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irak1 is a critical mediator of inflammation-induced preterm birth.preterm birth (ptb) is a major cause of neonatal mortality and morbidity, often triggered by chorioamnionitis or intrauterine inflammation (iui) with or without infection. recently, there has been a strong association of il-1 with ptb. we hypothesized that il-1r-associated kinase 1 (irak1), a key signaling mediator in the tlr/il-1 pathway, plays a critical role in ptb. in human fetal membranes (fm) collected immediately after birth from women delivering preterm, p-irak1 was significantly increas ...202032238461
correction for mavigner et al., "simian immunodeficiency virus persistence in cellular and anatomic reservoirs in antiretroviral therapy-suppressed infant rhesus macaques". 202032234801
primate version of modified rankin scale for classifying dysfunction in rhesus monkeys.background and purpose- nonhuman primates are increasingly used in translational studies of ischemic stroke. however, current scoring systems in monkeys (eg, nonhuman primate stroke scale) do not focus on impairments in activities of daily living, so clinically relevant data are scarce for evaluating functional deficits in this model. methods- here, we referenced the modified rankin scale to provide a primate version of rankin scale (prs) for ranking neurological dysfunction in monkeys following ...202032233743
conditionally reprogrammed macaque endocervical cells retain steroid receptor expression and produce mucus.cervical mucus produced by the endocervix plays an essential role as a hormonally induced regulator of female fertility. cervical mucus fluctuates in both physical characteristics and in sperm penetrability in response to estrogens and progestogens. however, the mechanisms by which steroid hormones change mucus remains poorly understood. current in vitro models have limited capability to study these questions as primary endocervical cells possess limited expansion potential, and immortalized cel ...202032232331
melengestrol acetate (veterinary medicinal products).food safety commission of japan (fscj) conducted a risk assessment of melengestrol acetate (mga, cas no. 2919-66-6), a synthetic hormone, based on results from various studies. mga was recognized to have no genotoxicity relevant to human health, and it enabled fscj to specify an acceptable daily intake (adi) in the assessment. in vitro studies using various human hormone-receptors showed that mga exerts biological action primarily as progestogens and secondarily as glucocorticoids. major adverse ...201732231940
a state-based probabilistic method for decoding hand position during movement from ecog signals in non-human primate.in this study, we proposed a state-based probabilistic method for decoding hand positions during unilateral and bilateral movements using the ecog signals recorded from the brain of rhesus monkey.202032224511
tuberculosis-associated ifn-i induces siglec-1 on tunneling nanotubes and favors hiv-1 spread in macrophages.while tuberculosis (tb) is a risk factor in hiv-1-infected individuals, the mechanisms by which mycobacterium tuberculosis (mtb) worsens hiv-1 pathogenesis remain scarce. we showed that hiv-1 infection is exacerbated in macrophages exposed to tb-associated microenvironments due to tunneling nanotube (tnt) formation. to identify molecular factors associated with tnt function, we performed a transcriptomic analysis in these macrophages, and revealed the up-regulation of siglec-1 receptor. siglec-1 ...202032223897
daily ethanol drinking followed by an abstinence period impairs bone marrow niche and mitochondrial function of hematopoietic stem/progenitor cells in rhesus macaques.unhealthy consumption of alcohol is a major public health crisis with strong associations between immunological dysfunctions, high vulnerability to infectious disease, anemia, and an increase in the risk of hematological malignancies. however, there is a lack of studies addressing alcohol-induced changes in bone marrow (bm) and hematopoiesis as fundamental aspects of immune system function.202032220015
immunohistochemical distribution of 10 gabaa receptor subunits in the forebrain of the rhesus monkey macaca mulatta.gabaa receptors are composed of five subunits arranged around a central chloride channel. their subunits originate from different genes or gene families. the majority of gabaa receptors in the mammalian brain consist of two α-, two β- and one γ- or δ-subunit. this subunit organization crucially determines the physiological and pharmacological properties of the gabaa receptors. using immunohistochemistry, we investigated the distribution of 10 gabaa receptor subunits (α1, α2, α3, α4, α5, β1, β2, ...202032220012
rhesus macaques are most likely the ancestral source of helicobacter suis infection in pigs and not cynomolgus macaques. 202032219893
distinguishing between parallel and serial processing in visual attention from neurobiological data.serial and parallel processing in visual search have been long debated in psychology, but the processing mechanism remains an open issue. serial processing allows only one object at a time to be processed, whereas parallel processing assumes that various objects are processed simultaneously. here, we present novel neural models for the two types of processing mechanisms based on analysis of simultaneously recorded spike trains using electrophysiological data from prefrontal cortex of rhesus monk ...202032218974
characterisation of the gut microbial community of rhesus macaques in high-altitude environments.the mammal intestinal microbiota is involved in various physiological processes and plays a key role in host environment adaption. however, for non-human primates (nhps), little is known about their gut microbial community in high-altitude environments and even less about their adaption to such habitats. we characterised the gut microbial community of rhesus macaques from multiple high-altitude environments and compared it to those of low-altitude populations.202032216756
immune responses of a designed hiv-1 dna vaccine on rhesus monkeys.an effective hiv-1 vaccine will be the ultimate solution for the prevention of hiv/aids, though haart plays important roles in treating the disease. in this study, a large-scale recombinant dna plasmid containing a designed hiv-1 multi-epitope-p24 chimeric gene was prepared and purified. rhesus monkeys were then inoculated muscularly with the plasmid for four times in week 0, 4, 8 and 18. whole blood was collected two weeks after the third and fourth inoculation, followed by serum and peripheral ...200632214722
hiv env-specific igg antibodies induced by vaccination of neonatal rhesus macaques persist and can be augmented by a late booster immunization in infancy.the hiv epidemics in infants and adolescent women are linked. young women of childbearing age are at high risk for hiv infection and, due to poor hiv testing rates and low adherence to antiretroviral therapy, are at high risk for mother-to-infant transmission. we hypothesize that hiv vaccine regimens initiated in early life would provide the necessary time frame to induce mature and highly functional env-specific antibody responses that could potentially also protect against hiv acquisition late ...202032213623
