Neural tube defects(NTDs)are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure.Although folate supplementation has been shown to mitigate the incidence of NTDs,some cases,often...Neural tube defects(NTDs)are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure.Although folate supplementation has been shown to mitigate the incidence of NTDs,some cases,often attributable to genetic factors,remain unpreventable.The SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation;at present,however,the underlying mechanism remains unclear.Neural tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural plate.To determine the role of SHROOM3 in early developmental morphogenesis,we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate phase.Loss of SHROOM3 resulted in shorter neuroepithelial cells and smaller nuclei.These morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins,namely fibrous actin(F-actin),myosin II,and phospho-myosin light chain(PMLC),to the apical side of the neuroepithelial cells.Notably,these defects were not rescued by folate supplementation.RNA sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ morphogenesis.In summary,we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.展开更多
DEAR EDITOR,The Myanmar or black snub-nosed monkey(Rhinopithecus strykeri) is a recently discovered and critically endangered colobus primate with an unknown gut microbiota. Here, we characterized and compared the gut...DEAR EDITOR,The Myanmar or black snub-nosed monkey(Rhinopithecus strykeri) is a recently discovered and critically endangered colobus primate with an unknown gut microbiota. Here, we characterized and compared the gut microbiota of R. strykeri with those of two closely related snub-nosed monkey species.展开更多
Accurately recognizing facial expressions is essential for effective social interactions.Non-human primates(NHPs)are widely used in the study of the neural mechanisms underpinning facial expression processing,yet it r...Accurately recognizing facial expressions is essential for effective social interactions.Non-human primates(NHPs)are widely used in the study of the neural mechanisms underpinning facial expression processing,yet it remains unclear how well monkeys can recognize the facial expressions of other species such as humans.In this study,we systematically investigated how monkeys process the facial expressions of conspecifics and humans using eye-tracking technology and sophisticated behavioral tasks,namely the temporal discrimination task(TDT)and face scan task(FST).We found that monkeys showed prolonged subjective time perception in response to Negative facial expressions in monkeys while showing longer reaction time to Negative facial expressions in humans.Monkey faces also reliably induced divergent pupil contraction in response to different expressions,while human faces and scrambled monkey faces did not.Furthermore,viewing patterns in the FST indicated that monkeys only showed bias toward emotional expressions upon observing monkey faces.Finally,masking the eye region marginally decreased the viewing duration for monkey faces but not for human faces.By probing facial expression processing in monkeys,our study demonstrates that monkeys are more sensitive to the facial expressions of conspecifics than those of humans,thus shedding new light on inter-species communication through facial expressions between NHPs and humans.展开更多
Fluoxetine(Prozac^(TM))is the only antidepressant approved by the US Food and Drug Administration(FDA)for the treatment of major depressive disorder(MDD)in children.Despite its considerable efficacy as a selective ser...Fluoxetine(Prozac^(TM))is the only antidepressant approved by the US Food and Drug Administration(FDA)for the treatment of major depressive disorder(MDD)in children.Despite its considerable efficacy as a selective serotonin reuptake inhibitor,the possible long-term effects of fluoxetine on brain development in children are poorly understood.In the current study,we aimed to delineate molecular mechanisms and protein biomarkers in the brains of juvenile rhesus macaques(Macaca mulatta)one year after the discontinuation of fluoxetine treatment using proteomic and phosphoproteomic profiling.We identified several differences in protein expression and phosphorylation in the dorsolateral prefrontal cortex(DLPFC)and cingulate cortex(CC)that correlated with impulsivity in animals,suggesting that the GABAergic synapse pathway may be affected by fluoxetine treatment.Biomarkers in combination with the identified pathways contribute to a better understanding of the mechanisms underlying the chronic effects of fluoxetine after discontinuation in children.展开更多
As a new bionic algorithm,Spider Monkey Optimization(SMO)has been widely used in various complex optimization problems in recent years.However,the new space exploration power of SMO is limited and the diversity of the...As a new bionic algorithm,Spider Monkey Optimization(SMO)has been widely used in various complex optimization problems in recent years.However,the new space exploration power of SMO is limited and the diversity of the population in SMO is not abundant.Thus,this paper focuses on how to reconstruct SMO to improve its performance,and a novel spider monkey optimization algorithm with opposition-based learning and orthogonal experimental design(SMO^(3))is developed.A position updatingmethod based on the historical optimal domain and particle swarmfor Local Leader Phase(LLP)andGlobal Leader Phase(GLP)is presented to improve the diversity of the population of SMO.Moreover,an opposition-based learning strategy based on self-extremum is proposed to avoid suffering from premature convergence and getting stuck at locally optimal values.Also,a local worst individual elimination method based on orthogonal experimental design is used for helping the SMO algorithm eliminate the poor individuals in time.Furthermore,an extended SMO^(3)named CSMO^(3)is investigated to deal with constrained optimization problems.The proposed algorithm is applied to both unconstrained and constrained functions which include the CEC2006 benchmark set and three engineering problems.Experimental results show that the performance of the proposed algorithm is better than three well-known SMO algorithms and other evolutionary algorithms in unconstrained and constrained problems.展开更多
