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follicular morphology in macaca fascicularis. 19714259425
induction of ovulation in macaca irus with clomiphene citrate and gonadotrophic hormones. 19704992612
evidence for a second haemoglobin alpha-locus duplication in macaca irus. 19704990772
investigation of nephrotoxic effects of adenine and its metabolic product, 2,8-dioxyadenine, on primates (macaca irus). 20134989592
a study of the menstrual cycle in macaca irus with special reference to the detection of ovulation. 19704983967
the chromosomes of the cynomolgus macaque (macaca fascicularis). 19705004699
effects of median nerve injury on some digital tissues of the hand of the macaque (macaca fascicularis). 19704193830
[erythrocyte carbonic anhydrases of men and some animals. 5. hemoglobin and carbonic anhydrase of primates, chimpanzees (pan troglodytes) and cynomolgus (macaca irus)]. 19694983302
[social play: playmates in the young. observations in macaca irus]. 19694979665
[on the medical brachial cutaneous nerve and the intercos to branchial nerve in macaca cyslopis swinhoe and macaca irus f. cuvier]. 19684975202
[the lea blood group substances in macaca irus]. 19684974276
weight and tooth development during the first year in macaca irus. 19684233368
[the patterns of isoniazid inactivation in macaca irus]. 19684971169
[the annual reproductive cycle of the macaque macaca irus]. 19684971242
social status of two hybrids in a wild troop of macaca irus. 19684967294
the types of keratinization occurring in the gingiva of macaca irus. 20144960523
[anatomical study on the plexus cervicalis of the crab-eating macaques]. 19674965416
naturally occurring primate hybrid.two members of a troop of wild macaca irus in malaysia have been tentatively identified as hybrids of m. irus and m. nemestrina. mechanisms prohibiting such hybridization in the natural habitat may have broken down under heavy predation pressure which finally resulted in the local extermination of m. nemestrinia.19664958933
[anatomical studies on the neck muscles of crab-eating macaques]. 19664959093
[studies on the plexus brachialis of crab-eating macaques]. 19664959092
[anatomical studies on the facial musculature of crab-eating macaques, macaca irus]. 19664959091
species and geographic differences in the transferrin polymorphism of macaques.eleven molecular forms and 34 phenotypes of transferrin have been detected in 372 serums from six macaque species. the tendency to polymorphism varies from species to species and from one local population to another. the most extensive polymorphism was observed in macaca mulatta, which showed at least ten transferrins and 24 phenotypes. transferrins present in stump-tail macaques (m. speciosa) from thailand were also found in crab-eating macaques (m. irus) from thailand, but not in crab-eating m ...196514245771
rhesus and crab-eating macaques: intergradation in thailand.conspecificity of the rhesus macaque, macaca mulatta mulatta (zimmermann, 1780), and the crab-eating macaque macaca mulatta fascicularis (raffles [1821]), is established by a geographically intermediate series of three specimens transitional in tail length and coat color.196417821058
hepatocystis from macaca irus in java. 196314084192
[the temporal muscle in macaca irus. supplement: a view on the origin of the torus supraorbitalis]. 196314095674
a contribution to the knowledge of some craniologic, craniometric, and growth changes in skulls of macaca mulatta and macaca irus (cynomolgus). 196314133062
[studies on the lymphatic system of the inguinal region and reproductive organs in male crab-eating macaques]. 196213923419
transferrin variations in sera of macaca irus. 196113688545
haptoglobulin types in macaca irus. 196013798151
haptoglobin types in macaca irus. 196013688544
dirofilaria magnilarvatum price, 1959 (nematoda: filarioidea) from macaca irus cuvier. iii. the behavior of the microfilariae in the mammalian host. 195914400251
dirofilaria magnilarvatum price, 1959 (nematoda: filarioidea) from macaca irus cuvier. iv. notes on larval development in mansonioides mosquitoes. 195913844259
dirofilaria magnilarvatum price, 1959 (nematoda: filarioidea) from macaca irus cuvier. ii. microscopical studies on the microfilariae. 195913837108
[further observations and investigations on reproduction in the java macaque (macaca irus mordax th. et wr., cynomolgus l.)]. 195014777537
from bench to almost bedside: the long road to a licensed ebola virus vaccine.the ebola virus (ebov) disease epidemic during 2014-16 in west africa has accelerated the clinical development of several vaccine candidates that have demonstrated efficacy in the gold standard nonhuman primate (nhp) model, namely cynomolgus macaques. areas covered: this review discusses the pre-clinical research and if available, clinical evaluation of the currently available ebov vaccine candidates, while emphasizing the translatability of pre-clinical data generated in the nhp model to clinic ...201729148858
novel full-length major histocompatibility complex class i allele discovery and haplotype definition in pig-tailed macaques.pig-tailed macaques (macaca nemestrina, mane) are important models for human immunodeficiency virus (hiv) studies. their infectability with minimally modified hiv makes them a uniquely valuable animal model to mimic human infection with hiv and progression to acquired immunodeficiency syndrome (aids). however, variation in the pig-tailed macaque major histocompatibility complex (mhc) and the impact of individual transcripts on the pathogenesis of hiv and other infectious diseases is understudied ...201729134258
