous nucleic acids digestion
with RNaseA, allowing the analysis of the specific inner cargo by Real-Time qPCR.
Conclusion: We confirmed the existence of exosome-like vesicles in the fluid fraction of uterine aspirates. They were
successfully isolated by differential centrifugation giving sufficient proteomic and transcriptomic material for further
analyses. The Standard protocol was the best performing procedure since the other two tested protocols did not
ameliorate neither yield nor purity of exosome-like vesicles. This study contributes to establishing the basis for future
comparative studies to foster the field of biomarker research in gynecology.
Keywords: Biomarker, Endometrial biopsy, Exosomes, Exosomes isolation protocols, Exosome-like vesicles,
Extracellular vesicles, Gynecological disorders, Microvesicles, RNA, Uterine aspirates
https://doi.org/10.1186/s12967-016-0935-4
1479-5876
http://hdl.handle.net/10459.1/57402
Exosome‑like vesicles in uterine aspirates: a comparison of ultracentrifugation‑based isolation protocols
oai:repositori.udl.cat:10459.1/591682021-08-30T15:04:34Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Bozić Stanojević, Milica
author
Guzmán, Carla
author
Benet, Marta
author
Sánchez-Campos, Sonia
author
García-Monzón, Carmelo
author
Garí Marsol, Eloi
author
Gatius Calderó, Sònia
author
Valdivielso Revilla, José Manuel
author
Jover, Ramiro
author
2016
Background & Aims
The pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD) is still incompletely understood. Several nuclear receptors play a role in liver lipid metabolism and can promote hepatosteatosis, but the possible role of vitamin D receptor (VDR) in NAFLD has not been investigated.
Methods
The expression of liver VDR was investigated in apolipoprotein E knockout (apoE−/−) mice on a high fat diet, in wild-type mice on methionine and choline deficient diet and in NAFLD patients with hepatosteatosis and non-alcoholic steatohepatitis. The relevance of VDR was assessed in apoE−/− mice by deletion of VDR or paricalcitol treatment and in human HepG2 cells by VDR transfection or silencing. The role of VDR in fibrosis was also determined in VDR knockout mice (VDR−/−) treated with thioacetamide.
Results
Expression of liver VDR was markedly induced in two mouse models of NAFLD, as well as in patients with hepatosteatosis, but decreased in non-alcoholic steatohepatitis. VDR deletion in high fat diet-fed apoE−/− mice protected against fatty liver, dyslipidemia and insulin resistance, and caused a decrease in taurine-conjugated bile acids, but did not influence fibrosis by thioacetamide. apoE−/−VDR−/− mouse livers showed decreased gene expression of CD36, DGAT2, C/EBPα and FGF21, and increased expression of PNPLA2, LIPIN1 and PGC1α. Treatment of apoE−/− mice on high fat diet with paricalcitol had modest opposite effects on steatosis and gene expression. Finally, this set of genes showed concordant responses when VDR was overexpressed or silenced in HepG2 cells.
Conclusions
Induced hepatocyte VDR in NAFLD regulates key hepatic lipid metabolism genes and promotes high fat diet-associated liver steatosis. Therapeutic inhibition of liver VDR may reverse steatosis in early NAFLD.
Lay summary
The amount of vitamin D receptor is induced early in the livers of mice and humans when they develop non-alcoholic fatty liver disease. If the gene for the vitamin D receptor is deleted, hepatic lipid metabolism changes and mice do not accumulate fat in the liver. We conclude that the vitamin D receptor can contribute to the fatty liver disease promoted by a high fat diet.
https://doi.org/10.1016/j.jhep.2016.05.031
024628
0168-8278
http://hdl.handle.net/10459.1/59168
Vitamin D receptor
Non-alcoholic fatty liver disease
High fat diet
Steatosis
Hepatocytes
Hepatocyte vitamin D receptor regulates lipid metabolism and mediates experimental diet-induced steatosis
oai:repositori.udl.cat:10459.1/594072021-05-25T10:50:31Zcom_10459.1_227com_10459.1_2com_10459.1_59360com_10459.1_47453com_10459.1_241com_10459.1_240col_10459.1_314col_10459.1_59361col_10459.1_59998col_10459.1_30324col_10459.1_333
00925njm 22002777a 4500
dc
Betriu i Bars, M. Àngels
author
Farràs-Sallés, Cristina
author
Abajo, María
author
Martínez Alonso, Montserrat
author
Arroyo, David
author
Barbé Illa, Ferran
author
Buti, Miquel
author
Lecube Torelló, Albert
author
Portero Otín, Manuel
author
Purroy Garcia, Francisco
author
Torres, Gerard
author
Valdivielso Revilla, José Manuel
author
Fernández i Giráldez, Elvira
author
2016
Antecedentes y objetivos: La enfermedad renal crónica (ERC) y la ateromatosis son 2 enfermedades interrelacionadas que aumentan el riesgo de morbimortalidad cardiovascular. Los objetivos del proyecto ILERVAS son: 1) conocer la prevalencia de enfermedad ateromatosa subclínica y de enfermedad renal oculta; 2) valorar el impacto de su diagnóstico precoz sobre la morbimortalidad cardiovascular y la progresión de la ERC; 3) disponer de una plataforma de datos y muestras biológicas. Métodos: Estudio de intervención aleatorizado. Entre 2015 y 2017 se incluirá a 19.800 personas (9.900 en el grupo de intervención y 9.900 en el grupo control) entre 45 y 70 años, sin antecedentes de enfermedad cardiovascular y que presenten al menos un factor de riesgo cardiovascular, seleccionadas aleatoriamente de los centros de atención primaria (AP) de la provincia de Lérida. Un equipo técnico experto se desplazará con una unidad móvil para realizar las exploraciones basales al grupo de intervención: ecografía arterial (carótida, femoral,transcraneal y aorta abdominal), medición del índice tobillo-brazo, espirometría, detección de los productos de glicación avanzada y analítica seca de sangre y orina. Adicionalmente, se recogerán muestras de sangre y orina que serán almacenadas en el biobanco para identificar nuevos biomarcadores con biología de sistemas. Los participantes serán seguidos hasta 2025 para la identificación de eventos cardiovasculares, cambios de tratamiento y modificación de estilos de vida.
Conclusiones: El proyecto ILERVAS permitirá conocer la prevalencia de enfermedad vascular y de enfermedad renal subclínicas, evaluar si su diagnóstico precoz tiene un beneficio en la salud e investigar factores de riesgo emergentes.
Background and objectives: Chronic kidney disease (CKD) and atherosclerosis are 2 interrelated diseases that increase the risk of cardiovascular morbidity and mortality. The objectives of the ILERVAS project are: 1) to determine the prevalence of subclinical arterial disease and hidden kidney disease; 2) to assess the impact of early diagnosis of both diseases on cardiovascular morbidity and mortality and also on the progression of CKD; 3) to have a platform of data and biological samples.
Methods: Randomized intervention study. From 2015 to 2017, 19,800 people (9,900 in the intervention group and 9,900 in the control group) aged between 45 and 70 years without previous history of cardiovascular disease and with at least one cardiovascular risk factor will be randomly selected from the primary health care centres across the province of Lérida. A team of experts will travel around in a mobile unit to carry out the following baseline tests on the intervention group: Artery ultrasound; (carotid, femoral, transcranial and abdominal aorta); ankle-brachial index; spirometry; determination of advanced glycation end products; dried blood spot and urine spot tests. Additionally, blood and urine samples will be collected and stored in the biobank to identify new biomarkers using omics studies. Participants will be followed up until 2025 for identification of cardiovascular events, treatment changes and changes in lifestyle.
Conclusions: The ILERVAS project will reveal the prevalence of subclinical vascular disease and hidden kidney disease, determine whether or not their early diagnosis brings health benefits and will also allow investigation of new risk factors.
https://doi.org/10.1016/j.nefro.2016.02.008
024182
0211-6995
http://hdl.handle.net/10459.1/59407
Enfermedad cardiovascular
Placa de ateroma
Enfermedad renal oculta
Diagnóstico precoz
Estudio de intervención aleatorizado para evaluar la prevalencia de enfermedad ateromatosa y renal ocultas y su impacto en la morbimortalidad: Proyecto ILERVA
oai:repositori.udl.cat:10459.1/845252022-12-12T00:06:02Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Belokopytova-Chakh, Alena
author
Ruiz González, Agustín
author
Vilardell, Felip
author
Porcel Pérez, José Manuel
author
2022
We report a 27-year-old man who presented with cardiac tamponade
and was eventually diagnosed of T-cell lymphoblastic lymphoma
(T-LBL) by the flow cytometric analysis of pericardial fluid. Despite
pericardiocentesis and institution of standard chemotherapy, the
patient developed malignant arrhythmia with hemodynamic instability,
and died soon after admission. Cardiac tamponade is rarely
the first manifestation of a T-LBL.
Describimos el caso de un varón de 27 años que se presentó con un
taponamiento cardiaco y fue diagnosticado de linfoma linfoblástico
de células (T-LBL) mediante citometría de flujo del líquido pericárdico.
A pesar de una pericardiocentesis y de la instauración de
quimioterapia estándar, el paciente desarrolló una arritmia maligna
con inestabilidad hemodinámica y falleció poco después de su
ingreso. El taponamiento cardiaco es rara vez la primera manifestación
de un T-LBL.
https://doi.org/10.22546/65/2775
0304-4866
http://hdl.handle.net/10459.1/84525
T-cell lymphoblastic lymphoma
Pericardial effusion
Cardiac tamponade
Taponamiento cardíaco
Linfoma linfoblástico
Cardiac tamponade as the initial presentation of a T-cell lymphoblastic lymphoma
oai:repositori.udl.cat:10459.1/4642932023-10-28T03:00:22Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
de Gonzalo Calvo, David
author
Molinero, Marta
author
Benítez, Iván
author
Perez-Pons, Manel
author
García Mateo, Nadia
author
Ortega, Alicia
author
Postigo, Tamara
author
García Hidalgo, María Coronada
author
Belmonte, Thalía
author
Rodríguez Muñoz, Carlos
author
González, Jessica
author
Torres, Gerard
author
Gort Paniello, Clara
author
Moncusí Moix, Anna
author
Estella, Ángel
author
Tamayo Lomas, Luis
author
Martínez de la Gándara, Amalia
author
Socias, Lorenzo
author
Peñasco, Yhivian
author
de la Torre, Maria del Carmen
author
Bustamante Munguira, Elena
author
Gallego, Elena
author
Martínez Varela, Ignacio
author
Martin Delgado, María Cruz
author
Vidal Cortés, Pablo
author
López Messa, Juan
author
Pérez García, Felipe
author
Caballero, Jesús
author
Añón, José M.
author
Loza Vázquez, Ana
author
Carbonell, Nieves
author
Marin Corral, Judith
author
Jorge García, Ruth Noemí
author
Barberà, Carme
author
Ceccato, Adrián
author
Fernández Barat, Laia
author
Ferrer, Ricard
author
García Gasulla, Darío
author
Lorente-Balanza, Jose Ángel
author
Menéndez, Rosario
author
Motos, Anna
author
Peñuelas, Oscar
author
Riera, Jordi
author
Bermejo Martin, Jesús F.
author
Torres, Antoni
author
Barbé Illa, Ferran
author
2023
Background: The identification of critically ill COVID-19 patients at risk of fatal outcomes remains a challenge. Here, we first validated candidate microRNAs (miRNAs) as biomarkers for clinical decision-making in critically ill patients. Second, we constructed a blood miRNA classifier for the early prediction of adverse outcomes in the ICU.
Methods: This was a multicenter, observational and retrospective/prospective study including 503 critically ill patients admitted to the ICU from 19 hospitals. qPCR assays were performed in plasma samples collected within the first 48 h upon admission. A 16-miRNA panel was designed based on recently published data from our group.
Results: Nine miRNAs were validated as biomarkers of all-cause in-ICU mortality in the independent cohort of critically ill patients (FDR < 0.05). Cox regression analysis revealed that low expression levels of eight miRNAs were associated with a higher risk of death (HR from 1.56 to 2.61). LASSO regression for variable selection was used to construct a miRNA classifier. A 4-blood miRNA signature composed of miR-16-5p, miR-192-5p, miR-323a-3p and miR-451a predicts the risk of all-cause in-ICU mortality (HR 2.5). Kaplan‒Meier analysis confirmed these findings. The miRNA signature provides a significant increase in the prognostic capacity of conventional scores, APACHE-II (C-index 0.71, DeLong test p-value 0.055) and SOFA (C-index 0.67, DeLong test p-value 0.001), and a risk model based on clinical predictors (C-index 0.74, DeLong test-p-value 0.035). For 28-day and 90-day mortality, the classifier also improved the prognostic value of APACHE-II, SOFA and the clinical model. The association between the classifier and mortality persisted even after multivariable adjustment. The functional analysis reported biological pathways involved in SARS-CoV infection and inflammatory, fibrotic and transcriptional pathways.
https://doi.org/10.1186/s12931-023-02462-x
2052-4439
https://repositori.udl.cat/handle/10459.1/464293
Biomarker
COVID-19
ICU
microRNA
Prognosis
SARS-CoV-2
A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
oai:repositori.udl.cat:10459.1/484082021-08-30T14:56:39Zcom_10459.1_227com_10459.1_2com_10459.1_59159com_10459.1_47453col_10459.1_314col_10459.1_59160col_10459.1_59998
00925njm 22002777a 4500
dc
Herrero Perpiñán, Enrique
author
Ros Salvador, Joaquim
author
Bellí i Martínez, Gemma
author
Cabiscol Català, Elisa
author
2008
Protein structure and function can be altered by reactive oxygen species produced either by cell metabolism or by external oxidants. Although
catalases, superoxide dismutases and peroxidases contribute to maintaining non-toxic levels of reactive oxygen species, modification of amino
acid side chains occurs. In particular, oxidative modification of sulphydryl groups in proteins can be a two-faceted process: it could lead to
impairment of protein function or, depending on the redox state of cysteine residues, may activate specific pathways involved in regulating key
cell functions. In yeast cells, the thioredoxin and glutaredoxin systems participate in such redox regulation in different cell compartments, and
interplay exists between both systems. In this context, glutaredoxins with monothiol activity initially characterised in Saccharomyces cerevisiae
may display specific regulatory functions at the mitochondria and nuclei. Furthermore, their structural conservation in other organisms point to a
conserved important role in metal homeostasis also in higher eukaryotes. Control of gene expression in response to oxidative stress is mediated by
several transcription factors, among which Yap1 has a predominant role in S. cerevisiae (Pap1 in Schizosaccharomyces pombe and Cap1 in
Candida albicans). In combination with Gpx3 peroxidase and Ybp1 protein, the activity of Yap1 is itself controlled depending on the redox
state of some of its cysteine residues, which determines the nucleocytoplasmic location of the Yap1 molecules.
https://doi.org/10.1016/j.bbagen.2007.12.004
013101
0006-3002
http://hdl.handle.net/10459.1/48408
Catalase
Superoxide dismutase
Peroxidase
Redox control and oxidative stress in yeast cells
oai:repositori.udl.cat:10459.1/492602021-08-30T15:04:33Zcom_10459.1_227com_10459.1_2com_10459.1_59159com_10459.1_47453col_10459.1_314col_10459.1_59160col_10459.1_59998
00925njm 22002777a 4500
dc
Torre Ruiz, M. A. de la
author
Pujol Carrión, Núria
author
Sundaram, Venkatraghavan
author
2015-01-22
Saccharomyces cerevisiae is an optimal model to study stress responses for various reasons: i) budding yeast genome presents a high degree of homology with the human genome; ii) there are many proteins that show an elevated functional homology with specific human proteins; iii) it is a system whose genetic manipulation is reasonably easy and cheaper than other models; iv) the possibility of working with an haploid state facilitates the study of multiple processes; v) databases are the most complete of all the eukaryotic models. Due to the latest information derived from proteomic and genomic analyses, the genetic, biochemical and molecular information available relative to this biological system is extraordinarily big and complete. In this review, we present an overview of the mechanisms unravelling sensing and transducing oxidative stress. TOR, RAS/PKA, CWI, SNF1, and HOG are the main pathways involved both in the oxidative response and in the correct entry in stationary phase. In general, TOR and RAS/PKA dowregulation and SNF1 and CWI upregulation favour both a correct defence against oxidative damage and the entry in the quiescent state. All of these pathways have counterparts in humans. The actin cytoskeleton plays a dual function as sensor and target of oxidation, in tight connection with the former signalling cascades. In budding yeast, progression through stationary phase and quiescence constitute an accepted current model to study some of the mechanisms that determine life span. Aging is a process associated to oxidative stress and it is in tight relationship with bulk autophagy and mitophagy, both are mechanisms belonging to the oxidative defence and promoters of life extension when correctly regulated by, among other elements, the signalling cascades. - See more at: http://www.eurekaselect.com/125474/article#sthash.AVRLn2Lq.dpuf
https://doi.org/10.2174/1389450115666141020160105
023563
1389-4501
http://hdl.handle.net/10459.1/49260
Aging
Glutaredoxins
MAPK
oxidative stress
signalling
Coping with oxidative stress. The yeast model
oai:repositori.udl.cat:10459.1/4632642023-05-03T09:11:18Zcom_10459.1_227com_10459.1_2com_10459.1_236com_10459.1_47453col_10459.1_314col_10459.1_297col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Fibla Palazón, Joan
author
Maceda, Iago
author
Laplana Lafaja, Marina
author
Guerrero i Lladós, Montse
author
Álvarez, Miguel Martín
author
Burgueño, Jesús
author
Camps, Agustí
author
Fàbrega, Jordi
author
Felisart, Josefina
author
Grané, Joan
author
Remón, José Luis
author
Serra, Jordi
author
Moral, Pedro
author
Lao, Oscar
author
2023
The genetic variation of the European population at a macro-geographic scale follows genetic gradients which reflect main migration events. However, less is known about factors affecting mating patterns at a micro-geographic scale. In this study we have analyzed 726,718 autosomal single nucleotide variants in 435 individuals from the catalan Pyrenees covering around 200 km of a vast and abrupt region in the north of the Iberian Peninsula, for which we have information about the geographic origin of all grand-parents and parents. At a macro-geographic scale, our analyses recapitulate the genetic gradient observed in Spain. However, we also identified the presence of micro-population substructure among the sampled individuals. Such micro-population substructure does not correlate with geographic barriers such as the expected by the orography of the considered region, but by the bishoprics present in the covered geographic area. These results support that, on top of main human migrations, long ongoing socio-cultural factors have also shaped the genetic diversity observed at rural populations.
