frontal and insular input to the dorsolateral temporal pole in primates: implications for auditory memory. | the temporal pole (tp) has been involved in multiple functions from emotional and social behavior, semantic processing, memory, language in humans and epilepsy surgery, to the fronto-temporal neurodegenerative disorder (semantic) dementia. however, the role of the tp subdivisions is still unclear, in part due to the lack of quantitative data about tp connectivity. this study focuses in the dorsolateral subdivision of the tp: area 38dl. area 38dl main input originates in the auditory processing a ... | 2019 | 31780878 |
547 transcriptomes from 44 brain areas reveal features of the aging brain in non-human primates. | brain aging is a complex process that depends on the precise regulation of multiple brain regions; however, the underlying molecular mechanisms behind this process remain to be clarified in non-human primates. | 2019 | 31779658 |
increased produce enrichment reduces trauma in socially-housed captive rhesus macaques (macaca mulatta). | due to primate adaptations for sociality, captive rhesus macaques have optimal welfare and utility as a biomedical model when they can be maintained in outdoor social groups. as a despotic species; however, aggression can result in costly injuries and may result in temporary or permanent removal of specific individuals from social housing. enrichment items, such as toys, climbing structures, and foraging material, are employed to keep captive animals occupied. we hypothesized that produce enrich ... | 2019 | 31778253 |
a muc16 igg binding activity selects for a restricted subset of igg enriched for certain simian immunodeficiency virus epitope specificities. | we have recently shown that muc16, a component of the glycocalyx of some mucosal barriers, has elevated binding to the g0 glycoform of the fc portion of igg. therefore, igg from patients chronically infected with human immunodeficiency virus (hiv), who typically exhibit increased amounts of g0 glycoforms, showed increased muc16 binding compared to uninfected controls. using the rhesus macaque simian immunodeficiency virus sivmac251 model, we can compare plasma antibodies before and after chronic ... | 2020 | 31776284 |
comparison of immunogenicity and safety outcomes of a malaria vaccine fmp013/alfq in rhesus macaques (macaca mulatta) of indian and chinese origin. | indian-origin rhesus (inr) are preferred for research, but strict export restrictions continue to limit their use. chinese-origin rhesus (chr), although easier to procure, are genetically distinct from inr and differ in their immune response to infectious agents, such as the simian immunodeficiency virus. the most advanced malaria vaccine, rts,s (glaxosmithkline), is based on the circumsporozoite protein (csp) of plasmodium falciparum. the efficacy of rts,s vaccine in the field remains low and s ... | 2019 | 31775762 |
fluctuations in intracranial pressure can be estimated non-invasively using near-infrared spectroscopy in non-human primates. | intracranial pressure (icp) is typically measured invasively through a sensor placed inside the brain or a needle inserted into the spinal canal, limiting the patient population on which this assessment can be performed. currently, non-invasive methods are limited due to lack of sensitivity and thus only apply to extreme cases of increased icp, instead of use in general clinical practice. we demonstrate a novel application for near-infrared spectroscopy (nirs) to accurately estimate icp changes ... | 2020 | 31775565 |
mucosal antibodies: defending epithelial barriers against hiv-1 invasion. | the power of mucosal anti-hiv-1 envelope immunoglobulins (igs) to block virus transmission is underappreciated. we used passive immunization, a classical tool to unequivocally prove whether antibodies are protective. we mucosally instilled recombinant neutralizing monoclonal antibodies (nmabs) of different ig classes in rhesus macaques (rms) followed by mucosal simian-human immunodeficiency virus (shiv) challenge. we gave anti-hiv-1 igm, igg, and dimeric iga (diga) versions of the same human nma ... | 2019 | 31771162 |
equal response rates maintained by concurrent drug and nondrug reinforcers: a design for treatment evaluation. | during daily 3-h sessions, four rhesus monkeys had concurrent access to 16% alcohol (w/v) and saccharin. a response occurred when a monkey made mouth contact with the metal spout and thereby completed a drinkometer circuit. the liquids were available under concurrent nonindependent fixed-ratio 32 schedules. with these schedules, responses on the right spout decremented both the right and left fixed-ratio counters and vice versa. responding was well maintained by both alcohol and saccharin. incre ... | 2020 | 31770113 |
molecular characterization of group a rotavirus from rhesus macaques (macaca mulatta) at human-wildlife interfaces in bangladesh. | group a rotavirus (rva) is an important cause of diarrhoea in people, especially children, and animals globally. due to the segmented nature of the rva genome, animal rva strains have the potential to adapt to the human host through reassortment with other co-infecting human viruses. macaques share food and habitat with people, resulting in close interaction between these two species. this study aimed to detect and characterize rva in rhesus macaques (macaca mulatta) in bangladesh. faecal sample ... | 2020 | 31765042 |
cannabinoids and inflammation: implications for people living with hiv. | : thanks to the success of modern antiretroviral therapy (art), people living with hiv (plwh) have life expectancies which approach that of persons in the general population. however, despite the ability of art to suppress viral replication, plwh have high levels of chronic systemic inflammation which drives the development of comorbidities such as cardiovascular disease, diabetes and non-aids associated malignancies. historically, cannabis has played an important role in alleviating many sympto ... | 2019 | 31764093 |
[cardiac magnetic resonance imaging study of ventricular myocardial deformation in spontaneous t2dm rhesus monkey]. | to assess biventricular, especially right ventricular, function and deformationin rhesus monkeys with spontaneous type 2 diabetes mellitus (t2dm) using cardiac magnetic resonance (cmr). | 2019 | 31762240 |
lactation and menstruation shift the vaginal microbiota in captive rhesus monkeys to be more similar to the male urethral microbiota. | the vaginal microbiota of nonhuman primates differs substantially from humans in terms of lactobacillus abundance, overall taxonomic diversity, and vaginal ph. given these differences, it remains unclear in what way the nonhuman primate genital microbiota protects against pathogens, in particular sexually transmitted infections. considering the effect that microbiota variations can have on disease acquisition and outcome, we examined endogenous and exogenous factors that influence the urogenital ... | 2019 | 31758047 |
orex-1019: a novel treatment of opioid use disorder and relapse prevention. | there is an urgent need for new pharmacological treatments for substance use disorders, including opioid use disorder, particularly for use in relapse prevention. a combination of buprenorphine with naltrexone has shown particular promise, with clinical studies indicating a substantial improvement over treatment with naltrexone alone. orex-1019 (formerly bu10119) is a compound that mimics the pharmacology of the buprenorphine/naltrexone combination. this study evaluated, in rhesus monkeys, the t ... | 2020 | 31748404 |
