29 research outputs found

    Nanomechanical sensing using spins in diamond

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    Nanomechanical sensors and quantum nanosensors are two rapidly developing technologies that have diverse interdisciplinary applications in biological and chemical analysis and microscopy. For example, nanomechanical sensors based upon nanoelectromechanical systems (NEMS) have demonstrated chip-scale mass spectrometry capable of detecting single macromolecules, such as proteins. Quantum nanosensors based upon electron spins of negatively-charged nitrogen-vacancy (NV) centers in diamond have demonstrated diverse modes of nanometrology, including single molecule magnetic resonance spectroscopy. Here, we report the first step towards combining these two complementary technologies in the form of diamond nanomechanical structures containing NV centers. We establish the principles for nanomechanical sensing using such nano-spin-mechanical sensors (NSMS) and assess their potential for mass spectrometry and force microscopy. We predict that NSMS are able to provide unprecedented AC force images of cellular biomechanics and to, not only detect the mass of a single macromolecule, but also image its distribution. When combined with the other nanometrology modes of the NV center, NSMS potentially offer unparalleled analytical power at the nanoscale.Comment: Errors in the stress susceptibility parameters present in the original arXiv version have been correcte

    Structure of Chimpanzee Gut Microbiomes across Tropical Africa

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    Understanding variation in host-associated microbial communities is important given the relevance of microbiomes to host physiology and health. Using 560 fecal samples collected from wild chimpanzees (Pan troglodytes) across their range, we assessed how geography, genetics, climate, vegetation, and diet relate to gut microbial community structure (prokaryotes, eukaryotic parasites) at multiple spatial scales. We observed a high degree of regional specificity in the microbiome composition, which was associated with host genetics, available plant foods, and potentially with cultural differences in tool use, which affect diet. Genetic differences drove community composition at large scales, while vegetation and potentially tool use drove within-region differences, likely due to their influence on diet. Unlike industrialized human populations in the United States, where regional differences in the gut microbiome are undetectable, chimpanzee gut microbiomes are far more variable across space, suggesting that technological developments have decoupled humans from their local environments, obscuring regional differences that could have been important during human evolution.Additional co-authors: Heather Cohen, Charlotte Coupland, Tobias Deschner, Villard Ebot Egbe, Annemarie Goedmakers, Anne-Céline Granjon, Cyril C. Grueter, Josephine Head, R. Adriana Hernandez-Aguilar, Sorrel Jones, Parag Kadam, Michael Kaiser, Juan Lapuente, Bradley Larson, Sergio Marrocoli, David Morgan, Badru Mugerwa, Felix Mulindahabi, Emily Neil, Protais Niyigaba, Liliana Pacheco, Alex K. Piel, Martha M. Robbins, Aaron Rundus, Crickette M. Sanz, Lilah Sciaky, Douglas Sheil, Volker Sommer, Fiona A. Stewart, Els Ton, Joost van Schijndel, Virginie Vergnes, Erin G. Wessling, Roman M. Wittig, Yisa Ginath Yuh, Kyle Yurkiw, Klaus Zuberbühler, Jan F. Gogarten, Anna Heintz-Buschart, Alexandra N. Muellner-Riehl, Christophe Boesch, Hjalmar S. Kühl, Noah Fierer, Mimi Arandjelovic, Robert R. Dun

    A global survey of mycobacterial diversity in soil

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    Mycobacteria are a diverse bacterial group ubiquitous in many soil and aquatic environments. Members of this group have been associated with human and other animal diseases, including the nontuberculous mycobacteria (NTM), which are of growing relevance to public health worldwide. Although soils are often considered an important source of environmentally acquired NTM infections, the biodiversity and ecological preferences of soil mycobacteria remain largely unexplored across contrasting climates and ecosystem types. Using a culture-independent approach by combining 16S rRNA marker gene sequencing with mycobacterium-specific hsp65 gene sequencing, we analyzed the diversity, distributions, and environmental preferences of soil-dwelling mycobacteria in 143 soil samples collected from a broad range of ecosystem types. The surveyed soils harbored highly diverse mycobacterial communities that span the full extent of the known mycobacterial phylogeny, with most soil mycobacteria (97% of mycobacterial clades) belonging to previously undescribed lineages. While mycobacteria tended to have higher relative abundances in cool, wet, and acidic soil environments, several individual mycobacterial clades had contrasting environmental preferences. We identified the environmental preferences of many mycobacterial clades, including the clinically relevant Mycobacterium avium complex that was more commonly detected in wet and acidic soils. However, most of the soil mycobacteria detected were not closely related to known pathogens, calling into question previous assumptions about the general importance of soil as a source of NTM infections. Together, this work provides novel insights into the diversity, distributions, and ecological preferences of soil mycobacteria and lays the foundation for future efforts to link mycobacterial phenotypes to their distributions

