A History of the Origin and Development of Japanese Society for Neurochemistry: International Cooperation to Overcome Dementia and Mental Illness

“Neurochemistry” in Japan was established by intensive cooperation between psychiatrists and their collaborators, biochemists, who have sought to investigate the etiology of mental illness to establish treatments. It was a completely different direction from the flow of modern biochemistry that was born using microorganisms or eukaryotic cells as research materials. Neurochemists aimed to elucidate the physiological or pathological functions of the brain through chemical analysis of the morphologically and functionally unique complexity and characteristics of brain. I here describe some of the origin and history of neurochemistry in Japan how researchers estabIished Japanese Society for Neurochemistry in1958 Yasuzo Tsukada as a president in collaboration with Isamu Sano, Genkichiro Takagaki and Masanori Kurokawa. The formation of research groups with the support of MEXT played a major role in promoting neurochemistry. Many international conferences held in Japan promoted the activity of neurochemistry: The International Society of Physiology (Tokyo) in 1965, and the Japan-US Neurochemistry Conference (Oiso) in 1965, and in 1967 the International Conference on Biochemistry (Tokyo). These meetings offered excitements to younger researchers by close interaction with the world top class researchers. Government established Brain Research Institutes in several national universities. The Asia–Pacific Society for Neurochemistry (APSN) was established in 1991 subsequent to an initiative by JSN. APSN presidents: Yasuzo Tsukada, Kazuhiro Ikenaka, and Akio Wanaka contributed to promote neurochemistry. The 4th ISN meeting was organized at Tokyo (Yasuzo Tsukada, president) in 1973 and the 15th ISN meeting at Kyoto (Kinya Kuriyama, president) in 1995. Kunihiko Suzuki and Kazuhiro Ikenaka as ISN Presidents greatly contributed in promoting the activity of ISN.

     

沙尘暴对北京市空气细菌多样性特征的影响

亚洲沙尘暴携带着各类污染物质,严重影响下风向地区大气过程及生态系统和相关人群的健康。然而,沙尘天气对中国华北地区空气细菌群落及多样性特征影响的研究较少。以北京市为例,系统研究了沙尘暴对城市空气细菌多样性特征的影响。2015年4月,通过定点采样连续收集了一次沙尘暴及其前后4天的空气颗粒物样本,DNA提取、PCR扩增后进行16S rRNA基因高通量测序。共获得169122条高质量序列,生物信息学分析表明,北京市空气细菌物种多样性较高,沙尘暴不能引起细菌OTU数目的增加,但沙尘暴天气下细菌群落Pielou、Shannon和Simpson指数显著增加。菌群分类分析发现,北京市空气细菌由35个细菌门构成,其中变形菌门(Proteobacteria)、放线菌门(Actinobacteria)、厚壁菌门(Firmicutes)和拟杆菌门(Bacteroidetes)相对丰度最高,分别占总序列的32.76%、28.09%、25.46%和6.32%;芽单胞菌门(Gemmatimonadetes)和酸杆菌门(Acidobacteria)次之,分别占序列总数的2.11%和1.81%,其他细菌门的相对丰度均低于1%。沙尘暴天气下,变形菌门(Proteobacteria)、拟杆菌门(Bacteroidetes)、芽单胞菌门(Gemmatimonadetes)和酸杆菌门(Acidobacteria)显著升高(P<0.05),分别由31.67%、5.74%、1.82%、1.51%升高至41.46%、10.98%、4.48%和4.26%;而放线菌门(Actinobacteria)、厚壁菌门(Firmicutes)显著降低(P <0.05),分别由28.84%、27.10%降低至22.13%和12.35%。冷杆菌属(Psychrobacter),纤维单胞菌属(Cellulomonas),不动杆菌属(Acinetobacter),假单胞菌属(Pseudomonas)和梭菌属(Clostridium)可能含有人类条件病原菌,其在沙尘暴天气中相对丰度下降,但绝对丰度会大幅增加。沙尘暴能降低人体免疫力,因此致病菌潜在健康风险可能显著增强。通过聚类分析和主成分分析发现,沙尘暴日与非沙尘暴日空气细菌群落差异较大,而沙尘暴前后群落结构差异较小。沙尘暴前后空气细菌群落α-多样性和β多样性均无显著差异,推测沙尘暴只能暂时影响空气细菌群落特征,不能显著改变其群落结构。本研究通过分析了沙尘暴侵袭下北京市空气细菌群落多样性特征及动态,为制定中国北方城市沙尘暴灾害预警措施和建立气传疾病的防控机制提供数据支持。     

