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candida albicans-associated sepsis in a pre-term neonatal rhesus macaque (macaca mulatta).invasive candida infections (ici) have been associated with neurodevelopmental impairment or death in human pre-term neonates. candidiasis in nonhuman primates is seen mostly in immunosuppressed animals, and ici is not commonly reported. here, we report a case of candida albicans-associated ici in a pre-term neonatal rhesus macaque.201930734326
evaluation of 11c-lsn3172176 as a novel pet tracer for imaging m1 muscarinic acetylcholine receptors in nonhuman primates.the m1 muscarinic acetylcholine receptor (machr) plays an important role in learning and memory, and therefore is a target for development of drugs for treatment of cognitive impairments in alzheimer disease and schizophrenia. the availability of m1-selective radiotracers for pet will help in developing therapeutic agents by providing an imaging tool for assessment of drug dose-receptor occupancy relationship. here we report the synthesis and evaluation of 11c-lsn3172176 (ethyl 4-(6-(methyl-11c) ...201930733324
preclinical evaluation and nonhuman primate receptor occupancy study of 18f-jnj-64413739, a pet radioligand for p2x7 receptors.the p2x7 receptor is an adenosine triphosphate-gated ion channel, which is abundantly expressed in glial cells within the central nervous system and in the periphery. p2x7 receptor activation leads to the release of the proinflammatory cytokine il-1β in the brain, and antagonism of the p2x7 receptor is a novel therapeutic strategy to dampen adenosine triphosphate-dependent il-1β signaling. pet ligands for the p2x7 receptor will not only be valuable to assess central target engagement of drug can ...201930733317
agglutination testing for human erythrocyte product in the rhesus macaque.there has been interest in using human blood products in nonhuman primate models of trauma to supplement human studies and to provide evidence to guide novel trauma resuscitation strategies. the compatibility of human rbcs has not been extensively studied in nonhuman primate species.201930730557
real-time experimental control using network-based parallel processing.modern neuroscience research often requires the coordination of multiple processes such as stimulus generation, real-time experimental control, as well as behavioral and neural measurements. the technical demands required to simultaneously manage these processes with high temporal fidelity is a barrier that limits the number of labs performing such work. here we present an open-source, network-based parallel processing framework that lowers this barrier. the real-time experimental control with g ...201930730290
a chemical approach for global protein knockdown from mice to non-human primates.although conventional genetic modification approaches for protein knockdown work very successfully due to the increasing use of crispr/cas9, effective techniques for achieving protein depletion in adult animals, especially in large animals such as non-human primates, are lacking. here, we report a chemical approach based on protacs technology that efficiently and quickly knocks down fkbp12 (12-kda fk506-binding) protein globally in vivo. both intraperitoneal and oral administration led to rapid, ...201930729032
distinct types of neural reorganization during long-term learning.what are the neural mechanisms of skill acquisition? many studies find that long-term practice is associated with a functional reorganization of cortical neural activity. however, the link between these changes in neural activity and the behavioral improvements that occur is not well understood, especially for long-term learning that takes place over several weeks. to probe this link in detail, we leveraged a brain-computer interface (bci) paradigm in which rhesus monkeys learned to master nonin ...201930726164
novel kappa opioid receptor agonist as improved pet radiotracer: development and in vivo evaluation.the kappa opioid receptor (kor) is involved in depression, alcoholism, and drug abuse. the current agonist radiotracer 11c-gr103545 is not ideal for imaging kor due to its slow tissue kinetics in human. the aim of our project was to develop novel kor agonist radiotracers with improved imaging properties. a novel compound fekap ((( r))-4-(2-(3,4-dichlorophenyl)acetyl)-3-((ethyl(2-fluoroethyl)amino)methyl) piperazine-1-carboxylate) was designed, synthesized, and assayed for in vitro binding affini ...201930726092
heart rate and heart rate variability of rhesus macaques (macaca mulatta) affected by left ventricular hypertrophy.hypertrophic cardiomyopathy (hcm) is frequently associated with sudden cardiac death, presumably due to the development of malignant arrhythmias. the risk of sudden cardiac death due to hcm has been reported to be predicted by assessing electrocardiographic (ecg) changes including frequencies and complexities of arrhythmias as well as heart rate variability (hrv) as an assessment of autonomic balance. sudden cardiac death in association with naturally-occurring left ventricular hypertrophy (lvh) ...201930723724
decreased complexity of glucose dynamics in diabetes in rhesus monkeys.until recently, preclinical and clinical work on diabetes has focused on the understanding of blood glucose elevation and its detrimental metabolic sequelae. the advent of continuous glucose monitoring (cgm) technology now allows real time monitoring of blood glucose levels as a time series, and thus the exploration of glucose dynamics at short time scales. previous work has shown decreases in the complexity of glucose dynamics, as measured by multiscale entropy (mse) analysis, in diabetes in hu ...201930723274
fructose-induced hypertriglyceridemia in rhesus macaques is attenuated with fish oil or apoc3 rna interference.dyslipidemia and insulin resistance are significant adverse outcomes of consuming high-sugar diets. conversely, dietary fish oil (fo) reduces plasma lipids. diet-induced dyslipidemia in a rhesus model better approximates the pathophysiology of human metabolic syndrome (mets) than rodent models. here, we investigated relationships between metabolic parameters and hypertriglyceridemia in rhesus macaques consuming a high-fructose diet (n = 59) and determined the effects of fo supplementation or rna ...201930723097
dynamics of motor cortical activity during naturalistic feeding behavior.the orofacial primary motor cortex (mio) plays a critical role in controlling tongue and jaw movements during oral motor functions, such as chewing, swallowing and speech. however, the neural mechanisms of mio during naturalistic feeding are still poorly understood. there is a strong need for a systematic study of motor cortical dynamics during feeding behavior.201930721881
novel technique for toe-to-hand transplantation: the fourth-toe as an alternative option for toe-to-hand transplantation for pediatric patients.the first toe-to-hand transplantation was done in 1898 by nicoladoni. it was a staged procedure and the toe flap was based on a pedicle. with advancement of optical instruments and microsurgeons' skills in 1964 the first microvascular toe-to-hand transplantation on a rhesus monkey was done. the technique's development has not stopped, many authors have modified it to achieve better outcomes for both traumatic and congenital hand defects. the most commonly used toes for transplantation are first, ...201930720566
