The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of ef...The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such patients.Despite the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more broadly.Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury.Such an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to humans.This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation.In addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.展开更多
Nonhuman primates （NHPs） provide powerful experimental models to study human development, cognitive functions and disturbances as well as complex behavior, because of their genetic and physiological similarities to ...Nonhuman primates （NHPs） provide powerful experimental models to study human development, cognitive functions and disturbances as well as complex behavior, because of their genetic and physiological similarities to humans. Therefore, NHPs are appropriate models for the study of human diseases, such as neurodegenerative diseases including Parkinson＇s, Alzheimer＇s and Huntington＇s diseases, which occur as a result of genetic mutations. However, such diseases afflicting humans do not occur naturally in NHPs. So transgenic NHPs need to be established to understand the etiology of disease pathology and pathogenesis. Compared to rodent genetic models, the generation of transgenic NHPs for human diseases is inefficient, and only a transgenic monkey model for Huntington＇s disease has been reported. This review focuses on potential approaches and contributing factors for generating transgenic NHPs to study human diseases.展开更多
Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested c...Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.展开更多
Animal model is an essential tool in the life sciences research, notably in understanding the pathogenesis of the diseases and for further therapeutic intervention success. Rodents have been the most frequently used a...Animal model is an essential tool in the life sciences research, notably in understanding the pathogenesis of the diseases and for further therapeutic intervention success. Rodents have been the most frequently used animals to model human disease since the establishment of gene manipulation technique. However, they remain inadequate to fully mimic the pathophysiology of human brain disease, partially due to huge differences between rodents and humans in terms of anatomy, brain function, and social behaviors. Nonhuman primates are more suitable in translational perspective. Thus, genetically modified animals have been generated to investigate neurologic and psychiatric disorders. The classical transgenesis technique is not efficient in that model; so, viral vector-mediated transgene delivery and the new genome-editing technologies have been promoted. In this review, we summarize some of the technical progress in the generation of an ad hoc animal model of brain diseases by gene delivery and real transgenic nonhuman primate.展开更多
Virtual simulated environments provide multiple ways of testing cognitive function and evaluatingproblem solving with humans （e.g., Woollett et al. 2009）. The use of such interactive technologyhas increasingly becom...Virtual simulated environments provide multiple ways of testing cognitive function and evaluatingproblem solving with humans （e.g., Woollett et al. 2009）. The use of such interactive technologyhas increasingly become an essential part of modern life （e.g., autonomously driving vehicles, glo-bal positioning systems （GPS）, and touchscreen computers; Chinn and Fairlie 2007; Brown 2011）.While many nonhuman animals have their own forms of technology, such as chimpanzees whocreate and use tools, in captive animal environments the opportunity to actively participate withinteractive technology is not often made available. Exceptions can be found in some state-of-the-art zoos and laboratory facilities （e.g., Mallavarapu and Kuhar 2005）. When interactive technologyis available, captive animals often selectively choose to engage with it. This enhances the animal＇ssense of control over their immediate surroundings （e.g., Clay et al. 2011; Ackerman 2012）. Suchself-efficacy may help to fulfill basic requirements in a species＇ daily activities using problem solv-ing that can involve foraging and other goal-oriented behaviors. It also assists in fulfilling thestrong underlying motivation for contrafreeloading and exploration expressed behaviorally bymany species in captivity （Young 1999）. Moreover, being able to present nonhuman primates vir-tual reality environments under experimental conditions provides the opportunity to gain insightinto their navigational abilities and spatial cognition. It allows for insight into the generation andapplication of internal mental representations of landmarks and environments under multiple con-ditions （e.g., small- and large-scale space） and subsequent spatial behavior. This paper reviewsmethods using virtual reality developed to investigate the spatial cognitive abilities of nonhumanprimates, and great apes in particular, in comparison with that of humans of multiple age groups.We make recommendations about training, best practices, and also pitfalls to avoid.展开更多