the pparα-dependent rodent liver tumor response is not relevant to humans: addressing misconceptions.a number of industrial chemicals and therapeutic agents cause liver tumors in rats and mice by activating the nuclear receptor peroxisome proliferator-activated receptor α (pparα). the molecular and cellular events by which pparα activators induce rodent hepatocarcinogenesis have been extensively studied elucidating a number of consistent mechanistic changes linked to the increased incidence of liver neoplasms. the weight of evidence relevant to the hypothesized mode of action (moa) for pparα ac ...201829197930
intranasal infection and contact transmission of zika virus in guinea pigs.zika virus (zikv) is primarily transmitted to humans through mosquito bites or sexual contact. the excretion and persistence of contagious zikv in various body fluids have been well documented in zikv patients; however, the risk of direct contact exposure remains unclear. here, we show that guinea pigs are susceptible to zikv infection via subcutaneous inoculation route; infected guinea pigs exhibit seroconversion and significant viral secretion in sera, saliva, and tears. notably, zikv is effic ...201729162827
discovery of furan and dihydrofuran-fused tricyclic benzo[d]imidazole derivatives as potent and orally efficacious microsomal prostaglandin e synthase-1 (mpges-1) inhibitors: part-1.this letter describes the synthesis and biological evaluation of furan and dihydrofuran-fused tricyclic benzo[d]imidazole derivatives as novel mpges-1 inhibitors, capable of inhibiting an increased pge2 production in the disease state. structure-activity optimization afforded many potent mpges-1 inhibitors having <50 nm potencies in the a549 cellular assay and adequate metabolic stability in liver microsomes. lead compounds 8l and 8m demonstrated reasonable in vitro pharmacology and pharmacokine ...201729100801
a dna vaccine delivered by dermal electroporation fully protects cynomolgus macaques against lassa fever.lassa virus (lasv) is an ambisense rna virus in the arenaviridae family and is the etiological agent of lassa fever, a severe hemorrhagic disease endemic to west and central africa. 1,2 there are no us food and drug administration (fda)-licensed vaccines available to prevent lassa fever. 1,2 in our previous studies, we developed a gene-optimized dna vaccine that encodes the glycoprotein precursor gene of lasv (josiah strain) and demonstrated that 3 vaccinations accompanied by dermal electroporat ...201729045192
species-specific involvement of aldehyde oxidase and xanthine oxidase in the metabolism of the pyrimidine-containing mglu5-negative allosteric modulator vu0424238 (auglurant).aldehyde oxidase (ao) and xanthine oxidase (xo) are molybdo-flavoenzymes that catalyze oxidation of aromatic azaheterocycles. differences in ao activity have been reported among various species, including rats, humans, and monkeys. herein we report a species difference in the enzymes responsible for the metabolism of the negative allosteric modulator of metabotropic glutamate receptor subtype 5 (mglu5 nam) vu0424238 (vu238, auglurant). hepatic s9 incubations with ao and xo specific inhibitors hy ...201728939686
phylogenetic analysis of simian plasmodium spp. infecting anopheles balabacensis baisas in sabah, malaysia.anopheles balabacensis of the leucospyrus group has been confirmed as the primary knowlesi malaria vector in sabah, malaysian borneo for some time now. presently, knowlesi malaria is the only zoonotic simian malaria in malaysia with a high prevalence recorded in the states of sabah and sarawak.201728968395
therapeutic effects of anti-cd154 antibody in cynomolgus monkeys with advanced rheumatoid arthritis.rheumatoid arthritis is one major chronic inflammatory systemic autoimmune disease. the cd154-cd40 interactions play a critical role in the regulation of immune responses and the maintenance of autoimmunity. therefore, we aimed to determine whether anti-cd154 antibody treatment show positive effects on immunomodulation and clinical improvement of sustained severe rheumatoid arthritis in cynomolgus monkeys. arthritis was induced using chicken type ii collagen (cii) and arthritic monkey were divid ...201829391506
prevalence and risk factors of japanese encephalitis virus (jev) in livestock and companion animal in high-risk areas in malaysia.japanese encephalitis (je) is vector-borne zoonotic disease which causes encephalitis in humans and horses. clinical signs for japanese encephalitis virus (jev) infection are not clearly evident in the majority of affected animals. in malaysia, information on the prevalence of jev infection has not been established. thus, a cross-sectional study was conducted during two periods, december 2015 to january 2016 and march to august in 2016, to determine the prevalence and risk factors in jev infecti ...201729243139
efficacy of recombinant measles virus expressing highly pathogenic avian influenza virus (hpaiv) antigen against hpaiv infection in monkeys.highly pathogenic avian influenza virus (hpaiv) is a serious threat not only to domestic fowls but also to humans. vaccines inducing long-lasting immunity against hpaiv are required. in the present study, we generated recombinant measles virus (mv) expressing the hemagglutinin protein of hpaiv without the multibasic site necessary for its pathogenicity in chickens using the backbone of an mv vaccine strain (rmv-ed-h5ha) or a wild-type mv-derived mutant (rmv-hl-vko-h5ha). we examined protective e ...201728931922
