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two human monoclonal hla-reactive antibodies cross-react with mamu-b*008, a rhesus macaque mhc allotype associated with control of simian immunodeficiency virus replication.mhc class i molecules play an important role in adaptive immune responses against intracellular pathogens. these molecules are highly polymorphic, and many allotypes have been characterized. in a transplantation setting, a mismatch between mhc allotypes may initiate an alloimmune response. rhesus macaques (macaca mulatta, mamu) are valuable as a preclinical model species in transplantation research as well as to evaluate the safety and efficacy of vaccine candidates. in both lines of research, t ...202133692147
development of a reverse transcription droplet digital pcr (rt-ddpcr) assay for sensitive detection of simian immunodeficiency virus (siv).simian immunodeficiency virus (siv)-infected rhesus macaques constitute an excellent model of human hiv infection. sensitive detection of siv rna in cell and tissue samples from infected animals subjected to treatment regimens becomes especially critical in determining which therapeutic attempts are successful, and consequently, which interventions should be prioritized in hiv cure research.202133588884
immune responses and viral persistence in simian/human immunodeficiency virus shiv.c.ch848-infected rhesus macaques.chimeric simian/human immunodeficiency viruses (shivs) are widely used in nonhuman primate models to recapitulate human immunodeficiency virus (hiv) infection in humans, yet most shivs fail to establish persistent viral infection. we investigated immunological and virological events in rhesus macaques infected with the newly developed shiv.c.ch848 (shivc) and treated with combined antiretroviral therapy (cart). similar to hiv/simian immunodeficiency virus (siv) infection, shiv.c.ch848 infection ...202133568508
combining in vivo corneal confocal microscopy with deep learning-based analysis reveals sensory nerve fiber loss in acute simian immunodeficiency virus infection.to characterize corneal subbasal nerve plexus features of normal and simian immunodeficiency virus (siv)-infected macaques by combining in vivo corneal confocal microscopy (ivcm) with automated assessments using deep learning-based methods customized for macaques.202133528225
a potent anti-simian immunodeficiency virus neutralizing antibody induction associated with a germline immunoglobulin gene polymorphism in rhesus macaques.virus infection induces b cells with a wide variety of b cell receptor (bcr) repertoires. patterns of induced bcr repertoires are different in individuals, while the underlying mechanism causing this difference remains largely unclear. in particular, the impact of germ line bcr immunoglobulin (ig) gene polymorphism on b cell/antibody induction has not fully been determined. in the present study, we found a potent antibody induction associated with a germ line bcr ig gene polymorphism. b404-class ...202133441342
increased proviral dna in circulating cells correlates with plasma viral rebound in simian immunodeficiency virus-infected rhesus macaques after antiretroviral therapy interruption.the human immunodeficiency virus (hiv) reservoir is responsible for persistent viral infection, and a small number of mosaic latent cellular reservoirs promote viral rebound upon antiretroviral therapy interruption, which is the major obstacle to a cure. however, markers that determine effective therapy and viral rebound posttreatment interruption remain unclear. in this study, we comprehensively and longitudinally tracked dynamic decay of cell-associated viral rna/dna in systemic and lymphoid t ...202133408173
brain tissue transcriptomic analysis of siv-infected macaques identifies several altered metabolic pathways linked to neuropathogenesis and poly (adp-ribose) polymerases (parps) as potential therapeutic targets.despite improvements in antiretroviral therapy, human immunodeficiency virus type 1 (hiv-1)-associated neurocognitive disorders (hand) remain prevalent in subjects undergoing therapy. hand significantly affects individuals' quality of life, as well as adherence to therapy, and, despite the increasing understanding of neuropathogenesis, no definitive diagnostic or prognostic marker has been identified. we investigated transcriptomic profiles in frontal cortex tissues of simian immunodeficiency vi ...202133405206
west nile virus seroprevalence in an outdoor nonhuman primate breeding colony in south florida.west nile virus (wnv) was first detected in florida in july 2001, with 404 human cases reported to the centers for disease control and prevention as of february 2020. the subtropical climate of florida is ideal for the mosquitoes that transmit wnv. we investigated the wnv seroprevalence in 3 nhp species housed outdoors at the mannheimer foundation in south florida. from january to december 2016, 520 3 to 30 y old nhp were sampled at our 2 closed sites in homestead and labelle: 200 rhesus macaque ...202133441221
virus infection of the cns disrupts the immune-neural-synaptic axis via induction of pleiotropic gene regulation of host responses.treatment for many viral infections of the central nervous system (cns) remains only supportive. here we address a remaining gap in our knowledge regarding how the cns and immune systems interact during viral infection. by examining the regulation of the immune and nervous system processes in a nonhuman primate model of west nile virus neurological disease, we show that virus infection disrupts the homeostasis of the immune-neural-synaptic axis via induction of pleiotropic genes with distinct fu ...202133599611
intracerebroventricular administration of aav9-php.b syn1-emgfp induces widespread transgene expression in the mouse and monkey central nervous system.viral vectors made from adeno-associated virus (aav) have emerged as preferred tools in basic and translational neuroscience research to introduce or modify genetic material in cells of interest. the use of viral vectors is particularly attractive in nontransgenic species, such as nonhuman primates. injection of aav solutions into the cerebrospinal fluid is an effective method to achieve a broad distribution of a transgene in the central nervous system. in this study, we conducted injections of ...202133860682
plxdc family members are novel receptors for the rhesus monkey rhadinovirus (rrv).the rhesus monkey rhadinovirus (rrv), a γ2-herpesvirus of rhesus macaques, shares many biological features with the human pathogenic kaposi's sarcoma-associated herpesvirus (kshv). both viruses, as well as the more distantly related epstein-barr virus, engage cellular receptors from the eph family of receptor tyrosine kinases (ephs). however, the importance of the eph interaction for rrv entry varies between cell types suggesting the existence of eph-independent entry pathways. we therefore aime ...202133657166
neutralizing antibodies against epstein-barr virus infection of b cells can protect from oral viral challenge in the rhesus macaque animal model.epstein-barr virus (ebv) and related lymphocryptoviruses (lcvs) from nonhuman primates are transmitted through oral secretions, penetrate the mucosal epithelium, and establish persistent infection in b cells. to determine whether neutralizing antibodies against epithelial or b cell infection could block oral transmission and persistent lcv infection, we use rhesus macaques, the most accurate animal model for ebv infection by faithfully reproducing acute and persistent infection in humans. naive ...202134337567