a multiplex centrality metric for complex social networks: sex, social status, and family structure predict multiplex centrality in rhesus macaques.members of a society interact using a variety of social behaviors, giving rise to a multi-faceted and complex social life. for the study of animal behavior, quantifying this complexity is critical for understanding the impact of social life on animals' health and fitness. multilayer network approaches, where each interaction type represents a different layer of the social network, have the potential to better capture this complexity than single layer approaches. calculating individuals' centrali ...202032211232
a combination of two human monoclonal antibodies limits fetal damage by zika virus in macaques.human infection by zika virus (zikv) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. prophylactic administration of antibodies can diminish or prevent zikv infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. z004 and z021 are neutralizing monoclonal antibodies to domain iii of the envelope (ediii) of zikv. together the two antibodies protect nonpreg ...202032209664
route of vaccine administration alters antigen trafficking but not innate or adaptive immunity.although intramuscular (i.m.) administration is the most commonly used route for licensed vaccines, subcutaneous (s.c.) delivery is being explored for several new vaccines under development. here, we use rhesus macaques, physiologically relevant to humans, to identify the anatomical compartments and early immune processes engaged in the response to immunization via the two routes. administration of fluorescently labeled hiv-1 envelope glycoprotein trimers displayed on liposomes enables visualiza ...202032209459
cross-species cortical alignment identifies different types of anatomical reorganization in the primate temporal lobe.evolutionary adaptations of temporo-parietal cortex are considered to be a critical specialization of the human brain. cortical adaptations, however, can affect different aspects of brain architecture, including local expansion of the cortical sheet or changes in connectivity between cortical areas. we distinguish different types of changes in brain architecture using a computational neuroanatomy approach. we investigate the extent to which between-species alignment, based on cortical myelin, ca ...202032202497
evaluation of the immune response of a h7n9 candidate vaccine virus derived from the fifth wave a/guangdong/17sf003/2016.highly pathogenic influenza h7n9 viruses that emerged in the fifth wave of h7n9 outbreak pose a risk to human health. the world health organization has updated the candidate vaccine viruses for h7n9 viruses recently. in this study, we evaluated the immune response to an updated h7n9 candidate vaccine virus, which derived from the highly pathogenic a/guangdong/17sf003/2016 (gd/16) in mice and rhesus macaques. gd/16 vaccination elicited robust neutralizing, virus-specific immunoglobulin g antibodi ...202032201204
generation and functional assessment of nonhuman primate regulatory dendritic cells and their therapeutic efficacy in renal transplantation.nonhuman primates (nhp) are important pre-clinical models for evaluation of the safety and efficacy of the most promising potential therapeutic advances in organ transplantation based on rodent studies. although rare, dendritic cells (dc) play important roles in preservation of self tolerance and dc with immunoregulatory properties (regulatory dc; dcreg) can promote transplant tolerance in rodents when adoptively transferred to allograft recipients. nhp dcreg can be generated ex vivo from bone m ...202032197811
contexts and messages in macaque social communication.using a previously developed quantitative scale of social behavior, interactions between group members in seven groups of rhesus macaques were studied. analysis of 636 behavior chains showed that the large number of different chain sequences (445) was due in part to the large number of contexts in which interactions were occurring. a catalog of 33 contexts of interaction was empirically developed. particular behaviors were found to have different frequencies of occurrence in different contexts. ...198232197558
female mating relationships in rhesus monkeys.descriptions of the sexual behavior of social-living rhesus monkeys have indicated that mating patterns are characterized by the formation of consort pairs (mutually exclusive male-female associations) and also that females typically mate with multiple males. these reports raise the question of whether these are two different mating strategies or merely sequential phases in a unitary mating pattern. in order to examine this issue, the copulatory behavior of 27 adult females living in a heterosex ...198232197557
opioid receptors in immune and glial cells-implications for pain control.opioid receptors comprise μ (mop), δ (dop), κ (kop), and nociceptin/orphanin fq (nop) receptors. opioids are agonists of mop, dop, and kop receptors, whereas nociceptin/orphanin fq (n/ofq) is an agonist of nop receptors. activation of all four opioid receptors in neurons can induce analgesia in animal models, but the most clinically relevant are mop receptor agonists (e.g., morphine, fentanyl). opioids can also affect the function of immune cells, and their actions in relation to immunosuppressi ...202032194554
effect of chemogenetic actuator drugs on prefrontal cortex-dependent working memory in nonhuman primates.the most common chemogenetic neuromodulatory system, designer receptors exclusively activated by designer drugs (dreadds), uses a non-endogenous actuator ligand to activate a modified muscarinic acetylcholine receptor that is insensitive to acetylcholine. it is crucial in studies using these systems to test the potential effects of dreadd actuators prior to any dreadd transduction, so that effects of dreadds can be attributed to the chemogenetic system rather than the actuator drug, particularly ...202032193513
rhesus monkey rhadinovirus isolated from hemangioma tissue.we isolated a rhesus monkey rhadinovirus, isolate rrvmmu 209-07, from hemangioma tissue. the virion dna was sequenced by illumina-based sequencing. isolate rrvmmu 209-07 is highly similar overall to rrv 26-95, but considerable differences exist in the 3' region of the genome.202032193241
clinical note: calcium bilirubinate gallstones in an aged rhesus monkey (macaca mulatta).severe gallstone disease was found at necropsy in a 24-year-old female monkey which died of pyelonephritis. reports of spontaneous cholelithiasis in rhesus monkeys are rare. this is the first description of gallstone disease in a non-human primate caused by calcium bilirubinate choleliths.198232192244
decrease in sexual initiative and responsiveness in female rhesus macaques (macaca mulatta) during pregnancy.although the sexual behavior of female rhesus macaques (macaca mulatta) has been reported to decrease during pregnancy, systematic studies have been largely confined to reports of male behavior. therefore, we designed a study to examine changes in female sexual behavior during pregnancy. six cycling multiparous female rhesus macaques were paired during the periovulatory period of the menstrual cycle and during the first and second halves of pregnancy with six sexually experienced males of the sa ...198232192243