https://doi.org/10.3389/fgene.2022.1100440
033004
1664-8021
https://repositori.udl.cat/handle/10459.1/463264
Genetic variation
Rural population
Inbreeding
Population differentiation
Bishopric boundaries
Rural catalan Pyrenees
The power of geohistorical boundaries for modeling the genetic background of human populations: The case of the rural catalan Pyrenees
oai:repositori.udl.cat:10459.1/486642017-03-14T13:29:56Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Cardona, Maria
author
López, Juan Antonio
author
Serafín, Anna
author
Rongvaux, Anthony
author
Inserte Igual, Javier
author
García-Dorado, David
author
Flavell, Richard
author
Llovera i Tomàs, Marta
author
Cañas, Xavier
author
Vázquez, Jesús
author
Sanchis, Daniel
author
2015-06-29
Executioner caspase-3 and -7 are proteases promoting cell death but non-apoptotic roles
are being discovered. The heart expresses caspases only during development, suggesting they contribute to the organ maturation process. Therefore, we aimed at identifying novel functions of caspases in heart development. We induced simultaneous deletion of executioner caspase-3 and -7 in the mouse myocardium and studied its effects. Caspase knockout hearts are hypoplastic at birth, reaching normal weight progressively through myocyte hypertrophy. To identify the molecular pathways involved in these effects, we used microarray-based transcriptomics and multiplexed quantitative proteomics to compare wild type and executioner caspase-deficient myocardium at different developmental stages. Transcriptomics showed reduced expression of genes promoting DNA replication and cell cycle progression in the neonatal caspase-deficient heart suggesting reduced myocyte proliferation, and expression of non-cardiac isoforms of structural proteins in the adult null myocardium. Proteomics showed reduced abundance of proteins involved in oxidative phosphorylation accompanied by increased abundance of glycolytic enzymes underscoring retarded metabolic maturation of the caspase-null myocardium. Correlation between mRNA expression and protein abundance of relevant genes was confirmed, but transcriptomics and proteomics indentified complementary molecular pathways influenced by caspases in the developing heart. Forced expression of wild type or proteolytically inactive caspases in cultured cardiomyocytes induced expression of genes promoting cell division. The results reveal that executioner caspases can modulate heart’s cellularity and maturation during development, contributing novel information about caspase biology and heart development.
https://doi.org/10.1371/ journal.pone.0131411
023097
1932-6203
http://hdl.handle.net/10459.1/48664
Heart
Gene expression
Muscle cells
Mitochondria
Proteomics
Cell division
Executioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the Developing Mouse Heart
oai:repositori.udl.cat:10459.1/590772021-08-30T15:04:27Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Ferrezuelo, Francisco
author
Colomina i Gabarrella, Neus
author
Palmisano, Alida
author
Garí Marsol, Eloi
author
Gallego, Carme
author
Csikász-Nagy, Attila
author
Aldea, Martí
author
2012
Budding yeast cells are assumed to trigger Start and enter the cell cycle only after they attain a critical size set by external conditions. However, arguing against deterministic models of cell size control, cell volume at Start displays great individual variability even under constant conditions. Here we show that cell size at Start is robustly set at a single-cell level by the volume growth rate in G1, which explains the observed variability. We find that this growth-rate-dependent sizer is intimately hardwired into the Start network and the Ydj1 chaperone is key for setting cell size as a function of the individual growth rate. Mathematical modelling and experimental data indicate that a growth-rate-dependent sizer is sufficient to ensure size homeostasis and, as a remarkable advantage over a rigid sizer mechanism, it reduces noise in G1 length and provides an immediate solution for size adaptation to external conditions at a population level.
https://doi.org/10.1038/ncomms2015
018469
2041-1723
http://hdl.handle.net/10459.1/59077
The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation
oai:repositori.udl.cat:10459.1/570842021-08-30T15:04:32Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Ye, Junmei
author
Cardona, Maria
author
Llovera i Tomàs, Marta
author
Comella i Carnicé, Joan Xavier
author
Sanchis, Daniel
author
2012
The Myocyte Enhancer Factor-2 (MEF2) family of transcription factors regulates gene expression during
cardiomyocyte differentiation and adaptation of the myocardium to stress. MEF2 activity is enhanced by increasing
its transcription and by MAPK-dependent phosphorylation, and is reduced by binding to class-II
Histone Deacetylases and by miR-1-mediated degradation of its transcript. Here we show that MEF2 protein
abundance is regulated at the translational level, determining myocyte size, during hypertrophy. In order to
reduce MEF2 protein expression, its silencing through RNA interference required serum deprivation and,
even in this condition, MEF2 protein abundance recovered to basal levels in presence of phenylephrine.
Hypertrophic agonist stimulation of neonatal ventricular cardiomyocytes increased Mef2 expression by enhancing
its translation, without changing its transcription or blocking degradation of the protein. MEF2 abundance
was increased by Calcineurin overexpression in vivo and was reduced by Calcineurin inhibition in
vitro, without affecting Mef2 mRNA levels. Calcineurin activity influenced expression of Polypyrimidine
Tract Protein (PTB), contributing to MEF2 translation. Thus, our results show a previously unrecognized
but relevant level of MEF2 activity regulation through the control of its translation that involves Calcineurin
and PTB.
https://doi.org/10.1016/j.yjmcc.2012.07.013
018064
0022-2828
http://hdl.handle.net/10459.1/57084
Cardiomyocyte
Hypertrophy
Myocyte Enhancer Factor-2
Translation of Myocyte Enhancer Factor-2 is induced by hypertrophic stimuli in cardiomyocytes through a Calcineurin-dependent pathway
oai:repositori.udl.cat:10459.1/570392021-08-30T15:04:34Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Fonseca, Rafael
author
Blood, Emily
author
Rué i Monné, Montserrat
author
Harrington, David
author
Oken, Martin M.
author
Kyle, Robert A.
author
Dewald, Gordon W.
author
Van Ness, Brian
author
Van Wier, Scott A.
author
Henderson, Kimberly J.
author
Bailey, Richard J.
author
Greipp, Philip R.
author
2003
Nonrandom recurrent chromosomal abnormalities
are ubiquitous in multiple myeloma
(MM) and include, among others,
translocations of the immunoglobulin
heavy chain locus (IgH). IgH translocations
in MM result in the up-regulation of
oncogenes, and include more commonly
t(11;14)(q13;q32), t(4;14)(p16;q32), and
t(14;16)(q32;q23). Based on the recurrent
nature of these translocations and their
finding since the early stages of the
plasma cell (PC) disorders, we hypothesized
that they would confer biologic
and clinical variability. In addition, deletions
of 13q14 and 17p13 have also been
associated with a shortened survival. We
used cytoplasmic Ig–enhanced interphase
fluorescent in situ hybridization to detect
deletions (13q14 and 17p13.1), and translocations
involving IgH in 351 patients
treated with conventional chemotherapy
entered into the Eastern Cooperative Oncology
Group clinical trial E9486/9487.
Translocations were frequently unbalanced
with loss of one of the derivative
chromosomes. The presence of t(4;
14)(p16;q32) (n 42; 26 vs 45 months,
P < .001), t(14;16)(q32;q23) (n 15; 16 vs
41 months, P .003), 17p13 (n 37; 23
vs 44 months, P .005), and 13q14
(n 176; 35 vs 51 months, P .028) were
associated with shorter survival. A strati-
fication of patients into 3 distinct categories
allowed for prognostication: poor
prognosis group (t(4;14)(p16;q32), t(14;
16)(q32;q23), and 17p13), intermediate
prognosis ( 13q14), and good prognosis
group (all others), with median
survivals of 24.7, 42.3, and 50.5 months,
respectively (P < .001). This molecular cytogenetic
classification identifies patients
into poor, intermediate, and good risk
categories. More importantly it provides
further compelling evidence that MM is
composed of subgroups of patients categorized
according to their underlying
genomic aberrations.
https://doi.org/10.1182/blood-2002-10-3017
009171
0006-4971
http://hdl.handle.net/10459.1/57039
Clinical and biologic implications of recurrent genomic aberrations in myeloma
oai:repositori.udl.cat:10459.1/694662023-03-03T19:09:54Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Rahman, M.M.
author
Franch-Marro, X.
author
Maestro, J.L.
author
Martin, D.
author
Casali, Andreu
author
2017-09-15
Hormones play essential roles during development and maintaining homeostasis in adult organisms, regulating a plethora of biological processes. Generally, hormones are secreted by glands and perform a systemic action. Here we show that Juvenile Hormones (JHs), insect sesquiterpenoids synthesized by the corpora allata, are also synthesized by the adult Drosophila gut. This local, gut specific JH activity, is synthesized by and acts on the intestinal stem cell and enteroblast populations, regulating their survival and cellular growth through the JH receptors Gce/Met and the coactivator Tai. Furthermore, we show that this local JH activity is important for damage response and is necessary for intestinal tumor growth driven by activating mutations in Wnt and EGFR/Ras pathways. Together, our results identify JHs as key hormonal regulators of gut homeostasis and open the possibility that analogous hormones may play a similar role in maintaining vertebrate adult intestinal stem cell population and sustaining tumor growth.
https://doi.org/10.1038/s41598-017-11199-9
030291
2045-2322
http://hdl.handle.net/10459.1/69466
Local juvenile hormone activity regulates gut homeostasis and tumor growth in adult Drosophila
oai:repositori.udl.cat:10459.1/491922023-04-25T12:44:44Zcom_10459.1_227com_10459.1_2com_10459.1_463061com_10459.1_47453col_10459.1_314col_10459.1_463062col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Abella i Pons, Francesc
author
Vilarasau, Assumpció
author
Cuadrado, Josep
author
Solsona Tehàs, Francesc
author
Alves, Rui
author
Vilaplana Mayoral, Jordi
author
Serra, Joan
author
2014
El consumo de tabaco continúa siendo una importante causa de morbilidad y mortalidad. El proceso terapéutico para abandonar el tabaco consiste en la desintoxicación física de la nicotina y en el mantenimiento de la abstinencia de su consumo. Nuestro estudio se
sitúa en este contexto, ofreciendo una estrategia de apoyo por SMS y monitorizando al paciente a lo largo del tratamiento.
Material y método. Este estudio longitudinal compara dos grupos de pacientes: uno con apoyo a través de SMS y otro, de control, que no disfruta de dicho apoyo. Los pacientes recibieron aleatoriamente mensajes de apoyo y refuerzo positivo, así como preguntas
sobre su estado. El resto de la terapia es igual para ambos grupos.
Resultados. El grupo que recibía apoyo por SMS presentó unas tasas de abstinencia mejores que el otro (57,1% frente a 42,9%). Los mismos participantes valoran positivamente la metodología y admiten que les ahorra tiempo y viajes. Conclusión. El uso de las TIC para monitorizar y reforzar el proceso de desintoxicación del consumo de tabaco parece ser efectivo y bien acogido por los pacientes.
022357
0213-7615
http://hdl.handle.net/10459.1/49192
Seguimiento y control de pacientes fumadores en proceso de deshabituación mediante SMS. Una experiencia en e-salud
oai:repositori.udl.cat:10459.1/570872022-02-16T11:00:20Zcom_10459.1_227com_10459.1_2col_10459.1_314col_10459.1_49291
00925njm 22002777a 4500
dc
Dolcet Roca, Xavier
author
Llobet Navàs, David
author
Pallares, Judit
author
Rué i Monné, Montserrat
author
Comella i Carnicé, Joan Xavier
author
Matias-Guiu, Xavier
author
2005
The FLICE-inhibitory protein (FLIP) plays a key role in the regulation of apoptosis triggered by death ligands.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in some
types of tumor but not in others. To assess the possible role of FLIP in apoptosis resistance in endometrial
carcinoma, we performed an immunohistochemical study on a tissue microarray composed of 95 endometrial
carcinomas. We found positive signals in 43% of the cases, as well as a significant difference in FLIP
expression between stage I and II tumors. Moreover, we observed that endometrial carcinoma cell lines
Ishikawa and KLE did not undergo apoptosis after TRAIL treatment. Cotreatment of these cells with the inhibitor
of transcription actinomycin D resulted in a dramatic decrease in cell viability and induced activation of
caspase-8. These events coincided with downregulation of FLIP mRNA and protein. Inhibitors of caspase-8 or
overexpression of FLIP completely blocked apoptosis induced by actinomycin D plus TRAIL cotreatment. More
importantly, downregulation of endogenous FLIP expression by specific siRNAs sensitized endometrial
carcinoma cells to TRAIL-induced apoptosis in the absence of actinomycin D. Taken together, our results
suggest for the first time a critical role for FLIP in the regulation apoptosis triggered by TRAIL in endometrial
carcinoma cells.
https://doi.org/10.1038/labinvest.3700286
008550
0023-6837
http://hdl.handle.net/10459.1/57087
Endometrial carcinoma
FLIP
TRAIL
Tissue microarray
FLIP is frequently expressed in endometrial carcinoma and has a role in resistance to TRAIL-induced apoptosis
oai:repositori.udl.cat:10459.1/570882022-11-28T20:07:24Zcom_10459.1_227com_10459.1_2col_10459.1_314col_10459.1_49291
00925njm 22002777a 4500
dc
Pallares, Judit
author
Bussaglia, Elena
author
Martínez-Guitarte, Jose Luis
author
Dolcet Roca, Xavier
author
Llobet Navàs, David
author
Rué i Monné, Montserrat
author
Sanchez-Verde, Lidia
author
Palacios, José
author
Prat, Jaime
author
Matias-Guiu, Xavier
author
2005
The tumor suppressor gene PTEN/MMAC1 is located on chromosome 10q23.3. Inactivation of PTEN, either by
mutations, deletions, or promoter hypermethylation, has been identified in a wide variety of tumors. Inactivation
of the two alleles of PTEN is required, because it is a tumor suppressor gene. Immunohistochemical staining
may be an effective screening method to demonstrate the absence of the protein in tumors exhibiting PTEN
inactivation. We studied a tissue microarray, constructed from paraffin-embedded blocks of 95 endometrial
carcinomas, 38 of them previously evaluated for alterations in PTEN. We also studied cell blocks obtained from
one PTEN-defective endometrial cancer cell line, after transfection with either a plasmid encoding wild-type
PTEN or the empty vector. The tumor samples were tested with four different anti-PTEN commercial antibodies:
a polyclonal antibody, the monoclonal antibody 28H6, the monoclonal antibody 10P03, and the monoclonal
antibody 6.H2.1. Results were correlated with the presence of abnormalities in PTEN, as well as with the
immunohistochemical expression of phosphorylated AKT. Antibody 28H6 produced a predominant nuclear
staining, while the other three antibodies produced a predominant cytoplasmic staining. There was no
significant correlation between the results obtained with the four antibodies. The monoclonal antibody 6.H2.1
was the only one that exhibited a correlation with the presence of molecular alterations in PTEN, and a
statistically significant association with immunostaining for phosphorylated AKT (r ¼ 0.249, P ¼ 0.037). The
monoclonal antibody 10P03 exhibited an association with phospho-AKT that did not have statistical
significance. Both 6.H2.1 and 10P03 antibodies stained PTEN-transfected cells, and were negative in the
PTEN-deficient cell line blocks. The polyclonal antibody and the monoclonal antibody 28H6 produced positive
staining in PTEN-deficient cell line blocks, suggesting nonspecific staining. The results indicate that
monoclonal antibody 6.H2.1 may be a suitable alternative for tumors with inactivation of PTEN.
https://doi.org/10.1038/modpathol.3800347
002567
0893-3952
http://hdl.handle.net/10459.1/57088
Endometrial carcinoma
PTEN
Tissue microarray
Molecular pathology
Immunohistochemical analysis of PTEN in endometrial carcinoma: a tissue microarray study with a comparison of four commercial antibodies in correlation with molecular abnormalities
oai:repositori.udl.cat:10459.1/570322021-08-30T15:04:30Zcom_10459.1_227com_10459.1_2col_10459.1_314col_10459.1_49291
00925njm 22002777a 4500
dc
Fernández Hernández, Rita
author
Rafel i Borrell, Marta
author
Pérez Fusté, Noel
author
Aguayo Ortiz, Rafael
author
Casanova i Seuma, Josep M. (Josep Manel)
author
Egea Navarro, Joaquim
author
Ferrezuelo, Francisco
author
Garí Marsol, Eloi
author
2013
The function of Cyclin D1 (CycD1) has been widely studied in the cell nucleus as a regulatory subunit of the cyclindependent
kinases Cdk4/6 involved in the control of proliferation and development in mammals. CycD1 has been also
localized in the cytoplasm, where its function nevertheless is poorly characterized. In this work we have observed that
in normal skin as well as in primary cultures of human keratinocytes, cytoplasmic localization of CycD1 correlated with
the degree of differentiation of the keratinocyte. In these conditions, CycD1 co-localized in cytoplasmic foci with exocyst
components (Sec6) and regulators (RalA), and with β1 integrin, suggesting a role for CycD1 in the regulation of keratinocyte
adhesion during differentiation. Consistent with this hypothesis, CycD1 overexpression increased β1 integrin
recycling and drastically reduced the ability of keratinocytes to adhere to the extracellular matrix. We propose that localization
of CycD1 in the cytoplasm during skin differentiation could be related to the changes in detachment ability of
keratinocytes committed to differentiation.
https://doi.org/10.4161/cc.25590
021252
1538-4101
http://hdl.handle.net/10459.1/57032
Cyclin D1
Cytoplasm
Keratinocytes
Cyclin D1 localizes in the cytoplasm of keratinocytes during skin differentiation and regulates cell–matrix adhesion
oai:repositori.udl.cat:10459.1/566962021-08-30T15:04:33Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Soler González, Jorge
author
Serna Arnaiz, Catalina
author
Bosch, Anna
author
Ruiz-Magaz, Maria Cristina
author
Huertas, E.
author
Rué i Monné, Montserrat
author
2008
Objectives The incidence and duration of sick leave were studied among immigrants and the native-born
population in Spain.
Methods This observational follow-up study included 1427 immigrants and 2793 Spanish natives treated at five
primary care centers in Lleida in 2005 and followed for 6 months. The sick leave causes were coded according
to the International Classification of Diseases (10th revision). Multivariate Poisson regressions estimated the rate
ratio (RR) for sick leave adjusted for age, and linear regressions evaluated the effect of age, gender, and region
of origin on the total number of sick-leave days.
Results Altogether 19.5% of the natives and 12.7% of the immigrants had at least one sick-leave episode. The
incidence of new episodes per 100 person-years was lower for the immigrants than for the natives (32.5 versus
43.3 for the men and 18.6 versus 35.6 for the women, respectively). The mean duration of sick leave in the 6-
month period was 19.4 (SD 29.4) days for the immigrants and 33.5 (SD 39.2) days for the natives. For the men,
the risk of sick leave was greater for the natives than for the immigrants (adjusted RR 1.70, 95% confidence
interval 1.43–2.02). After adjustment for age, the duration of sick leave for the native workers was 1.5 times
greater than for the immigrants.
