DNA methylation plays a crucial role in environmental adaptations.Here,using whole-genome bisulfite sequencing,we generated comprehensive genome-wide DNA methylation profiles for the high-altitude Yunnan snub-nosed mo...DNA methylation plays a crucial role in environmental adaptations.Here,using whole-genome bisulfite sequencing,we generated comprehensive genome-wide DNA methylation profiles for the high-altitude Yunnan snub-nosed monkey(Rhinopithecus bieti)and the closely related golden snub-nosed monkey(R.roxellana).Our findings indicated a slight increase in overall DNA methylation levels in golden snub-nosed monkeys compared to Yunnan snub-nosed monkeys,suggesting a higher prevalence of hypermethylated genomic regions in the former.Comparative genomic methylation analysis demonstrated that genes associated with differentially methylated regions were involved in membrane fusion,vesicular formation and trafficking,hemoglobin function,cell cycle regulation,and neuronal differentiation.These results suggest that the high-altitude-related epigenetic modifications are extensive,involving a complete adaptation process from the inhibition of single Ca^(2+)channel proteins to multiple proteins collaboratively enhancing vesicular function or inhibiting cell differentiation and proliferation.Functional assays demonstrated that overexpression or down-regulation of candidate genes,such as SNX10,TIMELESS,and CACYBP,influenced cell viability under stress conditions.Overall,this research suggests that comparing DNA methylation across closely related species can identify novel candidate genomic regions and genes associated with local adaptations,thereby deepening our understanding of the mechanisms underlying environmental adaptations.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
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
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
We examined time allocation by Sichuan snub-nosed monkeys Rhinopithecus roxellana in the montane, temperate and highly seasonal forests of the Shennongjia Nature Reserve in China, in order to improve our understanding...We examined time allocation by Sichuan snub-nosed monkeys Rhinopithecus roxellana in the montane, temperate and highly seasonal forests of the Shennongjia Nature Reserve in China, in order to improve our understanding of the ecological and social influences on monkey behavior. We collected data on activity budgets in relation to food availability in a group of monkeys from July 2003 to September 2004 （except February 2004）, using instantaneous scan samples. The monkeys spent 36.21% of daytime moving （ n = 21, 269 records）, 24.39% foraging, 9.33% inactive, 11,7% performing social behaviors, and 18.38% performing other behaviors. There were seasonal and annual variations in the proportions of time devoted to some activities. These variations were largely attributed to seasonal or annual fluctuations in the distribution and quality of food resources. Adult males spent more time moving, searching, and displaying other behaviors, but less time feeding and performing social behaviors than adult females. Adults performed other behaviors more often and moving less often than juveniles. These differences in activity budgets may reflect fundamental differences in reproductive biology, parental investment, and development among the different age/sex classes [ Current Zoology 55 （3） ： 173 - 179, 2009] .展开更多
At the beginning of 2016, I returned to the Baima Snow Mountain with a CC＇I-V film crew. As the birth place of the Yunnan snub-nosed monkey, Baima Snow Mountain in northwest Yunnan belongs to the transition zone betw...At the beginning of 2016, I returned to the Baima Snow Mountain with a CC＇I-V film crew. As the birth place of the Yunnan snub-nosed monkey, Baima Snow Mountain in northwest Yunnan belongs to the transition zone between the Qinghai-Tibet and Yunnan-Guizhou plateaus, and is regarded as the most magnificent of the Yunling Mountains. Revisiting my old haunt, I cannot help but recall the international snub-nosed monkey research launched by the Kunming Institute of Zoology （KIZ） so many years ago.展开更多
Relaxed open-mouth display serves important social functions in relation to submission, reconciliation affiliation and reassurance among non-human primate societies; however, quantitative evidence on this behavior rem...Relaxed open-mouth display serves important social functions in relation to submission, reconciliation affiliation and reassurance among non-human primate societies; however, quantitative evidence on this behavior remains insufficient among multi-level social groups. From July to November 2016, we examined four potential functions of the relaxed open-mouth display during pairwise, intra-unit social interactions among 18 free-ranging adult and sub-adult golden snub-nosed monkeys(Rhinopithecus roxellana) who belonged to three one-male, multi-female units(OMU) at Dalongtan, Shennongjia National Park China. Results showed that: compared with no relaxed open-mouth display,(1) the occurrence of displacement by a dominant individual approaching a subordinate was lower and the distance of the subordinate to the approaching dominant was shorter when the subordinate showed open-mouth display;(2) relaxed open-mouth display reduced the probability of continued attack for victims of aggression and allowed victims to achieve closer proximity to the aggressor during post-conflict periods;(3) relaxed open-mouth display by dominant individuals allowed them to achieve closer proximity to subordinates; and(4) the exchange of relaxed open-mouth display had a greater impact on the outcome of interactions than one individual alone giving this signal. These findings suggest that relaxed open-mouth display serves important functions regarding submission, reconciliation, affiliation and reassurance in coordinating social interactions within OMUs in golden snub-nosed monkeys.展开更多
