翻译 | 宗华
Science, 08 FEBRUARY 2019, VOL 363, ISSUE 6427
《科学》2019年2月8日，第6427期363卷
医学Medicine
An ingestible self-orienting system fororal delivery of macromolecules
用于大分子口服输送的可吸收自定位系统
▲ 作者：Alex Abramson, Ester Caffarel-Salvador, Minsoo Khang, et al
▲ 链接：
http://science.sciencemag.org/content/363/6427/611
▲ 摘要：
生物大分子改变了人类有效治疗疾病的能力。不过，它们在胃肠道（GI）中的快速降解和吸收不良，通常限制了其肠外途径给药。
口服生物输送系统必须辅以定位和渗透上的帮助，才能实现系统性药物吸收。受豹纹陆龟被动重定位能力启发，我们开发了一种可吸收的自定位毫米级点药器（SOMA）。
SOMA可自动实现自我定位，从而参与GI组织。随后，它使由药物活性成分制成的毫米级小管直接通过胃黏膜并且避免了穿孔。
我们在小鼠和猪身上开展了体内研究，从而为点药器的安全性提供支撑，同时用胰岛素作为模型药物，证实SOMA输送的药物活性成分血浆水平可同皮下毫米级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
将宿主和微生物菌群对药物药代动力学和毒性的贡献分离
▲ 作者：Michael Zimmermann, Maria Zimmermann-Kogadeeva, Rebekka Wegmann,Andrew L. Goodman
▲ 链接：
http://science.sciencemag.org/content/363/6427/eaat9931
▲ 摘要：
肠道菌群与很多医疗药物的代谢有关，导致药效及其毒性因人而异。
我们将肠道共生遗传学和择生生物学结合，测量了小鼠组织中的溴夫定药物代谢。这些组织在单个微生物菌群编码的酶上出现差异。
根据这些测量结果，我们建立了药代动力学模型作为生物药效率、寄主和微生物药物代谢活性、药物和代谢物吸收以及肠道输送动力学的函数。该模型可定量预测微生物菌群对系统性药物和代谢物暴露的贡献。
▲ 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.
生物学Biology
Schema cells in the macaque hippocampus
猕猴海马体中的模式细胞
▲ 作者：P. Baraduc, J.-R. Duhamel, S. Wirth1
▲ 链接：
http://science.sciencemag.org/content/363/6427/635
▲ 摘要：
人类海马体中的概念细胞编码通过感官刺激传达的意义。这里，我们探寻了猕猴体内的类似细胞能否形成对空间环境的概念框图。
每天，呈现在这些猴子面前的是一个熟悉的和一个新的虚拟迷宫。它们拥有共同的模式，但在表面特征（地标）上不同。在两种环境下，动物寻找隐藏的奖励目标。这些目标仅被定义为同地标相关。
通过学习，很多神经元形成了将新迷宫以目标为中心和同任务相关信息结合起来的放电地图。这可同针对熟悉迷宫形成的放电地图媲美。因此，这些海马体细胞将来自环境中表面细节的空间概念抽象出来，并将空间编码进像框架一样的模型中。
▲ 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
对聚糖的先天免疫识别将HIV纳米颗粒免疫原靶向生发中心
▲ 作者：Talar Tokatlian, Benjamin J. Read, Christopher A. Jones, et al
▲ 链接：
http://science.sciencemag.org/content/363/6427/649
▲ 摘要：
在疫苗设计中，抗原通常以多价纳米颗粒的形式排列，但这些疫苗促使免疫力增强背后的体内机制一直知之甚少。
我们比较了两种不同的高度糖基化的HIV抗原的命运：一种是来自gp120的迷你蛋白质，另一种是蛋白质纳米颗粒中大的、稳定的包膜三聚体或者初次免疫后的“自由”形式。
和单体抗原不同，纳米颗粒被迅速运送到滤泡树突状细胞（FDC）网络，然后以一种依赖于补体、甘露糖结合凝集素（MBL）和免疫原多糖的方式集中在生发中心。缺少MBL的小鼠体内FDC定位的失去或者通过免疫原去糖基化都会显著影响抗体反应。
▲ 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
硅藻中绿—蓝光捕捉和能量耗散的结构基础
▲ 作者：Wenda Wang, Long-Jiang Yu2, Caizhe Xu, et al
▲ 链接：
http://science.sciencemag.org/content/363/6427/eaav0365
▲ 摘要：
硅藻是水生环境中一种含量丰富的光合生物，贡献了40%的初级生产力。促使硅藻成功的一个重要因素是它们的岩藻黄质叶绿素a/c结合蛋白（FCPs）。
FCPs拥有超强的光捕获和光损伤防护能力。这里，我们报告了来自一种海洋硅藻——三角褐指藻的FCP的晶体结构。
这揭示了7个叶绿素（Chls）a、2个Chls c、7个岩藻黄质（Fxs）以及蛋白质支架中可能的1个硅甲藻黄素。
▲ 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.
气候科学Climate Science
Aerosol-driven droplet concentrations dominate coverage and water of oceanic low-level clouds
气溶胶驱动的液滴浓度主导海洋低空云层覆盖和水分
▲ 作者：Daniel Rosenfeld, Yannian Zhu, Minghuai Wang, et al
▲ 链接：
http://science.sciencemag.org/content/363/6427/eaav0566
▲ 摘要：
对海洋上空云凝结核（CCN）气溶胶可靠估测的缺失，严重限制了量化其对云层性质的影响以及通过反射太阳辐射的冷却程度。
这是源于人类活动的气候强迫作用的关键不确定性。我们引入一种方法用于分析CCN对云层性质的影响并将气溶胶影响同气象效应相分离。
该方法的应用显示，对于特定气象状态，CCN解释了云层辐射冷却效果的3/4的变化性。这主要是通过影响浅云层覆盖和水分路径实现的。
▲ 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
狐獴对极端环境中季节性变化的生活史应对
▲ 作者：Maria Paniw, Nino Maag, Gabriele Cozzi, Tim Clutton-Brock, ArpatOzgul
▲ 链接：
http://science.sciencemag.org/content/363/6427/631
▲ 摘要：
极端栖息地中的物种日益面临着季节性气候带来的挑战，但这些变化通过哪些分布机制影响种群持续性仍然未知。
我们研究了季节性降水和温度的变化如何通过对体重产生的效应影响干旱环境“专家”——喀拉哈里狐獴。
我们证实，在繁殖前季节中，气候变化诱导的成年狐獴体重的下降使繁殖季节期间的生育力下降并且增加了灭绝风险，尤其是在狐獴种群密度低的地区。
▲ 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.
物理学Physics
Supersymmetric laser arrays
超对称性的激光阵列
▲ 作者：Mohammad P. Hokmabadi, Nicholas S. Nye, Ramy El-Ganainy, et al
▲ 链接：
http://science.sciencemag.org/content/363/6427/623
▲ 摘要：
放大耦合激光阵列的辐射率一直是光子学领域面临的一个长期挑战。
在这项研究中，我们证实，来自超对称性——高能物理中的一个理论框架——的概念可被巧妙地运用于光学来解决这个问题。
就这一点而言，超对称性激光阵列得以实现。其能以稳定的方式专门发射基横模。
我们的结果不仅为设计放大集成激光器辐射率的新框架奠定了基础，还在更加基础的层面为了解非厄米性和超对称性之间有趣的协同作用铺平了道路。
▲ 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.
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