Conclusions Even though sick leave was less frequent among the immigrants than among the natives and the
immigrant sick-leave periods were of shorter duration, the two study populations did not show differences in
the causes of disability.
https://doi.org/10.5271/sjweh.1288
013071
0355-3140
http://hdl.handle.net/10459.1/56696
Absenteeism
Immigration
Job satisfaction
Migrant worker
Sick leave among native and immigrant workers in Spain: a 6-month follow-up study
oai:repositori.udl.cat:10459.1/694692020-09-09T00:19:35Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Tarragona Foradada, Jordi
author
Pallarés, J.
author
Buetas, P.
author
Subirats, A.
author
Matias-Guiu, Xavier
author
2019-10
030051
2013-5238
http://hdl.handle.net/10459.1/69469
Punción-aspiración con aguja fina
Melanoma
Metástasis
Pulmón
Metàstasis de melanoma maligne en nòduls pulmonar múltiples
oai:repositori.udl.cat:10459.1/567522021-08-30T15:04:33Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Echave Lozano, Pedro
author
Esparza-Cerón, M. Angel
author
Cabiscol Català, Elisa
author
Tamarit Sumalla, Jordi
author
Ros Salvador, Joaquim
author
Membrillo-Hernández, Jorge
author
Lin, Edmund C. C.
author
2002
The adhE gene of Escherichia coli encodes a multifunctional ethanol
oxidoreductase (AdhE) that catalyzes successive reductions of
acetyl-CoA to acetaldehyde and then to ethanol reversibly at the
expense of NADH. Mutant JE52, serially selected for acquired and
improved ability to grow aerobically on ethanol, synthesized an
AdhEA267T/E568K with two amino acid substitutions that sequentially
conferred improved catalytic properties and stability. Here
we show that the aerobic growth ability on ethanol depends also
on protection of the mutant AdhE against metal-catalyzed oxidation
by the chaperone DnaK (a member of the Hsp70 family). No
DnaK protection of the enzyme is evident during anaerobic growth
on glucose. Synthesis of DnaK also protected E. coli from H2O2
killing under conditions when functional AdhE is not required. Our
results therefore suggest that, in addition to the known role of
protecting cells against heat stress, DnaK also protects numerous
kinds of proteins from oxidative damage.
https://doi.org/10.1073/pnas.072504199
000008
1091-6490
http://hdl.handle.net/10459.1/56752
DnaK dependence of mutant ethanol oxidoreductases evolved for aerobic function and protective role of the chaperone against protein oxidative damage in Escherichia coli
oai:repositori.udl.cat:10459.1/4640632023-10-03T03:00:25Zcom_10459.1_227com_10459.1_2com_10459.1_237com_10459.1_47453col_10459.1_314col_10459.1_354col_10459.1_59998
00925njm 22002777a 4500
dc
Targa, Adriano
author
Benítez, Iván
author
Moncusí Moix, Anna
author
Dakterzada, Farida
author
Minguez Roure, Olga
author
Vaca, Rafaela
author
Dalmases, Mireia
author
Sánchez de la Torre, Manuel
author
Barbé Illa, Ferran
author
Piñol Ripoll, Gerard
author
2023
Background Previous studies challenge the impact of obstructive sleep apnea (OSA) once patients are diagnosed with Alzheimer’s disease (AD). Nevertheless, OSA recognizably disrupts sleep, and relevant associations between sleep, AD pathological markers, and cognition have been demonstrated. We aimed to further explore this, evaluating the associations between each breathing cessation event that compose the apnea–hypopnea index (AHI) and the sleep structure to finally investigate whether this was related to increased levels of AD markers and higher cognitive decline.
Methods Observational, prospective study, including consecutive patients diagnosed with mild-moderate AD. The participants were submitted to overnight polysomnography followed by a cerebrospinal fluid collection for AD pathological markers levels determination. Neuropsychological assessment was performed at baseline and after 12 months of follow-up.
Results The cohort was composed of 116 patients (55.2% females) with a median [p25;p75] age of 76.0 [72.0;80.0] years and an AHI of 25.9 [15.1;48.5], which was mainly defined by the presence of hypopneas and obstructive apneas.
These were distinctively associated with the sleep structure, with obstructive apneas being related to arousals and sleep lightening and hypopneas being related to an increased number of arousals only. Despite having a lower
frequency, mixed and central apneas also presented associations with the sleep structure, particularly increasing the time spent in the lighter sleep stages. In relation to AD pathological markers, obstructive and mixed apneas were related to an augment in neurofilament light levels while hypopneas were associated with a higher phosphorylated- tau/amyloid-beta protein ratio. Hypopneas were the most important event for an increased cognitive decline
at the 12-month follow-up.
Conclusions Our findings highlight the importance of a patient-centered approach, with a comprehensive and detailed analysis of the AHI to effectively predict the different outcomes and tailor the appropriate therapeutic strategies.
https://doi.org/10.1186/s13195-023-01266-x
033426
1758-9193
https://repositori.udl.cat/handle/10459.1/464063
Alzheimer’s disease
Obstructive sleep apnea
Apnea–hypopnea index
Hypopneas
Cognitive decline
Breathing cessation events that compose the apnea–hypopnea index are distinctively associated with the adverse outcomes in Alzheimer’s disease
oai:repositori.udl.cat:10459.1/707772021-03-18T00:24:59Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Bersweiler, Antoine
author
d’Autréaux, Benoît
author
Mazon, Hortense
author
Kriznik, Alexandre
author
Bellí i Martínez, Gemma
author
Delaunay-Moisan, Agnès
author
Toledano, Michel B.
author
Rahuel-Clermont, Sophie
author
2017
In Saccharomyces cerevisiae, Yap1 regulates an H2O2-inducible transcriptional response that controls cellular H2O2 homeostasis. H2O2 activates Yap1 by oxidation through the intermediacy of the thiol-peroxidase Orp1. Upon reacting with H2O2, Orp1 catalytic cysteine oxidizes to a sulfenic acid, which then engages either into an intermolecular disulfide with Yap1 that leads to Yap1 activation, or an intramolecular disulfide that commits the enzyme into its peroxidatic cycle. Of these two competing reactions, how the former one, which is kinetically unfavorable, occurs? We show that the Yap1-binding-protein Ybp1 brings together Orp1 and Yap1 into a ternary complex that selectively activates condensation of the Orp1 sulfenylated cysteine with one of the six Yap1 cysteines, while inhibiting Orp1 intramolecular disulfide formation. We propose that Ybp1 operates as a scaffold protein and as a sulfenic acid chaperone to provide specificity into the transfer of oxidizing equivalents by a reactive sulfenic acid species.
https://doi.org/10.1038/nchembio.2412
026782
1552-4469
http://hdl.handle.net/10459.1/70777
A scaffold protein that chaperones a cysteine-sulfenic acid in H2O2 signaling
oai:repositori.udl.cat:10459.1/603282022-01-12T12:23:37Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Ramírez-Morros, Anna
author
Granado Casas, Minerva
author
Alcubierre Calvo, Núria
author
Martínez Alonso, Montserrat
author
Real, Jordi
author
Castelblanco Echavarría, Esmeralda
author
Esquerda, Aureli
author
Cao, Gonzalo
author
Rubinat, Esther
author
Hernández García, Marta
author
Alonso, Núria
author
Fernández i Giráldez, Elvira
author
Mauricio Puente, Dídac
author
2017
Aims. To assess whether circulating 25-hydroxyvitamin D3 (25OHD) and mineral metabolism-related factors (serum phosphate, calcium, and parathormone) are associated with subclinical carotid atherosclerosis (SCA), defined as the presence of carotid atherosclerotic plaques (main study outcome), in patients with type 2 diabetes mellitus (T2DM) without kidney disease or previous cardiovascular disease. Methods. We undertook a post hoc analysis of a cross-sectional study in adults with T2DM in whom we evaluated SCA. A total of 303 subjects with T2DM were included. Clinical variables and carotid ultrasound imaging were obtained. Results. We found no association of 25OHD with the presence of SCA. However, calcium phosphate (CaP; mg2/dL2) product was positively associated with the presence of carotid plaques (ORadj = 1.078; 95% CI: 1.017–1.142). An inverse association was observed between higher levels of 25OHD (≥30 ng/mL versus <20 ng/mL concentrations) and common carotid intima-media thickness (cIMT; mm) (βadj ± SE = −0.055 ± 0.024). We conclude that the CaP product is independently associated with the presence of established subclinical carotid atherosclerosis in patients with T2DM.
https://doi.org/10.1155/2017/3498368
026043
2314-6745
http://hdl.handle.net/10459.1/60328
Calcium phosphate product is associated with subclinical carotid atherosclerosis in type 2 diabetes
oai:repositori.udl.cat:10459.1/679972020-02-13T00:15:28Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Herrero, Rocío
author
Real, Luis M.
author
Rivero-Juárez, Antonio
author
Pineda, Juan Antonio
author
Camacho, Ángela
author
Macías, Juan
author
Laplana Lafaja, Marina
author
Konieczny, Piotr
author
Márquez, Francisco J.
author
Souto, Juan Carlos
author
Soria, José Manuel
author
Saulle, Irma
author
Lo Caputo, Sergio
author
Biasin, Mara
author
Rivero, Antonio
author
Fibla Palazón, Joan
author
Caruz, Antonio
author
2015-03
HIV-1 induces activation of complement through the classical and lectin pathways. However, the virus incorporates several membrane-bound or soluble regulators of complement activation (RCA) that inactivate complement. HIV-1 can also use the complement receptors (CRs) for complement-mediated antibody-dependent enhancement of infection (Ć-ADE). We hypothesize that hypofunctional polymorphisms in RCA or CRs may protect from HIV-1 infection. For this purpose, 139 SNPs located in 19 RCA and CRs genes were genotyped in a population of 201 Spanish HIV-1-exposed seronegative individuals (HESN) and 250 HIV-1-infected patients. Two SNPs were associated with infection susceptibility, rs1567190 in CR2 (odds ratio (OR)=2.27, P=1 × 10-4) and rs2842704 in C4BPA (OR=2.11, P=2 × 10-4). To replicate this finding, we analyzed a cohort of Italian, sexually HESN individuals. Although not significant (P=0.25, OR=1.57), similar genotypic proportions were obtained for the CR2 marker rs1567190. The results of the two association analyses were combined through a random effect meta-analysis, with a significant P-value of 2.6x10-5 (OR=2.07). Furthermore, we found that the protective CR2 genotype is correlated with lower levels CR2 mRNA as well as differences in the ratio of the long and short CR2 isoforms.Genes and Immunity advance online publication, 8 January 2015; doi:10.1038/gene.2014.71.
https://doi.org/10.1038/gene.2014.71
022124
1466-4879
http://hdl.handle.net/10459.1/67997
HIV infection
genetica asociación
genes complemento
Association of complement receptor 2 polymorphisms withinnate resistance to HIV-1 infection
oai:repositori.udl.cat:10459.1/472172017-08-03T09:27:45Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Barreto Parra, Lina Patricia
author
Garcera, Ana
author
Jansson, Kristina
author
Sunnerhagen, Per
author
Herrero Perpiñán, Enrique
author
2006
Saccharomyces cerevisiae cells contain three omega-class glutathione transferases with glutaredoxin activity (Gto1, Gto2, and Gto3), in addition to two glutathione transferases (Gtt1 and Gtt2) not classifiable into standard classes. Gto1 is located at the peroxisomes, where it is targeted through a PTS1-type sequence, whereas Gto2 and Gto3 are in the cytosol. Among the GTO genes, GTO2 shows the strongest induction of expression by agents such as diamide, 1-chloro-2,4-dinitrobenzene, tert-butyl hydroperoxide or cadmium, in a manner that is dependent on transcriptional factors Yap1 and/or Msn2/4. Diamide and 1-chloro-2,4-dinitrobenzene (causing depletion of reduced glutathione) also induce expression of GTO1 over basal levels. Phenotypic analyses with single and multiple mutants in the S. cerevisiae glutathione transferase genes show that, in
the absence of Gto1 and the two Gtt proteins, cells display increased sensitivity to cadmium. A gto1-null mutant also shows growth defects on oleic acid-based medium, which is indicative of abnormal peroxisomal functions, and altered expression of genes related to sulfur amino acid metabolism. As a consequence, growth of the gto1 mutant is delayed in growth medium without lysine, serine, or threonine, and the mutant cells have low levels of reduced glutathione. The role of Gto1 at the S. cerevisiae peroxisomes could be related to the redox regulation
of the Str3 cystathionine -lyase protein. This protein is also located at the peroxisomes in S. cerevisiae, where it is involved in transulfuration of cysteine into homocysteine, and requires a conserved cysteine residue for its biological activity.
https://doi.org/10.1128/EC.00216-06
010456
1535-9778 (versió paper)
1535-9786
http://hdl.handle.net/10459.1/47217
Llevat de cervesa
A peroxisomal glutathione transferase of Saccharomyces cerevisiae is functionally related to sulfur amino acid metabolism
oai:repositori.udl.cat:10459.1/566942021-08-30T15:04:33Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Séculi, E.
author
Fusté Sugrañes, Josep
author
Brugulat, Pilar
author
Juncà, S.
author
Rué i Monné, Montserrat
author
Guillén, M.
author
2001
Objetivo: Analizar las diferencias en la percepción del estado
de salud de los varones y mujeres en las últimas etapas
de la vida y explorar su relación con variables sociodemográficas
y de salud.
Métodos: Datos procedentes de la Encuesta de Salud de
Cataluña de 1994, de 1.459 varones y 1.993 mujeres de 60
y más años. Se realizó un análisis de la autovaloración del
estado de salud según la edad, el sexo, la clase social, la declaración
de enfermedades crónicas y la discapacidades y se
aplicó un modelo de análisis multivariable de regresión logística
teniendo en cuenta el diseño muestral.
Resultados: El 57,3% de las mujeres de 60 y más años declaraba
no tener buena salud, frente al 43,6% de los varones.
También fue superior la proporción de mujeres que padecía
una o más discapacidades (41,2%) respecto a los varones
(28,7%), así como la de enfermedades crónicas, el 92,2% de
las mujeres y el 85,6% de los varones. En el modelo de regresión
logística multivariable continúa manteniéndose una percepción
de mala salud superior en las mujeres y aparecen
como factores explicativos el número de enfermedades cró-
nicas, padecer discapacidades y pertenecer a las clases sociales
más desfavorecidas. La edad en interacción con las enfermedades
crónicas amortigua el efecto de éstas en la
valoración del estado de salud.
Conclusiones: Entre la población anciana, la percepción de
mala salud fue superior en las mujeres incluso ajustando por
otras variables explicativas significativas (clase social, edad,
discapacidades y enfermedades crónicas). Padecer enfermedades
crónicas y/o discapacidades constituyen los factores
explicativos más importantes en la percepción del estado
de salud. El impacto del padecimiento de enfermedades
crónicas en relación con la percepción de mala salud disminuye
a medida que los grupos son de mayor edad.
https://doi.org/10.1016/S0213-9111(01)71550-6
009175
0213-9111
http://hdl.handle.net/10459.1/56694
Género
Estado de salud percibido
Desigualdades en salud
Encuestas de salud
Percepción del estado de salud en varones y mujeres en las últimas etapas de la vida
oai:repositori.udl.cat:10459.1/570292021-08-30T15:04:34Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Akita, Tenpei
author
Kumada, Tatsuro
author
Yoshihara, Sei-ichi
author
Egea Navarro, Joaquim
author
Yamagishi, Satoru
author
2015
Our sophisticated thoughts and behaviors are based on the miraculous development of our complex nervous network system, in which many different types of proteins and signaling cascades are regulated in a temporally and spatially ordered manner. Here we review our recent attempts to grasp the principles of nervous system development in terms of general cellular phenomena and molecules, such as volume-regulated anion channels, intracellular Ca2+ and cyclic nucleotide signaling, the Npas4 transcription factor and the FLRT family of axon guidance molecules. We also present an example illustrating that the same FLRT family may regulate the development of vascular networks as well. The aim of this review is to open up new vistas for understanding the intricacy of nervous and vascular system development.
https://doi.org/10.1007/s12576-015-0416-1
023960
1880-6546
http://hdl.handle.net/10459.1/57029
Nervous system development
Anion channel
Intracellular signaling
Transcription factor
Ion channels, guidance molecules, intracellular signaling and transcription factors regulating nervous and vascular system development
oai:repositori.udl.cat:10459.1/472002017-08-02T12:22:46Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Herrero Perpiñán, Enrique
author
Jackson, Maria
author
Bassford, Phillip J.
author
Sinden, David
author
Holland, I. Barry
author
1982
The synthesis of a membrane-bound MalE ,B-galactosidase hybrid protein,
when induced by growth of Escherichia coli on maltose, leads to inhibition of cell
division and eventually a reduced rate of mass increase. In addition, the relative
rate of synthesis of outer membrane proteins, but not that of inner membrane
proteins, was reduced by about 50%o. Kinetic experiments demonstrated that this
reduction coincided with the period of maximum synthesis of the hybrid protein
(and another maltose-inducible protein, LamB). The accumulation of this abnormal
protein in the envelope therefore appeared specifically to inhibit the synthesis,
the assembly of outer membrane proteins, or both, indicating that the hybrid
protein blocks some export site or causes the sequestration of some limiting
factor(s) involved in the export process. Since the MalE protein is normally
located in the periplasm, the results also suggest that the synthesis of periplasmic
and outer membrane proteins may involve some steps in common. The reduced
rate of synthesis of outer membrane proteins was also accompanied by the
accumulation in the envelope of at least one outer membrane protein and at least
two inner membrane proteins as higher-molecular-weight forms, indicating that
processing (removal of the N-terminal signal sequence) was also disrupted by the
presence of the hybrid protein. These results may indicate that the assembly of
these membrane proteins is blocked at a relatively late step rather than at the level
of primary recognition of some site by the signal sequence. In addition, the results
suggest that some step common to the biogenesis of quite different kinds of
envelope protein is blocked by the presence of the hybrid protein.
004171
0021-9193 (versió paper)
1098-5530
http://hdl.handle.net/10459.1/47200
Escheríchia coli
Proteïnes
Insertion of a malE B-Galactosidase fusion protein into the envelope of Escherichia coli disrupts biogenesis of outer membrane proteins and processing of inner membrane proteins
oai:repositori.udl.cat:10459.1/571042021-08-30T15:04:33Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Friedenberg, William R.
author
Rué i Monné, Montserrat
author
Blood, Emily
author
Dalton, William S.
author
Shustik, Chaim
author
Larson, Richard A.
author
Sonneveld, Pieter
author
Greipp, Philip R.
author
2006
BACKGROUND. Preliminary studies have shown valspodar (PSC-833: Novartis Pharmaceuticals,
East Hanover, NJ) to be a potent inhibitor of multidrug resistance
(MDR), one cause of resistance to chemotherapy. An international randomized
control study (Phase III) evaluated the use of vincristine, doxorubicin, and dexamethasone
(VAD) with (n 46) and without (n 48) valspodar in the treatment of
patients with recurring or refractory multiple myeloma.
