| intermittent convection-enhanced delivery of gdnf into rhesus monkey putamen: absence of local or cerebellar toxicity. | glial cell line-derived neurotrophic factor (gdnf) has demonstrated neurorestorative and neuroprotective effects in rodent and nonhuman primate models of parkinson's disease. however, continuous intraputamenal infusion of gdnf (100 µg/day) resulted in multifocal cerebellar purkinje cell loss in a 6-month toxicity study in rhesus monkeys. it was hypothesized that continuous leakage of gdnf into the cerebrospinal fluid compartment during the infusions led to down-regulation of gdnf receptors on pu ... | 2018 | 29785638 |
| progressive assessment of ischemic injury to white matter using diffusion tensor imaging: a preliminary study of a macaque model of stroke. | previous diffusion tensor imaging (dti) studies have demonstrated the temporal evolution of stroke injury in grey matter and white matter can be characterized by dti indices. however, it still remains not fully understood how the dti indices of white matter are altered progressively during the hyperacute (first 6 hours) and acute stage of stroke (≤ 1 week). in the present study, dti was employed to characterize the temporal evolution of infarction and white matter injury after stroke insult usin ... | 2018 | 29785226 |
| hiv vaccine candidate activation of hypoxia and the inflammasome in cd14+ monocytes is associated with a decreased risk of sivmac251 acquisition. | qualitative differences in the innate and adaptive responses elicited by different hiv vaccine candidates have not been thoroughly investigated. we tested the ability of the aventis pasteur live recombinant canarypox vector (alvac)-siv, dna-siv and ad26-siv vaccine prime modalities together with two alvac-siv + gp120 protein boosts to reduce the risk of sivmac251 acquisition in rhesus macaques. we found that the dna and alvac prime regimens were effective, but the ad26 prime was not. the activat ... | 2018 | 29785023 |
| genetic screening and multipotency in rhesus monkey haploid neural progenitor cells. | haploid embryonic stem cells (haescs) have been extensively applied in forward and reverse genetic screening. however, a mammalian haploid somatic cell line is difficult to achieve because of spontaneous diploidization in differentiation. as a non-human primate species, monkeys are widely used in basic and pre-clinical research in which haploid cells are restricted to escs. here, we report that rhesus monkey haescs in an optimized culture medium show naïve-state pluripotency and stable haploidy. ... | 2018 | 29784672 |
| the immune response of rhesus macaques to novel vaccines comprising hepatitis b virus s, pres1, and core antigens. | therapeutic vaccines represent a unique approach to hepatitis b virus (hbv) treatment and have the potential to induce long-term control of infection. this study explored the immune responses of rhesus macaques to novel vaccines comprising the s, pres1, and core antigens of the hbv that showed promise as prophylactic and therapeutic approaches in a mouse model. the tested vaccines included two dna vaccines (pvrc-ss1, pvrc-cs1), an hbv particle subunit (hbss1) vaccine and the recombinant vaccinia ... | 2018 | 29778513 |
| a novel approach to probabilistic characterisation of neural firing patterns. | the advances in extracellular neural recording techniques result in big data volumes that necessitate fast, reliable, and automatic identification of statistically similar units. this study proposes a single framework yielding a compact set of probabilistic descriptors that characterise the firing patterns of a single unit. | 2018 | 29777726 |
| tacrolimus-induced asymptomatic thrombotic microangiopathy diagnosed by laboratory tests in pig-to-rhesus corneal xenotransplantation: a case report. | tacrolimus-associated thrombotic microangiopathy (ta-tma) is a rare complication. ta-tma is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage due to thrombus. we report asymptomatic ta-tma diagnosed by laboratory tests in pig-to-rhesus corneal xenotransplantation. corneal transplantation had been conducted from a wild-type snu miniature pig to a rhesus macaque. the veterinary records were retrospectively reviewed in this case. the immunosuppressive regimen co ... | 2018 | 29777547 |
| hydrocephalus after intrathecal administration of dextran to rhesus macaques (macaca mulatta). | dextrans have been used extensively as medical therapies and labeling agents in biomedical research to investigate the blood-brain barrier and csf flow and absorption. adverse effects from dextrans include anaphylactic reaction and dilation of the cerebral ventricles due to administration into the subarachnoid space. this retrospective study describes 51 rhesus macaques (macaca mulatta) that received dextran intrathecally. the purpose of intrathecal administration was to enable detection of long ... | 2018 | 29776458 |
| gp120 v5 is targeted by the first wave of sequential neutralizing antibodies in shivsf162p3n-infected rhesus macaques. | simian-human immunodeficiency virus (shiv) infection provides a relevant animal model to study hiv-1 neutralization breadth. with previously identified shivsf162p3n infected rhesus macaques that did or did not develop neutralization breadth, we characterized the transmitted/founder viruses and initial autologous/homologous neutralizing antibodies in these animals. the plasma viral load and blood cd4 count did not distinguish macaques with and without breadth, and only one tested homologous envel ... | 2018 | 29772652 |
| the kinematic recovery process of rhesus monkeys after spinal cord injury. | after incomplete spinal cord injury (sci), neural circuits may be plastically reconstructed to some degree, resulting in extensive functional locomotor recovery. the present study aimed to observe the post-sci locomotor recovery of rhesus monkey hindlimbs and compare the recovery degrees of different hindlimb parts, thus revealing the recovery process of locomotor function. four rhesus monkeys were chosen for thoracic hemisection injury. the hindlimb locomotor performance of these animals was re ... | 2018 | 29769463 |
| frontal eye field inactivation reduces saccade preparation in the superior colliculus but does not alter how preparatory activity relates to saccades of a given latency. | a neural correlate for saccadic reaction times (srts) in the gap saccade task is the level of low-frequency activity in the intermediate layers of the superior colliculus (isc) just before visual target onset: greater levels of such preparatory isc low-frequency activity precede shorter srts. the frontal eye fields (fefs) are one likely source of isc preparatory activity, since fef preparatory activity is also inversely related to srt. to better understand the fef's role in saccade preparation, ... | 2019 | 29766038 |
| effect of chronic social stress on prenatal transfer of antitetanus immunity in captive breeding rhesus macaques (macaca mulatta). | because tetanus can cause significant morbidity and mortality in nhp, colonywide vaccination with tetanus toxoid is recommended for outdoor breeding colonies of rhesus macaques, with primary immunizations commonly given to infants at 6 mo of age followed by booster vaccines every 10 y. maternal antibodies are thought to offer protective immunity to infants younger than 6 mo. however, historical colony data from the yerkes national primate research center show a higher incidence of tetanus among ... | 2018 | 29764539 |