No study has reported the safety, effectiveness, and consistency of endovascular middle cerebral artery occlusion in a chronic cerebral ischemia model. Nor have studies verified the safest and most effective segment, ...No study has reported the safety, effectiveness, and consistency of endovascular middle cerebral artery occlusion in a chronic cerebral ischemia model. Nor have studies verified the safest and most effective segment, or branch, in the embolic middle cerebral artery. In this experiment, cerebral infarction models were established at M1, and on the upper and lower trunks on the contralateral side of the handedness of rhesus monkeys by using endovascular intervention. The results confirmed a high animal survival rate in stroke models of middle cerebral artery upper trunk occlusion. There was pronounced paralysis at the acute phase, long-term upper extremity dysfunction at the chronic phase, and the models showed good repeatability and consistency. Thus, this study describes a safe and effective model of chronic stroke.展开更多
The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acu...The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acute phase proteins in zoo animals,particularly in nonhuman primates and feline carnivores was evaluate.Results showed that hCRP and vSAA methods were applicable to measure CRP and SAA in Haplorhini.There was a highly signifcant correlation between both parameters with remarkably high correlation coefcient.A higher proportion of Bonnet macaques in Haplorhini,and the linear regression with good correlation between hCRP and vSAA levels were observed.Reference values in healthy Bonnet macaques were hCRP(46.86±30.97 nmol/L)and vSAA(9.06±1.95μg/mL).Although Ring-tailed lemur,which belonging to Strepsirrhini,showed low vSAA concentrations(reference values:1.08±0.47μg/mL),vSAA in patients was apparently elevated.The vCRP and vSAA methods were applicable to measurements of CRP and SAA in feline carnivores for highly signifcant correlation between both parameters.Theses two methods were also been deteded in lions,tigers and cheetahs.vSAA assays can be applied to measure SAA levels in other carnivores and herbivores.In conclusion,vSAA systems have potential utility as diagnostic tools for health screening and prediction in zoo animals.展开更多
Advanced atherosclerotic lesions and vascular calcification substantially increase the risk of cardiovascular events.However,effective strategies for preventing or treating advanced atherosclerosis and calcification a...Advanced atherosclerotic lesions and vascular calcification substantially increase the risk of cardiovascular events.However,effective strategies for preventing or treating advanced atherosclerosis and calcification are currently lacking.This study investigated the efficacy of DT-109(Gly-Gly-Leu)in attenuating atherosclerosis and calcification in nonhuman primates,exploring its broader therapeutic potential.In this study,twenty male cynomolgus monkeys were administered a cholesterol-rich diet ad libitum for 10 months.Then,the animals were treated either orally with DT-109(150 mg/kg/day)or a vehicle(H2O)for 5 months while continuing on the same diet.Plasma lipid levels were measured monthly and at the end of the experiment,pathological examinations of the aortas and coronary arteries and RNA sequencing of the coronary arteries were performed.To explore possible molecular mechanisms,the effects of DT-109 on smooth muscle cells(SMCs)were examined in vitro.We found that DT-109 administration significantly suppressed atherosclerotic lesion formation in both the aorta and coronary arteries.Pathological examinations revealed that DT-109 treatment reduced lesional macrophage content and calcification.RNA sequencing analysis showed that DT-109 treatment significantly downregulated the pro-inflammatory factors NLRP3,AIM2,and CASP1,the oxidative stress factors NCF2 and NCF4,and the osteogenic factors RUNX2,COL1A1,MMP2,and MMP9,while simultaneously upregulating the expression of the SMCs contraction markers ACTA2,CNN1,and TAGLN.Furthermore,DT-109 inhibited SMC calcification and NLRP3 inflammasome activation in vitro.These results demonstrate that DT-109 effectively suppresses both atherosclerosis and calcification.These findings,in conjunction with insights from our previous studies,position DT-109 as a novel multifaceted therapeutic agent for cardiovascular diseases.展开更多