the small scale functional topology of movement control: hierarchical organization of local activity anticipates movement generation in the premotor cortex of primates. | how neurons coordinate their collective activity for behavioural control is an open question in neuroscience. several studies have progressively proven, on various scales, that the patterns of neural synchronization change accordingly with behavioural events. however, the topological features of the neural dynamics that underlie task-based cognitive decisions on the small scale level are not understood. we analysed the multiunit activity (mua) from a multielectrode (96 channels) array of the dor ... | 2020 | 31743791 |
pulmonary amniotic fluid embolism in a rhesus macaque (macaca mulatta). | a pregnant female rhesus macaque died spontaneously during stage two labor. gross and histopathologic findings included severe pulmonary edema, with low numbers of blood vessels containing pale basophilic mucinous material (alcian blue positive and ptah negative), consistent with intravascular amniotic fluid-derived mucin resulting in pulmonary amniotic fluid embolism. | 2020 | 31742695 |
utility of automated feeding data to detect social instability in a captive breeding colony of rhesus macaques (macaca mulatta): a case study of intrafamily aggression. | some captive breeding colonies of rhesus macaques live in large outdoor multimale, multifemale social groups. these groups are composed of several matrilineal families, governed by a clear female dominance hierarchy. aggression within the same or between different matrilineal families due to social instability can result in trauma and mortality. therefore, a primary management goal is to detect emerging social unrest before the onset of significant fighting and wounding. accordingly, groups are ... | 2020 | 31739825 |
loneliness in monkeys: neuroimmune mechanisms. | loneliness, or perceived social isolation, may be evident in any group-living species, although its assessment in nonhumans provides some measurement challenges. it is well-known that loneliness in humans confers significant risk for morbidity and mortality, although mechanisms remain unclear. the authors describe a naturally-occurring model of loneliness in adult male rhesus monkeys that shows many parallels with the phenomenon in humans. lonely monkeys (those that display high frequencies of s ... | 2019 | 31737750 |
the mechanical effect of the periodontal ligament on bone strain regimes in a validated finite element model of a macaque mandible. | the primary anatomical function of the periodontal ligament (pdl) is to attach teeth to their sockets. however, theoretical and constitutive mechanical models have proposed that during mastication the pdl redistributes local occlusal loads and reduces the jaw's resistance to torsional deformations. these hypotheses imply that accurately modeling the pdl's material properties and geometry in finite element analysis (fea) is a prerequisite to obtaining precise strain and deformation data. yet, man ... | 2019 | 31737614 |
a new algorithm for identifying genome rearrangements in the mammalian evolution. | genome rearrangements are the evolutionary events on level of genomes. it is a global view on evolution research of species to analyze the genome rearrangements. we introduce a new method called rgrpt (recovering the genome rearrangements based on phylogenetic tree) used to identify the genome rearrangements. we test the rgrpt using simulated data. the results of experiments show that rgrpt have high sensitivity and specificity compared with other tools when to predict rearrangement events. we u ... | 2019 | 31737036 |
comparative analysis of gene expression patterns for oral epithelium-related functions with aging. | epithelial cells and functions of the epithelium are critical to the health of the oral cavity. we used a nonhuman primate model to profile the transcriptome of gingival tissues in health across the lifespan and hypothesized that in older animals, epithelial-related transcriptome patterns would reflect epithelial cells that are aggressively responsive to the surrounding environment and less able to modulate and resolve the noxious challenge from the bacteria. rhesus monkeys (n = 34) with a healt ... | 2019 | 31732940 |
construction of a novel staphylokinase (sak) mutant with low immunogenicity and its evaluation in rhesus monkey. | the heterologous nature of sak, a thrombolytic drug, elicits high titers of neutralizing antibodies, which limits its clinical use. here, we aim to establish a sak mutant with equivalent activity to the wild type but reduced antigenicity, which may allow for multiple injections. biosun software was used to predict sak antigenic epitopes, and several main epitopes were modified by gene deletion and mutation. ten sak mutants were constructed, and their thrombolytic activity and immunogenicity were ... | 2020 | 31730959 |
training rhesus macaques to take daily oral antiretroviral therapy for preclinical evaluation of hiv prevention and treatment strategies. | macaque models of simian or simian/human immunodeficiency virus (siv or shiv) infection are critical for the evaluation of antiretroviral (arv)-based hiv treatment and prevention strategies. however, modelling human oral arv administration is logistically challenging and fraught by limited adherence. here, we developed a protocol for administering daily oral doses of arvs to macaques with a high rate of compliance. | 2019 | 31730629 |
quantitative proteomics of enriched esophageal and gut tissues from the human blood fluke schistosoma mansoni pinpoints secreted proteins for vaccine development. | schistosomes are blood-dwelling helminth parasites that cause schistosomiasis, a debilitating disease resulting in inflammation and, in extreme cases, multiple organ damage. major challenges to control the transmission persist, and the discovery of protective antigens remains of critical importance for vaccine development. rhesus macaques can self-cure following schistosome infection, generating antibodies that target proteins from the tegument, gut, and esophagus, the last of which is the least ... | 2020 | 31729880 |
immunogenicity comparison of a next generation pneumococcal conjugate vaccine in animal models and human infants. | evaluation of a pneumococcal conjugate vaccine (pcv) in an animal model provides an initial assessment of the performance of the vaccine prior to evaluation in humans. cost, availability, study duration, cross-reactivity and applicability to humans are several factors which contribute to animal model selection. pcv15 is an investigational 15-valent pcv which includes capsular polysaccharides from pneumococcal serotypes (st) 1, 3, 4, 5, 6a, 6b, 7f, 9v, 14, 18c, 19a, 19f, 22f, 23f and 33f all indi ... | 2020 | 31725555 |
despite early antiretroviral therapy effector memory and follicular helper cd4 t cells are major reservoirs in visceral lymphoid tissues of siv-infected macaques. | whereas antiretroviral therapy (art) suppresses viral replication, art discontinuation results in viral rebound, indicating the presence of viral reservoirs (vrs) established within lymphoid tissues. herein, by sorting cd4 t-cell subsets from the spleen, mesenteric and peripheral lymph nodes (lns) of sivmac251-infected rhesus macaques (rms), we demonstrate that effector memory (tem) and follicular helper (tfh) cd4+ t cells harbor the highest frequency of viral dna and rna, as well of early r-u5 ... | 2020 | 31723251 |
