Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and behavior.These advanced neuromodulatio...Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and behavior.These advanced neuromodulation techniques offer accurate manipulation of targeted areas,even selectively modulating specific neurons,in the brain.This makes it possible to investigate the cause-and-effect connections between neural activity and behavior,allowing for a better comprehension of the intricate brain dynamics towards complex environments.Non-human primates serve as an essential animal model for investigating these complex functions in brain research,bridging the gap between the basic research and clinical applications.One of the earliest optical studies utilizing optogenetic neuromodulation in monkeys was conducted in 2009.Since then,the optical-neural stimulations have been effectively applied in non-human primates.This review summarises recent research that employed optogenetics or infrared neurostimulation techniques to regulate brain function and behavior in non-human primates.The current state of optical-neural stimulations discussed here demonstrates their efficacy in advancing the understanding of brain systems.Nevertheless,there are still challenges that need to be addressed before they can fully achieve their potential.展开更多
Cancer is the second leading disease causing human death.Pre-clinical in vivo studies are essential for translating in vitro laboratory research results into the clinic.Rodents,including the mouse and rat,have been wi...Cancer is the second leading disease causing human death.Pre-clinical in vivo studies are essential for translating in vitro laboratory research results into the clinic.Rodents,including the mouse and rat,have been widely used for pre-clinical studies due to their small size,clear genetic backgrounds,rapid propagation,and mature transgenic technologies.However,because rodents are evolutionarily distinct from humans,many pre-clinical research results using rodent models cannot be reproduced in the clinic.Non-human primates(NHPs) may be better animal models than rodents for human cancer research because NHPs and humans share greater similarity in regards to their genetic evolution,immune system,physiology and metabolism.This article reviews the latest progress of cancer research in NHPs by focusing on the carcinogenesis of different NHPs induced by chemical and biological carcinogens.Finally,future research directions for the use of NHPs in cancer research are discussed.展开更多
Most extant nonhuman primates occasionally prey on fast-moving, warm-blooded animals; however, Indriidae, Lepilemuridae, and Colobinae either scavenged for meat or did not eat meat at all. Here we report six cases of ...Most extant nonhuman primates occasionally prey on fast-moving, warm-blooded animals; however, Indriidae, Lepilemuridae, and Colobinae either scavenged for meat or did not eat meat at all. Here we report six cases of animal consumption by the snub-nosed monkey Rhinopithecus bieti in a wild, habituated group between 2004 and 2009 in Yunnan, China. At present, only males in an all-male unit within the study group were involved in active hunting. Such a male-biased activity may be related to the group structure and spatial spread of R. bieti. Two females were observed eating freshly killed birds. The findings confirmed that R. bieti engaged in scavenging and, when hunting, employed a cranio-cervical bite to kill their prey. Meat eating is likely a nutrient maximization feeding strategy in R. bieti, especially in males. A begging behavior occurred after successful prey capture. Although begging was observed, no sharing of the meat was seen. The present findings illuminate the dietary diversity of R. bieti and their ability to expand their dietary spectrum.展开更多
Self-directed behavior(SDB) is characterized as an indicator of anxiety, frustration and stress in nonhuman primates. In this study, we collected self-directed behavior data from one group of free-ranging Tibetan maca...Self-directed behavior(SDB) is characterized as an indicator of anxiety, frustration and stress in nonhuman primates. In this study, we collected self-directed behavior data from one group of free-ranging Tibetan macaques(Macaca thibetana) at Mt. Huangshan, China(September 2012–May 2013) using a combination of behavioral sampling methods including focal animal sampling, behavioral sampling, continuous sampling and instantaneous sampling. Our results showed that females engaged in significantly higher rates of self-directed behavior when they were in proximity to dominant individuals compared to subordinate ones. Conflict losers significantly increased their SDB rates after agonistic episodes, indicating that SDB might also serve as an index of anxiety in M. thibetana. We further found that females significantly increased their SDB rates when focal individual was proximity to weakly affiliation relationship higher rank members than to strongly affiliation relationship higher rank members. If conflicts were not reconciled, the postconflict SDB rates of losers were higher when they stayed with strongly affiliation opponents; if conflicts were reconciled, victims of strongly affiliation relationships opponents engaged in more SDB rates before reconciliation than after reconciliation, while victims of moderately affiliation relationships opponents did not engaged in more SDB rates before reconciliation than after reconciliation. We conclude that both of dominance rank and affiliation relationships might both influence the SDB rates of female Tibetan macaques significantly, suggesting that SDB is not only an index of anxiety in Tibetan macaques, but also can provide a new insight into evaluation of social relationships between individuals.展开更多