Dysphagia is a common complication of stroke,Parkinson's disease(PD),and amyotrophic lateral sclerosis(ALS).The construction of animal models of dysphagia is an important way to explore its pathogenesis and treatm...Dysphagia is a common complication of stroke,Parkinson's disease(PD),and amyotrophic lateral sclerosis(ALS).The construction of animal models of dysphagia is an important way to explore its pathogenesis and treatment.At present,the animal models of dysphagia mainly include rodents,nonhuman primates,and other mammals,such as pigs and dogs.This review systematically summarizes the establishment and evaluation of dysphagia animal models in stroke,PD,and ALS in three kinds of experimental animals,providing a basis for the selection of appropriate animal models of dysphagia.展开更多
Unlike traditional literature where animals are often portrayed allegorically as mere symbols,in Pulitzer Prize winner Jane Smiley’s The Horses of Oak Valley Ranch series,the portrayal of horses underscores their dis...Unlike traditional literature where animals are often portrayed allegorically as mere symbols,in Pulitzer Prize winner Jane Smiley’s The Horses of Oak Valley Ranch series,the portrayal of horses underscores their distinct individuality and autonomy.Focusing on three novels in the series-A Good Horse,True Blue,and Pie in the Sky,this paper analyzes how Smiley crafts a narrative that resists anthropocentrism and validates the subjectivity of nonhuman animals.By examining the unique reactions of horses in various situations,such as their differing facial expressions before a jump,their various responses to feeding and grooming,and their individualistic moving behaviors,this study reveals how Smiley highlights the psychological and physical diversity within a single species.The horses’individual traits are portrayed not as mere animal instinct but as conscious,intentional responses that signify their agency.Drawing on Marc Bekoff’s defense of animal individuality,Val Plumwood’s condemnation of anthropocentrism,and Cynthia Willett’s critique of speciesism,the paper argues that Smiley’s representation of equine individualistic behaviors is an affirmation of the inherent subjectivity of animals.Through these detailed descriptions,Smiley challenges the Cartesian notion of animals as mere automatons and encourages readers to recognize animals as complex individuals.Ultimately,this study emphasizes the significance of acknowledging animal subjectivity in fostering a more ethical and harmonious human-animal relationship.展开更多
Retinitis pigmentosa(RP)is a form of inherited retinal degenerative diseases that ultimately involves the macula,which is present in primates but not in the rodents.Therefore,creating nonhuman primate(NHP)models of RP...Retinitis pigmentosa(RP)is a form of inherited retinal degenerative diseases that ultimately involves the macula,which is present in primates but not in the rodents.Therefore,creating nonhuman primate(NHP)models of RP is of critical importance to study its mechanism of pathogenesis and to evaluate potential therapeutic options in the future.Here we applied adeno-associated virus(AAV)-delivered CRISPR/SaCas9 technology to knockout the RHO gene in the retinae of the adult rhesus macaque(Macaca mulatta)to investigate the hypothesis whether non-germline mutation of the RHO gene is sufficient to recapitulate RP.Through a series of studies,we were able to demonstrate successful somatic editing of the RHO gene and reduced RHO protein expression.More importantly,the mutant macaque retinae displayed clinical RP phenotypes,including photoreceptor degeneration,retinal thinning,abnormal rod subcellular structures,and reduced photoresponse.Therefore,we suggest somatic editing of the RHO gene is able to phenocopy RP,and the reduced time span in generating NHP mutant accelerates RP research and expands the utility of NHP model for human disease study.展开更多
