PU.1 controls fibroblast polarization and tissue fibrosis

 

PU.1控制纤维母细胞极化和组织纤维化

 

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

 

▲ 链接：

 

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

 

 

 

▲ 摘要：

 

纤维母细胞是一种多态性细胞，在器官形态发生、组织稳态和免疫应答中具有多效性。在纤维化疾病中，纤维母细胞能合成大量的细胞外基质，导致瘢痕和器官衰竭。

 

 

 

但迄今为止，科学家还未找到修复过程在纤维化疾病中发生故障的原因。

 

 

 

本研究破解出一种负责持续激活纤维母细胞的分子机制。在实验研究中，他们着重关注蛋白PU.1。

 

 

 

在正常的伤口愈合中，身体抑制PU.1的形成，从而使得在正常的愈合过程结束时，纤维母细胞能够返回到静止状态。

 

 

 

研究发现，PU.1能结合到纤维母细胞的DNA上，对它们进行重编程，从而导致组织成分长时间沉积。PU.1并不是参与纤维化的唯一因子，但它在控制这种过程的因子网络中起着核心作用。

 

 

 

▲ 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

 

恐惧障碍心理治疗方案的神经回路

 

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

 

▲ 链接：

 

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

 

 

 

▲ 摘要：

 

一种采用双侧交替感觉刺激（ABS）的心理治疗方案已被用于治疗创伤后应激障碍。然而，这种治疗长期效果的神经基础——被描述为眼球运动脱敏和再处理——还没有被确定。

 

 

 

这里研究人员描述了一个由上丘（SC）驱动的神经通路，它介导了恐惧的持续衰减。

 

 

 

研究人员成功地通过将视觉ABS与恐惧消退过程中的条件刺激相结合，在小鼠中诱导了恐惧的持续减少。在被测试的视觉刺激类型中，ABS具有最强的消除恐惧的效果，并能使SC和背内侧丘脑（MD）活动持续增加。

 

 

 

光遗传学操作显示，SC-MD回路是必要的，并足以防止恐惧的返回。ABS通过来自MD的前馈抑制回路，抑制了恐惧编码细胞的活性，并稳定了基底外侧杏仁核的抑制性神经传导。

 

 

 

这些结果共同揭示了该神经回路是有效地持续衰减创伤记忆策略的基础。

 

 

 

▲ 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

 

睡眠调节造血功能，预防动脉粥样硬化

 

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

 

▲ 链接：

 

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

 

 

 

▲ 摘要：

 

动脉粥样硬化是一种常见的心脏病起因。睡眠不足或睡眠质量差与多种健康状况相关，包括心脏病患病风险的增加。

 

 

 

然而，研究人员对于睡眠可能影响心血管健康的细胞机制和分子机制，却知之甚少。

 

 

 

这里，研究人员研究了长期睡眠片段化（睡眠中断或睡眠不足）对于易发动脉粥样硬化的基因改造小鼠的影响。

 

 

 

研究人员报告称，长期睡眠片段化的小鼠比对照组小鼠更加焦虑，会产生更多的炎症细胞，并且会形成更大的动脉粥样硬化斑块。这些小鼠的大脑外侧下丘脑区域产生的食欲肽（一种调节觉醒的神经肽）也较少。

 

 

 

研究人员表示，在睡眠不足的小鼠体内，生成的免疫细胞增加，且动脉粥样硬化加速发展。他们认为这是由食欲肽减少和CSF1水平升高引起的。恢复这些小鼠的食欲肽水平，动脉粥样硬化便减少。

 

 

 

▲ 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-null and haematopoietic hypocretin-receptor-null 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.

 

 

 

气象学Aerology

 

 

 

Complex networks reveal global pattern of extreme-rainfall teleconnections

 

复杂网络揭示了极端降水遥相关的全球模式

 

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

 

▲ 链接：

 

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

 

 

 

▲ 摘要：

 

气候观测结果往往与空间距离有关，而极端事件，如热浪或洪水，也通常被认为与遥相关有关。

 

 

 

揭示大气遥相关模式及其潜在机制，对于一般天气预报，特别是极端事件预报具有重要意义。

 

 

 

本文将复杂网络方法应用于高分辨率卫星数据，并引入一种修正功能网络多比较偏差的技术，揭示了极端降水事件的全局耦合模式。

 

 

 

结果发现，根据幂次法则，全球重要相关的距离分布（P < 0.005) 衰减的距离约为2500公里。研究人员将这种较短的、幂律分布的联系归因于区域天气系统。

 

 

 

超幂律分布连接越长，形成的全球降雨遥相关模式可能受高层罗斯比波控制。该结果提供了罗斯比波在创造稳定的、全球范围的极端降雨事件方面的作用，以及相关自然灾害的潜在可预测性方面的见解。

 

 

 

▲ 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

 

海王星的第七颗内卫星

 

链接：

 

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

 

 

 

▲ 摘要：

 

旅行者2号航天器在1989年飞掠海王星时发现有六颗内卫星绕其运行。

 

 

 

据了解，这些内卫星都比海王星年轻，形成于海王星捕获其最大的卫星崔顿（Triton，海卫一）后不久。

 

 

 

此次，研究人员使用哈勃太空望远镜研究海王星的内卫星和环，发现了旅行者2号飞掠海王星时未观测到的第七颗内卫星，这意味着海王星总共有14颗卫星。

 

 

 

这颗新卫星被命名为马头鱼尾怪——希腊神话中的一种海怪。它是目前海王星最小的卫星，平均直径约34千米。马头鱼尾怪的轨道靠近普罗透斯（Proteus，海卫八）——最大最外层的内卫星。

 

 

 

研究人员认为马头鱼尾怪可能是由普罗透斯被一颗大型彗星撞击后喷射的碎片形成的。

 

 

 

▲ 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

 

大团队发展且小团队打破科学和技术

 

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

 

▲ 链接：

 

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

 

 

 

▲ 摘要：

 

在许多科学和技术领域，大型科研团队越来越多。这种联合的力量加快了科学和技术取得重大进步的速度——这在没有这种集体资源和专业知识的情况下难以实现。

 

 

 

但是，小型团队和大型团队的科学产出是否存在系统性差异尚不十分明了。

 

 

 

本研究分析了1954年至2014年间的逾6500万个论文、专利和软件产品，考察了团队合作情况，结果显示较小的团队倾向于提出新的想法和概念，而较大的团队倾向于发展现有的想法和概念。

 

 

 

研究人员采用一种指标来衡量论文或产品如何建立在以前的工作基础上，发现在研究期限内，一到十人的小团队倾向于利用新的想法和概念来颠覆科学和技术。相比之下，较大的团队倾向于发展现有的想法。

 

 

 

因此，小型团队和大型团队对于科学和技术的蓬勃发展都至关重要。

 

 

 

▲ 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.

 

 

（唐一尘）