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differences in frontal network anatomy across primate species.the frontal lobe is central to distinctive aspects of human cognition and behavior. some comparative studies link this to a larger frontal cortex and even larger frontal white matter in humans compared with other primates, yet others dispute these findings. the discrepancies between studies could be explained by limitations of the methods used to quantify volume differences across species, especially when applied to white matter connections. in this study, we used a novel tractography approach t ...202031949106
strategy use in probabilistic categorization by rhesus macaques (macaca mulatta) and capuchin monkeys (cebus [sapajus] apella).probabilistic categorization tasks present the learner with a set of possible responses and imperfect cue evidence of which response will be rewarded. a single, optimal integration of all available cues into an optimal response is possible given any set of evidence. in contrast, there are many possible uses of the cues that offer the learner suboptimal (but better than chance) responding. we presented a classic probabilistic categorization task to 3 rhesus macaques (macaca mulatta) and 13 capuch ...202032406716
the density bias: capuchin monkeys (sapajus apella) prefer densely arranged items in a food-choice task.in the current work, we investigated whether capuchin monkeys preferred densely distributed resources to sparsely distributed resources in a 2-choice discrimination task with edible rewards. capuchin monkeys were biased to select a denser food set over the same number of food items in a sparsely arranged set. furthermore, increased density of the larger food set facilitated discrimination performance in quantity comparisons with a true difference in set size. these results align with previous st ...202031971398
gibbons exploit information about what a competitor can see.how much nonhuman animals understand about seeing has been the focus of comparative cognition research for decades. many social primates (and other species) are sensitive to cues about what others can and cannot see. whether this sensitivity evolved in primates through shared descent or convergent evolution remains unclear. the current study tested gibbons-the apes that are least studied yet most distantly related to humans and one of the less social primates-in two food-competition tasks. speci ...202031781885
predicted structural differences of four fertility-related y-chromosome proteins in macaca mulatta, m. fascicularis, and their indochinese hybrids.species in the genus macaca typically live in multimale-multifemale social groups with male macaques exhibiting some of the largest testis:body weight ratios among primates. males are believed to experience intense levels of sperm competition. several spermatogenesis genes are located on the y-chromosome and, interestingly, occasional hybridization between two species has led to the introgression of the rhesus macaque (macaca mulatta) y-chromosome deep into the range of the long-tailed macaque ( ...202033146441
cd8 t cells show protection against highly pathogenic simian immunodeficiency virus (siv) after vaccination with siv gene-expressing bcg prime and vaccinia virus/sendai virus vector boosts.toward development of a dual vaccine for human immunodeficiency virus (hiv)-1 and tuberculosis infections, we developed a urease-deficient bacillus calmette-guérin (bcg) strain tokyo172 (bcgδurease) to enhance its immunogenicity. bcgδurease expressing simian immunodeficiency virus (siv) gag induced bcg antigen-specific cd4+ and cd8+ t cells more efficiently, and more gag-specific cd8+ t cells. we evaluated its protective efficacy against siv infection in cynomolgus monkeys of asian origin, shown ...202033087465
factors influencing taxonomic unevenness in scientific research: a mixed-methods case study of non-human primate genomic sequence data generation.scholars have noted major disparities in the extent of scientific research conducted among taxonomic groups. such trends may cascade if future scientists gravitate towards study species with more data and resources already available. as new technologies emerge, do research studies employing these technologies continue these disparities? here, using non-human primates as a case study, we identified disparities in massively parallel genomic sequencing data and conducted interviews with scientists ...202033047065
differences in xanthotoxin metabolites in seven mammalian liver microsomes.xanthotoxin, abundantly occurring in fruits, vegetables, grapefruit juice and oils, is widely used in medicine for the treatment of psoriasis and vitiligo. xanthotoxin possesses the ability to inhibit mechanism-based cytochrome p450 (cyp450)-mediated activities in rats and mice. furthermore, it time-dependently obstructs a number of cyp450-mediated functions in humans. cyp450 enzymes are most abundant in the liver and induce metabolic activation of numerous xenobiotic compounds. the present stud ...202032855735
