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Work 1-7 of 7

Sorted by relevance

Article

Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent

by Adrienne King; David J. Polhemus; Shashi Bhushan; Hiroyuki Otsuka; Kazuhisa Kondo; Chad K. Nicholson; Jessica M. Bradley; Kazi N. Islam; John Calvert; Ya-Xiong Tao; Tammy R. Dugas; Eric E. Kelley; John W. Elrod; Paul L. Huang; Rui Wang; David J. Lefer

2014

Subjects
  • Health Sciences, Medicine and Surgery
  • Health Sciences, Pharmacology
  • File Download
  • View Abstract

Abstract:Close

Previous studies have demonstrated that hydrogen sulfide (H 2 S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO). H 2 S therapy also has been shown to augment NO bioavailability and signaling. The purpose of this study was to investigate the impact of H 2 S deficiency on endothelial NO synthase (eNOS) function, NO production, and ischemia/reperfusion (I/R) injury. We found that mice lacking the H 2 S-producing enzyme cystathionine γ-lyase (CSE) exhibit elevated oxidative stress, dysfunctional eNOS, diminished NO levels, and exacerbated myocardial and hepatic I/R injury. In CSE KO mice, acute H 2 S therapy restored eNOS function and NO bioavailability and attenuated I/R injury. In addition, we found that H 2 S therapy fails to protect against I/R in eNOS phosphomutant mice (S1179A). Our results suggest that H 2 S-mediated cytoprotective signaling in the setting of I/R injury is dependent in large part on eNOS activation and NO generation.

Article

Nematode sperm maturation triggered by protease involves sperm-secreted serine protease inhibitor (Serpin)

by Yanmei Zhao; Wei Sun; Pan Zhang; Hao Chi; Mei-Jun Zhang; Chun-Qing Song; Xuan Ma; Yunlong Shang; Bin Wang; Youqiao Hu; Zhiqi Hao; Andreas F. Huehmer; Fanxia Meng; Steven L'Hernault; Si-Min He; Meng-Qiu Dong; Long Miao

2012

Subjects
  • Biology, General
  • File Download
  • View Abstract

Abstract:Close

Spermiogenesis is a series of poorly understood morphological, physiological and biochemical processes that occur during the transition of immotile spermatids into motile, fertilization-competent spermatozoa. Here, we identified a Serpin (serine protease inhibitor) family protein (As-SRP-1) that is secreted from spermatids during nematode Ascaris suum spermiogenesis (also called sperm activation) and we showed that As-SRP-1 has two major functions. First, As-SRP-1 functions in cis to supportmajor spermprotein (MSP)- based cytoskeletal assembly in the spermatid that releases it, thereby facilitating sperm motility acquisition. Second, As-SRP-1 released froman activated sperminhibits, in trans, the activation of surrounding spermatids by inhibiting vas deferens-derived As-TRY-5, a trypsin- like serine protease necessary for sperm activation. Because vesicular exocytosis is necessary to create fertilization-competent sperm in many animal species, components released during this process might be more important modulators of the physiology and behavior of surrounding sperm than was previously appreciated.

Article

The Anticipated Severity of a "1918-Like" Influenza Pandemic in Contemporary Populations: The Contribution of Antibacterial Interventions

by Yu-Wen Chien; Bruce Levin; Keith Klugman

2012

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Public Health
  • File Download
  • View Abstract

