34 research outputs found

    Nano dust impacts on spacecraft and boom antenna charging

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    High rate sampling detectors measuring the potential difference between the main body and boom antennas of interplanetary spacecraft have been shown to be efficient means to measure the voltage pulses induced by nano dust impacts on the spacecraft body itself (see Meyer-Vernet et al, Solar Phys. 256, 463 (2009)). However, rough estimates of the free charge liberated in post impact expanding plasma cloud indicate that the cloud's own internal electrostatic field is too weak to account for measured pulses as the ones from the TDS instrument on the STEREO spacecraft frequently exceeding 0.1 V/m. In this paper we argue that the detected pulses are not a direct measure of the potential structure of the plasma cloud, but are rather the consequence of a transitional interruption of the photoelectron return current towards the portion of the antenna located within the expanding cloud

    Gut microbiota alteration in adolescent anorexia nervosa does not normalize with short-term weight restoration

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    Objective: Gut microbiota are linked to metabolic function, body weight regulation, and brain and behavioral changes. Alteration of gut microbiota is repeatedly demon- strated in adults with anorexia nervosa (AN) and transplantation of stool from adult patients with AN reduces weight gain, food consumption and food efficiency in germ-free mice. No similar data are available for adolescents, who might differ from adults due to their shorter duration of illness. Method: Nineteen female adolescent patients with AN at admission and after short-term weight recovery were included in a longitudinal study and compared to 20 healthy controls (HC). DNA was extracted from stool samples and subjected to 16S rRNA gene sequencing and analysis. Group comparisons, indicator genera and simper analysis were applied. Taxon abundances at admission was used to predict inpatient treatment duration. Results: Alpha diversity is increased in patients with AN after short-term weight recov- ery, while beta diversity shows clear group differences with HC before and after weight gain. A reduction in Romboutsia and taxa belonging to Enterobacteriaceae at both timepoints and an increase in taxa belonging to Lachnospiraceae at discharge are most indicative of patients. Lachnospiraceae abundance at admission helped to predict shorter inpatient treatment duration. Discussion: This pilot study provides first evidence of gut microbiota alterations in adolescent patients with AN that do not normalize with weight gain. If verified in larger studies, the predictive power of taxa belonging to Lachnospiraceae for clinical outcome could complement known predictors at admission, inform clinicians and serve as a target for nutritional interventions

    Characterization of the skin microbiota in bullous pemphigoid patients and controls reveals novel microbial indicators of disease

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    Introduction: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. It predominately afflicts the elderly and is significantly associated with increased mortality. The observation of age-dependent changes in the skin microbiota as well as its involvement in other inflammatory skin disorders suggests that skin microbiota may play a role in the emergence of BP blistering. We hypothesize that changes in microbial diversity associated with BP might occur before the emergence of disease lesions, and thus could represent an early indicator of blistering risk. Objectives: The present study aims to investigate potential relationships between skin microbiota and BP and elaborate on important changes in microbial diversity associated with blistering in BP. Methods: The study consisted of an extensive sampling effort of the skin microbiota in patients with BP and age- and sex-matched controls to analyze whether intra-individual, body site, and/or geographical variation correlate with changes in skin microbial composition in BP and/or blistering status. Results: We find significant differences in the skin microbiota of patients with BP compared to that of controls, and moreover that disease status rather than skin biogeography (body site) governs skin microbiota composition in patients with BP. Our data reveal a discernible transition between normal skin and the skin surrounding BP lesions, which is characterized by a loss of protective microbiota and an increase in sequences matching Staphylococcus aureus, a known inflammation-promoting species. Notably, Staphylococcus aureus is ubiquitously associated with BP disease status, regardless of the presence of blisters. Conclusion: The present study suggests Staphylococcus aureus may be a key taxon associated with BP disease status. Importantly, we however find contrasting patterns in the relative abundances of Staphylococcus hominis and Staphylococcus aureus reliably discriminate between patients with BP and matched controls. This may serve as valuable information for assessing blistering risk and treatment outcomes in a clinical setting

    Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line

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    Phenotypic variation of quantitative traits is orchestrated by a complex interplay between the environment (e.g. diet) and genetics. However, the impact of gene-environment interactions on phenotypic traits mostly remains elusive. To address this, we feed 1154 mice of an autoimmunity-prone intercross line (AIL) three different diets. We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL). By performing whole-genome sequencing of the AIL founder strains, we resolve these QTLs to few or single candidate genes. To address whether diet can also modulate genetic predisposition towards a given trait, we set NZM2410/J mice on similar dietary regimens as AIL mice. Our data suggest that diet modifies genetic susceptibility to lupus and shifts intestinal bacterial and fungal community composition, which precedes clinical disease manifestation. Collectively, our study underlines the importance of including environmental factors in genetic association studies

    Analysis of the skin microbiota in house mice using genetic, evolutionary and ecological approaches

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    Throughout their evolutionary history, animals have been continuously exposed to a great diversity of microbial species with which they have co-existed across various types of environments. So far, our knowledge about the co-evolutionary dynamics between hosts and their symbiotic microbial communities remains poor and is nearly exclusively derived from gut-associated microbiota, while further barrier organs including the skin harbor diverse and complex microbial communities. Indeed, only few studies addressed the impact of skinassociated microbiota on host fitness, and even fewer inspected the forces shaping interindividual variability of the skin microbiota. Using the house mouse as a model organism, in my thesis projects, I aimed to bring new insights into the evolutionary and ecological processes that govern the skin-associated bacterial communities. In a first study, by employing several mouse lines that represent various evolutionary distances, I evaluated the effects of environment and host genetics in shaping the composition and diversity of the standing (DNA-based profiling) skin microbiota. I found a large influence of the external environment and a moderate effect of host genetics on the composition and diversity of skin bacterial communities. Second, to further quantify and define host genomic regions that co-vary with abundances of skin bacterial taxa, I performed high-resolution QTL mapping on standing and active (RNA-based profiling) skin microbiota using the fifteenth generation of an advanced intercross mouse population. The defined QTLs span narrow intervals, while some target single host genes. Additionally, the number of QTLs within the active communities is considerably higher compared to the standing communities, suggesting that profiling the skin microbiota at the transcript level provides stronger signals about host-microbiota interactions. Finally, in order to uncover similarities and divergences in community diversity and structure of the skin microbiota between natural and laboratory reared populations of house mice, I thoroughly compared the composition and structure of both standing and active bacterial communities of wild and laboratory individuals. This first of its kind investigation reveals extensive overlap in the community membership of wild and laboratory mice, indicating that communities assembled in a similar manner. Interestingly, we report significant structural changes between these two mouse groups along with a greater inter-individual variation within the laboratory reared mice. Together, these findings meaningfully extend our current knowledge about the forces that govern the diversity of skin-associated bacterial communities

    Methods for microbiota analysis: sample collection and laboratory methods

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    The human body hosts a myriad of complex and diversified microbial assemblages on various barrier organs. The symbiotic microbial communities impact several aspects of the host’s biology in health and disease. Nowadays, microbiota research has become a central area of investigation involving diverse fields such as immunology, nutrition, and genetics. Consequently, methods for microbiota studies, comprising study design and laboratory techniques, are central in addressing general and specific research questions and especially in providing clear and reliable insights. Fortunately, approaches that investigate different aspects of microbial communities have greatly improved and expanded allowing unprecedented levels of characterization of host-microbiota interactions. Through this chapter, we aim to describe the diverse techniques available for researchers to examine bacterial communities associated with numerous human body sites. We describe various culture-based and sequencing methods, additional techniques that characterize several aspects of the entire bacterial community, as well as approaches that define the status of single cells. Moreover, we describe the advantageous strategy of combining distinct approaches in a microbiota study to collect different and complementary insights on the community and/or to confirm each different method’s outcome. Additionally, we thoroughly discuss the crucial steps of study design, sampling strategies, and sample collection and processing which influence the interpretation and conclusions of microbiota study. Overall, this chapter clarifies the critical steps and available investigation tools in a microbiota study and thus assists researchers in defining the experimental design and laboratory methods to conduct a microbiota study

    El Diario de Pontevedra : periĂłdico liberal: Ano XXII NĂşmero 4007 - 1905 novembro 16

