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Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is complicated by the virus's direct interactions with immune cells, the induction of persistent reservoirs in the immune system cells, and multiple strategies developed by the virus for immune evasion. Meanwhile, HIV and SIV infections induce a pandysfunction of the immune cell populations, making it difficult to untangle the various concurrent mechanisms of HIV pathogenesis. Over the years, one of the most successful approaches for dissecting the immune correlates of protection in HIV/SIV infection has been the in vivo depletion of various immune cell populations and assessment of the impact of these depletions on the outcome of infection in non-human primate models. Here, we present a detailed analysis of the strategies and results of manipulating SIV pathogenesis through in vivo depletions of key immune cells populations. Although each of these methods has its limitations, they have all contributed to our understanding of key pathogenic pathways in HIV/SIV infection. [ABSTRACT FROM AUTHOR]

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]

Iron (Fe), sulfur (S), and molybdenum (Mo) geochemistry in marine sediments impacted by hydrothermal plumes and/or cold seeps is complex and has not been systematically documented. Here we characterize Fe, S, and Mo diagenesis in sediments between the Minami‐Ensei Knoll hydrothermal field and a cold‐seep site of the middle Okinawa Trough. Results show that distances away from the hydrothermal field and the steep trough slope may significantly affect the transport of hydrothermal Fe. The transformation of hydrothermal reactive Fe to poorly reactive or unreactive Fe‐bearing phyllosilicates decreased the relative fractions of highly reactive Fe (FeHR) in total Fe (FeHR/FeT). Despite this, the standing stocks of Fe oxides in the methane‐free sediments have not been dampened, indicating no net impacts of hydrothermal Fe inputs on the size of Fe oxides. In the methane‐free sediments, low ratios of total reduced inorganic sulfide (TRIS) to total organic carbon (TOC) (TRIS/TOC), highly 34S‐depleted pyrite, and low Mo contents suggest that organoclastic sulfate reduction is at low rates and plays a limited role in carbon cycle. In the cold‐seep sediments, however, intense sulfate reduction coupled to anaerobic methane oxidation significantly elevate TRIS/TOC ratios, Mo enrichment, and isotope compositions of Mo and pyrite‐S. This pathway is expected to be important in carbon cycle in the basin due to the wide occurrence of cold seeps. Our results highlight the important controls of the local extreme depositional/diagenetic conditions on sedimentary S and Mo records, with implications for the reconstruction of paleoredox states of the past earth's surface. Plain Language Summary: Submarine methane‐rich cold seeps and hydrothermal venting exert important influences on the geochemistry of iron, sulfur, and molybdenum. However, the influences of the two extreme environments on the three interlinked elements in seafloor have not been well documented. Here, we used solid‐phase chemistry of four sediment cores located between a hydrothermal field and a cold‐seep site in the middle Okinawa Trough to document the impacts of the two extreme environments on the geochemistry of iron, sulfur, and molybdenum. Results show that hydrothermal Fe signature in the sediments is largely controlled by the distances away from the hydrothermal field and the steep slope of the trough; the hydrothermal Fe inputs have no net impacts on sedimentary iron oxide contents due to simultaneous inactivation of reactive Fe. In the methane‐free sediments, sulfate reduction (SR) is coupled mainly to oxidation of sedimentary organic carbon. In the cold‐seep site, however, SR coupled to anaerobic methane oxidation is the main pathway of carbon cycle, leading to significant enrichments of molybdenum and isotopically heavy pyrite. The differences highlight the important control of local extreme depositional/diagenetic conditions on geochemical records of iron, sulfur, and molybdenum, with implications for the reconstruction of paleoredox states in the past. Key Points: Distances away from the vent, steep basin slope and Fe inactivation control the signature of hydrothermal Fe in the basin sedimentsLow lability of organics limits sulfate reduction (SR) in CH4‐free sediments, while CH4 largely facilitates SR in cold‐seep sedimentsLocal extreme conditions exert key controls on S‐Fe‐Mo diagenesis in the basin [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]

