《自然》（20190110出版）一周論文導讀

知識 01-12

Nature, 10 January 2019, Volume 565 Issue 7738

《自然》2019年1月10日第7738期565卷

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天文學Astronomy

The corona contracts in a black-hole transient

黑洞暫現源中冕的縮小

作者：E. Kara, J. F. Steiner, A. C. Fabian, E. M. Cackett, et al

鏈接：

https://www.nature.com/articles/s41586-018-0803-x

摘要：

恆星級黑洞附近吸積流的幾何結構會在幾天到數月的時間尺度上變化。

這裡，我們報告了對黑洞暫現源MAXI J1820+070的X射線觀測結果。

我們發現，持續發射的黑洞冕與輻照吸積盤之間的混響時間滯後比此前認為的短6~20倍。

混響滯後的時間尺度在幾周內縮短了一個數量級，而拓寬的鐵K發射線形狀仍然相當恆定。

這表明了黑洞冕空間幅度的減少，而非吸積盤內在邊緣的變化。

Abstract

The geometry of the accretion flow around stellar-mass black holes can change on timescales of days to months. Here we report X-ray observations of the black-hole transient MAXI J1820+070. We find that the reverberation time lags between the continuum-emitting corona and the irradiated accretion disk are 6 to 20 times shorter than previously seen. The timescale of the reverberation lags shortens by an order of magnitude over a period of weeks, whereas the shape of the broadened iron K emission line remains remarkably constant. This suggests a reduction in the spatial extent of the corona, rather than a change in the inner edge of the accretion disk.

A warped disk around an infant protostar

嬰兒原恆星附近的彎麴塵埃盤

作者：Nami Sakai, Tomoyuki Hanawa, Yichen Zhang, et al

鏈接：

https://www.nature.com/articles/s41586-018-0819-2

摘要：

最新的系外行星研究表明，行星的軌道面並非總是彼此對齊，或者同中央星的赤道平面對齊。

這裡，我們報告了對137秒差距外的年輕嵌入原恆星IRAS 04368+2557的毫米波長塵埃連續觀測結果。

該原恆星位於原星系核心L1527，其塵埃盤幾乎是側立的。

塵埃盤的內部和外部擁有稍微不同的軌道平面，在距離該恆星40~60天文單位處相連接。

但該塵埃盤擁有同原恆星位置相關的點對稱。我們認為，它是一個得到旋轉支持的彎麴塵埃盤。

由於沒有同伴來源的證據，這個彎曲結構肯定歸結於擁有不同軸的氣體各向異性吸積，或者擁有磁場定向的塵埃盤旋轉軸的未對準。

Abstract

Recent exoplanet studies have revealed that the orbital planes of planets are not always aligned with one another or with the equatorial plane of the central star.Here we report millimetre-wavelength dust continuum observations of the young embedded protostar IRAS 04368+2557 in the protostellar core L1527 at a distance of 137 parsecs; the protostar』s disk is almost edge-on. The inner and outer parts of the disk have slightly different orbital planes, connected at 40 to 60 astronomical units from the star, but the disk has point symmetry with respect to the position of the protostar. We interpret it as a warped disk that is rotationally supported. Because there is no evidence for a companion source, the warped structure must be due to either anisotropic accretion of gas with different rotational axes, or misalignment of the rotation axis of the disk with the magnetic field direction.

健康Health

Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial

新抗原疫苗在Ib期惡性膠質瘤試驗中產生瘤內T細胞反應

作者：Derin B. Keskin, Annabelle J. Anandappa, Jing Sun, et al

鏈接：

https://www.nature.com/articles/s41586-018-0792-9

摘要：

源自腫瘤特異性蛋白質編碼突變的新抗原免除了中樞耐受，能產生強大的免疫反應並且可作為促進腫瘤排斥的「善意」抗原。

這裡，我們報告稱，一種利用多表位、個性化新抗原免疫接種的策略對於諸如惡性膠質瘤等腫瘤是可行的。

這些腫瘤通常擁有相對較低的突變負載以及免疫上的「冷」腫瘤微環境。

該策略此前在高風險黑色素瘤患者中被測試。

利用單細胞T細胞受體分析，我們提供了來自外周血的新抗原特異性T細胞能遷移進惡性膠質瘤內的證據。

因此，新抗原靶向疫苗擁有有利於改變惡性膠質瘤免疫環境的潛力。

Abstract

Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses and can function as bona fide antigens that facilitate tumour rejection. Here we demonstrate that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma, is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load and an immunologically 『cold』 tumour microenvironment. Using single-cell T cell receptor analysis, we provide evidence that neoantigen-specific T cells from the peripheral blood can migrate into an intracranial glioblastoma tumour. Neoantigen-targeting vaccines thus have the potential to favourably alter the immune milieu of glioblastoma.

