The microbial communities that inhabit the distal gut of humans and other mammals exhibit large inter-individual variation. While host genetics is a known factor that influences gut microbiota ...composition, the mechanisms underlying this variation remain largely unknown. Bile acids (BAs) are hormones that are produced by the host and chemically modified by gut bacteria. BAs serve as environmental cues and nutrients to microbes, but they can also have antibacterial effects. We hypothesized that host genetic variation in BA metabolism and homeostasis influence gut microbiota composition. To address this, we used the Diversity Outbred (DO) stock, a population of genetically distinct mice derived from eight founder strains. We characterized the fecal microbiota composition and plasma and cecal BA profiles from 400 DO mice maintained on a high-fat high-sucrose diet for ~22 weeks. Using quantitative trait locus (QTL) analysis, we identified several genomic regions associated with variations in both bacterial and BA profiles. Notably, we found overlapping QTL for Turicibacter sp. and plasma cholic acid, which mapped to a locus containing the gene for the ileal bile acid transporter, Slc10a2. Mediation analysis and subsequent follow-up validation experiments suggest that differences in Slc10a2 gene expression associated with the different strains influences levels of both traits and revealed novel interactions between Turicibacter and BAs. This work illustrates how systems genetics can be utilized to generate testable hypotheses and provide insight into host-microbe interactions.
The International Linear Collider (ILC) Time Projection Chamber (TPC) transverse space-point resolution goal is
100
μ
m
for all tracks including stiff
90
∘
tracks with the full
∼
2
m
drift. A ...Micro-Pattern Gas Detector (MPGD) readout TPC can achieve the target resolution with existing techniques using 1
mm or narrower pads at the expense of increased detector cost and complexity. The new MPGD readout technique of charge dispersion can achieve good resolution without resorting to narrow pads. This has been demonstrated previously for
2
mm
×
6
mm
pads with GEMs and Micromegas in cosmic ray tests and in a KEK beam test in a 1
T magnet. We have recently tested a Micromegas-TPC using the charge dispersion readout concept in a high field super-conducting magnet at DESY. The measured Micromegas gain was found to be constant within 0.5% for magnetic fields up to 5
T. With the strong suppression of transverse diffusion at high magnetic fields, we measure a flat
50
μ
m
resolution at 5
T over the full 15
cm drift length of our prototype TPC.
Genotyping microarrays are an important resource for genetic mapping, population genetics, and monitoring of the genetic integrity of laboratory stocks. We have developed the third generation of the ...Mouse Universal Genotyping Array (MUGA) series, GigaMUGA, a 143,259-probe Illumina Infinium II array for the house mouse (Mus musculus). The bulk of the content of GigaMUGA is optimized for genetic mapping in the Collaborative Cross and Diversity Outbred populations, and for substrain-level identification of laboratory mice. In addition to 141,090 single nucleotide polymorphism probes, GigaMUGA contains 2006 probes for copy number concentrated in structurally polymorphic regions of the mouse genome. The performance of the array is characterized in a set of 500 high-quality reference samples spanning laboratory inbred strains, recombinant inbred lines, outbred stocks, and wild-caught mice. GigaMUGA is highly informative across a wide range of genetically diverse samples, from laboratory substrains to other Mus species. In addition to describing the content and performance of the array, we provide detailed probe-level annotation and recommendations for quality control.
Genetic variation drives phenotypic diversity and influences the predisposition to metabolic disease. Here, we characterize the metabolic phenotypes of eight genetically distinct inbred mouse strains ...in response to a high-fat/high-sucrose diet. We found significant variation in diabetes-related phenotypes and gut microbiota composition among the different mouse strains in response to the dietary challenge and identified taxa associated with these traits. Follow-up microbiota transplant experiments showed that altering the composition of the gut microbiota modifies strain-specific susceptibility to diet-induced metabolic disease. Animals harboring microbial communities with enhanced capacity for processing dietary sugars and for generating hydrophobic bile acids showed increased susceptibility to metabolic disease. Notably, differences in glucose-stimulated insulin secretion between different mouse strains were partially recapitulated via gut microbiota transfer. Our results suggest that the gut microbiome contributes to the genetic and phenotypic diversity observed among mouse strains and provide a link between the gut microbiome and insulin secretion.
