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The gut microbiota can modulate human metabolism through interactions with macronutrients. However, microbiota-diet-host interactions are difficult to study because bacteria interact in complex food webs in concert with the host, and many of the bacteria are not yet characterized. To reduce the complexity, we colonize mice with a simplified intestinal microbiota (SIM) composed of ten sequenced strains isolated from the human gut with complementing pathways to metabolize dietary fibers. We feed the SIM mice one of three diets (chow [fiber rich], high-fat/high-sucrose, or zero-fat/high-sucrose diets [both low in fiber]) and investigate (1) how dietary fiber, saturated fat, and sucrose affect the abundance and transcriptome of the SIM community, (2) the effect of microbe-diet interactions on circulating metabolites, and (3) how microbiota-diet interactions affect host metabolism. Our SIM model can be used in future studies to help clarify how microbiota-diet interactions contribute to metabolic diseases.

The gut microbiota can modulate human metabolism through interactions with macronutrients. However, microbiota-diet-host interactions are difficult to study because bacteria interact in complex food webs in concert with the host, and many of the bacteria are not yet characterized. To reduce the complexity, we colonize mice with a simplified intestinal microbiota (SIM) composed of ten sequenced strains isolated from the human gut with complementing pathways to metabolize dietary fibers. We feed the SIM mice one of three diets (chow [fiber rich], high-fat/high-sucrose, or zero-fat/high-sucrose diets [both low in fiber]) and investigate (1) how dietary fiber, saturated fat, and sucrose affect the abundance and transcriptome of the SIM community, (2) the effect of microbe-diet interactions on circulating metabolites, and (3) how microbiota-diet interactions affect host metabolism. Our SIM model can be used in future studies to help clarify how microbiota-diet interactions contribute to metabolic diseases.

A new screen for proteins that bind cholesterol in vivo has identified synaptophysin I. This protein’s cholesterol-binding ability may be of key importance in the generation of synaptic vesicles at plasma membranes.

A new screen for proteins that bind cholesterol in vivo has identified synaptophysin I. This protein’s cholesterol-binding ability may be of key importance in the generation of synaptic vesicles at plasma membranes.

Objective: Concentrations of tenofovir diphosphate (TFV-DP) and lamivudine triphosphate (3TC-TP) in cells are correlates of medication adherence and antiviral activity. However, studies have yet to characterize the simultaneous relationship between TFV-DP and 3TC-TP concentrations with HIV and hepatitis B virus (HBV) suppression. Methods: Individuals with HIV/HBV coinfection on tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy (ART) were enrolled. Peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS) samples were collected and steady-state TFV-DP and 3TC-TP concentrations quantified using validated methods. The relationship between patient factors, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS with HBV and HIV viral suppression were examined. Results: Of 138 participants on TDF-containing ART for a median duration (range) of 6 (0.75–15) years, the median age was 43 years and 64% were women. Overall, 128 (92.8%) and 129 (93.5%) had suppressed HIV and HBV viral loads, respectively. Of the 128 participants with suppressed HIV, 122 (95.3%) had suppressed HBV. Self-reported ART adherence, recent change to dolutegravir-based ART, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS were associated with HIV RNA suppression, while HBe antigen positivity, HIV suppression, and TFV-DP concentrations in DBS were associated with HBV DNA suppression (including six persons with HBV nonsuppression and HIV suppression). Conclusion: Long-term TDF/3TC-conatining ART was highly efficacious in individuals with HIV/HBV coinfection. Higher TFV-DP concentrations were predictive of suppression for both viruses. Persistent HBV viremia on TDF/3TC-containg ART requires additional research, but may represent poor adherence and the need for adherence interventions or novel antivirals.

Objective: Concentrations of tenofovir diphosphate (TFV-DP) and lamivudine triphosphate (3TC-TP) in cells are correlates of medication adherence and antiviral activity. However, studies have yet to characterize the simultaneous relationship between TFV-DP and 3TC-TP concentrations with HIV and hepatitis B virus (HBV) suppression. Methods: Individuals with HIV/HBV coinfection on tenofovir disoproxil fumarate (TDF)-containing antiretroviral therapy (ART) were enrolled. Peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS) samples were collected and steady-state TFV-DP and 3TC-TP concentrations quantified using validated methods. The relationship between patient factors, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS with HBV and HIV viral suppression were examined. Results: Of 138 participants on TDF-containing ART for a median duration (range) of 6 (0.75–15) years, the median age was 43 years and 64% were women. Overall, 128 (92.8%) and 129 (93.5%) had suppressed HIV and HBV viral loads, respectively. Of the 128 participants with suppressed HIV, 122 (95.3%) had suppressed HBV. Self-reported ART adherence, recent change to dolutegravir-based ART, TFV-DP, and 3TC-TP concentrations in PBMCs and DBS were associated with HIV RNA suppression, while HBe antigen positivity, HIV suppression, and TFV-DP concentrations in DBS were associated with HBV DNA suppression (including six persons with HBV nonsuppression and HIV suppression). Conclusion: Long-term TDF/3TC-conatining ART was highly efficacious in individuals with HIV/HBV coinfection. Higher TFV-DP concentrations were predictive of suppression for both viruses. Persistent HBV viremia on TDF/3TC-containg ART requires additional research, but may represent poor adherence and the need for adherence interventions or novel antivirals.

