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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
increased 27-hydroxycholesterol production during luteolysis may mediate the progressive decline in progesterone secretion.does 27-hydroxycholesterol (27oh) actively facilitate the progression of luteolysis?201829177442
sex and rank affect how infant rhesus macaques look at faces.we investigated how differences in infant sex and mothers' dominance status affect infant rhesus macaques' (macaca mulatta) interest in visually exploring emotional facial expressions. thirty-eight infants were presented with animated avatars of macaque facial expressions during the first month of life. sons of high-ranking mothers looked more at faces, especially the eye region, than sons of low-ranking mothers, but no difference in looking duration was found for daughters. males looked signifi ...201829165801
generation of complement molecular complex c5b-9 (c5b-9) in response to poly-traumatic hemorrhagic shock and evaluation of c5 cleavage inhibitors in non-human primates.severe trauma initiates a systemic inflammatory cascade and that involves early activation of complement and cleavage of c5 into c5a (anaphylatoxin) and c5b (c5b-9 membrane attack complex). we examined activation of c5 in non-human primate (nhp) models of hemorrhagic shock. blood plasma concentrations of c5b-9 were significantly increased in nhps in response to hemorrhage alone and were further increased with the addition of tissue trauma. the onset of increased c5 cleavage was accelerated in nh ...201829156357
the efficacy, biodistribution and safety of an inhibin dna vaccine delivered by attenuated salmonella choleraesuis.dna vaccines, the third-generation vaccines, were extensively studied. the attenuated salmonella choleraesuis (s. choleraesuis) was widely focused as a carrier to deliver dna vaccines in the chromosome-plasmid balanced-lethal system. the efficacy of inhibin dna vaccine delivered by attenuated s. choleraesuis was proved in mice and cows in our previous studies. in this study, the efficacy of inhibin dna vaccine was confirmed in rhesus monkeys. to further study the biodistribution and safety, the ...201829205848
therapeutic targeting of membrane-associated grp78 in leukemia and lymphoma: preclinical efficacy in vitro and formal toxicity study of bmtp-78 in rodents and primates.translation of drug candidates into clinical settings requires demonstration of preclinical efficacy and formal toxicology analysis for filling an investigational new drug (ind) application with the us food and drug administration (fda). here, we investigate the membrane-associated glucose response protein 78 (grp78) as a therapeutic target in leukemia and lymphoma. we evaluated the efficacy of the grp78-targeted proapoptotic drug bone metastasis targeting peptidomimetic 78 (bmtp-78), a member o ...201829205207
chronic δ9-thc in rhesus monkeys: effects on cognitive performance and dopamine d2/d3 receptor availability.cannabis-related impairments to cognitive function may represent novel therapeutic targets for cannabis-use disorder, although the nature, persistence, and reversibility of such deficits remain unclear. adult male rhesus monkeys (n = 6) responded in the morning on tasks designed to assess different cognitive domains using the cambridge neuropsychological test automated battery (cantab) touchscreens followed by responding maintained under a fixed-ratio (fr) 10 schedule of food presentation in dif ...201829203575
rhesus monkeys (macaca mulatta) remember agency information from past events and integrate this knowledge with spatial and temporal features in working memory.the purpose of the present study was to examine whether rhesus monkeys remember information about their own agency-along with spatial, temporal and contextual properties-from a previously experienced event. in experiment 1, rhesus monkeys (n = 4) used symbols to reliably indicate whether they had performed or observed an event on a computer screen. in experiment 2, naïve and experienced monkeys (n = 8) reported agency information when stringent controls for perceptual and proprioceptive cues wer ...201829196909
integrin α4β7 blockade preferentially impacts ccr6+ lymphocyte subsets in blood and mucosal tissues of naive rhesus macaques.infusion of a simianized anti-α4β7 mab (rh-α4β7) just before and following siv infection protected rhesus macaques from developing aids and partially from vaginal siv acquisition. recently, short-term treatment with rh-α4β7 in combination with cart was found to lead to prolonged viral suppression after withdrawal of all therapeutic interventions. the humanized form of rh-α4β7, vedolizumab, is a highly effective treatment for inflammatory bowel disease. to clarify the mechanism of action of rh-α4 ...201829196458
chronic hyperandrogenemia in the presence and absence of a western-style diet impairs ovarian and uterine structure/function in young adult rhesus monkeys.does chronic hyperandrogenemia beginning at menarche, in the absence and presence of a western-style diet (wsd), alter ovarian and uterine structure-function in young adult rhesus monkeys?201829190387
memory t cells are significantly increased in rejected liver allografts of rhesus monkeys.the rhesus monkey (rm) is an excellent preclinical model in kidney, heart, and islet transplantation that has provided the basis for new immunosuppressive protocols for clinical studies. however, there remain relatively few liver transplantation (lt) models in nonhuman primates. in this study, we analyzed the immune cell populations of peripheral blood mononuclear cells (pbmcs) and secondary lymphoid organs along with livers of normal rms and compared them with those of rejected lt recipients fo ...201829150986
electrical activity of sensory pathways in female and male geriatric rhesus monkeys (macaca mulatta), and its relation to oxidative stress.synapses loss during aging has been related to decreased neuronal excitability and reduced electrophysiological activity in the nervous system, as well as to increased brain damage. those physiological and biochemical alterations have been related to the oxidative stress increase associated with old age. the main substrate of lipid peroxidation (lpx) in the central and peripheral nervous systems are the myelin sheaths, and their damage generates a delayed nerve conduction velocity. however, stud ...201829146475
standardized automated training of rhesus monkeys for neuroscience research in their housing environment.teaching nonhuman primates the complex cognitive behavioral tasks that are central to cognitive neuroscience research is an essential and challenging endeavor. it is crucial for the scientific success that the animals learn to interpret the often complex task rules and reliably and enduringly act accordingly. to achieve consistent behavior and comparable learning histories across animals, it is desirable to standardize training protocols. automatizing the training can significantly reduce the ti ...201829142094