high-dimensional representation of texture in somatosensory cortex of primates.in the somatosensory nerves, the tactile perception of texture is driven by spatial and temporal patterns of activation distributed across three populations of afferents. these disparate streams of information must then be integrated centrally to achieve a unified percept of texture. to investigate the representation of texture in somatosensory cortex, we scanned a wide range of natural textures across the fingertips of rhesus macaques and recorded the responses evoked in brodmann's areas 3b, 1, ...201930718436
monotherapy with a low-dose lipopeptide hiv fusion inhibitor maintains long-term viral suppression in rhesus macaques.combination antiretroviral therapy (cart) dramatically improves survival of hiv-infected patients, but lifelong treatment can ultimately result in cumulative toxicities and drug resistance, thus necessitating the development of new drugs with significantly improved pharmaceutical profiles. we recently found that the fusion inhibitor t-20 (enfuvirtide)-based lipopeptides possess dramatically increased anti-hiv activity. herein, a group of novel lipopeptides were designed with different lengths of ...201930716118
surface color and predictability determine contextual modulation of v1 firing and gamma oscillations.the integration of direct bottom-up inputs with contextual information is a core feature of neocortical circuits. in area v1, neurons may reduce their firing rates when their receptive field input can be predicted by spatial context. gamma-synchronized (30-80 hz) firing may provide a complementary signal to rates, reflecting stronger synchronization between neuronal populations receiving mutually predictable inputs. we show that large uniform surfaces, which have high spatial predictability, str ...201930714900
maternal neglect and the serotonin system are associated with daytime sleep in infant rhesus monkeys.environmental and biological factors contribute to sleep development during infancy. parenting plays a particularly important role in modulating infant sleep, potentially via the serotonin system, which is itself involved in regulating infant sleep. we hypothesized that maternal neglect and serotonin system dysregulation would be associated with daytime sleep in infant rhesus monkeys. subjects were nursery-reared infant rhesus macaques (n = 287). during the first month of life, daytime sleep-wak ...202030712526
evolutionarily significant a-to-i rna editing events originated through g-to-a mutations in primates.recent studies have revealed thousands of a-to-i rna editing events in primates, but the origination and general functions of these events are not well addressed.201930712515
nicotine-like discriminative stimulus effects of acetylcholinesterase inhibitors and a muscarinic receptor agonist in rhesus monkeys.acetylcholinesterase (ache) inhibitors and positive allosteric nicotinic acetylcholine receptor (nachr) modulators are potential pharmacotherapies for nicotine dependence. because some smoking cessation aids (e.g. varenicline) appear to work by mimicking the effects of nicotine, we used drug discrimination to examine whether ache inhibitors and nachr allosteric modulators mimic the effects of nicotine. rhesus monkeys discriminated 1.78 mg/kg of nicotine s.c. under an fr5 schedule of stimulus-sho ...201930712397
eye position error influence over "open-loop" smooth pursuit initiation.the oculomotor system integrates a variety of visual signals into appropriate motor plans, but such integration can have widely varying time scales. for example, smooth pursuit eye movements to follow a moving target are slower and longer lasting than saccadic eye movements and it has been suggested that initiating a smooth pursuit eye movement involves an obligatory "open-loop" interval in which new visual motion signals presumably cannot influence the ensuing motor plan for up to 100 ms after ...201930709895
probability distortion depends on choice sequence in rhesus monkeys.humans and other primates share many decision biases, among them our subjective distortion of objective probabilities. when making choices between uncertain rewards we typically treat probabilities nonlinearly: overvaluing low probabilities of reward and undervaluing high ones. a growing body of evidence, however, points to a more flexible pattern of distortion than the classical inverse-s one, highlighting the effect of experimental conditions in shifting the weight assigned to probabilities, s ...201930705103
anti-drug antibody responses impair prophylaxis mediated by aav-delivered hiv-1 broadly neutralizing antibodies.adeno-associated virus (aav) delivery of potent and broadly neutralizing antibodies (bnabs is a promising approach for the prevention of hiv-1 infection. the immunoglobulin g (igg)1 subtype is usually selected for this application, because it efficiently mediates antibody effector functions and has a somewhat longer half-life. however, the use of igg1-fc has been associated with the generation of anti-drug antibodies (adas) that correlate with loss of antibody expression. in contrast, we have sh ...201930704961
identification of variable and joining germline genes and alleles for rhesus macaque from b cell receptor repertoires.the rhesus macaque is a valuable preclinical animal model to estimate vaccine effectiveness and is also important for understanding ab maturation and b cell repertoire evolution responding to vaccination. however, incomplete mapping of rhesus ig germline genes hinders the research efforts. to address this deficiency, we sequenced the bcr repertoires of 75 indian rhesus macaques. using a bioinformatic method that has been validated with bcr repertoire analysis of three human donors, we were able ...201930700589
modeling diverse responses to filled and outline shapes in macaque v4.visual area v4 is an important midlevel cortical processing stage that subserves object recognition in primates. studies investigating shape coding in v4 have largely probed neuronal responses with filled shapes, i.e., shapes defined by both a boundary and an interior fill. as a result, we do not know whether form-selective v4 responses are dictated by boundary features alone or if interior fill is also important. we studied 43 v4 neurons in two male macaque monkeys ( macaca mulatta) with a set ...201930699004
temporal patterns of gene regulation and upstream regulators contributing to major developmental transitions during rhesus macaque preimplantation development.the preimplantation period of life in mammals encompasses a tremendous amount of restructuring and remodeling of the embryonic genome and reprogramming of gene expression. these vast changes support metabolic activation and cellular processes that drive early cleavage divisions and enable the creation of the earliest primitive cell lineages. a major question in mammalian embryology is how such vast, sweeping changes in gene expression are orchestrated, so that changes in gene expression are exac ...201930698740
