《自然》（20190221出版）一周論文導讀

知識 02-24

翻譯 | 唐一塵

Nature, 21, February 2019, Volume 566 Issue 7744

《自然》2019年2月21日第7744期566卷

《自然》（20190221出版）一周論文導讀

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生理學Physiology

PU.1 controls fibroblast polarization and tissue fibrosis

PU.1控制纖維母細胞極化和組織纖維化

作者：ThomasWohlfahrt、Simon Rauber、Steffen Uebe、Markus Luber、Alina Soare、AndreasRamming，et al

鏈接：

https://www.nature.com/articles/s41586-019-0896-x

摘要：

纖維母細胞是一種多態性細胞，在器官形態發生、組織穩態和免疫應答中具有多效性。在纖維化疾病中，纖維母細胞能合成大量的細胞外基質，導致瘢痕和器官衰竭。

但迄今為止，科學家還未找到修復過程在纖維化疾病中發生故障的原因。

本研究破解出一種負責持續激活纖維母細胞的分子機制。在實驗研究中，他們著重關注蛋白PU.1。

在正常的傷口癒合中，身體抑制PU.1的形成，從而使得在正常的癒合過程結束時，纖維母細胞能夠返回到靜止狀態。

研究發現，PU.1能結合到纖維母細胞的DNA上，對它們進行重編程，從而導致組織成分長時間沉積。PU.1並不是參與纖維化的唯一因子，但它在控制這種過程的因子網路中起著核心作用。

Abstract

Fibroblasts are polymorphic cells with pleiotropic roles in organ morphogenesis, tissue homeostasis and immune responses. In fibrotic diseases, fibroblasts synthesize abundant amounts of extracellular matrix, which induces scarring and organ failure. By contrast, a hallmark feature of fibroblasts in arthritis isdegradation of the extracellular matrix because of the release of metallo proteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms that drive these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts remain unknown. Here we identify the transcription factor PU.1 as an essential regulator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms that normally control the expression of PU.1 expression is perturbed in various fibrotic diseases, resulting in the upregulation of PU.1, induction of fibrosis-associated gene sets and aphenotypic switch in extracellular matrix-producing pro-fibrotic fibroblasts. By contrast, pharmacological and genetic inactivation of PU.1 disrupts the fibrotic network and enables reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs.

Neuralcircuits underlying a psychotherapeutic regimen for fear disorders

恐懼障礙心理治療方案的神經迴路

作者：Jinhee Baek、Sukchan Lee、Jaeseung Jeong、Hee-Sup Shin，etal

鏈接：

https://www.nature.com/articles/s41586-019-0931-y

摘要：

一種採用雙側交替感覺刺激（ABS）的心理治療方案已被用於治療創傷後應激障礙。然而，這種治療長期效果的神經基礎——被描述為眼球運動脫敏和再處理——還沒有被確定。

這裡研究人員描述了一個由上丘（SC）驅動的神經通路，它介導了恐懼的持續衰減。

研究人員成功地通過將視覺ABS與恐懼消退過程中的條件刺激相結合，在小鼠中誘導了恐懼的持續減少。在被測試的視覺刺激類型中，ABS具有最強的消除恐懼的效果，並能使SC和背內側丘腦（MD）活動持續增加。

光遺傳學操作顯示，SC-MD迴路是必要的，並足以防止恐懼的返回。ABS通過來自MD的前饋抑制迴路，抑制了恐懼編碼細胞的活性，並穩定了基底外側杏仁核的抑制性神經傳導。

這些結果共同揭示了該神經迴路是有效地持續衰減創傷記憶策略的基礎。

Abstract

A psychotherapeutic regimen that uses alternating bilateral sensory stimulation(ABS) has been used to treat post-traumatic stress disorder. However, the neural basis that underlies the long-lasting effect of this treatment—described as eye movement desensitization and reprocessing—has not been identified. Herewe describe a neuronal pathway driven by the superior colliculus (SC) that mediates persistent attenuation of fear. We successfully induced a lasting reduction in fear in mice by pairing visual ABS with conditioned stimuli during fear extinction. Among the types of visual stimulation tested, ABS provided the strongest fear-reducing effect and yielded sustained increases in the activities of the SC and mediodorsal thalamus (MD). Optogenetic manipulation revealed that the SC–MD circuit was necessary and sufficient to prevent the return of fear. ABS suppressed the activity of fear-encoding cells and stabilized inhibitory neuro transmission in the basolateral amygdala through a feedforward inhibitory circuit from the MD. Together, these results reveal theneural circuit that underlies an effective strategy for sustainably attenuating traumatic memories.