Strategies to fill the huge gap in supply versus demand of human organs include bioartificial organs, growing humanized organs in animals, cell therapy, and implantable bioengineered constructs. Reproducing the comple...Strategies to fill the huge gap in supply versus demand of human organs include bioartificial organs, growing humanized organs in animals, cell therapy, and implantable bioengineered constructs. Reproducing the complex relations between different cell types, generation of adequate vasculature, and immunological complications are road blocks in generation of bioengineered organs, while immunological complications limit the use of humanized organs produced in animals. Recent developments in induced pluripotent stem cell (iPSC) biology offer a possibility of generating human, patient-specific organs in non-human primates (NHP) using patient-derived iPSC and NHP-derived iPSC lacking the critical developmental genes for the organ of interest complementing a NHP tetraploid embryo. The organ derived in this way will have the same human leukocyte antigen (HLA) profile as the patient. This approach can be curative in genetic disorders as this offers the possibility of gene manipulation and correction of the patient's genome at the iPSC stage before tetraploid complementation. The process of generation of patient-specific organs such as the liver in this way has the great advantage of making use of the natural signaling cascades in the natural milieu probably resulting in organs of great quality for transplantation. However, the inexorable scientific developments in this direction involve several social issues and hence we need to educate and prepare society in advance to accept the revolutionary consequences, good, bad and ugly.展开更多
Filoviruses are hemorrhagic fever viruses endemic to parts of Africa and the Philippines. Infection carries with it a mortality rate of up to 90% and currently there are no effective vaccines or therapeutics available...Filoviruses are hemorrhagic fever viruses endemic to parts of Africa and the Philippines. Infection carries with it a mortality rate of up to 90% and currently there are no effective vaccines or therapeutics available to combat infection. However, the filovirus virus-like particles (VLP), which are currently under development, have been shown to be a promising vaccine candidate. They provide protection from infection in the mouse, guinea pig, and nonhuman primate models of infection, eliciting high anti-glycoprotein antibody titers and T cell responses to viral proteins. In this review, we will highlight the development of the filovirus VLP and describe the current understanding of VLP immunogenicity and correlates of protection.展开更多
In animal societies, some stressful events can lead to higher levels of physiological stress. Such stressors, like social rank, also predict an increased vulnerability to an array of diseases. However, the physiologic...In animal societies, some stressful events can lead to higher levels of physiological stress. Such stressors, like social rank, also predict an increased vulnerability to an array of diseases. However, the physiological relationship between social rank and stress varies between different species, as well as within groups of a single species. For example, dominant individuals are more socially stressed at times, while at other times it is the subordinate ones who experience this stress. Together, these variations make it difficult to assess disease vulnerability as connected to social interactions. In order to learn more about how physiological rank relationships vary between groups of a single species, cortisol measurements from hair samples were used to evaluate the effects of dominance rank on long-term stress levels in despotic and less stringent female rhesus macaque hierarchal groups. In despotic groups, cortisol levels were found not to be correlated with social rank, but a negative correlation was found between social rank and cortisol levels in less stringent hierarchies. Low ranking monkeys in less stringent groups secreted elevated levels of cortisol compared to higher ranking animals. These data suggest that variations in the strictness of the dominance hierarchy are determining factors in rank related stress physiology. The further consideration of nonhuman primate social system diversity and the linear degree of their hierarchies may allow for the development of valid rank-related stress models that will help increase our understanding and guide the development of new therapeutics for diseases related to human socioeconomic status.展开更多
This paper presents some human-inspired strategies for lighting control in a robot system for best scene interpretation,where the main intention is to avoid possible glares or highlights occurring in images. It firstl...This paper presents some human-inspired strategies for lighting control in a robot system for best scene interpretation,where the main intention is to avoid possible glares or highlights occurring in images. It firstly compares the characteristics of human eyes and robot eyes. Then some evaluation criteria are addressed to assess the lighting conditions. A bio-inspired method is adopted to avoid the visual glare which is caused by either direct illumination from large light sources or indirect illumination reflected by smooth surfaces. Appropriate methods are proposed to optimize the pose and optical parameters of the light source and the vision camera.展开更多
Clothing is the human culture and the historical development of the witness, also the combination of human science and new technology and the art of the perfect embodiment. In the modem fashion design, No color depart...Clothing is the human culture and the historical development of the witness, also the combination of human science and new technology and the art of the perfect embodiment. In the modem fashion design, No color department -- has been like a flag stand at the top of the fashion.. No color clothing brand has a good plasticity and explores the market potential. This is no color system as never eliminate color elements and design inspiration in widespread use in the clothing design by designers.展开更多
