94 research outputs found

    Chicken anaemia virus evades host immune responses in transformed lymphocytes

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    Chicken anaemia virus (CAV) is a lymphotropic virus that causes anaemia and immunosuppression in chickens. Previously, we proposed that CAV evades host antiviral responses in vivo by disrupting T-cell signalling, but the precise cellular targets and modes of action remain elusive. In this study, we examined gene expression in Marek’s disease virus-transformed chicken T-cell line MSB-1 after infection with CAV using both a custom 5K immune-focused microarray and quantitative realtime PCR at 24, 48 and 72 h post-infection. The data demonstrate an intricate equilibrium between CAV and the host gene expression, displaying subtle but significant modulation of transcripts involved in the T-cell, inflammation and NF-kB signalling cascades. CAV efficiently blocked the induction of type-I interferons and interferon-stimulated genes at 72 h. The cell expression pattern implies that CAV subverts host antiviral responses and that the transformed environment of MSB-1 cells offers an opportunistic advantage for virus growth

    Ecological consequences of early Late Pleistocene megadroughts in tropical Africa

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    Extremely arid conditions in tropical Africa occurred in several discrete episodes between 135 and 90 ka, as demonstrated by lake core and seismic records from multiple basins [Scholz CA, Johnson TC, Cohen AS, King JW, Peck J, Overpeck JT, Talbot MR, Brown ET, Kalindekafe L, Amoako PYO, et al. (2007) Proc Natl Acad Sci USA 104:16416–16421]. This resulted in extraordinarily low lake levels, even in Africa\u27s deepest lakes. On the basis of well dated paleoecological records from Lake Malawi, which reflect both local and regional conditions, we show that this aridity had severe consequences for terrestrial and aquatic ecosystems. During the most arid phase, there was extremely low pollen production and limited charred-particle deposition, indicating insufficient vegetation to maintain substantial fires, and the Lake Malawi watershed experienced cool, semidesert conditions (\u3c400 mm/yr precipitation). Fossil and sedimentological data show that Lake Malawi itself, currently 706 m deep, was reduced to an ≈125 m deep saline, alkaline, well mixed lake. This episode of aridity was far more extreme than any experienced in the Afrotropics during the Last Glacial Maximum (≈35–15 ka). Aridity diminished after 95 ka, lake levels rose erratically, and salinity/alkalinity declined, reaching near-modern conditions after 60 ka. This record of lake levels and changing limnological conditions provides a framework for interpreting the evolution of the Lake Malawi fish and invertebrate species flocks. Moreover, this record, coupled with other regional records of early Late Pleistocene aridity, places new constraints on models of Afrotropical biogeographic refugia and early modern human population expansion into and out of tropical Africa

    Constraints from observations and modeling on atmosphere-surface exchange of mercury in eastern North America

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    Atmosphere-surface exchange of mercury, although a critical component of its global cycle, is currently poorly constrained. Here we use the GEOS-Chem chemical transport model to interpret atmospheric Hg-0 (gaseous elemental mercury) data collected during the 2013 summer Nitrogen, Oxidants, Mercury and Aerosol Distributions, Sources and Sinks (NOMADSS) aircraft campaign as well as ground-and ship-based observations in terms of their constraints on the atmosphere-surface exchange of Hg-0 over eastern North America. Model-observation comparison suggests that the Northwest Atlantic may be a net source of Hg-0, with high evasion fluxes in summer (our best sensitivity simulation shows an average oceanic Hg-0 flux of 3.3 ng m(-2) h(-1) over the Northwest Atlantic), while the terrestrial ecosystem in the summer of the eastern United States is likely a net sink of Hg-0 (our best sensitivity simulation shows an average terrestrial Hg-0 flux of -0.6 ng m(-2) h(-1) over the eastern United States). The inferred high Hg-0 fluxes from the Northwest Atlantic may result from high wet deposition fluxes of oxidized Hg, which are in turn related to high precipitation rates in this region. We also find that increasing simulated terrestrial fluxes of Hg-0 in spring compared to other seasons can better reproduce observed seasonal variability of Hg-0 concentration at ground-based sites in eastern North America.Peer reviewe

    The Alaska Arctic Vegetation Archive (AVA-AK)

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    The Alaska Arctic Vegetation Archive (AVA-AK, GIVD-ID: NA-US-014) is a free, publically available database archive of vegetation-plot data from the Arctic tundra region of northern Alaska. The archive currently contains 24 datasets with 3,026 non-overlapping plots. Of these, 74% have geolocation data with 25-m or better precision. Species cover data and header data are stored in a Turboveg database. A standardized Pan Arctic Species List provides a consistent nomenclature for vascular plants, bryophytes, and lichens in the archive. A web-based online Alaska Arctic Geoecological Atlas (AGA-AK) allows viewing and downloading the species data in a variety of formats, and provides access to a wide variety of ancillary data. We conducted a preliminary cluster analysis of the first 16 datasets (1,613 plots) to examine how the spectrum of derived clusters is related to the suite of datasets, habitat types, and environmental gradients. Here, we present the contents of the archive, assess its strengths and weaknesses, and provide three supplementary files that include the data dictionary, a list of habitat types, an overview of the datasets, and details of the cluster analysis

