Publications

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simultaneous subtotal pancreatectomy and streptozotocin injection for diabetes modeling in cynomolgus monkeys.in an experimental animal model of islet transplantation, stable induction of insulin-dependent diabetes mellitus (iddm) and islet isolation from donor pancreas are essential. total pancreatectomy for iddm induction and islet procurement in nonhuman primates leads to unwanted loss of exocrine function and may lead to morbidities associated with iddm.201728583545
chronic ketamine exposure causes white matter microstructural abnormalities in adolescent cynomolgus monkeys.acute and repeated exposures to ketamine mimic aspects of positive, negative, and cognitive symptoms of schizophrenia in humans. recent studies by our group and others have shown that chronicity of ketamine use may be a key element for establishing a more valid model of cognitive symptoms of schizophrenia. however, current understanding on the long-term consequences of ketamine exposure on brain circuits has remained incomplete, particularly with regard to microstructural changes of white matter ...201728579941
translational research in the nonhuman primate model of tuberculosis.infection with mycobacterium tuberculosis predominantly establishes subclinical latent infection over the lifetime of an individual, with a fraction of infected individuals rapidly progressing to active disease. the immune control in latent infection can be perturbed by comorbidities such as diabetes mellitus, obesity, smoking, and coinfection with helminthes or hiv. modeling the varying aspects of natural infection remains incomplete when using zebrafish and mice. however, the nonhuman primate ...201728575319
testicular fibrous hypoplasia in cynomolgus monkeys ( macaca fascicularis): an incidental, congenital lesion.testicular fibrous hypoplasia is an incidental lesion characterized by replacement of the testicular parenchyma by mature collagen. a retrospective survey of hematoxylin and eosin-stained testicular sections from 722 purpose-bred asian and 90 mauritian cynomolgus monkeys from 56 safety assessment studies conducted between 1999 and 2011 was performed. the incidence of the lesion increased markedly over time. no cases occurred between 1999 and 2004. between 2005 and 2009, the incidence ranged betw ...201728573934
obiltoxaximab: adding to the treatment arsenal for bacillus anthracis infection.to review the safety and efficacy of obiltoxaximab, a monoclonal antibody indicated for the treatment of bacillus anthracis inhalational anthrax in adult and pediatric patients.201728573869
characterization of a pristane-induced lupus-associated model in the non-human primate cynomolgus monkey.lupus is an autoimmune disease with complex syndrome. rodent models have limitations for recapitulating the spectrum of the disease. a more powerful translational model is desirable.201728573661
relationship between elevated intraocular pressure and divided peripapillary sector retinal nerve fiber layer thickness in a cynomolgus monkey laser-induced ocular hypertension model.we investigated the relationship between elevated intraocular pressure (iop) and changes in global and peripapillary sector retinal nerve fiber layer (rnfl) thickness around the optic nerve head (onh) in the laser-induced ocular hypertension monkey model.201728564657
the fluorocycline tp-271 is efficacious in models of aerosolized francisella tularensis schu s4 infection in balb/c mice and cynomolgus macaques.tp-271 is a novel, fully synthetic fluorocycline in development for complicated bacterial respiratory infections. tp-271 was active in vitro against a panel of 29 francisella tularensis isolates, showing mics against 50% and 90% of isolates of 0.25 and 0.5 μg/ml, respectively. in a mouse model of inhalational tularemia, animals were exposed by aerosol to 91 to 283 50% lethal doses (ld50)/mouse of f. tularensis schu s4. following 21 days of once-daily intraperitoneal dosing with tp-271 at 3, 6, 1 ...201728559261
comparative evaluation of αcd40 (2c10r4) and αcd154 (5c8h1 and idec-131) in a nonhuman primate cardiac allotransplant model.specific blockade of t cell costimulation pathway is a promising immunomodulatory approach being developed to replace our current clinical immunosuppression therapies. the goal of this study is to compare results associated with 3 monoclonal antibodies directed against the cd40/cd154 t cell costimulation pathway.201728557955
morphological evaluation of retinal ganglion cells expressing the l132c/t159c chr2 mutant transgene in young adult cynomolgus monkeys.to characterize recombinant aav2 (raav2)-mediated expression of l132c/t159c chr2 mutant in retinal ganglion cells (rgcs) of young adult cynomolgus monkeys. raav2 vectors carrying a fusion construct of the chr2 mutant and gfp (chr2-gfp) were delivered to the vitreous chamber by intravitreal injection. expression patterns of the chr2 mutant in rgcs were examined by immunohistochemical methods three months after injection. the rna-binding protein with multiple splicing (rbpms) was used as an rgc sp ...201728550523
prolonged deficits of associative motor learning in cynomolgus monkeys after long-term administration of phencyclidine.phencyclidine (pcp) is a potent drug of abuse that induces sustained schizophrenia-like symptoms in humans by blocking neurotransmission at n-methyl-d-aspartate (nmda)-type glutamate receptors. alterations in nmda receptor function have been linked to numerous behavioral deficits and cognitive dysfunction. classical eye-blink conditioning (ebc), including delay (debc) and trace (tebc) paradigms, provides an effective means to study the neurobiology of associative motor learning in rodents, mamma ...201728549649
high infection rates for adult macaques after intravaginal or intrarectal inoculation with zika virus.unprotected sexual intercourse between persons residing in or traveling from regions with zika virus transmission is a risk factor for infection. to model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with zika virus by intravaginal or intrarectal routes. in macaques inoculated intravaginally, we detected viremia and virus rna in 50% of macaques, followed by seroconversion. in macaques inoculated intrarectally, we detected viremia, virus rna, or both, ...201728548637
insights into reston virus spillovers and adaption from virus whole genome sequences.reston virus (family filoviridae) is unique among the viruses of the ebolavirus genus in that it is considered non-pathogenic in humans, in contrast to the other members which are highly virulent. the virus has however, been associated with several outbreaks of highly lethal hemorrhagic fever in non-human primates (nhps), specifically cynomolgus monkeys (macaca fascicularis) originating in the philippines. in addition, reston virus has been isolated from domestic pigs in the philippines. to bett ...201728542463
discovery of clinical candidate 2-((2s,6s)-2-phenyl-6-hydroxyadamantan-2-yl)-1-(3'-hydroxyazetidin-1-yl)ethanone [bms-816336], an orally active novel selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor.bms-816336 (6n-2), a hydroxy-substituted adamantyl acetamide, has been identified as a novel, potent inhibitor against human 11β-hydroxysteroid dehydrogenase type 1 (11β-hsd1) enzyme (ic50 3.0 nm) with >10000-fold selectivity over human 11β-hydroxysteroid dehydrogenase type 2 (11β-hsd2). 6n-2 exhibits a robust acute pharmacodynamic effect in cynomolgus monkeys (ed50 0.12 mg/kg) and in dio mice. it is orally bioavailable (%f ranges from 20 to 72% in preclinical species) and has a predicted pharma ...201728537398