genetic variants of udp-glucuronosyltransferases 1a1, 1a6, and 1a9 in cynomolgus and rhesus macaques.1. in the cynomolgus macaque, udp-glucuronosyltransferases (ugts) 1as have similar molecular and enzymatic characteristics to those of their human orthologs. however, genetic polymorphisms in major cynomolgus ugt1a1/6/9 have not been investigated. 2. we re-sequenced ugt1a1, ugt1a6, and ugt1a9 in 186 cynomolgus macaques (bred in cambodia, china, or indonesia) and 54 rhesus macaques and found 15, 13, and 26 non-synonymous variants, respectively. 3. of these ugt1a1, ugt1a6, and ugt1a9 variants, res ...202032811258
development of an inactivated vaccine candidate, bbibp-corv, with potent protection against sars-cov-2.the coronavirus disease 2019 (covid-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) threatens global public health. the development of a vaccine is urgently needed for the prevention and control of covid-19. here, we report the pilot-scale production of an inactivated sars-cov-2 vaccine candidate (bbibp-corv) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (cynomolgus monkeys and rhesus maca ...202032778225
macaque gaze responses to the primatar: a virtual macaque head for social cognition research.following the expanding use and applications of virtual reality in everyday life, realistic virtual stimuli are of increasing interest in cognitive studies. they allow for control of features such as gaze, expression, appearance, and movement, which may help to overcome limitations of using photographs or video recordings to study social responses. in using virtual stimuli however, one must be careful to avoid the uncanny valley effect, where realistic stimuli can be perceived as eerie, and indu ...202032765373
immune outcomes of zika virus infection in nonhuman primates.although the zika virus (zikv) epidemic is subsiding, immune responses that are important for controlling acute infection have not been definitively characterized. nonhuman primate (nhp) models were rapidly developed to understand the disease and to test vaccines, and these models have since provided an understanding of the immune responses that correlate with protection during natural infection and vaccination. here, we infected a small group of male rhesus (macaca mulatta) and cynomolgus (maca ...202032747639
a dedicated eight-channel receive rf coil array for monkey brain mri at 9.4 t.the neuroimaging of nonhuman primates (nhps) realised with magnetic resonance imaging (mri) plays an important role in understanding brain structures and functions, as well as neurodegenerative diseases and pathological disorders. theoretically, an ultrahigh field mri (≥7 t) is capable of providing a higher signal-to-noise ratio (snr) for better resolution; however, the lack of appropriate radiofrequency (rf) coils for 9.4 t monkey mri undermines the benefits provided by a higher field strength. ...202032729642
variability in the number of infraorbital foramina in rhesus macaques (macaca mulatta) and cynomolgus macaques (macaca fascicularis).this study aimed to determine the number of infraorbital foramina in monkeys of the papionini tribe. the authors performed a μct analysis of the morphology of the infraorbital foramina. a total number of 52 simian skulls belonged to two macaque species: macaca mulatta and macaca fascicularis were used in the study. the number of infraorbital foramina was counted macroscopically and with the use of a magnifying glass. next, the skull representing the most common morphological type was selected an ...202032558307
cell atlas of aqueous humor outflow pathways in eyes of humans and four model species provides insight into glaucoma pathogenesis.increased intraocular pressure (iop) represents a major risk factor for glaucoma, a prevalent eye disease characterized by death of retinal ganglion cells; lowering iop is the only proven treatment strategy to delay disease progression. the main determinant of iop is the equilibrium between production and drainage of aqueous humor, with compromised drainage generally viewed as the primary contributor to dangerous iop elevations. drainage occurs through two pathways in the anterior segment of the ...202032341164
genetic variants of n-acetyltransferases 1 and 2 (nat1 and nat2) in cynomolgus and rhesus macaques.in humans, polymorphic n-acetyltransferases nat1 and nat2 are important enzymes that metabolize endogenous and exogenous compounds, including drugs. these enzymes exhibit considerable inter-individual variability in humans. the cynomolgus macaque is a nonhuman primate species that is widely used in drug metabolism studies. nat1/2 in these macaques have molecular and enzymatic similarities to their human orthologs; however, genetic polymorphisms in nat1/2 have not been fully investigated in this ...202032339492
a single lentivector dna based immunization contains a late heterologous sivmac251 mucosal challenge infection.variety of conventional vaccine strategies tested against hiv-1 have failed to induce protection against hiv acquisition or durable control of viremia. therefore, innovative strategies that can induce long lasting protective immunity against hiv chronic infection are needed. recently, we developed an integration-defective hiv lentidna vaccine that undergoes a single cycle of replication in target cells in which most viral antigens are produced. a single immunization with such lentidna induced lo ...202032278522
