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progesterone increases mitochondria membrane potential in non-human primate oocytes and embryos.mitochondrial activity is critical and correlates with embryo development. the identification of a novel human mitochondrial progesterone receptor (pr-m) that increases cellular respiration brings into question a role for progesterone in oocyte and preimplantation embryo development. oocytes and embryos were generated from three rhesus non-human primates (macaca mulatta) undergoing in vitro fertilization. immunohistochemical (ihc) staining for the progesterone receptor and mitochondria, rt-pcr w ...202032046426
postural control of arm and fingers through integration of movement commands.every movement ends in a period of stillness. current models assume that commands that hold the limb at a target location do not depend on the commands that moved the limb to that location. here, we report a surprising relationship between movement and posture in primates: on a within-trial basis, the commands that hold the arm and finger at a target location depend on the mathematical integration of the commands that moved the limb to that location. following damage to the corticospinal tract, ...202032043973
associative models fail to characterize transitive inference performance in rhesus monkeys (macaca mulatta).it has been suggested that non-verbal transitive inference (if a > b and b > c, then a > c) can be accounted for by associative models. however, little is known about the applicability of such models to primate data. in experiment 1, we tested the fit of two associative models to primate data from both sequential training, in which the training pairs were presented in a backward order, and simultaneous training, in which all training pairs are presented intermixed from the beginning. we found th ...202032040696
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
imgt® biocuration and comparative study of the t cell receptor beta locus of veterinary species based on homo sapiens trb.imgt®, the international immunogenetics information system® is the global reference in immunogenetics and immunoinformatics. by its creation in 1989 by marie-paule lefranc (université de montpellier and cnrs), imgt® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. imgt® is specialized in the immunoglobulins (ig) or antibodies, t cell receptors (tr), major histocompatibility (mh), and proteins of the igsf and mhsf superfamilies. t c ...202032431713
virological and immunological outcomes in rhesus monkeys after exposure to dengue virus-infected aedes aegypti mosquitoes.this study describes the natural history of dengue virus (denv) infection in rhesus monkeys exposed to the bites of denv-infected aedes aegypti mosquitoes. dengue virus-infected mosquitoes were generated by either intrathoracic inoculation or by oral feeding on viremic blood meals. each of the six rhesus monkeys that were fed upon by intrathoracically infected mosquitoes developed non-structural protein 1 (ns1) antigenemia and an igm response; viremia was detected in 4/6 individuals. no virologi ...202032431270
human and monkey infant attention to dynamic social and nonsocial stimuli.the present study explored behavioral norms for infant social attention in typically developing human and nonhuman primate infants. we examined the normative development of attention to dynamic social and nonsocial stimuli longitudinally in macaques (macaca mulatta) at 1, 3, and 5 months of age (n = 75) and humans at 2, 4, 6, 8, and 13 months of age (n = 69) using eye tracking. all infants viewed concurrently played silent videos-one social video and one nonsocial video. both macaque and human i ...202032424813
persistence dynamics of antimicrobial-resistant neisseria in the pharynx of rhesus macaques.pharyngeal infections by neisseria gonorrhoeae are often asymptomatic, making them difficult to treat. however, in vivo animal modeling of human pharyngeal infections by pathogenic neisseria species is challenging due to numerous host tropism barriers. we have relied on rhesus macaques to investigate pharyngeal persistence of naturally occurring neisseria species in response to antibiotics. these species include neisseria mucosa, neisseria oralis, and a species unique to macaques. four animals p ...202032423958
safety and immunogenicity of a recombinant vaccine against trypanosoma cruzi in rhesus macaques.chagas disease, caused by the protozoan parasite trypanosoma cruzi is one of the most important neglected parasitic diseases in the americas. vaccines represent an attractive complementary strategy for the control of t. cruzi infection and pre-clinical studies in mice demonstrated that trypomastigote surface antigen (tsa-1) and the flagellar calcium-binding (tc24) parasite antigens are promising candidates for vaccine development. we performed here the first evaluation of the safety and immunoge ...202032417142
the evolutionary origins of natural pedagogy: rhesus monkeys show sustained attention following nonsocial cues versus social communicative signals.the natural pedagogy hypothesis proposes that human infants preferentially attend to communicative signals from others, facilitating rapid cultural learning. in this view, sensitivity to such signals is a uniquely human adaptation and as such nonhuman animals should not produce or utilize these communicative signals. we test these evolutionary predictions by examining sensitivity to communicative cues in 206 rhesus monkeys (macaca mulatta) using an expectancy looking time task modeled on prior w ...202032412163
delineation and modulation of the natural killer cell transcriptome in rhesus macaques during zikv and siv infections.natural killer (nk) cells are crucial regulators of antiviral and anti-tumor immune responses. although in humans some nk cell transcriptional programs are relatively well-established, nk cell transcriptional networks in non-human primates (nhp) remain poorly delineated. here we performed rna-seq experiments using purified nk cells from experimentally naïve rhesus macaques, providing the first transcriptional characterization of pure nk cells in any nhp species. this novel nk cell transcriptomic ...202032411625
monkeycbp: a toolbox for connectivity-based parcellation of monkey brain.non-human primate models are widely used in studying the brain mechanism underlying brain development, cognitive functions, and psychiatric disorders. neuroimaging techniques, such as magnetic resonance imaging, play an important role in the examinations of brain structure and functions. as an indispensable tool for brain imaging data analysis, brain atlases have been extensively investigated, and a variety of versions constructed. these atlases diverge in the criteria based on which they are pl ...202032410977