discovery of n-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (vu0424238): a novel negative allosteric modulator of metabotropic glutamate receptor subtype 5 selected for clinical evaluation.preclinical evidence in support of the potential utility of mglu5 nams for the treatment of a variety of psychiatric and neurodegenerative disorders is extensive, and multiple such molecules have entered clinical trials. despite some promising results from clinical studies, no small molecule mglu5 nam has yet to reach market. here we present the discovery and evaluation of n-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (27, vu0424238), a compound selected for clinical evalua ...201728530802
septicemic invasive klebsiella pneumoniae infection in a cynomolgus monkey (macaca fascicularis) with severe diffused suppurative meningoencephalitis.a 2-year-old male cynomolgus monkey (macaca fascicularis) showed neurological symptoms during quarantine for importation into japan, and was euthanized due to poor prognosis. gross anatomical examination revealed a hemorrhagic lesion around the lateral ventricle in the cerebrum. histologically, severe diffused suppurative meningitis and ventriculitis were detected with numerous gram-negative bacilli in the cerebrum. immunohistochemically, the bacilli were positively stained with an antibody agai ...201728529273
discovery of bi 135585, an in vivo efficacious oxazinanone-based 11β hydroxysteroid dehydrogenase type 1 inhibitor.a potent, in vivo efficacious 11β hydroxysteroid dehydrogenase type 1 (11β hsd1) inhibitor (11j) has been identified. compound 11j inhibited 11β hsd1 activity in human adipocytes with an ic50 of 4.3nm and in primary human adipose tissue with an ic80 of 53nm. oral administration of 11j to cynomolgus monkey inhibited 11β hsd1 activity in adipose tissue. compound 11j exhibited >1000× selectivity over other hydroxysteroid dehydrogenases, displays desirable pharmacodynamic properties and entered huma ...201728528082
modeling rett syndrome using talen-edited mecp2 mutant cynomolgus monkeys.gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. here, we report detailed genotypes and phenotypes of talen-edited mecp2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, rett syndrome (rtt), which is caused by loss-of-function mutations in the human mecp2 gene. male mutant monkeys were embryonic lethal, reiterating that rtt is a disease of females. through a battery of behavioral analyses, including prim ...201728525759
from the cover: evaluation of the effects of tanezumab, a monoclonal antibody against nerve growth factor, on the sympathetic nervous system in adult cynomolgus monkeys (macaca fascicularis): a stereologic, histomorphologic, and cardiofunctional assessment.tanezumab, a humanized monoclonal antibody against nerve growth factor is in development for treatment of chronic pain. three nonclinical studies assessed effects of clinically relevant and supratherapeutic doses of tanezumab on the sympathetic nervous system (sns) of adult nonhuman primates. study 1 evaluated potential effects of subcutaneous (sc) tanezumab (1.2 mg/kg every 8 weeks [q8w]) on sns in cynomolgus monkeys for 3 or 6 months and reversibility or persistence of any effects through a no ...201728525647
effects of olanexidine gluconate on preoperative skin preparation: an experimental study in cynomolgus monkeys.to determine the bactericidal efficacy of a new topical antiseptic for preoperative skin preparation, olanexidine gluconate (development code: opb-2045g), against transient or resident bacterial flora on the skin of cynomolgus monkeys.201728516852
mechanistic modeling of the pharmacodynamic and pharmacokinetic relationship of tissue factor pathway inhibitor-neutralizing antibody (bay 1093884) in cynomolgus monkeys.bay 1093884 is a fully human monoclonal antibody against the tissue factor pathway inhibitor (tfpi) in development as prophylaxis in patients with hemophilia with or without inhibitors. in vitro, bay 1093884 binds to human, mouse, and monkey tfpi. the objective of this study was to find a pharmacodynamic (pd) biomarker after administration of bay 1093884 to normal monkeys. in monkey plasma, bay 1093884 exhibited an ic50 (concentration that inhibits 50%) of 4.65 and 6.19 nm for free tfpi and dilu ...201728516358
intergroup variation in robbing and bartering by long-tailed macaques at uluwatu temple (bali, indonesia).robbing and bartering (rb) is a behavioral practice anecdotally reported in free-ranging commensal macaques. it usually occurs in two steps: after taking inedible objects (e.g., glasses) from humans, the macaques appear to use them as tokens, returning them to humans in exchange for food. while extensively studied in captivity, our research is the first to investigate the object/food exchange between humans and primates in a natural setting. during a 4-month study in 2010, we used both focal and ...201728516338
a neutralizing anti-g-csfr antibody blocks g-csf-induced neutrophilia without inducing neutropenia in nonhuman primates.neutrophils are the most abundant wbcs and have an essential role in the clearance of pathogens. tight regulation of neutrophil numbers and their recruitment to sites of inflammation is critical in maintaining a balanced immune response. in various inflammatory conditions, such as rheumatoid arthritis, vasculitis, cystic fibrosis, and inflammatory bowel disease, increased serum g-csf correlates with neutrophilia and enhanced neutrophil infiltration into inflamed tissues. we describe a fully huma ...201728515226
effects of sa237, a humanized anti-interleukin-6 receptor monoclonal antibody, on pre- and postnatal development in cynomolgus monkey.sa237 is a humanized anti-interleukin-6 receptor (il-6r) monoclonal antibody in which the constant and variable regions have been engineered for a longer plasma half-life. according to literature, blocking of il-6 related functions could have an influence on pregnancy sustainment, development of the immune system, and brain growth.201728504465
investigating biogeographic boundaries of the sunda shelf: a phylogenetic analysis of two island populations of macaca fascicularis.cyclical submergence and re-emergence of the sunda shelf throughout the pleistocene served as a dynamic biogeographic landscape, across which long-tailed macaques (macaca fascicularis) have migrated and evolved. here, we tested the integrity of the previously reported continental-insular haplotype divide reported among y and mitochondrial dna lineages across multiple studies.201728500747
first molecular identification and genetic diversity of strongyloides stercoralis and strongyloides fuelleborni in human communities having contact with long-tailed macaques in thailand.the parasitic nematodes, strongyloides stercoralis and strongyloides fuelleborni, can infect humans and non-human primates. we amplified and sequenced a portion of the 18s ribosomal rna gene (rrna) and of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of strongyloides from humans in the study area in thailand, where people have frequent contact with long-tailed macaques. fresh stool samples were obtained from 213 people and were examined using the agar plate culture method. the ove ...201728500375
