847 research outputs found
Nuevos hábitos en la gestión fotográfica en smartphone
This article study the habits in the use and manage of smartphone images. Being smartphones the most universal product, and their camera a key element, this research is bases on the hypothesis that current photo habits exceed mobile photo manage tools. A survey to smartphone users sought a general view of current situation about their photographic habits in the taking, manage and store of photos inside their phones. The survey also has questions about the long term expectations. Results show lack of adequacy of current systems to smartphone pictures and open a discussion about how to adapt current photo manage systems to a long term vision.En este artículo se revisan los hábitos de uso y gestión de las fotografías en los teléfonos inteligentes. En un momento en que el smartphone es el producto tecnológico más universal siendo su cámara de fotos uno de sus elementos más importantes, se plantea la hipótesis de que los actuales hábitos fotográficos de los usuarios desbordan la capacidad de gestión de los sistemas operativos y las aplicaciones móviles. Para obtener una mejor visión de la situación actual se realizó una encuesta a usuarios de smartphone acerca de sus hábitos en la captura y gestión de las imágenes, propias y ajenas, dentro del teléfono, preguntando también sobre sus expectativas de futuro de cara al uso y almacenamiento a largo plazo de esas imágenes. Los resultados muestran una falta de adecuación de los actuales sistemas de gestión y almacenamiento de imágenes en smartphone al largo plazo, profundizando en los problemas que la llegada de la cámara compacta digital supuso en la gestión de la fotografía personal y familiar, y que están ampliamente documentados. Los resultados de este estudio invitan a una reflexión sobre cómo adaptar los actuales sistemas de gestión fotográfica a una visión a largo plazo en el ámbito personal
Involvement of HisF in the persistence of Acinetobacter baumannii during a pneumonia infection
[Abstract] Acinetobacter baumannii is currently considered one of themost problematic nosocomial microorganisms. In the present work the hisF gene from the ATCC 17978 strain and the AbH12O-A2 clinical isolate of A. baumannii was found over-expressed during the course of murine pneumonia infections. The study demonstrated that the A. baumannii ATCC 17978 mutant strain lacking the hisF gene induces a sub-lethal pneumonia infection in mice, while the complemented mutant strain increased its virulence. This histidine auxotroph mutant showed an increase on IL-6 secretion and leukocytes recruitment during infections. Furthermore, data revealed that the hisF gene, implicated in the innate immunity and inflammation, is involved in virulence during a pneumonia infection, which may partly explain the ability of this strain to persist in the lung. We suggest that HisF, essential for full virulence in this pathogen, should be considered a potential target for developing new antimicrobial therapies against A. baumannii.Instituto de Salud Carlos III; PI15/00860Instituto de Salud Carlos III; PI14/00059Instituto de Salud Carlos III; PI17/01482Axencia Galega de Innovación; IN607A 2016/22Spanish Network for Research in Infectious Diseases; REIPI RD12/0015/0014Spanish Network for Research in Infectious Diseases; REIPI RD16/0016/006Instituto de Salud Carlos III; FI18/00315Xunta de Galicia; IN606A-2019/029Xunta de Galicia; IN607A 2016/2
Contribution of the a-baumannii A1S_0114 gene to the interaction with eukaryotic cells and virulence
Genetic and functional studies showed that some components of the Acinetobacter
baumannii ATCC 17978 A1S_0112-A1S_0119 gene cluster are critical for biofilm
biogenesis and surface motility. Recently, our group has shown that the A1S_0114 gene
was involved in biofilm formation, a process related with pathogenesis. Confirming our
previous results, microscopy images revealed that the ATCC 17978 10114 derivative
lacking this gene was unable to form a mature biofilm structure. Therefore, other bacterial
phenotypes were analyzed to determine the role of this gene in the pathogenicity of
A. baumannii ATCC 17978. The interaction of the ATCC 17978 parental strain and the
10114 mutant with A549 human alveolar epithelial cells was quantified revealing that the
A1S_0114 gene was necessary for proper attachment to A549 cells. This dependency
correlates with the negative effect of the A1S_0114 deletion on the expression of genes
coding for surface proteins and pili-assembly systems, which are known to play a
role in adhesion. Three different experimental animal models, including vertebrate and
invertebrate hosts, confirmed the role of the A1S_0114 gene in virulence. All of the
experimental infection assays indicated that the virulence of the ATCC 17978 was
significantly reduced when this gene was inactivated. Finally, we discovered that the
A1S_0114 gene was involved in the production of a small lipopeptide-like compound
herein referred to as acinetin 505 (Ac-505). Ac-505 was isolated from ATCC 17978
spent media and its chemical structure was interpreted by mass spectrometry. Overall,
our observations provide novel information on the role of the A1S_0114 gene in A.
baumannii’s pathobiology and lay the foundation for future work to determine the
mechanisms by which Ac-505, or possibly an Ac-505 precursor, could execute critical
functions as a secondary metaboliteS
Epigenetic loss of RNA‑methyltransferase NSUN5 in glioma targets ribosomes to drive stress adaptive translational program
Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. We also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S rRNA that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme NQO1. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease
Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA
Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. clinicaltrials.gov identifier:02869074
An RNAi in silico approach to find an optimal shRNA cocktail against HIV-1
<p>Abstract</p> <p>Background</p> <p>HIV-1 can be inhibited by RNA interference <it>in vitro </it>through the expression of short hairpin RNAs (shRNAs) that target conserved genome sequences. <it>In silico </it>shRNA design for HIV has lacked a detailed study of virus variability constituting a possible breaking point in a clinical setting. We designed shRNAs against HIV-1 considering the variability observed in naïve and drug-resistant isolates available at public databases.</p> <p>Methods</p> <p>A Bioperl-based algorithm was developed to automatically scan multiple sequence alignments of HIV, while evaluating the possibility of identifying dominant and subdominant viral variants that could be used as efficient silencing molecules. Student t-test and Bonferroni Dunn correction test were used to assess statistical significance of our findings.</p> <p>Results</p> <p>Our <it>in silico </it>approach identified the most common viral variants within highly conserved genome regions, with a calculated free energy of ≥ -6.6 kcal/mol. This is crucial for strand loading to RISC complex and for a predicted silencing efficiency score, which could be used in combination for achieving over 90% silencing. Resistant and naïve isolate variability revealed that the most frequent shRNA per region targets a maximum of 85% of viral sequences. Adding more divergent sequences maintained this percentage. Specific sequence features that have been found to be related with higher silencing efficiency were hardly accomplished in conserved regions, even when lower entropy values correlated with better scores. We identified a conserved region among most HIV-1 genomes, which meets as many sequence features for efficient silencing.</p> <p>Conclusions</p> <p>HIV-1 variability is an obstacle to achieving absolute silencing using shRNAs designed against a consensus sequence, mainly because there are many functional viral variants. Our shRNA cocktail could be truly effective at silencing dominant and subdominant naïve viral variants. Additionally, resistant isolates might be targeted under specific antiretroviral selective pressure, but in both cases these should be tested exhaustively prior to clinical use.</p
Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality
CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative
Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research
CIBERER: Spanish national network for research on rare diseases: A highly productive collaborative initiative
13 páginas,1 figura, 3 tablas, 1 apéndice. Se extraen los autores pertenecientes a The CIBERER network que trabajan en Centros del CSIC del Appendix ACIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research.This study has been funded by Instituto de Salud Carlos III (ISCIII) and Spanish Ministry of Science and InnovationPeer reviewe
MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV
Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe
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