Background:Reports of natural infections of Schistosoma mansoni in a number of species of nonhuman primates(NHPs)in Africa,coupled with the substantial overlap of NHP habitats and human schistosomiasis endemic areas,h...Background:Reports of natural infections of Schistosoma mansoni in a number of species of nonhuman primates(NHPs)in Africa,coupled with the substantial overlap of NHP habitats and human schistosomiasis endemic areas,has led to concerns about the role of NHPs in the transmission of human schistosomiasis.We conducted a systematic review of the literature to describe the current scope of knowledge for Africa,for the NHP species implicated,their geographical distribution,infection rates with 5.mansoni,and to discuss the implications for public health and conservation.Main text:A systematic search of the literature was performed using PubMed,Web of Science,Google Scholar,the World Health Organization(WHO)library database,World Cat,and ScienceDirect without any language restriction.Studies examining 5.monsoni infeaion of any African NHP species were included.Study types,primate species,their geographical distribution,and parasite diagnostic techniques reported in the studies were qualitatively summarized.Data for species with sample sizes>10 were included in the meta-analysis.We assessed the reported infection rate,and used a random-effeas model to estimate the summary infeaion rates and 95%confidence intervals(C/s).We assessed heterogeneity among studies using the I2 statistics.Twenty-nine publications,from 1960 to 2018,were identified and included in the review.The studies examined a total of 2962 primates belonging to 22 species in 11 genera across ten countries(Cameroon,Eritrea,Ethiopia,Gabon,Kenya,Nigeria,Senegal,Tanzania,Uganda,and Zimbabwe),and 5.mansoni infeaions were found in nine species of five genera in all countries.When we excluded studies with sample sizes<10,data from 24 studies on 11 species of primates in three genera in ten countries remained in the meta-analysis.The overall pooled estimate of infection rate was 10%(95%Cl:6-16%)with high heterogeneity(I^2=9477%)across countries and species/genera.Among the three genera,Pan had the highest infection rate of 15%(95%CI:0-55%),followed by Popio at 11%(95%Cl:6-18%),and Cercopithecus at 5%(95%CI:0-14%).The association between NHP and human infections was positive,but not significant,due to low study sample matches and high variation.Conclusions:Our findings suggest that 5.mansoni infection rate is high in African NHPs,with substantial heterogeneities across spedes/genera and countries in Africa.Given the evidence for potential spillover and spillback of S.mansoni between African NHPs and humans,further research is urgently needed to understand ecology and mechanisms of transmission of the parasite between NHP and human hosts,in order to inform control strategies of this important neglected tropical disease.展开更多
The aim of this article is to form a conceptual framework for analyzing and understanding the latest intermedial practice within the field of new technologies.In order to achieve this,it suggests two converging theore...The aim of this article is to form a conceptual framework for analyzing and understanding the latest intermedial practice within the field of new technologies.In order to achieve this,it suggests two converging theoretical strategies.Firstly,the introduction emphasizes on concept of"excommunication,"coined by Alexander R.Galloway in his 2013 book,in order to provide a better understanding of the scenic mediation that encompasses a great number of contemporary productions.More specifically,by both following and criticizing Galloway’s stance on three different media modalities,a fourth mediation vector will be isolated—The Water Principle—incorporated in the mythology of Neptune.Such a theoretical orientation is primarily guided by an ambition to associate intermedial theory with watery elements that appear in two different stage examples analyzed within this paper.Secondly,two different performances will be analyzed:Romeo Castellucci’s"M.#10 Marseille"(2002)and"Fontaine Boréale"(2018).Prompted by intermedial issues,these two productions question the ontological claims of the human presence on stage by establishing digital stage simulation as a para-performative phenomenon.By analyzing these plays,I will demonstrate that in both examples,the Water Principle delivers a privileged media model through which aesthetic force is achieved.Finally,on a broader level,the paper suggests that the artistic trajectory of these productions calls for a new perspective on the nature of performance;a perspective emphasizing an aesthetics of disappearance and nonhuman structural impact.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
基金supported by Onassis Foundation(to MT)the National Center for Complementary and Integrative Health(NCCIH),No.R21AT008865(to NM)National Institute of Aging(NIA)/National Institute of Mental Health(NIMH),No.R01AG042512(to NM)
文摘The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such patients.Despite the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more broadly.Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury.Such an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to humans.This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation.In addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.