自然资本科学和决策实践:宜居城市和可持续发展——2018年自然资本项目年会述评

2018年自然资本项目年会(Natural Capital Project Symposium)于3月19日至22日在美国斯坦福大学举行。自然资本项目由美国斯坦福大学、世界自然基金会和大自然保护协会发起,旨在推进将科学和融入自然多元价值的实践纳入管理决策过程。本次会议正式邀请并宣布中国科学院生态环境研究中心为项目伙伴。会议吸引了来自33个国家363名政府工作人员、非政府组织成员、企业家和专家学者参加。本届年会的两大主题是宜居城市和可持续发展。会议包含9个大会主题报告和3个平行分会场,平行分会场归纳为宜居城市、可持续发展、淡水和流域管理、海岸带恢复力、投资标准化制定、模型培训和探索等六个方面;会议同时设有专题讨论和小组研讨、InVEST模型培训和讨论、墙报展示等。会议推进了生态系统服务的科学发展和实践应用,将自然资本纳入科学决策体系,在全球范围内推动科学和决策的融合、促进可持续发展。     

百日咳免疫保护相关机制及评价指标的研究进展

百日咳是目前世界上普遍采用疫苗可进行免疫预防策略的疾病之一。近十年来包括中国在内的许多国家出现的百日咳发病率上升的现象已引起了全球极大关注。其主要原因可能与疫苗接种尤其是无细胞百日咳疫苗(acellular pertussis vaccine, APV)诱导产生的免疫力不断衰减有关。血清中的抗百日咳毒素特异性IgG抗体检测是最重要的免疫力评价方法之一,但到目前为止,感染百日咳菌或接种百日咳疫苗后的免疫力保护相关机制及评价指标尚无统一的标准。现就国内外百日咳相关研究进展作一概述。     

衰老与血管钙化

血管钙化是指体内钙磷在血管壁的异常沉积,是一个主动的、高度可调节的、类似于骨形成的生物学过程。血管钙化是引起心血管疾病发病率、病死率升高的重要原因,也是危害中老年人身体健康的广泛存在的病理现象。近年研究表明,衰老与血管钙化存在密切关系,衰老可以通过诱导血管平滑肌细胞成骨样转化、内皮细胞释放囊泡、细胞外基质重塑、DNA损伤、炎症反应、磷代谢失衡以及抗衰老因子如Klotho和Sirtuin 1的表达减少而促进血管钙化。     

心肌组织特异性Isca1敲除造成新生大鼠心脏结构异常

目的通过对心肌组织特异性Isca1敲除大鼠进行磁共振分析及病理学分析,探究心肌特异性敲除Isca1对大鼠心脏结构影响。方法繁育心肌组织特异性Isca1敲除大鼠,PCR技术鉴定大鼠基因型及基因敲除效率,对新出生0.5d及2.5d心肌组织特异性Isca1敲除大鼠进行核磁共振影像分析,对新出生2.5d心肌组织特异性Isca1敲除大鼠心肌组织进行H&E染色及透射电镜分析。结果心肌组织特异性Isca1敲除大鼠敲除效率大于78%;与野生型相比,0.5d心肌组织特异性Isca1敲除大鼠心脏未见显著扩张;2.5d心肌组织特异性Isca1敲除大鼠心脏右室呈扩张趋势;2.5d心肌组织特异性Isca1敲除大鼠肌纤维排列不齐,出现排列紊乱,无层次或极向,部分心肌纤维出现溶解断裂,肌节和Z线模糊,出现肌膜损伤,线粒体嵴断裂,肿胀明显。结论心肌组织特异性Isca1敲除造成新生大鼠心脏结构异常。     