METHODS. Patients with documented recurrence or refractory myeloma were stratified
based on prior treatment exposure and creatinine and randomized. Because
of interaction of valspodar with vincristine and doxorubicin, the doses of these
drugs were reduced compared with the VAD-alone arm, and the doxorubicin was
further reduced in the last 15 patients when given with valspodar based on
pharmacokinetic and toxicity studies.
RESULTS. There were no complete or near-complete responses. There were 29%
partial responses (PRs) in the VAD-alone arm and 44% with valspodar (P 0.2).
Median progression-free survival was 7 months with VAD alone and 4.9 months
with valspodar (P 0.50). Subjective response was 19% with VAD alone and 17%
with valspodar (P 1.0). Median survival with VAD alone was 18.5 months and
15.3 with the addition of valspodar (P 0.055). Toxicity of Grade 3 or greater
was higher (P 0.0001) in the valspodar arm (89%) compared with the VAD-alone
arm (58%). The reduction of doxorubicin dose reduced toxicity but not significantly
(P 0.11).
CONCLUSION. The addition of the MDR-modulating agent valspodar to VAD did not
improve treatment outcome. Toxicity was increased in the valspodar-treated group
compared with VAD alone.
https://doi.org/10.1002/cncr.21666
009155
0008-543X
http://hdl.handle.net/10459.1/57104
Refractory multiple myeloma
VAD
Valspodar
PSC-833
Phase III Study of PSC-833 (Valspodar) in Combination with Vincristine, Doxorubicin, and Dexamethasone (Valspodar/VAD) versus VAD Alone in Patients with Recurring or Refractory Multiple Myeloma (E1A95)
oai:repositori.udl.cat:10459.1/569132022-05-26T13:19:42Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Barceló Bennasar, Antònia
author
Bauçà, Josep Miquel
author
Yañez, Aina
author
Fueyo, Laura
author
Gomez, Cristina
author
Peña, Mónica de la
author
Pierola, Javier
author
Rodriguez, Alberto
author
Sánchez de la Torre, Manuel
author
Abad, Jorge
author
Mediano, Olga
author
Amilibia, Jose
author
Masdeu, María José
author
Terán, Joaquin
author
Montserrat i Capdevila, Josep
author
Mayós Pérez, Mercè
author
Sánchez de la Torre, Alicia
author
Barbé Illa, Ferran
author
2016
Background
Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and
plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently,
the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our
objective was to evaluate the relationships between PlGF levels and both the severity of
acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and
without OSA.
Methods
A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS
were included in this study. All patients underwent polygraphy in the first 72 hours after hospital
admission. The severity of disease and short-term prognoses were evaluated during
the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence
immunoassay.
Results
Patients with OSA were significantly older and more frequently hypertensive and had higher
BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with
patients without OSA (19.9 pg/mL, interquartile range: 16.6–24.5 pg/mL; 18.5 pg/mL, interquartile
range: 14.7–22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was
associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF
had also an increased odds ratio for the presence of 3 or more diseased vessels and for a
Killip score>1, even after adjustment.
Conclusions
The results of this study show that in patients with ACS, elevated plasma levels of PlGF are
associated with the presence of OSA and with adverse outcomes during short-term followup.
Trial Registration
ClinicalTrials.gov NCT01335087
https://doi.org/10.1371/journal.pone.0147686
026715
1932-6203
http://hdl.handle.net/10459.1/56913
Impact of obstructive sleep apnea on the levels of placental growth factor (PlGF) and their value for predicting short-term adverse outcomes in patients with acute coronary syndrome
oai:repositori.udl.cat:10459.1/474442017-07-12T15:32:47Zcom_10459.1_227com_10459.1_2com_10459.1_59159com_10459.1_47453col_10459.1_314col_10459.1_59160col_10459.1_59998
00925njm 22002777a 4500
dc
Izquierdo Álvarez, Alicia
author
Casas Herranz, Celia
author
Herrero Perpiñán, Enrique
author
2010
Unlike in higher organisms, selenium is not essential for growth in Saccharomyces cerevisiae. In this species, it causes toxic effects at high concentrations. In the present study, we show that when supplied as selenite to yeast cultures growing under fermentative metabolism, its effects can be dissected into two death phases. From the time of initial treatment, it causes loss of membrane integrity and genotoxicity. Both effects occur at higher levels in mutants lacking Grx1p and Grx2p than in wild-type cells, and are reversed by expression of a cytosolic version of the membrane-associated Grx7p glutaredoxin. Grx7p can also rescue the high levels of protein carbonylation damage that occur in selenite-treated cultures of the grx1 grx2 mutant. After longer incubation times, selenite causes abnormal nuclear morphology and the appearance of TUNEL-positive cells, which are considered apoptotic markers in yeast cells. This effect is independent of Grx1p and Grx2p. Therefore, the protective role of the two glutaredoxins is restricted to the initial stages of selenite treatment. Lack of Yca1p metacaspase or of a functional mitochondrial electron transport chain only moderately diminishes apoptotic-like death by selenite. In contrast, selenite-induced apoptosis is dependent on the apoptosis-inducing factor Aif1p. In the absence of the latter, intracellular protein carbonylation is reduced after prolonged selenite treatment, supporting the supposition that part of the oxidative damage is contributed by apoptotic cells.
https://doi.org/10.1099/mic.0.039719-0
16085
2608–2620 (versió paper)
1465-2080
http://hdl.handle.net/10459.1/47444
Llevat de cervesa
Glutaredoxin
Estrès oxidatiu
Selenite-induced cell death in Saccharomyces cerevisiae: protective role of glutaredoxins
oai:repositori.udl.cat:10459.1/679992022-11-23T14:51:05Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Laplana Lafaja, Marina
author
Sánchez de la Torre, Manuel
author
Puig, Teresa
author
Caruz, Antonio
author
Fibla Palazón, Joan
author
2014-04-21
Vitamin-D has pleiotropic effects on calcium and bone metabolism, cellular growth control, cell differentiation and modulation of both innate and acquired immune response. Previous studies revealed the association of vitamin-D receptor gene (VDR) polymorphism with infection diseases including HIV-1 infection. To assess for association between polymorphisms of vitamin-D pathway genes CYP27B1, vitamin-D binding protein (VDBP) and VDRwith HIV-1 infection, disease progression to acquired immunodeficiency syndrome (AIDS) was analysed according to CDC93 criteria in a cohort of 185 HIV-1 seroprevalent patients belonging to the injection drug users. Genotype data was obtained from rs10877012, rs3782130 and rs4646536 markers at CYP27B1 locus; rs7041 and rs4588 at VDBP locus; and rs11568820, rs4516035, rs2228570, rs1544410 and rs17878969 at VDR locus. Distribution of genotypes between patients grouped by outcome was compared by contingency table analysis. Marker-marker interaction was assessed by a MDR analysis. Assuming an additive model for VDR markers, a Kaplan-Meier survival analysis was employed to evaluate association with disease progression. Among vitamin-D pathway genes, VDR locus reveals specific 5′UTR and 3′UTR diplotype combinations associated with both, slower and faster progression to AIDS. Marker-marker interaction analysis indicates a strong interaction between VDR markers and a redundant effect for CYP27B1 markers. According to our results, VDR locus association follows an additive model in which increased genetic risk score for the VDR is directly correlated with AIDS progression rates. Our data supports a role of vitamin-D pathway gene variability on HIV-1 disease progression
https://doi.org/10.1016/j.gene.2014.04.035
021488
0378-1119
http://hdl.handle.net/10459.1/67999
Vitamina D
VDR
Vitamin D Pathaway
Polymorphism
Progression to AIDS
Vitamin-D pathway genes and HIV-1 disease progression in injection drug users
oai:repositori.udl.cat:10459.1/571062022-09-27T15:13:21Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Zhang, Jisheng
author
Bahi i Pla, Núria
author
Zubiaga, Ana M.
author
Comella i Carnicé, Joan Xavier
author
Llovera i Tomàs, Marta
author
Sanchis, Daniel
author
2007
The involvement of caspases in postmitotic cell death
is controversial. Here we report that adult brain and heart are
devoid of many key pro-apoptotic proteins due to a progressive
postnatal silencing event involving a reduction of their transcript
levels. E2F has been shown to control cell cycle progression and
to be transcriptional activator of apoptotic genes. However, our
data demonstrate that apoptotic gene expression in heart, brain
and liver, as well as cardiac and neuronal apoptotic gene silencing
during development, are E2F-independent events. Therefore,
the genes regulating caspase-dependent cell death are expressed
in embryonic organs in an E2F-independent manner and a developmental-related
silencing event represses these genes in postmitotic
adult tissues.
https://doi.org/10.1016/j.febslet.2007.11.046
011262
0014-5793
http://hdl.handle.net/10459.1/57106
Heart
Brain
Development
Apoptosis
Developmental silencing and independency from E2F of apoptotic gene expression in postmitotic tissues
oai:repositori.udl.cat:10459.1/570432021-08-30T15:04:34Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Li, Aihong
author
Zhou, Jianbiao
author
Zuckerman, David
author
Dalton, Virginia
author
Lyons, Cheryl
author
Silverman, Lewis B.
author
Sallan, Stephen E.
author
Gribben, John G.
author
Rué i Monné, Montserrat
author
2003
Immunoglobulin (Ig) and T-cell receptor
(TCR) gene rearrangements provide clonal
markers useful for diagnosis and measurement
of minimal residual disease
(MRD) in acute lymphoblastic leukemia
(ALL). We analyzed the sequences of Ig
and TCR gene rearrangements obtained
at presentation and relapse in 41 children
with ALL to study clonal stability, which
has important implications for monitoring
MRD, during the course of the disease.
In 42%, all original Ig and/or TCR
sequences were conserved. In 24%, one
original sequence was preserved but the
other lost, and in 14% the original sequences
were conserved with new sequences
identified at relapse. In 20% only
new sequences were found at relapse.
Using primers designed from the novel
relapse sequences, the relapse clone
could be identified as subdominant clones
in the diagnostic sample in 8 of 14 patients.
Alteration of these clonal gene
rearrangements is a common feature in
childhood ALL. MRD detection should
include multiple gene targets to minimize
false-negative samples or include also
multicolor flow cytometry. In some cases
the leukemic progenitor cell might arise
earlier in lineage before DHJH recombination
but retain the capacity to further
differentiate into cells capable of altering
the pattern of Ig and/or TCR rearrangements.
https://doi.org/10.1182/blood-2003-05-1455
009166
0006-4971
http://hdl.handle.net/10459.1/57043
Sequence analysis of clonal immunoglobulin and T-cell receptor gene rearrangements in children with acute lymphoblastic leukemia at diagnosis and at relapse: implications for pathogenesis and for the clinical utility of PCR-based methods of minimal residual disease detection
oai:repositori.udl.cat:10459.1/659262020-11-06T10:05:09Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Fernández Armenteros, José Manuel
author
Gómez Arbonés, Javier
author
Buti, Miquel
author
Betriu i Bars, M. Àngels
author
Sanmartín Novell, Verònica
author
Ortega Bravo, Marta
author
Martínez Alonso, Montserrat
author
Garí Marsol, Eloi
author
Portero Otín, Manuel
author
Santamaria-Babi, L.
author
Casanova i Seuma, Josep M. (Josep Manel)
author
2019
Abstract Background: Psoriasis is a very prevalent systemic chronic inflammatory disease. Major cardiovascular events are the main cause of mortality in these patients which suggests an association between psoriasis and traditional cardiovascular risk factors. Objective: Identify classic cardiovascular risk factors and metabolic syndrome (MS) in patients with psoriasis, their possible association with its severity and compare it with the non-psoriatic population. Methods: This is an observational and cross-sectional population study in Lleida (Spain) from a joint hospital / primary care database. Results: The database comprised 398,701 individuals. There were 6,868 cases registered as psoriasis (1.7%), and 499 of them (7.3%) were classified as moderate-severe psoriasis. Patients with psoriasis had a higher prevalence of traditional cardiovascular risk factors than non-psoriatic population: diabetes mellitus 2 (13.9% vs 7.4%, OR 2.01), dyslipidemia (28.8% vs 17.4%, OR 1.92), arterial hypertension (31.2% vs 19.0%, OR 1.93), obesity (33.7% vs 28.1%, OR 1.30), altered fasting basal glycaemia (21.4% vs 15.1%, OR 1.54), low cholesterol-HDL (38.1% vs 32.3%, OR 1.29), hypertriglyceridemia (45.7% vs 35.2%, OR 1.55) and high waist circumference (75.7% vs 72.3%, OR 1.19). MS was more prevalent in psoriatic patients (28.3% vs 15.1%, OR 2.21) and cardiovascular risk factors were similar between psoriasis severity groups. Psoriatic patients had a higher prevalence of ischemic heart disease (3.3% vs 1.8%, OR 1.87) and vascular-cerebral accidents (1.8% vs 1.2%, OR 1.55). A model for MS showed a significant non-linear relationship with age and sex, and significant differences between patients with and without psoriasis. Conclusion: We found statistically differences in relation to the prevalence of cardiovascular risk factors, MS and major cardiovascular events in psoriatic patients. However, differences were not seen between psoriasis severity groups. Our work reinforces the need for a multidisciplinary approach and close monitoring of cardiovascular risk factors in these patients to prevent a cardiovascular event.
https://doi.org/10.1111/jdv.15159
027663
0926-9959
http://hdl.handle.net/10459.1/65926
Psoriasis
Epidemiology
Metabolic syndrome
Cardiovascular risk factors
Psoriasis, metabolic syndrome and cardiovascular risk factors. A population-based study.
oai:repositori.udl.cat:10459.1/683202020-03-25T00:20:34Zcom_10459.1_227com_10459.1_2col_10459.1_314col_10459.1_44504
00925njm 22002777a 4500
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Cárdenas, Pablo D.
author
Sonawane, Prashant D.
author
Heinig, Uwe
author
Jozwiak, Adam
author
Panda, Sayantan
author
Abebie, Bekele
author
Kazachkova, Yana
author
Pliner, Margarita
author
Unger, Tamar
author
Wolf, Dalia
author
Ofner, Itai
author
Vilaprinyo Terré, Ester
author
Meir, Sagit
author
Davydov, Olga
author
Gal-on, Amit
author
Burdman, Saul
author
Gir, Ashok
author
Zamir, Dani
author
Scherf, Tali
author
Szymanski, Jedrzej
author
Rogachev, Ilana
author
Aharoni, Asaph
author
2019
The genus Solanum comprises three food crops (potato, tomato, and eggplant), which are consumed on daily basis worldwide and also producers of notorious anti-nutritional steroidal glycoalkaloids (SGAs). Hydroxylated SGAs (i.e. leptinines) serve as precursors for leptines that act as defenses against Colorado Potato Beetle (Leptinotarsa decemlineata Say), an important pest of potato worldwide. However, SGA hydroxylating enzymes remain unknown. Here, we discover that 2-OXOGLUTARATE-DEPENDENT-DIOXYGENASE (2-ODD) enzymes catalyze SGA-hydroxylation across various Solanum species. In contrast to cultivated potato, Solanum chacoense, a widespread wild potato species, has evolved a 2-ODD enzyme leading to the formation of leptinines. Furthermore, we find a related 2-ODD in tomato that catalyzes the hydroxylation of the bitter α-tomatine to hydroxytomatine, the first committed step in the chemical shift towards downstream ripening-associated non-bitter SGAs (e.g. esculeoside A). This 2-ODD enzyme prevents bitterness in ripe tomato fruit consumed today which otherwise would remain unpleasant in taste and more toxic.
https://doi.org/10.1038/s41467-019-13211-4
029707
2041-1723
http://hdl.handle.net/10459.1/68320
Pathways to defense metabolites and evading fruit bitterness in genus Solanum evolved through 2-oxoglutarate-dependent dioxygenases
oai:repositori.udl.cat:10459.1/577952022-10-21T17:17:44Zcom_10459.1_227com_10459.1_2com_10459.1_463061com_10459.1_47453com_10459.1_56939col_10459.1_314col_10459.1_463062col_10459.1_59998col_10459.1_56959col_10459.1_49291
00925njm 22002777a 4500
dc
Alves, Rui
author
Piñol, Marc
author
Vilaplana Mayoral, Jordi
author
Teixidó Torrelles, Ivan
author
Cruz, Joaquim
author
Comas, Jorge
author
Vilaprinyo Terré, Ester
author
Sorribas Tello, Albert
author
Solsona Tehàs, Francesc
author
2016
Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype.
Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient’s symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis.
Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms.
Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers.
https://doi.org/10.7717/peerj.2211
024564
2167-8359
http://hdl.handle.net/10459.1/57795
Computer assisted diagnosis
Rare diseases
eHealth
Family doctors
User-friendly webserver
Computer-assisted initial diagnosis of rare diseases
oai:repositori.udl.cat:10459.1/571542021-08-30T15:04:33Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Ros, Clara
author
Miret, Marta
author
Rué i Monné, Montserrat
author
2009
Objective: In the last few years, the number of unplanned pregnancies has increased, especially in young
women. Among other measures, emergency contraception (EC) was introduced by the Health Department
to reduce unwanted pregnancies. The aim of this study was to analyze EC use in Catalonia, and to compare
a rural with an urban area (Lleida province and the metropolitan area of Barcelona).
Methods: We performed a descriptive study that included 17,149 women of fertile age who sought access
to the EC pill between October 2004 and August 2007. Data were provided by the Maternal/Infant Health
Program of the Public Health Department.
Results: EC was used primarily by women between 16 and 24 years of age, usually on the weekends. Most
of these women (78.5%) had used EC twice and only 1.8% had used this medication once. Consumption was
higher in Lleida, with a comparative utilization figure and 95% confidence interval of 1.42 (1.35–1.50) with
respect to Barcelona.
