《自然》（20181025出版）一周論文導讀

Nature，Volume 562 Issue 7728，25 OCTOBER 2018

《自然》2018年10月25日第7728期562卷

醫學Medicine

Temporal development of the gut microbiomein early childhood from the TEDDY study

來自TEDDY研究的兒童早期腸道微生物隨時間的發育規律

作者：Christopher J. Stewart, Nadim J. Ajami, Jacqueline L. O』Brien, DianeS. Hutchinson, et al

鏈接：

摘要：

微生物組從嬰兒到兒童的發育取決於一系列因素。

同時，這一階段的微生物—免疫「交叉對話」被認為涉及晚年疾病的病理學，比如持續的胰島自身免疫和1型糖尿病。

不過，據我們所知，尚未有研究對大規模、多中心人群生命早期的微生物組進行廣泛描述。

這裡，我們通過16S rRNA基因測序（n = 12005）和宏基因組測序（n = 10867），對年齡在3~46個月的903名兒童的糞便樣本進行了分析。這是青少年糖尿病環境決定因素研究的一部分。

我們證實，發育中的腸道微生物組經歷了3個不同的階段：發育階段（3~14個月）、過渡階段（15~30個月）和穩定階段（31~46個月）。

Abstract

The development of the microbiome from infancy to childhood is dependent on a range of factors, with microbial–immune crosstalk during this time thought to be involved in the pathobiology of later life diseases such as persistent islet autoimmunity and type 1 diabetes. However, to our knowledge, no studies have performed extensive characterization of the microbiome in early life in a large, multi-centre population. Here we analyse longitudinal stool samples from 903 children between 3 and 46 months of age by 16S rRNA gene sequencing (n = 12,005) and metagenomic sequencing (n = 10,867), as part of The Environmental Determinants of Diabetes in the Young (TEDDY) study. We show that the developing gut microbiome undergoes three distinct phases of microbiome progression: a developmental phase (months 3–14), a transitional phase (months15–30), and a stable phase (months 31–46).

LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration

白血病細胞中LILRB4信號調停T細胞抑制和腫瘤滲透

作者：Mi Deng, Xun Gui, Jaehyup Kim, Li Xie, Weina Chen, Zunling Li, et al

鏈接：

摘要：

免疫檢查點阻斷療法在治療一些類型的癌症上取得了成功，但在治療白血病上並未顯示出臨床效果。這表明白血病利用獨特機制躲避該療法。

由正常免疫細胞表達的特定免疫抑制性受體也出現在白血病細胞中。這些受體能否啟動腫瘤細胞中同免疫相關的主要信號仍然未知。

這裡，我們利用小鼠模型和人類細胞證實，LILRB4為腫瘤細胞滲透進組織和通過一個涉及急性髓性白血病細胞中APOE、LILRB4、SHP-2、uPAR和ARG1的信號通路抑制T細胞活性提供了支撐。

LILRB4是一種基於免疫受體酪氨酸的抑制基序的受體和單核細胞白血病（AML）的標記物。

Abstract

Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia. This result suggests that leukaemia uses unique mechanisms to evade this therapy. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukaemia cells. Whether these receptors can initiate immune-related primary signalling in tumour cells remains unknown. Here we use mouse models and human cells to show that LILRB4, an immunoreceptor tyrosine-based inhibition motif-containing receptor and a marker of monocytic leukaemia, supports tumour cell infiltration into tissues and suppresses T cell activity via a signalling pathway that involves APOE, LILRB4, SHP-2, uPAR and ARG1 in acute myeloid leukaemia (AML) cells.

生物學Biology

Social regulation of a rudimentary organ generates complex worker-caste systems in ants

