Publications

TitleAbstractYear
Filter
PMID(sorted descending)
Filter
combination of cd8β depletion and interleukin-15 superagonist n-803 induces virus reactivation in simian-human immunodeficiency virus-infected, long-term art-treated rhesus macaques.the "shock and kill" strategy predicates that virus reactivation in latently infected cells is required to eliminate the human immunodeficiency virus (hiv) reservoir. in a recent study, we showed robust and persistent induction of plasma viremia in antiretroviral therapy (art)-treated simian immunodeficiency virus-infected rhesus macaques (rms) undergoing cd8α depletion and treated with the interleukin-15 (il-15) superagonist n-803 (j. b. mcbrien et al., nature 578:154-159, 2020, https://doi.org ...202032669328
nonhuman primate testing of the impact of different regulatory t cell depletion strategies on reactivation and clearance of latent simian immunodeficiency virus.regulatory t cells (tregs) may be key contributors to the hiv/siv latent reservoir, since they harbor high levels of hiv/siv; reverse cd4+ t cell immune activation status, increasing the pool of resting cd4+ t cells; and impair cd8+ t cell function, favoring hiv persistence. we tested the hypothesis that treg depletion is a valid intervention toward an hiv cure by depleted tregs in 14 rhesus macaque (rm) controllers infected with sivsab, the virus that naturally infects sabaeus monkeys, through ...202032669326
potently neutralizing and protective human antibodies against sars-cov-2.the ongoing pandemic of coronavirus disease 2019 (covid-19), which is caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2), is a major threat to global health1 and the medical countermeasures available so far are limited2,3. moreover, we currently lack a thorough understanding of the mechanisms of humoral immunity to sars-cov-24. here we analyse a large panel of human monoclonal antibodies that target the spike (s) glycoprotein5, and identify several that exhibit potent neutral ...202032668443
using raav2-retro in rhesus macaques: promise and caveats for circuit manipulation.recent genetic technologies such as opto- and chemogenetics allow for the manipulation of brain circuits with unprecedented precision. most studies employing these techniques have been undertaken in rodents, but a more human-homologous model for studying the brain is the nonhuman primate (nhp). optimizing viral delivery of transgenes encoding actuator proteins could revolutionize the way we study neuronal circuits in nhps. new method: raav2-retro, a popular new capsid variant, produces robust re ...202032668316
new approaches to quantify social development in rhesus macaques (macaca mulatta): integrating eye tracking with traditional assessments of social behavior.the nonhuman primate provides a sophisticated animal model system both to explore neurobiological mechanisms underlying complex behaviors and to facilitate preclinical research for neurodevelopmental and neuropsychiatric disease. a better understanding of evolutionarily conserved behaviors and brain processes between humans and nonhuman primates will be needed to successfully apply recently released nimh guidelines (not-mh-19-053) for conducting rigorous nonhuman primate neurobehavioral research ...202032666534
quantifying the contribution of fc-mediated effector functions to the antiviral activity of anti-hiv-1 igg1 antibodies in vivo.in combating viral infections, the fab portion of an antibody could mediate virus neutralization, whereas fc engagement of fc-γ receptors (fcγrs) could mediate an array of effector functions. evidence abounds that effector functions are important in controlling infections by influenza, ebola, or hiv-1 in animal models. however, the relative contribution of virus neutralization versus effector functions to the overall antiviral activity of an antibody remains unknown. to address this fundamental ...202032665438
quantitative fundus autofluorescence in rhesus macaques in aging and age-related drusen.to employ quantitative fundus autofluorescence (qaf) imaging in rhesus macaques to noninvasively assess retinal pigment epithelial (rpe) lipofuscin in nonhuman primates (nhps) as a model of aging and age-related macular degeneration (amd).202032663290
siv infection duration largely determines broadening of neutralizing antibody response in macaques.the development of broadly neutralizing antibodies (bnabs) in hiv infection is a result of long-term coevolutionary interaction between viruses and antibodies. understanding how this interaction promotes the increase of neutralization breadth during infection will improve the way in which aids vaccine strategies are designed. in this paper, we used siv-infected rhesus macaques as a model to study the development of neutralization breadth by infecting rhesus macaques with longitudinal nab escape ...202032663192
broad and differential animal angiotensin-converting enzyme 2 receptor usage by sars-cov-2.the covid-19 pandemic has caused an unprecedented global public health and economic crisis. the origin and emergence of its causal agent, sars-cov-2, in the human population remains mysterious, although bat and pangolin were proposed to be the natural reservoirs. strikingly, unlike the sars-cov-2-like coronaviruses (covs) identified in bats and pangolins, sars-cov-2 harbors a polybasic furin cleavage site in its spike (s) glycoprotein. sars-cov-2 uses human angiotensin-converting enzyme 2 (ace2) ...202032661139
antiretroviral penetration and drug transporter concentrations in the spleens of three preclinical animal models and humans.adequate antiretroviral (arv) concentrations in lymphoid tissues are critical for optimal antiretroviral therapy (art). while the spleen contains 25% of the body's lymphocytes, there are minimal data on arv penetration in this organ. this study quantified total and protein-unbound splenic arv concentrations and determined whether drug transporters, sex, or infection status were modifiers of these concentrations in animal models and humans. two humanized mice models (hu-hsc-rag [n = 36; 18 hiv-po ...202032661005
safety, pharmacokinetics, and activity of high-dose ivermectin and chloroquine against the liver stage of plasmodium cynomolgi infection in rhesus macaques.previously, ivermectin (1 to 10 mg/kg of body weight) was shown to inhibit the liver-stage development of plasmodium berghei in orally dosed mice. here, ivermectin showed inhibition of the in vitro development of plasmodium cynomolgi schizonts (50% inhibitory concentration [ic50], 10.42 μm) and hypnozoites (ic50, 29.24 μm) in primary macaque hepatocytes when administered as a high dose prophylactically but not when administered in radical cure mode. the safety, pharmacokinetics, and efficacy of ...202032660993
glucocorticoid-induced eosinopenia results from cxcr4-dependent bone marrow migration.glucocorticoids are considered first-line therapy in a variety of eosinophilic disorders. they lead to a transient, profound drop in circulating human eosinophils within hours of administration. this phenomenon of glucocorticoid-induced eosinopenia was the basis for the use of glucocorticoids in eosinophilic disorders and it has intrigued clinicians for seven decades, yet it remains unexplained. to address this, we first studied the response of circulating eosinophils to in vivo glucocorticoid a ...202032659786
