224 research outputs found

    A large-scale study of a poultry trading network in Bangladesh: implications for control and surveillance of avian influenza viruses

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    Since its first report in 2007, avian influenza (AI) has been endemic in Bangladesh. While live poultry marketing is widespread throughout the country and known to influence AI dissemination and persistence, trading patterns have not been described. The aim of this study is to assess poultry trading practices and features of the poultry trading networks which could promote AI spread, and their potential implications for disease control and surveillance. Data on poultry trading practices was collected from 849 poultry traders during a cross-sectional survey in 138 live bird markets (LBMs) across 17 different districts of Bangladesh. The quantity and origins of traded poultry were assessed for each poultry type in surveyed LBMs. The network of contacts between farms and LBMs resulting from commercial movements of live poultry was constructed to assess its connectivity and to identify the key premises influencing it

    Dendritic Spike Saturation of Endogenous Calcium Buffer and Induction of Postsynaptic Cerebellar LTP

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    The architecture of parallel fiber axons contacting cerebellar Purkinje neurons retains spatial information over long distances. Parallel fiber synapses can trigger local dendritic calcium spikes, but whether and how this calcium signal leads to plastic changes that decode the parallel fiber input organization is unknown. By combining voltage and calcium imaging, we show that calcium signals, elicited by parallel fiber stimulation and mediated by voltage-gated calcium channels, increase non-linearly during high-frequency bursts of electrically constant calcium spikes, because they locally and transiently saturate the endogenous buffer. We demonstrate that these non-linear calcium signals, independently of NMDA or metabotropic glutamate receptor activation, can induce parallel fiber long-term potentiation. Two-photon imaging in coronal slices revealed that calcium signals inducing long-term potentiation can be observed by stimulating either the parallel fiber or the ascending fiber pathway. We propose that local dendritic calcium spikes, evoked by synaptic potentials, provide a unique mechanism to spatially decode parallel fiber signals into cerebellar circuitry changes

    Yeast Based Small Molecule Screen for Inhibitors of SARS-CoV

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    Severe acute respiratory coronavirus (SARS-CoV) emerged in 2002, resulting in roughly 8000 cases worldwide and 10% mortality. The animal reservoirs for SARS-CoV precursors still exist and the likelihood of future outbreaks in the human population is high. The SARS-CoV papain-like protease (PLP) is an attractive target for pharmaceutical development because it is essential for virus replication and is conserved among human coronaviruses. A yeast-based assay was established for PLP activity that relies on the ability of PLP to induce a pronounced slow-growth phenotype when expressed in S. cerevisiae. Induction of the slow-growth phenotype was shown to take place over a 60-hour time course, providing the basis for conducting a screen for small molecules that restore growth by inhibiting the function of PLP. Five chemical suppressors of the slow-growth phenotype were identified from the 2000 member NIH Diversity Set library. One of these, NSC158362, potently inhibited SARS-CoV replication in cell culture without toxic effects on cells, and it specifically inhibited SARS-CoV replication but not influenza virus replication. The effect of NSC158362 on PLP protease, deubiquitinase and anti-interferon activities was investigated but the compound did not alter these activities. Another suppressor, NSC158011, demonstrated the ability to inhibit PLP protease activity in a cell-based assay. The identification of these inhibitors demonstrated a strong functional connection between the PLP-based yeast assay, the inhibitory compounds, and SARS-CoV biology. Furthermore the data with NSC158362 suggest a novel mechanism for inhibition of SARS-CoV replication that may involve an unknown activity of PLP, or alternatively a direct effect on a cellular target that modifies or bypasses PLP function in yeast and mammalian cells

    Regional mitochondrial DNA and cell-type changes in post-mortem brains of non-diabetic Alzheimer’s disease are not present in diabetic Alzheimer’s disease