Objectives: In mainland China, the disease burden of influenza is not yet fully understood. Based on population‐based data, we aimed to estimate incidence rates of medically attended influenza and influenza virus infections in Ningbo City. Methods: We used data for outpatient acute respiratory illness (OARI) from a platform covering all health and medical institutes in Yingzhou District, Ningbo City. We applied generalized additive regression models to estimate influenza‐associated excess incidence rate of OARI by age. We recruited local residents aged ≥60 years in the autumn of 2019 and conducted follow‐up nearly 9 months later. Every survey, the sera were collected for testing hemagglutination inhibition antibody. Results: From 2017–2018 to 2019–2020, the annual average of influenza‐associated incidence rate of OARI in all ages was 10.9%. The influenza‐associated incidence rate of OARI was the highest in 2017–2018 (16.9%) and the lowest in 2019–2020 (4.8%). Regularly, influenza‐associated incidence rates of OARI were the highest in children aged 5–14 years (range: 44.1–77.6%) and 0–4 years (range: 8.3–46.6%). The annual average of excess OARI incidence rate in all ages was the highest for influenza B/Yamagata (3.9%). The overall incidence rate of influenza infections indicated by serology in elderly people was 21% during the winter season of 2019–2020. Conclusions: We identified substantial outpatient influenza burden in all ages in Ningbo. Our cohort study limited in elderly people found that this age group had a high risk of seasonal influenza infections. Our study informs the importance of increasing influenza vaccine coverage in high‐risk population including elderly people. [ABSTRACT FROM AUTHOR]

Background: Deep-sea mussels living in the cold seeps with enormous biomass act as the primary consumers. They are well adapted to the extreme environment where light is absent, and hydrogen sulfide, methane, and other hydrocarbon-rich fluid seepage occur. Despite previous studies on diversity, role, evolution, and symbiosis, the changing adaptation patterns during different developmental stages of the deep-sea mussels remain largely unknown. Results: The deep-sea mussels (Bathymodiolus platifrons) of two developmental stages were collected from the cold seep during the ocean voyage. The gills, mantles, and adductor muscles of these mussels were used for the Illumina sequencing. A total of 135 Gb data were obtained, and subsequently, 46,376 unigenes were generated using de-novo assembly strategy. According to the gene expression analysis, amounts of genes were most actively expressed in the gills, especially genes involved in environmental information processing. Genes encoding Toll-like receptors and sulfate transporters were up-regulated in gills, indicating that the gill acts as both intermedium and protective screen in the deep-sea mussel. Lysosomal enzymes and solute carrier responsible for nutrients absorption were up-regulated in the older mussel, while genes related to toxin resistance and autophagy were up-regulated in the younger one, suggesting that the older mussel might be in a vigorous stage while the younger mussel was still paying efforts in survival and adaptation. Conclusions: In general, our study suggested that the adaptation capacity might be formed gradually during the development of deep-sea mussels, in which the gill and the symbionts play essential roles. [ABSTRACT FROM AUTHOR]

Active cold seeps in the Okinawa Trough (OT) have been widely identified, but the sediment microbial communities associated with these sites are still poorly understood. Here, we investigated the distribution and biomass of the microbial communities, particularly those associated with the anaerobic oxidation of methane (AOM), in sediments from an active cold seep in the mid-Okinawa Trough. Methane-oxidizing archaea, including ANME-1a, ANME-1b, ANME-2a/b, ANME-2c, and ANME-3, were detected in the OT cold seep sediments. Vertical stratification of anaerobic methanotrophic archaea (ANME) communities was observed in the following order: ANME-3, ANME-1a, and ANME-1b. In addition, the abundance of methyl coenzyme M reductase A (mcrA) genes corresponded to high levels of dissolved iron, suggesting that methane-metabolizing archaea might participate in iron reduction coupled to methane oxidation (Fe-AOM) in the OT cold seep. Furthermore, the relative abundance of ANME-1a was strongly related to the concentration of dissolved iron, indicating that ANME-1a is a key microbial player for Fe-AOM in the OT cold seep sediments. Co-occurrence analysis revealed that methane-metabolizing microbial communities were mainly associated with heterotrophic microorganisms, such as JS1, Bathy-1, and Bathy-15. [ABSTRACT FROM AUTHOR]

Seasonal influenza A (H3N2) virus has been a concern since its first introduction in humans in 1968. Accumulating antigenic changes in viral hemagglutinin (HA), particularly recent cocirculations of multiple HA genetic clades, allow H3N2 virus evade into humans annually. From 2010, the binding of neuraminidase (NA) to sialic acid made the traditional assay for HA inhibition antibodies (Abs) unsuitable for antigenicity characterization. Here, we investigated the serum anti-NA response in a cohort with a seroconversion of microneutralizing (MN) Abs targeting the circulating strain, A/Singapore/INFIMH-16-0019/2016 (H3N2, 3C.2a1)-like, a virus during 2018/2019 flu seasons. We discovered that MN Ab titers show no difference between children and adults. Nevertheless, higher titers of Abs with NA activity inhibition (NI) activity of 129 and seroconversion rate of 68.42% are presented in children aged 7–17 years (n = 19) and 73.47 and 41.17% in adults aged 21–59 years (n = 17), respectively. The MN Abs generated in children display direct correlations with HA- and NA-binding Abs or NI Abs. The NI activity exhibited cross-reactivity to N2 of H3N2 viruses of 2007 and 2013, commonly with 329- N -glycosylation and E344 in N2, a characteristic of earlier 3C.2a H3N2 virus in 2014. The percentage of such viruses pronouncedly decreased and was even replaced by those dominant H3N2 viruses with E344K and 329 non-glycosylation, which have a significantly low activity to the tested antisera. Our findings suggest that NI assay is a testable assay applied in H3N2 infection in children, and the antigenic drift of current N2 should be considered for vaccine selection. [ABSTRACT FROM AUTHOR]