reduced midbrain dopamine neuron number in the adult non-human primate brain after fetal radiation exposure.early gestation is a neurodevelopmental period that is especially vulnerable to environmental insult and one in which neurogenesis features prominently. prenatal perturbation during early gestation has been linked to neuropsychiatric illnesses such as autism and schizophrenia, and severe environmental insult during this period can result in profound mental impairment. midbrain dopamine neurons are generated during early gestation and play a key role in the motor, cognitive and reward circuitries ...202032659340
sofosbuvir shows a protective effect against vertical transmission of zika virus and the associated congenital syndrome in rhesus monkeys.the outbreaks of zika virus (zikv) infection in brazil, 2015-2016, were associated with severe congenital malformations. our translational study aimed to test the efficacy of the antiviral agent sofosbuvir (sof) against vertical transmission of zikv and the associated congenital syndrome (czs), using a rhesus monkey model. eight pregnant macaques were successfully infected during the organogenesis phase with a brazilian zikv strain; five of them received sof from two to fifteen days post-infecti ...202032649965
diversification of cpg-island promoters revealed by comparative analysis between human and rhesus monkey genomes.while cpg dinucleotides are significantly reduced compared to other dinucleotides in mammalian genomes, they can congregate and form cpg islands, which localize around the 5' regions of genes, where they function as promoters. cpg-island promoters are generally unmethylated and are often found in housekeeping genes. however, their nucleotide sequences and existence per se are not conserved between humans and mice, which may be due to evolutionary gain and loss of the regulatory regions. in this ...202032647942
therapeutic vaccine-mediated gag-specific cd8+ t-cell induction under anti-retroviral therapy augments anti-virus efficacy of cd8+ cells in simian immunodeficiency virus-infected macaques.anti-retroviral therapy (art) can inhibit hiv proliferation but not achieve virus eradication from hiv-infected individuals. under art-based hiv control, virus-specific cd8+ t-cell responses are often reduced. here, we investigated the impact of therapeutic vaccination inducing virus-specific cd8+ t-cell responses under art on viral control in a macaque aids model. twelve rhesus macaques received art from week 12 to 32 after simian immunodeficiency virus (siv) infection. six of them were vaccina ...202032647227
degenerative joint disease in the temporomandibular joint with fibrous ankylosis in a rhesus macaque (macaca mulatta).ankylosis in the temporomandibular joint (tmj) is known to have various etiologies in veterinary medicine. we observed a case of fibrous ankylosis of the tmj in a newly imported rhesus monkey (macaca mulatta).202032642457
deficits in the igg+ memory b-cell recovery after anthracycline treatment is confined to the spleen of rhesus macaques.loss of vaccine-induced antibodies (abs) after chemotherapy against paediatric acute lymphoblastic leukaemia (all) is common and often necessitates re-immunisation after cessation of treatment. even so, some all survivors fail to mount or to maintain protective abs. germinal centres (gcs) are clusters of proliferating b cells in follicles of secondary lymphoid tissues (slts) formed during adaptive immune responses and the origins of long-lived memory b and plasma cells that are the source of abs ...202032642064
evaluation of chimpanzee adenovirus and mva expressing trap and csp from plasmodium cynomolgi to prevent malaria relapse in nonhuman primates.plasmodium vivax is the world's most widely distributed human malaria parasite, with over 2.8 billion people at risk in asia, the americas, and africa. the 80-90% new p. vivax malaria infections are due to relapses which suggest that a vaccine with high efficacy against relapses by prevention of hypnozoite formation could lead to a significant reduction in the prevalence of p. vivax infections. here, we describe the development of new recombinant chadox1 and mva vectors expressing p. cynomolgi t ...202032640702
cognitive control of working memory but not familiarity in rhesus monkeys (macaca mulatta).directed forgetting paradigms assess cognitive control by determining whether memory accuracy is superior in trials on which subjects were instructed to remember compared with accuracy in trials on which they were instructed to forget. we used a directed forgetting paradigm to compare the extent to which working memory and familiarity are subject to rehearsal-like cognitive control in rhesus monkeys. monkeys studied a sample image, then saw one of two distinctive cues during a retention interval ...202032638291
vaccine-mediated protection against campylobacter-associated enteric disease.campylobacter coli and campylobacter jejuni are responsible for 400 million to 500 million cases of enteric disease each year and represent the most common cause of bacterial gastroenteritis worldwide. despite its global importance, campylobacter vaccine development has been hampered by the lack of animal models that recapitulate human disease pathogenesis. here, we describe a naturally occurring campylobacter-associated diarrhea model in outdoor-housed rhesus macaques. using this model, we deve ...202032637610
infection with novel coronavirus (sars-cov-2) causes pneumonia in rhesus macaques.the 2019 novel coronavirus (sars-cov-2) outbreak is a major challenge for public health. sars-cov-2 infection in human has a broad clinical spectrum ranging from mild to severe cases, with a mortality rate of ~6.4% worldwide (based on world health organization daily situation report). however, the dynamics of viral infection, replication and shedding are poorly understood. here, we show that rhesus macaques are susceptible to the infection by sars-cov-2. after intratracheal inoculation, the firs ...202032636454
long-term exposure to ephedrine leads to neurotoxicity and neurobehavioral disorders accompanied by up-regulation of crf in prefrontal cortex and hippocampus in rhesus macaques.drug addiction continues to threaten the health and welfare of people worldwide, and ephedrine abuse is a serious drug problem in many areas of the world. ephedrine toxicity is thought to induce behavioral effects primarily through actions on the central nervous system. the corticotropin-releasing factor (crf) system plays an important role in regulating behavioral effects induced by addictive drugs, but whether crf is related to ephedrine toxicity remains unclear. this study seeks to examine wh ...202032634541
dopamine role in learning and action inference.this paper describes a framework for modelling dopamine function in the mammalian brain. it proposes that both learning and action planning involve processes minimizing prediction errors encoded by dopaminergic neurons. in this framework, dopaminergic neurons projecting to different parts of the striatum encode errors in predictions made by the corresponding systems within the basal ganglia. the dopaminergic neurons encode differences between rewards and expectations in the goal-directed system, ...202032633715
