Publications

quantitative analysis of 18f-pf-06684511, a novel pet radioligand for selective β-secretase 1 imaging, in nonhuman primate brain.	β-secretase 1 (bace1) is a key enzyme in the generation of β-amyloid, which is accumulated in the brain of alzheimer disease patients. pf-06684511 was identified as a candidate pet ligand for imaging bace1 in the brain and showed high specific binding in an initial assessment in a nonhuman primate (nhp) pet study using 18f-pf-06684511. in this effort, we aimed to quantitatively evaluate the regional brain distribution of 18f-pf-06684511 in nhps under baseline and blocking conditions and to asses ...	2019	30530832
characterization of mauritian cynomolgus macaque fcγr alleles using long-read sequencing.	the fcγrs are immune cell surface proteins that bind igg and facilitate cytokine production, phagocytosis, and ab-dependent, cell-mediated cytotoxicity. fcγrs play a critical role in immunity; variation in these genes is implicated in autoimmunity and other diseases. cynomolgus macaques are an excellent animal model for many human diseases, and mauritian cynomolgus macaques (mcms) are particularly useful because of their restricted genetic diversity. previous studies of mcm immune gene diversity ...	2019	30530595
cnb-001, a pleiotropic drug is efficacious in embolized agyrencephalic new zealand white rabbits and ischemic gyrencephalic cynomolgus monkeys.	ischemic stroke is an acute neurodegenerative disease that is extremely devastating to patients, their families and society. stroke is inadequately treated even with endovascular procedures and reperfusion therapy. using an extensive translational screening process, we have developed a pleiotropic cytoprotective agent with the potential to positively impact a large population of brain ischemia patients and revolutionize the process used for the development of new drugs to treat complex brain dis ...	2019	30521790
isolation and characterization of camelid single-domain antibodies against her2.	to isolate and characterize novel high-affinity llama single-domain antibodies against human her2.	2018	30518413
pharmacokinetics and metabolism of pemafibrate, a novel selective peroxisome proliferator-activated receptor-alpha modulator, in rats and monkeys.	the metabolic profiles and pharmacokinetics of pemafibrate, a novel selective peroxisome proliferator activated receptor-alpha modulator currently launched as an antidyslipidemic drug, were investigated in vitro using hepatocytes from rats, monkeys and humans and in vivo in rats and monkeys. hepatocytes from rats, monkeys and humans all biotransformed pemafibrate to its demethylated form (m1). the bioavailabilities of pemafibrate in sprague-dawley rats and cynomolgus monkeys were 15% and 87%, re ...	2019	30517973
therapeutic expression of human clotting factors ix and x following adeno-associated viral vector-mediated intrauterine gene transfer in early-gestation fetal macaques.	adeno-associated viral vectors (aavs) achieve stable therapeutic expression without long-term toxicity in adults with hemophilia. to avert irreversible complications in congenital disorders producing early pathogenesis, safety and efficacy of aav-intrauterine gene transfer (iugt) requires assessment. we therefore performed iugt of aav5 or -8 with liver-specific promoter-1 encoding either human coagulation factors ix (hfix) or x (hfx) into macaca fascicularis fetuses at ∼0.4 gestation. the initia ...	2019	30517034
preclinical pharmacokinetic evaluation to facilitate repurposing of tyrosine kinase inhibitors nilotinib and imatinib as antiviral agents.	several tyrosine kinase inhibitors (tkis) developed as anti-cancer drugs, also have anti-viral activity due to their ability to disrupt productive replication and dissemination in infected cells. consequently, such drugs are attractive candidates for "repurposing" as anti-viral agents. however, clinical evaluation of therapeutics against infectious agents associated with high mortality, but low or infrequent incidence, is often unfeasible. the united states food and drug administration formulate ...	2018	30514402
engineering of a glp-1 analogue peptide/anti-pcsk9 antibody fusion for type 2 diabetes treatment.	type 2 diabetes (t2d) is a complex and progressive disease requiring polypharmacy to manage hyperglycaemia and cardiovascular risk factors. however, most patients do not achieve combined treatment goals. to address this therapeutic gap, we have developed medi4166, a novel glucagon-like peptide-1 (glp-1) receptor agonist peptide fused to a proprotein convertase subtilisin/kexin type 9 (pcsk9) neutralising antibody that allows for glycaemic control and low-density lipoprotein cholesterol (ldl-c) l ...	2018	30510163
preliminary validation of natural depression in macaques with acute treatments of the fast-acting antidepressant ketamine.	non-human primates have become one of the most important model animals for the investigation of brain diseases because they share a wide-range of genetics and social similarities with human beings. naturally-evoked depression models in macaques may offer a full spectrum of similarity to human depression states, but they require validation and corroboration of specific phenotypes to depression-associated states before they can be used in research into more effective interventions. it is reported ...	2019	30508610
preclinical development of the tlr9 agonist dv281 as an inhaled aerosolized immunotherapeutic for lung cancer: pharmacological profile in mice, non-human primates, and human primary cells.	cpg-motif-containing oligodeoxynucleotides (cpg-odn) activate innate immunity through toll-like receptor (tlr) 9 signaling and generate local immune responses when delivered directly to the lung. herein we describe pharmacological studies in mice, cynomolgus monkeys, and in human primary cells which support the development of dv281, a c-class cpg-odn, as an inhaled aerosolized immunotherapeutic for lung cancer to be combined with an inhibitor of the anti-programmed cell death protein 1 (pd‑1) im ...	2019	30502651
preclinical safety evaluation of oncolytic herpes simplex virus type 2.	oncolytic virotherapy is a new and safe therapeutic strategy based on the inherent cytotoxicity of oncolytic viruses and their ability to replicate and spread within tumors in a selective manner. in a previous study, a new type of oncolytic herpes simplex virus type 2 (ohsv-2, named oh2) was constructed to treat human cancers. that study demonstrated that oh2 is genetically and biologically stable. its antitumor activity was maintained, even after passaging the virus for >20 generations. to adva ...	2019	30499341