small incision femtosecond laser-assisted x-ray-irradiated corneal intrastromal xenotransplantation in rhesus monkeys: a preliminary study.gamma-ray irradiation could significantly induce widespread apoptosis in corneas and reduced the allogenicity of donor cornea. and the x-rays may have similar biological effects. the feasibility and effects of x-ray-irradiated corneal lamellae have not been assessed yet.201830698112
white matter is the predilection site of late-delayed radiation-induced brain injury in non-human primates.fractionated whole-brain irradiation for the treatment of intracranial neoplasia causes progressive neurodegeneration and neuroinflammation. the long-term consequences of single-fraction high-dose irradiation to the brain are unknown. to assess the late effects of brain irradiation we compared transcriptomic gene expression profiles from nonhuman primates (nhp; rhesus macaques macaca mulatta) receiving single-fraction total-body irradiation (tbi; n = 5, 6.75-8.05 gy, 6-9 years prior to necropsy) ...201930694733
persistent viral reservoirs in lymphoid tissues in siv-infected rhesus macaques of chinese-origin on suppressive antiretroviral therapy.understanding hiv latent reservoirs in tissues is essential for the development of new strategies targeting these sites for eradication. here, we assessed the size of latent reservoirs and the source of residual viruses in multiple lymphoid tissues of siv-infected and fully suppressed rhesus macaques of chinese-origin (crms). eight crms were infected with sivmac251 and treated with tenofovir and emtricitabine daily for 24 weeks initiated 4 weeks post-infection. four of the eight animals reached ...201930691203
a novel 18f-labeled radioligand for positron emission tomography imaging of 11β-hydroxysteroid dehydrogenase (11β-hsd1): synthesis and preliminary evaluation in nonhuman primates.11β-hydroxysteroid dehydrogenase type 1 (11β-hsd1) catalyzes the conversion of cortisone to cortisol and controls a key pathway in the regulation of stress. studies have implicated 11β-hsd1 in metabolic diseases including type 2 diabetes and obesity, as well as stress-related disorders and neurodegenerative diseases, such as depression and alzheimer's disease (ad). we have previously developed [11c]as2471907 as a pet radiotracer to image 11β-hsd1 in the brain of nonhuman primates and humans. how ...201930689943
effects of reducing norepinephrine levels via dsp4 treatment on amyloid-β pathology in female rhesus macaques (macaca mulatta).the degeneration in the locus coeruleus associated with alzheimer's disease suggests an involvement of the noradrenergic system in the disease pathogenesis. the role of depleted norepinephrine was tested in adult and aged rhesus macaques to develop a potential model for testing alzheimer's disease interventions. monkeys were injected with the noradrenergic neurotoxin n-(2-chloroethyl)-n-ethyl-2-bromobenzylamine (dsp4) or vehicle at 0, 3, and 6 months; brains were harvested at 9 months. reduced n ...201930689563
lung and heart injury in a nonhuman primate model of partial-body irradiation with minimal bone marrow sparing: histopathological evidence of lung and heart injury.male rhesus macaques were subjected to partial-body irradiation at 10, 11, or 12 gy with 5% bone marrow protection. animals were euthanized when dictated by prospectively determined clinical parameters or at approximately 180 d following irradiation. histological sections of lung and heart were stained with hematoxylin and eosin as well as a battery of histochemical and immunohistochemical stains. histopathological alterations in the lung were centered on fibrosis, inflammation, and reactive/pro ...201930688698
a comparative dose-response relationship between sexes for mortality and morbidity of radiation-induced lung injury in the rhesus macaque.radiation-induced lung injury is a characteristic, dose- and time-dependent sequela of potentially lethal, delayed effects of acute radiation exposure. understanding of these delayed effects to include development of medical countermeasures requires well-characterized and validated animal models that mimic the human response to acute radiation and adhere to the criteria of the us food and drug administration animal rule. the objective herein was to establish a nonhuman primate model of whole-tho ...201930688697
early amygdala damage alters the way rhesus macaques process species-specific audio-visual vocalizations.perceiving, integrating, and interpreting multimodal signals are essential for social success, but the neural substrates mediating these functions are not fully understood. this study examined the role of the amygdala in processing bimodal species-specific vocalizations using eye tracking in rhesus macaques. looking behavior of 6 adult rhesus monkeys with neonatal amygdala lesions (neo-aibo; 3m, 3f) was compared with that of 6 sham-operated controls (neo-c; 3m, 3f). two side-by-side videos of un ...201930688484
modeling the encoding of saccade kinematic metrics in the purkinje cell layer of the cerebellar vermis.recent electrophysiological observations related to saccadic eye movements in rhesus monkeys, suggest a prediction of the sensory consequences of movement in the purkinje cell layer of the cerebellar oculomotor vermis (omv). a definite encoding of real-time motion of the eye has been observed in simple-spike responses of the combined burst-pause purkinje cell populations, organized based upon their complex-spike directional tuning. however, the underlying control mechanisms that could lead to su ...201830687055
safety, tolerability, pharmacokinetics, and immunogenicity of the therapeutic monoclonal antibody mab114 targeting ebola virus glycoprotein (vrc 608): an open-label phase 1 study.mab114 is a single monoclonal antibody that targets the receptor-binding domain of ebola virus glycoprotein, which prevents mortality in rhesus macaques treated after lethal challenge with zaire ebolavirus. here we present expedited data from vrc 608, a phase 1 study to evaluate mab114 safety, tolerability, pharmacokinetics, and immunogenicity.201930686586
omip-052: an 18-color panel for measuring th1, th2, th17, and tfh responses in rhesus macaques. 201930681265
identification of premeiotic, meiotic, and postmeiotic cells in testicular biopsies without sperm from sertoli cell-only syndrome patients.sertoli cell-only syndrome (scos) affects about 26.3⁻57.8% of azoospermic men, with their seminiferous tubules containing only sertoli cells. recently, it was reported that testicular biopsies from nonobstructive azoospermic (noa) patients contained germ cells, and that sperm could be found in the tubules of 20% of scos patients using testicular sperm extraction technology. since the patients without sperm in their testicular biopsies do not have therapy to help them to father a biological child ...201930678285