孕烷X受体配体结合结构域蛋白晶体的X线衍射结构解析

目的:利用X线衍射技术解析孕烷X受体(PXR)配体结合结构域(LBD)蛋白晶体的3维结构。方法:对PXR蛋白LBD(130~434氨基酸残基)序列进行密码子优化并化学合成后克隆至pRSFDuet-1表达载体,再将载体导入大肠杆菌BL21(DE3),对PXR-LBD蛋白进行原核表达与分离纯化;采用晶体筛选试剂盒筛选蛋白结晶条件,采用悬滴法获得目标蛋白的晶体;对获得的蛋白晶体进行X线晶体衍射检测,并收集相关数据建立PXR-LBD的三维结构。结果:获得了PXR-LBD的高质量晶体并利用X线衍射解析了该蛋白质晶体的结构数据,使用Phenix.refine软件和COOT软件等对结构进行修正,最终获得了高分辨率的3维结构数据。结论:完成了孕烷X受体配体结合结构域蛋白晶体的X线衍射结构解析,为研究和开发PXR相关药物奠定了基础。     

Keystone Symposium on Antibodies as Drugs: March 27–April 1, 2009, Whistler,BC CA

The symposium on Antibodies as Drugs, organized by Keystone Symposia and chaired by J. Marks, (University of California Los Angeles, USA), E.S. Ward (University of Texas Southwestern Medical Center, USA) and L. Weiner (Georgetown University Medical Center, USA), was held in Whistler, British Columbia. This Canadian Rockies village, which will host the 2010 Olympic Games, served as an enchanting backdrop to the meeting. The more than 350 speakers and attendees included scientists from major pharmaceutical firms, e.g., Abbott, MedImmune/Astra Zeneca, Bristol-Myers Squibb, Merck & Co., Pfizer, Sanofi-Aventis, Schering, GlaxoSmithKline, Eli Lilly, Hoffmann LaRoche, Novartis, Wyeth, and biotechnology companies, e.g., Ablynx, Medarex, Morphosys, GenMab, Amgen, Genentech, ImmunoGen, Agensys, Domantis, Biogen Idec, Centocor, LFB, Micromet, PDL Biopharma, Borean Pharma, Dyax Corp., Symphogen and Syntonix. Academic research groups at Imperial College London, University of Oxford, ETH Zürich, Scripps, Institute Cochin, Karolinska Institute, Utrecht University, Harvard Medical School, Massachusetts Institute of Technology, Baylor College, Paul Ehrlich Institute, University of California San Francisco, University of California San Diego, University of Nantes, University of Tours and Ludwig Institute were also represented, as were regulatory authorities, including the US Food and Drug Administration, National Institutes of Health and the Public Health Agency of Canada). The meeting was very interactive and included thoughtful exchanges during the different sessions and networking events.     

Keystone Symposium on Antibodies as Drugs

The symposium on Antibodies as Drugs, organized by Keystone Symposia and chaired by J. Marks, (University of California Los Angeles, USA), E.S. Ward (University of Texas Southwestern Medical Center, USA) and L. Weiner (Georgetown University Medical Center, USA), was held in Whistler, British Columbia. This Canadian Rockies village, which will host the 2010 Olympic Games, served as an enchanting backdrop to the meeting. The >350 speakers and attendees included scientists from major pharmaceutical firms, e.g., Abbott, MedImmune/Astra Zeneca, Bristol-Myers Squibb, Merck & Co, Pfizer, Sanofi-Aventis, Schering, GlaxoSmithKline, Eli Lilly, Hoffmann LaRoche, Novartis, Wyeth, and biotechnology companies, e.g., Ablynx, Medarex, Morphosys, GenMab, Amgen, Genentech, ImmunoGen, Agensys, Domantis, Biogen Idec, Centocor, LFB, Micromet, PDL Biopharma, Borean Pharma, Dyax Corp, Symphogen, Syntonix. Academic research groups at Imperial College London, University of Oxford, ETH Zürich, Scripps, Institute Cochin, Karolinska Institute, Utrecht University, Harvard Medical School, Massachusetts Institute of Technology, Baylor College, Paul Ehrlich Institute, University of California San Francisco, University of California San Diego, University of Nantes, University of Tours, and Ludwig Institute were also represented, as were regulatory authorities, including the US Food and Drug Administration, National Institutes of Health and the Public Health Agency of Canada). The meeting was very interactive, and included thoughtful exchanges during the different sessions and networking events.     