angiogenic factor with g patch and fha domains 1 protects retinal vascular endothelial cells under hyperoxia by inhibiting autophagy.angiogenic factor with g patch and fha domains 1 (aggf1) has strong proangiogenic effects on embryonic vascular development and angiogenesis in disease; however, its role in retinopathy has not been elucidated. retinopathy of prematurity is a serious retinal disorder of premature infants, which is caused by the arrest of immature retinal vascular growth under hyperoxia. this study aims to investigate the effects of aggf1 on retinal vascular endothelial cells under hyperoxia and the association w ...202032633013
histological assessment of optogenetic tools to study fronto-visual and fronto-parietal cortical networks in the rhesus macaque.optogenetics offers unprecedented possibilities to investigate cortical networks. yet, the number of successful optogenetic applications in non-human primates is still low, and the consequences of opsin expression in the primate brain are not well documented. we assessed histologically if we can target cerebrocortical networks with three common optogenetic constructs (aav2/5-camkiiα-enphr3.0-mcherry, -chr2-eyfp, -c1v1-mcherry). the frontal eye field or the dorsal premotor area of rhesus macaques ...202032632196
long term delta-9-tetrahydrocannabinol administration inhibits proinflammatory responses in minor salivary glands of chronically simian immunodeficieny virus infected rhesus macaques.hiv/siv-associated oral mucosal disease/dysfunction (haomd) (gingivitis/periodontitis/salivary adenitis) represents a major comorbidity affecting hiv patients on anti-retroviral therapy. using a systems biology approach, we investigated molecular changes (mrna/microrna) underlying haomd and its modulation by phytocannabinoids (delta-9-tetrahydrocannabinol (∆9-thc)) in uninfected (n = 5) and siv-infected rhesus macaques untreated (veh-untreated/siv; n = 7) or treated with vehicle (veh/siv; n = 3) ...202032630206
stable and dynamic representations of value in the prefrontal cortex.optimal decision-making requires that stimulus-value associations are kept up to date by constantly comparing the expected value of a stimulus with its experienced outcome. to do this, value information must be held in mind when a stimulus and outcome are separated in time. however, little is known about the neural mechanisms of working memory (wm) for value. contradicting theories have suggested wm requires either persistent or transient neuronal activity, with stable or dynamic representations ...202032628108
movement initiation and grasp representation in premotor and primary motor cortex mirror neurons.pyramidal tract neurons (ptns) within macaque rostral ventral premotor cortex (f5) and (m1) provide direct input to spinal circuitry and are critical for skilled movement control. contrary to initial hypotheses, they can also be active during action observation, in the absence of any movement. a population-level understanding of this phenomenon is currently lacking. we recorded from single neurons, including identified ptns, in (m1) (n = 187), and f5 (n = 115) as two adult male macaques executed ...202032628107
sars-cov-2 surveillance for a non-human primate breeding research facility.the emergence of sars-cov-2 and the ensuing covid-19 pandemic prompted the need for a surveillance program to determine the viral status of the california national primate research center non-human primate breeding colony, both for reasons of maintaining colony health and minimizing the risk of interference in covid-19 and other research studies.202032621339
effects of iron deficiency anemia and its rapid correction on the serum metabolomic profile of rhesus infants.to determine whether rapid correction of iron deficiency using intramuscular iron dextran normalizes serum metabolomic changes in a nonhuman primate model of iron deficiency anemia (ida).202032617457
transgenerational propensities for infant birth weight reflect fetal growth history of the mother in rhesus monkeys.birth weight (bw) at delivery is an important developmental milestone indicative of prenatal conditions and portends of the postnatal growth trajectory that will occur during infancy and childhood. previous research has documented that there are also many physiological and health consequences of being born either small-for-gestational age (sga) or large-for-gestational age (lga). analyses of breeding animals have demonstrated further that a gravid female exerts a strong influence on the size of ...201932616989
primary exposure to sars-cov-2 protects against reinfection in rhesus macaques.coronavirus disease 2019 (covid-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (sars-cov-2), has become a global pandemic. it is unclear whether convalescing patients have a risk of reinfection. we generated a rhesus macaque model of sars-cov-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. rhesus macaques reinfected with the identical sars-cov-2 strain ...202032616673
hiv-1 subtype c transmitted founders modulate dendritic cell inflammatory responses.heterosexual transmission remains the main route of hiv-1 transmission and female genital tract (fgt) inflammation increases the risk of infection. however, the mechanism(s) by which inflammation facilitates infection is not fully understood. in rhesus macaques challenged with simian immunodeficiency virus, dendritic cell (dc) mediated recruitment of cd4+ t cells to the fgt was critical for infection. the aim of this study was to delineate the mechanisms underlying dc-mediated hiv infection by c ...202032615983
intranasal salvinorin a improves neurological outcome in rhesus monkey ischemic stroke model using autologous blood clot.salvinorin a (sa) exerts neuroprotection and improves neurological outcomes in ischemic stroke models in rodents. in this study, we investigated whether intranasal sa administration could improve neurological outcomes in a monkey ischemic stroke model. the stroke model was induced in adult male rhesus monkeys by occluding the middle cerebral artery m2 segment with an autologous blood clot. eight adult rhesus monkeys were randomly administered sa or 10% dimethyl sulfoxide as control 20 min after ...202032615886
m-like protein srm is not crucial to the virulence of a novel isolate of streptococcus equi subsp. ruminatorum from macaca mulatta.in this study, a streptococcus strainnamed fj1804, was isolated from a blood sample collected from a dead macaca mulatta in china and, was subsequently classified as streptococcus equi subsp. ruminatorum (s.e. ruminatorum) through 16s rrna gene sequence analysis. after whole genome sequencing and analysis, an m-like protein encoding gene that encodes an srm protein that is homologous to the crucial s.e. zooepidemicus crucial virulence factor szp, was identified in the genome of fj1804. to determ ...202032615343