Extractive foraging(EF)involves the exploitation of hidden or embedded foods,generally any food that is not visible to the naked eye.Therefore,EF is particularly important for survival in marginal habitats as it provi...Extractive foraging(EF)involves the exploitation of hidden or embedded foods,generally any food that is not visible to the naked eye.Therefore,EF is particularly important for survival in marginal habitats as it provides seasonal fallback foods in low food availability seasons.Although many studies consider primates’EF behavior and category,colobine species are usually categorized as non-extractive foragers and few studies quantitatively examine their EF behavior.In this study,we examined the EF behavior of one colobine species,the gray snub-nosed monkey(Rhinopithecus brelichi),at Yangaoping in Fanjingshan National Nature Reserve,Guizhou.We recorded 6 categories of EF behaviors.The most frequently sought-out foods were seeds,young bamboo and invertebrates.Extracted foods accounted for an average of 26.02%of feeding records.As the monkey engages in little EF behavior in the winter when the food availability is low,these results seem to do not support the hypothesis that EF serves to secure additional resources during lean times in marginal or seasonal habitats.According to these findings,we suggest R.brelich should be considered as an extractive forager.Our study also highlights the need for increased representation of colobines in the EF literature to better inform the discussion concerning its link to primate brain evolution.展开更多
Group living provides various advantages to individuals in regards to protection avoidance,intergroup competition,productive success and social information.Stable one-male units(OMUs)consist of relationships between t...Group living provides various advantages to individuals in regards to protection avoidance,intergroup competition,productive success and social information.Stable one-male units(OMUs)consist of relationships between the adult females and the resident male as well as the relationships among adult females.Based on continuous observation of a reproductive group of golden snub-nosed monkeys(Rhinopithecus roxellana)in the Qinling Mountains,we analyzed the relationships among adult individual dyads within 4 OMUs.The results indicated that in golden snub-nosed monkey societies,females not only had no strong tendency to build a relationship with the resident male in the OMU but also had no strong tendency to build relationships with other females in the OMU.In comparison with hamadryas(Papio hamadryas)and gelada baboons(Theropithecus gelada),the relationships within golden snub-nosed monkeys OMUs showed neither the star-shaped pattern observed in hamadryas baboons nor the net-shaped pattern observed in gelada baboons.We concluded that the relationships within golden snub-nosed monkey OMUs indicated a third pattern in nonhuman primate societies.Future research is required to determine the potential mechanisms for such a pattern.展开更多
Environmental barriers and habitat fragmentation can restrict gene flow,leading to genetic divergence among animal populations.The golden snub-nosed monkey,Rhinopithecus roxellana,is endemic to China,and ranges ...Environmental barriers and habitat fragmentation can restrict gene flow,leading to genetic divergence among animal populations.The golden snub-nosed monkey,Rhinopithecus roxellana,is endemic to China,and ranges across 4 provinces.However,over the past 40 years its populations have become fragmented.We investigated the genetic diversity,demographic history and population structure of R.roxellana in 5 reserves in one of its strongholds,the Qinling Mountain forests of Shaanxi.We collected genetic material from 11 monkey bands(a group of individuals containing multiple 1-male units)with a total of 428 samples genotyped at 20 microsatellite loci.Allelic richness and heterozygosity suggested a relatively high level of intra-band genetic diversity.We found no evidence of any genetic bottleneck in these R.roxellana populations.AMOVA and Bayesian cluster analysis revealed that R.roxellana in the 5 reserves are highly structured and form at least 3 distinct subpopulations.These subpopulations concur with major topographical features in the study area,such as mountain ridges,suggesting that dispersal of R.roxellana may be restricted by geographical barriers.展开更多
