Dataset Information

The Phylogeographic and Spatiotemporal Spread of HCV in Pakistani Population.

ABSTRACT: Hepatitis C Virus (HCV) is the most prevalent human pathogen in Pakistan and is the major cause of liver cirrhosis and hepatocellular carcinoma in infected patients. It has shifted from being hypo-endemic to being hyper-endemic. There was no information about the origin and evolution of the local variants. Here we use newly developed phyloinformatic methods of sequence analysis to conduct the first comprehensive investigation of the evolutionary and biogeographic history in unprecedented detail and breadth. Considering evolutionary rate and molecular-clock hypothesis in context, we reconstructed the spatiotemporal spread of HCV in the whole territory of its circulation using a combination of Bayesian MCMC methods utilizing all sequences available in GenBank. Comparative analysis were performed and were addressed. Whole genome and individual gene analysis have shown that sub-types 1a, 1b and 3a are recognized as epidemic strains and are distributed globally. Here we confirm that the origin of HCV 3a genotypes is in South Asia and HCV has evolved in the region to become stably adapted to the host environment.

SUBMITTER: Ghori NU

PROVIDER: S-EPMC5072696 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The Phylogeographic and Spatiotemporal Spread of HCV in Pakistani Population.

Ghori Noor-Ul-Huda NU Shafique Atif A Hayat Muhammad Qasim MQ Anjum Sadia S

PloS one 20161020 10

Hepatitis C Virus (HCV) is the most prevalent human pathogen in Pakistan and is the major cause of liver cirrhosis and hepatocellular carcinoma in infected patients. It has shifted from being hypo-endemic to being hyper-endemic. There was no information about the origin and evolution of the local variants. Here we use newly developed phyloinformatic methods of sequence analysis to conduct the first comprehensive investigation of the evolutionary and biogeographic history in unprecedented detail ...[more]

PMID: 27764129

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Project description:Microdomains that emerge from spatially constricted spread of biochemical signaling components play a central role in several neuronal computations. Although dendrites, endowed with several voltage-gated ion channels, form a prominent structural substrate for microdomain physiology, it is not known if these channels regulate the spatiotemporal spread of signaling microdomains. Here, we employed a multiscale, morphologically realistic, conductance-based model of the hippocampal pyramidal neuron that accounted for experimental details of electrical and calcium-dependent biochemical signaling. We activated synaptic N-Methyl-d-Aspartate receptors through theta-burst stimulation (TBS) or pairing (TBP) and assessed microdomain propagation along a signaling pathway that included calmodulin, calcium/calmodulin-dependent protein kinase II (CaMKII) and protein phosphatase 1. We found that the spatiotemporal spread of the TBS-evoked microdomain in phosphorylated CaMKII (pCaMKII) was amplified in comparison to that of the corresponding calcium microdomain. Next, we assessed the role of two dendritically expressed inactivating channels, one restorative (A-type potassium) and another regenerative (T-type calcium), by systematically varying their conductances. Whereas A-type potassium channels suppressed the spread of pCaMKII microdomains by altering the voltage response to TBS, T-type calcium channels enhanced this spread by modulating TBS-induced calcium influx without changing the voltage. Finally, we explored cross-dependencies of these channels with other model components, and demonstrated the heavy mutual interdependence of several biophysical and biochemical properties in regulating microdomains and their spread. Our conclusions unveil a pivotal role for dendritic voltage-gated ion channels in actively amplifying or suppressing biochemical signals and their spatiotemporal spread, with critical implications for clustered synaptic plasticity, robust information transfer and efficient neural coding.

Dataset Information

The Phylogeographic and Spatiotemporal Spread of HCV in Pakistani Population.

Publications

The Phylogeographic and Spatiotemporal Spread of HCV in Pakistani Population.

Similar Datasets

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