To solve the problem of slow convergence and easy to get into the local optimum of the spider monkey optimization algorithm,this paper presents a new algorithm based on multi-strategy(ISMO).First,the initial populatio...To solve the problem of slow convergence and easy to get into the local optimum of the spider monkey optimization algorithm,this paper presents a new algorithm based on multi-strategy(ISMO).First,the initial population is generated by a refracted opposition-based learning strategy to enhance diversity and ergodicity.Second,this paper introduces a non-linear adaptive dynamic weight factor to improve convergence efficiency.Then,using the crisscross strategy,using the horizontal crossover to enhance the global search and vertical crossover to keep the diversity of the population to avoid being trapped in the local optimum.At last,we adopt a Gauss-Cauchy mutation strategy to improve the stability of the algorithm by mutation of the optimal individuals.Therefore,the application of ISMO is validated by ten benchmark functions and feature selection.It is proved that the proposed method can resolve the problem of feature selection.展开更多
Background:The monkey pox virus is caused by monkey pox(MPX),which is similar to both smallpox and cowpox.Near tropical rain forests,it usually occurs in isolated communities in Central and West Africa.The monkey pox ...Background:The monkey pox virus is caused by monkey pox(MPX),which is similar to both smallpox and cowpox.Near tropical rain forests,it usually occurs in isolated communities in Central and West Africa.The monkey pox virus,a member of the family Poxviridae and belongs to the genus Orthopoxvirus.Close contact with infected animals,sick people,or contaminated inanimate things can cause the virus to spread to humans.The illness typically takes 7 to 14 days to incubate and is characterized by fever,headache,lethargy,myalgia,generalized body pains,lymph node swelling,and skin lesions.Given the variety of illnesses that can result in skin rashes,it could be challenging to differentiate monkey pox solely based on clinical presentation,particularly for patients with an uncommon look.Objective:The main objective of the study is to evaluate public perceptions regarding the emerging human monkey pox disease and vaccination.Methods:The study was conducted using a cross-sectional study design.The sample size was 472 participants;however,10 questionnaires were excluded because of invalid data.The 462 questionnaires were included by expert validation from the general public of Rawalpindi and Islamabad,Pakistan.The data were analyzed using Chi-squared tests.Results:This questionnaire-based cross-sectional study was conducted from 15 Sep to 15 Oct 2022.The participants’perceptions,knowledge,and attitudes were collected via a 24-item-based questionnaire survey.The survey was based on 462 participants,196(42.4%)were females,and 266(57.6%)were males.The results reveal that out of 462 participants,clinical symptoms of monkey pox disease 82.7%(382),complications of monkey pox disease 81.2%(375),lymphadenopathy(swollen lymph nodes)is one clinical feature that could be used to differentiate between monkey pox and smallpox 81.2%(375)and monkey pox is common in Western and Central Africa 24.2%(112).Furthermore,the majority of participants(P≤0.05)agreed that health officials should start a vaccination campaign to combat monkey pox.Regarding preventive measures and vaccination campaigns,health officials should take public preventive measures 79.7%(368)and health officials start a vaccination campaign against monkey pox disease 56.3%(260).Conclusion:There was a significant difference seen in the public perception regarding monkey pox preventive measures and vaccination.The International health authorities must take priority-based preventative measures to prevent the spread of monkey pox disease around the world.展开更多
Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(...Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.展开更多
The objective of this study was to set up a rhesus monkey model of polycystic ovary syndrome(PCOS),which is globally prevalent among reproductive-aged human women,and to understand the reproductive traits of PCOS fe...The objective of this study was to set up a rhesus monkey model of polycystic ovary syndrome(PCOS),which is globally prevalent among reproductive-aged human women,and to understand the reproductive traits of PCOS female monkeys.Six adult female rhesus monkeys aged 6-10 a,were divided into a PCOS group and a control group.The PCOS group were given two cycles of subcutaneous injections of propionic acid testosterone(PAT),3.5 mg/kg body weight,on day 1,day 3,and day 5 of the menstrual cycle,respectively,and then given muscle injections of human chorionic gonadotropin(HCG),350 IU/kg body wtight,on day 7,day 9,and day 11,respectively.Results showed that high levels of serum LH and T [(5.35±0.17) IU/L and(7.58±0.14) ng/mL,respectively],and a high ratio value of LH/FSH(5.35/1.30=4.12) were observed in the PCOS group.No significant differences were found in serum FSH,E2,and P in the PCOS group compared with those of the control.Polycystic ovaries in the PCOS monkeys were recorded by live ultrasound.The blastocysts rates of the PCOS vs.the control were 23.53% vs.66.67%,and there was a significant difference between the two groups.This study shows that PAT coupled with HCG can induce PCOS in rhesus monkeys in the short term.The reproductive features of PCOS monkeys were similar to those of PCOS patients.展开更多
Rhesus monkey embryonic stem(rES) cells have similar characteristics to human ES cells,and might be useful as a substitute model for preclinical research.Notch signaling is involved in the formation of bile ducts,wh...Rhesus monkey embryonic stem(rES) cells have similar characteristics to human ES cells,and might be useful as a substitute model for preclinical research.Notch signaling is involved in the formation of bile ducts,which are composed of cholangiocytes.However,little is known about the role of Notch signaling in cholangiocytic commitment of ES cells.We analyzed the effect of Notch signaling on the induction of cholangiocyte-like cells from rES cells.About 80% of definitive endoderm(DE) cells were generated from rES cells after treatment with activin A.After treatment with BMP4 and FGF1 on matrigel coated wells in serum-free medium,rES-derived DE gave rise to cholangiocyte-like cells by expression of cholangiocytic specific proteins(CK7,CK18,CK19,CK20,and OV-6) and genes(GSTPi,IB4,and HNF1β).At the same time,expression of Notch 1 and Notch 2 mRNA were detected during cell differentiation,as well as their downstream target genes such as Hes 1 and Hes 5.Inhibition of the Notch signal pathway by L-685458 resulted in decreased expression of Notch and their downstream genes.In addition,the proportion of cholangiocyte-like cells declined from ~90% to ~20%.These results suggest that Notch signaling may play a critical role in cholangiocytic development from ES cells.展开更多
