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Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang Mengen Xing Zhengkai Bao Lu Xu Yang Bai Wanqi Chen Wenhao Pan Fang Cai Qunxian Wang Shipeng Guo Jing Zhang Zhe Wang Yili Wu Yun Zhang Jia-Da Li Weihong Song Oujiang laboratory(Zhejiang lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Medical genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its function.However,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain elusive.In this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent y-secretase.We identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in mice.Finaly,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout mice.This data demonstrates that the a-secretase is essential for CNTNAP2 processing and its function.Our study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

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Population structuring of the ubiquitous stingless bee Tetragonisca angustula in southern Brazil as revealed by microsatellite and mitochondrial markers

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Insect Science 2017年第5期24卷 877-890页

作者： Flavio O. Francisco Leandro R. Santiago Yuri M. Mizusawa Benjamin P. Oldroyd Maria C. Arias Departamento de Genetica e Biologia Evolutiva Instituto de Biociencias Universidade de Sao Paulo Rua do MatZo 277 - sala 320Sao Paulo SP Brazi behaviour and genetics of social insects lab School of Life and Environmental Sciences A 12 University of Sydney Sydney NSW Australia

Tetragonisca angustula is one of the most widespread stingless bees in the Neotropics. This species swarms frequently and is extremely successful in urban envi- ronments. In addition, it is one of the most popular stingless bee species for beekeeping in Latin America, so nest transportation and trading is common. Nest transportation can change the genetic structure of the host population, reducing inbreeding and increasing homogenization. Here, we evaluate the genetic structure of 17 geographic populations of T. angustula in southern Brazil to quantify the level of genetic differentiation between populations. Analyses were conducted on partially sequenced mitochondrial genes and 11 microsatellite loci of 1002 workers from 457 sites distributed on the mainland and on 3 islands. Our results show that T. angustula populations are highly differentiated as demon- strated by mitochondrial DNA （mtDNA） and microsatellite markers. Of 73 haplotypes, 67 were population-specific. MtDNA diversity was low in 9 populations but microsatellite diversity was moderate to high in all populations. Microsatellite data suggest 10 genetic clusters and low level of gene flow throughout the studied area. However, physical barri- ers, such as rivers and mountain ranges, or the presence or absence of forest appear to be unrelated to population clusters. Factors such as low dispersal, different ecological con- ditions, and isolation by distance are most likely shaping the population structure of this species. Thus far, nest transportation has not influenced the general population structure in the studied area. However, due to the genetic structure we found, we recommend that nest transportation should only occur within and between populations that are genetically similar.

关键词： genetic structure islands Meliponini microsatellites mtDNA nest transportation

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Population and conservation status of a transboundary group of black snub-nosed monkeys(Rhinopithecus strykeri)between China and Myanmar

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Zoological Research 2022年第4期43卷 523-527页

作者： Yi-Xin Chen Yang Yu Cheng Li Zhi-Shu Xiao Guo-Wei Zhou Zhong-Jian Zhang Xin-Wen Wang Zuo-Fu Xiang Jiang Chang Ming Li Institute of Evolutionary Ecology and Conservation Biology Central South University of Forestry&TechnologyChangshaHunan 410004China College of Life Science and Technology Central South University of Forestry&TechnologyChangshaHunan 410004China State Key lab of Integrated Management of Pest insects and Rodents Institute of ZoologyChinese Academy of SciencesBeijing 100101China Lushui Bureau of Mt.Gaoligong National Nature Reserve LiukuYunnan 673229China College of Forestry Central South University of Forestry&TechnologyChangshaHunan 410004China State Key laboratory of Environmental Criteria and Risk Assessment Chinese Research Academy of Environmental SciencesBeijing 100012China Key lab of Animal Ecology and Conservation Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Center for Excellence in Animal Evolution and genetics Chinese Academy of SciencesKunmingYunnan 650223China

DEAR EDITOR,We examined the distribution,population,and conservation status of the critically endangered Myanmar or black snub-nosed monkey(Rhinopithecus strykeri)via field surveys over 26 months(2019-2021)in the Pianma region of the China-Myanmar border.Contrary to previous reports,we only identified one group in the region,which was a cross-border group occupying a multi-year home range of 51.50-57.02 km^(2).The current group size was much larger(155-160 individuals)than that in 2012-2014(ca 100 individuals),and the group appeared to be growing.However,confirmed poaching,mining,and transboundary forest fires on the Myanmar side of the border threaten their survival.

