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Deficiency of transmembrane AMPA receptor regulatory protein γ-8 leads to attention-deficit hyperactivity disorder-like behavior in mice

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Zoological Research 2022年第5期43卷 851-870页

作者： Wan-Jun Bai Xing-Guang Luo Bao-Hua Jin Kang-Sheng Zhu Wen-Yan Guo Xiao-Que Zhu Xia Qin Zu-Xiao Yang Jiao-Jiao Zhao Si-Ruan Chen Ri Wang Jie Hao Fei Wang Yun stone Shi De-Zhi Kong Wei Zhang Department of Pharmacology Institution of Chinese Integrative MedicineKey Laboratory of Neural and Vascular BiologyMinistry of EducationKey Laboratory of New Drug Pharmacology and ToxicologyHebei Medical UniversityResearch Unit of Digestive Tract Microecosystem Pharmacology and ToxicologyChinese Academy of Medical SciencesShijiazhuangHebei 050017China Department of Pharmacy Hebei General HospitalShijiazhuangHebei 050051China Beijing Huilongguan Hospital Peking University Huilongguan School of Clinical MedicineBeijing 100096China Fourth Hospital of Hebei Medical University ShijiazhuangHebei 050017China Department of Psychiatry Affiliated Nanjing Brain HospitalNanjing Medical UniversityNanjingJiangsu 210029China State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study Model Animal Research CenterNanjing UniversityNanjingJiangsu 210061China

Attention-deficit hyperactivity disorder(ADHD) is a neurodevelopmental disorder prevalent in schoolage children. At present, however, its etiologies and risk factors are unknown. Transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazolepropionicacid(AMPA) receptor regulatory protein γ-8(TARP γ-8,also known as calcium voltage-gated channel auxiliary subunit gamma 8(CACNG8)) is an auxiliary AMPA receptor(AMPAR) subunit. Here, we report an association between TARP γ-8 and ADHD,whereby adolescent TARP γ-8 knockout(KO) mice exhibitedADHD-likebehaviors,including hyperactivity, impulsivity, anxiety, impaired cognition,and memory deficits. Human single-nucleotide polymorphism(SNP) analysis also revealed strong associations between intronic alleles in CACNG8genes and ADHD susceptibility. In addition,synaptosomal proteomic analysis revealed dysfunction of the AMPA glutamate receptor complex in the hippocampi of TARP γ-8 KO *** analysis also revealed dysregulation of dopaminergic and glutamatergic transmissions in the prefrontal cortices of TARP γ-8 KO ***(MPH), which is commonly used to treat ADHD, significantly rescued the major behavioral deficits and abnormal synaptosomal proteins in TARP γ-8 KO mice. Notably, MPH significantly reversed the up-regulation of Grik2 and Slc6a3 in the prefrontal cortex. MPH also significantly improved synaptic AMPAR complex function by up-regulating other AMPAR auxiliary proteins in hippocampal synaptosomes. Taken together, our results suggest that TARP γ-8 is involved in the development of ADHD in *** study provides a useful alternative animal model with ADHD-like phenotypes related to TARP γ-8deficiency, which has great potential for the development of new therapies.

关键词： Attention-deficit hyperactivity disorder TARPγ-8 Methylphenidate Proteomics Phenome-wide association study

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激发你想象力的世界遗产地

英语画刊(高中版) 2022年第27期 12-13页

作者： George W.stone

一起去探索这些世界文化遗产地，看看人类最令人敬畏的地方。See Northern Ireland’s coastal wonderland看看北爱尔兰的沿海仙境Giant’s Causeway is a volcanic formation of nearly 40, 000 hexagonal columns, forged 60 million ...

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科技业大萧条

商业周刊（中文版） 2022年第17期 44-73页

作者： Brad stone Lizette Chapman 杨飞(译) 不详

半个世纪以来,硅谷一直在两个听起来相似但经常相互冲突的追求之间来回切换:创造财富和赚钱。创造财富是发明活动以及耐心和长期的业务建设行为。它如同涨潮,能让员工、股东和其他所有人跟着水涨船高。赚钱则是更基本的冲动:猎取快钱。... 详细信息

半个世纪以来,硅谷一直在两个听起来相似但经常相互冲突的追求之间来回切换:创造财富和赚钱。创造财富是发明活动以及耐心和长期的业务建设行为。它如同涨潮,能让员工、股东和其他所有人跟着水涨船高。赚钱则是更基本的冲动:猎取快钱。是追求短期暴利,还是让公司稳定发展从而创造出一些很酷的东西?科技行业及其乐于冒险的资助者一次又一次地得到教训,当他们优先考虑前者时会发生什么。然而,我们还是又一次重蹈覆辙。多年来疯狂膨胀的估值、加密货币式的传销骗局以及各种赤裸裸的机会主义导致我们走向了2022年的萧条。

