《科學》（20190419出版）一周論文導讀

翻譯 | 宗華

Science, 19 April 2019, Volume 364 Issue 6437

《科學》2019年4月19日，第6437期364卷

生物Biology

Thirst regulates motivated behavior through modulation of brainwide neural population dynamics

口渴通過調整大腦範圍神經群動態調節動機行為

作者：William E. Allen, Michael Z. Chen, Nandini Pichamoorthy, et al

鏈接：

https://science.sciencemag.org/content/364/6437/253

摘要：

生理需求產生動機驅動，比如口渴和飢餓。這些驅動調節對生存至關重要的行為。

下丘腦神經元感知這些需求，並且必須協調相關的全腦神經元活動，以產生適當的行為。

我們研究了21隻小鼠在喝水並且得到滿足時由口渴驅動的選擇行為期間，34個大腦區域的2.4萬餘個神經元的動態變化。預測水的感覺線索引發了迅速擴散到口渴動物整個大腦的活動。

這些動態由編碼動機狀態的大腦範圍內的群體活動模式控制。飽足後，下丘腦口渴感覺神經元的局灶性光生激活使整體活動恢復到飽足前狀態。

因此，動機狀態指定了初始條件，而這些條件決定了整個大腦動力系統如何將感覺輸入轉化為行為輸出。

Abstract

Physiological needs produce motivational drives, such as thirst and hunger, that regulate behaviors essential to survival. Hypothalamic neurons sense these needs and must coordinate relevant brainwide neuronal activity to produce the appropriate behavior. We studied dynamics from ~24,000 neurons in 34 brain regions during thirst-motivated choice behavior in 21 mice as they consumed water and became sated. Water-predicting sensory cues elicited activity that rapidly spread throughout the brain of thirsty animals. These dynamics were gated by a brainwide mode of population activity that encoded motivational state. After satiation, focal optogenetic activation of hypothalamic thirst-sensing neuronsre turned global activity to the pre-satiation state. Thus, motivational states specify initial conditions that determine how a brainwide dynamical system transforms sensory input into behavioral output.

Spontaneous behaviors drive multidimensional, brainwide activity

自發行為驅動多維、大腦範圍的活動

作者：Carsen Stringer, Marius Pachitariu, Nicholas Steinmetz, et al

鏈接：

https://science.sciencemag.org/content/364/6437/255

摘要：

感覺皮層的神經元群對感覺刺激產生不同的反應，並且在沒有外部感覺輸入的情況下，也能表現出複雜的自發活動。

曾有各種研究假設，大腦皮層的可變性和自發活動代表了隨機噪音、對先前經驗的回憶，或對正在進行的行為和認知變數的編碼。

我們通過記錄小鼠視覺皮層的1萬餘個神經元，觀察到自發活動可靠地編碼一種高維「潛伏」狀態。這種狀態與小鼠正在進行的行為存在部分關聯，而且不僅在視覺皮層，還在整個前腦中呈現。

感官輸入並沒有中斷這個正在進行的信號，而是在其上添加了一個正交維度的外部刺激呈現。因此，儘管存在明顯的噪音結構，但視覺皮層群的活動可靠地編碼了感官和多維行為信息的正交融合。

Abstract

Neuronal populations in sensory cortex produce variable responses to sensory stimuli and exhibit intricate spontaneous activity even without external sensory input. Cortical variability and spontaneous activity have been variously proposed to represent random noise, recall of prior experience, or encoding of ongoing behavioral and cognitive variables. Recording more than 10,000 neurons in mousevisual cortex, we observed that spontaneous activity reliably encoded a high-dimensional latent state, which was partially related to the mouse』s ongoing behavior and was represented not just in visual cortex but also acrossthe forebrain. Sensory inputs did not interrupt this ongoing signal but added onto it a representation of external stimuli in orthogonal dimensions. Thus, visual cortical population activity, despite its apparently noisy structure, reliably encodes an orthogonal fusion of sensory and multidimensional behavioral information.

物理/天文

Physics/Astronomy

Probing Rényi entanglement entropy via randomized measurements

通過隨機測量探索瑞利糾纏熵

作者：Tiff Brydges, Andreas Elben, Petar Jurcevic, et al

鏈接：

https://science.sciencemag.org/content/364/6437/260

摘要：

糾纏是多體量子系統的一個重要特徵。測量量子系統不同分區的熵提供了一種探測其糾纏結構的方法。這裡，我們提出並實驗驗證了一種基於隨機測量之間統計相關性的二階瑞利熵測量方案。

我們的實驗是在一個分區尺寸達10個量子比特的陷俘離子量子模擬器上進行的。我們證明了該系統動力學的整體相干性特徵，並揭示了在無序缺失和無序存在的情況下，系統各部分之間糾纏的增長。

我們的方案代表了一種在實驗室中探測和表徵工程量子系統的通用工具，適用於多達幾十個量子比特的任意量子態。

Abstract

Entanglement is a key feature of many-body quantum systems. Measuring the entropy of different partitions of a quantum system provides a way to probe its entanglement structure. Here, we present and experimentally demonstrate a protocol for measuring the second-order Rényi entropy based on statistical correlations between randomized measurements. Our experiments, carried out with a trapped-ion quantum simulator with partition sizes of up to 10 qubits, provethe overall coherent character of the system dynamics and reveal the growth of entanglement between its parts, in both the absence and presence of disorder.Our protocol represents a universal tool for probing and characterizing engineered quantum systems in the laboratory, which is applicable to arbitrary quantum states of up to several tens of qubits.

