The pluripotent mammalian epiblast undergoes unusually fast cell proliferation. This rapid growth is expected to generate a high transcriptional demand, but the underlying mechanisms remain unknown. We show here that the chromatin remodeler Chd1 is required for transcriptional output and development of the mouse epiblast. Chd1 embryos exhibit proliferation defects and increased apoptosis, are s...

Relapses and disease exacerbations are vexing features of multiple sclerosis. Osteopontin (Opn), which is expressed in multiple sclerosis lesions, is increased in patients’ plasma during relapses. Here, in models of multiple sclerosis including relapsing, progressive and multifocal experimental autoimmune encephalomyelitis (EAE), Opn triggered recurrent relapses, promoted worsening paralysis an...

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a critical modulator of cholesterol homeostasis. Whereas PCSK9 gain-of-function (GOF) mutations are associated with autosomal dominant hypercholesterolemia (ADH) and premature atherosclerosis, PCSK9 loss-of-function (LOF) mutations have a cardio-protective effect and in some cases can lead to familial hypobetalipoproteinemia (FHBL). Howev...

ht D ow nladed from Ceramide, the central molecule of sphingolipid metabolism, is an important bioactive molecule that participates in various cellular regulatory events and that has been implicated in disease. Deciphering ceramide signaling is challenging because multiple ceramide species exist, and many of them may have distinct functions. We applied systems biology and molecular approaches t...

Due to the pivotal role played by human serum albumin (HSA) in the transport and cytotoxicity of titanocene complexes, a docking study has been performed on a selected set of titanocene complexes to aid in the current understanding of the potential mode of action of these titanocenes upon binding HSA. Analysis of the docking results has revealed potential binding at the known drug binding sites...

The Heteroptera have holocentric chromosomes with kinetic activity restricted to the end of chromosomes.The first meiotic division is reductional for the autosomes and equational for the sexual. Only a few species of this suborder have been analyzed. In this study, we observed the morphologies of the testes of the Heteroptera species Belostoma anurum (Herrich-Schäffer, 1948), Belostoma micantul...

To strengthen Haiti’s primary health care (PHC) system, the country first piloted performance-based financing (PBF) in 1999 and subsequently expanded the approach to most internationally funded non-government organizations. PBF complements support (training and technical assistance). This study evaluates (a) the separate impact of PBF and international support on PHC’s service delivery; (b) the...

The selective degeneration of dopaminergic (DA) midbrain neurons in the substantia nigra (SN) is a hallmark of Parkinson disease. DA neurons in the neighboring ventral tegmental area (VTA) are significantly less affected. The mechanisms for this differential vulnerability of DA neurons are unknown. We identified selective activation of ATP-sensitive potassium (K-ATP) channels as a potential mec...

Social phobia (SP) has been associated with amygdala hyperreactivity to fear-relevant stimuli. However, little is known about the neural basis of SP individuals capacity to downregulate their responses to such stimuli and how such regulation varies as a function of comorbid depression and anxiety. We completed an functional magnetic resonance imaging (fMRI) study wherein SP participants without...

Tissue damage and repair involves the complex interactions between different populations of cells and their coordinated cell movement (Nathan, 2006; Silva, 2010; Sindrilaru and Scharffetter-Kochanek, 2013; Abtin et al., 2014). The mechanisms through which these interactions are orchestrated to mediate resolution of inflammation, a key step in tissue repair, remain largely unknown (Nathan and Di...