关键词：机会主义资助者创造财富萧条相互冲突科技

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硅谷期待人工智能领域的iPhone

商业周刊（中文版） 2023年第17期 20-21页

作者： Brad stone 竹西(译) 不详

●科技公司正在探索人工智能硬件设备的新形式整个科技界似乎正在形成一种共识:在iPhone推出15年后,ChatGPT和其他生成式人工智能(AI)服务可能会催生一种新型硬件设备,并带来人与计算机之间完全不同的互动方式。

关键词：互动方式 iPhone 硬件设备 Chat 硅谷生成式计算机

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学者利用计算机算法破解历史之谜

商业周刊（中文版） 2023年第16期 22-23页

作者： Jeff stone 融汐(译) 不详

四百多年前,苏格兰女王玛丽(Mary)被关押在英格兰城堡,罪名是密谋反对她的表妹伊丽莎白一世(Queen Elizabeth I)。为了保住自已的脑袋,玛丽给朋友和盟友写了几十封密信。在其中几封信中,她与法国大使讨论了对手如何绑架了她的儿子;在其... 详细信息

四百多年前,苏格兰女王玛丽(Mary)被关押在英格兰城堡,罪名是密谋反对她的表妹伊丽莎白一世(Queen Elizabeth I)。为了保住自已的脑袋,玛丽给朋友和盟友写了几十封密信。在其中几封信中,她与法国大使讨论了对手如何绑架了她的儿子;在其他信件中,她抱怨了自已被囚禁的状况,并表示她支持一场有争议的婚姻,因为那将有助于法国和英国之间的政治联盟.

关键词：玛丽伊丽莎白一世计算机算法历史之谜英格兰苏格兰

Swimming in the Sahara

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科技英语学习 2007年第2期 2-3页

作者： Alex stone 于文

非洲的撒哈拉大沙漠总会使人想起干旱、贫瘠和荒凉的画面。然而,是不是盘古开天地以来,它就是一望无际、了无人烟的沙漠呢?历史上的撒哈拉沙漠究竟是什么样子?德国科隆大学的地质考古学家Stefan Kropclin通过对东撒哈拉长达30年的挖掘,... 详细信息

非洲的撒哈拉大沙漠总会使人想起干旱、贫瘠和荒凉的画面。然而,是不是盘古开天地以来,它就是一望无际、了无人烟的沙漠呢?历史上的撒哈拉沙漠究竟是什么样子?德国科隆大学的地质考古学家Stefan Kropclin通过对东撒哈拉长达30年的挖掘,以及对其出土的文物,例如动物骨骼、山洞艺术品等研究,对以上问题给出了明确的答案。他认为,过去的撒哈拉大沙漠曾是一个生机勃勃的绿色伊甸园,将来它必将重现昔日草木葱茏的景像。

关键词：撒哈拉大沙漠 Swimming in the Sahara

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Breakfast Can Wait,The Day＇s First Stop Is Online

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英语画刊（高三·社会综合版） 2009年第12期 28-29页

作者： Brad stone

网络改变了很多美国家庭的清晨生活：一家人起床后，不一起屹饭、聊天，而是马上就上网，看有没有新邮件，网页有否更新。从成人到小孩，仿佛上网成了生活中的头等大事。

关键词：中学英语教学教学方法阅读

Germany in Defeat, 1945

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英语学习 2013年第7期 20-23页

作者： William stone

Brain reward circuitry:The overlapping neurobiology of trauma and substance use disorders

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World Journal of Psychiatry 2021年第6期11卷 222-231页

作者： Timothy I Michaels Emily stone Sonali Singal Vladan Novakovic Robert L Barkin Stacy Barkin Department of Psychiatry The Zucker Hillside HospitalNorthwell HealthGlen OaksNY 11004United States Department of Psychiatry The Donald and Barbara Zucker School of MedicineHofstra/NorthwellGlen OaksNY 11004United States Department of Anesthesiology Rush University Medical CollegeChicagoIL 60612United States Private Practice ScottsdaleAZ 85250United States

Mental health symptoms secondary to trauma exposure and substance use disorders(SUDs)co-occur frequently in both clinical and community *** possibility of a shared aetiology remains an important question in translational *** in genetics,basic science,and neuroimaging have led to an improved understanding of the neural basis of these disorders,their frequent comorbidity and high rates of relapse remain a clinical *** project aimed to conduct a review of the field’s current understanding regarding the neural circuitry underlying posttraumatic stress disorder and SUD.A comprehensive review was conducted of available published literature regarding the shared neurobiology of these disorders,and is summarized in detail,including evidence from both animal and clinical *** summarizing the relevant literature,this review puts forth a hypothesis related to their shared neurobiology within the context of fear processing and reward *** provides an overview of brain reward circuitry and its relation to the neurobiology,symptomology,and phenomenology of trauma and substance *** review provides clinical insights and implications of the proposed theory,including the potential development of novel pharmacological and therapeutic treatments to address this shared *** and extensions of this theory are discussed to provide future directions and insights for this shared phenomena.

关键词： Posttraumatic stress disorder Substance abuse Reward circuitry Mesolimbic Neurobiology