early-life iron deficiency and its natural resolution are associated with altered serum metabolomic profiles in infant rhesus monkeys. | iron deficiency is the most common nutrient deficiency in human infants aged 6 to 24 mo, and negatively affects many cellular metabolic processes, including energy production, electron transport, and oxidative degradation of toxins. there can be persistent influences on long-term metabolic health beyond its acute effects. | 2020 | 31722400 |
rapid germinal center and antibody responses in non-human primates after a single nanoparticle vaccine immunization. | the first immunization in a protein prime-boost vaccination is likely to be critical for how the immune response unfolds. using fine needle aspirates (fnas) of draining lymph nodes (lns), we tracked the kinetics of the primary immune response in rhesus monkeys immunized intramuscularly (im) or subcutaneously (s.c.) with an eod-gt8 60-mer nanoparticle immunogen to facilitate clinical trial design. significant numbers of germinal center b (bgc) cells and antigen-specific cd4 t cells were detectabl ... | 2019 | 31722194 |
brain findings associated with risperidone in rhesus monkeys: magnetic resonance imaging and pathology perspectives. | brain changes associated with risperidone, a dopamine-2/serotonin-2 receptor antagonist, have been documented in rats and humans, but not in nonhuman primates. this study characterized brain changes associated with risperidone in nonhuman primates. rhesus monkeys were orally administered risperidone in a dose-escalation paradigm up to a maximum tolerated dose of 0.5 mg/kg/day for 3 weeks, or 3 months followed by a 3-month recovery period. transient and fully reversible neurological signs consist ... | 2019 | 31719750 |
siv infection aggravates malaria in a chinese rhesus monkey coinfection model. | the co-occurrence of human immunodeficiency virus (hiv) infection and malaria in humans in endemic areas raises the question of whether one of these infections affects the course of the other. although epidemiological studies have shown the impact of hiv infection on malaria, the mechanism(s) are not yet fully understood. using a chinese rhesus macaque coinfection model with simian immunodeficiency virus (siv) and plasmodium cynomolgi (pc) malaria, we investigated the effect of concurrent siv in ... | 2019 | 31718574 |
inflammaging phenotype in rhesus macaques is associated with a decline in epithelial barrier-protective functions and increased pro-inflammatory function in cd161-expressing cells. | the development of chronic inflammation, called inflammaging, contributes to the pathogenesis of age-related diseases. although it is known that both b and t lymphocyte compartments of the adaptive immune system deteriorate with advancing age, the impact of aging on immune functions of th17-type cd161-expressing innate immune cells and their role in inflammaging remain incompletely understood. here, utilizing the nonhuman primate model of rhesus macaques, we report that a dysregulated th17-type ... | 2019 | 31713098 |
a hominid-specific shift in cerebellar expression, upstream retrotransposons, and a potential cis-regulatory mechanism: bioinformatics analyses of the mu-opioid receptor gene. | the mu-opioid receptors (mor, oprm1) mediate the effects of beta-endorphin and modulate many biological functions including reward processing and addiction. the present study aimed to use bioinformatics to determine oprm1 brain expression profiles in higher primates and to look for regulatory mechanisms. we used the same computational pipeline to analyze publicly available expression data from postmortem brain regions across humans, chimpanzees, and rhesus macaques. the most intriguing finding w ... | 2020 | 31712748 |
accelerated evolution of oligodendrocytes in the human brain. | recent discussions of human brain evolution have largely focused on increased neuron numbers and changes in their connectivity and expression. however, it is increasingly appreciated that oligodendrocytes play important roles in cognitive function and disease. whether both cell types follow similar or distinctive evolutionary trajectories is not known. we examined the transcriptomes of neurons and oligodendrocytes in the frontal cortex of humans, chimpanzees, and rhesus macaques. we identified h ... | 2019 | 31712436 |
determination of a t cell receptor of potent cd8+ t cells against simian immunodeficiency virus infection in burmese rhesus macaques. | cumulative studies on human immunodeficiency virus (hiv)-infected individuals have shown association of major histocompatibility complex class i (mhc-i) polymorphisms with lower viral load and delayed aids progression, suggesting that hiv replication can be controlled by potent cd8+ t-cell responses. we have previously established an aids model of simian immunodeficiency virus (siv) infection in burmese rhesus macaques and found a potent cd8+ t cell targeting the mamu-a1*065:01-restricted gag241 ... | 2020 | 31711644 |
proteome profiling of cerebral vessels in rhesus macaques: dysregulation of antioxidant activity and extracellular matrix proteins contributes to cerebrovascular aging in rhesus macaques. | aging is a major risk factor for cerebrovascular disease; however, the molecular mechanisms of cerebrovascular aging remain to be clarified. the aim of this study was to reveal the molecular signaling pathways involved in cerebrovascular aging. this study used high-resolution liquid chromatography coupled to tandem mass spectrometry (lc-ms/ms), in combination with quantitative 6-plex tandem mass tag labeling, to profile protein changes in brain vessels from three groups of healthy rhesus macaque ... | 2019 | 31708766 |
the effect of 5-ht1a receptor antagonist on reward-based decision-making. | when choosing the best action from several alternatives, we compare each value that depends on the balance between benefit and cost. previous studies have shown that animals and humans with low brain serotonin (5-ht) level tend to choose smaller immediate reward. we used a decision-making schedule task to investigate whether 5-ht1a receptor is responsible for the decisions related to reward. in this task, the monkeys chose either of two different alternatives that were comprised of 1-4 drops of ... | 2019 | 31705485 |
effects of the mglur2/3 receptor agonist ly379268 on the reinforcing strength of cocaine in rhesus monkeys. | because chronic cocaine exposure produces profound effects on brain glutamate function, this system has been investigated as a target for novel medications for cocaine use disorder. studies in animal models have provided encouraging results for drugs that target metabotropic glutamate receptors (mglur), particularly group ii mglurs which includes mglur2 and mglur3 receptors. | 2020 | 31705165 |
extensive dissemination and intraclonal maturation of hiv env vaccine-induced b cell responses. | well-ordered hiv-1 envelope glycoprotein (env) trimers are prioritized for clinical evaluation, and there is a need for an improved understanding about how elicited b cell responses evolve following immunization. to accomplish this, we prime-boosted rhesus macaques with clade c nfl trimers and identified 180 unique ab lineages from ∼1,000 single-sorted env-specific memory b cells. we traced all lineages in high-throughput heavy chain (hc) repertoire (rep-seq) data generated from multiple immune ... | 2020 | 31704807 |