interleukin-15 response signature predicts rhcmv/siv vaccine efficacy.simian immunodeficiency virus (siv) challenge of rhesus macaques (rms) vaccinated with strain 68-1 rhesus cytomegalovirus (rhcmv) vectors expressing siv proteins (rhcmv/siv) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic siv in ~55% of vaccinated rms with no protection in the remaining 45%. although previous work indicates that unconventionally restricted, siv-specific, effector-memory (em)-biased cd8+ t cell responses are necessary for efficacy, the ...202134228762
cytomegaloviral determinants of cd8+ t cell programming and rhcmv/siv vaccine efficacy.simian immunodeficiency virus (siv) insert-expressing, 68-1 rhesus cytomegalovirus (rhcmv/siv) vectors elicit major histocompatibility complex e (mhc-e)- and mhc-ii-restricted, siv-specific cd8+ t cell responses, but the basis of these unconventional responses and their contribution to demonstrated vaccine efficacy against siv challenge in the rhesus monkeys (rms) have not been characterized. we show that these unconventional responses resulted from a chance genetic rearrangement in 68-1 rhcmv t ...202133766849
high-resolution quantitative mapping of macaque cervicovaginal epithelial thickness: implications for mucosal vaccine delivery.vaginal mucosal surfaces naturally offer some protection against sexually transmitted infections (stis) including human immunodeficiency virus-1, however topical preventative medications or vaccine designed to boost local immune responses can further enhance this protection. we previously developed a novel mucosal vaccine strategy using viral vectors integrated into mouse dermal epithelium to induce virus-specific humoral and cellular immune responses at the site of exposure. since vaccine integ ...202134262561
immunoprofiling correlates of protection against shiv infection in adjuvanted hiv-1 pox-protein vaccinated rhesus macaques.human immunodeficiency virus type 1 (hiv-1) infection remains a major public health threat due to its incurable nature and the lack of a highly efficacious vaccine. the rv144 vaccine trial is the only clinical study to date that demonstrated significant but modest decrease in hiv infection risk. to improve hiv-1 vaccine immunogenicity and efficacy, we recently evaluated pox-protein vaccination using a next generation liposome-based adjuvant, army liposomal formulation adsorbed to aluminum (alfa) ...202134046030
exploration of a sequential gp140-gp145 immunization regimen with heterologous envs to induce a protective cross-reactive hiv neutralizing antibody response in non-human primates.raising a heterologous tier 2 neutralizing antibody (nab) response remains a daunting task for hiv vaccine development. in this study, we explored the utility of diverse hiv-1 envelope (env) immunogens in a sequential immunization scheme as a solution to this task. this exploration stemmed from the rationale that gp145, a membrane-bound truncation form of hiv env, may facilitate the focusing of induced antibody response on neutralizing epitopes when sequentially combined with the soluble gp140 f ...202133723807
human trim5α: autophagy connects cell-intrinsic hiv-1 restriction and innate immune sensor functioning.human immunodeficiency virus-1 (hiv-1) persists as a global health concern, with an incidence rate of approximately 2 million, and estimated global prevalence of over 35 million. combination antiretroviral treatment is highly effective, but hiv-1 patients that have been treated still suffer from chronic inflammation and residual viral replication. it is therefore paramount to identify therapeutically efficacious strategies to eradicate viral reservoirs and ultimately develop a cure for hiv-1. it ...202133669846
embryotoxic impact of zika virus in a rhesus macaque in vitro implantation model.zika virus infection (zikv) is associated with adverse pregnancy outcomes in humans, and infection in the first trimester can lead to miscarriage and stillbirth. vertical and sexual transmission of zikv have been demonstrated, yet the impact of infection during the initial stages of pregnancy remains unexplored. here we defined the impact of zikv on early embryonic and placental development with a rhesus macaque model. during in vitro fertilization (ivf), macaque gametes were inoculated with a p ...202031901091
anatomy of the dura mater venous sinus of alouatta belzebul.the anatomy of the dura mater's venous sinuses is important in the veterinary clinical and surgical area, for cranial procedures and interventions of wild animals, in addition to assisting in the management of neurological diseases, which can prevent serious complications. the macroscopic anatomy of the venous sinuses of the dura mater of alouatta belzebul was studied. five adult specimens, males and females, were dissected and fixed in 10% formaldehyde solution. in the dura mater of the alouatt ...202032738181
skeletal morphology of the lesula (cercopithecus lomamiensis) and the evolution of guenon locomotor behavior.the guenons (tribe cercopithecini) are a diverse and primarily arboreal radiation of old world monkeys from africa. however, preliminary behavioral observations of the lesula (cercopithecus lomamiensis), a little-known guenon species described in 2012, report it spending substantial amounts of time on the ground. new specimens allow us to present the first description of lesula postcranial morphology and apply a comparative functional morphology approach to supplement our knowledge of its locomo ...202032124976
age-related gene expression and dna methylation changes in rhesus macaque.aging is a very complicated biological process that can change gene expressions. the chinese rhesus macaque (macaca mulatta lasiota; cr) is closely related to humans. we explored gene expression with increasing age and dna methylation changes in young and old crs. results showed blood transcriptome and dna methylome significantly changed from young to old crs. the age-associated differentially expressed genes (degs) and differentially methylated regions (dmrs) were associated with age-related bi ...202032927008
the anatomy of the skin of the chinese tree shrew is very similar to that of human skin.the chinese tree shrew (tupaia belangeri chinensis) is a small mammal closely related to primates. it has a small body size, low maintenance cost, and a relatively short reproductive cycle, all of which has made it the ideal model for the study of a variety of human diseases. in this study, we compared the anatomy of the skin of the chinese tree shrew with that of the rhesus macaque, mouse and human, with the intention of providing the basic data required for the creation of skin disease models ...202032135581
irisin is expressed by undifferentiated spermatogonia and modulates gene expression in organotypic primate testis cultures.the molecular mechanisms regulating undifferentiated spermatogonial cell proliferation and differentiation are still not fully understood. irisin is an exercise-induced hormone, which is a cleaved and secreted fragment of the fibronectin type iii repeat containing 5 (fndc5) transmembrane protein. recent studies have demonstrated the role of irisin in cell proliferation and differentiation in various tissues. however, testicular irisin expression and its potential action have not been analyzed. h ...202031801682
