321 research outputs found

    Taxonomic Features and Comparison of the Gut Microbiome from Two Edible Fungus-Farming Termites (Macrotermes falciger, M. natalensis) Harvested in the Vhembe District of Limpopo, South Africa

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    Background Termites are an important food resource for many human populations around the world, and are a good supply of nutrients. The fungus-farming ‘higher’ termite members of Macrotermitinae are also consumed by modern great apes and are implicated as critical dietary resources for early hominins. While the chemical nutritional composition of edible termites is well known, their microbiomes are unexplored in the context of human health. Here we sequenced the V4 region of the 16S rRNA gene of gut microbiota extracted from the whole intestinal tract of two Macrotermes sp. soldiers collected from the Limpopo region of South Africa. Results Major and minor soldier subcastes of M. falciger exhibit consistent differences in taxonomic representation, and are variable in microbial presence and abundance patterns when compared to another edible but less preferred species, M. natalensis. Subcaste differences include alternate patterns in sulfate-reducing bacteria and methanogenic Euryarchaeota abundance, and differences in abundance between Alistipes and Ruminococcaceae. M. falciger minor soldiers and M. natalensissoldiers have similar microbial profiles, likely from close proximity to the termite worker castes, particularly during foraging and fungus garden cultivation. Compared with previously published termite and cockroach gut microbiome data, the taxonomic representation was generally split between termites that directly digest lignocellulose and humic substrates and those that consume a more distilled form of nutrition as with the omnivorous cockroaches and fungus-farming termites. Lastly, to determine if edible termites may point to a shared reservoir for rare bacterial taxa found in the gut microbiome of humans, we focused on the genus Treponema. The majority of Treponemasequences from edible termite gut microbiota most closely relate to species recovered from other termites or from environmental samples, except for one novel OTU strain, which clustered separately with Treponema found in hunter-gatherer human groups. Conclusions Macrotermes consumed by humans display special gut microbial arrangements that are atypical for a lignocellulose digesting invertebrate, but are instead suited to the simplified nutrition in the fungus-farmer diet. Our work brings to light the particular termite microbiome features that should be explored further as avenues in human health, agricultural sustainability, and evolutionary research

    The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1–6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7–34 pathogenic variant

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    Purpose: CADASIL is a small-vessel disease caused by a cysteine-altering pathogenic variant in one of the 34 epidermal growth factor-like repeat (EGFr) domains of the NOTCH3 protein. We recently found that pathogenic variant in EGFr domains 7\u201334 have an unexpectedly high frequency in the general population (1:300). We hypothesized that EGFr 7\u201334 pathogenic variant more frequently cause a much milder phenotype, thereby explaining an important part of CADASIL disease variability. Methods: Age at first stroke, survival and white matter hyperintensity volume were compared between 664 CADASIL patients with either a NOTCH3 EGFr 1\u20136 pathogenic variant or an EGFr 7\u201334 pathogenic variant. The frequencies of NOTCH3 EGFr 1\u20136 and EGFr 7\u201334 pathogenic variant were compared between individuals in the genome Aggregation Database and CADASIL patients. Results: CADASIL patients with an EGFr 1\u20136 pathogenic variant have a 12-year earlier onset of stroke than those with an EGFr 7\u201334 pathogenic variant, lower survival, and higher white matter hyperintensity volumes. Among diagnosed CADASIL patients, 70% have an EGFr 1\u20136 pathogenic variant, whereas EGFr 7\u201334 pathogenic variant strongly predominate in the population. Conclusion: NOTCH3 pathogenic variant position is the most important determinant of CADASIL disease severity, with EGFr 7\u201334 pathogenic variant predisposing to a later onset of stroke and longer survival

    Polarization of Lambda^0 hyperons in nucleus-nucleus collisions at high energies

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    The measurement of Lambda^0 hyperons polarization in nucleus-nucleus collisions is considered as one of possible tools to study the phase transition. Fixed target and collider experiments are discussed for the case of Lambda^0's production from Au-Au central collisions at \sqrt{s_{NN}} of several GeV.Comment: 15 pages, 6 figure

