来自杂志 Nature 的文献。
当前共找到 95 篇文献分享,本页显示第 1 - 20 篇。
1.
哪有情可长
(2025-07-28 14:14):
#paper Massive haplotypes underlie ecotypic differentiation in sunflowers,Nature,27 August 2020,doi.org/10.1038/s41586-020-2467-6。 该论文通过对1,506株野生向日葵(包括三个物种:Helianthus annuus、H. petiolaris 和 H. argophyllus)的重测序分析,发现了37个大型(1-100 Mbp)、非重组的单倍型区块(haploblocks)。这些单倍型区块与多个生态相关性状(如开花时间、种子大小)以及土壤和气候特征显著相关。主要发现包括:
1)单倍型区块的生态适应性作用:例如,在 H. argophyllus 中,一个约30 Mbp的单倍型区块(包含 HaFT1 基因)控制沿海与内陆种群之间77天的开花时间差异,且该区块可能是从 H. annuus 通过渐(introgression)引入的。
2)沙丘适应:在 H. petiolaris 中,多个单倍型区块与沙丘适应性相关,包括种子大小和土壤养分利用效率的差异。
3)结构变异的作用:大多数单倍型区块与大型结构变异(如倒位)相关,这些变异通过抑制重组维持适应性等位基因的组合。
2.
小年
(2025-07-27 22:43):
#paper doi:10.1101/2022.09.13.507640, Nature, David T.et al. The genomic basis of childhood T-lineage acute lymphoblastic leukaemia
研究团队对 1300 多例接受统一治疗的儿童 T 系急性淋巴细胞白血病(T-ALL)患者的肿瘤及缓解样本进行全基因组、转录组测序,并结合恶性和正常 T 细胞前体的表观基因组及单细胞分析,构建了包含 15 种亚型的 T-ALL 基因组特征图谱。发现 T-ALL 中存在广泛的非编码基因组改变,例如增强子失调通过多种机制导致癌基因表达异常,部分亚型中造血干细胞发育调节基因存在显著基因组改变。团队通过整合染色质拓扑分析,揭示了非编码区域在 T-ALL 发病中的关键作用,鉴定出 “ETP 样” 白血病这一具有多样免疫表型和独特基因组特征的亚型。基因组分析显示,多种遗传改变和疾病亚型是生存和治疗失败的独立预测因素,部分亚型呈现出与预后密切相关的特定基因表达模式。该研究建立了全面的儿童 T-ALL 基因组学数据库,揭示了非编码基因组调控异常和疾病亚型异质性的核心作用,提示基于基因组特征的亚型分类和风险分层可作为潜在治疗策略优化的依据。
3.
颜林林
(2025-07-26 13:41):
#paper doi:10.1038/s41586-025-09290-7, Nature, 2025, Structural variation in 1,019 diverse humans based on long-read sequencing. 这项工作相当于是“千人基因组项目的结构变异版”:基于千人基因组项目的1,019例代表性人群样本的中等深度长读长测序,构建了目前最全面的SV图谱之一。研究团队开发了SAGA分析框架,结合线性与图参考,系统地识别、分型并注释了超17万个SV位点,特别提升了插入、VNTR、多等位位点等此前难以准确解析的类型。文章从方法、数据到机制探索均具高完成度。其深入分析了SV在人群间的分布特征、形成机制(如NAHR、HDR、微同源介导修复等),以及移动元件转导事件的谱系和位点偏好,提供了关于SV发生、演化与功能影响的一系列重要观察。相比此前基于短读长的研究,本项目对稀有变异、多态性、反复事件等均有数量级上的提升。最终发布的pangenome资源,为今后的SV研究、图基因组方法开发和临床变异注释奠定了重要基础。整体现为“图基因组+长读长”模式在人群尺度研究中的一个范式转折点。对于SV感兴趣的,也可以深入研究和重复一下这篇文章中的方法。
Abstract:
Abstract Genomic structural variants (SVs) contribute substantially to genetic diversity and human diseases1–4, yet remain under-characterized in population-scale cohorts5. Here we conducted long-read sequencing6 in 1,019 humans to construct an …
>>>
Abstract Genomic structural variants (SVs) contribute substantially to genetic diversity and human diseases1–4, yet remain under-characterized in population-scale cohorts5. Here we conducted long-read sequencing6 in 1,019 humans to construct an intermediate-coverage resource covering 26 populations from the 1000 Genomes Project. Integrating linear and graph genome-based analyses, we uncover over 100,000 sequence-resolved biallelic SVs and we genotype 300,000 multiallelic variable number of tandem repeats7, advancing SV characterization over short-read-based population-scale surveys3,4. We characterize deletions, duplications, insertions and inversions in distinct populations. Long interspersed nuclear element-1 (L1) and SINE-VNTR-Alu (SVA) retrotransposition activities mediate the transduction8,9 of unique sequence stretches in 5′ or 3′, depending on source mobile element class and locus. SV breakpoint analyses point to a spectrum of homology-mediated processes contributing to SV formation and recurrent deletion events. Our open-access resource underscores the value of long-read sequencing in advancing SV characterization and enables guiding variant prioritization in patient genomes.