基金supported by the grants from the Major State Basic Development Program(No. 2012CBA01300)the National High Technology Research and Development Program(No.2012AA020701)+1 种基金the National Science and Technology Major Project(No.2009ZX09501- 028)the Social Science and Technology Development Program of Yunnan Province(No.2007GH)
文摘Nonhuman primates （NHPs） provide powerful experimental models to study human development, cognitive functions and disturbances as well as complex behavior, because of their genetic and physiological similarities to humans. Therefore, NHPs are appropriate models for the study of human diseases, such as neurodegenerative diseases including Parkinson＇s, Alzheimer＇s and Huntington＇s diseases, which occur as a result of genetic mutations. However, such diseases afflicting humans do not occur naturally in NHPs. So transgenic NHPs need to be established to understand the etiology of disease pathology and pathogenesis. Compared to rodent genetic models, the generation of transgenic NHPs for human diseases is inefficient, and only a transgenic monkey model for Huntington＇s disease has been reported. This review focuses on potential approaches and contributing factors for generating transgenic NHPs to study human diseases.
基金supported by the National Natural Science Foundation of China,No.81000852 and 81301677the AHA Award,No.17POST32530004+1 种基金the Supporting Project of Science & Technology of Sichuan Province of China,No.2012SZ0140the Research Foundation of Zhejiang Province of China,No.201022896
文摘Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.
文摘Animal model is an essential tool in the life sciences research, notably in understanding the pathogenesis of the diseases and for further therapeutic intervention success. Rodents have been the most frequently used animals to model human disease since the establishment of gene manipulation technique. However, they remain inadequate to fully mimic the pathophysiology of human brain disease, partially due to huge differences between rodents and humans in terms of anatomy, brain function, and social behaviors. Nonhuman primates are more suitable in translational perspective. Thus, genetically modified animals have been generated to investigate neurologic and psychiatric disorders. The classical transgenesis technique is not efficient in that model; so, viral vector-mediated transgene delivery and the new genome-editing technologies have been promoted. In this review, we summarize some of the technical progress in the generation of an ad hoc animal model of brain diseases by gene delivery and real transgenic nonhuman primate.
文摘Virtual simulated environments provide multiple ways of testing cognitive function and evaluatingproblem solving with humans （e.g., Woollett et al. 2009）. The use of such interactive technologyhas increasingly become an essential part of modern life （e.g., autonomously driving vehicles, glo-bal positioning systems （GPS）, and touchscreen computers; Chinn and Fairlie 2007; Brown 2011）.While many nonhuman animals have their own forms of technology, such as chimpanzees whocreate and use tools, in captive animal environments the opportunity to actively participate withinteractive technology is not often made available. Exceptions can be found in some state-of-the-art zoos and laboratory facilities （e.g., Mallavarapu and Kuhar 2005）. When interactive technologyis available, captive animals often selectively choose to engage with it. This enhances the animal＇ssense of control over their immediate surroundings （e.g., Clay et al. 2011; Ackerman 2012）. Suchself-efficacy may help to fulfill basic requirements in a species＇ daily activities using problem solv-ing that can involve foraging and other goal-oriented behaviors. It also assists in fulfilling thestrong underlying motivation for contrafreeloading and exploration expressed behaviorally bymany species in captivity （Young 1999）. Moreover, being able to present nonhuman primates vir-tual reality environments under experimental conditions provides the opportunity to gain insightinto their navigational abilities and spatial cognition. It allows for insight into the generation andapplication of internal mental representations of landmarks and environments under multiple con-ditions （e.g., small- and large-scale space） and subsequent spatial behavior. This paper reviewsmethods using virtual reality developed to investigate the spatial cognitive abilities of nonhumanprimates, and great apes in particular, in comparison with that of humans of multiple age groups.We make recommendations about training, best practices, and also pitfalls to avoid.