关键词： black boundary Myanmar

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Network approach to understanding the organization of and the consequence of targeted leader removal on an end-oriented task

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Current Zoology 2017年第3期63卷 269-277页

作者： Sumana ANNAGIRI Swetashree KOLAY Bishwarup PAUL Chandan SONA behaviour & Ecology lab Department of Biological Sciences Indian Institute of Science Education and Research Kolkata Mohanpur West Bengal 741246 India Department of Pharmacology CSIR-CDRI Jankipurm Vistar Lucknow Uttar Pradesh 226021 India

Relocation is an important event in the lives of several social insects whereby all colony members have to be transferred to a new nest when conditions in the old nest become unfavorable. In the current study, network tools were used to examine the organization of this goal-oriented task in the Indian queenless ant which relocate their colonies by means of tandem running. Individual ants were used as nodes and tandem runs as directed edges to construct unweighted networks. Network parameters were characterized in control relocations (CRs) and in relocations where the node with the highest outdegree, that is, the Maximum tandem leader (Max TL) was experimentally removed. These were then compared to 1) randomized networks, 2) simulated networks in which Max TL was removed, and 3) simulated networks with removal of a random leader. Not only was there complete recovery of the task, but the manner in which it was organized when Max TL was removed was comparable to CRs. The results obtained from our empirical study were significantly different from the results predicted by simulations of leader removal. At an individual level, the Max TL had a significantly higher outdegree than expected by chance alone and in her absence the substitute Max TL did comparable work. In addition, the position of the Max TL in the pathway of information flow was conserved in control and experimentally manipulated conditions. Understanding the organization of this critical event as more than the sum of individual interactions using network parameters allows us to appreciate the dynamic response of groups to perturbations.

关键词：网络工具组织导向法理串联运行网络参数特征控制加权网络

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Independent variations in genome-wide expression, alternative splicing, and DNA methylation in brain tissues among castes of the buff-tailed bumblebee, Bombus terrestris

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Journal of genetics and Genomics 2021年第8期48卷 681-694页

作者： Dan Zhu Jin Ge Siyuan Guo Li Hou Rangjun Shi Xian Zhou Xin Nie Xianhui Wang State Key laboratory of Integrated Management of Pest insects and Rodents Institute of ZoologyChinese Academy of SciencesBeijing 100080China CAS Centre for Excellence in Biotic Interactions University of Chinese Academy of SciencesBeijing 100049China

Caste differentiation in social hymenopterans is an intriguing example of phenotypic plasticity. However, the co-ordination among gene regulatory factors to mediate caste differentiation remains inconclusive. In this study, we determined the role of gene regulation and related epigenetic processes in pre-imaginal caste differentiation in the primitively eusocial bumblebee Bombus terrestris. By combining RNA-Seq data from Illumina and Pac Bio and accurately quantifying methylation at whole-genomic base pair resolution, we found that queens, workers, and drones mainly differentiate in gene expression but not in alternative splicing and DNA methylation. Gynes are the most distinct with the lowest global level of whole-genomic methylation and with the largest number of caste-specific transcripts and alternative splicing events. By contrast, workers exhibit few uniquely expressed or alternatively spliced genes. Moreover, several genes involved in hormone and neurotransmitter metabolism are related to caste differentiation, whereas several neuropeptides are linked with sex differentiation. Despite little genome-wide association among differential gene expression, splicing, and differential DNA methylation, the overlapped gene ontology(GO) terms point to nutrition-related activity. Therefore, variations in gene regulation correlate with the behavioral differences among castes and highlight the specialization of toolkit genes in bumblebee gynes at the beginning of the adult stage.