improving cell survival in injected embryos allows primed pluripotent stem cells to generate chimeric cynomolgus monkeys.	monkeys are an optimal model species for developing stem cell therapies. we previously reported generating chimeric cynomolgus monkey fetuses using dome-shaped embryonic stem cells (descs). however, conventional primed pluripotent stem cells (ppscs) lack chimera competency. here, by altering the media in which injected morulae are cultured, we observed increased survival of cynomolgus monkey primed escs, induced pscs, and somatic cell nuclear transfer-derived escs, thereby enabling chimeric cont ...	2018	30485820
encoding prediction signals during appetitive and aversive pavlovian conditioning in the primate lateral hypothalamus.	the lateral hypothalamus (lh), which plays a role in homeostatic functions such as appetite regulation, is also linked to arousal and motivational behavior. however, little is known about how these components are encoded in the lh. thus cynomolgus monkeys were conditioned with two distinct contexts, i.e., an appetitive context with available rewards and an aversive context with predicted air puffs. different lh neuron groups encoded different degrees of expectation, predictability, and risks of ...	2019	30485150
withdrawn: indel-informed bayesian analysis suggests cryptic divisions between plasmodium knowlesi of humans and long-tailed macaques (macaca fascicularis) in malaysian borneo.	this article has been withdrawn at the request of the author(s) and/or editor. the publisher apologizes for any inconvenience this may cause. the full elsevier policy on article withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.	2018	30481580
stroke longitudinal volumetric measures correlate with the behavioral score in non-human primates.	stroke is the second leading cause of death worldwide. brain imaging data from experimental rodent stroke models suggest that size and location of the ischemic lesion relate to behavioral outcome. however, such a relationship between these two variables has not been established in non-human primate (nhp) models. thus, we aimed to evaluate whether size, location, and severity of stroke following controlled middle cerebral artery occlusion (mcao) in nhp model correlated to neurological outcome. fo ...	2019	30481566
mhc-identical and transgenic cynomolgus macaques for preclinical studies.	cynomolgus macaques are useful experimental animals that are physiologically and genetically close to humans. we have developed two kinds of experimental usage of cynomolgus macaque: transplantation and disease models. first, we identified certain major histocompatibility complex (mhc) haplotypes including homozygotes and heterozygotes in cynomolgus macaques native to the philippines, because they have less polymorphism in the mhc than that in other origins such as vietnam and indonesia. as a pr ...	2018	30479676
validation of sysmex xt-2000iv analyzer-generated quantitative bone marrow differential counts in cynomolgus monkeys, beagle dogs, and cd-1 mice.	in a previous study, the validation of rat bone marrow (bm) collection, processing, and analysis using the sysmex xt-2000iv (sysmex corporation, kobe, japan) hematology analyzer showed that the sysmex hematology analyzer produced bm differential counts that were comparable to those obtained with microscopic differential counts.	2018	30476353
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 ...	2018	30469417
virulence of marburg virus angola compared to mt. elgon (musoke) in macaques: a pooled survival analysis.	angola variant (marv/ang) has replaced mt. elgon variant musoke isolate (marv/mte-mus) as the consensus standard variant for marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the higher virulence of marv/ang. in this retrospective study, we used data pooled from eight separate studies in nonhuman primates experimentally exposed with either 1000 pfu intramuscular (im) marv/ang or m ...	2018	30469360
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 ...	2018	30467501
nonclinical safety assessment of a human interleukin-22fc ig fusion protein demonstrates in vitro to in vivo and cross-species translatability.	although interleukin-22 (il-22) is produced by various leukocytes, it preferentially targets cells with epithelial origins. il-22 exerts essential roles in modulating various tissue epithelial functions, such as innate host defense against extracellular pathogens, barrier integrity, regeneration, and wound healing. therefore, il-22 is thought to have therapeutic potential in treating diseases associated with infection, tissue injury or chronic tissue damage. a number of in vitro and in vivo nonc ...	2018	30464842
successful inflammation imaging of non-human primate hearts using an antibody specific for tenascin-c.	inflammation after myocardial infarction (mi) may be a major factor influencing ventricular remodeling, leading to congestive heart failure and arrhythmia. therefore, inflammation in the heart needs to be monitored. tenascin-c (tnc) is an extracellular matrix molecule not normally expressed, but it is strongly upregulated when associated with active inflammation. based on this characteristic, we successfully imaged in vivo inflammatory lesions in rat models using 111indium (111in)-labeled anti-t ...	2019	30464121
an investigational rnai therapeutic targeting factor xii (aln-f12) for the treatment of hereditary angioedema.	hereditary angioedema (hae) is a genetic disorder mostly caused by mutations in the c1 esterase inhibitor gene (c1inh) that results in poor control of contact pathway activation and excess bradykinin generation. bradykinin increases vascular permeability and is ultimately responsible for the episodes of swelling characteristic of hae. we hypothesized that the use of rna interference (rnai) to reduce plasma factor xii (fxii), which initiates the contact pathway signaling cascade, would reduce con ...	2019	30463937