talaromycosis (penicilliosis) in a cynomolgus macaque.a sexually mature chinese-origin female macaca fascicularis assigned to the high-dose group in a 26-week toxicology study with an experimental immunomodulatory therapeutic antibody (a cd40 l antagonist fusion protein) was euthanized at the scheduled terminal sacrifice on study day 192. the animal was healthy at study initiation and remained clinically normal throughout the study. on study day 141, abnormal clinical pathology changes were found during a scheduled evaluation; splenomegaly was dete ...201829444633
marmoset cytochrome p450 2b6, a propofol hydroxylase expressed in liver.1. the common marmoset (callithrix jacchus) is a useful experimental animal to evaluate the pharmacokinetics of drug candidates. cytochrome p450 (p450) 2b enzyme in marmoset livers has been identified; however, only limited information on the enzymatic properties and distribution has been available. 2. marmoset p450 2b6 amino acids showed high sequence identities (>86%) with those of primates including humans and cynomolgus monkeys. phylogenetic analysis using amino acid sequences indicated that ...201829417863
preclinical evaluation of the mono-pegylated recombinant human interleukin-11 in cynomolgus monkeys.the mono-pegylated recombinant human interleukin-11 (rhil-11) was evaluated for its pharmacology and toxicology profile in non-human primates. this pegylated il-11 (peg-il11) showed a much prolonged circulating half-life of 67h in cynomolgus monkeys as compared to its un-pegylated counterpart (~3h) through subcutaneous administration, implicating that a single injection of the recommended dose will effectively enhance thrombopoiesis in humans for a much longer period of time compared to rhil-11 ...201829407773
in vivo study of paraspinal muscle weakness using botulinum toxin in one primate model.it has been generally speculated that paraspinal muscle weakness is related to the spinal degeneration including intervertebral disc failure. the purpose of this study was to investigate the effects of paraspinal muscle weakness induced by the botulinum toxin type-a on the lumbar spine and behavior pattern in an in-vivo primate model which has an upright locomotion similar to that of humans.201829407350
mycobacterium leprae genomes from naturally infected nonhuman primates.leprosy is caused by the bacterial pathogens mycobacterium leprae and mycobacterium lepromatosis. apart from humans, animals such as nine-banded armadillos in the americas and red squirrels in the british isles are naturally infected with m. leprae. natural leprosy has also been reported in certain nonhuman primates, but it is not known whether these occurrences are due to incidental infections by human m. leprae strains or by m. leprae strains specific to nonhuman primates. in this study, compl ...201829381722
human gip(3-30)nh2inhibits g protein-dependent as well as g protein-independent signaling and is selective for the gip receptor with high-affinity binding to primate but not rodent gip receptors.gip(3-30)nh2is a high affinity antagonist of the gip receptor (gipr) in humans inhibiting insulin secretion via g protein-dependent pathways. however, its ability to inhibit g protein-independent signaling is unknown. here we determine its action on arrestin-recruitment and receptor internalization in recombinant cells. as gip is adipogenic, we evaluate the inhibitory actions of gip(3-30)nh2in human adipocytes. finally, we determine the receptor selectivity of gip(3-30)nh2among other human and a ...201829378179
both systemic and intra-articular immunization with citrullinated peptides are needed to induce arthritis in the macaque.anti-citrullinated peptides antibodies (acpas) have high specificity for the diagnosis of rheumatoid arthritis (ra), but their role in the pathophysiology is not fully established. the main genetic risk factor for ra, the shared epitope in major histocompatibility complex class ii, is associated with acpas. among certain non-human primates, 8% carry the shared epitope called h6 haplotype, and being similar to humans, are ideal candidates to study the role of acpas in ra. the goal of this study w ...201729326703
blood rna signatures prospectively discriminate controllers from progressors early after low-dose m. tuberculosis infection of cynomolgus macaques.the cynomolgus macaque model of low-dose mycobacterium tuberculosis (mtb) infection recapitulates clinical aspects of human tb pathology but it is unknown whether the two systems are sufficiently similar that host-based signatures of tb will be predictive across species. by blind prediction, we demonstrate that a subset of genes comprising a human signature for tb risk is simultaneously predictive in humans and macaques and prospectively discriminates progressor from controller animals 3-6 weeks ...201829325117
genetic polymorphisms of drug-metabolizing cytochrome p450 enzymes in cynomolgus and rhesus monkeys and common marmosets in preclinical studies for humans.cynomolgus monkeys (macaca fascicularis, old world monkeys) and common marmosets (callithrix jacchus, new world monkeys) have been widely, and expectedly, used as non-human primate models in drug development studies. major drug-metabolizing cytochrome p450 (p450) enzymes information is now available that supports these primate species as animal models, and it is established that multiple forms of cynomolgus monkey and common marmoset p450 enzymes have generally similar substrate recognition func ...201729277691