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•Host genotype affects the abundance of taxa associated with metabolic disease•Gut microbiota affects susceptibility to diet-induced metabolic disease•The gut microbiome modulates insulin secretion
Host genetics modulates the development of metabolic disease and shapes the composition of the gut microbiota. Kreznar et al. demonstrate that the gut microbiota contributes to strain-specific susceptibility to diet-induced metabolic disease and identify links between microbial metabolism and insulin secretion.
Operation of a resistive Micromegas in air Procureur, S.; Attié, D.; Aune, S. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
10/2012, Letnik:
688
Journal Article
Recenzirano
The recent developments on resistive Micromegas have enhanced the performance of this detector, and in particular have offered the possibility to reach higher amplification gains in stable operation. ...In this paper, the detection capabilities of a resistive Micromegas in air have been investigated. A clear Fe55 spectrum has been obtained, as well as MIP signals using cosmic rays. In the latter case, the detection efficiency reaches 42%, and could probably be further improved. The stable operation of a gaseous detector in air, i.e. without bottles, pipes or safety systems, can lead to many new applications or simplifications of existing setups.
Mitochondria are dynamic organelles that play a central role in a diverse array of metabolic processes. Elucidating mitochondrial adaptations to changing metabolic demands and the pathogenic ...alterations that underlie metabolic disorders represent principal challenges in cell biology. Here, we performed multiplexed quantitative mass spectrometry-based proteomics to chart the remodeling of the mouse liver mitochondrial proteome and phosphoproteome during both acute and chronic physiological transformations in more than 50 mice. Our analyses reveal that reversible phosphorylation is widespread in mitochondria, and is a key mechanism for regulating ketogenesis during the onset of obesity and type 2 diabetes. Specifically, we have demonstrated that phosphorylation of a conserved serine on Hmgcs2 (S456) significantly enhances its catalytic activity in response to increased ketogenic demand. Collectively, our work describes the plasticity of this organelle at high resolution and provides a framework for investigating the roles of proteome restructuring and reversible phosphorylation in mitochondrial adaptation.
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▸ MS/MS identified 811 phosphorylation sites on 295 mitochondrial proteins in liver ▸ More than 41% of mitochondrial phosphoisoforms changed across metabolic conditions ▸ Phosphorylation of serine 456 on Hmgcs2 correlates with ketone body levels in mice ▸ Hmgcs2 S456 phosphorylation increases enzyme activity and ketogenesis
Strong ULF wave activity has been observed at magnetopause crossings over a long time. Those turbulent like waves are possibly one of the contributors to particle penetration from the solar wind to ...the magnetosphere through the magnetopause. Spatio Temporal Analysis of Field Fluctuations wave experiments onboard Cluster and Double Star TC1 spacecraft permit the comparison of those waves during quasi‐simultaneous magnetopause crossings, some being at the same local time but at different latitude, the TC1 Double Star orbit being nearly equatorial and the Cluster orbit being polar. From a survey of the first half of year 2004 and beginning of 2005 data, 23 coordinated magnetopause crossings have been identified, out of which 11 are at the same local time, for which the wave power density has been calculated. No clear dependence in local time has been found; in particular, the wave power density is not stronger at noon in the vicinity of the subsolar point than at other local times, the morning hour data showing more dispersed values than afternoon ones. For most of the events occurring at the same local time, the wave power density measured by Double Star (at low latitude) is stronger than the one measured by the Cluster spacecraft (at much higher latitude). If those first results were to be confirmed, it could imply a predominant role of the equatorial plane in the solar wind/ magnetosphere coupling via ULF wave turbulence, with no preference for the subsolar region.
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