    Antigen Recognition in the Islets Changes with Progression of Autoimmune Islet Infiltration

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    In type 1 diabetes, the pancreatic islets are an important site for therapeutic intervention since immune infiltration of the islets is well established at diagnosis. Therefore, understanding the events that underlie the continued progression of the autoimmune response and islet destruction is critical. Islet infiltration and destruction is an asynchronous process, making it important to analyze the disease process on a single islet basis. To understand how T cell stimulation evolves through the process of islet infiltration we analyzed the dynamics of T cell movement and interactions within individual islets of spontaneously autoimmune non-obese diabetic (NOD) mice. Using both intra-vital and explanted 2-photon islet imaging, we defined a correlation between increased islet infiltration and increased T cell motility. Early T cell arrest was antigen dependent and due, at least in part, to antigen recognition through sustained interactions with CD11c(+) antigen presenting cells (APCs). As islet infiltration progressed, T cell motility became antigen-independent, with a loss of T cell arrest and sustained interactions with CD11c(+) APCs. These studies suggest that the autoimmune T cell response in the islets may be temporarily dampened during the course of islet infiltration and disease progression

    Alterations in the Gut Microbiota Associated with HIV-1 Infection

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    Understanding gut microbiota alterations associated with HIV infection and factors that drive these alterations may help explain gut-linked diseases prevalent with HIV. 16S rRNA sequencing of feces from HIV-infected individuals revealed that HIV infection is associated with highly characteristic gut community changes, and antiretroviral therapy does not consistently restore the microbiota to an HIV-negative state. Despite the chronic gut inflammation characteristic of HIV infection, the associated microbiota showed limited similarity with other inflammatory states and instead showed increased, rather than decreased, diversity. Meta-analysis revealed that the microbiota of HIV-infected individuals in the U.S. was most similar to a Prevotella-rich community composition typically observed in healthy individuals in agrarian cultures of Malawi and Venezuela and related to that of U.S. individuals with carbohydrate-rich, protein- and fat-poor diets. By evaluating innate and adaptive immune responses to lysates from bacteria that differ with HIV, we explore the functional drivers of these compositional differences

    Decreasing Wapl dosage partially corrects embryonic growth and brain transcriptome phenotypes in Nipbl+/− embryos

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    Cohesin rings interact with DNA and modulate the expression of thousands of genes. NIPBL loads cohesin onto chromosomes, and WAPL takes it off. Haploinsufficiency for NIPBL causes a developmental disorder, Cornelia de Lange syndrome (CdLS), that is modeled by Nipbl+/- mice. Mutations in WAPL have not been shown to cause disease or gene expression changes in mammals. Here, we show dysregulation of >1000 genes in WaplΔ/+ embryonic mouse brain. The patterns of dysregulation are highly similar in Wapl and Nipbl heterozygotes, suggesting that Wapl mutations may also cause human disease. Since WAPL and NIPBL have opposite effects on cohesin's association with DNA, we asked whether decreasing Wapl dosage could correct phenotypes seen in Nipbl+/- mice. Gene expression and embryonic growth are partially corrected, but perinatal lethality is not. Our data are consistent with the view that cohesin dynamics play a key role in regulating gene expression

    Coastal landfills and rising sea levels: a challenge for the 21st century

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    Populated coastal areas worldwide have a legacy of numerous solid waste disposal sites. At the same time, mean sea level is rising and likely to accelerate, increasing flooding and/or erosion. There is therefore concern that landfill sites located at and near the coast pose a growing risk to the environment from the potential release of liquid and solid waste materials. This paper aims to assess our present understanding of this issue as well as research and practise needs by synthesising the available evidence across a set of developed country cases, comprising England, France, Germany, the Netherlands and the USA (Florida). Common insights gained here include: (1) a lack of data and limited appreciation of waste release from coastal landfill as a potential problem; (2) recognition of the scale and diversity of coastal landfill waste within a range of generic settings (or situations); and (3) a lack of robust protocols that allow the impact of different categories of waste release to the coast to be assessed in a consistent and evidence-based manner, most particularly for solid waste. Hence, a need for greater understanding of the following issues is identified: (1) the amount, character and impact of waste that could be released from landfill sites; (2) the acceptability and regulation of waste eroding from coastal landfills; (3) present and future erosion rates at landfill sites suggesting the need for more monitoring and relevant predictive tools; (4) the full range of possible management methods for dealing with waste release from landfills and the science to support them; and (5) relevant long-term funding mechanisms to address this issue. The main focus and experience of current management practise has been protection/retention, or removal of landfills, with limited consideration of other feasible solutions and how they might be facilitated. Approaches to assess and address solid waste release to the marine/coastal environment represent a particular gap. Lastly as solid waste will persist indefinitely and sea levels will rise for many centuries, the long timescale of this issue needs wider appreciation and should be included in coastal and waste policy
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