<<<
翻译
4.
惊鸿
(2025-07-10 23:31):
#paper 《Coherent bunching of anyons and dissociation in an interference experiment》25 June 2025 doi:10.1038/s41586-025-09143-3
该研究通过精密的纳米器件设计与极低温量子输运测量,首次观测到分数量子霍尔态中任意子的相干“成团”与可控“解离”现象。实验中,团队利用砷化镓/铝镓砷(GaAs/AlGaAs)异质结材料构建手性马赫-曾德尔干涉仪,在15 mK超低温与强磁场(>10 T)下,发现填充因子ν=2/3、3/5、4/7时出现异常通量周期ΔΦ=νΦ₀(Φ₀为磁通量子),而非理论预期的(e/e*)Φ₀周期。这一反常现象源于多个基本准粒子自发聚集成相干“束团”,如四重态(ν=4/7)或三重态(ν=3/5),形成集体干涉行为。更关键的是,通过调节沉积在器件中心的金属栅极电压(Vₜ₉),研究者成功诱导局域准粒子态,使“束团”解离为单个准粒子,恢复常规通量周期,首次实现任意子集体行为的主动调控。
此项工作揭示了拓扑量子物态中未被理论预见的多体关联效应,挑战了现有分数量子霍尔理论框架。其技术突破在于将纳米尺度静电操控与量子相干测量结合,为设计具有动态拓扑保护能力的量子计算材料提供了新范式。实验揭示的“成团-解离”相变机制,暗示任意子可能通过集体态增强对环境噪声的鲁棒性,这对开发容错量子比特具有重要启示——若能操控此类相变,或可构建自适应拓扑保护的量子信息存储单元。
Nature,
2025-6-26.
DOI: 10.1038/s41586-025-09143-3
Abstract:
No abstract available.
5.
孤舟蓑笠翁
(2025-06-29 09:36):
#paper 【doi】10.1038/s41586-025-09182-w;【发表年份】2025年;【期刊】Nature;【标题】In vivo mapping of mutagenesis sensitivity of human enhancers。【内容总结】这篇论文想搞清楚人类增强子(控制基因开关的DNA片段)中哪些小片段对胚胎发育最关键。科学家选了7个控制大脑、心脏和四肢发育的增强子,用转基因小鼠做实验:先把这些增强子切成12碱基的小块,用CRISPR技术突变每个小块,然后观察突变后胚胎器官发育的变化(主要看颜色标记的LacZ基因表达)。他们发现69%的小块突变会影响发育(60%让增强子失效,9%反而增强活性),并用机器学习模型预测出88%的关键位点与实验结果吻合。简单说就是:像拆乐高一样把增强子拆成小零件,发现大部分零件都重要,突变会搞乱发育;还训练AI模型来预测哪些零件最关键,结果挺准。主要方法包括:转基因小鼠胚胎实验(enSERT技术)、12bp块突变策略、ChromBPNet机器学习模型分析染色质开放信号、DeepLIFT算法定位关键碱基。
6.
孤舟蓑笠翁
(2025-06-29 09:18):
#paper 【doi】10.1038/s41586-025-09154-0;【发表年份】2025年;【期刊】Nature;【标题】Major expansion in the human niche preceded out of Africa dispersal。【内容总结】这篇论文研究了为什么现代人类(智人)大约5万年前能成功走出非洲并扩散到全球,而更早的非洲外扩散(如12.5万年前)却未能留下遗传痕迹。研究者通过分析非洲479个放射性定年的考古遗址(图1显示分布),结合两种古气候模型(HadCM3和PCESM),使用物种分布模型(SDMs)和广义加性模型(GAMs)量化了人类生态位变化。结果发现,从约7万年前开始,人类逐渐适应了更广泛的生境(如森林和沙漠,图4b),这种生态灵活性在5万年前达到高峰,正好与成功扩散的时间吻合。研究认为,这种生态位扩张(可能是由于技术革新或人口压力)让人类能够应对走出非洲后遇到的各种环境挑战,而早期群体因适应性不足而失败。方法上,团队通过重采样解决考古数据的时间偏差(Extended Data Fig.1),并用主成分分析量化生态位空间变化(Extended Data Fig.3)。
Nature,
2025-6-18.
