《科學》（20190208出版）一周論文導讀

知識 02-10

翻譯 | 宗華

Science, 08 FEBRUARY 2019, VOL 363, ISSUE 6427

《科學》2019年2月8日，第6427期363卷

《科學》（20190208出版）一周論文導讀

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醫學Medicine

An ingestible self-orienting system fororal delivery of macromolecules

用於大分子口服輸送的可吸收自定位系統

作者：Alex Abramson, Ester Caffarel-Salvador, Minsoo Khang, et al

鏈接：

http://science.sciencemag.org/content/363/6427/611

摘要：

生物大分子改變了人類有效治療疾病的能力。不過，它們在胃腸道（GI）中的快速降解和吸收不良，通常限制了其腸外途徑給葯。

口服生物輸送系統必須輔以定位和滲透上的幫助，才能實現系統性藥物吸收。受豹紋陸龜被動重定位能力啟發，我們開發了一種可吸收的自定位毫米級點葯器（SOMA）。

SOMA可自動實現自我定位，從而參與GI組織。隨後，它使由藥物活性成分製成的毫米級小管直接通過胃黏膜並且避免了穿孔。

我們在小鼠和豬身上開展了體內研究，從而為點葯器的安全性提供支撐，同時用胰島素作為模型藥物，證實SOMA輸送的藥物活性成分血漿水平可同皮下毫米級小管注射的效果媲美。

Abstract

Biomacromolecules have transformed our capacity to effectively treat diseases; however, their rapid degradation and poor absorption in the gastrointestinal (GI) tract generally limit their administration to parenteral routes. An oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake. Inspired by the leopard tortoise』s ability to passively reorient, we developed an ingestible self-orienting millimeter-scale applicator (SOMA) that autonomouslypositions itself to engage with GI tissue. It then deploys milliposts fabricated from active pharmaceutical ingredients directly through the gastric mucosa while avoiding perforation. We conducted in vivo studies in rats and swine that support the applicator』s safety and, using insulin as a model drug, demonstrated that the SOMA delivers active pharmaceutical ingredient plasmalevels comparable to those achieved with subcutaneous millipost administration.

Separating host and microbiome contributions to drug pharmacokinetics and toxicity

將宿主和微生物菌群對藥物葯代動力學和毒性的貢獻分離

作者：Michael Zimmermann, Maria Zimmermann-Kogadeeva, Rebekka Wegmann,Andrew L. Goodman

鏈接：

http://science.sciencemag.org/content/363/6427/eaat9931

摘要：

腸道菌群與很多醫療藥物的代謝有關，導致藥效及其毒性因人而異。

我們將腸道共生遺傳學和擇生生物學結合，測量了小鼠組織中的溴夫定藥物代謝。這些組織在單個微生物菌群編碼的酶上出現差異。

根據這些測量結果，我們建立了葯代動力學模型作為生物藥效率、寄主和微生物藥物代謝活性、藥物和代謝物吸收以及腸道輸送動力學的函數。該模型可定量預測微生物菌群對系統性藥物和代謝物暴露的貢獻。

Abstract

The gut microbiota is implicated in the metabolism of many medical drugs, with consequences for interpersonal variationin drug efficacy and toxicity. We combined gut commensal genetics with gnotobiotics to measure brivudine drug metabolism across tissues in mice that vary in a single microbiome-encoded enzyme. Informed by these measurements, we built a pharmacokinetic model that quantitatively predicts microbiome contributions to systemic drug and metabolite exposure, as a function of bioavailability, host and microbial drug-metabolizing activity, drug andmetabolite absorption, and intestinal transit kinetics.