Abstract:Close

Recent studies have shown that most of deaths in the 1918 influenza pandemic were caused by secondary bacterial infections, primarily pneumococcal pneumonia. Given the availability of antibiotics and pneumococcal vaccination, how will contemporary populations fare when they are next confronted with pandemic influenza due to a virus with the transmissibility and virulence of that of 1918? To address this question we use a mathematical model and computer simulations. Our model considers the epidemiology of both the influenza virus and pneumonia-causing bacteria and allows for co-infection by these two agents as well as antibiotic treatment, prophylaxis and pneumococcal vaccination. For our simulations we use influenza transmission and virulence parameters estimated from 1918 pandemic data. We explore the anticipated rates of secondary pneumococcal pneumonia and death in populations with different prevalence of pneumococcal carriage and contributions of antibiotic prophylaxis, treatment, and vaccination to these rates. Our analysis predicts that in countries with lower prevalence of pneumococcal carriage and access to antibiotics and pneumococcal conjugate vaccines, there would substantially fewer deaths due to pneumonia in contemporary populations confronted with a 1918-like virus than that observed in the 1918. Our results also predict that if the pneumococcal carriage prevalence is less than 40%, the positive effects of antibiotic prophylaxis and treatment would be manifest primarily at of level of individuals. These antibiotic interventions would have little effect on the incidence of pneumonia in the population at large. We conclude with the recommendation that pandemic preparedness plans should consider co-infection with and the prevalence of carriage of pneumococci and other bacteria responsible for pneumonia. While antibiotics and vaccines will certainly reduce the rate of individual mortality, the factor contributing most to the relatively lower anticipated lethality of a pandemic with a 1918-like influenza virus in contemporary population is the lower prevalence of pneumococcal carriage.

Article

Effector CD8 T cells dedifferentiate into long-lived memory cells

by Ben Youngblood; J. Scott Hale; Haydn Thomas Kissick; Eunseon Ahn; Xiaojin Xu; Andreas M. Wieland; Koichi Araki; Erin E. West; Hazem E. Ghoneim; Yiping Fan; Pranay Dogra; Carl W. Davis; Bogumila T. Konieczny; Rustom Antia; Xiaodong Cheng; Rafi Ahmed

2017

Subjects
  • Health Sciences, Immunology
  • Biology, Microbiology
  • File Download
  • View Abstract

Abstract:Close

Memory CD8 T cells that circulate in the blood and are present in lymphoid organs are an essential component of long-lived T cell immunity. These memory CD8 T cells remain poised to rapidly elaborate effector functions upon re-exposure to pathogens, but also have many properties in common with naive cells, including pluripotency and the ability to migrate to the lymph nodes and spleen. Thus, memory cells embody features of both naive and effector cells, fuelling a long-standing debate centred on whether memory T cells develop from effector cells or directly from naive cells. Here we show that long-lived memory CD8 T cells are derived from a subset of effector T cells through a process of dedifferentiation. To assess the developmental origin of memory CD8 T cells, we investigated changes in DNA methylation programming at naive and effector cell-associated genes in virus-specific CD8 T cells during acute lymphocytic choriomeningitis virus infection in mice. Methylation profiling of terminal effector versus memory-precursor CD8 T cell subsets showed that, rather than retaining a naive epigenetic state, the subset of cells that gives rise to memory cells acquired de novo DNA methylation programs at naive-associated genes and became demethylated at the loci of classically defined effector molecules. Conditional deletion of the de novo methyltransferase Dnmt3a at an early stage of effector differentiation resulted in reduced methylation and faster re-expression of naive-associated genes, thereby accelerating the development of memory cells. Longitudinal phenotypic and epigenetic characterization of the memory-precursor effector subset of virus-specific CD8 T cells transferred into antigen-free mice revealed that differentiation to memory cells was coupled to erasure of de novo methylation programs and re-expression of naive-associated genes. Thus, epigenetic repression of naive-associated genes in effector CD8 T cells can be reversed in cells that develop into long-lived memory CD8 T cells while key effector genes remain demethylated, demonstrating that memory T cells arise from a subset of fate-permissive effector T cells.

Article

Leaky resistance and the conditions for the existence of lytic bacteriophage

by Waqas N. Chaudhry; Maros Pleska; Nilang N. Shah; Howard Weiss; Ingrid C. McCall; Justin R. Meyer; Animesh Gupta; Calin C. Guet; Bruce Levin

2018

Subjects
  • Biology, Molecular
  • Chemistry, Biochemistry
  • File Download
  • View Abstract