geographic clonal tracking in macaques provides insights into hspc migration and differentiation.the geographic distribution of hematopoiesis at a clonal level is of interest in understanding how hematopoietic stem and progenitor cells (hspcs) and their progeny interact with bone marrow (bm) niches during regeneration. we tagged rhesus macaque autologous hspcs with genetic barcodes, allowing clonal tracking over time and space after transplantation. we found marked geographic segregation of cd34+ hspcs for at least 6 mo posttransplantation, followed by very gradual clonal mixing at differen ...201829141868
the bat as a new model of cortical development.the organization of the mammalian cerebral cortex shares fundamental features across species. however, while the radial thickness of grey matter varies within one order of magnitude, the tangential spread of the cortical sheet varies by orders of magnitude across species. a broader sample of model species may provide additional clues for understanding mechanisms that drive cortical expansion. here, we introduce the bat carollia perspicillata as a new model species. the brain of c. perspicillata ...201829136119
the use of desflurane for neurosurgical procedures in rhesus macaque ( macaca mulatta).volatile agents are widely used to anaesthetise laboratory non-human primates as they allow a rapid induction and recovery as well as an easy adjustment of the anaesthesia plan. desflurane is currently the volatile agent with the lowest solubility in blood, and hence enables the most rapid onset of anaesthesia and most rapid recovery. this study aimed to investigate the suitability of desflurane for maintenance of general anaesthesia in rhesus macaques undergoing elective experimental neurosurge ...201829132231
the effect of epitope-based ligation of icam-1 on survival and retransplantation of pig islets in nonhuman primates.pig islet xenotransplantation is a promising alternative to allogeneic transplantation. however, the wide immunologic barrier between pigs and primates limits the long-term survival of the graft. md-3, a novel monoclonal antibody (mab) that recognizes a particular epitope of human icam-1, can render t cells tolerant to a xenograft by arresting dendritic cell maturation. we report the long-term survival of adult wild-type pig islets and successful retransplantation in nonhuman primates using a pr ...201829131413
progress in developing transgenic monkey model for huntington's disease.huntington's disease (hd) is a complex neurodegenerative disorder that has no cure. although treatments can often be given to relieve symptoms, the neuropathology associated with hd cannot be stopped or reversed. hd is characterized by degeneration of the striatum and associated pathways that leads to impairment in motor and cognitive functions as well as psychiatric disturbances. although cell and rodent models for hd exist, longitudinal study in a transgenic hd nonhuman primate (i.e., rhesus m ...201829127484
preclinical profile of a dopamine d1 potentiator suggests therapeutic utility in neurological and psychiatric disorders.detq, an allosteric potentiator of the dopamine d1 receptor, was tested in therapeutic models that were known to respond to d1 agonists. because of a species difference in affinity for detq, all rodent experiments used transgenic mice expressing the human d1 receptor (hd1 mice). when given alone, detq reversed the locomotor depression caused by a low dose of reserpine. detq also acted synergistically with l-dopa to reverse the strong hypokinesia seen with a higher dose of reserpine. these result ...201829102759
ontogeny of hallucal metatarsal rigidity and shape in the rhesus monkey (macaca mulatta) and chimpanzee (pan troglodytes).life history variables including the timing of locomotor independence, along with changes in preferred locomotor behaviors and substrate use during development, influence how primates use their feet throughout ontogeny. changes in foot function during development, in particular the nature of how the hallux is used in grasping, can lead to different structural changes in foot bones. to test this hypothesis, metatarsal midshaft rigidity [estimated from the polar second moment of area (j) scaled to ...201829098692
hypo-osmolar formulation of tenofovir (tfv) enema promotes uptake and metabolism of tfv in tissues, leading to prevention of shiv/siv infection.oral preexposure prophylaxis (prep) has been approved for prophylaxis of hiv-1 transmission but is associated with high costs and issues of adherence. protection from anal transmission of hiv using topical microbicides and methods congruent with sexual behavior offers the promise of improved adherence. we compared the pharmacokinetics (pk) and ex vivo efficacy of iso-osmolar (iosm) and hypo-osmolar (hosm) rectal enema formulations of tenofovir (tfv) in rhesus macaques. single-dose pk of iosm or ...201829084755
comparative analysis of microbial sensing molecules in mucosal tissues with aging.host-bacterial interactions at mucosal surfaces require recognition of the bacteria by host cells enabling targeted responses to maintain tissue homeostasis. it is now well recognized that an array of host-derived pattern recognition receptors (prrs), both cell-bound and soluble, are critical to innate immune engagement of microbes via microbial-associated molecular patterns (mamp). this report describes the use of a nonhuman primate model to evaluate changes in the expression of these sensing m ...201829066255
low inherent sensitivity to the intoxicating effects of ethanol in rhesus monkeys with low csf concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid.type 2 alcoholism is characterized by low serotonin system functioning and has a high degree of heritability, with offspring of alcoholics often showing a reduced response to the intoxicating effects of ethanol (etoh), which is thought to be marker for future alcohol use disorders (auds). as such, an important aim of studies investigating the origins of auds is to understand the relationship between serotonin system functioning and level of intoxication. a nonhuman primate model was used to eval ...201829125625
pharmacokinetics of a long-acting nanoformulated dolutegravir prodrug in rhesus macaques.a nanoformulated myristoylated dolutegravir prodrug (nmdtg) was prepared using good laboratory practice protocols. intramuscular injection of nmdtg (118 ± 8 mg/ml, 25.5 mg of dtg equivalents/kg of body weight) to three rhesus macaques led to plasma dtg levels of 86 ± 12 and 28 ± 1 ng/ml on days 35 and 91, respectively. the nmdtg platform showed no significant adverse events. further modification may further extend the drug's apparent half-life for human use.201829061742
pre-clinical results in pig-to-non-human primate islet xenotransplantation using anti-cd40 antibody (2c10r4)-based immunosuppression.islet transplantation is an effective therapy for selected patients with type 1 diabetes with labile glycemic control and hypoglycemic unawareness, but donor organs are limited. islet xenotransplantation using porcine islets will potentially solve this problem. although successful proof of concept studies using clinically inapplicable anti-cd154 monoclonal antibody (mab) in pig-to-non-human primate (nhp) islet xenotransplantation has been demonstrated by several groups worldwide, potentially cli ...201829057561
