Publications

myeloid cells in intact human cervical explants capture hiv and can transmit it to cd4 t cells.	the importance of myeloid cells in hiv transmission in the female genital tract is uncertain. because it is difficult to study the early events in hiv transmission in humans, most of our knowledge is based on animal models of siv infection in rhesus macaques and more recently hiv infection in humanized mice. however, these models may not accurately recapitulate transmission in the human genital tract. cd14+ myeloid cells are the most abundant hematopoietic cells in the human cervical mucosa, com ...	2018	30532754
dominance rank-associated gene expression is widespread, sex-specific, and a precursor to high social status in wild male baboons.	in humans and other hierarchical species, social status is tightly linked to variation in health and fitness-related traits. experimental manipulations of social status in female rhesus macaques suggest that this relationship is partially explained by status effects on immune gene regulation. however, social hierarchies are established and maintained in different ways across species: while some are based on kin-directed nepotism, others emerge from direct physical competition. we investigated ho ...	2018	30538194
author correction: transcription start site profiling of 15 anatomical regions of the macaca mulatta central nervous system.	the authors regret that luba m. pardo was omitted in error from the author list of the original version of this data descriptor. this omission has now been corrected in the html and pdf versions. the authors also regret that anemieke rozemuller was omitted in error from the acknowledgements of the original version of this data descriptor. this omission has now been corrected in the html and pdf versions.	2018	30538238
longitudinal evaluation of pulmonary arterial hypertension in a rhesus macaque (macaca mulatta) model of hiv infection.	pulmonary arterial hypertension (pah) is a life-threatening disease with higher incidence in hiv-infected compared with noninfected patients. siv-infected nhp develop clinical manifestations of hiv infection, including pah. to understand the pathogenesis of pah and determine the relationship between hemodynamic changes and clinical characteristics associated with siv infection, we performed right heart catheterization and echocardiographic imaging of 21 rhesus macaques before and after siv infec ...	2018	30541636
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 ...	2018	30561328
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 ...	2018	30555564
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% ( ...	2018	30575753
quantification of infectious sendai virus using plaque assay.	sendai virus (sev) is an enveloped, single-stranded rna virus of the family paramyxoviridae. sev is a useful tool to study its infectious pathomechanism in immunology and the pathomechanism of a murine model of iga nephropathy. virus quantification is essential not only to determine the original viral titers for an appropriate application, but also to measure the viral titers in samples from the harvests from experiments. there are mainly a couple of units/titers for sendai viral quantification: ...	2018	30547053
aav8 gene therapy for crigler-najjar syndrome in macaques elicited transgene t cell responses that are resident to the liver.	systemic delivery of adeno-associated viral (aav) vectors has been evaluated for the treatment of several liver diseases, including homozygous familial hypercholesterolemia, ornithine transcarbamylase deficiency, and hemophilia. here, we evaluated this approach for the treatment of crigler-najjar syndrome. we administered wild-type rhesus macaques with 1.0 × 1013 or 2.5 × 1013 genome copies/kg of an aav serotype 8 vector expressing a codon-optimized version of human uridine diphosphate glucurono ...	2018	30547050
barcoding of macaque hematopoietic stem and progenitor cells: a robust platform to assess vector genotoxicity.	gene therapies using integrating retrovirus vectors to modify hematopoietic stem and progenitor cells have shown great promise for the treatment of immune system and hematologic diseases. however, activation of proto-oncogenes via insertional mutagenesis has resulted in the development of leukemia. we have utilized cellular bar coding to investigate the impact of different vector designs on the clonal behavior of hematopoietic stem and progenitor cells (hspcs) during in vivo expansion, as a quan ...	2018	30547048
spatiotemporal transcriptomic divergence across human and macaque brain development.	human nervous system development is an intricate and protracted process that requires precise spatiotemporal transcriptional regulation. we generated tissue-level and single-cell transcriptomic data from up to 16 brain regions covering prenatal and postnatal rhesus macaque development. integrative analysis with complementary human data revealed that global intraspecies (ontogenetic) and interspecies (phylogenetic) regional transcriptomic differences exhibit concerted cup-shaped patterns, with a ...	2018	30545855
subclinical infection of macaques and baboons with a baboon simarterivirus.	simarteriviruses (arteriviridae: simarterivirinae) are commonly found at high titers in the blood of african monkeys but do not cause overt disease in these hosts. in contrast, simarteriviruses cause severe disease in asian macaques upon accidental or experimental transmission. here, we sought to better understand the host-dependent drivers of simarterivirus pathogenesis by infecting olive baboons (n = 4) and rhesus monkeys (n = 4) with the simarterivirus southwest baboon virus 1 (swbv-1). surpr ...	2018	30544677
immunotoxin-induced ablation of the intrinsically photosensitive retinal ganglion cells in rhesus monkeys.	purpose: intrinsically photosensitive retinal ganglion cells (iprgcs) contain the photopigment melanopsin, and are primarily involved in non-image forming functions, such as the pupillary light reflex and circadian rhythm entrainment. the goal of this study was to develop and validate a targeted iprgc immunotoxin to ultimately examine the role of iprgcs in macaque monkeys. methods: an immunotoxin for the macaque melanopsin gene (opn4), consisting of a saporin-conjugated antibody directed at the ...	2018	30542318
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 ...	2018	30564524
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 ...	2018	30564240
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.	2018	30562730
'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 ...	2018	30570484