syntheses and in vitro biological evaluation of s1pr1 ligands and pet studies of four f-18 labeled radiotracers in the brain of nonhuman primates.	a series of seventeen hydroxyl-containing sphingosine 1-phosphate receptor 1 (s1pr1) ligands were designed and synthesized. their in vitro binding potencies were determined using [32p]s1p competitive binding assays. compounds 10a, 17a, 17b, and 24 exhibited high s1pr1 binding potencies with ic50 values ranging from 3.9 to 15.4 nm and also displayed high selectivity for s1pr1 over other s1p receptor subtypes (ic50 > 1000 nm for s1pr2-5). the most potent compounds 10a, 17a, 17b, and 24 were subseq ...	2018	30462126
humanised effector-null fcγriia antibody inhibits immune complex-mediated proinflammatory responses.	immune complexes (ics) play a critical role in the pathology of autoimmune diseases. the aim of this study was to generate and characterise a first-in-class anti-fcγriia antibody (ab) vib9600 (previously known as medi9600) that blocks igg immune complex-mediated cellular activation for clinical development.	2019	30459279
establishment of a transplantation - immunotolerant cynomolgus monkey colony and application to regenerative medicine.		2015	30458081
intramuscular exposure of macaca fascicularis to low doses of low passage- or cell culture-adapted sudan virus or ebola virus.	the filoviruses ebola virus (ebov) and sudan virus (sudv) can cause severe diseases, and there are currently no licensed countermeasures available for use against them. transmission occurs frequently via contact with bodily fluids from infected individuals. however, it can be difficult to determine when or how someone became infected, or the quantity of infectious virus to which they were exposed. evidence suggests the infectious dose is low, but the majority of published studies use high exposu ...	2018	30453499
elevated membrane cholesterol disrupts lysosomal degradation to induce β-amyloid accumulation: the potential mechanism underlying augmentation of β-amyloid pathology by type 2 diabetes mellitus.	the endocytic membrane trafficking system is altered in the brains of early-stage alzheimer disease (ad) patients, and endocytic disturbance affects the metabolism of β-amyloid (aβ) protein, a key molecule in ad pathogenesis. it is widely accepted that type 2 diabetes mellitus (t2dm) is one of the strongest risk factors for development of ad. supporting this link, experimentally induced t2dm enhances ad pathology in various animal models. spontaneous t2dm also enhances aβ pathology with severe e ...	2019	30448407
a long-lived il-2 mutein that selectively activates and expands regulatory t cells as a therapy for autoimmune disease.	susceptibility to multiple autoimmune diseases is associated with common gene polymorphisms influencing il-2 signaling and treg function, making treg-specific expansion by il-2 a compelling therapeutic approach to treatment. as an in vivo il-2 half-life enhancer we used a non-targeted, effector-function-silent human igg1 as a fusion protein. an il-2 mutein (n88d) with reduced binding to the intermediate affinity il-2rβγ receptor was engineered with a stoichiometry of two il-2n88d molecules per i ...	2018	30446251
experimental co-transmission of simian immunodeficiency virus (siv) and the macaque homologs of the kaposi sarcoma-associated herpesvirus (kshv) and epstein-barr virus (ebv).	macaque rfhv and lcv are close homologs of human kshv and ebv, respectively. no experimental model of rfhv has been developed due to the lack of a source of culturable infectious virus. screening of macaques at the washington national primate research center detected rfhv in saliva of siv-infected macaques from previous vaccine studies. a pilot experimental infection of two naïve juvenile pig-tailed macaques was initiated by inoculation of saliva from siv-infected pig-tailed and cynomolgus macaq ...	2018	30444879
a cynomolgus monkey model of temporal lobe epilepsy.	temporal lobe epilepsy (tle) with hippocampal sclerosis is the most common type of drug-resistant epilepsy. non-human primates are attractive models for studying the pathogenic mechanisms of tle, with the goal of developing new drugs and interventions. in this study, we developed and tested a cynomolgus monkey (macaca fascicularis) model of tle. a total of 5 cynomolgus monkeys received3-4 weekly unilateral hippocampal injections of kainic acid (ka) to induce repetitive acute seizures. animals we ...	2019	30423353
establishment of retinal degeneration model in rat and monkey by intravitreal injection of sodium iodate.	animal models play critical roles in studies of the etiology and therapy of retinal degeneration (rd).	2018	30421676
non-synonymous genetic variants of flavin-containing monooxygenase 3 (fmo3) in cynomolgus macaques.	polymorphic human flavin-containing monooxygenase (fmo) 3 is an important drug-metabolizing enzyme for nitrogen- or sulfur-containing compounds. cynomolgus macaques, a non-human primate species widely used in drug metabolism studies, have corresponding fmo3 molecular and enzymatic similarities to humans; however, genetic polymorphisms have not been investigated in macaques. in this study, re-sequencing of fmo3 in 64 cynomolgus and 32 rhesus macaques found a total of 18 non-synonymous variants. n ...	2019	30420260
cytochrome p450 1a1, 2c9, 2c19, and 3a4 polymorphisms account for interindividual variability of toxicological drug metabolism in cynomolgus macaques.	cytochromes p450 (p450s) and their genetic variants in humans are important drug-metabolizing enzymes partly accounting for interindividual variations in drug metabolism and toxicity. however, these genetic variants in p450s have not been fully investigated in cynomolgus macaques, a nonhuman primate species widely used in toxicological studies. in this study, genetic variants found in cynomolgus cyp1a1, cyp2c9 (formerly cyp2c43), cyp2c19 (cyp2c75), and cyp3a4 (cyp3a8) were assessed on functional ...	2018	30412386
cathepsin k inhibition preserves compressive load in lumbar vertebrae of osteoporotic monkeys.	anti-resorptive drugs treat bone loss by blocking osteoclast activity through a variety of mechanisms of action. once significant bone loss has occurred, the ability to restore biomechanical function may differ based on the drug chosen. to assess this question, bisphosphonate (alendronate, aln) and cathepsin k inhibitor (mk-0674, catki) were employed in treatment mode to compare the relative changes to cancellous bone microstructure and mechanical properties in ovariectomized (ovx) cynomolgus mo ...	2018	30406161