rhesus macaques are most likely the ancestral source of helicobacter suis infection in pigs and not cynomolgus macaques. 202032219893
unparalleled rapid evolution of kir genes in rhesus and cynomolgus macaque populations.the killer cell ig-like receptors (kir) modulate immune responses through interactions with mhc class i molecules. the kir region in large cohorts of rhesus and cynomolgus macaque populations were characterized, and the experimental design enabled the definition of a considerable number of alleles (n = 576) and haplotypes, which are highly variable with regard to architecture. although high levels of polymorphism were recorded, only a few alleles are shared between species and populations. the r ...202032111732
the effects of population tuning and trial-by-trial variability on information encoding and behavior.identifying the features of population responses that are relevant to the amount of information encoded by neuronal populations is a crucial step toward understanding population coding. statistical features, such as tuning properties, individual and shared response variability, and global activity modulations, could all affect the amount of information encoded and modulate behavioral performance. we show that two features in particular affect information: the modulation of population responses a ...202031754013
inhibition of allergen-induced dermal eosinophilia by an oxoeicosanoid receptor antagonist in non-human primates.5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ete), acting via the oxe receptor, is unique among 5-lipoxygenase products in its ability to directly induce human eosinophil migration, suggesting its involvement in eosinophilic diseases. to address this hypothesis, we synthesized selective indole-based oxe receptor antagonists. because rodents lack an oxe receptor orthologue, we sought to determine whether these antagonists could attenuate allergen-induced skin eosinophilia in sensitized monkeys.202031655023
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
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
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
effects of cardiac sympathetic neurodegeneration and pparγ activation on rhesus macaque whole blood mirna and mrna expression profiles.degeneration of sympathetic innervation of the heart occurs in numerous diseases, including diabetes, idiopathic rem sleep disorder, and parkinson's disease (pd). in pd, cardiac sympathetic denervation occurs in 80-90% of patients and can begin before the onset of motor symptoms. today, there are no disease-modifying therapies for cardiac sympathetic neurodegeneration, and biomarkers are limited to radioimaging techniques. analysis of expression levels of coding mrna and noncoding rnas, such as ...202032462037
paternal age in rhesus macaques is positively associated with germline mutation accumulation but not with measures of offspring sociability.mutation is the ultimate source of all genetic novelty and the cause of heritable genetic disorders. mutational burden has been linked to complex disease, including neurodevelopmental disorders such as schizophrenia and autism. the rate of mutation is a fundamental genomic parameter and direct estimates of this parameter have been enabled by accurate comparisons of whole-genome sequences between parents and offspring. studies in humans have revealed that the paternal age at conception explains m ...202032461224
a human neutralizing antibody targets the receptor-binding site of sars-cov-2.an outbreak of coronavirus disease 2019 (covid-19)1-3, caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2)4, has spread globally. countermeasures are needed to treat and prevent further dissemination of the virus. here we report the isolation of two specific human monoclonal antibodies (termed ca1 and cb6) from a patient convalescing from covid-19. ca1 and cb6 demonstrated potent sars-cov-2-specific neutralization activity in vitro. in addition, cb6 inhibited infection with sa ...202032454512
hiv-1 tat-mediated astrocytic amyloidosis involves the hif-1α/lncrna bace1-as axis.increased life expectancy of patients diagnosed with hiv in the current era of antiretroviral therapy is unfortunately accompanied with the prevalence of hiv-associated neurocognitive disorders (hands) and risk of comorbidities such as alzheimer-like pathology. hiv-1 transactivator of transcription (tat) protein has been shown to induce the production of toxic neuronal amyloid protein and also enhance neurotoxicity. the contribution of astrocytes in tat-mediated amyloidosis remains an enigma. we ...202032453744