evaluation of prolonged administration of isoflurane on cerebral blood flow and default mode network in macaque monkeys anesthetized with different maintenance doses.isoflurane is a commonly used volatile anesthetic agent in clinical anesthesia and biomedical research. prior study suggested the cerebral blood flow (cbf) and default mode network (dmn) could be changed after prolonged administration of isoflurane. the normal maintenance doses of isoflurane may vary from light (∼0.75%) to deep (∼1.5 or 2%) anesthesia. however, it is not clear how the duration effects are affected by the altered doses. the present study is aimed to examine if the duration effect ...201829055725
effects of a bone graft substitute consisting of porous gradient ha/zro2 and gelatin/chitosan slow-release hydrogel containing bmp-2 and bmscs on lumbar vertebral defect repair in rhesus monkey.dense biomaterial plays an important role in bone replacement. however, it fails to induce bone cell migration into graft material. in the present study, a novel bone graft substitute (bgs) consisting of porous gradient hydroxyapatite/zirconia composite (pghc) and gelatin/chitosan slow-release hydrogel containing bone morphogenetic protein 2 and bone mesenchymal stem cells was designed and prepared to repair lumbar vertebral defects. the morphological characteristics of the bgs evaluated by a sc ...201829055138
effect of repeated abstinence on chronic ethanol self-administration in the rhesus monkey.abstinence-based approaches to treating alcohol use disorder (aud) are highly prevalent, but abstinence from chronic drinking may exacerbate subsequent levels of alcohol intake in relapse.201829051997
what do monkeys know about others' knowledge?recently, comparative psychologists have suggested that primates represent others' knowledge states. evidence for this claim comes from studies demonstrating that primates expect others to maintain representations of objects when those objects are not currently visible. however, little work has explored whether nonhuman primates expect others to share the more sophisticated kinds of object knowledge that they themselves possess. we therefore investigated whether primates attribute to others know ...201829040907
serial decision-making in monkeys during an oculomotor task.much of everyday behavior involves serial decision-making, in which the outcome of 1 choice affects another. an example is setting rules for oneself: choosing a behavioral rule guides appropriate choices in the future. how the brain links decisions across time is poorly understood. neural mechanisms could be studied in monkeys, as it is known that they can select and use behavioral rules, but existing psychophysical paradigms are poorly suited for the constraints of neurophysiology. therefore, w ...201829035065
prepulse inhibition of auditory cortical responses in the caudolateral superior temporal gyrus in macaca mulatta.prepulse inhibition (ppi) refers to a decreased response to a startling stimulus when another weaker stimulus precedes it. most ppi studies have focused on the physiological startle reflex and fewer have reported the ppi of cortical responses. we recorded local field potentials (lfps) in four monkeys and investigated whether the ppi of auditory cortical responses (alpha, beta, and gamma oscillations and evoked potentials) can be demonstrated in the caudolateral belt of the superior temporal gyru ...201829022224
objectively measuring effects of electro-acupuncture in parkinsonian rhesus monkeys.acupuncture has increasingly been used as an alternative therapy for treatment of parkinson's disease (pd). however, the efficacy of acupunture for pd still remains unclear. the present study was designed to objectively and safely monitor anti-parkinsonian effects of electroacupuncture (ea) and brain activity in nonhuman primates modeling human pd. six middle-aged rhesus monkeys were extensively studied by a computerized behavioral testing battery and by pharmacological mri (phmri) scans with sp ...201829017909
the search for a subtype-selective pet imaging agent for the gabaa receptor complex: evaluation of the radiotracer [11c]ado in nonhuman primates.the myriad physiological functions of γ-amino butyric acid (gaba) are mediated by the gaba-benzodiazepine receptor complex comprising of the gabaa, gabab, and gabac groups. the various gabaa subunits with region-specific distributions in the brain subserve different functional and physiological roles. for example, the sedative and anticonvulsive effects of classical benzodiazepines are attributed to the α1 subunit, and the α2 and α3 subunits mediate the anxiolytic effect. to optimize pharmacothe ...201828929924
alpha male status and availability of conceptive females are associated with high glucocorticoid concentrations in high-ranking male rhesus macaques (macaca mulatta) during the mating season.the relationship between male mating opportunities, stress, and glucocorticoid concentrations is complicated by the fact that physiological stress and glucocorticoid concentrations can be influenced by dominance rank, group size, and the stability of the male dominance hierarchy, along with ecological factors. we studied the three highest-ranking males in nine different social groups within the same free-ranging population of rhesus macaques on cayo santiago, puerto rico, during the mating seaso ...201828954215
effects of morphine/cp55940 mixtures on an impulsive choice task in rhesus monkeys.µ-opioid receptor agonists are commonly used to treat pain despite their adverse effects. in preclinical studies, cannabinoid receptor agonists increase the potency of opioids for producing antinociceptive but not reinforcing effects. it is unknown whether other adverse effects of these drugs, such as impairment of complex behavior, are enhanced by their co-administration. this study characterized the effects of morphine (µ-opioid receptor agonist; 0.32-5.6 mg/kg, subcutaneously) and cp55940 (cb ...201828952976
previously unreported population of rhesus macaques macaca mulatta in chiang rai province, thailand: preliminary observations.efforts to document the distribution of macaques in thailand have been gradually improving over the past several years. here we add to the growing database with a summary of a previously unreported population of rhesus macaque macaca mulatta located at wat phrabuddhabat pa reau in chiang rai province. this work is part of an on-going study addressing human-primate conflict and coexistence in thailand. the wat covers an area of about 53 ha consisting of forest and ponds surrounded by an agricultu ...201831844847
comparative genome-wide survey of single nucleotide variation uncovers the genetic diversity and potential biomedical applications among six macaca species.macaca is of great importance in evolutionary and biomedical research. aiming at elucidating genetic diversity patterns and potential biomedical applications of macaques, we characterized single nucleotide variations (snvs) of six macaca species based on the reference genome of macaca mulatta. using eight whole-genome sequences, representing the most comprehensive genomic snv study in macaca to date, we focused on discovery and comparison of nonsynonymous snvs (nssnvs) with bioinformatic tools. ...201830314376