validation of a noninvasive hair trapping method for extractive-foraging primates.	hair is a useful source of biological information. for example, the bulb can be a source of high-quality genetic material, whereas the shaft can be useful for measuring heavy metals and some hormones, such as cortisol. the stable isotope composition of hair is another valuable source of biological information. consequently, noninvasive methods of hair sampling have become important research tools. several hair-trapping methods have been developed for use on mammals, but these are rarely deployed ...	2018	30404083
evaluation of a potential clinical significant drug-drug interaction between digoxin and bupropion in cynomolgus monkeys.	a three-period digoxin-bupropion drug-drug interaction study was performed in cynomolgus monkeys to assess the effect of bupropion and its metabolites on digoxin disposition.	2018	30402714
alterations in the spinal cord and ventral root after cerebral infarction in non-human primates.	cerebral infarction does not only cause focal injury in the ischemic site, but also secondary non-ischemic damage at the remote areas of nervous system associated with the primary focus.	2018	30400121
oral delivery of the anti-tumor necrosis factor α domain antibody, v565, results in high intestinal and fecal concentrations with minimal systemic exposure in cynomolgus monkeys.	v565 is a novel oral anti-tumor necrosis factor (tnf)-α domain antibody being developed for topical treatment of inflammatory bowel disease (ibd) patients. protein engineering rendered the molecule resistant to intestinal proteases. here we investigate the formulation of v565 required to provide gastro-protection and enable optimal delivery to the lower intestinal tract in monkeys.	2019	30395728
[establishment and evaluation of a triple-color human papillomavirus pseudovirion neutralization assay].	objective: to establish a triple-color pseudovirion-based neutralization assay (pbna) and evaluate its capability of detecting immunogenicity of the sera generated by the immunization of hpv 9-valent vaccine. methods: hpv pseudovirus (psvs) 6/11/16/18/31/33/45/52/58 with the encapsidated fluorescence expressing red fluorescent plasmid n31-mchreey, green fluorescent n31-egfp or blue fluorescent n31-mtagbfp were generated. the concentration of hpv psvs and the infection titers of hpv psvs were det ...	2018	30392324
population genetics of the abo locus within the rhesus (macaca mulatta) and cynomolgus (m. fascicularis) macaque hybrid zone.	knowledge of the macaque abo blood group system has been critical in the development of nonhuman primates (nhps) as a translational model. serving not only as a useful homologue of the disease-linked abo system in humans, macaque abo blood groups must be typed in colonies prior to performing experimental procedures requiring blood transfusion or transplantation. while the rates of blood type incompatibility and the distributions of a, b and ab blood groups are known in large samples of rhesus (m ...	2019	30387553
lymph nodes are sites of prolonged bacterial persistence during mycobacterium tuberculosis infection in macaques.	tuberculosis is commonly considered a chronic lung disease, however, extrapulmonary infection can occur in any organ. even though lymph nodes (ln) are among the most common sites of extrapulmonary mycobacterium tuberculosis (mtb) infection, and thoracic lns are frequently infected in humans, bacterial dynamics and the effect of mtb infection in ln structure and function is relatively unstudied. we surveyed thoracic lns from mtb-infected cynomolgus and rhesus macaques analyzing pet ct scans, bact ...	2018	30383808
development and long-term evaluation of ocular surface conditions using ovariectomized cynomolgus monkey.	we aim to use the ovariectomized cynomolgus monkey to observe the effect of long-term changes of sex hormone levels on ocular surface.	2019	30383547
improved macaca fascicularis gene annotation reveals evolution of gene expression profiles in multiple tissues.	macaca fascicularis (m. fascicularis) is a primate model organism that played important role in studying human health. it is vital to better understand the similarity and differences of gene regulation between m. fascicularis and human. current comparative study of gene regulation between the two species are limited by low quality of gene annotation and lack of regulatory element data on m. fascicularis genome.	2018	30382841
development of cdx-1140, an agonist cd40 antibody for cancer immunotherapy.	limitations of immunotherapy include poorly functioning events early in the immune response cycle, such as efficient antigen presentation and t cell priming. cd40 signaling in dendritic cells leads to upregulation of cell surface costimulatory and mhc molecules and the generation of cytokines, which promotes effective priming of cd8+ effector t cells while minimizing t cell anergy and the generation of regulatory t cells. this naturally occurs through interaction with cd40 ligand (cd40l) express ...	2019	30382327
safe and effective superoxide dismutase 1 silencing using artificial microrna in macaques.	amyotrophic lateral sclerosis (als) is a fatal neurological disease caused by degeneration of motor neurons leading to rapidly progressive paralysis. about 10% of cases are caused by gain-of-function mutations that are transmitted as dominant traits. a potential therapy for these cases is to suppress the expression of the mutant gene. here, we investigated silencing of sod1, a gene commonly mutated in familial als, using an adeno-associated virus (aav) encoding an artificial microrna (mirna) tha ...	2018	30381409
a pre-clinical quantitative model predicts the pharmacokinetics/pharmacodynamics of an anti-bdca2 monoclonal antibody in humans.	biib059 is a novel humanized monoclonal antibody (mab) that is currently under development for the treatment of systemic lupus erythematosus and cutaneous lupus erythematosus. biib059 is targeted against the blood dendritic cell antigen 2 (bdca2), a receptor exclusively expressed on the surface of plasmacytoid dendritic cells (pdcs). herein, we utilized pre-clinical pharmacokinetic (pk) and pharmacodynamic (pd) data to develop a non-human primate (nhp) model and to address whether the nhp model ...	2018	30377889
