132 research outputs found
Mixed reproductive strategies of the Common moorhen on a microscale as revealed by genetic data
A031 DĂ©veloppement dâun peptido-mimĂ©tique de la glycorpotein VI plaquettaire comme outil dâimagerie de la fibrose
ObjectifLa glycoprotĂ©ine VI est le rĂ©cepteur dâactivation des plaquettes par les collagĂšnes de type I et de type III. Nous avons Ă©mis lâhypothĂšse que nous pourrions dĂ©velopper une sonde spĂ©cifique du collagĂšne basĂ©e sur la spĂ©cificitĂ© de GPVI et que cette sonde permettrait de visualiser la fibrose in vivo par une mĂ©thode non invasive.MĂ©thodesUn anticorps bloquant la liaison de GPVI au collagĂšne a Ă©tĂ© utilisĂ© pour cribler une banque peptidique permettant dâidentifier un motif peptidique cyclique. La capacitĂ© du peptide Ă mimer la GPVI a Ă©tĂ© analysĂ©e par des Ă©tudes de liaison et de compĂ©tition en phase solide. La liaison au collagĂšne tissulaire a Ă©tĂ© analysĂ©e par histochimie. Lâimagerie in vivo a Ă©tĂ© rĂ©alisĂ©e par injection du peptide-marquĂ© au Tc-99m dans un modĂšle de fibrose cicatricielle sur infarctus du myocarde chez le rat, scintigraphie et autoradiographieRĂ©sultatsLe peptide, nommĂ© collagelin, se lie de maniĂšre spĂ©cifique Ă lâanticorps anti GPVI 9O12.2 et aux collagĂšnes I et III in vitro et la liaison est inhibĂ©e par GPVI indiquant que le peptide mime GPVI. Cependant le collagelin nâinhibe pas lâagrĂ©gation des plaquettes induite par le collagĂšne. Les Ă©tudes dâhistochimie montrent que le collagelin se lie au collagĂšne tissulaire sur coupe dâaorte et de queue de rat indiquant que le collagelin se comporte comme un traceur du collagĂšne. Dans le modĂšle dâinfarctus cicatriciel, une accumulation du collagelin radiomarquĂ© est observĂ©e dans la zone cardiaque par scintigraphie planaire et tomographie chez les animaux avec MI mais pas chez les animaux contrĂŽles ni avec un peptide contrĂŽle. Lâaccumulation du traceur dans les zones de fibrose a Ă©tĂ© mise en Ă©vidence ex vivo par superposition des images dâautoradiographies et dâhistologie sur coupes congelĂ©es.ConclusionNous avons produit un peptide qui mime en partie le site de liaison de GPVI au collagĂšne. Ce peptide se comporte comme un traceur spĂ©cifique du collagĂšne in vitro et in vivo. Nous proposons que ce traceur pourrait ĂȘtre utile pour le diagnostic et le suivi Ă©volutif de la fibrose dans un grand nombre de pathologies
Environment is associated with chytrid infection and skin microbiome richness on an amphibian rich island (Taiwan)
Growing evidence suggests that the origins of the panzootic amphibian pathogens Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal) are in Asia. In Taiwan, an island hotspot of high amphibian diversity, no amphibian mass mortality events linked to Bd or Bsal have been reported. We conducted a multi-year study across this subtropical island, sampling 2517 individuals from 30 species at 34 field sites, between 2010 and 2017, and including 171 museum samples collected between 1981 and 2009. We analyzed the skin microbiome of 153 samples (6 species) from 2017 in order to assess any association between the amphibian skin microbiome and the probability of infection amongst different host species. We did not detect Bsal in our samples, but found widespread infection by Bd across central and northern Taiwan, both taxonomically and spatially. Museum samples show that Bd has been present in Taiwan since at least 1990. Host species, geography (elevation), climatic conditions and microbial richness were all associated with the prevalence of infection. Host life-history traits, skin microbiome composition and phylogeny were associated with lower prevalence of infection for high altitude species. Overall, we observed low prevalence and burden of infection in host populations, suggesting that Bd is enzootic in Taiwan where it causes subclinical infections. While amphibian species in Taiwan are currently threatened by habitat loss, our study indicates that Bd is in an endemic equilibrium with the populations and species we investigated. However, ongoing surveillance of the infection is warranted, as changing environmental conditions may disturb the currently stable equilibrium
Transcriptomic profiles of muscle, heart, and spleen in reaction to circadian heat stress in Ethiopian highland and lowland male chicken
