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isoxpressor: a tool to assess transcriptional activity within isochores.genomes are characterized by large regions of homogeneous base compositions known as isochores. the latter are divided into gc-poor and gc-rich classes linked to distinct functional and structural properties. several studies have addressed how isochores shape function and structure. to aid in this important subject, we present isoxpressor, a tool designed for the analysis of the functional property of transcription within isochores. isoxpressor allows users to process rna-seq data in relation to ...202032857856
neural signatures of α2-adrenergic agonist-induced unconsciousness and awakening by antagonist.how the brain dynamics change during anesthetic-induced altered states of consciousness is not completely understood. the α2-adrenergic agonists are unique. they generate unconsciousness selectively through α2-adrenergic receptors and related circuits. we studied intracortical neuronal dynamics during transitions of loss of consciousness (loc) with the α2-adrenergic agonist dexmedetomidine and return of consciousness (roc) in a functionally interconnecting somatosensory and ventral premotor netw ...202032857037
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
characterization of rhesus macaque liver-resident cd49a+ nk cells during retrovirus infections.cd49a+ tissue resident nk cells have been implicated in memory-like nk cell responses, but while this population is well-characterized in mice and in humans, they are poorly described in non-human primates (nhp) which are particularly critical for modeling human viral infections. others and we have shown that memory-like nk cells are enriched in the liver and because of the importance of nhp in modeling hiv infection, understanding the immunobiology of cd49a+ nk cells in siv-infected rhesus maca ...202032849583
absolute numerosity discrimination as a case study in comparative vertebrate intelligence.the question of whether some non-human animal species are more intelligent than others is a reoccurring theme in comparative psychology. to convincingly address this question, exact comparability of behavioral methodology and data across species is required. the current article explores one of the rare cases in which three vertebrate species (humans, macaques, and crows) experienced identical experimental conditions during the investigation of a core cognitive capability - the abstract categoriz ...202032849085
statistical learning signals for complex visual images in macaque early visual cortex.animals of several species, including primates, learn the statistical regularities of their environment. in particular, they learn the temporal regularities that occur in streams of visual images. previous human neuroimaging studies reported discrepant effects of such statistical learning, ranging from stronger occipito-temporal activations for sequences in which image order was fixed, compared with sequences of randomly ordered images, to weaker activations for fixed-order sequences compared wi ...202032848562
reduced meiotic recombination in rhesus macaques and the origin of the human recombination landscape.characterizing meiotic recombination rates across the genomes of nonhuman primates is important for understanding the genetics of primate populations, performing genetic analyses of phenotypic variation and reconstructing the evolution of human recombination. rhesus macaques (macaca mulatta) are the most widely used nonhuman primates in biomedical research. we constructed a high-resolution genetic map of the rhesus genome based on whole genome sequence data from indian-origin rhesus macaques. th ...202032841250
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
confluence of timing and reward biases in perceptual decision-making dynamics.although the decisions of our daily lives often occur in the context of temporal and reward structures, the impact of such regularities on decision-making strategy is poorly understood. here, to explore how temporal and reward context modulate strategy, we trained 2 male rhesus monkeys to perform a novel perceptual decision-making task with asymmetric rewards and time-varying evidence reliability. to model the choice and response time patterns, we developed a computational framework for fitting ...202032839233
curvature processing in human visual cortical areas.curvature is one of many visual features shown to be important for visual perception. we recently showed that curvilinear features provide sufficient information for categorizing animate vs. inanimate objects, while rectilinear features do not (zachariou et al., 2018). results from our fmri study in rhesus monkeys (yue et al., 2014) have shed light on some of the neural substrates underlying curvature processing by revealing a network of visual cortical patches with a curvature response preferen ...202032835823
dysregulation of behavioral and autonomic responses to emotional and social stimuli following bidirectional pharmacological manipulation of the basolateral amygdala in macaques.the amygdala is a key component of the neural circuits mediating the processing and response to emotionally salient stimuli. amygdala lesions dysregulate social interactions, responses to fearful stimuli, and autonomic functions. in rodents, the basolateral and central nuclei of the amygdala have divergent roles in behavioral control. however, few studies have selectively examined these nuclei in the primate brain. moreover, the majority of non-human primate studies have employed lesions, which ...202032835765
preserved visual memory and relational cognition performance in monkeys with selective hippocampal lesions.the theory that the hippocampus is critical for visual memory and relational cognition has been challenged by discovery of more spared hippocampal tissue than previously reported in h.m., previously unreported extra-hippocampal damage in developmental amnesiacs, and findings that the hippocampus is unnecessary for object-in-context memory in monkeys. these challenges highlight the need for causal tests of hippocampal function in nonhuman primate models. here, we tested rhesus monkeys on a batter ...202032832615
affiliation and disease risk: social networks mediate gut microbial transmission among rhesus macaques.in social animals, affiliative behaviours bring many benefits, but also costs such as disease risk. the ways in which affiliation may affect the risk of infectious agent transmission remain unclear. moreover, studies linking variation in affiliative interactions to infectious agent incidence/diversity have speculated that disease transmission may have occurred, rather than revealing that transmission did occur. we address these gaps using the phylogenetics of commensal gut escherichia coli to de ...201932831349
