翻译 | 宗华
Nature, 20 June 2019, Volume 570 Issue 7761
《自然》 2019年6月20日，第7761期570卷
健康 Health
Genome-wide cell-free DNA fragmentation in patients with cancer
全基因组游离DNA在癌症患者体内的裂解
作者：Stephen Cristiano, Alessandro Leal, Jillian Phallen, et al
链接：
https://www.nature.com/articles/s41586-019-1272-6
摘要：
血液中的游离DNA为癌症患者提供了一种非侵入性的诊断途径。然而，目前对游离DNA的起源特征和分子特征的了解甚少。
这里，我们开发了一种方法来评估基因组中游离DNA的裂解模式，并发现健康个体的图谱反映了白细胞的核小体模式，而癌症患者改变了裂解模式。
我们采用该方法对236例乳腺癌、结直肠癌、肺癌、卵巢癌、胰腺癌、胃癌、胆道癌患者和245例健康人的游离DNA裂解图谱进行了分析。
一个包含全基因组裂解特征的机器学习模型，在7种癌症类型中的检测灵敏度从57%到超过99%不等，特异性为98%，曲线下面积值为0.94。
Abstract
Cell-free DNA in the blood provides a non-invasive diagnostic avenue for patients with cancer. However, characteristics of the origins and molecular features of cell-free DNA are poorly understood. Here we developed an approach to evaluate fragmentation patterns of cell-free DNA across the genome, and found that profiles of healthy individuals reflected nucleosomal patterns of white blood cells, whereas patients with cancer had altered fragmentation profiles. We used this method to analyse the fragmentation profiles of 236 patients with breast, colorectal, lung, ovarian, pancreatic, gastric or bile duct cancer and 245 healthy individuals. A machine learning model that incorporated genome-wide fragmentation features had sensitivities of detection ranging from 57% to more than 99% among the seven cancer types at 98% specificity, with an overall area under the curve value of 0.94.
Single-cell transcriptomic analysis of Alzheimer’s disease
对阿尔茨海默氏症的单细胞转录组分析
作者：Hansruedi Mathys, Jose Davila-Velderrain, Zhuyu Peng, Fan Gao, et al
链接：
https://www.nature.com/articles/s41586-019-1195-2
摘要：
阿尔茨海默氏症是一种广泛存在的神经退行性疾病，其分子复杂性至今仍不为人所知。
这里，我们分析了来自48名拥有不同程度阿尔茨海默氏症病理的患者前额皮质的80660个单核转录组。在6种主要的脑细胞类型中，我们确认了转录上不同的亚群，包括那些与病理相关并以髓鞘形成、炎症和神经元存活的调节因子为特征的亚群。
与该疾病相关的最强烈变化出现在病理进展的早期，且具有高度的细胞类型特异性，而在晚期基因上调在细胞类型中很常见，主要参与整个机体的应激反应。
Abstract
Alzheimer’s disease is a pervasive neurodegenerative disorder, the molecular complexity of which remains poorly understood. Here, we analysed 80,660 single-nucleus transcriptomes from the prefrontal cortex of 48 individuals with varying degrees of Alzheimer’s disease pathology. Across six major brain cell types, we identified transcriptionally distinct subpopulations, including those associated with pathology and characterized by regulators of myelination, inflammation, and neuron survival. The strongest disease-associated changes appeared early in pathological progression and were highly cell-type specific, whereas genes upregulated atlate stages were common across cell types and primarily involved in the global stress response.
物理学 Physics
Enhanced intrinsic photovoltaic effect intungsten disulfide nanotubes
二硫化钨纳米管中增强的本征光生伏特效应
作者：Y. J. Zhang, T. Ideue, M. Onga, F. Qin, R. Suzuki, et al
链接：
https://www.nature.com/articles/s41586-019-1303-3
摘要：
传统p-n结中的光生伏特效应涉及光诱导的电子空穴对的产生及其随后的分离，从而产生电流。在p-n结，p型材料（有多余的空穴）与n型材料（有多余的电子）相连接。
这种光生伏特对无害环境的能源收集特别重要，并且其效率已大大提高，几乎达到理论极限。
利用批量光生伏特效应（BPVE）预期会带来进一步的进展。这种效应不需要p-n结，只发生在反转对称性被破坏的晶体中。
这里，我们报告了过渡性金属双硫属化合物（TMD）家族成员——二硫化钨器件中BPVE的发现。我们发现，系统地将晶体对称性降到单纯的破缺反转对称性之外（从二维单层到具有极性的纳米管），可大大增强BPVE。
Abstract
The photovoltaic effect in traditional p–n junctions—where a p-type material (with an excess of holes) abuts an n-type material (with an excess of electrons)—involves the light-induced creation of electron–hole pairs and their subsequent separation, generating a current. This photovoltaic effect is particularly important for environmentally benign energy harvesting, and its efficiency has been increased dramatically, almost reaching the theoretical limit. Further progress is anticipated by making use of the bulk photovoltaic effect (BPVE), which does not require a junction and occurs onlyin crystals with broken inversion symmetry. Here we report the discovery of the BPVE in devices based on tungsten disulfide, a member of the TMD family. We find that systematically reducing the crystal symmetry beyond mere broken inversion symmetry—moving from a two-dimensional monolayer to a nanotube with polar properties—greatly enhances the BPVE.