how we see the forest and the trees.signaling pathways in the retina help us see spatial detail in our visual world.201830311913
perceptual processing in the ventral visual stream requires area te but not rhinal cortex.there is an on-going debate over whether area te, or the anatomically adjacent rhinal cortex, is the final stage of visual object processing. both regions have been implicated in visual perception, but their involvement in non-perceptual functions, such as short-term memory, hinders clear-cut interpretation. here, using a two-interval forced choice task without a short-term memory demand, we find that after bilateral removal of area te, monkeys trained to categorize images based on perceptual si ...201830311907
cd8+ lymphocyte control of siv infection during antiretroviral therapy.cd8+ lymphocytes play an important role in suppressing in vivo viral replication in hiv infection. however, both the extent to which and the mechanisms by which cd8+ lymphocytes contribute to viral control are not completely understood. a recent experiment depleted cd8+ lymphocytes in simian immunodeficiency virus (siv)-infected rhesus macaques (rms) on antiretroviral treatment (art) to study the role of cd8+ lymphocytes. cd8+ lymphocytes depletion resulted in temporary plasma viremia in all stu ...201830308068
vista expression by microglia decreases during inflammation and is differentially regulated in cns diseases.v-type immunoglobulin domain-containing suppressor of t-cell activation (vista) is a negative checkpoint regulator (ncr) involved in inhibition of t cell-mediated immunity. expression changes of other ncrs (pd-1, pd-l1/l2, ctla-4) during inflammation of the central nervous system (cns) were previously demonstrated, but vista expression in the cns has not yet been explored. here, we report that in the human and mouse cns, vista is most abundantly expressed by microglia, and to lower levels by end ...201830306644
estrogens, aging, and working memory.working memory (wm) is a key process that is integral to many complex cognitive tasks, and it declines significantly with advancing age. this review will survey recent evidence supporting the idea that the functioning of the wm system in women is modulated by circulating estrogens.201830306352
lawful tracking of visual motion in humans, macaques, and marmosets in a naturalistic, continuous, and untrained behavioral context.much study of the visual system has focused on how humans and monkeys integrate moving stimuli over space and time. such assessments of spatiotemporal integration provide fundamental grounding for the interpretation of neurophysiological data, as well as how the resulting neural signals support perceptual decisions and behavior. however, the insights supported by classical characterizations of integration performed in humans and rhesus monkeys are potentially limited with respect to both general ...201830322919
single-cell quantitation of mrna and surface protein expression in simian immunodeficiency virus-infected cd4+ t cells isolated from rhesus macaques.single-cell analysis is an important tool for dissecting heterogeneous populations of cells. the identification and isolation of rare cells can be difficult. to overcome this challenge, a methodology combining indexed flow cytometry and high-throughput multiplexed quantitative polymerase chain reaction (qpcr) was developed. the objective was to identify and characterize simian immunodeficiency virus (siv)-infected cells present within rhesus macaques. through quantitation of surface protein by f ...201830320741
a comprehensive analysis of the t and b lymphocytes repertoire shaped by hiv vaccines.the exploitation of various human immunodeficiency virus type-1 (hiv-1) vaccines has posed great challenges for the researchers in precisely evaluating the vaccine-induced immune responses, however, the understanding of vaccination response suffers from the lack of unbiased characterization of the immune landscape. the rapid development of high throughput sequencing (hts) makes it possible to scrutinize the extremely complicated immunological responses during vaccination. in the current study, t ...201830319643
modeling large fluctuations of thousands of clones during hematopoiesis: the role of stem cell self-renewal and bursty progenitor dynamics in rhesus macaque.in a recent clone-tracking experiment, millions of uniquely tagged hematopoietic stem cells (hscs) and progenitor cells were autologously transplanted into rhesus macaques and peripheral blood containing thousands of tags were sampled and sequenced over 14 years to quantify the abundance of hundreds to thousands of tags or "clones." two major puzzles of the data have been observed: consistent differences and massive temporal fluctuations of clone populations. the large sample-to-sample variabili ...201830335762
impact of dengue virus serotype 2 strain diversity on serological immune responses to dengue.dengue is a mosquito-borne disease caused by four dengue virus serotypes (denv1-4) that are loosely categorized by sequence commonalities and antibody recognition profiles. the highly variable envelope protein (e) that is prominently displayed on the surface of denv is an essential component of vaccines currently under development, yet the impact of using single strains to represent each serotype in tetravalent vaccines has not been adequately studied. we synthesized chimeric e by replacing high ...201830347144
entrainment and maintenance of an internal metronome in supplementary motor area.to prepare timely motor actions, we constantly predict future events. regularly repeating events are often perceived as a rhythm to which we can readily synchronize our movements, just as in dancing to music. however, the neuronal mechanisms underlying the capacity to encode and maintain rhythms are not understood. we trained nonhuman primates to maintain the rhythm of a visual metronome of diverse tempos and recorded neural activity in the supplementary motor area (sma). sma exhibited rhythmic ...201830346275
a comparative analysis of gut microbiota disturbances in the gottingen minipig and rhesus macaque models of acute radiation syndrome following bioequivalent radiation exposures.in rodent studies, the gut microbiota has been implicated in facilitating both radioresistance, by protecting the epithelium from apoptotic responses and radiosensitivity, inducing endothelial apoptotic responses. despite the observation that large animal models, such as the chinese rhesus macaque and the gottingen minipig, demonstrate similarity to human physiologic responses to radiation, little is known about radiation-induced changes of the gut microbiome in these models. to compare the two ...201830343431
natural history of postnatal rhesus cytomegalovirus shedding by dams and acquisition by infant rhesus monkeys.human infants frequently acquire human cytomegalovirus (hcmv) through breastfeeding, resulting in persistent high-level viral shedding in saliva and urine and infectivity to others, including pregnant women. thus, vaccination to interrupt postnatal hcmv transmission is an attractive strategy to prevent hcmv spread and congenital infection. rhesus cmv (rhcmv) in nonhuman primates is a valuable model for the study of immune strategies to prevent cmv transmission. although rhesus monkeys typically ...201830356332