Th2与ILC2细胞在哮喘模型中的数量及产生细胞因子的比较研究

目的比较过敏原依赖和非依赖性哮喘模型中2型辅助性T细胞(Th2 cell)和固有淋巴样2型细胞(type 2innate lymphoid cell,ILC2)的功能。方法滴鼻法制备过敏原卵清蛋白(ovalbumin,OVA)和上皮源性细胞因子(IL-25、IL-33)诱导的亚急性和慢性哮喘小鼠模型。收集小鼠肺泡灌洗液(bronchoalvelar lavage fluid,BALF)进行细胞计数;取左肺进行石蜡包埋、切片和HE染色;右肺行流式细胞术,以分析在不同时间点各组小鼠Th2细胞和ILC2细胞数目和占肺组织总细胞比例,并对Th2型细胞因子的来源进行分析。结果与生理盐水组相比,各实验组BALF中总细胞数明显增加; HE染色可见OVA、IL-25和IL-33均可诱导哮喘典型病理学改变;各实验组肺组织中Th2细胞与ILC2细胞均明显上升,数量上以Th2细胞为主,两者均可产生Th2型细胞因子IL-5和IL-13,且以Th2细胞为主。而在致哮喘样改变、促进Th2细胞和ILC2细胞在小鼠肺部聚集等方面,以IL-33的效应最强。结论在过敏原OVA和非过敏原IL-25、IL-33诱导的哮喘模型中,Th2型细胞因子主要来源均为Th2细胞,提示Th2细胞在哮喘的发生、发展中起到主要作用。IL-33可能是过敏性和非过敏性哮喘患者个体化治疗的潜在靶点。     

两种荧光探针标记鹿茸提取物的稳定性和生物活性比较研究

比较两种荧光探针异硫氰酸荧光素FITC和Cy5标记鹿茸提取物PAEs的最佳方法。用FITC和Cy5分别标记PAEs得到标记物FITC-PAEs和Cy5-PAEs;用SDS-PAGE凝胶电泳检测并比较两种荧光染料标记蛋白分子量的差异;用酶标仪检测在特定波长处OD值计算其标记率;用PC12细胞验证两种荧光染料的生物安全性;将荧光标记物分别与人工胃液和人工肠液共孵育,观察它们在其中的稳定性。结果表明,两种荧光染料标记PAEs蛋白分子量并无明显差异,但FITC-PAEs荧光强度稍强。通过计算标记率表明两种荧光染料均可充分标记PAEs,但Cy5价格昂贵。相比于FITC-PAEs,Cy5-PAEs在人工胃液和人工肠液中稳定性较差。因此,我们选择标记率高,在人工胃液和人工肠液中较为稳定且对机体无毒副作用,价格合理的FITC荧光染料标记PAEs并用于后续实验研究。这为建立蛋白类中药大分子的活性示踪方法,开发口服蛋白类药物奠定基础。     

Synaptopathies: synaptic dysfunction in neurological disorders – A review written by students for students,and a story of success for ISN schools

One of the major endeavors of the International Society for Neurochemistry (ISN) is the promotion and support of young researchers, for instance at ‘schools’ that offer young students an opportunity to closely interact with renowned researchers as well as with each other. As a result of the 13th International Society for Neurochemistry Advanced School on ‘Synapses’ held in Mission Beach, Australia, prior to the Biennial Meeting of the International Society for Neurochemistry in August 2016 in Cairns, we are pleased to publish this comprehensive Review article, written from students for students. Read the highlighted article  ‘Synaptopathies: synaptic dysfunction in neurological disorders – A review from students to students’ on page 785 .     