higher early life mortality with lower infant body mass in a free-ranging primate.traits that reflect the amount of energy allocated to offspring by mothers, such as infant body mass, are predicted to have long-lasting effects on offspring fitness. in very long-lived species, such as anthropoid primates, where long-lasting and obligate parental care is required for successful recruitment of offspring, there are few studies on the fitness implications of low body mass among infants. using body mass data collected from 253 free-ranging rhesus macaque macaca mulatta infants on c ...202032614977
robust expansion of hiv car t cells following antigen boosting in art-suppressed nonhuman primates.chimeric antigen receptor (car) t cells targeting cd19+ hematologic malignancies have rapidly emerged as a promising, novel therapy. in contrast, results from the few car t-cell studies for infectious diseases such as hiv-1 have been less convincing. these challenges are likely due to the low level of antigen present in antiretroviral therapy (art)-suppressed patients in contrast to those with hematologic malignancies. using our well-established nonhuman primate model of art-suppressed hiv-1 inf ...202032614969
infant rhesus macaque brain α-tocopherol stereoisomer profile is differentially impacted by the source of α-tocopherol in infant formula.α-tocopherol (αt) in its natural form [2'r, 4'r, 8'r αt (rrr-αt)] is more bioactive than synthetic α-tocopherol (all rac-αt). all rac-αt is widely used in infant formulas, but its accretion in formula-fed infant brain is unknown.202032614402
receptor-driven, multimodal mapping of cortical areas in the macaque monkey intraparietal sulcus.the intraparietal sulcus (ips) is structurally and functionally heterogeneous. we performed a quantitative cyto-/myelo- and receptor architectonical analysis to provide a multimodal map of the macaque ips. we identified 17 cortical areas, including novel areas peipe, peipi (external and internal subdivisions of peip), and mipd. multivariate analyses of receptor densities resulted in a grouping of areas based on the degree of (dis)similarity of their receptor architecture: a cluster encompassing ...202032613942
exciting inhibition in primates.a new genetic marker enables precise control over a group of inhibitory neurons in monkeys.202032609086
in vivo evaluation of retinal ganglion cells and optic nerve's integrity in large animals by multi-modality analysis.large animal models of optic nerve injury are essential for translating novel findings into effective therapies due to their similarity to humans in many respects. however, most current tests evaluating the integrity of retinal ganglion cells (rgcs) and optic nerve (on) are based on rodent animal models. we aimed to evaluate and optimize the in vivo methods to assess rgcs and on's function and structure in large animals in terms of reproducibility, simplicity and sensitivity. both goats and rhes ...202032598972
a zika virus primary isolate induces neuroinflammation, compromises the blood-brain barrier and upregulates cxcl12 in adult macaques.zika virus (zikv) is a flavivirus that can cause neuropathogenesis in adults and fetal neurologic malformation following the infection of pregnant women. we used a nonhuman primate model, the indian-origin rhesus macaque (irm), to gain insight into virus-associated hallmarks of zikv-induced adult neuropathology. we find that the virus causes prevalent acute and chronic neuroinflammation and chronic disruption of the blood-brain barrier (bbb) in adult animals. zikv infection resulted in specific ...202032585067
a longitudinal study of brain volume changes in rhesus macaque model infected with siv.given the current lack of understanding of brain volume changes caused by hiv infection, this study aimed to longitudinally assess the changes in regional brain tissue volume following hiv infection and to explore its relationship with peripheral blood absolute cd4+ lymphocyte count (cd4+), the percentage of monocytes in plasma(mon%) and cerebrospinal fluid viral load (cfvl).four adult male rhesus monkeys were examined in healthy status and following infection with simian immunodeficiency virus ...202032583233
differential accumulation of storage bodies with aging defines discrete subsets of microglia in the healthy brain.to date, microglia subsets in the healthy cns have not been identified. utilizing autofluorescence (af) as a discriminating parameter, we identified two novel microglia subsets in both mice and non-human primates, termed autofluorescence-positive (af+) and negative (af-). while their proportion remained constant throughout most adult life, the af signal linearly and specifically increased in af+ microglia with age and correlated with a commensurate increase in size and complexity of lysosomal st ...202032579115
hydroxychloroquine proves ineffective in hamsters and macaques infected with sars-cov-2.we remain largely without effective prophylactic/therapeutic interventions for covid-19. although many human clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies. here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (hcq), a drug of interest for covid-19 management, in two animal models. when used for prophylaxis or treatment neither the standard human malaria dose (6.5 mg/kg) nor a high dose (50 mg/kg) of hcq had any ben ...202032577633
a single dose of chadox1 mers provides protective immunity in rhesus macaques.developing a vaccine to protect against the lethal effects of the many strains of coronavirus is critical given the current global pandemic. for middle east respiratory syndrome coronavirus (mers-cov), we show that rhesus macaques seroconverted rapidly after a single intramuscular vaccination with chadox1 mers. the vaccine protected against respiratory injury and pneumonia and reduced viral load in lung tissue by several orders of magnitude. mers-cov replication in type i and ii pneumocytes of c ...202032577525
evolution and transition of expression trajectory during human brain development.the remarkable abilities of the human brain are distinctive features that set us apart from other animals. however, our understanding of how the brain has changed in the human lineage remains incomplete, but is essential for understanding cognition, behavior, and brain disorders in humans. here, we compared the expression trajectory in brain development between humans and rhesus macaques (macaca mulatta) to explore their divergent transcriptome profiles.202032576137
comparison of proteome alterations during aging in the temporal lobe of humans and rhesus macaques.rhesus macaques are widely used as animal models for studies of the nervous system; however, it is unknown whether the alterations in the protein profile of the brain during aging are conserved between humans and rhesus macaques. in this study, temporal cortex samples from old and young humans (84 vs. 34 years, respectively) or rhesus macaques (20 vs. 6 years, respectively) were subjected to tandem mass tag-labeled proteomic analysis followed by bioinformatic analysis. a total of 3861 homologous ...202032572507
mucosal-associated invariant t (mait) cells provide b-cell help in vaccinated and subsequently siv-infected rhesus macaques.mucosal-associated invariant t (mait) cells help combat opportunistic infections. thus, mait cells are of interest in hiv/siv vaccination and infection. we investigated mait cell dynamics and function in rhesus macaque blood and bronchoalveolar lavage (bal) following mucosal adenovirus (ad)-siv recombinant priming, intramuscular siv envelope boosting and infection following repeated low-dose intravaginal siv exposures. increased frequencies of blood mait cells over the course of vaccination were ...202032572140