encoding of reward and decoding movement from the frontal eye field during smooth pursuit eye movements.expectation of reward potentiates sensorimotor transformations to drive vigorous movements. one of the main challenges in studying reward is to determine how representations of reward interact with the computations that drive behavior. we recorded activity in smooth pursuit neurons in the frontal eye field (fef) of two male rhesus monkeys while controlling the eye speed by manipulating either reward size or target speed. the neurons encoded the different reward conditions more strongly than the ...201830355635
selective loss of thin spines in area 7a of the primate intraparietal sulcus predicts age-related working memory impairment.brodmann area 7a of the parietal cortex is active during working memory tasks in humans and nonhuman primates, but the composition and density of dendritic spines in area 7a and their relevance both to working memory and cognitive aging remain unexplored. aged monkeys have impaired working memory, and we have previously shown that this age-induced cognitive impairment is partially mediated by a loss of thin spines in prefrontal cortex area 46, a critical area for working memory. because area 46 ...201830355632
functional mri in macaque monkeys during task switching.nonhuman primates have proven to be a valuable animal model for exploring neuronal mechanisms of cognitive control. one important aspect of executive control is the ability to switch from one task to another, and task-switching paradigms have often been used in human volunteers to uncover the underlying neuronal processes. to date, however, no study has investigated task-switching paradigms in nonhuman primates during functional magnetic resonance imaging (fmri). we trained two rhesus macaques t ...201830355629
diversity of macaque microbiota compared to the human counterparts.studies on the microbial communities in non-human primate hosts provide unique insights in both evolution and function of microbes related to human health and diseases. using 16s rrna gene amplicon profiling, we examined the oral, anal and vaginal microbiota in a group of non-captive rhesus macaques (n = 116) and compared the compositions with the healthy communities from human microbiome project. the macaque microbiota was dominated by bacteroidetes, firmicutes and proteobacteria; however, ther ...201830349024
microbial structure and function in infant and juvenile rhesus macaques are primarily affected by age, not vaccination status.although thimerosal, an ethylmercury-based preservative, has been removed from most pediatric vaccines in the united states, some multidose vaccines, such as influenza vaccines, still contain thimerosal. considering that a growing number of studies indicate involvement of the gut microbiome in infant immune development and vaccine responses, it is important to elucidate the impact of pediatric vaccines, including thimerosal-containing vaccines, on gut microbial structure and function. here, a no ...201830367140
evidence for persistence of the shiv reservoir early after mhc haploidentical hematopoietic stem cell transplantation.allogeneic transplantation (allo-hct) has led to the cure of hiv in one individual, raising the question of whether transplantation can eradicate the hiv reservoir. to test this, we here present a model of allo-hct in shiv-infected, cart-suppressed nonhuman primates. we infect rhesus macaques with shiv-1157ipd3n4, suppress them with cart, then transplant them using mhc-haploidentical allogeneic donors during continuous cart. transplant results in ~100% myeloid donor chimerism, and up to 100% t-c ...201830361514
neonatal hippocampal lesions facilitate biconditional contextual discrimination learning in monkeys.this study examined whether selective neonatal hippocampal lesions in monkeys (macaca mulatta), which left the surrounding cortical areas (parahippocampal cortex) intact, affect contextual learning and memory compared with controls. monkeys were tested with an automated touch-screen apparatus so that stimuli and contextual cues could be manipulated independently of one another. the data suggest that animals with neonatal hippocampal lesions have sparing of function with regard to contextual lear ...201830359064
donor spermatogenesis in de novo formed seminiferous tubules from transplanted testicular cells in rhesus monkey testis.can transplanted primate testicular cells form seminiferous tubules de novo, supporting complete spermatogenesis?201830358843
static magnetic fields reduce epileptiform activity in anesthetized rat and monkey.increasing evidence indicates that static magnetic fields (smf) reduce cortical activity in both human and animal models. the aim of this work was to investigate the effect of smf on epileptiform cortical activity, a condition related to an abnormal increase in neuronal excitability. the first experimental block included a pilocarpine rat model of epilepsy, in which a magnetic neodymium nickel-plated cylinder, a magnetic field of 0.5 t, or "sham" were placed over the skull. in the second experim ...201830375430
stage-specific modulation of antimüllerian hormone promotes primate follicular development and oocyte maturation in the matrix-free three-dimensional culture.to study whether follicular growth and oocyte maturation can be improved by antimüllerian hormone (amh) modulation at specific stages of follicular development.201830396561
presence of pig igg and igm in sera samples from baboons after an orthotopic liver xenotransplantation.the immunorejection in xenotransplantation has mostly been studied from the host's immune system activation point of view and there is very little information about the graft-vs-host reaction.201830401409
analysis of erythrocyte dynamics in rhesus macaque monkeys during infection with plasmodium cynomolgi.malaria is a major mosquito transmitted, blood-borne parasitic disease that afflicts humans. the disease causes anaemia and other clinical complications, which can lead to death. plasmodium vivax is known for its reticulocyte host cell specificity, but many gaps in disease details remain. much less is known about the closely related species, plasmodium cynomolgi, although it is naturally acquired and causes zoonotic malaria. here, a computational model is developed based on longitudinal analyses ...201830400896
tafenoquine and primaquine do not exhibit clinical neurologic signs associated with central nervous system lesions in the same manner as earlier 8-aminoquinolines.tafenoquine was recently approved for plasmodium vivax radical cure (krintafel™) and malaria prevention (arakoda™).201830400893
2-(4-methylsulfonylphenyl)pyrimidines as prospective radioligands for imaging cyclooxygenase-2 with pet-synthesis, triage, and radiolabeling.cyclooxygenase 2 (cox-2) is an inducible enzyme responsible for the conversion of arachidonic acid into the prostaglandins, pgg2 and pgh2. expression of this enzyme increases in inflammation. therefore, the development of probes for imaging cox-2 with positron emission tomography (pet) has gained interest because they could be useful for the study of inflammation in vivo, and for aiding anti-inflammatory drug development targeting cox-2. nonetheless, effective pet radioligands are still lacking. ...201830400142
