Background:Non-human primates(NPHs),such as rhesus macaques,cynomol-gus monkeys,and Assamese macaques,play a crucial role in biomedical research.However,baseline cytokine and electrolyte data for these three species,p...Background:Non-human primates(NPHs),such as rhesus macaques,cynomol-gus monkeys,and Assamese macaques,play a crucial role in biomedical research.However,baseline cytokine and electrolyte data for these three species,particularly data stratified by age and sex,are limited.Therefore,the aim of this study was to establish and analyze age-and sex-specific cytokine and electrolyte profiles in these three species.Methods:This study included 40 rhesus macaques(21 males,19 females),33 cyn-omolgus monkeys(17 males,16 females),and 45 Assamese macaques(25 males,20 females)classified by age(1-5 years,6-12 years,>13 years)and sex.The levels of 23 immune function indicators and 5 electrolyte indicators were measured.Results:Among the three monkey species,the levels of sCD40L,IL-18,MCP-1,MIP-1β,TGFa,K^(+),Na^(+),and Cl^(-)exhibited species-,sex-,and age-related differences.Comparison within the same species,sex had no significant impact on cytokine levels in NHPs but did affect electrolyte levels,particularly Cl^(-)and Na^(+)levels,in cynomol-gus monkeys and Assamese macaques.Electrolyte levels in NHPs were not affected by age,whereas the levels of certain cytokines,particularly sCD40L,GM-CSF,and IL-10,varied with age.The remaining 21 cytokines demonstrated no significant age-related changes.Conclusions:Significant variations in cytokine and electrolyte levels exist among dif-ferent monkey species,sexes,and age groups.This research provides valuable re-sources for NHP researchers and sets the stage for further exploring the impacts of sex and age on NHP physiology and immune function.展开更多
Adolescent depression is increasingly recognized as a serious mental health disorder with distinct clinical and molecular features.Using single-nucleus RNA sequencing,we identified cell-specific transcriptomic changes...Adolescent depression is increasingly recognized as a serious mental health disorder with distinct clinical and molecular features.Using single-nucleus RNA sequencing,we identified cell-specific transcriptomic changes in the nucleus accumbens(NAc),particularly in astrocytes,of adolescent macaques exhibiting depressive-like behaviors.The level of diacylglycerol kinase beta was significantly reduced in neurons and glial cells of depressed macaques,while FKBP5 levels increased in glial cells.Disruption of GABAergic synapses and disruption of D-glutamine and D-glutamate metabolism were linked to depressive phenotypes in medium spiny neurons(MSNs)and subtypes of astrocytes.Communication pathways between astrocytes and D1/D2-MSNs were also disrupted,involving factors like bone morphogenetic protein-6 and Erb-B2 receptor tyrosine kinase-4.Bulk transcriptomic and proteomic analyses corroborated these findings,and FKBP5 upregulation was confirmed by qRT-PCR,western blotting,and immunofluorescence in the NAc of rats and macaques with chronic unpredictable mild stress.Our results highlight the specific roles of different cell types in adolescent depression in the NAc,offering potential targets for new antidepressant therapies.展开更多
Automated behavior monitoring of macaques offers transformative potential for advancing biomedical research and animal welfare.However,reliably identifying individual macaques in group environments remains a significa...Automated behavior monitoring of macaques offers transformative potential for advancing biomedical research and animal welfare.However,reliably identifying individual macaques in group environments remains a significant challenge.This study introduces ACE-YOLOX,a lightweight facial recognition model tailored for captive macaques.ACE-YOLOX incorporates Efficient Channel Attention(ECA),Complete Intersection over Union loss(CIoU),and Adaptive Spatial Feature Fusion(ASFF)into the YOLOX framework,enhancing prediction accuracy while reducing computational complexity.These integrated approaches enable effective multiscale feature extraction.Using a dataset comprising 179400 labeled facial images from 1196 macaques,ACE-YOLOX surpassed the performance of classical object detection models,demonstrating superior accuracy and real-time processing capabilities.An Android application was also developed to deploy ACE-YOLOX on smartphones,enabling on-device,real-time macaque recognition.Our experimental results highlight the potential of ACE-YOLOX as a non-invasive identification tool,offering an important foundation for future studies in macaque facial expression recognition,cognitive psychology,and social behavior.展开更多
Infant-care behavior,a range of caring behaviors by parental or alloparental individuals towards infants unable to live independently,plays asignifcant role in the survival of infants and the continuation of the speci...Infant-care behavior,a range of caring behaviors by parental or alloparental individuals towards infants unable to live independently,plays asignifcant role in the survival of infants and the continuation of the species in non-human primates.During a behavioral ecological study ofTaihangshan macaques,we observed 2 cases of infant adoptions by unrelated adult females.In case 1,a multiparous female adopted a lostinfant from a neighboring group,with the infant being snatched back by her biological mother 35 days after the adoption.This is the frst report ofcross-group adoption in Macaca.In case 2,a nulliparous adult female,who had been once adopted by her elder sister,adopted an orphan fromher group for 36 days.We describe the details of adoptions in Taihangshan macaques and explore possible reasons for adoptions to contributeto understanding the evolution of infant-care behavior and altruistic behavior of adoption in primates.展开更多
Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques(Macaca mulatta, MMU)and crab-eating macaques(M. fascicularis, MFA) serve as...Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques(Macaca mulatta, MMU)and crab-eating macaques(M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from84 samples(41 MFA samples and 43 MMU samples)encompassing 14 common tissues. Our findings revealed a small fraction of genes(3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover,19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary,this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics.展开更多
