《自然》（20190404出版）一周論文導讀

翻譯 | 唐一塵

Nature, 4 April 2019, Volume 568 Issue 7750

《自然》2019年4月4日，第7750期568卷

生物學Biology

Visualizing DNA folding and RNA in embryos at single-cell resolution

以單細胞解析度觀察胚胎中的DNA摺疊和RNA

作者：Leslie J.Mateo、Sedona E.Murphy、AntoninaHafner、Isaac S.Cinquini、Carly A.Walker、Alistair N.Boettiger

鏈接：

https://www.nature.com/articles/s41586-019-1035-4

摘要：

在發育過程中，細胞類型的建立需要基因和遠端調控序列之間精確的相互作用。但人們對這些相互作用在三維空間中的表現、在複雜組織中的不同細胞類型中的變化以及與轉錄的關係了解有限。

本研究把染色質DNA檢測的解析度提高到2kb，能清晰得看到增強子與啟動子相互作用，並且同時檢測新生RNA水平，以便研究增強子與啟動子相互作用對基因轉錄的影響。

利用該方法，研究人員做到了在胚胎中上千個細胞中同時原位檢測染色質三維結構和基因表達。這個名為ORCA的技術為研究基因在細胞分化、胚胎髮育和疾病發生過程中的作用機制打開一扇新的大門。

Abstract

The establishment of cell types during development requires precise interactions between genes and distal regulatory sequences. We have a limited understanding of how these interactions look in three dimensions, vary across cell types in complex tissue, and relate to transcription. Here we describe optical reconstruction of chromatin architecture (ORCA), a method that can trace the DNA path in single cells with nanoscale accuracy and genomic resolution reaching two kilo bases. We used ORCA to study a Hox gene cluster in cryosectioned Drosophila embryos and labelled around 30 RNA species in parallel. We identified cell-type-specific physical borders between active and Polycomb-repressed DNA, and unexpected Polycomb-independent borders. Deletion of Polycomb-independentborders led to ectopic enhancer–promoter contacts, aberrant gene expression,and developmental defects. Together, these results illustrate an approach for high-resolution, single-cell DNA domain analysis in vivo, identify domain structures that change with cell identity, and show that border elements contribute to the formation of physical domains in Drosophila.

Structural variation in the gut microbiome associates with host health

腸道微生物群結構變化與宿主的健康有關

作者：David Zeevi、Tal Korem、Anastasia Godneva、Noam Bar、Alexandra Zhernakova、Eran Segal，et al

鏈接：

https://www.nature.com/articles/s41586-019-1065-y

摘要：

在其他方面相同的菌株之間，即使只存在少數基因的差異，也可能導致關鍵的表型差異。在這裡，研究人員系統地識別了微生物基因組結構變異，並發現它們在人類腸道微生物群落中普遍存在，並在不同的類群中複製。

這種變異在微生物適應中發揮了作用。研究人員發現微生物基因組結構變異宿主疾病風險因素之間存在多種關聯。

通過研究聚集在同一變異群體中的基因，研究人員發現了微生物群和宿主之間可能存在的幾種機制聯繫，包括在Anaerostipes hadrus中編碼合成肌醇分解代謝—丁酸酯生物合成通路的區域，該區域與降低宿主代謝疾病風險有關。

總的來說，該研究結果揭示了微生物群落中與微生物適應和宿主健康相關的新變異機制。

Abstract

Differences in the presence of even a few genes between otherwise identical bacterial strains may result in critical phenotypic differences. Here we systematically identify microbial genomic structural variants (SVs) and find them to be prevalent in the human gut microbiome across phyla and to replicate in different cohorts. SVs are enriched for CRISPR-associated and antibiotic-producing functions and depleted from housekeeping genes, suggesting that they have a role in microbial adaptation. We find multiple associations between SVs and host disease risk factors, many of which replicate in an independent cohort. Exploring genes that are clustered in the same SV, we uncover several possible mechanistic links between the microbiome and its host, including a region in Anaerostipes hadrusthat encodes a composite inositol catabolism-butyrate biosynthesis pathway, the presence of which is associated with lower host metabolic disease risk. Overall, our results uncover a nascent layer of variability in the microbiome that is associated with microbial adaptation and host health.

神經學Neurology

A gut-to-brain signal of fluid osmolarity controls thirst satiation

腸腦信號控制口渴感

作者：Christopher A. Zimmerman、Ling Bai、Yiming Chen、Hongkui Zeng、Zachary A.Knight，et al

鏈接：

https://www.nature.com/articles/s41586-019-1066-x

摘要：

腸道不僅參與了「渴感」的調控，而且似乎是主導者。之前研究認為大腦中下丘腦在檢測到血液中水合作用降落時，就會發出口渴的信息。

而且，當小鼠喝水時，只要當水接觸到嘴部和喉嚨，大腦中的一些神經元就會被關閉。這暗示這些神經元可能起到了促進喝水的作用，而信號則是來自口腔和喉嚨等部位。

這裡，研究人員發現，腸道內有鹽分感受器，它能直接和大腦對話。如果是普通的水輸入到腸道內後，控制渴感的神經元會保持關閉。而一旦進入腸道的是鹽水，就會激活渴感神經元，讓動物繼續飲水。