Actively personalized vaccination trial for newly diagnosed glioblastoma

針對新診斷惡性膠質瘤的積極個性化疫苗試驗

作者：Norbert Hilf, Sabrina Kuttruff-Coqui, Katrin Frenzel, et al

鏈接：

https://www.nature.com/articles/s41586-018-0810-y

摘要：

惡性膠質瘤患者目前並未從利用檢查點抑製劑的癌症療法的最新突破中獲得足夠多的益處。

利用檢查點抑製劑的療法要想成功，高突變負載和對新表位的反應被認為至關重要。

這裡，在膠質瘤積極個性化疫苗聯盟（GAPVAC）一期試驗GAPVAC-101中，我們將擁有兩種腫瘤抗原的高度個性化疫苗接種同標準療法結合，以便為最新診斷患有惡性膠質瘤的病人更好地開發有限的靶向空間。

Abstract

Patients with glioblastoma currently do not sufficiently benefit from recent breakthroughs in cancer treatment that use checkpoint inhibitors. For treatments using checkpoint inhibitors to be successful, a high mutational load and responses to neoepitopes are thought to be essential. Here, in the phase I trial GAPVAC-101 of the Glioma Actively Personalized Vaccine Consortium (GAPVAC), we integrated highly individualized vaccinations with both types of tumour antigens into standard care to optimally exploit the limited target space for patients with newly diagnosed glioblastoma.

生物學Biology

Structural basis of Notch recognition by human γ-secretase

人類γ -促分泌酶引發的Notch識別的結構基礎

作者：Guanghui Yang, Rui Zhou, Qiang Zhou, et al

鏈接：

https://www.nature.com/articles/s41586-018-0813-8

摘要：

γ -促分泌酶引發的Notch異常分裂會導致若干種癌症，但γ -促分泌酶如何識別其底物仍然未知。

這裡，我們報告了2.7 ?解析度下人類γ -促分泌酶與一個Notch碎片的複合物冷凍電鏡結構。

Notch的穿膜螺旋由3個PS1跨膜區包圍，而Notch碎片的羧基末端β-鏈在細胞內側形成擁有兩個PS1底物誘導β-鏈的β-摺疊。

混合β-摺疊的形成對於底物分裂至關重要。底物分裂發生在Notch穿膜螺旋的羧基末端盡頭。

這些特徵解釋了Notch識別的結構基礎，並且對研究γ -促分泌酶引發的澱粉樣前體蛋白招募具有重要意義。

Abstract

Aberrant cleavage of Notch by γ-secretase leads to several types of cancer, but how γ-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of human γ-secretase in complex with a Notch fragment at a resolution of 2.7 ?. The transmembrane helix of Notch is surrounded by three transmembrane domains of PS1, and the carboxyl-terminal β-strand of the Notch fragment forms a β-sheet with two substrate-induced β-strands of PS1 on the intracellular side. Formation of the hybrid β-sheet is essential for substrate cleavage, which occurs at the carboxyl-terminal end of the Notch transmembrane helix. These features reveal the structural basis of Notch recognition and have implications for the recruitment of the amyloid precursor protein by γ-secretase.

Genomic encoding of transcriptional burst kinetics

轉錄爆發動力學的基因組編碼

作者：Anton J. M. Larsson, Per Johnsson, Michael Hagemann-Jensen, et al

鏈接：

https://www.nature.com/articles/s41586-018-0836-1

摘要

哺乳動物基因表達在本質上是隨機的，並且導致由每個等位基因合成的離散的RNA分子。

儘管轉錄被認為受到啟動子和增強子的調控，但目前尚不明確順式調控序列如何編碼轉錄爆發動力學。

這裡，我們利用對等位基因敏感的單細胞RNA測序，確定了內源性小鼠和人類基因的轉錄組範圍爆發頻率和規模。

我們證實，核心啟動子元件影響爆發規模，並且揭示了TATA和啟動子元件之間的協同效應。

Abstract

Mammalian gene expression is inherently stochastic, and results in discrete bursts of RNA molecules that are synthesized from each allele. Although transcription is known to be regulated by promoters and enhancers, it is unclear how cis-regulatory sequences encode transcriptional burst kinetics. Here we determine transcriptome-wide burst frequencies and sizes for endogenous mouse and human genes using allele-sensitive single-cell RNA sequencing. We show that core promoter elements affect burst size and uncover synergistic effects between TATA and initiator elements.