immune-mediated systemic vasculitis as the proposed cause of sudden-onset sensorineural hearing loss following lassa virus exposure in cynomolgus macaques.	lassa virus (lasv) causes a severe, often fatal hemorrhagic disease in regions in africa where the disease is endemic, and approximately 30% of patients develop sudden-onset sensorineural hearing loss after recovering from acute disease. the causal mechanism of hearing loss in lasv-infected patients remains elusive. here, we report findings after closely examining the chronic disease experienced by surviving macaques assigned to lasv exposure control groups in two different studies. all nonhuman ...	2018	30377282
implicit preference for human trustworthy faces in macaque monkeys.	it has been shown that human judgements of trustworthiness are based on subtle processing of specific facial features. however, it is not known if this ability is a specifically human function, or whether it is shared among primates. here we report that macaque monkeys (macaca mulatta and macaca fascicularis), like humans, display a preferential attention to trustworthiness-associated facial cues in computer-generated human faces. monkeys looked significantly longer at faces categorized a priori ...	2018	30375399
choroid changes in vortex vein-occluded monkeys.	to determine acute and chronic choroidal vascular changes after vortex vein occlusion in monkeys.	2018	30364268
intravenous toxicity and toxicokinetics of an hdl mimetic, fx-5a peptide complex, in cynomolgus monkeys.	fx-5a peptide complex (fx-5a), a high density lipoproteins (hdl) mimetic, has been shown to reduce atherosclerosis. the safety and toxicokinetics of fx-5a administered iv by 30 min infusion at 8, 25 or 75 mg/kg body weight or vehicle, once every other day for 27 days, were assessed in cynomolgus monkeys. the fx-5a was well tolerated at all doses. at the highest dose, there were statistically significant effects on hematology and clinical chemistry parameters that were considered non-adverse. dos ...	2018	30359697
molecular and functional characterization of n-acetyltransferases nat1 and nat2 in cynomolgus macaque.	arylamine n-acetyltransferases (nats) are drug-metabolizing enzymes essential for the metabolism of endogenous substrates and xenobiotics, and their molecular characteristics have been extensively investigated in humans, but not in cynomolgus macaques, nonhuman primate species important for drug metabolism studies. in this study, cynomolgus nat1 and nat2 cdnas were isolated from livers. nat1 and nat2 were characterized by molecular analyses and drug-metabolizing assays. a total of 9 transcript v ...	2018	30358977
aromatase and estrogen receptor immunoreactivity in the coronary arteries of monkeys and human subjects.	the objective of this study was to determine whether estrogen could be formed locally in the coronary arteries.	2018	30358714
the japan monkey centre primates brain imaging repository for comparative neuroscience: an archive of digital records including records for endangered species.	advances in magnetic resonance imaging (mri) and computational analysis technology have enabled comparisons among various primate brains in a three-dimensional electronic format. results from comparative studies provide information about common features across primates and species-specific features of neuroanatomy. investigation of various species of non-human primates is important for understanding such features, but the majority of comparative mri studies have been based on experimental primat ...	2018	30357587
cortical bone mineral density is increased by the cathepsin k inhibitor ono-5334, which leads to a robust increase in bone strength: results from a 16-month study in ovariectomised cynomolgus monkeys.	this study evaluated the long-term effects of the cathepsin k inhibitor ono-5334 on bone mass and strength in ovariectomised (ovx) cynomolgus monkeys. animals were assigned to one of the following six groups: sham (non-ovx), ovx control treated with vehicle, ono-5334 1.2, 6 or 30 mg/kg/day, p.o., or alendronate (aln) 0.05 mg/kg/2 weeks, i.v. for 16 months. peripheral quantitative computed tomography (pqct) analysis revealed that ono-5334 increased not only trabecular bone mineral density (bmd) b ...	2019	30357565
molecular analysis of two different mrsa clones st188 and st3268 from primates (macaca spp.) in a united states primate center.	methicillin-resistant staphylococcus aureus (mrsa) were identified in macaques, their environmental facility, and nasal cultures of personnel from the washington national primate research center [wanprc] and included mrsa st188 sccmec iv and mrsa st3268 sccmec v. the aim of the current study was to determine the carriage of virulence genes, antibiotic resistance genes, and other characteristics of the primate mrsa isolates to determine if there were any obvious differences that would account for ...	2018	30356855
comprehensive preclinical pharmacokinetic evaluations of trastuzumab deruxtecan (ds-8201a), a her2-targeting antibody-drug conjugate, in cynomolgus monkeys.	trastuzumab deruxtecan (ds-8201a) is an antibody-drug conjugate (adc) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (her2) conjugated to a topoisomerase i inhibitor (dxd) at a drug-to-antibody ratio (dar) of 7-8. here, we examined the pharmacokinetic (pk) profiles of ds-8201a and dxd in cynomolgus monkeys, a cross-reactive species. following intravenous (iv) administration of ds-8201a, the linker was stable in plasma, and systemic dxd exposure was low. dxd ...	2019	30351177
gene expression dataset for whole cochlea of macaca fascicularis.	macaca fascicularis is a highly advantageous model in which to study human cochlea with regard to both evolutionary proximity and physiological similarity of the auditory system. to better understand the properties of primate cochlear function, we analyzed the genes predominantly expressed in m. fascicularis cochlea. we compared the cochlear transcripts obtained from an adult male m. fascicularis by macaque and human genechip microarrays with those in multiple macaque and human tissues or cells ...	2018	30349143
serotonin and norepinephrine transporter occupancy of tramadol in nonhuman primate using positron emission tomography.	tramadol, a centrally acting analgesic drug, has relatively high affinity to serotonin transporter and norepinephrine transporter in addition to μ-opioid receptor. based on this characteristic, tramadol is expected to have an antidepressant effect.	2019	30346535