predicting efavirenz concentrations in the brain tissue of hiv-infected individuals and exploring their relationship to neurocognitive impairment.sparse data exist on the penetration of antiretrovirals into brain tissue. in this work, we present a framework to use efavirenz (efv) pharmacokinetic (pk) data in plasma, cerebrospinal fluid (csf), and brain tissue of eight rhesus macaques to predict brain tissue concentrations in hiv-infected individuals. we then perform exposure-response analysis with the model-predicted efv area under the concentration-time curve (auc) and neurocognitive scores collected from a group of 24 hiv-infected parti ...201930675981
macaque monkeys learn by observation in the ghost display condition in the object-in-place task with differential reward to the observer.observational learning has been investigated in monkeys mainly using conspecifics or humans as models to observe. some studies attempted to clarify the social agent's role and to test whether non-human primates could learn from observation of a non-social agent, usually mentioned as a 'ghost display' condition, but they reported conflicting results. to address this question, we trained three rhesus monkeys in an object-in-place task consisting of the presentation of five subsequent problems comp ...201930674953
cytomegalovirus vectors expressing plasmodium knowlesi antigens induce immune responses that delay parasitemia upon sporozoite challenge.the development of a sterilizing vaccine against malaria remains one of the highest priorities for global health research. while sporozoite vaccines targeting the pre-erythrocytic stage show great promise, it has not been possible to maintain efficacy long-term, likely due to an inability of these vaccines to maintain effector memory t cell responses in the liver. vaccines based on human cytomegalovirus (hcmv) might overcome this limitation since vectors based on rhesus cmv (rhcmv), the homologo ...201930673723
s-cone photoreceptors in the primate retina are functionally distinct from l and m cones.daylight vision starts with signals in three classes of cone photoreceptors sensitive to short (s), middle (m), and long (l) wavelengths. psychophysical studies show that perceptual sensitivity to rapidly varying inputs differs for signals originating in s cones versus l and m cones; notably, s-cone signals appear perceptually delayed relative to l- and m-cone signals. these differences could originate in the cones themselves or in the post-cone circuitry. to determine if the cones could contrib ...201930672735
molecular characterization of entamoeba spp. in wild taihangshan macaques (macaca mulatta tcheliensis) in china.entamoeba spp. is one of the most common enteric parasites of humans and animals.201930671772
blinded by the light: a nonhuman primate model of achromatopsia.achromatopsia is an inherited retinal degeneration characterized by the loss of cone photoreceptor function. in this issue of the jci, moshiri et al. characterize a naturally occurring model of the disease in the rhesus macaque caused by homozygous mutations in the phototransduction enzyme pde6c. using retinal imaging, and electrophysiologic and biochemical methods, the authors report a clinical phenotype nearly identical to the human condition. these findings represent the first genetic nonhuma ...201930667378
a behavioral face preference deficit in a monkey with an incomplete face patch system.primates are experts in face perception and naturally show a preference for faces under free-viewing conditions. the primate ventral stream is characterized by a network of face patches that selectively responds to faces, but it remains uncertain how important such parcellation is for face perception. here we investigated free-viewing behavior in a female monkey who naturally lacks fmri-defined posterior and middle lateral face patches. we presented a series of content-rich images of scenes that ...201930665007
prevention of tuberculosis infection and disease by local bcg in repeatedly exposed rhesus macaques.tuberculosis (tb) remains the deadliest infectious disease1, and the widely used bacillus calmette-guérin (bcg) vaccine fails to curb the epidemic. an improved vaccination strategy could provide a cost-effective intervention to break the transmission cycle and prevent antimicrobial resistance2,3. limited knowledge of the host responses critically involved in protective immunity hampers the development of improved tb vaccination regimens. therefore, assessment of new strategies in preclinical mod ...201930664782
correction for mavigner et al., "simian immunodeficiency virus persistence in cellular and anatomic reservoirs in antiretroviral therapy-suppressed infant rhesus macaques". 201930655382
simian immunodeficiency virus transiently increases brain temperature in rhesus monkeys: detection with magnetic resonance spectroscopy thermometry.to evaluate brain temperature effects of early simian immunodeficiency virus (siv) infection in rhesus macaques using proton magnetic resonance spectroscopy (mrs) thermometry (mrst) and to determine whether temperature correlates with brain choline or myo-inositol levels.201930652349
functional characterization for polymorphic organic anion transporting polypeptides (oatp/slco1b1, 1b3, 2b1) of monkeys recombinantly expressed with various oatp probes.the hepatic uptake of clinical drugs mediated by human hepatic organic anion transporting polypeptides (oatp/slco) has been reported extensively. in this study, hepatic uptake by recombinantly expressed monkey oatp1b1, oatp1b3 and oatp2b1 was investigated using three human oatp1b1 and oatp1b3 substrates (pitavastatin, pravastatin and rosuvastatin) and one oatp1b3 substrate (telmisartan), as the governmental drug interaction guidelines recommend, and seven reported clinical drugs. the uptake of k ...201930652318
clade c hiv-1 envelope vaccination regimens differ in their ability to elicit antibodies with moderate neutralization breadth against genetically diverse tier 2 hiv-1 envelope variants.the goals of preclinical hiv vaccine studies in nonhuman primates are to develop and test different approaches for their ability to generate protective immunity. here, we compared the impact of 7 different vaccine modalities, all expressing the hiv-1 1086.c clade c envelope (env), on (i) the magnitude and durability of antigen-specific serum antibody responses and (ii) autologous and heterologous neutralizing antibody capacity. these vaccination regimens included immunization with different comb ...201930651354
altered expression of p63 isoforms and expansion of p63- and club cell secretory protein-positive epithelial cells in the lung as novel features of aging.aging is a key contributor for subclinical progression of late-onset lung diseases. basal, club, and type ii alveolar epithelial cells (aecs) are lung epithelial progenitors whose capacities of differentiation are extensively studied. the timely transition of these cells in response to environmental changes helps maintain the intricate organization of lung structure. however, it remains unclear how aging affects their behavior. this paper demonstrates that the protein expression profiles of a ty ...201930649915
chronic ethanol drinking increases during the luteal menstrual cycle phase in rhesus monkeys: implication of progesterone and related neurosteroids.sporadic reports of alcohol consumption being linked to menstrual cycle phase highlight the need to consider hormonally characterized menstrual cycle phase in understanding the sex-specific effects of risk for alcohol drinking in women.201930645681