combined model-free and model-sensitive reinforcement learning in non-human primates.contemporary reinforcement learning (rl) theory suggests that potential choices can be evaluated by strategies that may or may not be sensitive to the computational structure of tasks. a paradigmatic model-free (mf) strategy simply repeats actions that have been rewarded in the past; by contrast, model-sensitive (ms) strategies exploit richer information associated with knowledge of task dynamics. mf and ms strategies should typically be combined, because they have complementary statistical and ...202032569311
the caudate nucleus contributes causally to decisions that balance reward and uncertain visual information.our decisions often balance what we observe and what we desire. a prime candidate for implementing this complex balancing act is the basal ganglia pathway, but its roles have not yet been examined experimentally in detail. here, we show that a major input station of the basal ganglia, the caudate nucleus, plays a causal role in integrating uncertain visual evidence and reward context to guide adaptive decision-making. in monkeys making saccadic decisions based on motion cues and asymmetric rewar ...202032568068
3m-052, a synthetic tlr-7/8 agonist, induces durable hiv-1 envelope-specific plasma cells and humoral immunity in nonhuman primates.a fundamental challenge in vaccinology is learning how to induce durable antibody responses. live viral vaccines induce antibody responses that last a lifetime, but those induced with subunit vaccines wane rapidly. studies in mice and humans have established that long-lived plasma cells (llpcs) in the bone marrow (bm) are critical mediators of durable antibody responses. here, we present data that adjuvanting an hiv-1 clade c 1086.c-derived gp140 immunogen (env) with a novel synthetic toll-like ...202032561559
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
topological atlas of the hypothalamus in adult rhesus monkey.the prosomeric model explains the embryological development of the central nervous system (cns) shared by all vertebrates as a bauplan. as a primary event, the early neural plate is patterned by intersecting longitudinal plates and transverse segments, forming a mosaic of progenitor units. the hypothalamus is specified by three prosomeres (hp1, hp2, and the acroterminal domain) of the secondary prosencephalon with corresponding alar and basal plate parts, which develop apart from the diencephalo ...202032556476
pulmonary mycobacterium tuberculosis control associates with cxcr3- and ccr6-expressing antigen-specific th1 and th17 cell recruitment.mycobacterium tuberculosis-specific (m. tuberculosis-specific) t cell responses associated with immune control during asymptomatic latent tuberculosis infection (ltbi) remain poorly understood. using a nonhuman primate aerosol model, we studied the kinetics, phenotypes, and functions of m. tuberculosis antigen-specific t cells in peripheral and lung compartments of m. tuberculosis-infected asymptomatic rhesus macaques by longitudinally sampling blood and bronchoalveolar lavage, for up to 24 week ...202032554933
an hiv vaccine targeting the v2 region of the hiv envelope induces a highly durable polyfunctional fc-mediated antibody response in rhesus macaques.the hiv vaccine field now recognizes the potential importance of generating polyfunctional antibodies (abs). the only clinical hiv vaccine trial to date to show significant efficacy (rv144) found that reduced infection rates correlated with the level of nonneutralizing abs specific for the v2 region of the envelope glycoprotein. we have conducted a comprehensive preclinical reverse vaccinology-based vaccine program that has included the design and production and testing of numerous scaffolded v2 ...202032554699
cage position and response to humans in singly-housed rhesus macaques (macaca mulatta).traditional laboratory caging for nonhuman primates is typically configured in a 2-tiered manner, with caging arranged in 2 horizontal rows stacked vertically. studies of the effects of cage row have yielded inconsistent results with respect to impacts on psychological well-being. this study tests whether rhesus macaques (macaca mulatta) housed in the bottom tier of caging display poorer responses to attempted positive human interaction than those in the upper tier, suggesting that humans are a ...202032553049
the vaccinia virus based sementis copenhagen vector vaccine against zika and chikungunya is immunogenic in non-human primates.the sementis copenhagen vector (scv) is a new vaccinia virus-derived, multiplication-defective, vaccine technology assessed herein in non-human primates. indian rhesus macaques (macaca mulatta) were vaccinated with a multi-pathogen recombinant scv vaccine encoding the structural polyproteins of both zika virus (zikv) and chikungunya virus (chikv). after one vaccination, neutralising antibody responses to zikv and four strains of chikv, representative of distinct viral genotypes, were generated. ...202032550013
age-associated changes in amyloid-β and formaldehyde concentrations in cerebrospinal fluid of rhesus monkeys.rhesus monkeys ( macaca mulatta) are valuable experimental animals for studies on neurodegenerative diseases due to their evolutionarily close relationship to humans (zhang et al., 2014). rhesus monkeys also display similar hallmarks of aging and neurodegeneration as humans, including formation of senile plaques in the brain (beckman et al., 2019; paspalas et al., 2018). however, changes in formaldehyde (fa) levels in the cerebrospinal fluid (csf) of rhesus monkeys with aging have not been repor ...202032543791
exogenous sex steroids regulate genital epithelial barrier function in female rhesus macaques.there is concern that using depot-medroxyprogesterone acetate (dmpa) for pregnancy prevention heightens hiv susceptibility. while no clinical data establishes causal link between hiv acquisition and use of this injectable progestin, prior work from our laboratory showed that dmpa comparably lowers genital levels of the cell-cell adhesion molecule desmoglein-1 (dsg1) and weakens genital epithelial barrier function in female mice and women. we likewise saw dmpa increase mouse susceptibility to mul ...202032542371
changes of the end plate cartilage are associated with intervertebral disc degeneration: a quantitative magnetic resonance imaging study in rhesus monkeys and humans.the end plate plays an important role in intervertebral disc degeneration progression. the aim of the study was to examine the compositional and structural changes of the end plate with age and to investigate the correlation between end plate and disc degeneration by t1ρ and t2 map magnetic resonance imaging.202032542179
