《自然》(20190207出版)一周论文导读

《自然》(20190207出版)一周论文导读
2019年02月08日 21:10 科学网

翻译 | 唐一尘

Nature, 7 February 2019, Volume 566 Issue 7742

《自然》2019年2月7日第7742期566卷

环境Environment

Global environmental consequences of twenty-first-century ice-sheet melt

21世纪冰盖融化的全球环境影响

▲ 作者:Nicholas R. Golledge、Elizabeth D. Keller、Natalya Gomez、Kaitlin A. Naughten、Jorge Bernales、Luke D. Trusel、Tamsin L. Edwards

▲ 链接:

https://www.nature.com/articles/s41586-019-0889-9

▲ 摘要:

目前,各国政府承诺到2100年,将保持地球表面温度比工业化前水平上升3至4摄氏度,而这将导致冰盖进一步融化。耦合模型相互比较项目第5阶段并没有明确地将冰盖排放包括在内,因此目前政府政策制定的最常用模拟方法并没有涉及冰盖融化对气候的影响。

这里,研究人员使用格陵兰岛和南极洲冰盖卫星测量数据进行模拟,并增加了格陵兰岛融水将大幅放缓大西洋环流,以及南极洲融水将把温水困于海平面下等相关数据。

结果显示,未来冰盖的融化将加剧全球温度的变化,到2100年将导致海平面上升25厘米。然而,相关模拟存在不确定性,仍需要继续进行观测和多模型评估。

▲ Abstract

Government policies currently commit us to surface warming of three to four degrees Celsius above pre-industrial levels by 2100, which will lead to enhanced ice-sheet melt. Ice-sheet discharge was not explicitly included in Coupled Model Intercomparison Project phase 5, so effects on climate from this melt are not currently captured in the simulations most commonly used to inform governmental policy. Here we show, using simulations of the Greenland and Antarctic ice sheets constrained by satellite-based measurements of recent changes in ice mass, that increasing meltwater from Greenland will lead to substantial slowing of the Atlantic overturning circulation, and that meltwater from Antarctica will trap warm water below the sea surface, creating a positive feedback that increases Antarctic ice loss. In our simulations, future ice-sheet melt enhances global temperature variability and contributes up to 25 centimetres to sea level by 2100. However, uncertainties in the way in which future changes in ice dynamics are modelled remain, underlining the need for continued observations and comprehensive multi-model assessments.

Revisiting Antarctic ice loss due to marine ice-cliff instability

重新考察海洋冰崖不稳定造成的南极冰损失

▲ 作者:Tamsin L. Edwards、Mark A. Brandon、Gael Durand、Neil R. Edwards、Nicholas R. Golledge、Philip B. Holden、Isabel J. Nias、Antony J. Payne、Catherine Ritz、Andreas Wernecke

▲ 链接:

https://www.nature.com/articles/s41586-019-0901-4

▲ 摘要:

由于南极洲的融化,人们对本世纪海平面上升的预测范围从0到1米多不等。最高的预测值是由有争议的海洋冰崖不稳定性(MICI)假说得出的,该假说认为,由于全球变暖导致的地表和次冰架融化,沿海冰崖在冰架解体后会迅速崩塌。但是人们在现代尚未观测到MICI,而且还不清楚它是否需要重现过去地质时期的海平面变化。

在这里,研究人员量化了原始MICI研究的冰盖建模不确定性,并表明概率分布倾向于较低的值。然而,由于上新世中期、上一个间冰期或1992至2017年的南极冰川消融,MICI不需要重现海平面变化,并且我们发现预测结果与以前的研究一致(95%的小于43厘米)。