doppler and oscillometric mean blood pressure best represent direct blood pressure measurements in anesthetized rhesus macaques (macaca mulatta).indirect blood pressure measurements are often used to guide clinical decisions, but few studies have verified their agreement with direct arterial blood pressure in nonhuman primates. here, the accuracy and precision of doppler (dop) and oscillometric (os) [systolic (ossys), mean (osmean), and diastolic (osdias)] blood pressure readings were assessed in rhesus macaques.201930644561
mr extracellular volume mapping and non-contrast t1ρ mapping allow early detection of myocardial fibrosis in diabetic monkeys.to detect diffuse myocardial fibrosis in different severity levels of left ventricular diastolic dysfunction (dd) in spontaneous type 2 diabetes mellitus (t2dm) rhesus monkeys.201930643944
vaccine protection against sivmac239 acquisition.the biological characteristics of hiv pose serious difficulties for the success of a preventive vaccine. molecularly cloned sivmac239 is difficult for antibodies to neutralize, and a variety of vaccine approaches have had great difficulty achieving protective immunity against it in rhesus monkey models. here we report significant protection against i.v. acquisition of sivmac239 using a long-lasting approach to vaccination. the vaccine regimen includes a replication-competent herpesvirus engineer ...201930642966
immunological responses to the relapsing fever spirochete borrelia turicatae in infected rhesus macaques: implications for pathogenesis and diagnosis.the global public health impact of relapsing fever (rf) spirochetosis is significant, since the pathogens exist on five of seven continents. the hallmark sign of infection is episodic fever and the greatest threat is to the unborn. with the goal of better understanding the specificity of b-cell responses and the role of immune responses in pathogenicity, we infected rhesus macaques with borrelia turicatae (a new world rf spirochete species) by tick bite and monitored the immune responses generat ...201930642902
needle-free delivery of dna: targeting of hemagglutinin to mhc class ii molecules protects rhesus macaques against h1n1 influenza.conventional influenza vaccines are hampered by slow and limited production capabilities, whereas dna vaccines can be rapidly produced for global coverage in the event of an emerging pandemic. however, a drawback of dna vaccines is their generally low immunogenicity in non-human primates and humans. we have previously demonstrated that targeting of influenza hemagglutinin to human hla class ii molecules can increase antibody responses in larger animals such as ferrets and pigs. here, we extend t ...201930638800
very long-chain c24:1 ceramide is increased in serum extracellular vesicles with aging and can induce senescence in bone-derived mesenchymal stem cells.extracellular vesicles (evs), including exosomes and microvesicles, function in cell-to-cell communication through delivery of proteins, lipids and micrornas to target cells via endocytosis and membrane fusion. these vesicles are enriched in ceramide, a sphingolipid associated with the promotion of cell senescence and apoptosis. we investigated the ceramide profile of serum exosomes from young (24⁻40 yrs.) and older (75⁻90 yrs.) women and young (6⁻10 yrs.) and older (25⁻30 yrs.) rhesus macaques ...201930634626
development and in vivo evaluation of a κ-opioid receptor agonist as a pet radiotracer with superior imaging characteristics.studies have shown κ-opioid receptor (kor) abnormalities in addictive disorders, other central nervous system diseases, and alzheimer's disease. we have developed the first set of agonist 11c-gr103545 and antagonist 11c-ly2795050 radiotracers for pet imaging of kor in humans. nonetheless, 11c-gr103545 displays protracted uptake kinetics and is not an optimal radiotracer. here, we report the development and evaluation of 11c-methyl-(r)-4-(2-(3,4-dichlorophenyl)acetyl)-3-((diethylamino)methyl)pipe ...201930630942
regional anesthesia for dentistry and orofacial surgery in rhesus macaques (macaca mulatta).regional anesthesia is a commonly used adjunct to orofacial dental and surgical procedures in companion animals and humans. however, appropriate techniques for anesthetizing branches of the mandibular and maxillary nerves have not been described for rhesus monkeys. skulls of 3 adult rhesus monkeys were examined to identify relevant foramina, establish appropriate landmarks for injection, and estimate injection angles and depth. cadaver heads of 7 adult rhesus monkeys (4 male, 3 female) were then ...201930630557
a computational model of dual competition between the basal ganglia and the cortex.we propose a model that includes interactions between the cortex, the basal ganglia (bg), and the thalamus based on a dual competition. we hypothesize that the striatum, the subthalamic nucleus (stn), the internal globus pallidus (gpi), the thalamus, and the cortex are involved in closed feedback loops through the hyperdirect and direct pathways. these loops support a competition process that results in the ability of bg to make a cognitive decision followed by a motor one. considering lateral c ...202030627653
rescue of rhesus macaques from the lethality of aerosolized ricin toxin.ricin toxin (rt) ranks at the top of the list of bioweapons of concern to civilian and military personnel alike, due to its high potential for morbidity and mortality after inhalation. in nonhuman primates, aerosolized ricin triggers severe acute respiratory distress characterized by perivascular and alveolar edema, neutrophilic infiltration, and severe necrotizing bronchiolitis and alveolitis. there are currently no approved countermeasures for ricin intoxication. here, we report the therapeuti ...201930626745
rhesus macaque rhadinovirus encodes a viral interferon regulatory factor to disrupt promyelocytic leukemia nuclear bodies and antagonize type i interferon signaling.interferon (ifn) production and the subsequent induction of ifn-stimulated genes (isgs) are highly effective innate strategies utilized by cells to protect against invading pathogens, including viruses. critical components involved in this innate process are promyelocytic leukemia nuclear bodies (pml-nbs), which are subnuclear structures required for the development of a robust ifn response. as such, pml-nbs serve as an important hurdle for viruses to overcome to successfully establish an infect ...201930626678
histopathological features of the development of intestine and mesenteric lymph node injury in a nonhuman primate model of partial-body irradiation with minimal bone marrow sparing.male rhesus macaques were subjected to partial-body irradiation at 10, 11, or 12 gy with 5% bone marrow protection. animals were euthanized when dictated by prospectively determined clinical parameters or at approximately 180 d following irradiation. histological sections of jejunum, colon, and mesenteric lymph node were stained with hematoxylin and eosin as well as a battery of histochemical and immunohistochemical stains. the immediate postirradiation histopathological alterations in the jejun ...201930624355
