▲ 作者：Hamish D. Pritchard
▲ 链接：
https://www.nature.com/articles/s41586-019-1240-1
▲ 摘要：
大约有8亿人在一定程度上依赖于亚洲高山地区数千条冰川的融水。水资源短缺使相关地区容易遭受干旱，但冰川是一种独特的抗旱水源。
本研究发现，季节性冰川融水相当于221±59百万人的基本用水需求，或者说相当于巴基斯坦、阿富汗、塔吉克斯坦、土库曼斯坦、乌兹别克斯坦和吉尔吉斯斯坦每年城市和工业的大部分需求。
在干旱的夏季，融水是印度河上游、咸海和Chu/Issyk-Kul河流域的主要水源输入。这就减少了因缺水而引起的社会不稳定和冲突等危险。目前，这些地区的缺水已经与庞大、迅速增长的人口和水经济联系在一起。
▲ Abstract
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 These results update and reinforce a previous publication in Nature on this topic, which was retracted after an inadvertent error was discovered.
微生物学Microbiology
Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases
炎症性肠病肠道微生物生态系统的多重组学研究
▲ 作者：Jason Lloyd-Price、Cesar Arze、Curtis Huttenhower，etal
▲ 链接：
https://www.nature.com/articles/s41586-019-1237-9
▲ 摘要：
人体微生物组因个体、群体和环境而异，并且已知会影响人类的健康和疾病状态。
人类微生物组整合计划（iHMP）采用多组学方法探索了微生物组和宿主的时间动态变化（如免疫响应和新陈代谢），以便理解这些疾病中的微生物—宿主互作。
这里，研究人员研究了132名炎症性肠病（IBD）患者和健康的对照组被试。研究人员鉴定出了微生物组组成的变化、肠道内宿主源和微生物组源分子的变化以及基因表达的转变。
他们表示，这项研究对IBD中的宿主和微生物活动进行了迄今为止最全面的描述，有望为理解疾病发病和进展带来深刻见解。
▲ Abstract
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
前驱糖尿病宿主—微生物动态的纵向多组学研究
▲ 作者：Wenyu Zhou、M. RezaSailani、MichaelSnyder，etal
▲ 链接：
https://www.nature.com/articles/s41586-019-1236-x
▲ 摘要：
Ⅱ型糖尿病是一个日益严重的健康问题，但人们对其早期疾病阶段、其对生物过程的影响或向临床的过渡知之甚少。
为了更好地理解Ⅱ型糖尿病早期阶段，本研究报告了前驱糖尿病中宿主和微生物组之间的互作。前驱糖尿病会导致糖尿病，但是经常得不到确诊。
研究小组对106名健康个体和前驱糖尿病个体进行了为期4年的研究，分析了分子变化、遗传变化和微生物变化。他们发现了可以定义早期疾病发展的规律——在某些情况下，这可能有助于及早检测出Ⅱ型糖尿病。
▲ Abstract
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.
人工智能Artificial Intelligence
Learning the signatures of the human grasp using a scalable tactile glove
使用可伸缩触觉手套学习人类抓握的特征
▲ 作者：SubramanianSundaram、Yunzhu Li、WojciechMatusik，etal
▲ 链接：
https://www.nature.com/articles/s41586-019-1234-z
▲ 摘要：
人类能够以适当的力度抓握和感受物体。但是这种感觉反馈很难在机器人身上实现。
近年来，基于计算机视觉的抓握策略在新兴机器学习工具的帮助下，取得了长足进步，但是仍缺少依赖于触觉信息的平台。
本研究设计了一种简易廉价的可伸缩触觉手套，上面布置了548个传感器和64个导电线电极。
该传感器阵列由一张力敏薄膜和导电线网络组成。电极与薄膜之间的每一个重合点都对垂直力敏感，并会记录通过薄膜的电阻。
研究人员带上手套单手操控物体，由此记录下了一个大规模的触觉图谱数据集。数据集包含手指区域的空间关联和对应，它们代表了人类抓握的触觉特征。
这种策略或有助于未来设计假体、机械工具和人机交互。
▲ Abstract
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.
生物学Biology
Mitochondrial protein translocation-associated degradation
线粒体蛋白易位相关降解
▲ 作者：Christoph U.Mårtensson、Chantal Priesnitz、Thomas Becker，etal
▲ 链接：
https://www.nature.com/articles/s41586-019-1227-y
▲ 摘要：
线粒体生物发生和功能依赖于通过“外膜的转位酶”（TOM复合物）导入前体蛋白。蛋白质导入的缺陷导致线粒体前体蛋白的积累，并诱导一系列细胞应激反应。
然而，在非胁迫条件下从TOM通道中清除被捕获的前体蛋白的组成型质量控制机制仍然未知。
本研究发现，酿酒酵母Ubx2对于这种质量控制过程至关重要。Ubx2池与TOM复合物结合以募集AAA ATP酶Cdc48以从TOM通道中去除被捕获的前体蛋白。
这种线粒体蛋白易位相关降解（mitoTAD）途径在非应激条件下持续监测TOM复合物，以防止TOM通道被前体蛋白堵塞。
mitoTAD途径确保线粒体保持其完整的蛋白质输入能力，并保护细胞免受蛋白质转运到线粒体中所引起的蛋白质毒性应激。
▲ Abstract
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
中枢神经系统祖细胞驱动癌症的神经发生
▲ 作者：Philippe Mauffrey、Nicolas Tchitchek、Claire Magnon，etal
▲ 链接：
https://www.nature.com/articles/s41586-019-1219-y
▲ 摘要：
肿瘤微环境中的自主神经纤维调节癌症的发生和扩散，但是目前尚不清楚神经是如何在肿瘤中出现的。
本研究发现，发现来自中枢神经系统的表达双皮质素神经祖细胞能浸润到前列腺瘤和转移瘤中，在那里，它们启动神经发生。
这些细胞随后浸润并停留在前列腺瘤中，并且能够产生新的肾上腺素能神经元。
在前列腺癌小鼠模型中，选择性遗传剔除这些细胞会抑制早期的肿瘤产生阶段，然而，移植这些细胞能够促进肿瘤生长和转移。
这些结果揭示了中枢神经系统和前列腺肿瘤之间的独特交流，并指出了治疗癌症的神经靶标。
▲ Abstract
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 (