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.	2018	30568388
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 ...	2018	30568166
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.	2018	30574659
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 ...	2018	30573765
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 ...	2018	30586383
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 ...	2018	30592772
using imaging photoplethysmography for heart rate estimation in non-human primates.	for humans and for non-human primates heart rate is a reliable indicator of an individual's current physiological state, with applications ranging from health checks to experimental studies of cognitive and emotional state. in humans, changes in the optical properties of the skin tissue correlated with cardiac cycles (imaging photoplethysmogram, ippg) allow non-contact estimation of heart rate by its proxy, pulse rate. yet, there is no established simple and non-invasive technique for pulse rate ...	2018	30169537
population genomics of wild chinese rhesus macaques reveals a dynamic demographic history and local adaptation, with implications for biomedical research.	the rhesus macaque (rm, macaca mulatta) is the most important nonhuman primate model in biomedical research. we present the first genomic survey of wild rms, sequencing 81 geo-referenced individuals of five subspecies from 17 locations in china, a large fraction of the species' natural distribution.	2018	30165519
intrinsic neuronal dynamics predict distinct functional roles during working memory.	working memory (wm) is characterized by the ability to maintain stable representations over time; however, neural activity associated with wm maintenance can be highly dynamic. we explore whether complex population coding dynamics during wm relate to the intrinsic temporal properties of single neurons in lateral prefrontal cortex (lpfc), the frontal eye fields (fef), and lateral intraparietal cortex (lip) of two monkeys (macaca mulatta). we find that cells with short timescales carry memory info ...	2018	30158572
single-cell rna-sequencing reveals the existence of naive and primed pluripotency in pre-implantation rhesus monkey embryos.	naive pluripotency exists in epiblast cells of mouse pre-implantation embryos. however, whether the naive pluripotency is transient or nonexistent in primate embryos remains unclear. using rna-seq in single blastomeres from 16-cell embryos through to hatched blastocysts of rhesus monkey, we constructed the lineage segregation roadmap in which the specification of trophectoderm, epiblast, and primitive endoderm is initiated simultaneously at the early blastocyst stage. importantly, we uncovered t ...	2018	30154223
personality, environmental stressors, and diarrhea in rhesus macaques: an interactionist perspective.	previous research has repeatedly shown both personality and psychological stress to predict gastrointestinal disorders and chronic diarrhea in humans. the goal of the present research was to evaluate the role of personality, as well as psychological stressors (i.e., housing relocations and rearing environment), in predicting chronic diarrhea in captive rhesus macaques, with particular attention to how personality regulated the impact of such stressors. subjects were 1,930 r. macaques at the cali ...	2018	30152539
muscle synergies obtained from comprehensive mapping of the cortical forelimb representation using stimulus triggered averaging of emg activity.	neuromuscular control of voluntary movement may be simplified using muscle synergies similar to those found using non-negative matrix factorization. we recently identified synergies in electromyography (emg) recordings associated with both voluntary movement and movement evoked by high-frequency long-duration intracortical microstimulation applied to the forelimb representation of the primary motor cortex (m1). the goal of this study was to use stimulus-triggered averaging (stta) of emg activity ...	2018	30150363
identification of cholecystokinin tetrapeptide amide metabolites in liver microsomes of human, rhesus monkey, sprague-dawley rat and cd1 mouse using ultra-high performance liquid chromatography coupled to high resolution mass spectrometer.	endogenous cholecystokinin tetrapeptide (cck-4, trp-met-asp-phe-nh2) is a fragment derived from a larger peptide hormone, cholecystokinin (or gastrin). as a panicogenic agent, cck-4 is commonly used in clinic settings to induce panic attacks for the study of new anxiolytic drugs. however, few studies on cck-4 metabolism have been published to date. in the present study, we investigate the metabolism of cck-4 in liver microsomes of human (hlm), rhesus monkey (rmlm), sprague-dawley rat (rlm) and c ...	2018	30149298
type i ifn signaling blockade by a pasylated antagonist during chronic siv infection suppresses specific inflammatory pathways but does not alter t cell activation or virus replication.	chronic activation of the immune system in hiv infection is one of the strongest predictors of morbidity and mortality. as such, approaches that reduce immune activation have received considerable interest. previously, we demonstrated that administration of a type i interferon receptor antagonist (ifn-1ant) during acute siv infection of rhesus macaques results in increased virus replication and accelerated disease progression. here, we administered a long half-life pasylated ifn-1ant to art-trea ...	2018	30142226
acute abdominal distension due to disseminated peritoneal neoplasia in a rhesus macaque (macaca mulatta).	this report describes the clinical, radiographic, and pathologic findings in a female rhesus macaque that presented with acute abdominal distension and tympany. the macaque was euthanized after evidence of severe colonic distension on radiography and observation of widespread peritoneal adhesions on exploratory laparotomy. gross and histopathologic evaluation revealed extensive entrapment of gastrointestinal and reproductive tracts by serosal fibrovascular proliferative tissue containing foci of ...	2018	30139414
polymorphisms in rhesus macaque tetherin are associated with differences in acute viremia in simian immunodeficiency virus δnef-infected animals.	tetherin (bst-2 or cd317) is an interferon-inducible transmembrane protein that inhibits virus release from infected cells. to determine the extent of sequence variation and the impact of polymorphisms in rhesus macaque tetherin on simian immunodeficiency virus (siv) infection, tetherin alleles were sequenced from 146 rhesus macaques, including 68 animals infected with wild-type sivmac239 and 47 animals infected with sivmac239δnef since nef is the viral gene product of siv that counteracts restr ...	2018	30135127