| development of positron emission tomography radiotracers for the gaba transporter 1. | in vivo positron emission tomography (pet) imaging of the γ-aminobutyric acid (gaba) receptor complex has been accomplished using radiolabeled benzodiazepine derivatives, but development of specific presynaptic radioligands targeting the neuronal membrane gaba transporter type 1 (gat-1) has been less successful. the availability of new structure-activity studies of gat-1 inhibitors and the introduction of a gat-1 inhibitor (tiagabine, gabatril) into clinical use prompted us to reinvestigate the ... | 2018 | 29763549 |
| anti-hiv igm protects against mucosal shiv transmission. | worldwide, most new hiv infections occur through mucosal exposure. immunoglobulin m (igm) is the first antibody class generated in response to infectious agents; igm is present in the systemic circulation and in mucosal fluids as secretory igm. we sought to investigate for the first time the role of igm in preventing aids virus acquisition in vivo. | 2018 | 29762161 |
| establishing a surgical procedure for rhesus epiretinal scaffold implantation with hipsc-derived retinal progenitors. | to develop an effective surgical procedure for cellular scaffold epiretinal implantation in rhesus, facilitating subsequent epiretinal stem cell transplantation. | 2018 | 29760741 |
| epigenetic promoter dna methylation of mir-124 promotes hiv-1 tat-mediated microglial activation via mecp2-stat3 axis. | the present study demonstrates hiv-1 tat-mediated epigenetic downregulation of microglial mir-124 and its association with microglial activation. exposure of mouse primary microglia isolated from newborn pups of either sex to hiv-1 tat resulted in decreased expression of primary mir-124-1, primary mir-124-2 as well as the mature mir-124. in parallel, hiv-1 tat exposure to mouse primary microglial cells resulted in increased expression of dna methylation enzymes, such as dnmt1, dnmt3a, and dnmt3b ... | 2018 | 29760177 |
| measuring peripheral oxytocin and vasopressin in nonhuman primates. | studying the neural and hormonal changes that modulate behavior is critical to understanding social relationships. of particular interest is measuring oxytocin (ot) and arginine vasopressin (avp) peripherally, and preferably, non-invasively, in nonhuman primates. due to these peptides' neural origin and their stimulation of brain areas that influence social behavior, there has been debate whether peripheral measures in blood, urine, and saliva reflect central levels in the brain. this review elu ... | 2018 | 29756649 |
| temporal/compartmental changes in viral rna and neuronal injury in a primate model of neuroaids. | despite the advent of highly active anti-retroviral therapy hiv-associated neurocognitive disorders (hand) continue to be a significant problem. furthermore, the precise pathogenesis of this neurodegeneration is still unclear. the objective of this study was to examine the relationship between infection by the simian immunodeficiency virus (siv) and neuronal injury in the rhesus macaque using in vivo and postmortem sampling techniques. the effect of siv infection in 23 adult rhesus macaques was ... | 2018 | 29750804 |
| whole brain comparative anatomy using connectivity blueprints. | comparing the brains of related species faces the challenges of establishing homologies whilst accommodating evolutionary specializations. here we propose a general framework for understanding similarities and differences between the brains of primates. the approach uses white matter blueprints of the whole cortex based on a set of white matter tracts that can be anatomically matched across species. the blueprints provide a common reference space that allows us to navigate between brains of diff ... | 2018 | 29749930 |
| novel strategy to adapt simian-human immunodeficiency virus e1 carrying env from an rv144 volunteer to rhesus macaques: coreceptor switch and final recovery of a pathogenic virus with exclusive r5 tropism. | the phase iii rv144 human immunodeficiency virus (hiv) vaccine trial conducted in thailand remains the only study to show efficacy in decreasing the hiv acquisition risk. in thailand, circulating recombinant forms of hiv clade a/e (crf01_ae) predominate; in such viruses, env originates from clade e (hiv-e). we constructed a simian-human immunodeficiency virus (shiv) chimera carrying env isolated from an rv144 placebo recipient in the shiv-1157ipd3n4 backbone. the latter contains long terminal re ... | 2018 | 29743361 |
| the antiviral activity of the cellular glycoprotein lgals3bp/90k is species specific. | cellular antiviral proteins interfere with distinct steps of replication cycles of viruses. the galectin 3 binding protein (lgals3bp, also known as 90k) was previously shown to lower the infectivity of nascent human immunodeficiency virus type 1 (hiv-1) virions when expressed in virus-producing cells. this antiviral effect was accompanied by impaired gp160env processing and reduced viral incorporation of mature env glycoproteins. here, we examined the ability of 90k orthologs from primate specie ... | 2018 | 29743357 |
| gene expression profiling of the scn in young and old rhesus macaques. | in mammals, the suprachiasmatic nucleus (scn) is the location of a master circadian pacemaker. it receives photic signals from the environment via the retinal hypothalamic tract, which play a key role in synchronizing the body's endogenously generated circadian rhythms with the 24-h rhythm of the environment. therefore, it is plausible that age-related changes within the scn contribute to the etiology of perturbed activity-rest cycles that become prevalent in humans during aging. to test this hy ... | 2018 | 29743294 |
| recently identified mutations in the ebola virus-makona genome do not alter pathogenicity in animal models. | ebola virus (ebov), isolate makona, the causative agent of the west african ebov epidemic, has been the subject of numerous investigations to determine the genetic diversity and its potential implication for virus biology, pathogenicity, and transmissibility. despite various mutations that have emerged over time through multiple human-to-human transmission chains, their biological relevance remains questionable. recently, mutations in the glycoprotein gp and polymerase l, which emerged and stabi ... | 2018 | 29742435 |
| cortical thinning and structural bone changes in non-human primates after single-fraction whole-chest irradiation. | stereotactic body radiation therapy (sbrt) is associated with an increased risk of vertebral compression fracture. while bone is typically considered radiation resistant, fractures frequently occur within the first year of sbrt. the goal of this work was to determine if rapid deterioration of bone occurs in vertebrae after irradiation. sixteen male rhesus macaque non-human primates (nhps) were analyzed after whole-chest irradiation to a midplane dose of 10 gy. ages at the time of exposure varied ... | 2018 | 29738279 |
| neuronal connections of direct and indirect pathways for stable value memory in caudal basal ganglia. | direct and indirect pathways in the basal ganglia work together for controlling behavior. however, it is still a controversial topic whether these pathways are segregated or merged with each other. to address this issue, we studied the connections of these two pathways in the caudal parts of the basal ganglia of rhesus monkeys using anatomical tracers. our previous studies showed that the caudal basal ganglia control saccades by conveying long-term values (stable values) of many visual objects t ... | 2019 | 29737578 |