研究结论是,由于MICI假设未被准确利用,预测结果高估了本世纪海平面的上升,仍需要更大范围的冰架脆弱性和冰崖崩塌的观测模型。

▲ Abstract

Predictions for sea-level rise this century due to melt from Antarctica range from zero to more than one metre. The highest predictions are driven by the controversial marine ice-cliff instability (MICI) hypothesis, which assumes that coastal ice cliffs can rapidly collapse after ice shelves disintegrate, as a result of surface and sub-shelf melting caused by global warming. But MICI has not been observed in the modern era and it remains unclear whether it is required to reproduce sea-level variations in the geological past. Here we quantify ice-sheet modelling uncertainties for the original MICI study and show that the probability distributions are skewed towards lower values (under very high greenhouse gas concentrations, the most likely value is 45 centimetres). However, MICI is not required to reproduce sea-level changes due to Antarctic ice loss in the mid-Pliocene epoch, the last interglacial period or 1992–2017; without it we find that the projections agree with previous studies (all 95th percentiles are less than 43 centimetres). We conclude that previous interpretations of these MICI projections over-estimate sea-level rise this century; because the MICI hypothesis is not well constrained, confidence in projections with MICI would require a greater range of observationally constrained models of ice-shelf vulnerability and ice-cliff collapse.

生物Biology

L1 drives IFN in senescent cells and promotes age-associated inflammation

L1在衰老细胞中驱动IFN并促进年龄相关性炎症

▲ 作者:Marco De Cecco、Takahiro Ito、Anna P. Petrashen、Amy E. Elias、Nicholas J. Skvir、Steven W. Criscione、John M. Sedivy,et al

▲ 链接:

https://www.nature.com/articles/s41586-018-0784-9

▲ 摘要:

逆转录转座子在许多层面上是有害的,因此宿主监测系统对这些因子的失效可能会产生负面后果。然而,逆转录转座子活性对衰老和年龄相关疾病的作用尚不清楚。

在本研究中,科学家发现在细胞衰老过程中,L1(也称为LINE-1)逆转录转座子被转录解除抑制,并激活I型干扰素(IFN-I)反应。IFN-I反应是一种晚期衰老的表型,有助于维持衰老相关分泌表型。IFN-I反应由细胞质L1 cDNA触发,并被L1逆转录酶抑制剂拮抗。

而衰老小鼠使用了核苷逆转录酶抑制剂拉米夫定后IFN-I的激活和多个组织的年龄相关性炎症降低。研究人员认为,逆转录转座子的激活是无菌炎症的重要组成部分,无菌炎症是衰老的标志,L1逆转录酶是治疗年龄相关疾病的相关靶点。

▲ Abstract

Retrotransposable elements are deleterious at many levels, and the failure of host surveillance systems for these elements can thus have negative consequences. However, the contribution of retrotransposon activity to ageing and age-associated diseases is not known. Here we show that during cellular senescence, L1 (also known as LINE-1) retrotransposable elements become transcriptionally derepressed and activate a type-I interferon (IFN-I) response. The IFN-I response is a phenotype of late senescence and contributes to the maintenance of the senescence-associated secretory phenotype. The IFN-I response is triggered by cytoplasmic L1 cDNA, and is antagonized by inhibitors of the L1 reverse transcriptase. Treatment of aged mice with the nucleoside reverse transcriptase inhibitor lamivudine downregulated IFN-I activation and age-associated inflammation (inflammaging) in several tissues. We propose that the activation of retrotransposons is an important component of sterile inflammation that is a hallmark of ageing, and that L1 reverse transcriptase is a relevant target for the treatment of age-associated disorders.

Super-Mendelian inheritance mediated by CRISPR–Cas9 in the female mouse germline

雌性小鼠生殖系中CRISPR-Cas9调节的超孟德尔遗传

▲ 作者:Hannah A. Grunwald、Valentino M. Gantz、Gunnar Poplawski、Xiang-Ru S. Xu、Ethan Bier、Kimberly L. Cooper

▲ 链接:

https://www.nature.com/articles/s41586-019-0875-2

▲ 摘要:

基因驱动能将外源基因快速引入动物群体,并由此消除相关疾病,或者对害虫和入侵物种进行控制。近年来,高效的基因驱动系统在昆虫中得到了发展,科学家利用CRISPR-Cas9的序列靶向DNA切割活性和内源性同源导向修复机制,将杂合子基因型转化为纯合子。然而,这种理论尚未在哺乳动物身上得到全面证实。

在这项研究中,研究人员利用CRISPR-Cas9改变雌性小鼠生殖系细胞,从而促进小鼠后代出现白色毛发和表达一种红色荧光蛋白。研究人员着重关注了酪氨酸酶的编码基因(它决定着毛发颜色)。他们将含有gRNA的基因驱动插入到酪氨酸酶基因的某个外显子中,gRNA能够将Cas9引导到酪氨酸酶基因和一个编码红色荧光蛋白的基因上。

这些结果证明了CRISPR-Cas9介导系统的可行性,该系统可以在小鼠中对所需等位基因进行编辑,并有可能改变啮齿类动物模型在基础和生物医学研究中的应用。

▲ Abstract

A gene drive biases the transmission of one of the two copies of a gene such that it is inherited more frequently than by random segregation. Highly efficient gene drive systems have recently been developed in insects, which leverage the sequence-targeted DNA cleavage activity of CRISPR–Cas9 and endogenous homology-directed repair mechanisms to convert heterozygous genotypes to homozygosity. If implemented in laboratory rodents, similar systems would enable the rapid assembly of currently impractical genotypes that involve multiple homozygous genes (for example, to model multigenic human diseases). To our knowledge, however, such a system has not yet been demonstrated in mammals. Here we use an active genetic element that encodes a guide RNA, which is embedded in the mouse tyrosinase (Tyr) gene, to evaluate whether targeted gene conversion can occur when CRISPR–Cas9 is active in the early embryo or in the developing germline. Although Cas9 efficiently induces double-stranded DNA breaks in the early embryo and male germline, these breaks are not corrected by homology-directed repair. By contrast, Cas9 expression limited to the female germline induces double-stranded breaks that are corrected by homology-directed repair, which copies the active genetic element from the donor to the receiver chromosome and increases its rate of inheritance in the next generation. These results demonstrate the feasibility of CRISPR–Cas9-mediated systems that bias inheritance of desired alleles in mice and that have the potential to transform the use of rodent models in basic and biomedical research.

Tissue curvature and apicobasal mechanical tension imbalance instruct cancer morphogenesis

组织曲度和机械张力失衡指导肿瘤形态发生

▲ 作者:Hendrik A. Messal、Silvanus Alt、Rute M. M. Ferreira、Christopher Gribben、Victoria Min-Yi Wang、Corina G. Cotoi、Guillaume Salbreux、Axel Behrens

▲ 链接:

https://www.nature.com/articles/s41586-019-0891-2

▲ 摘要:

管状上皮细胞是器官的基本组成部分,也是肿瘤发生的常见部位。在肿瘤发生过程中,转化细胞会过度增殖和上皮结构被破坏。然而,决定肿瘤组织形状异常的生物物理参数是未知的。

本研究在小鼠胰腺中发现,上皮肿瘤的形态是由转化细胞的细胞支架变化和现有管状结构的相互作用决定的。为了分析肿瘤发生过程中组织结构的变化,研究人员发展了一种三维全器官成像技术,可以在单细胞分辨率下进行组织活检。研究结果表明,源上皮的直径决定生长肿瘤的形态。而且,肿瘤生长的不同机制是由于系统的内在物理机制:张力不平衡和组织曲度是上皮性肿瘤发生的基本决定因素。

