《科学》（20230915出版）一周论文导读

编译 | 未玖

Science, 15 SEP 2023, VOL 381, ISSUE 6663

《科学》2023年9月15日，第381卷，6663期

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人工智能Artificial Intelligence

Edge learning using a fully integrated neuro-inspired memristor chip

使用全集成类脑忆阻器芯片进行边缘学习

▲ 作者：Wenbin Zhang, Peng Yao, Bin Gao, Qi Liu, Dong Wu, Qingtian Zhang, et al.

▲ 链接：https://www.science.org/doi/full/10.1126/science.ade3483

▲ 摘要：

学习对于边缘智能设备适应不同的应用场景和用户非常重要。当前训练神经网络的技术需要在计算和存储单元之间移动大量数据，这阻碍了在边缘设备上实现学习。

研究组开发了一种全集成忆阻器芯片，提高了学习能力，降低了能耗。STELLAR架构中包括学习算法、硬件实现和并行电导调制策略的方案，是通过使用忆阻器交叉阵列来促进片上学习的通用方法，而与忆阻器器件类型无关。

在这项研究中执行的任务包括运动控制、图像分类和语音识别。

▲ Abstract：

Learning is highly important for edge intelligence devices to adapt to different application scenes and owners. Current technologies for training neural networks require moving massive amounts of data between computing and memory units, which hinders the implementation of learning on edge devices. We developed a fully integrated memristor chip with the improvement learning ability and low energy cost. The schemes in the STELLAR architecture, including its learning algorithm, hardware realization, and parallel conductance tuning scheme, are general approaches that facilitate on-chip learning by using a memristor crossbar array, regardless of the type of memristor device. Tasks executed in this study included motion control, image classification, and speech recognition.

Powerful, soft combustion actuators for insect-scale robots

用于昆虫级机器人的强大、软燃烧致动器

▲ 作者：Cameron A. Aubin, Ronald H. Heisser, Ofek Peretz, Julia Timko, Jacqueline Lo, E. Farrell Helbling, et al.

▲ 链接：https://www.science.org/doi/full/10.1126/science.adg5067

▲ 摘要：

昆虫相对于其较小的身体，拥有惊人的强大力量和耐力。昆虫级机器人尽管遵循相同的缩放定律，但与昆虫相比性能却大大下降，这是因为当前微致动器技术由低能量密度电源驱动，产生的力和/或位移都很小。使用高能量密度化学燃料为小型软致动器提供动力是一种潜在解决方案。

研究组展示了一个325毫克的软燃烧微致动器，可实现140%的位移，工作频率>100赫兹，并产生>9.5牛顿的力。利用这些致动器为一个昆虫大小的四足机器人提供动力，该机器人展示了各种步态模式、方向控制和22倍于其体重的有效载荷能力。这些特征使昆虫机器人能够在崎岖地形和障碍物上移动。

▲ Abstract：

Insects perform feats of strength and endurance that belie their small stature. Insect-scale robots—although subject to the same scaling laws—demonstrate reduced performance because existing microactuator technologies are driven by low–energy density power sources and produce small forces and/or displacements. The use of high–energy density chemical fuels to power small, soft actuators represents a possible solution. We demonstrate a 325-milligram soft combustion microactuator that can achieve displacements of 140%, operate at frequencies >100 hertz, and generate forces >9.5 newtons. With these actuators, we powered an insect-scale quadrupedal robot, which demonstrated a variety of gait patterns, directional control, and a payload capacity 22 times its body weight. These features enabled locomotion through uneven terrain and over obstacles.

医学Medicine

MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer’s disease

在模拟阿尔茨海默病的人类神经元异种移植物中MEG3激活坏死性凋亡

▲ 作者：Sriram Balusu, Katrien Horré, Nicola Thrupp, Katleen Craessaerts, An Snellinx, Lutgarde Serneels, et al.