comparison of the vaginal environment in rhesus and cynomolgus macaques pre- and post-lactobacillus colonization.rhesus and cynomologus macaques are valuable animal models for the study of human immunodeficiency virus (hiv) prevention strategies. however, for such studies focused on the vaginal route of infection, differences in vaginal environment may have deterministic impact on the outcome of such prevention, providing the rationale for this study.201728488364
interplay between grip and vision in the monkey medial parietal lobe.we aimed at understanding the relative contribution of visual information and hand shaping to the neuronal activity of medial posterior parietal area v6a, a newly added area in the monkey cortical grasping circuit. two macaca fascicularis performed a reach-to-grasp task in the dark and in the light, grasping objects of different shapes. we found that v6a contains visual cells, activated only during grasping in the light; motor neurons, equally activated during grasping in the dark and in the lig ...201728472262
low potential for mechanical transmission of ebola virus via house flies (musca domestica).ebola virus (ebov) infection results in high morbidity and mortality and is primarily transmitted in communities by contact with infectious bodily fluids. while clinical and experimental evidence indicates that ebov is transmitted via mucosal exposure, the ability of non-biting muscid flies to mechanically transmit ebov following exposure to the face had not been assessed.201728468673
activation of skeletal muscle ampk promotes glucose disposal and glucose lowering in non-human primates and mice.the amp-activated protein kinase (ampk) is a potential therapeutic target for metabolic diseases based on its reported actions in the liver and skeletal muscle. we evaluated two distinct direct activators of ampk: a non-selective activator of all ampk complexes, pf-739, and an activator selective for ampk β1-containing complexes, pf-249. in cells and animals, both compounds were effective at activating ampk in hepatocytes, but only pf-739 was capable of activating ampk in skeletal muscle. in dia ...201728467931
pharmacokinetic de-risking tools for selection of monoclonal antibody lead candidates.pharmacokinetic studies play an important role in all stages of drug discovery and development. recent advancements in the tools for discovery and optimization of therapeutic proteins have created an abundance of candidates that may fulfill target product profile criteria. implementing a set of in silico, small scale in vitro and in vivo tools can help to identify a clinical lead molecule with promising properties at the early stages of drug discovery, thus reducing the labor and cost in advanci ...201728463063
in utero transfer of adeno-associated viral vectors produces long-term factor ix levels in a cynomolgus macaque model.the safe correction of an inherited bleeding disorder in utero prior to the onset of organ damage is highly desirable. here, we report long-term transgene expression over more than 6 years without toxicity following a single intrauterine gene transfer (iugt) at 0.9g using recombinant adeno-associated vector (aav)-human factor ix (hfix) in the non-human primate model we have previously described. four of six treated animals monitored for around 74 months expressed hfix at therapeutic levels (3.9% ...201728462816
a simple way to eradicate methicillin-resistant staphylococcus aureus in cynomolgus macaques (macaca fascicularis).our investigation of indoor-housed cynomolgus macaques (macaca fascicularis) by using automated identification followedbyantibiotic susceptibility testing revealed 1 of 7 immunocompetent animals and 2 of 9 immunosuppressed monkeys as carriers ofmethicillin-resistant staphylococcus aureus (mrsa). follow-up management involving mupirocin treatment resulted in the conversion of the 3 mrsa carriers into mrsa-negative cases. prospective assessment of newly imported monkeys involving 24-h culture of n ...201728462776
nonuniform moving boundary method for computational fluid dynamics simulation of intrathecal cerebrospinal flow distribution in a cynomolgus monkey.a detailed quantification and understanding of cerebrospinal fluid (csf) dynamics may improve detection and treatment of central nervous system (cns) diseases and help optimize csf system-based delivery of cns therapeutics. this study presents a computational fluid dynamics (cfd) model that utilizes a nonuniform moving boundary approach to accurately reproduce the nonuniform distribution of csf flow along the spinal subarachnoid space (sas) of a single cynomolgus monkey. a magnetic resonance ima ...201728462417
comprehensive analysis of circulating microrna specific to the liver, heart, and skeletal muscle of cynomolgus monkeys.circulating micrornas (mirnas) could represent sensitive and specific biomarkers for tissue injury. however, their utility as biomarkers in nonclinical toxicological studies using nonhuman primates is limited by a lack of information on their organ specificity and circulating levels under resting condition of the animals. herein, liver, heart, and skeletal muscle-specific expression patterns of mirnas were determined in 27 tissues/organs from male and female monkeys (n =2/sex) by next-generation ...201728460582
localization of zinc transporters in the spinal cord of cynomolgus monkey.zinc is abundant in the spinal cord, where it participates in several physiological and pathophysiological processes, including neurotransmission, spinal cord injury, and amyotrophic lateral sclerosis. however, the mechanisms underlying zinc homeostasis in the spinal cord are largely unknown. zinc transporters (znts) are responsible for transporting zinc from the cytoplasm to the extracellular space or to intracellular compartments. in the present study, we examined the distribution of znt1-10 p ...201728455213
role of regional absorption and gastrointestinal motility on variability in oral absorption of a model drug.variability in oral absorption in pre-clinical species makes human dose projection challenging. in this study, we investigated the mechanistic basis of variability in oral absorption of a model hydrophobic compound with ph-dependent solubility, bms-955829, after oral dosing in rats, dogs, and cynomolgus monkeys. the contribution of regional absorption to pharmacokinetic variability was assessed in ported monkeys by direct intraduodenal and intraileal administration. the effect of bms-955829 on g ...201728455207
in depth comparative phenotyping of blood innate myeloid leukocytes from healthy humans and macaques using mass cytometry.comparative immune-profiling of innate responses in humans and non-human primates is important to understand the pathogenesis of infectious and chronic inflammatory diseases as well as for the preclinical development of vaccines and immune therapies. however, direct comparisons of the two species are rare and were never performed using mass cytometry. here, whole-blood-derived leukocytes from healthy humans and cynomolgus macaques were analyzed with mass cytometry. two similar panels of around 3 ...201728444973