Objective To investigate the expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) in monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood ...Objective To investigate the expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) in monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood flow occlusion. Methods The monkeys were immediately removed brain after death in operation of group A (identical temperature perfusion group) and group B (ultraprofound hypothermia perfusion group). Immunohistochemical technique was used to determine frontal cellular expression of NGF and GDNF. Statistics were analyzed by ANOVA analyses with significance level at P 〈 0.05. Results The expressions of NGF and GDNF in the group B were significantly higher than those in the group A (P 〈 0.05). Conclusion NGF and GDNF increased significantly in the monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood flow occlusion. It may be a protective mechanism for neuron survival and neural function recovery.展开更多
Go/NoGo tasks are a useful behavioral model in the study of cognitive neurosciences. The present developmental study is aimed at establishing a developmental protocol of Go/NoGo visual-discrimination tasks to investig...Go/NoGo tasks are a useful behavioral model in the study of cognitive neurosciences. The present developmental study is aimed at establishing a developmental protocol of Go/NoGo visual-discrimination tasks to investigate more cognitive process. We used two rhesus monkeys to test our procedures. Our results suggested that the monkeys quickly learned Go/NoGo visual-discrimination tasks, and performed NoGo tasks better and easier than Go tasks. Using this visual-discrimination task, we can easily study related cognitive neurosciences.展开更多
For group-living primates, the information on postconflict management is crucial for understanding primate competition and cooperation. However, such information is poorly known for snub-nosed monkeys, especially for ...For group-living primates, the information on postconflict management is crucial for understanding primate competition and cooperation. However, such information is poorly known for snub-nosed monkeys, especially for wild populations. In this study, from September 2007 to June 2008, we investigated postconflict behavior among adult females Sichuan snub-nosed monkeys Rhinopithecus roxellana within one-male units in a wild, provisioned group in the Qinling Mountains of China by means of the time-rule method and the PC-MC method. We obtained a total of 81 PC-MC pairs and each individual was involved in only 0.004 aggressive behavior per observation hour. The first affiliative behavior was more likely to occur within the first minute after a conflict. The postconflict affiliative behaviors most often seen were contact-sit, embrace and grooming. The affiliative contacts between adult females occur due to selective attraction, i.e. reconciliation. The pattern of postconflict affiliation demonstrates that the R. roxellana belongs to a tolerant species.展开更多
The purpose of this research was to study the pharmacokinetics and the bioavailability of recombinant human parathyroid hormone [rhPTH (1-34)] in Rhesus monkeys after single and multiple subcutaneous administration....The purpose of this research was to study the pharmacokinetics and the bioavailability of recombinant human parathyroid hormone [rhPTH (1-34)] in Rhesus monkeys after single and multiple subcutaneous administration. An immunoradiometric assay (IRMA) was used to determine the plasma drug concentration of rhFFH (1-34) after giving single dose of 10, 20 and 40 ug/kg and daily dose of 40 ug/kg for 7 d by subcutaneous administration, and intravenous injection of 20 ug/kg in Rhesus monkeys. The pharmacokinetic parameters were calculated by noncompartmental analysis. The drug plasma level quantitation range was from 0.027 to 2.22 ng/mL. The intra- and inter-assay precision (CV) of analysis were less than 15%, and the average recovery was about 93.0% ± 8.6% - 116.5% ± 14.0%. After subcutaneous administration of rhPTH(1-34) at dose of 10, 20 and 40 ug/kg, the average Tmax was 0.67, 0.5 and 0.83 h, Cmax were 1.85 ± 0.05, 3.23 ± 0.25 and 7.15 ± 1.19 ng/mL, the AUC(0-∞) were 3.4 ± 0.6, 10.7 ± 1.3 and 12.6 ± 1.5 ng/h/mL, and terminal-phase elimination T1/2 were 0.72 ± 0.10, 1.15 ± 0.10 and 1.03 ± 0.06 h, respectively. The absolute bioavailability of rhPTH (1-34) was 46.96% after subcutaneous administration of 20 ug/kg. There was no evidence of accumulation during systemic exposure of rhPTH (1-34) upon multiple dosing in Rhesus monkeys. The IRMA assay method provide reasonable sensitivity and specificity for the pharrnacokinetic study of rhPTH (1-34) after subcutaneous or intravenous administration in Rhesus monkeys. The pharmacokinetic characteristic of rhPTH (1-34) in monkeys shows linear relationship with the dose administered subcutaneously.展开更多