current status of uterus transplantation and approaches for future clinical application in japan.	uterus transplantation (utx) has become an alternative to gestational surrogacy and adoption for women with uterine factor infertility (ufi). brännström et al achieved the first human delivery after utx in 2014, and to date a total of 8 babies have been born after utx from living donors. this outcome has attracted much attention worldwide, and many countries are now preparing for utx. there are an estimated 60,000 women of reproductive age with ufi in japan, and these patients cannot have biolog ...	2018	30343882
system for on- and off-axis volumetric oct imaging and ray tracing aberrometry of the crystalline lens.	we present a new in vitro instrument for measuring shape and wavefront aberrations of the primate crystalline lens, both on- and off-axis, while simulating accommodation with a motorized lens stretching system. the instrument merges spectral domain optical coherence tomography (sd-oct) imaging and ray tracing aberrometry using an approach that senses wavefront aberrations of the lens with the oct probing beam. accuracy and repeatability of aberration measurements were quantified. preliminary exp ...	2018	30338159
negative lusitropic property of nifekalant identified using ventricular pressure-volume loop analyses in anesthetized monkeys.	the present study was conducted to clarify multiple cardiohemodynamic and electrophysiological properties including inotropic/lusitropic effects of nifekalant, a class iii antiarrhythmic drug, in an isoflurane-anesthetized monkey. nifekalant was administered intravenously at the therapeutic dose of 0.3 mg/kg over 10 min to male cynomolgus monkeys (n=4), followed by higher dose of 1 (n=3) or 3 mg/kg (n=1) that was limited due to arrythmogenicity. left ventricular (lv) pressure-volume (pv) analysi ...	2019	30333366
differences in cytoarchitecture of broca's region between human, ape and macaque brains.	areas 44 and 45 have been identified in non-human primates as homologs of the human broca region. distribution of large and smaller pyramids and the ventro-lateral localization in the posterior frontal lobe enable their identification in non-human primates. since only humans hold the ability of language, it has been hypothesized that differences in microstructure may, together with other anatomical factors, e.g., white matter tract connectivity, volumes of cortical areas and their molecular diff ...	2019	30333085
mass spectrometry-based identification and whole-genome characterisation of the first pteropine orthoreovirus isolated from monkey faeces in thailand.	the pteropine orthoreovirus (prv) was isolated from monkey (macaca fascicularis) faecal samples collected from human-inhabited areas in lopburi province, thailand. these samples were initially obtained to survey for the presence of hepatitis e virus (hev).	2018	30332986
crispr/cas9-mediated disruption of shank3 in monkey leads to drug-treatable autism-like symptoms.	monogenic mutations in the shank3 gene, which encodes a postsynaptic scaffold protein, play a causative role in autism spectrum disorder (asd). although a number of mouse models with shank3 mutations have been valuable for investigating the pathogenesis of asd, species-dependent differences in behaviors and brain structures post considerable challenges to use small animals to model asd and to translate experimental therapeutics to the clinic. we have used clustered regularly interspersed short p ...	2019	30329048
genetic diversity in the env v1-v2 region of proviral quasispecies from long-term controller mhc-typed cynomolgus macaques infected with shivsf162p4cy.	intra-host evolution of human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) has been shown by viral rna analysis in subjects who naturally suppress plasma viremia to low levels, known as controllers. however, little is known about the variability of proviral dna and the inter-relationships among contained systemic viremia, rate of reservoir reseeding and specific major histocompatibility complex (mhc) genotypes, in controllers. here, we analysed the proviral dna quasispeci ...	2018	30311877
aging results in iron accumulations in the non-human primate choroid of the eye without an associated increase in zinc, copper or sulphur.	we present further analyses of a previous experiment published in 2016 where the distribution, concentration and correlation of iron, zinc, copper and sulphur in the choroid of the eye in young and aged old world primates (macaca fascicularis) was studied with synchrotron x-ray fluorescence with a 2 μm resolution. the results indicate that iron accumulates in hotspots in the choroid with age with fluorescence intensity ranging from 2- to 7-fold (1002-3752 ppm) the mean level in the choroidal str ...	2018	30306383
protective efficacy and long-term immunogenicity in cynomolgus macaques by ebola virus glycoprotein synthetic dna vaccines.	there remains an important need for prophylactic anti-ebola virus vaccine candidates that elicit long-lasting immune responses and can be delivered to vulnerable populations that are unable to receive live-attenuated or viral vector vaccines.	2019	30304515
profiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structure.	the specific interactions of mycobacterium tuberculosis (mtb), the causative agent of tuberculosis (tb), and the lung microbiota in infection are entirely unexplored. studies in cancer and other infectious diseases suggest that there are important exchanges occurring between host and microbiota that influence the immunological landscape. this can result in alterations in immune regulation and inflammation both locally and systemically. to assess whether mtb infection modifies the lung microbiome ...	2018	30301469
serum anti-mullerian hormone predicts ovarian response in (macaca fascicularis) monkeys	amh as a promising predictor of ovarian response has been studied extensively in women undergoing assisted reproductive technology treatment, but little is known about its prediction value in monkeys undergoing ovarian stimulation. in the current study, a total of 380 cynomolgus monkeys ranging from 5 to 12 years received 699 ovarian stimulation cycles. serum samples were collected for amh measure with enzyme-linked immunosorbent assay. it was found that serum amh levels were positive correlated ...	2018	30300541
