摘要：为了设计能够特异性靶向中枢神经系统（CNS）的细胞，我们鉴定了细胞外中枢神经系统特异性抗原，包括中枢神经系统细胞外基质的成分和在神经元或胶质细胞上表达的表面分子。
编译|李言
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
编程改造组织感应T细胞直达大脑进行治疗
▲ 作者：MILOS S. SIMIC, PAYAL B. WATCHMAKER et al.
▲链接：
▲摘要：
为了设计能够特异性靶向中枢神经系统（CNS）的细胞，我们鉴定了细胞外中枢神经系统特异性抗原，包括中枢神经系统细胞外基质的成分和在神经元或胶质细胞上表达的表面分子。
用于检测这些抗原的合成Notch受体被用于编程改造T细胞，仅在大脑中诱导不同有效载荷的表达。诱导嵌合抗原受体表达的CNS靶向T细胞有效清除了原发性和继发性脑肿瘤，而不损害脑外交叉反应细胞。
此外，局部递送免疫抑制细胞因子白介素—10的中枢神经系统靶向细胞可改善小鼠神经炎症模型的症状。
▲ 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
完整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：
▲摘要：
目前小鼠的参考基因组GRCm39在与重复序列相关的正染色质和异染色质区域都存在较大的空白。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。
结果揭示了超过7.7%此前未发现的小鼠基因组序列，包括核糖体DNA阵列、周中心粒和亚端粒区域，以及另外140个全新的蛋白质编码基因。这项研究有助于填补小鼠基因组的知识空白。
▲ 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控制鱼的孵化时间
▲ 作者：DEODATTA S. GAJBHIYE, GENEVIEVE L. FERNANDES et al.
▲链接：
▲摘要：
孵化是卵生物种生命史上的重要事件。孵化的时间通常是配合有利的条件精心挑选的，以提高生命早期的存活率。然而，相关的线索如何传递以触发孵化仍然是未知的。
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分泌激活剂。为了诱导孵化，Trh神经元形成一个短暂的回路，将肽沉积到胚胎的循环中。Trh还激活了2亿多年前就已分离的远亲鱼类的孵化。研究结果揭示了一个在进化上保守的神经内分泌回路，它控制着卵生鱼类的一个主要生命事件。
▲ 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
鲨鱼和鳐鱼遭受生态侵蚀和灭绝风险扩大
▲ 作者：NICHOLAS K. DULVY, NATHAN PACOUREAU et al.
▲链接：
▲摘要：
海洋生物多样性的真实状况很难评估，而且几乎没有全球指标来追踪过度捕捞这一主要威胁。
我们计算了1199条鲨鱼和鳐鱼50年的灭绝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量减少了一半，红色名录指数恶化了19%。过度捕捞近岸和远洋栖息地中最大的物种，可能会导致生态形态的丧失和5%至22%的功能多样性侵蚀。
在沿海人口众多的国家，灭绝风险较高，但在治理更好、经济规模更大、有益渔业补贴更多的国家，灭绝风险较低。将捕捞（包括偶尔捕捞）和贸易限制在可持续水平，同时保护高度受威胁物种，可以避免族群的进一步减少、种群连通性的广泛丧失以及自上而下的捕食者控制。
▲ 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. Extinction 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
气候变化加剧物种灭绝
▲ 作者：MARK C. URBAN
▲链接：
▲摘要：
人们预测气候变化会对生物多样性造成不可逆转的变化，但对这些风险的预测仍然不确定。研究人员综合了485项研究和500多万个估算结果，对气候变化导致的物种灭绝进行了定量的全球评估。
随着确定性的增加，这项荟萃分析表明，如果全球气温超过1.5°C，物种灭绝将迅速加速。最高排放量将威胁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，生活在南美洲、澳大利亚和新西兰的物种以及两栖动物都面临最大威胁。
与预测一致，自1970年以来，气候变化导致观测到的全球物种灭绝比例不断上升。除了限制温室气体排放，在人为气候变化停止和逆转之前，确定要优先保护哪些物种对于保护生物多样性至关重要。
▲ 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年减少全球塑料废物管理不善和温室气体排放的途径
▲ 作者：A. SAMUEL POTTINGER, ROLAND GEYER et al.
▲链接：
▲摘要：
塑料生产和塑料污染对我们的环境、环境公正和气候变化都有负面影响。利用详细的全球和区域塑料数据集以及社会经济数据，我们利用机器学习进行预测，如果不加干预，到2050年，每年管理不善的塑料废物将增加近一倍，达到1.21亿吨（Mt）。
同时，塑料体系产生的年度温室气体排放量预计将增长37%，达到33.5亿吨二氧化碳当量。联合国塑料污染条约提供了机会改写这一结果。
我们模拟了8项候选条约政策，发现其中只有4项可以将管理不善的塑料废物减少91%，并将于塑料相关的温室气体总排放量减少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.
来源：新浪财经