▲ Abstract

Tubular epithelia are a basic building block of organs and a common site of cancer occurrence. During tumorigenesis, transformed cells overproliferate and epithelial architecture is disrupted. However, the biophysical parameters that underlie the adoption of abnormal tumour tissue shapes are unknown. Here we show in the pancreas of mice that the morphology of epithelial tumours is determined by the interplay of cytoskeletal changes in transformed cells and the existing tubular geometry. To analyse the morphological changes in tissue architecture during the initiation of cancer, we developed a three-dimensional whole-organ imaging technique that enables tissue analysis at single-cell resolution. Oncogenic transformation of pancreatic ducts led to two types of neoplastic growth: exophytic lesions that expanded outwards from the duct and endophytic lesions that grew inwards to the ductal lumen. Myosin activity was higher apically than basally in wild-type cells, but upon transformation this gradient was lost in both lesion types. Three-dimensional vertex model simulations and a continuum theory of epithelial mechanics, which incorporate the cytoskeletal changes observed in transformed cells, indicated that the diameter of the source epithelium instructs the morphology of growing tumours. Three-dimensional imaging revealed that—consistent with theory predictions—small pancreatic ducts produced exophytic growth, whereas large ducts deformed endophytically. Similar patterns of lesion growth were observed in tubular epithelia of the liver and lung; this finding identifies tension imbalance and tissue curvature as fundamental determinants of epithelial tumorigenesis.

天文Astronomy

Formation of massive black holes in rapidly growing pre-galactic gas clouds

在快速增长的前星系气体云中大质量黑洞的形成

▲ 作者:John H. Wise、John A. Regan、Brian W. O’Shea、Michael L. Norman、Turlough P. Downes、Hao Xu

▲ 链接:

https://www.nature.com/articles/s41586-019-0873-4

▲ 摘要:

大质量星系中心的超大质量黑洞的起源尚不清楚。直接坍缩的黑洞——质量约为太阳1万倍的超大质量恒星的残余——是理想的候选者。然而,它们在早期宇宙中的存在和形成环境仍然存在争议,而且它们被认为是稀有的,这使得对它们的形成进行建模变得困难。模型表明,无金属晕中前星系气体云的快速坍缩是形成原恒星核的必要条件,而原恒星核随后将形成一颗超大质量恒星。

在这里,研究人员报告了早期星系形成的辐射流体动力学模拟,它产生的无金属晕质量足够大,并且有足够高的质量入射率形成超大质量恒星。结果发现,前星系晕及其伴生气体云暴露在莱曼—沃纳强度下(大约是背景辐射强度的3倍),并且在演化早期经历至少一个质量快速增长时期,是形成超大质量恒星的理想环境。

这种快速增长导致了大量的动力加热,放大了源自20千秒差距之外的年轻星系群的莱曼—沃纳抑制。结果表明,结构形成的动力学是早期宇宙大质量黑洞形成的主要驱动力,而且大质量黑洞的种子可能比以前认为的更为常见。

▲ Abstract

The origin of the supermassive black holes that inhabit the centres of massive galaxies remains unclear. Direct-collapse black holes—remnants of supermassive stars, with masses around 10,000 times that of the Sun—are ideal seed candidates. However, their very existence and their formation environment in the early Universe are still under debate, and their supposed rarity makes modelling their formation difficult. Models have shown that rapid collapse of pre-galactic gas (with a mass infall rate above some critical value) in metal-free haloes is a requirement for the formation of a protostellar core that will then form a supermassive star. Here we report a radiation hydrodynamics simulation of early galaxy formation that produces metal-free haloes massive enough and with sufficiently high mass infall rates to form supermassive stars. We find that pre-galactic haloes and their associated gas clouds that are exposed to a Lyman–Werner intensity roughly three times the intensity of the background radiation and that undergo at least one period of rapid mass growth early in their evolution are ideal environments for the formation of supermassive stars. The rapid growth induces substantial dynamical heating amplifying the Lyman–Werner suppression that originates from a group of young galaxies 20 kiloparsecs away. Our results strongly indicate that the dynamics of structure formation, rather than a critical Lyman–Werner flux, is the main driver of the formation of massive black holes in the early Universe. We find that the seeds of massive black holes may be much more common than previously considered in overdense regions of the early Universe, with a co-moving number density up to 10−3 per cubic megaparsec.

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