《自然》（20190530出版）一周論文導讀

翻譯 | 唐一塵

Nature, 30 MAY 2019, Volume 569 Issue 7758

《自然》2019年5月30日，第7758期569卷

生態學Ecology

Asia』s shrinking glaciers protect large populations from drought stress

亞洲冰川融水保護大量人口免受乾旱壓力

作者：Hamish D. Pritchard

鏈接：

https://www.nature.com/articles/s41586-019-1240-1

摘要：

大約有8億人在一定程度上依賴於亞洲高山地區數千條冰川的融水。水資源短缺使相關地區容易遭受乾旱，但冰川是一種獨特的抗旱水源。

本研究發現，季節性冰川融水相當於221±59百萬人的基本用水需求，或者說相當於巴基斯坦、阿富汗、塔吉克、土庫曼、烏茲別克和吉爾吉斯斯坦每年城市和工業的大部分需求。

在乾旱的夏季，融水是印度河上游、鹹海和Chu/Issyk-Kul河流域的主要水源輸入。這就減少了因缺水而引起的社會不穩定和衝突等危險。目前，這些地區的缺水已經與龐大、迅速增長的人口和水經濟聯繫在一起。

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 These results update and reinforce a previous publication in Nature on this topic, which was retracted after an inadvertent error was discovered.

微生物學Microbiology

Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases

炎症性腸病腸道微生物生態系統的多重組學研究

作者：Jason Lloyd-Price、Cesar Arze、Curtis Huttenhower，etal

鏈接：

https://www.nature.com/articles/s41586-019-1237-9

摘要：

人體微生物組因個體、群體和環境而異，並且已知會影響人類的健康和疾病狀態。

人類微生物組整合計劃（iHMP）採用多組學方法探索了微生物組和宿主的時間動態變化（如免疫響應和新陳代謝），以便理解這些疾病中的微生物—宿主互作。

這裡，研究人員研究了132名炎症性腸病（IBD）患者和健康的對照組被試。研究人員鑒定出了微生物組組成的變化、腸道內宿主源和微生物組源分子的變化以及基因表達的轉變。

他們表示，這項研究對IBD中的宿主和微生物活動進行了迄今為止最全面的描述，有望為理解疾病發病和進展帶來深刻見解。

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 (//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

前驅糖尿病宿主—微生物動態的縱向多組學研究

作者：Wenyu Zhou、M. RezaSailani、MichaelSnyder，etal

鏈接：

https://www.nature.com/articles/s41586-019-1236-x

摘要：

Ⅱ型糖尿病是一個日益嚴重的健康問題，但人們對其早期疾病階段、其對生物過程的影響或向臨床的過渡知之甚少。

為了更好地理解Ⅱ型糖尿病早期階段，本研究報告了前驅糖尿病中宿主和微生物組之間的互作。前驅糖尿病會導致糖尿病，但是經常得不到確診。

研究小組對106名健康個體和前驅糖尿病個體進行了為期4年的研究，分析了分子變化、遺傳變化和微生物變化。他們發現了可以定義早期疾病發展的規律——在某些情況下，這可能有助於及早檢測出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.

人工智慧Artificial Intelligence

Learning the signatures of the human grasp using a scalable tactile glove

使用可伸縮觸覺手套學習人類抓握的特徵

作者：SubramanianSundaram、Yunzhu Li、WojciechMatusik，etal

鏈接：

https://www.nature.com/articles/s41586-019-1234-z

摘要：

人類能夠以適當的力度抓握和感受物體。但是這種感覺反饋很難在機器人身上實現。

近年來，基於計算機視覺的抓握策略在新興機器學習工具的幫助下，取得了長足進步，但是仍缺少依賴於觸覺信息的平台。

本研究設計了一種簡易廉價的可伸縮觸覺手套，上面布置了548個感測器和64個導電線電極。

該感測器陣列由一張力敏薄膜和導電線網路組成。電極與薄膜之間的每一個重合點都對垂直力敏感，並會記錄通過薄膜的電阻。

研究人員帶上手套單手操控物體，由此記錄下了一個大規模的觸覺圖譜數據集。數據集包含手指區域的空間關聯和對應，它們代表了人類抓握的觸覺特徵。

這種策略或有助於未來設計假體、機械工具和人機交互。

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.

生物學Biology

Mitochondrial protein translocation-associated degradation

線粒體蛋白易位相關降解

作者：Christoph U.M?rtensson、Chantal Priesnitz、Thomas Becker，etal

鏈接：

https://www.nature.com/articles/s41586-019-1227-y

摘要：

線粒體生物發生和功能依賴於通過「外膜的轉位酶」（TOM複合物）導入前體蛋白。蛋白質導入的缺陷導致線粒體前體蛋白的積累，並誘導一系列細胞應激反應。

然而，在非脅迫條件下從TOM通道中清除被捕獲的前體蛋白的組成型質量控制機制仍然未知。

本研究發現，釀酒酵母Ubx2對於這種質量控制過程至關重要。Ubx2池與TOM複合物結合以募集AAA ATP酶Cdc48以從TOM通道中去除被捕獲的前體蛋白。

這種線粒體蛋白易位相關降解（mitoTAD）途徑在非應激條件下持續監測TOM複合物，以防止TOM通道被前體蛋白堵塞。

mitoTAD途徑確保線粒體保持其完整的蛋白質輸入能力，並保護細胞免受蛋白質轉運到線粒體中所引起的蛋白質毒性應激。

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 cescerevisiaeUbx2, 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

中樞神經系統祖細胞驅動癌症的神經發生

作者：Philippe Mauffrey、Nicolas Tchitchek、Claire Magnon，etal

鏈接：

https://www.nature.com/articles/s41586-019-1219-y

摘要：

腫瘤微環境中的自主神經纖維調節癌症的發生和擴散，但是目前尚不清楚神經是如何在腫瘤中出現的。

本研究發現，發現來自中樞神經系統的表達雙皮質素神經祖細胞能浸潤到前列腺瘤和轉移瘤中，在那裡，它們啟動神經發生。

這些細胞隨後浸潤並停留在前列腺瘤中，並且能夠產生新的腎上腺素能神經元。

在前列腺癌小鼠模型中，選擇性遺傳剔除這些細胞會抑制早期的腫瘤產生階段，然而，移植這些細胞能夠促進腫瘤生長和轉移。

這些結果揭示了中樞神經系統和前列腺腫瘤之間的獨特交流，並指出了治療癌症的神經靶標。

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 (DCX⁺) infiltrate prostate tumours and metastases, in which they initiate neurogenesis. In mouse models of prostate cancer, oscillations of DCX⁺neural progenitors in the subventricular zone—a neurogenic area of the central nervous system—are associated with disruption of the blood–brain barrier, and with the egress of DCX⁺cells into the circulation. These cells then infiltrate and reside in the tumour, and can generate new adrenergic neurons. Selective genetic depletion of DCX⁺cells inhibits the early phases of tumour development in our mouse models of prostate cancer, whereas transplantation of DCX⁺neural progenitors promotes tumour growth and metastasis. In humans, the density of DCX⁺neural progenitors is strongly associated with the aggressiveness and recurrence of prostate adenocarcinoma. These results reveala unique crosstalk between the central nervous system and prostate tumours, and indicate neural targets for the treatment of cancer.

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