As an essential transcriptional activator,PDX1 plays a crucial role in pancreatic development andβ-cell function.Mutations in the PDX1 gene may lead to type 4 maturityonset diabetes of the young(MODY4)and neonatal di...As an essential transcriptional activator,PDX1 plays a crucial role in pancreatic development andβ-cell function.Mutations in the PDX1 gene may lead to type 4 maturityonset diabetes of the young(MODY4)and neonatal diabetes mellitus.However,the precise mechanisms underlying MODY4 remain elusive due to the paucity of clinical samples and pronounced differences in pancreatic architecture and genomic composition between humans and existing animal models.In this study,three PDX1-mutant cynomolgus macaques were generated using CRISPR/Cas9 technology,all of which succumbed shortly postpartum,exhibiting pancreatic agenesis.Notably,one tri-allelic PDX1-mutant cynomolgus macaque(designated as M4)developed a pancreas,whereas the two monoallelic PDX1-mutant cynomolgus macaques displayed no anatomical evidence of pancreatic formation.RNA sequencing of the M4 pancreas revealed substantial molecular changes in both endocrine and exocrine functions,indicating developmental delay and PDX1haploinsufficiency.A marked change in m6A methylation was identified in the M4 pancreas,confirmed through cultured PDX1-mutantisletorganoids.Notably,overexpression of the m6A modulator METTL3 restored function in heterozygous PDX1-mutant islet organoids.This study highlights a novel role of m6A methylation modification in the progression of MODY4 and provides valuable molecular insights for preclinical research.展开更多
Although seasonal breeding has been documented in many non-human primates, it is not clear whether sexual behaviors show seasonal variation among male individuals. To test this hypothesis, the focal animal sampling me...Although seasonal breeding has been documented in many non-human primates, it is not clear whether sexual behaviors show seasonal variation among male individuals. To test this hypothesis, the focal animal sampling method and continuous recording were used to investigate seasonal variation and synchronization of sexual behaviors in five male Tibetan macaques （Macaca thibetana） at Mt. Huangshan from Oct 2005 to Sept 2006. Both copulatory and sexually motivated behaviors （i.e., sexual chase, grimace, and sexual-inspection）, which were significantly higher in the mating season than non-mating season. Furthermore, seasonal variations of sexual behaviors, including copulatory and sexually motivated behaviors, were synchronized among males. The results shed light on sexual competition and tactics for reproductive success of male M. thibetana and other non-human primates with seasonal breeding.展开更多
Microbial translocation is a cause of systemic immune activation in HIV/SIV infection. In the present study, we found a lower CD8+ T cell activation level in Macaca leonina (northern pig-tailed macaques, NPMs) than in...Microbial translocation is a cause of systemic immune activation in HIV/SIV infection. In the present study, we found a lower CD8+ T cell activation level in Macaca leonina (northern pig-tailed macaques, NPMs) than in Macaca mulatta (Chinese rhesus macaques, ChRMs) during SIVmac239 infection. Furthermore, the levels of plasma LPS-binding protein and soluble CD14 in NPMs were lower than those in ChRMs. Compared with ChRMs, SIV-infected NPMs had lower Chiu scores, representing relatively normal intestinal mucosa. In addition, no obvious damage to the ileum or colon epithelial barrier was observed in either infected or uninfected NPMs, which differed to that found in ChRMs. Furthermore, no significant microbial translocation (Escherichia coli) was detected in the colon or ileum of infected or uninfected NPMs, which again differed to that observed in ChRMs. In conclusion, NPMs retained superior intestinal integrity and limited microbial translocation during SIV infection, which may contribute to their lower immune activation compared with ChRMs.展开更多
The northem pig-tailed macaque （NPM, Macaca leonina） has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3...The northem pig-tailed macaque （NPM, Macaca leonina） has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3-11 year old captive northem pig-tailed macaques using HITACHI 7600-20 automated chemistry analyzer in order to determine the influences of age and gender on these items. The results showed that serum IgA, IgM, C3 and C4 levels were not correlated with age （P〉0.05）, while serum IgG levels increased progressively with age （r=0.202; P=0.045）. Serum IgG, IgA, IgM and C3 levels were higher in females than in males （P〈0.05）. Moreover, serum C3 concentration was both positively and strongly correlated with that of C4 （r=0.700; P〈0.0001）. This study provides basic serum immunoglobulin and complement data of captive northem pig-tailed macaques, which may prove useful for future breeding efforts and biomedical research.展开更多
Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of internatio...Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.展开更多
The complex and dynamic vaginal microbial ecosystem is critical to both health and disease of the host. Studies focusing on how vaginal microbiota influences HIV-1 infection may face limitations in selecting proper an...The complex and dynamic vaginal microbial ecosystem is critical to both health and disease of the host. Studies focusing on how vaginal microbiota influences HIV-1 infection may face limitations in selecting proper animal models. Given that northern pig-tailed macaques （Macaca leonina） are susceptible to HIV-1 infection, they may be an optimal animal model for elucidating the mechanisms by which vaginal microbiota contributes to resistance and susceptibility to HIV-1 infection. However, little is known about the composition and temporal variability of vaginal microbiota of the northern pig-tailed macaque. Here, we present a comprehensive catalog of the composition and temporal dynamics of vaginal microbiota of two healthy northern pig-tailed macaques over 19 weeks using 454-pyrosequencing of 16S rRNA genes. We found remarkably high proportions of a diverse array of anaerobic bacteria associated with bacterial vaginosis. Atopobium and Sneathia were dominant genera, and interestingly, we demonstrated the presence of Lactobacillus-dominated vaginal microbiota. Moreover, longitudinal analysis demonstrated that the temporal dynamics of the vaginal microbiota were considerably individualized. Finally, network analysis revealed that vaginal pH may influence the temporal dynamics of the vaginal microbiota, suggesting that inter-subject variability of vaginal bacterial communities could be mirrored in inter-subject variation in correlation profiles of species with each other and with vaginal pH over time. Our results suggest that the northern pig-tailed macaque could be an ideal animal model for prospective investigation of the mechanisms by which vaginal microbiota influence susceptibility and resistance to HIV-1 infection in the context of highly polymicrobial and Lactobacillus-dominated states.展开更多
Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs.However, cellular and molecular understanding of SARS-CoV-2 infe...Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs.However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000single-nucleus transcriptomes of the lung, liver,kidney, and cerebral cortex in rhesus macaques(Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multiorgan dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019(COVID-19).Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway,which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy(an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection,which may facilitate the development of therapeutic interventions for COVID-19.展开更多