基金the National Key Technology Research and Development Program during Eleventh Five-Year Plan, No. 2006BAI01A14
文摘No study has reported the safety, effectiveness, and consistency of endovascular middle cerebral artery occlusion in a chronic cerebral ischemia model. Nor have studies verified the safest and most effective segment, or branch, in the embolic middle cerebral artery. In this experiment, cerebral infarction models were established at M1, and on the upper and lower trunks on the contralateral side of the handedness of rhesus monkeys by using endovascular intervention. The results confirmed a high animal survival rate in stroke models of middle cerebral artery upper trunk occlusion. There was pronounced paralysis at the acute phase, long-term upper extremity dysfunction at the chronic phase, and the models showed good repeatability and consistency. Thus, this study describes a safe and effective model of chronic stroke.
文摘The feasibility of a commercially available assay for C-reactive protein(CRP,CRP for humans:hCRP,and CRP for dogs:vCRP)and a trial reagent of serum amyloid A(SAA,vSAA for animals)were applied to the measurement of acute phase proteins in zoo animals,particularly in nonhuman primates and feline carnivores was evaluate.Results showed that hCRP and vSAA methods were applicable to measure CRP and SAA in Haplorhini.There was a highly signifcant correlation between both parameters with remarkably high correlation coefcient.A higher proportion of Bonnet macaques in Haplorhini,and the linear regression with good correlation between hCRP and vSAA levels were observed.Reference values in healthy Bonnet macaques were hCRP(46.86±30.97 nmol/L)and vSAA(9.06±1.95μg/mL).Although Ring-tailed lemur,which belonging to Strepsirrhini,showed low vSAA concentrations(reference values:1.08±0.47μg/mL),vSAA in patients was apparently elevated.The vCRP and vSAA methods were applicable to measurements of CRP and SAA in feline carnivores for highly signifcant correlation between both parameters.Theses two methods were also been deteded in lions,tigers and cheetahs.vSAA assays can be applied to measure SAA levels in other carnivores and herbivores.In conclusion,vSAA systems have potential utility as diagnostic tools for health screening and prediction in zoo animals.
基金partially supported by the National Key R&D Program of China(No.2020YFA0803700)National Natural Science Foundation of China(No.81970425 and No.81941001)+6 种基金Natural Science Foundation of Shaanxi Province(No.2020PT-001)Innovation team program supported by Guangdong Province(2020KCXTD038)Guangdong Province Key Program of Discipline(2021ZDJS091)National Key Research and Development Program of China(2022YFA1105403)Science and Technology Planning Project of Guangdong Province(2021A1515110916)the Hong Kong-Macao Joint Research and Development Fund of Wuyi UniversityFrederick G.L.Huetwell Endowed Professor of Cardiovascular Medicine at University of Michigan(Y.E.C.).
文摘Advanced atherosclerotic lesions and vascular calcification substantially increase the risk of cardiovascular events.However,effective strategies for preventing or treating advanced atherosclerosis and calcification are currently lacking.This study investigated the efficacy of DT-109(Gly-Gly-Leu)in attenuating atherosclerosis and calcification in nonhuman primates,exploring its broader therapeutic potential.In this study,twenty male cynomolgus monkeys were administered a cholesterol-rich diet ad libitum for 10 months.Then,the animals were treated either orally with DT-109(150 mg/kg/day)or a vehicle(H2O)for 5 months while continuing on the same diet.Plasma lipid levels were measured monthly and at the end of the experiment,pathological examinations of the aortas and coronary arteries and RNA sequencing of the coronary arteries were performed.To explore possible molecular mechanisms,the effects of DT-109 on smooth muscle cells(SMCs)were examined in vitro.We found that DT-109 administration significantly suppressed atherosclerotic lesion formation in both the aorta and coronary arteries.Pathological examinations revealed that DT-109 treatment reduced lesional macrophage content and calcification.RNA sequencing analysis showed that DT-109 treatment significantly downregulated the pro-inflammatory factors NLRP3,AIM2,and CASP1,the oxidative stress factors NCF2 and NCF4,and the osteogenic factors RUNX2,COL1A1,MMP2,and MMP9,while simultaneously upregulating the expression of the SMCs contraction markers ACTA2,CNN1,and TAGLN.Furthermore,DT-109 inhibited SMC calcification and NLRP3 inflammasome activation in vitro.These results demonstrate that DT-109 effectively suppresses both atherosclerosis and calcification.These findings,in conjunction with insights from our previous studies,position DT-109 as a novel multifaceted therapeutic agent for cardiovascular diseases.