| effects of aav2-mediated co-transfection of ctgf and timp1 genes on degenerative lumbar intervertebral discs in rhesus monkeys in vivo. | this study aims to investigate the effects of co-transfection of the genes for connective tissue growth factor (ctgf) and tissue inhibitor of metalloproteinase-1 (timp1) mediated by adeno-associated virus 2 (aav2) on degenerative lumbar intervertebral discs in a primate model. | 2018 | 29736202 |
| progressive lentivirus infection induces natural killer cell receptor-expressing b cells in the gastrointestinal tract. | recently, a seemingly novel innate immune cell subset bearing features of natural killer and b cells was identified in mice. so-called nkb cells appear as first responders to infections, but whether this cell population is truly novel or is in fact a subpopulation of b cells and exists in higher primates remains unclear. the objective of this study was to identify nkb cells in primates and study the impact of hiv/siv infections. | 2018 | 29734222 |
| compressive mechanical characterization of non-human primate spinal cord white matter. | the goal of developing computational models of spinal cord injury (sci) is to better understand the human injury condition. however, finite element models of human sci have used rodent spinal cord tissue properties due to a lack of experimental data. central nervous system tissues in non human primates (nhp) closely resemble that of humans and therefore, it is expected that material constitutive models obtained from nhps will increase the fidelity and the accuracy of human sci models. human sci ... | 2018 | 29729417 |
| effects of systemic cholinergic antagonism on reinforcer devaluation in macaques. | the capacity to adjust actions based on new information is a vital cognitive function. an animal's ability to adapt behavioral responses according to changes in reward value can be measured using a reinforcer devaluation task, wherein the desirability of a given object is reduced by decreasing the value of the associated food reinforcement. elements of the neural circuits serving this ability have been studied in both rodents and nonhuman primates. specifically, the basolateral amygdala, orbitof ... | 2018 | 29729357 |
| computed tomography is a feasible method for quantifying bone density in macaca mulatta. | osteopathologies are a result of advanced age and decreased bone density and represent a global health problem. it is therefore important to generate models for longitudinal studies of the pathophysiology in order to improve early diagnosis and develop preventive therapies. for this kind of research, the use of computed tomography (ct) to evaluate bone health offers advantages over other techniques since it provides more complete information. the aim of this prospective, pilot study was to obtai ... | 2018 | 29729053 |
| rapid turnover and high production rate of myeloid cells in adult rhesus macaques with compensations during aging. | neutrophils, basophils, and monocytes are continuously produced in bone marrow via myelopoiesis, circulate in blood, and are eventually removed from circulation to maintain homeostasis. to quantitate the kinetics of myeloid cell movement during homeostasis, we applied 5-bromo-2'-deoxyuridine pulse labeling in healthy rhesus macaques (macaca mulatta) followed by hematology and flow cytometry analyses. results were applied to a mathematical model, and the blood circulating half-life and daily prod ... | 2018 | 29728510 |
| determination of single embryo sex in macaca mulatta and mus musculus rna-seq transcriptome profiles. | to account for sex as a biological variable, it is sometimes necessary to identify the sex of an embryo or embryonic cell that was used to generate libraries for rna sequencing, without the sex being known a priori. the preferred approach for this would take advantage of the mrna data, rather than relying on other methods that require separation and analysis of genomic dna or diversion of limiting rna for other assays. we describe here a method that has been optimized for this purpose in samples ... | 2018 | 29727590 |
| top-down beta oscillatory signaling conveys behavioral context in early visual cortex. | top-down modulation of sensory processing is a critical neural mechanism subserving numerous important cognitive roles, one of which may be to inform lower-order sensory systems of the current 'task at hand' by conveying behavioral context to these systems. accumulating evidence indicates that top-down cortical influences are carried by directed interareal synchronization of oscillatory neuronal populations, with recent results pointing to beta-frequency oscillations as particularly important fo ... | 2018 | 29725028 |
| attenuated phenotype and immunogenic characteristics of a mutated herpes simplex virus 1 strain in the rhesus macaque. | herpes simplex virus type 1(hsv-1) presents a conundrum to public health worldwide because of its specific pathogenicity and clinical features. some experimental vaccines, such as the recombinant viral glycoproteins, exhibit the viral immunogenicity of a host-specific immune response, but none of these has achieved a valid epidemiological protective efficacy in the human population. in the present study, we constructed an attenuated hsv-1 strain m3 through the partial deletion of ul7, ul41, and ... | 2018 | 29724057 |
| intermittent pair-housing, pair relationship qualities, and hpa activity in adult female rhesus macaques. | laboratory rhesus macaques are often housed in pairs and may be temporarily or permanently separated for research, health, or management reasons. while both long-term social separations and introductions can stimulate a stress response that impacts inflammation and immune function, the effects of short-term overnight separations and whether qualities of the pair relationship mediate these effects are unknown. in this study, we investigated the effects of overnight separations on the urinary cort ... | 2018 | 29722048 |
| evidence that sedative effects of benzodiazepines involve unexpected gabaa receptor subtypes: quantitative observation studies in rhesus monkeys. | in nonhuman primates we tested a new set of behavioral categories for observable sedative effects using pediatric anesthesiology classifications as a basis. using quantitative behavioral observation techniques in rhesus monkeys, we examined the effects of alprazolam and diazepam (nonselective benzodiazepines), zolpidem (preferential binding to α1 subunit-containing gabaa receptors), hz-166 (8-ethynyl-6-(2'-pyridine)-4h-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester; functionally se ... | 2018 | 29720564 |
| short-term pegylated interferon α2a treatment does not significantly reduce the viral reservoir of simian immunodeficiency virus-infected, antiretroviral therapy-treated rhesus macaques. | the major obstacle to human immunodeficiency type 1 (hiv-1) eradication is a reservoir of latently infected cells that persists despite long-term antiretroviral therapy (art) and causes rapid viral rebound if treatment is interrupted. type i interferons are immunomodulatory cytokines that induce antiviral factors and have been evaluated for the treatment of hiv-infected individuals, resulting in moderate reduction of viremia and inconclusive data about their effect on reservoir size. here, we as ... | 2018 | 29720521 |