It has been two decades since the cold seeps were firstly found in the Okinawa Trough (OT). The scientific cruises and the geological surveys since then have unveiled the currently active submarine methane seeps and significantly improved the understanding of methane seeps in the back-arc basin of the OT. In this paper, we review the up-to-date progress of the research of methane seepages then put forward the promising, yet challenging, outlook by listing the unsolved questions of the cold seeps in the OT. Multiple approaches and techniques, including seismic and echo-sounder recording, dredging, gravity-piston and ROV coring, seafloor drilling, and isotopic and microarray-based genomic analysis, have been used to reveal the geological processes responsible for the seeping activities and the biogeochemical processes related to them. The geophysical signature associated with gas seeps mainly includes the acoustic turbidity in the subsurface, the anomaly of the backscattering intensity at the seabed, and the gas plumes observed in the water column. Pore water and methane-derived authigenic carbonate archive the intensification of methane seepage and the paleoenvironment changes at different time scales. The methane feeding of the seeps in the OT was generated mostly via the microbially mediated process and has an origin mixed by thermogenic hydrocarbon gas in the middle OT. Sulfate-driven and Fe-driven anaerobic oxidations of methane are suggested to be the key biogeochemical processes, which would shape the material cycling in the seeping environment. The future research on the cold seeps in the OT is worth looking forward to due to its geographic and potential geologic links with the nearby hydrothermal activities. Multidisciplinary studies are expected to concentrate on their link with the undiscovered gas hydrates, the amount of methane transferring into the oceans and its impact on the climatic change, and the evolution of the seeping activities accompanied by the biogeochemical processes. [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]

Background: In mainland China, seasonal influenza disease burden at community level is unknown. The incidence rate of influenza virus infections in the community is difficult to determine due to the lack of well‐defined catchment populations of influenza‐like illness surveillance sentinel hospitals. Objectives: We established a community‐based cohort to estimate incidence of seasonal influenza infections indicated by serology and protection conferred by antibody titers against influenza infections during 2018‐2019 influenza season in northern China. Methods: We recruited participants in November 2018 and conducted follow‐up in May 2019 with collection of sera every survey. Seasonal influenza infections were indicated by a 4‐fold or greater increase of hemagglutination inhibition (HI) antibody between paired sera. Results: Two hundred and three children 5‐17 years of age and 413 adults 18‐59 years of age were followed up and provided paired sera. The overall incidence of seasonal influenza infection and incidence of A(H3N2) infection in children (31% and 17%, respectively) were significantly higher than those in adults (21% and 10%, respectively). The incidences of A(H1N1)pdm09 infection in children and adults were both about 10%, while the incidences of B/Victoria and/Yamagata infection in children and adults were from 2% to 4%. HI titers of 1:40 against A(H1N1)pdm09 and A(H3N2) viruses were associated with 63% and 75% protection against infections with the two subtypes, respectively. Conclusions: In the community, we identified considerable incidence of seasonal influenza infections. A HI titer of 1:40 could be sufficient to provide 50% protection against influenza A virus infections indicated by serology. [ABSTRACT FROM AUTHOR]

HIV/SIV persistence in latent reservoirs requires lifelong antiretroviral treatment and calls for effective cure strategies. Romidepsin (RMD), a histone deacetylase inhibitor, was reported to reactivate HIV/SIV from reservoirs in virus-suppressed individuals. We characterized in detail the pharmacokinetics and safety profile of RMD in three SIV-naïve rhesus macaques which received two rounds of treatment. In plasma, RMD mean terminal half-life was 15.3 h. In comparison, RMD mean terminal half-life was much longer in tissues: 110 h in the lymph nodes (LNs) and 28 h in gastrointestinal tract. RMD administration was accompanied by transient liver and systemic toxicity. Isoflurane anesthesia induced near-immediate transient lymphopenia, which was further exacerbated and extended with the extensive immune modifications by RMD. The effect of RMD on circulating immune cells was complex: (i) slight increase in lymphocyte death rates; (ii) transient, robust increase in neutrophils; (iii) massive downregulation of lymphocyte surface markers; (iv) important migration of CD3+ T cells to the gut and LNs; and (v) hindrance to CD8+ T cell functionality, yet without reaching significance. Our results show that, in contrast to transient plasma concentrations, RMD has a long-term presence in tissues, with multiple immunomodulatory effects and minimal to moderate kidney, liver, and lymphocyte toxicities. As such, we concluded that RMD can be used for "shock and kill" approaches, preferentially in combination with other latency reversal agents or cytotoxic T lymphocyte boosting strategies with consideration taken for adverse effects. [ABSTRACT FROM AUTHOR]