DOI: 10.1038/s41586-025-09154-0
Abstract:
Abstract All contemporary Eurasians trace most of their ancestry to a small population that dispersed out of Africa about 50,000 years ago (ka)1–9. By contrast, fossil evidence attests to earlier …
>>>
Abstract All contemporary Eurasians trace most of their ancestry to a small population that dispersed out of Africa about 50,000 years ago (ka)1–9. By contrast, fossil evidence attests to earlier migrations out of Africa10–15. These lines of evidence can only be reconciled if early dispersals made little to no genetic contribution to the later, major wave. A key question therefore concerns what factors facilitated the successful later dispersal that led to long-term settlement beyond Africa. Here we show that a notable expansion in human niche breadth within Africa precedes this later dispersal. We assembled a pan-African database of chronometrically dated archaeological sites and used species distribution models (SDMs) to quantify changes in the bioclimatic niche over the past 120,000 years. We found that the human niche began to expand substantially from 70 ka and that this expansion was driven by humans increasing their use of diverse habitat types, from forests to arid deserts. Thus, humans dispersing out of Africa after 50 ka were equipped with a distinctive ecological flexibility among hominins as they encountered climatically challenging habitats, providing a key mechanism for their adaptive success.
<<<
翻译
7.
孤舟蓑笠翁
(2025-06-29 09:11):
#paper 【doi】10.1038/s41586-025-09151-3;【发表年份】2025年;【期刊】Nature;【标题】Morphodynamics of human early brain organoid development。【内容总结】这项研究想了解人类大脑早期发育过程中细胞外基质(ECM)如何影响脑类器官的形状变化和区域形成。科学家们开发了新技术:1)用荧光标记不同细胞结构(细胞膜、细胞骨架等),2)用光片显微镜长期观察类器官生长,3)计算机分析细胞形状变化。他们发现:1)脑类器官发育分三个阶段(快速生长、腔室融合、成熟),2)添加外源ECM(如Matrigel)能帮助形成更规则的神经上皮结构,3)缺少ECM会导致类器官发育异常,出现更多神经嵴细胞,4)ECM通过WNT和Hippo信号通路影响类器官发育。具体来说,研究团队标记了肌动蛋白、微管等结构,用显微镜追踪数周,发现ECM能促进细胞排列整齐和腔室融合;没有ECM时,YAP1蛋白会上调,激活WNT通路基因WLS,导致类器官尾部化(更像脊髓而不是大脑)。这些发现帮助我们理解ECM在人类大脑发育中的重要作用。
Nature,
2025-6-18.
DOI: 10.1038/s41586-025-09151-3
Abstract:
Abstract Brain organoids enable the mechanistic study of human brain development and provide opportunities to explore self-organization in unconstrained developmental systems1–3. Here we establish long-term, live light-sheet microscopy on unguided …
>>>
Abstract Brain organoids enable the mechanistic study of human brain development and provide opportunities to explore self-organization in unconstrained developmental systems1–3. Here we establish long-term, live light-sheet microscopy on unguided brain organoids generated from fluorescently labelled human induced pluripotent stem cells, which enables tracking of tissue morphology, cell behaviours and subcellular features over weeks of organoid development4. We provide a novel dual-channel, multi-mosaic and multi-protein labelling strategy combined with a computational demultiplexing approach to enable simultaneous quantification of distinct subcellular features during organoid development. We track actin, tubulin, plasma membrane, nucleus and nuclear envelope dynamics, and quantify cell morphometric and alignment changes during tissue-state transitions including neuroepithelial induction, maturation, lumenization and brain regionalization. On the basis of imaging and single-cell transcriptome modalities, we find that lumenal expansion and cell morphotype composition within the developing neuroepithelium are associated with modulation of gene expression programs involving extracellular matrix pathway regulators and mechanosensing. We show that an extrinsically provided matrix enhances lumen expansion as well as telencephalon formation, and unguided organoids grown in the absence of an extrinsic matrix have altered morphologies with increased neural crest and caudalized tissue identity. Matrix-induced regional guidance and lumen morphogenesis are linked to the WNT and Hippo (YAP1) signalling pathways, including spatially restricted induction of the WNT ligand secretion mediator (WLS) that marks the earliest emergence of non-telencephalic brain regions. Together, our work provides an inroad into studying human brain morphodynamics and supports a view that matrix-linked mechanosensing dynamics have a central role during brain regionalization.