| arginine vasopressin in cerebrospinal fluid is a marker of sociality in nonhuman primates. | autism spectrum disorder (asd) is a neurodevelopmental condition characterized by core social impairments. asd remains poorly understood because of the difficulty in studying disease biology directly in patients and the reliance on mouse models that lack clinically relevant, complex social cognition abilities. we use ethological observations in rhesus macaques to identify male monkeys with naturally occurring low sociality. these monkeys showed differences in specific neuropeptide and kinase sig ... | 2018 | 29720452 |
| tlr7 agonists induce transient viremia and reduce the viral reservoir in siv-infected rhesus macaques on antiretroviral therapy. | antiretroviral therapy (art) can halt hiv-1 replication but fails to target the long-lived latent viral reservoir. several pharmacological compounds have been evaluated for their ability to reverse hiv-1 latency, but none has demonstrably reduced the latent hiv-1 reservoir or affected viral rebound after the interruption of art. we evaluated orally administered selective toll-like receptor 7 (tlr7) agonists gs-986 and gs-9620 for their ability to induce transient viremia in rhesus macaques infec ... | 2018 | 29720451 |
| encoding of serial order in working memory: neuronal activity in motor, premotor, and prefrontal cortex during a memory scanning task. | we have adapted sternberg's context-recall task to investigate the neural mechanisms of encoding serial order information in working memory, in 2 male rhesus monkeys. we recorded from primary motor, premotor, and dorsolateral prefrontal cortex while the monkeys performed the task. in each cortical area, most neurons displayed marked modulation of activity during the list presentation period of the task, whereas the serial order of the stimuli needed to be encoded in working memory. the activity ... | 2018 | 29712786 |
| intermittent stimulation in the nucleus basalis of meynert improves sustained attention in rhesus monkeys. | sustained attention is essential in important behaviors in daily life. many neuropsychiatric disorders are characterized by a compromised ability to sustain attention, making this cognitive domain an important therapeutic target. in this study, we tested a novel method of improving sustained attention. monkeys were engaged in a continuous performance task (cpt) while the nucleus basalis of meynert (nb), the main source of cholinergic innervation of the neocortex, was stimulated. intermittent nb ... | 2018 | 29704983 |
| a lipid/dna adjuvant-inactivated influenza virus vaccine protects rhesus macaques from uncontrolled virus replication after heterosubtypic influenza a virus challenge. | influenza a virus (iav) vaccines offer little protection from mismatched viruses with antigenically distant hemagglutinin (ha) glycoproteins. we sought to determine if a cationic lipid/dna complex (cldc) adjuvant could induce heterosubtypic protection if added to a whole inactivated iav vaccine (wiv). | 2018 | 29701840 |
| a microneedle patch for measles and rubella vaccination is immunogenic and protective in infant rhesus macaques. | new methods to increase measles and rubella (mr) vaccination coverage are needed to achieve global and regional mr elimination goals. | 2018 | 29701813 |
| lifespan trajectories of white matter changes in rhesus monkeys. | progress in neurodevelopmental brain research has been achieved through the use of animal models. such models not only help understanding biological changes that govern brain development, maturation and aging, but are also essential for identifying possible mechanisms of neurodevelopmental and age-related chronic disorders, and to evaluate possible interventions with potential relevance to human disease. genetic relationship of rhesus monkeys to humans makes those animals a great candidate for s ... | 2019 | 29701751 |
| large-scale two-photon imaging revealed super-sparse population codes in the v1 superficial layer of awake monkeys. | one general principle of sensory information processing is that the brain must optimize efficiency by reducing the number of neurons that process the same information. the sparseness of the sensory representations in a population of neurons reflects the efficiency of the neural code. here, we employ large-scale two-photon calcium imaging to examine the responses of a large population of neurons within the superficial layers of area v1 with single-cell resolution, while simultaneously presenting ... | 2018 | 29697371 |
| interferon-stimulated gene (isg)-expression screening reveals the specific antibunyaviral activity of isg20. | bunyaviruses pose a significant threat to human health, prosperity, and food security. in response to viral infections, interferons (ifns) upregulate the expression of hundreds of interferon-stimulated genes (isgs), whose cumulative action can potently inhibit the replication of bunyaviruses. we used a flow cytometry-based method to screen the ability of ∼500 unique isgs from humans and rhesus macaques to inhibit the replication of bunyamwera orthobunyavirus (bunv), the prototype of both the per ... | 2018 | 29695422 |
| customizable cap implants for neurophysiological experimentation. | several primate neurophysiology laboratories have adopted acrylic-free, custom-fit cranial implants. these implants are often comprised of titanium or plastic polymers, such as polyether ether ketone (peek). titanium is favored for its mechanical strength and osseointegrative properties whereas peek is notable for its lightweight, machinability, and mri compatibility. recent titanium/peek implants have proven to be effective in minimizing infection and implant failure, thereby prolonging experim ... | 2018 | 29694848 |
| characterization of recent and minimally passaged brazilian dengue viruses inducing robust infection in rhesus macaques. | the macaque is widely accepted as a suitable model for preclinical characterization of dengue vaccine candidates. however, the only vaccine for which both preclinical and clinical efficacy results were reported so far showed efficacy levels that were substantially different between macaques and humans. we hypothesized that this model's predictive capacity may be improved using recent and minimally passaged dengue virus isolates, and by assessing vaccine efficacy by characterizing not only the po ... | 2018 | 29694440 |
| uremic encephalopathy in a rhesus macaque (macaca mulatta): a case report and a brief review of the veterinary literature. | uremic encephalopathy is uncommon yet is one of the most severe complications of renal failure. we present a case of acute renal failure and associated cerebral and vascular lesions consistent with uremic encephalopathy in a rhesus macaque (macaca mulatta). | 2018 | 29693270 |
| detection of circulating mycobacterium tuberculosis-specific dna by droplet digital pcr for vaccine evaluation in challenged monkeys and tb diagnosis. | mycobacterium tuberculosis (m. tb) is emerging as a more serious pathogen due to the increased multidrug-resistant tb and co-infection of human immunodeficiency virus (hiv). the development of an effective and sensitive detection method is urgently needed for bacterial load evaluation in vaccine development, early tb diagnosis, and tb treatment. droplet digital polymerase chain reaction (ddpcr) is a newly developed sensitive pcr method for the absolute quantification of nucleic acid concentratio ... | 2018 | 29691363 |