conservation of preparatory neural events in monkey motor cortex regardless of how movement is initiated.	a time-consuming preparatory stage is hypothesized to precede voluntary movement. a putative neural substrate of motor preparation occurs when a delay separates instruction and execution cues. when readiness is sustained during the delay, sustained neural activity is observed in motor and premotor areas. yet whether delay-period activity reflects an essential preparatory stage is controversial. in particular, it has remained ambiguous whether delay-period-like activity appears before non-delayed ...	2018	30132759
odontogenic abscesses in rhesus macaques (macaca mulatta) of cayo santiago.	odontogenic abscesses are one of the most common dental diseases causing maxillofacial skeletal lesions. they affect the individual's ability to maintain the dental structures necessary to obtain adequate nutrition for survival and reproduction. in this study, the prevalence and pattern of odontogenic abscesses in relation to age, sex, matriline, and living periods were investigated in adult rhesus macaque skeletons of the free-ranging colony on cayo santiago, puerto rico.	2018	30129143
whole blood mitigates the acute coagulopathy of trauma and avoids the coagulopathy of crystalloid resuscitation.	the contributions of type and timing of fluid resuscitation to coagulopathy in trauma remain controversial. as part of a multifunctional resuscitation fluid research effort, we sought to further characterize the coagulation responses to resuscitation, specifically as compared to whole blood. we hypothesized that early whole blood administration mitigates the acute coagulopathy of trauma by avoiding the coagulopathy of cr resuscitation.	2018	30124622
polyclonal hiv envelope-specific breast milk antibodies limit founder shiv acquisition and cell-associated virus loads in infant rhesus monkeys.	breast milk hiv-1 transmission is currently the predominant contributor to pediatric hiv infections. yet, only ~10% of breastfeeding infants born to untreated hiv-infected mothers become infected. this study assessed the protective capacity of natural hiv envelope-specific antibodies isolated from the milk of hiv-infected women in an infant rhesus monkey (rm), tier 2 shiv oral challenge model. to mimic placental and milk maternal antibody transfer, infant rms were i.v. infused and orally treated ...	2018	30115994
coding of self and other's future choices in dorsal premotor cortex during social interaction.	representing others' intentions is central to primate social life. we explored the role of dorsal premotor cortex (pmd) in discriminating between self and others' behavior while two male rhesus monkeys performed a non-match-to-goal task in a monkey-human paradigm. during each trial, two of four potential targets were randomly presented on the right and left parts of a screen, and the monkey or the human was required to choose the one that did not match the previously chosen target. each agent ha ...	2018	30110624
constraints on neural redundancy.	millions of neurons drive the activity of hundreds of muscles, meaning many different neural population activity patterns could generate the same movement. studies have suggested that these redundant (i.e. behaviorally equivalent) activity patterns may be beneficial for neural computation. however, it is unknown what constraints may limit the selection of different redundant activity patterns. we leveraged a brain-computer interface, allowing us to define precisely which neural activity patterns ...	2018	30109848
receptive field center-surround interactions mediate context-dependent spatial contrast encoding in the retina.	antagonistic receptive field surrounds are a near-universal property of early sensory processing. a key assumption in many models for retinal ganglion cell encoding is that receptive field surrounds are added only to the fully formed center signal. but anatomical and functional observations indicate that surrounds are added before the summation of signals across receptive field subunits that creates the center. here, we show that this receptive field architecture has an important consequence for ...	2018	30188320
antibody-mediated cd4 depletion induces homeostatic cd4+ t cell proliferation without detectable virus reactivation in antiretroviral therapy-treated simian immunodeficiency virus-infected macaques.	a major barrier to human immunodeficiency virus (hiv) eradication is the long-term persistence of latently infected cd4+ t cells harboring integrated replication-competent virus. it has been proposed that the homeostatic proliferation of these cells drives long-term reservoir persistence in the absence of virus reactivation, thus avoiding cell death due to either virus-mediated cytopathicity or immune effector mechanisms. here, we conducted an experimental depletion of cd4+ t cells in eight anti ...	2018	30185596
alzheimer's disease-like pathologies and cognitive impairments induced by formaldehyde in non-human primates.	formaldehyde (fa) has been implicated in alzheimer's disease (ad) pathology as an age-related factor and as a protein cross-linker known to aggregate amyloid-beta (aβ) and tau protein in vitro. higher levels of fa have also been found in patients with greater cognitive impairment and in ad patient brains.	2018	30182853
effect of season on 25-oh vitamin d in serum of rhesus monkeys housed in puerto rico.	vitamin d blood levels have been shown to be partially dependent upon season in temperate climates, however, this same evaluation has not yet been reported in fully tropical climates. herein, we assessed the vitamin d levels in the blood of rhesus monkeys housed at the puerto rico caribbean primate research center collected in the island's "summer"(may-october) and "winter" (november-april) months.	2018	30188557
preclinical pharmacology in the rhesus monkey of cw 1759-50, a new ultra-short acting nondepolarizing neuromuscular blocking agent, degraded and antagonized by l-cysteine.	what this article tells us that is new: background:: structure-activity studies were performed to identify a new neuromuscular blocking agent retaining the ultra-short acting characteristics of gantacurium, including degradation and reversal by l-cysteine, but lacking its histaminoid properties in man. cw 1759-50 has emerged from this program.	2018	30212413
