6,924 research outputs found

    Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor

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    Viruses have evolved a myriad of evasion strategies focused on undermining chemokine-mediated immune surveillance, exemplified by the mouse γ-herpesvirus 68 M3 decoy receptor. Crystal structures of M3 in complex with C chemokine ligand 1/lymphotactin and CC chemokine ligand 2/monocyte chemoattractant protein 1 reveal that invariant chemokine features associated with G protein–coupled receptor binding are primarily recognized by the decoy C-terminal domain, whereas the N-terminal domain (NTD) reconfigures to engage divergent basic residue clusters on the surface of chemokines. Favorable electrostatic forces dramatically enhance the association kinetics of chemokine binding by M3, with a primary role ascribed to acidic NTD regions that effectively mimic glycosaminoglycan interactions. Thus, M3 employs two distinct mechanisms of chemical imitation to potently sequester chemokines, thereby inhibiting chemokine receptor binding events as well as the formation of chemotactic gradients necessary for directed leukocyte trafficking

    Marine Reserves and Reproductive Biomass: A Case Study of a Heavily Targeted Reef Fish

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    Recruitment overfishing (the reduction of a spawning stock past a point at which the stock can no longer replenish itself) is a common problem which can lead to a rapid and irreversible fishery collapse. Averting this disaster requires maintaining a sufficient spawning population to buffer stochastic fluctuations in recruitment of heavily harvested stocks. Optimal strategies for managing spawner biomass are well developed for temperate systems, yet remain uncertain for tropical fisheries, where the danger of collapse from recruitment overfishing looms largest. In this study, we explored empirically and through modeling, the role of marine reserves in maximizing spawner biomass of a heavily exploited reef fish, Lethrinus harak around Guam, Micronesia. On average, spawner biomass was 16 times higher inside the reserves compared with adjacent fished sites. Adult density and habitat-specific mean fish size were also significantly greater. We used these data in an age-structured population model to explore the effect of several management scenarios on L. harak demography. Under minimum-size limits, unlimited extraction and all rotational-closure scenarios, the model predicts that preferential mortality of larger and older fish prompt dramatic declines in spawner biomass and the proportion of male fish, as well as considerable declines in total abundance. For rotational closures this occurred because of the mismatch between the scales of recovery and extraction. Our results highlight how alternative management scenarios fall short in comparison to marine reserves in preserving reproductively viable fish populations on coral reefs

    Changing the direction of environmental investment in Australia: Learnings from implementing INFFER

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    Investment in natural resource management (NRM) by regional organisations in Australia has been widely criticised for failing to achieve substantial environmental outcomes. The Investment Framework for Environmental Resources (INFFER) is a tool for developing and prioritising projects to address environmental issues such as water quality, biodiversity decline, environmental pest impacts and land degradation. INFFER is an asset-based, targeted, and outcome-focussed approach to environmental investment, and as such is a very different and more rigorous approach to prioritising possible environmental projects than used previously by most catchment management organisations (CMOs) in Australia. From 2008 to 2010 INFFER has been trialled with CMOs. Evaluation and benchmarking data obtained at 2-day INFFER training sessions with seven CMOs in three eastern Australia states are reported. Before commencing to use INFFER, CMO staff are generally confident about the current decision-making processes for environmental investment used within their organisation. In some cases, this initial perception challenges their acceptance of a new approach to investment decisionmaking. Key issues when implementing INFFER include concerns about changing the direction of CMO investment, concerns about compatibility with funder requirements, and various issues associated with specific aspects of the Framework. Perceived complexity of INFFER, existing institutional arrangements, and the legacy of past institutional arrangements remain serious barriers to the adoption of methods to improve environmental outcomes from NRM investment. Despite these difficulties INFFER is being used by a number of CMOs. However, it is likely that widespread adoption of INFFER, or indeed any other transparent and robust process, will only occur with greater requirement from governments for environmental decision making by regional NRM bodies that is more focused on outcomes and cost-effectiveness.NRM investment planning, NRM investment prioritisation, regional catchment management organisations, NRM policy, environmental planning, environmental prioritisation, environmental policy, Environmental Economics and Policy, Research and Development/Tech Change/Emerging Technologies, Q50, Q58,

    A rare schizophrenia risk variant of CACNA1I disrupts CaV3.3 channel activity

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    CACNA1I is a candidate schizophrenia risk gene. It encodes the pore-forming human CaV3.3 α1 subunit, a subtype of voltage-gated calcium channel that contributes to T-type currents. Recently, two de novo missense variations, T797M and R1346H, of hCaV3.3 were identified in individuals with schizophrenia. Here we show that R1346H, but not T797M, is associated with lower hCaV3.3 protein levels, reduced glycosylation, and lower membrane surface levels of hCaV3.3 when expressed in human cell lines compared to wild-type. Consistent with our biochemical analyses, whole-cell hCaV3.3 currents in cells expressing the R1346H variant were ~50% of those in cells expressing WT hCaV3.3, and neither R1346H nor T797M altered channel biophysical properties. Employing the NEURON simulation environment, we found that reducing hCaV3.3 current densities by 22% or more eliminates rebound bursting in model thalamic reticular nucleus (TRN) neurons. Our analyses suggest that a single copy of Chr22: 39665939G > A CACNA1I has the capacity to disrupt CaV3.3 channel-dependent functions, including rebound bursting in TRN neurons, with potential implications for schizophrenia pathophysiology

    Factor Analysis of the Milwaukee Inventory for Subtypes of Trichotillomania-Adult Version

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    The Milwaukee Inventory for Subtypes of Trichotillomania-Adult Version (MIST-A; Flessner et al., 2008) measures the degree to which hair pulling in Trichotillomania (TTM) can be described as “automatic” (i.e., done without awareness and unrelated to affective states) and/or “focused” (i.e., done with awareness and to regulate affective states). Despite preliminary evidence in support of the psychometric properties of the MIST-A, emerging research suggests the original factor structure may not optimally capture TTM phenomenology. Using data from a treatment-seeking TTM sample, the current study examined the factor structure of the MIST-A via exploratory factor analysis. The resulting two factor solution suggested the MIST-A consists of a 5-item “awareness of pulling” factor that measures the degree to which pulling is done with awareness and an 8-item “internal-regulated pulling” factor that measures the degree to which pulling is done to regulate internal stimuli (e.g., emotions, cognitions, and urges). Correlational analyses provided preliminary evidence for the validity of these derived factors. Findings from this study challenge the notions of “automatic” and “focused” pulling styles and suggest that researchers should continue to explore TTM subtypes
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