    RNIE: genome-wide prediction of bacterial intrinsic terminators

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    Bacterial Rho-independent terminators (RITs) are important genomic landmarks involved in gene regulation and terminating gene expression. In this investigation we present RNIE, a probabilistic approach for predicting RITs. The method is based upon covariance models which have been known for many years to be the most accurate computational tools for predicting homology in structural non-coding RNAs. We show that RNIE has superior performance in model species from a spectrum of bacterial phyla. Further analysis of species where a low number of RITs were predicted revealed a highly conserved structural sequence motif enriched near the genic termini of the pathogenic Actinobacteria, Mycobacterium tuberculosis. This motif, together with classical RITs, account for up to 90% of all the significantly structured regions from the termini of M. tuberculosis genic elements. The software, predictions and alignments described below are available from http://github.com/ppgardne/RNIE

    Adipocyte ATP-binding cassette G1 promotes triglyceride storage, fat mass growth, and human obesity

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    The role of ATP-binding Cassette G1 (ABCG1) transporter in human pathophysiology is still largely unknown. Indeed, beyond its role in mediating free cholesterol efflux to HDL, ABCG1 transporter equally promotes lipid accumulation in a triglyceride (TG)-rich environment through regulation of the bioavailability of Lipoprotein Lipase (LPL).As both ABCG1 and LPL are expressed in adipose tissue, we hypothesize that ABCG1 is implicated in adipocyte TG storage and could be then a major actor in adipose tissue fat accumulation.Silencing of Abcg1 expression by RNAi in 3T3-L1 preadipocytes compromised LPL-dependent TG accumulation during initial phase of differentiation. Generation of stable Abcg1 Knockdown 3T3-L1 adipocytes revealed that Abcg1 deficiency reduces TG storage and diminishes lipid droplet size through inhibition of Pparγ expression. Strikingly, local inhibition of adipocyte Abcg1 in adipose tissue from mice fed a high fat diet led to a rapid decrease of adiposity and weight gain. Analysis of two frequent ABCG1 SNPs (rs1893590 (A/C) and rs1378577 (T/G)) in morbidly obese individuals indicated that elevated ABCG1 expression in adipose tissue was associated with an increased PPARγ expression and adiposity concomitant to an increased fat mass and BMI (haplotype AT>GC). The critical role of ABCG1 regarding obesity was further confirmed in independent populations of severe obese and diabetic obese individuals.For the first time, this study identifies a major role of adipocyte ABCG1 in adiposity and fat mass growth and suggests that adipose ABCG1 might represent a potential therapeutic target in obesity

    Genome-wide genotyping demonstrates a polygenic risk score associated with white matter hyperintensity volume in CADASIL

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    Background and Purpose—White matter hyperintensities (WMH) on MRI are a quantitative marker for sporadic cerebral small vessel disease and are highly heritable. To date, large-scale genetic studies have identified only a single locus influencing WMH burden. This might in part relate to biological heterogeneity of sporadic WMH. The current study searched for genetic modifiers of WMH volume in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a monogenic small vessel disease. Methods—We performed a genome-wide association study to identify quantitative trait loci for WMH volume by combining data from 517 CADASIL patients collected through 7 centers across Europe. WMH volumes were centrally analyzed and quantified on fluid attenuated inversion recovery images. Genotyping was performed using the Affymetrix 6.0 platform. Individuals were assigned to 2 distinct genetic clusters (cluster 1 and cluster 2) based on their genetic background. Results—Four hundred sixty-six patients entered the final genome-wide association study analysis. The phenotypic variance of WMH burden in CADASIL explained by all single nucleotide polymorphisms in cluster 1 was 0.85 (SE=0.21), suggesting a substantial genetic contribution. Using cluster 1 as derivation and cluster 2 as a validation sample, a polygenic score was significantly associated with WMH burden (P=0.001) after correction for age, sex, and vascular risk factors. No single nucleotide polymorphism reached genome-wide significance. Conclusions—We found a polygenic score to be associated with WMH volume in CADASIL subjects. Our findings suggest that multiple variants with small effects influence WMH burden in CADASIL. The identification of these variants and the biological pathways involved will provide insights into the pathophysiology of white matter disease in CADASIL and possibly small vessel disease in general
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