痕迹器官的社會調控在螞蟻中產生複雜的階層制度

作者：Rajendhran Rajakumar, Sophie Koch, Mélanie Couture, Marie-Julie Favé, et al

鏈接：

摘要：

螞蟻中複雜階層制度的起源讓達爾文困惑不已，並且是進化和發育生物學中一個由來已久的問題。

螞蟻起源於約1.5億年前，產生了包括有翅蜂王、雄蟻和無翅工蟻在內的蟻群。

在大頭蟻屬中，無翅工蟻進化出兩種形態上不同的亞階層——低級小頭工蟻和大頭兵蟻。蜂王和雄蟻的翅膀由卵中被稱為翅膀成蟲盤的細胞群發育而來。

儘管低級工蟻和兵蟻是沒有翅膀的，但翅膀成蟲盤的痕迹在兵蟻發育期間短暫出現。

此類特徵在動植物演化史上很普遍，並且主要被用作共同起源的證據，儘管其功能重要性仍然模稜兩可。

這裡，我們證實，翅膀成蟲盤的生長對於調控頭和身體大小的異速生長——不成比例的縮放——很有必要，從而在大頭蟻屬中產生大頭兵蟻。

Abstract

The origin of complex worker-caste systems in ants perplexed Darwin and has remained an enduring problem for evolutionary and developmental biology. Ants originated approximately 150 million years ago, and produce colonies with winged queen and male castes as well as a wingless worker caste. In the hyperdiverse genusPheidole, the wingless worker caste has evolved into two morphologically distinct subcastes—small-headed minor workers and large-headed soldiers8. The wings of queens and males develop from populations of cells in larvae that are called wing imaginal discs. Although minor workers and soldiers are wingless, vestiges or rudiments of wing imaginal discs appear transiently during soldier development. Such rudimentary traits are phylogenetically widespread and are primarily used as evidence of common descent, yet their functional importance remains equivocal. Here we show that the growth of rudimentary wing discs is necessary for regulating allometry—disproportionate scaling—between head and body size to generate large-headed soldiers in the genus Pheidole.

OTX2 restricts entry to the mouse germline

OTX2限制小鼠生殖系入口

作者：Jingchao Zhang, Man Zhang, Dario Acampora, Matú? Vojtek, et al

鏈接：

摘要：

生殖細胞同體細胞譜系的成功分離對於有性生殖和物種生存至關重要。

在小鼠中，所有生殖細胞的前體——原始生殖細胞（PGCs）由植入後外胚層誘導而來。誘導需要發送給PGCs 的BMP4信號以及PGC轉錄因子的自向性行為。

不過，將BMP4和PGC轉錄因子誘導（負責將PGCs同體細胞譜系分離）連接起來的分子機制一直未知。

這裡，我們證實轉錄因子OTX2是這些過程的關鍵調控者。

Otx2的下調先於PGC程序在體內和體外的啟動。體外刪除Otx2增加了類PGC細胞的分離效率，並且延長了PGC的能力期限。

Abstract

The successful segregation of germ cells from somatic lineages is vital for sexual reproduction and species survival. In the mouse, primordial germ cells (PGCs), precursors of all germ cells, are induced from the post-implantation epiblast. Induction requires BMP4 signalling to prospective PGCs and the intrinsic action of PGC transcription factors. However, the molecular mechanisms that connectBMP4 to induction of the PGC transcription factors that are responsible for segregating PGCs from somatic lineages are unknown. Here we show that the transcription factor OTX2 is a key regulator of these processes. Downregulation of Otx2 precedes the initiation of the PGC programme both in vitro and in vivo. Deletion of Otx2 in vitro markedly increases the efficiency of PGC-like cell differentiation and prolongs the period of PGC competence.

材料學Materials Science

Exciton-polariton topological insulator

激子—極化激元拓撲絕緣體

作者：S. Klembt, T. H. Harder, O. A. Egorov, K. Winkler, R. Ge, et al

鏈接：

摘要：

拓撲絕緣體——大部分絕緣但允許電子在其表面流動的材料——是一類材料的突出例子。

在這類材料中，拓撲不變數在對抗諸如缺陷、無序等擾動的魯棒性中表現出來。其最重要的特徵是在擁有不同拓撲屬性的區域邊界處出現邊緣狀態。

可觀測到的物理效應是這些邊緣狀態的單向魯棒傳輸。

拓撲絕緣體最初在整數量子霍爾效應（電導在強磁場中被量子化）中被觀察到，並且隨後被觀察到可在沒有磁場的情況下存在。

這裡，我們實驗驗證了一種激子—極化激元拓撲絕緣體。

耦合半導體微腔的晶格被激光以非共振的形式激發，同時施加的磁場帶來了陣列邊緣附近極化激元波包的單向流動。這種手性邊緣模式由極化激元凝結機制填充。

Abstract

Topological insulators—materials that are insulating in the bulk but allow electrons to flow on their surface—are striking examples of materials in which topological invariants are manifested in robustness against perturbations such as defects and disorder. Their most prominent feature is the emergence of edge states at the boundary between areas with different topological properties. The observable physical effect is unidirectional robust transport of these edge states. Topological insulators were originally observed in the integer quantum Hall effect (in which conductance is quantized in a strong magnetic field) and subsequently suggested and observed to exist without a magnetic field.

Here we demonstrate experimentally an exciton-polariton topological insulator. Our lattice of coupled semiconductor microcavities is excited non-resonantly by a laser, and an applied magnetic field leads to the unidirectional flow of a polariton wavepacket around the edge of the array. This chiral edge mode is populated by a polariton condensation mechanism.