Conclusions: The finding that EC use was higher in younger women coincides with the goal of distributing
this medication. EC seems not to be associated with a decrease in voluntary pregnancy terminations. More
reproductive information is required from all the actors involved in policies and health interventions,
encouraging healthier sexual behavior.
https://doi.org/10.1016/j.gaceta.2009.05.010
013930
0213-9111
http://hdl.handle.net/10459.1/57154
Emergency contraception
Estudio descriptivo sobre el uso de la anticoncepción de emergencia en Cataluña. Comparación entre una zona rural y una urbana
oai:repositori.udl.cat:10459.1/570642021-08-30T15:04:33Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Egea Navarro, Joaquim
author
Vig Nissen, Ulla
author
Dufour, Audrey
author
Sahin, Mustafa
author
Greer, Paul
author
Kullander, Klas
author
Mrsic-Flogel, Thomas D.
author
Greenberg, Michael E.
author
Kiehn, Ole
author
Vanderhaeghen, Pierre
author
Klein, Rüdiger
author
2005
Signaling by receptor tyrosine kinases (RTKs) is mediated by their intrinsic kinase activity. Typically, kinase-activating mutations result in ligand-independent signaling and gain-of-function phenotypes. Like other RTKs, Ephs require kinase activity to signal, but signaling by Ephs in vitro also requires clustering by their membrane bound ephrin ligands. The relative importance of Eph kinase activity and clustering for in vivo functions is unknown. We find that knockin mice expressing a mutant form of EphA4 (EphA4EE), whose kinase is constitutively activated in the absence of ephrinB ligands, are deficient in the development of thalamocortical projections and some aspects of central pattern generator rhythmicity. Surprisingly, other functions of EphA4 were regulated normally by EphA4EE, including midline axon guidance, hindlimb locomotion, in vitro growth cone collapse, and phosphorylation of ephexin1. These results suggest that signaling of Eph RTKs follows a multistep process of induced kinase activity and higher-order clustering different from RTKs responding to soluble ligands.
https://doi.org/10.1016/j.neuron.2005.06.029
017843
0896-6273
http://hdl.handle.net/10459.1/57064
Regulation of EphA4 Kinase Activity Is Required for a Subset of Axon Guidance Decisions Suggesting a Key Role for Receptor Clustering in Eph Function
oai:repositori.udl.cat:10459.1/657502019-02-20T00:32:21Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Murali, Rajmohan
author
Davidson, Ben
author
Fadare, Oluwole
author
Carlson, Joseph A.
author
Crum, Christopher
author
Gilks, C. Blake
author
Irving, Julie A.
author
Malpica, Anais
author
Matias-Guiu, Xavier
author
McCluggage, W. Glenn
author
Mittal, Khush
author
Oliva, Esther
author
Parkash, Vinita
author
Rutgers, Joanne
author
Staats, Paul
author
Stewart, Colin
author
Tornos, Carmen
author
Soslow, Robert A.
author
2019
This review of challenging diagnostic issues concerning high-grade endometrial carcinomasisderivedfromtheauthors’ reviewoftheliteraturefollowedbydiscussionsatthe Endometrial Cancer Workshop sponsored by the International Society of Gynecological Pathologists in 2016. Recommendations presented are evidence-based, insofar as this is possible,giventhatthelevelsofevidenceareweakormoderateduetosmallsamplesizesand nonuniform diagnostic criteria used in many studies. High-grade endometrioid carcinomas include FIGO grade 3 endometrioid carcinomas, serous carcinomas, clear cell carcinomas, undifferentiated carcinomas, and carcinosarcomas. FIGO grade 3 endometrioid carcinoma is diagnosed when an endometrioid carcinoma exhibits >50% solid architecture (excluding squamousareas), orwhenan architecturallyFIGOgrade2endometrioid carcinomaexhibits marked cytologic atypia, provided that a glandular variant of serous carcinoma has been excluded. The most useful immunohistochemical studies to make the distinction between these 2 histotypes are p53, p16, DNA mismatch repair proteins, PTEN, and ARID1A. Endometrial clear cell carcinomas must display prototypical architectural and cytologic features for diagnosis. Immunohistochemical stains, including, Napsin A and p504s can be used as ancillary diagnostic tools; p53 expression is aberrant in a minority of clear cell carcinomas. Of note, clear cells are found in all types of high-grade endometrial carcinomas, leading to a tendency to overdiagnose clear cell carcinoma. Undifferentiated carcinoma (which when associated with a component of low-grade endometrioid carcinoma is termed “dedifferentiated carcinoma”) is composed of sheets of monotonous, typically dyscohesive cells, which can have a rhabdoid appearance; they often exhibit limited expression of cytokeratins and epithelial membrane antigen, are usually negative for PAX8 and hormone receptors, lack membranous e-cadherin and commonly demonstrate loss of expression of DNA mismatch repair proteins and SWI-SNF chromatin remodeling proteins. Carcinosarcomas must show unequivocal morphologic evidence of malignant epithelial and mesenchymal differentiation.
https://doi.org/10.1097/PGP.0000000000000491
0277-1691
http://hdl.handle.net/10459.1/65750
Carcinosarcoma
Clear cell carcinoma
Dedifferentiated carcinoma
Endometrioid carcinoma
High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations
oai:repositori.udl.cat:10459.1/651752018-11-27T12:43:27Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Argilés, Josep M.
author
Llovera i Tomàs, Marta
author
López-Soriano, Francisco J.
author
1993
L'etiologia del càncer es basa fonamentalment en l'aparició d'un dany genètic en una cèl·lula que ocasiona una expressió anormal de determinats gens, els productes dels quals canvien dramàticament el fenotip cel·lular. Com a conseqüència d 'aquest fet, les cèl·lules transformades adquireixen tota una sèrie de característiques bioquímiques que els donen un gran avantatge en la seva competició per substrats i factors tròfics amb les cèl·lules normals. El creixement tumoral indueix en l'hoste tot un seguit de canvis metabòlics que es tradueix en un profund desequilibri energètic com a conseqüència de l'elevat grau d'ineficiència metabòlica generat per la massa tumoral en creixement. El conjunt d 'alteracions porta al pacient a una profunda caquèxia caracteritzada per una massiva pèrdua de pes i desgast muscular que sovint acaba amb la mort abans que el tumor hagi arribat a adquirir el màxim grau de malignitat. En els darrers anys s'ha pogut comprovar que gran part de les adaptacions metabòliques generades en resposta a l'estímul invasiu són conseqüència de l'acció de compostos alliberats per les pròpies cèl·lules del sistema immunitari de l 'animal o individu portador del tumor. Per tot això, la futura recerca en el tractament del càncer ha d'ésser dirigida, d 'una banda, a un millor coneixement del sistema bioquímic hoste-tumor i, d'una altra, al desenvolupament de nous fàrmacs antitumorals que tinguin en compte no només l'anihilació del tumor, sinó també la resposta metabòlica de l'hoste, responsable, en molts casos, de l'aparició del síndrome caquèctic i, conseqüentment, de la mort del pacient.
008543
http://hdl.handle.net/10459.1/65175
Creixement tumoral
Hoste
Metabolisme
Citocines
Caquèxia
Creixement tumoral i metabolisme de l'hoste: dues cares d'una mateixa moneda
oai:repositori.udl.cat:10459.1/725302023-02-09T08:27:18Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Pérez Fusté, Noel
author
Ferrezuelo, Francisco
author
Garí Marsol, Eloi
author
2016-06-27
Amplification of cyclin D1 is a frequent alteration in many cancers of different type and origin. We recently described a novel regulatory axis involving cyclin D1 in the regulation of tumor invasion and metastasis. Membrane-associated cyclin D1-CDK4 complexes promote activation of the small GTPase RAC1 through phosphorylation of the regulatory protein paxillin.
https://doi.org/10.1080/23723556.2016.1203471
024629
2372-3556
http://hdl.handle.net/10459.1/72530
Cyclin D1
Cell invasion
Metastasis
Cyclin D1 promotes tumor cell invasion and metastasis by cytoplasmic mechanisms
oai:repositori.udl.cat:10459.1/675982020-07-13T10:33:47Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_314col_10459.1_59998col_10459.1_30324
00925njm 22002777a 4500
dc
Bhardwaj, Deepshikha
author
Nàger Grifo, Mireia
author
Visa Pretel, Anna
author
Crespí Sallán, Marta
author
Coopman, PJ
author
Cantí Nicolás, Carles
author
Herreros Danés, Judit
author
2018-04-01
β-catenin is a central component of adherent junctions and a key effector of canonical Wnt signalling, in which dephosphorylated Ser/Thr β-catenin regulates gene transcription. β-catenin phosphorylation at Tyr142 (PTyr142 β-catenin), which is induced by receptor and Src family Tyr kinases, represents a previously described β- catenin switch from adhesive to migratory roles. In addition to classical β-catenin roles, phosphorylated Ser/Thr β-catenin and total β-catenin were involved in centrosomal functions, including mitotic spindle formation and centrosome separation. Here we find that PTyr142 β-catenin is present in centrosomes in non-transformed and glioblastoma cells and that, in contrast to the Ser/Thr phosphorylated β-catenin, PTyr142 β-catenin centrosomal levels drop in mitosis. Furthermore, we show that the inhibitor of Spleen Tyrosine Kinase (Syk) piceatannol decreases centrosomal PTyr142 β-catenin levels, indicating that Syk regulates centrosome PTyr142 β-catenin. Our findings suggest that PTyr142 β-catenin negatively regulates mitotic progression and highlight the contribution of different phosphorylated β-catenin forms in the coordination of the cell and centrosome cycles.
https://doi.org/10.1002/jcb.26571
026372
0730-2312
http://hdl.handle.net/10459.1/67598
Phosphorylated Tyr142 β-catenin localizes to centrosomes and is regulated by Syk
oai:repositori.udl.cat:10459.1/733182022-12-02T09:37:43Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Solache Berrocal, Guillermo
author
Rolle Sóñora, Valeria
author
Martín Fernández, Noelia
author
Cambray Carner, Serafí
author
Valdivielso Revilla, José Manuel
author
Rodríguez, Isabel
author
2020
Background: Novel ways of determining cardiovascular risk are needed as a consequence of population ageing and the increased prevalence of chronic kidney disease (CKD), both of which favour vascular calcification. Since the formation of arterial calcium deposits has a genetic component, single nucleotide polymorphisms (SNPs) could predict cardiovascular events.
Methods: A selection of 1927 CKD patients and controls recruited by the NEFRONA study were genotyped for 60 SNPs from 22 candidate genes. A calcium score was calculated from the echogenicity of arterial atherosclerotic plaques and the presence of cardiovascular events during a 4-year period was recorded. Association of SNPs with the calcium score was identified by multiple linear regression models and their capacity to predict events was assessed by means of Cox proportional hazards regression and receiver operating characteristics curves.
Results: Two variants, rs2296241 of CYP24A1 and rs495392 of KL, were associated with the calcium score. Despite this, only heterozygotes for rs495392 had a lower risk of suffering an event compared with homozygotes for the major allele {hazard ratio (HR) 0.67 [95% confidence interval (CI) 0.48-0.93]}. Of note, the calcium score was associated with an increased risk of cardiovascular events [HR 1.71 (95% CI 1.35-2.17)]. The addition of the rs495392 genotype to classical cardiovascular risk factors did not increase the predictive power [area under the curve (AUC) 71.3 (95% CI 61.1-85.5) versus 71.4 (61.5-81.4)].
Conclusions: Polymorphisms of CYP24A1 and KL are associated with the extent of calcification but do not predict cardiovascular events. However, the echogenic determination of the extent of calcium deposits seems a promising non-irradiating method for the scoring of calcification in high-risk populations.
https://doi.org/10.1093/ndt/gfaa240
032813
0931-0509
1460-2385
http://hdl.handle.net/10459.1/73318
Calcium score
Cardiovascular risk
Klotho
Single nucleotide polymorphism
Vitamin D 24-hydroxylase
CYP24A1 and KL polymorphisms are associated with the extent of vascular calcification but do not improve prediction of cardiovascular events
oai:repositori.udl.cat:10459.1/4646672024-03-12T14:12:38Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Ruiz Mitjana, Anna
author
Vidal Sabanés, Maria
author
Navaridas Fernández de Bobadilla, Raúl
author
Perramon Güell, Aida
author
Yeramian Hakim, Andree
author
Nicholson Sabaté, Nathan
author
Egea Navarro, Joaquim
author
Encinas Martín, Mario
author
Matias-Guiu, Xavier
author
Dolcet Roca, Xavier
author
2023
Metformin is a widespread antidiabetic agent that is commonly used as a treatment against type 2 diabetes mellitus patients. Regarding its therapeutic potential, multiple studies have concluded that Metformin exhibits antineoplastic activity on several types of cancer, including endometrial carcinoma. Although Metformin’s antineoplastic activity is well documented, its cellular and molecular anticancer mechanisms are still a matter of controversy because a plethora of anticancer mechanisms have been proposed for different cancer cell types. In this study, we addressed the cellular and molecular mechanisms of Metformin’s antineoplastic activity by using both in vitro and in vivo studies of Pten-loss driven carcinoma mouse models. In vivo, Metformin reduced endometrial neoplasia initiated by Pten-deficiency. Our in vitro studies using Pten-deficient endometrial organoids focused on both cellular and molecular levels in Metformin’s tumor suppressive action. At cellular level, we showed that Metformin is involved in not only the proliferation of endometrial epithelial cells but also their regulation via a variety of mechanisms of epithelial-to-mesenchymal transition (EMT) as well as TGF-β-induced apoptosis. At the molecular level, Metformin was shown to affect the TGF-β signalling., a widely known signal that plays a pivotal role in endometrial carcinogenesis. In this respect, Metformin restored TGF-β-induced apoptosis of Pten-deficient endometrial organoids through a p38-dependent mechanism and inhibited TGF-β-induced EMT on no-polarized endometrial epithelial cells by inhibiting ERK/MAPK signalling. These results provide new insights into the link between the cellular and molecular mechanism for Metformin’s antineoplastic activity in Pten-deficient endometrial cancers.
https://doi.org/10.1016/j.biopha.2023.115817
033971
0753-3322
https://repositori.udl.cat/handle/10459.1/464667
Metformin
Endometrial cancer
Pten
Mouse model of cancer
Drug repurposing
Metformin exhibits antineoplastic effects on Pten-deficient endometrial cancer by interfering with TGF-β and p38/ERK MAPK signalling
oai:repositori.udl.cat:10459.1/628442018-03-21T00:48:10Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Alcubierre Calvo, Núria
author
Castelblanco Echavarría, Esmeralda
author
Martínez Alonso, Montserrat
author
Granado Casas, Minerva
author
Esquerda, Aureli
author
Traveset Maeso, Alicia
author
Martínez González, María Dolores
author
Franch-Nadal, Josep
author
Mauricio Puente, Dídac
author
2018-03-12
Background: In this cross-sectional study, we assessed the possible association of vitamin D deficiency with self-reported treatment satisfaction and health-related quality of life in patients with type 2 diabetes. Methods: We performed a sub-analysis of a previous study and included a total of 292 type 2 diabetic patients. We evaluated treatment satisfaction and health-related quality of life through specific tools: the Diabetes Treatment Satisfaction Questionnaire and the Audit of Diabetes-Dependent Quality of Life. Vitamin D deficiency was defined as 25 (OH) D serum levels < 15 ng/mL. Results: Multivariable linear regression models were used to estimate the relationship of vitamin D deficiency with both outcomes once adjusted for self-reported patient characteristics. Vitamin D deficiency was significantly associated with the final score of the Diabetes Treatment Satisfaction Questionnaire and the single "diabetes-specific quality of life" dimension of the Audit of Diabetes-Dependent Quality of Life (p = 0.0198 and p = 0.0070, respectively). However, lower concentrations of 25-OH vitamin D were not associated with the overall quality of life score or the perceived frequency of hyperglycaemia and hypoglycaemia. Conclusions: Our study shows the association between vitamin D deficiency and both the self-reported diabetes treatment satisfaction and the diabetes-specific quality of life in patients with type 2 diabetes.
https://doi.org/10.1186/s12955-018-0873-3
026784
1477-7525
http://hdl.handle.net/10459.1/62844
Vitamin D deficiency is associated with poorer satisfaction with diabetes-related treatment and quality of life in patients with type 2 diabetes: a cross-sectional study
oai:repositori.udl.cat:10459.1/570032021-08-30T15:04:33Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Ammarguellat, Fatima
author
Llovera i Tomàs, Marta
author
Kelly, Paul A.
author
Goffin, Vincent
author
2001
Previous reports have shown a direct effect of erythropoietin
(Epo) on vascular smooth muscle cells
(VSMCs). Our aim was to assess expression of the Epo
receptor (EpoR) on VSMCs and to study the activation
of two major signaling cascades activated by Epo,
namely JAK2/STAT5 and MAPK pathways. All experiments
were performed in parallel using the Eporesponsive
UT7 cell line. From semiquantitative RTPCR
experiments, VSMCs were estimated to express
;30-fold less EpoR mRNA than UT7 cells. Epo-induced
phosphorylation of proteins involved in the EpoR/
JAK2/STAT5 cascade could not be detected in VSMCs,
even using pharmacological doses of Epo (250 IU/ml).
In contrast, a strong activation of MAP kinase pathway
was detected with as low as 10 IU/ml Epo. We
suggest that MAPK activation reflects a physiologically
relevant effect of Epo on VSMCs that may be
correlated to cell proliferation.
https://doi.org/10.1006/bbrc.2001.5085
008512
0006-291X
http://hdl.handle.net/10459.1/57003
Epo
Epo receptor
MAP kinase
VSMC
Low Doses of EPO Activate MAP Kinases but Not JAK2–STAT5 in Rat Vascular Smooth Muscle Cells
oai:repositori.udl.cat:10459.1/570532021-08-30T15:04:34Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Torres-Arzayus, Maria I.
author
Font de Mora, Jaime
author
Yuan, Jing
author
Vazquez, Francisca
author
Bronson, Roderick
author
Rué i Monné, Montserrat
author
Sellers, William R.
author
Brown, Myles
author
2004
The gene encoding AIB1, an estrogen receptor coactivator, is amplified in a subset of human breast cancers. Here we
show that overexpression of AIB1 in transgenic mice (AIB1-tg) leads to mammary hypertrophy, hyperplasia, abnormal
postweaning involution, and the development of malignant mammary tumors. Tumors are also increased in other organs,
including the pituitary and uterus. AIB1 overexpression increases mammary IGF-I mRNA and serum IGF-I protein levels.
In addition, IGF-I receptor and downstream signaling molecules are activated in primary mammary epithelial cells and
mammary tumor cells derived from AIB1-tg mice. Knockdown of AIB1 expression in cultured AIB1-tg mammary tumor
cells leads to reduced IGF-I mRNA levels and increased apoptosis, suggesting that an autocrine IGF-I loop underlies the
mechanism of AIB1-induced oncogenesis.
https://doi.org/10.1016/j.ccr.2004.06.027
009164
1535-6108
http://hdl.handle.net/10459.1/57053
High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene
oai:repositori.udl.cat:10459.1/4650782024-02-14T03:00:30Zcom_10459.1_227com_10459.1_2col_10459.1_314col_10459.1_49291col_10459.1_44504
00925njm 22002777a 4500
dc
Bayona, Clara
author
Alza, Lía
author
Ranđelović, Teodora
author
Sallán, Marta C.
author
Visa Pretel, Anna
author
Cantí Nicolás, Carles
author
Ochoa, Ignacio
author
Oliván, Sara
author
Herreros Danés, Judit
author
2024-02-12
Glioblastoma (GBM) is a highly malignant brain tumour characterised by limited treatment options and poor prognosis. The tumour microenvironment, particularly the central hypoxic region of the tumour, is known to play a pivotal role in GBM progression. Cells within this region adapt to hypoxia by stabilising transcription factor HIF1-α, which promotes cell proliferation, dedifferentiation and chemoresistance. In this study we sought to examine the effects of NNC-55-0396, a tetralol compound which overactivates the unfolded protein response inducing apoptosis, using the organ-on-chip technology. We identified an increased sensitivity of the hypoxic core of the chip to NNC, which correlates with decreasing levels of HIF1-α in vitro. Moreover, NNC blocks the macroautophagic process that is unleashed by hypoxia as revealed by increased levels of autophagosomal constituent LC3-II and autophagy chaperone p62/SQSTM1. The specific effects of NNC in the hypoxic microenvironment unveil additional anti-cancer abilities of this compound and further support investigations on its use in combined therapies against GBM.
https://doi.org/10.1038/s41419-024-06492-1
034008
2041-4889
https://repositori.udl.cat/handle/10459.1/465078
Cancer microenvironment
Cancer models
Microfluidics
Tetralol derivative NNC-55-0396 targets hypoxic cells in the glioblastoma microenvironment: an organ-on-chip approach
oai:repositori.udl.cat:10459.1/3172020-07-14T08:39:35Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Alves, Rui
author
Sorribas Tello, Albert
author
2007
Background: Current advances in genomics, proteomics and other areas of molecular biology make the identification and reconstruction of novel pathways an emerging area of great interest. One such class of pathways is involved in the biogenesis of Iron-Sulfur Clusters (ISC).