hepatitis b vaccination using a dissolvable microneedle patch is immunogenic in mice and rhesus macaques.chronic hepatitis b virus infection remains a major global public health problem, accounting for about 887,000 deaths in 2015. perinatal and early childhood infections are strongly associated with developing chronic hepatitis b. adding a birth dose of the hepatitis b vaccine (hepb bd) to routine childhood vaccination can prevent over 85% of these infections. however, hepb bd coverage remains low in many global regions, with shortages of birth attendants trained to vaccinate and limited hepb bd s ...201830377659
[expression of b7 family co-inhibitory molecules in the establishment of pulmonary regional immunity].to identify the temporal-spatial expression of b7 family co-inhibitory molecules during lung development, and to explore the roles of b7 family co-inhibitory molecules in the developmental process of pulmonary regional immunity.201832677398
[the thyroid hormone receptor mediated luciferase reporter gene assays screening for edcs].this study in order to use report gene assay based on the thyroid hormone receptor (tr) α/β from human origin for screening endocrine disruptors chemicals (edcs), evaluating the thyroid hormone activity of bisphenol (bpa), 1-naphthaleny methyl carbamate and 1-naphthol (1-nap).201832677397
immune priming and long-term persistence of memory b cells after inactivated poliovirus vaccine in macaque models: support for at least 2 doses.as a risk-mitigation strategy to minimize paralytic polio following withdrawal of sabin type 2 from the oral poliovirus vaccine in april 2016, a single full dose or 2 fractional doses of inactivated poliovirus vaccine (ipv) are recommended. however, limited knowledge exists on long-term persistence of immune memory following 1- or 2-dose ipv schedules.201830376091
clonal expansion and compartmentalized maintenance of rhesus macaque nk cell subsets.natural killer (nk) cells recognize and eliminate infected and malignant cells. their life histories are poorly understood, particularly in humans, due to lack of informative models and endogenous clonal markers. here, we apply transplantation of barcoded rhesus macaque hematopoietic cells to interrogate the landscape of nk cell production, expansion, and life histories at a clonal level long term and after proliferative challenge. we identify oligoclonal populations of rhesus cd56-cd16+ nk cell ...201830389798
plasma derived exosomal biomarkers of exposure to ionizing radiation in nonhuman primates.exposure to ionizing radiation induces a cascade of molecular events that ultimately impact endogenous metabolism. qualitative and quantitative characterization of metabolomic profiles is a pragmatic approach to studying the risks of radiation exposure since it provides a phenotypic readout. studies were conducted in irradiated nonhuman primates (nhp) to investigate metabolic changes in plasma and plasma-derived exosomes. specifically, rhesus macaques (macaca mulatta) were exposed to cobalt-60 g ...201830388807
two herpesviral noncoding pan rnas are functionally homologous but do not associate with common chromatin loci.during lytic replication of kaposi's sarcoma-associated herpesvirus (kshv), a nuclear viral long noncoding rna known as pan rna becomes the most abundant polyadenylated transcript in the cell. knockout or knockdown of kshv pan rna results in loss of late lytic viral gene expression and, consequently, reduction of progeny virion release from the cell. here, we demonstrate that knockdown of pan rna from the related rhesus macaque rhadinovirus (rrv) phenocopies that of kshv pan rna. these two pan r ...201830383841
model of parafoveal chromatic and luminance temporal contrast sensitivity of humans and monkeys.rhesus monkeys are a valuable model for studies of primate visual contrast sensitivity. their visual systems are similar to that of humans, and they can be trained to perform detection tasks at threshold during neurophysiological recording. however, the stimulus dependence of rhesus monkey contrast sensitivity has not been well characterized. temporal frequency, color, and retinal eccentricity affect the contrast sensitivity of humans in reasonably well-understood ways. to ask whether these fact ...201830383213
high-throughput sequencing of putative novel micrornas in rhesus monkey peripheral blood mononuclear cells following ev71 and ca16 infection.enterovirus 71 (ev71) and coxsackievirus a16 (ca16) remain the major pathogens in hand, foot, and mouth disease (hfmd) cases, but the mechanisms of the different pathogeneses that follow ev71 and ca16 infection remain largely unknown.201830404089
optimization of preclinical metabolism for somatostatin receptor subtype 5-selective antagonists.a series of structurally diverse azaspirodecanone and spirooxazolidinone analogues were designed and synthesized as potent and selective somatostatin receptor subtype 5 (sstr5) antagonists. four optimized compounds each representing a subseries showed improvement in their metabolic stability and pharmacokinetic profiles compared to those of the original lead compound 1 while maintaining pharmacodynamic efficacy. the optimized cyclopropyl analogue 13 demonstrated efficacy in a mouse oral glucose ...201830429950
immune protection of siv challenge by pd-1 blockade during vaccination in rhesus monkeys.though immune correlates for protection are still under investigation, potent cytotoxic t lymphocyte responses are desirable for an ideal hiv-1 vaccine. pd-1 blockade enhances siv-specific cd8+ t cells. however, little information has been reported about how it affects the immunogenicity and protection of prophylactic siv vaccines in nonhuman primates. here, we show that pd-1 blockade during vaccination substantially improved protective efficacy in siv challenged macaques. the pd-1 pathway was b ...201830405615
cxcr4- and ccr5-tropic hiv-1 clones are both tractable to grow in rhesus macaques.a major issue for present hiv-1 research is to establish model systems that reflect or mimic viral replication and pathogenesis actually observed in infected humans. to this end, various strategies using macaques as infection targets have long been pursued. in particular, experimental infections of rhesus macaques by hiv-1 derivatives have been believed to be best suited, if practicable, for studies on interaction of hiv-1 and humans under various circumstances. recently, through in vitro geneti ...201830405570
construction of spatiotemporal infant cortical surface atlas of rhesus macaque.as a widely used animal model in mr imaging studies, rhesus macaque helps to better understand both normal and abnormal neural development in the human brain. however, the available adult macaque brain atlases are not well suitable for study of brain development at the early postnatal stage, since this stage undergoes dramatic changes in brain appearances and structures. building age matched atlases for this critical period is thus highly desirable yet still lacking. in this paper, we construct ...201830416671