tonic exploration governs both flexibility and lapses. | in many cognitive tasks, lapses (spontaneous errors) are tacitly dismissed as the result of nuisance processes like sensorimotor noise, fatigue, or disengagement. however, some lapses could also be caused by exploratory noise: randomness in behavior that facilitates learning in changing environments. if so, then strategic processes would need only up-regulate (rather than generate) exploration to adapt to a changing environment. this view predicts that more frequent lapses should be associated w ... | 2019 | 31703063 |
red blood cell metabolism in rhesus macaques and humans: comparative biology of blood storage. | macaques are emerging as a critical animal model in transfusion medicine, because of their evolutionary similarity to humans and perceived utility in discovery and translational science. however, little is known about the metabolism of rhesus macaque red blood cells (rbc) and how this compares to human rbc metabolism under standard blood banking conditions. metabolomic and lipidomic analyses, and tracing experiments with [1,2,3-13c3]glucose, were performed using fresh and stored rbc (sampled wee ... | 2020 | 31699790 |
extracellular vesicles from mesenchymal stem cells reduce microglial-mediated neuroinflammation after cortical injury in aged rhesus monkeys. | cortical injury, such as injuries after stroke or age-related ischemic events, triggers a cascade of degeneration accompanied by inflammatory responses that mediate neurological deficits. therapeutics that modulate such neuroinflammatory responses in the aging brain have the potential to reduce neurological dysfunction and promote recovery. extracellular vesicles (evs) from mesenchymal stem cells (mscs) are lipid-bound, nanoscale vesicles that can modulate inflammation and enhance recovery in ro ... | 2020 | 31691891 |
dynamic changes in ultrastructure of the primary cilium in migrating neuroblasts in the postnatal brain. | new neurons, referred to as neuroblasts, are continuously generated in the ventricular-subventricular zone of the brain throughout an animal's life. these neuroblasts are characterized by their unique potential for proliferation, formation of chain-like cell aggregates, and long-distance and high-speed migration through the rostral migratory stream (rms) toward the olfactory bulb (ob), where they decelerate and differentiate into mature interneurons. the dynamic changes of ultrastructural featur ... | 2019 | 31685650 |
role of rhesus macaque ifitm3(2) in simian immunodeficiency virus infection of macaques. | the experimental infection of rhesus macaques (rh) with simian immunodeficiency virus (siv) is an important model for human immunodeficiency virus (hiv) infection of humans. the interferon-induced transmembrane protein 3 (ifitm3) inhibits hiv and siv infection at the stage of host cell entry. however, it is still unclear to what extent the antiviral activity of ifitm3 observed in cell culture translates into inhibition of hiv/siv spread in the infected host. we have shown previously that althoug ... | 2019 | 31682595 |
phenotypic characterization of chinese rhesus macaque plasmablasts for cloning antigen-specific monoclonal antibodies. | rhesus macaques (macaca mulatta) are used as a human-relevant animal species for the evaluation of vaccines and as a source for cloning monoclonal antibodies (mabs) that are highly similar to human-derived antibodies. although antibody-secreting plasmablasts in humans are well-defined and can be easily isolated for mab cloning, it remains unclear whether the same phenotypic markers could be applied for isolating antibody-secreting plasmablasts from chinese rhesus macaques. in this study, we eval ... | 2019 | 31681312 |
epd in 2020: enhanced data visualization and extension to ncrna promoters. | the eukaryotic promoter database (epd), available online at https://epd.epfl.ch, provides accurate transcription start site (tss) information for promoters of 15 model organisms plus corresponding functional genomics data that can be viewed in a genome browser, queried or analyzed via web interfaces, or exported in standard formats (fasta, bed, csv) for subsequent analysis with other tools. recent work has focused on the improvement of the epd promoter viewers, which use the ucsc genome browser ... | 2020 | 31680159 |
biomimetic surgical mesh to replace fascia with tunable force-displacement. | here we mimic the mechanical properties of native fascia to design surgical mesh for fascia replacement. despite the widespread acceptance of synthetic materials as tissue scaffolds for pelvic floor disorders, mechanical property mismatch between mesh and adjacent native tissue drives fibrosis and erosion, leading the fda to remove several surgical meshes from the market. however, autologous tissue does not induce either fibrosis or adjacent tissue erosion, suggesting the potential for biomimeti ... | 2020 | 31678097 |
evaluation of the guaiac fecal occult blood test for detection of gastrointestinal bleeding in the rhesus macaque (macaca mulatta). | gastrointestinal (gi) hemorrhage accompanies several common diseases of rhesus macaques (macaca mulatta). guaiac fecal occult blood testing (gfobt) is a non-invasive means to detect such bleeding in several species; however, there are currently no data indicating reliability of this test to detect gi hemorrhage in macaques. | 2020 | 31674042 |
rapid transduction and expansion of transduced t cells with maintenance of central memory populations. | chimeric antigen receptor (car)-t cells show great promise in treating cancers and viral infections. however, most protocols developed to expand t cells require relatively long periods of time in culture, potentially leading to progression toward populations of terminally differentiated effector memory cells. here, we describe in detail a 9-day protocol for car gene transduction and expansion of primary rhesus macaque peripheral blood mononuclear cells (pbmcs). cells produced and expanded with t ... | 2020 | 31673565 |
approach-avoidance conflict in major depressive disorder: congruent neural findings in humans and nonhuman primates. | maladaptive approach-avoidance behavior has been implicated in the pathophysiology of major depressive disorder (mdd), but the neural basis of these abnormalities in decision making remains unclear. capitalizing on recent preclinical findings, we adapted an approach-avoidance conflict task from nonhuman primate research for use in human functional magnetic resonance imaging (fmri). | 2020 | 31672243 |
evaluation of the anti-conflict, reinforcing, and sedative effects of yt-iii-31, a ligand functionally selective for α3 subunit-containing gabaa receptors. | in recent years, pharmacological strategies have implicated α3 subunit-containing gabaa (α3gabaa) receptor subtypes in the anxiety-reducing effects of benzodiazepines, whereas transgenic mouse approaches have implicated α2 or α5 subunit-containing gabaa receptors. | 2020 | 31670615 |
early life temperamental anxiety is associated with excessive alcohol intake in adolescence: a rhesus monkey (macaca mulatta) model. | teenage alcohol abuse is a major health concern, particularly because the majority of alcohol consumed by teenagers is via binge drinking, a known risk factor for increasing the likelihood for the development of future alcohol use disorders (auds). identifying individuals at risk for excessive alcohol intake in adolescence is a step toward developing effective preventative measures and intervention programs. as adults with auds tend to self-medicate their anxiety with alcohol, this longitudinal ... | 2020 | 31670432 |