nicotinic alpha 7 receptor agonists evp-6124 and bms-933043, attenuate scopolamine-induced deficits in visuo-spatial paired associates learning.agonists at the nicotinic acetylcholine alpha 7 receptor (nachr α7) subtype have the potential to treat cognitive deficits in patients with alzheimer's disease (ad) or schizophrenia. visuo-spatial paired associates learning (vspal) is a task that has been shown to reliably predict conversion from mild cognitive impairment to ad in humans and can also be performed by nonhuman primates. reversal of scopolamine-induced impairment of vspal performance may represent a translational approach for the d ...201729261656
sensory properties of the caudal aspect of the macaque's superior parietal lobule.in the superior parietal lobule (spl), the anterior part (area pe) is known to process somatosensory information, while the caudalmost part (areas v6av and v6) processes visual information. here we studied the visual and somatosensory properties of the areas pec and v6ad located in between the somatosensory and visual domains of spl. about 1500 neurons were extracellularly recorded in 19 hemispheres of 12 monkeys (macaca fascicularis). visual and somatosensory properties of single neurons were g ...201729260370
translational development of microbiome-based therapeutics: kinetics of e. coli nissle and engineered strains in humans and nonhuman primates.understanding the pharmacology of microbiome-based therapeutics is required to support the development of new medicines. strains of e. coli nissle (ecn) were genetically modified and administered to cynomolgus monkeys at doses of 1 × 109and 1 × 1012colony-forming units (cfu)/day for 28 days. a clinical study to evaluate the exposure and clearance of ecn in healthy volunteers was also performed. healthy subjects received oral doses of ecn, 2.5 to 25 × 109cfu 3 times daily for 28 days or a single ...201729194983
discovery and validation of pyridoxic acid and homovanillic acid as novel endogenous plasma biomarkers of organic anion transporter (oat) 1 and oat3 in cynomolgus monkeys.perturbation of organic anion transporter (oat) 1- and oat3-mediated transport can alter the exposure, efficacy, and safety of drugs. although there have been reports of the endogenous biomarkers for oat1/3, none of these have all of the characteristics required for a clinical useful biomarker. cynomolgus monkeys were treated with intravenous probenecid (prob) at a dose of 40 mg/kg in this study. as expected, prob increased the area under the plasma concentration-time curve (auc) of coadminister ...201829162614
the role of mhc-e in t cell immunity is conserved among humans, rhesus macaques, and cynomolgus macaques.mhc-e is a highly conserved nonclassical mhc class ib molecule that predominantly binds and presents mhc class ia leader sequence-derived peptides for nk cell regulation. however, mhc-e also binds pathogen-derived peptide ags for presentation to cd8+t cells. given this role in adaptive immunity and its highly monomorphic nature in the human population, hla-e is an attractive target for novel vaccine and immunotherapeutic modalities. development of hla-e-targeted therapies will require a physiolo ...201829150562
toxicokinetics and physiologically based pharmacokinetic modeling of the shellfish toxin domoic acid in nonhuman primates.domoic acid (da), a neurotoxin, is produced by marine algae and has caused toxications worldwide in animals and humans. however, the toxicokinetics of da have not been fully evaluated, and information is missing on the disposition of da following oral exposures at doses that are considered safe for human consumption. in this study, toxicokinetics of da were investigated in cynomolgus monkeys following single doses of 5µg/kg da intravenously, 0.075 mg/kg da orally, and 0.15 mg/kg da orally. after ...201829150543
high expression of ugt1a1/1a6 in monkey small intestine: comparison of protein expression levels of cytochromes p450, udp-glucuronosyltransferases, and transporters in small intestine of cynomolgus monkey and human.cynomolgus monkeys have been widely used for the prediction of drug absorption in humans. the purpose of this study was to clarify the regional protein expression levels of cytochromes p450 (cyps), udp-glucuronosyltransferases (ugts), and transporters in small intestine of cynomolgus monkey using liquid chromatography-tandem mass spectrometry, and to compare them with the corresponding levels in human. ugt1a1 in jejunum and ileum were >4.57- and >3.11-fold and ugt1a6 in jejunum and ileum were >1 ...201829140712
behavioral depression is associated with increased vagally mediated heart rate variability in adult female cynomolgus monkeys (macaca fascicularis).depressive symptoms (ds) in humans are associated with decreased resting state vagal activity, but sex seems to moderate this association. recently, in human females ds have been associated with greater or similar cardiac vagal activity compared to men in both, clinical and non-clinical samples. a previously validated animal model of behavioral depression was used in the present study to investigate the association of ds and cardiac vagal activity in non-human primates.201729128294
development of a lethal intranasal exposure model of ebola virus in the cynomolgus macaque.ebola virus (ebov) is a filovirus that can cause ebola virus disease (evd). no approved vaccines or therapies exist for filovirus infections, despite an urgent need. the development and testing of effective countermeasures against ebov requires use of animal models and a thorough understanding of how the model aligns with evd in humans. the majority of published studies report outcomes of parenteral exposures for emulating needle stick transmission. however, based on data from evd outbreaks, clo ...201729109373