Results: Our goal is the development of a new approach based on the use and combination of mathematical, theoretical and computational methods to identify the topology of a target network. In this approach, mathematical models play a central role for the evaluation of the alternative
network structures that arise from literature data-mining, phylogenetic profiling, structural methods, and human curation. As a test case, we reconstruct the topology of the reaction and regulatory network for the mitochondrial ISC biogenesis pathway in S. cerevisiae. Predictions
regarding how proteins act in ISC biogenesis are validated by comparison with published
experimental results. For example, the predicted role of Arh1 and Yah1 and some of the interactions we predict for Grx5 both matches experimental evidence. A putative role for frataxin in directly regulating mitochondrial iron import is discarded from our analysis, which agrees with also published experimental results. Additionally, we propose a number of experiments for testing other predictions and further improve the identification of the network structure.
Conclusion: We propose and apply an iterative in silico procedure for predictive reconstruction of the network topology of metabolic pathways. The procedure combines structural bioinformatics tools and mathematical modeling techniques that allow the reconstruction of biochemical networks. Using the Iron Sulfur cluster biogenesis in S. cerevisiae as a test case we indicate how this procedure can be used to analyze and validate the network model against experimental results. Critical evaluation of the obtained results through this procedure allows devising new wet lab experiments to confirm its predictions or provide alternative explanations for further improving the models.
https://doi.org/10.1186%2F1752-0509-1-10
010678
1752-0509
http://hdl.handle.net/10459.1/317
In silico pathway reconstruction: Iron-sulfur cluster biogenesis in Saccharomyces cerevisiae
oai:repositori.udl.cat:10459.1/591122021-08-30T15:04:34Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Aldea, Martí
author
Garí Marsol, Eloi
author
Colomina i Gabarrella, Neus
author
2007
Cells adapt their size to both intrinsic and extrinsic demands and, among them, those that stem from growth and proliferation rates are crucial for cell size homeostasis. Here we revisit mechanisms that regulate cell cycle and cell growth in budding yeast. Cyclin Cln3, the most upstream activator of Start, is retained at the endoplasmic reticulum in early G1 and released by specific chaperones in late G1 to initiate the cell cycle. On one hand, these chaperones are rate-limiting for release of Cln3 and cell cycle entry and, on the other hand, they are required for key biosynthetic processes. We propose a model whereby the competition for specialized chaperones between growth and cycle machineries could gauge biosynthetic rates and set a critical size threshold at Start.
https://doi.org/10.4161/cc.6.21.4920
012041
1538-4101
http://hdl.handle.net/10459.1/59112
Cell cycle
Start
Critical cell size
Growth rate
Chaperones
Cln3
Ydj1
Control of cell cycle and cell growth by molecular chaperones
oai:repositori.udl.cat:10459.1/697082023-01-24T15:59:11Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Romero, Antonia María
author
Ramos-Alonso, Lucía
author
Montellá-Manuel, Sandra
author
García-Martínez, José
author
Torre Ruiz, M. A. de la
author
Pérez-Ortín, José E.
author
Martínez-Pastor, María Teresa
author
Puig, Sergi
author
2019-09
Iron is an essential micronutrient that participates as a cofactor in a broad range of metabolic processes including mitochondrial respiration, DNA replication, protein translation and lipid biosynthesis. Adaptation to iron deficiency requires the global reorganization of cellular metabolism directed to optimize iron utilization. The budding yeast Saccharomyces cerevisiae has been widely used to characterize the responses of eukaryotic microorganisms to iron depletion. In this report, we used a genomic approach to investigate the contribution of transcription rates to the modulation of mRNA levels during adaptation of yeast cells to iron starvation. We reveal that a decrease in the activity of all RNA polymerases contributes to the down-regulation of many mRNAs, tRNAs and rRNAs. Opposite to the general expression pattern, many genes including components of the iron deficiency response, the mitochondrial retrograde pathway and the general stress response display a remarkable increase in both transcription rates and mRNA levels upon iron limitation, whereas genes encoding ribosomal proteins or implicated in ribosome biogenesis exhibit a pronounced fall. This expression profile is consistent with an activation of the environmental stress response. The phosphorylation stage of multiple regulatory factors strongly suggests that the conserved nutrient signaling pathway TORC1 is inhibited during the progress of iron deficiency. These results suggest an intricate crosstalk between iron metabolism and the TORC1 pathway that should be considered in many disorders.
https://doi.org/10.1016/j.bbagrm.2019.194414
029476
1874-9399
http://hdl.handle.net/10459.1/69708
A genome-wide transcriptional study reveals that iron deficiency inhibits the yeast TORC1 pathway
oai:repositori.udl.cat:10459.1/629712018-04-06T09:59:06Zcom_10459.1_242com_10459.1_2com_10459.1_227com_10459.1_47453col_10459.1_10990col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Royo Sánchez-Palencia, José Luis
author
Valls Marsal, Joan
author
Acemel, Rafael D.
author
Gómez-Marin, Carlos
author
Pascual Pons, Mariona
author
Lupiañez, Arantxa
author
Gomez-Skarmeta, Jose Luis
author
Fibla Palazón, Joan
author
2018
Previous reports have proposed that personality may have played a role on human Out-Of-
Africa migration, pinpointing some genetic variants that were positively selected in the migrating
populations. In this work, we discuss the role of a common copy-number variant within
the SIRPB1 gene, recently associated with impulsive behavior, in the human Out-Of-Africa
migration. With the analysis of the variant distribution across forty-two different populations,
we found that the SIRPB1 haplotype containing duplicated allele significantly correlated with
human migratory distance, being one of the few examples of positively selected loci found
across the human world colonization. Circular Chromosome Conformation Capture (4C-seq)
experiments from the SIRPB1 promoter revealed important 3D modifications in the locus
depending on the presence or absence of the duplication variant. In addition, a 3' enhancer
showed neural activity in transgenic models, suggesting that the presence of the CNV may
compromise the expression of SIRPB1 in the central nervous system, paving the way to construct
a molecular explanation of the SIRPB1 variants role in human migration.
https://doi.org/10.1371/journal.pone.0193614
026796
1932-6203
http://hdl.handle.net/10459.1/62971
A common copy-number variant within SIRPB1 correlates with human Out-of-Africa migration after genetic drift correction
oai:repositori.udl.cat:10459.1/677792022-01-12T12:24:53Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Granado Casas, Minerva
author
Martín, Mariona
author
Martínez Alonso, Montserrat
author
Alcubierre Calvo, Núria
author
Hernández García, Marta
author
Alonso, Núria
author
Castelblanco Echavarría, Esmeralda
author
Mauricio Puente, Dídac
author
2020-01-02
This study aimed to assess the potential association between dietary patterns (i.e., the Mediterranean Diet (MedDiet) and healthy eating) and patient-reported quality of life (QoL) and treatment satisfaction (TS) in adults with type 1 diabetes (T1D). A food frequency questionnaire, the Audit of Diabetes-Dependent Quality of Life (ADDQoL-19), and the Diabetes Treatment Satisfaction Questionnaire-status version (DTSQ-s) were administered via personal interviews to 258 participants with T1D. Multivariable analysis showed that a moderate or high adherence to the MedDiet was associated with greater diabetes-specific QoL (β = 0.32, 95% CI = 0.03; 0.61; p = 0.029). None of the dietary quality indexes (i.e., the alternate Mediterranean Diet Score (aMED) and the alternate Healthy Eating Index (aHEI)) were associated with the overall TS. However, the aHEI was positively associated with the specific items of TS "convenience" and "flexibility" (β = 0.03, 95% CI = 0.00; 0.06; p = 0.042 and β = 0.04; 95% CI = 0.01; 0.06; p = 0.011, respectively). On the other hand, the aHEI was negatively associated with the dimension "recommend to others" (β = −0.5, 95% CI = −0.99; −0.02; p = 0.042). In conclusion, a moderate and high adherence to the MedDiet was associated with greater QoL. Although neither aMED nor aHEI were associated with the overall TS, some specific items were positively (i.e., "convenience", "flexibility") or negatively ("recommend to others") related to the aHEI. Further research is needed to assess how to improve medical nutrition therapy and its impact on patient-reported outcomes in people with T1D.
https://doi.org/10.3390/nu12010131
029408
2072-6643
http://hdl.handle.net/10459.1/67779
The Mediterranean Diet is Associated with an Improved Quality of Life in Adults with Type 1 Diabetes
oai:repositori.udl.cat:10459.1/844612022-12-04T00:06:41Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Forné Izquierdo, Carles
author
Yuguero Torres, Oriol
author
2022
Background: The Maslach Burnout Inventory (MBI) is an instrument commonly used to evaluate burnout syndrome.
The goal of the present study was to assess the internal reliability and the performance of the items and the subscales
of the MBI-HSS (the version for professionals working in human services) by validating its factorial structure in Spanish
urgency healthcare personnel.
Methods: Cross-sectional study including 259 healthcare emergency professionals (physicians and nurses) in the
Spanish health region of Lleida and the Pyrenees. Burnout was measured using the Spanish validated version of the
MBI-HSS. Internal reliability was estimated using Cronbach’s alpha coefcient. The sampling adequacy was assessed
using the Kaiser-Meyer-Olkin measure along with the Bartlett’s test of sphericity. A principal axis exploratory factor
analysis with an oblique transformation of the solution and a confrmatory factor analysis with maximum likelihood
estimation were performed. Goodness-of-ft was assessed by means of the chi-square ratio by the degrees of free dom, the standardized root mean square residual (SRMR), the root mean square error of approximation (RMSEA), the
Tucker-Lewis Index (TLI) and the comparative ft index (CFI).
Results: The three subscales showed good internal reliability with Cronbach’s alpha coefcients exceeding the
critical value of 0.7. Exploratory factor analysis revealed fve factors with eigenvalues greater than 1. Nevertheless,
confrmatory factor analysis showed a relatively satisfactory ft of the three-factor structure (χ2
/df=2.6, SRMR=0.07,
RMSEA=0.08, TLI=0.87, CFI=0.89), which was improved when several items were removed (χ2
/df=1.7, SRMR=0.04,
RMSEA=0.05, TLI=0.97, CFI=0.98).
Conclusions: Although it is necessary exploring new samples to get to more consistent conclusions, the MBI-HSS
is a reliable and factorially valid instrument to evaluate burnout syndrome in health professionals from the Spanish
emergency services.
https://doi.org/10.1186/s12909-022-03666-3
1472-6920
http://hdl.handle.net/10459.1/84461
Burnout
Psychological
Factor Analysis
Statistical
Maslach Burnout Inventory - Human Services Survey
Emergencies
Factor structure of the Maslach Burnout Inventory Human Services Survey in Spanish urgency healthcare personnel: a cross-sectional study
oai:repositori.udl.cat:10459.1/716312021-07-15T00:09:59Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Porcel Pérez, José Manuel
author
Esquerda, Aureli
author
Martínez Alonso, Montserrat
author
Bielsa Martín, Silvia
author
Salud Salvia, Maria Antonieta
author
2016-03-01
The diagnosis of malignant pleural effusions may be challenging when cytological examination of aspirated pleural fluid is equivocal or noncontributory. The purpose of this study was to identify protein candidate biomarkers differentially expressed in the pleural fluid of patients with mesothelioma, lung adenocarcinoma, lymphoma, and tuberculosis (TB).A multiplex protein biochip comprising 120 biomarkers was used to determine the pleural fluid protein profile of 29 mesotheliomas, 29 lung adenocarcinomas, 12 lymphomas, and 35 tuberculosis. The relative abundance of these predetermined biomarkers among groups served to establish the differential diagnosis of: malignant versus benign (TB) effusions, lung adenocarcinoma versus mesothelioma, and lymphoma versus TB. The selected putative markers were validated using widely available commercial techniques in an independent sample of 102 patients.Significant differences were found in the protein expressions of metalloproteinase-9 (MMP-9), cathepsin-B, C-reactive protein, and chondroitin sulfate between malignant and TB effusions. When integrated into a scoring model, these proteins yielded 85% sensitivity, 100% specificity, and an area under the curve (AUC) of 0.98 for labeling malignancy in the verification sample. For lung adenocarcinoma-mesothelioma discrimination, combining CA19-9, CA15-3, and kallikrein-12 had maximal discriminatory capacity (65% sensitivity, 100% specificity, AUC 0.94); figures which also refer to the validation set. Last, cathepsin-B in isolation was only moderately useful (sensitivity 89%, specificity 62%, AUC 0.75) in separating lymphomatous and TB effusions. However, this last differentiation improved significantly when cathepsin-B was used with respect to the patient's age (sensitivity 72%, specificity 100%, AUC 0.94).In conclusion, panels of 4 (i.e., MMP-9, cathepsin-B, C-reactive protein, chondroitin sulfate), or 3 (i.e., CA19-9, CA15-3, kallikrein-12) different protein biomarkers on pleural fluid samples are highly discriminative for signaling a malignant versus tuberculous effusion, or lung adenocarcinoma versus mesothelioma, respectively. Cathepsin-B could also be helpful in establishing the presence of a lymphomatous effusion versus that of TB, if the patient's age is simultaneously taken into consideration.
https://doi.org/10.1097/MD.0000000000003044
024149
0025-7974
http://hdl.handle.net/10459.1/71631
Identifying thoracic malignancies through pleural fluid biomarkers: a predictive multivariate model
oai:repositori.udl.cat:10459.1/4642782023-10-27T03:00:33Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_314col_10459.1_59998col_10459.1_30324col_10459.1_49291
00925njm 22002777a 4500
dc
Navaridas Fernández de Bobadilla, Raúl
author
Vidal Sabanés, Maria
author
Ruiz Mitjana, Anna
author
Perramon Güell, Aida
author
Megino-Luque, Cristina
author
Llobet Navàs, David
author
Matias-Guiu, Xavier
author
Egea Navarro, Joaquim
author
Encinas Martín, Mario
author
Bardia, Lídia
author
Colombelli, Julien
author
Dolcet Roca, Xavier
author
2023
https://doi.org/10.1002/cac2.12409
033221
2523-3548
2523-3548
https://repositori.udl.cat/handle/10459.1/464278
Transient and DNA-free in vivo CRISPR/Cas9 genome editing for flexible modeling of endometrial carcinogenesis
oai:repositori.udl.cat:10459.1/482842023-01-02T14:36:23Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Arrospide, Arantzazu
author
Forné Izquierdo, Carles
author
Rué i Monné, Montserrat
author
Torà, Núria
author
Mar, Javier
author
Baré, Marisa
author
2013
Background: The aim of this study was to evaluate the calibration and discriminatory power of three predictive
models of breast cancer risk.
Methods: We included 13,760 women who were first-time participants in the Sabadell-Cerdanyola Breast Cancer
Screening Program, in Catalonia, Spain. Projections of risk were obtained at three and five years for invasive cancer
using the Gail, Chen and Barlow models. Incidence and mortality data were obtained from the Catalan registries.
The calibration and discrimination of the models were assessed using the Hosmer-Lemeshow C statistic, the area
under the receiver operating characteristic curve (AUC) and the Harrell’s C statistic.
Results: The Gail and Chen models showed good calibration while the Barlow model overestimated the number of
cases: the ratio between estimated and observed values at 5 years ranged from 0.86 to 1.55 for the first two models
and from 1.82 to 3.44 for the Barlow model. The 5-year projection for the Chen and Barlow models had the highest
discrimination, with an AUC around 0.58. The Harrell’s C statistic showed very similar values in the 5-year projection
for each of the models. Although they passed the calibration test, the Gail and Chen models overestimated the
number of cases in some breast density categories.
Conclusions: These models cannot be used as a measure of individual risk in early detection programs to
customize screening strategies. The inclusion of longitudinal measures of breast density or other risk factors in joint
models of survival and longitudinal data may be a step towards personalized early detection of BC.
https://doi.org/10.1186/1471-2407-13-587
020551
1471-2407
http://hdl.handle.net/10459.1/48284
Breast cancer
Screening
Risk models
An assessment of existing models for individualized breast cancer risk estimation in a screening program in Spain
oai:repositori.udl.cat:10459.1/600182020-06-25T09:36:45Zcom_10459.1_227com_10459.1_2col_10459.1_314
00925njm 22002777a 4500
dc
Hidalgo, Manuel
author
Galan, Jose J.
author
Sáez, Carmen
author
Ferrero, Eduardo
author
Castilla, Carolina
author
Ramirez Lorca, Reposo
author
Pelaez, Pablo
author
Ruiz, Agustín
author
Japón, Miguel A.
author
Royo Sánchez-Palencia, José Luis
author
2008
Background: On its physiological cellular context, PTTG1 controls sister chromatid segregation
during mitosis. Within its crosstalk to the cellular arrest machinery, relies a checkpoint of integrity
for which gained the over name of securin. PTTG1 was found to promote malignant transformation
in 3T3 fibroblasts, and further found to be overexpressed in different tumor types. More recently,
PTTG1 has been also related to different processes such as DNA repair and found to trans-activate
different cellular pathways involving c-myc, bax or p53, among others. PTTG1 over-expression has
been correlated to a worse prognosis in thyroid, lung, colorectal cancer patients, and it can not be
excluded that this effect may also occur in other tumor types. Despite the clinical relevance and
the increasing molecular characterization of PTTG1, the reason for its up-regulation remains
unclear.
Method: We analysed PTTG1 differential expression in PC-3, DU-145 and LNCaP tumor cell
lines, cultured in the presence of the methyl-transferase inhibitor 5-Aza-2'-deoxycytidine. We also
tested whether the CpG island mapping PTTG1 proximal promoter evidenced a differential
methylation pattern in differentiated thyroid cancer biopsies concordant to their PTTG1
immunohistochemistry status. Finally, we performed whole-genome LOH studies using Affymetix
50 K microarray technology and FRET analysis to search for allelic imbalances comprising the
PTTG1 locus.