mitigating gyral bias in cortical tractography via asymmetric fiber orientation distributions. | diffusion tractography in brain connectomics often involves tracing axonal trajectories across gray-white matter boundaries in gyral blades of complex cortical convolutions. to date, gyral bias is observed in most tractography algorithms with streamlines predominantly terminating at gyral crowns instead of sulcal banks. this work demonstrates that asymmetric fiber orientation distribution functions (afodfs), computed via a multi-tissue global estimation framework, can mitigate the effects of gyr ... | 2020 | 31670139 |
anatomical and diffusion mri brain atlases of the fetal rhesus macaque brain at 85, 110 and 135 days gestation. | recent advances in image reconstruction techniques have enabled high resolution mri studies of fetal brain development in human subjects. rhesus macaques (macaca mulatta) are valuable animal models for use in studies of fetal brain development due to the similarities between this species and humans in brain development and anatomy. there is a need to develop fetal brain templates for the rhesus macaque to facilitate the characterization of the normal brain growth trajectory and departures from t ... | 2020 | 31669303 |
high angular resolution diffusion mri reveals conserved and deviant programs in the paths that guide human cortical circuitry. | diffusion magnetic resonance (mr) tractography represents a novel opportunity to investigate conserved and deviant developmental programs between humans and other species such as mice. to that end, we acquired high angular resolution diffusion mr scans of mice [embryonic day (e) 10.5 to postnatal week 4] and human brains [gestational week (gw) 17-30] at successive stages of fetal development to investigate potential evolutionary changes in radial organization and emerging pathways between humans ... | 2020 | 31667494 |
siv-specific cd8+ t cells are clonotypically distinct across lymphoid and mucosal tissues. | cd8+ t cell responses are necessary for immune control of simian immunodeficiency virus (siv). however, the key parameters that dictate antiviral potency remain elusive, conceivably because most studies to date have been restricted to analyses of circulating cd8+ t cells. we conducted a detailed clonotypic, functional, and phenotypic survey of siv-specific cd8+ t cells across multiple anatomical sites in chronically infected rhesus macaques with high (>10,000 copies/ml plasma) or low burdens of ... | 2020 | 31661461 |
islatravir for the treatment and prevention of infection with the human immunodeficiency virus type 1. | to discuss the potential role of islatravir (isl), a novel reverse transcriptase translocation inhibitor, in the treatment and prevention of human immunodeficiency virus type 1 (hiv-1) infection. | 2020 | 31658118 |
the role of oxytocin in regulation of appetitive behaviour, body weight and glucose homeostasis. | obesity and its associated complications have reached epidemic proportions in the usa and also worldwide, highlighting the need for new and more effective treatments. although the neuropeptide oxytocin (oxt) is well recognised for its peripheral effects on reproductive behaviour, the release of oxt from somatodendrites and axonal terminals within the central nervous system (cns) is also implicated in the control of energy balance. in this review, we summarise historical data highlighting the eff ... | 2020 | 31657509 |
computed tomographic excretory urography for diagnosing ectopic ureter in a female rhesus macaque (macaca mulatta). | ectopic ureter is a congenital abnormality where the ureter terminates at a site other than the urinary bladder. a five-year-old female rhesus monkey presented with a urine odor, a wet perineum, and persistent dribbling of urine. an ultrasound examination revealed a cyst-like structure (1 × 0.75 cm) on the left side of the bladder. computed tomographic excretory urography (cteu) imaging revealed a left unilateral extramural ectopic ureter, which was connected to the vagina. the perineum and wet ... | 2020 | 31657019 |
quantitative ferumoxytol-enhanced mri in pregnancy: a feasibility study in the nonhuman primate. | to assess the feasibility of ferumoxytol-enhanced mri in pregnancy with a nonhuman primate model. | 2020 | 31655139 |
role of il-15 signaling in the pathogenesis of simian immunodeficiency virus infection in rhesus macaques. | although il-15 has been implicated in the pathogenic hyperimmune activation that drives progressive hiv and siv infection, as well as in the generation of hiv/siv target cells, it also supports nk and t cell homeostasis and effector activity, potentially benefiting the host. to understand the role of il-15 in siv infection and pathogenesis, we treated two cohorts of sivmac239-infected rhesus macaques (rm; macaca mulatta), one with chronic infection, the other with primary infection, with a rhesu ... | 2019 | 31653683 |
impact of cmv infection on natural killer cell clonal repertoire in cmv-naïve rhesus macaques. | recent functional, gene expression, and epigenetic studies have suggested the presence of a subset of mature natural killer (nk) cells responsible for maintaining nk cell memory. the lack of endogenous clonal markers in nk cells impedes understanding the genesis of these cell populations. in humans, primates, and mice, this phenotype and memory or adaptive functions have been strongly linked to cytomegalovirus or related herpes virus infections. we have used transplantation of lentivirally-barco ... | 2019 | 31649681 |
intranasal oxytocin selectively modulates the behavior of rhesus monkeys in an expression matching task. | although the neuropeptide oxytocin (ot) is thought to regulate prosocial behavior in mammals, there is considerable debate as to how intranasal ot influences primate behavior. the aim of this study was to determine whether intranasal ot has a general anxiolytic effect on the performance of rhesus monkeys tasked with matching face stimuli, or a more selective effect on their behavior towards aversive facial expressions. to this end, we developed an innovative delayed match-to-sample task where th ... | 2019 | 31645593 |
a recombinant rhesus monkey rhadinovirus deleted of glycoprotein l establishes persistent infection of rhesus macaques and elicits conventional t cell responses. | a replication-competent, recombinant strain of rhesus monkey rhadinovirus (rrv) expressing the gag protein of sivmac239 was constructed in the context of a glycoprotein l (gl) deletion mutation. deletion of gl detargets the virus from eph family receptors. the ability of this gl-minus gag recombinant rrv to infect, persist, and elicit immune responses was evaluated after intravenous inoculation of two mamu-a*01+ rrv-naive rhesus monkeys. both monkeys responded with an anti-rrv antibody response, ... | 2020 | 31645449 |
proceedings of the 2019 national toxicology program satellite symposium. | the 2019 annual national toxicology program satellite symposium, entitled "pathology potpourri," was held in raleigh, north carolina, at the society of toxicologic pathology's 38th annual meeting. the goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. this article presents summaries of the speakers' talks along with select images that were used by the audience for voting and discussion. various lesions and topics covered during the symp ... | 2019 | 31645210 |