efficacy of camera traps in detecting primates in hue saola nature reserve.camera trapping has been demonstrated to be an effective tool in surveying a suite of species, especially elusive mammals in rough terrains. the method has become increasingly common in primate surveys for both ground-dwelling and arboreal taxa in many tropical regions of the world. however, camera trapping has rarely been used to inventory primates in vietnam, although many species are under severe threats and in critical need of surveying for improved conservation measures. in this study, we e ...202032383126
comparison of nonhuman primates identified the suitable model for covid-19.identification of a suitable nonhuman primate (nhp) model of covid-19 remains challenging. here, we characterized severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection in three nhp species: old world monkeys macaca mulatta (m. mulatta) and macaca fascicularis (m. fascicularis) and new world monkey callithrix jacchus (c. jacchus). infected m. mulatta and m. fascicularis showed abnormal chest radiographs, an increased body temperature and a decreased body weight. viral genomes wer ...202032814760
nhp-immunome: a translational research-oriented database of non-human primate immune system proteins.we are currently living the advent of a new age for medicine in which basic research is being quickly translated into marketable drugs, and the widespread access to genomics data is allowing the design and implementation of personalized solutions to medical conditions. non-human primates (nhp) have gained an essential role in drug discovery and safety testing due to their close phylogenetic relationship to humans. in this study, a collection of well characterized genes of the human immune system ...202031733823
strategy use in probabilistic categorization by rhesus macaques (macaca mulatta) and capuchin monkeys (cebus [sapajus] apella).probabilistic categorization tasks present the learner with a set of possible responses and imperfect cue evidence of which response will be rewarded. a single, optimal integration of all available cues into an optimal response is possible given any set of evidence. in contrast, there are many possible uses of the cues that offer the learner suboptimal (but better than chance) responding. we presented a classic probabilistic categorization task to 3 rhesus macaques (macaca mulatta) and 13 capuch ...202032406716
the density bias: capuchin monkeys (sapajus apella) prefer densely arranged items in a food-choice task.in the current work, we investigated whether capuchin monkeys preferred densely distributed resources to sparsely distributed resources in a 2-choice discrimination task with edible rewards. capuchin monkeys were biased to select a denser food set over the same number of food items in a sparsely arranged set. furthermore, increased density of the larger food set facilitated discrimination performance in quantity comparisons with a true difference in set size. these results align with previous st ...202031971398
acute respiratory distress in aged, sars-cov-2 infected african green monkeys but not rhesus macaques.sars-cov-2 induces a wide range of disease severity ranging from asymptomatic infection, to a life-threating illness, particularly in the elderly and persons with comorbid conditions. among those persons with serious covid-19 disease, acute respiratory distress syndrome (ards) is a common and often fatal presentation. animal models of sars-cov-2 infection that manifest severe disease are needed to investigate the pathogenesis of covid-19 induced ards and evaluate therapeutic strategies. here we ...202033171111
non-human primate determinants of natural killer cells in tissues at steady-state and during simian immunodeficiency virus infection.natural killer (nk) cells play essential roles in immunity to viruses and tumors. their function is genetically determined but also modulated by environmental factors. the distribution and functional regulation of these cells vary depending on the tissue. nk cell behavior in lymphoid tissues is so far understudied. non-human primate (nhp) models are essential for the development of therapies and vaccines against human diseases, and access to nhp tissues allows insights into spatial regulations o ...202033013901
potential for virus endogenization in humans through testicular germ cell infection: the case of hiv.viruses have colonized the germ line of our ancestors at several occasions during evolution, leading to the integration in the human genome of viral sequences from over 30 retroviral groups and a few non-retroviruses. among the recently emerged viruses infecting humans, several target the testis (eg hiv, zika and ebola viruses). here we aimed to investigate whether human testicular germ cells (tgcs) can support integration by hiv, a contemporary retrovirus that started to spread in the human pop ...202032999017
epigenetic silencing of cd4 expression in nonpathogenic siv infection in african green monkeys.african green monkeys (agms) are natural hosts of siv that postthymically downregulate cd4 to maintain a large population of cd4-cd8aa+ virus-resistant cells with th functionality, which can result in agms becoming apparently cured of sivagm infection. to understand the mechanisms of this process, we performed genome-wide transcriptional analysis on t cells induced to downregulate cd4 in vitro from agms and closely related patas monkeys and t cells that maintain cd4 expression from rhesus macaqu ...202032841214
immune profiling of influenza-specific b- and t-cell responses in macaques using flow cytometry-based assays.influenza remains a significant global public health burden, despite substantial annual vaccination efforts against circulating virus strains. as a result, novel vaccine approaches are needed to generate long-lasting and universal broadly cross-reactive immunity against distinct influenza virus strains and subtypes. several new vaccine candidates are currently under development and/or in clinical trials. the successful development of new vaccines requires testing in animal models, other than mic ...202032741011
genome analysis and replication studies of the african green monkey simian foamy virus serotype 3 strain fv2014.african green monkey (agm) spumaretroviruses have been less well-studied than other simian foamy viruses (sfvs). we report the biological and genomic characterization of sfvcae_fv2014, which was the first foamy virus isolated from an african green monkey (agm) and was found to be serotype 3. infectivity studies in various cell lines from different species (mouse, dog, rhesus monkey, agm, and human) indicated that like other sfvs, sfvcae_fv2014 had broad species and cell tropism, and in vitro cel ...202032268512
pharmacological characterization of the novel and selective α7 nicotinic acetylcholine receptor-positive allosteric modulator bnc375.treatments for cognitive deficits associated with central nervous system (cns) disorders such as alzheimer disease and schizophrenia remain significant unmet medical needs that incur substantial pressure on the health care system. the α7 nicotinic acetylcholine receptor (nachr) has garnered substantial attention as a target for cognitive deficits based on receptor localization, robust preclinical effects, genetics implicating its involvement in cognitive disorders, and encouraging, albeit mixed, ...202032094294
