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Foley P.L.,Skirball Institute | Hsieh P.-K.,Skirball Institute | Luciano D.J.,Skirball Institute | Belasco J.G.,Skirball Institute | Belasco J.G.,New York University
Journal of Biological Chemistry | Year: 2015

Bacterial RNA degradation often begins with conversion of the 5″-terminal triphosphate to a monophosphate by the RNA pyrophosphohydrolase RppH, an event that triggers rapid ribonucleolytic attack. Besides its role as the master regulator of 5″-end-dependentmRNAdecay, RppH is important for the ability of pathogenic bacteria to invade host cells, yet little is known about how it chooses its targets. Here, we show that Escherichia coli RppH (EcRppH) requires at least two unpaired nucleotides at the RNA 5″ end and prefers three or more such nucleotides. It can tolerate any nucleotide at the first three positions but has a modest preference forAat the 5″ terminus and eitheraGorAat the second position. Mutational analysis has identified EcRppH residues crucial for substrate recognition or catalysis. The promiscuity of EcRppH differentiates it from its Bacillus subtilis counterpart, which has a strict RNA sequence requirement. EcRppH orthologs likely to share its relaxed sequence specificity are widespread in all classes of Proteobacteria, except Deltaproteobacteria, and in flowering plants. By contrast, the phylogenetic range of recognizable B. subtilis RppH orthologs appears to be restricted to the order Bacillales. These findings help to explain the selective influence of RppH on bacterial mRNA decay and show that RppH-dependent degradation has diversified significantly during the course of evolution. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A. Source


Tucker A.M.,MedStar Sports Medicine | Lincoln A.E.,MedStar Research Institute | Vogel R.A.,Cardiology Section 11B | Black H.R.,Skirball Institute | And 4 more authors.
Journal of the American Society of Hypertension | Year: 2015

Previous findings suggest that professional American football players have higher blood pressures (BP) and a higher prevalence of pre-hypertension and hypertension than the general population. We sought to determine whether race is associated with differences in BP and prevalence of pre-hypertension and hypertension among a large sample of professional football players. BP was measured at 2009 team mini-camps for 1484 black (n = 1007) and white (n = 477) players from 27 National Football League (NFL) teams. Players were categorized into three position groups based on body mass index (BMI). There was no racial difference in mean systolic or diastolic BP in any of the three position groups. There were no racial differences in prevalence of hypertension (99 [9.8%] black players vs. 39 [8.2%] white players; P =.353) or pre-hypertension (557 [55.3%] black players vs. 264 [55.3%] white players; P = 1.0). Contrary to findings in the general population, BP and prevalence of pre-hypertension/hypertension did not vary with race in a large population of active NFL players. © 2015 American Society of Hypertension. All rights reserved. Source


Oyallon J.,UK National Institute for Medical Research | Oyallon J.,Skirball Institute | Apitz H.,UK National Institute for Medical Research | Miguel-Aliaga I.,University of Cambridge | And 4 more authors.
Developmental Biology | Year: 2012

During the development of locomotion circuits it is essential that motoneurons with distinct subtype identities select the correct trajectories and target muscles. In vertebrates, the generation of motoneurons and myelinating glia depends on Olig2, one of the five Olig family bHLH transcription factors. We investigated the so far unknown function of the single Drosophila homolog Oli. Combining behavioral and genetic approaches, we demonstrate that oli is not required for gliogenesis, but plays pivotal roles in regulating larval and adult locomotion, and axon pathfinding and targeting of embryonic motoneurons. In the embryonic nervous system, Oli is primarily expressed in postmitotic progeny, and in particular, in distinct ventral motoneuron subtypes. oli mediates axonal trajectory selection of these motoneurons within the ventral nerve cord and targeting to specific muscles. Genetic interaction assays suggest that oli acts as part of a conserved transcription factor ensemble including Lim3, Islet and Hb9. Moreover, oli is expressed in postembryonic leg-innervating motoneuron lineages and required in glutamatergic neurons for walking. Finally, over-expression of vertebrate Olig2 partially rescues the walking defects of oli-deficient flies. Thus, our findings reveal a remarkably conserved role of Drosophila Oli and vertebrate family members in regulating motoneuron development, while the steps that require their function differ in detail. © 2012. Source


Anastasia A.,New York Medical College | Deinhardt K.,Skirball Institute | Deinhardt K.,University of Southampton | Wang S.,New York Medical College | And 8 more authors.
PLoS ONE | Year: 2014

Pericyte and vascular smooth muscle cell (SMC) recruitment to the developing vasculature is an important step in blood vessel maturation. Brain-derived neurotrophic factor (BDNF), expressed by endothelial cells, activates the receptor tyrosine kinase TrkB to stabilize the cardiac microvasculature in the perinatal period. However, the effects of the BDNF/TrkB signaling on pericytes/SMCs and the mechanisms downstream of TrkB that promote vessel maturation are unknown. To confirm the involvement of TrkB in vessel maturation, we evaluated TrkB deficient (trkb-/-) embryos and observed severe cardiac vascular abnormalities leading to lethality in late gestation to early prenatal life. Ultrastructural analysis demonstrates that trkb-/- embryos exhibit defects in endothelial cell integrity and perivascular edema. As TrkB is selectively expressed by pericytes and SMCs in the developing cardiac vasculature, we generated mice deficient in TrkB in these cells. Mice with TrkB deficiency in perivascular cells exhibit reduced pericyte/SMC coverage of the cardiac microvasculature, abnormal endothelial cell ultrastructure, and increased vascular permeability. To dissect biological actions and the signaling pathways downstream of TrkB in pericytes/SMCs, human umbilical SMCs were treated with BDNF. This induced membranous protrusions and cell migration, events dependent on myosin light chain phosphorylation. Moreover, inhibition of Rho GTPase and the Rho-associated protein kinase (ROCK) prevented membrane protrusion and myosin light chain phosphorylation in response to BDNF. These results suggest an important role for BDNF in regulating migration of TrkB-expressing pericytes/SMCs to promote cardiac blood vessel ensheathment and functional integrity during development. © 2014 Anastasia et al. Source


Ravel J.,University of Maryland Baltimore County | Blaser M.J.,New York University | Braun J.,University of California at Los Angeles | Brown E.,University of British Columbia | And 29 more authors.
Microbiome | Year: 2014

A conference entitled 'Human microbiome science: Vision for the future' was organized in Bethesda, MD from July 24 to 26, 2013. The event brought together experts in the field of human microbiome research and aimed at providing a comprehensive overview of the state of microbiome research, but more importantly to identify and discuss gaps, challenges and opportunities in this nascent field. This report summarizes the presentations but also describes what is needed for human microbiome research to move forward and deliver medical translational applications. © 2014 Ravel et al. Source

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