進一步的研究表明，坐落於下丘腦內的神經元能夠從腸道、喉嚨、血液中獲得大量信號，然後進行綜合評估，決定動物是否處於口渴的狀態。

Abstract

Satiation is the process by which eating and drinking reduce appetite. For thirst, oropharyngeal cues have a critical role in driving satiation by reporting to the brain the volume of fluid that has been ingested. By contrast, the mechanisms that relay the osmolarity of ingested fluids remain poorly understood. Here we show that the water and salt content of the gastrointestinal tract are precisely measured and then rapidly communicated to the brain to control drinking behaviour in mice. We demonstrate that this osmosensory signal is necessary and sufficient for satiation during normal drinking, involves the vagus nerve and is transmitted to key forebrain neurons that control thirst and vasopress in secretion. Using micro endoscopic imaging,we show that individual neurons compute homeostatic need by integrating this gastrointestinal osmosensory information with oropharyngeal and blood-bornesignals. These findings reveal how the fluid homeostasis system monitors the osmolarity of ingested fluids to dynamically control drinking behaviour.

Chemosensory modulation of neural circuits for sodium appetite

鈉嗜好神經迴路的化學感覺調節

作者：Sangjun Lee、VineetAugustine、Yuan Zhao、Dong Kong、Yuki Oka，et al

鏈接：

https://www.nature.com/articles/s41586-019-1053-2

摘要：

許多人口味比其他人要「重」，也就是說，他們對鹽「愛不釋手」。一方面，攝入鈉對身體有重要的意義：人體需要攝入鈉離子，才能控制體液平衡，並讓神經信號的傳導成為可能。

由於動物自身不能合成鈉離子，食物也成了獲取鈉的重要渠道。但另一方面，攝入太多的鈉離子又有可能帶來心血管疾病的風險。但人們對大腦如何控制鈉離子攝入的尚不清楚。

這裡，研究人員使用光來激活不同的小鼠神經元，並觀察小鼠行為上的變化。

他們發現，在對小鼠後腦的一些神經元進行刺激後，這些小鼠的口味突然變重，開始重複舔舐岩鹽。這表明這些神經元能促進動物攝取鹽分的慾望。研究人員表示，存在一條從舌頭到腦部的神經環路，調控動物對鹽分的攝取。

Abstract

Sodium is the main cation in the extra cellular fluid andit regulates various physiological functions. Depletion of sodium in the body increases the hedonic value of sodium taste, which drives animals towards sodium consumption. By contrast, oral sodium detection rapidly quenches sodium appetite , suggesting that taste signals have a central role in sodium appetite and its satiation. Nevertheless, the neural mechanisms of chemosensory-based appetite regulation remain poorly understood. Here we identify genetically defined neural circuits in mice that control sodium intake by integrating chemo sensory and internal depletion signals. We show that a subset of excitatory neurons in the pre-locus coeruleus express prodynorphin, and that these neurons are a critical neural substrate for sodium-intake behaviour. Acute stimulation of this population triggered robust ingestion of sodium evenfrom rock salt, while evoking a versive signals. Inhibition of the same neurons reduced sodium consumption selectively. We further demonstrate that the oral detection of sodium rapidly suppresses these sodium-appetite neurons. Simultaneous in vivo optical recording and gastric infusion revealed that sodium taste—butnot sodium ingestion per se—is required for the acute modulation of neurons in the pre-locus coeruleus that express prodynorphin, and for satiation of sodium appetite. Moreover, retrograde-virus tracing showed that sensory modulation is in part mediated by specific GABA (γ-aminobutyric acid)-producing neurons in the bed nucleus of the stria terminalis. This inhibitory neural population isactivated by sodium ingestion, and sends rapid inhibitory signals to sodium-appetite neurons. Together, this study reveals a neural architecture that integrates chemosensory signals and the internal need to maintain sodium balance.

空間/生態Space/Ecology

The unexpected surface of asteroid (101955) Bennu

小行星貝努「不可思議」的表面

作者：D. S.Lauretta、D. N.DellaGiustina、TheOSIRIS-REx Team

鏈接：

https://www.nature.com/articles/s41586-019-1033-6

摘要：

最近，《自然》《自然—天文學》《自然—地球科學》和《自然—通訊》共發表了7篇論文報道了近地小行星（101955）貝努出人意料的表面特徵。

最新發現證實了地面雷達和光變曲線的一部分觀測結果，而且最新報道的表面特徵帶來了有關貝努起源的線索，暗示貝努的誕生時間可能早於此前預期。

2018年12月3日，NASA的OSIRIS-REx航天器抵達貝努，對該小行星進行表徵探測並帶回樣本。

初步觀測數據證實貝努表面存在廣泛而豐富的含水礦物。另外一個出人意料的發現是，貝努表面存在大量圓形巨石。貝努的若干特徵，比如缺乏小型撞擊坑，表面外觀異質多樣，這些都表明貝努表面有源自不同時期的不同區域，比如貝努母體的殘餘和近期活動的痕迹。