validation of radioimmunoassays for lh and fsh in the sooty mangabey (cercocebus atys): characterization of lh and the response to gnrh.heterologous radioimmunoassays (ria) for macaque lh and fsh were validated for the measurement of these hormones in the sooty mangabey and mangabey pituitary lh was characterized relative to rhesus monkey lh. dilutions of a pituitary mangabey extract and a partially purified preparation of mangabey lh ran parallel to a rhesus monkey standard (ler 1909-2) in the ovine-ovine (o-o) lh assay but showed some deviation from parallelism in the rhesus monkey fsh assay. the lh potency of the mangabey ext ...198232192239
characterization and comparison of testicular lh/hcg receptors of rhesus monkeys (macaca mulatta) and green monkeys (cercopithecus aethiops).testicular luteinizing hormone (lh/hcg) receptors were characterized in seven green monkeys and compared with those of four rhesus monkeys. testicular tissue showed high binding affinity for 125 i-hcg, (0.9-2.5 × 109 m-1 , and 0.7-1.64 × 109 m-1 respectively, for green and rhesus monkeys) and low binding capacity (0.343-0.682 fmol/mg and 0.198-0.355 fmol/mg testicular homogenate, respectively). there was no difference in binding affinity between the two groups. testicular lh/hcg receptors in bot ...198232192236
the effects of intramuscular naloxone dose on mu receptor displacement of carfentanil in rhesus monkeys.naloxone (nlx) is a mu receptor antagonist used to treat acute opioid overdoses. currently approved doses of naloxone to treat opioid overdoses are 4 mg intranasal (in) and 2 mg intramuscular (im). however, higher mu receptor occupancy (ro) may be required to treat overdoses due to more potent synthetic opioids such as fentanyl and carfentanil that have entered the illicit drug market recently. to address this need, a higher dose of nlx has been investigated in a 5 mg im formulation called zimhi ...202032192089
patterns of sexual behavior in male macaques.one large social group of each of three species of macaques (macaca mulatta, m. fascicularis, m. radiata), housed in half-acre field cages at the california primate research center, were observed for a total of 150 h. data on sexual behavior and dominance interactions were recorded by pairs of experienced observers using a focal animal technique. single or multiple mount-to-ejaculation sequences, number of thrusts per mount, number of mounts per sequence, duration of mounts per sequence, duratio ...198232188180
conservation note: socioecology and conservation of macaques and langurs in varanasi, india.a survey of rhesus monkeys (macaca mulatta) and hanuman langurs (presbytis entellus) was conducted in urban and forest areas of varanasi, india. data were collected on group size and composition. nine groups of rhesus monkeys inhabited various urban niches, but langurs were completely absent from urban areas. approximately 159 rhesus monkeys and 720 langurs lived in the forested area. both the urban and the forested habitats of this area are being reduced in size, and it is suggested that these ...198232188177
placental transfer of synthetic and endogenous estrogen conjugates in the rhesus monkey (macaca mulatta).the placental transfer of conjugated and nonconjugated estrogens was compared in the pregnant rhesus monkey. placement of catheters in the maternal and fetal circulation allowed for the sampling of blood after the administration of radiolabeled naturally occurring and synthetic estrogens to mother or fetus. in all cases, nonconjugated-estrogen placental transfer was greater than conjugated-estrogen transfer. comparison of the conjugated estrogens suggested that diethylstilbestrol-monoglucuronide ...198232188175
a new look at neurobehavioral development in rhesus monkey neonates (macaca mulatta).the brazelton neonatal behavioral assessment scale (nbas) evaluates a newborn infant's autonomic, motor, state, temperament, and social-attentional systems, which can help to identify infants at risk of developmental problems. given the prevalence of rhesus monkeys being used as an animal model for human development, here we aimed to validate a standardized test battery modeled after the nbas for use with nonhuman primates called the infant behavioral assessment scale (ibas), employing explorato ...202032187719
reproductive outcomes in rhesus macaques (macaca mulatta) with naturally-acquired trypanosoma cruzi infection.chagas disease is a zoonotic vector-borne disease caused by infection with the protozoan parasite trypanosoma cruzi. t. cruzi is found in latin america and the southern united states, where it infects many species, including humans and nonhuman primates (nhps). nhps are susceptible to natural infection and can develop clinical symptoms consistent with human disease, including chagasic cardiomyopathy, gastrointestinal disease and transplacental transmission, leading to congenital infection. due t ...202032183928
itr-seq, a next-generation sequencing assay, identifies genome-wide dna editing sites in vivo following adeno-associated viral vector-mediated genome editing.identifying nuclease-induced double-stranded breaks in dna on a genome-wide scale is critical for assessing the safety and efficacy of genome editing therapies. we previously demonstrated that after administering adeno-associated viral (aav) vector-mediated genome-editing strategies in vivo, vector sequences integrated into the host organism's genomic dna at double-stranded breaks. thus, identifying the genomic location of inserted aav sequences would enable us to identify dsb events, mainly der ...202032183699
is human-rhesus macaque (macaca mulatta) conflict in india a case of human-human conflict?the perceptions of wildlife managers regarding human-wildlife conflict (hwc) scenarios are likely to affect the outcomes of conflict mitigation measures. we studied the attitudes and perceptions of forest department personnel regarding the management of human-rhesus macaque conflict (hrmc) in himachal pradesh, northern india. we collected data through a questionnaire survey and used frameworks from organizational psychology to draw insights from our results. forest department personnel belonging ...202032180172
comparative ecological and behavioral study of macaca assamensis and m. mulatta in shivapuri nagarjun national park, nepal.resource partitioning reduces the competition between different species within the same habitat, promoting their coexistence. to understand how such species co-adapt to reduce conflicts, we examined the behavior of two primates, assamese macaque (macaca assamensis) and rhesus macaque (macaca mulatta), from april 2017 to march 2018 in sivapuri nagarjun national park (snnp), kathmandu valley, nepal. we performed 1580 and 1261 scan sessions on wild multi-male/multi-female groups of assamese and rhe ...202032180044