AbstractAimAgriculture is one of the greatest pressures on biodiversity. Regional studies have shown that the presence of natural habitat and landscape heterogeneity are beneficial for biodiversity in agriculture, but it remains unclear whether their importance varies geographically. Here, we use local biodiversity data to determine which local and landscape variables are most associated with biodiversity patterns and whether their association varies between tropical and non‐tropical regions.LocationGlobal terrestrial area in forest biomes.Major taxa studiedMore than 21,000 species of vertebrates, invertebrates, plants and other taxa.MethodsWe used generalized linear mixed‐effects models to analyse the relationships between either community total abundance or species richness (derived from the PREDICTS database) and a number of site‐level (predominant land use and land‐use intensity) and landscape‐level variables (distance to forest, the percentage of natural habitat in the surrounding landscape, landscape homogeneity, the number of land‐cover types in the landscape, and total fertilizer application). We compared the associations of these variables with biodiversity in tropical and non‐tropical regions.ResultsIn most cases, changes in biodiversity associated with landscape‐level variables were greater than those associated with local land use and land‐use intensity. Increased natural habitat availability was associated with the most consistent increases in biodiversity. Landscape homogeneity was also important but showed different directions of biodiversity change between regions. Associations with fertilizer application or the number of land‐cover types were generally weaker, although still of greater magnitude than for the local land‐use measures.Main conclusionsOur results highlight similarities and differences in the association of local‐ and landscape‐scale variables with local biodiversity in tropical and non‐tropical regions. Landscape natural habitat availability had a consistent positive association with biodiversity, highlighting the key role of landscape management in the maintenance of biodiversity in croplands. Landscape‐scale variables were almost always associated with greater changes in biodiversity than the local‐scale measures.

AbstractAimAgriculture is one of the greatest pressures on biodiversity. Regional studies have shown that the presence of natural habitat and landscape heterogeneity are beneficial for biodiversity in agriculture, but it remains unclear whether their importance varies geographically. Here, we use local biodiversity data to determine which local and landscape variables are most associated with biodiversity patterns and whether their association varies between tropical and non‐tropical regions.LocationGlobal terrestrial area in forest biomes.Major taxa studiedMore than 21,000 species of vertebrates, invertebrates, plants and other taxa.MethodsWe used generalized linear mixed‐effects models to analyse the relationships between either community total abundance or species richness (derived from the PREDICTS database) and a number of site‐level (predominant land use and land‐use intensity) and landscape‐level variables (distance to forest, the percentage of natural habitat in the surrounding landscape, landscape homogeneity, the number of land‐cover types in the landscape, and total fertilizer application). We compared the associations of these variables with biodiversity in tropical and non‐tropical regions.ResultsIn most cases, changes in biodiversity associated with landscape‐level variables were greater than those associated with local land use and land‐use intensity. Increased natural habitat availability was associated with the most consistent increases in biodiversity. Landscape homogeneity was also important but showed different directions of biodiversity change between regions. Associations with fertilizer application or the number of land‐cover types were generally weaker, although still of greater magnitude than for the local land‐use measures.Main conclusionsOur results highlight similarities and differences in the association of local‐ and landscape‐scale variables with local biodiversity in tropical and non‐tropical regions. Landscape natural habitat availability had a consistent positive association with biodiversity, highlighting the key role of landscape management in the maintenance of biodiversity in croplands. Landscape‐scale variables were almost always associated with greater changes in biodiversity than the local‐scale measures.

Clostridium autoethanogenum is an acetogenic bacterium capable of producing high value commodity chemicals and biofuels from the C1 gases present in synthesis gas. This common industrial waste gas can act as the sole energy and carbon source for the bacterium that converts the low value gaseous components into cellular building blocks and industrially relevant products via the action of the reductive acetyl-CoA (Wood-Ljungdahl) pathway. Current research efforts are focused on the enhancement and extension of product formation in this organism via synthetic biology approaches. However, crucial to metabolic modelling and directed pathway engineering is a reliable and comprehensively annotated genome sequence.We performed next generation sequencing using Illumina MiSeq technology on the DSM10061 strain of Clostridium autoethanogenum and observed 243 single nucleotide discrepancies when compared to the published finished sequence (NCBI: GCA_000484505.1), with 59.1 % present in coding regions. These variations were confirmed by Sanger sequencing and subsequent analysis suggested that the discrepancies were sequencing errors in the published genome not true single nucleotide polymorphisms. This was corroborated by the observation that over 90 % occurred within homopolymer regions of greater than 4 nucleotides in length. It was also observed that many genes containing these sequencing errors were annotated in the published closed genome as encoding proteins containing frameshift mutations (18 instances) or were annotated despite the coding frame containing stop codons, which if genuine, would severely hinder the organism's ability to survive. Furthermore, we have completed a comprehensive manual curation to reduce errors in the annotation that occur through serial use of automated annotation pipelines in related species. As a result, different functions were assigned to gene products or previous functional annotations rejected because of missing evidence in various occasions.We present a revised manually curated full genome sequence for Clostridium autoethanogenum DSM10061, which provides reliable information for genome-scale models that rely heavily on the accuracy of annotation, and represents an important step towards the manipulation and metabolic modelling of this industrially relevant acetogen.