effects of repeated restraint and blood sampling with needle injection on blood cardiac troponins in rats, dogs, and cynomolgus monkeys.while cardiac troponins (ctnt and ctni) have been used as blood biomarkers of myocardial injury such as myocardial infarction in both humans and animals, their high diagnostic sensitivity inevitably leads to decreased diagnostic specificity. for example, it is difficult to judge whether a slight increase of cardiac troponins in toxicological studies is a treatment-related response or not. drawing an accurate conclusion requires reliable background data and definitive criteria based on that data. ...201729081730
long-acting mic-1/gdf15 molecules to treat obesity: evidence from mice to monkeys.in search of metabolically regulated secreted proteins, we conducted a microarray study comparing gene expression in major metabolic tissues of fed and fasted ob/ob mice and c57bl/6 mice. the array used in this study included probes for ~4000 genes annotated as potential secreted proteins. circulating macrophage inhibitory cytokine 1 (mic-1)/growth differentiation factor 15 (gdf15) concentrations were increased in obese mice, rats, and humans in comparison to age-matched lean controls. adeno-ass ...201729046435
evolutionarily distinctive transcriptional and signaling programs drive human germ cell lineage specification from pluripotent stem cells.germline specification underlies human reproduction and evolution, but it has proven difficult to study in humans since it occurs shortly after blastocyst implantation. this process can be modeled with human induced pluripotent stem cells (hipscs) by differentiating them into primordial germ cell-like cells (hpgclcs) through an incipient mesoderm-like cell (imelc) state. here, we elucidate the key transcription factors and their interactions with important signaling pathways in driving hpgclc di ...201728985527
preclinical characterization of (r)-3-((3s,4s)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one (bms-986169), a novel, intravenous, glutamaten-methyl-d-aspartate 2b receptor negative allosteric modulator with potential in major depressive disorder.(r)-3-((3s,4s)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one (bms-986169) and the phosphate prodrug 4-((3s,4s)-3-fluoro-1-((r)-1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-4-yl)phenyl dihydrogen phosphate (bms-986163) were identified from a drug discovery effort focused on the development of novel, intravenous glutamaten-methyl-d-aspartate 2b receptor (glun2b) negative allosteric modulators (nams) for treatment-resistant depression (trd). bms-986169 showed h ...201728954811
allowable warm ischemic time and morphological and biochemical changes in uterine ischemia/reperfusion injury in cynomolgus macaque: a basic study for uterus transplantation.how long is the allowable warm ischemic time of the uterus and what morphological and biochemical changes are caused by uterine ischemia/reperfusion injury in cynomolgus macaques?201728938750
analysis of nuclear and organellar genomes of plasmodium knowlesi in humans reveals ancient population structure and recent recombination among host-specific subpopulations.the macaque parasite plasmodium knowlesi is a significant concern in malaysia where cases of human infection are increasing. parasites infecting humans originate from genetically distinct subpopulations associated with the long-tailed (macaca fascicularis (mf)) or pig-tailed macaques (macaca nemestrina (mn)). we used a new high-quality reference genome to re-evaluate previously described subpopulations among human and macaque isolates from malaysian-borneo and peninsular-malaysia. nuclear genome ...201728922357
using a cageside device for testing glycosylated hemoglobin in cynomolgus macaques (macaca fascicularis).nonhuman primates naturally develop type 2 diabetes mellitus and exhibit clinical features that are similar to those observed in humans, including obesity, insulin resistance, dyslipidemia, and pancreatic pathology. the glycosylated hemoglobin (hba1c) test is the primary test used for diabetes management in humans because it reflects the average blood glucose levels over the previous 3 mo. the hba1c results are a better predictor of potential risk of complications than are single or episodic mea ...201728905721
superior retinal gene transfer and biodistribution profile of subretinal versus intravitreal delivery of aav8 in nonhuman primates.to investigate shedding and biodistribution characteristics of recombinant adeno-associated virus serotype 8 (raav8) after single-dose subretinal or intravitreal injection in nonhuman primates (nhp, macaca fascicularis) as a surrogate for environmental hazard and patient safety.201729117317
a conserved transcriptional response to intranasal ebola virus exposure in nonhuman primates prior to onset of fever.ebola virus disease (evd), caused by ebola virus (ebov), is a severe illness characterized by case fatality rates of up to 90%. the sporadic nature of outbreaks in resource-limited areas has hindered the ability to characterize the pathogenesis of evd at all stages of infection but particularly early host responses. pathogenesis is often studied in nonhuman primate (nhp) models of disease that replicate major aspects of human evd. typically, nhp models use a large infectious dose, are carried ou ...201829593102