Aim: To examine the possible effect of heat treatment on expression of heat shock proteins (Hsps) 105, 70, and 60 in primary monkey Sertoli cells and to evaluate the possible signal pathways. Methods: Western blot...Aim: To examine the possible effect of heat treatment on expression of heat shock proteins (Hsps) 105, 70, and 60 in primary monkey Sertoli cells and to evaluate the possible signal pathways. Methods: Western blot analysis, realtime polymerase chain reaction (PCR), and confocal immunohistochemistry were used to analyze mRNA and protein levels of the Hsps in response to 43~C treatment of Sertoli cells isolated from pubertal monkey testes. Results: Staining with Hoechst 33342 indicated Sertoli cells did not undergo apoptosis after heat treatment. Hspl05 was expressed in cytoplasm of untreated Sertoli cells. Both Hspl05 mRNA and protein levels were increased approximately 20-fold compared to those of the untreated controls at 12 h after heat treatment. Untreated Sertoli cells did not express Hsp70, but heat stress induced its expression in the cell cytoplasm. The time-course of changes in Hsp70 was similar to that of Hsp105. In contrast to Hsp105 and Hsp70, the change in Hsp60 expression was much less obvious. The protein level between 12 h and 48 h after heat treatment was only approximately 1.5-fold that of the untreated control. Extracellular regulated kinase (ERK) 1/2 inhibitor (U0126) or phosphoinositide kinase-3 (PI3K) inhibitor (LY294002) could partially block the response of Hspl05 and Hsp70 induced by heat treatment. Conclusion: These results indicate that the heat-induced expression of the three types of Hsp in monkey Sertoli cells might be regulated by ERK and/or PI3K signal pathways, but the profile of their expression is different, suggesting that they might have different regulatory functions in Sertoli cells.展开更多
Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily us...Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.展开更多
Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system. In brain research, a series of powerful and novel gene editing technolo...Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system. In brain research, a series of powerful and novel gene editing technologies are based on these systems. Although many viral vectors are used in rodents, their full application has been limited in non-human primates. To identify viral vectors that can stably and effectively express exogenous genes within non- human primates, eleven commonly used recombinant adeno-associated viral and lentiviral vectors, each carrying a gene to express green or red fluorescence, were injected into the parietal cortex of four rhesus monkeys. The expression of fluorescent cells was used to quantify transfection efficiency. Histological results revealed that recombinant adeno-associated viral vectors, especially the serotype 2/9 coupled with the cytomegalovirus, human synapsin I, or Ca2~/calmodulin-dependent protein kinase II promoters, and lentiviral vector coupled with the human ubiquitin C promoter, induced higher expression of fluorescent cells, representing high transfection efficiency. This is the first comparison of transfection efficiencies of different viral vectors carrying different promoters and serotypes in non-human primates (NHPs). These results can be used as an aid to select optimal vectors to transfer exogenous genes into the central nervous system of non-human primates.展开更多
Monkeypox is a rare viral infection caused by the monkeypox virus,which is similar to human smallpox.It is also a zoonosis which is found mainly in tropical rain forests of central and western Africa.The monkeypox vir...Monkeypox is a rare viral infection caused by the monkeypox virus,which is similar to human smallpox.It is also a zoonosis which is found mainly in tropical rain forests of central and western Africa.The monkeypox virus was first detected in grivet at a laboratory in Copenhagen,Denmark,in 1958,and was later found in many African rodents,such as murine and squirrels.Therefore,it is believed that the primary way of infection is through direct human contact with these infected animals.In May 2003,human monkeypox appeared in the Western Hemisphere in the United States and spreaded rapidly,which immediately attracted the attention of all countries.展开更多
Aim: To assess the spatiotemporal changes in the expression of extracellular signal-regulated kinases 1 and 2 (ERK1/ 2), c-Jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinases (MAPK) in respon...Aim: To assess the spatiotemporal changes in the expression of extracellular signal-regulated kinases 1 and 2 (ERK1/ 2), c-Jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinases (MAPK) in response to heat stress in the cryptorchid testis, and to investigate a possible relation to Sertoli cell dedifferentiation. Methods: Immunohistochemistry and western blot were used to examine the expression and activation of ERK1/2, p38 and JNK in the cryptorchid testis at various stages after experimental cryptorchidism. Results: The abdominal temperature did not obviously change the total ERK1/2 expression but significantly activated phospho-ERK1/2 in the Sertoli cells of the cryptorchid testis. Heat stress increased total JNK expression in the Sertoli cells of the cryptorchid testis but did not activate phospho-JNK. Neither total p38 nor phospho-p38 was induced by heat stress in the Sertoli cells of the cryptorchid testis. Changes in the spatiotemporal expression of cytokeratin 18 (CK18), a marker of immature or undifferentiated Sertoli cells, were induced in the cryptorchid testis in a pattern similar to the activation of ERK1/2. Condusion: The activation of ERK1/2 in the testis may be related to dedifferentiation of Sertoli cells under heat stress induced by experimental cryptorchidism.展开更多
基金supported by the National Natural Science Foundation of China (81930121,82125008 to Y.C.C.)National Key Research and Development Program of China (2018YFA0107902 to Y.C.C.and 2018YFA0801403 to Z.B.W.)+1 种基金Major Basic Research Project of Science and Technology of Yunnan (202001BC070001 to Y.C.C.)Natural Science Foundation of Yunnan Province (202102AA100053 to Y.C.C.)。
文摘Neural tube defects(NTDs)are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure.Although folate supplementation has been shown to mitigate the incidence of NTDs,some cases,often attributable to genetic factors,remain unpreventable.The SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation;at present,however,the underlying mechanism remains unclear.Neural tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural plate.To determine the role of SHROOM3 in early developmental morphogenesis,we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate phase.Loss of SHROOM3 resulted in shorter neuroepithelial cells and smaller nuclei.These morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins,namely fibrous actin(F-actin),myosin II,and phospho-myosin light chain(PMLC),to the apical side of the neuroepithelial cells.Notably,these defects were not rescued by folate supplementation.RNA sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ morphogenesis.In summary,we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.