clinical and pathologic features of spontaneous klebsiella pneumoniae infection in 9 rhesus macaques (macaca mulatta).klebsiella pneumoniae is a gram-negative bacterium found in the environment and as a commensal in humans and animals. in humans, k. pneumoniae is one of the most serious nosocomial infections encountered currently and is characterized by liver abscesses, pneumonia, and bacteremia resulting in meningoencephalitis and endophthalmitis. k. pneumoniae in veterinary medicine is rarely reported in nhp, and recent literature describing this disease is sparse. in our colony of predominantly outdoor-house ...202032178759
emotional responses in monkeys differ depending on the stimulus type, sex, and neonatal amygdala lesion status.the amygdala plays an essential role in evaluating social information, threat detection, and learning fear associations. yet, most of that knowledge comes from studies in adult humans and animals with a fully developed amygdala. given the considerable protracted postnatal development of the amygdala, it is important to understand how early damage to this structure may impact the long-term development of behavior. the current study examined behavioral responses toward social, innate, or learned a ...202032175761
[markers of hepatitis a in the monkeys of the adlers primate center.]hepatitis a is a widespread viral infection. the hav strains of "human" and "monkey" origin are similar in their morphological and antigenic properties, but differ genotypically.201932167690
engagement of monocytes, nk cells, and cd4+ th1 cells by alvac-siv vaccination results in a decreased risk of sivmac251 vaginal acquisition.the recombinant canarypox alvac-hiv/gp120/alum vaccine regimen was the first to significantly decrease the risk of hiv acquisition in humans, with equal effectiveness in both males and females. similarly, an equivalent siv-based alvac vaccine regimen decreased the risk of virus acquisition in indian rhesus macaques of both sexes following intrarectal exposure to low doses of sivmac251. here, we demonstrate that the alvac-siv/gp120/alum vaccine is also efficacious in female chinese rhesus macaque ...202032163525
the human il-15 superagonist n-803 promotes migration of virus-specific cd8+ t and nk cells to b cell follicles but does not reverse latency in art-suppressed, shiv-infected macaques.despite the success of antiretroviral therapy (art) to halt viral replication and slow disease progression, this treatment is not curative and there remains an urgent need to develop approaches to clear the latent hiv reservoir. the human il-15 superagonist n-803 (formerly alt-803) is a promising anti-cancer biologic with potent immunostimulatory properties that has been extended into the field of hiv as a potential "shock and kill" therapeutic for hiv cure. however, the ability of n-803 to reac ...202032163523
intergenerational effects of mother's early rearing experience on offspring treatment and socioemotional development.this longitudinal study spans two generations of rhesus monkeys. first, the study investigates the effects of early rearing experiences on the maternal behavior of first-generation mothers (rates of premature infant rejection) and, second, the study investigates the effects of maternal rejection on the behavior of second-generation infants. rhesus macaque mother-infant dyads (macaca mulatta-n = 176) were observed twice weekly, with each session lasting 300 s. first-generation mothers were raised ...202032162325
mhc-e-restricted cd8+ t cells target hepatitis b virus-infected human hepatocytes.currently 247 million people are living with chronic hepatitis b virus infection (chb), and the development of novel curative treatments is urgently needed. immunotherapy is an attractive approach to treat chb, yet therapeutic approaches to augment the endogenous hepatitis b virus (hbv)-specific t cell response in chb patients have demonstrated little success. in this study, we show that strain 68-1 rhesus macaque (rm) cmv vaccine vectors expressing hbv ags engender hbv-specific cd8+ t cells unc ...202032161099
safety and immunogenicity of an experimental live combination vaccine against enterovirus 71 and coxsackievirus a16 in rhesus monkeys.enterovirus 71 (ev-a71) and coxsackievirus a16 (cv-a16) are the two most common pathogens causing hand, foot, and mouth disease (hfmd). previously, we obtained one candidate live attenuated strain each for ev-a71 and cv-a16; here, we evaluated the safety and immunogenicity of a combinedlive vaccine against ev-a71 and cv-a16 generated from these two candidate strains. rhesus monkeys were intramuscularly treated with a live combinationvaccine against both ev-a71 and cv-a16 or with either vaccine a ...202032159429
behavioural variability contributes to over-staying in patchy foraging.foragers often systematically deviate from rate-maximizing choices in two ways: accuracy and precision. that is, they use suboptimal threshold values and also show variability in their application of those thresholds. we hypothesized that these biases are related and, more specifically, that foragers' widely known accuracy bias--over-staying--could be explained, at least in part, by their imprecision. to test this hypothesis, we analysed choices made by three rhesus macaques in a computerized pa ...202032156171
monitoring compound-related effects on coagulability in rats and cynomolgus and rhesus monkeys by thrombin generation kinetic measurement.thrombin generation assay (tga) is a sensitive method for the assessment of the global clotting potential of plasma. this kinetic assay can detect both hypocoagulable and hypercoagulable conditions: delayed or reduced thrombin generation leading to a prolonged clotting time, or induced thrombin activity, shifting the coagulation cascade toward thrombosis. the purpose of this study is to qualify the tga in nonhuman primates (nhp) and rats for its use during nonclinical in vivo and in vitro studie ...202032153221
inference of nonlinear receptive field subunits with spike-triggered clustering.responses of sensory neurons are often modeled using a weighted combination of rectified linear subunits. since these subunits often cannot be measured directly, a flexible method is needed to infer their properties from the responses of downstream neurons. we present a method for maximum likelihood estimation of subunits by soft-clustering spike-triggered stimuli, and demonstrate its effectiveness in visual neurons. for parasol retinal ganglion cells in macaque retina, estimated subunits partit ...202032149600
native chemical ligation via n-acylurea thioester surrogates obtained by fmoc solid-phase peptide synthesis.native chemical ligation (ncl) enables the direct chemical synthesis and semisynthesis of proteins of different sizes and compositions, streamlining the access to proteins containing posttranslational modifications (ptms). ncl assembles peptide fragments through the chemoselective reaction of a c-terminal α-thioester peptide, prepared either by chemical synthesis or via intein-splicing technology, and a recombinant or synthetic peptide containing an n-terminal cys. whereas the generation of c-te ...202032144666
the lateral prefrontal cortex of primates encodes stimulus colors and their behavioral relevance during a match-to-sample task.the lateral prefrontal cortex of primates (lpfc) plays a central role in complex cognitive behavior, in decision-making as well as in guiding top-down attention. however, how and where in lpfc such behaviorally relevant signals are computed is poorly understood. we analyzed neural recordings from chronic microelectrode arrays implanted in lpfc region 8av/45 of two rhesus macaques. the animals performed a feature match-to-sample task requiring them to match both motion and color information in a ...202032144331