cd4+ /cd8+ t-cell ratio correlates with the graft fate in pig-to-non-human primate islet xenotransplantation. | xenogeneic islet transplantation using porcine pancreata has been a promising option for substituting human islet transplantation. moreover, recent advances in pre-clinical results have put islet xenotransplantation closer to the possibility of clinical application. while preparing for the era of clinical xenotransplantation, developing non-invasive immune monitoring method which could predict the graft fate could benefit the patient. however, there are few reports showing predictive immune para ... | 2020 | 31642566 |
developing broad-spectrum antivirals using porcine and rhesus macaque models. | isg15-deficient humans exhibit permanent, low-level expression of antiviral effectors that safely protect them from various viruses. because the murine isg15 axis functions differently, we identified animal models that recapitulate the human condition for the development of isg15-targeting broad-spectrum antivirals. canine, porcine, and rhesus macaque isg15, such as human isg15, stabilize usp18, a potent inhibitor of type i interferon (ifn)-i. type i interferon-primed isg15-knockout porcine and ... | 2020 | 31637432 |
low-dimensional motor cortex dynamics preserve kinematics information during unconstrained locomotion in nonhuman primates. | the dynamical systems view of movement generation in motor cortical areas has emerged as an effective way to explain the firing properties of populations of neurons recorded from these regions. recently, many studies have focused on finding low-dimensional representations of these dynamical systems during voluntary reaching and grasping behaviors carried out by the forelimbs. one such model, the poisson linear-dynamical-system (plds) model, has been shown to extract dynamics which can be used to ... | 2019 | 31636530 |
macaques are risk-averse in a freely moving foraging task. | rhesus macaques (macaca mulatta) appear to be robustly risk-seeking in computerized gambling tasks typically used for electrophysiology. this behavior distinguishes them from many other animals, which are risk-averse, albeit measured in more naturalistic contexts. we wondered whether macaques' risk preferences reflect their evolutionary history or derive from the less naturalistic elements of task design associated with the demands of physiological recording. we assessed macaques' risk attitudes ... | 2019 | 31636348 |
cytomegalovirus-vectored vaccines for hiv and other pathogens. | : the use of cytomegalovirus (cmv) as a vaccine vector to express antigens against multiple infectious diseases, including simian immunodeficiency virus, ebola virus, plasmodium, and mycobacterium tuberculosis, in rhesus macaques has generated extraordinary levels of protective immunity against subsequent pathogenic challenge. moreover, the mechanisms of immune protection have altered paradigms about viral vector-mediated immunity against ectopically expressed vaccine antigens. further optimizat ... | 2020 | 31634191 |
direct sunlight exposure reduces hair cortisol levels in rhesus monkeys (macaca mulatta). | major depressive disorder (mdd), commonly known as depression, is a mental disease characterized by a core symptom of low mood. it lasts at least two weeks (badamasi et al., 2019; wang et al., 2019) and is frequently accompanied by low self-esteem, loss of interest in routinely enjoyable activities, low energy, and unexplained pain (huey et al., 2018; park et al., 2012; post & warden, 2018; rice et al., 2019; xiao et al., 2018). approximately 2%-8% of adults with mdd commit suicide (richards & o ... | 2019 | 31631590 |
ozone-induced enhancement of airway hyperreactivity in rhesus macaques: effects of antioxidant treatment. | ozone (o3) inhalation elicits airway inflammation and impairs treatment responsiveness in asthmatic patients. the underlying immune mechanisms have been difficult to study because of the lack of relevant experimental models. rhesus macaques spontaneously have asthma and have a similar immune system to human subjects. | 2020 | 31627909 |
pharmacokinetics of pegylated recombinant human endostatin in rhesus monkeys. | to investigate the pharmacokinetics of pegylated recombinant human endostatin (m2es) in rhesus monkey. m2es was administered to rhesus monkeys by intravenous bolus injection, and serum m2es concentration was determined by a self-developed elisa assay. pharmacokinetic parameters were calculated using a non-compartmental model of winnonlin v2.1a software. the standard curve of self-developed elisa assay was fitted by four-parameter method. the limit of detection (lod) and loq were 0.3050 ng/ml and ... | 2019 | 31626794 |
fingolimod retains cytolytic t cells and limits t follicular helper cell infection in lymphoid sites of siv persistence. | lymph nodes (ln) and their resident t follicular helper cd4+ t cells (tfh) are a critical site for hiv replication and persistence. therefore, optimizing antiviral activity in lymphoid tissues will be needed to reduce or eliminate the hiv reservoir. in this study, we retained effector immune cells in ln of cart-suppressed, siv-infected rhesus macaques by treatment with the lysophospholipid sphingosine-1 phosphate receptor modulator fty720 (fingolimod). fty720 was remarkably effective in reducing ... | 2019 | 31626660 |
independent representations of ipsilateral and contralateral limbs in primary motor cortex. | several lines of research demonstrate that primary motor cortex (m1) is principally involved in controlling the contralateral side of the body. however, m1 activity has been correlated with both contralateral and ipsilateral limb movements. why does ipsilaterally-related activity not cause contralateral motor output? to address this question, we trained monkeys to counter mechanical loads applied to their right and left limbs. we found >50% of m1 neurons had load-related activity for both limbs. ... | 2019 | 31625506 |
reading-out task variables as a low-dimensional reconstruction of neural spike trains in single trials. | we propose a new model of the read-out of spike trains that exploits the multivariate structure of responses of neural ensembles. assuming the point of view of a read-out neuron that receives synaptic inputs from a population of projecting neurons, synaptic inputs are weighted with a heterogeneous set of weights. we propose that synaptic weights reflect the role of each neuron within the population for the computational task that the network has to solve. in our case, the computational task is d ... | 2019 | 31622346 |
recovery from impaired working memory performance during chronic δ-9-tetrahydrocannabinol administration to adolescent rhesus monkeys. | the relationship between adolescent cannabis use and susceptibility to persistent cognitive impairments is poorly understood. | 2020 | 31621487 |
transduction of craniofacial motoneurons following intramuscular injections of canine adenovirus type-2 (cav-2) in rhesus macaques. | reliable viral vector-mediated transgene expression in primate motoneurons would improve our ability to anatomically and physiologically interrogate motor systems. we therefore investigated the efficacy of replication defective, early region 1-deleted canine adenovirus type-2 (cav-2) vectors for mediating transgene expression of fluorescent proteins into brainstem motoneurons following craniofacial intramuscular injections in four rhesus monkeys (macaca mulatta). vector injections were placed in ... | 2019 | 31619971 |