| efficacy and safety of methylene blue in the treatment of malaria: a systematic review. | methylene blue (mb) was the first synthetic antimalarial to be discovered and was used during the late 19th and early 20th centuries against all types of malaria. mb has been shown to be effective in inhibiting plasmodium falciparum in culture, in the mouse model and in rhesus monkeys. mb was also shown to have a potent ex vivo activity against drug-resistant isolates of p. falciparum and p. vivax. in preclinical studies, mb acted synergistically with artemisinin derivates and demonstrated a str ... | 2018 | 29690878 |
| specificity and affinity of neuraminic acid exhibited by canine rotavirus strain k9 carbohydrate-binding domain (vp8*). | the outer capsid spike protein vp4 of rotaviruses is a major determinant of infectivity and serotype specificity. proteolytic cleavage of vp4 into 2 domains, vp8* and vp5*, enhances rotaviral infectivity. interactions between the vp4 carbohydrate-binding domain (vp8*) and cell surface glycoconjugates facilitate initial virus-cell attachment and subsequent cell entry. our saturation transfer difference nuclear magnetic resonance (std nmr) and isothermal titration calorimetry (itc) studies demonst ... | 2018 | 29687510 |
| correlates of protection against sivmac251 infection in rhesus macaques immunized with chimpanzee-derived adenovirus vectors. | we report on prime-boost vaccine regimens with two simian adenovirus (ad) vectors (sadv) or two human serotype ad vectors (hadv) expressing gag and gp160 of simian immunodeficiency virus (siv)mac239 tested in hadv-seropositive rhesus macaques (rms) repeatedly challenged rectally with low doses of sivmac251. both vaccine regimens reduced set point and peak viral loads (pvl) and accelerated viral clearance. in sadv-vaccinated controller genotype rms resistance against infection correlated with lev ... | 2018 | 29685793 |
| evidence for the speed-value trade-off: human and monkey decision making is magnitude sensitive. | complex natural systems from brains to bee swarms have evolved to make adaptive multifactorial decisions. recent theoretical and empirical work suggests that many evolved systems may take advantage of common motifs across multiple domains. we are particularly interested in value sensitivity (i.e., sensitivity to the magnitude or intensity of the stimuli or reward under consideration) as a mechanism to resolve deadlocks adaptively. this mechanism favours long-term reward maximization over accurac ... | 2018 | 29682592 |
| role of kisspeptin and neurokinin b in puberty in female non-human primates. | in human patients, loss-of-function mutations in the genes encoding kisspeptin (kiss1) and neurokinin b (nkb) and their receptors (kiss1r and nk3r, respectively) result in an abnormal timing of puberty or the absence of puberty. to understand the neuroendocrine mechanism of puberty, we investigated the contribution of kisspeptin and nkb signaling to the pubertal increase in gnrh release using rhesus monkeys as a model. direct measurements of gnrh and kisspeptin in the median eminence of the hypo ... | 2018 | 29681889 |
| recombinant bcg::rv2645 elicits enhanced protective immunity compared to bcg in vivo with induced isgylation-related genes and th1 and th17 responses. | there is a need to develop protective vaccines against tuberculosis (tb). recently, we identified an immunodominant t-cell antigen, rv2645, from the region of deletion 13 (rd13) of m. tuberculosis (m. tb) h37rv, which is absent in bacille calmette-guérin (bcg). here, a recombinant bcg expressing rv2645, namely, bcg::rv2645, was constructed. compared to bcg, we found that bcg::rv2645 improved the antigen presentation capacity of dendritic cells (dcs) and elicited much stronger th1 and th17 respon ... | 2018 | 29681409 |
| gene expression analysis of neuropeptides in oral mucosa during periodontal disease in non-human primates. | neuropeptides (nps) are innate pivotal regulators of the immunoinflammatory response. nevertheless, their role in the pathogenesis of periodontal disease remains unknown. changes in gene expression of 10 nps and 16 np receptors (nprs) coincident with the initiation, progression, and resolution of periodontitis were determined. | 2018 | 29676776 |
| selection on the regulation of sympathetic nervous activity in humans and chimpanzees. | adrenergic α2c receptor (adra2c) is an inhibitory modulator of the sympathetic nervous system. knockout mice for this gene show physiological and behavioural alterations that are associated with the fight-or-flight response. there is evidence of positive selection on the regulation of this gene during chicken domestication. here, we find that the neuronal expression of adra2c is lower in human and chimpanzee than in other primates. on the basis of three-dimensional chromatin structure, we identi ... | 2018 | 29672586 |
| higher-order partial least squares for predicting gene expression levels from chromatin states. | extensive studies have shown that gene expression levels are strongly affected by chromatin mark combinations via at least two mechanisms, i.e., activation or repression. but their combinatorial patterns are still unclear. to further understand the relationship between histone modifications and gene expression levels, here in this paper, we introduce a purely geometric higher-order representation, tensor (also called multidimensional array), which might borrow more unknown interactions in chroma ... | 2018 | 29671394 |
| subclinical cytomegalovirus infection is associated with altered host immunity, gut microbiota, and vaccine responses. | subclinical viral infections (svi), including cytomegalovirus (cmv), are highly prevalent in humans, resulting in lifelong persistence. however, the impact of svi on the interplay between the host immunity and gut microbiota in the context of environmental exposures is not well defined. we utilized the preclinical nonhuman primate (nhp) model consisting of svi-free (specific-pathogen-free [spf]) rhesus macaques and compared them to the animals with svi (non-spf) acquired through natural exposure ... | 2018 | 29669841 |
| the human clone st22 sccmec iv methicillin-resistant staphylococcus aureus isolated from swine herds and wild primates in nepal: is man the common source? | swine nasal samples [n = 282] were collected from 12 randomly selected farms around kathmandu, nepal, from healthy animals. in addition, wild monkey (macaca mulatta) saliva samples [n = 59] were collected near temples areas in kathmandu using a non-invasive sampling technique. all samples were processed for mrsa using standardized selective media and conventional biochemical tests. mrsa verification was done and isolates characterized by sccmec, multilocus sequence typing, whole genome sequencin ... | 2018 | 29668933 |
| evaluation of a therapy for idiopathic chronic enterocolitis in rhesus macaques (macaca mulatta) and linked microbial community correlates. | idiopathic chronic enterocolitis (ice) is one of the most commonly encountered and difficult to manage diseases of captive rhesus macaques (macaca mulatta). the etiology is not well understood, but perturbations in gut microbial communities have been implicated. here we evaluated the effects of a 14-day course of vancomycin, neomycin, and fluconazole on animals affected with ice, comparing treated, untreated, and healthy animals. we performed microbiome analysis on duodenal and colonic mucosal s ... | 2018 | 29666764 |