基金supported by the National Natural Science Foundation of China (31821001, 32070404)Strategic Priority Research Program of the Chinese Academy of Sciences (XDB31000000,XDA23080000)State Forestry Administration of China。
文摘DEAR EDITOR,The Myanmar or black snub-nosed monkey(Rhinopithecus strykeri) is a recently discovered and critically endangered colobus primate with an unknown gut microbiota. Here, we characterized and compared the gut microbiota of R. strykeri with those of two closely related snub-nosed monkey species.
基金supported by the National Natural Science Foundation of China (U20A2017)Guangdong Basic and Applied Basic Research Foundation (2022A1515010134,2022A1515110598)+2 种基金Youth Innovation Promotion Association of Chinese Academy of Sciences (2017120)Shenzhen-Hong Kong Institute of Brain Science–Shenzhen Fundamental Research Institutions (NYKFKT2019009)Shenzhen Technological Research Center for Primate Translational Medicine (F-2021-Z99-504979)。
文摘Accurately recognizing facial expressions is essential for effective social interactions.Non-human primates(NHPs)are widely used in the study of the neural mechanisms underpinning facial expression processing,yet it remains unclear how well monkeys can recognize the facial expressions of other species such as humans.In this study,we systematically investigated how monkeys process the facial expressions of conspecifics and humans using eye-tracking technology and sophisticated behavioral tasks,namely the temporal discrimination task(TDT)and face scan task(FST).We found that monkeys showed prolonged subjective time perception in response to Negative facial expressions in monkeys while showing longer reaction time to Negative facial expressions in humans.Monkey faces also reliably induced divergent pupil contraction in response to different expressions,while human faces and scrambled monkey faces did not.Furthermore,viewing patterns in the FST indicated that monkeys only showed bias toward emotional expressions upon observing monkey faces.Finally,masking the eye region marginally decreased the viewing duration for monkey faces but not for human faces.By probing facial expression processing in monkeys,our study demonstrates that monkeys are more sensitive to the facial expressions of conspecifics than those of humans,thus shedding new light on inter-species communication through facial expressions between NHPs and humans.
基金supported by the Max Planck Society to C.W.T.and National Institutes of Health USDHHS(R01-HD065826to M.G.,OD011107 to Harris Lewin)。
文摘Fluoxetine(Prozac^(TM))is the only antidepressant approved by the US Food and Drug Administration(FDA)for the treatment of major depressive disorder(MDD)in children.Despite its considerable efficacy as a selective serotonin reuptake inhibitor,the possible long-term effects of fluoxetine on brain development in children are poorly understood.In the current study,we aimed to delineate molecular mechanisms and protein biomarkers in the brains of juvenile rhesus macaques(Macaca mulatta)one year after the discontinuation of fluoxetine treatment using proteomic and phosphoproteomic profiling.We identified several differences in protein expression and phosphorylation in the dorsolateral prefrontal cortex(DLPFC)and cingulate cortex(CC)that correlated with impulsivity in animals,suggesting that the GABAergic synapse pathway may be affected by fluoxetine treatment.Biomarkers in combination with the identified pathways contribute to a better understanding of the mechanisms underlying the chronic effects of fluoxetine after discontinuation in children.
基金supported by the First Batch of Teaching Reform Projects of Zhejiang Higher Education“14th Five-Year Plan”(jg20220434)Special Scientific Research Project for Space Debris and Near-Earth Asteroid Defense(KJSP2020020202)+1 种基金Natural Science Foundation of Zhejiang Province(LGG19F030010)National Natural Science Foundation of China(61703183).
文摘As a new bionic algorithm,Spider Monkey Optimization(SMO)has been widely used in various complex optimization problems in recent years.However,the new space exploration power of SMO is limited and the diversity of the population in SMO is not abundant.Thus,this paper focuses on how to reconstruct SMO to improve its performance,and a novel spider monkey optimization algorithm with opposition-based learning and orthogonal experimental design(SMO^(3))is developed.A position updatingmethod based on the historical optimal domain and particle swarmfor Local Leader Phase(LLP)andGlobal Leader Phase(GLP)is presented to improve the diversity of the population of SMO.Moreover,an opposition-based learning strategy based on self-extremum is proposed to avoid suffering from premature convergence and getting stuck at locally optimal values.Also,a local worst individual elimination method based on orthogonal experimental design is used for helping the SMO algorithm eliminate the poor individuals in time.Furthermore,an extended SMO^(3)named CSMO^(3)is investigated to deal with constrained optimization problems.The proposed algorithm is applied to both unconstrained and constrained functions which include the CEC2006 benchmark set and three engineering problems.Experimental results show that the performance of the proposed algorithm is better than three well-known SMO algorithms and other evolutionary algorithms in unconstrained and constrained problems.