the contribution of primary auditory cortex to auditory categorization in behaving monkeys.	the specific contribution of core auditory cortex to auditory perception -such as categorization- remains controversial. to identify a contribution of the primary auditory cortex (a1) to perception, we recorded a1 activity while monkeys reported whether a temporal sequence of tone bursts was heard as having a "small" or "large" frequency difference. we found that a1 had frequency-tuned responses that habituated, independent of frequency content, as this auditory sequence unfolded over time. we a ...	2018	30210282
parent-offspring facial resemblance increases with age in rhesus macaques.	kin recognition is a key ability which facilitates the acquisition of inclusive fitness benefits and enables optimal outbreeding. in primates, phenotype matching is considered particularly important for the recognition of patrilineal relatives, as information on paternity is unlikely to be available via social familiarity. phenotypic cues to both paternal and maternal relatedness exist in the facial features of humans and other primates. however, theoretical models suggest that in systems with u ...	2018	30209226
iop, iop transient impulse, ocular perfusion pressure, and mean arterial pressure relationships in nonhuman primates instrumented with telemetry.	to characterize relationships between intraocular pressure (iop), mean arterial pressure (map), ocular perfusion pressure (opp), iop transient impulse, and iop baseline impulse using continuous telemetry in nonhuman primates.	2018	30208417
context-dependent tactile texture-sensitivity in monkey m1 and s1 cortex.	caudal primary motor cortex (m1, area 4) is sensitive to cutaneous inputs, but the extent to which the physical details of complex stimuli are encoded is not known. we investigated the sensitivity of m1 neurons (4 macaca mulatta monkeys) to textured stimuli (smooth/rough or rough/rougher) during the performance of a texture discrimination task and, for some cells, during a no-task condition (same surfaces; no response). the recordings were made from the hemisphere contralateral to the stimulated ...	2018	30207868
a simultaneous oral and intramuscular prime/sublingual boost with a dna/modified vaccinia ankara viral vector-based vaccine induces simian immunodeficiency virus-specific systemic and mucosal immune responses in juvenile rhesus macaques.	a pediatric vaccine to prevent breast milk transmission of human immunodeficiency virus (hiv) may generate greater immune responses at viral entry sites if given by an oral route.	2018	30204253
limited pulmonary mucosal-associated invariant t cell accumulation and activation during mycobacterium tuberculosis infection in rhesus macaques.	mucosal-associated invariant t cells (maits) are positioned in airways and may be important in the pulmonary cellular immune response against mycobacterium tuberculosis infection, particularly prior to priming of peptide-specific t cells. accordingly, there is interest in the possibility that boosting maits through tuberculosis (tb) vaccination may enhance protection, but mait responses in the lungs during tuberculosis are poorly understood. in this study, we compared pulmonary mait and peptide- ...	2018	30201702
mir-1303 regulates bbb permeability and promotes cns lesions following ca16 infections by directly targeting mmp9.	coxsackievirus a16 (ca16) is a member of the picornaviridae family and causes mild and self-limiting hand, foot, and mouth disease (hfmd) in infants and young children. ca16 infection can also progress to central nervous system (cns) complications; however, the underlying mechanism by which ca16 penetrates the blood-brain barrier (bbb) and then causes cns damage remains unclear. this study aimed to explore the mechanism of ca16 neurotropic tropism by establishing an in vitro bbb model with ca16 ...	2018	30228270
blood-brain barrier transport, plasma pharmacokinetics, and neuropathology following chronic treatment of the rhesus monkey with a brain penetrating humanized monoclonal antibody against the human transferrin receptor.	a monoclonal antibody (mab) against the blood-brain barrier (bbb) transferrin receptor (tfr) is a potential agent for delivery of biologic drugs to the brain across the bbb. however, to date, no tfrmab has been tested with chronic dosing in a primate model. a humanized tfrmab against the human (h) tfr1, which cross reacts with the primate tfr, was genetically engineered with high affinity (ed50 = 0.18 ± 0.04 nm) for the human tfr type 1 (tfr1). for acute dosing, the htfrmab was tritiated and inj ...	2018	30226787
seroepidemiology of burkholderia pseudomallei, etiologic agent of melioidosis, in the ouest and sud-est departments of haiti.	burkholderia pseudomallei, the etiological agent of melioidosis, has been hypothesized to be endemic throughout the caribbean, including the impoverished nation of haiti. however, because of the protean clinical manifestations, presence of asymptomatic infections, and limited medical diagnostic capacity, the identification of active melioidosis cases remains challenging. a seroepidemiological study was conducted using a novel enzyme-linked immunosorbent assay (elisa) to detect antibodies toward ...	2018	30226137
neutrophil vaccination dynamics and their capacity to mediate b cell help in rhesus macaques.	neutrophils are the most abundant leukocyte and play a critical role in the initial response to an ag. recently, their ability to contribute to adaptive immunity has been highlighted. we evaluated the ability of neutrophils from blood to contribute to the adaptive immune response in a preclinical rhesus macaque siv vaccine trial. replication-competent adenovirus-siv recombinants induced neutrophil activation, b cell help markers, and enhanced ability to generate reactive oxygen species. boosting ...	2018	30217830
characterization of spontaneously-developed non-alcoholic fatty liver disease in aged rhesus monkeys.	non-alcoholic fatty liver disease (nafld) is a global epidemic afflicting 20-30% in the general population. the animal model of nafld available at the present are less clinically relevant. in this study. we aimed to establish a nafld model of rhesus monkeys and develop an ultrasonographic steatosis score (uss) system to grade hepatic steatosis in this model.	2018	30214501
long-term safety outcome of systemic immunosuppression in pig-to-nonhuman primate corneal xenotransplantation.	safety concerns exist for corneal recipients under immunosuppression. we report long-term safety results of porcine corneal xenotransplantation under immunosuppression in nonhuman primates.	2018	30264877