the gastrointestinal subsyndrome of the acute radiation syndrome in rhesus macaques: a systematic review of the lethal dose-response relationship with and without medical management.well-characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the us food and drug administration's animal rule. development of a model for the gastrointestinal acute radiation syndrome requires knowledge of the radiation dose-response relationship and time course of mortality and morbidity across the acute and prolonged gastrointestinal radiation syndrome. the nonhuman ...201930624353
radiation nephropathy in a nonhuman primate model of partial-body irradiation with minimal bone marrow sparing-part 2: histopathology, mediators, and mechanisms.male rhesus macaques were subjected to partial-body irradiation at 10, 11, or 12 gy with 5% bone marrow protection. animals were euthanized when dictated by prospectively determined clinical parameters or at approximately 180 d following irradiation. histological sections of kidney were stained with hematoxylin and eosin as well as a battery of histochemical and immunohistochemical stains. histopathological alterations were centered on glomerular changes and fibrosis of glomeruli and the interst ...201930624348
plasma lipidomic signatures of spontaneous obese rhesus monkeys.obesity plays crucial roles in the pathogenesis of metabolic diseases such as hyperlipidemia, nonalcoholic fatty liver disease (nafld), and type 2 diabetes (t2d). the underlying mechanisms linking obesity to metabolic diseases are still less understandable.201930621707
contrast sensitivity reveals an oculomotor strategy for temporally encoding space.the contrast sensitivity function (csf), how sensitivity varies with the frequency of the stimulus, is a fundamental assessment of visual performance. the csf is generally assumed to be determined by low-level sensory processes. however, the spatial sensitivities of neurons in the early visual pathways, as measured in experiments with immobilized eyes, diverge from psychophysical csf measurements in primates. under natural viewing conditions, as in typical psychophysical measurements, humans con ...201930620333
rotavirus is associated with decompensated diarrhea among young rhesus macaques (macaca mulatta).diarrhea with secondary decompensation is the main cause of morbidity and mortality in captive young rhesus macaque (macaca mulatta) colonies. approximately 25% of diarrhea cases with secondary decompensation are considered to be idiopathic chronic diarrhea. the purpose of this study was to investigate the suspected but not systematically examined association between rotavirus infection and diarrhea with secondary decompensation among young rhesus macaques at the california national primate rese ...201930620103
varicella virus-host interactions during latency and reactivation: lessons from simian varicella virus.varicella zoster virus (vzv) is a neurotropic alphaherpesvirus and the causative agent of varicella (chickenpox) in humans. following primary infection, vzv establishes latency in the sensory ganglia and can reactivate to cause herpes zoster, more commonly known as shingles, which causes significant morbidity, and on rare occasions mortality, in the elderly. because vzv infection is highly restricted to humans, the development of a reliable animal model has been challenging, and our understandin ...201830619226
anti-hypercholesterolemic effects and a good safety profile of scm-198 in animals: from apoe knockout mice to rhesus monkeys.although several lipid-lowering agents have been introduced for the treatment of atherosclerosis (as), currently marketed medications have not solved the problem completely. this study aims to investigate the effects of leonurine (scm-198) on dyslipidemia in mammals with apoe knockout (apoe-/-) mice, new zealand white rabbits and senile rhesus monkeys fed with high fat diet were dosed daily with leonurine or atorvastatin. the serum total cholesterol (tc), triglyceride (tg), low density lipoprote ...201830618759
a method to investigate astrocyte and microglial morphological changes in the aging brain of the rhesus macaque.with a rapidly aging population, studies of neuroinflammation and degeneration associated with eugeric aging are becoming critical. using the unique archive at the tulane national primate research center as a resource, we have developed tools to quantify morphological changes in astrocytes and microglia across the life span of monkeys. this method can be used for morphometric studies of multiple parameters simultaneously in an unbiased manner.201930617987
modulation of gpr39, a g-protein coupled receptor associated with alcohol use in non-human primates, curbs ethanol intake in mice.alcohol use disorder (aud) is a chronic condition with devastating health and socioeconomic effects. still, pharmacotherapies to treat aud are scarce. in a prior study aimed at identifying novel aud therapeutic targets, we investigated the dna methylome of the nucleus accumbens core (nacc) of rhesus macaques after chronic alcohol use. the g-protein coupled receptor 39 (gpr39) gene was hypermethylated and its expression downregulated in heavy alcohol drinking macaques. gpr39 encodes a zn2+-bindin ...201930610192
frequency shifts and depth dependence of premotor beta band activity during perceptual decision-making.neural activity in the premotor and motor cortices shows prominent structure in the beta frequency range (13-30 hz). currently, the behavioral relevance of this beta band activity (bba) is debated. the underlying source of motor bba and how it changes as a function of cortical depth are also not completely understood. here, we addressed these unresolved questions by investigating bba recorded using laminar electrodes in the dorsal premotor cortex of 2 male rhesus macaques performing a visual rea ...201930606756
sevoflurane exposure has minimal effect on cognitive function and does not alter microglial activation in adult monkeys.postoperative cognitive dysfunction (pocd) is a complication that has been observed in a subset of adult and elderly individuals after general anesthesia and surgery. although the pathogenesis of pocd is largely unknown, a growing body of preclinical research suggests that pocd may be caused by general anesthesia. a significant amount of research has examined the effects of general anesthesia on neurocognitive function in rodents, yet no studies have assessed the adverse effects of general anest ...201930605762
the concentration of copper, zinc, manganese and selenium in the serum and liver of goats with caprine arthritis-encephalitis.concentrations of four trace elements, copper (cu), zinc (zn), manganese (mn) and seleni- um (se), have thus far proven to be affected by lentiviral infections in people and rhesus monkeys. as small ruminant lentivirus (srlv) infection is responsible for one of the most important goat diseases, caprine arthritis-encephalitis (cae), we evaluated serum and liver concentrations of cu, zn, mn, se in goats severely affected by symptomatic cae and compared them with litera- ture reference intervals. s ...201830605285