The northern pig-tailed macaque （Macaca leonina） has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus...The northern pig-tailed macaque （Macaca leonina） has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus type 1 （HIV-1）, which may be due to the absence of a TRIM5 protein restricting HIV-1 replication. Here we investigated the infection potentials of six laboratory adapted HIV-1 strains and three primary HIV-1 isolates in PBMCs from M. leonina. The results indicate that these strains are characterized by various but low replication levels, and among which, HIV-INL4-3 shows the highest replication ability. Based on the abundant evidence of species-specific interactions between restriction factors APOBEC3 and HIV/SIV-derived Vif protein, we subsequently examined the replication potentials of v/f-substituted HIV-1 （HSIV） in M. leonina PBMCs. Notably, HSIV-vifmac and stHIV-lsv chimeras, two HIV-1Ni.4-3-derived viruses encoding the viral infectivity factor （Vif） protein from SIVmac239, replicated robustly in cells from M. leonina, which suggests that HSIV could effectively antagonize the antiviral activity of APOBEC3 proteins expressed in cells of M. leonina. Therefore, our data demonstrate that M. leonina has the potential to be developed into a promising animal model for human AIDS.展开更多
Objective To develop a model of SHIV-KB9/Chinese origin rhesus （Ch Rh） macaques for vaccine research and to compare the pathogenesis of SHIV-KB9 in Ch Rh macaques with that reported in Indian rhesus （Ind Rh） macaq...Objective To develop a model of SHIV-KB9/Chinese origin rhesus （Ch Rh） macaques for vaccine research and to compare the pathogenesis of SHIV-KB9 in Ch Rh macaques with that reported in Indian rhesus （Ind Rh） macaques. Methods Seven mamu-A＊01 negative Ch Rh macaques were inoculated intravenously with 1-10000 MID50 of SHIV-KB9. The monkeys were monitored for viral load, CD4, CDS, SHIV-specific antibody and virus genetic variation. The results were compared with those previously observed in Ind Rh macaques. Results As compared to that observed in Ind Rh macaques, SHIV-KB9 in Ch Rh macaques displayed three identical disease progression patterns. However, the primary pattern was not identical between the two subspecies. The level of plasma viremia differed in SHIV-KB9-infected Ch Rh macaques which exhibited different outcomes from those in Ind Rh macaques. Generally, the values of viral load and the maintenance of CD4^＋ T cells were associated with humoral responses. Otherwise, the viral genetic distances （divergence, diversity） were larger in animals （M419, M425） with their CD4^＋ T cells profoundly depleted. Conclusion The model of SHIV-KB9/Ch Rh macaques displays a relatively slow progression to AIDS compared with Ind Rh macaques, which may more accurately reflect the potential of candidate vaccines in humans.展开更多
To enhance our understanding of dietary adaptations in macaques we studied the diet of the Assamese macaque Macaca assamensis in limestone seasonal rain forests at Nonggang Nature Reserve, China from September 2005 to...To enhance our understanding of dietary adaptations in macaques we studied the diet of the Assamese macaque Macaca assamensis in limestone seasonal rain forests at Nonggang Nature Reserve, China from September 2005 to August 2006. Our results show that although macaques fed on many plant species, 85.2% of the diet came from only 12 species, of which a bamboo species, Indocalamus calcicolus contributed to 62% of the diet. Young leaves were staple food items （74.1% of the diet） for Assamese macaques at Nonggang, and constituted the bulk of monthly diets almost year-round, ranging from 44.9% （July） to 92.9% （May）. Young parts of Indocalamus calcicolus unexpanded leaves contributed to a large proportion of the young leaf diet in most months. Fruit accounted for only 17.4% of the diet, with a peak of consumption in July. We suggest that this highly fo- livorous diet may be related to the long lean season of fruit availability in limestone habitats as well as the utilization of cliffs of low fruit availability展开更多
The frontal pole cortex(FPC)plays key roles in various higher-order functions and is highly developed in non-human primates.An essential missing piece of information is the detailed anatomical connections for finer pa...The frontal pole cortex(FPC)plays key roles in various higher-order functions and is highly developed in non-human primates.An essential missing piece of information is the detailed anatomical connections for finer parcellation of the macaque FPC than provided by the previous tracer results.This is important for understanding the functional architecture of the cerebral cortex.Here,combining cross-validation and principal component analysis,we formed a tractography-based parcellation scheme that applied a machine learning algorithm to divide the macaque FPC(2 males and 6 females)into eight subareas using high-resolution diffusion magnetic resonance imaging with the 9.4 T Bruker system,and then revealed their subregional connections.Furthermore,we applied improved hierarchical clustering to the obtained parcels to probe the modular structure of the subregions,and found that the dorsolateral FPC,which contains an extension to the medial FPC,was mainly connected to regions of the default-mode network.The ventral FPC was mainly involved in the social-interaction network and the dorsal FPC in the metacognitive network.These results enhance our understanding of the anatomy and circuitry of the macaque brain,and contribute to FPC-related clinical research.展开更多
Pig-tailed macaques(Macaca nemistrina group) have been extensively used as non-human primate animal models for various human diseases in recent years, notably for AIDS research due to their sensitivity to HIV-1. North...Pig-tailed macaques(Macaca nemistrina group) have been extensively used as non-human primate animal models for various human diseases in recent years, notably for AIDS research due to their sensitivity to HIV-1. Northern pig-tailed macaques(M. leonina) are distributed in China and other surrounding Southeast Asia countries. Although northern pig-tailed macaques have been bred on a large scale as experimental animals since 2012, the reference value of normal levels of leukocytes is not available. To obtain such information, 62 blood samples from male and female healthy northern pig-tailed macaques at different ages were collected. The normal range of major leukocyte subpopulations, such as T lymphocytes, B lymphocytes, natural killer(NK) cells, monocytes, and the expression levels of activation or differentiation related molecules(CD38, HLA-DR, CCR5, CD21, IgD, CD80 and CD86) on lymphocytes were analyzed by flow cytometry. The counts of B cells decreased with age, but those of CD8+ T cells and NK cells and the frequency of CD38+HLA-DR+CD4+ T cells were positively correlated with age. The counts of leukocyte subpopulations were higher in males than those in females except for CD4+ T cells. Males also showed higher expression levels of Ig D and CD21 within B cells. This study provides basic data about the leukocyte subpopulations of northern pig-tailed macaques and compares this species with commonly used Chinese rhesus macaques(M. mulatta), which is meaningful for the biomedical application of northern pig-tailed macaques.展开更多