behavioral shaping of rhesus macaques using the cambridge neuropsychological automated testing battery.the cambridge neuropsychological test automated battery (cantab) is a set of computerized visuospatial tests used to probe cognition in humans. the non-human primate (nhp) version of the battery is a valuable translational research tool to quantify cognitive changes in nhp models of disease by allowing direct comparison with performance data from human patient populations. one limitation is the long training times required for nhps to reach appropriate levels of task performance, which is prohib ...202032534008
resource: a multi-species multi-timepoint transcriptome database and webpage for the pineal gland and retina.the website and database https://snengs.nichd.nih.gov provides rna sequencing data from multi-species analysis of the pineal glands from zebrafish (danio rerio), chicken (white leghorn), rat (rattus novegicus), mouse (mus musculus), rhesus macaque (macaca mulatta), and human (homo sapiens); in most cases, retinal data are also included along with results of the analysis of a mixture of rna from tissues. studies cover day and night conditions; in addition, a time series over multiple hours, a dev ...202032533862
flow augmentation in the myocardium by ultrasound cavitation of microbubbles: role of shear-mediated purinergic signaling.ultrasound-mediated cavitation of microbubble contrast agents produces high intravascular shear. we hypothesized that microbubble cavitation increases myocardial microvascular perfusion through shear-dependent purinergic pathways downstream from atp release that is immediate and sustained through cellular atp channels such as pannexin-1.202032532642
long-term value memory in the primate posterior thalamus for fast automatic action.the thalamus is known to process information from various brain regions and relay it to other brain regions, serving an essential role in sensory perception and motor execution. the thalamus also receives inputs from basal ganglia nuclei (bg) involved in value-based decision making, suggesting a role in the value process. we found that neurons in a particular area of the rhesus macaque posterior thalamus encoded the historical value memory of visual objects. many of these value-coding neurons we ...202032531286
the anterior cingulate cortex is necessary for forming prosocial preferences from vicarious reinforcement in monkeys.a key feature of most social relationships is that we like seeing good things happen to others. research has implicated the anterior cingulate cortex (acc) in attaching value to social outcomes. for example, single neurons in macaque acc selectively code reward delivery to the self, a partner, both monkeys, or neither monkey. here, we assessed whether the acc's contribution to social cognition is causal by testing rhesus monkeys (macaca mulatta) on a vicarious reinforcement task before and after ...202032530910
immune cells in the placental villi contribute to intra-amniotic inflammation.intra-amniotic (ia) inflammation is associated with significant morbidities for both the mother and the fetus. prior studies have illustrated many of the effects of ia inflammation on the uterine lining (decidua) and membranous layers of the placenta at the fetal-maternal interface. however, much less is known about the immunological response occurring within the villous placenta. using a rhesus macaque model of lipopolysaccharide (lps)-induced ia inflammation, we showed that pregnancy-matched c ...202032528468
a direct-acting antiviral drug abrogates viremia in zika virus-infected rhesus macaques.zika virus infection in humans has been associated with serious reproductive and neurological complications. at present, no protective antiviral drug treatment is available. here, we describe the testing and evaluation of the antiviral drug, galidesivir, against zika virus infection in rhesus macaques. we conducted four preclinical studies in rhesus macaques to assess the safety, antiviral efficacy, and dosing strategies for galidesivir (bcx4430) against zika virus infection. we treated 70 rhesu ...202032522808
successful implementation of intestinal resection and anastomosis in non-human primates suggests the possibility of longitudinal intestinal research.intestinal biopsy is a basic experimental method for studying pathological changes in the intestinal tract during human immunodeficiency virus (hiv) infection. in this study, jejunal resection and anastomosis were successfully performed in 12 chinese rhesus macaques ( macacamulatta). the sampled gut tissues were then examined by hematoxylin and eosin (h&e) staining, electron microscopy, flow cytometry, immunofluorescence detection, and rna quality analysis to ensure suitability for histological, ...202032521575
the neurons that mistook a hat for a face.despite evidence that context promotes the visual recognition of objects, decades of research have led to the pervasive notion that the object processing pathway in primate cortex consists of multiple areas that each process the intrinsic features of a few particular categories (e.g. faces, bodies, hands, objects, and scenes). here we report that such category-selective neurons do not in fact code individual categories in isolation but are also sensitive to object relationships that reflect stat ...202032519949
in vitro differentiation of rhesus macaque bone marrow- and adipose tissue-derived mscs into hepatocyte-like cells.orthotopic liver or hepatocyte transplantation is effective for the treatment of acute liver injury and end-stage chronic liver disease. however, both of these therapies are hampered by the extreme shortage of organ donors. the clinical application of cell therapy through the substitution of hepatocytes with mesenchymal stem cells (mscs) that have been differentiated into hepatocyte-like cells (hlcs) for liver disease treatment is expected to overcome this shortage. bone marrow and adipose tissu ...202032518605
tolerant and intolerant macaques show different levels of structural complexity in their vocal communication.we tested the social complexity hypothesis which posits that animals living in complex social environments should use complex communication systems. we focused on two components of vocal complexity: diversity (number of categories of calls) and flexibility (degree of gradation between categories of calls). we compared the acoustic structure of vocal signals in groups of macaques belonging to four species with varying levels of uncertainty (i.e. complexity) in social tolerance (the higher the deg ...202032517610
clinical benefit of remdesivir in rhesus macaques infected with sars-cov-2.effective therapies to treat coronavirus disease 2019 (covid-19) are urgently needed. while many investigational, approved, and repurposed drugs have been suggested as potential treatments, preclinical data from animal models can guide the search for effective treatments by ruling out those that lack efficacy in vivo. remdesivir (gs-5734) is a nucleotide analogue prodrug with broad antiviral activity1,2 that is currently being investigated in covid-19 clinical trials and recently received emerge ...202032516797