基金National Natural Science Foundation of China,Grant/Award Number:82172531Joint Funds for the Innovation of Science and Technology,Fujian Province,Grant/Award Number:2021Y9105。
文摘Dysphagia is a common complication of stroke,Parkinson's disease(PD),and amyotrophic lateral sclerosis(ALS).The construction of animal models of dysphagia is an important way to explore its pathogenesis and treatment.At present,the animal models of dysphagia mainly include rodents,nonhuman primates,and other mammals,such as pigs and dogs.This review systematically summarizes the establishment and evaluation of dysphagia animal models in stroke,PD,and ALS in three kinds of experimental animals,providing a basis for the selection of appropriate animal models of dysphagia.
文摘Unlike traditional literature where animals are often portrayed allegorically as mere symbols,in Pulitzer Prize winner Jane Smiley’s The Horses of Oak Valley Ranch series,the portrayal of horses underscores their distinct individuality and autonomy.Focusing on three novels in the series-A Good Horse,True Blue,and Pie in the Sky,this paper analyzes how Smiley crafts a narrative that resists anthropocentrism and validates the subjectivity of nonhuman animals.By examining the unique reactions of horses in various situations,such as their differing facial expressions before a jump,their various responses to feeding and grooming,and their individualistic moving behaviors,this study reveals how Smiley highlights the psychological and physical diversity within a single species.The horses’individual traits are portrayed not as mere animal instinct but as conscious,intentional responses that signify their agency.Drawing on Marc Bekoff’s defense of animal individuality,Val Plumwood’s condemnation of anthropocentrism,and Cynthia Willett’s critique of speciesism,the paper argues that Smiley’s representation of equine individualistic behaviors is an affirmation of the inherent subjectivity of animals.Through these detailed descriptions,Smiley challenges the Cartesian notion of animals as mere automatons and encourages readers to recognize animals as complex individuals.Ultimately,this study emphasizes the significance of acknowledging animal subjectivity in fostering a more ethical and harmonious human-animal relationship.
基金the National Key Research and Development Program of China(2020YFA0112200,2016YFA0400900,and 2018YFA0801403)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16020603,XDB39000000,and XDB32060200)+3 种基金the National Natural Science Foundation of China(81925009,81790644,61890953,31322024,81371066,91432104,81900855,31900712,and 31800901)Guangdong Provincial Key Research and Development Program(2019B030335001 and 2018B030338001)Anhui Provincial Natural Science Foundation(1808085MH289 and 1908085MC66)the Fundamental Research Funds for the Central Universities(WK2070000174 and WK2090050048)。
文摘Retinitis pigmentosa(RP)is a form of inherited retinal degenerative diseases that ultimately involves the macula,which is present in primates but not in the rodents.Therefore,creating nonhuman primate(NHP)models of RP is of critical importance to study its mechanism of pathogenesis and to evaluate potential therapeutic options in the future.Here we applied adeno-associated virus(AAV)-delivered CRISPR/SaCas9 technology to knockout the RHO gene in the retinae of the adult rhesus macaque(Macaca mulatta)to investigate the hypothesis whether non-germline mutation of the RHO gene is sufficient to recapitulate RP.Through a series of studies,we were able to demonstrate successful somatic editing of the RHO gene and reduced RHO protein expression.More importantly,the mutant macaque retinae displayed clinical RP phenotypes,including photoreceptor degeneration,retinal thinning,abnormal rod subcellular structures,and reduced photoresponse.Therefore,we suggest somatic editing of the RHO gene is able to phenocopy RP,and the reduced time span in generating NHP mutant accelerates RP research and expands the utility of NHP model for human disease study.