treatment of latent m. tuberculosis infection and use of antiretroviral therapy to prevent tuberculosis.even with treatment of hiv with antiretroviral therapy (art), the risk of tuberculosis (tb) reactivation remains higher in hiv-infected than hiv-uninfected persons. in this issue of the jci, ganatra et al. explored tb reactivation in the context of art using tb and simian immunodeficiency virus-coinfected (tb/siv-coinfected) nonhuman primates. the authors found that treating rhesus macaques with art restored cd4+ t cells in whole blood, spleen, and bronchoalveolar lavage (bal) fluid, but not in ...202032831291
assessing antigen-specific cellular immune responses upon hiv /siv plasmid dna vaccination in the nonhuman primate model.reliable detection and quantification of antigen-specific t cells are critical for assessing the immunogenicity of vaccine candidates. in this chapter, we describe the use of elispot and flow cytometry-based assays for efficient detection, mapping, and functional characterization of memory t lymphocytes in different tissues of rhesus macaques immunized with plasmid dna. flow cytometric assays provide a large amount of information, both phenotypic and functional, about individual cells, while the ...202132827134
an adenovirus-vectored covid-19 vaccine confers protection from sars-cov-2 challenge in rhesus macaques.the rapid spread of coronavirus sars-cov-2 greatly threatens global public health but no prophylactic vaccine is available. here, we report the generation of a replication-incompetent recombinant serotype 5 adenovirus, ad5-s-nb2, carrying a codon-optimized gene encoding spike protein (s). in mice and rhesus macaques, intramuscular injection with ad5-s-nb2 elicits systemic s-specific antibody and cell-mediated immune (cmi) responses. intranasal inoculation elicits both systemic and pulmonary anti ...202032826924
palmitic acid targets human testicular peritubular cells and causes a pro-inflammatory response.palmitic acid (pa) is a major fatty acid, derived from diet and endogenous production, which is being linked to inflammation. while such actions of pa at the level of the testis remain difficult to examine, we reasoned that studies in human testicular cells may be instructive. human testicular peritubular cells (htpcs) can be isolated from men and cultured. they have contractile properties but also produce interleukin 6 (il6), express the inflammasome member nlrp3, and via glia cell line derived ...202032824411
effects of early life stress on cocaine intake in male and female rhesus macaques.it is critical to identify potential risk factors, such as a history of early life stress (els), that may confer specific vulnerabilities to increased drug intake.202032821985
rhcmv serostatus and vaccine adjuvant impact immunogenicity of rhcmv/siv vaccines.rhesus cytomegalovirus (rhcmv) strain 68-1-vectored simian immunodeficiency virus (rhcmv/siv) vaccines are associated with complete clearance of pathogenic siv challenge virus, non-canonical major histocompatibility complex restriction, and absent antibody responses in recipients previously infected with wild-type rhcmv. this report presents the first investigation of rhcmv/siv vaccines in rhcmv-seronegative macaques lacking anti-vector immunity. fifty percent of rhesus macaques (rm) vaccinated ...202032820216
prevention and treatment of shivad8 infection in rhesus macaques by a potent d-peptide hiv entry inhibitor.cholesterol-pie12-trimer (cpt31) is a potent d-peptide hiv entry inhibitor that targets the highly conserved gp41 n-peptide pocket region. cpt31 exhibited strong inhibitory breadth against diverse panels of primary virus isolates. in a simian-hiv chimeric virus ad8 (shivad8) macaque model, cpt31 prevented infection from a single high-dose rectal challenge. in chronically infected animals, cpt31 monotherapy rapidly reduced viral load by ∼2 logs before rebound occurred due to the emergence of drug ...202032820072
antinociceptive, reinforcing, and pruritic effects of the g-protein signalling-biased mu opioid receptor agonist pzm21 in non-human primates.a novel g-protein signalling-biased mu opioid peptide (mop) receptor agonist, pzm21, was recently developed with a distinct chemical structure. it is a potent gi/o activator with minimal β-arrestin-2 recruitment. despite intriguing activity in rodent models, pzm21 function in non-human primates is unknown. the aim of this study was to investigate pzm21 actions after systemic or intrathecal administration in primates.202032819621
sars-cov-2 infection induces robust germinal center cd4 t follicular helper cell responses in rhesus macaques.cd4 t follicular helper (t fh ) cells are important for the generation of durable and specific humoral protection against viral infections. the degree to which sars-cov-2 infection generates t fh cells and stimulates the germinal center response is an important question as we investigate vaccine options for the current pandemic. here we report that sars-cov-2 infection resulted in transient accumulation of pro-inflammatory monocytes and proliferating t fh cells with a t h 1 profile in peripheral ...202032818217
covariation of fetal skull and maternal pelvis during the perinatal period in rhesus macaques and evolution of childbirth in primates.a large brain combined with an upright posture in humans has resulted in a high cephalopelvic proportion and frequently obstructed labor. fischer and mitteroecker [b. fischer, p. mitteroecker, proc. natl. acad. sci. u.s.a. 112, 5655-5660 (2015)] proposed that the morphological covariations between the skull and pelvis could have evolved to ameliorate obstructed labor in humans. the availability of quantitative data of such covariation, especially of the fetal skull and maternal pelvis, however, ...202032817513
laminar subnetworks of response suppression in macaque primary visual cortex.cortical inhibition plays an important role in information processing in the brain. however, the mechanisms by which inhibition and excitation are coordinated to generate functions in the six layers of the cortex remain unclear. here, we measured laminar-specific responses to stimulus orientations in primary visual cortex (v1) of awake monkeys (male, macaca mulatta). we distinguished inhibitory effects (suppression) from excitation, by taking advantage of the separability of excitation and inhib ...202032817246