hallmarks of primate lentiviral immunodeficiency infection recapitulate loss of innate lymphoid cells.	innate lymphoid cells (ilcs) play critical roles in mucosal barrier defense and tissue homeostasis. while ilcs are depleted in hiv-1 infection, this phenomenon is not a generalized feature of all viral infections. here we show in untreated siv-infected rhesus macaques (rms) that ilc3s are lost rapidly in mesenteric lymph nodes (mlns), yet preserved in siv+ rms with pharmacologic or natural control of viremia. in healthy uninfected rms, experimental depletion of cd4+ t cells in combination with d ...	2018	30262807
a brief review-epr dosimetry and the use of animal teeth as dosimeters.	the technique of electron paramagnetic resonance dosimetry using tooth enamel was established in the late 1960s, and considerable research has been conducted to learn more about the benefits of using human teeth as dosimeters for the purpose of retrospective dose reconstruction. comparatively few studies have been done which have investigated animal teeth for the same purpose. the potential exists for utilizing animal teeth as dosimeters to reconstruct doses received by a species, as well as by ...	2018	30260850
neuroprotective efficacy of p7c3 compounds in primate hippocampus.	there is a critical need for translating basic science discoveries into new therapeutics for patients suffering from difficult to treat neuropsychiatric and neurodegenerative conditions. previously, a target-agnostic in vivo screen in mice identified p7c3 aminopropyl carbazole as capable of enhancing the net magnitude of postnatal neurogenesis by protecting young neurons from death. subsequently, neuroprotective efficacy of p7c3 compounds in a broad spectrum of preclinical rodent models has also ...	2018	30258178
indirect activation of rhesus macaque (macaca mulatta) nk cells in oral and mucosal draining lymph nodes.	the oral mucosae and draining lymph nodes are primary entry points for invading pathogens, particularly during immunosuppressive hiv/siv infections. innate immunity against oral stimuli, including natural killer (nk) cells, is understudied. herein, we demonstrate functional nk cell responses to pathogen-associated molecular patterns (pamps) of potential oral pathogens in rhesus macaques.	2018	30256418
griffithsin carrageenan fast dissolving inserts prevent shiv hsv-2 and hpv infections in vivo.	human immunodeficiency virus (hiv) pre-exposure prophylaxis (prep) strategies with proven in vivo efficacy rely on antiretroviral drugs, creating the potential for drug resistance and complicated treatment options in individuals who become infected. moreover, on-demand products are currently missing from the prep development portfolio. griffithsin (grft) is a non-antiretroviral hiv entry inhibitor derived from red algae with an excellent safety profile and potent activity in vitro. when combined ...	2018	30250170
specificity of primate amygdalar pathways to hippocampus.	the amygdala projects to hippocampus in pathways through which affective or social stimuli may influence learning and memory. we investigated the still unknown amygdalar termination patterns and their postsynaptic targets in hippocampus from system to synapse in rhesus monkeys of both sexes. the amygdala robustly innervated the stratum lacunosum-moleculare layer of cornu ammonis fields and uncus anteriorly. sparser terminations in posterior hippocampus innervated the radiatum and pyramidal layer ...	2018	30249799
improved tolerability of a salmonella enterica serovar typhimurium live-attenuated vaccine strain achieved by balancing inflammatory potential with immunogenicity.	a notable proportion of salmonella-associated gastroenteritis in the united states is attributed to salmonella enterica serovar typhimurium. we have previously shown that live-attenuated s typhimurium vaccine candidate cvd 1921 (i77 δguaba δclpp) was safe and immunogenic in rhesus macaques but was shed for an undesirably long time postimmunization. in mice, occasional mortality postvaccination was also noted (approximately 1 in every 15 mice). here we describe a further attenuated vaccine candid ...	2018	30249748
annotation and functional clustering of circrna expression in rhesus macaque brain during aging.	the abundance and function of circular rnas (circrnas) in mammalian brain have been reported, but their alterations in the biology of brain aging remain elusive. here, using deep rna profiling with linear rna digestion by rnase r we explored a comprehensive map of changes in circrna expression in rhesus macaque (macaca mulatta) brain in two age groups from adult (10 y) to aged (20 y) periods. total 17,050 well expressed, stable circrnas were identified. cluster analysis reveals that dynamic chan ...	2018	30245844
s-plot2: rapid visual and statistical analysis of genomic sequences.	with the daily release of data from whole genome sequencing projects, tools to facilitate comparative studies are hard-pressed to keep pace. graphical software solutions can readily recognize synteny by measuring similarities between sequences. nevertheless, regions of dissimilarity can prove to be equally informative; these regions may harbor genes acquired via lateral gene transfer (lgt), signify gene loss or gain, or include coding regions under strong selection. previously, we developed the ...	2018	30245567
immunomodulatory effects of rhesus monkey bone marrow-derived mesenchymal stem cells in serum-free conditions.	mesenchymal stem cells (mscs) have generated tremendous interest for treating various diseases due to their self-renewal and differentiation capacities. many studies have demonstrated the immunoregulatory capability of mscs; however, most of these studies were conducted with fetal bovine serum (fbs), which has an uncertain composition. in this study, we established a serum-free, xeno-free, completely chemically defined medium for the proliferation and expansion of rhesus monkey bone marrow (bm)- ...	2018	30245347
ebola virus causes intestinal tract architectural disruption and bacterial invasion in non-human primates.	in the 2014⁻2016 west africa ebola virus (ebov) outbreak, there was a significant concern raised about the potential for secondary bacterial infection originating from the gastrointestinal tract, which led to the empiric treatment of many patients with antibiotics. this retrospective pathology case series summarizes the gastrointestinal pathology observed in control animals in the rhesus ebov-kikwit intramuscular 1000 plaque forming unit infection model. all 31 non-human primates (nhps) exhibite ...	2018	30241284