Abstract

NASA』S Origins, Spectral Interpretation, Resource Identification and Security-Regolith Explorer (OSIRIS-REx) spacecraft recently arrived at the near-Earth asteroid(101955) Bennu, a primitive body that represents the objects that may have brought prebiotic molecules and volatiles such as water to Earth. Bennu is alow-albedo B-type asteroid that has been linked to organic-rich hydrated carbonaceous chondrites. Suchmeteorites are altered by ejection from their parent body and contaminated by atmospheric entry and terrestrial microbes. Therefore, the primary mission objective is to return a sample of Bennu to Earth that is pristine—that is, not affected by these processes. The OSIRIS-REx spacecraft carries a sophisticated suite of instruments to characterize Bennu』s global properties, support the selection of a sampling site and document that site at a sub-centimetre scale. Here we consider early OSIRIS-REx observations of Bennu to understand how the asteroid』s properties compare to pre-encounter expectations and to assess the prospects for sample return. The bulk composition of Bennu appears to behydrated and volatile-rich, as expected. However, in contrast to pre-encounter modelling of Bennu』s thermal inertia and radar polarization ratios—which indicated a generally smooth surface covered by centimetre-scale particles—resolved imaging reveals an unexpected surficial diversity. The albedo, texture, particle size and roughness are beyond the spacecraft design specifications. On the basis of our pre-encounter knowledge, we developed a sampling strategy to target 50-metre-diameter patches of loose regolith with grain sizes smaller than two centimetres 4.We observe only a small number of apparently hazard-free regions, of the order of 5 to 20 metres in extent, the sampling of which poses a substantial challenge to mission success.

Climate–land-use interactions shape tropical mountain biodiversity and ecosystem functions

氣候—土地利用相互作用塑造了熱帶山地生物多樣性和生態系統功能

作者：Marcell K.Peters、Andreas Hemp、IngolfSteffan-Dewenter，et al

鏈接：

https://www.nature.com/articles/s41586-019-1048-z

摘要：

農業和自然資源的開發已經改變了世界各地的熱帶山區生態系統，但這些變化對生物多樣性和生態系統功能的影響在很大程度上是未知的。

非山區研究結論不適合預測熱帶山區土地利用變化的影響，因為氣候環境隨海拔高度迅速變化，可能會減輕或擴大土地利用的影響。而了解氣候和土地利用的相互作用如何限制生物多樣性和生態系統功能，以確定全球變化對山區生態系統的影響，是至關重要的。

在這裡，研究人員展示了氣候和土地利用的相互作用，重塑了非洲最大的山脈乞力馬扎羅山的生物多樣性和生態系統功能的海拔趨勢。結果發現，與潮濕的山地相比，增加土地利用強度會對乾旱低地造成更大的動植物物種豐富度損失。

而且，土地利用強度的增加與動植物和微生物群落組成的顯著變化有關。溫度、降水和土地利用共同調節土壤性質、養分周轉、溫室氣體排放、植物生物量和生產力，以及動物之間的相互作用。

此外，數據表明，生態系統功能對土地利用強度的響應強烈地依賴於氣候，而乾旱低地和寒冷山區的生態系統功能發生了更為嚴重的變化。

Abstract

Agriculture and the exploitation of natural resources have transformed tropical mountain ecosystems across the world, and the consequences of these transformations for biodiversity and ecosystem functioning are largely unknown. Conclusions that are derived from studies in non-mountainous areas are not suitable for predicting the effects of land-use changes on tropical mountains because the climatic environment rapidly changes with elevation, which may mitigate oramplify the effects of land use. It is of key importance to understand how the interplay of climate and land use constrains biodiversity and ecosystem functions to determine the consequences of global change for mountain ecosystems. Here we show that the interacting effects of climate and land use reshape elevational trends in biodiversity and ecosystem functions on Africa』s largest mountain, Mount Kilimanjaro (Tanzania). We find that increasing land-use intensity causes larger losses of plant and animal species richness in the arid lowlands than inhumid submontane and montane zones. Increases in land-use intensity are associated with significant changes in the composition of plant, animal and microorganism communities; stronger modifications of plant and animal communities occur in arid and humid ecosystems, respectively. Temperature, precipitation and land use jointly modulate soil properties, nutrient turnover, greenhouse gas emissions, plant biomass and productivity, as well as animal interactions. Our data suggest that the response of ecosystem functions to land-use intensity depends strongly on climate; more-severe changes inecosystem functioning occur in the arid lowlands and the cold montane zone. Interactions between climate and land use explained—on average—54% of the variation in species richness, species composition and ecosystem functions, whereas only 30% of variation was related to single drivers. Our study reveals that climate can modulate the effects of land use on biodiversity and ecosystem functioning, and points to a lowered resistance of ecosystems in climatically challenging environments to ongoing land-use changes in tropical mountainous regions.

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