induction of rhesus keratinocytes into functional ameloblasts by mouse embryonic dental mesenchyme.fast progresses in stem cell-based tooth tissue engineering have been achieved in recent years in several animal models including the mouse, rat, dog, and pig. moreover, various postnatal mesenchymal stem cells of dental origin have been isolated and shown capable of differentiating into odontoblasts and generating dentin. meanwhile, human keratinocyte stem/progenitor cells, gingival epithelial cells, and even ipsc-derived epithelium have been demonstrated to be able to differentiate into functi ...201830603545
functionally defined white matter of the macaque monkey brain reveals a dorso-ventral attention network.classical studies of attention have identified areas of parietal and frontal cortex as sources of attentional control. recently, a ventral region in the macaque temporal cortex, the posterior infero-temporal dorsal area pitd, has been suggested as a third attentional control area. this raises the question of whether and how spatially distant areas coordinate a joint focus of attention. here we tested the hypothesis that parieto-frontal attention areas and pitd are directly interconnected. by com ...201930601116
aging affects correlation within the v1 neuronal population in rhesus monkeys.visual function declines with age. this deterioration results not only from changes in the optical system but also from the functional degradation of the central visual cortex. although numerous studies have explored the mechanisms of age-related influences on vision, they have failed to acknowledge the significance of neuronal correlation in dysfunction of the visual cortex. previous research has focused on the functional degradation of individual neurons, with age-induced changes in correlatio ...201930599290
modeling the measles paradox reveals the importance of cellular immunity in regulating viral clearance.measles virus (mv) is a highly contagious member of the morbillivirus genus that remains a major cause of childhood mortality worldwide. although infection induces a strong mv-specific immune response that clears viral load and confers lifelong immunity, transient immunosuppression can also occur, leaving the host vulnerable to colonization from secondary pathogens. this apparent contradiction of viral clearance in the face of immunosuppression underlies what is often referred to as the 'measles ...201830592772
ratio of the bronchial lumen to pulmonary artery diameter in rhesus macaques (macaca mulatta) without clinical pulmonary disease.in human medicine, ct is widely used to detect changes in bronchial luminal diameter. the diameter of the artery that runs adjacent to the bronchus does not change dramatically along the airway path, such that this artery can be used as a reference to detect changes in the bronchial luminal diameter. the bronchoarterial ratio is increasingly used in veterinary medicine for the detection of lower airway diseases in animals. the purpose of this study was to establish the bronchoarterial ratio in r ...201930591089
gonadotrophin-mediated mirna expression in testis at onset of puberty in rhesus monkey: predictions on regulation of thyroid hormone activity and dlk1-dio3 locus.molecular mechanisms responsible for the initiation of primate spermatogenesis remain poorly characterized. previously, 48 h stimulation of the testes of three juvenile rhesus monkeys with pulsatile lh and fsh resulted in down-regulation of a cohort of genes recognized to favor spermatogonia stem cell renewal. this change in genetic landscape occurred in concert with amplification of sertoli cell proliferation and the commitment of undifferentiated spermatogonia to differentiate. in this report, ...201930590698
a likelihood approach to testing hypotheses on the co-evolution of epigenome and genome.central questions to epigenome evolution include whether interspecies changes of histone modifications are independent of evolutionary changes of dna, and if there is dependence whether they depend on any specific types of dna sequence changes. here, we present a likelihood approach for testing hypotheses on the co-evolution of genome and histone modifications. the gist of this approach is to convert evolutionary biology hypotheses into probabilistic forms, by explicitly expressing the joint pro ...201830586383
testosterone augments fsh signaling by upregulating the expression and activity of fsh-receptor in pubertal primate sertoli cells.the synergistic actions of testosterone (t) and fsh via testicular sertoli cells (sc) regulate male fertility. we have previously reported that the actions of these hormones (t and fsh) in infant monkey testes are restricted only to the expansion of sc and spermatogonial cells. the robust differentiation of male germ cells (gc) occurs after pubertal maturation of testis. the present study was aimed to investigate the molecular basis of the synergy between t and fsh action in pubertal primate (ma ...201930579957
prevention of sivmac251 reservoir seeding in rhesus monkeys by early antiretroviral therapy.the precise time when the viral reservoir is seeded during acute hiv-1 infection remains unclear. we previously demonstrated that the viral reservoir was seeded by day 3 following sivmac251 infection in rhesus monkeys. here we report the impact of initiating art on day 0 (6 h), 1, 2, or 3 following intrarectal sivmac251 infection in 20 rhesus monkeys (n = 5/group). after 6 months of daily suppressive art, antiretroviral drugs were discontinued, and viral rebound was monitored. 0% (0 of 5), 20% ( ...201830575753
the scalar property during isochronous tapping is disrupted by a d2-like agonist in the nonhuman primate.dopamine, and specifically the d2 system, has been implicated in timing tasks where the absolute duration of individual time intervals is encoded discretely, yet the role of d2 during beat perception and entrainment remains largely unknown. in this type of timing, a beat is perceived as the pulse that marks equally spaced points in time and, once extracted, produces the tendency in humans to entrain or synchronize their movements to it. hence, beat-based timing is crucial for musical execution. ...201930575431
dynamic changes in insulin and glucagon during disease progression in rhesus monkeys with obesity-related type 2 diabetes mellitus.to investigate the progression of obesity-related type 2 diabetes mellitus (t2dm) in rhesus monkeys, especially dynamic changes in insulin and glucagon.201930575251
optic nerve degeneration and reduced contrast sensitivity due to folic acid deficiency: a behavioral and electrophysiological study in rhesus monkeys.the purpose of the research was to elucidate the role of folic acid (b9) deficiency in the development of nutritional optic neuritis and to characterize the neurophysiological consequences of optic nerve degeneration in the cortical visual system.201830574659