combination anti-pd-1 and antiretroviral therapy provides therapeutic benefit against siv.	therapeutic strategies that augment antiviral immunity and reduce the viral reservoir are critical to achieving durable remission of hiv. the coinhibitory receptor programmed death-1 (pd-1) regulates cd8+ t cell dysfunction during chronic hiv and siv infections. we previously demonstrated that in vivo blockade of pd-1 during chronic siv infection improves the function of antiviral cd8+ t cells and b cells. here, we tested the immunological and virological effects of pd-1 blockade combined with a ...	2018	30232277
diversification of bw4 specificity and recognition of a nonclassical mhc class i molecule implicated in maternal-fetal tolerance by killer cell ig-like receptors of the rhesus macaque.	the rhesus macaque is an important animal model for aids and other infectious diseases; however, studies to address nk cell function in this species have been limited by the lack of defined ligands for killer cell ig-like receptors (kirs). to identify ligands for rhesus macaque kirs, we adopted a novel approach based on a pair of stable cell lines. nfat-responsive luciferase reporter cell lines expressing the extracellular domains of macaque kirs fused to the transmembrane and cytoplasmic domain ...	2018	30232137
neural activity predicts reaction in primates long before a behavioral response.	how neural activity is linked to behavior is a critical question in neural engineering and cognitive neurosciences. it is crucial to predict behavior as early as possible, to plan a machine response in real-time brain computer interactions. however, previous studies have studied the neural readout of behavior only within a short time before the action is performed. this leaves unclear, if the neural activity long before a decision could predict the upcoming behavior. by recording extracellular n ...	2018	30271333
lorcaserin decreases the reinforcing effects of heroin, but not food, in rhesus monkeys.	preclinical studies indicate that lorcaserin (belviq®), an fda-approved serotonin 2 c receptor agonist, may be a promising medication for the treatment of stimulant addiction. however, few studies have investigated its effects on self-administration of drugs of abuse from other pharmacological classes, including opioids. here, adult male rhesus macaques (n = 3) responded under a fixed ratio 30 schedule of food (1-g banana-flavored pellets) and iv heroin delivery. following stable self-administra ...	2018	30268662
standard growth and diarrhea-associated growth faltering in captive infant rhesus macaques (macaca mulatta).	reference growth studies of captive rhesus macaque infants have not accounted for diarrhea and the potential for growth stunting or growth faltering. healthy infants without diarrhea could be used to build a standard growth chart and a tool used to detect growth faltering associated with diarrhea. we hypothesized infants who develop diarrhea during the first year of life would experience decreased linear weight gain compared to healthy infants, and we used healthy infants to establish standard g ...	2018	30281825
opportunities and challenges for intranasal oxytocin treatment studies in nonhuman primates.	nonhuman primates provide a human-relevant experimental model system to explore the mechanisms by which oxytocin (ot) regulates social processing and inform its clinical applications. here, we highlight contributions of the nonhuman primate model to our understanding of ot treatment and address unique challenges in administering ot to awake behaving primates. prior preclinical research utilizing macaque monkeys has demonstrated that ot can modulate perception of other individuals and their expre ...	2018	30281820
instantaneous midbrain control of saccade velocity.	the ability to interact with our environment requires the brain to transform spatially represented sensory signals into temporally encoded motor commands for appropriate control of the relevant effectors. for visually guided eye movements, or saccades, the superior colliculus (sc) is assumed to be the final stage of spatial representation, and instantaneous control of the movement is achieved through a rate code representation in the lower brain stem. we investigated whether sc activity in nonhu ...	2018	30291204
antibody and tlr7 agonist delay viral rebound in shiv-infected monkeys.	the latent viral reservoir is the critical barrier for the development of a cure for hiv-1 infection. previous studies have shown direct antiviral activity of potent hiv-1 env-specific broadly neutralizing antibodies (bnabs) administered when antiretroviral therapy (art) was discontinued, but it remains unclear whether bnabs can target the viral reservoir during art. here we show that administration of the v3 glycan-dependent bnab pgt121 together with the toll-like receptor 7 (tlr7) agonist vesa ...	2018	30283138
a novel neutralizing antibody specific to the de loop of vp1 can inhibit ev-d68 infection in mice.	enterovirus d68 (ev-d68) belongs to the picornavirus family and was first isolated in ca, usa, in 1962. ev-d68 can cause severe cranial nerve system damage such as flaccid paralysis and acute respiratory diseases such as pneumonia. there are currently no efficient therapeutic methods or effective prophylactics. in this study, we isolated the mab a6-1 from an ev-d68-infected rhesus macaque (macaca mulatta) and found that the ab provided effective protection in ev-d68 intranasally infected sucklin ...	2018	30282753
nonlinear lateral interactions in v1 population responses explained by a contrast gain control model.	how do cortical responses to local image elements combine to form a spatial pattern of population activity in primate v1? here, we used voltage-sensitive dye imaging, which measures summed membrane potential activity, to examine the rules that govern lateral interactions between the representations of two small local-oriented elements in macaque (macaca mulatta) v1. we find strong subadditive and mostly orientation-independent interactions for nearby elements [2-4 mm interelement cortical distan ...	2018	30282725
effects of aging and environmental tobacco smoke exposure on ocular and plasma circulatory micrornas in the rhesus macaque.	to identify changes induced by environmental tobacco smoke (ets) in circulatory microrna (mirna) in plasma and ocular fluids of the rhesus macaque and compare these changes to normal age-related changes. tobacco smoke has been identified as the leading environmental risk factor for age-related macular degeneration (amd).	2018	30294202
