JN江南体育《科学》（20241206出版）一周论文导读

Science, 6 DEC 2024, Volume 386 Issue 6726

《科学》2024年12月6日，第386卷，6726期

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生物学Biology

Programming tissue-sensing T cells that deliver therapies to the brain

编程革新组织感应T细胞直达年夜脑进行医治

▲ 作者：MILOS S. SIMIC, PAYAL B. WATCHMAKER et al.

▲链接：

https://www.science.org/doi/10.1126/science.adl4237

▲摘要：

为了设计可以或许特异性靶向中枢神经系统（CNS）的细胞，我们判定了细胞外中枢神经系统特异性抗原，包罗中枢神经系统细胞外基质的成份和在神经元或胶质细胞上表达的概况份子。

用在检测这些抗原的合成Notch受体被用在编程革新T细胞，仅在年夜脑中引诱分歧有用载荷的表达。引诱嵌合抗原受体表达的CNS靶向T细胞有用断根了原发性和继发性脑肿瘤，而不侵害脑交际叉反映细胞。

另外，局部递送免疫按捺细胞因子白介素—10的中枢神经系统靶向细胞可改良小鼠神经炎症模子的症状。

▲ Abstract：

To engineer cells that can specifically target the central nervous system (CNS), we identified extracellular CNS-specific antigens, including components of the CNS extracellular matrix and surface molecules expressed on neurons or glial cells. Synthetic Notch receptors engineered to detect these antigens were used to program T cells to induce the expression of diverse payloads only in the brain. CNS-targeted T cells that induced chimeric antigen receptor expression efficiently cleared primary and secondary brain tumors without harming cross-reactive cells outside of the brain. Conversely, CNS-targeted cells that locally delivered the immunosuppressive cytokine interleukin-10 ameliorated symptoms in a mouse model of neuroinflammation.

动物学Zoology

The complete telomere-to-telomere sequence of a mouse genome

完全的端粒到端粒小鼠参考基因组序列

▲ 作者：JUNLI LIU, QILIN LI et al.

▲链接：

https://www.science.org/doi/10.1126/science.adq8191

▲摘要：

今朝小鼠的参考基因组GRCm39在与反复序列相干的正染色质和异染色质区域都存在较年夜的空白。在这项研究中，我们对小鼠单倍体胚胎干细胞的端粒到端粒基因组进行了测序和组装。

成果揭露了跨越7.7%此前未发现的小鼠基因组序列，包罗核糖体DNA阵列、周中间粒和亚端粒区域，和别的140个全新的卵白质编码基因。这项研究有助在弥补小鼠基因组的常识空白。

▲ Abstract：

The current reference genome of Mus musculus, GRCm39, has major gaps in both euchromatic and heterochromatic regions associated with repetitive sequences. In this work, we have sequenced and assembled the telomere-to-telomere genome of mouse haploid embryonic stem cells. The results reveal more than 7.7% of previously uncovered sequences of the mouse genome, including ribosomal DNA arrays and pericentromeric and subtelomeric regions, as well as an additional 140 genes predicted to be protein-coding. This study helps to address knowledge gaps in the mouse genome.

A transient neurohormonal circuit controls hatching in fish

一种短暂的神经激素回路节制鱼的孵化时候

▲ 作者：DEODATTA S. GAJBHIYE, GENEVIEVE L. FERNANDES et al.

▲链接：

https://www.science.org/doi/10.1126/science.ado8929

▲摘要：

孵化是卵生物种生命史上的主要事务。孵化的时候凡是是共同有益的前提精心遴选的，以提高生命初期的存活率。但是，相干的线索若何传递以触发孵化依然是未知的。

在这项研究中，我们发现促甲状腺激素释放激素（Trh）是斑马鱼孵化的神经内排泄激活剂。为了引诱孵化，Trh神经元构成一个短暂的回路，将肽沉积到胚胎的轮回中。Trh还激活了2亿多年前就已分手的远亲鱼类的孵化。研究成果揭露了一个在进化上守旧的神经内排泄回路，它节制着卵生鱼类的一个首要生命事务。

▲ Abstract：

Hatching is a critical event in the life history of oviparous species. The decision to hatch is often carefully timed to coincide with favorable conditions that will improve survival through early life stages. However, how the relevant cues are relayed to trigger hatching remains unknown. In this work, we show that thyrotropin-releasing hormone (Trh) is the neuroendocrine activator of hatching in zebrafish. To elicit hatching, Trh neurons form a transient circuit that deposits the peptide into the embryo’s circulation. Trh also activates hatching in a distantly related fish species that separated more than 200 million years ago. Our results reveal an evolutionarily conserved neuroendocrine circuit that controls a major life event in oviparous fish species.

地球科学Earth Science

Ecological erosion and expanding extinction risk of sharks and rays

沙鱼和鳐鱼蒙受生态腐蚀和灭尽风险扩年夜

▲ 作者：NICHOLAS K. DULVY, NATHAN PACOUREAU et al.