antigenicity and immunogenicity of hiv-1 envelope trimers complexed to a small-molecule viral entry inhibitor.small-molecule viral entry inhibitors, such as bms-626529 (bms-529), allosterically block cd4 binding to hiv-1 envelope (env) and inhibit cd4-induced structural changes in env trimers. here, we show that the binding of bms-529 to clade c soluble chimeric gp140 sosip (ch.sosip) and membrane-bound trimers with intact transmembrane domain (gp150) prevented trimer conformational transitions and enhanced their immunogenicity. when complexed to bms-529, ch.sosip trimers retained their binding to broad ...202032817216
smac mimetic plus triple-combination bispecific hivxcd3 retargeting molecules in shiv.c.ch505-infected, antiretroviral therapy-suppressed rhesus macaques.the "shock-and-kill" human immunodeficiency virus type 1 (hiv-1) cure strategy involves latency reversal followed by immune-mediated clearance of infected cells. we have previously shown that activation of the noncanonical nf-κb pathway using an inhibitor of apoptosis (iap), azd5582, reverses hiv/simian immunodeficiency virus (siv) latency. here, we combined azd5582 with bispecific hivxcd3 dart molecules to determine the impact of this approach on persistence. rhesus macaques (rms) (n = 13) were ...202032817214
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
the rate of dasotraline brain entry is slow following intravenous administration.drugs that rapidly increase dopamine levels have an increased risk of abuse. dasotraline (das) is a dopamine and norepinephrine reuptake inhibitor characterized by slow oral absorption with low potential for abuse. however, it remains unclear whether intravenous (i.v.) administration would facilitate the rapid elevation of dopamine levels associated with stimulant drugs.202032813030
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
gulosibacter macacae sp. nov., a novel actinobacterium isolated from macaca mulatta faeces.a novel gram-stain-positive, aerobic, non-spore-forming, irregular short rod-shaped actinobacterial strain, designated yim 102482-1t, was isolated from the faeces of macaca mulatta. strain yim 102482-1t grew optimally at 30-37 °c, at ph 8.0 and in the presence of 1.0-3.0% (w/v) nacl. similarly, analysis based on 16s rrna gene sequences showed that strain yim 102482-1t was a member of the genus gulosibacter and most closely related to gulosibacter feacalis nbrc 15706t (97.6 %), gulosibacter bifid ...202032809927
targeting hiv env immunogens to b cell follicles in nonhuman primates through immune complex or protein nanoparticle formulations.following immunization, high-affinity antibody responses develop within germinal centers (gcs), specialized sites within follicles of the lymph node (ln) where b cells proliferate and undergo somatic hypermutation. antigen availability within gcs is important, as b cells must acquire and present antigen to follicular helper t cells to drive this process. however, recombinant protein immunogens such as soluble human immunodeficiency virus (hiv) envelope (env) trimers do not efficiently accumulate ...202032802411
anti-pig ige and iga antibodies in naive primates and nonhuman primates with pig xenografts.natural preformed anti-pig igm/igg antibodies in primates play an important role in xenograft rejection. as it is not clear how ige and iga engage in the immune system in xenotransplantation, we investigated natural preformed and elicited anti-pig ige/iga in naïve primates and after xenotransplantation in nonhuman primates.202032796494
l226q mutation on influenza h7n9 virus hemagglutinin increases receptor-binding avidity and leads to biased antigenicity evaluation.since the first outbreak in 2013, the influenza a (h7n9) virus has continued emerging and has caused over five epidemic waves. suspected antigenic changes of the h7n9 virus based on hemagglutination inhibition (hi) assay during the fifth outbreak have prompted the update of h7n9 candidate vaccine viruses (cvvs). in this study, we comprehensively compared the serological cross-reactivities induced by the hemagglutinins (has) of the earlier cvv a/anhui/1/2013 (h7/ah13) and the updated a/guangdong/ ...202032796071
ifn signaling and neutrophil degranulation transcriptional signatures are induced during sars-cov-2 infection.the novel virus sars-cov-2 has infected more than 14 million people worldwide resulting in the coronavirus disease 2019 (covid-19). limited information on the underlying immune mechanisms that drive disease or protection during covid-19 severely hamper development of therapeutics and vaccines. thus, the establishment of relevant animal models that mimic the pathobiology of the disease is urgent. rhesus macaques infected with sars-cov-2 exhibit disease pathobiology similar to human covid-19, thus ...202032793903
evaluation of topical lysostaphin as a novel treatment for instrumented rhesus macaques (macaca mulatta) infected with methicillin- resistant staphylococcus aureus.lytic enzymes are novel antimicrobial agents that degrade bacterial cell walls, resulting in cell rupture and death. we tested one enzyme, the bacteriocin lysostaphin, for treatment of nonhuman primates (macaca mulatta) with persistent methicillinresistantstaphylococcus aureus (mrsa) infection of their cranial implant margins. the goal of this study was to determine if topical lysostaphin, either alone or as an adjunct therapy, could eliminate mrsa. lysostaphin had in vitro lytic activity agains ...202032792040
the diet of the striped hyena in nepal's lowland regions.striped hyenas (hyaena hyaena) are extremely rare in nepal, and only a few people have studied them in their natural forest and grassland habitat. their rarity is due to anthropogenic pressures such as hunting, habitat modification, being killed on roads, and depletion of their natural prey. here, we studied the feeding ecology of hyenas in lowland, nepal. we employed an opportunistic sampling to collect hyena scats in a range of habitats and the line transect sampling to identify the prey of th ...202032788952
pharmacokinetic modeling of [18f]mc225 for quantification of the p-glycoprotein function at the blood-brain barrier in non-human primates with pet.[18f]mc225 has been developed as a weak substrate of p-glycoprotein (p-gp) aimed to measure changes in the p-gp function at the blood-brain barrier with positron emission tomography. this study evaluates [18f]mc225 kinetics in non-human primates and investigates the effect of both scan duration and p-gp inhibition. three rhesus monkeys underwent two 91-min dynamic scans with blood sampling at baseline and after p-gp inhibition (8 mg/kg tariquidar). data were analyzed using the 1-tissue compartme ...202032787277