<<<
翻译
8.
孤舟蓑笠翁
(2025-06-29 09:01):
#paper 【doi】;【发表年份】2025年;【期刊】Nature;【标题】Targeting de novo purine biosynthesis for tuberculosis treatment。【内容总结】这篇研究想解决结核病治疗中药物耐药和疗程长的问题,科学家们发现了一种叫JNJ-6640的新药,它能精准打击结核菌制造嘌呤(DNA的原料)的第一步关键酶PurF。他们先筛了4924种化合物找到苗头,再改进结构让药效更强(MIC90=8.6 nM),用基因敲除、显微镜看细菌分裂、测肺里化学物质浓度等方法证明这药只杀结核菌不伤人类细胞。重要发现包括:药能让结核菌的DNA复制停工(看图3的细菌分裂动画),肺里的嘌呤原料太少救不了被药打击的细菌(表1数据),动物实验用长效针剂打两针就能减少近99%病菌。这药还能替换现有方案里毒性大的药物,可能让未来治疗更短更安全。简单说就是:找到新靶点→设计特效药→证明它管用且安全→能改进现有疗法。
9.
孤舟蓑笠翁
(2025-06-29 08:54):
#paper 【doi】10.1038/s41586-025-09160-2;【发表年份】2025年;【期刊】Nature;【标题】Machine-learning design of ductile FeNiCoAlTa alloys with high strength。【内容总结】这篇论文的目标是开发同时具备高强度和高延展性的新型合金,突破传统合金强度与延展性此消彼长的限制。研究者采用机器学习结合领域知识(如原子尺寸错配最大化、L12/B2相调控)设计了Fe35Ni29Co21Al12Ta3高熵合金,通过冷轧和热处理工艺获得含66.6% L12纳米沉淀相和15% B2微米相的双相结构。实验结果惊人:屈服强度达1.8GPa的同时保持25%均匀延伸率,远超现有钢材和传统高熵合金。具体而言,团队首先构建包含20种物理特征的数据库,通过六步主动学习循环(数据收集→物性描述符筛选→模型训练→知识引导虚拟筛选→效用函数设计→实验验证)优化成分,最终材料中L12相提供主要强化(859MPa),可变形B2相通过位错积累维持高加工硬化率,两者协同作用使性能突破现有材料极限。关键创新在于机器学习指导下的多组元沉淀相设计,以及通过高体积分数可变形B2相(传统硬脆相经Ta合金化后变为韧性相)实现强度-延展性协同提升。
10.
孤舟蓑笠翁
(2025-06-29 08:37):
#paper 【doi】10.1038/s41586-025-09190-w;【发表年份】2025年;【期刊】Nature;【标题】Kupffer cell programming by maternal obesity triggers fatty liver disease。【内容总结】这篇论文研究了母亲肥胖如何通过影响胎儿肝脏中的Kupffer细胞(KC)导致后代成年后出现脂肪肝疾病。简单来说,科学家发现肥胖母亲体内的高脂肪饮食会让胎儿KC细胞从正常代谢模式(氧化磷酸化)转变为异常模式(糖酵解),这种变化会持续到成年并促进肝细胞脂肪堆积。他们用小鼠实验证明,通过基因敲除KC中的HIF1α蛋白可以阻止这种代谢转变,从而预防脂肪肝。主要方法包括:建立母体肥胖小鼠模型、流式细胞术分析免疫细胞、RNA测序分析基因表达、单细胞多组学测序(RNA+ATAC)、脂质组学和代谢组学分析、体外肝细胞共培养实验等。详细来说,研究发现母体肥胖会重编程KC细胞的代谢和免疫功能,使其分泌更多载脂蛋白(如APOE和APOA1),这些蛋白会促进肝细胞吸收脂质;通过KC特异性基因敲除和细胞移植实验证实,发育期KC的异常编程是导致成年脂肪肝的关键因素,而补充正常KC可以逆转这一过程。
11.