文摘To solve the problem of slow convergence and easy to get into the local optimum of the spider monkey optimization algorithm,this paper presents a new algorithm based on multi-strategy(ISMO).First,the initial population is generated by a refracted opposition-based learning strategy to enhance diversity and ergodicity.Second,this paper introduces a non-linear adaptive dynamic weight factor to improve convergence efficiency.Then,using the crisscross strategy,using the horizontal crossover to enhance the global search and vertical crossover to keep the diversity of the population to avoid being trapped in the local optimum.At last,we adopt a Gauss-Cauchy mutation strategy to improve the stability of the algorithm by mutation of the optimal individuals.Therefore,the application of ISMO is validated by ten benchmark functions and feature selection.It is proved that the proposed method can resolve the problem of feature selection.
文摘Background:The monkey pox virus is caused by monkey pox(MPX),which is similar to both smallpox and cowpox.Near tropical rain forests,it usually occurs in isolated communities in Central and West Africa.The monkey pox virus,a member of the family Poxviridae and belongs to the genus Orthopoxvirus.Close contact with infected animals,sick people,or contaminated inanimate things can cause the virus to spread to humans.The illness typically takes 7 to 14 days to incubate and is characterized by fever,headache,lethargy,myalgia,generalized body pains,lymph node swelling,and skin lesions.Given the variety of illnesses that can result in skin rashes,it could be challenging to differentiate monkey pox solely based on clinical presentation,particularly for patients with an uncommon look.Objective:The main objective of the study is to evaluate public perceptions regarding the emerging human monkey pox disease and vaccination.Methods:The study was conducted using a cross-sectional study design.The sample size was 472 participants;however,10 questionnaires were excluded because of invalid data.The 462 questionnaires were included by expert validation from the general public of Rawalpindi and Islamabad,Pakistan.The data were analyzed using Chi-squared tests.Results:This questionnaire-based cross-sectional study was conducted from 15 Sep to 15 Oct 2022.The participants’perceptions,knowledge,and attitudes were collected via a 24-item-based questionnaire survey.The survey was based on 462 participants,196(42.4%)were females,and 266(57.6%)were males.The results reveal that out of 462 participants,clinical symptoms of monkey pox disease 82.7%(382),complications of monkey pox disease 81.2%(375),lymphadenopathy(swollen lymph nodes)is one clinical feature that could be used to differentiate between monkey pox and smallpox 81.2%(375)and monkey pox is common in Western and Central Africa 24.2%(112).Furthermore,the majority of participants(P≤0.05)agreed that health officials should start a vaccination campaign to combat monkey pox.Regarding preventive measures and vaccination campaigns,health officials should take public preventive measures 79.7%(368)and health officials start a vaccination campaign against monkey pox disease 56.3%(260).Conclusion:There was a significant difference seen in the public perception regarding monkey pox preventive measures and vaccination.The International health authorities must take priority-based preventative measures to prevent the spread of monkey pox disease around the world.
基金supported by the National Key Research and Development Program of China (2021YFF0702201)National Natural Science Foundation of China (81873736,31872779,81830032)+2 种基金Guangzhou Key Research Program on Brain Science (202007030008)Department of Science and Technology of Guangdong Province (2021ZT09Y007,2020B121201006,2018B030337001,2021A1515012526)Natural Science Foundation of Guangdong Province (2021A1515012526,2022A1515012651)。
文摘Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.
基金supported by Yunnan Key Laboratory of Animal Reproductive Biology(2010-03)
文摘The objective of this study was to set up a rhesus monkey model of polycystic ovary syndrome(PCOS),which is globally prevalent among reproductive-aged human women,and to understand the reproductive traits of PCOS female monkeys.Six adult female rhesus monkeys aged 6-10 a,were divided into a PCOS group and a control group.The PCOS group were given two cycles of subcutaneous injections of propionic acid testosterone(PAT),3.5 mg/kg body weight,on day 1,day 3,and day 5 of the menstrual cycle,respectively,and then given muscle injections of human chorionic gonadotropin(HCG),350 IU/kg body wtight,on day 7,day 9,and day 11,respectively.Results showed that high levels of serum LH and T [(5.35±0.17) IU/L and(7.58±0.14) ng/mL,respectively],and a high ratio value of LH/FSH(5.35/1.30=4.12) were observed in the PCOS group.No significant differences were found in serum FSH,E2,and P in the PCOS group compared with those of the control.Polycystic ovaries in the PCOS monkeys were recorded by live ultrasound.The blastocysts rates of the PCOS vs.the control were 23.53% vs.66.67%,and there was a significant difference between the two groups.This study shows that PAT coupled with HCG can induce PCOS in rhesus monkeys in the short term.The reproductive features of PCOS monkeys were similar to those of PCOS patients.
基金supported by research grants from Zhejiang Natural Sciences Foundation of China (Y2110911 Y2080996)the National Key Technologies R&D Program of China (2007CB947701)
文摘Rhesus monkey embryonic stem(rES) cells have similar characteristics to human ES cells,and might be useful as a substitute model for preclinical research.Notch signaling is involved in the formation of bile ducts,which are composed of cholangiocytes.However,little is known about the role of Notch signaling in cholangiocytic commitment of ES cells.We analyzed the effect of Notch signaling on the induction of cholangiocyte-like cells from rES cells.About 80% of definitive endoderm(DE) cells were generated from rES cells after treatment with activin A.After treatment with BMP4 and FGF1 on matrigel coated wells in serum-free medium,rES-derived DE gave rise to cholangiocyte-like cells by expression of cholangiocytic specific proteins(CK7,CK18,CK19,CK20,and OV-6) and genes(GSTPi,IB4,and HNF1β).At the same time,expression of Notch 1 and Notch 2 mRNA were detected during cell differentiation,as well as their downstream target genes such as Hes 1 and Hes 5.Inhibition of the Notch signal pathway by L-685458 resulted in decreased expression of Notch and their downstream genes.In addition,the proportion of cholangiocyte-like cells declined from ~90% to ~20%.These results suggest that Notch signaling may play a critical role in cholangiocytic development from ES cells.