In some non-human primates, infants function as a social tool that can bridge relationships among group members. Infants are a desired commodity for group members, and mothers control access to them. The biological ma...In some non-human primates, infants function as a social tool that can bridge relationships among group members. Infants are a desired commodity for group members, and mothers control access to them. The biological market theory suggests that grooming is widespread and represents a commodity that can be exchanged for infant handling. As a limited resource, however, the extent to which infants are interchanged between mothers(females with an infant) and non-mothers(potential handlers,females without an infant) remains unclear. In this study, we collected behavioral data to investigate the relationship between grooming and infant handling in free-ranging Tibetan macaques(Macaca thibetana)at Mt. Huangshan, China. Our results showed that females with infants received more grooming than females without infants. After her infant was handled,mother females received more grooming than they did during daily grooming interactions. However, with the increasing number of infants within the social group, both the grooming that mothers received and the grooming that non-mothers invested for handling infants decreased. We also found that non-mothers invested more time in grooming to gain access to younger infants than older infants. Our results provide evidence that infants are social commodities for both mother and non-mother females. Mothers use infants for obtain grooming and non-mothers use grooming to gain access to infants. The current study implies a bidirectional and complex interchange pattern between grooming and infant handling to compensate for the dyadic grooming disparity in non-human primates.展开更多
Inhibitory coupled bursting Hindmarsh-Rose neurons are considered as constitutive units of the Macaque corti- cal network. In the absence of information transmission delay the bursting activity is desynchronized, givi...Inhibitory coupled bursting Hindmarsh-Rose neurons are considered as constitutive units of the Macaque corti- cal network. In the absence of information transmission delay the bursting activity is desynchronized, giving rise to spatiotemporally disordered dynamics. This paper shows that the introduction of finite delays can lead to the synchro- nization of bursting and thus to the emergence of coherent propagating fronts of excitation in the space-time domain. Moreover, it shows that the type of synchronous bursting is uniquely determined by the delay length, with the transi- tions from one type to the other occurring in a step-like manner depending on the delay. Interestingly, as the delay is tuned close to the transition points, the synchronization deteriorates, which implies the coexistence of different bursting attractors. These phenomena can be observed by different but fixed coupling strengths, thus indicating a new role for information transmission delays in realistic neuronal networks.展开更多
There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts.Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been cruci...There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts.Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been crucial for improving our understanding of the role of the microbiome on the host mucosal surface;however,studies on the mechanisms involved in microbiome-host interactions remain limited to small animal models.Here,we demonstrated that rhesus monkeys under short-term broad-spectrum antibiotic treatment could be used as a model to study the gut mucosal host-microbiome niche and immune balance with steady health status.Results showed that the diversity and community structure of the gut commensal bacteria in rhesus monkeys were both disrupted after antibiotic treatment.Furthermore,the 16S rDNA amplicon sequencing results indicated that Escherichia-Shigella were predominant in stool samples 9 d of treatment,and the abundances of bacterial functional genes and predicted KEGG pathways were significantly changed.In addition to inducing aberrant morphology of small intestinal villi,the depletion of gut commensal bacteria led to increased proportions of CD3+T,CD4+T,and CD16+NK cells in peripheral blood mononuclear cells(PBMCs),but decreased numbers of Treg and CD20+B cells.The transcriptome of PBMCs from antibiotic-treated monkeys showed that the immune balance was affected by modulation of the expression of many functional genes,including IL-13,VCAM1,and LGR4.展开更多
基金National Resources Center for Non Human PrimatesNational Key R&D Project of China,Grant/Award Number:2021YFF0702804。
文摘Background:Non-human primates(NPHs),such as rhesus macaques,cynomol-gus monkeys,and Assamese macaques,play a crucial role in biomedical research.However,baseline cytokine and electrolyte data for these three species,particularly data stratified by age and sex,are limited.Therefore,the aim of this study was to establish and analyze age-and sex-specific cytokine and electrolyte profiles in these three species.Methods:This study included 40 rhesus macaques(21 males,19 females),33 cyn-omolgus monkeys(17 males,16 females),and 45 Assamese macaques(25 males,20 females)classified by age(1-5 years,6-12 years,>13 years)and sex.The levels of 23 immune function indicators and 5 electrolyte indicators were measured.Results:Among the three monkey species,the levels of sCD40L,IL-18,MCP-1,MIP-1β,TGFa,K^(+),Na^(+),and Cl^(-)exhibited species-,sex-,and age-related differences.Comparison within the same species,sex had no significant impact on cytokine levels in NHPs but did affect electrolyte levels,particularly Cl^(-)and Na^(+)levels,in cynomol-gus monkeys and Assamese macaques.Electrolyte levels in NHPs were not affected by age,whereas the levels of certain cytokines,particularly sCD40L,GM-CSF,and IL-10,varied with age.The remaining 21 cytokines demonstrated no significant age-related changes.Conclusions:Significant variations in cytokine and electrolyte levels exist among dif-ferent monkey species,sexes,and age groups.This research provides valuable re-sources for NHP researchers and sets the stage for further exploring the impacts of sex and age on NHP physiology and immune function.