Hayabusa2 arrives at the carbonaceous asteroid 162173 Ryugu—A spinning top–shaped rubblepile

「隼鳥二號」抵達162173號碳質小行星「龍宮」—— 一個旋轉的陀螺形碎石堆

作者：S. Watanabe, M. Hirabayashi, N. Hirata, et al

鏈接：

https://science.sciencemag.org/content/364/6437/268

摘要：

「隼鳥二號」飛船於2018年抵達162173號近地碳質小行星「龍宮」。我們展示了「隼鳥二號」對「龍宮」形狀、質量和地貌的觀測結果。

「龍宮」擁有扁圓的「旋轉陀螺」形狀，且赤道脊突出。其體積密度為1.19±0.02克/立方厘米，表明內部具有高孔隙度（>50%）。較大的表面礫石表明是其為碎石樁結構。

表面坡度分析表明，「龍宮」的形狀可能由一次以兩倍於當前轉速的旋轉形成。結合觀察到的整個小行星的材料均勻性，這表明「龍宮」是在快速旋轉期間由離心誘導變形重塑的。

通過這些遙感調查，我們在其赤道脊上確定了一個合適的樣品採集點。

Abstract

The Hayabusa2 spacecraft arrived at the near-Earth carbonaceous asteroid 162173 Ryugu in 2018. We present Hayabusa2 observations of Ryugu』s shape, mass, and geomorphology. Ryugu has an oblate 「spinning top」 shape, with a prominent circular equatorial ridge. Its bulk density, 1.19 ± 0.02 grams per cubic centimeter, indicates a high-porosity (>50%) interior. Large surface boulders suggest a rubble-pile structure. Surface slope analysis shows Ryugu』s shape may have been produced from having once spun at twice the current rate. Coupled with the observed global material homogeneity, this suggests that Ryuguwas reshaped by centrifugally induced deformation during a period of rapid rotation. From these remote-sensing investigations, we identified a suitable sample collection site on the equatorial ridge.

基因編輯Gene Editing

Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos

胞嘧啶鹼基編輯器在小鼠胚胎中產生大量脫靶的單核苷酸變異

作者：Erwei Zuo, Yidi Sun, Wu Wei, et al

鏈接：

https://science.sciencemag.org/content/364/6437/289

摘要：

基因組編輯有望糾正致病突變。然而，由於個體的單核苷酸多態性，很難確定編輯的脫靶效應。

這裡，我們開發了一種名為GOTI（雙細胞胚胎注射全基因組脫靶點分析）的方法，通過使用CRISPR-Cas9或鹼基編輯器編輯雙細胞小鼠胚胎的一個胚粒來檢測脫靶點突變。

對胚胎第14.5天的編輯胚泡和未編輯胚泡後代細胞進行的全基因組序列比較表明，在CRISPR-Cas9或腺嘌呤鹼基編輯器編輯的胚胎中，脫靶單核苷酸變異（SNVs）很罕見，頻率接近於自發突變率。

相比之下，胞嘧啶鹼基編輯誘導SNVs的頻率超過20倍，因此需要一種解決其精確度的方案。

Abstract

Genome editing holds promise for correcting pathogenic mutations. However, it is difficult to determine off-target effects of editing due to single-nucleotide polymorphismin individuals. Here we developed a method named GOTI (genome-wide off-targetanalysis by two-cell embryo injection) to detect off-target mutations by editing one blastomere of two-cell mouse embryos using either CRISPR-Cas9 orbase editors. Comparison of the whole-genome sequences of progeny cells of edited and nonedited blastomeres at embryonic day 14.5 showed that off-target single-nucleotide variants (SNVs) were rare in embryos edited by CRISPR-Cas9 oradenine base editor, with a frequency close to the spontaneous mutation rate. By contrast, cytosine base editing induced SNVs at more than 20-fold higher frequencies, requiring a solution to address its fidelity.

Unbiased detection of CRISPR off-targets in vivo using DISCOVER-Seq

利用DISCOVER-Seq在體內對CRISPR脫靶點的無偏倚檢測

作者：Beeke Wienert, Stacia K. Wyman, Christopher D. Richardson, et al

鏈接：

https://science.sciencemag.org/content/364/6437/286

摘要：

CRISPR-Cas基因組編輯可誘導靶向DNA損傷，但也可影響靶外位點。目前的脫靶發現方法利用純化的DNA或特定細胞模型，但無法在體內直接檢測。

我們開發了Discovery – Seq（原位Cas脫靶點的發現和測序驗證）。這是一種普遍適用的方法，用於無偏倚的脫靶點識別，並且利用了細胞和生物體中DNA修復因子的招募。

跟蹤MRE11的精確招募在單鹼基解析度水平上揭示了細胞中Cas活性的分子本質。Discovery - Seq適用於多重引導RNA格式和多種Cas酶，並且使描述新的編輯工具成為可能。

在小鼠腺病毒編輯過程中，脫靶點可在細胞系和患者來源的誘導多能幹細胞中被識別到，從而為治療性基因組編輯期間單個患者基因型中原位脫靶點的發現鋪平了道路。

Abstract

CRISPR-Casgenome editing induces targeted DNA damage but can also affect off-target sites. Current off-target discovery methods work using purified DNA or specific cellular models but are incapable of direct detection in vivo. We developed DISCOVER-Seq (discovery of in situ Cas off-targets and verification by sequencing), a universally applicable approach for unbiased off-target identification that leverages the recruitment of DNA repair factors in cells and organisms. Tracking the precise recruitment of MRE11 uncovers the molecular nature of Cas activity in cells with single-base resolution. DISCOVER-Seq works with multiple guide RNA formats and types of Cas enzymes, allowing characterization of new editing tools. Off-targets can be identified in celllines and patient-derived induced pluripotent stem cells and during adenoviral editing of mice, paving the way for in situ off-target discovery within individual patient genotypes during therapeutic genome editing.

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