the effects of extended time in the laboratory on selected aspects of reproduction in the female rhesus monkey (macaca mulatta).reproduction data from 60 wild-caught and 16 captive-born, hand-reared female rhesus monkeys (macaca mulatta) were examined. both groups had been maintained in a controlled laboratory environment, the wild-caught for a minimum of 10 years and the captive-born for a minimum of 5 years. all were bred to wild-caught males. animals of both sexes were individually caged unless being bred. data from 662 pregnancies indicated that, although seasonal breeding became attenuated in the laboratory, it did ...198432138461
effects of age, lactation, and repeated cycles on rhesus monkey copulatory intervals.young, sexually mature female rhesus monkeys copulate on more days prior to conception than do older females, and this prolonged discrete mating period is associated with an earlier rise in serum estradiol prior to the first ovulation of the breeding season. the influence of repeated ovulatory cycles and the presence of a suckling infant on the copulatory patterns were examined in two separate analyses. extending previous work, young, nulliparous females copulated on more days at the first ovula ...198432138457
specific substitutions in region v2 of gp120 env confer shiv neutralisation resistance.a tier 2 shiv-mk38 strain was obtained after two in vivo passages of tier 1 shiv-mk1. shiv-mk38#818, cloned from the mk38 strain, was neutralisation-resistant, like the parental mk38 strain, to shiv-infected monkey plasma (mp), hiv-1-infected human pooled plasma (hpp), and kd247 monoclonal antibody (mab) (anti-v3 gp120 env). we investigated the mechanisms underlying the resistance of #818, specifically the amino acid substitutions that confer resistance to mk1. we introduced amino acid substitut ...202032138199
the anatomy of the skin of the chinese tree shrew is very similar to that of human skin.the chinese tree shrew (tupaia belangeri chinensis) is a small mammal closely related to primates. it has a small body size, low maintenance cost, and a relatively short reproductive cycle, all of which has made it the ideal model for the study of a variety of human diseases. in this study, we compared the anatomy of the skin of the chinese tree shrew with that of the rhesus macaque, mouse and human, with the intention of providing the basic data required for the creation of skin disease models ...202032135581
animal models of congenital cytomegalovirus transmission: implications for vaccine development.although cytomegaloviruses (cmvs) are species-specific, the study of nonhuman cmvs in animal models can help to inform and direct research aimed at developing a human cmv (hcmv) vaccine. because the driving force behind the development of hcmv vaccines is to prevent congenital infection, the animal model in question must be one in which vertical transmission of virus occurs to the fetus. fortunately, two such animal models-the rhesus macaque cmv and guinea pig cmv-are characterized by congenital ...202032134481
postnatal development of the entorhinal cortex: a stereological study in macaque monkeys.the entorhinal cortex is the main gateway for interactions between the neocortex and the hippocampus. distinct regions, layers, and cells of the hippocampal formation exhibit different profiles of structural and molecular maturation during postnatal development. here, we provide estimates of neuron number, neuronal soma size, and volume of the different layers and subdivisions of the monkey entorhinal cortex (eo, er, elr, ei, elc, ec, ecl) during postnatal development. we found different develop ...202032134112
differential outcomes following optimization of simian-human immunodeficiency viruses from clades ae, b, and c.simian-human immunodeficiency virus (shiv) infection of rhesus monkeys is an important preclinical model for human immunodeficiency virus type 1 (hiv-1) vaccines, therapeutics, and cure strategies. shivs have been optimized by incorporating hiv-1 env residue 375 mutations that mimic the bulky or hydrophobic residues typically found in simian immunodeficiency virus (siv) env to improve rhesus cd4 binding. we applied this strategy to three shiv challenge stocks (shiv-sf162p3, shiv-ae16, and shiv-3 ...202032132241
establishment and evaluation of a monkey acute cerebral ischemia model.cerebral ischemia seriously threatens human health and is characterized by high rates of incidence, disability and death. developing an ideal animal model of cerebral ischemia that reflects the human clinical features is critical for pathological studies and clinical research. the goal of this study is to establish a local cerebral ischemia model in rhesus macaque, thereby providing an optimal animal model to study cerebral ischemia.202032130353
immunotherapy with dna vaccine and live attenuated rubella/siv gag vectors plus early art can prevent sivmac251 viral rebound in acutely infected rhesus macaques.anti-retroviral therapy (art) has been highly successful in controlling hiv replication, reducing viral burden, and preventing both progression to aids and viral transmission. yet, art alone cannot cure the infection. even after years of successful therapy, art withdrawal leads inevitably to viral rebound within a few weeks or months. our hypothesis: effective therapy must control both the replicating virus pool and the reactivatable latent viral reservoir. to do this, we have combined art and i ...202032130229
passive immunization with an extended half-life monoclonal antibody protects rhesus macaques against aerosolized ricin toxin.inhalation of ricin toxin (rt), a category b biothreat agent, provokes an acute respiratory distress syndrome marked by pro-inflammatory cytokine and chemokine production, neutrophilic exudate, and pulmonary edema. the severity of rt exposure is attributed to the tropism of the toxin's b subunit (rtb) for alveolar macrophages and airway epithelial cells, coupled with the extraordinarily potent ribosome-inactivating properties of the toxin's enzymatic subunit (rta). while there are currently no v ...202032128254
interspecies comparison of simultaneous thrombin and plasmin generation.animal models of hemostasis are often extrapolated to humans; however, only a few studies have compared coagulation and fibrinolysis across species. simultaneous thrombin (tg) and plasmin (pg) generation is useful to assessing coagulation and fibrinolysis within the same sample. in this study, we performed simultaneous tg and pg analysis in blood plasma samples from humans and 6 species commonly evaluated in pre-clinical research. tg and pg were investigated in male and female donor platelet-poo ...202032127577
