Terminal neuron localization to the upper cortical plate is controlled by the transcription factor NEUROD2

Excitatory neurons of the mammalian cerebral cortex are organized into six functional layers characterized by unique patterns of connectivity, as well as distinctive physiological and morphological properties. Cortical layers appear after a highly regulated migration process in which cells move from the deeper, proliferative zone toward the superficial layers. Importantly, defects in this radial migration process have been implicated in neurodevelopmental and psychiatric diseases. Here we report that during the final stages of migration, transcription factor Neurogenic Differentiation 2 (Neurod2) contributes to terminal cellular localization within the cortical plate. In mice, in utero knockdown of Neurod2 resulted in reduced numbers of neurons localized to the uppermost region of the developing cortex, also termed the primitive cortical zone. Our ChIP-Seq and RNA-Seq analyses of genes regulated by NEUROD2 in the developing cortex identified a number of key target genes with known roles in Reelin signaling, a critical regulator of neuronal migration. Our focused analysis of regulation of the Reln gene, encoding the extracellular ligand REELIN, uncovered NEUROD2 binding to conserved E-box elements in multiple introns. Furthermore, we demonstrate that knockdown of NEUROD2 in primary cortical neurons resulted in a strong increase in Reln gene expression at the mRNA level, as well as a slight upregulation at the protein level. These data reveal a new role for NEUROD2 during the late stages of neuronal migration, and our analysis of its genomic targets offers new genes with potential roles in cortical lamination.Peer reviewe

The effects of atorvastatin therapy on endothelıal function in patients with coronary artery disease

<p>Abstract</p> <p>Background</p> <p>Statins improve the endothelial function in patients with coronary artery disease (CAD). However, they contribute to the substantial decrease in coronary heart disease by reducing plasma cholesterol levels. They also, reduce oxidative stress, stabilize the atherosclerotic plaque and inhibit inflammatory response. These functions of statins have been briefly described as pleiotropic effects. The aim of our study was to evaluate the effect of atorvastatin therapy on endothelial functions in patients with CAD.</p> <p>Methods</p> <p>Fourty-nine patients (40 men, 9 women, mean age 59 +/- 11 years) with diagnosed CAD were selected as the study group. The patients were given 10 mg/day atorvastatin for 12 weeks. If the target cholesterol levels has not been achieved 6 weeks after the treatment, then the daily atorvastatin dosage has been increased. The endothelial function was evaluated by flow mediated dilatation (FMD) of the brachial artery.</p> <p>Results</p> <p>It has been figured out that 12 weeks later, atorvastatin caused a statistically significant decrease in the plasma levels of LDL-cholesterol and total cholesterol (p < 0,0001). Meanwhile, it was determined that the FMD got statistically significant improved 12 weeks after the atorvastatin therapy (8,1%–4,2%, p < 0,001). However there was no statistically significant change in non-endothelium dependent dilatation (NID).</p> <p>Conclusion</p> <p>Endothelium derived vasodilatation (EBD), which was non-invasively detected via brachial artery ultrasonography, had statistically significant improvment within 12 weeks of atorvastatin therapy whereas non-endothelium dependent dilatation (NID) had no change.</p

Verifying integer programming results

Software for mixed-integer linear programming can return incorrect results for a number of reasons, one being the use of inexact floating-point arithmetic. Even solvers that employ exact arithmetic may suffer from programming or algorithmic errors, motivating the desire for a way to produce independently verifiable certificates of claimed results. Due to the complex nature of state-of-the-art MIP solution algorithms, the ideal form of such a certificate is not entirely clear. This paper proposes such a certificate format designed with simplicity in mind, which is composed of a list of statements that can be sequentially verified using a limited number of inference rules. We present a supplementary verification tool for compressing and checking these certificates independently of how they were created. We report computational results on a selection of MIP instances from the literature. To this end, we have extended the exact rational version of the MIP solver SCIP to produce such certificates

Effect of quinapril on the attenuated heart rate recovery of type 2 diabetic subjects without known coronary artery disease

Background: Heart rate (HR) recovery at I min is a measure of the vagal reactivation that occurs after cessation of exercise. Despite ample evidence about the association of attenuated HR recovery with increased mortality, pharmacologic modification of this predictor has not been shown. On the other hand, angiotensin-converting enzyme (ACE) inhibitors are known to have vagomimetic activity

The safety of low-molecular weight heparins for the prevention of thromboembolic events after cardioversion of atrial fibrillation

Transesophageal echocardiography (TEE) guided early cardioversion (CV) in conjunction with short-term anticoagulation has been shown to be safe, and an alternative to prolonged conventional anticoagulation therapy. Recently, low molecular weight heparins (LMWHs) have been used successfully as an alternative to standard heparin therapy obviating the need for hospitalization and APTT monitoring. The aim of this study was to determine the feasibility and safety of TEE guided early cardioversion in conjunction with short-term LMWH use in patients with nonvalvular atrial fibrillation (NVAF)