Background: Brief assessments of functional status for community-dwelling older adults are needed given expanded interest in the measurement of functional decline. Methods: As part of a 2015 prospective cohort study of older adults aged 60–89 years in Jiangsu Province, China, 1506 participants were randomly assigned to two groups; each group was administered one of two alternative 20-item versions of a scale to assess activities of daily living (ADL) and instrumental activities of daily living (IADL) drawn from multiple commonly-used scales. One version asked if they required help to perform activities (ADL-IADL-HELP-20), while the other version provided additional response options if activities could be done alone but with difficulty (ADL-IADL-DIFFICULTY-20). Item responses to both versions were compared using the binomial test for differences in proportion (with Wald 95% confidence interval [CI]). A brief 9-item scale (ADL-IADL-DIFFICULTY-9) was developed favoring items identified as difficult or requiring help by ≥4%, with low redundancy and/or residual correlations, and with significant correlations with age and other health indicators. We repeated assessment of the measurement properties of the brief scale in two subsequent samples of older adults in Hong Kong in 2016 (aged 70–79 years; n = 404) and 2017 (aged 65–82 years; n = 1854). Results: Asking if an activity can be done alone but with difficulty increased the proportion of participants reporting restriction on 9 of 20 items, for which 95% CI for difference scores did not overlap with zero; the proportion with at least one limitation increased from 28.6% to 34.2% or an absolute increase of 5.6% (95% CI = 0.9–10.3%), which was a relative increase of 19.6%. The brief ADL-IADL-DIFFICULTY-9 maintained excellent internal consistency (α = 0.93) and had similar ceiling effect (68.1%), invariant item ordering (H trans =.41; medium), and correlations with age and other health measures compared with the 20-item version. The brief scale performed similarly when subsequently administered to older adults in Hong Kong. Conclusions: Asking if tasks can be done alone but with difficulty can modestly reduce ceiling effects. It's possible that the length of commonly-used scales can be reduced by over half if researchers are primarily interested in a summed indicator rather than an inventory of specific types of deficits. [ABSTRACT FROM AUTHOR]

Unlike HIV infection, SIV infection is generally nonpathogenic in natural hosts, such as African green monkeys (AGMs), despite life-long high viral replication. Lack of disease progression was reportedly based on the ability of SIV-infected AGMs to prevent gut dysfunction, avoiding microbial translocation and the associated systemic immune activation and chronic inflammation. Yet, the maintenance of gut integrity has never been documented, and the mechanism(s) by which gut integrity is preserved are unknown. We sought to investigate the early events of SIV infection in AGMs, specifically examining the impact of SIVsab infection on the gut mucosa. Twenty-nine adult male AGMs were intrarectally infected with SIVsab92018 and serially sacrificed at well-defined stages of SIV infection, preramp-up (1–3 days post-infection (dpi)), ramp-up (4–6 dpi), peak viremia (9–12 dpi), and early chronic SIV infection (46–55 dpi), to assess the levels of immune activation, apoptosis, epithelial damage and microbial translocation in the GI tract and peripheral lymph nodes. Tissue viral loads, plasma cytokines and plasma markers of gut dysfunction were also measured throughout the course of early infection. While a strong, but transient, interferon-based inflammatory response was observed, the levels of plasma markers linked to enteropathy did not increase. Accordingly, no significant increases in apoptosis of either mucosal enterocytes or lymphocytes, and no damage to the mucosal epithelium were documented during early SIVsab infection of AGMs. These findings were supported by RNAseq of the gut tissue, which found no significant alterations in gene expression that would indicate microbial translocation. Thus, for the first time, we confirmed that gut epithelial integrity is preserved, with no evidence of microbial translocation, in AGMs throughout early SIVsab infection. This might protect AGMs from developing intestinal dysfunction and the subsequent chronic inflammation that drives both HIV disease progression and HIV-associated comorbidities. Author summary: African nonhuman primates that are natural hosts to SIVs can provide us with unique insight into the pathogenesis of HIV disease due to their remarkable ability to avoid progression to AIDS, despite high levels of viral replication. A key question of SIV pathogenesis in natural hosts is whether the lack of disease progression is due to an exquisite ability to repair lesions occurring during the acute infection or to completely maintain the integrity of the mucosal barrier throughout the SIV infection. In pathogenic HIV/SIV infections of humans and macaques, the mucosal integrity is compromised during acute infection, leading to leakage of gut microbial byproducts and to the occurrence of chronic local and systemic inflammation, which plays a crucial role in driving progression to AIDS. Our study shows that the mucosal barrier integrity is never lost in African green monkeys, thereby avoiding the effects of chronic inflammation and disease progression. [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]