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    Background: Mitochondrial dysfunction is implicated in both diabetes and Alzheimer’s disease (AD), and diabetes also increases the risk of AD, however the combined impact of AD and diabetes on brain mitochondria is unknown. The purpose of this study was to test the hypothesis that the combination of both diabetes and AD exacerbates mitochondrial dysfunction. Methods: Post-mortem human brains (n=74), were used to determine mitochondrial DNA (mtDNA) content of cerebellum, frontal cortex and parietal cortex by quantifying absolute mtDNA copy number/cell using real time qPCR. mtDNA content was compared between diabetic and non-diabetic cases representing non-cognitively impaired controls (NCI), mildly cognitively impaired (MCI) and AD. A subset of parietal cortex samples was used to quantify mRNAs corresponding to cell types and mitochondrial function. Immune-staining of parietal cortex sections followed by semi-automated stereological assessment was performed to assess cell types. Results. Using mtDNA as an indicator of mitochondrial content, we observed significant regional variation, being highest in the parietal cortex, and lowest in the cerebellum. In the absence of diabetes, AD cases had decreased parietal cortex mtDNA, reduced MAP2 (neuronal) mRNA and increased GFAP (astrocyte) mRNA, relative to NCI. However, in the presence of both diabetes and AD, we did not observe these changes in the parietal cortex. Irrespective of cognitive status, all 3 brain regions in diabetic cases had significantly higher mtDNA than the non-diabetic cases. Conclusion. Our data show that the parietal cortex has the highest mitochondrial content but is also the most vulnerable to changes in AD, as shown by reduced mtDNA and neurones in this region. In contrast, when patients have both diabetes and AD, the AD associated parietal cortex changes are no longer seen, suggesting that the pathology observed in diabetic AD may be different to that seen in non-diabetic AD. The lack of clear functional changes in mitochondrial parameters in diabetic AD suggest that there may be different mechanisms contributing to cognitive impairment in diabetes and their impact on the respective disease neuro-pathologies remain to be fully understood

    The effects of crude oil price volatility, stock price, exchange rate and interest rate on Malaysia’s economic growth

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    This study examines the effects and relationships between Malaysia’s economic growth and selected variables which are oil price volatility, stock price, real exchange rate and real interest rate. Using time-series data methodology, the study employs unit root test using Augmented Dickey–Fuller (ADF) and Phillips–Perron (PP), Auto-Regressive Distribution Lag (ARDL) model supplemented by Bounds F-Testing, Johansen-Julius Co-integration test and Granger causality test. The long�run equation derived from ARDL shows that there are positive relationships for stock price and real exchange rate whilst there are negative relationships between oil price volatility and real interest rate. Furthermore, Granger causality test shows that only stock price and real interest rates have an impact on Malaysia’s gross domestic product (GDP) in the short run. Finally, sound policy recommendations are suggested, in particular, to address oil price volatility in a forward looking manner as well as monetary-friendly measures to further support Malaysia’s economic growth

    A Systems Biology Approach Reveals the Role of a Novel Methyltransferase in Response to Chemical Stress and Lipid Homeostasis

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    Using small molecule probes to understand gene function is an attractive approach that allows functional characterization of genes that are dispensable in standard laboratory conditions and provides insight into the mode of action of these compounds. Using chemogenomic assays we previously identified yeast Crg1, an uncharacterized SAM-dependent methyltransferase, as a novel interactor of the protein phosphatase inhibitor cantharidin. In this study we used a combinatorial approach that exploits contemporary high-throughput techniques available in Saccharomyces cerevisiae combined with rigorous biological follow-up to characterize the interaction of Crg1 with cantharidin. Biochemical analysis of this enzyme followed by a systematic analysis of the interactome and lipidome of CRG1 mutants revealed that Crg1, a stress-responsive SAM-dependent methyltransferase, methylates cantharidin in vitro. Chemogenomic assays uncovered that lipid-related processes are essential for cantharidin resistance in cells sensitized by deletion of the CRG1 gene. Lipidome-wide analysis of mutants further showed that cantharidin induces alterations in glycerophospholipid and sphingolipid abundance in a Crg1-dependent manner. We propose that Crg1 is a small molecule methyltransferase important for maintaining lipid homeostasis in response to drug perturbation. This approach demonstrates the value of combining chemical genomics with other systems-based methods for characterizing proteins and elucidating previously unknown mechanisms of action of small molecule inhibitors

    The Western Channel Observatory: a century of physical, chemical and biological data compiled from pelagic and benthic habitats in the western English Channel