representation of the observer's predicted outcome value in mirror and nonmirror neurons of macaque f5 ventral premotor cortex.in the search for the function of mirror neurons, a previous study reported that f5 mirror neuron responses are modulated by the value that the observing monkey associates with the grasped object. yet we do not know whether mirror neurons are modulated by the expected reward value for the observer or also by other variables, which are causally dependent on value (e.g., motivation, attention directed at the observed action, arousal). to clarify this, we trained two rhesus macaques to observe a gr ...202032783574
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
identifying cardiac diseases using cardiac biomarkers in rhesus macaques (macaca mulatta).cardiac biomarkers are an important tool for diagnosing cardiac diseases in both human and veterinary patients. serum concentrations of n-terminal probrain natriuretic peptide (nt-probnp) and cardiac troponin i (ctni) have been used to indicate the presence of various cardiac diseases including hypertrophic cardiomyopathy (hcm) in various species including humans. however, these cardiac biomarkers have not been established as a diagnostic tool for detecting cardiac disease in rhesus macaques. in ...202032778203
effects of low intensity ambient lighting on refractive development in infant rhesus monkeys (macaca mulatta).studies in chickens suggest low intensity ambient lighting causes myopia. the purpose of this experiment was to examine the effects of low intensity ambient lighting (dim light) on normal refractive development in macaque monkeys. seven infant rhesus monkeys were reared under dim light (room illumination level: ~55 lx) from 24 to ~310 days of age with otherwise unrestricted vision. refractive error, corneal power, ocular axial dimensions, and choroidal thickness were measured in anesthetized ani ...202032777589
a hsv1 mutant leads to an attenuated phenotype and induces immunity with a protective effect.herpes simplex virus type 1 (hsv1) is a complicated structural agent with a sophisticated transcription process and a high infection rate. a vaccine against hsv1 is urgently needed. as multiple viral-encoded proteins, including structural and nonstructural proteins, contribute to immune response stimulation, an attenuated or deficient hsv1 vaccine may be relatively reliable. advances in genomic modification technologies provide reliable means of constructing various hsv vaccine candidates. based ...202032776994
gingival tissue autophagy pathway gene expression profiles in periodontitis and aging.we hypothesized that autophagy-related genes will be differentially expressed in periodontitis, suggesting an impaired gingival autophagic response associated with disease.202032776336
delayed severe cytokine storm and immune cell infiltration in sars-cov-2-infected aged chinese rhesus macaques.as of june 2020, coronavirus disease 2019 (covid-19) has killed an estimated 440 000 people worldwide, 74% of whom were aged ≥65 years, making age the most significant risk factor for death caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection. to examine the effect of age on death, we established a sars-cov-2 infection model in chinese rhesus macaques ( macaca mulatta) of varied ages. results indicated that infected young macaques manifested impaired respiratory funct ...202032772513
methocinnamox (mcam) antagonizes the behavioral suppressant effects of morphine without impairing delayed matching-to-sample accuracy in rhesus monkeys.opioid abuse remains a serious public health problem. the pseudoirreversible mu opioid receptor antagonist methocinnamox (mcam) might be useful for treating opioid abuse and overdose. because endogenous opioid systems can modulate cognition and decision-making, it is important to evaluate whether long-term blockade of mu opioid receptors by mcam adversely impacts complex operant behavior involving memory.202032772146
clinical and immunological metrics during pediatric rhesus macaque development.background: clinical measurements commonly used to evaluate overall health of laboratory animals including complete blood count, serum chemistry, weight, and immunophenotyping, differ with respect to age, development, and environment. this report provides comprehensive clinical and immunological reference ranges for pediatric rhesus macaques over the first year of life. methods: we collected and analyzed blood samples from 151 healthy rhesus macaques, aged 0-55 weeks, and compared mother-reared ...202032766187
safety and immunological evaluation of interleukin-21 plus anti-α4β7 mab combination therapy in rhesus macaques.human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) infections compromise gut immunological barriers, inducing high levels of inflammation and a severe depletion of intestinal cd4+ t cells. expression of α4β7 integrin promotes homing of activated t cells to intestinal sites where they become preferentially infected; blockade of α4β7 with an anti-α4β7 monoclonal antibody (mab) prior to infection has been reported to reduce gut siv viremia in rhesus macaques (rms). interleuk ...202032765488
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
[18f]feppa pet imaging for monitoring cd68-positive microglia/macrophage neuroinflammation in nonhuman primates.the aim of this study was to examine whether the translocator protein 18-kda (tspo) pet ligand [18f]feppa has the sensitivity for detecting changes in cd68-positive microglial/macrophage activation in hemiparkinsonian rhesus macaques treated with allogeneic grafts of induced pluripotent stem cell-derived midbrain dopaminergic neurons (ipsc-mda).202032761399
zika virus in rhesus macaque semen and reproductive tract tissues: a pilot study of acute infection†.although sexual transmission of zika virus (zikv) is well-documented, the viral reservoir(s) in the male reproductive tract remains uncertain in humans and immune-intact animal models. we evaluated the presence of zikv in a rhesus macaque pilot study to determine persistence in semen, assess the impact of infection on sperm functional characteristics, and define the viral reservoir in the male reproductive tract. five adult male rhesus monkeys were inoculated with 105 pfu of asian-lineage zikv i ...202032761051
correction: rhesus macaques form preferences for brand logos through sex and social status based advertising.[this corrects the article doi: 10.1371/journal.pone.0193055.].202032760130
