Multi-Modal Proteomic Analysis of Retinal Protein Expression Alterations in a Rat Model of Diabetic Retinopathy

As a leading cause of adult blindness, diabetic retinopathy is a prevalent and profound complication of diabetes. We have previously reported duration-dependent changes in retinal vascular permeability, apoptosis, and mRNA expression with diabetes in a rat model system. The aim of this study was to identify retinal proteomic alterations associated with functional dysregulation of the diabetic retina to better understand diabetic retinopathy pathogenesis and that could be used as surrogate endpoints in preclinical drug testing studies.A multi-modal proteomic approach of antibody (Luminex)-, electrophoresis (DIGE)-, and LC-MS (iTRAQ)-based quantitation methods was used to maximize coverage of the retinal proteome. Transcriptomic profiling through microarray analysis was included to identify additional targets and assess potential regulation of protein expression changes at the mRNA level. The proteomic approaches proved complementary, with limited overlap in proteomic coverage. Alterations in pro-inflammatory, signaling and crystallin family proteins were confirmed by orthogonal methods in multiple independent animal cohorts. In an independent experiment, insulin replacement therapy normalized the expression of some proteins (Dbi, Anxa5) while other proteins (Cp, Cryba3, Lgals3, Stat3) were only partially normalized and Fgf2 and Crybb2 expression remained elevated.These results expand the understanding of the changes in retinal protein expression occurring with diabetes and their responsiveness to normalization of blood glucose through insulin therapy. These proteins, especially those not normalized by insulin therapy, may also be useful in preclinical drug development studies

Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management

Atrioventricular block is classified as congeni- tal if diagnosed in utero, at birth, or within the first month of life. The pathophysiological process is believed to be due to immune-mediated injury of the conduction system, which occurs as a result of transplacental pas- sage of maternal anti-SSA/Ro-SSB/La antibodies. Childhood atrioventricular block is therefore diagnosed between the first month and the 18th year of life. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited progressive car- diac conduction disorders. Indications and techniques of cardiac pacing have also evolved to allow safe perma- nent cardiac pacing in almost all patients, including those with structural heart abnormalities

The modular systems biology approach to investigate the control of apoptosis in Alzheimer's disease neurodegeneration

Apoptosis is a programmed cell death that plays a critical role during the development of the nervous system and in many chronic neurodegenerative diseases, including Alzheimer's disease (AD). This pathology, characterized by a progressive degeneration of cholinergic function resulting in a remarkable cognitive decline, is the most common form of dementia with high social and economic impact. Current therapies of AD are only symptomatic, therefore the need to elucidate the mechanisms underlying the onset and progression of the disease is surely needed in order to develop effective pharmacological therapies. Because of its pivotal role in neuronal cell death, apoptosis has been considered one of the most appealing therapeutic targets, however, due to the complexity of the molecular mechanisms involving the various triggering events and the many signaling cascades leading to cell death, a comprehensive understanding of this process is still lacking. Modular systems biology is a very effective strategy in organizing information about complex biological processes and deriving modular and mathematical models that greatly simplify the identification of key steps of a given process. This review aims at describing the main steps underlying the strategy of modular systems biology and briefly summarizes how this approach has been successfully applied for cell cycle studies. Moreover, after giving an overview of the many molecular mechanisms underlying apoptosis in AD, we present both a modular and a molecular model of neuronal apoptosis that suggest new insights on neuroprotection for this disease

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Riesgo cardiovascular en estudiantes de medicina del municipio Puerto Padre de Las Tunas

Introduction: cardiovascular diseases are the first cause of death in Cuba; as a result, the identification of cardiovascular risks from early ages allows the implementation of health promotion and prevention strategies to reduce their impact in the futureObjective: to identify the cardiovascular risk in medical students in Puerto Padre Municipality, Las Tunas province.Methods: an observational, descriptive and cross-sectional study was conducted. The target group included 545 medical students, 237 of whom were selected by means of a simple random sample. The body mass index and waist-hip ratio were studied. Descriptive statistics was applied.Results: the predominant age group was 18-21 years old (50,2 %). The 51,47 % of the students presented a high waist-hip ratio, 54,02 % a high abdominal circumference, 52,74 % a high body mass index, and in all groups 35,44 % presented blood pressure figures lower than 120/80 mmHg; 39 % had a cardiovascular risk.Conclusions: low percentages of cardiovascular risk were identified in medical students from Puerto Padre Municipality, Las Tunas province, determined by high values of waist-hip index, body mass index and abdominal circumference.Introducción: las enfermedades cardiovasculares constituyen la primera causa de mortalidad en Cuba; por lo cual la identificación de riesgos cardiovasculares desde edades tempranas permite implementar estrategias de promoción y prevención de salud para disminuir su impacto en el futuroObjetivo: identificar el riesgo cardiovascular en estudiantes de medicina del municipio Puerto Padre de Las Tunas.Método: se realizó un estudio observacional, descriptivo y transversal. El universo estuvo constituido por 545 estudiantes de medicina, seleccionándose 237 mediante un muestreo aleatorio simple. Se estudió el índice de masa corporal, la circunferencia abdominal y la índice cintura cadera. Se empleó estadística descriptiva.Resultados: se encontró predominio del grupo etario de 18 a 21 años (50,2 %). El 51,47 % de los estudiantes presentó un índice cintura-cadera alto, el 54,02 % una circunferencia abdominal alta, el 52,74 % un índice de masa corporal alta, así como en todos los grupos el 35,44 % presentó cifras de tensión arterial inferiores a 120/80 mmHg. El 39 % presentó riesgo cardiovascular.Conclusiones: se identificaron bajos porcientos de riesgo cardiovascular en los estudiantes de medicina del municipio Puerto Padre de Las Tunas, determinado por altos valores los índice cintura-cadera, índice de masa corporal y circunferencia abdominal

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Not AvailableThe Near Infrared Reflectance Spectroscopy (NIRS), a non-destructive and robust tool was calibrated for rapid estimation of moisture content (MC) in whole groundnut kernels. A set of 8 groundnut genotypes were soaked overnight, followed by drying in hot air oven at 60⁰ C. Data were recorded after every 2 hrs drying using a moisture meter followed by scanning in NIRS, till constant MC was obtained. NIR absorption spectral data from 400 to 2500 nm in 2 mm intervals were collected. Modified partial least squares (MPLS) regression was applied to scatter-corrected spectra (SNV and detrend). Calibration equation with high values for the coefficient of determination (R2), the coefficient of determination for cross-validation (1-VR) and low values for the standard error of calibration or standard error of crossvalidation were estimated. Among the various models employed, model 2 with pretreatment 2,4,4,1 was best with an R2 of 0.99 in the calibration set, 1-VR value of 0.99 in the cross-validation set, lowest values for the standard error of calibration (0.33) and standard error of cross-validation (0.55). Calibration equations for moisture content showed a close relationship between NIRS predicted and lab values in this model. Thus, the selected model can act as the best models for prediction of moisture content in groundnut kernels with high accuracy. This study shows the potential of NIRS to predict the moisture content of groundnut seeds as a routine method in breeding programs, processing industries and for farmer’s advice.Not Availabl