iohexol clearance for determination of glomerular filtration rate in cynomolgus monkeys (macaca fascicularis).the purpose of this study was to validate a method for determine the glomerular filtration rate (gfr) in healthy cynomolgus monkeys by using iohexol. eighteen healthy cynomolgus macaque monkeys (age, 4 to 6 y [mean, 5 y]; weight, 2 to 6 kg [mean, 4 kg]) were randomly entered into 3 different doses groups (3 male and 3 female macaques per group) of 30, 60, 90 mg i/kg to receive an intravenous bolus injection of iohexol. serum iohexol concentrations were determined by using liquid chromatography-t ...201728443538
effects of an ep2 and ep3 receptor dual agonist, ono-8055, on a radical hysterectomy-induced underactive bladder model in monkeys.the objective was to develop an underactive bladder (uab) model in primates and to evaluate the potential of prostanoid ep2 and ep3 receptor dual agonist ono-8055 to become a therapeutic agent for uab.201728439968
herpes b virus replication and viral lesions in the liver of a cynomolgus macaque which died from severe disease with rapid onset.herpes b virus (bv, macacine alphaherpesvirus 1) infects macaques asymptomatically, with rare exceptions, but can cause fatal encephalitis in humans. here, we report disseminated bv infection in a cynomolgus macaque that had died within 12 hour after the onset of unspecific symptoms. multifocal lesions surrounded by viral antigen were detected in liver while other organs remained inconspicuous, indicating that the liver is a major target. moreover, high copy numbers of viral dna were found in fe ...201728439900
long lasting neutralization of c5 by sky59, a novel recycling antibody, is a potential therapy for complement-mediated diseases.dysregulation of the complement system is linked to the pathogenesis of a variety of hematological disorders. eculizumab, an anti-complement c5 monoclonal antibody, is the current standard of care for paroxysmal nocturnal hemoglobinuria (pnh) and atypical hemolytic uremic syndrome (ahus). however, because of high levels of c5 in plasma, eculizumab has to be administered biweekly by intravenous infusion. by applying recycling technology through ph-dependent binding to c5, we generated a novel hum ...201728439081
pharmacokinetic and toxicology comparator testing of biosimilar drugs - assessing need.a key element in the development of a biosimilar molecule is the comparability of the biological activity/nonclinical similarity to the innovator drug. although some regulatory guidelines are encouraging little or no in vivo testing, currently a common practice is to perform at least one toxicology and/or one pharmacokinetic (pk) study to assess if any different findings occur for in-life, clinical pathology and histopathological parameters or in exposure. an exercise was performed in which the ...201728433587
preclinical study of raav2-strail: pharmaceutical efficacy, biodistribution and safety in animals.the recombinant strail has been in clinical trial for various human malignancies. however, the half-life time of strail is very short, which might be an important factor influencing its clinical efficacy for cancer therapy. we previously reported the recombinant adeno-associated virus (aav)-encoding strail95-281-mediated strail expression in vivo up to 8 months and suppressed tumor growth markedly in mouse xenografts. in the present study, we further evaluated the clinical potency for cancer gen ...201728429751
kinetic reconstruction reveals time-dependent effects of romosozumab on bone formation and osteoblast function in vertebral cancellous and cortical bone in cynomolgus monkeys.romosozumab, a humanized monoclonal sclerostin antibody under development for the treatment of osteoporosis, has a unique mechanism of action on bone-increasing bone formation and decreasing bone resorption. the effects on bone formation are transient, eliciting a rapid increase in bone formation that attenuates with continued treatment. although bone formation attenuates, bone mineral density (bmd) continues to increase. to explore potential tissue-level mechanisms that could contribute to a pr ...201728428078
alveolar ridge dimensional changes following ridge preservation procedure with novel devices: part 3 - histological analysis in non-human primate model.this study sought to investigate the histological changes following tooth extraction, ridge preservation and augmentation, using novel devices designed to obturate the oral orifice of extraction sockets (socketkap™) and provide structural support for sockets with defective bony walls (socketkage™) in a non-human primate model.201728422326
pharmacokinetics of monoclonal antibodies and fc-fusion proteins.there are many factors that can influence the pharmacokinetics (pk) of a mab or fc-fusion molecule with the primary determinant being fcrn-mediated recycling. through fab or fc engineering, igg-fcrn interaction can be used to generate a variety of therapeutic antibodies with significantly enhanced half-life or ability to remove unwanted antigen from circulation. glycosylation of a mab or fc-fusion protein can have a significant impact on the pk of these molecules. mab charge can be important and ...201728421387
urban primate ranging patterns: gps-collar deployments for macaca fascicularis and m. sylvanus.the global increase in urbanization is leading to heavier interface between humans and wildlife. within these anthropogenic landscapes, little is known about ranging patterns, particularly with regard to urban primates. here we present the results of the first long-term deployment of multiple gps collars on two species of macaques to investigate the impacts of urbanization on urban primate ranging patterns in singapore and gibraltar. collars data acquisition were excellent with respect to the am ...201728419550
evaluation of the physiotel™ digital m11 cardiovascular telemetry implant in socially housed cynomolgus monkeys up to 16weeks after surgery.the novel physiotel™ digital m11 telemetry implant was evaluated in socially housed monkeys with respect to both safety pharmacological cardiovascular (arterial blood pressure (bp), heart rate (hr) and electrocardiogram (ecg)) and toxicological (clinical pathology and histopathology) endpoints.201728416413
distribution of fcrn across species and tissues.the neonatal fc receptor (fcrn) is a major histocompatibility complex class i type molecule that binds to, transports, and recycles immunoglobulin g (igg) and albumin, thereby protecting them from lysosomal degradation. therefore, besides the knowledge of fcrn affinity, fcrn protein expression is critical in understanding the pharmacokinetic behavior of fc-containing biotherapeutics such as monoclonal antibodies. the goal of this investigation was to achieve for the first time a comparative asse ...201728402755
collagen sponge functionalized with chimeric anti-bmp-2 monoclonal antibody mediates repair of critical-size mandibular continuity defects in a nonhuman primate model.antibody-mediated osseous regeneration (amor) has been introduced by our research group as a tissue engineering approach to capture of endogenous growth factors through the application of specific monoclonal antibodies (mabs) immobilized on a scaffold. specifically, anti-bone morphogenetic protein- (bmp-) 2 mabs have been demonstrated to be efficacious in mediating bone repair in a number of bone defects. the present study sought to investigate the application of amor for repair of mandibular co ...201728401163