single-dose administration of recombinant human thrombopoietin mitigates total body irradiation-induced hematopoietic system injury in mice and nonhuman primates.recombinant human thrombopoietin (rhtpo) has been evaluated as a therapeutic intervention for radiation-induced myelosuppression. however, the immunogenicity induced by a repeated-dosing strategy raises concerns about the therapeutic use of rhtpo. in this study, single-dose administration of rhtpo was evaluated for efficacy in the hematopoietic response and survival effect on mice and nonhuman primates exposed to total body irradiation (tbi).202032758640
rapid stimulus-driven modulation of slow ocular position drifts.the eyes are never still during maintained gaze fixation. when microsaccades are not occurring, ocular position exhibits continuous slow changes, often referred to as drifts. unlike microsaccades, drifts remain to be viewed as largely random eye movements. here we found that ocular position drifts can, instead, be very systematically stimulus-driven, and with very short latencies. we used highly precise eye tracking in three well trained macaque monkeys and found that even fleeting (~8 ms durati ...202032758358
mybpc3 haplotype linked to hypertrophic cardiomyopathy in rhesus macaques (macaca mulatta).in humans, abnormal thickening of the left ventricle of the heart clinically defines hypertrophic cardiomyopathy (hcm), a common inherited cardiovascular disorder that can precede a sudden cardiac death event. the wide range of clinical presentations in hcm obscures genetic variants that may influence an individual's susceptibility to sudden cardiac death. although exon sequencing of major sarcomere genes can be used to detect high-impact causal mutations, this strategy is successful in only hal ...202032753092
innovative hbv animal models based on the entry receptor ntcp.hepatitis b is a major global health problem, with an estimated 257 million chronically infected patients and almost 1 million deaths per year. the causative agent is hepatitis b virus (hbv), a small, enveloped, partially double-stranded dna virus. hbv has a strict species specificity, naturally infecting only humans and chimpanzees. sodium taurocholate co-transporting polypeptide (ntcp), a bile acid transporter expressed on hepatocytes, has been shown to be one of the key factors in hbv infecti ...202032751581
dietary gluten and neurodegeneration: a case for preclinical studies.although celiac disease (cd) is an autoimmune disease that primarily involves the intestinal tract, mounting evidence suggests that a sizeable number of patients exhibit neurological deficits. about 40% of the celiac patients with neurological manifestations have circulating antibodies against neural tissue transglutaminase-6 (ttg6). while early diagnosis and strict adherence to a gluten-free diet (gfd) have been recommended to prevent neurological dysfunction, better therapeutic strategies are ...202032751379
an exploration of the relationships among facial dimensions, age, sex, dominance status, and personality in rhesus macaques (macaca mulatta).aspects of personality in nonhuman primates have been linked to health, social relationships, and life history outcomes. in humans as well as nonhuman primates, facial morphology is associated with assertiveness, aggression, and measures of dominance status. in this study we aimed to examine the relationship among facial morphology, age, sex, dominance status, and ratings on the personality dimensions confidence, openness, assertiveness, friendliness, activity, and anxiety in rhesus macaques (ma ...201932747846
power-saving design opportunities for wireless intracortical brain-computer interfaces.the efficacy of wireless intracortical brain-computer interfaces (ibcis) is limited in part by the number of recording channels, which is constrained by the power budget of the implantable system. designing wireless ibcis that provide the high-quality recordings of today's wired neural interfaces may lead to inadvertent over-design at the expense of power consumption and scalability. here, we report analyses of neural signals collected from experimental ibci measurements in rhesus macaques and f ...202032747834
age negatively impacts reproduction in high-ranking male rhesus macaques on cayo santiago, puerto rico.based on sexual selection theory, the reproductive potential of male primates is expected to be limited by access to fertile females. alpha males, the highest ranking males in a social group, are predicted to have better access to mates and produce more offspring until they are no longer dominant, which usually corresponds with age. little is known about male reproductive senescence independent of rank changes in nonhuman primates. here, we examine variation in the reproductive success of high-r ...202032747726
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
protective immune responses elicited by deglycosylated live-attenuated simian immunodeficiency virus vaccine are associated with il-15 effector functions.deglycosylated, live-attenuated siv vaccines elicited protective immune responses against heterologous sivsme543-3, which differs from the vaccine strain sivmac239 to levels similar to those across hiv-1 clades. two thirds of the vaccinees contained the chronic sivsme543-3 infection (controllers), whereas one third did not (noncontrollers). in this study, we investigated immune correlates of heterologous challenge control in rhesus macaques of burmese origin. because depletion of cd8+ cells in t ...202032747501
5ht expression in the stomach and duodenum of the rhesus monkey (macaca mulatta).this study aims to provide a histological description of different regions of the gastric and duodenal mucosa in rhesus monkey, as well as to analyze the distribution and the relative frequency of 5-ht. the cardia region mucosa consists of simple columnar epithelium pas + and ab + and the 5-ht cells were observed at the base of the gland (qa [5-ht cells]/mm²) = 8.72 ± 4.98). the body region, has a smaller number of glands. the 5-ht cells were found predominant in the base of the gastric glands. ...202032746994
establishment of a non-human primate model for menopausal hot flushes.menopause affects the quality of life of millions of women. with modern lifespan the postmenopausal attenuation of circulating estrogen levels can negatively impact a women's life for 30-40 years. the major hypoestrogenic consequence is hot flushes but decline in cognitive function, sleep disorders, depression/anxiety, cardiovascular disease, and osteoporosis are also characteristic for the menopause. current treatments of hot flushes include estrogen therapy alone or in combination with progest ...202032743563
