37 research outputs found
Genome-wide DNA methylation analysis of transient neonatal diabetes type 1 patients with mutations in ZFP57
Ventricular repolarization dispersion during ischemia course measured by temporal and spatial electrocardiographic parameters
In this work we studied the evolution of increased ventricular repolarization dispersion (VRD) in the ECG during ischemia induced by Percutaneous Transluminal Coronary Angioplasty (PTCA). T-wave duration is measured by an automatic delineator and proposed as a index to quantify increased VRD. Moreover, spatial complexity of repolarization is measured by Singular Value Decomposition (SVD) related indexes. Results showed a statistically significant widening of T-wave peak-to-end during PTCA procedure in RCA and LAD occluded patients. Besides, a statistically significant dynamic change of the dipolar components was observed during PTCA in RCA, LAD and LCx occluded patients. On the other hand, the relative energy of non-dipolar components did not change during the time course of increased VRD evolution.Fil: Arini, Pedro David. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Argentino de Matemática Alberto Calderón; Argentina. Universidad de Buenos Aires. Facultad de IngenierÃa; ArgentinaFil: Baglivo, F. H.. Universidad de Buenos Aires. Facultad de IngenierÃa; ArgentinaFil: Martinez, J. P.. Universidad de Zaragoza; EspañaFil: Laguna, P.. Universidad de Zaragoza; EspañaXXXV International Conference on Computers in CardiologyBolognaItaliaIEEE Computer Societ
Two rare PROX1 variants in patients with lymphedema
Background: The PROX1 gene is specifically expressed in a subpopulation of endothelial cells that, by budding and sprouting, give rise to the lymphatic system. It also plays a critical role in neurogenesis and during development of many organs, such as the eye lens, liver, and pancreas. Methods: We used next-generation sequencing (NGS) to sequence the DNA of a cohort of 246 Italian patients with lymphatic malformations. We first investigated 29 known disease-causing genes: 235 of 246 patients tested negative and were then retested for a group of candidate genes, including PROX1, selected from a database of mouse models. The aim of the study was to define these patients’ genotypes and explore the role of the candidate gene PROX1 in lymphedema. Results: Two of 235 probands were found to carry rare heterozygous missense variants in PROX1. In silico analysis of these variants—p.(Leu590His) and p.(Gly106Asp)—indicates that the overall protein structure was altered by changes in interactions between nearby residues, leading to functional protein defects. Conclusions: Our results suggest that PROX1 is a new candidate gene for predisposition to lymphedema
Polygenic burden associated to oligodendrocyte precursor cells and radial glia influences the hippocampal volume changes induced by aerobic exercise in schizophrenia patients
Hippocampal volume decrease is a structural hallmark of schizophrenia (SCZ), and convergent evidence from postmortem and imaging studies suggests that it may be explained by changes in the cytoarchitecture of the cornu ammonis 4 (CA4) and dentate gyrus (DG) subfields. Increasing evidence indicates that aerobic exercise increases hippocampal volume in CA subfields and improves cognition in SCZ patients. Previous studies showed that the effects of exercise on the hippocampus might be connected to the polygenic burden of SCZ risk variants. However, little is known about cell type-specific genetic contributions to these structural changes. In this secondary analysis, we evaluated the modulatory role of cell type-specific SCZ polygenic risk scores (PRS) on volume changes in the CA1, CA2/3, and CA4/DG subfields over time. We studied 20 multi-episode SCZ patients and 23 healthy controls who performed aerobic exercise, and 21 multi-episode SCZ patients allocated to a control intervention (table soccer) for 3 months. Magnetic resonance imaging-based assessments were performed with FreeSurfer at baseline and after 3 months. The analyses showed that the polygenic burden associated with oligodendrocyte precursor cells (OPC) and radial glia (RG) significantly influenced the volume changes between baseline and 3 months in the CA4/DG subfield in SCZ patients performing aerobic exercise. A higher OPC- or RG-associated genetic risk burden was associated with a less pronounced volume increase or even a decrease in CA4/DG during the exercise intervention. We hypothesize that SCZ cell type-specific polygenic risk modulates the aerobic exercise-induced neuroplastic processes in the hippocampus
Effects of Ramipril and Rosiglitazone on Cardiovascular and Renal Outcomes in People With Impaired Glucose Tolerance or Impaired Fasting Glucose : Results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial
OBJECTIVE—Impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) are risk factors for diabetes, cardiovascular disease (CVD), and kidney disease. We determined the effects of ramipril and rosiglitazone on combined and individual CVD and renal outcomes in people with IGT and/or IFG in the Diabetes REduction Assessment With ramipril and rosiglitazone Medication (DREAM) trial.
RESEARCH DESIGN AND METHODS—A total of 5,269 people aged ≥30 years, with IGT and/or IFG without known CVD or renal insufficiency, were randomized to 15 mg/day ramipril versus placebo and 8 mg/day rosiglitazone versus placebo. A composite cardiorenal outcome and its CVD and renal components were assessed during the 3-year follow-up.