Conclusion: Our data suggest that neither methylation alterations nor LOH are involved in
PTTG1 over-expression. These data, together with those previously reported, point towards a
post-transcriptional level of missregulation associated to PTTG1 over-expression.
https://doi.org/10.1186/1471-2407-8-110
019954
1471-2458
http://hdl.handle.net/10459.1/60018
Methylation alterations are not a major cause of PTTG1 missregulation
oai:repositori.udl.cat:10459.1/588422020-01-20T12:22:08Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Lecube Torelló, Albert
author
Valladares, Silvia
author
López Cano, Carolina
author
Gutiérrez Carrasquilla, Liliana
author
Ciudin, Andreea
author
Fort, José Manuel
author
Reñé Espinet, Josep Maria
author
Matias-Guiu, Xavier
author
Torres, Inés de
author
Bueno Díez, Marta
author
Pallares, Judit
author
Baena-Fustegueras, Juan A
author
2016
Helicobacter pylory (HP) infection has been associated to an increased rate of type 2 diabetes
(T2D) and liver disease through its effect on insulin resistance and systemic inflammation.
However, results are inconstant and no studies exist in morbidly obese patients, in
which both insulin resistance and inflammation coexist.
https://doi.org/10.1371/journal.pone.0166741
024913
1932-6203
http://hdl.handle.net/10459.1/58842
The role of morbid obesity in the promotion of metabolic disruptions and non-alcoholic steatohepatitis by Helicobacter Pylori
oai:repositori.udl.cat:10459.1/657492019-02-20T00:32:16Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Cho, Kathleen R.
author
Cooper, Kumarasen
author
Croce, Sabrina
author
Djordevic, Bojana
author
Herrington, Simon
author
Howitt, Brooke
author
Ip, Philip
author
Koebel, Martin
author
Lax, Sigurd
author
Quade, Bradley
author
Shaw, Patricia
author
Vidal, August
author
Yemelyanova, Anna
author
Clarke, Blaise
author
Hedrick Ellenson, Lora
author
Longacre, Teri A
author
Shih, Ie-Ming
author
McCluggage, W. Glenn
author
Malpica, Anais
author
Oliva, Esther
author
Parkash, Vinita
author
Matias-Guiu, Xavier
author
2019
The aim of this article is to propose guidelines and recommendations in problematic areas in pathologic reporting of endometrial carcinoma (EC) regarding special techniques and ancillary studies. An organizing committee designed a comprehensive survey with different questions related to pathologic features, diagnosis, and prognosis of EC that was sent to all members of the International Society of Gynecological Pathologists. The special techniques/ancillary studies group received 4 different questions to be addressed. Five members of the group reviewed the literature and came up with recommendations and an accompanying text which were discussed and agreed upon by all members of the group. Twelve different recommendations are made. They address the value of immunohistochemistry, ploidy, and molecular analysis for assessing prognosis in EC, the value of steroid hormone receptor analysis to predict response to hormone therapy, and parameters regarding applying immunohistochemistry and molecular tests for assessing mismatch deficiency in EC.
https://doi.org/10.1097/PGP.0000000000000496
0277-1691
http://hdl.handle.net/10459.1/65749
Endometrial carcinoma
Guidelines
ISGyP
Molecular pathology
International Society of Gynecological Pathologists (ISGyP) Endometrial Cancer Project: Guidelines From the Special Techniques and Ancillary Studies Group
oai:repositori.udl.cat:10459.1/843602023-05-02T13:47:02Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998col_10459.1_44504
00925njm 22002777a 4500
dc
Lucido, Abel
author
Basallo, Oriol
author
Sorribas Tello, Albert
author
Marin-Sanguino, Alberto
author
Vilaprinyo Terré, Ester
author
Alves, Rui
author
2022
Strigolactones mediate plant development, trigger symbiosis with arbuscular
mycorrhizal fungi, are abundant in 80% of the plant kingdom and help plants
gain resistance to environmental stressors. They also induce germination
of parasitic plant seeds that are endemic to various continents, such as
Orobanche in Europe or Asia and Striga in Africa. The genes involved in the
early stages of strigolactones biosynthesis are known in several plants. The
regulatory structure and the latter parts of the pathway, where flux branching
occurs to produce alternative strigolactones, are less well-understood. Here
we present a computational study that collects the available experimental
evidence and proposes alternative biosynthetic pathways that are consistent
with that evidence. Then, we test the alternative pathways through in silico
simulation experiments and compare those experiments to experimental
information. Our results predict the differences in dynamic behavior between
alternative pathway designs. Independent of design, the analysis suggests
that feedback regulation is unlikely to exist in strigolactone biosynthesis. In
addition, our experiments suggest that engineering the pathway to modulate
the production of strigolactones could be most easily achieved by increasing
the flux of b-carotenes going into the biosynthetic pathway. Finally, we find
that changing the ratio of alternative strigolactones produced by the pathway
can be done by changing the activity of the enzymes after the flux branching
points.
https://doi.org/10.3389/fpls.2022.979162
033199
2296-6463
http://hdl.handle.net/10459.1/84360
Strigolactones
Arbuscular mycorrhizal fungi
Mathematical modeling
Computational biology
Feedback regulation
Biosynthetic pathway
A mathematical model for strigolactone biosynthesis in plants
oai:repositori.udl.cat:10459.1/732452022-03-11T00:14:46Zcom_10459.1_227com_10459.1_2com_10459.1_237com_10459.1_47453col_10459.1_314col_10459.1_354col_10459.1_59998col_10459.1_44504
00925njm 22002777a 4500
dc
Laza-Vásquez, Celmira
author
Hernández-Leal, María José
author
Carles Lavila, Misericordia
author
Pérez Lacasta, María José
author
Cruz Esteve, María Inés
author
Rué i Monné, Montserrat
author
2022
Abstract:This study explored the barriers and facilitators to the implementation of a risk-basedbreast cancer screening program from the point of view of Spanish health professionals. A cross-sectional study with 220 Spanish health professionals was designed. Data were collected in 2020 viaa web-based survey and included the advantages and disadvantages of risk-based screening andbarriers and facilitators for the implementation of the program. Descriptive statistics and Likert scaleresponses analyzed as category-ordered data were obtained. The risk-based screening was consideredimportant or very important to reduce breast cancer mortality and promote a more proactive role forwomen in breast cancer prevention, to increase coverage for women under 50 years, to promote abreast cancer prevention strategy for women at high risk, and to increase efficiency and effectiveness.Switching to a risk-based program from an age-based program was rated as important or veryimportant by 85% of participants. As barriers for implementation, risk communication, the workloadof health professionals, and limited human and financial resources were mentioned. Despite thebarriers, there is good acceptance, and it seems feasible, from the perspective of health professionals,to implement a risk-based breast cancer screening program in Spain. However, this poses a numberof organizational and resource challenges.
https://doi.org/10.3390/ijerph19031406
032032
1660-4601
http://hdl.handle.net/10459.1/73245
Breast cancer
Personalized screening
Barriers
Facilitators
Health professionals
Barriers and facilitators to the implementation of a personalized breast cancer screening program: Views of Spanish health professionals
oai:repositori.udl.cat:10459.1/482712017-07-26T09:23:00Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Landa, Iñigo
author
Ruiz-Llorente, Sergio
author
Montero-Conde, Cristina
author
Inglada-Pérez, Lucía
author
Schiavi, Francesca
author
Leskelä, Susanna
author
Pita, Guillermo
author
Milne, Roger
author
Maravall Royo, Javier
author
Ramos, Ignacio
author
Andía, Víctor
author
Rodríguez-Poyo, Paloma
author
Jara-Albarrán, Antonino
author
Meoro, Amparo
author
Peso, Cristina del
author
Arribas, Luis
author
Iglesias, Pedro
author
Caballero, Javier
author
Serrano, Joaquín
author
Picó, Antonio
author
Pomares, Francisco
author
Giménez, Gabriel
author
López-Mondéjar, Pedro
author
Castello, Roberto
author
Merante-Boschin, Isabella
author
Pelizzo, Maria-Rosa
author
Mauricio Puente, Dídac
author
Opocher, Giuseppe
author
Rodríguez-Antona, Cristina
author
González- Neira, Anna
author
Matias-Guiu, Xavier
author
Santisteban, Pilar
author
Robledo, Mercedes
author
2009
In order to identify genetic factors related to thyroid cancer susceptibility, we adopted a candidate gene approach. We studied
tag- and putative functional SNPs in genes involved in thyroid cell differentiation and proliferation, and in genes found to be
differentially expressed in thyroid carcinoma. A total of 768 SNPs in 97 genes were genotyped in a Spanish series of 615 cases
and 525 controls, the former comprising the largest collection of patients with this pathology froma single population studied
to date. SNPs in an LD block spanning the entire FOXE1 gene showed the strongest evidence of association with papillary
thyroid carcinoma susceptibility. This association was validated in a second stage of the study that included an independent
Italian series of 482 patients and 532 controls. The strongest association results were observed for rs1867277 (OR[perallele]
= 1.49; 95%CI = 1.30–1.70; P = 5.961029). Functional assays of rs1867277 (NM_004473.3:c.2283G.A) within the FOXE1
59 UTR suggested that this variant affects FOXE1 transcription. DNA-binding assays demonstrated that, exclusively, the
sequence containing the A allele recruited the USF1/USF2 transcription factors, while both alleles formed a complex in which
DREAM/CREB/aCREM participated. Transfection studies showed an allele-dependent transcriptional regulation of FOXE1. We
propose a FOXE1 regulation model dependent on the rs1867277 genotype, indicating that this SNP is a causal variant in
thyroid cancer susceptibility. Our results constitute the first functional explanation for an association identified by a GWAS and
thereby elucidate a mechanism of thyroid cancer susceptibility. They also attest to the efficacy of candidate gene approaches
in the GWAS era.
https://doi.org/10.1371/journal.pgen.1000637
015925
1553-7390
http://hdl.handle.net/10459.1/48271
The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors
oai:repositori.udl.cat:10459.1/484182021-08-30T14:56:39Zcom_10459.1_227com_10459.1_2com_10459.1_59159com_10459.1_47453col_10459.1_314col_10459.1_59160col_10459.1_59998
00925njm 22002777a 4500
dc
Matias, Ana C.
author
Marinho, H. Susana
author
Cyrne, Luísa
author
Herrero Perpiñán, Enrique
author
Antunes, Fernando
author
2011
Taking into account published contradictory results concerning the regulation of fatty acid synthase (Fas)
by H2O2, we carried out a systematic study where two methods of H2O2 delivery (steady-state and bolus
addition) and the effect of a wide range of H2O2 concentrations were investigated. A decrease in Fas activity
was observed for cells exposed to 100 and 150 lMH2O2 in a steady-state, while a bolus addition of the
same H2O2 concentrations did not alter Fas activity. Similar results were observed for the mRNA levels of
FAS1, the gene that encodes Fas subunit b. However, the exposure to a steady-state 50 lMH2O2 dose lead
to an increase in FAS1 mRNA levels, showing a biphasic modulation of Fas by H2O2. The results obtained
emphasize that cellular effects of H2O2 can vary over a narrow range of concentrations. Therefore, a tight
control of H2O2 exposure, which can be achieved by exposing H2O2 in a steady-state, is important for cellular
studies of H2O2-dependent redox regulation.
https://doi.org/10.1016/j.abb.2011.08.009
017835
0003-9861
http://hdl.handle.net/10459.1/48418
H2O2
Adaptation
Fatty acid synthase
Biphasic modulation of fatty acid synthase by hydrogen peroxide in Saccharomyces cerevisiae
oai:repositori.udl.cat:10459.1/463672023-01-27T20:01:54Zcom_10459.1_227com_10459.1_2com_10459.1_59159com_10459.1_47453col_10459.1_314col_10459.1_59160col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Díaz de la Loza, María del Carmen
author
Gallardo, Mercedes
author
García-Rubio, María Luisa
author
Izquierdo, Alicia
author
Herrero Perpiñán, Enrique
author
Aguilera, Andrés
author
Wellinger, Ralf Erik
author
2011
Genomic instability is related to a wide-range of human diseases. Here, we show that mitochondrial iron–sulfur cluster biosynthesis is important for the maintenance of nuclear genome stability in Saccharomyces cerevisiae. Cells lacking the mitochondrial chaperone Zim17 (Tim15/Hep1), a component of the iron–sulfur biosynthesis machinery, have limited respiration activity, mimic the metabolic response to iron starvation and suffer a dramatic increase in nuclear genome recombination. Increased oxidative damage or deficient DNA repair do not account for the observed genomic hyperrecombination. Impaired cell-cycle progression and genetic interactions of ZIM17 with components of the RFC-like complex involved in mitotic checkpoints indicate that replicative stress causes hyperrecombination in zim17Δ mutants. Furthermore, nuclear accumulation of pre-ribosomal particles in zim17Δ mutants reinforces the importance of iron–sulfur clusters in normal ribosome biosynthesis. We propose that compromised ribosome biosynthesis and cell-cycle progression are interconnected, together contributing to replicative stress and nuclear genome instability in zim17Δ mutants.
https://doi.org/10.1093/nar/gkr193
016913
0305-1048
http://hdl.handle.net/10459.1/46367
Iron-Sulfur Proteins
Mitochondrial proteins
Saccharomyces cerevisiae proteins
Zim 17 protein
Zim17/Tim15 links mitochondrial iron–sulfur cluster biosynthesis to nuclear genome stability
oai:repositori.udl.cat:10459.1/492862016-09-06T13:03:57Zcom_10459.1_227com_10459.1_2com_10459.1_240col_10459.1_314col_10459.1_333
00925njm 22002777a 4500
dc
Cardús i Figueras, Anna
author
Gallego, Carme
author
Muray, S.
author
Marco, M. P.
author
Parisi Capdevila, Eva
author
Aldea, Martí
author
Fernández i Giráldez, Elvira
author
2003
Existen datos experimentales contradictorios respecto al comportamiento de
las células de músculo liso vascular (CMLV) expuestas al calcitriol. Determinar
el efecto del calcitriol y de sus análogos a nivel vascular tiene una considerable
trascendencia clínica ya que la proliferación de las CMLV está implicada
en el mecanismo patogénico de la arteriosclerosis y de la resistencia tras angioplastia.
En este trabajo demostramos mediante incorporación de BrdU que el calcitriol
estimula la proliferación en las CMLV. La proliferación es menor al añadir
al medio de cultivo Paracalcitol o EB1089 a dosis equimolar. En concordancia
con estos hechos, también observamos que el calcitriol induce la expresión del
mRNA VDR mientras que no existe este efecto con ninguno de los análogos estudiados.
En conclusión, el calcitriol tiene un efecto directo estimulador de la proliferación
de las CMLV que no se observa con el Paracalcitol y EB1089 a concentración
equimolar.
0211-6995
http://hdl.handle.net/10459.1/49286
Células músculo liso vascular
Proliferación
Calcitriol
Efecto diferencial de los análogos de la vitamina D en la proliferación de células de músculo liso vascular
oai:repositori.udl.cat:10459.1/571222021-08-30T15:04:29Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Reverter Branchat, Gemma
author
Cabiscol Català, Elisa
author
Tamarit Sumalla, Jordi
author
Sorolla Bardají, Maria Alba
author
Torre Ruiz, M. A. de la
author
Ros Salvador, Joaquim
author
2007
Alcohol dehydrogenase 1 (Adh1)p catalyses the conversion of acetaldehyde to ethanol,
regenerating NAD+. In Saccharomyces cerevisiae, Adh1p is oxidatively modified during ageing
and, consequently, its activity becomes reduced. To analyse whether maintaining this activity is
advantageous for the cell, a yeast strain with an extra copy of the ADH1 gene (2 ADH1) was
constructed, and the effects on chronological and replicative ageing were analysed. The strain
showed increased survival in stationary phase (chronological ageing) due to induction of
antioxidant enzymes such as catalase and superoxide dismutases. In addition, 2 ADH1 cells
displayed an increased activity of silent information regulator 2 (Sir2)p, an NAD+-dependent
histone deacetylase, due to a higher NAD+/NADH ratio. As a consequence, a 30 % extension in
replicative life span was observed. Taken together, these results suggest that the maintenance of
enzymes that participate in NAD+/NADH balancing is important to chronological and
replicative life-span parameters.
https://doi.org/10.1099/mic.0.2007/009340-0
011503
1350-0872
http://hdl.handle.net/10459.1/57122
Chronological and replicative life-span extension in Saccharomyces cerevisiae by increased dosage of alcohol dehydrogenase 1
oai:repositori.udl.cat:10459.1/676812023-11-15T10:29:55Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_241col_10459.1_314col_10459.1_59998col_10459.1_30324col_10459.1_49291
00925njm 22002777a 4500
dc
Vaquero, Marta
author
Cuesta, Sara
author
Anerillas Aljama, Carlos
author
Altés Bargalló, Gisela
author
Ribera i Calvet, Joan
author
Basson, M. Albert
author
Licht, Jonathan D.
author
Egea Navarro, Joaquim
author
Encinas Martín, Mario
author
2019-08-01
Background: Congenital anomalies of the kidney and urinary tract (CAKUT) is a group of diseases that include a broad spectrum of developmental defects of the genitourinary system. Mouse models indicate that perturbations of the GDNF-Ret signaling pathway are a major genetic cause of CAKUT. Sprouty1 is an intracellular Ret inhibitor whose mutation results in supernumerary kidneys, megaureters, and hydronephrosis in mice. Both the molecular mechanisms and the structural domains critical for Sprouty function are a matter of controversy, partly because studies pursuing this objective rely on ectopic overexpression in cell lines. A conserved N-terminal tyrosine has been frequently, but not always, identified as critical for their function in vitro. Methods: We have generated Sprouty1 knockin mice bearing a tyrosine-to-alanine substitution in position 53, corresponding to the conserved N-terminal tyrosine of Sprouty1. We have characterized development of the genitourinary systems of these mice via different methods, including the use of reporter mice expressing EGFP form the Ret locus, and whole mount cytokeratin staining. Results: Mice lacking this tyrosine grow ectopic ureteric buds that ultimately will form supernumerary kidneys, a phenotype indistinguishable to that of Sprouty1 knockout mice. Sprouty1 knockin mice also present megaureters and vesicoureteral reflux, caused by failure of ureters to separate from Wolffian ducts and migrate to their definitive position. Conclusions: Tyrosine 53 is absolutely necessary to convey Sprouty1 function during genitourinary development.
https://doi.org/10.1681/ASN.2018111085
028598
1046-6673
http://hdl.handle.net/10459.1/67681
Sprouty
Ret
Genitourinary Development
Wolffian Duct
Ureteric bud
Sprouty1 controls genitourinary development via its N-terminal tyrosine
oai:repositori.udl.cat:10459.1/416622020-07-14T08:39:35Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Martínez Alonso, Montserrat
author
Llecha Cano, Núria
author
Mayorga Mayorga, Maritza Elfride
author
Sorolla Bardají, Anabel
author
Dolcet Roca, Xavier
author
Sanmartín Novell, Verònica
author
Abal Diaz, Leandro
author
Casanova i Seuma, Josep M. (Josep Manel)
author
Baradad Brusau, Manuel
author
Yeramian Hakim, Andree
author
Egido Garcia, Ramon Maria
author
Puig, Susana
author
Vilella, Ramón
author
Matias-Guiu, Xavier
author
Martí Laborda, Rosa Ma.
author
2009
Somatostatin analogues (SAs) are potential anticancer agents. This study was designed to investigate the expression of somatostatin receptors (SSTRs) in melanoma cells and the effect of two SAs on cell proliferation and viability. Eighteen primary and metastatic human cutaneous melanoma cell lines were treated with octreotide and SOM230. Expression of SSTR1, SSTR2, SSTR3 and SSTR5 was assessed by real-time polymerase chain reaction. Proliferation, viability and cell death were assessed using standard assays. Inhibition was modelled by mixed-effect regression. Melanoma cells expressed one or more SSTR. Both SAs inhibited proliferation of most melanoma cell lines, but inhibition was less than 50%. Neither SA affected cell viability or induced cell death. The results suggest that melanoma cell lines express SSTRs. The SAs investigated, under the conditions used in this study, did not, however, significantly inhibit melanoma growth or induce cell death. Novel SAs, combination therapy with SAs and their anti-angiogenic properties should be further investigated.