antidiabetic effect of abextide, a long-acting exendin-4 analogue in cynomolgus monkeys.	abextide, synthesized by conjugating an albumin-binding moiety-truncated evans blue-to glucagon-like peptide 1 receptor (glp-1r) agonist exendin-4, shows extended drug release and enhanced hypoglycemic effect in diabetic mice. the aim of this study is to evaluate the pharmacodynamics of abextide in nonhuman primates. two batches of elderly cynomolgus monkeys with naturally occurring diabetes are used for this study. during the whole experiment period, no abnormalities such as swelling at the inj ...	2019	30300471
tissue physiology of cynomolgus monkeys: cross-species comparison and implications for translational pharmacology.	we previously performed a comparative assessment of tissue-level vascular physiological parameters in mice and rats, two of the most commonly utilized species in translational drug development. the present work extends this effort to non-human primates by measuring tissue- and organ-level vascular volumes (vv), interstitial volumes (vi), and blood flow rates (q) in cynomolgus monkeys. these measurements were accomplished by red blood cell labeling, extracellular marker infusion, and rubidium chl ...	2018	30298434
asymptomatic natural human infections with the simian malaria parasites plasmodium cynomolgi and plasmodium knowlesi.	in southeast asia, plasmodium knowlesi, a parasite of long-tailed macaques (macaca fascicularis), is an important cause of human malaria. plasmodium cynomolgi also commonly infects these monkeys, but only one naturally acquired symptomatic human case has been reported previously.	2019	30295822
inhibition of catechol-o-methyltransferase in the cynomolgus monkey by opicapone after acute and repeated administration.	the aim of the study was to clarify the dose response for inhibition of catechol-o-methyltransferase (comt) by opicapone, a third generation comt inhibitor, after acute and repeated administration to the cynomolgus monkey with pharmacokinetic evaluation at the higher dose.	2018	30290160
an ex vivo bladder model with detrusor smooth muscle removed to analyse biologically active mediators released from the suburothelium.	studies of urothelial cells, bladder sheets or lumens of filled bladders have suggested that mediators released from urothelium into suburothelium (subu)/lamina propria (lp) activate mechanisms controlling detrusor excitability. none of these approaches, however, has enabled direct assessment of availability of mediators at subu/lp during filling. we developed an ex vivo mouse bladder preparation with intact urothelium and subu/lp but no detrusor, which allows direct access to the subu/lp surfac ...	2019	30289177
evaluation of deuterium-labeled jnj38877605: pharmacokinetic, metabolic, and in vivo antitumor profiles.	c-met inhibitor jnj38877605 has proven curative as an antitumor agent, while its clinical study was terminated due to renal toxicity. it was reported that the renal toxicity was caused by the poor solubility of its aldehyde oxidase (ao) metabolites. therefore, blocking ao oxidation of jnj38877605 might diminish the toxic metabolites and overcome the renal toxicity. compound 3, the ao metabolic site deuterated jnj38877605, was then synthesized as the target molecule. in vitro monkey liver s9 frac ...	2018	30284817
rolipram plus sivelestat inhibits bone marrow-derived leukocytic lung recruitment after cardiopulmonary bypass in a primate model.	cardiopulmonary bypass (cpb) recovery is complicated by lung inflammation from bone marrow (bm)-derived polymorphonuclear leukocytes (pmns) and monocytes (mo). although sivelestat reduces inflammatory mediators and rolipram inhibits pmn and mo activation, any kinetic effects to improve cpb recovery in vivo are unknown. we hypothesized that intraoperative co-administration of these compounds would reduce cpb-induced lung inflammation through downregulation of pmn and mo recruitment. a 2-h cpb was ...	2019	30284168
proceedings of the 2018 national toxicology program satellite symposium.	the 2018 annual national toxicology program satellite symposium, entitled "pathology potpourri," was held in indianapolis, indiana, at the society of toxicologic pathology's 37th annual meeting. the goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. this article presents summaries of the speakers' talks along with select images that were used by the audience for voting and discussion. various lesions and other topics covered during the ...	2018	30282530
survey of drug oxidation activities in hepatic and intestinal microsomes of individual common marmosets, a new nonhuman primate animal model.	common marmosets (callithrix jacchus) are potentially useful nonhuman primate models for preclinical studies. information for major drug-metabolizing cytochrome p450 (p450) enzymes is now available that supports the use of this primate species as an animal model for drug development. here, we collect and provide an overview of information on the activities of common marmoset hepatic and intestinal microsomes with respect to 28 typical human p450 probe oxidations.	2019	30280664
a safety study of newly generated anti-podoplanin-neutralizing antibody in cynomolgus monkey (macaca fascicularis).	hematogenous metastases are enhanced by platelet aggregation induced by tumor cell-platelet interaction. podoplanin is a key molecule to enhance the platelet aggregation and interacts with c-type lectin-like receptor 2 (clec-2) on platelet via plag domains. our previous reports have shown that blocking podoplanin binding to platelets by neutralizing antibody specific to plag4 domain strongly reduces hematogenous metastasis. however, podoplanin is expressed in a variety of normal tissues such as ...	2018	30279963
high resolution hard x-ray 3d mapping of a macaca fascicularis eye: a feasibility study without contrast agents.	several complementary methods able to visualize the internal structures of eyes are used in the clinical practice in the diagnosis of pathologies affecting a specific zone of the eye. despite the significant technological progress, the visualization of the entire eyeball at micrometric resolution is yet an unsolved task both in clinical diagnostics and in laboratory research. with this respect, high resolution 3d images of the eyeball would be extremely useful, in the study of various pathologie ...	2018	30278983