基金supported by STI2030-Major Projects(2022ZD0212900)the Joint Project of Chongqing Municipal Science and Technology Bureau and Chongqing Health Commission(2023CCXM003)+4 种基金the National Key Research and Development Program of China(2017YFA0505700)the National Natural Science Foundation of China(82271565 and 82301714)the China Postdoctoral Science Foundation(2023TQ0398,GZB20230916,2023MD734124)the Natural Science Foundation of Chongqing,China(CSTB2023NSCQ-BHX0106)the Postdoctoral Innovation Talents Support Program of Chongqing,China(2208013341918508).
文摘Adolescent depression is increasingly recognized as a serious mental health disorder with distinct clinical and molecular features.Using single-nucleus RNA sequencing,we identified cell-specific transcriptomic changes in the nucleus accumbens(NAc),particularly in astrocytes,of adolescent macaques exhibiting depressive-like behaviors.The level of diacylglycerol kinase beta was significantly reduced in neurons and glial cells of depressed macaques,while FKBP5 levels increased in glial cells.Disruption of GABAergic synapses and disruption of D-glutamine and D-glutamate metabolism were linked to depressive phenotypes in medium spiny neurons(MSNs)and subtypes of astrocytes.Communication pathways between astrocytes and D1/D2-MSNs were also disrupted,involving factors like bone morphogenetic protein-6 and Erb-B2 receptor tyrosine kinase-4.Bulk transcriptomic and proteomic analyses corroborated these findings,and FKBP5 upregulation was confirmed by qRT-PCR,western blotting,and immunofluorescence in the NAc of rats and macaques with chronic unpredictable mild stress.Our results highlight the specific roles of different cell types in adolescent depression in the NAc,offering potential targets for new antidepressant therapies.
基金supported by the grants from Yunnan Province(202305AH340006,202305AH340007)CAS Light of West China Program(xbzg-zdsys-202213)。
文摘Automated behavior monitoring of macaques offers transformative potential for advancing biomedical research and animal welfare.However,reliably identifying individual macaques in group environments remains a significant challenge.This study introduces ACE-YOLOX,a lightweight facial recognition model tailored for captive macaques.ACE-YOLOX incorporates Efficient Channel Attention(ECA),Complete Intersection over Union loss(CIoU),and Adaptive Spatial Feature Fusion(ASFF)into the YOLOX framework,enhancing prediction accuracy while reducing computational complexity.These integrated approaches enable effective multiscale feature extraction.Using a dataset comprising 179400 labeled facial images from 1196 macaques,ACE-YOLOX surpassed the performance of classical object detection models,demonstrating superior accuracy and real-time processing capabilities.An Android application was also developed to deploy ACE-YOLOX on smartphones,enabling on-device,real-time macaque recognition.Our experimental results highlight the potential of ACE-YOLOX as a non-invasive identification tool,offering an important foundation for future studies in macaque facial expression recognition,cognitive psychology,and social behavior.
基金fnancially supported by the National Natural Science Foundation of China(No.32070446).
文摘Infant-care behavior,a range of caring behaviors by parental or alloparental individuals towards infants unable to live independently,plays asignifcant role in the survival of infants and the continuation of the species in non-human primates.During a behavioral ecological study ofTaihangshan macaques,we observed 2 cases of infant adoptions by unrelated adult females.In case 1,a multiparous female adopted a lostinfant from a neighboring group,with the infant being snatched back by her biological mother 35 days after the adoption.This is the frst report ofcross-group adoption in Macaca.In case 2,a nulliparous adult female,who had been once adopted by her elder sister,adopted an orphan fromher group for 36 days.We describe the details of adoptions in Taihangshan macaques and explore possible reasons for adoptions to contributeto understanding the evolution of infant-care behavior and altruistic behavior of adoption in primates.
基金supported by the National Natural Science Foundation of China (82021001 and 31825018 to Q.S., 32370658 to Y.M.,82001372 to X.Y.)National Key Research and Development Program of China (2022YFF0710901)+2 种基金National Science and Technology Innovation2030 Major Program (2021ZD0200900) to Q.S.Shanghai Pujiang Program (22PJ1407300)Shanghai Jiao Tong University 2030 Initiative (WH510363001-7) to Y.M。
文摘Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques(Macaca mulatta, MMU)and crab-eating macaques(M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from84 samples(41 MFA samples and 43 MMU samples)encompassing 14 common tissues. Our findings revealed a small fraction of genes(3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover,19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary,this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics.
基金supported by the National Key R&D Program of China(2018YFA0801404,2023YFC3403400)National Natural Science Foundation of China(81941006,32371190,32370878)+2 种基金Guangdong Special Support Program(2019BT02Y276,2024A1515012868)Double First-Class Discipline Promotion Project(2023B10564003)Program for Scientific Research Start-up Funds of Guangdong Ocean University(060302052408)。
文摘As an essential transcriptional activator,PDX1 plays a crucial role in pancreatic development andβ-cell function.Mutations in the PDX1 gene may lead to type 4 maturityonset diabetes of the young(MODY4)and neonatal diabetes mellitus.However,the precise mechanisms underlying MODY4 remain elusive due to the paucity of clinical samples and pronounced differences in pancreatic architecture and genomic composition between humans and existing animal models.In this study,three PDX1-mutant cynomolgus macaques were generated using CRISPR/Cas9 technology,all of which succumbed shortly postpartum,exhibiting pancreatic agenesis.Notably,one tri-allelic PDX1-mutant cynomolgus macaque(designated as M4)developed a pancreas,whereas the two monoallelic PDX1-mutant cynomolgus macaques displayed no anatomical evidence of pancreatic formation.RNA sequencing of the M4 pancreas revealed substantial molecular changes in both endocrine and exocrine functions,indicating developmental delay and PDX1haploinsufficiency.A marked change in m6A methylation was identified in the M4 pancreas,confirmed through cultured PDX1-mutantisletorganoids.Notably,overexpression of the m6A modulator METTL3 restored function in heterozygous PDX1-mutant islet organoids.This study highlights a novel role of m6A methylation modification in the progression of MODY4 and provides valuable molecular insights for preclinical research.