孤舟蓑笠翁
(2025-06-19 20:25):
#paper 【doi】10.1038/s41586-025-09083-y;【发表年份】2025年;【期刊】Nature;【标题】Single-cell transcriptomic and chromatin dynamics of the human brain in PTSD。【内容总结】这篇论文想弄清楚创伤后应激障碍(PTSD)如何改变大脑细胞的分子工作机制,帮助理解为什么患者会有长期症状。他们用了单核RNA测序和单核ATAC测序来分析超过200万个来自111个人类大脑前额叶皮层的细胞核,比较了PTSD患者、重度抑郁症(MDD)患者和健康对照组的差异,还结合了空间转录组学技术验证结果。主要方法包括:细胞类型聚类找不同脑细胞、差异基因分析看哪些基因表达变了、基因本体论分析看功能变化、细胞间通讯分析测信号传递、以及整合遗传数据找风险基因。结果发现PTSD会让抑制性神经元、内皮细胞和小胶质细胞的基因表达出问题,比如内皮细胞中应激相关基因FKBP5明显升高,SST神经元信号输出减少导致脑细胞沟通变差;还鉴定出ELFN1等风险基因的调控机制,这些变化在糖皮质激素信号和神经炎症通路中特别突出,而和抑郁症相比,PTSD有独特的分子特征比如微胶质细胞活动更低。简而言之,研究用前沿技术扫描PTSD大脑细胞,发现特定细胞的功能紊乱是症状持续的关键,并锁定了几个潜在治疗靶点。
Abstract:
Post-traumatic stress disorder (PTSD) is a polygenic disorder occurring after extreme trauma exposure. Recent studies have begun to detail the molecular biology of PTSD. However, given the array of PTSD-perturbed …
>>>
Post-traumatic stress disorder (PTSD) is a polygenic disorder occurring after extreme trauma exposure. Recent studies have begun to detail the molecular biology of PTSD. However, given the array of PTSD-perturbed molecular pathways identified so far, it is implausible that a single cell type is responsible. Here we profile the molecular responses in over two million nuclei from the dorsolateral prefrontal cortex of 111 human brains, collected post-mortem from individuals with and without PTSD and major depressive disorder. We identify neuronal and non-neuronal cell-type clusters, gene expression changes and transcriptional regulators, and map the epigenomic regulome of PTSD in a cell-type-specific manner. Our analysis revealed PTSD-associated gene alterations in inhibitory neurons, endothelial cells and microglia and uncovered genes and pathways associated with glucocorticoid signalling, GABAergic transmission and neuroinflammation. We further validated these findings using cell-type-specific spatial transcriptomics, confirming disruption of key genes such as SST and FKBP5. By integrating genetic, transcriptomic and epigenetic data, we uncovered the regulatory mechanisms of credible variants that disrupt PTSD genes, including ELFN1, MAD1L1 and KCNIP4, in a cell-type-specific context. Together, these findings provide a comprehensive characterization of the cell-specific molecular regulatory mechanisms that underlie the persisting effects of traumatic stress response on the human prefrontal cortex.
<<<
翻译
12.
惊鸿
(2025-06-13 23:47):
#paper
Nature
Pub Date : 2025-06-11
DOI : 10.1038/d41586-025-01453-w
Computer processors built from 2D materials
2025年6月《自然》期刊报道的两项独立研究(Ghosh等和Ao等)首次实现了基于二维材料的完整计算机处理器原型。Ghosh团队构建了约1000个二硫化钼晶体管的单指令集芯片,Ao团队则集成了约2500个二维晶体管制成兼容RISC-V架构的32位微处理器。这两项突破验证了二维材料(如过渡金属硫化物)在系统级集成电路中的可行性,其核心价值在于:二维材料的原子级厚度(约0.7纳米)可突破硅基晶体管在10纳米尺度以下性能衰减的物理限制。
然而,当前技术仍面临三重挑战:一是材料缺陷导致器件均一性不足,实验室原型良率远低于商用硅芯片;二是制造工艺不兼容现有半导体产线,需开发全新的二维材料晶圆级集成技术;三是载流子迁移率等关键性能参数仍需优化。研究团队通过创新设计(如Ao采用双栅结构提升稳定性)部分缓解了这些问题,但距离产业化尚有距离。
从技术演进角度看,这两项工作标志着二维电子学从器件研究迈向系统集成的重要转折点。短期看,二维材料可能作为硅基芯片的补充模块(如特定低功耗单元);长期若突破规模化瓶颈,或将为后摩尔时代提供新的技术路径。其科学意义在于实证了原子级薄层材料承载复杂计算架构的能力,为纳米尺度电子器件发展提供了关键数据支撑。
Nature,
2025-6-12.