safety and biocompatibility of aflibercept-loaded microsphere thermo-responsive hydrogel drug delivery system in a nonhuman primate model.to evaluate the safety and tolerability of a microsphere thermo-responsive hydrogel drug delivery system (dds) loaded with aflibercept in a nonhuman primate model.202032742760
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
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
fallacious reversal of event-order during recall reveals memory reconstruction in rhesus monkeys.whether nonhuman primate species can construct, still less reconstruct, order of past events remains controversial. here we show that rhesus macaques are capable of reconstructing the temporal order of memory traces of dynamic videos. we made use of 2000 unseen naturalistic videos of wildlife content for encoding, and then probed monkeys' recollection of temporal-order of events with a temporal-order judgement (toj) test. this encoding-toj procedure was repeated at three different time points (d ...202032735819
pre-treatment with ranibizumab aggravates pdt injury and alleviates inflammatory response in choroid-retinal endothelial cells.polypoidal choroidal vasculopathy (pcv) is the predominant subtype of exudative age-related macular degeneration in asians. although photodynamic therapy (pdt) is widely used for pcv treatment, its long-term beneficial effects are unsatisfactory. accumulating clinical investigations suggest that combined therapy with anti-vascular endothelial growth factor (anti-vegf) and pdt is superior to pdt monotherapy. however, the optimal time of anti-vegf before or after pdt remains controversial, hence i ...202032733897
chadox1 ncov-19 vaccine prevents sars-cov-2 pneumonia in rhesus macaques.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) emerged in december 20191,2 and is responsible for the coronavirus disease 2019 (covid-19) pandemic3. vaccines are an essential countermeasure and are urgently needed to control the pandemic4. here we show that the adenovirus-vector-based vaccine chadox1 ncov-19, which encodes the spike protein of sars-cov-2, is immunogenic in mice and elicites a robust humoral and cell-mediated response. this response was predominantly mediated by typ ...202032731258
single-shot ad26 vaccine protects against sars-cov-2 in rhesus macaques.a safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (sars-cov-2) may be required to end the coronavirus disease 2019 (covid-19) pandemic1-8. for global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (ad26) vector-based vaccines expressing the sars-cov-2 spike (s) protein in non-human primates. fifty-two rhesus macaq ...202032731257
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
monkeys and humans implement causal inference to simultaneously localize auditory and visual stimuli.the environment is sampled by multiple senses, which are woven together to produce a unified perceptual state. however, optimally unifying such signals requires assigning particular signals to the same or different underlying objects or events. many prior studies (especially in animals) have assumed fusion of cross-modal information, whereas recent work in humans has begun to probe the appropriateness of this assumption. here we present results from a novel behavioral task in which both monkeys ...202032727263
a vaccine targeting the rbd of the s protein of sars-cov-2 induces protective immunity.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) causes a respiratory disease called coronavirus disease 2019 (covid-19), the spread of which has led to a pandemic. an effective preventive vaccine against this virus is urgently needed. as an essential step during infection, sars-cov-2 uses the receptor-binding domain (rbd) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ace2) on host cells1,2. here we show that a recombinant vaccine that comprises re ...202032726802
neutralizing antibodies protect against oral transmission of lymphocryptovirus.epstein-barr virus (ebv) is a cancer-associated pathogen for which there is no vaccine. successful anti-viral vaccines elicit antibodies that neutralize infectivity; however, it is unknown whether neutralizing antibodies prevent ebv acquisition. here we assessed whether passively delivered ammo1, a monoclonal antibody that neutralizes ebv in a cell-type-independent manner, could protect against experimental ebv challenge in two animal infection models. when present prior to a high-dose intraveno ...202032724901
comparative gross anatomy of the forelimb arteries of the japanese monkey (macaca fuscata) and a comparative pattern of forelimb arterial distribution in primates.macaca fuscata displays characteristic behaviours, such as stone handling, locomotor behaviour, gait position, and intermittent bipedalism. differences in characteristic behaviours among primate species/genera could be explained by anatomical details of the body. however, the anatomical details have not been well studied in macaca fuscata. arterial models could be one of the anatomical bases for the phylogenetic and functional differences among species, since the arterial supply could be associa ...202032724814
prior vaccination with rvsv-zebov does not interfere with but improves efficacy of postexposure antibody treatment.a replication-competent vesicular stomatitis virus vaccine expressing the ebola virus (ebov) glycoprotein (gp) (rvsv-zebov) was successfully used during the 2013-16 ebov epidemic. additionally, chimeric and human monoclonal antibodies (mab) against the ebov gp have shown promise in animals and humans when administered therapeutically. uncertainty exists regarding the efficacy of postexposure antibody treatments in the event of a known exposure of a recent rvsv-zebov vaccinee. here, we model a wo ...202032719371
quantification of common and planar bile acids in tissues and cultured cells.bile acids (bas) have been established as ubiquitous regulatory molecules implicated in a large variety of healthy and pathological processes. however, the scope of ba heterogeneity is often underrepresented in current literature. this is due in part to inadequate detection methods, which fail to distinguish the individual constituents of the ba pool. thus, the primary aim of this study was to develop a method that would allow the simultaneous analysis of specific c24 ba species, and to apply th ...202032718973