differences in frontal network anatomy across primate species.the frontal lobe is central to distinctive aspects of human cognition and behavior. some comparative studies link this to a larger frontal cortex and even larger frontal white matter in humans compared with other primates, yet others dispute these findings. the discrepancies between studies could be explained by limitations of the methods used to quantify volume differences across species, especially when applied to white matter connections. in this study, we used a novel tractography approach t ...202031949106
gibbons exploit information about what a competitor can see.how much nonhuman animals understand about seeing has been the focus of comparative cognition research for decades. many social primates (and other species) are sensitive to cues about what others can and cannot see. whether this sensitivity evolved in primates through shared descent or convergent evolution remains unclear. the current study tested gibbons-the apes that are least studied yet most distantly related to humans and one of the less social primates-in two food-competition tasks. speci ...202031781885
predicted structural differences of four fertility-related y-chromosome proteins in macaca mulatta, m. fascicularis, and their indochinese hybrids.species in the genus macaca typically live in multimale-multifemale social groups with male macaques exhibiting some of the largest testis:body weight ratios among primates. males are believed to experience intense levels of sperm competition. several spermatogenesis genes are located on the y-chromosome and, interestingly, occasional hybridization between two species has led to the introgression of the rhesus macaque (macaca mulatta) y-chromosome deep into the range of the long-tailed macaque ( ...202033146441
cd8 t cells show protection against highly pathogenic simian immunodeficiency virus (siv) after vaccination with siv gene-expressing bcg prime and vaccinia virus/sendai virus vector boosts.toward development of a dual vaccine for human immunodeficiency virus (hiv)-1 and tuberculosis infections, we developed a urease-deficient bacillus calmette-guérin (bcg) strain tokyo172 (bcgδurease) to enhance its immunogenicity. bcgδurease expressing simian immunodeficiency virus (siv) gag induced bcg antigen-specific cd4+ and cd8+ t cells more efficiently, and more gag-specific cd8+ t cells. we evaluated its protective efficacy against siv infection in cynomolgus monkeys of asian origin, shown ...202033087465
factors influencing taxonomic unevenness in scientific research: a mixed-methods case study of non-human primate genomic sequence data generation.scholars have noted major disparities in the extent of scientific research conducted among taxonomic groups. such trends may cascade if future scientists gravitate towards study species with more data and resources already available. as new technologies emerge, do research studies employing these technologies continue these disparities? here, using non-human primates as a case study, we identified disparities in massively parallel genomic sequencing data and conducted interviews with scientists ...202033047065
differences in xanthotoxin metabolites in seven mammalian liver microsomes.xanthotoxin, abundantly occurring in fruits, vegetables, grapefruit juice and oils, is widely used in medicine for the treatment of psoriasis and vitiligo. xanthotoxin possesses the ability to inhibit mechanism-based cytochrome p450 (cyp450)-mediated activities in rats and mice. furthermore, it time-dependently obstructs a number of cyp450-mediated functions in humans. cyp450 enzymes are most abundant in the liver and induce metabolic activation of numerous xenobiotic compounds. the present stud ...202032855735
genetic variants of udp-glucuronosyltransferases 1a1, 1a6, and 1a9 in cynomolgus and rhesus macaques.1. in the cynomolgus macaque, udp-glucuronosyltransferases (ugts) 1as have similar molecular and enzymatic characteristics to those of their human orthologs. however, genetic polymorphisms in major cynomolgus ugt1a1/6/9 have not been investigated. 2. we re-sequenced ugt1a1, ugt1a6, and ugt1a9 in 186 cynomolgus macaques (bred in cambodia, china, or indonesia) and 54 rhesus macaques and found 15, 13, and 26 non-synonymous variants, respectively. 3. of these ugt1a1, ugt1a6, and ugt1a9 variants, res ...202032811258
development of an inactivated vaccine candidate, bbibp-corv, with potent protection against sars-cov-2.the coronavirus disease 2019 (covid-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) threatens global public health. the development of a vaccine is urgently needed for the prevention and control of covid-19. here, we report the pilot-scale production of an inactivated sars-cov-2 vaccine candidate (bbibp-corv) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (cynomolgus monkeys and rhesus maca ...202032778225
macaque gaze responses to the primatar: a virtual macaque head for social cognition research.following the expanding use and applications of virtual reality in everyday life, realistic virtual stimuli are of increasing interest in cognitive studies. they allow for control of features such as gaze, expression, appearance, and movement, which may help to overcome limitations of using photographs or video recordings to study social responses. in using virtual stimuli however, one must be careful to avoid the uncanny valley effect, where realistic stimuli can be perceived as eerie, and indu ...202032765373
immune outcomes of zika virus infection in nonhuman primates.although the zika virus (zikv) epidemic is subsiding, immune responses that are important for controlling acute infection have not been definitively characterized. nonhuman primate (nhp) models were rapidly developed to understand the disease and to test vaccines, and these models have since provided an understanding of the immune responses that correlate with protection during natural infection and vaccination. here, we infected a small group of male rhesus (macaca mulatta) and cynomolgus (maca ...202032747639
a dedicated eight-channel receive rf coil array for monkey brain mri at 9.4 t.the neuroimaging of nonhuman primates (nhps) realised with magnetic resonance imaging (mri) plays an important role in understanding brain structures and functions, as well as neurodegenerative diseases and pathological disorders. theoretically, an ultrahigh field mri (≥7 t) is capable of providing a higher signal-to-noise ratio (snr) for better resolution; however, the lack of appropriate radiofrequency (rf) coils for 9.4 t monkey mri undermines the benefits provided by a higher field strength. ...202032729642
variability in the number of infraorbital foramina in rhesus macaques (macaca mulatta) and cynomolgus macaques (macaca fascicularis).this study aimed to determine the number of infraorbital foramina in monkeys of the papionini tribe. the authors performed a μct analysis of the morphology of the infraorbital foramina. a total number of 52 simian skulls belonged to two macaque species: macaca mulatta and macaca fascicularis were used in the study. the number of infraorbital foramina was counted macroscopically and with the use of a magnifying glass. next, the skull representing the most common morphological type was selected an ...202032558307