014917
0300-0605
http://hdl.handle.net/10459.1/41662
Malignant melanoma
Somatostatin analogues
Octreotide
SOM230
Expression of somatostatin receptors in human melanoma cell lines: effect of two different somatostatin analogues, octreotide and SOM230, on cell proliferation
oai:repositori.udl.cat:10459.1/303302020-07-14T08:39:35Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Rué i Monné, Montserrat
author
Serna Arnaiz, Catalina
author
Soler González, Jorge
author
Bosch, Anna
author
Ruiz-Magaz, Maria Cristina
author
Galván, Leonardo
author
2008
Background: There are few studies comparing pharmaceutical costs and the use of medications between immigrants and the autochthonous population in Spain. The objective of this study is to evaluate whether there are differences in pharmaceutical consumption and expenses between immigrant and Spanish-born populations.
Methods: Prospective observational study in 1,630 immigrants and 4,154 Spanish-born individuals visited by fifteen primary care physicians at five public Primary Care Clinics (PCC) during 2005 in the city of Lleida, Catalonia (Spain). Data on pharmaceutical consumption and expenses was
obtained from a comprehensive computerized data-collection system. Multinomial regression models were used to estimate relative risks and confidence intervals of pharmaceutical expenditure, adjusting for age and sex.
Results: The percentage of individuals that purchased medications during a six-month period was 53.7% in the immigrant group and 79.2% in the autochthonous group. Pharmaceutical expenses and consumption were lower in immigrants than in autochthonous patients in all age groups and both genders. The relative risks of being in the highest quartile of expenditure, for Spanish-born versus immigrants, were 6.9, 95% CI = (4.2, 11.5) in men and 5.3, 95% CI = (3.5, 8.0) in women, with the reference category being not having any pharmaceutical expenditure.
Conclusion: Pharmaceutical expenses are much lower for immigrants with respect to
autochthonous patients, both in the percentage of prescriptions filled at pharmacies and the number of containers of medication obtained, as well as the prices of the medications used. Future studies should explore which factors explain the observed differences in pharmaceutical expenses and if these disparities produce health inequalities.
https://doi.org/10.1186/1472-6963-8-35
011824
1472-6963
http://hdl.handle.net/10459.1/30330
Differences in pharmaceutical consumption and expenses between immigrant and Spanish-born populations in Lleida, (Spain): a 6-months prospective observational study
oai:repositori.udl.cat:10459.1/710182022-03-16T12:23:19Zcom_10459.1_227com_10459.1_2com_10459.1_241col_10459.1_314col_10459.1_30324
00925njm 22002777a 4500
dc
Klionsky, Daniel J.
author
Cantí Nicolás, Carles
author
Garcera, Ana
author
Herreros Danés, Judit
author
Soler i Tatché, Rosa Ma.
author
others
author
2021-02-08
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
https://doi.org/10.1080/15548627.2020.1797280
031126
1554-8627
http://hdl.handle.net/10459.1/71018
Autophagosome
LC3
Cancer
Macroautophagy
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
oai:repositori.udl.cat:10459.1/691382022-09-27T14:59:10Zcom_10459.1_242com_10459.1_2com_10459.1_227com_10459.1_47453col_10459.1_10990col_10459.1_314col_10459.1_59998col_10459.1_49291
00925njm 22002777a 4500
dc
Laplana Lafaja, Marina
author
Bravo, M. J.
author
Fernández-Fuertes, M.
author
Ruiz-García, C.
author
Alarcón-Martin, E.
author
Colmenero, J. D.
author
Caruz, Antonio
author
Fibla Palazón, Joan
author
Real, Luis M.
author
Royo Sánchez-Palencia, José Luis
author
2020-06-09
TLR2 plays a key role in innate immune response recognizing molecular patterns expressed by pathogens. rs111200466 is a TLR2 promoter Insertion/Deletion polymorphism with contradictory data about its role in HIV-1 infection. We analyzed rs111200466 in HIV-1 disease progression and showed a correlation with a faster progression to the CD4+<200cells/μL outcome for Deletion allele carriers (Cox regression analysis: Hazard Ratio=2.4; 95%CI:1.4-4, P=0.001). When naïve patients with CD4+<200cells/μL start antiretroviral treatment, rs111200466-Deletion carriers showed a trend towards a slower, recovery rate (time required to reach CD4+>350cells/μL, Cox P=0.36). Our data suggests rs111200466 as a prognosis factor for HIV-1 disease progression.
https://doi.org/10.1093/infdis/jiaa327
030102
0022-1899
http://hdl.handle.net/10459.1/69138
Polymorphism
HIV infection
HIV progression
Toll Like Receptor 2 promoter -196 to -174 deletion affects CD4 levels along HIV infection progression
oai:repositori.udl.cat:10459.1/486182021-08-30T15:04:33Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Molina Navarro, Maria Micaela
author
Casas Herranz, Celia
author
Piedrafita Llorens, Lídia
author
Bellí i Martínez, Gemma
author
Herrero Perpiñán, Enrique
author
2003
The Saccharomyces cerevisiae monothiol glutare-
doxin Grx5 participates in the mitochondrial biogenesis of
iron–sulfur clusters. Grx5 homologues exist in organisms from
bacteria to humans. Chicken (cGRX5) and human (hGRX5)
homologues contain a mitochondrial targeting sequence, suggest-
ing a mitochondrial localization for these two proteins. We have
compartmentalized the Escherichia coli and Synechocystis sp.
homologues, and also cGRX5 and hGRX5, in the mitochondrial
matrix of a yeast grx5 mutant. All four heterologous proteins
rescue the defects of the mutant. The chicken cGRX5 gene was
significantly expressed throughout the embryo stages in different
tissues. These results underline the functional conservation of
Grx5 homologues throughout evolution.
https://doi.org/10.1016/j.febslet.2006.03.037
009696
0014-5793
http://hdl.handle.net/10459.1/48618
Glutaredoxin
Iron–sulfur cluster
Mitochondria
Redox regulation
Glutathione
Prokaryotic and eukaryotic monothiol glutaredoxins are able to perform the functions of Grx5 in the biogenesis of Fe/S clusters in yeast mitochondria
oai:repositori.udl.cat:10459.1/4638632023-10-27T08:57:05Zcom_10459.1_56965com_10459.1_2com_10459.1_243com_10459.1_227com_10459.1_47453col_10459.1_57707col_10459.1_3332col_10459.1_314col_10459.1_59998col_10459.1_49291col_10459.1_44504
00925njm 22002777a 4500
dc
Basallo, Oriol
author
Pérez, Lucía
author
Lucido, Abel
author
Sorribas Tello, Albert
author
Marin-Saguino, Alberto
author
Vilaprinyo Terré, Ester
author
Perez‑Fons, Laura
author
Albacete, Alfonso
author
Martínez-Andújar, Cristina
author
Fraser, Paul D.
author
Christou, Paul
author
Capell Capell, Teresa
author
Alves, Rui
author
2023
Many highly valued chemicals in the pharmaceutical, biotechnological, cosmetic, and biomedical industries belong to the terpenoid family. Biosynthesis of these chemicals relies on polymerization of Isopentenyl di-phosphate (IPP) and/or dimethylallyl diphosphate (DMAPP) monomers, which plants synthesize using two alternative pathways: a cytosolic mevalonic acid (MVA) pathway and a plastidic methyleritritol-4-phosphate (MEP) pathway. As such, developing plants for use as a platform to use IPP/DMAPP and produce high value terpenoids is an important biotechnological goal. Still, IPP/DMAPP are the precursors to many plant developmental hormones. This creates severe challenges in redirecting IPP/DMAPP towards production of non-cognate plant metabolites. A potential solution to this problem is increasing the IPP/DMAPP production flux in planta. Here, we aimed at discovering, understanding, and predicting the effects of increasing IPP/DMAPP production in plants through modelling. We used synthetic biology to create rice lines containing an additional ectopic MVA biosynthetic pathway for producing IPP/DMAPP. The rice lines express three alternative versions of the additional MVA pathway in the plastid, in addition to the normal endogenous pathways. We collected data for changes in macroscopic and molecular phenotypes, gene expression, isoprenoid content, and hormone abundance in those lines. To integrate the molecular and macroscopic data and develop a more in depth understanding of the effects of engineering the exogenous pathway in the mutant rice lines, we developed and analyzed data-centric, line-specific, multilevel mathematical models. These models connect the effects of variations in hormones and gene expression to changes in macroscopic plant phenotype and metabolite concentrations within the MVA and MEP pathways of WT and mutant rice lines. Our models allow us to predict how an exogenous IPP/DMAPP biosynthetic pathway affects the flux of terpenoid precursors. We also quantify the long-term effect of plant hormones on the dynamic behavior of IPP/DMAPP biosynthetic pathways in seeds, and predict plant characteristics, such as plant height, leaf size, and chlorophyll content from molecular data. In addition, our models are a tool that can be used in the future to help in prioritizing re-engineering strategies for the exogenous pathway in order to achieve specific metabolic goals
https://doi.org/10.3389/fpls.2023.1133299
033497
1664-462X
https://repositori.udl.cat/handle/10459.1/463863
MEP pathway
Metabolic engineering
Multi level modelling
Terpenoid synthetic biology
MVA (mevalonic acid) pathway
Changing biosynthesis of terpenoid percursors in rice through synthetic biology
oai:repositori.udl.cat:10459.1/4642602024-03-12T23:01:09Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Parisi, Eva
author
Hidalgo, Iván
author
Montal Roura, Robert
author
Pallisé, Ona
author
Tarragona Foradada, Jordi
author
Sorolla Bardají, Anabel
author
Novell, Anna
author
Campbell, Kyra
author
Sorolla Bardají, Maria Alba
author
Casali, Andreu
author
Salud Salvia, Maria Antonieta
author
2023
Metastasis is the leading cause of colorectal cancer (CRC)-related deaths. Therefore, the identification of accurate biomarkers predictive of metastasis is needed to better stratify high-risk patients to provide preferred management and reduce mortality. In this study, we identified 13 new genes that modified circulating tumor cell numbers using a genome-wide genetic screen in a whole animal CRC model. Candidate genes were subsequently evaluated at the gene expression level in both an internal human CRC cohort of 153 patients and an independent cohort from the TCGA including 592 patients. Interestingly, the expression of one candidate, PLA2G12A, significantly correlated with both the time to recurrence and overall survival in our CRC cohort, with its low expression being an indicator of a poor clinical outcome. By examining the TCGA cohort, we also found that low expression of PLA2G12A was significantly enriched in epithelial–mesenchymal transition signatures. Finally, the candidate functionality was validated in vitro using three different colon cancer cell lines, revealing that PLA2G12A deficiency increases cell proliferation, migration, and invasion. Overall, our study identifies PLA2G12A as a prognostic biomarker of early-stage CRC, providing evidence that its deficiency promotes tumor growth and dissemination.
https://doi.org/10.3390/ijms241310889
034039
1422-0067
https://repositori.udl.cat/handle/10459.1/464260
PLA2G12A
Colorectal cancer
Prognosis
Drosophila
PLA2G12A as a Novel Biomarker for Colorectal Cancer with Prognostic Relevance
oai:repositori.udl.cat:10459.1/603462023-05-02T11:05:24Zcom_10459.1_227com_10459.1_2com_10459.1_47453com_10459.1_240col_10459.1_314col_10459.1_59998col_10459.1_333
00925njm 22002777a 4500
dc
Carles Lavila, Misericòrdia
author
Martínez Alonso, Montserrat
author
Pons Rodríguez, Anna
author
Pérez Lacasta, María José
author
Perestelo Pérez, Lilisbeth
author
Sala, Maria Rosa
author
Vidal, Carmen
author
Garcia, Montse
author
Toledo Chávarri, Ana
author
Codern-Bové, Núria
author
Feijoo Cid, Maria
author
Romero, Anabel
author
Pla, Roger
author
Soler González, Jorge
author
Castells, Xavier
author
Rué i Monné, Montserrat
author
2017
The decision to participate or not in breast cancer screening is complex due to the trade-off between the expected benefit of breast cancer mortality reduction and the major harm of overdiagnosis. It seems ethically necessary to inform women so that they can actively participate in decision-making and make an informed choice based on their values and preferences.
The objective of this study is to assess the effects of receiving information about the benefits and harms of screening on decision-making, in women approaching the age of invitation to mammography screening.
https://doi.org/10.1186/s13063-017-2161-7
025931
1745-6215
http://hdl.handle.net/10459.1/60346
Screening
Breast cancer
Informed choice
Early detection
The effect of information about the benefits and harms of mammography on women’s decision-making: study protocol for a randomized controlled trial
oai:repositori.udl.cat:10459.1/600102021-04-29T09:27:09Zcom_10459.1_227com_10459.1_2com_10459.1_59360com_10459.1_47453com_10459.1_241col_10459.1_314col_10459.1_59361col_10459.1_59998col_10459.1_30324
00925njm 22002777a 4500
dc
Cabré Cucó, Rosanna
author
Naudí i Farré, Alba
author
Dominguez Gonzalez, Mayelin
author
Ayala Jové, Ma. Victoria (Maria Victoria)
author
Jové Font, Mariona
author
Mota Martorell, Natàlia
author
Piñol Ripoll, Gerard
author
Gil Villar, M. Pilar
author
Rué i Monné, Montserrat
author
Portero Otín, Manuel
author
Ferrer, Isidre
author
Pamplona Gras, Reinald
author
2017
Human brain aging is the physiological process which underlies as cause of cognitive decline in the elderly and the main risk factor for neurodegenerative diseases such as Alzheimer's disease. Human neurons are functional throughout a healthy adult lifespan, yet the mechanisms that maintain function and protect against neurodegenerative processes during aging are unknown. Here we show that protein oxidative and glycoxidative damage significantly increases during human brain aging, with a breakpoint at 60 years old. This trajectory is coincident with a decrease in the content of the mitochondrial respiratory chain complex I–IV. We suggest that the deterioration in oxidative stress homeostasis during aging induces an adaptive response of stress resistance mechanisms based on the sustained expression of REST, and increased or decreased expression of Akt and mTOR, respectively, over the adult lifespan in order to preserve cell neural survival and function.
https://doi.org/10.1016/j.freeradbiomed.2016.12.010
025637
0891-5849
http://hdl.handle.net/10459.1/60010
Cell survival pathways
Mechanistic target of rapamycin (mTOR)
Mitochondria respiratory chain
Mitochondrial stress
Protein oxidation
Repressor element 1-silencing transcription factor (REST)
Sixty years old is the breakpoint of human frontal cortex aging
oai:repositori.udl.cat:10459.1/661612022-06-14T12:58:49Zcom_10459.1_227com_10459.1_2com_10459.1_47453col_10459.1_314col_10459.1_59998
00925njm 22002777a 4500
dc
Pérez Lacasta, María José
author
Martínez Alonso, Montserrat
author
Garcia, Montse
author
Sala, Maria
author
Perestelo Pérez, Lilisbeth
author
Vidal, Carmen
author
Codern-Bové, Núria
author
Feijoo Cid, Maria
author
Toledo Chávarri, Ana
author
Cardona, Àngels
author
Pons Rodríguez, Anna
author
Carles Lavila, Misericordia
author
Rué i Monné, Montserrat
author
2019-03-26
BACKGROUND:
In Spain, women invited to breast screening are not usually informed about potential harms of screening. The objective of the InforMa study is to assess the effect of receiving information about the benefits and harms of breast screening on informed choice and other decision-making outcomes, in women approaching the age of invitation to mammography screening.
METHODS:
Two-stage randomised controlled trial. In the first stage, 40 elementary territorial units of the public healthcare system were selected and randomised to intervention or control. In the second stage, women aged 49-50 years were randomly selected. The target sample size was 400 women. Women in the intervention arm received a decision aid (DA) with detailed information on the benefits and harms of screening. Women in the control arm received a standard leaflet that did not mention harms and recommended accepting the invitation to participate in the Breast Cancer Screening Program (BCSP). The primary outcome was informed choice, defined as adequate knowledge and intentions consistent with attitudes. Secondary outcomes included decisional conflict, worry about breast cancer, time perspective, opinions about the DA or the leaflet, and participation in the BCSP.
RESULTS:
In the intervention group, 23.2% of 203 women made an informed choice compared to only 0.5% of 197 women in the control group (p < 0.001). Attitudes and intentions were similar in both study groups with a high frequency of women intending to be screened, 82.8% vs 82.2% (p = 0.893). Decisional conflict was significantly lower in the intervention group. No differences were observed in confidence in the decision, anxiety, and participation in BCSP.
CONCLUSIONS:
Women in Spain lack knowledge on the benefits and harms of breast screening. Providing quantitative information on benefits and harms has produced a considerable increase in knowledge and informed choice, with a high acceptance of the informative materials.
TRIAL REGISTRATION:
Trial identifier NCT03046004 at ClinicalTrials.gov registry. Registered on February 4 2017. Trial name: InforMa study.
https://doi.org/10.1371/journal.pone.0214057
028527
1932-6203
http://hdl.handle.net/10459.1/66161
Effect of information about the benefits and harms of mammography on women's decision making: The InforMa randomised controlled trial
marc///col_10459.1_314/100