lipidomics reveals a systemic energy deficient state that precedes neurotoxicity in neonatal monkeys after sevoflurane exposure.	although numerous studies have raised public concerns regarding the safety of anesthetics including sevoflurane in children, the biochemical mechanisms leading to anesthetics-induced neurotoxicity remain elusive. moreover, potential biomarker(s) for early detection of general anesthetics-induced brain injury are urgent for public health. we employed an enabling technology of shotgun lipidomics and analyzed nearly 20 classes and subclasses of lipids present in the blood serum of postnatal day (pn ...	2018	30292318
low level expression of the mitochondrial antiviral signaling protein (mavs) associated with long-term nonprogression in siv-infected rhesus macaques.	abnormally increased immune activation is one of the main pathological features of acquired immunodeficiency syndrome (aids). this study aimed to determine whether long-term nonprogression (ltnp) suppresses the upregulation of immune activation and to elucidate the mechanisms whereby the ltnp state is maintained.	2018	30326919
range, routing and kinetics of rod signaling in primate retina.	stimulus- or context-dependent routing of neural signals through parallel pathways can permit flexible processing of diverse inputs. for example, work in mouse shows that rod photoreceptor signals are routed through several retinal pathways, each specialized for different light levels. this light-level-dependent routing of rod signals has been invoked to explain several human perceptual results, but it has not been tested in primate retina. here, we show, surprisingly, that rod signals traverse ...	2018	30299254
baba-mediated adherence of pediatric ulcerogenic h. pylori strains to gastric mucins at neutral and acidic ph.	helicobacter pylori infection can result in non-ulcer dyspepsia (nud), peptic ulcer disease (pud), adenocarcinoma, and gastric lymphoma. h. pylori reside within the gastric mucus layer, mainly composed of mucins carrying an array of glycan structures that can serve as bacterial adhesion epitopes. the aim of the present study was to characterize the binding ability, adhesion modes, and growth of h. pylori strains from pediatric patients with nud and pud to gastric mucins. our results showed an in ...	2018	30298790
low-ranking individuals present high and unstable fecal cortisol levels in provisioned free-ranging adult male rhesus macaques (macaca mulatta) during the birth season in a mountain area of northern china.	social hierarchy commonly exists in animal societies, affecting both the endocrine functioning and the behavior of animals. in nonhuman primates, the relationship between social rank and cortisol levels varies across species and even within species. here, we assessed the relationships between social rank and fecal cortisol levels in adult male taihangshan macaques (rhesus macaques, macaca mulatta tcheliensis) from the provisioned, free-ranging wulongkou-2 (wlk-2) group inhabiting wulongkou sceni ...	2018	30298460
sex differences in rhesus monkeys' digit ratio (2d:4d ratio) and its association with maternal social dominance rank.	prenatal androgen exposure (pae) plays a pivotal role in masculinizing the developing body and brain, and extreme exposure may contribute to autism, anxiety disorder and schizophrenia. one commonly used biomarker for pae is the pointer-to-ring-finger digit length (2d:4d) ratio. although this biomarker is widely used in human studies, relatively few studies have investigated 2d:4d ratio in nonhuman primates, particularly rhesus macaques (macaca mulatta), one of the most commonly used animals in b ...	2018	30297989
intranasal oxytocin in rhesus monkeys alters brain networks that detect social salience and reward.	in primates, resting state functional neuroimaging (rsfcmri) has identified several large-scale, intrinsic brain networks, including the salience network (sn), which is involved in detecting stimulus salience. intranasal oxytocin (in-ot) has been shown to modulate the salience and rewarding quality of social stimuli in mammals and numerous studies have shown that it can affect the functional connectivity between brain regions. less is known, however, about how these effects unfold over time foll ...	2018	30295946
system for scoring severity of acute radiation syndrome response in rhesus macaques (macaca mulatta).	we developed a clinical assessment tool for use in an nhp radiation model to 1) quantify severity responses for subsyndromes of the acute radiation syndrome (ars; that is, hematopoietic and others) and 2) identify animals that required enhanced monitoring. our assessment tool was based primarily on the medical treatment protocols for radiation accident victims (metrepol) scoring system but was adapted for nhp to include additional indices (for example, behaviors) for use in nhp studies involving ...	2018	30305197
ongoing, rational calibration of reward-driven perceptual biases.	decision-making is often interpreted in terms of normative computations that maximize a particular reward function for stable, average behaviors. aberrations from the reward-maximizing solutions, either across subjects or across different sessions for the same subject, are often interpreted as reflecting poor learning or physical limitations. here we show that such aberrations may instead reflect the involvement of additional satisficing and heuristic principles. for an asymmetric-reward percept ...	2018	30303484
plasmodium 18s rrna of intravenously administered sporozoites does not persist in peripheral blood.	plasmodium 18s rrna is a biomarker used to monitor blood-stage infections in malaria clinical trials. plasmodium sporozoites also express this biomarker, and there is conflicting evidence about how long sporozoite-derived 18s rrna persists in peripheral blood. if present in blood for an extended timeframe, sporozoite-derived 18s rrna could complicate use as a blood-stage biomarker.	2018	30053881
radiolabel validation of cortisol in the hair of rhesus monkeys.	analysis of cortisol in hair has become a widespread tool for assessment of hypothalamic-pituitary-adrenal (hpa) axis activity because of its ease of collection and its ability to provide cumulative data over a period of months. in order to meaningfully interpret hair cortisol, however a direct validation by radio-metabolism is required to understand cortisol incorporation into hair. tritiated [3h]-cortisol was iv administered to adult rhesus monkeys to determine 1) if [3h] is found in the hair ...	2018	30053699