文摘Although seasonal breeding has been documented in many non-human primates, it is not clear whether sexual behaviors show seasonal variation among male individuals. To test this hypothesis, the focal animal sampling method and continuous recording were used to investigate seasonal variation and synchronization of sexual behaviors in five male Tibetan macaques （Macaca thibetana） at Mt. Huangshan from Oct 2005 to Sept 2006. Both copulatory and sexually motivated behaviors （i.e., sexual chase, grimace, and sexual-inspection）, which were significantly higher in the mating season than non-mating season. Furthermore, seasonal variations of sexual behaviors, including copulatory and sexually motivated behaviors, were synchronized among males. The results shed light on sexual competition and tactics for reproductive success of male M. thibetana and other non-human primates with seasonal breeding.
基金partly supported by grants from the National Natural Science Foundation of China(U1802284 81471620,81671627,81771770,81571606)+1 种基金13th Five-Year Key Scientific and Technological Program of China(2017ZX10304402-002-004,2017ZX10202102-001-005,2018ZX10301101-002-003,2018ZX10301406-003)Knowledge Innovation Program of the Chinese Academy of Sciences(ZDRW-ZS-2016-4)
文摘Microbial translocation is a cause of systemic immune activation in HIV/SIV infection. In the present study, we found a lower CD8+ T cell activation level in Macaca leonina (northern pig-tailed macaques, NPMs) than in Macaca mulatta (Chinese rhesus macaques, ChRMs) during SIVmac239 infection. Furthermore, the levels of plasma LPS-binding protein and soluble CD14 in NPMs were lower than those in ChRMs. Compared with ChRMs, SIV-infected NPMs had lower Chiu scores, representing relatively normal intestinal mucosa. In addition, no obvious damage to the ileum or colon epithelial barrier was observed in either infected or uninfected NPMs, which differed to that found in ChRMs. Furthermore, no significant microbial translocation (Escherichia coli) was detected in the colon or ileum of infected or uninfected NPMs, which again differed to that observed in ChRMs. In conclusion, NPMs retained superior intestinal integrity and limited microbial translocation during SIV infection, which may contribute to their lower immune activation compared with ChRMs.
基金Foundation items： This work was supported by the National Natural Science Foundation of China （81172876, U0832601, 81273251, U1202228） the National Special Science Research Program of China （2012CBA01305） the National Science and Technology Major Project （2013ZX10001-002, 2012ZX10001-007） and the Knowledge Innovation Program of CAS （KSCX2-EW-R-13）.
文摘The northem pig-tailed macaque （NPM, Macaca leonina） has become a widely used animal model in biomedical research. In this study, we measured serum immunoglobulin IgG, IgM, IgA, complement C3, C4 and CRP levels in 3-11 year old captive northem pig-tailed macaques using HITACHI 7600-20 automated chemistry analyzer in order to determine the influences of age and gender on these items. The results showed that serum IgA, IgM, C3 and C4 levels were not correlated with age （P〉0.05）, while serum IgG levels increased progressively with age （r=0.202; P=0.045）. Serum IgG, IgA, IgM and C3 levels were higher in females than in males （P〈0.05）. Moreover, serum C3 concentration was both positively and strongly correlated with that of C4 （r=0.700; P〈0.0001）. This study provides basic serum immunoglobulin and complement data of captive northem pig-tailed macaques, which may prove useful for future breeding efforts and biomedical research.
基金This work was supported by the National Research and Development Project of China(Grant No.2020YFC0841100)Fundamental Research Funds for CAMS of China(Grant No.2020HY320001)+3 种基金National Key Research and Development Project of China(Grant No.2016YFD0500304)CAMS initiative for Innovative Medicine of China(Grant No.2016-I2M-2-006)National Mega projects of China for Major Infectious Diseases(Grant No.2017ZX10304402)and National Key Research and Development Programme of China(2016YFD0500301,2020YFC0840800,2020YFC0840900).
文摘Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.
基金supported in part by the Key Scientific and Technological Program of China(2012ZX10001-0072013ZX10001-002)+5 种基金the National Basic Research Program of China(2012CBA01305)the National Natural Science Foundation of China(8117287681273251U1202228)the Knowledge Innovation Program of CAS(KSCX2-EW-R-13KJZD-EW-L10-02)
文摘The complex and dynamic vaginal microbial ecosystem is critical to both health and disease of the host. Studies focusing on how vaginal microbiota influences HIV-1 infection may face limitations in selecting proper animal models. Given that northern pig-tailed macaques （Macaca leonina） are susceptible to HIV-1 infection, they may be an optimal animal model for elucidating the mechanisms by which vaginal microbiota contributes to resistance and susceptibility to HIV-1 infection. However, little is known about the composition and temporal variability of vaginal microbiota of the northern pig-tailed macaque. Here, we present a comprehensive catalog of the composition and temporal dynamics of vaginal microbiota of two healthy northern pig-tailed macaques over 19 weeks using 454-pyrosequencing of 16S rRNA genes. We found remarkably high proportions of a diverse array of anaerobic bacteria associated with bacterial vaginosis. Atopobium and Sneathia were dominant genera, and interestingly, we demonstrated the presence of Lactobacillus-dominated vaginal microbiota. Moreover, longitudinal analysis demonstrated that the temporal dynamics of the vaginal microbiota were considerably individualized. Finally, network analysis revealed that vaginal pH may influence the temporal dynamics of the vaginal microbiota, suggesting that inter-subject variability of vaginal bacterial communities could be mirrored in inter-subject variation in correlation profiles of species with each other and with vaginal pH over time. Our results suggest that the northern pig-tailed macaque could be an ideal animal model for prospective investigation of the mechanisms by which vaginal microbiota influence susceptibility and resistance to HIV-1 infection in the context of highly polymicrobial and Lactobacillus-dominated states.