maximizing viral detection with siv droplet digital pcr (ddpcr) assays.highly sensitive detection of hiv-1 nucleic acids is of critical importance for evaluating treatment interventions superimposed on combination antiretroviral therapy (cart) in hiv-1 infected individuals. siv infection of rhesus macaques models many key aspects of human hiv-1 infection and plays a key role in evaluation of approaches for prevention, treatment and attempted eradication of hiv infection. here we describe two droplet digital pcr (ddpcr) assays, a ddpcr dna assay and an rt-ddpcr rna ...202032407343
monkeys (macaca mulatta) learn two-choice discriminations under displaced reinforcement.to explain animal learning, researchers invoke a dominant associative construct. in contrast, researchers freely acknowledge humans' explicit-declarative learning capacity. here, we stretched animals' learning performance toward the explicit pole of cognition. we tested four macaques (macaca mulatta) in new discrimination-learning paradigms. monkeys learned a series of two-choice discrimination tasks. but immediate reinforcement was denied. instead, reinforcement was lagged-monkeys received feed ...202032406719
therapeutic efficacy and resistance selection of a lipopeptide fusion inhibitor in simian immunodeficiency virus-infected rhesus macaques.we recently reported a group of lipopeptide-based membrane fusion inhibitors with potent antiviral activities against human immunodeficiency virus type 1 (hiv-1), hiv-2, and simian immunodeficiency virus (siv). in this study, the in vivo therapeutic efficacy of such a lipopeptide, lp-52, was evaluated in rhesus macaques chronically infected with pathogenic sivmac239. in a pilot study with one monkey, monotherapy with low-dose lp-52 rapidly reduced the plasma viral loads to below the limit of det ...202032404526
polyethylene glycol 40-modified peptide with high therapeutic efficacy in simian-human immunodeficiency virus-acutely infected rhesus monkeys.anti-human immunodeficiency virus type 1 (anti-hiv-1) fusion peptides have been studied for nearly 2 decades, but few candidates have found useful clinical applications. one factor underlying the failure of such agents to reach the clinic is their poor pharmacokinetic properties, and many efforts have been made to overcome this problem. in this study, we modified c34, a peptide inhibitor of hiv-1 fusion, at its conserved glycosylation site using polyethylene glycols (pegs) of different molecular ...202032404523
co-immunization of dna and protein in the same anatomical sites induces superior protective immune responses against shiv challenge.we compare immunogenicity and protective efficacy of an hiv vaccine comprised of env and gag dna and env (envelope) proteins by co-administration of the vaccine components in the same muscles or by separate administration of dna + protein in contralateral sites in female rhesus macaques. the 6-valent vaccine includes gp145 env dnas, representing six sequentially isolated envs from the hiv-infected individual ch505, and matching gla-se-adjuvanted gp120 env proteins. interestingly, only macaques i ...202032402293
blood transcriptome analysis reveals gene expression features of breast-feeding rhesus macaque ( macaca mulatta) infants.during the breast-feeding period, infants undergo remarkable changes, including rapid physiological and developmental growth. however, little is known about gene expression features and sex-specific gene expression in breast-feeding infants. in this study, we sequenced 32 blood transcriptomes from 16 breast-feeding rhesus macaque ( macaca mulatta) infants and their lactating mothers. we identified 218 differentially expressed genes (degs) between infants and mothers, including 91 up-regulated an ...202032400975
respiratory disease in rhesus macaques inoculated with sars-cov-2.an outbreak of coronavirus disease 2019 (covid-19), which is caused by a novel coronavirus (named sars-cov-2) and has a case fatality rate of approximately 2%, started in wuhan (china) in december 20191,2. following an unprecedented global spread3, the world health organization declared covid-19 a pandemic on 11 march 2020. although data on covid-19 in humans are emerging at a steady pace, some aspects of the pathogenesis of sars-cov-2 can be studied in detail only in animal models, in which rep ...202032396922
development of an anti-human complement c6 monoclonal antibody that inhibits the assembly of membrane attack complexes.membrane attack complexes (macs; c5b-9) assembled after complement activation can directly injure self-tissues, leading to various diseases. eculizumab, a monoclonal antibody (mab) against complement component c5, is being used in the clinic to treat diseases in which mac-mediated tissue damage is a primary cause. however, c5 is not a selective target for mac assembly inhibition, and some patients respond incompletely or not at all to the eculizumab treatment. therefore, c6, the next essential c ...202032396613
an samt-247 microbicide provides potent protection against intravaginal simian immunodeficiency virus infection of rhesus macaques, whereas an added vaccine component elicits mixed outcomes.because of microbicide noncompliance and lack of a durable, highly effective vaccine, a combined approach might improve hiv prophylaxis. we tested whether a vaccine-microbicide combination would enhance protection against siv infection in rhesus macaques. four macaque groups included vaccine only, vaccine-microbicide, microbicide only, and controls. vaccine groups were primed twice mucosally with replicating adenovirus type 5 host range mutant siv env/rev, gag, and nef recombinants and boosted t ...202032393514
copy number variants and fixed duplications among 198 rhesus macaques (macaca mulatta).the rhesus macaque is an abundant species of old world monkeys and a valuable model organism for biomedical research due to its close phylogenetic relationship to humans. copy number variation is one of the main sources of genomic diversity within and between species and a widely recognized cause of inter-individual differences in disease risk. however, copy number differences among rhesus macaques and between the human and macaque genomes, as well as the relevance of this diversity to research ...202032392208
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