leveraging of rifampicin-dosed cynomolgus monkeys to identify bile acid 3-o-sulfate conjugates as potential novel biomarkers for organic anion-transporting polypeptides.in the search for novel bile acid (ba) biomarkers of liver organic anion-transporting polypeptides (oatps), cynomolgus monkeys received oral rifampicin (rif) at four dose levels (1, 3, 10, and 30 mg/kg) that generated plasma-free cmax values (0.06, 0.66, 2.57, and 7.79 µm, respectively) spanning the reported in vitro ic50 values for oatp1b1 and oatp1b3 (≤1.7 μm). as expected, the area under the plasma concentration-time curve (auc) of an oatp probe drug (i.v. (2)h4-pitavastatin, 0.2 mg/kg) was i ...201728396527
identification of human igg1 variant with enhanced fcrn binding and without increased binding to rheumatoid factor autoantibody.various studies have demonstrated that fc engineering to enhance neonatal fc receptor (fcrn) binding is effective for elongating half-life or increasing cellular uptake of igg. a previous study has shown that a n434h mutation to enhance fcrn binding resulted in increased binding to rheumatoid factor (rf) autoantibody, which is not desirable for therapeutic use in autoimmune disease. in this study, we first showed that all the existing fc variants with enhanced fcrn binding also show increased rf ...201728387635
establishment of reference values for complete blood count and blood gases in cynomolgus monkeys (macaca fascicularis).cynomolgus monkeys are closely related to humans phylogenetically, and this has resulted in their widespread use as a preclinical model. hematological data with regard to these monkeys are thus important. although reference values for blood components and sex hormones have been established for cynomolgus monkeys, those for arterial blood gases have not. the arterial blood gases quickly reflect respiratory and circulatory dynamics, and are thus useful for animal management and safe general anesth ...201728381665
evidence of simian retrovirus type d by polymerase chain reaction.over the past few years, there have been reports of finding simian retrovirus type d (srv) in macaque colonies where some animals were characterized as antibody positive but virus negative raising questions about how srv was transmitted or whether there is a variant strain detected by antibody but not polymerase chain reaction (pcr) in current use.201728370081
long-term blood glucose monitoring with implanted telemetry device in conscious and stress-free cynomolgus monkeys.continuous blood glucose monitoring, especially long-term and remote, in diabetic patients or research is very challenging. nonhuman primate (nhp) is an excellent model for metabolic research, because nhps can naturally develop type 2 diabetes mellitus (t2dm) similarly to humans. this study was to investigate blood glucose changes in conscious, moving-free cynomolgus monkeys (macaca fascicularis) during circadian, meal, stress and drug exposure.201728365864
establishing a large-animal model for in vivo reprogramming of bile duct cells into insulin-secreting cells to treat diabetes.type 1 diabetes manifests as autoimmune destruction of beta cells requiring metabolic management with an exogenous replacement of insulin, either by repeated injection of recombinant insulin or by transplantation of allogeneic islets from cadaveric donors. both of these approaches have severe limitations. repeated insulin injection requires intensive blood glucose monitoring, is expensive, and is associated with decreased quality-of-life measures. islet transplantation, while highly effective, i ...201728363269
long noncoding rna mantis facilitates endothelial angiogenic function.the angiogenic function of endothelial cells is regulated by numerous mechanisms, but the impact of long noncoding rnas (lncrnas) has hardly been studied. we set out to identify novel and functionally important endothelial lncrnas.201728351900
discrimination of stem cell status after subjecting cynomolgus monkey pluripotent stem cells to naïve conversion.experimental animal models have played an indispensable role in the development of human induced pluripotent stem cell (ipsc) research. the derivation of high-quality (so-called "true naïve state") ipscs of non-human primates enhances their application and safety for human regenerative medicine. although several attempts have been made to convert human and non-human primate pscs into a truly naïve state, it is unclear which evaluation methods can discriminate them as being truly naïve. here we a ...201728349944
adipokines (leptin, adiponectin, resistin) differentially regulate all hormonal cell types in primary anterior pituitary cell cultures from two primate species.adipose-tissue (at) is an endocrine organ that dynamically secretes multiple hormones, the adipokines, which regulate key physiological processes. however, adipokines and their receptors are also expressed and regulated in other tissues, including the pituitary, suggesting that locally- and at-produced adipokines might comprise a regulatory circuit that relevantly modulate pituitary cell-function. here, we used primary pituitary cell-cultures from two normal nonhuman-primate species [papio-anubi ...201728349931
improved full-length killer cell immunoglobulin-like receptor transcript discovery in mauritian cynomolgus macaques.killer cell immunoglobulin-like receptors (kirs) modulate disease progression of pathogens including hiv, malaria, and hepatitis c. cynomolgus and rhesus macaques are widely used as nonhuman primate models to study human pathogens, and so, considerable effort has been put into characterizing their kir genetics. however, previous studies have relied on cdna cloning and sanger sequencing that lack the throughput of current sequencing platforms. in this study, we present a high throughput, full-len ...201728343239
preclinical development of a humanized neutralizing antibody targeting hgf.hepatocyte growth factor (hgf) and its receptor, cmet, play critical roles in cell proliferation, angiogenesis and invasion in a wide variety of cancers. we therefore examined the anti-tumor activity of the humanized monoclonal anti-hgf antibody, yyb-101, in nude mice bearing human glioblastoma xenografts as a single agent or in combination with temozolomide. hgf neutralization, the extracellular signal-related kinases 1 and 2 (erk1/2) phosphorylation, and hgf-induced scattering were assessed in ...201728336956
social setting, social rank and hpa axis response in cynomolgus monkeys.hypothalamic-pituitary-adrenal (hpa) axis activity under different social settings in non-human primates is understudied.201728332004
a novel fc-fgf21 with improved resistance to proteolysis, increased affinity toward β-klotho, and enhanced efficacy in mice and cynomolgus monkeys.fibroblast growth factor (fgf) 21 is a natural hormone that modulates glucose, lipid, and energy metabolism. previously, we engineered an fc fusion fgf21 variant with two mutations, fc-fgf21(rg), to extend the half-life and reduce aggregation and in vivo degradation of fgf21. we now describe a new variant developed to reduce the extreme c-terminal degradation and improve the binding affinity to β-klotho. we demonstrate, by introducing one additional mutation located at the c terminus of fgf21 (a ...201728324011
