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Whether CD8+ T lymphocytes control human immunodeficiency virus infection by cytopathic or non-cytopathic mechanisms is not fully understood. Multiple studies highlighted non-cytopathic effects, but one hypothesis is that cytopathic effects of CD8+ T cells occur before viral production. Here, to examine the role of CD8+ T cells prior to virus production, we treated SIVmac251-infected macaques with an integrase inhibitor combined with a CD8-depleting antibody, or with either reagent alone. We analyzed the ensuing viral dynamics using a mathematical model that included infected cells pre- and post- viral DNA integration to compare different immune effector mechanisms. Macaques receiving the integrase inhibitor alone experienced greater viral load decays, reaching lower nadirs on treatment, than those treated also with the CD8-depleting antibody. Models including CD8+ cell-mediated reduction of viral production (non-cytolytic) were found to best explain the viral profiles across all macaques, in addition an effect in killing infected cells pre-integration (cytolytic) was supported in some of the best models. Our results suggest that CD8+ T cells have both a cytolytic effect on infected cells before viral integration, and a direct, non-cytolytic effect by suppressing viral production. Control of HIV and SIV infection is largely thought to be achieved through direct lysis of target cells. Here, using mathematical modelling of viral load data from rhesus macaques, the authors propose that virus control is best explained by the combination of cytolytic and non-cytolytic effects. [ABSTRACT FROM AUTHOR]

CD4+ T-cell depletion is a hallmark of HIV infection, leading to impairment of cellular immunity and opportunistic infections, but its contribution to SIV/HIV-associated gut dysfunction is unknown. Chronically SIV-infected African Green Monkeys (AGMs) partially recover mucosal CD4+ T-cells, maintain gut integrity and do not progress to AIDS. Here we assess the impact of prolonged, antibody-mediated CD4 + T-cell depletion on gut integrity and natural history of SIV infection in AGMs. All circulating CD4+ T-cells and >90% of mucosal CD4+ T-cells are depleted. Plasma viral loads and cell-associated viral RNA in tissues are lower in CD4+-cell-depleted animals. CD4+-cell-depleted AGMs maintain gut integrity, control immune activation and do not progress to AIDS. We thus conclude that CD4+ T-cell depletion is not a determinant of SIV-related gut dysfunction, when gastrointestinal tract epithelial damage and inflammation are absent, suggesting that disease progression and resistance to AIDS are independent of CD4+ T-cell restoration in SIVagm-infected AGMs.HIV infection results in the depletion of CD4+ T cells overtime and the loss of coordinated cellular immunity, but how this corresponds to the SIV infected African Green Monkey (AGM) model of non-progressive disease is not known. Here the authors assess the impact of experimental CD4+ T cell depletion in AGM and show that lack of disease progression and resistance to AIDS in this model are independent of CD4+ T cell loss. [ABSTRACT FROM AUTHOR]

Cold seeps are pervasive along the continental margin worldwide, and are recognized as hotspots for elemental cycling pathway on Earth. In this study, analyses of pore water geochemical compositions of one ∼400 cm piston core (S3) and the application of a mass balance model are conducted to assess methane-associated biogeochemical reactions and uncover the relationship of methane in shallow sediment with gas hydrate reservoir at the Makran accretionary wedge off Pakistan. The results revealed that approximately 77% of sulfate is consumed by the predominant biogeochemical process of anaerobic oxidation of methane. However, the estimated sulfate-methane interface depth is ∼400 cm below sea floor with the methane diffusive flux of 0.039 mol/(m2·a), suggesting the activity of methane seepage. Based on the δ13CDIC mass balance model combined with the contribution proportion of different dissolved inorganic carbon sources, this study calculated the δ13C of the exogenous methane to be −57.9‰, indicating that the exogenous methane may be a mixture source, including thermogenic and biogenic methane. The study of pore water geochemistry at Makran accretionary wedge off Pakistan may have considerable implications for understanding the specific details on the dynamics of methane in cold seeps and provide important evidence for the potential occurrence of subsurface gas hydrate in this area. [ABSTRACT FROM AUTHOR]