基金supported by the National Basic Research Program of China(2020YFA0804000,2020YFC0842000,2020YFA0112200,2021YFC2301703)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32010100)+6 种基金Special Associate Research Program of the Chinese Academy of Sciences(E1290601)National Natural Science Foundation of China(32122037,81891001,32192411,32100512,U1902215)Collaborative Research Fund of the Chinese Institute for Brain Research,Beijing(2020-NKX-PT-03)CAS Project for Young Scientists in Basic Research(YSBR-013)Young Elite Scientist Sponsorship Program by the China Association for Science and Technology(2020QNRC001)National Resource Center for Non-Human Primates。
文摘Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs.However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000single-nucleus transcriptomes of the lung, liver,kidney, and cerebral cortex in rhesus macaques(Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multiorgan dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019(COVID-19).Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway,which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy(an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection,which may facilitate the development of therapeutic interventions for COVID-19.
基金Foundation items： This work was supported by the National Basic Research Program （2012CBA01305） the National Natural Science Foundation of China （81172876, U0832601, 81273251 and U 1202228） the Knowledge Innovation Program of CAS （KSCX2-EW-R-13, Y206A- 71181）, and the Key Scientific and Technological Program of China （2012ZX10001-007, 2013ZX10001-002）. Acknowledgements： We thank Prof. Guang-Xia GAO （Institute of Biophysics, Chinese Academy of Sciences） for kindly providing HSIV proviral plasmids.We also thank Long-Bao LV, Gui LI and Dong- Ti HUANG of Kunming Primate Research Center for their assistance in obtaining blood samples from northem pig-tailed macaques （M. leonina） and Chinese rhesus macaques.
文摘The northern pig-tailed macaque （Macaca leonina） has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus type 1 （HIV-1）, which may be due to the absence of a TRIM5 protein restricting HIV-1 replication. Here we investigated the infection potentials of six laboratory adapted HIV-1 strains and three primary HIV-1 isolates in PBMCs from M. leonina. The results indicate that these strains are characterized by various but low replication levels, and among which, HIV-INL4-3 shows the highest replication ability. Based on the abundant evidence of species-specific interactions between restriction factors APOBEC3 and HIV/SIV-derived Vif protein, we subsequently examined the replication potentials of v/f-substituted HIV-1 （HSIV） in M. leonina PBMCs. Notably, HSIV-vifmac and stHIV-lsv chimeras, two HIV-1Ni.4-3-derived viruses encoding the viral infectivity factor （Vif） protein from SIVmac239, replicated robustly in cells from M. leonina, which suggests that HSIV could effectively antagonize the antiviral activity of APOBEC3 proteins expressed in cells of M. leonina. Therefore, our data demonstrate that M. leonina has the potential to be developed into a promising animal model for human AIDS.
文摘Objective To develop a model of SHIV-KB9/Chinese origin rhesus （Ch Rh） macaques for vaccine research and to compare the pathogenesis of SHIV-KB9 in Ch Rh macaques with that reported in Indian rhesus （Ind Rh） macaques. Methods Seven mamu-A＊01 negative Ch Rh macaques were inoculated intravenously with 1-10000 MID50 of SHIV-KB9. The monkeys were monitored for viral load, CD4, CDS, SHIV-specific antibody and virus genetic variation. The results were compared with those previously observed in Ind Rh macaques. Results As compared to that observed in Ind Rh macaques, SHIV-KB9 in Ch Rh macaques displayed three identical disease progression patterns. However, the primary pattern was not identical between the two subspecies. The level of plasma viremia differed in SHIV-KB9-infected Ch Rh macaques which exhibited different outcomes from those in Ind Rh macaques. Generally, the values of viral load and the maintenance of CD4^＋ T cells were associated with humoral responses. Otherwise, the viral genetic distances （divergence, diversity） were larger in animals （M419, M425） with their CD4^＋ T cells profoundly depleted. Conclusion The model of SHIV-KB9/Ch Rh macaques displays a relatively slow progression to AIDS compared with Ind Rh macaques, which may more accurately reflect the potential of candidate vaccines in humans.
基金Acknowledgements This study was supported by the National Nature Science Foundation of China （No 30860050）, Guangxi Science Foundation （0991095）, Monitoring and Conservation of Assamese macaques Project of National Forestry Administration of China, Guangxi Beibu Gulf Serious Specialization of Guangxi Natural Sciences Foundation （2010GXNSFE013004）, and Project of Creative Team from Colleges and Universities in Guangxi. We thank the Guangxi Forestry Bureau and Nonggang National Nature Reserve. We also acknowledge the critical comments of two anonymous reviewers.
文摘To enhance our understanding of dietary adaptations in macaques we studied the diet of the Assamese macaque Macaca assamensis in limestone seasonal rain forests at Nonggang Nature Reserve, China from September 2005 to August 2006. Our results show that although macaques fed on many plant species, 85.2% of the diet came from only 12 species, of which a bamboo species, Indocalamus calcicolus contributed to 62% of the diet. Young leaves were staple food items （74.1% of the diet） for Assamese macaques at Nonggang, and constituted the bulk of monthly diets almost year-round, ranging from 44.9% （July） to 92.9% （May）. Young parts of Indocalamus calcicolus unexpanded leaves contributed to a large proportion of the young leaf diet in most months. Fruit accounted for only 17.4% of the diet, with a peak of consumption in July. We suggest that this highly fo- livorous diet may be related to the long lean season of fruit availability in limestone habitats as well as the utilization of cliffs of low fruit availability
基金the National Natural Science Foundation of China(91432302 and 31620103905)the Science Frontier Program of the Chinese Academy of Sciences(QYZDJ-SSW-SMC019)+3 种基金the National Key R&D Program of China(2017YFA0105203)Beijing Municipal Science and Technology Commission(Z161100000216152,Z161100000216139,Z181100001518004and Z171100000117002)the Beijing Brain Initiative of Beijing Municipal Science and Technology Commission(Z181100001518004)the Guangdong Pearl River Talents Plan(2016ZT06S220)。
文摘The frontal pole cortex(FPC)plays key roles in various higher-order functions and is highly developed in non-human primates.An essential missing piece of information is the detailed anatomical connections for finer parcellation of the macaque FPC than provided by the previous tracer results.This is important for understanding the functional architecture of the cerebral cortex.Here,combining cross-validation and principal component analysis,we formed a tractography-based parcellation scheme that applied a machine learning algorithm to divide the macaque FPC(2 males and 6 females)into eight subareas using high-resolution diffusion magnetic resonance imaging with the 9.4 T Bruker system,and then revealed their subregional connections.Furthermore,we applied improved hierarchical clustering to the obtained parcels to probe the modular structure of the subregions,and found that the dorsolateral FPC,which contains an extension to the medial FPC,was mainly connected to regions of the default-mode network.The ventral FPC was mainly involved in the social-interaction network and the dorsal FPC in the metacognitive network.These results enhance our understanding of the anatomy and circuitry of the macaque brain,and contribute to FPC-related clinical research.