comparison of multiplexed immunofluorescence imaging to chromogenic immunohistochemistry of skin biomarkers in response to monkeypox virus infection.over the last 15 years, advances in immunofluorescence-imaging based cycling methods, antibody conjugation methods, and automated image processing have facilitated the development of a high-resolution, multiplexed tissue immunofluorescence (mxif) method with single cell-level quantitation termed cell divetm. originally developed for fixed oncology samples, here it was evaluated in highly fixed (up to 30 days), archived monkeypox virus-induced inflammatory skin lesions from a retrospective study ...202032717786
immunophenotyping of rhesus cmv-specific cd8 t-cell populations.a vaccine to ameliorate cytomegalovirus (cmv)-related pathogenicity in transplantation patients is considered a top priority. a therapeutic vaccine must include components that elicit both neutralizing antibodies, and highly effective cd8 t-cell responses. the most important translational model of vaccine development is the captive-bred rhesus macaque (macaca mulatta) of indian origin. there is a dearth of information on rhesus cytomegalovirus (rhcmv)-specific cd8 t cells due to the absence of w ...202032713108
microglia, inflammation and gut microbiota responses in a progressive monkey model of parkinson's disease: a case series.inflammation has been linked to the development of nonmotor symptoms in parkinson's disease (pd), which greatly impact patients' quality of life and can often precede motor symptoms. suitable animal models are critical for our understanding of the mechanisms underlying disease and the associated prodromal disturbances. the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp)-treated monkey model is commonly seen as a "gold standard" model that closely mimics the clinical motor symptoms ...202032712266
reperfusion plus selective intra-arterial cooling (si-ac) improve recovery in a nonhuman primate model of stroke.early reperfusion is increasingly prioritized in ischemic stroke care, but outcomes remain suboptimal. therefore, there is an urgent need to find neuroprotective approaches that can be combined with reperfusion to maximize efficacy. here, the neuroprotective mechanisms behind therapeutic hypothermia were evaluated in a monkey model of ischemic stroke. focal ischemia was induced in adult rhesus monkeys by placing autologous clots in the middle cerebral artery. monkeys were treated with tissue pla ...202032710291
transcriptional profiling of primate central nucleus of the amygdala neurons to understand the molecular underpinnings of early-life anxious temperament.children exhibiting extreme anxious temperament (at) are at an increased risk for developing anxiety and depression. our previous mechanistic and neuroimaging work in young rhesus monkeys linked the central nucleus of the amygdala to at and its underlying neural circuit.202032709417
maintained representations of the ipsilateral and contralateral limbs during bimanual control in primary motor cortex.primary motor cortex (m1) almost exclusively controls the contralateral side of the body. however, m1 activity is also modulated during ipsilateral body movements. previous work has shown that m1 activity related to the ipsilateral arm is independent of the m1 activity related to the contralateral arm. how do these patterns of activity interact when both arms move simultaneously? we explored this problem by training 2 monkeys (male, macaca mulatta) in a postural perturbation task while recording ...202032703902
micro-anatomic alterations of the placenta in a non-human primate model of gestational protein-restriction.maternal protein malnutrition is associated with impaired fetal growth, and lifetime consequences for the offspring. our group has previously developed a model of protein-restriction in the non-human primate, which was associated with fetal growth restriction, stillbirth, decreased placental perfusion, and evidence of fetal hypoxia, suggesting perturbed vascular development. our objective was to histologically characterize the micro-anatomic alterations associated with adverse pregnancy outcomes ...202032702025
search for antiviral functions of potentially protective antibodies against v2 region of hiv-1.in the only successful rv144 vaccine trial to date, high levels of antibodies (abs) against the v2 region of the virus envelope protein gp120 correlated with reduced hiv-1 infection. the protective role of v2 abs has not yet been determined, and the antiviral function of v2 abs that mediate protection against hiv-1 in humans or shiv infection in rhesus macaques remains unclear. v2 abs do not neutralize resistant tier 2 viruses; their fc-mediated activities are modest and similar to those of anot ...202032701369
crispr/cas9-mediated introduction of the sodium/iodide symporter gene enables noninvasive in vivo tracking of induced pluripotent stem cell-derived cardiomyocytes.techniques that enable longitudinal tracking of cell fate after myocardial delivery are imperative for optimizing the efficacy of cell-based cardiac therapies. however, these approaches have been underutilized in preclinical models and clinical trials, and there is considerable demand for site-specific strategies achieving long-term expression of reporter genes compatible with safe noninvasive imaging. in this study, the rhesus sodium/iodide symporter (nis) gene was incorporated into rhesus maca ...202032700830
clindamycin protects nonhuman primates against inhalational anthrax but does not enhance reduction of circulating toxin levels when combined with ciprofloxacin.inhalational anthrax is rare and clinical experience limited. expert guidelines recommend treatment with combination antibiotics including protein synthesis-inhibitors to decrease toxin production and increase survival, although evidence is lacking.202032697310
fc-mediated effector function contributes to the in vivo antiviral effect of an hiv neutralizing antibody.treatment of hiv infection with either antiretroviral (arv) therapy or neutralizing monoclonal antibodies (nabs) leads to a reduction in hiv plasma virus. both arvs and nabs prevent new rounds of viral infection, but nabs may have the additional capacity to accelerate the loss of virus-infected cells through fc gamma receptor (fcγr)-mediated effector functions, which should affect the kinetics of plasma-virus decline. here, we formally test the role of effector function in vivo by comparing the ...202032690707
novel acute retinal artery ischemia and reperfusion model in nonhuman primates.the retina, as an externally located neural tissue, offers unique advantages in investigating the effect of therapeutic intervention on the brain. in this study, we put forth a clinically relevant model of retinal ischemia and reperfusion in nonhuman primates.202032684142