cell atlas of aqueous humor outflow pathways in eyes of humans and four model species provides insight into glaucoma pathogenesis.increased intraocular pressure (iop) represents a major risk factor for glaucoma, a prevalent eye disease characterized by death of retinal ganglion cells; lowering iop is the only proven treatment strategy to delay disease progression. the main determinant of iop is the equilibrium between production and drainage of aqueous humor, with compromised drainage generally viewed as the primary contributor to dangerous iop elevations. drainage occurs through two pathways in the anterior segment of the ...202032341164
genetic variants of n-acetyltransferases 1 and 2 (nat1 and nat2) in cynomolgus and rhesus macaques.in humans, polymorphic n-acetyltransferases nat1 and nat2 are important enzymes that metabolize endogenous and exogenous compounds, including drugs. these enzymes exhibit considerable inter-individual variability in humans. the cynomolgus macaque is a nonhuman primate species that is widely used in drug metabolism studies. nat1/2 in these macaques have molecular and enzymatic similarities to their human orthologs; however, genetic polymorphisms in nat1/2 have not been fully investigated in this ...202032339492
establishment of an african green monkey model for covid-19.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is responsible for an unprecedented global pandemic of covid-19. animal models are urgently needed to study the pathogenesis of covid-19 and to screen candidate vaccines and treatments. nonhuman primates (nhp) are considered the gold standard model for many infectious pathogens as they usually best reflect the human condition. here, we show that african green monkeys support a high level of sars-cov-2 replication and develop pronounced ...202032511377
a single lentivector dna based immunization contains a late heterologous sivmac251 mucosal challenge infection.variety of conventional vaccine strategies tested against hiv-1 have failed to induce protection against hiv acquisition or durable control of viremia. therefore, innovative strategies that can induce long lasting protective immunity against hiv chronic infection are needed. recently, we developed an integration-defective hiv lentidna vaccine that undergoes a single cycle of replication in target cells in which most viral antigens are produced. a single immunization with such lentidna induced lo ...202032278522
rhesus macaques are most likely the ancestral source of helicobacter suis infection in pigs and not cynomolgus macaques. 202032219893
unparalleled rapid evolution of kir genes in rhesus and cynomolgus macaque populations.the killer cell ig-like receptors (kir) modulate immune responses through interactions with mhc class i molecules. the kir region in large cohorts of rhesus and cynomolgus macaque populations were characterized, and the experimental design enabled the definition of a considerable number of alleles (n = 576) and haplotypes, which are highly variable with regard to architecture. although high levels of polymorphism were recorded, only a few alleles are shared between species and populations. the r ...202032111732
the effects of population tuning and trial-by-trial variability on information encoding and behavior.identifying the features of population responses that are relevant to the amount of information encoded by neuronal populations is a crucial step toward understanding population coding. statistical features, such as tuning properties, individual and shared response variability, and global activity modulations, could all affect the amount of information encoded and modulate behavioral performance. we show that two features in particular affect information: the modulation of population responses a ...202031754013
inhibition of allergen-induced dermal eosinophilia by an oxoeicosanoid receptor antagonist in non-human primates.5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ete), acting via the oxe receptor, is unique among 5-lipoxygenase products in its ability to directly induce human eosinophil migration, suggesting its involvement in eosinophilic diseases. to address this hypothesis, we synthesized selective indole-based oxe receptor antagonists. because rodents lack an oxe receptor orthologue, we sought to determine whether these antagonists could attenuate allergen-induced skin eosinophilia in sensitized monkeys.202031655023
predicting the radiation sensitivity of male and female rhesus macaques using gene expression.radiosensitivity differs in humans and likely among closely-related primates. reasons for variation in radiosensitivity are not well known. we examined preirradiation gene expression in peripheral blood among male and female rhesus macaques which did or did not survive (up to 60 days) after whole-body irradiation with 700 cgy (ld66/60). rna samples originated from a blinded randomized good laboratory practice study in 142 irradiated rhesus macaques. animals were untreated (placebo), or treated u ...202033181854
virulence and pathogenesis of sars-cov-2 infection in rhesus macaques: a nonhuman primate model of covid-19 progression.the covid-19 has emerged as an epidemic, causing severe pneumonia with a high infection rate globally. to better understand the pathogenesis caused by sars-cov-2, we developed a rhesus macaque model to mimic natural infection via the nasal route, resulting in the sars-cov-2 virus shedding in the nose and stool up to 27 days. importantly, we observed the pathological progression of marked interstitial pneumonia in the infected animals on 5-7 dpi, with virus dissemination widely occurring in the l ...202033180882
evolution of ocular defects in infant macaques following in utero zika virus infection.congenital zika syndrome (czs) is associated with microcephaly and various neurological, musculoskeletal, and ocular abnormalities, but the long-term pathogenesis and postnatal progression of ocular defects in infants are not well characterized. rhesus macaques are superior to rodents as models of czs because they are natural hosts of the virus and share similar immune and ocular characteristics, including blood-retinal barrier characteristics and the unique presence of a macula. using a previou ...202033180748
corrigendum to "prime-boost vaccination using chemokine-fused gp120 dna and hiv envelope peptides activates both immediate and long-term memory cellular responses in rhesus macaques".[this corrects the article doi: 10.1155/2010/860160.].202033178829
inflammation, hiv, and immune quiescence: leveraging on immunomodulatory products to reduce hiv susceptibility.the relationship between inflammation and hiv has been a focus of research over the last decade. in hiv-infected individuals, increased hiv-associated immune activation significantly correlated to disease progression. while genital inflammation (gi) has been shown to significantly increase the risk of hiv acquisition and transmission, immune correlates for reduced risk remain limited. in certain hiv-exposed seronegative individuals, an immune quiescent phenotype characterized reduced risk. immun ...202033178456