pharmacological modulation of the wnt/β-catenin pathway inhibits proliferation and promotes differentiation of long-lived memory cd4+ t cells in antiretroviral therapy-suppressed simian immunodeficiency virus-infected macaques. | the major obstacle to human immunodeficiency type 1 virus (hiv-1) eradication is a reservoir of latently infected cells that persists despite long-term antiretroviral therapy (art) and is maintained through cellular proliferation. long-lived memory cd4+ t cells with high self-renewal capacity, such as central memory (cm) t cells and stem cell memory (scm) t cells, are major contributors to the viral reservoir in hiv-infected individuals on art. the wnt/β-catenin signaling pathway regulates the b ... | 2019 | 31619550 |
the integration of visual and target signals in v4 and it during visual object search. | searching for a specific visual object requires our brain to compare the items in view with a remembered representation of the sought target to determine whether a target match is present. this comparison is thought to be implemented, in part, via the combination of top-down modulations reflecting target identity with feed-forward visual representations. however, it remains unclear whether top-down signals are integrated at a single locus within the ventral visual pathway (e.g., v4) or at multip ... | 2019 | 31618085 |
correction for kibler et al., "replication-competent nyvac-kc yields improved immunogenicity to hiv-1 antigens in rhesus macaques compared to nonreplicating nyvac". | | 2019 | 31615930 |
complementary encoding of priors in monkey frontoparietal network supports a dual process of decision-making. | prior expectations of movement instructions can promote preliminary action planning and influence choices. we investigated how action priors affect action-goal encoding in premotor and parietal cortices and if they bias subsequent free choice. monkeys planned reaches according to visual cues that indicated relative probabilities of two possible goals. on instructed trials, the reach goal was determined by a secondary cue respecting these probabilities. on rarely interspersed free-choice trials w ... | 2019 | 31612855 |
aggregatibacter actinomycetemcomitans colonization and persistence in a primate model. | aggregatibacter actinomycetemcomitans is associated with aggressive periodontitis resulting in premature tooth loss in adolescents. tooth adherence and biofilm persistence are prerequisites for survival in the oral domain. here, using a rhesus monkey model, 16s rrna sequencing, and weighted network analysis, we assessed colonization of a. actinomycetemcomitans variants and ascertained microbial interactions in biofilm communities. variants in a. actinomycetemcomitans leukotoxin (ltx) were create ... | 2019 | 31611409 |
social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques. | social experience is an important predictor of disease susceptibility and survival in humans and other social mammals. chronic social stress is thought to generate a proinflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. here we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. as predicted by current models, bact ... | 2020 | 31611381 |
[study on the method of microelectrodes implantation of artificial facial nerve prosthesis in closed mouth of orbicularis oris muscle in monkeys with facial nerve paralysis]. | objective: to explore the optimal method of microelectrode implantation that can produce efficient mouth closure with microelectrode for orbicularis oris muscle (oom) in rhesus monkeys with unilateral peripheral facial paralysis (upfp) in order to provide basis for the research and development of artificial facial nerve prosthesis (afnp). methods: right lateral peripheral facial paralysis model on four healthy rhesus monkeys (two males and two femles, aged 5-6 years, weighed 2.0-3.0 kg) were pre ... | 2019 | 31607002 |
transient immune activation in bcg-vaccinated infant rhesus macaques is not sufficient to influence oral simian immunodeficiency virus infection. | bcg vaccination has been demonstrated to increase levels of activated cd4+ t cells, thus potentially influencing mother-to-child transmission of human immunodeficiency virus (hiv). to assess the risk of bcg vaccination in hiv infection, we randomly assigned newborn rhesus macaques to receive bcg vaccine or remain unvaccinated and then undergo oral simian immunodeficiency virus (siv) challenges 3 weeks later. we observed elevated levels of activated peripheral cd4+ t cells (ie, hla-dr+cd38+ccr5+ ... | 2020 | 31605528 |
evaluating chromatin accessibility differences across multiple primate species using a joint modeling approach. | changes in transcriptional regulation are thought to be a major contributor to the evolution of phenotypic traits, but the contribution of changes in chromatin accessibility to the evolution of gene expression remains almost entirely unknown. to address this important gap in knowledge, we developed a new method to identify dnase i hypersensitive (dhs) sites with differential chromatin accessibility between species using a joint modeling approach. our method overcomes several limitations inherent ... | 2019 | 31599933 |
interest in non-social novel stimuli as a function of age in rhesus monkeys. | human cognitive and affective life changes with healthy ageing; cognitive capacity declines while emotional life becomes more positive and social relationships are prioritized. this may reflect an awareness of limited lifetime unique to humans, leading to a greater interest in maintaining social relationships at the expense of the non-social world in the face of limited cognitive and physical resources. alternately, fundamental biological processes common to other primate species may direct pref ... | 2019 | 31598275 |
evaluating the intactness of persistent viral genomes in simian immunodeficiency virus-infected rhesus macaques after initiating antiretroviral therapy within one year of infection. | the major obstacle to more-definitive treatment for hiv infection is the early establishment of virus that persists despite long-term combination antiretroviral therapy (cart) and can cause recrudescent viremia if cart is interrupted. previous studies of hiv dna that persists despite cart indicated that only a small fraction of persistent viral sequences was intact. experimental simian immunodeficiency virus (siv) infections of nonhuman primates (nhps) are essential models for testing interventi ... | 2019 | 31597776 |
in vivo validation of the viral barcoding of simian immunodeficiency virus sivmac239 and the development of new barcoded siv and subtype b and c simian-human immunodeficiency viruses. | genetically barcoded viral populations are powerful tools for evaluating the overall viral population structure as well as assessing the dynamics and evolution of individual lineages in vivo over time. barcoded viruses are generated by inserting a small, genetically unique tag into the viral genome, which is retained in progeny virus. we recently reported barcoding the well-characterized molecular clone simian immunodeficiency virus (siv) sivmac239, resulting in a synthetic swarm (sivmac239m) co ... | 2019 | 31597757 |