Studies on positional behavior and canopy use are essential for understanding how arboreal animals adapt their morphological characteristics and behaviors to the challenges of their environment.This study explores can...Studies on positional behavior and canopy use are essential for understanding how arboreal animals adapt their morphological characteristics and behaviors to the challenges of their environment.This study explores canopy and substrate use along with positional behavior in adult black snub-nosed monkeys Rhinopithecus strykeri,an endemic,critically endangered primate species in Gaoligong Mountains,southwest China.Using continuous focal animal sampling,we collected data over a 52-month period and found that R.strykeri is highly arboreal primarily using the high layers of the forest canopy(15–30 m),along with the terminal zone of tree crowns(52.9%),medium substrates(41.5%),and oblique substrates(56.8%).We also found sex differences in canopy and substrate use.Females use the terminal zones(56.7%versus 40.4%),small/medium(77.7%versus 60.1%),and oblique(59.9%versus 46.5%)substrates significantly more than males.On the other hand,males spend more time on large/very large(39.9%versus 22.3%)and horizontal(49.7%versus 35.2%)substrates.Whereas both sexes mainly sit(84.7%),and stand quadrupedally(9.1%),males stand quadrupedally(11.5%versus 8.3%),and bipedally(2.9%versus 0.8%)more often than females.Clamber,quadrupedalism,and leap/drop are the main locomotor modes for both sexes.Rhinopithecus strykeri populations never enter canopies of degenerated secondary forest and mainly use terminal branches in the middle and upper layers of canopies in intact mid-montane moist evergreen broadleaf forest and hemlock coniferous broadleaf mixed forests across their habitat.展开更多
In Southwest China, five Nature Reserves(NRs)(Mangkang, Baimaxueshan, Yunling, Habaxueshan, and Yunlongtianchi) play a key role in protecting the endemic and endangered Yunnan snub-nosed monkey(YSM)(Rhinopithecus biet...In Southwest China, five Nature Reserves(NRs)(Mangkang, Baimaxueshan, Yunling, Habaxueshan, and Yunlongtianchi) play a key role in protecting the endemic and endangered Yunnan snub-nosed monkey(YSM)(Rhinopithecus bieti). However, increasing human activities threaten its habitats and corridors. We used a GIS-based Niche Model to delineate potential core habitats(PCHs) of the YSMs and a Linkage Mapper corridor simulation tool to restore potential connectivity corridors(PCCs), and defined five scenarios. A normalized importance value index(NIVI) was established to identify the protection priority areas(PPAs) for the YSMs for five scenarios. The results indicated that locations of the habitats and corridors were different in the five scenarios, thereby influencing the distribution of the PPAs and protection network of the YSMs. The NIVI value of Baimaxueshan nature reserve was 1 in the five scenarios, which implied the maximum importance. There were only 7 PCHs and 16 PCCs(with the longest average length of 223.13 km) which were mainly located around 5 NRs in scenario III. The protection network of the YSMs was composed of 16 PCHs, 18 PCCs, and 5 NRs. Under each scenario, most of the PCHs and the PCCs were located in the south of the study area. The five NRs only covered 2 PPAs of the YSMs. We suggest that the southern part of the study area needs to be strictly protected and human activities should be limited. The area of the five NRs should be expanded to maximize protection of the YSMs in the future.展开更多
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
The experimental plots in representative areas of the Shennongjia Nature Reserve were established.The forest communities in Shennongjia were investigated by using TWINSPAN.The plant communities in these plots were inv...The experimental plots in representative areas of the Shennongjia Nature Reserve were established.The forest communities in Shennongjia were investigated by using TWINSPAN.The plant communities in these plots were investigated to discern the pattern of species diversity distribution along the altitudinal gradient.Theα-diversity andβ- diversity were calculated by using the data collected. Theα-diversity of the tree layer peaked in the evergreen broadleaved forest zone at low-elevation, theα-diversity of the shrub layer increased gradually at first and then decreased along the altitudinal gradient,while theα-diversity of the herb layer peaked in mid-altitude.Theβ-diversity peaked at mid-elevations where the composition of edificatory species changed.The transition zone was characterized by relatively high levels of species diversity and species turn-over rate.The overall species richness peaked in mid-altitude.The results of this research could provide a sound basis for reserve management and planning,as well as preservation of Sichuan snub-nosed monkey in this reserve.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
基金supported by the National Natural Science Foundation of China(32330015,31821001)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB31000000)。