考古學Archaeology

U–Pb-dated flowstones restrict South African early hominin record to dry climate phases

鈾—鉛定年流石將南非早期古人類記錄限制在乾旱氣候階段

作者：Robyn Pickering, Andy I. R. Herries, Jon D. Woodhead, et al

鏈接：

https://www.nature.com/articles/s41586-018-0711-0

摘要：

南非「人類搖籃」保存了豐富的代表南方古猿、傍人和人屬的古人類化石。

這些化石的年齡具有爭議性，並且另南非古人類記錄可在多大程度上被用於測試人類進化假說打了折扣。

不過，對水平層狀碳化鈣（流石）的鈾—鉛（U–Pb）分析提供了獲得可靠年表的潛在機會。

我們利用核密度估測，將29個U–Pb測年結果同流石生長區間的單一記錄相結合。

我們將其詮釋為重要濕潤階段，即增加的水供應、更加廣泛的植物覆蓋和至少部分關閉的洞穴促成了流石不受干擾且半連續的增長。

介於中間的時間代表了更加乾旱的階段。其間，古人類化石和其他化石在開放洞穴中累積。

儘管洞穴關閉階段在南非化石記錄中留下了時間差距，但流石本身提供了了解當地和整個非洲氣候變異的重要視角。

Abstract

The Cradle of Humankind (Cradle) in South Africa preserves a rich collection of fossil hominins representing Australopithecus, Paranthropus and Homo. The ages of these fossils are contentious and have compromised the degree to which the South African hominin record can be used to test hypotheses of human evolution. However, uranium–lead (U–Pb) analyses of horizontally bedded layers of calcium carbonate (flowstone) provide a potential opportunity to obtain a robust chronology. We use a kernel density estimate to combine 29 U–Pb ages into a single record of flowstone growth intervals. We interpret these as major wet phases, when an increased water supply, more extensive vegetation cover and at least partially closed caves allowed for undisturbed, semi-continuous growth of the flowstones. The intervening times represent substantially drier phases, during which fossils of hominins and other fossils accumulated in open caves. Although the periods of cave closure leave temporal gaps in the South African fossil record, the flowstones themselves provide valuable insights into both local and pan-African climate variability.

物理學Physics

The ultrafast Einstein–de Haas effect

超快速愛因斯坦德哈斯效應

作者：C. Dornes, Y. Acremann, M. Savoini, M. Kubli, M. J. Neugebauer, et al

鏈接：

https://www.nature.com/articles/s41586-018-0822-7

摘要：

愛因斯坦德哈斯效應最初在一項具有里程碑意義的實驗中被觀察到。

該實驗證實，同鐵磁物質中對齊的電子自旋相關的角動量可被轉化成機械角動量。

這是通過利用外磁場逆轉磁化方向實現的。

這裡，我們利用飛秒時間分辨X射線衍射證實，對激光誘導的鐵磁體去磁時從自旋系統中失去的角動量被轉移到亞皮秒時間尺度的晶格，從而啟動了從表面傳播到鐵磁體內的橫嚮應變波。

我們的結果證實，同晶格的相互作用在該系統超快速去磁過程中扮演了重要角色。

Abstract

The Einstein-de Haas effect was originally observed in a landmark experiment demonstrating that the angular momentum associated with aligned electron spins in a ferromagnet can be converted to mechanical angular momentum by reversing the direction of magnetization using an external magnetic field. Here we use femtosecond time-resolved X-ray diffraction to show that most of the angular momentum lost from the spin system upon laser-induced demagnetization of ferromagnetic iron is transferred to the lattice on sub-picosecond timescales, launching a transverse strain wave that propagates from the surface into the bulk. Our results show that interaction with the lattice has an essential role in the process of ultrafast demagnetization in this system.

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《自然》（20190110出版）一周論文導讀