comparison of small-incision femtosecond laser-assisted intrastromal keratoplasty and lamellar keratoplasty in rhesus monkeys using xenogenic corneal lamellae.in our previous study, both allogeneic and xenogeneic smallincision femtosecond laser-assisted intrastromal keratoplasty were demonstrated to be safe and effective surgeries. glycerol-dehydrated corneal lamellae could serve as alternative xenogeneic inlay grafts. however, these xenogeneic lamellae have not been explored in lamellar keratoplasty (lk). the immunoreactivity differences between corneal intrastromal xenotransplantation and xenogeneic lk have not been assessed.201830411683
estimation of neural inputs and detection of saccades and smooth pursuit eye movements by sparse bayesian learning.eye movements reveal a great wealth of information about the visual system and the brain. therefore, eye movements can serve as diagnostic markers for various neurological disorders. for an objective analysis, it is crucial to have an automatic and robust procedure to extract relevant eye movement parameters. an essential step towards this goal is to detect and separate different types of eye movements such as fixations, saccades and smooth pursuit. we have developed a model-based approach to pe ...201830440945
self-injurious behaviours in rhesus macaques: potential glial mechanisms.self-injurious behaviour (sib) can be classified as intentional, direct injuring of body tissue usually without suicidal intent. in its non-suicidal form it is commonly seen as a clinical sign of borderline personality disorder, autism, ptsd, depression, and anxiety affecting a wide range of ages and conditions. in rhesus macaques sib is most commonly manifested through hair plucking, self-biting, self-hitting, and head banging. sib in the form of self-biting is observed in approximately 5-15% o ...201830450801
effect of vasopressin v1b receptor blockade on activity of the hypothalamic-pituitary-adrenal axis in old monkeys with depression-like and anxious behavior subjected to stress or injected with vasopressin.the effect of selective antagonist of the arginine vasopressin (avp) v1b receptors on the secretion of acth and corticosteroids in response to insulin-induced hypoglycemia and injection of avp is studied in old macaca mulatta females with depression-like and anxious behavior. intravenous antagonist in a dose of 1.1-1.7 μg/kg inhibits the increase of acth concentration, induced by hypoglycemia or injection of avp. the degree of increase in the concentrations of hydrocortisone and dehydroepiandros ...201830450521
macro-connectomics and microstructure predict dynamic plasticity patterns in the non-human primate brain.the brain displays a remarkable ability to adapt following injury by altering its connections through neural plasticity. many of the biological mechanisms that underlie plasticity are known, but there is little knowledge as to when, or where in the brain plasticity will occur following injury. this knowledge could guide plasticity-promoting interventions and create a more accurate roadmap of the recovery process following injury. we causally investigated the time-course of plasticity after hippo ...201830462609
multisensory perception of looming and receding objects in human newborns.when newborns leave the enclosed spatial environment of the uterus and arrive in the outside world, they are faced with a new audiovisual environment of dynamic objects, actions and events both close to themselves and further away. one particular challenge concerns matching and making sense of the visual and auditory cues specifying object motion [1-5]. previous research shows that adults prioritise the integration of auditory and visual information indicating looming (for example [2]) and that ...201830458145
cortical decoding of individual finger group motions using refit kalman filter.objective: to date, many brain-machine interface (bmi) studies have developed decoding algorithms for neuroprostheses that provide users with precise control of upper arm reaches with some limited grasping capabilities. however, comparatively few have focused on quantifying the performance of precise finger control. here we expand upon this work by investigating online control of individual finger groups. approach: we have developed a novel training manipulandum for non-human primate (nhp) studi ...201830455621
which male and female characteristics influence the probability of extragroup paternities in rhesus macaques, macaca mulatta?extragroup paternity (egp) is found across a wide range of species and may entail reproductive benefits, but may also entail costs to both sexes. while population and group parameters affecting the degree of egps are relatively well established, less is known about the individual characteristics that make males and females engage in alternative reproductive tactics such as egp. applying a combination of long-term demographic and genetic data from the rhesus macaque population of cayo santiago (p ...201830455506
methylome profiling of healthy and central precocious puberty girls.recent studies demonstrated that changes in dna methylation (dnam) and inactivation of two imprinted genes (mkrn3 and dlk1) alter the onset of female puberty. we aimed to investigate the association of dnam profiling with the timing of human puberty analyzing the genome-wide dnam patterns of peripheral blood leukocytes from ten female patients with central precocious puberty (cpp) and 33 healthy girls (15 pre- and 18 post-pubertal). for this purpose, we performed comparisons between the groups: ...201830466473
2d/3d cmr tissue tracking versus cmr tagging in the assessment of spontaneous t2dm rhesus monkeys with isolated diastolic dysfunction.spontaneous t2dm in rhesus monkeys manifests as isolated diastolic dysfunction in the early stage of diabetic cardiomyopathy, similar to humans. myocardial deformation measurements have emerged as a superior way to measure left ventricular (lv) function in the early stage of cardiac dysfunction, making it possible to further evaluate early-stage lv dysfunction in spontaneous t2dm rhesus monkeys.201830477437
neural intrinsic timescales in the macaque dorsal premotor cortex predict the strength of spatial response coding.our brain continuously receives information over multiple timescales that are differently processed across areas. in this study, we investigated the intrinsic timescale of neurons in the dorsal premotor cortex (pmd) of two rhesus macaques while performing a non-match-to-goal task. the task rule was to reject the previously chosen target and select the alternative one. we defined the intrinsic timescale as the decay constant of the autocorrelation structure computed during a baseline period of th ...201830529952
longitudinal mri evaluation of ischemic stroke in the basal ganglia of a rhesus macaque (macaca mulatta) with seizures.an adult rhesus macaque developed seizures after the induction of ischemic stroke. initially, on the day of surgery, a focal ischemic lesion was present exclusively in the right caudate nucleus. by 48 h after stroke induction, the lesion had extended into the putamen, when a seizure was observed. our report highlights the temporal changes in infarction of unilateral basal ganglia after acute stroke and the accompanying clinical symptoms. this unusual case may provide additional information regar ...201830486918