antibody development and property analysis of rhbst2 for accurate cell biological and viral research.bst2 is a single-pass type ii transmembrane (tm) protein, which has a cytoplasmic domain, a transmembrane domain, and an extracellular domain, each domain is important for biologic function of bst2. bst2 is a host restriction factor that can effectively inhibit retrovirus release. rhesus monkeys are considered as relevant natural animal models for studying aids in humans. in order to recognize rhesus bst2 (rhbst2) protein and detect its function accurately, we prepared a polyclonal antibody (pab ...202032681953
circgria1 shows an age-related increase in male macaque brain and regulates synaptic plasticity and synaptogenesis.circular rnas (circrnas) are abundant in mammalian brain and some show age-dependent expression patterns. here, we report that circgria1, a conserved circrna isoform derived from the genomic loci of α-mino-3-hydroxy-5-methyl-4-isoxazole propionic acid (ampa) receptor subunit gria1, shows an age-related and male-specific increase in expression in the rhesus macaque prefrontal cortex and hippocampus. we show circgria1 is predominantly localized to the nucleus, and find an age-related increase in i ...202032681011
organization of corollary discharge neurons in monkey medial dorsal thalamus.a corollary discharge (cd) is a copy of a neuronal command for movement sent to other brain regions to inform them of the impending movement. in monkeys, a circuit from superior colliculus (sc) through medial-dorsal nucleus of the thalamus (md) to frontal eye field (fef) carries such a cd for saccadic eye movements. this circuit provides the clearest example of such internal monitoring reaching cerebral cortex. in this report we first investigated the functional organization of the critical md r ...202032680937
[expression of b7 family co-inhibitory molecules in the establishment of pulmonary regional immunity].to identify the temporal-spatial expression of b7 family co-inhibitory molecules during lung development, and to explore the roles of b7 family co-inhibitory molecules in the developmental process of pulmonary regional immunity.201832677398
[the thyroid hormone receptor mediated luciferase reporter gene assays screening for edcs].this study in order to use report gene assay based on the thyroid hormone receptor (tr) α/β from human origin for screening endocrine disruptors chemicals (edcs), evaluating the thyroid hormone activity of bisphenol (bpa), 1-naphthaleny methyl carbamate and 1-naphthol (1-nap).201832677397
a psychometrically robust screening tool to rapidly identify socially impaired monkeys in the general population.naturally, low-social rhesus macaques exhibit social impairments with direct relevance to autism spectrum disorder (asd). to more efficiently identify low-social individuals in a large colony, we exploited, refined, and psychometrically assessed the macaque social responsiveness scale (msrs), an instrument previously derived from the human asd screening tool. we performed quantitative social behavior assessments and msrs ratings on a total of n = 349 rhesus macaques (macaca mulatta) housed in la ...202032677285
distribution and overlap of entorhinal, premotor, and amygdalar connections in the monkey anterior cingulate cortex.the anterior cingulate cortex (acc) is important for decision-making as it integrates motor plans with affective and contextual limbic information. disruptions in these networks have been observed in depression, bipolar disorder, and post-traumatic stress disorder. yet, overlap of limbic and motor connections within subdivisions of the acc is not well understood. hence, we administered a combination of retrograde and anterograde tracers into structures important for contextual memories (entorhin ...202032677044
sars-cov-2 infection induces germinal center responses with robust stimulation of cd4 t follicular helper cells in rhesus macaques.cd4 t follicular helper (t fh ) cells are important for the generation of long-lasting and specific humoral protection against viral infections. the degree to which sars-cov-2 infection generates t fh cells and stimulates the germinal center response is an important question as we investigate vaccine options for the current pandemic. here we report that, following infection with sars-cov-2, adult rhesus macaques exhibited transient accumulation of activated, proliferating t fh cells in their per ...202032676606
kikwit ebola virus disease progression in the rhesus monkey animal model.ongoing ebola virus disease outbreaks in the democratic republic of the congo follow the largest recorded outbreak in western africa (2013-2016). to combat outbreaks, testing of medical countermeasures (therapeutics or vaccines) requires a well-defined, reproducible, animal model. here we present ebola virus disease kinetics in 24 chinese-origin rhesus monkeys exposed intramuscularly to a highly characterized, commercially available kikwit ebola virus filovirus animal non-clinical group (fang) s ...202032674252
longitudinal effects of immediate and delayed estradiol on cognitive performance in a spatial maze and hippocampal volume in menopausal macaques under an obesogenic diet.the consumption of a diet high in fat and refined sugars has several health risks, including the development of cognitive decline and neurodegeneration. for women, menopause carries additional health risks that may interact with a high-fat diet in negative ways. some symptoms of menopause, including cognitive impairments, can be modulated by hormone replacement therapy (hrt), but the hormonal formulation and the timing of the treatment relative to the onset of menopause are critical factors dete ...202032670182
regional brain recovery from acute synaptic injury in simian immunodeficiency virus-infected rhesus macaques associates with heme oxygenase isoform expression.brain injury occurs within days in simian immunodeficiency virus (siv) or human immunodeficiency virus (hiv) infection, and some recovery may occur within weeks. inflammation and oxidative stress associate with such injury, but what drives recovery is unknown. chronic hiv infection associates with reduced brain frontal cortex expression of the antioxidant/anti-inflammatory enzyme heme oxygenase-1 (ho-1) and increased neuroinflammation in individuals with cognitive impairment. we hypothesized tha ...202032669339
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