文摘DNA methylation plays a crucial role in environmental adaptations.Here,using whole-genome bisulfite sequencing,we generated comprehensive genome-wide DNA methylation profiles for the high-altitude Yunnan snub-nosed monkey(Rhinopithecus bieti)and the closely related golden snub-nosed monkey(R.roxellana).Our findings indicated a slight increase in overall DNA methylation levels in golden snub-nosed monkeys compared to Yunnan snub-nosed monkeys,suggesting a higher prevalence of hypermethylated genomic regions in the former.Comparative genomic methylation analysis demonstrated that genes associated with differentially methylated regions were involved in membrane fusion,vesicular formation and trafficking,hemoglobin function,cell cycle regulation,and neuronal differentiation.These results suggest that the high-altitude-related epigenetic modifications are extensive,involving a complete adaptation process from the inhibition of single Ca^(2+)channel proteins to multiple proteins collaboratively enhancing vesicular function or inhibiting cell differentiation and proliferation.Functional assays demonstrated that overexpression or down-regulation of candidate genes,such as SNX10,TIMELESS,and CACYBP,influenced cell viability under stress conditions.Overall,this research suggests that comparing DNA methylation across closely related species can identify novel candidate genomic regions and genes associated with local adaptations,thereby deepening our understanding of the mechanisms underlying environmental adaptations.
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.
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 grants from the"973"program(code:2007CB411600)the National Science Foundation(code:30670354)
文摘We examined time allocation by Sichuan snub-nosed monkeys Rhinopithecus roxellana in the montane, temperate and highly seasonal forests of the Shennongjia Nature Reserve in China, in order to improve our understanding of the ecological and social influences on monkey behavior. We collected data on activity budgets in relation to food availability in a group of monkeys from July 2003 to September 2004 （except February 2004）, using instantaneous scan samples. The monkeys spent 36.21% of daytime moving （ n = 21, 269 records）, 24.39% foraging, 9.33% inactive, 11,7% performing social behaviors, and 18.38% performing other behaviors. There were seasonal and annual variations in the proportions of time devoted to some activities. These variations were largely attributed to seasonal or annual fluctuations in the distribution and quality of food resources. Adult males spent more time moving, searching, and displaying other behaviors, but less time feeding and performing social behaviors than adult females. Adults performed other behaviors more often and moving less often than juveniles. These differences in activity budgets may reflect fundamental differences in reproductive biology, parental investment, and development among the different age/sex classes [ Current Zoology 55 （3） ： 173 - 179, 2009] .
文摘At the beginning of 2016, I returned to the Baima Snow Mountain with a CC＇I-V film crew. As the birth place of the Yunnan snub-nosed monkey, Baima Snow Mountain in northwest Yunnan belongs to the transition zone between the Qinghai-Tibet and Yunnan-Guizhou plateaus, and is regarded as the most magnificent of the Yunling Mountains. Revisiting my old haunt, I cannot help but recall the international snub-nosed monkey research launched by the Kunming Institute of Zoology （KIZ） so many years ago.
基金supported by the National Natural Science Foundation of China(31670397,31870509)Science Foundation of the State Forestry Administration of China
文摘Relaxed open-mouth display serves important social functions in relation to submission, reconciliation affiliation and reassurance among non-human primate societies; however, quantitative evidence on this behavior remains insufficient among multi-level social groups. From July to November 2016, we examined four potential functions of the relaxed open-mouth display during pairwise, intra-unit social interactions among 18 free-ranging adult and sub-adult golden snub-nosed monkeys(Rhinopithecus roxellana) who belonged to three one-male, multi-female units(OMU) at Dalongtan, Shennongjia National Park China. Results showed that: compared with no relaxed open-mouth display,(1) the occurrence of displacement by a dominant individual approaching a subordinate was lower and the distance of the subordinate to the approaching dominant was shorter when the subordinate showed open-mouth display;(2) relaxed open-mouth display reduced the probability of continued attack for victims of aggression and allowed victims to achieve closer proximity to the aggressor during post-conflict periods;(3) relaxed open-mouth display by dominant individuals allowed them to achieve closer proximity to subordinates; and(4) the exchange of relaxed open-mouth display had a greater impact on the outcome of interactions than one individual alone giving this signal. These findings suggest that relaxed open-mouth display serves important functions regarding submission, reconciliation, affiliation and reassurance in coordinating social interactions within OMUs in golden snub-nosed monkeys.