immunolocalization of novel corticomedullary tubule injury markers in cynomolgus monkeys treated with amphotericin b.amphotericin b (ampb) nephrotoxicity was used to assess the utility of drug‑induced kidney injury (diki) biomarkers in an exploratory study in male cynomolgus monkeys. all animals had quantifiable levels of ampb in plasma on days 1 and 4. there were no clinical signs of ampb‑induced toxicity in this study. the gold standard method used to confirm ampb‑induced diki was anatomic pathology which revealed microscopic lesions with varying grades of severity. immunolocalization of alpha‑1 microglobuli ...201728321043
decoding information for grasping from the macaque dorsomedial visual stream.neurodecoders have been developed by researchers mostly to control neuroprosthetic devices, but also to shed new light on neural functions. in this study, we show that signals representing grip configurations can be reliably decoded from neural data acquired from area v6a of the monkey medial posterior parietal cortex. two macaca fascicularis monkeys were trained to perform an instructed-delay reach-to-grasp task in the dark and in the light toward objects of different shapes. population neural ...201728320845
from play to proficiency: the ontogeny of stone-tool use in coastal-foraging long-tailed macaques (macaca fascicularis) from a comparative perception-action perspective.macaques crack shellfish in coastal environments with specialized stone-hammering techniques. i provide the first examination of skill development from 866 object-manipulation and 7,400 tool-use bouts, collected over 15 months, using longitudinal analyses of infants' object manipulation (n = 7) and cross-sectional comparisons of manipulative and tool-use behavior (n = 69). i adopt a perception-action approach, examining how the emergence of actions on objects relate to the spatial-relational and ...201728318292
preclinical evaluation of the efficacy, pharmacokinetics and immunogenicity of js-001, a programmed cell death protein-1 (pd-1) monoclonal antibody.js-001 is the first monoclonal antibody (mab) against programmed cell death protein-1 (pd-1) approved by the china food and drug administration (cfda) into the clinical trails. to date, however, no pre-clinical pharmacological and pharmacokinetic (pk) data are available. in this study, we investigated the efficacy of js-001 and conducted a preclinical pk study, including the monitoring of anti-drug antibodies (adas). we found that js-001 specifically bound to pd-1 antigen with an ec50 of 21 nmol ...201728317872
radiological and microsurgical anatomy for variation of the mandible: comparative study of human and macaca fascicularis.recent studies using cone-beam computer tomography (cbct) have added to our understanding of anatomical variation in the mandible of humans. however, the distribution of nerves cannot be revealed by cbct. there have been investigations of the distribution of nerves relating to the mandible, but some proposed causes of these variations remain controversial. in this study, we observed a total of 10 sides from five mandibles of macaca fascicularis of unknown age and sex using cbct and dissection un ...201728317283
morphologic and doppler findings from hepatic ultrasonography of normal cynomolgus monkeys (macaca fascicularis).the present study evaluated the anatomic and ultrasonographic features of the liver in normal cynomolgus monkeys (macaca fascicularis). healthy, male, cynomolgus monkeys from cambodia (n = 25; mean age, 58.1 mo) were sedated with ketamine (7 mg/kg) and examined by using 2d and doppler ultrasonography. we measured the diameters of the vascular structures and bile duct, determined the velocities of the hepatic artery and portal vein, and calculated the resistance index of the hepatic artery. vesse ...201728315648
the effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-β concentrations and clearance in the cynomolgus monkey.sacubitril/valsartan (lcz696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. as neprilysin (nep) is one of several enzymes known to degrade amyloid-β (aβ), there is a theoretical risk of aβ accumulation following long-term nep inhibition. the primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system cl ...201728315356
[(3)h]bmt-046091 a potent and selective radioligand to determine aak1 distribution and target engagement.adaptor-associated kinase 1 (aak1), a member of the ark1/prk1 family of serine/threonine kinases, plays a role in modulating clatherin coated endocytosis of specific surface receptors. we have demonstrated that aak1 inhibitors are efficacious in rodent models of neuropathic pain (kostich et al., 2016). here we have characterized the binding properties and distribution pattern of the tritiated aak1 radioligand, [(3)h]bmt-046091, in rodents and cynomolgus monkeys, and used the radioligand to measu ...201728315351
nutritional composition of fruits selected by long-tailed macaques (macaca fascicularis) in kuala selangor, malaysia.proximate analysis of twelve species of fruits commonly consumed by long-tailed macaques (macaca fascicularis), i.e., arenga pinnata, areca catechu, terminalia catappa, elaeis guineensis, lagerstroemia tomentosa, mangifera indica, cascabela thevetia, muntingia calabura, musa sp., artocarpus heterophyllus, ficus tinctoria ssp. gibbosa and ficus microcarpa, was conducted with the specific objective to determine the nutritional composition of the foodstuffs of long-tailed macaques. the results show ...201728228918
convergent balancing selection on the mu-opioid receptor in primates.the mu opioid receptor is involved in many natural processes including stress response, pleasure, and pain. mutations in the gene also have been associated with opiate and alcohol addictions as well as with responsivity to medication targeting these disorders. two common and mutually exclusive polymorphisms have been identified in humans, a118g (n40d), found commonly in non-african populations, and c17t (v6a), found almost exclusively in african populations. while a118g has been studied extensiv ...201728333316
investigation of sleep-wake rhythm in non-human primates without restraint during data collection.to understand sleep mechanisms and develop treatments for sleep disorders, investigations using animal models are essential. the sleep architecture of rodents differs from that of diurnal mammals including humans and non-human primates. sleep studies have been conducted in non-human primates; however, these sleep assessments were performed on animals placed in a restraint chair connected via the umbilical area to the recording apparatus. to avoid restraints, cables, and other stressful apparatus ...201727760892