DOI: 10.1038/d41586-025-01453-w
Abstract:
No abstract available.
13.
孤舟蓑笠翁
(2025-05-30 22:24):
#paper 【doi】10.1038/s41586-025-09053-4;【发表年份】2025年;【期刊】Nature;【标题】Cross-tissue multicellular coordination and its rewiring in cancer。这篇论文研究了人体组织中不同细胞类型如何协同工作维持健康,以及这种协同在癌症中如何被破坏。科学家们整合了35种健康组织和29种癌症类型的单细胞数据,开发了CoVarNet计算工具,发现了12种跨组织的"细胞模块"(CMs)——这些是经常一起出现的细胞组合。比如在脾脏中,某些免疫细胞模块会随着年龄增长而改变;在乳腺中,特定成纤维细胞模块与绝经相关。更惊人的是,癌症会破坏健康组织的细胞模块,同时形成新的、促进肿瘤生长的模块。通过分析这些模块,研究者还找到了可能用于癌症早期诊断的分子标志物。简单来说,这项工作就像绘制了一幅"细胞社交网络"地图,展示了健康时细胞如何团队合作,而癌症时这些团队如何重组——这为理解疾病机制和开发新疗法提供了重要线索。
Abstract:
The multicellular coordination that underlies tissue homeostasis and disease progression is of fundamental interest. However, how diverse cell types are organized within tissue niches for cohesive functioning remains largely unknown. …
>>>
The multicellular coordination that underlies tissue homeostasis and disease progression is of fundamental interest. However, how diverse cell types are organized within tissue niches for cohesive functioning remains largely unknown. Here we systematically characterized cross-tissue coordinated cellular modules in healthy tissues, uncovering their spatiotemporal dynamics and phenotypic associations, and examined their rewiring in cancer. We first compiled a comprehensive single-cell transcriptomic atlas from 35 human tissues, revealing substantial inter-tissue variability in cellular composition. By leveraging covariance in cellular abundance, we identified 12 cellular modules with distinct cellular compositions, tissue prevalences and spatial organizations, and demonstrated coordinated intercellular communication within cellular modules using in situ spatial and in vivo perturbation data. Among them, two immune cellular modules in the spleen showed contrasting chronological dynamics with ageing. Analysis of multicellular changes in the breast revealed a menopausal trajectory associated with fibroblast dynamics. Furthermore, interrogation across cancer types uncovered simultaneous rewiring of two types of multicellular ecosystem during tumour progression, including the loss of tissue-specific healthy organization and the emergence of a convergent cancerous ecosystem. These findings reveal fundamental organizing principles of multicellular ecosystems in health and cancer, laying a foundation for further investigations into tissue-level functional coordination across diverse contexts.
<<<
翻译
14.
惊鸿
(2025-04-14 22:39):
#paper Will AI improve your life? Here’s what 4,000 researchers think Pub Date : 2025-04-09
DOI : 10.1038/d41586-025-01123-x
这是一篇对4260名AI研究员调查AI是否会使人类受益的评价,研究者中54%认为技术利大于弊,仅13%英国公众认同;双方均担忧虚假信息与数据滥用,但科学家更反对企业滥用盗版数据训练模型,呼吁审慎政策。
调查显示,科学家对AI的教育(75%)、医疗(57%)潜力高度乐观,但警惕数据伦理风险:仅25%支持企业使用盗版书籍/论文训练模型,近半数(49%)要求明确用户授权。研究负责人Cian O'Donovan指出,政策需平衡创新与风险,例如建立数据补偿机制,而非简单“选择退出”规则。牛津专家Robert Trager强调,AI安全需结合技术优化与数据伦理,各国政策应纳入“红队测试”等防护机制。
Nature,
2025-4-17.
DOI: 10.1038/d41586-025-01123-x
Abstract:
No abstract available.
15.