motor cortex signals for each arm are mixed across hemispheres and neurons yet partitioned within the population response. | motor cortex (m1) has lateralized outputs, yet neurons can be active during movements of either arm. what is the nature and role of activity across the two hemispheres? we recorded muscles and neurons bilaterally while monkeys cycled with each arm. most neurons were active during movement of either arm. responses were strongly arm-dependent, raising two possibilities. first, population-level signals might differ depending on the arm used. second, the same population-level signals might be presen ... | 2019 | 31596230 |
development and characterization of two gp-specific monoclonal antibodies, which synergistically protect non-human primates against ebola lethal infection. | ebola fever is an acute highly contagious viral disease characterized by severe course, high mortality and development of hemorrhagic syndrome (tendency to skin hemorrhage and bleeding of mucous membranes). the mortality rate of the disease 60-90%. nowadays, there are no licensed specific therapeutic agents for ebola in the world. monoclonal antibodies (mabs) having viral neutralizing activity with high specificity to the gp protein of the ebola virus are considered as candidate highly effective ... | 2019 | 31593751 |
creating a neuroprosthesis for active tactile exploration of textures. | intracortical microstimulation (icms) of the primary somatosensory cortex (s1) can produce percepts that mimic somatic sensation and, thus, has potential as an approach to sensorize prosthetic limbs. however, it is not known whether icms could recreate active texture exploration-the ability to infer information about object texture by using one's fingertips to scan a surface. here, we show that icms of s1 can convey information about the spatial frequencies of invisible virtual gratings through ... | 2019 | 31591224 |
bardet-biedl syndrome in rhesus macaques: a nonhuman primate model of retinitis pigmentosa. | the development of therapies for retinal disorders is hampered by a lack of appropriate animal models. higher nonhuman primates are the only animals with retinal structure similar to humans, including the presence of a macula and fovea. however, few nonhuman primate models of genetic retinal disease are known. we identified a lineage of rhesus macaques with a frameshift mutation in exon 3 of the bbs7 gene c.160delg (p.ala54fs) that is predicted to produce a non-functional protein. in humans, mut ... | 2019 | 31589838 |
an intranasally administered monoclonal antibody cocktail abrogates ricin toxin-induced pulmonary tissue damage and inflammation. | ricin toxin, a plant-derived, mannosylated glycoprotein, elicits an incapacitating and potentially lethal inflammatory response in the airways following inhalation. uptake of ricin by alveolar macrophages (am) and other pulmonary cell types occurs via two parallel pathways: one mediated by ricin's b subunit (rtb), a galactose-specific lectin, and one mediated by the mannose receptor (mr;cd206). ricin's a subunit (rta) is a ribosome-inactivating protein that triggers apoptosis in mammalian cells. ... | 2020 | 31589555 |
transplantation of human esc-derived mesenchymal stem cell spheroids ameliorates spontaneous osteoarthritis in rhesus macaques. | it has been demonstrated that mesenchymal stem cells (mscs) differentiated from human embryonic stem cells (hescs), name emscs, can treat a variety of autoimmune and inflammatory diseases, with similar efficacies to those achieved with mscs derived from somatic tissues such as bone marrow (bmscs). the chance increases even higher for emscs, than somatic tissue derived mscs, to become a cell drug as the former can be produced in large scale from an unlimited hesc line with easier quality control ... | 2019 | 31588237 |
flavobacterium macacae sp. nov., isolated from macaca mulatta faeces. | a yellow, gram-stain-negative, aerobic, non-gliding, non-spore-forming, rod-shaped strain, designated yim 102600t, was isolated from the faeces of macaca mulatta dwelling in the yunnan wild animal park, yunnan province, south-west pr china. phylogenetic analysis based on 16s rrna gene sequences showed that strain yim 102600t was a member of the genus flavobacterium, and closely related to flavobacterium qiangtangense f3t (96.9 % similarity) and flavobacterium noncentrifugens r-hls-17t (96.0 % si ... | 2020 | 31584868 |
clonal tracking of erythropoiesis in rhesus macaques. | the classical model of hematopoietic hierarchies is being reconsidered on the basis of data from in vitro assays and single cell expression profiling. recent experiments suggested that the erythroid lineage might differentiate directly from multipotent hematopoietic stem cells / progenitors or from a highly biased subpopulation of stem cells, rather than transiting through common myeloid progenitors or megakaryocyte-erythrocyte progenitors. we genetically barcoded autologous rhesus macaque stem ... | 2020 | 31582555 |
premotor cortical-cerebellar reorganization in a macaque model of primary motor cortical lesion and recovery. | neuromotor systems have the capacity for functional recovery following local damage. the literature suggests a possible role for the premotor cortex and cerebellum in motor recovery. however, the specific changes to interactions between these areas following damage remain unclear. here, we demonstrate potential rewiring of connections from the ipsilesional ventral premotor cortex (ip-pmv) to cerebellar structures in a nonhuman primate model of primary motor cortex (m1) lesion and motor recovery. ... | 2019 | 31582526 |
isolation, maintenance and differentiation of primary tracheal basal cells from adult rhesus macaque. | in this report, we describe methodologies for the isolation and culture of primary rhesus macaque tracheal basal cells, their cryopreservation, long term storage and differentiation. these are comparable to state-of-the-art protocols that have been developed for mouse and human airway basal cells. this method is based on the use of proprietary media, providing an easily reproducible and applicable protocol for usage in biosafety level 2 (bsl2) settings. tracheas from rhesus macaques were isolate ... | 2019 | 31581513 |
sub-acute toxicological study of artemisinin-piperaquine tablets in rhesus monkeys. | artemisinin-piperaquine tablet (trade name artequick, atq), is a novel combination therapy for the treatment of malaria and especially for resistant p.falciparum malaria. the aim of our study was to assess the potential sub-acute toxicity profile of atq by oral administration route in rhesus monkeys. monkeys were administrated once daily with doses of atq (39.1, 78.2, 156.4 mg/kg) for 21 days and then followed-up a 56-day recovery period. the administration of atq at high dose produced significa ... | 2019 | 31580888 |
development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders. | hematopoietic stem cell (hsc) gene therapy is being evaluated for hemoglobin disorders including sickle cell disease (scd). therapeutic globin vectors have demanding requirements including high-efficiency transduction at the hsc level and high-level, erythroid-specific expression with long-term persistence. the requirement of intron 2 for high-level β-globin expression dictates a reverse-oriented globin-expression cassette to prevent its loss from rna splicing. current reverse-oriented globin ve ... | 2019 | 31578323 |