selective intra-arterial brain cooling improves long-term outcomes in a non-human primate model of embolic stroke: efficacy depending on reperfusion status.nearly all stroke neuroprotection modalities, including selective intra-arterial cooling (si-ac), have failed to be translated from bench to bed side. potentially overlooked reasons may be biological gaps, inadequate attention to reperfusion states and mismatched attention to neurological benefits. to advance stroke translation, we describe a novel thrombus-based stroke model in adult rhesus macaques. intra-arterial thrombolysis with tissue plasminogen activator leads to three clinically relevan ...202032126876
skeletal morphology of the lesula (cercopithecus lomamiensis) and the evolution of guenon locomotor behavior.the guenons (tribe cercopithecini) are a diverse and primarily arboreal radiation of old world monkeys from africa. however, preliminary behavioral observations of the lesula (cercopithecus lomamiensis), a little-known guenon species described in 2012, report it spending substantial amounts of time on the ground. new specimens allow us to present the first description of lesula postcranial morphology and apply a comparative functional morphology approach to supplement our knowledge of its locomo ...202032124976
characterization of two neutralizing antibodies against rift valley fever virus gn protein.the rift valley fever virus (rvfv) is an arthropod-borne virus that can not only cause severe disease in domestic animals but also in humans. however, the licensed vaccines or available therapeutics for humans do not exist. here, we report two gn-specific neutralizing antibodies (nabs), isolated from a rhesus monkey immunized with recombinant human adenoviruses type 4 expressing rift valley fever virus gn and gc protein (rhadv4-gngcopt). the two nabs were both able to protect host cells from rvf ...202032120864
development of an effective alternative model for in vivo hypnozoite-induced relapse infection: a japanese macaque (macaca fuscata) model experimentally infected with plasmodium cynomolgi.in the present study, we demonstrate that the japanese macaque (macaca fuscata) can be used as an effective alternative in vivo model for investigating hypnozoite-induced relapsing infection caused by plasmodium cynomolgi b strain, and that this model is comparable to the rhesus macaque model. two female japanese macaques (jm-1 and jm-2; aged 5 years; weighing about 4.0 kg) were used for the experiment. to produce sporozoites in mosquitoes, blood infected with p. cynomolgi b strain was collected ...202032114084
potential effects of antibiotic-induced gut microbiome alteration on blood-brain barrier permeability compromise in rhesus monkeys.the blood-brain barrier (bbb) contributes to the maintenance of brain homeostasis. gut microbiome composition affects bbb development and expression of tight junction proteins in rodents. however, we still do not know if there is any direct effect of gut microbial composition on bbb permeability and function in normal adult animals. in the current study, we determined temporal and spatial changes in bbb permeability of rhesus monkeys receiving amoxicillin-clavulanic acid (ac) by monitoring the c ...202032112442
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
anti-pd-1 treatment disrupts the painkilling effects of morphine.pd-1 depletion or nivolumab treatment dampened morphine antinociception in mice and rhesus macaques.202032111598
male migration and inbreeding avoidance in wild rhesus monkeys.genetic, demographic, and behavioral evidence from a population of wild rhesus monkeys (macaca mulatta) were analyzed to test the widely held assumption that social subdivision of mammalian populations, as seen in the rhesus monkey, results in inbreeding. this assumption has been important in attempts to explain rapid rates of evolution among mammals. demographic records were kept over a period of 42 months on a study population comprising 292 animals, subdivided into seven social groups. blood ...198432111112
segregation distortion and differential fitness at the albumin locus in rhesus monkeys (macaca mulatta).the observed patterns of segregation of two co-dominant alleles at the macaque albumin locus in 400 rhesus monkey offspring were compared with those expected for five segregating mating phenotypes. rates of reproductive loss and conception were also compared among females of each albumin phenotype. the common albumin allele in macaques, alamac , segregated more frequently than expected when the mother was heterozygous but less frequently than expected when she was homozygous for albmac . in both ...198432111109
preface: franz-josef kaup and the development of the pathology unit at the german primate center.this special issue about selected diseases of nonhuman primates was created in honor of franz-josef kaup, who worked as a primate pathologist at the german primate center (dpz) for 25 years. in 1992, franz-josef kaup started his career at the dpz as head of the working group experimental pathology. prior to that he worked as a research assistant in the division electron microscopy at the institute of pathology of the university of veterinary medicine in hanover. he was very experienced in the fi ...201732110708
limited susceptibility of rhesus macaques to a cowpox virus isolated from a lethal outbreak among new world monkeys.this study was undertaken to investigate the susceptibility of rhesus monkeys to the calpox virus, an orthopoxvirus (opxv) of the cowpox virus species (cpxv), which is uniformly lethal in common marmosets. six rhesus monkeys were either intravenously (i.v.) or intranasally (i.n.) exposed to the virus. monitoring of the macaques after viral exposure included physical examinations, the determination of viral load by real-time pcr and plaque assay, and the analysis of humoral responses. two i.v. in ...201732110704
spontaneous endometriosis in rhesus macaques: evidence for a genetic association with specific mamu-a1 alleles.endometriosis is a poorly understood common debilitating women's reproductive disorder resulting from proliferative and ectopic endometrial tissue associated with variable clinical symptoms including dysmenorrhea (painful menstrual periods), dyspareunia (pain on intercourse), female infertility, and an increased risk of malignant transformation. the rhesus macaque (macaca mulatta) develops a spontaneous endometriosis that is very similar to that seen in women. we hypothesized that specific major ...201732110699
revisiting a quarter of a century of simian immunodeficiency virus (siv)-associated cardiovascular diseases at the german primate center.human immunodeficiency virus (hiv) comorbidities have become clinically more important due to antiretroviral therapy. although therapy increases life expectancy, it does not completely suppress immune activation and its associated complications. the simian immunodeficiency virus (siv)-infected rhesus macaque (macaca mulatta) represents a valuable model for the investigation of siv-associated diseases. although cardiovascular (cv) changes are common in hiv-infected patients, there are only a few ...201732110698
morphological and immunohistochemical characterization of spontaneous endometriosis in rhesus macaques (macaca mulatta).several cases of spontaneous endometriosis in middle-aged to old rhesus macaques (macaca mulatta) from the breeding colony of the german primate center were thoroughly characterized with regards to anatomical distribution and macroscopic appearance, histological differentiation and immunohistochemical profile including somatic markers, hormonal receptors, and proliferation indices. more than half of the examined animals (five of nine) were directly related to one breeding male, supporting a stro ...201732110695