Abstract:Close

In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage, bacterial cells resistant to the phage commonly emerge and become the dominant population of bacteria. Following the ascent of resistant mutants, the densities of bacteria in these simple communities become limited by resources rather than the phage. Despite the evolution of resistant hosts, upon which the phage cannot replicate, the lytic phage population is most commonly maintained in an apparently stable state with the resistant bacteria. Several mechanisms have been put forward to account for this result. Here we report the results of population dynamic/evolution experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli in serial transfer cultures. We show that, following the ascent of λVIR-resistant bacteria, λVIRis maintained in the majority of cases in maltose-limited minimal media and in all cases in nutrient-rich broth. Using mathematical models and experiments, we show that the dominant mechanism responsible for maintenance of λVIRin these resource-limited populations dominated by resistant E. coli is a high rate of either phenotypic or genetic transition from resistance to susceptibility—a hitherto undemonstrated mechanism we term "leaky resistance." We discuss the implications of leaky resistance to our understanding of the conditions for the maintenance of phage in populations of bacteria—their “existence conditions.”.

Article

Dynamic corticostriatal activity biases social bonding in monogamous female prairie voles

by Elizabeth A. Amadei; Zachary V. Johnson; Yong Jun Kwon; Aaron C. Shpiner; Varun Saravanan; Wittney D. Mays; Steven J. Ryan; Hasse Walum; Donald Rainnie; Larry J Young; Robert C Liu

2017

Subjects
  • Biology, Neuroscience
  • Psychology, Social
  • Psychology, Behavioral
  • File Download
  • View Abstract

Abstract:Close

Adult pair bonding involves dramatic changes in the perception and valuation of another individual. One key change is that partners come to reliably activate the brain's reward system, although the precise neural mechanisms by which partners become rewarding during sociosexual interactions leading to a bond remain unclear. Here we show, using a prairie vole (Microtus ochrogaster) model of social bonding, how a functional circuit from the medial prefrontal cortex to nucleus accumbens is dynamically modulated to enhance females' affiliative behaviour towards a partner. Individual variation in the strength of this functional connectivity, particularly after the first mating encounter, predicts how quickly animals begin affiliative huddling with their partner. Rhythmically activating this circuit in a social context without mating biases later preference towards a partner, indicating that this circuit's activity is not just correlated with how quickly animals become affiliative but causally accelerates it. These results provide the first dynamic view of corticostriatal activity during bond formation, revealing how social interactions can recruit brain reward systems to drive changes in affiliative behaviour.

Article

A compendium of RNA-binding motifs for decoding gene regulation

by Debashish Ray; Hilal Kazan; Kate B. Cook; Matthew T. Weirauch; Hamed S. Najafabadi; Xiao Li; Serge Gueroussov; Mihai Albu; Hong Zheng; Ally Yang; Hong Na; Manuel Irimia; Leah H. Matzat; Ryan K. Dale; Sarah A. Smith; Christopher A. Yarosh; Seth Kelly; Behnam Nabet; Desirea Mecenas; Weimin Li; Rakesh S. Laishram; Mei Qiao; Howard D. Lipshitz; Fabio Piano; Anita Corbett; Russ P. Carstens; Brendan J. Frey; Richard A. Anderson; Kristen W. Lynch; Luiz O. F. Penalva

2013

Subjects
  • Biology, Cell
  • Biology, Genetics
  • File Download
  • View Abstract

Abstract:Close

RNA-binding proteins are key regulators of gene expression, yet only a small fraction have been functionally characterized. Here we report a systematic analysis of the RNA motifs recognized by RNA-binding proteins, encompassing 205 distinct genes from 24 diverse eukaryotes. The sequence specificities of RNA-binding proteins display deep evolutionary conservation, and the recognition preferences for a large fraction of metazoan RNA-binding proteins can thus be inferred from their RNA-binding domain sequence. The motifs that we identify in vitro correlate well with in vivo RNA-binding data. Moreover, we can associate them with distinct functional roles in diverse types of post-transcriptional regulation, enabling new insights into the functions of RNA-binding proteins both in normal physiology and in human disease. These data provide an unprecedented overview of RNA-binding proteins and their targets, and constitute an invaluable resource for determining post-transcriptional regulatory mechanisms in eukaryotes.
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