《自然》（20190620出版）一周論文導讀
翻譯 | 宗華
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
全基因組遊離DNA在癌症患者體內的裂解
作者：Stephen Cristiano, Alessandro Leal, Jillian Phallen, et al
鏈接：
https://www.nature.com/articles/s41586-019-1272-6
摘要：
血液中的遊離DNA為癌症患者提供了一種非侵入性的診斷途徑。然而，目前對遊離DNA的起源特徵和分子特徵的了解甚少。
這裡，我們開發了一種方法來評估基因組中遊離DNA的裂解模式，並發現健康個體的圖譜反映了白細胞的核小體模式，而癌症患者改變了裂解模式。
我們採用該方法對236例乳腺癌、結直腸癌、肺癌、卵巢癌、胰腺癌、胃癌、膽道癌患者和245例健康人的遊離DNA裂解圖譜進行了分析。
一個包含全基因組裂解特徵的機器學習模型，在7種癌症類型中的檢測靈敏度從57%到超過99%不等，特異性為98%，曲線下面積值為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
對阿爾茨海默氏症的單細胞轉錄組分析
作者：Hansruedi Mathys, Jose Davila-Velderrain, Zhuyu Peng, Fan Gao, et al
鏈接：
https://www.nature.com/articles/s41586-019-1195-2
摘要：
阿爾茨海默氏症是一種廣泛存在的神經退行性疾病，其分子複雜性至今仍不為人所知。
這裡，我們分析了來自48名擁有不同程度阿爾茨海默氏症病理的患者前額皮質的80660個單核轉錄組。在6種主要的腦細胞類型中，我們確認了轉錄上不同的亞群，包括那些與病理相關並以髓鞘形成、炎症和神經元存活的調節因子為特徵的亞群。
與該疾病相關的最強烈變化出現在病理進展的早期，且具有高度的細胞類型特異性，而在晚期基因上調在細胞類型中很常見，主要參與整個機體的應激反應。
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.
物理學Physics
Enhanced intrinsic photovoltaic effect intungsten disulfide nanotubes
二硫化鎢納米管中增強的本徵光生伏特效應
作者：Y. J. Zhang, T. Ideue, M. Onga, F. Qin, R. Suzuki, et al
鏈接：
https://www.nature.com/articles/s41586-019-1303-3
摘要：
傳統p-n結中的光生伏特效應涉及光誘導的電子空穴對的產生及其隨後的分離，從而產生電流。在p-n結，p型材料（有多餘的空穴）與n型材料（有多餘的電子）相連接。
這種光生伏特對無害環境的能源收集特別重要，並且其效率已大大提高，幾乎達到理論極限。
利用批量光生伏特效應（BPVE）預期會帶來進一步的進展。這種效應不需要p-n結，只發生在反轉對稱性被破壞的晶體中。
這裡，我們報告了過渡性金屬雙硫屬化合物（TMD）家族成員——二硫化鎢器件中BPVE的發現。我們發現，系統地將晶體對稱性降到單純的破缺反轉對稱性之外（從二維單層到具有極性的納米管），可大大增強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
拓撲超導態中克萊因佯謬引起的完美安德烈夫反射
作者：Seunghun Lee, Valentin Stanev, Xiaohang Zhang, et al
鏈接：
https://www.nature.com/articles/s41586-019-1305-1
摘要：
1928年，狄拉克提出了一個描述相對論電子的波動方程。不久之後，克萊因解決了針對狄拉克方程的一個簡單的電位階躍問題，並遇到了一個明顯的悖論：當勢壘的高度大於電子能量時，勢壘就會變得透明。
對於無質量粒子來說，反向散射在克萊因隧穿過程中是被完全禁止的，使其在任何勢壘中都能實現完美透射。
這裡，我們報告了在點接觸光譜中觀察到的完美安德烈夫反射——克萊因隧穿的清晰特徵，以及近藤拓撲絕緣體中接近誘導的超導態的潛在「相對論」物理的出現。
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.
生物學Biology
Mitochondrial fragmentation drives selective removal of deleterious mtDNA in the germline
線粒體分裂驅動生殖系中有害mtDNA的選擇性清除
作者：Toby Lieber, Swathi P. Jeedigunta, Jonathan M. Palozzi, et al
鏈接：
https://www.nature.com/articles/s41586-019-1213-4
摘要：
線粒體包含自己的基因組。與核基因組不同，這些基因組只在母系中遺傳。由於線粒體DNA （mtDNA）的高突變率和低水平重組，雌性生殖系存在特殊的選擇機制，以防止有害突變的累積。
這裡，我們利用一種等位基因特異性熒光原位雜交方法觀察了果蠅的種系選擇，以區分野生型和突變型mtDNA。
選擇首先表現在果蠅卵形成的早期階段，並且由前融合蛋白Mitofusin的減少觸發。這導致線粒體基因組物理分離成不同的線粒體片段，從而阻止了基因組及其產物的混合，並因此減少了互補。
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
自私性染色體的交配偏好
作者：Pavitra Muralidhar
鏈接：
https://www.nature.com/articles/s41586-019-1271-7
摘要：
雌性對有害於雄性的特徵的交配偏好進化是性別選擇的一個核心悖論。
對這一悖論的兩種主流解釋是Fisher的失控過程（基於偏好和特質之間的基因關聯）和Zahavi的缺陷原則（該原則認為特質是雄性品質的一個誠實而昂貴的信號）。
這裡，我提出了一種雌性對有害於雄性的特徵的交配偏好進化機制。其基於性染色體的自私進化利益。我證明，雌性偏向的基因元素，如W和X性染色體，會進化出雄性的擇偶偏好。
這些雄性表現出的特徵會降低它們和/或男性後代的適應性，但會提高雌性後代的適應性。尤其是，與w相關的偏好會導致幾乎致命的雄性特徵被徹底固定。
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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