diagnosis and surgical management of an intraocular foreign body secondary to ballistic wound in a rhesus macaque (macaca mulatta).intraocular foreign bodies (iofbs) such as air gun pellet is a rare finding in wild animals like rhesus macaque (macaca mulatta). the purpose of the present scientific report is to describe the surgical retrieval of iofb secondary to ballistic wound in a wild rhesus macaque.202033178304
effects of social housing changes on immunity and vaccine-specific immune responses in adolescent male rhesus macaques.nonhuman primates (nhps) in research institutions may be housed in a variety of social settings, such as group housing, pair housing or single housing based on the needs of studies. furthermore, housing may change over the course of studies. the effects of housing and changes in housing on cell activation and vaccine mediated immune responses are not well documented. we hypothesized that animals moved indoors from group to single housing (gh-sh) would experience more stress than those separated ...202033178191
a novel live attenuated rsv vaccine candidate with mutations in the l protein sam binding site and the g protein cleavage site is protective in cotton rats and a rhesus macaque.respiratory syncytial virus (rsv) is the leading cause of acute lower respiratory tract infections in children < 5 years of age worldwide, infecting the majority of infants in their first year of life. despite the widespread impact of this virus, no vaccine is currently available. for over 50 years, live attenuated vaccines (lav) have been shown to protect against other childhood viral infections, offering the advantage of presenting all viral proteins to the immune system for stimulation of bot ...202033177201
a new no-report paradigm reveals that face cells encode both consciously perceived and suppressed stimuli.a powerful paradigm to identify neural correlates of consciousness is binocular rivalry, wherein a constant visual stimulus evokes a varying conscious percept. it has recently been suggested that activity modulations observed during rivalry may represent the act of report rather than the conscious percept itself. here, we performed single-unit recordings from face patches in macaque inferotemporal (it) cortex using a no-report paradigm in which the animal's conscious percept was inferred from ey ...202033174836
a cervical mass in a laboratory rhesus macaque (macaca mulatta): suspicion of air sacculitis.a 13-year-old rhesus macaque presented a cervical swelling associated with sudden deterioration of its condition. this mass was surgically removed, and its histopathological examination revealed a stratified squamous epithelium. this appearance has been reported in some case of air sacculitis in others non-human primate species.202033169830
ketamine reduces temporal expectation in the rhesus monkey.ketamine, a well-known general dissociative anesthetic agent that is a non-competitive antagonist of the n-methyl-d-aspartate receptor, perturbs the perception of elapsed time and the expectation of upcoming events.202033169200
single-cell profiling of ebola virus disease in vivo reveals viral and host dynamics.ebola virus (ebov) causes epidemics with high mortality yet remains understudied due to the challenge of experimentation in high-containment and outbreak settings. here, we used single-cell transcriptomics and cytof-based single-cell protein quantification to characterize peripheral immune cells during ebov infection in rhesus monkeys. we obtained 100,000 transcriptomes and 15,000,000 protein profiles, finding that immature, proliferative monocyte-lineage cells with reduced antigen-presentation ...202033159858
hair dyes: a systematic review of pertinent in vivo human studies.what is the safety of hair dyes in human use? to address this, the penetration of hair dyes into human bodies must be quantified. this article provides a critical overview to update work published in the area of in vivo hair dye penetration in humans. studies are in humans, with one including rhesus monkey and one including in vitro human skin. medline, pubmed, embase, scopus, web of science, and google scholar databases were searched from 2004 to october 2019 for articles with experimental meth ...202033151347
alterations of the gut bacterial microbiota in rhesus macaques with siv infection and on short- or long-term antiretroviral therapy.gut dysbiosis and microbial translocation are associated with chronic systemic immune activation and inflammation in hiv-1 infection. however, the extent of restoration of gut microbiota in hiv-1 patients with short or long-term antiretroviral therapy (art) is unclear. to understand the impact of art on the gut microbiota, we used the rhesus macaque model of siv infection to characterize and compare the gut microbial community upon siv infection and during art. we observed altered taxonomic comp ...202033149234
reconstruction of natural images from responses of primate retinal ganglion cells.the visual message conveyed by a retinal ganglion cell (rgc) is often summarized by its spatial receptive field, but in principle also depends on the responses of other rgcs and natural image statistics. this possibility was explored by linear reconstruction of natural images from responses of the four numerically-dominant macaque rgc types. reconstructions were highly consistent across retinas. the optimal reconstruction filter for each rgc - its visual message - reflected natural image statist ...202033146609
epidemiological investigation and genotypes of enterocytozoon bieneusi in 11 captive rhesus macaque populations.enterocytozoon bieneusi is an obligate intracellular parasite and the most common pathogen of microsporidiosis in humans and animals. in this study, a total of 198 fecal samples were collected from 11 captive populations of rhesus macaque in chinese zoos, to investigate the prevalence and analyze the zoonotic potential of e. bieneusi by genotype of the internal transcribed spacer (its) gene on the rrna of e. bieneusi via nested pcr. results showed that the average infection rate of e. bieneusi i ...202033145162
values encoded in orbitofrontal cortex are causally related to economic choices.in the eighteenth century, daniel bernoulli, adam smith and jeremy bentham proposed that economic choices rely on the computation and comparison of subjective values1. this hypothesis continues to inform modern economic theory2 and research in behavioural economics3, but behavioural measures are ultimately not sufficient to verify the proposal4. consistent with the hypothesis, when agents make choices, neurons in the orbitofrontal cortex (ofc) encode the subjective value of offered and chosen go ...202033139951
neural control of rapid binocular eye movements: saccade-vergence burst neurons.during normal viewing, we direct our eyes between objects in three-dimensional (3d) space many times a minute. to accurately fixate these objects, which are usually located in different directions and at different distances, we must generate eye movements with appropriate versional and vergence components. these combined saccade-vergence eye movements result in disjunctive saccades with a vergence component that is much faster than that generated during smooth, symmetric vergence eye movements. ...202033139553