Sleep modulates haematopoiesis and protects against atherosclerosis

睡眠調節造血功能，預防動脈粥樣硬化

作者：Cameron S. McAlpine、Máté G. Kiss、Sara Rattik、Matthias Nahrendorf、Filip K. Swirski，et al

鏈接：

https://www.nature.com/articles/s41586-019-0948-2

摘要：

動脈粥樣硬化是一種常見的心臟病起因。睡眠不足或睡眠質量差與多種健康狀況相關，包括心臟病患病風險的增加。

然而，研究人員對於睡眠可能影響心血管健康的細胞機制和分子機制，卻知之甚少。

這裡，研究人員研究了長期睡眠片段化（睡眠中斷或睡眠不足）對於易發動脈粥樣硬化的基因改造小鼠的影響。

研究人員報告稱，長期睡眠片段化的小鼠比對照組小鼠更加焦慮，會產生更多的炎症細胞，並且會形成更大的動脈粥樣硬化斑塊。這些小鼠的大腦外側下丘腦區域產生的食慾肽（一種調節覺醒的神經肽）也較少。

研究人員表示，在睡眠不足的小鼠體內，生成的免疫細胞增加，且動脈粥樣硬化加速發展。他們認為這是由食慾肽減少和CSF1水平升高引起的。恢復這些小鼠的食慾肽水平，動脈粥樣硬化便減少。

Abstract

Sleep is integral to life. Although insufficient or disrupted sleep increases the risk of multiple pathological conditions, including cardiovascular disease, we know little about the cellular and molecular mechanisms by which sleep maintains cardiovascular health. Here we report that sleep regulates haematopoiesis and protects against atherosclerosis in mice. We show that mice subjected to sleep fragmentation produce more Ly-6Chigh monocytes, develop larger atherosclerotic lesions and produce less hypocretin—a stimulatory and wake-promoting neuropeptide—in the lateral hypothalamus. Hypocretin controls myelopoiesis by restricting the production of CSF1 by hypocretin-receptor-expressing pre-neutrophils in the bone marrow. Whereas hypocretin- and haematopoietic hypocretin-receptor- mice develop monocytosis and accelerated atherosclerosis, sleep-fragmented mice with either haematopoietic CSF1 deficiency or hypocretin supplementation have reduced numbers of circulating monocytes and smaller atherosclerotic lesions. Together, these results identify a neuro-immune axis that links sleep to haematopoiesis and atherosclerosis.

氣象學Aerology

Complex networks reveal global pattern of extreme-rainfall teleconnections

複雜網路揭示了極端降水遙相關的全球模式

作者：Niklas Boers、Bedartha Goswami、Aljoscha Rheinwalt、Bodo Bookhagen、Brian Hoskins、Jürgen Kurths

鏈接：

https://www.nature.com/articles/s41586-018-0872-x

摘要：

氣候觀測結果往往與空間距離有關，而極端事件，如熱浪或洪水，也通常被認為與遙相關有關。

揭示大氣遙相關模式及其潛在機制，對於一般天氣預報，特別是極端事件預報具有重要意義。

本文將複雜網路方法應用於高解析度衛星數據，並引入一種修正功能網路多比較偏差的技術，揭示了極端降水事件的全局耦合模式。

結果發現，根據冪次法則，全球重要相關的距離分布（P < 0.005) 衰減的距離約為2500公里。研究人員將這種較短的、冪律分布的聯繫歸因於區域天氣系統。

超冪律分布連接越長，形成的全球降雨遙相關模式可能受高層羅斯比波控制。該結果提供了羅斯比波在創造穩定的、全球範圍的極端降雨事件方面的作用，以及相關自然災害的潛在可預測性方面的見解。

Abstract

Climatic observables are often correlated across long spatial distances, and extreme events, such as heat waves or floods, are typically assumed to be related to such teleconnections. Revealing atmospheric teleconnection patterns and understanding their underlying mechanisms is of great importance for weather forecasting in general and extreme-event prediction in particular especially considering that the characteristics of extreme events have been suggested to change under ongoing anthropogenic climate change. Here we reveal the global coupling pattern of extreme-rainfall events by applying complex-network methodology to high-resolution satellite data and introducing a technique that corrects for multiple-comparison bias in functional networks. We find that the distance distribution of significant connections (P < 0.005) around the globe decays according to a power law up to distances of about 2,500 kilometres. For longer distances, the probability of significant connections is much higher than expected from the scaling of the power law. We attribute the shorter, power-law-distributed connections to regional weather systems. The longer, super-power-law-distributed connections form a global rainfall teleconnection pattern that is probably controlled by upper-level Rossby waves. We show that extreme-rainfall events in the monsoon systems of south-central Asia, east Asia and Africa are significantly synchronized. Moreover, we uncover concise links between south-central Asia and the European and North American extratropics, as well as the Southern Hemisphere extratropics. Analysis of the atmospheric conditions that lead to these teleconnections confirms Rossby waves as the physical mechanism underlying these global teleconnection patterns and emphasizes their crucial role in dynamical tropical–extratropical couplings. Our results provide insights into the function of Rossby waves in creating stable, global-scale dependencies of extreme-rainfall events, and into the potential predictability of associated natural hazards.