▲链接：

https://www.science.org/doi/10.1126/science.adn1477

▲摘要：

海洋生物多样性的真实状态很难评估，并且几近没有全球指标来追踪过度捕捞这一首要要挟。

我们计较了1199条沙鱼和鳐鱼50年的灭尽风险和生态功能红色名录指数，发现自1970年以来，过度捕捞使它们的数目削减了一半，红色名录指数恶化了19%。过度捕捞近岸和远洋栖息地中最年夜的物种，可能会致使生态形态的损失和5%至22%的功能多样性腐蚀。

在沿海生齿浩繁的国度，灭尽风险较高，但在治理更好、经济范围更年夜、有益渔业补助更多的国度，灭尽风险较低。将捕捞（包罗偶然捕捞）和商业限制在可延续程度，同时庇护高度受要挟物种，可以免族群的进一步削减、种群连通性的普遍损失和自上而下的捕食者节制。

▲ Abstract：

The true state of ocean biodiversity is difficult to assess, and there are few global indicators to track the primary threat of overfishing. We calculated a 50-year Red List Index of extinction risk and ecological function for 1199 sharks and rays and found that since 1970, overfishing has halved their populations and their Red List Index has worsened by 19%. Overfishing the largest species in nearshore and pelagic habitats risks loss of ecomorphotypes and a 5 to 22% erosion of functional diversity. ExtincJN江南·(中国区)体育官方网站-JN SPORTStion risk is higher in countries with large human coastal populations but lower in nations with stronger governance, larger economies, and greater beneficial fisheries subsidies. Restricting fishing (including incidental catch) and trade to sustainable levels combined with prohibiting retention of highly threatened species can avert further depletion, widespread loss of population connectivity, and top-down predator control.

Climate change extinctions

天气转变加重物种灭尽

▲ 作者：MARK C. URBAN

▲链接：

https://www.science.org/doi/10.1126/science.adp4461

▲摘要：

人们猜测天气转变会对生物多样性造成不成逆转的转变，但对这些风险的猜测依然不肯定。研究人员综合了485项研究和500多万个估算成果，对天气转变致使的物种灭尽进行了定量的全球评估。

跟着肯定性的增添，这项荟萃阐发注解，假如全球气温跨越1.5°C，物种灭尽将敏捷加快。最高排放量将要挟到全球约三分之一的物种。来自山地、岛屿和淡水生态系统的物种，糊口在南美洲、Australia和新西兰的物种和两栖动物都面对最年夜要挟。

与猜测一致，自1970年以来，天气转变致使不雅测到的全球物种灭尽比例不竭上升。除限制温室气体排放，在报酬天气转变住手和逆转之前，肯定要优先庇护哪些物种对庇护生物多样性相当主要。

▲ Abstract：

Climate change is expected to cause irreversible changes to biodiversity, but predicting those risks remains uncertain. I synthesized 485 studies and more than 5 million projections to produce a quantitative global assessment of climate change extinctions. With increased certainty, this meta-analysis suggests that extinctions will accelerate rapidly if global temperatures exceed 1.5°C. The highest-emission scenario would threaten approximately one-third of species, globally. Amphibians; species from mountain, island, and freshwater ecosystems; and species inhabiting South America, Australia, and New Zealand face the greatest threats. In line with predictions, climate change has contributed to an increasing proportion of observed global extinctions since 1970. Besides limiting greenhouse gases, pinpointing which species to protect first will be critical for preserving biodiversity until anthropogenic climate change is halted and reversed.

Pathways to reduce global plastic waste mismanagement and greenhouse gas emissions by 2050

到2050年削减全球塑料废料治理不善和温室气体排放的路子

▲ 作者：A. SAMUEL POTTINGER, ROLAND GEYER et al.

▲链接：

https://www.science.org/doi/10.1126/science.adr3837

▲摘要：

塑料出产和塑料污染对我们的情况、情况公道和蔼候转变都有负面影响。操纵具体的全球和区域塑料数据集和社会经济数据，我们操纵机械进修进行猜测，假如不加干涉干与，到2050年，每一年治理不善的塑料废料将增添近一倍，到达1.21亿吨（Mt）。

同时，塑料系统发生的年度温室气体排放量估计将增加37%，到达33.5亿吨二氧化碳当量。结合国塑料污染公约供给了机遇改写这一成果。

我们摹拟了8项候选公约政策，发现此中只有4项可以将治理不善的塑料废料削减91%，并将在塑料相干的温室气体总排放量削减1/3。

▲ Abstract：

Plastic production and plastic pollution have a negative effect on our environment, environmental justice, and climate change. Using detailed global and regional plastics datasets coupled with socioeconomic data, we employ machine learning to predict that, without intervention, annual mismanaged plastic waste will nearly double to 121 million metric tonnes (Mt) [100 to 139 Mt 95% confidence interval] by 2050. Annual greenhouse gas emissions from the plastic system are projected to grow by 37% to 3.35 billion tonnes CO2 equivalent (3.09 to 3.54) over the same period. The United Nations plastic pollution treaty presents an opportunity to reshape these outcomes. We simulate eight candidate treaty policies and find that just four could together reduce mismanaged plastic waste by 91% (86 to 98%) and gross plastic–related greenhouse gas emissions by one-third.