Nonhuman culture was first considered in nonhuman primates because they are genetically similar to humans. How- ever, evolution is not progressive and therefore many species may occupy niches that favor socially trans...Nonhuman culture was first considered in nonhuman primates because they are genetically similar to humans. How- ever, evolution is not progressive and therefore many species may occupy niches that favor socially transmitted, group specific behavior. Not surprisingly, evidence for culture has accrued in several taxonomic groups, including cetaceans. If culture is an ada- ptation, it is imperative we understand the factors that favor its formation. Understanding the evolutionary origin of culture will allow for a wider range of species to be studied, including those that are difficult to test in the laboratory. I propose a broad-based functional paradigm for evaluating nonhuman culture; based on the idea that while not all cultural behaviors may garner fitness benefits to the individual, the ecological and social environments in which cultural behaviors evolved must have favored the physical attributes and social learning capabilities that allow for cultural formation. Specifically this framework emphasizes the relationships between social learning, ecology, social systems, and biology in relation to culture. I illustrate the utility of the func- tional paradigm with evidence from the ceteacean group, while setting the stage for a stringent species by species analysis. By means of contextualizing culture, the Functional Paradigm can evaluate a species' potential to exhibit culture and can investigate potentially cultural behaviors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
p53 is a transcription factor that governs numerous stress response pathways within the ceil. Maintaining the right levels of p53 is crucial for ceil survival and proper cellular homeostasis, The tight regulation of p...p53 is a transcription factor that governs numerous stress response pathways within the ceil. Maintaining the right levels of p53 is crucial for ceil survival and proper cellular homeostasis, The tight regulation of p53 involves many cellular components, most notably its major negative regulators Mdm2 and Mdm4, which maintain p53 protein amount and activity in tight check, microRNAs (miRNAs) are small non-coding RNAs that target specific mRNAs to translational arrest and degradation, miRNAs are also key compo- nents of the normal p53 pathway, joining forces with Mdm2 and Mdm4 to maintain proper p53 activity. Here we review the current knowledge of miRNAs targeting Mdm2 and Mdm4, and their importance in different tissues and in pathological states such as cancer. In addition, we address the role of Alu sequences-highly abundant retroelements spread throughout the human genome, and their impact on gene regulation via the miRNA machinery. Aius occupy a significant portion of genes' 31UTR, and as such they have the potential to impact mRNA regulation. Since Alus are primate-specific, they introduce a new regulatory layer into primate genomes. Atus can influence and alter gene regulation, creating primate-specific cancer-preventive regulatory mechanisms to sustain the transition to longer life span in primates. We review the possible influence of Alu sequences on miRNA functionality in general and specifically within the p53 network.展开更多
Black capuchin monkeys Sapajus nigritus are among several mammalian species that damage forest plantations, pri- marily plantations of pine trees (Pinus spp.) in South Brazil. Management practices to reduce these da...Black capuchin monkeys Sapajus nigritus are among several mammalian species that damage forest plantations, pri- marily plantations of pine trees (Pinus spp.) in South Brazil. Management practices to reduce these damages include supplemen- tary food offerings and plantation surveillance. To assess the efficiency of these techniques, four treatments were evaluated: feeding (F, with supplementary bananas and maize), surveillance (S, in situ, wherein men patrolled the plantations, deterring the monkeys), feeding + surveillance (FS) and control (no procedures) (C). The efficiency assessment of each treatment involved the number of recorded primate sightings in the treatments with the presence of guards (S and FS) and a damage inventory of the outskirts of the experimental points immediately before and after the experiment. These data were complemented by a simulta- neous study of the availability of fruit, the primary item in the diet of this primate species, in the remnant native forest in the study area. Most sightings of S. nigritus occurred early in the morning, and in general, sightings were inversely proportional to the availability of native fruits. This trend was most evident in treatment FS, most likely due to the presence of food. Treatments F and FS exhibited higher percentages of damage, indicating that these are inefficient management techniques. Treatment S exhi- bited the lowest damage rate, but at a high cost, making this technique difficult to apply over large expanses. The development of other management techniques, such as environmental enrichment and the use of deterrents, is recommended to minimize the damage caused by capuchins in forest plantations [Current Zoology 60 (5): 581-590, 2014].展开更多
文摘Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and behavior.These advanced neuromodulation techniques offer accurate manipulation of targeted areas,even selectively modulating specific neurons,in the brain.This makes it possible to investigate the cause-and-effect connections between neural activity and behavior,allowing for a better comprehension of the intricate brain dynamics towards complex environments.Non-human primates serve as an essential animal model for investigating these complex functions in brain research,bridging the gap between the basic research and clinical applications.One of the earliest optical studies utilizing optogenetic neuromodulation in monkeys was conducted in 2009.Since then,the optical-neural stimulations have been effectively applied in non-human primates.This review summarises recent research that employed optogenetics or infrared neurostimulation techniques to regulate brain function and behavior in non-human primates.The current state of optical-neural stimulations discussed here demonstrates their efficacy in advancing the understanding of brain systems.Nevertheless,there are still challenges that need to be addressed before they can fully achieve their potential.