基金SL is supported in part by the National Institutes of Health(grant R01AI125842)and a grant from the World Health OrganizationPublication of this article was funded in part by the University of Florida Open Access Publishing Fund.
文摘Background:Reports of natural infections of Schistosoma mansoni in a number of species of nonhuman primates(NHPs)in Africa,coupled with the substantial overlap of NHP habitats and human schistosomiasis endemic areas,has led to concerns about the role of NHPs in the transmission of human schistosomiasis.We conducted a systematic review of the literature to describe the current scope of knowledge for Africa,for the NHP species implicated,their geographical distribution,infection rates with 5.mansoni,and to discuss the implications for public health and conservation.Main text:A systematic search of the literature was performed using PubMed,Web of Science,Google Scholar,the World Health Organization(WHO)library database,World Cat,and ScienceDirect without any language restriction.Studies examining 5.monsoni infeaion of any African NHP species were included.Study types,primate species,their geographical distribution,and parasite diagnostic techniques reported in the studies were qualitatively summarized.Data for species with sample sizes>10 were included in the meta-analysis.We assessed the reported infection rate,and used a random-effeas model to estimate the summary infeaion rates and 95%confidence intervals(C/s).We assessed heterogeneity among studies using the I2 statistics.Twenty-nine publications,from 1960 to 2018,were identified and included in the review.The studies examined a total of 2962 primates belonging to 22 species in 11 genera across ten countries(Cameroon,Eritrea,Ethiopia,Gabon,Kenya,Nigeria,Senegal,Tanzania,Uganda,and Zimbabwe),and 5.mansoni infeaions were found in nine species of five genera in all countries.When we excluded studies with sample sizes<10,data from 24 studies on 11 species of primates in three genera in ten countries remained in the meta-analysis.The overall pooled estimate of infection rate was 10%(95%Cl:6-16%)with high heterogeneity(I^2=9477%)across countries and species/genera.Among the three genera,Pan had the highest infection rate of 15%(95%CI:0-55%),followed by Popio at 11%(95%Cl:6-18%),and Cercopithecus at 5%(95%CI:0-14%).The association between NHP and human infections was positive,but not significant,due to low study sample matches and high variation.Conclusions:Our findings suggest that 5.mansoni infection rate is high in African NHPs,with substantial heterogeneities across spedes/genera and countries in Africa.Given the evidence for potential spillover and spillback of S.mansoni between African NHPs and humans,further research is urgently needed to understand ecology and mechanisms of transmission of the parasite between NHP and human hosts,in order to inform control strategies of this important neglected tropical disease.
文摘The aim of this article is to form a conceptual framework for analyzing and understanding the latest intermedial practice within the field of new technologies.In order to achieve this,it suggests two converging theoretical strategies.Firstly,the introduction emphasizes on concept of"excommunication,"coined by Alexander R.Galloway in his 2013 book,in order to provide a better understanding of the scenic mediation that encompasses a great number of contemporary productions.More specifically,by both following and criticizing Galloway’s stance on three different media modalities,a fourth mediation vector will be isolated—The Water Principle—incorporated in the mythology of Neptune.Such a theoretical orientation is primarily guided by an ambition to associate intermedial theory with watery elements that appear in two different stage examples analyzed within this paper.Secondly,two different performances will be analyzed:Romeo Castellucci’s"M.#10 Marseille"(2002)and"Fontaine Boréale"(2018).Prompted by intermedial issues,these two productions question the ontological claims of the human presence on stage by establishing digital stage simulation as a para-performative phenomenon.By analyzing these plays,I will demonstrate that in both examples,the Water Principle delivers a privileged media model through which aesthetic force is achieved.Finally,on a broader level,the paper suggests that the artistic trajectory of these productions calls for a new perspective on the nature of performance;a perspective emphasizing an aesthetics of disappearance and nonhuman structural impact.
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.