neural dynamics at successive stages of the ventral visual stream are consistent with hierarchical error signals.ventral visual stream neural responses are dynamic, even for static image presentations. however, dynamical neural models of visual cortex are lacking as most progress has been made modeling static, time-averaged responses. here, we studied population neural dynamics during face detection across three cortical processing stages. remarkably,~30 milliseconds after the initially evoked response, we found that neurons in intermediate level areas decreased their responses to typical configurations of ...201830484773
estrogen alters the synaptic distribution of phospho-glun2b in the dorsolateral prefrontal cortex while promoting working memory in aged rhesus monkeys.age- and menopause-related deficits in working memory can be partially restored with estradiol replacement in women and female nonhuman primates. working memory is a cognitive function reliant on persistent firing of dorsolateral prefrontal cortex (dlpfc) neurons that requires the activation of glun2b-containing glutamate nmda receptors. we tested the hypothesis that the distribution of phospho-tyr1472-glun2b (pglun2b), a predominant form of glun2b seen at the synapse, is sensitive to aging or e ...201830482274
coping style and cortisol levels in infancy predict hair cortisol following new group formation in captive rhesus macaques (macaca mulatta).social instability in primate groups has been used as a model to understand how social stress affects human populations. while it is well established that individual cercopithecines have different temperaments or personalities, little is known about how temperament mediates the experience of social instability in large, naturalistic groups. here, we report findings from a study tracking a newly formed group of captive rhesus macaques (macaca mulatta). we examine whether inter-individual differen ...201830480316
genetic and environmental factors in the intergenerational transmission of maternal care in rhesus macaques: preliminary findings.early life experiences reorganize the brain and behavior of the developing infant, often with lifelong consequences. there is perhaps no more potent developmental influence than the quality of parental care: it is an experience common to all mammals, and its effects have been observed across species. the effects of parental care can be particularly difficult to abolish, as levels of care are often perpetuated across generations. however, genetic relatedness between parents can obscure the true m ...201830512216
hiv-1 t cell epitopes targeted to rhesus macaque cd40 and dcir: a comparative study of prototype dendritic cell targeting therapeutic vaccine candidates.hiv-1 infection can be controlled by anti-retroviral drug therapy, but this is a lifetime treatment and the virus remains latent and rapidly rebounds if therapy is stopped. hiv-1-infected individuals under this drug regimen have increased rates of cancers, cardiovascular diseases, and autoimmunity due to compromised immunity. a therapeutic vaccine boosting cellular immunity against hiv-1 is therefore desirable and, possibly combined with other immune modulating agents, could obviate the need for ...201830500852
vitamin d3 regulates follicular development and intrafollicular vitamin d biosynthesis and signaling in the primate ovary.there is an increasing recognition that vitamin d plays important roles in female reproduction. recent studies demonstrated that 1α,25-dihydroxyvitamin d3 (vd3), the biologically active form of vitamin d, improved ovarian follicle survival and growth in vitro. therefore, we investigated the direct effects of vd3 at the specific preantral and antral stages of follicular development, and tested the hypothesis that vitamin d receptor (vdr) and enzymes critical for vitamin d biosynthesis are express ...201830487754
nonverbal working memory for novel images in rhesus monkeys.human working memory is greatly facilitated by linguistic representations-for example, by verbal rehearsal and by verbal recoding of novel stimuli. the absence of language in nonhumans raises questions about the extent to which nonhuman working memory includes similar mechanisms. there is strong evidence for rehearsal-like active maintenance in working memory when monkeys are tested with highly familiar stimuli, but not when tested with novel stimuli, suggesting that working memory depends on th ...201830503618
cmv primes functional alternative signaling in adaptive δg nk cells but is subverted by lentivirus infection in rhesus macaques.despite burgeoning evidence demonstrating the adaptive properties of natural killer (nk) cells, mechanistic data explaining these phenomena are lacking. following antibody sensitization, nk cells lacking the fc receptor (fcr) signaling chain (δg) acquire adaptive features, including robust proliferation, multifunctionality, rapid killing, and mobilization to sites of virus exposure. using the rhesus macaque model, we demonstrate the systemic distribution of δg nk cells expressing memory features ...201830517864
vectored delivery of anti-siv envelope targeting mab via aav8 protects rhesus macaques from repeated limiting dose intrarectal swarm sivsme660 challenge.gene based delivery of immunoglobulins promises to safely and durably provide protective immunity to individuals at risk of acquiring infectious diseases such as hiv. we used a rhesus macaque animal model to optimize delivery of naturally-arising, autologous anti-siv neutralizing antibodies expressed by adeno-associated virus 8 (aav8) vectors. vectored transgene expression was confirmed by quantitation of target antibody abundance in serum and mucosal surfaces. we tested the expression achieved ...201830517201
altering alpha-frequency brain oscillations with rapid analog feedback-driven neurostimulation.oscillations of the brain's local field potential (lfp) may coordinate neural ensembles and brain networks. it has been difficult to causally test this model or to translate its implications into treatments, because there are few reliable ways to alter lfp oscillations. we developed a closed-loop analog circuit to enhance brain oscillations by feeding them back into cortex through phase-locked transcranial electrical stimulation. we tested the system in a rhesus macaque with chronically implante ...201830517149
complete genome sequences of six novel macaca mulatta papillomavirus types isolated from genital sites of rhesus monkeys in hong kong sar, china.the complete genomes of six macaca mulatta papillomavirus types isolated from genital sites of rhesus monkeys were characterized, and less than 72% identity with the complete l1 genes of known papillomaviruses was found. macaca mulatta papillomavirus type 2 (mmpv2), mmpv3, and mmpv6 cluster into the genus alphapapillomavirus, and mmpv4, mmpv5, and mmpv7 cluster into the genus gammapapillomavirus.201830533857
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