基金supported in part by a grant from Yunnan Province High-Profile Talent Project 2010CI114grants from Chinese Academy of Sciences(Basic frontier project,KSCX2-EW-J-23)~~
文摘Cancer is the second leading disease causing human death.Pre-clinical in vivo studies are essential for translating in vitro laboratory research results into the clinic.Rodents,including the mouse and rat,have been widely used for pre-clinical studies due to their small size,clear genetic backgrounds,rapid propagation,and mature transgenic technologies.However,because rodents are evolutionarily distinct from humans,many pre-clinical research results using rodent models cannot be reproduced in the clinic.Non-human primates(NHPs) may be better animal models than rodents for human cancer research because NHPs and humans share greater similarity in regards to their genetic evolution,immune system,physiology and metabolism.This article reviews the latest progress of cancer research in NHPs by focusing on the carcinogenesis of different NHPs induced by chemical and biological carcinogens.Finally,future research directions for the use of NHPs in cancer research are discussed.
基金granted by the key project of NSFC (No.30630016)the 973 Program (2007CB411600)+1 种基金the project of NSFC (No.30970442) China Program of TNC
文摘Most extant nonhuman primates occasionally prey on fast-moving, warm-blooded animals; however, Indriidae, Lepilemuridae, and Colobinae either scavenged for meat or did not eat meat at all. Here we report six cases of animal consumption by the snub-nosed monkey Rhinopithecus bieti in a wild, habituated group between 2004 and 2009 in Yunnan, China. At present, only males in an all-male unit within the study group were involved in active hunting. Such a male-biased activity may be related to the group structure and spatial spread of R. bieti. Two females were observed eating freshly killed birds. The findings confirmed that R. bieti engaged in scavenging and, when hunting, employed a cranio-cervical bite to kill their prey. Meat eating is likely a nutrient maximization feeding strategy in R. bieti, especially in males. A begging behavior occurred after successful prey capture. Although begging was observed, no sharing of the meat was seen. The present findings illuminate the dietary diversity of R. bieti and their ability to expand their dietary spectrum.
基金supported by the National Science Foundation of China(31172106,31372215)the Program of University Innovation Team of Anhui Province(TD200703)+1 种基金the Specialized Research Fund for the Master’s Program of Higher Education(01001770-10117700618)the Science Foundation of Anhui Province(1408085QC56)
文摘Self-directed behavior(SDB) is characterized as an indicator of anxiety, frustration and stress in nonhuman primates. In this study, we collected self-directed behavior data from one group of free-ranging Tibetan macaques(Macaca thibetana) at Mt. Huangshan, China(September 2012–May 2013) using a combination of behavioral sampling methods including focal animal sampling, behavioral sampling, continuous sampling and instantaneous sampling. Our results showed that females engaged in significantly higher rates of self-directed behavior when they were in proximity to dominant individuals compared to subordinate ones. Conflict losers significantly increased their SDB rates after agonistic episodes, indicating that SDB might also serve as an index of anxiety in M. thibetana. We further found that females significantly increased their SDB rates when focal individual was proximity to weakly affiliation relationship higher rank members than to strongly affiliation relationship higher rank members. If conflicts were not reconciled, the postconflict SDB rates of losers were higher when they stayed with strongly affiliation opponents; if conflicts were reconciled, victims of strongly affiliation relationships opponents engaged in more SDB rates before reconciliation than after reconciliation, while victims of moderately affiliation relationships opponents did not engaged in more SDB rates before reconciliation than after reconciliation. We conclude that both of dominance rank and affiliation relationships might both influence the SDB rates of female Tibetan macaques significantly, suggesting that SDB is not only an index of anxiety in Tibetan macaques, but also can provide a new insight into evaluation of social relationships between individuals.