| silac-based quantitative proteomic analysis of the livers of spontaneous obese and diabetic rhesus monkeys. | type 2 diabetes mellitus (t2dm) is a severe metabolic disorder that affects more than 10% of the population worldwide. obesity is a major cause of insulin resistance and contributes to the development of t2dm. liver is an essential metabolic organ that plays crucial roles in the pathogenesis of obesity and diabetes. however, the underlying mechanisms of liver in the transition of obesity to diabetes are not fully understood. the nonhuman primate rhesus monkey is an appropriate animal for researc ... | 2018 | 29664677 |
| silicon foreign body in the cerebrum of a rhesus macaque (macaca mulatta). | a male rhesus macaque with a cephalic chamber implant for neurophysiology recording presented with hemiparesis affecting the left thoracic and pelvic limbs at approximately 5 wk after craniotomy surgery. mri indicated a 1×2-cm ovoid cerebrocortical cystic lesion immediately subjacent to the right hemisphere craniotomy and recording chamber. transdural aspiration of sterile transudate and resultant decompression resolved the hemiparesis, and follow-up mri at 1 mo indicated resolution of the lesio ... | 2018 | 29663945 |
| repair of a large ventral hernia in a rhesus macaque (macaca mulatta) by using an abdominal component separation technique. | here we present a 32-y-old rhesus macaque (macaca mulatta) with a large recurrent ventral incisional hernia. the initial surgery included midline celiotomy for treatment of endometriosis, in which the animal developed a hernia that was repaired with interposition of mesh. hernia recurrence at 1 y resulted in a defect measuring 7 × 13 cm, with loss of abdominal domain. skin breakdown was noted with areas of exposed mesh through the skin with associated acute on chronic infection. clinically, the ... | 2018 | 29663944 |
| retrospective review of surgical outcomes and pair-housing success in vasectomized rhesus macaques (macaca mulatta). | providing social housing for adult male macaques can be challenging. one successful strategy for long-term social housing of adult male macaques is to pair them with adult females; however, unwanted breeding must be prevented by sterilization of the male or female. vasectomy is a simple, highly effective, and minimally invasive method of contraception that is used at our institution to facilitate social housing. we performed a retrospective review to analyze the surgical outcomes and rate of pos ... | 2018 | 29663943 |
| longitudinal anthropometric assessment of rhesus macaque (macaca mulatta) model of huntington disease. | the neurodegeneration associated with huntington disease (hd) leads to the onset of motor and cognitive impairment and their advancement with increased age in humans. in children at risk for hd, body measurement growth abnormalities include a reduction in bmi, weight, height, and head circumference. the transgenic hd nhp model was first reported in 2008, and progressive decline in cognitive behaviors and motor impairment have been reported. this study focuses on longitudinal body measurements in ... | 2018 | 29663942 |
| positron emission tomography imaging of cerebral glucose metabolism and type 1 cannabinoid receptor availability during temporal lobe epileptogenesis in the amygdala kindling model in rhesus monkeys. | we investigated changes in the endocannabinoid system and glucose metabolism during temporal lobe epileptogenesis. | 2018 | 29663353 |
| a single injection of crystallizable fragment domain-modified antibodies elicits durable protection from shiv infection. | in the absence of an effective and safe vaccine against hiv-1, the administration of broadly neutralizing antibodies (bnabs) represents a logical alternative approach to prevent virus transmission. here, we introduced two mutations encoding amino acid substitutions (m428l and n434s, collectively referred to as 'ls') into the genes encoding the crystallizable fragment domains of the highly potent hiv-specific 3bnc117 and 10-1074 bnabs to increase their half-lives and evaluated their efficacy in b ... | 2018 | 29662199 |
| i scan, therefore i decline: the time course of difficulty monitoring in humans (homo sapiens) and macaques (macaca mulatta). | the study of nonhumans' metacognitive judgments about trial difficulty has grown into an important comparative literature. however, the potential for associative-learning confounds in this area has left room for behaviorist interpretations that are strongly asserted and hotly debated. this article considers how researchers may be able to observe animals' strategic cognitive processes more clearly by creating temporally extended problems within which associative cues are not always immediately av ... | 2018 | 29658725 |
| motor selection dynamics in fef explain the reaction time variance of saccades to single targets. | in studies of voluntary movement, a most elemental quantity is the reaction time (rt) between the onset of a visual stimulus and a saccade toward it. however, this rt demonstrates extremely high variability which, in spite of extensive research, remains unexplained. it is well established that, when a visual target appears, oculomotor activity gradually builds up until a critical level is reached, at which point a saccade is triggered. here, based on computational work and single-neuron recordin ... | 2018 | 29652247 |
| identification of unequally represented founder viruses among tissues in very early siv rectal transmission. | characterizing the transmitted/founder (t/f) viruses of multi-variant siv infection may shed new light on the understanding of mucosal transmission. we intrarectally inoculated six chinese rhesus macaques with a single high dose of sivmac251 (3.1 × 104 tcid50) and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (sga). all 6 monkeys were infected with a range of 2 to 8 t/f viruses and the dominant variants from the inocul ... | 2018 | 29651274 |
| efficient differentiation of cardiomyocytes and generation of calcium-sensor reporter lines from nonhuman primate ipscs. | nonhuman primate (nhp) models are more predictive than rodent models for developing induced pluripotent stem cell (ipsc)-based cell therapy, but robust and reproducible nhp ipsc-cardiomyocyte differentiation protocols are lacking for cardiomyopathies research. we developed a method to differentiate integration-free rhesus macaque ipscs (rhipscs) into cardiomyocytes with >85% purity in 10 days, using fully chemically defined conditions. to enable visualization of intracellular calcium flux in bea ... | 2018 | 29651156 |
| an experimental staphylococcus aureus carriage and decolonization model in rhesus macaques (macaca mulatta). | our human model of nasal colonization and eradication of s. aureus is limited by safety issues. as rhesus macaques are closely related to humans and natural hosts for s. aureus, we developed an experimental decolonization and inoculation protocol in these animals. animals were screened for nasal carriage of s. aureus and 20 carriers were selected. decolonization was attempted using nasal mupirocin (10 animals) or mupirocin plus trimethoprim/sulfadiazine intramuscularly (10 animals) both once dai ... | 2018 | 29649257 |