Natural gas hydrates have been hailed as a new and promising unconventional alternative energy, especially as fossil fuels approach depletion, energy consumption soars, and fossil fuel prices rise, owing to their extensive distribution, abundance, and high fuel efficiency. Gas hydrate reservoirs are similar to a storage cupboard in the global carbon cycle, containing most of the world's methane and accounting for a third of Earth's mobile organic carbon. We investigated gas hydrate stability zone burial depths from the viewpoint of conditions associated with stable existence of gas hydrates, such as temperature, pressure, and heat flow, based on related data collected by the global drilling programs. Hydrate‐related areas are estimated using various biological, geochemical and geophysical tools. Based on a series of previous investigations, we cover the history and status of gas hydrate exploration in the USA, Japan, South Korea, India, Germany, the polar areas, and China. Then, we review the current techniques for hydrate exploration in a global scale. Additionally, we briefly review existing techniques for recovering methane from gas hydrates, including thermal stimulation, depressurization, chemical injection, and CH4–CO2 exchange, as well as corresponding global field trials in Russia, Japan, United States, Canada and China. In particular, unlike diagenetic gas hydrates in coarse sandy sediments in Japan and gravel sediments in the United States and Canada, most gas hydrates in the northern South China Sea are non‐diagenetic and exist in fine‐grained sediments with a vein‐like morphology. Therefore, especially in terms of the offshore production test in gas hydrate reservoirs in the Shenhu area in the north slope of the South China Sea, Chinese scientists have proposed two unprecedented techniques that have been verified during the field trials: solid fluidization and formation fluid extraction. Herein, we introduce the two production techniques, as well as the so‐called "four‐in‐one" environmental monitoring system employed during the Shenhu production test. Methane is not currently commercially produced from gas hydrates anywhere in the world; therefore, the objective of field trials is to prove whether existing techniques could be applied as feasible and economic production methods for gas hydrates in deep‐water sediments and permafrost zones. Before achieving commercial methane recovery from gas hydrates, it should be necessary to measure the geologic properties of gas hydrate reservoirs to optimize and improve existing production techniques. Herein, we propose horizontal wells, multilateral wells, and cluster wells improved by the vertical and individual wells applied during existing field trials. It is noteworthy that relatively pure gas hydrates occur in seafloor mounds, within near‐surface sediments, and in gas migration conduits. Their extensive distribution, high saturation, and easy access mean that these types of gas hydrate may attract considerable attention from academia and industry in the future. Herein, we also review the occurrence and development of concentrated shallow hydrate accumulations and briefly introduce exploration and production techniques. In the closing section, we discuss future research needs, key issues, and major challenges related to gas hydrate exploration and production. We believe this review article provides insight on past, present, and future gas hydrate exploration and production to provide guidelines and stimulate new work into the field of gas hydrates. [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 reactive dispersant (SMA–ESA) was synthesised from poly(styrene‐alt‐maleic anhydride) (SMA) and 4‐(beta‐sulfatoethylsulfonyl)aniline (ESA), and its dispersing ability for carbon black (CB) was investigated. Fourier transform infrared (FTIR) and 1H–nuclear magnetic resonance (NMR) spectroscopies showed that an amidation reaction took place between ESA and SMA. The optimal preparation conditions for reactive nanoscale CB dispersion were a mole ratio of ESA to SMA of 4:3, with a mass ratio of SMA–ESA and CB at 3%, sonication time 20 min, and pH 8. The reactive nanoscale CB dispersion prepared under optimal conditions showed excellent stability and small mean particle size. A cotton fabric coloured with reactive nanoscale CB dispersion could obtain a high K/S value, and excellent rubbing and washing fastness. [ABSTRACT FROM AUTHOR]

Two SIVmac251-infected rhesus macaques received tenofovir/emtricitabine with raltegravir intensification. Viral rebound occurred during treatment and sequencing of reverse transcriptase and integrase genes identified multiple resistance mutations. Similar to HIV infection, antiretroviral-resistance mutations may occur in SIV-infected nonhuman primates receiving nonsuppressive ART. As ART administration to nonhuman primates is currently dramatically expanding, fueled by both cure research and the study of HIV-related comorbidities, viral resistance should be factored in the study design and data interpretation. [ABSTRACT FROM AUTHOR]