antiviral efficacy of favipiravir against ebola virus: a translational study in cynomolgus macaques.despite repeated outbreaks, in particular the devastating 2014-2016 epidemic, there is no effective treatment validated for patients with ebola virus disease (evd). among the drug candidates is the broad-spectrum polymerase inhibitor favipiravir, which showed a good tolerance profile in patients with evd (jiki trial) but did not demonstrate a strong antiviral efficacy. in order to gain new insights into the antiviral efficacy of favipiravir and improve preparedness and public health management o ...201829584730
experimental infection of cynomolgus macaques with highly pathogenic h5n1 influenza virus through the aerosol route.several animal models are used to study influenza viruses. intranasal inoculation of animals with a liquid inoculum is one of the main methods used to experimentally infect animals with influenza virus; however, this method does not reflect the natural infection with influenza virus by contact or aerosol route. aerosol inhalation methods have been established with several influenza viruses for mouse and ferret models, but few studies have evaluated inoculation routes in a nonhuman primates (nhp) ...201829556081
prime and boost vaccination elicit a distinct innate myeloid cell immune response.understanding the innate immune response to vaccination is critical in vaccine design. here, we studied blood innate myeloid cells after first and second immunization of cynomolgus macaques with the modified vaccinia virus ankara. the inflammation at the injection site was moderate and resolved faster after the boost. the blood concentration of inflammation markers increased after both injections but was lower after the boost. the numbers of neutrophils, monocytes, and dendritic cells were trans ...201829449630
molecular genetic identification of isolates of the hepatitis a virus (hav) from monkeys at adler primate center.the aim of this study was to assess prevalence and genetic variability of hepatitis a virus (hav) isolates in monkeys born and kept at adler primate center, as well as in imported animals.201829380396
adjuvanting influenza hemagglutinin vaccine with a human pulmonary surfactant-mimicking synthetic compound sf-10 induces local and systemic cell-mediated immunity in mice.we reported previously that intranasal instillation of a synthetic human pulmonary surfactant with a carboxy vinyl polymer as a viscosity improver, named sf-10, shows potent adjuvanticity for humoral immunity in mice and cynomolgus monkeys. sf-10 effectively induces influenza hemagglutinin vaccine (hav)-specific iga in nasal and lung washes and igg in sera with their neutralizing activities. since cd8+ t cell-mediated protection is an important requirement for adaptive immunity, we investigated ...201829370185
a single amino acid change in the marburg virus glycoprotein arises during serial cell culture passages and attenuates the virus in a macaque model of disease.marburg virus (marv) causes disease with high case fatality rates, and there are no approved vaccines or therapies. licensing of marv countermeasures will likely require approval via the fda's animal efficacy rule, which requires well-characterized animal models that recapitulate human disease. this includes selection of the virus used for exposure and ensuring that it retains the properties of the original isolate. the consequences of amplification of marv for challenge studies are unknown. her ...201829299527
characterization of a candidate tetravalent vaccine based on 2'-o-methyltransferase mutants.dengue virus (denv) is one of the most widespread arboviruses. the four denv serotypes infect about 400 million people every year, causing 96 million clinical dengue cases, of which approximately 500'000 are severe and potentially life-threatening. the only licensed vaccine has a limited efficacy and is only recommended in regions with high endemicity. we previously reported that 2'-o-methyltransferase mutations in denv-1 and denv-2 block their capacity to inhibit type i ifns and render the viru ...201829298302
treatment of paraquat-induced lung injury with an anti-c5a antibody: potential clinical application.complement activation product c5a plays a critical role in systemic inflammatory response syndrome induced by viruses, bacteria, and toxic agents including paraquat poisoning. this study is to explore the efficiency of anti-c5a-based intervention on systemic inflammatory responses induced by paraquat poisoning.201829293144
multigenic dna vaccine induces protective cross-reactive t cell responses against heterologous influenza virus in nonhuman primates.recent avian and swine-origin influenza virus outbreaks illustrate the ongoing threat of influenza pandemics. we investigated immunogenicity and protective efficacy of a multi-antigen (ma) universal influenza dna vaccine consisting of ha, m2, and np antigens in cynomolgus macaques. following challenge with a heterologous pandemic h1n1 strain, vaccinated animals exhibited significantly lower viral loads and more rapid viral clearance when compared to unvaccinated controls. the ma dna vaccine indu ...201729267331
needle-free delivery of measles virus vaccine to the lower respiratory tract of non-human primates elicits optimal immunity and protection.needle-free measles virus vaccination by aerosol inhalation has many potential benefits. the current standard route of vaccination is subcutaneous injection, whereas measles virus is an airborne pathogen. however, the target cells that support replication of live-attenuated measles virus vaccines in the respiratory tract are largely unknown. the aims of this study were to assess the in vivo tropism of live-attenuated measles virus and determine whether respiratory measles virus vaccination shoul ...201729263877