基金This work was supported by the Key Program of Natural Science Foundation of Yunnan Province, China (No. 2003C0010Z).
文摘Objective To investigate the expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) in monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood flow occlusion. Methods The monkeys were immediately removed brain after death in operation of group A (identical temperature perfusion group) and group B (ultraprofound hypothermia perfusion group). Immunohistochemical technique was used to determine frontal cellular expression of NGF and GDNF. Statistics were analyzed by ANOVA analyses with significance level at P 〈 0.05. Results The expressions of NGF and GDNF in the group B were significantly higher than those in the group A (P 〈 0.05). Conclusion NGF and GDNF increased significantly in the monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood flow occlusion. It may be a protective mechanism for neuron survival and neural function recovery.
基金Chinese Academy of Science Grants (KSCX2-SWfor M.Y.) , National Basic Research Programof China , Chinese NationalScience Foundation (30470553) Programof Chinese Academy of Science (KJCX1-01 , KJCX1-09)
文摘Go/NoGo tasks are a useful behavioral model in the study of cognitive neurosciences. The present developmental study is aimed at establishing a developmental protocol of Go/NoGo visual-discrimination tasks to investigate more cognitive process. We used two rhesus monkeys to test our procedures. Our results suggested that the monkeys quickly learned Go/NoGo visual-discrimination tasks, and performed NoGo tasks better and easier than Go tasks. Using this visual-discrimination task, we can easily study related cognitive neurosciences.
基金The Natural Science Foundation of China (No.30970444, No. 30770375, No. 30630016)the Cosmo Oil Eco Card Fund of Japan (2005-2010) support
文摘For group-living primates, the information on postconflict management is crucial for understanding primate competition and cooperation. However, such information is poorly known for snub-nosed monkeys, especially for wild populations. In this study, from September 2007 to June 2008, we investigated postconflict behavior among adult females Sichuan snub-nosed monkeys Rhinopithecus roxellana within one-male units in a wild, provisioned group in the Qinling Mountains of China by means of the time-rule method and the PC-MC method. We obtained a total of 81 PC-MC pairs and each individual was involved in only 0.004 aggressive behavior per observation hour. The first affiliative behavior was more likely to occur within the first minute after a conflict. The postconflict affiliative behaviors most often seen were contact-sit, embrace and grooming. The affiliative contacts between adult females occur due to selective attraction, i.e. reconciliation. The pattern of postconflict affiliation demonstrates that the R. roxellana belongs to a tolerant species.
文摘The purpose of this research was to study the pharmacokinetics and the bioavailability of recombinant human parathyroid hormone [rhPTH (1-34)] in Rhesus monkeys after single and multiple subcutaneous administration. An immunoradiometric assay (IRMA) was used to determine the plasma drug concentration of rhFFH (1-34) after giving single dose of 10, 20 and 40 ug/kg and daily dose of 40 ug/kg for 7 d by subcutaneous administration, and intravenous injection of 20 ug/kg in Rhesus monkeys. The pharmacokinetic parameters were calculated by noncompartmental analysis. The drug plasma level quantitation range was from 0.027 to 2.22 ng/mL. The intra- and inter-assay precision (CV) of analysis were less than 15%, and the average recovery was about 93.0% ± 8.6% - 116.5% ± 14.0%. After subcutaneous administration of rhPTH(1-34) at dose of 10, 20 and 40 ug/kg, the average Tmax was 0.67, 0.5 and 0.83 h, Cmax were 1.85 ± 0.05, 3.23 ± 0.25 and 7.15 ± 1.19 ng/mL, the AUC(0-∞) were 3.4 ± 0.6, 10.7 ± 1.3 and 12.6 ± 1.5 ng/h/mL, and terminal-phase elimination T1/2 were 0.72 ± 0.10, 1.15 ± 0.10 and 1.03 ± 0.06 h, respectively. The absolute bioavailability of rhPTH (1-34) was 46.96% after subcutaneous administration of 20 ug/kg. There was no evidence of accumulation during systemic exposure of rhPTH (1-34) upon multiple dosing in Rhesus monkeys. The IRMA assay method provide reasonable sensitivity and specificity for the pharrnacokinetic study of rhPTH (1-34) after subcutaneous or intravenous administration in Rhesus monkeys. The pharmacokinetic characteristic of rhPTH (1-34) in monkeys shows linear relationship with the dose administered subcutaneously.
基金Acknowledgment This study was supported by the "973" project (No. 2006CB504001), the Major Research Plan (No. 2006CB944001), the CAS Innovation Project (KSCA2- YW-R-55), the National Natural Science Foundation of China (No. 3061800530230190 30600311), and the Beijing Natural Science Foundation (No. 5073032).