the macaque brain onprc18 template with combined gray and white matter labelmap for multimodal neuroimaging studies of nonhuman primates.macaques are the most common nonhuman primate (nhp) species used in neuroscience research. with the advancement of many neuroimaging techniques, new studies are beginning to apply multiple types of in vivo magnetic resonance imaging (mri), such as structural imaging (smri) with t1 and t2 weighted contrasts alongside diffusion weighed (dw) imaging. in studies involving rhesus macaques, this approach can be used to better understand micro-structural changes that occur during development, in variou ...202033137475
sharing voxelwise neuroimaging results from rhesus monkeys and other species with neurovault.animal neuroimaging studies can provide unique insights into brain structure and function, and can be leveraged to bridge the gap between animal and human neuroscience. in part, this power comes from the ability to combine mechanistic interventions with brain-wide neuroimaging. due to their phylogenetic proximity to humans, nonhuman primate neuroimaging holds particular promise. because nonhuman primate neuroimaging studies are often underpowered, there is a great need to share data amongst tran ...202033137472
atomoxetine modulates the contribution of low-level signals during free viewing of natural images in rhesus monkeys.visuo-spatial attentional orienting is fundamental to selectively process behaviorally relevant information, depending on both low-level visual attributes of stimuli in the environment and higher-level factors, such as goals, expectations and prior knowledge. growing evidence suggests an impact of the locus-cœruleus-norepinephrine (lc-ne) system in attentional orienting that depends on task-context. nonetheless, most of previous studies used visual displays encompassing a target and various dist ...202033137343
characterization of nef expression in different brain regions of siv-infected macaques.hiv-associated cns dysfunction is a significant problem among people with hiv (pwh), who now live longer due to viral suppression from combined anti-retroviral therapy (art). over the course of infection, hiv generates toxic viral proteins and induces inflammatory cytokines that have toxic effects on neurons in the cns. among these viral proteins, hiv nef has been found in neurons of postmortem brain specimens from pwh. however, the source of nef and its impact on neuronal cell homeostasis are s ...202033137166
retraction: conversion of human umbilical cord mesenchymal stem cells in wharton's jelly to dopamine neurons mediated by the lmx1a and neurturin in vitro: potential therapeutic application for parkinson's disease in a rhesus monkey model. 202033137132
isolation of a highly purified hsc-enriched cd34+cd90+cd45ra- cell subset for allogeneic transplantation in the nonhuman primate large-animal model.allogeneic hematopoietic stem cell transplantation (allo-hct) is a common treatment for patients suffering from different hematological disorders. allo-hct in combination with hematopoietic stem cell (hsc) gene therapy is considered a promising treatment option for millions of patients with hiv+ and acute myeloid leukemia. most currently available hsc gene therapy approaches target cd34-enriched cell fractions, a heterogeneous mix of mostly progenitor cells and only very few hscs with long-term ...202033134503
protective cranial implant caps for macaques.neuroscience studies with macaque monkeys may require cranial implants to stabilize the head or gain access to the brain for scientific purposes. wound management that promotes healing after the cranial implant surgery in non-human primates can be difficult as it is not necessarily possible to cover the wound margins.202033130051
effects of alfaxalone on cerebral blood flow and intrinsic neural activity of rhesus monkeys: a comparison study with ketamine.alfaxalone has been used increasingly in biomedical research and veterinary medicine of large animals in recent years. however, its effects on the cerebral blood flow (cbf) physiology and intrinsic neuronal activity of anesthetized brains remain poorly understood.202033127411
correction to: quantification of neurons in the hippocampal formation of chimpanzees: comparison to rhesus monkeys and humans.the original version of this article contained a mistake in figs. 3 and 4.202033124675
lipid metabolism is associated with temperament, corticosteroid, and hematological measures in infant rhesus monkeys ( macaca mulatta).individuals can differ in how their behavioral and physiological systems are organized. the fact that these individual differences persist across life suggests they are supported by physical structures that may co-vary. here, we explored three datasets associated with health and behavioral outcomes, which were obtained from infant rhesus monkeys during standardized assessment of biobehavioral organization. variation in biobehavioral measures was related to variation in molecular pathways, as ass ...202033124219
shared functional connectivity between the dorso-medial and dorso-ventral streams in macaques.manipulation of an object requires us to transport our hand towards the object (reach) and close our digits around that object (grasp). in current models, reach-related information is propagated in the dorso-medial stream from posterior parietal area v6a to medial intraparietal area, dorsal premotor cortex, and primary motor cortex. grasp-related information is processed in the dorso-ventral stream from the anterior intraparietal area to ventral premotor cortex and the hand area of primary motor ...202033122655
differential functional connectivity underlying asymmetric reward-related activity in human and nonhuman primates.the orbitofrontal cortex (ofc) is a key brain region involved in complex cognitive functions such as reward processing and decision making. neuroimaging studies have reported unilateral ofc response to reward-related variables; however, those studies rarely discussed this observation. nevertheless, some lesion studies suggest that the left and right ofc contribute differently to cognitive processes. we hypothesized that the ofc asymmetrical response to reward could reflect underlying hemispheric ...202033122437
a mucosal adenovirus prime/systemic envelope boost vaccine regimen elicits responses in cervicovaginal and alveolar macrophages of rhesus macaques associated with delayed siv acquisition and b cell help.vaccine strategies targeting the mucosal portal of entry may prevent hiv acquisition and systemic infection. macrophages in cervicovaginal compartments are one of the first cell types to encounter virus upon vaginal exposure. their activation can lead to recruitment of additional macrophages and cd4+ t-cells susceptible to viral infection. however, they are also critical in providing early protection against invading pathogens. therefore, understanding their response to immunization is important ...202033117363
nonhuman primates exposed to zika virus in utero are not protected against reinfection at 1 year postpartum.there is limited information about the impact of zika virus (zikv) exposure in utero on the anti-zikv immune responses of offspring. we infected six rhesus macaque dams with zikv early or late in pregnancy and studied four of their offspring over the course of a year postpartum. despite evidence of zikv exposure in utero, we observed no structural brain abnormalities in the offspring. we detected infant-derived zikv-specific immunoglobulin a antibody responses and t cell memory responses during ...202033115950