immunogenicity of recombinant measles vaccine expressing fusion protein of respiratory syncytial virus in cynomolgus monkeys.respiratory syncytial virus (rsv) is a common cause of respiratory infections in infants. effective vaccines are currently being sought, but no vaccine is thus far available. in our previous study, recombinant aik-c measles vaccine expressing the rsv fusion protein (mvaik/rsv/f) was developed and protective immunity against rsv demonstrated in cotton rats. in the present study, the immunogenicity and protective effects were investigated in three cynomolgus monkeys immunized with mvaik/rsv/f. neu ...201829194753
pigeon paramyxovirus type 1 from a fatal human case induces pneumonia in experimentally infected cynomolgus macaques (macaca fascicularis).although avian paramyxovirus type 1 is known to cause mild transient conjunctivitis in human beings, there are two recent reports of fatal respiratory disease in immunocompromised human patients infected with the pigeon lineage of the virus (ppmv-1). in order to evaluate the potential of ppmv-1 to cause respiratory tract disease, we inoculated a ppmv-1 isolate (hppmv-1/netherlands/579/2003) from an immunocompromised human patient into three healthy cynomolgus macaques (macaca fascicularis) and e ...201729162154
transcriptome analysis of circulating immune cell subsets highlight the role of monocytes in zaire ebola virus makona pathogenesis.existing models of ebola virus disease (evd) suggest antigen-presenting cells are initial targets ofzaire ebolavirus(zebov).in vitrostudies have shown that zebov infection of monocytes and macrophages results in the production of inflammatory mediators, which may cause lymphocyte apoptosis. however, these findings have not been corroborated byin vivostudies. in this study, we report the first longitudinal analysis of transcriptional changes in purified monocytes, t-cells, and b-cells isolated fr ...201729123522
comparison of transcriptomic platforms for analysis of whole blood from ebola-infected cynomolgus macaques.ebola virus disease (evd) is a serious illness with mortality rates of 20-90% in various outbreaks. evd is characterized by robust virus replication and strong host inflammatory response. analyzing host immune responses has increasingly involved multimodal approaches including transcriptomics to profile gene expression. we studied cynomolgus macaques exposed to ebola virus makona via different routes with the intent of comparing rna-seq to a nanostring ncounter codeset targeting 769 non-human pr ...201729116224
validation of a pan-orthopox real-time pcr assay for the detection and quantification of viral genomes from nonhuman primate blood.in 1980, smallpox disease was eradicated from nature and variola virus, the etiological agent of smallpox, was confined to two laboratories, one located in russia (moscow) later moved to vector (novosibirsk, siberia) and one in the united states (cdc atlanta). vaccinations among the general public ceased shortly after the successful eradication campaign, resulting in an increasingly immunologically susceptible population. because of the possibility of intentional reintroduction of variola virus ...201729100534
pegivirus avoids immune recognition but does not attenuate acute-phase disease in a macaque model of hiv infection.human pegivirus (hpgv) protects hiv+ people from hiv-associated disease, but the mechanism of this protective effect remains poorly understood. we sequentially infected cynomolgus macaques with simian pegivirus (spgv) and simian immunodeficiency virus (siv) to model hiv+hpgv co-infection. spgv had no effect on acute-phase siv pathogenesis-as measured by siv viral load, cd4+ t cell destruction, immune activation, or adaptive immune responses-suggesting that hpgv's protective effect is exerted pri ...201729073258
perspectives on using a multiplex human kidney safety biomarker panel to detect cisplatin-induced tubular toxicity in male and female cynomolgus monkeys.multiplex biomarker panel assays would enable early de-risking of discovery compound related kidney safety liabilities. the objective of this study was to evaluate the usefulness of the myriad rbm human kidneymap (multi-analyte profile)® v.1.0 panel to detect experimental nephrotoxicity in cynomolgus monkeys following a single intravenous administration of cisplatin (2.5mg/kg). urine samples were collected at baseline on day -2; at approximately 4hr post-dose on day 1; and on days 4, 9, 15 and/o ...201729051111
hm10660a, a long-acting hifn-α-2b, is a potent candidate for the treatment of hepatitis c through an enhanced biological half-life.interferon-α (ifn-α) has been widely used for the treatment of infections due to the hepatitis c virus (hcv). because of the short half-life of ifn-α in serum, it must be administered three times per week. to increase the half-life of ifn-α, the immunoglobulin g4 (igg4) fc fragment (hmc001) was conjugated with human ifn-α-2b to develop a long-acting ifn-α-2b, hm10660a. an analysis of the antiviral efficacy of hm10660a in a human hepatocyte-engrafted mouse model found that hm10660a reduced serum ...201728982547
natural and cross-inducible anti-siv antibodies in mauritian cynomolgus macaques.cynomolgus macaques are an increasingly important nonhuman primate model for hiv vaccine research. siv-free animals without pre-existing anti-siv immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. here, in order to select such animals for vaccine studies, we screened 108 naïve female mauritian cynomolgus macaques for natural (baseline) antibodies to siv antigens using a bio-plex multiplex system. the antigens included tw ...201728982126