human polyclonal antibodies produced by transchromosomal cattle provide partial protection against lethal zaire ebolavirus challenge in rhesus macaques.	antibody therapy has been used to treat a variety of diseases and the success of zmapp and other monoclonal antibody-based therapies during the 2014-2016 west african ebola outbreak has shown this countermeasure can be a successful therapy for ebola hemorrhagic fever. this study utilized transchromosomal bovines (tcb) vaccinated with a dna plasmid encoding ebola virus glycoprotein sequence to produce human polyclonal antibodies directed against ebola virus glycoprotein. when administered 1 day p ...	2018	30053153
new insights into marburg virus disease pathogenesis in the rhesus macaque model.	previously, several studies have been performed to delineate the development and progression of marburg virus infection in nonhuman primates (nhps), primarily to clarify the mechanisms of severe (fatal) disease. after the 2013-2016 ebola virus disease (evd) epidemic in western africa, there has been a reassessment of the available filovirus animal models and the utility of these to faithfully recapitulate human disease. the high lethality of the nhp models has raised doubts as to their ability t ...	2018	30053050
focal optogenetic suppression in macaque area mt biases direction discrimination and decision confidence, but only transiently.	insights from causal manipulations of brain activity depend on targeting the spatial and temporal scales most relevant for behavior. using a sensitive perceptual decision task in monkeys, we examined the effects of rapid, reversible inactivation on a spatial scale previously achieved only with electrical microstimulation. inactivating groups of similarly tuned neurons in area mt produced systematic effects on choice and confidence. behavioral effects were attenuated over the course of each sessi ...	2018	30051817
beneficial effects of human anti-interleukin-15 antibody in gluten-sensitive rhesus macaques with celiac disease.	overexpression of interleukin-15 (il-15) is linked with immunopathology of several autoimmune disorders including celiac disease. here, we utilized an anti-human il-15 antibody 04h04 (anti-il-15) to reverse immunopathogenesis of celiac disease. anti-il-15 was administered to six gluten-sensitive rhesus macaques with celiac disease characteristics including gluten-sensitive enteropathy (gse), and the following celiac-related metrics were evaluated: morphology (villous height/crypt depth ratio) of ...	2018	30050538
the rhesus monkey hippocampus critically contributes to scene memory retrieval, but not new learning.	humans can recall a large number of memories years after the initial events. patients with amnesia often have lesions to the hippocampus, but human lesions are imprecise, making it difficult to identify the anatomy underlying memory impairments. rodent studies enable great precision in hippocampal manipulations, but not investigation of many interleaved memories. thus it is not known how lesions restricted to the hippocampus affect the retrieval of multiple sequentially encoded memories. further ...	2018	30049888
xenoantigen deletion and chemical immunosuppression can prolong renal xenograft survival.	xenotransplantation using pig organs could end the donor organ shortage for transplantation, but humans have xenoreactive antibodies that cause early graft rejection. genome editing can eliminate xenoantigens in donor pigs to minimize the impact of these xenoantibodies. here we determine whether an improved cross-match and chemical immunosuppression could result in prolonged kidney xenograft survival in a pig-to-rhesus preclinical model.	2018	30048323
evaluation of a mosaic hiv-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (approach) and in rhesus monkeys (nhp 13-19).	more than 1·8 million new cases of hiv-1 infection were diagnosed worldwide in 2016. no licensed prophylactic hiv-1 vaccine exists. a major limitation to date has been the lack of direct comparability between clinical trials and preclinical studies. we aimed to evaluate mosaic adenovirus serotype 26 (ad26)-based hiv-1 vaccine candidates in parallel studies in humans and rhesus monkeys to define the optimal vaccine regimen to advance into clinical efficacy trials.	2018	30047376
figure and ground: how the visual cortex integrates local cues for global organization.	inferring figure-ground organization in two-dimensional images may require different complementary strategies. for isolated objects, it has been shown that mechanisms in visual cortex exploit the overall distribution of contours, but in images of cluttered scenes where the grouping of contours is not obvious, that strategy would fail. however, natural scenes contain local features, specifically contour junctions, that may contribute to the definition of object regions. to study the role of local ...	2018	30044171
clonal expansion of mitochondrial dna deletions is a private mechanism of aging in long-lived animals.	disruption of mitochondrial metabolism and loss of mitochondrial dna (mtdna) integrity are widely considered as evolutionarily conserved (public) mechanisms of aging (lópez-otín et al., cell, 153, 2013 and 1194). human aging is associated with loss in skeletal muscle mass and function (sarcopenia), contributing significantly to morbidity and mortality. muscle aging is associated with loss of mtdna integrity. in humans, clonally expanded mtdna deletions colocalize with sites of fiber breakage and ...	2018	30043489
in vivo imaging of inflammation and oxidative stress in a nonhuman primate model of cardiac sympathetic neurodegeneration.	loss of cardiac postganglionic sympathetic innervation is a characteristic pathology of parkinson's disease (pd). it progresses over time independently of motor symptoms and is not responsive to typical anti-parkinsonian therapies. cardiac sympathetic neurodegeneration can be mimicked in animals using systemic dosing of the neurotoxin 6-hydroxydopamine (6-ohda). as in pd, 6-ohda-induced neuronal loss is associated with increased inflammation and oxidative stress. to assess the feasibility of det ...	2018	30038956
assessment of bias in morphological identification of carnivore scats confirmed with molecular scatology in north-eastern himalayan region of pakistan.	scats are often used to study ecological parameters of carnivore species. however, field identification of carnivore scats, based on their morphological characteristics, becomes difficult if many carnivore species are distributed in the same area. we assessed error rates in morphological identification of five sympatric carnivores' scats in north-eastern himalayan region of pakistan during 2013-2017. a sample of 149 scats were subjected to molecular identification using fecal dna. we used a conf ...	2018	30038872