基金supported by grants from the Project of Public Benefit for Forestry(201104073)the National Natural Science Foundation of China(31071937)+1 种基金the State Forestry Administration of ChinaInnovation Platform Open Projects of Education Bureau of Hunan Province(11K078).
文摘Extractive foraging(EF)involves the exploitation of hidden or embedded foods,generally any food that is not visible to the naked eye.Therefore,EF is particularly important for survival in marginal habitats as it provides seasonal fallback foods in low food availability seasons.Although many studies consider primates’EF behavior and category,colobine species are usually categorized as non-extractive foragers and few studies quantitatively examine their EF behavior.In this study,we examined the EF behavior of one colobine species,the gray snub-nosed monkey(Rhinopithecus brelichi),at Yangaoping in Fanjingshan National Nature Reserve,Guizhou.We recorded 6 categories of EF behaviors.The most frequently sought-out foods were seeds,young bamboo and invertebrates.Extracted foods accounted for an average of 26.02%of feeding records.As the monkey engages in little EF behavior in the winter when the food availability is low,these results seem to do not support the hypothesis that EF serves to secure additional resources during lean times in marginal or seasonal habitats.According to these findings,we suggest R.brelich should be considered as an extractive forager.Our study also highlights the need for increased representation of colobines in the EF literature to better inform the discussion concerning its link to primate brain evolution.
基金funded by grants from the Key Program of National Natural Science Fund(31130061)the Special Foundation of Shaanxi Academy of Sciences,China(2012K-01)+4 种基金the Youth Foundation of Shaanxi Academy of Sciences,China(2013K-35)the Western Light Talent Culture Project(2011DF05)the National Nature Science Foundation of China(30970444,30970168,30970379)the Research Fund for the Doctoral Program of Higher Education of China(20106101110005)the Cosmo Oil Eco Card Fund of Japan(2005–2012).
文摘Group living provides various advantages to individuals in regards to protection avoidance,intergroup competition,productive success and social information.Stable one-male units(OMUs)consist of relationships between the adult females and the resident male as well as the relationships among adult females.Based on continuous observation of a reproductive group of golden snub-nosed monkeys(Rhinopithecus roxellana)in the Qinling Mountains,we analyzed the relationships among adult individual dyads within 4 OMUs.The results indicated that in golden snub-nosed monkey societies,females not only had no strong tendency to build a relationship with the resident male in the OMU but also had no strong tendency to build relationships with other females in the OMU.In comparison with hamadryas(Papio hamadryas)and gelada baboons(Theropithecus gelada),the relationships within golden snub-nosed monkeys OMUs showed neither the star-shaped pattern observed in hamadryas baboons nor the net-shaped pattern observed in gelada baboons.We concluded that the relationships within golden snub-nosed monkey OMUs indicated a third pattern in nonhuman primate societies.Future research is required to determine the potential mechanisms for such a pattern.
基金supported by the National Nature Science Foundation of China(31130061,31501872,31270441,31470455,31672301).
文摘Environmental barriers and habitat fragmentation can restrict gene flow,leading to genetic divergence among animal populations.The golden snub-nosed monkey,Rhinopithecus roxellana,is endemic to China,and ranges across 4 provinces.However,over the past 40 years its populations have become fragmented.We investigated the genetic diversity,demographic history and population structure of R.roxellana in 5 reserves in one of its strongholds,the Qinling Mountain forests of Shaanxi.We collected genetic material from 11 monkey bands(a group of individuals containing multiple 1-male units)with a total of 428 samples genotyped at 20 microsatellite loci.Allelic richness and heterozygosity suggested a relatively high level of intra-band genetic diversity.We found no evidence of any genetic bottleneck in these R.roxellana populations.AMOVA and Bayesian cluster analysis revealed that R.roxellana in the 5 reserves are highly structured and form at least 3 distinct subpopulations.These subpopulations concur with major topographical features in the study area,such as mountain ridges,suggesting that dispersal of R.roxellana may be restricted by geographical barriers.