| dynamics of simian immunodeficiency virus two-long-terminal-repeat circles in the presence and absence of cd8+ cells. | cd8+ cells play a key role in human immunodeficiency virus (hiv)/simian immunodeficiency virus (siv) infection, but their specific mechanism(s) of action in controlling the virus is unclear. two-long-terminal-repeat (2-ltr) circles are extrachromosomal products generated upon failed integration of hiv/siv. to understand the specific effects of cd8+ cells on infected cells, we analyzed the dynamics of 2-ltr circles in sivmac251-infected rhesus macaques (rms) treated with an integrase inhibitor (i ... | 2018 | 29643246 |
| the ultrastructure, spatial distribution, and osmium tetroxide binding of lipofuscin and melanosomes in aging monkey retinal epithelium. | to examine the ultrastructure of lipofuscin bodies and melanosomes in retinal epithelium of elderly rhesus monkeys and determines changes in their number and morphology as a function of retinal eccentricity. | 2018 | 29641909 |
| vascularized thymosternal composite tissue allo- and xenotransplantation in nonhuman primates: initial experience. | vascularized composite allotransplantation is constrained by complications associated with standard immunosuppressive strategies. vascularized thymus and bone marrow have been shown to promote prolonged graft survival in composite organ and soft-tissue vascularized composite allotransplantation models. we report development of a nonhuman primate vascularized thymosternal composite tissue transplant model as a platform to address donor-specific immune tolerance induction strategies. | 2017 | 29632759 |
| neuroestradiol in regulation of gnrh release. | contribution to special issue on fast effects of steroids. the concept that the positive feedback effect of ovarian estradiol (e2) results in gnrh and gonadotropin surges is a well-established principle. however, a series of studies investigating the rapid action of e2 in female rhesus monkeys has led to a new concept that neuroestradiol, synthesized and released in the hypothalamus, also contributes to regulation of the preovulatory gnrh surge. this unexpected finding started from our surprisin ... | 2018 | 29626484 |
| allogeneic ipsc-derived rpe cell graft failure following transplantation into the subretinal space in nonhuman primates. | to characterize the intraocular immune response following transplantation of ips-derived allogeneic rpe cells into the subretinal space of non-immune-suppressed rhesus macaques. | 2018 | 29625461 |
| is male rhesus macaque facial coloration under intrasexual selection? | exaggerated male traits can evolve under intra- or intersexual selection, but it remains less clear how often both mechanisms act together on trait evolution. while the males of many anthropoid primate species exhibit colorful signals that appear to be badges of status under intrasexual selection, the red facial coloration of male rhesus macaques (macaca mulatta) appears to have evolved primarily under intersexual selection and female mate choice. nonetheless, experiments show that red color is ... | 2020 | 29622929 |
| simian immunodeficiency virus vif and human apobec3b interactions resemble those between hiv-1 vif and human apobec3g. | several members of the apobec3 dna cytosine deaminase family can potently inhibit vif-deficient human immunodeficiency virus type 1 (hiv-1) by catalyzing cytosine deamination in viral cdna and impeding reverse transcription. hiv-1 counteracts restriction with the virally encoded vif protein, which targets relevant apobec3 proteins for proteasomal degradation. hiv-1 vif is optimized for degrading the restrictive human apobec3 repertoire, and, in general, lentiviral vif proteins specifically targe ... | 2018 | 29618650 |
| simultaneous time-concentration analysis of soman and vx adducts to butyrylcholinesterase and albumin by lc-ms-ms. | a sensitive method for the purification and determination of two protein adducts, organophosphorus (op)-bche and op-albumin adducts, in a single sample using a simultaneous sample preparation method was developed and validated using liquid chromatography-tandem mass spectrometry. first, we isolated o-ethyl s-2-diisopropylaminoethyl methyl phosphonothiolate (vx) and o-pinacolyl methylphosphonofluoridate (soman, gd)-bche adducts using an immunomagnetic separation (ims) method and the hitrap™ blue ... | 2018 | 29618078 |
| methodology and effects of repeated intranasal delivery of dnsp-11 in awake rhesus macaques. | to determine if the intranasal delivery of neuroactive compounds is a viable, long-term treatment strategy for progressive, chronic neurodegenerative disorders, such as parkinson's disease (pd), intranasal methodologies in preclinical models comparable to humans are needed. | 2018 | 29614295 |
| assessment of pre-operative maropitant citrate use in macaque (macaca fasicularis & macaca mulatta) neurosurgical procedures. | retrospective analysis of post-operative vomiting (pov) in non-human primates at our institution was 11%. based on this additional risk factor for post-operative complications, we aimed to eliminate or decrease pov by adding an antiemetic, maropitant citrate, to the pre-medication protocol. | 2018 | 29611200 |
| chemical composition of axillary odorants reflects social and individual attributes in rhesus macaques. | scents play an important role in the life of most terrestrial mammals and may transmit valuable information about conspecifics. olfaction was long considered of low importance in old world monkeys due to their relative reduction of olfactory structures and low incidence of scent-marking behavior but has been increasingly recognized for mediating social relationships in recent years. yet, studies investigating the composition of their chemical cues remain scarce. in the present study, we analyzed ... | 2018 | 29606788 |
| chronic administration of amphetamines disturbs development of neural progenitor cells in young adult nonhuman primates. | the detrimental effects of amphetamines on developmental stages of npcs are limited to rodent brain and it is not known if these effects occur in nonhuman primates which are the focus of the current investigation. young adult rhesus macaques either experienced mdma only, a combination of amphetamines (mdma, mda and methamphetamine) or no amphetamines (controls) and hippocampal tissue was processed for immunohistochemical analysis.quantitative stereological analysis showed that intermittent expos ... | 2018 | 29601895 |
| auditory and audio-vocal responses of single neurons in the monkey ventral premotor cortex. | monkey vocalization is a complex behavioral pattern, which is flexibly used in audio-vocal communication. a recently proposed dual neural network model suggests that cognitive control might be involved in this behavior, originating from a frontal cortical network in the prefrontal cortex and mediated via projections from the rostral portion of the ventral premotor cortex (pmvr) and motor cortex to the primary vocal motor network in the brainstem. for the rapid adjustment of vocal output to exter ... | 2018 | 29598839 |
| differential mobility spectrometry (dms) reveals the elevation of urinary acetylcarnitine in non-human primates (nhps) exposed to radiation. | acetylcarnitine has been identified as one of several urinary biomarkers indicative of radiation exposure in adult rhesus macaque monkeys (non-human primates, nhps). previous work has demonstrated an up-regulated dose-response profile in a balanced male/female nhp cohort. as a contribution toward the development of metabolomics-based radiation biodosimetry in human populations and other applications of acetylcarnitine screening, we have developed a quantitative, high-throughput method for the an ... | 2018 | 29596720 |