dissociating cholinergic influence on alertness and temporal attention in primates in a simple reaction time paradigm.the ability to promptly respond to behaviourally relevant events depends on both general alertness and phasic changes in attentional state driven by temporal expectations. using a variable foreperiod simple reaction time (rt) task in four adult male rhesus macaques, we investigated the role of the cholinergic system in alertness and temporal expectation. foreperiod effects on rt reflect temporal expectation, while alertness is quantified as overall response speed. we measured these rt parameters ...202032516489
a naturalistic dynamic monkey head avatar elicits species-typical reactions and overcomes the uncanny valley.research on social perception in monkeys may benefit from standardized, controllable, and ethologically valid renditions of conspecifics offered by monkey avatars. however, previous work has cautioned that monkeys, like humans, show an adverse reaction toward realistic synthetic stimuli, known as the "uncanny valley" effect. we developed an improved naturalistic rhesus monkey face avatar capable of producing facial expressions (fear grin, lip smack and threat), animated by motion capture data of ...202032513660
the forearm and hand musculature of semi-terrestrial rhesus macaques (macaca mulatta) and arboreal gibbons (fam. hylobatidae). part i. description and comparison of the muscle configuration.primates live in very diverse environments and, as a consequence, show an equally diverse locomotor behaviour. during locomotion, the primate hand interacts with the superstrate and/or substrate and will therefore probably show adaptive signals linked with this locomotor behaviour. whereas the morphology of the forearm and hand bones have been studied extensively, the functional adaptations in the hand musculature have been documented only scarcely. to evaluate whether there are potential adapta ...202032511764
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
chadox1 ncov-19 vaccination 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 covid-19 pandemic3. vaccines are an essential countermeasure urgently needed to control the pandemic4. here, we show that the adenovirus-vectored vaccine chadox1 ncov-19, encoding the spike protein of sars-cov-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. this response was not th2 dominated, as demonstrated by igg subclass and cytokine expression ...202032511340
comparative ace2 variation and primate covid-19 risk.the emergence of the novel coronavirus sars-cov-2, which in humans is highly infectious and leads to the potentially fatal disease covid-19, has caused tens of thousands of deaths and huge global disruption. the viral infection may also represent an existential threat to our closest living relatives, the nonhuman primates, many of which have already been reduced to small and endangered populations. the virus engages the host cell receptor, angiotensin-converting enzyme-2 (ace2), through the rece ...202032511330
clinical benefit of remdesivir in rhesus macaques infected with sars-cov-2.effective therapeutics to treat covid-19 are urgently needed. remdesivir is a nucleotide prodrug with in vitro and in vivo efficacy against coronaviruses. here, we tested the efficacy of remdesivir treatment in a rhesus macaque model of sars-cov-2 infection.202032511319
respiratory disease and virus shedding in rhesus macaques inoculated with sars-cov-2.an outbreak of a novel coronavirus, now named sars-cov-2, causing respiratory disease and a ~2% case fatality rate started in wuhan, china in december 2019. following unprecedented rapid global spread, the world health organization declared covid-19 a pandemic on march 11, 2020. although data on disease in humans are emerging at a steady pace, certain aspects of the pathogenesis of sars-cov-2 can only be studied in detail in animal models, where repeated sampling and tissue collection is possibl ...202032511299
early developmental changes in visual social engagement in infant rhesus monkeys.impairments in social interaction in autism spectrum disorder (asd) differ greatly across individuals and vary throughout an individual's lifetime. yet, an important marker of asd in infancy is deviations in social-visual engagement, such as the reliably detectable early deviations in attention to the eyes or to biological movement (klin et al., 2015). given the critical nature of these early developmental periods, understanding its neurobehavioral underpinnings by means of a nonhuman primate mo ...202032510341
il-15 in the combination immunotherapy of cancer.we completed clinical trials of rhil-15 by bolus, subcutaneous, and continuous intravenous infusions (civ). il-15 administered by civ at 2 mcg/kg/day yielded a 38-fold increase in 10- day number of circulating nk cells, a 358-fold increase in cd56bright nk cells and a 5.8-fold increase in cd8 t cells. however, il-15 preparations administered as monotherapy were ineffective, due to actions of immunological checkpoints and due to the lack of tumor specific targeting by nk cells. to circumvent chec ...202032508818
in vitro effects of ligand bias on primate mu opioid receptor downstream signaling.interest has emerged in biased agonists at the mu opioid receptor (mor) as a possible means for maintaining potent analgesis with reduced side effect profiles. while approaches measuring in vitro biased agonism are used in the development of these compounds, their therapeutic utility will ultimately be determined by in vivo functional effects. nonhuman primates (nhps) are the most translational model for evaluating the behavioral effects of candidate medications, but biased signaling of these dr ...202032503269
revisiting 35 and 94 ghz millimeter wave exposure to the non-human primate eye.a previous study reported thermal effects resulting from millimeter wave exposures at 35 and 94 ghz on non-human primates, specifically rhesus monkeys' (macaca mulatta) corneas, but the data exhibited large variations in the observed temperatures and uncertainties in the millimeter wave dosimetry. by incorporating improvements in models and dosimetry, a non-human primate experiment was conducted involving corneal exposures that agreed well with a three-layer, one-dimensional, thermodynamic model ...202032501817
commentary: derivation of simian tropic hiv-1 infectious clone reveals virus adaptation to a new host. 202032500043
peripheral neuronopathy associated with ebola virus infection in rhesus macaques: a possible cause of neurological signs and symptoms in human ebola patients.neurological signs and symptoms are the most common complications of ebola virus disease. however, the mechanisms underlying the neurologic manifestations in ebola patients are not known. in this study, peripheral ganglia were collected from 12 rhesus macaques that succumbed to ebola virus (ebov) disease from 5 to 8 days post exposure. ganglionitis, characterized by neuronal degeneration, necrosis, and mononuclear leukocyte infiltrates, was observed in the dorsal root, autonomic, and enteric gan ...202032498080
interactions between opioids and cannabinoids: economic demand for opioid/cannabinoid mixtures.opioid abuse remains a significant public health challenge. with continuing emergence of novel psychoactive substances (e.g., synthetic cannabinoids found in "k2" or "spice" preparations), the co-administration of opioids and other novel drugs is likely to become more prevalent, which might increase the risk for abuse and other adverse effects. this study examined whether the synthetic cannabinoid receptor agonist jwh-018 alters the reinforcing effectiveness of the mu opioid receptor agonist rem ...202032497977