neural coding of intended and executed grasp force in macaque areas aip, f5, and m1.considerable progress has been made over the last decades in characterizing the neural coding of hand shape, but grasp force has been largely ignored. we trained two macaque monkeys (macaca mulatta) on a delayed grasping task where grip type and grip force were instructed. neural population activity was recorded from areas relevant for grasp planning and execution: the anterior intraparietal area (aip), f5 of the ventral premotor cortex, and the hand area of the primary motor cortex (m1). grasp ...201830573765
the caudal part of putamen represents the historical object value information.the basal ganglia, especially the circuits originating from the putamen, are essential for controlling normal body movements. notably, the putamen receives inputs not only from motor cortical areas but also from multiple sensory cortices. however, how these sensory signals are processed in the putamen remains unclear. we recorded the activity of tentative medium spiny neurons in the caudal part of the putamen when the monkey viewed many fractal objects. we found many neurons that responded to th ...201930573645
'artiphysiology' reveals v4-like shape tuning in a deep network trained for image classification.deep networks provide a potentially rich interconnection between neuroscientific and artificial approaches to understanding visual intelligence, but the relationship between artificial and neural representations of complex visual form has not been elucidated at the level of single-unit selectivity. taking the approach of an electrophysiologist to characterizing single cnn units, we found many units exhibit translation-invariant boundary curvature selectivity approaching that of exemplar neurons ...201830570484
neonatal rhesus monkeys as an animal model for rotavirus infection.to establish a rotavirus (rv)-induced diarrhea model using rv sa11 in neonatal rhesus monkeys for the study of the pathogenic and immune mechanisms of rv infection and evaluation of candidate vaccines.201830568388
concurrent influence of top-down and bottom-up inputs on correlated activity of macaque extrastriate neurons.correlations between neurons can profoundly impact the information encoding capacity of a neural population. we studied how maintenance of visuospatial information affects correlated activity in visual areas by recording the activity of neurons in visual area mt of rhesus macaques during a spatial working memory task. correlations between mt neurons depended upon the spatial overlap between neurons' receptive fields. these correlations were influenced by the content of working memory, but the ef ...201830568166
comparative analysis of gammaherpesvirus circular rna repertoires: conserved and unique viral circular rnas.recent studies have identified circular rnas (circrnas) expressed from the epstein-barr virus (ebv) and kaposi's sarcoma herpesvirus (kshv) human dna tumor viruses. to gain initial insights into the potential relevance of ebv circrnas in virus biology and disease, we assessed the circrnaome of the interspecies homologue rhesus macaque lymphocryptovirus (rlcv) in a naturally occurring lymphoma from a simian immunodeficiency virus (siv)-infected rhesus macaque. this analysis revealed rlcv ortholog ...201930567979
conservation implications of primate trade in china over 18 years based on web news reports of confiscations.primate species have been increasingly threatened by legal and illegal trade in china, mainly for biomedical research or as pets and traditional medicine, yet most reports on trade from china regard international trade. to assess a proxy for amount of national primate trades, we quantified the number of reports of native primate species featuring in unique web news reports from 2000 to 2017, including accuracy of their identification, location where they were confiscated or rescued, and their co ...201830564524
extensive alternative splicing of kir transcripts.the killer-cell ig-like receptors (kir) form a multigene entity involved in modulating immune responses through interactions with mhc class i molecules. the complexity of the kir cluster is reflected by, for instance, abundant levels of allelic polymorphism, gene copy number variation, and stochastic expression profiles. the current transcriptome study involving human and macaque families demonstrates that kir family members are also subjected to differential levels of alternative splicing, and ...201830564240
the foxk1-ccdc43 axis promotes the invasion and metastasis of colorectal cancer cells.the ccdc43 gene is conserved in human, rhesus monkey, mouse and zebrafish. bioinformatics studies have demonstrated the abnormal expression of ccdc43 gene in colorectal cancer (crc). however, the role and molecular mechanism of ccdc43 in crc remain unknown.201830562730
human cytomegalovirus-vectored vaccines against hiv.cmv-vectored vaccines expressing siv antigens have mediated unprecedented levels of virus control following siv challenge in rhesus macaques. remarkably, protection was dependent on nonclassically restricted cd8 t cells. here, we review the latest research in cmv-vectored vaccines in both humans and nonhuman primates as well as recent advances in the understanding nonclassically restricted t cells, particularly mhc-e-restricted cd8 t cells.201930562176
neuronal variability and tuning are balanced to optimize naturalistic self-motion coding in primate vestibular pathways.it is commonly assumed that the brain's neural coding strategies are adapted to the statistics of natural stimuli. specifically, to maximize information transmission, a sensory neuron's tuning function should effectively oppose the decaying stimulus spectral power, such that the neural response is temporally decorrelated (i.e. 'whitened'). however, theory predicts that the structure of neuronal variability also plays an essential role in determining how coding is optimized. here, we provide expe ...201830561328
novel spheroid reservoir bioartificial liver improves survival of nonhuman primates in a toxin-induced model of acute liver failure.this study aims to evaluate the effectiveness and safety of the spheroid reservoir bioartificial liver (srbal) with porcine hepatocyte organoids in a preclinical nonhuman primate model of acute liver failure (alf). methods: thirty healthy rhesus monkeys were infused with α-amanitin and lipopolysaccharide and randomized into five groups (alf alone control group; sham no-cell srbal treatment group; groups a, b and c with srbal treatment started at 12 h, 24 h and 36 h after induction of alf, respec ...201830555564
synaptic adaptations in the central amygdala and hypothalamic paraventricular nucleus associated with protracted ethanol abstinence in male rhesus monkeys.alcohol use disorder is a significant global burden. stress has been identified as an etiological factor in the initiation and continuation of ethanol consumption. understanding adaptations within stress circuitry is an important step toward novel treatment strategies. the effects of protracted abstinence following long-term ethanol self-administration on the central nucleus of the amygdala (cea) and the hypothalamic paraventricular nucleus (pvn) were evaluated in male rhesus monkeys. using whol ...201930555160
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