▲ 链接：https://www.science.org/doi/full/10.1126/science.abp9556

▲ 摘要：

神经元丢失是阿尔茨海默病（AD）的一个决定性特征，但其潜在机制尚不清楚。

研究组将人类或小鼠神经元异种移植到AD小鼠模型的大脑中。结果只有人类神经元显示缠结、Gallyas银染色、颗粒空泡变性（GVD）、磷酸化tau血液生物标志物和相当大的神经元丢失。长非编码RNA MEG3在人类神经元中被强烈上调。这种神经元特异性长非编码RNA在AD患者中也被上调。

MEG3单独表达足以在体外诱导人神经元坏死性凋亡。通过受体相互作用蛋白激酶1（RIPK1）、RIPK3或混合谱系激酶结构域样蛋白（MLKL）的药理学或基因学操作来下调MEG3和抑制坏死性凋亡，可挽救异种移植人类神经元中的神经元丢失。该模型提供了潜在的AD治疗方法，并揭示了人类对AD的特定易感性。

▲ Abstract：

Neuronal cell loss is a defining feature of Alzheimer’s disease (AD), but the underlying mechanisms remain unclear. We xenografted human or mouse neurons into the brain of a mouse model of AD. Only human neurons displayed tangles, Gallyas silver staining, granulovacuolar neurodegeneration (GVD), phosphorylated tau blood biomarkers, and considerable neuronal cell loss. The long noncoding RNA MEG3 was strongly up-regulated in human neurons. This neuron-specific long noncoding RNA is also up-regulated in AD patients. MEG3 expression alone was sufficient to induce necroptosis in human neurons in vitro. Down-regulation of MEG3 and inhibition of necroptosis using pharmacological or genetic manipulation of receptor-interacting protein kinase 1 (RIPK1), RIPK3, or mixed lineage kinase domain-like protein (MLKL) rescued neuronal cell loss in xenografted human neurons. This model suggests potential therapeutic approaches for AD and reveals a human-specific vulnerability to AD.

Conserved γδ T cell selection by BTNL proteins limits progression of human inflammatory bowel disease

BTNL蛋白保守的γδ T细胞选择限制了人类炎症性肠病的进展

▲ 作者：Robin J. Dart, Iva Zlatareva, Pierre Vantourout, Efstathios Theodoridis, Ariella Amar, Shichina Kannambath, et al.

▲ 链接：https://www.science.org/doi/full/10.1126/science.adh0301

▲ 摘要：

小鼠上皮内γδ T细胞包括不同的组织保护细胞，由上皮嗜丁酸蛋白样（BTNL）异构体选择。

为了确定这种生物学是否在人类中保守，研究组对人结肠γδ T细胞区室进行了表征，确定了一个包括共表达T细胞受体Vγ4和上皮结合整合素CD103的表型不同亚群的多样性库。该亚群在炎症性肠病中不成比例地减少和失调，而治疗中CD103+γδ T细胞恢复与炎症性肠病的持续缓解相关。

此外，具有种系BTNL3/BTNL8亚型的人也表现出CD103+Vγ4+细胞失调和缺失，研究组确定这是穿透性克罗恩病（CD）的一个危险因素。因此，BTNL依赖性的选择和/或维持不同的组织内在γδ T细胞似乎是一个进化上保守的轴，限制了全球发病率不断上升的复杂、多因素、组织损伤疾病的进展。

▲ Abstract：

Murine intraepithelial γδ T cells include distinct tissue-protective cells selected by epithelial butyrophilin-like (BTNL) heteromers. To determine whether this biology is conserved in humans, we characterized the colonic γδ T cell compartment, identifying a diverse repertoire that includes a phenotypically distinct subset coexpressing T cell receptor Vγ4 and the epithelium-binding integrin CD103. This subset was disproportionately diminished and dysregulated in inflammatory bowel disease, whereas on-treatment CD103+γδ T cell restoration was associated with sustained inflammatory bowel disease remission. Moreover, CD103+Vγ4+cell dysregulation and loss were also displayed by humans with germline BTNL3/BTNL8 hypomorphism, which we identified as a risk factor for penetrating Crohn’s disease (CD). Thus, BTNL-dependent selection and/or maintenance of distinct tissue-intrinsic γδ T cells appears to be an evolutionarily conserved axis limiting the progression of a complex, multifactorial, tissue-damaging disease of increasing global incidence.