| phosphorylated α-synuclein accumulations and lewy body-like pathology distributed in parkinson's disease-related brain areas of aged rhesus monkeys treated with mptp. | phosphorylation of α-synuclein at serine 129 (p-ser 129 α-syn) is involved in the pathogenesis of parkinson's disease (pd) and lewy body (lb) formation. however, there is no clear evidence indicates the quantitative relation of p-ser 129 α-syn accumulation and dopaminergic cell loss, lbs pathology and the affected brain areas in pd monkeys. here, pathological changes in the substantia nigra (sn) and pd-related brain areas were measured in aged monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetra ... | 2018 | 29592843 |
| correction: transduction of siv-specific tcr genes into rhesus macaque cd8+ t cells conveys the ability to suppress siv replication. | [this corrects the article doi: 10.1371/journal.pone.0023703.]. | 2018 | 29590210 |
| primary sensorimotor cortex exhibits complex dependencies of spike-field coherence on neuronal firing rates, field power, and behavior. | spike-field coherence (sfc) is widely used to assess cortico-cortical interactions during sensorimotor behavioral tasks by measuring the consistency of the relative phases between the spike train of a neuron and the concurrent local field potentials (lfps). interpretations of sfc as a measure of functional connectivity are complicated by theoretical work suggesting that estimates of sfc depend on overall neuronal activity. we evaluated the dependence of sfc on neuronal firing rates, lfp power, a ... | 2018 | 29589815 |
| analysis of the expression pattern of the schizophrenia-risk and intellectual disability gene tcf4 in the developing and adult brain suggests a role in development and plasticity of cortical and hippocampal neurons. | haploinsufficiency of the class i bhlh transcription factor tcf4 causes pitt-hopkins syndrome (pths), a severe neurodevelopmental disorder, while common variants in the tcf4 gene have been identified as susceptibility factors for schizophrenia. it remains largely unknown, which brain regions are dependent on tcf4 for their development and function. | 2018 | 29588831 |
| eb 2017 article: changes in advanced glycation end products, beta-defensin-3, and interleukin-17 during diabetic periodontitis development in rhesus monkeys. | the bidirectional relationship between diabetes mellitus (dm) and periodontal disease has drawn great attention; however, the mechanisms underlying their association remain unclear. in this study, we aimed to develop a rhesus monkey model of diabetic periodontitis and explore the potential mechanisms by which dm affects the progression of periodontal disease. three healthy rhesus monkeys were selected as the control group. five streptozotocin-induced diabetic rhesus monkeys were chosen as the ex ... | 2018 | 29587489 |
| the tyrosine phosphatase step is involved in age-related memory decline. | cognitive disabilities that occur with age represent a growing and expensive health problem. age-associated memory deficits are observed across many species, but the underlying molecular mechanisms remain to be fully identified. here, we report elevations in the levels and activity of the striatal-enriched phosphatase (step) in the hippocampus of aged memory-impaired mice and rats, in aged rhesus monkeys, and in people diagnosed with amnestic mild cognitive impairment (amci). the accumulation of ... | 2018 | 29576474 |
| persistent alteration in behavioural reactivity to a mild social stressor in rhesus monkeys repeatedly exposed to sevoflurane in infancy. | socio-emotional development is the expression and management of emotions, which in non-human primates can be examined using responses toward increasing levels of threat. damage to the limbic system alters socio-emotional development in primates. thus, neuronal and glial cell loss caused by exposure to general anaesthesia early in infancy might also impact socio-emotional development. we recently reported that repeated sevoflurane exposure in the first month of life alters emotional behaviours at ... | 2018 | 29576116 |
| diet matters: glucocorticoid-related neuroadaptations associated with calorie intake in female rhesus monkeys. | exposure to psychosocial stressors increases consumption of palatable, calorically dense diets (cdd) and the risk for obesity, especially in females. while consumption of an obesogenic diet and chronic stress have both been shown to decrease dopamine 2 receptor (d2r) binding and alter functional connectivity (fc) within the prefrontal cortex (pfc) and the nucleus accumbens (nacc), it remains uncertain how social experience and dietary environment interact to affect reward pathways critical for t ... | 2018 | 29567621 |
| il-1 signaling mediates intrauterine inflammation and chorio-decidua neutrophil recruitment and activation. | neutrophil infiltration of the chorioamnion-decidua tissue at the maternal-fetal interface (chorioamnionitis) is a leading cause of prematurity, fetal inflammation, and perinatal mortality. we induced chorioamnionitis in preterm rhesus macaques by intraamniotic injection of lps. here, we show that, during chorioamnionitis, the amnion upregulated phospho-irak1-expressed neutrophil chemoattractants cxcl8 and csf3 in an il-1-dependent manner. il-1r blockade decreased chorio-decidua neutrophil accum ... | 2018 | 29563340 |
| preclinical to human translational pharmacology of the novel m1 positive allosteric modulator mk-7622. | the current standard of care for treating alzheimer's disease is acetylcholinesterase inhibitors, which nonselectively increase cholinergic signaling by indirectly enhancing activity of nicotinic and muscarinic receptors. these drugs improve cognitive function in patients, but also produce unwanted side effects that limit their efficacy. in an effort to selectively improve cognition and avoid the cholinergic side effects associated with the standard of care, various efforts have been aimed at de ... | 2018 | 29563325 |
| chimeric antigen receptor t cell-mediated neurotoxicity in nonhuman primates. | chimeric antigen receptor (car) t-cell immunotherapy has revolutionized the treatment of refractory leukemias and lymphomas, but is associated with significant toxicities, namely cytokine release syndrome (crs) and neurotoxicity. a major barrier to developing therapeutics to prevent car t cell-mediated neurotoxicity is the lack of clinically relevant models. accordingly, we developed a rhesus macaque (rm) model of neurotoxicity via adoptive transfer of autologous cd20-specific car t cells. follo ... | 2018 | 29563103 |
| the anti-caspase inhibitor q-vd-oph prevents aids disease progression in siv-infected rhesus macaques. | apoptosis has been proposed as a key mechanism responsible for cd4+ t cell depletion and immune dysfunction during hiv infection. we demonstrated that q-vd-oph, a caspase inhibitor, inhibits spontaneous and activation-induced death of t cells from siv-infected rhesus macaques (rms). when administered during the acute phase of infection, q-vd-oph was associated with (a) reduced levels of t cell death, (b) preservation of cd4+/cd8+ t cell ratio in lymphoid organs and in the gut, (c) maintenance of ... | 2018 | 29553486 |