unique case of granulomatous arteritis in a grey mouse lemur (microcebus murinus) - first case description.overall, diseases of the vascular system are rarely observed entities among nonhuman primates that are commonly associated with systemic infections, septicemia or bacteremia. rhesus monkeys infected with simian immunodeficiency virus (siv) may develop a chronic occlusive arteriopathy of unknown etiology in late stages of the disease. this siv associated arteriopathy is the only well-known specific vascular entity described in nonhuman primates. we herein report a unique case of granulomatous art ...201732110694
suspect guillain-barré syndrome in a male rhesus macaque (macaca mulatta).guillain-barré syndrome (gbs) is a rare, mainly acute inflammatory polyneuropathy in humans. it is frequently post-infectious with auto antibodies being formed against myelin sheaths, resulting in a progressive and more-or-less severe paralysis of the motor neuron and cranial nerves. mortality is low and 60 % of the patients recover completely from the disease after intensive treatment. in animals, there are a few diseases that closely resemble gbs, but cases of gbs in monkeys seem to be scarce. ...201732110689
mapping the epitopes of schistosoma japonicum esophageal gland proteins for incorporation into vaccine constructs.the development of a schistosome vaccine has proved challenging but we have suggested that characterisation of the self-cure mechanism in rhesus macaques might provide a route to an effective product. the schistosome esophagus is a complex structure where blood processing is initiated by secretions from anterior and posterior glands, achieved by a mixture of ~40 unique proteins. the mechanism of self-cure in macaques involves cessation of feeding, after which worms slowly starve to death. antibo ...202032107503
circulating steroids and the relationship between ovarian and placental secretion during early and mid pregnancy in the baboon.ovarian and placental steroid secretion was examined at intervals during early and mid-pregnancy in the olive baboon, papio anubis. progesterone, androstenedione, testosterone, estrone, and estradiol-17β were measured after celite chromatography in samples from peripheral circulation and from utero-ovarian veins draining ovaries with and without corpora lutea at the following stages of pregnancy: days 8-9 (unconfirmed pregnant), 10-19, 34-40, 60-66, and 104-106 after ovulation. the pattern of ho ...198432106637
population growth of free-ranging rhesus monkeys at tughlaqabad.a population of rhesus monkeys (macaca mulatta) at the ancient site of tughlaqabad on the southern outskirts of new delhi, india, showed moderate growth throughout the 1960s and 1970s and very rapid growth in the last 4 years. between july 1980 and july 1983, the population increased 79%, from two groups of 160 monkeys to five groups of 286 monkeys, an average annual increase of 21.4%. the natality of the population has been high, averaging 82.4% over three birth seasons. mortality and disappear ...198432106633
chloroquine and rapamycin augment interleukin-37 expression via the lc3, erk, and ap-1 axis in the presence of lipopolysaccharides.il-37 is a cytokine that plays critical protective roles in many metabolic inflammatory diseases, and its therapeutic potential has been confirmed by exogenous il-37 administration. however, its regulatory mechanisms remain unclear. u937 cells were treated with autophagy-modifying reagents (3-ma, chloroquine, and rapamycin) with or without lps stimulation. thereafter, il-37 expression and autophagic markers (beclin1, p62/sqstm1, and lc3) were determined. for regulatory signal pathways, phosphory ...202032104716
complete protection in macaques conferred by purified inactivated zika vaccine: defining a correlate of protection.a critical global health need exists for a zika vaccine capable of mitigating the effects of future zika epidemics. in this study we evaluated the antibody responses and efficacy of an aluminum hydroxide adjuvanted purified inactivated zika vaccine (pizv) against challenge with zika virus (zikv) strain prvabc59. indian rhesus macaques received two doses of pizv at varying concentrations ranging from 0.016 µg - 10 µg and were subsequently challenged with zikv six weeks or one year following the s ...202032103097
climate and seasonal reproduction in the cayo santiago macaques.this paper reports the results of an eight-year study of seasonal reproduction in the free-ranging colony of rhesus monkeys on cayo santiago, puerto rico. there was a significant correlation between the start of the annual spring rainy season and the estimated median conception date (r = .94, p < .001) and median birth date (r = .94, p < .001). conceptions followed the commencement of spring rains by 70 days. significant and negative correlations were found between the number of days from the st ...198532102495
the formal hierarchy of rhesus macaques: an investigation of the bared-teeth display.teeth-baring in a large captive rhesus monkey group (macaca mulatta) was observed over a 30-month period. its directional consistency among adults was significantly higher than that of aggression. the unidirectionality was so extreme that the facial display must be seen as a formal status indicator; ie, a signal of which the direction is independent of short-term contextual variation. as such, it seems adapted for communication about the state of the relationship. formal dominance relationships ...198532102494
effects of opioid/cannabinoid mixtures on impulsivity and memory in rhesus monkeys.the opioid epidemic underscores the need for safer and more effective treatments for pain. combining opioid receptor agonists with drugs that relieve pain through nonopioid mechanisms could be a useful strategy for reducing the dose of opioid needed to treat pain, thereby reducing risks associated with opioids alone. opioid/cannabinoid mixtures might be useful in this context; individually, opioids and cannabinoids have modest effects on cognition, and it is important to determine whether those ...202032101988
a neural network for online spike classification that improves decoding accuracy.separating neural signals from noise can improve brain-computer interface performance and stability. however, most algorithms for separating neural action potentials from noise are not suitable for use in real time and have shown mixed effects on decoding performance. with the goal of removing noise that impedes online decoding, we sought to automate the intuition of human spike-sorters to operate in real time with an easily tunable parameter governing the stringency with which spike waveforms a ...202032101491