生物學Biology

Schema cells in the macaque hippocampus

獼猴海馬體中的模式細胞

作者：P. Baraduc, J.-R. Duhamel, S. Wirth1

鏈接：

http://science.sciencemag.org/content/363/6427/635

摘要：

人類海馬體中的概念細胞編碼通過感官刺激傳達的意義。這裡，我們探尋了獼猴體內的類似細胞能否形成對空間環境的概念框圖。

每天，呈現在這些猴子面前的是一個熟悉的和一個新的虛擬迷宮。它們擁有共同的模式，但在表面特徵（地標）上不同。在兩種環境下，動物尋找隱藏的獎勵目標。這些目標僅被定義為同地標相關。

通過學習，很多神經元形成了將新迷宮以目標為中心和同任務相關信息結合起來的放電地圖。這可同針對熟悉迷宮形成的放電地圖媲美。因此，這些海馬體細胞將來自環境中表面細節的空間概念抽象出來，並將空間編碼進像框架一樣的模型中。

Abstract

Concept cells in the human hippocampus encode the meaning conveyed by stimuli over their perceptual aspects. Here we investigate whether analogous cells in the macaque can form conceptual schemas of spatial environments. Each day, monkeys were presented with a familiar and anovel virtual maze, sharing a common schema but differing by surface features(landmarks). In both environments, animals searched for a hidden reward goalonly defined in relation to landmarks. With learning, many neurons developed a firing map integrating goal-centered and task-related information of the novelmaze that matched that for the familiar maze. Thus, these hippocampal cells abstract the spatial concepts from the superficial details of the environment and encode space into a schema-like representation.

Innate immune recognition of glycanstargets HIV nanoparticle immunogens to germinal centers

對聚糖的先天免疫識別將HIV納米顆粒免疫原靶向生髮中心

作者：Talar Tokatlian, Benjamin J. Read, Christopher A. Jones, et al

鏈接：

http://science.sciencemag.org/content/363/6427/649

摘要：

在疫苗設計中，抗原通常以多價納米顆粒的形式排列，但這些疫苗促使免疫力增強背後的體內機制一直知之甚少。

我們比較了兩種不同的高度糖基化的HIV抗原的命運：一種是來自gp120的迷你蛋白質，另一種是蛋白質納米顆粒中大的、穩定的包膜三聚體或者初次免疫後的「自由」形式。

和單體抗原不同，納米顆粒被迅速運送到濾泡樹突狀細胞（FDC）網路，然後以一種依賴於補體、甘露糖結合凝集素（MBL）和免疫原多糖的方式集中在生髮中心。缺少MBL的小鼠體內FDC定位的失去或者通過免疫原去糖基化都會顯著影響抗體反應。

Abstract

In vaccine design, antigens are often arrayed in a multivalent nanoparticle form, but in vivo mechanisms underlying the enhanced immunity elicited by such vaccines remain poorly understood. We compared the fates of two different heavily glycosylated HIV antigens, agp120-derived mini-protein and a large, stabilized envelope trimer, in protein nanoparticle or 「free」 forms after primary immunization. Unlike monomeric antigens,nanoparticles were rapidly shuttled to the follicular dendritic cell (FDC) network and then concentrated in germinal centers in a complement-, mannose-binding lectin (MBL)–, and immunogen glycan–dependent manner. Loss of FDC localization in MBL-deficient mice or via immunogen deglycosylation significantly affected antibody responses.

Structural basis for blue-green lightharvesting and energy dissipation in diatoms

硅藻中綠—藍光捕捉和能量耗散的結構基礎

作者：Wenda Wang, Long-Jiang Yu2, Caizhe Xu, et al

鏈接：

http://science.sciencemag.org/content/363/6427/eaav0365

摘要：

硅藻是水生環境中一種含量豐富的光合生物，貢獻了40%的初級生產力。促使硅藻成功的一個重要因素是它們的岩藻黃質葉綠素a/c結合蛋白（FCPs）。

FCPs擁有超強的光捕獲和光損傷防護能力。這裡，我們報告了來自一種海洋硅藻——三角褐指藻的FCP的晶體結構。

這揭示了7個葉綠素（Chls）a、2個Chls c、7個岩藻黃質（Fxs）以及蛋白質支架中可能的1個硅甲藻黃素。

Abstract

Diatoms are abundant photosynthetic organisms in aquatic environments and contribute 40% of its primary productivity. An important factor that contributes to the success of diatoms is their fucoxanthin chlorophyll a/c-binding proteins (FCPs), which have exceptional light-harvesting and photo protection capabilities. Here, we report the crystal structure of an FCP from the marine diatom Phaeodactylum tricornutum, which reveals the binding of seven chlorophylls (Chls) a, two Chlsc, seven fucoxanthins (Fxs), and probably one diadinoxanthin within the proteinscaffold.

