▲ 作者：Hamish D. Pritchard
About 800 millionpeople depend in part on meltwater from the thousands of glaciers in the high mountains of Asia. Water stress makes this region vulnerable to drought, but glaciers are a uniquely drought-resilient source of water. Here I show that seasonal glacier meltwater is equivalent to the basic needs of 221 ± 59 million people, or most of the annual municipal and industrial needs of Pakistan, Afghanistan, Tajikistan, Turkmenistan, Uzbekistanand Kyrgyzstan. During drought summers, meltwater dominates water inputs to the upper Indus, Aral and Chu/Issyk-Kul river basins. This reduces the risk ofsocial instability, conflict and sudden migrations triggered by water scarcity, which is already associated with the large, rapidly growing populations and hydro-economies of these basins. Regional meltwater production is, however, unsustainably high—at 1.6 times the balance rate—and is expected to increase in future decades before ultimately declining. These results update and reinforce a previous publication in Nature on this topic, which was retracted after an inadvertent error was discovered.
Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases
▲ 作者：Jason Lloyd-Price、Cesar Arze、Curtis Huttenhower，etal
Inflammatory bowel diseases, which include Crohn’s disease and ulcerative colitis, affect several million individuals worldwide. Crohn’s disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbiallevels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 timepoints each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosisin the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools( acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study’s infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi’omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.
Longitudinal multi-omics of host–microbe dynamics in prediabetes
▲ 作者：Wenyu Zhou、M. RezaSailani、MichaelSnyder，etal
Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal dataset revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host–microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signalling. Our study reveals insights into pathways and responses that differ between glucose-dysregulated and healthy individuals during health and disease and provides an open-access data resource to enable further research into healthy, prediabetic and T2D states.
Learning the signatures of the human grasp using a scalable tactile glove
▲ 作者：SubramanianSundaram、Yunzhu Li、WojciechMatusik，etal
Humans can feel, weigh and grasp diverse objects, and simultaneously infer their material properties while applying the right amount of force—a challenging set of tasks for a modern robot. Mechanoreceptor networks that provide sensory feedback and enable the dexterity of the human grasp remain difficult to replicate in robots. Whereas computer-vision-based robot grasping strategies have progressed substantially with the abundance of visual data and emerging machine-learning tools, there are as yet no equivalent sensing platforms and large-scale datasets with which to probe the use of the tactile information that humans rely on when grasping objects. Studying the mechanics of how humans grasp objects will complement vision-based robotic object handling. Importantly, the inability to record and analyse tactile signals currently limits our understanding of the role of tactile informationin the human grasp itself—for example, how tactile maps are used to identify objects and infer their properties is unknown. Here we use a scalable tactile glove and deep convolutional neural networks to show that sensors uniformly distributed over the hand can be used to identify individual objects, estimate their weight and explore the typical tactile patterns that emerge while grasping objects. The sensor array (548 sensors) is assembled on a knitted glove, and consists of a piezoresistive film connected by a network of conductive thread electrodes that are passively probed. Using alow-cost (about US$10) scalable tactile glove sensor array, we record a large-scale tactile dataset with 135,000 frames, each covering the full hand, while interacting with 26 different objects. This set of interactions with different objects reveals the key correspondences between different regions of a human hand while it is manipulating objects. Insights from the tactile signatures of the human grasp—through the lens of an artificial analogue of the natural mechano receptor network—can thus aid the future design of prosthetics, robot grasping tools and human–robot interactions.
Mitochondrial protein translocation-associated degradation
▲ 作者：Christoph U.Mårtensson、Chantal Priesnitz、Thomas Becker，etal
Mitochondrial biogenesis and functions depend on the import of precursor proteins via the ‘translocase ofthe outer membrane’ (TOM complex). Defects in protein import lead to an accumulation of mitochondrial precursor proteins that induces a range of cellular stress responses. However, constitutive quality-control mechanisms that clear trapped precursor proteins from the TOM channel under non-stress conditions have remained unknown. Here we report that in Saccharomy cescerevisiae Ubx2, which functions in endoplasmic reticulum-associated degradation, is crucial for this quality-control process. A pool of Ubx2 binds to the TOM complex to recruit the AAA ATPase Cdc48 for removal of arrested precursor proteins from the TOM channel. This mitochondrial protein translocation-associated degradation (mitoTAD) pathway continuously monitors the TOM complex under non-stress conditions to prevent clogging of the TOM channel with precursor proteins. The mitoTAD pathway ensures that mitochondria maintain their full protein-import capacity, and protects cells against proteotoxic stress induced by impaired transport of proteins into mitochondria.
Progenitors from the central nervous system drive neurogenesis in cancer
▲ 作者：Philippe Mauffrey、Nicolas Tchitchek、Claire Magnon，etal
Autonomic nerve fibres in the tumour micro environment regulate cancer initiation and dissemination, but how nerves emerge in tumours is currently unknown. Here we show that neural progenitors from the central nervous system that express doublecortin (
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