关键词： social insects Caste determination PacBio Epigenetics Methylome RNA-seq WGBS-seq

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Assessing the spread risk of COVID-19 associated with multi-mode transportation networks in China

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Fundamental Research 2023年第2期3卷 305-310页

作者： Xiao-Ke Xu Xiao Fan Liu Lin Wang Ye Wu Xin Lu Xianwen Wang Sen Pei College of Information and Communication Engineering Dalian Minzu UniversityDalian 116600China Web Mining laboratory Department of Media and CommunicationCity University of Hong KongHong Kong SARChina Department of genetics University of CambridgeCambridge CB23EHUK School of Information Engineering Putian UniversityPutian 351100China School of Journalism and Communication Beijing Normal UniversityBeijing 100875China College of Systems Engineering National University of Defense TechnologyChangshaChina Department of Global Public Health Karolinska InstituteStockholmSweden WISE lab Faculty of Humanities and Social SciencesDalian University of TechnologyDalian 116085China Department of Environmental Health Sciences Mailman School of Public HealthColumbia UniversityNew YorkNY 10032USA

The spatial spread of COVID-19 during early 2020 in China was primarily driven by outbound travelers leaving the epicenter,Wuhan,Hubei province.Existing studies focus on the influence of aggregated out-bound population flows originating from Wuhan;however,the impacts of different modes of transportation and the network structure of transportation systems on the early spread of COVID-19 in China are not well understood.Here,we assess the roles of the road,railway,and air transportation networks in driving the spatial spread of COVID-19 in China.We find that the short-range spread within Hubei province was dominated by ground traffic,notably,the railway transportation.In contrast,long-range spread to cities in other provinces was mediated by multiple factors,including a higher risk of case importation associated with air transportation and a larger outbreak size in hub cities located at the center of transportation networks.We further show that,although the dissemination of SARS-CoV-2 across countries and continents is determined by the worldwide air transportation network,the early geographic dispersal of COVID-19 within China is better predicted by the railway traffic.Given the recent emergence of multiple more transmissible variants of SARS-CoV-2,our findings can support a better assessment of the spread risk of those variants and improve future pandemic preparedness and responses.

关键词： Complex network Human mobility COVID-19 Spatial spread Transportation networks

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CNTNAP2 intracellular domain(CICD)generated byγ-secretase cleavage improves autism-related behaviors

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3415-3426页

作者： Jing Zhang Fang Cai Renbin Lu Xiaoliang Xing Lu Xu Kunyang Wu Zishan Gong Qing Zhang Yun Zhang Mengen Xing Weihong Song Jia-Da Li Furong laboratory Center for Medical GeneticsHunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina Oujiang laboratory(Zhejiang lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325000China Townsend Family laboratories Department of PsychiatryThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Institute of Aging Key Laboratory of Alzheimer’s Disease of Zhejiang ProvinceSchool of Mental Health and Kangning HospitalThe Second Affiliated Hospital and Yuying Children’s HospitalWenzhou Medical UniversityWenzhouZhejiang 325035China Advanced Innovation Center for Human Brain Protection The National Clinical Research Center for Geriatric DiseaseXuanwu HospitalCapital Medical UniversityBeijing 100053China

As the most prevalent neurodevelopmental disorders in children,autism spectrum disorders(ASD)are characterized by deficits in language development,social interaction,and repetitive behaviors or inflexible interests.Contactin associated protein like 2(CNTNAP2),encoding a single transmembrane protein(CNTNAP2)with 1331 amino acid residues,is a widely validated ASD-susceptible gene.

关键词： behaviors cleavage residues

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Extreme polyandry aids the establishment of invasive populations of a social insect

Extreme polyandry aids the establishment of invasive populat...

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21世纪第三届全国蜂业科技与海峡两岸蜂产业发展大会暨首...