Background: Some studies have hypothesized that vitamin D may have a role to play in protection against influenza virus infections and illnesses, and that seasonal fluctuation in serum 25-hydroxyvitamin D [25(OH)D] may affect seasonal patterns of influenza virus infections.Objective: We aimed to investigate whether serum 25(OH)D concentrations were associated with the incidence of influenza virus infections and illnesses in children and adults in Hong Kong.Methods: In 2009-2010, 3030 children and adults of all ages from 796 households in Hong Kong were followed up to identify acute respiratory illnesses. Sera from 2694 participants were collected at baseline and after ∼1 mo, 6 mo, and 12 mo. Influenza virus infections were confirmed by reverse transcriptase-polymerase chain reaction performed on nasal and throat swab samples collected during illness episodes. Serologic evidence of influenza virus infection was measured by hemagglutination inhibition assays in unvaccinated participants. The serum 25(OH)D concentrations were measured after collection of all specimens. Each individual's baseline serum 25(OH)D concentration on 1 January 2010 was predicted by a random-effects linear regression model.Results: We found that, in children and adults who had not received a seasonal influenza vaccine, baseline serum 25(OH)D concentrations (<50 nmol/L compared with ≥50 nmol/L) were not statistically significantly associated with serologic evidence of influenza A(H1N1)pdm09 (RR, 1.18; 95% CI: 0.85, 1.65) or seasonal influenza virus infections [including A(H3N2) and B virus] (RR, 1.13; 95% CI: 0.86, 1.49). In all participants, baseline serum 25(OH)D concentrations were not statistically significantly associated with polymerase chain reaction-confirmed influenza virus infection (RR, 1.15; 95% CI: 0.73, 1.83) and influenza-like illness (RR, 1.18; 95% CI: 0.98, 1.43).Conclusions: These findings indicate that lower serum vitamin D concentrations may not contribute to the seasonality of influenza and are not associated with an increased risk of influenza virus infections in persons of all ages in Hong Kong. [ABSTRACT FROM AUTHOR]

We collected 2768 Influenza-like illness emergency public health incidents from April 1, 2005 to November 30, 2013reported in the Emergency Public Reporting System. After screening by strict inclusion and exclusion criteria, there were 613 outbreaks analyzed with susceptible–exposed–infectious/asymptomatic–removed model in order to estimate the proportion of asymptomatic individuals (p) and the effective reproduction number (Rt). The relation between Rt and viral subtypes, regions, outbreak sites, populations, and seasons were analyzed. The mean values of p of different subtypes ranged from 0.09 to 0.15, but could be as high as up to 0.94. Different subtypes, provinces, regions, and sites of outbreak had statistically significantly different Rt. In particular, the southern region also manifested different Rt by affected population size and seasonality. Our results provide China and also the rest of the world a reference to understand characteristics of transmission and develop prevention and control strategies. [ABSTRACT FROM AUTHOR]

Viruses that persist despite seemingly effective antiretroviral treatment (ART) and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the “shock and kill” strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis)] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD) to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to <10 SIV RNA copies/mL with ART, without viral blips. At ART cessation, initial rebound viremia to ~106 copies/mL was followed by a decline to < 10 copies/mL, suggesting effective immune control. Three post-treatment controller RMs received three doses of RMD every 35–50 days, followed by in vivo experimental depletion of CD8+ cells using monoclonal antibody M-T807R1. RMD was well-tolerated and resulted in a rapid and massive surge in T cell activation, as well as significant virus rebounds (~104 copies/ml) peaking at 5–12 days post-treatment. CD8+ cell depletion resulted in a more robust viral rebound (107 copies/ml) that was controlled upon CD8+ T cell recovery. Our results show that RMD can reactivate SIV in vivo in the setting of post-ART viral control. Comparison of the patterns of virus rebound after RMD administration and CD8+ cell depletion suggested that RMD impact on T cells is only transient and does not irreversibly alter the ability of SIV-specific T cells to control the reactivated virus. [ABSTRACT FROM AUTHOR]

New Sr, Nd, and Pb isotopic data of seven basalt samples from the middle Mariana Trough were analysed together with existing geochemical data of basalts from the middle Mariana Trough (MMT), the northern Mariana Trough (NMT), the middle Okinawa Trough (MOT), and the southern Okinawa Trough (SOT). Basalts from the Mariana and Okinawa troughs have similarities to island arc lavas and are enriched in large ion lithophile elements but depleted in high field strength elements compared with normal mid-ocean ridge basalt (N-MORB). The Sr, Nd, and Pb isotopic compositions of the back-arc basin basalts maybe modelled by a mixing between end-member components of N-MORB-like mantle and enriched mantle end-member. Modelling results suggest that as the degree of back-arc extension increases, the proportion of subduction components in the source magma decreases. The compositions of SOT basalts can be explained by the mixing of subduction components in the proportion 16%, followed by MOT at 14%, NMT at 7%, and MMT at 4%. This result indicates that the contribution of subduction components to the composition of source magmas for back-arc basalts is closely related to the tectonic evolution of the entire back-arc system. The proportions of subduction components in basaltic magma sources can be used as an indicator of the extent of evolution of a back-arc basin or the development of a back-arc spreading system. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab–infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection. [ABSTRACT FROM AUTHOR]