comparison of saliva collection methods for the determination of salivary cortisol levels in rhesus macaques (macaca mulatta), cynomolgus macaques (macaca fascicularis), and african green monkeys (chlorocebus aethiops).the ability to quickly and accurately determine cortisol as a biomarker for stress is a valuable tool in assessing the wellbeing of nhp. in this study, 2 methods of collecting saliva (a commercial collection device and passive drool) and the resulting free salivary cortisol levels were compared with total serum cortisol concentration in rhesus macaques (macaca mulatta), cynomolgus macaques (macaca fascicularis) and african green monkeys (chlorocebus aethiops) at 2 collection time points. serum a ...201728315649
comparison of saliva collection methods for the determination of salivary cortisol levels in rhesus macaques (macaca mulatta), cynomolgus macaques (macaca fascicularis), and african green monkeys (chlorocebus aethiops).the ability to quickly and accurately determine cortisol as a biomarker for stress is a valuable tool in assessing thewellbeing of nhp. in this study, 2 methods of collecting saliva (a commercial collection device and passive drool) and the resulting free salivary cortisol levels were compared with total serum cortisol concentration in rhesus macaques (macaca mulatta),cynomolgus macaques (macaca fascicularis) and african green monkeys (chlorocebus aethiops) at 2 collection time points.serum and ...201728256186
behavioral determinants of cannabinoid self-administration in old world monkeys.reinforcing effects of δ(9)-tetrahydrocannabinol (thc), the primary active ingredient in marijuana, as assessed with self-administration (sa), has only been established in new world primates (squirrel monkeys). the objective of this study was to investigate some experimental factors that may enhance intravenous sa of thc and the cannabinoid receptor (cbr) agonist cp 55 940 in old world monkeys (rhesus and cynomolgus), a species that has been used extensively in biomedical research. in one experi ...201728059083
structure and evolution of the filaggrin gene repeated region in primates.the evolutionary dynamics of repeat sequences is quite complex, with some duplicates never having differentiated from each other. two models can explain the complex evolutionary process for repeated genes-concerted and birth-and-death, of which the latter is driven by duplications maintained by selection. copy number variations caused by random duplications and losses in repeat regions may modulate molecular pathways and therefore affect phenotypic characteristics in a population, resulting in i ...201728077068
pathogenic analysis of the pandemic 2009 h1n1 influenza a viruses in ferrets.the pandemic 2009 h1n1 influenza a virus emerged in humans and caused the first influenza pandemic of the 21st century. mexican isolates, a/mexico/4108/2009 (h1n1) (mex4108) and a/mexico/indre4478/2009 (h1n1) (mex4487) derived from a mild case and from a cluster of severe cases, showed heterogeneity in virulence in a cynomolgus macaque model. to compare the more pathogenic differences, we generated recombinant viruses and compared their virulence in ferrets. ferrets infected with recombinant mex ...201728674309
nectin-4 interactions govern measles virus virulence in a new model of pathogenesis, the squirrel monkey (saimiri sciureus).in addition to humans, only certain nonhuman primates are naturally susceptible to measles virus (mev) infection. disease severity is species dependent, ranging from mild to moderate for macaques to severe and even lethal for certain new world monkey species. to investigate if squirrel monkeys (saimiri sciureus), which are reported to develop a course of disease similar to humans, may be better suited than macaques for the identification of virulence determinants or the evaluation of therapeutic ...201728331086
(18)f-gp1, a novel pet tracer designed for high-sensitivity, low-background detection of thrombi.thromboembolic diseases such as myocardial infarction, stroke, transient ischemic attacks, and pulmonary embolism are major causes of morbidity and mortality worldwide. glycoprotein iib/iiia (gpiib/iiia) is the key receptor involved in platelet aggregation and is a validated target for therapeutic approaches and diagnostic imaging. the aim of this study was to develop and characterize a specific small-molecule tracer for pet imaging that binds with high affinity to gpiib/iiia receptors and has s ...201728302764
improvement of adeno-associated virus-mediated liver transduction efficacy by regional administration in macaca fascicularis.the liver is a central organ in metabolism and can be affected by numerous inherited metabolic disorders. recombinant adeno-associated virus (aav)-based gene therapy represents a promising therapeutic approach for such diseases. aavs have been demonstrated to be safe, and resulted in high and long-term expression in preclinical and clinical studies. however, there are still some concerns regarding the expression levels that can be achieved and the percentage of hepatocytes that can be transduced ...201728285544
an aerosol challenge model of tuberculosis in mauritian cynomolgus macaques.new interventions for tuberculosis are urgently needed. non-human primate (nhp) models provide the most relevant pre-clinical models of human disease and play a critical role in vaccine development. models utilising asian cynomolgus macaque populations are well established but the restricted genetic diversity of the mauritian cynomolgus macaques may be of added value.201728273087
characterization of the anti-pd-1 antibody regn2810 and its antitumor activity in human pd-1 knock-in mice.the programmed death-1 (pd-1) receptor delivers inhibitory checkpoint signals to activated t cells upon binding to its ligands pd-l1 and pd-l2 expressed on antigen-presenting cells and cancer cells, resulting in suppression of t-cell effector function and tumor immune evasion. clinical antibodies blocking the interaction between pd-1 and pd-l1 restore the cytotoxic function of tumor antigen-specific t cells, yielding durable objective responses in multiple cancers. this report describes the prec ...201728265006
membrane-proximal epitope facilitates efficient t cell synapse formation by anti-fcrh5/cd3 and is a requirement for myeloma cell killing.the anti-fcrh5/cd3 t cell-dependent bispecific antibody (tdb) targets the b cell lineage marker fcrh5 expressed in multiple myeloma (mm) tumor cells. we demonstrate that tdbs trigger t cell receptor activation by inducing target clustering and exclusion of cd45 phosphatase from the synapse. the dimensions of the target molecule play a key role in the efficiency of the synapse formation. the anti-fcrh5/cd3 tdb kills human plasma cells and patient-derived myeloma cells at picomolar concentrations ...201728262555
target expression, generation, preclinical activity, and pharmacokinetics of the bcma-t cell bispecific antibody em801 for multiple myeloma treatment.we identified b cell maturation antigen (bcma) as a potential therapeutic target in 778 newly diagnosed and relapsed myeloma patients. we constructed an igg-based bcma-t cell bispecific antibody (em801) and showed that it increased cd3(+) t cell/myeloma cell crosslinking, followed by cd4(+)/cd8(+) t cell activation, and secretion of interferon-γ, granzyme b, and perforin. this effect is cd4 and cd8 t cell mediated. em801 induced, at nanomolar concentrations, myeloma cell death by autologous t ce ...201728262554