In-plane anisotropic andultra-low-loss polaritonsin a natural van der Waals crystal

天然vdW晶體中平面各向異性和超低損耗極化激元

作者：Weiliang Ma, Pablo Alonso-González, Shaojuan Li, Alexey Y. Nikitin, JianYuan, et al

鏈接：

摘要：

極化激元——混合的光—物質激發——使納米尺度的光控制成為可能。

尤其大的極化激元場約束和長壽命可在石墨烯以及含有由弱范德華力綁定在一起的二維層的材料（vdW材料）中看到。

這些極化激元可通過電場或者材料厚度得到調整，帶來包括納米激光器、可調諧紅外和太赫茲探測器以及分子感測器在內的應用。

這裡，我們報告了沿著一種天然vdW材料——α-MoO₃表面的各向異性極化激元傳播。

通過對具有半導體性質的α-MoO₃薄片和圓盤進行紅外納米成像和納米光譜學，我們形象地展示並證實了表現出橢圓型和雙曲線型平面分散以及波長是相應光子波長1/60的光子極化激元。

Abstract

Polaritons—hybrid light—matter excitations—enable nanoscale control of light. Particularly large polariton field confinement and long lifetimes can be found in graphene and materials consisting of two-dimensional layers bound by weak van der Waals forces (vdW materials). These polaritons can be tuned by electric fields or by material thickness, leading to applications including nanolasers, tunable infrared and terahertz detectors, and molecular sensors.

Here we report anisotropic polariton propagation along the surface of α-MoO₃, a natural vdWmaterial. By infrared nano-imaging and nano-spectroscopy of semiconducting α-MoO₃flakes and disks, we visualize and verify phonon polaritons with elliptic and hyperbolic in-plane dispersion, and with wavelengths (up to 60times smaller than the corresponding photon wavelengths).

物理學Physics

Device-independent quantum random-number generation

獨立於設備的量子隨機數發生器

作者：Yang Liu, Qi Zhao, Ming-Han Li, Jian-Yu Guan, Yanbao Zhang, et al

鏈接：

摘要：

隨機性對於很多信息處理應用非常重要，包括數值模擬和密碼學。

獨立於設備的量子隨機數發生器（DIQRNG）基於貝爾不等式的無漏洞違反，產生了真正的、不可預知的隨機性。這不需要任何關於設備內部工作方式的假設。DIQRNG也因此成為量子信息科學領域的終極目標。

這裡，我們報告了可抵抗量子對手和經典對手的DIQRNG。

我們利用最先進的量子光學技術創建、調製並探測到糾纏的光子對，同時實現了在約200米的距離內從創建到探測的超過78%的效率。這遠遠超過關閉貝爾測試「探測」漏洞的閾值。

Abstract

Randomness is important for many information processing applications, including numerical modelling and cryptography. Device-independent quantum random-number generation ( DIQRNG ) based on the loophole-free violation of a Bell inequality produces genuine, unpredictable randomness without requiring any assumptions about the inner workings of the devices, and is therefore an ultimate goal in the field of quantum information science.

Here we present DIQRNG that is secure against quantum and classical adversaries. We use state-of-the-art quantum optical technology to create, modulate and detectent angled photon pairs, achieving an efficiency of more than 78 percent from creation to detection at a distance of about 200 metres that greatly exceeds the threshold for closing the 『detection』 loophole of the Bell test.

地球科學Geoscience

CO₂storage and release in the deep Southern Ocean on millennial to centennial timescales

南大洋深處千年到百年時間尺度上的二氧化碳儲存和釋放

作者：J. W. B. Rae, A. Burke, L. F. Robinson, J. F. Adkins, T. Chen, et al

鏈接：

摘要：

最近的冰河時代期間大氣二氧化碳（CO₂）的變化起因尚未完全得到解答。

冰期—間冰期CO₂變化的大多數機制集中在同深海的碳交換上，而這歸因於深海體積巨大且同大氣層的交換相對較快。

南大洋被認為在這一交換中發揮了關鍵作用，因為南大洋大部分深海同該地區的大氣層保持著空氣交換。

不過，由於很難重構南大洋深海碳儲存的變化，因此關於這一假設的直接測試幾乎沒有開展過。

這裡，我們展示了追蹤過去4萬年間南大洋深海pH以及CO₂化學性質的深海珊瑚硼同位素數據。

在最靠近南極大陸邊緣和最受南大洋深層海水影響的地方，我們找到了海洋pH和CO₂之間的緊密關聯。

Abstract

The cause of changes in atmospheric carbon dioxide (CO₂) during the recent ice ages is yet to be fully explained. Most mechanisms for glacial–interglacial CO₂ change have centred on carbon exchange with the deep ocean, owing to its large size and relatively rapid exchange with the atmosphere. The Southern Ocean is thought to have a key role in this exchange, as much of the deep ocean is ventilated to the atmosphere in this region. However, it is difficult to reconstruct changes in deep Southern Ocean carbon storage, so few direct tests of this hypothesis have been carried out. Here we present deep-sea coral boron isotope data that track the pH—and thus the CO₂chemistry—of the deep Southern Ocean over the past forty thousand years. At sites closest to the Antarctic continental margin, and most influenced by the deep southern waters, we find a close relationship between ocean pH and atmospheric CO₂.

（宗華）

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