    Endemic Acinetobacter baumannii in a New York Hospital

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    Acinetobacter baumannii is an increasingly multidrug-resistant (MDR) cause of hospital-acquired infections, often associated with limited therapeutic options. We investigated A. baumannii isolates at a New York hospital to characterize genetic relatedness.Thirty A. baumannii isolates from geographically-dispersed nursing units within the hospital were studied. Isolate relatedness was assessed by repetitive sequence polymerase chain reaction (rep-PCR). The presence and characteristics of integrons were assessed by PCR. Metabolomic profiles of a subset of a prevalent strain isolates and sporadic isolates were characterized and compared.We detected a hospital-wide group of closely related carbapenem resistant MDR A. baumannii isolates. Compared with sporadic isolates, the prevalent strain isolates were more likely to be MDR (p = 0.001). Isolates from the prevalent strain carried a novel Class I integron sequence. Metabolomic profiles of selected prevalent strain isolates and sporadic isolates were similar.The A. baumannii population at our hospital represents a prevalent strain of related MDR isolates that contain a novel integron cassette. Prevalent strain and sporadic isolates did not segregate by metabolomic profiles. Further study of environmental, host, and bacterial factors associated with the persistence of prevalent endemic A. baumannii strains is needed to develop effective prevention strategies

    Transcriptomic Profiling of Virus-Host Cell Interactions following Chicken Anaemia Virus (CAV) Infection in an In Vivo Model.

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    Chicken Anaemia Virus (CAV) is an economically important virus that targets lymphoid and erythroblastoid progenitor cells leading to immunosuppression. This study aimed to investigate the interplay between viral infection and the host's immune response to better understand the pathways that lead to CAV-induced immunosuppression. To mimic vertical transmission of CAV in the absence of maternally-derived antibody, day-old chicks were infected and their responses measured at various time-points post-infection by qRT-PCR and gene expression microarrays. The kinetics of mRNA expression levels of signature cytokines of innate and adaptive immune responses were determined by qRT-PCR. The global gene expression profiles of mock-infected (control) and CAV-infected chickens at 14 dpi were also compared using a chicken immune-related 5K microarray. Although in the thymus there was evidence of induction of an innate immune response following CAV infection, this was limited in magnitude. There was little evidence of a Th1 adaptive immune response in any lymphoid tissue, as would normally be expected in response to viral infection. Most cytokines associated with Th1, Th2 or Treg subsets were down-regulated, except IL-2, IL-13, IL-10 and IFNγ, which were all up-regulated in thymus and bone marrow. From the microarray studies, genes that exhibited significant (greater than 1.5-fold, false discovery rate <0.05) changes in expression in thymus and bone marrow on CAV infection were mainly associated with T-cell receptor signalling, immune response, transcriptional regulation, intracellular signalling and regulation of apoptosis. Expression levels of a number of adaptor proteins, such as src-like adaptor protein (SLA), a negative regulator of T-cell receptor signalling and the transcription factor Special AT-rich Binding Protein 1 (SATB1), were significantly down-regulated by CAV infection, suggesting potential roles for these genes as regulators of viral infection or cell defence. These results extend our understanding of CAV-induced immunosuppression and suggest a global immune dysregulation following CAV infection

    The Human Operculo-Insular Cortex Is Pain-Preferentially but Not Pain-Exclusively Activated by Trigeminal and Olfactory Stimuli

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    Increasing evidence about the central nervous representation of pain in the brain suggests that the operculo-insular cortex is a crucial part of the pain matrix. The pain-specificity of a brain region may be tested by administering nociceptive stimuli while controlling for unspecific activations by administering non-nociceptive stimuli. We applied this paradigm to nasal chemosensation, delivering trigeminal or olfactory stimuli, to verify the pain-specificity of the operculo-insular cortex. In detail, brain activations due to intranasal stimulation induced by non-nociceptive olfactory stimuli of hydrogen sulfide (5 ppm) or vanillin (0.8 ppm) were used to mask brain activations due to somatosensory, clearly nociceptive trigeminal stimulations with gaseous carbon dioxide (75% v/v). Functional magnetic resonance (fMRI) images were recorded from 12 healthy volunteers in a 3T head scanner during stimulus administration using an event-related design. We found that significantly more activations following nociceptive than non-nociceptive stimuli were localized bilaterally in two restricted clusters in the brain containing the primary and secondary somatosensory areas and the insular cortices consistent with the operculo-insular cortex. However, these activations completely disappeared when eliminating activations associated with the administration of olfactory stimuli, which were small but measurable. While the present experiments verify that the operculo-insular cortex plays a role in the processing of nociceptive input, they also show that it is not a pain-exclusive brain region and allow, in the experimental context, for the interpretation that the operculo-insular cortex splay a major role in the detection of and responding to salient events, whether or not these events are nociceptive or painful

    Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

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    The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants
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