romosozumab treatment converts trabecular rods into trabecular plates in male cynomolgus monkeys.treatment with sclerostin antibody (romosozumab) increases bone formation while reducing bone resorption, leading to increases in bone volume and bone mineral density. sclerostin antibody treatment may also provide beneficial changes in trabecular microarchitecture and strength that are not reflected in bone volume and density. here we use three-dimensional dynamic histomorphometry to determine longitudinal changes in vertebral trabecular microarchitecture in adolescent male cynomolgus monkeys ( ...201728246926
anti-leukemic activity and tolerability of anti-human cd47 monoclonal antibodies.cd47, a broadly expressed cell surface protein, inhibits cell phagocytosis via interaction with phagocyte-expressed sirpα. a variety of hematological malignancies demonstrate elevated cd47 expression, suggesting that cd47 may mediate immune escape. we discovered three unique cd47-sirpα blocking anti-cd47 monoclonal antibodies (mabs) with low nano-molar affinity to human and cynomolgus monkey cd47, and no hemagglutination and platelet aggregation activity. to characterize the anti-cancer activity ...201728234345
adaptations in basal and hypothalamic-pituitary-adrenal-activated deoxycorticosterone responses following ethanol self-administration in cynomolgus monkeys.acute ethanol activates the hypothalamic-pituitary-adrenal (hpa) axis, while long-term exposure results in a blunted neuroendocrine state, particularly with regards to the primary endpoint, cortisol, the primary glucocorticoid produced in the adrenal cortex. however, it is unknown if this dampened neuroendocrine status also influences other adrenocortical steroids. plasma concentration of the mineralocorticoid and neuroactive steroid precursor deoxycorticosterone (doc) is altered by pharmacologi ...201728220108
morphologic and doppler findings from hepatic ultrasonography of normal cynomolgus monkeys (macaca fascicularis).the present study evaluated the anatomic and ultrasonographic features of the liver in normal cynomolgus monkeys (macacafascicularis). healthy, male, cynomolgus monkeys from cambodia (n = 25; mean age, 58.1 mo) were sedated with ketamine (7mg/kg) and examined by using 2d and doppler ultrasonography. we measured the diameters of the vascular structures and bile duct, determined the velocities of the hepatic artery and portal vein, and calculated the resistance index of the hepatic artery. vessel ...201728211310
the laminar organization of the motor cortex in monodactylous mammals: a comparative assessment based on horse, chimpanzee, and macaque.the architecture of the neocortex classically consists of six layers, based on cytological criteria and on the layout of intra/interlaminar connections. yet, the comparison of cortical cytoarchitectonic features across different species proves overwhelmingly difficult, due to the lack of a reliable model to analyze the connection patterns of neuronal ensembles forming the different layers. we first defined a set of suitable morphometric cell features, obtained in digitized nissl-stained sections ...201728210850
angptl8 blockade with a monoclonal antibody promotes triglyceride clearance, energy expenditure, and weight loss in mice.angiopoietin-like protein (angptl)8 is a negative regulator of lipoprotein lipase-mediated plasma triglyceride (tg) clearance. in this study, we describe a fully human monoclonal antibody (regn3776) that binds monkey and human angptl8 with high affinity. inhibition of angptl8 with regn3776 in humanized angptl8 mice decreased plasma tgs and increased lipoprotein lipase activity. additionally, regn3776 reduced body weight and fat content. the reduction in body weight was secondary to increased ene ...201728204173
vascular endothelial growth factors c and d may promote angiogenesis in the primate ovulatory follicle.angiogenesis in the ovary occurs rapidly as the ovarian follicle transforms into a mature corpus luteum. granulosa cells produce vascular endothelial growth factor a (vegfa) in response to the ovulatory gonadotropin surge. vegfa is established as a key mediator of angiogenesis in the primate ovulatory follicle. to determine if additional vegf family members may be involved in angiogenesis within the ovulatory follicle, cynomolgus monkeys (macaca fascicularis) received gonadotropins to stimulate ...201728203718
novel mechanism of decyanation of gdc-0425 by cytochrome p450.gdc-0425 [5-((1-ethylpiperidin-4-yl)oxy)-9h-pyrrolo[2,3-b:5,4-c']dipyridine-6-carbonitrile] is an orally bioavailable small-molecule inhibitor of checkpoint kinase 1 that was investigated as a novel cotherapy to potentiate chemotherapeutic drugs, such as gemcitabine. in a radiolabeled absorption, distribution, metabolism, and excretion study in sprague-dawley rats, trace-level but long-lived (14)c-labeled thiocyanate was observed in circulation. this thiocyanate originated from metabolic decyana ...201728188299
translational repression of a splice variant of cynomolgus macaque cxcl1l by its c-terminal sequence.we previously isolated a cdna clone from cynomolgus macaque encoding a novel cxc chemokine that we termed cxcl1l from its close similarity to cxcl1. however, the cdna consisted of 3 exons instead of 4 exons that were typically seen in other cxc chemokines. here, we isolated a cdna encoding the full-length variant of cxcl1l that we termed cxcl1lβ. cxcl1lβ is 50 amino acids longer than the original cxcl1l, which we now term cxcl1lα. the cxcl1lβ mrna is much more abundantly expressed in the cynomol ...201728186423
diversity and regulatory impact of copy number variation in the primate macaca fascicularis.copy number variations (cnvs) are a significant source of genetic diversity and commonly found in mammalian genomes. we have generated a genome-wide cnv map for cynomolgus monkeys (macaca fascicularis). this crab-eating macaque is the closest animal model to humans that is used in biomedical research.201728183275
a central mesencephalic reticular formation projection to medial rectus motoneurons supplying singly and multiply innervated extraocular muscle fibers.we recently demonstrated a bilateral projection to the supraoculomotor area from the central mesencephalic reticular formation (cmrf), a region implicated in horizontal gaze changes. c-group motoneurons, which supply multiply innervated fibers in the medial rectus muscle, are located within the primate supraoculomotor area, but their inputs and function are poorly understood. here, we tested whether c-group motoneurons in macaca fascicularis monkeys receive a direct cmrf input by injecting this ...201728177529
corrigendum: zika viral dynamics and shedding in rhesus and cynomolgus macaques. 201728170376
genome-wide mining and comparative analysis of microsatellites in three macaque species.microsatellites are found in taxonomically different organisms, and such repeats are related with genomic structure, function and certain diseases. to characterize microsatellites for macaques, we searched and compared ssrs with 1-6 bp nucleotide motifs in rhesus, cynomolgus and pigtailed macaque. a total of 1395671, 1284929 and 1266348 perfect ssrs were mined, respectively. the most frequent perfect ssrs were mononucleotide ssrs. the most gc-content was in dinucleotide ssrs and the least was in ...201728160080
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