That the high frequency and good replication capacity of strains with reduced susceptibility to neuraminidase inhibitors (NAIs) in highly pathogenic avian influenza H7N9 (HPAI H7N9) virus made it a significance to further study its drug resistance. HPAI H7N9 viruses bearing NA I222L or E119V substitution and two mutations of I222L-E119V as well as their NAIs-sensitive counterpart were generated by reverse genetics for NA inhibition test and replication capability evaluation in vitro. The attenuated H7N9/PR8 recombinant viruses were developed to study the pathogenicity and drug resistance brought by the above substitutions to mice. The IC50 fold change of oseltamivir to HPAI H7N9 with NA222L-119V is 306.34 times than that of its susceptible strain, and 3.5 times than the E119V mutant virus. HPAI H7N9 bearing NA222L-119V had good replication ability with peak value of more than 6log10 TCID50/ml in MDCK cells. H7N9/PR8 virus bearing NA222L-119V substitutions leaded to diffuse pneumonia, significant weight loss and fatality in mice. NA E119V made H7N9/PR8 virus resistant to oseltamivir, and I222L-E119V had synergistic resistance to oseltamivir in mice. Due to the good fitness of drug resistant strains of HPAI H7N9 virus, it is necessary to strengthen drug resistance surveillance and new drug research. [ABSTRACT FROM AUTHOR]

Seafloor pockmarks are important indicators of submarine methane seepages and slope instabilities. In order to promote the understanding of submarine pockmarks and their relationship with sediment instabilities and climate changes, here we summarize the research results of pockmarks in the spatio-temporal distributions and shaping factors. Most of pockmarks occur along active or passive continental margins during the last 25 kyr B.P.. Circular and ellipse are the most common forms of pockmarks, whereas pockmarks in a special crescent or elongated shape are indicators of slope instabilities, and ring-shape pockmarks are endemic to the gas hydrate zones. Further researches should be focused on the trigger mechanism of climate changes based on the pockmarks in the high latitudes formed during the deglaciation periods, and the role of gas hydrates in the seafloor evolution should be elucidated. In addition, the feature of pockmarks at their early stage (e.g., developing gas chimneys and gas driving sedimentary doming) and the relations between pockmarks and mass movements, mud diapirs could be further studied to clarify the influences of rapid methane release from submarine sediments on the atmospheric carbon contents. [ABSTRACT FROM AUTHOR]

Natural hosts of simian immunodeficiency virus (SIV) avoid AIDS despite lifelong infection. Here, we examined how this outcome is achieved by comparing a natural SIV host, African green monkey (AGM) to an AIDS susceptible species, rhesus macaque (RM). To asses gene expression profiles from acutely SIV infected AGMs and RMs, we developed a systems biology approach termed Conserved Gene Signature Analysis (CGSA), which compared RNA sequencing data from rectal AGM and RM tissues to various other species. We found that AGMs rapidly activate, and then maintain, evolutionarily conserved regenerative wound healing mechanisms in mucosal tissue. The wound healing protein fibronectin shows distinct tissue distribution and abundance kinetics in AGMs. Furthermore, AGM monocytes exhibit an embryonic development and repair/regeneration signature featuring TGF-β and concomitant reduced expression of inflammatory genes compared to RMs. This regenerative wound healing process likely preserves mucosal integrity and prevents inflammatory insults that underlie immune exhaustion in RMs. Here, the authors compare gene expression signatures in rectal tissues of African green monkeys (AGMs) and rhesus macaques (RMs) acutely infected with simian immunodeficiency virus and find that AGMs rapidly activate and maintain evolutionarily conserved regenerative wound healing mechanisms. [ABSTRACT FROM AUTHOR]

Seafloor elongated depressions are indicators of gas seepage or slope instability. Here we report a sequence of slopeparallel elongated depressions that link to headwalls of sediment slides on upper slope. The depressions of about 250 m in width and several kilometers in length are areas of focused gas discharge indicated by bubble-release into the water column and methane enriched pore waters. Sparker seismic profiles running perpendicular and parallel to the coast, show gas migration pathways and trapped gas underneath these depressions with bright spots and seismic blanking. The data indicate that upward gas migration is the initial reason for fracturing sedimentary layers. In the top sediment where two young stages of landslides can be detected, the slopeparallel sediment weakening lengthens and deepens the surficial fractures, creating the elongated depressions in the seafloor supported by sediment erosion due to slope-parallel water currents. [ABSTRACT FROM AUTHOR]

A modified electrode, based on a hexadecane (C16)-coated glassy-carbon electrode (GCE) has been developed for the determination of parathion. The electrochemical behavior of parathion was investigated by cyclic voltammetry (CV). The peak potential and peak current were found to depend on the supporting electrolyte and the pH of the buffer solution. The reduction currents for parathion were proportional to parathion concentration over the range 8×10–8–2×10–5 mol L–1. The detection limit was 2×10–8 mol L–1 parathion for an accumulation time of 30 s. The effects of organic and inorganic species on the determination of parathion were also studied. A procedure was developed to extract parathion from spiked soil samples using a mixture of dichloromethane and acetone as the extraction solvent. The complete extraction and analytical procedure are simple, inexpensive and rapid. Parathion was determined in a soil sample by use of linear scan voltammetry (LSV). [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]