RESULTS—Compared with placebo, neither ramipril (15.7% [412 of 2,623] vs. 16.0% [424 of 2,646]; hazard ratio [HR] 0.98 [95% CI 0.84–1.13]; P = 0.75) nor rosiglitazone (15.0% [394 of 2,635] vs. 16.8% [442 of 2,634]; 0.87 [0.75–1.01]; P = 0.07) reduced the risk of the cardiorenal composite outcome. Ramipril had no impact on the CVD and renal components. Rosiglitazone increased heart failure (0.53 vs. 0.08%; HR 7.04 [95% CI 1.60–31.0]; P = 0.01) but reduced the risk of the renal component (0.80 [0.68–0.93]; P = 0.005); prevention of diabetes was independently associated with prevention of the renal component (P < 0.001).
CONCLUSIONS—Ramipril did not alter the cardiorenal outcome or its components. Rosiglitazone, which reduced diabetes, also reduced the development of renal disease but not the cardiorenal outcome and increased the risk of heart failure.The DREAM Trial Investigator
The stem cell transcription factor ZFP57 induces IGF2 expression to promote anchorage-independent growth in cancer cells
Several common biological properties between cancer cells and embryonic stem (ES) cells suggest the possibility that some genes expressed in ES cells might have important roles in cancer cell growth. The transcription factor ZFP57 is expressed in self-renewing ES cells and its expression level decreases during ES cell differentiation. This study showed that ZFP57 is involved in the anchorage-independent growth of human fibrosarcoma HT1080 cells in soft agar. ZFP57 overexpression enhanced, whereas knockdown suppressed, HT1080 tumor formation in nude mice. Furthermore, ZFP57 regulates the expression of insulin-like growth factor 2 (IGF2), which has a critical role in ZFP57-induced anchorage-independent growth. ZFP57 also promotes anchorage-independent growth in ES cells and immortal fibroblasts. Finally, immunohistochemical analysis revealed that ZFP57 is overexpressed in human cancer clinical specimens. Taken together, these results suggest that the ES-specific transcription factor ZFP57 is a novel oncogene.Oncogene advance online publication, 27 January 2014; doi:10.1038/onc.2013.599
First Results of the Regional Earthquake Likelihood Models Experiment
The ability to successfully predict the future behavior of a system is a strong indication that the system is well understood. Certainly many details of the earthquake system remain obscure, but several hypotheses related to earthquake occurrence and seismic hazard have been proffered, and predicting earthquake behavior is a worthy goal and demanded by society. Along these lines, one of the primary objectives of the Regional Earthquake Likelihood Models (RELM) working group was to formalize earthquake occurrence hypotheses in the form of prospective earthquake rate forecasts in California. RELM members, working in small research groups, developed more than a dozen 5-year forecasts; they also outlined a performance evaluation method and provided a conceptual description of a Testing Center in which to perform predictability experiments. Subsequently, researchers working within the Collaboratory for the Study of Earthquake Predictability (CSEP) have begun implementing Testing Centers in different locations worldwide, and the RELM predictability experiment—a truly prospective earthquake prediction effort—is underway within the U.S. branch of CSEP. The experiment, designed to compare time-invariant 5-year earthquake rate forecasts, is now approximately halfway to its completion. In this paper, we describe the models under evaluation and present, for the first time, preliminary results of this unique experiment. While these results are preliminary—the forecasts were meant for an application of 5 years—we find interesting results: most of the models are consistent with the observation and one model forecasts the distribution of earthquakes best. We discuss the observed sample of target earthquakes in the context of historical seismicity within the testing region, highlight potential pitfalls of the current tests, and suggest plans for future revisions to experiments such as this one.ISSN:0033-4553ISSN:1420-9136ISSN:1557-736
Overview of the Rosetta Fly-by of 21-Lutetia as Observed by the OSIRIS Camera System
On July 10th 2010 the ESA Rosetta spacecraft flew past the asteroid 21-Lutetia on the way to it's 2014 rendezvous with Comet 67P/Churyumov-Gerasimenko. The closest distance to the asteroid was 3160 km. During the fly-by the scientific camera system OSIRIS observed the asteroid. The resolved observations started 9hours 30min before the closest approach and finished 18 min after the closest approach. During this period the camera system acquired 234 images with the Narrow Angle Camera (NAC) and 228 images with the Wide Angle Camera (WAC). The highest resolution obtained on the surface was 59 m/pixel.
21-Lutetia is the largest asteroid yet visited by a spacecraft. The surface shows a highly impacted surface with the largest impact craters reaching 60km. The surface also shows evidence of thick regolith layers and grooves as previously seen on the moon Phobos. This paper will give an overview of the observations made by the OSIRIS cameras