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    BACKGROUND: Recent studies highlight the utility of quantitative trait locus (QTL) mapping for determining the contribution of host genetics to interindividual variation in the microbiota. We previously demonstrated that similar to the gut microbiota, abundances of bacterial taxa in the skin are significantly influenced by host genetic variation. In this study, we analyzed the skin microbiota of mice from the 15th generation of an advanced intercross line using a novel approach of extending bacterial trait mapping to both the 16S rRNA gene copy (DNA) and transcript (RNA) levels, which reflect relative bacterial cell number and activity, respectively. RESULTS: Remarkably, the combination of highly recombined individuals and 53,203 informative SNPs allowed the identification of genomic intervals as small as <0.1 megabases containing single genes. Furthermore, the inclusion of 16S rRNA transcript-level mapping dramatically increased the number of significant associations detected, with five versus 21 significant SNP-bacterial trait associations based on DNA- compared to RNA-level profiling, respectively. Importantly, the genomic intervals identified contain many genes involved in skin inflammation and cancer and are further supported by the bacterial traits they influence, which in some cases have known genotoxic or probiotic capabilities. CONCLUSIONS: These results indicate that profiling based on the relative activity levels of bacterial community members greatly enhances the capability of detecting interactions between the host and its associated microbes. Finally, the identification of several genes involved in skin cancer suggests that similar to colon carcinogenesis, the resident microbiota may play a role in skin cancer susceptibility and its potential prevention and/or treatment

    Assessing similarities and disparities in the skin microbiota between wild and laboratory populations of house mice

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    The house mouse is a key model organism in skin research including host–microbiota interactions, yet little is known about the skin microbiota of free-living mice. It is similarly unclear how closely laboratory mice, which typically live under exceptionally hygienic conditions, resemble the ancestral state of microbial variation in the wild. In this study, we sampled an area spanning 270 km2 in south-west France and collected 203 wild Mus musculus domesticus. We profiled the ear skin microbiota on standing and active communities (DNA-based and RNA-based 16 rRNA gene sequencing, respectively), and compared multiple community aspects between wild-caught and laboratory-reared mice kept in distinct facilities. Compared to lab mice, we reveal the skin microbiota of wild mice on the one hand to be unique in their composition within the Staphylococcus genus, with a majority of sequences most closely matching known novobiocin-resistant species, and display evidence of a rare biosphere. On the other hand, despite drastic disparities between natural and laboratory environments, we find that shared taxa nonetheless make up the majority of the core skin microbiota of both wild- and laboratory skin communities, suggesting that mammalian skin is a highly specialized habitat capable of strong selection from available species pools. Finally, the influence of environmental factors suggests RNA-based profiling as a preferred method to reduce environmental noise

    Genome-wide mapping of gene-microbe interactions in the murine lung microbiota based on quantitative microbial profiling

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    Abstract Background Mammalian lungs comprise a complex microbial ecosystem that interacts with host physiology. Previous research demonstrates that the environment significantly contributes to bacterial community structure in the upper and lower respiratory tract. However, the influence of host genetics on the makeup of lung microbiota remains ambiguous, largely due to technical difficulties related to sampling, as well as challenges inherent to investigating low biomass communities. Thus, innovative approaches are warranted to clarify host-microbe interactions in the mammalian lung. Results Here, we aimed to characterize host genomic regions associated with lung bacterial traits in an advanced intercross mouse line (AIL). By performing quantitative microbial profiling (QMP) using the highly precise method of droplet digital PCR (ddPCR), we refined 16S rRNA gene amplicon-based traits to identify and map candidate lung-resident taxa using a QTL mapping approach. In addition, the two abundant core taxa Lactobacillus and Pelomonas were chosen for independent microbial phenotyping using genus-specific primers. In total, this revealed seven significant loci involving eight bacterial traits. The narrow confidence intervals afforded by the AIL population allowed us to identify several promising candidate genes related to immune and inflammatory responses, cell apoptosis, DNA repair, and lung functioning and disease susceptibility. Interestingly, one genomic region associated with Lactobacillus abundance contains the well-known anti-inflammatory cytokine Il10, which we confirmed through the analysis of Il10 knockout mice. Conclusions Our study provides the first evidence for a role of host genetic variation contributing to variation in the lung microbiota. This was in large part made possible through the careful curation of 16S rRNA gene amplicon data and the incorporation of a QMP-based methods. This approach to evaluating the low biomass lung environment opens new avenues for advancing lung microbiome research using animal models. Graphical Abstrac
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