emergence of oseltamivir-resistant h7n9 influenza viruses in immunosuppressed cynomolgus macaques.antiviral compounds (eg, the neuraminidase inhibitor oseltamivir) are invaluable for the treatment of individuals infected with influenza a viruses of the h7n9 subtype (a[h7n9]), which have infected and killed hundreds of persons. however, oseltamivir treatment often leads to the emergence of resistant viruses in immunocompromised individuals. to better understand the emergence and properties of oseltamivir-resistant a(h7n9) viruses in immunosuppressed individuals, we infected immunosuppressed c ...201728931216
zikv demonstrates minimal pathologic effects and mosquito infectivity in viremic cynomolgus macaques.to evaluate the effects of zikv infection on non-human primates (nhps), as well as to investigate whether these nhps develop sufficient viremia to infect the major urban vector mosquito, aedes aegypti, four cynomolgus macaques (macaca fascicularis) were subcutaneously infected with 5.0 log10 focus-forming units (ffu) of dna clone-derived zikv strain fss13025 (asian lineage, cambodia, 2010). following infection, the animals were sampled (blood, urine, tears, and saliva), underwent daily health mo ...201830469417
high susceptibility, viral dynamics and persistence of south american zika virus in new world monkey species.south american zika virus (zikv) recently emerged as a novel human pathogen, linked with neurological disorders. however, comparative zikv infectivity studies in new world primates are lacking. two members of the callitrichidae family, common marmosets (callithrix jacchus) and red-bellied tamarins (saguinus labiatus), were highly susceptible to sub-cutaneous challenge with the puerto rico-origin zikvprvabc59 strain. both exhibited rapid, high, acute viraemia with early neuroinvasion (3 days) in ...201931601848
primary infection with dengue or zika virus does not affect the severity of heterologous secondary infection in macaques.zika virus (zikv) and dengue virus (denv) are genetically and antigenically related flaviviruses that now co-circulate in much of the tropical and subtropical world. the rapid emergence of zikv in the americas in 2015 and 2016, and its recent associations with guillain-barré syndrome, birth defects, and fetal loss have led to the hypothesis that denv infection induces cross-reactive antibodies that influence the severity of secondary zikv infections. it has also been proposed that pre-existing z ...201931369649
little evidence of zika virus infection in wild long-tailed macaques, peninsular malaysia.we tested a sample of 234 wild long-tailed macaques (macaca fascicularis) trapped in peninsular malaysia in 2009, 2010, and 2016 for zika virus rna and antibodies. none were positive for rna, and only 1.3% were seropositive for neutralizing antibodies. long-tailed macaques are unlikely to be reservoirs for zika virus in malaysia.201930666941
a recombinant subunit based zika virus vaccine is efficacious in non-human primates.zika virus (zikv), a virus with no severe clinical symptoms or sequelae previously associated with human infection, became a public health threat following an epidemic in french polynesia 2013-2014 that resulted in neurological complications associated with infection. although no treatment currently exists, several vaccines using different platforms are in clinical development. these include nucleic acid vaccines based on the prm-e protein from the virus and purified formalin-inactivated zikv va ...201830467501
habitat use by a primate community in a lowland dipterocarp forest in danum valley, borneo.knowledge of niche partitioning with respect to habitat is indispensable to understand the mechanism of coexistence of multiple species. among primates, however, data are still deficient because repeated survey for a sufficiently long time, covering seasonal changes over a large area, is the only way to clarify habitat segregation within a seasonally fluctuating environment. southeast asia is particularly interesting because of the supra-annual, highly unpredictable seasonality in fruiting known ...202032515849
relationship of incisor size to diet and anterior tooth use in sympatric sumatran anthropoids.researchers often relate anthropoid incisor size to diet and ingestive behaviors. it is suggested that primates that frequently consume large, tough foods (i.e., fruits) require large incisors to process these items. this idea has been difficult to test because of a lack of data on anterior tooth use in wild primates, and a lack of understanding concerning the relationships between food properties and ingestive behaviors. the first field study of primate ingestive behaviors has recently been com ...199631918473
anatomy of the dura mater venous sinus of alouatta belzebul.the anatomy of the dura mater's venous sinuses is important in the veterinary clinical and surgical area, for cranial procedures and interventions of wild animals, in addition to assisting in the management of neurological diseases, which can prevent serious complications. the macroscopic anatomy of the venous sinuses of the dura mater of alouatta belzebul was studied. five adult specimens, males and females, were dissected and fixed in 10% formaldehyde solution. in the dura mater of the alouatt ...202032738181
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