discovery of [11c]mk-6884: a positron emission tomography (pet) imaging agent for the study of m4muscarinic receptor positive allosteric modulators (pams) in neurodegenerative diseases.the measurement of receptor occupancy (ro) using positron emission tomography (pet) has been instrumental in guiding discovery and development of cns directed therapeutics. we and others have investigated muscarinic acetylcholine receptor 4 (m4) positive allosteric modulators (pams) for the treatment of symptoms associated with neuropsychiatric disorders. in this article, we describe the synthesis, in vitro, and in vivo characterization of a series of central pyridine-related m4 pams that can be ...202032101422
mineralized trichobezoars in a rhesus macaque (macaca mulatta).a five-year-old female rhesus macaque (macaca mulatta) presented with a thin body condition and multiple palpable mid-abdominal masses. mineralized cecal trichobezoars were removed surgically. thirteen months later, similar masses recurred and were confirmed with radiographs. this is the first case report of a mineralized cecal trichobezoar in a rhesus macaque.202032100304
neural correlates of strategy switching in the macaque orbital prefrontal cortex.we can adapt flexibly to environment changes and search for the most appropriate rule to a context. the orbital prefrontal cortex (pfo) has been associated with decision making, rule generation and maintenance, and more generally has been considered important for behavioral flexibility. to better understand the neural mechanisms underlying the flexible behavior, we studied the ability to generate a switching signal in monkey pfo when a strategy is changed. in the strategy task, we used a visual ...202032098903
identification of hiv-1 envelope mutations that enhance entry using macaque cd4 and ccr5.although rhesus macaques are an important animal model for hiv-1 vaccine development research, most transmitted hiv-1 strains replicate poorly in macaque cells. a major genetic determinant of this species-specific restriction is a non-synonymous mutation in macaque cd4 that results in reduced hiv-1 envelope (env)-mediated viral entry compared to human cd4. recent research efforts employing either laboratory evolution or structure-guided design strategies have uncovered several mutations in env's ...202032098152
spontaneous krt5 gene mutation in rhesus macaques (macaca mulatta): a novel nonhuman primate model of epidermolysis bullosa simplex.epidermolysis bullosa simplex (ebs) is an inherited skin disorder characterized by increased skin and mucous membrane fragility. most cases are caused by mutations in keratin 5 (krt5) and keratin 14 (krt14). mutations of these genes result in cytoskeletal disruption of the basal keratinocytes. gross and histopathologic findings of 2 clinically affected homozygous rhesus macaques with an insertion variant mutation in krt5 are described and compared with 6 deceased phenotypically normal animals th ...202032096448
myocardial changes in diabetic and nondiabetic nonhuman primates.diabetic human patients have increased risk of heart failure compared to healthy subjects. the underlying mechanisms for this are not fully understood, and to help develop improved treatment strategies, well-characterized animal models are essential. to investigate cardiac dysfunction in diabetes, this study evaluated myocardial changes in 10 aging rhesus monkeys with and without diabetes. based on evaluation of plasma glycosylated hemoglobin and glucose, 7 of 10 rhesus macaques had diabetes for ...202032096447
correction: antibiotic-induced microbiome perturbations are associated with significant alterations to colonic mucosal immunity in rhesus macaques.an amendment to this paper has been published and can be accessed via a link at the top of the paper.202032094503
pharmacological characterization of the novel and selective α7 nicotinic acetylcholine receptor-positive allosteric modulator bnc375.treatments for cognitive deficits associated with central nervous system (cns) disorders such as alzheimer disease and schizophrenia remain significant unmet medical needs that incur substantial pressure on the health care system. the α7 nicotinic acetylcholine receptor (nachr) has garnered substantial attention as a target for cognitive deficits based on receptor localization, robust preclinical effects, genetics implicating its involvement in cognitive disorders, and encouraging, albeit mixed, ...202032094294
variations in the expression of terminal oligosaccharide units and glycosylation of poly(n-acetyllactosamine) chain in the helicobacter pylori lipopolysaccharide upon colonization of rhesus macaques.helicobacter pylori is an important human pathogen that causes gastritis, gastric and duodenal ulcers, and gastric cancer. o-polysaccharides of h. pylori lipopolysaccharide (lps) are composed of (β1→3)-poly(n-acetyllactosamine) (polylacnac) decorated with multiple α-l-fucose residues. in many strains, their terminal lacnac units are mono- or di-fucosylated to mimic lewis x (lex) and/or lewis y (ley) oligosaccharides. the studies in rhesus macaques as a model of human infection by h. pylori showe ...202032093599
a nonintrusive method for determining relative body fat in free-ranging monkeys.a procedure is described for designing simple obesity rating scales for use with free-ranging rhesus monkeys (macaca mulatta). ratings are based on observers' judgments of degree of overall obesity of individual monkeys. the procedure was tested separately on samples of males and females over 2 successive years. within each of these four samples, observers' judgments were both highly reliable and highly correlated with actual measures of body weight and with estimates of body fat based on morpho ...198832093435
differentiall behavioral and adrenocortical responses to stress among three macaque species.behavioral and adrenocortical responses of rhesus (macaca mulatta), bonnet (m. radiata), and crabeating (m. fascicularis) macaques were compared in their home cages, during exposure to novelty and during physical restraint. both behavioral and adrenocortical responses differentiated species in each condition. in all conditions, post-test corticosteroid levels were highest for crabeaters and lowest for rhesus. rhesus were the most active behaviorally, and bonnets were the most passive, while crab ...198832093434
enzootic hepatitis a infection in cynomolgus monkeys (macaca fascicularis).during a toxicology study in cynomolgus (long-tailed or crab-eating) monkeys (macaca fascicularis), a randomly distributed incidence of significantly increased hepatic enzyme activity was observed. premedication hepatic enzyme activity in all monkeys of this study was normal, but increased alanine aminotransferase (alt) activity was found in 4 of the 24 animals 2 weeks after initiation of the study and in 10 of 24 at 4 weeks. a drug-related effect was considered unlikely initially because the in ...198832093430
selectivity to approaching motion in retinal inputs to the dorsal visual pathway.to efficiently navigate through the environment and avoid potential threats, an animal must quickly detect the motion of approaching objects. current models of primate vision place the origins of this complex computation in the visual cortex. here, we report that detection of approaching motion begins in the retina. several ganglion cell types, the retinal output neurons, show selectivity to approaching motion. synaptic current recordings from these cells further reveal that this preference for ...202032091390
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