应用流式细胞Index Sorting技术研究小鼠胚胎生血内皮细胞

目的:应用流式Index Sorting技术鉴定小鼠胚胎期d10(E10)的主动脉中生血内皮细胞(HEC)的表面分子表达特征,并结合体外孵育实验及免疫组化染色验证HEC的生血潜能。方法:已有研究显示细胞表面分子Kit和CD47均能标记造血相关群体。在此基础上,应用流式细胞Index Sorting技术分选单个分子表型为CD41^-CD43^-CD45^-CD31^+Kit^+的主动脉内皮细胞,并与基质细胞OP9-DL1共孵育诱导培养7 d,进而结合单个内皮细胞的流式分选特征参数,及诱导后生成CD45^+造血细胞和CD31^+内皮细胞的效率,综合回溯分析Kit和CD47富集HEC的效果。结果:具有生血潜能的HEC均富集在CD47^+内皮细胞群体中,CD47分子将HEC群体的精度提高1.5倍;CD47^+内皮群体中,仍有60%以上的内皮不具备生血能力,提示进一步探索寻找富集HEC表面标志的必要性。结论:应用流式细胞Index Sorting技术发现CD47分子能显著富集小鼠胚胎期HEC,为进一步精准富集并研究HEC提供了重要的技术手段。     

小鼠胚胎干细胞定向血管内皮和造血细胞分化体系的建立

目的:建立小鼠胚胎干细胞体外定向分化为血管内皮细胞和造血细胞的体系,并验证诱导后2种细胞的表面分子特征。方法:以小鼠胚胎成纤维细胞为饲养层,首先在无血清培养基StemPro中加入骨形态发生蛋白4(BMP4)、激活素A、碱性成纤维细胞生长因子(FGF-Basic)和血管内皮细胞生长因子(VEGF),诱导小鼠胚胎干细胞系R1/E 4 d后形成拟胚体;再将拟胚体消化后与OP9-DL1基质细胞共孵育,分别用干细胞因子(SCF)、VEGF和SCF、FLt3、白细胞介素3(IL-3)诱导向内皮和造血2个方向分化,并以CD31、CD45、CD144、Kit、CD201作为表面标志,流式检测诱导后细胞的表面分子特征和诱导效率;诱导10 d后免疫组化染色,进行内皮细胞的形态学鉴定。结果:诱导分化10 d后,免疫组化染色观察到多个内皮管状结构,流式检测CD31^+的内皮细胞比例为1.35%±0.05%,进一步分析CD31^+CD144^+CD45^-群体,有3.0%±0.2%的细胞表型为Kit^+CD201^+,提示该部分细胞可能是处于分化上游的内皮干祖细胞;CD45^+的造血细胞比例为35.0%±0.5%,其中0.35%±0.05%的细胞表达Kit和CD201,提示该部分细胞可能是处于分化上游的造血干祖细胞。结论:本研究将胚胎干细胞诱导为内皮细胞和造血细胞,并且能诱导出具有内皮、造血干祖细胞分子特征的细胞,可作为理想的体外诱导分化体系。     

Editorial for ‘Issue focus on 2nd Costa Rica biophysics symposium — March 11th–12th, 2021’

This Editorial describes both the motivation for, and the five articles appearing in, the Issue Focus dedicated to the 2nd Costa Rica Biophysics Symposium which was held in March 2021. Some recent history about both the symposium and developments in science occurring within Costa Rica is described. 