文摘Strategies to fill the huge gap in supply versus demand of human organs include bioartificial organs, growing humanized organs in animals, cell therapy, and implantable bioengineered constructs. Reproducing the complex relations between different cell types, generation of adequate vasculature, and immunological complications are road blocks in generation of bioengineered organs, while immunological complications limit the use of humanized organs produced in animals. Recent developments in induced pluripotent stem cell (iPSC) biology offer a possibility of generating human, patient-specific organs in non-human primates (NHP) using patient-derived iPSC and NHP-derived iPSC lacking the critical developmental genes for the organ of interest complementing a NHP tetraploid embryo. The organ derived in this way will have the same human leukocyte antigen (HLA) profile as the patient. This approach can be curative in genetic disorders as this offers the possibility of gene manipulation and correction of the patient's genome at the iPSC stage before tetraploid complementation. The process of generation of patient-specific organs such as the liver in this way has the great advantage of making use of the natural signaling cascades in the natural milieu probably resulting in organs of great quality for transplantation. However, the inexorable scientific developments in this direction involve several social issues and hence we need to educate and prepare society in advance to accept the revolutionary consequences, good, bad and ugly.
基金funded by the Chemical-Biological Medical System-Joint Vaccine Acquisition Program (CBMS-JVAP) as well as the Defense Threat Reduction Agency (DTRA) (CBM.VAXV.03.11.RD.009 and A151 A.41)
文摘Filoviruses are hemorrhagic fever viruses endemic to parts of Africa and the Philippines. Infection carries with it a mortality rate of up to 90% and currently there are no effective vaccines or therapeutics available to combat infection. However, the filovirus virus-like particles (VLP), which are currently under development, have been shown to be a promising vaccine candidate. They provide protection from infection in the mouse, guinea pig, and nonhuman primate models of infection, eliciting high anti-glycoprotein antibody titers and T cell responses to viral proteins. In this review, we will highlight the development of the filovirus VLP and describe the current understanding of VLP immunogenicity and correlates of protection.
基金funded by the National Science Foundation of China (NSFC 31271167, and 31070963)the 973 program (2007CB947703 and 2011CB707800)the Key Program of the Chinese Academy of Sciences, China (KSCX2-EW-R-13)
文摘In animal societies, some stressful events can lead to higher levels of physiological stress. Such stressors, like social rank, also predict an increased vulnerability to an array of diseases. However, the physiological relationship between social rank and stress varies between different species, as well as within groups of a single species. For example, dominant individuals are more socially stressed at times, while at other times it is the subordinate ones who experience this stress. Together, these variations make it difficult to assess disease vulnerability as connected to social interactions. In order to learn more about how physiological rank relationships vary between groups of a single species, cortisol measurements from hair samples were used to evaluate the effects of dominance rank on long-term stress levels in despotic and less stringent female rhesus macaque hierarchal groups. In despotic groups, cortisol levels were found not to be correlated with social rank, but a negative correlation was found between social rank and cortisol levels in less stringent hierarchies. Low ranking monkeys in less stringent groups secreted elevated levels of cortisol compared to higher ranking animals. These data suggest that variations in the strictness of the dominance hierarchy are determining factors in rank related stress physiology. The further consideration of nonhuman primate social system diversity and the linear degree of their hierarchies may allow for the development of valid rank-related stress models that will help increase our understanding and guide the development of new therapeutics for diseases related to human socioeconomic status.
基金supported by the National Natural Science Foundation of China and Microsoft Research Asia ( No.NSFC-61173096 No.61103140),NCET+3 种基金the Science and Technology Department of Zhejiang Province ( No.R1110679 No.2010R10006 No.2010C33095 No.Y1090592)
文摘This paper presents some human-inspired strategies for lighting control in a robot system for best scene interpretation,where the main intention is to avoid possible glares or highlights occurring in images. It firstly compares the characteristics of human eyes and robot eyes. Then some evaluation criteria are addressed to assess the lighting conditions. A bio-inspired method is adopted to avoid the visual glare which is caused by either direct illumination from large light sources or indirect illumination reflected by smooth surfaces. Appropriate methods are proposed to optimize the pose and optical parameters of the light source and the vision camera.