The seventh inner moon of Neptune

海王星的第七顆內衛星

作者：M. R. Showalter、I. de Pater、J. J. Lissauer、R. S. French

鏈接：

https://www.nature.com/articles/s41586-019-0909-9

摘要：

旅行者2號航天器在1989年飛掠海王星時發現有六顆內衛星繞其運行。

據了解，這些內衛星都比海王星年輕，形成於海王星捕獲其最大的衛星崔頓（Triton，海衛一）後不久。

此次，研究人員使用哈勃太空望遠鏡研究海王星的內衛星和環，發現了旅行者2號飛掠海王星時未觀測到的第七顆內衛星，這意味著海王星總共有14顆衛星。

這顆新衛星被命名為馬頭魚尾怪——希臘神話中的一種海怪。它是目前海王星最小的衛星，平均直徑約34千米。馬頭魚尾怪的軌道靠近普羅透斯（Proteus，海衛八）——最大最外層的內衛星。

研究人員認為馬頭魚尾怪可能是由普羅透斯被一顆大型彗星撞擊後噴射的碎片形成的。

Abstract

During its 1989 flyby, the Voyager 2 spacecraft imaged six small moons of Neptune, all with orbits well interior to that of the large, retrograde moon Triton. Along with a set ofnearby rings, these moons are probably younger than Neptune itself; they formed shortly after the capture of Triton and most of them have probably been fragmented multiple times by cometary impacts. Here we report Hubble Space Telescope observations of a seventh inner moon, Hippocamp. It is smaller than the other six, with a mean radius of about 17 kilometres. We also observe Naiad, Neptune』s innermost moon, which was last seen in 1989, and provide astrometry, orbit determinations and size estimates for all the inner moons, using an analysis technique that involves distorting consecutive images to compensate for each moon』s orbital motion and that is potentially applicable to searches for other moons and exoplanets. Hippocamp orbits close to Proteus, the outermost and largest of these moons, and the orbital semimajor axes of the two moons differ by only ten per cent. Proteus has migrated outwards because of tidal interactions with Neptune. Our results suggest that Hippocamp is probably an ancient fragment of Proteus, providing further support for the hypothesis that the inner Neptune system has been shaped by numerous impacts.

科研Research

Large teamsdevelop and small teams disrupt science and technology

大團隊發展且小團隊打破科學和技術

作者：Lingfei Wu、Dashun Wang、James A. Evans

鏈接：

https://www.nature.com/articles/s41586-019-0941-9

摘要：

在許多科學和技術領域，大型科研團隊越來越多。這種聯合的力量加快了科學和技術取得重大進步的速度——這在沒有這種集體資源和專業知識的情況下難以實現。

但是，小型團隊和大型團隊的科學產出是否存在系統性差異尚不十分明了。

本研究分析了1954年至2014年間的逾6500萬個論文、專利和軟體產品，考察了團隊合作情況，結果顯示較小的團隊傾向於提出新的想法和概念，而較大的團隊傾向於發展現有的想法和概念。

研究人員採用一種指標來衡量論文或產品如何建立在以前的工作基礎上，發現在研究期限內，一到十人的小團隊傾向於利用新的想法和概念來顛覆科學和技術。相比之下，較大的團隊傾向於發展現有的想法。

因此，小型團隊和大型團隊對於科學和技術的蓬勃發展都至關重要。

Abstract

One of the most universal trends in science and technology today is the growth of large teamsin all areas, as solitary researchers and small teams diminish in prevalence. Increases in team size have been attributed to the specialization of scientific activities, improvements in communication technology or the complexity of modern problems that require interdisciplinary solutions. This shift in teamsize raises the question of whether and how the character of the science and technology produced by large teams differs from that of small teams. Here we analyse more than 65 million papers, patents and software products that span the period 1954–2014, and demonstrate that across this period smaller teams have tended to disrupt science and technology with new ideas and opportunities, whereas larger teams have tended to develop existing ones. Work from larger teams builds on more-recent and popular developments, and attention to their work comes immediately. By contrast, contributions by smaller teams search more deeply into the past, are viewed as disruptive to science and technology and succeed further into the future—if at all. Observed differences between small and large teams are magnified for higher-impact work, with small teams known for disruptive work and large teams for developing work. Differences in topic and research design account for a small part of the relationship between team size and disruption; most of the effect occurs at the level of the individual, as people move between smaller and larger teams. These results demonstrate that both small and large teams are essential to a flourishing ecology of science and technology, and suggest that, to achieve this, science policies should aim to support a diversity of team sizes.

《自然》（20190221出版）一周論文導讀