Perfect Andreev reflection due to the Klein paradox in a topological superconducting state
拓扑超导态中克莱因佯谬引起的完美安德烈夫反射
作者：Seunghun Lee, Valentin Stanev, Xiaohang Zhang, et al
链接：
https://www.nature.com/articles/s41586-019-1305-1
摘要：
1928年，狄拉克提出了一个描述相对论电子的波动方程。不久之后，克莱因解决了针对狄拉克方程的一个简单的电位阶跃问题，并遇到了一个明显的悖论：当势垒的高度大于电子能量时，势垒就会变得透明。
对于无质量粒子来说，反向散射在克莱因隧穿过程中是被完全禁止的，使其在任何势垒中都能实现完美透射。
这里，我们报告了在点接触光谱中观察到的完美安德烈夫反射——克莱因隧穿的清晰特征，以及近藤拓扑绝缘体中接近诱导的超导态的潜在“相对论”物理的出现。
Abstract
In 1928, Dirac proposed a wave equation to describe relativistic electrons. Shortly afterwards, Klein solved a simple potential step problem for the Dirac equation and encountered an apparent paradox: the potential barrier becomes transparent when its height is larger than the electron energy. For massless particles, backscattering is completely forbiddenin Klein tunnelling, leading to perfect transmission through any potential barrier. Here we report the observation of perfect Andreev reflection inpoint-contact spectros copy—a clear signature of Klein tunnelling and a manifestation of the underlying ‘relativistic’ physics of a proximity-induced superconducting state in a topological Kondo insulator.
生物学 Biology
Mitochondrial fragmentation drives selective removal of deleterious mtDNA in the germline
线粒体分裂驱动生殖系中有害mtDNA的选择性清除
作者：Toby Lieber, Swathi P. Jeedigunta, Jonathan M. Palozzi, et al
链接：
https://www.nature.com/articles/s41586-019-1213-4
摘要：
线粒体包含自己的基因组。与核基因组不同，这些基因组只在母系中遗传。由于线粒体DNA （mtDNA）的高突变率和低水平重组，雌性生殖系存在特殊的选择机制，以防止有害突变的累积。
这里，我们利用一种等位基因特异性荧光原位杂交方法观察了果蝇的种系选择，以区分野生型和突变型mtDNA。
选择首先表现在果蝇卵形成的早期阶段，并且由前融合蛋白Mitofusin的减少触发。这导致线粒体基因组物理分离成不同的线粒体片段，从而阻止了基因组及其产物的混合，并因此减少了互补。
Abstract
Mitochondria contain their own genomes that, unlike nuclear genomes, are inherited only in the maternal line. Owing to a high mutation rate and low levels of recombination of mitrochondrial DNA (mtDNA), special selection mechanisms exist in the female germline to prevent the accumulation of deleterious mutations. Here we visualize germline selection in Drosophila using an allele-specific fluorescent in situ-hybridization approach to distinguish wild-type from mutant mtDNA. Selection first manifests in the early stages of Drosophila oogenesis, triggered by reduction of the pro-fusion protein Mitofusin. This leads to the physical separation of mitochondrial genomes into different mitochondrial fragments, which prevents the mixing of genomes and their products and thereby reduces complementation.
Mating preferences of selfish sex chromosomes
自私性染色体的交配偏好
作者：Pavitra Muralidhar
链接：
https://www.nature.com/articles/s41586-019-1271-7
摘要：
雌性对有害于雄性的特征的交配偏好进化是性别选择的一个核心悖论。
对这一悖论的两种主流解释是Fisher的失控过程（基于偏好和特质之间的基因关联）和Zahavi的缺陷原则（该原则认为特质是雄性品质的一个诚实而昂贵的信号）。
这里，我提出了一种雌性对有害于雄性的特征的交配偏好进化机制。其基于性染色体的自私进化利益。我证明，雌性偏向的基因元素，如W和X性染色体，会进化出雄性的择偶偏好。
这些雄性表现出的特征会降低它们和/或男性后代的适应性，但会提高雌性后代的适应性。尤其是，与w相关的偏好会导致几乎致命的雄性特征被彻底固定。
Abstract
The evolution of female mating preferences for harmful male traits is a central paradox of sexual selection. Two dominant explanations for this paradox are Fisher’s runaway process, which is based on genetic correlations between preference and trait, and Zahavi’s handicap principle, in which the trait is an honest costly signal of male quality. Here I present a mechanism for the evolution of female mating preferences for harmful male traits that is based on the selfish evolutionary interests of sex chromosomes. I demonstrate that female-biased genetic elements—such as the Wand X sex chromosomes—will evolve mating preferences for males who display traits that reduce their fitness and/or that of their male offspring, but increase fitness in female offspring. In particular, W-linked preferences can cause nearly lethal male traits to sweep to fixation.
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