孤舟蓑笠翁
(2025-04-05 09:05):
#paper 【doi】10.1038/s41586-025-08732-6;【发表年份】2025年;【期刊】Nature;【标题】VDAC2 loss elicits tumour destruction and inflammation for cancer therapy。本研究发现,电压依赖性阴离子通道2(VDAC2)在肿瘤免疫逃逸中起关键作用。研究者利用CRISPR–Cas9基因筛选技术,发现VDAC2是免疫信号依赖的检查点,限制了干扰素-γ(IFNγ)介导的肿瘤破坏和肿瘤微环境的炎症重编程。研究中,靶向肿瘤细胞中的VDAC2能够增强IFNγ诱导的细胞死亡和cGAS–STING信号通路的激活,显著改善抗肿瘤效果和免疫治疗反应。通过全基因组遗传互作筛选,研究者确定BAK是VDAC2缺失诱导效应的介质。机制上,IFNγ刺激增加了BIM、BID和BAK的表达,而VDAC2的缺失则导致IFNγ诱导的BAK激活失控,进而引发线粒体损伤。随后,线粒体DNA异常释放到细胞质中,触发了cGAS–STING信号通路和I型干扰素反应的强烈激活。重要的是,共同缺失STING信号通路组分会削弱肿瘤细胞中VDAC2耗竭的治疗效果,这表明靶向VDAC2整合了CD8+ T细胞和IFNγ介导的适应性免疫与肿瘤内源性类固有免疫反应。研究结果揭示了VDAC2作为一个双重作用靶点,能够克服肿瘤免疫逃逸,并强调了协同破坏和炎症化肿瘤以实现有效癌症免疫治疗的重要性。
16.
孤舟蓑笠翁
(2025-03-05 21:45):
#paper 【doi】10.1038/s41586-024-07954-4;【发表年份】2024年;【期刊】Nature;【标题】Temporal recording of mammalian development and precancer。该研究旨在突破传统细胞事件追踪技术的局限性,通过开发基于CRISPR的单细胞分子钟平台,实现哺乳动物发育和肿瘤起源的精准时空记录。研究者利用自突变CRISPR条形码技术,在单细胞水平同步捕获基因表达和遗传变异信息,系统解析了小鼠胚胎器官形成过程中细胞增殖、分化和克隆动态,揭示出肠道发育中未被识别的新型祖细胞群体及其功能特征。进一步将此技术应用于人类结直肠癌前病变样本(包含116个息肉的转录组和418个息肉的突变组数据),首次证实约15-30%的腺瘤起源于多个独立正常干细胞,挑战了传统单克隆致癌假说,为癌症早期起源机制研究提供了多维证据支持。
17.
孤舟蓑笠翁
(2025-02-28 21:55):
#paper 10.1038/s41586-025-08622-x. 2025. Nature. Comparative characterization of human accelerated regions in neurons. 这项研究通过比较人类和黑猩猩诱导多能干细胞(iPS细胞)诱导的兴奋性神经元中的HARs,揭示了HARs在人类大脑进化中的潜在作用。研究发现,HAR202在人类神经元中通过改变多个转录因子的结合亲和力来降低NPAS3的表达,而在黑猩猩神经元中,HAR202的同源区域则增强了NPAS3的表达。此外,2xHAR.319在人类神经元中特异性地增强了PUM2的表达,这对于维持iPS细胞的多能性和神经元分化至关重要。敲除2xHAR.319会导致PUM2表达下降,影响细胞的自我更新和分化能力。最后,HAR26;2xHAR.178在人类神经元中通过增强SOCS2的表达来促进神经突起的生长,而在黑猩猩神经元中,这一区域的同源区域则没有这种作用。这些发现为理解HARs在人类大脑进化中的作用提供了新的见解。
18.