The Costa Rica Biophysics Symposium was conceived as a forum for faculty, scholars and students interested on cutting-edge topics in biophysics and related fields. Following the success of the first event organized in 2019 (Solís et al (2020), the second edition of the symposium took place on March 2021 with the support of the Academia Nacional de Ciencias de Costa Rica (ANC, National Academy of Sciences of Costa Rica), the International Union of Pure and Applied Biophysics (IUPAB), the German Society of Biophysics (DGfB), and the Universidad Nacional of Costa Rica (UNA). The symposium aimed to reinforce and enhance the novel network of investigators established in the 2019 event. Participation of Costa Rican presenters, either located in the country or abroad, and foreign scientists from the USA, Germany, France, and Switzerland (Solís et al. (2021a) translated into an expansion and internationalization of the previous network. Moreover, the symposium attracted a broad international audience, which increases the opportunities of further international collaboration.The meeting was organized into 14 presentations and one keynote lecture. It was attended by researchers of the three main universities of Costa Rica: Universidad Nacional (UNA), Universidad de Costa Rica (UCR) and Tecnológico de Costa Rica (TEC). Presenters from international universities were also present, including UT Southwestern Medical Center, USA; Klinikum Nürnberg Medical School, Germany; École Polytechnique Fédérale de Lausanne, Switzerland; Institut de Neurosciences de Montpellier, France; University of California Berkeley, USA; and The University of Chicago, USA. The topics presented in the symposium were diverse and covered cutting-edge biophysical research areas. The presentations ranged from channel electrophysiology, machine learning focused on cellular microscopy, prediction of protein–protein interactions, channelopathies and novel biophysical techniques, among others (Solís et al., 2021a). Furthermore, each lecture was followed by questions from the audience, allowing discussion, engagement and interaction between researchers in spite of the limitations of a virtual symposium. The closing event for the symposium was a lecture by the world-renowned biophysicist Francisco Bezanilla from the University of Chicago, who engaged the audience into a master presentation of his vast research on protein voltage-sensor domains (VSD) with a focus on his recent work on the non-canonical mechanisms for VSD-mediated regulation of pore domains in voltage-gated potassium channels (Carvalho-de-Souza and Bezanilla 2019). After the consequent discussion, the symposium finished with a networking activity, where audience and presenters were able to socialize and share experiences.     

基于转录组测序探索创伤弧菌MO6-24/O小RNA

目的:基于转录组测序注释,探索创伤弧菌MO6-24/O小RNA(sRNA)。方法:在海洋培养基2216E中培养创伤弧菌MO6-24/O,收集从对数生长期到静止期不同时间点的细菌,提取细菌RNA,通过富集sRNA以及去除核糖体RNA进行建库和测序,然后将读段匹配到创伤弧菌MO6-24/O基因组并进行注释,最后进行验证。结果:发现59个顺式编码sRNA、102个反式编码sRNA,并进行了部分验证。结论:鉴定出创伤弧菌MO6-24/OsRNA。     

斑马鱼胚胎背腹轴建立的分子机制

脊椎动物胚胎发育起始于体轴的建立,是胚胎早期发育过程中最重要的事件之一。Wnt、BMP、Nodal和FGF等多个信号通路协同调控细胞分化和细胞运动,促进胚胎胚层的形成和空间上的分离,调控胚胎背腹轴、前后轴和左右轴线的分化,为胚胎进一步发育勾勒出蓝图。本文主要综述斑马鱼胚胎背腹轴建立的分子机制,包括背部组织中心简介;母源Wnt/β-catenin信号调控背部组织中心形成的分子机制;BMP信号调控背腹轴建立的分子机制。     

中国城市化速度区域差异及其主要影响因素分析

在分析2000—2014年全国地级及以上城市的人口城市化速度和建成区面积城市化速度的基础上, 评价了城市化发展与城市规模、资源、环境、经济、社会等相关指标的关系, 明确了影响中国城市化速度区域差异的关键因子。结果表明: ①人口平均年增长率的范围在-2.18%—6.74%之间, 均值为1.06%;建成区面积平均年增长率的范围在0%—15.00%之间, 均值为5.35%。建成区面积城市化速度总体上远高于人口城市化速度, 不利于集约型和节约型社会建设。②西北地区和华北地区的人口城市化速度较快, 主要受到资源因素尤其是水资源的影响;华东、西南和中南地区的建成区面积城市化速度较快, 主要受到地理因子的影响, 具有地理区位优势地区(东南沿海)的城市化速度较快。但长此以往, 将会造成东南地区的资源(尤其是土地资源)紧张及环境污染的加重, 不利于城市的可持续发展。因此, 在城市化发展的过程中, 应该遵循集约、紧凑的发展理念, 不仅要考虑每个区域的资源环境承载力, 也要提高资源开发利用和输送调配的效率, 减小对资源的浪费和生态环境的破坏。