Human infection with avian influenza A H7N9 virus was first identified in March 2013 and represents an ongoing threat to public health. There is a need to optimize serological methods for this new influenza virus. Here, we compared the sensitivity and specificity of the hemagglutinin inhibition (HI), microneutralization (MN), and Western blot (WB) assays for the detection of human antibodies against avian influenza A (H7N9) virus. HI with horse erythrocytes (hRBCs) and a modified MN assay possessed greater sensitivity than turkey erythrocytes and the standard MN assay, respectively. Using these assays, 80% of tested sera from confirmed H7N9 cases developed detectable antibody to H7N9 after 21 days. To balance sensitivity and specificity, we found serum titers of ≥20 (MN) or 160 (HI) samples were most effective in determining seropositive to H7N9 virus. Single serum with HI titers of 20–80 or MN titer of 10 could be validated by each other or WB assay. Unlike serum collected from adult or elderly populations, the antibody response in children with mild disease was low or undetectable. These combinations of assays will be useful in case diagnosis and serologic investigation of human cases. [ABSTRACT FROM AUTHOR]

We assessed the role of myeloid dendritic cells (mDCs) in the outcome of SIV infection by comparing and contrasting their frequency, mobilization, phenotype, cytokine production and apoptosis in pathogenic (pigtailed macaques, PTMs), nonpathogenic (African green monkeys, AGMs) and controlled (rhesus macaques, RMs) SIVagmSab infection. Through the identification of recently replicating cells, we demonstrated that mDC mobilization from the bone marrow occurred in all species postinfection, being most prominent in RMs. Circulating mDCs were depleted with disease progression in PTMs, recovered to baseline values after the viral peak in AGMs, and significantly increased at the time of virus control in RMs. Rapid disease progression in PTMs was associated with low baseline levels and incomplete recovery of circulating mDCs during chronic infection. mDC recruitment to the intestine occurred in all pathogenic scenarios, but loss of mucosal mDCs was associated only with progressive infection. Sustained mDC immune activation occurred throughout infection in PTMs and was associated with increased bystander apoptosis in blood and intestine. Conversely, mDC activation occurred only during acute infection in nonprogressive and controlled infections. Postinfection, circulating mDCs rapidly became unresponsive to TLR7/8 stimulation in all species. Yet, stimulation with LPS, a bacterial product translocated in circulation only in SIV-infected PTMs, induced mDC hyperactivation, apoptosis and excessive production of proinflammatory cytokines. After infection, spontaneous production of proinflammatory cytokines by mucosal mDCs increased only in progressor PTMs. We thus propose that mDCs promote tolerance to SIV in the biological systems that lack intestinal dysfunction. In progressive infections, mDC loss and excessive activation of residual mDCs by SIV and additional stimuli, such as translocated microbial products, enhance generalized immune activation and inflammation. Our results thus provide a mechanistic basis for the role of mDCs in the pathogenesis of AIDS and elucidate the causes of mDC loss during progressive HIV/SIV infections. [ABSTRACT FROM AUTHOR]

In China during March 4-April 28, 2013, avian influenza A(H7N9) virus testing was performed on 20,739 specimens from patients with influenza-like illness in 10 provinces with confirmed human cases: 6 (0.03%) were positive, and increased numbers of unsubtypeable influenza-positive specimens were not seen. Careful monitoring and rapid characterization of influenza A(H7N9) and other influenza viruses remain critical. [ABSTRACT FROM AUTHOR]