3d printed porous titanium cages filled with simvastatin hydrogel promotes bone ingrowth and spinal fusion in rhesus macaques.three-dimensional (3d) printing technology can be used to manufacture implants with individualized external shapes, internal porous structures and elastic moduli similar to those of natural bone, although such implants lack biological activity. here, we developed a porous titanium cage by electron beam melting that was filled with simvastatin/poloxamer 407 hydrogel and evaluated bone ingrowth and spinal fusion. six adult male rhesus macaques underwent interbody fusion of the l3/4 (cage without s ...202032496502
microstructural organization of human insula is linked to its macrofunctional circuitry and predicts cognitive control.the human insular cortex is a heterogeneous brain structure which plays an integrative role in guiding behavior. the cytoarchitectonic organization of the human insula has been investigated over the last century using postmortem brains but there has been little progress in noninvasive in vivo mapping of its microstructure and large-scale functional circuitry. quantitative modeling of multi-shell diffusion mri data from 413 participants revealed that human insula microstructure differs significan ...202032496190
in situ repair abilities of human umbilical cord-derived mesenchymal stem cells and autocrosslinked hyaluronic acid gel complex in rhesus monkeys with intrauterine adhesion.increasing occurrence of moderate to severe intrauterine adhesion (iua) is seriously affecting the quality of human life. the aim of the study was to establish iua models in nonhuman primates and to explore the dual repair effects of human umbilical cord-derived mesenchymal stem cells (humscs) loaded on autocrosslinked hyaluronic acid gel (ha-gel) on endometrial damage and adhesion. here, we recorded the menstrual cycle data in detail with uterine cavities observed and endometrial tissues detect ...202032494750
labeled oxytocin administered via the intranasal route reaches the brain in rhesus macaques.oxytocin may have promise as a treatment for neuropsychiatric disorders. its therapeutic effect may depend on its ability to enter the brain and bind to the oxytocin receptor. to date, the brain tissue penetrance of intranasal oxytocin has not been demonstrated. in this nonhuman primate study, we administer deuterated oxytocin intranasally and intravenously to rhesus macaques and measure, with mass spectrometry, concentrations of labeled (exogenously administered) and endogenous oxytocin in 12 b ...202032494001
non-human primate ipsc generation, cultivation, and cardiac differentiation under chemically defined conditions.non-human primates (nhp) are important surrogate models for late preclinical development of advanced therapy medicinal products (atmps), including induced pluripotent stem cell (ipsc)-based therapies, which are also under development for heart failure repair. for effective heart repair by remuscularization, large numbers of cardiomyocytes are required, which can be obtained by efficient differentiation of ipscs. however, nhp-ipsc generation and long-term culture in an undifferentiated state unde ...202032485910
filoviruses infect rhesus macaque synoviocytes in vivo and primary human synoviocytes in vitro.the most commonly reported symptom of post-ebola virus disease syndrome in survivors is arthralgia, yet involvement of the joints in acute or convalescent ebola virus infection is not well characterized in human patients or animal models. through immunohistochemistry, we found that the lining synovial intima of the stifle (knee) is a target for acute infection by ebola virus/kikwit, ebola virus/makona-c05, and marburg virus/angola in the rhesus macaque model. furthermore, histologic analysis, im ...202032479821
protection against siv in rhesus macaques using albumin and cd4-based vector-mediated gene transfer.antibody-like molecules were evaluated with potent simian immunodeficiency virus (siv) neutralizing properties (immunoadhesins) that were delivered by a recombinant adeno-associated virus (raav) vector in the siv-infected rhesus macaque model. when injected intramuscularly into the host, the vector directs in vivo production of the transgenes with antibody-like binding properties that lead to serum neutralizing activity against siv. to extend the half-life of the immunoadhesins, rhesus cluster o ...202032478124
optimization of ultrasound backscatter spectroscopy to assess neurotoxic effects of anesthesia in the newborn non-human primate brain.studies in animal models have revealed that long exposures to anesthetics can induce apoptosis in the newborn and young developing brain. these effects have not been confirmed in humans because of the lack of a non-invasive, practical in vivo imaging tool with the ability to detect these changes. following the successful use of ultrasound backscatter spectroscopy (ubs) to monitor in vivo cell death in breast tumors, we aimed to use ubs to assess the neurotoxicity of the anesthetic sevoflurane (s ...202032475715
gabaa receptor subtypes and the reinforcing effects of benzodiazepines in remifentanil-experienced rhesus monkeys.opioid-use disorder is associated with a high degree of co-abuse with benzodiazepines. while the mechanisms underlying the co-abuse of opioids and benzodiazepines remain unknown, α1 subunit-containing gabaa receptors may play a critical role in the reinforcing effects of benzodiazepine-type compounds, depending on whether the monkeys have a history of benzodiazepine or stimulant self-administration. the present study extended our prior research by comparing the reinforcing effects of a compound ...202032474260
multi-group multi-time point confirmatory factor analysis of the triadic structure of temperament: a nonhuman primate model.attempts to describe the latent structure of human infant temperament have led some to suggest the existence of three major dimensions. an earlier exploratory factor analysis (efa) supported a triadic structure of temperament in week-old rhesus monkey infants, paralleling the structure in human infants. this study sought to confirm the latent triadic structure of temperament across the first month of life in a larger sample of rhesus monkey infants (n = 668), reared by their mothers or in a neon ...202032469093
single b cells reveal the antibody responses of rhesus macaques immunized with an inactivated enterovirus d68 vaccine.enterovirus d68 (ev-d68) infection may cause severe respiratory system manifestations in pediatric populations. because of the lack of an effective preventive vaccine or specific therapeutic drug for this infection, the development of ev-d68-specific vaccines and antibodies has become increasingly important. in this study, we prepared an experimental ev-d68 vaccine inactivated by formaldehyde and found that the serum of rhesus macaques immunized with the inactivated ev-d68 vaccine exhibited pote ...202032462286
Refresh
firstprev
12345678910...
nextlast
Displaying items 401 - 500 of 30434