作者： Guiling Ding Huanli Xu Benjamin P.Oldroyd Rosalyn S.Gloag College of Plant Protection China Agricultural University Key laboratory of Pollinating Insect Biology of the Ministry of Agriculture Institute of Apicultural ResearchChinese Academy of Agricultural Sciences behaviour and genetics of social insects laboratory School of Life and Environmental SciencesThe University of Sydney

While monandry is believed to have facilitated the evolution of eusociality,many highly eusocial insects have since evolved extreme polyandry.The transition to extreme polyandry was likely driven by the benefits of within-colony genetic variance to task specialization and/or disease resistance,but the extent to which it confers secondary benefits,once evolved,is unclear.Here we investigate the consequences of extreme polyandry on the invasive potential of the Asian honey bee,Apis cerana.In honey bees and other Hymenoptera,small newly-founded invasive populations must overcome the genetic constraint of their sex determination system,which requires heterozygosity at a sex-determining locus to produce viable females.We find A.cerana queens in an invasive population mate with an average of 27 males（range:16-42）,which would result in the founding queen/s carrying 75% of their source population’s sex alleles in stored sperm.This mating frequency is similar to native-range Chinese A.cerana（mean:29 males,range:19-46）.Simulations reveal that extreme polyandry reduces the risk,relative to monandry or moderate polyandry,that colonies produce a high incidence of inviable brood in populations that have experienced a founder event,i.***.when sex allele diversity is low and/or allele frequencies are unequal.Thus,extreme polyandry aids the invasiveness of A.cerana in two ways:（i） by increasing the sex locus allelic richness carried to new populations with each founder,thereby increasing sex locus heterozygosity,and（ii） by reducing the population variance in colony fitness following a founder event.

关键词： diploid male production mating frequency honey bee polyandry invasive species

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social buffer or avoidance depends on the similarity of stress between queen ants

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Current Zoology 2023年第2期69卷 181-191页

作者： Iago Sanmartin-Villar Universidade de Vigo ECOEVO LabEscola de Enxenaria ForestalCampus Universitario A Xunqueira36005 PontevedraGalizaSpain

The association of unrelated ant queens(pleometrosis)is supposed to improve nest foundation and competitiveness under environmental stress,but its evolutionary maintenance is difficult to explain because only one of the queens survives after nest foundation.My aim was to test the potential effect of queen association as a social buffer,that is,as a mechanism reducing stress and improving fitness due to the benefits of social contact.I analyzed the survival,fecundity,and behavior of isolated and paired Lasius flavus queens exposed and not exposed to stressors(disturbing environmental conditions).I found no difference in survivorship between isolated and paired queens or between stressed and unstressed isolated queens.Groups in which 1 or 2 paired queens were stressed showed higher mortality.Unstressed queens died similarly to their stressed nestmates,suggesting stress transmission.A trend suggested that paired queens produced eggs more quickly,but eggs were produced similarly between isolated and paired queens.social avoidance was observed in groups with 1 stressed and 1 unstressed queen.However,the groups with 2 stressed queens showed the expected behaviors according to social buffering:lower mobility and more interindividual inspection.My findings suggest the synergistic effect of pleometrosis and stress and the dependence of stress level similarity between nestmates on social buffering or rejection on ant queens.

关键词： fitness haplometrosis population pressure reproductive strategy social insects

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Massive self-organized shape formation in grid environments

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Science China(Information Sciences) 2022年第6期65卷 256-257页

作者： Wenjie CHU Wei ZHANG Haiyan ZHAO Zhi JIN Hong MEI School of Computer Science Peking University Key lab of High Confidence Software Technologies (Peking University) Ministry of Education Key lab of High Confidence Software Technologies P(eking University) Ministry of Education

Self-organized shape formation can be observed in many natural processes [1, 2], involving crystallization, multi-cellular organism formation, and social insects collaboration. In these natural processes, complex stru... 详细信息

关键词： Shape Formation Self-Organization Artificial Light Field Multi-Agent Path Planning Collective Intelligence

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