developmental gene expression differences between humans and mammalian models.identifying the molecular programs underlying human organ development and how they differ from model species is key for understanding human health and disease. developmental gene expression profiles provide a window into the genes underlying organ development and a direct means to compare them across species. we use a transcriptomic resource covering the development of seven organs to characterize the temporal profiles of human genes associated with distinct disease classes and to determine, for ...202033113372
comparative analyses of transgene expression patterns after intra-striatal injections of raav2-retro in rats and rhesus monkeys: a light and electron microscopic study.retrogradely-transducing viral vectors are versatile tools for anatomical and functional interrogations of neural circuits. these vectors can be applied in nonhuman primates (nhps), powerful model species for neuroscientific studies with limited genetic tractability, but limited data are available regarding the tropism and transgene expression patterns of such viruses after injections in nhp brains. consequently, nhp researchers must often rely on related data available from other species for ex ...202033113247
origin of rebound virus in chronically siv-infected rhesus monkeys following treatment discontinuation.viral rebound following antiretroviral therapy (art) discontinuation in hiv-1-infected individuals is believed to originate from a small pool of cd4+ t cells harboring replication-competent provirus. however, the origin and nature of the rebound virus has remained unclear. recent studies have suggested that rebound virus does not originate directly from individual latent proviruses but rather from recombination events involving multiple proviruses. here we evaluate the origin of rebound virus in ...202033110078
evolution of regulatory signatures in primate cortical neurons at cell-type resolution.the human cerebral cortex contains many cell types that likely underwent independent functional changes during evolution. however, cell-type-specific regulatory landscapes in the cortex remain largely unexplored. here we report epigenomic and transcriptomic analyses of the two main cortical neuronal subtypes, glutamatergic projection neurons and gabaergic interneurons, in human, chimpanzee, and rhesus macaque. using genome-wide profiling of the h3k27ac histone modification, we identify neuron-su ...202033109720
fetal surgery in the primate 4.0: a new technique 30 years later.open fetal surgery requires a hemostatic hysterotomy that minimizes membrane separation. for over 30 years, the standard of care for hysterotomy in the gravid uterus has been the autosuture premium poly cs*-57 stapler.202033108788
multi-source domain adaptation for decoder calibration of intracortical brain-machine interface.for nonstationarity of neural recordings, daily retraining is required in the decoder calibration of intracortical brain-machine interfaces (ibmis). domain adaptation has started to be applied in ibmis to solve the problem of daily retraining by taking advantage of historical data. however, previous domain adaptation studies used only a single source domain, which might lead to performance instability. in this study, we proposed a multi-source domain adaptation algorithm, by fully utilizing the ...202033108775
feature-selection-based transfer learning for intracortical brain-machine interface decoding.the time spent in collecting current samples for decoder calibration and the computational burden brought by high-dimensional neural recordings remain two challenging problems in intracortical brain-machine interfaces (ibmis). decoder calibration optimization approaches have been proposed, and neuron selection methods have been used to reduce computational burden. however, few methods can solve both problems simultaneously. in this paper, we present a symmetrical-uncertaintybased transfer learni ...202033108289
therapeutic vaccination of siv-infected, art-treated infant rhesus macaques using ad48/mva in combination with tlr-7 stimulation.globally, 1.8 million children are living with hiv-1. while antiretroviral therapy (art) has improved disease outcomes, it does not eliminate the latent hiv-1 reservoir. interventions to delay or prevent viral rebound in the absence of art would be highly beneficial for hiv-1-infected children who now must remain on daily art throughout their lifespan. here, we evaluated therapeutic ad48-siv prime, mva-siv boost immunization in combination with the tlr-7 agonist gs-986 in rhesus macaque (rm) inf ...202033104758
crystal structure of a soluble apobec3g variant suggests ssdna to bind in a channel that extends between the two domains.apobec3g (a3g) is a single-stranded dna (ssdna) cytosine deaminase that can restrict hiv-1 infection by mutating the viral genome. a3g consists of a non-catalytic n-terminal domain (ntd) and a catalytic c-terminal domain (ctd) connected by a short linker. while the ctd catalyzes cytosine deamination, the ntd is believed to provide additional affinity for ssdna. structures of both a3g domains have been solved individually; however, a full-length a3g structure has been challenging. recently, cryst ...202033098858
in vivo evaluation and dosimetry estimate for a high affinity affibody pet tracer targeting pd-l1.in vivo imaging of programmed death ligand 1 (pd-l1) during immunotherapy could potentially monitor changing pd-l1 expression and pd-l1 expression heterogeneity within and across tumors. some protein constructs can be used for same-day positron emission tomography (pet) imaging. previously, we evaluated the pd-l1-targeting affibody molecule [18f]alf-nota-zpd-l1_1 as a pet tracer in a mouse tumor model of human pd-l1 expression. in this study, we evaluated the affinity-matured affibody molecule z ...202033098025
damage to orbitofrontal areas 12 and 13, but not area 14, results in blunted attention and arousal to socioemotional stimuli in rhesus macaques.an earlier study in monkeys indicated that lesions to the mid-portion of the ventral orbitofrontal cortex (ofc), including walker's areas 11 and 13 (ofc11/13), altered the spontaneous scanning of still pictures of primate faces (neutral and emotional) and the modulation of arousal. yet, these conclusions were limited by several shortcomings, including the lesion approach, use of static rather than dynamic stimuli, and manual data analyses. to confirm and extend these earlier findings, we compare ...202033093825
single-cell strand sequencing of a macaque genome reveals multiple nested inversions and breakpoint reuse during primate evolution.rhesus macaque is an old world monkey that shared a common ancestor with human ∼25 myr ago and is an important animal model for human disease studies. a deep understanding of its genetics is therefore required for both biomedical and evolutionary studies. among structural variants, inversions represent a driving force in speciation and play an important role in disease predisposition. here we generated a genome-wide map of inversions between human and macaque, combining single-cell strand sequen ...202033093070
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