基金funded by the National Science Foundation of China(31860168)Zoological Society for the Conservation of Species and Populations(Germany,Rhinopithecus.MMR.2015)+1 种基金the Australian National University Fieldwork Funding for Higher Degree Research Students(R61250FW)Young talents program of ten thousand talents plan of Yunnan(YNWRQNBJ-2019-262).
文摘Studies on positional behavior and canopy use are essential for understanding how arboreal animals adapt their morphological characteristics and behaviors to the challenges of their environment.This study explores canopy and substrate use along with positional behavior in adult black snub-nosed monkeys Rhinopithecus strykeri,an endemic,critically endangered primate species in Gaoligong Mountains,southwest China.Using continuous focal animal sampling,we collected data over a 52-month period and found that R.strykeri is highly arboreal primarily using the high layers of the forest canopy(15–30 m),along with the terminal zone of tree crowns(52.9%),medium substrates(41.5%),and oblique substrates(56.8%).We also found sex differences in canopy and substrate use.Females use the terminal zones(56.7%versus 40.4%),small/medium(77.7%versus 60.1%),and oblique(59.9%versus 46.5%)substrates significantly more than males.On the other hand,males spend more time on large/very large(39.9%versus 22.3%)and horizontal(49.7%versus 35.2%)substrates.Whereas both sexes mainly sit(84.7%),and stand quadrupedally(9.1%),males stand quadrupedally(11.5%versus 8.3%),and bipedally(2.9%versus 0.8%)more often than females.Clamber,quadrupedalism,and leap/drop are the main locomotor modes for both sexes.Rhinopithecus strykeri populations never enter canopies of degenerated secondary forest and mainly use terminal branches in the middle and upper layers of canopies in intact mid-montane moist evergreen broadleaf forest and hemlock coniferous broadleaf mixed forests across their habitat.
基金National Key Research and Development Program of China,No.2016YFC0502102
文摘In Southwest China, five Nature Reserves(NRs)(Mangkang, Baimaxueshan, Yunling, Habaxueshan, and Yunlongtianchi) play a key role in protecting the endemic and endangered Yunnan snub-nosed monkey(YSM)(Rhinopithecus bieti). However, increasing human activities threaten its habitats and corridors. We used a GIS-based Niche Model to delineate potential core habitats(PCHs) of the YSMs and a Linkage Mapper corridor simulation tool to restore potential connectivity corridors(PCCs), and defined five scenarios. A normalized importance value index(NIVI) was established to identify the protection priority areas(PPAs) for the YSMs for five scenarios. The results indicated that locations of the habitats and corridors were different in the five scenarios, thereby influencing the distribution of the PPAs and protection network of the YSMs. The NIVI value of Baimaxueshan nature reserve was 1 in the five scenarios, which implied the maximum importance. There were only 7 PCHs and 16 PCCs(with the longest average length of 223.13 km) which were mainly located around 5 NRs in scenario III. The protection network of the YSMs was composed of 16 PCHs, 18 PCCs, and 5 NRs. Under each scenario, most of the PCHs and the PCCs were located in the south of the study area. The five NRs only covered 2 PPAs of the YSMs. We suggest that the southern part of the study area needs to be strictly protected and human activities should be limited. The area of the five NRs should be expanded to maximize protection of the YSMs in the future.
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.
文摘The experimental plots in representative areas of the Shennongjia Nature Reserve were established.The forest communities in Shennongjia were investigated by using TWINSPAN.The plant communities in these plots were investigated to discern the pattern of species diversity distribution along the altitudinal gradient.Theα-diversity andβ- diversity were calculated by using the data collected. Theα-diversity of the tree layer peaked in the evergreen broadleaved forest zone at low-elevation, theα-diversity of the shrub layer increased gradually at first and then decreased along the altitudinal gradient,while theα-diversity of the herb layer peaked in mid-altitude.Theβ-diversity peaked at mid-elevations where the composition of edificatory species changed.The transition zone was characterized by relatively high levels of species diversity and species turn-over rate.The overall species richness peaked in mid-altitude.The results of this research could provide a sound basis for reserve management and planning,as well as preservation of Sichuan snub-nosed monkey in this reserve.
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.