基金This work was supported by the National Special Science Research Program of China （2012CBA01305） the National Natural Science Foundation of China （81172876, U0832601, 81273251, U1202228） the Knowledge Innovation Program of CAS （KSCX2-EW-R-13） and the National Science and Technology Major Project （2013ZX10001-002, 2012ZX10001-007）We thank Mr. Zhen-Fei Hu,Gui Li and Dong-Ti Huang of Kunming Primate Research Center for their assistance with the experiments.
文摘Pig-tailed macaques(Macaca nemistrina group) have been extensively used as non-human primate animal models for various human diseases in recent years, notably for AIDS research due to their sensitivity to HIV-1. Northern pig-tailed macaques(M. leonina) are distributed in China and other surrounding Southeast Asia countries. Although northern pig-tailed macaques have been bred on a large scale as experimental animals since 2012, the reference value of normal levels of leukocytes is not available. To obtain such information, 62 blood samples from male and female healthy northern pig-tailed macaques at different ages were collected. The normal range of major leukocyte subpopulations, such as T lymphocytes, B lymphocytes, natural killer(NK) cells, monocytes, and the expression levels of activation or differentiation related molecules(CD38, HLA-DR, CCR5, CD21, IgD, CD80 and CD86) on lymphocytes were analyzed by flow cytometry. The counts of B cells decreased with age, but those of CD8+ T cells and NK cells and the frequency of CD38+HLA-DR+CD4+ T cells were positively correlated with age. The counts of leukocyte subpopulations were higher in males than those in females except for CD4+ T cells. Males also showed higher expression levels of Ig D and CD21 within B cells. This study provides basic data about the leukocyte subpopulations of northern pig-tailed macaques and compares this species with commonly used Chinese rhesus macaques(M. mulatta), which is meaningful for the biomedical application of northern pig-tailed macaques.
基金supported in part by grants from the National Natural Science Foundation of China(31772475 31672307+1 种基金31401981 31372215)
文摘In some non-human primates, infants function as a social tool that can bridge relationships among group members. Infants are a desired commodity for group members, and mothers control access to them. The biological market theory suggests that grooming is widespread and represents a commodity that can be exchanged for infant handling. As a limited resource, however, the extent to which infants are interchanged between mothers(females with an infant) and non-mothers(potential handlers,females without an infant) remains unclear. In this study, we collected behavioral data to investigate the relationship between grooming and infant handling in free-ranging Tibetan macaques(Macaca thibetana)at Mt. Huangshan, China. Our results showed that females with infants received more grooming than females without infants. After her infant was handled,mother females received more grooming than they did during daily grooming interactions. However, with the increasing number of infants within the social group, both the grooming that mothers received and the grooming that non-mothers invested for handling infants decreased. We also found that non-mothers invested more time in grooming to gain access to younger infants than older infants. Our results provide evidence that infants are social commodities for both mother and non-mother females. Mothers use infants for obtain grooming and non-mothers use grooming to gain access to infants. The current study implies a bidirectional and complex interchange pattern between grooming and infant handling to compensate for the dyadic grooming disparity in non-human primates.
基金supported by the National Natural Science Foundation of China (Grant Nos. 10972001,10702023 and 10832006)Matjaz Perc individually acknowledges support from the Slovenian Research Agency (Grant No. Z1-2032)
文摘Inhibitory coupled bursting Hindmarsh-Rose neurons are considered as constitutive units of the Macaque corti- cal network. In the absence of information transmission delay the bursting activity is desynchronized, giving rise to spatiotemporally disordered dynamics. This paper shows that the introduction of finite delays can lead to the synchro- nization of bursting and thus to the emergence of coherent propagating fronts of excitation in the space-time domain. Moreover, it shows that the type of synchronous bursting is uniquely determined by the delay length, with the transi- tions from one type to the other occurring in a step-like manner depending on the delay. Interestingly, as the delay is tuned close to the transition points, the synchronization deteriorates, which implies the coexistence of different bursting attractors. These phenomena can be observed by different but fixed coupling strengths, thus indicating a new role for information transmission delays in realistic neuronal networks.
基金supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2016-I2M-1-014)
文摘There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts.Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been crucial for improving our understanding of the role of the microbiome on the host mucosal surface;however,studies on the mechanisms involved in microbiome-host interactions remain limited to small animal models.Here,we demonstrated that rhesus monkeys under short-term broad-spectrum antibiotic treatment could be used as a model to study the gut mucosal host-microbiome niche and immune balance with steady health status.Results showed that the diversity and community structure of the gut commensal bacteria in rhesus monkeys were both disrupted after antibiotic treatment.Furthermore,the 16S rDNA amplicon sequencing results indicated that Escherichia-Shigella were predominant in stool samples 9 d of treatment,and the abundances of bacterial functional genes and predicted KEGG pathways were significantly changed.In addition to inducing aberrant morphology of small intestinal villi,the depletion of gut commensal bacteria led to increased proportions of CD3+T,CD4+T,and CD16+NK cells in peripheral blood mononuclear cells(PBMCs),but decreased numbers of Treg and CD20+B cells.The transcriptome of PBMCs from antibiotic-treated monkeys showed that the immune balance was affected by modulation of the expression of many functional genes,including IL-13,VCAM1,and LGR4.