氣候科學Climate Science

Aerosol-driven droplet concentrations dominate coverage and water of oceanic low-level clouds

氣溶膠驅動的液滴濃度主導海洋低空雲層覆蓋和水分

作者：Daniel Rosenfeld, Yannian Zhu, Minghuai Wang, et al

鏈接：

http://science.sciencemag.org/content/363/6427/eaav0566

摘要：

對海洋上空雲凝結核（CCN）氣溶膠可靠估測的缺失，嚴重限制了量化其對雲層性質的影響以及通過反射太陽輻射的冷卻程度。

這是源於人類活動的氣候強迫作用的關鍵不確定性。我們引入一種方法用於分析CCN對雲層性質的影響並將氣溶膠影響同氣象效應相分離。

該方法的應用顯示，對於特定氣象狀態，CCN解釋了雲層輻射冷卻效果的3/4的變化性。這主要是通過影響淺雲層覆蓋和水分路徑實現的。

Abstract

A lack of reliable estimates of cloud condensation nuclei (CCN) aerosols over oceans has severely limited our ability to quantify their effects on cloud properties and extent of cooling by reflecting solar radiation—a key uncertainty in anthropogenic climate forcing. We introduce a methodology for ascribing cloud properties to CCN and isolating the aerosol effects from meteorological effects. Its application showed that for a given meteorology, CCN explains three-fourths of the variability in the radiative cooling effect of clouds, mainly through affecting shallow cloud cover andwater path.

Life history responses of meerkats toseasonal changes in extreme environments

狐獴對極端環境中季節性變化的生活史應對

作者：Maria Paniw, Nino Maag, Gabriele Cozzi, Tim Clutton-Brock, ArpatOzgul

鏈接：

http://science.sciencemag.org/content/363/6427/631

摘要：

極端棲息地中的物種日益面臨著季節性氣候帶來的挑戰，但這些變化通過哪些分布機制影響種群持續性仍然未知。

我們研究了季節性降水和溫度的變化如何通過對體重產生的效應影響乾旱環境「專家」——喀拉哈里狐獴。

我們證實，在繁殖前季節中，氣候變化誘導的成年狐獴體重的下降使繁殖季節期間的生育力下降並且增加了滅絕風險，尤其是在狐獴種群密度低的地區。

Abstract

Species in extreme habitats increasingly face changes in seasonal climate, but the demographic mechanisms through which these changes affect population persistence remain unknown. We investigated how changes in seasonal rainfall and temperature influence vital rates andviability of an arid environment specialist, the Kalahari meerkat, through effects on body mass. We show that climate change–induced reduction in adultmass in the prebreeding season would decrease fecundity during the breeding season and increase extinction risk, particularly at low population densities.

物理學Physics

Supersymmetric laser arrays

超對稱性的激光陣列

作者：Mohammad P. Hokmabadi, Nicholas S. Nye, Ramy El-Ganainy, et al

鏈接：

http://science.sciencemag.org/content/363/6427/623

摘要：

放大耦合激光陣列的輻射率一直是光子學領域面臨的一個長期挑戰。

在這項研究中，我們證實，來自超對稱性——高能物理中的一個理論框架——的概念可被巧妙地運用於光學來解決這個問題。

就這一點而言，超對稱性激光陣列得以實現。其能以穩定的方式專門發射基橫模。

我們的結果不僅為設計放大集成激光器輻射率的新框架奠定了基礎，還在更加基礎的層面為了解非厄米性和超對稱性之間有趣的協同作用鋪平了道路。

Abstract

Scaling up the radiance of coupled laser arrays has been a long-standing challenge in photonics. In this study, we demonstrate that notions from supersymmetry—a theoretical framework developedin high-energy physics—can be strategically used in optics to address this problem. In this regard, a super symmetric laser array is realized that is capable of emitting exclusively in its fundamental transverse mode in a stable manner. Our results not only pave the way toward devising new schemes forscaling up radiance in integrated lasers, but also, on a more fundamental level, could shed light on the intriguing synergy between non-Hermiticity and supersymmetry.

《科學》（20190208出版）一周論文導讀