Vincent
(2025-02-28 18:53):
#paper https://doi.org/10.1038/s41586-024-08328-6 nature. 2025. Accurate predictions on small data with a tabular foundation model. 过去二十年表格型数据预测一直是梯度提升决策树(gradient boosting decision tree)的天下,这篇文章开发了一种基于生成型transformer的表格基础模型。模型采用统一的嵌入方式来表示数值型和类别型特征,通过自注意力机制捕捉不同特征之间的复杂交互关系,并在数百万个合成数据上进行了大规模预训练,从而显著提升了对新任务的适应能力。实验结果显示,在多个真实小规模数据集上,该模型在预测准确度和训练效率方面都优于传统梯度提升决策树以及其他常见深度学习基线。研究还通过定量、定性和可解释性分析验证了模型在模型微调、数据生成、密度估计及表示学习等方面的多任务能力。尽管该模型在小数据场景中展现出显著优势,但真实数据分布的多样性、扩展到更高维度数据,理解模型的理论基础等问题仍有待进一步研究。
Abstract:
AbstractTabular data, spreadsheets organized in rows and columns, are ubiquitous across scientific fields, from biomedicine to particle physics to economics and climate science1,2. The fundamental prediction task of filling in …
>>>
AbstractTabular data, spreadsheets organized in rows and columns, are ubiquitous across scientific fields, from biomedicine to particle physics to economics and climate science1,2. The fundamental prediction task of filling in missing values of a label column based on the rest of the columns is essential for various applications as diverse as biomedical risk models, drug discovery and materials science. Although deep learning has revolutionized learning from raw data and led to numerous high-profile success stories3–5, gradient-boosted decision trees6–9 have dominated tabular data for the past 20 years. Here we present the Tabular Prior-data Fitted Network (TabPFN), a tabular foundation model that outperforms all previous methods on datasets with up to 10,000 samples by a wide margin, using substantially less training time. In 2.8 s, TabPFN outperforms an ensemble of the strongest baselines tuned for 4 h in a classification setting. As a generative transformer-based foundation model, this model also allows fine-tuning, data generation, density estimation and learning reusable embeddings. TabPFN is a learning algorithm that is itself learned across millions of synthetic datasets, demonstrating the power of this approach for algorithm development. By improving modelling abilities across diverse fields, TabPFN has the potential to accelerate scientific discovery and enhance important decision-making in various domains.
<<<
翻译
19.
林海onrush
(2025-02-28 16:21):
#paper, Nature, https://doi.org/10.1038/s41586-025-08613-y, Humans in Africa’s wet tropical forests 150 thousand years ago, 本文研究大约 15 万年前人类在非洲西部科特迪瓦湿润热带雨林中的活动,该研究挑战传统观点:热带雨林对早期智人(Homo sapiens)构成了生态障碍。研究通过光释光(OSL)和电子自旋共振(ESR)测年方法,确定 Bété I 遗址的人类占据时间,并结合植物蜡生物标记、稳定同位素、植物硅体和花粉分析,确认当时的环境是湿润的热带森林。这是迄今为止最早的确凿证据,证明智人早在 15 万年前就适应并生活在热带雨林中,非洲雨林在智人演化和迁徙中可能发挥了更重要的作用。
Nature,
2025-2-26.
DOI: 10.1038/s41586-025-08613-y
Abstract:
Abstract Humans emerged across Africa shortly before 300 thousand years ago (ka)1–3. Although this pan-African evolutionary process implicates diverse environments in the human story, the role of tropical forests remains …
>>>
Abstract Humans emerged across Africa shortly before 300 thousand years ago (ka)1–3. Although this pan-African evolutionary process implicates diverse environments in the human story, the role of tropical forests remains poorly understood. Here we report a clear association between late Middle Pleistocene material culture and a wet tropical forest in southern Côte d’Ivoire, a region of present-day rainforest. Twinned optically stimulated luminescence and electron spin resonance dating methods constrain the onset of human occupations at Bété I to around 150 ka, linking them with Homo sapiens. Plant wax biomarker, stable isotope, phytolith and pollen analyses of associated sediments all point to a wet forest environment. The results represent the oldest yet known clear association between humans and this habitat type. The secure attribution of stone tool assemblages with the wet forest environment demonstrates that Africa’s forests were not a major ecological barrier for H. sapiens as early as around 150 ka.
<<<
翻译
20.
李翛然
(2025-02-27 12:03):
#paper Biggest-ever AI biology model writes DNA on demand doi:https://doi.org/10.1038/d41586-025-00531-3 evo2 最近非常出名, 主要就是微软的ev2该研究可能开发了当前规模最大的基因组语言模型(Genomic Language Model, GLM),通过深度学习技术实现按需设计功能性DNA序列。其核心思路借鉴了大型语言模型(如ChatGPT)的自监督预训练方法,利用海量基因组数据学习DNA序列的“语法规则”,从而预测或生成具有特定调控功能的序列 。 虽然文章中揭示了bcra基因的突变相关影响基因。但是临床实践上,其实方法很多,暂时没有看出来哪些碾压的存在,倒是twitter讨论的很多,说是可以预测病毒突变,这个我有待观察。论文原文并没有提到这个
Nature,
2025-2-27.
DOI: 10.1038/d41586-025-00531-3
Abstract:
No abstract available.