fast and reversible neural inactivation in macaque cortex by optogenetic stimulation of gabaergic neurons.optogenetic techniques for neural inactivation are valuable for linking neural activity to behavior but they have serious limitations in macaques. to achieve powerful and temporally precise neural inactivation, we used an adeno-associated viral (aav) vector carrying the channelrhodopsin-2 gene under the control of a dlx5/6 enhancer, which restricts expression to gabaergic neurons. we tested this approach in the primary visual cortex, an area where neural inactivation leads to interpretable behav ...202032452766
abnormal tuning in nucleus prepositus hypoglossi of monkeys with "a" pattern exotropia.in many individuals with pattern strabismus, the vertical misalignment varies with horizontal eye position. it has been proposed that these cross-axis effects result from abnormal cross-talk between brainstem structures that would normally encode horizontal and vertical eye position and velocity. the nucleus prepositus hypoglossi (nph) is an ideal structure to test this overarching hypothesis. neurons in the nph are believed to mathematically integrate eye velocity signals to generate a tonic si ...202032446250
organized lymphatic tissue (balt) in lungs of rhesus monkeys after air pollutant exposure.the presence of bronchus-associated lymphoid tissue (balt) and its size in humans largely depends upon age. it is detected in 35% of children less than 2 years of age, but absent in the healthy adult lung. environmental gases or allergens may have an effect on the number of balt. lungs of rhesus macaque monkeys were screened by histology for the presence, size, and location of balt after exposure to filtered air for 2, 6, 12, or 36 months or 12 and 36 months to ozone or 2, 12, or 36 months of ho ...202032445535
quantification of radiation injury on neutropenia and the link between absolute neutrophil count time course and overall survival in nonhuman primates treated with g-csf.to model absolute neutrophil count (anc) suppression in response to acute radiation (ar) exposure and evaluate anc time course as a predictor of overall survival (os) in response to ar exposure with or without treatment with granulocyte colony-stimulating factor in nonhuman primates.202032440783
long-term alterations in brain and behavior after postnatal zika virus infection in infant macaques.zika virus (zikv) infection has a profound impact on the fetal nervous system. the postnatal period is also a time of rapid brain growth, and it is important to understand the potential neurobehavioral consequences of zikv infection during infancy. here we show that postnatal zikv infection in a rhesus macaque model resulted in long-term behavioral, motor, and cognitive changes, including increased emotional reactivity, decreased social contact, loss of balance, and deficits in visual recognitio ...202032439858
fecundity of adult female worms were affected when brugia malayi infected mongolian gerbils were immunized with a multivalent vaccine (rbmhaxt) against human lymphatic filarial parasite.a multivalent recombinant fusion protein prophylactic vaccine, rbmhaxt developed against lymphatic filariasis (lf) demonstrated over 57% protection against challenge infection in rhesus macaque model. currently, we do not know if the rbmhaxt vaccination has any effect on adult worms and/or on the fecundity of adult female worms. thus, the major focus of this study was to determine the effect of rbmhaxt vaccination on brugia malayi infected mongolian gerbils. we performed two sets of experiments. ...202032437645
evaluation of heterologous prime-boost vaccination strategies using chimpanzee adenovirus and modified vaccinia virus for tb subunit vaccination in rhesus macaques.tuberculosis (tb) still is the principal cause of death from infectious disease and improved vaccination strategies are required to reduce the disease burden and break tb transmission. here, we investigated different routes of administration of vectored subunit vaccines based on chimpanzee-derived adenovirus serotype-3 (chad3) for homologous prime-boosting and modified vaccinia virus ankara (mva) for heterologous boosting with both vaccine vectors expressing the same antigens from mycobacterium ...202032435513
sars-cov-2 infection protects against rechallenge in rhesus macaques.an understanding of protective immunity to severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is critical for vaccine and public health strategies aimed at ending the global coronavirus disease 2019 (covid-19) pandemic. a key unanswered question is whether infection with sars-cov-2 results in protective immunity against reexposure. we developed a rhesus macaque model of sars-cov-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humora ...202032434946
dna vaccine protection against sars-cov-2 in rhesus macaques.the global coronavirus disease 2019 (covid-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has made the development of a vaccine a top biomedical priority. in this study, we developed a series of dna vaccine candidates expressing different forms of the sars-cov-2 spike (s) protein and evaluated them in 35 rhesus macaques. vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers at levels comparable to those fou ...202032434945
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