文摘Aim: To examine the possible effect of heat treatment on expression of heat shock proteins (Hsps) 105, 70, and 60 in primary monkey Sertoli cells and to evaluate the possible signal pathways. Methods: Western blot analysis, realtime polymerase chain reaction (PCR), and confocal immunohistochemistry were used to analyze mRNA and protein levels of the Hsps in response to 43~C treatment of Sertoli cells isolated from pubertal monkey testes. Results: Staining with Hoechst 33342 indicated Sertoli cells did not undergo apoptosis after heat treatment. Hspl05 was expressed in cytoplasm of untreated Sertoli cells. Both Hspl05 mRNA and protein levels were increased approximately 20-fold compared to those of the untreated controls at 12 h after heat treatment. Untreated Sertoli cells did not express Hsp70, but heat stress induced its expression in the cell cytoplasm. The time-course of changes in Hsp70 was similar to that of Hsp105. In contrast to Hsp105 and Hsp70, the change in Hsp60 expression was much less obvious. The protein level between 12 h and 48 h after heat treatment was only approximately 1.5-fold that of the untreated control. Extracellular regulated kinase (ERK) 1/2 inhibitor (U0126) or phosphoinositide kinase-3 (PI3K) inhibitor (LY294002) could partially block the response of Hspl05 and Hsp70 induced by heat treatment. Conclusion: These results indicate that the heat-induced expression of the three types of Hsp in monkey Sertoli cells might be regulated by ERK and/or PI3K signal pathways, but the profile of their expression is different, suggesting that they might have different regulatory functions in Sertoli cells.
基金supported by the National Natural Science Foundation of China(81773711)to W.Y.Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000)+6 种基金Lundbeck Foundation Grant(R190-2014-2827)Carlsberg Foundation Grant(CF16-0663)to G.J.Z.Science and Technology Program of Guangzhou,China(201704020103)to W.Y.Introduction of Innovative R&D Team Program of Guangdong Province(2013Y104)Leading Talent Project in Science and Technology of Guangzhou Development District(2019-L002)National Major Scientific and Technological Special Project for “Significant New Drugs Development”(2016ZX09101026)to S.Z.L.Key Projects of the Military Science and Technology PLA(AWS14C007 and AWS16J023)to Y.Q.G
文摘Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.
基金supported by the National Program on Key Basic Research Project(973 Programs 2015CB755605)the National Natural Science Foundation of China(81471312)
文摘Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system. In brain research, a series of powerful and novel gene editing technologies are based on these systems. Although many viral vectors are used in rodents, their full application has been limited in non-human primates. To identify viral vectors that can stably and effectively express exogenous genes within non- human primates, eleven commonly used recombinant adeno-associated viral and lentiviral vectors, each carrying a gene to express green or red fluorescence, were injected into the parietal cortex of four rhesus monkeys. The expression of fluorescent cells was used to quantify transfection efficiency. Histological results revealed that recombinant adeno-associated viral vectors, especially the serotype 2/9 coupled with the cytomegalovirus, human synapsin I, or Ca2~/calmodulin-dependent protein kinase II promoters, and lentiviral vector coupled with the human ubiquitin C promoter, induced higher expression of fluorescent cells, representing high transfection efficiency. This is the first comparison of transfection efficiencies of different viral vectors carrying different promoters and serotypes in non-human primates (NHPs). These results can be used as an aid to select optimal vectors to transfer exogenous genes into the central nervous system of non-human primates.
文摘Monkeypox is a rare viral infection caused by the monkeypox virus,which is similar to human smallpox.It is also a zoonosis which is found mainly in tropical rain forests of central and western Africa.The monkeypox virus was first detected in grivet at a laboratory in Copenhagen,Denmark,in 1958,and was later found in many African rodents,such as murine and squirrels.Therefore,it is believed that the primary way of infection is through direct human contact with these infected animals.In May 2003,human monkeypox appeared in the Western Hemisphere in the United States and spreaded rapidly,which immediately attracted the attention of all countries.
基金Acknowledgment This study was supported by the National Natural Science Foundation of China (30230190), the National Basic Science Research and Development Project (973) (G1999055901) and the Chinese Academy of Sciences (CAS) Knowledge Innovation Program (KSCX-2-SW-201).
文摘Aim: To assess the spatiotemporal changes in the expression of extracellular signal-regulated kinases 1 and 2 (ERK1/ 2), c-Jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinases (MAPK) in response to heat stress in the cryptorchid testis, and to investigate a possible relation to Sertoli cell dedifferentiation. Methods: Immunohistochemistry and western blot were used to examine the expression and activation of ERK1/2, p38 and JNK in the cryptorchid testis at various stages after experimental cryptorchidism. Results: The abdominal temperature did not obviously change the total ERK1/2 expression but significantly activated phospho-ERK1/2 in the Sertoli cells of the cryptorchid testis. Heat stress increased total JNK expression in the Sertoli cells of the cryptorchid testis but did not activate phospho-JNK. Neither total p38 nor phospho-p38 was induced by heat stress in the Sertoli cells of the cryptorchid testis. Changes in the spatiotemporal expression of cytokeratin 18 (CK18), a marker of immature or undifferentiated Sertoli cells, were induced in the cryptorchid testis in a pattern similar to the activation of ERK1/2. Condusion: The activation of ERK1/2 in the testis may be related to dedifferentiation of Sertoli cells under heat stress induced by experimental cryptorchidism.