Background: Seasonal influenza epidemics occur annually with bimodality in southern China and unimodality in northern China. Regional differences exist in surveillance data collected by the National Influenza Surveillance Network of the Chinese mainland. Qualitative and quantitative analyses on the spatiotemporal rules of the influenza virus's activities are needed to lay the foundation for the surveillance, prevention and control of seasonal influenza. Methods: The peak performance analysis and Fourier harmonic extraction methods were used to explore the spatiotemporal characteristics of the seasonal influenza virus activity and to obtain geographic divisions. In the first method, the concept of quality control was introduced and robust estimators were chosen to make the results more convincing. The dominant Fourier harmonics of the provincial time series were extracted in the second method, and the VARiable CLUSter (VARCLUS) procedure was used to variably cluster the extracted results. On the basis of the above geographic division results, three typical districts were selected and corresponding sinusoidal models were applied to fit the time series of the virological data. Results: The predominant virus during every peak is visible from the bar charts of the virological data. The results of the two methods that were used to obtain the geographic divisions have some consistencies with each other and with the virus activity mechanism. Quantitative models were established for three typical districts: the south1 district, including Guangdong, Guangxi, Jiangxi and Fujian; the south2 district, including Hunan, Hubei, Shanghai, Jiangsu and Zhejiang; and the north district, including the 14 northern provinces except Qinghai. The sinusoidal fitting models showed that the south1 district had strong annual periodicity with strong winter peaks and weak summer peaks. The south2 district had strong semi-annual periodicity with similarly strong summer and winter peaks, and the north district had strong annual periodicity with only winter peaks. [ABSTRACT FROM AUTHOR]

Background: Influenza A (H1N1)pdm09 (2009 H1N1) re-circulated as the predominant virus from January through February 2011 in China. National surveillance of 2009 H1N1 as a notifiable disease was maintained to monitor potential changes in disease severity from the previous season. Methodology/Principal Findings: To describe the characteristics of hospitalized cases with 2009 H1N1 infection and analyze risk factors for severe illness during the 2010–2011winter season in China, we obtained surveillance data from hospitalized cases with 2009 H1N1 infection from November 2010 through May 2011, and reviewed medical records from 701 hospitalized cases. Age-standardized risk ratios were used to compare the age distribution of patients that were hospitalized and died due to 2009 H1N1 between the 2010–2011winter season to those during the 2009–2010 pandemic period. During the 2010–2011 winter season, children less than 5 years of age had the highest relative risk of hospitalization and death, followed by adults aged 65 years or older. Additionally, the relative risk of hospitalized cases aged 5–14 and 15–24 years was lower compared to children less than 5 years of age. During the winter season of 2010–2011, the proportions of adults aged 25 years or older for hospitalization and death were significantly higher than those during the 2009–2010 pandemic period. Being male, having a chronic medical condition, delayed hospital admission (≥3 days from onset) or delayed initiation of antiviral treatment (≥5 days from onset) were associated with severe illness among non-pregnant patients ≥2 years of age. Conclusions/Significance: We observed a change in high risk groups for hospitalization for 2009 H1N1 during the winter months immediately following the pandemic period compared to the high risk groups identified during the pandemic period. Our nationally notifiable disease surveillance system enabled us to understand the evolving epidemiology of 2009 H1N1 infection after the pandemic period. [ABSTRACT FROM AUTHOR]

We investigated potential sources of infection for 6 confirmed influenza A (H5N1) patients who resided in urban areas of People's Republic of China. None had known exposure to sick poultry or poultry that died from illness, but all had visited wet poultry markets before illness. [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]

We collected paired sera from live poultry workers in southern China and identified a high risk of asymptomatic influenza A(H7N9) virus infection, particularly in females and those with longer exposure to poultry.Background. Confirmed cases of avian influenza A(H7N9) virus infection in humans continue to occur in mainland China. Few confirmed cases have occurred in poultry workers despite potentially higher rates of exposure.Methods. A serological survey was conducted in May and December 2013 in poultry market workers, and in March and September 2013 in the general population. Blood samples were collected and tested for antibodies to H7N9 and H5N1 viruses by hemagglutination inhibition (HI) assays. Multivariable analysis was employed to identify risk factors related to H7N9 infection indicated by serology among poultry workers.Results. In the poultry workers, 36 of 501 (7.2%) in May and 56 of 375 (14.9%) in December had HI antibody titers ≥1:160 to H7N9. Of 96 individuals who participated in both surveys, 52 (54.2%) workers had a ≥4-fold rise in H7N9 antibody titers from May to December. In a multivariable analysis, female sex (odds ratio [OR], 2.713; 95% confidence interval [CI], 1.098–6.705) and ≥10 years of occupational exposure (OR, 3.592; 95% CI, 1.246–10.354) were identified as risk factors for infection. Seroprevalence against H5N1 at ≥1:160 was low in May (4/501 [0.8%]) and December (3/375 [0.8%]). In the general population, 0 of 417 individuals in March and 0 of 408 individuals in September had antibody titers ≥1:160 to H7N9 or to H5N1.Conclusions. Although none of the participants in our study had virologically confirmed H7N9 infection, the high proportion of poultry workers with serologic evidence of H7N9 infection between May and December 2013 suggests a substantial risk of mild H7N9 infections in this group, supporting stricter control measures in live poultry markets. [ABSTRACT FROM AUTHOR]