动物学Zoology

Songbird species that display more-complex vocal learning are better problem-solvers and have larger brains

鸣禽发声学习能力越强，越能更好地解决问题，大脑也越大

▲ 作者：Jean-Nicolas Audet, Mélanie Couture & Erich D. Jarvis

▲ 链接：https://www.science.org/doi/full/10.1126/science.adh3428

▲ 摘要：

复杂发声学习是人类口语的一个重要组成部分，一直被认为与更高级的认知能力有关。在同一物种内的个体之间对该假设的测试尚无定论，也尚未在整个物种间进行过测试。

在这项工作中，研究组评估了23种鸟类中214只个体的一系列认知技能（即解决问题、联想和反向学习以及自我控制），其中包括19种野生捕获的鸣禽、两种驯养鸣禽和两种野生捕获的无发声学习鸟类。

结果发现，一个物种的发声学习能力越强，其解决问题的能力就越好，大脑也相对越大。当控制非认知变量和系统发育时，该结论仍成立。研究结果支持了一种假设，即鸣禽在发声学习、解决问题和更大的大脑之间存在着共同的遗传和认知机制。

▲ Abstract：

Complex vocal learning, a critical component of human spoken language, has been assumed to be associated with more-advanced cognitive abilities. Tests of this hypothesis between individuals within a species have been inconclusive and have not been done across species. In this work, we measured an array of cognitive skills—namely, problem-solving, associative and reversal learning, and self-control—across 214 individuals of 23 bird species, including 19 wild-caught songbird species, two domesticated songbird species, and two wild-caught vocal nonlearning species. We found that the greater the vocal learning abilities of a species, the better their problem-solving skills and the relatively larger their brains. These conclusions held when controlling for noncognitive variables and phylogeny. Our results support a hypothesis of shared genetic and cognitive mechanisms between vocal learning, problem-solving, and bigger brains in songbirds.

神经科学Neuroscience

Presynaptic Ube3a E3 ligase promotes synapse elimination through down-regulation of BMP signaling

突触前Ube3a E3连接酶通过下调BMP信号促进突触消除

▲ 作者：Kotaro Furusawa, Kenichi Ishii, Masato Tsuji, Nagomi Tokumitsu, Eri Hasegawa & Kazuo Emoto

▲ 链接：https://www.science.org/doi/full/10.1126/science.ade8978

▲ 摘要：

泛素连接酶Ube3a失活导致发育障碍Angelman综合征，而Ube3a剂量增加与自闭症谱系障碍有关。尽管Ube3a在包括突触前的轴突末端有丰富定位，但人们对Ube3a的突触前功能及其突触前定位的机制知之甚少。

研究组发现发育性突触消除需要果蝇神经元的突触前Ube3a活性，并进一步确定了Ube3a与驱动蛋白马达相互作用所必需的结构域。

Angelman综合征相关的相互作用域错义突变减弱了Ube3a的突触前靶向并阻止突触消除。相反，突触前Ube3a活性的增加会导致早熟突触消除并损害突触传递。该研究结果揭示了Ube3a的生理作用，并提出了与Ube3a失调相关的潜在致病机制。

▲ Abstract：

Inactivation of the ubiquitin ligase Ube3a causes the developmental disorder Angelman syndrome, whereas increased Ube3a dosage is associated with autism spectrum disorders. Despite the enriched localization of Ube3a in the axon terminals including presynapses, little is known about the presynaptic function of Ube3a and mechanisms underlying its presynaptic localization. We show that developmental synapse elimination requires presynaptic Ube3a activity in Drosophila neurons. We further identified the domain of Ube3a that is required for its interaction with the kinesin motor. Angelman syndrome–associated missense mutations in the interaction domain attenuate presynaptic targeting of Ube3a and prevent synapse elimination. Conversely, increased Ube3a activity in presynapses leads to precocious synapse elimination and impairs synaptic transmission. Our findings reveal the physiological role of Ube3a and suggest potential pathogenic mechanisms associated with Ube3a dysregulation.