Temperature stress impacts both welfare and productivity of livestock. Global warming is expected to increase the impact, especially in tropical areas. We investigated the biological mechanisms regulated by temperature stress due to the circadian temperature cycle in temperature adapted and non-adapted chicken under tropical conditions. We studied transcriptome profiles of heart, breast muscle, and spleen tissues of Ethiopian lowland chicken adapted to high circadian temperatures and non-adapted Ethiopian highland chicken under lowland conditions at three points during the day: morning, noon, and evening. Functional annotations and network analyses of genes differentially expressed among the time points of the day indicate major differences in the reactions of the tissues to increasing and decreasing temperatures, and also the two chickens lines differ. However, epigenetic changes of chromatin methylation and histone (de)acetylation seemed to be central regulatory mechanisms in all tissues in both chicken lines. Finally, all tissues showed differentially expressed genes between morning and evening times indicating biological mechanisms that need to change during the night to reach morning levels again the next day.</p
Microbiome function predicts amphibian chytridiomycosis disease dynamics
[Background] The fungal pathogenBatrachochytrium dendrobatidis (Bd) threatens amphibian biodiversity and ecosystem stability worldwide. Amphibian skin microbial community structure has been linked to the clinical outcome of Bd infections, yet its overall functional importance is poorly understood. [Methods] Microbiome taxonomic and functional profiles were assessed using high-throughput bacterial 16S rRNA and fungal ITS2 gene sequencing, bacterial shotgun metagenomics and skin mucosal metabolomics. We sampled 56 wild midwife toads (Alytes obstetricans) from montane populations exhibiting Bd epizootic or enzootic disease dynamics. In addition, to assess whether disease-specific microbiome profiles were linked to microbe-mediated protection or Bd-induced perturbation, we performed a laboratory Bd challenge experiment whereby 40 young adult A. obstetricans were exposed to Bd or a control sham infection. We measured temporal changes in the microbiome as well as functional profiles of Bd-exposed and control animals at peak infection. [Results] Microbiome community structure and function differed in wild populations based on infection history and in experimental control versus Bd-exposed animals. Bd exposure in the laboratory resulted in dynamic changes in microbiome community structure and functional differences, with infection clearance in all but one infected animal. Sphingobacterium, Stenotrophomonas and an unclassified Commamonadaceae were associated with wild epizootic dynamics and also had reduced abundance in laboratory Bd-exposed animals that cleared infection, indicating a negative association with Bd resistance. This was further supported by microbe-metabolite integration which identified functionally relevant taxa driving disease outcome, of which Sphingobacterium and Bd were most influential in wild epizootic dynamics. The strong correlation between microbial taxonomic community composition and skin metabolome in the laboratory and field is inconsistent with microbial functional redundancy, indicating that differences in microbial taxonomy drive functional variation. Shotgun metagenomic analyses support these findings, with similar disease-associated patterns in beta diversity. Analysis of differentially abundant bacterial genes and pathways indicated that bacterial environmental sensing and Bd resource competition are likely to be important in driving infection outcomes. [Conclusions] Bd infection drives altered microbiome taxonomic and functional profiles across laboratory and field environments. Our application of multi-omics analyses in experimental and field settings robustly predicts Bd disease dynamics and identifies novel candidate biomarkers of infection. [MediaObject not available: see fulltext.]K.A.B. was funded by a CASE studentship from NERC, NERC Biomolecular Analysis Facility grant (NBAF939) and an E.P. Abraham Junior Research Fellowship from St Hildaâs College, University of Oxford. M.C.F and T.W.J.G. were funded by NERC award NE/E006701/1 and the Biodiversa project RACE: Risk Assessment of Chytridiomycosis to European Amphibian Biodiversity. T.W.J.G was also funded by Research England and NERC NE/S000062/1. D.S.S. and A.L. received funding through the project People, Pollution, and Pathogens financed through the call âMountains as Sentinels of Changeâ by the Belmont-Forum (ANR-15-MASC-0001 - P3, DFG-SCHM3059/6-1, NERC-1633948, NSFC-41661144004). D.S.S. holds the AXA Chair for Functional Mountain Ecology funded by the AXA Research Fund through the project GloMEc and M.C.F. is a fellow in the CIFAR âFungal Kingdomsâ Program
Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma
Antibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. ISB 1442 consists of two anti-CD38 arms targeting two distinct epitopes that preferentially drive binding to tumor cells and enable avidity-induced blocking of proximal CD47 receptors on the same cell while preventing on-target off-tumor binding on healthy cells. The Fc portion of ISB 1442 is engineered to enhance complement dependent cytotoxicity, antibody dependent cell cytotoxicity and antibody dependent cell phagocytosis. ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma
Immune-Mediated Change in the Expression of a Sexual Trait Predicts Offspring Survival in the Wild
BACKGROUND: The "good genes" theory of sexual selection postulates that females choose mates that will improve their offspring's fitness through the inheritance of paternal genes. In spite of the attention that this hypothesis has given rise to, the empirical evidence remains sparse, mostly because of the difficulties of controlling for the many environmental factors that may covary with both the paternal phenotype and offspring fitness. Here, we tested the hypothesis that offspring sired by males of a preferred phenotype should have better survival in an endangered bird, the houbara bustard (Chlamydotis undulata undulata). METHODOLOGY/PRINCIPAL FINDINGS: We tested if natural and experimentally-induced variation in courtship display (following an inflammatory challenge) predicts the survival of offspring. Chicks were produced by artificial insemination of females, ensuring that any effect on survival could only arise from the transfer of paternal genes. One hundred and twenty offspring were equipped with radio transmitters, and their survival monitored in the wild for a year. This allowed assessment of the potential benefits of paternal genes in a natural setting, where birds experience the whole range of environmental hazards. Although natural variation in sire courtship display did not predict offspring survival, sires that withstood the inflammatory insult and maintained their courtship activity sired offspring with the best survival upon release. CONCLUSIONS: This finding is relevant both to enlighten the debate on "good genes" sexual selection and the management of supportive breeding programs
Heritability of body surface temperature in hens estimated by infrared thermography at normal or hot temperatures and genetic correlations with egg and feather quality
People, pollution and pathogens â Global change impacts in mountain freshwater ecosystems
Mountain catchments provide for the livelihood of more than half of humankind, and have become a key destination for tourist and recreation activities globally. Mountain ecosystems are generally considered to be less complex and less species diverse due to the harsh environmental conditions. As such, they are also more sensitive to the various impacts of the Anthropocene. For this reason,mountain regions may serve as sentinels of change and provide ideal ecosystems for studying climate and global change impacts on biodiversity. We here review different facets of anthropogenic impacts on mountain freshwater ecosystems. We put particular focus on micropollutants and their distribution and redistribution due to hydrological extremes, their direct influence on water quality and their indirect influence on ecosystem health via changes of freshwater species and their interactions. We show that those changes may drive pathogen establishment in new environments with harmful consequences for freshwater species, but also for the human population. Based on the reviewed literature, we recommend reconstructing the recent past of anthropogenic impact through sediment analyses, to focus efforts on small, but highly productive waterbodies, and to collect data on the occurrence and variability of microorganisms, biofilms, plankton species and key species, such as amphibians due to their bioindicator value for ecosystem health and water quality. The newly gained knowledge can then be used to develop a comprehensive framework of indicators to robustly inform policy and decision making on current and future risks for ecosystem health and human well-being
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