文摘Clothing is the human culture and the historical development of the witness, also the combination of human science and new technology and the art of the perfect embodiment. In the modem fashion design, No color department -- has been like a flag stand at the top of the fashion.. No color clothing brand has a good plasticity and explores the market potential. This is no color system as never eliminate color elements and design inspiration in widespread use in the clothing design by designers.
文摘Nonhuman culture was first considered in nonhuman primates because they are genetically similar to humans. How- ever, evolution is not progressive and therefore many species may occupy niches that favor socially transmitted, group specific behavior. Not surprisingly, evidence for culture has accrued in several taxonomic groups, including cetaceans. If culture is an ada- ptation, it is imperative we understand the factors that favor its formation. Understanding the evolutionary origin of culture will allow for a wider range of species to be studied, including those that are difficult to test in the laboratory. I propose a broad-based functional paradigm for evaluating nonhuman culture; based on the idea that while not all cultural behaviors may garner fitness benefits to the individual, the ecological and social environments in which cultural behaviors evolved must have favored the physical attributes and social learning capabilities that allow for cultural formation. Specifically this framework emphasizes the relationships between social learning, ecology, social systems, and biology in relation to culture. I illustrate the utility of the func- tional paradigm with evidence from the ceteacean group, while setting the stage for a stringent species by species analysis. By means of contextualizing culture, the Functional Paradigm can evaluate a species' potential to exhibit culture and can investigate potentially cultural behaviors
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.
文摘p53 is a transcription factor that governs numerous stress response pathways within the ceil. Maintaining the right levels of p53 is crucial for ceil survival and proper cellular homeostasis, The tight regulation of p53 involves many cellular components, most notably its major negative regulators Mdm2 and Mdm4, which maintain p53 protein amount and activity in tight check, microRNAs (miRNAs) are small non-coding RNAs that target specific mRNAs to translational arrest and degradation, miRNAs are also key compo- nents of the normal p53 pathway, joining forces with Mdm2 and Mdm4 to maintain proper p53 activity. Here we review the current knowledge of miRNAs targeting Mdm2 and Mdm4, and their importance in different tissues and in pathological states such as cancer. In addition, we address the role of Alu sequences-highly abundant retroelements spread throughout the human genome, and their impact on gene regulation via the miRNA machinery. Aius occupy a significant portion of genes' 31UTR, and as such they have the potential to impact mRNA regulation. Since Alus are primate-specific, they introduce a new regulatory layer into primate genomes. Atus can influence and alter gene regulation, creating primate-specific cancer-preventive regulatory mechanisms to sustain the transition to longer life span in primates. We review the possible influence of Alu sequences on miRNA functionality in general and specifically within the p53 network.
文摘Black capuchin monkeys Sapajus nigritus are among several mammalian species that damage forest plantations, pri- marily plantations of pine trees (Pinus spp.) in South Brazil. Management practices to reduce these damages include supplemen- tary food offerings and plantation surveillance. To assess the efficiency of these techniques, four treatments were evaluated: feeding (F, with supplementary bananas and maize), surveillance (S, in situ, wherein men patrolled the plantations, deterring the monkeys), feeding + surveillance (FS) and control (no procedures) (C). The efficiency assessment of each treatment involved the number of recorded primate sightings in the treatments with the presence of guards (S and FS) and a damage inventory of the outskirts of the experimental points immediately before and after the experiment. These data were complemented by a simulta- neous study of the availability of fruit, the primary item in the diet of this primate species, in the remnant native forest in the study area. Most sightings of S. nigritus occurred early in the morning, and in general, sightings were inversely proportional to the availability of native fruits. This trend was most evident in treatment FS, most likely due to the presence of food. Treatments F and FS exhibited higher percentages of damage, indicating that these are inefficient management techniques. Treatment S exhi- bited the lowest damage rate, but at a high cost, making this technique difficult to apply over large expanses. The development of other management techniques, such as environmental enrichment and the use of deterrents, is recommended to minimize the damage caused by capuchins in forest plantations [Current Zoology 60 (5): 581-590, 2014].