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    Abstract. The Western Channel Observatory (WCO) comprises a series of pelagic, benthic and atmospheric sampling sites within 40 km of Plymouth, UK, that have been sampled by the Plymouth institutes on a regular basis since 1903. This longevity of recording and the high frequency of observations provide a unique combination of data; for example temperature data were first collected in 1903, and the reference station L4, where nearly 400 planktonic taxa have been enumerated, has been sampled on a weekly basis since 1988. While the component datasets have been archived, here we provide the first summary database bringing together a wide suite of the observations. This provides monthly average values of some of the key pelagic and benthic measurements for the inshore site L4 (50∘15.00′ N, 4∘13.02′ W; approx. depth 55 m), the offshore site E1 (50∘02.00′ N, 4∘22.00′ W; approx. depth 75 m) and the intermediate L5 site (50∘10.80′ N, 4∘18.00′ W; approx. depth 58 m). In brief, these data include the following: water temperature (from 1903); macronutrients (from 1934); dissolved inorganic carbon and total alkalinity (from 2008); methane and nitrous oxide (from 2011); chlorophyll a (from 1992); high-performance liquid chromatography (HPLC)-derived pigments (from 1999); <20 µm plankton by flow cytometry, including bacteria (8 functional groups from 2007); phytoplankton by microscopy (6 functional groups from 1992); microplankton and mesozooplankton from FlowCam (6 groups from 2012); Noctiluca sp. dinoflagellate (from 1997); mesozooplankton by microscopy (8 groups from 1988); Calanus helgolandicus egg production rates (from 1992); fish larvae from the Young Fish Trawl survey (4 groups from 1924); benthic macrofauna (4 groups from 2008); demersal fish (19 families from 2008); blue shark, Prionace glauca (from 1958); and 16S alpha diversity for sediment and water column (from 2012). These data have varying coverage with respect to time and depth resolution. The metadata tables describe each dataset and provide pointers to the source data and other related Western Channel Observatory datasets and outputs not compiled here. We provide summaries of the main trends in seasonality and some major climate-related shifts that have been revealed over the last century. The data are available from the Data Archive for Seabed Species and Habitats (DASSH): https://doi.org/10.17031/645110fb81749 (McEvoy and Atkinson, 2023). Making these data fully accessible and including units of both abundance and biomass will stimulate a variety of uptakes. These may include uses as an educational resource for projects, for models and budgets, for the analysis of seasonality and long-term change in a coupled benthic–pelagic system, or for supporting UK and north-eastern Atlantic policy and management

    The Western Channel Observatory: a century of physical, chemical and biological data compiled from pelagic and benthic habitats in the western English Channel

    Get PDF
    The Western Channel Observatory (WCO) comprises a series of pelagic, benthic and atmospheric sampling sites within 40 km of Plymouth, UK, that have been sampled by the Plymouth institutes on a regular basis since 1903. This longevity of recording and the high frequency of observations provide a unique combi�nation of data; for example temperature data were first collected in 1903, and the reference station L4, where nearly 400 planktonic taxa have been enumerated, has been sampled on a weekly basis since 1988. While the component datasets have been archived, here we provide the first summary database bringing together a wide suite of the observations. This provides monthly average values of some of the key pelagic and benthic measure�ments for the inshore site L4 (50◦15.000 N, 4◦13.020 W; approx. depth 55 m), the offshore site E1 (50◦02.000 N, 4 ◦22.000 W; approx. depth 75 m) and the intermediate L5 site (50◦10.800 N, 4◦18.000 W; approx. depth 58 m). In brief, these data include the following: water temperature (from 1903); macronutrients (from 1934); dissolved inorganic carbon and total alkalinity (from 2008); methane and nitrous oxide (from 2011); chlorophyll a (from 1992); high-performance liquid chromatography (HPLC)-derived pigments (from 1999); <20 µm plankton by flow cytometry, including bacteria (8 functional groups from 2007); phytoplankton by microscopy (6 functional groups from 1992); microplankton and mesozooplankton from FlowCam (6 groups from 2012); Noctiluca sp. dinoflagellate (from 1997); mesozooplankton by microscopy (8 groups from 1988); Calanus helgolandicus egg production rates (from 1992); fish larvae from the Young Fish Trawl survey (4 groups from 1924); benthic macrofauna (4 groups from 2008); demersal fish (19 families from 2008); blue shark, Prionace glauca (from 1958); and 16S alpha diversity for sediment and water column (from 2012). These data have varying coverage with respect to time and depth resolution. The metadata tables describe each dataset and provide pointers to the source data and other related Western Channel Observatory datasets and outputs not compiled here. We pro�vide summaries of the main trends in seasonality and some major climate-related shifts that have been revealed over the last century. The data are available from the Data Archive for Seabed Species and Habitats (DASSH): https://doi.org/10.17031/645110fb81749 (McEvoy and Atkinson, 2023). Making these data fully accessible and including units of both abundance and biomass will stimulate a variety of uptakes. These may include uses as an educational resource for projects, for models and budgets, for the analysis of seasonality and long-term change in a coupled benthic–pelagic system, or for supporting UK and north-eastern Atlantic policy and management
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