cynomolgus monkeys (macaca fascicularis) experimentally and naturally infected with hepatitis e virus: the bone marrow as a possible new viral target.	hepatitis e virus (hev) transmission through infected blood and blood products has already been described. however, little is known about the bone marrow (bm) as source of hev infection. our study aimed to investigate the presence of hev antigen (ag) and histological changes in bm of cynomolgus monkeys (macaca fascicularis) experimentally and naturally infected with hev. four cynomolgus monkeys with acute, and two with chronic hepatitis e ─ after immunosuppressive therapy with tacrolimus ─ were ...	2018	30278075
enhanced neutralizing antibody response induced by inactivated enterovirus 71 in cynomolgus monkeys.	enterovirus 71 (ev71) is a major etiological agent of various public health issues, particularly in the asia-pacific region. ev71 causes hand-foot-and-mouth disease (hfmd) and is associated with serious neurological disorders in young children. a formalin-inactivated ev71 candidate vaccine (kcdc-hfmdv1-ev71) based on the c4 subgenotype was previously developed and confirmed to be a potential candidate vaccine for prevention of ev71 infection in mice. in this study, an inactivated ev71 vaccine wa ...	2018	30278051
repeated injection of kmrc011, a medical countermeasure for radiation, can cause adverse health effects in cynomolgus monkeys.	high-dose radiation-induced tissue damage is a major limiting factor in the medical application of nuclear technology. herein, we tested 28-day repeated-dose toxicity of kmrc011, an agonist of toll-like receptor (tlr) 5, which is being developed as a medical countermeasure for radiation, using cynomolgus monkeys. kmrc011 (0.01, 0.02 or 0.04 mg/kg/day) was intramuscularly injected once daily for 4 weeks, and each two monkeys in both control and 0.04 mg/kg/day group were observed for an additional ...	2019	30277593
cigarette smoke and hiv synergistically affect lung pathology in cynomolgus macaques.	in the era of combined antiretroviral therapy (cart), lung diseases such as chronic bronchitis (cb) and chronic obstructive pulmonary disease (copd) are common among persons living with hiv (plwh), particularly smokers. although smoking is highly prevalent among plwh, hiv may be an independent risk factor for lung diseases; however, the role of hiv and cigarette smoke (cs) and their potential interaction in the development of chronic lung diseases among plwh has not been delineated. to investiga ...	2018	30277472
ebola viral dynamics in nonhuman primates provides insights into virus immuno-pathogenesis and antiviral strategies.	despite several clinical trials implemented, no antiviral drug could demonstrate efficacy against ebola virus. in non-human primates, early initiation of polymerase inhibitors favipiravir and remdesivir improves survival, but whether they could be effective in patients is unknown. here we analyze the impact of antiviral therapy by using a mathematical model that integrates virological and immunological data of 44 cynomolgus macaques, left untreated or treated with favipiravir. we estimate that f ...	2018	30275474
the mevalonate pathway is a druggable target for vaccine adjuvant discovery.	motivated by the clinical observation that interruption of the mevalonate pathway stimulates immune responses, we hypothesized that this pathway may function as a druggable target for vaccine adjuvant discovery. we found that lipophilic statin drugs and rationally designed bisphosphonates that target three distinct enzymes in the mevalonate pathway have potent adjuvant activities in mice and cynomolgus monkeys. these inhibitors function independently of conventional "danger sensing." instead, th ...	2018	30270039
establishment of an in vitro cytotoxicity assay platform using primary monkey cardiomyocytes.	to establish an in vitro cytotoxicity assay platform using monkey cardiomyocytes, we isolated primary cardiomyocytes from fetal cynomolgus monkeys at different gestation days (from day 39 to 90) using the trypsin and collagenase digestion method, which was identical to the standard procedure for rat cardiomyocytes. under these conditions, the primary cells obtained from monkeys at gestation day 63 or earlier showed spontaneous beating, with >80% cells being viable from all fetuses. transcriptome ...	2019	30261314
high order formation and evolution of hornerin in primates.	genomic duplication or loss can accelerate evolution because the number of repeats could affect molecular pathways and phenotypes. we have previously reported that the repeated region of filaggrin (flg), a crucial component of the outer layers of mammalian skin, had high levels of nucleotide diversity with species-specific divergence and expansion and that it evolved under the birth-and-death model. we focused on hornerin (hrnr), a member of the same gene family that harbor similar tandem repeat ...	2018	30256937
the properties of cysteine-conjugated antibody-drug conjugates are impacted by the igg subclass.	among the numerous antibody-drug conjugate (adc) clinical candidates, one of the most prevalent types utilizes the interchain cysteines in antibodies to conjugate auristatin via a maleimide-containing linker. in this class of adcs, there are a paucity of systematic studies characterizing how igg subclass influences the biophysical properties and in vivo pharmacokinetics of the adc molecules. in the current investigation, we studied cysteine-conjugated adcs using a model system consisting of huma ...	2018	30255287
expression and metabolic activity of flavin-containing monooxygenase 1 in cynomolgus macaque kidney.	flavin-containing monooxygenase 1 (fmo1) largely remains to be characterized in cynomolgus macaque kidney. immunoblotting showed expression of cynomolgus fmo1 in kidneys where activities of fmo1 (benzydamine n-oxygenation) were detected. no sex differences were observed in their contents or activities. these results suggest the functional role of cynomolgus fmo1 in kidney.	2019	30252147
whole body pet imaging with a norepinephrine transporter probe 4-[18f]fluorobenzylguanidine: biodistribution and radiation dosimetry.	4-[18f]fluorobenzylguanidine ([18f]pfbg) is a positron emission tomography (pet) probe for non-invasive targeting of the norepinephrine transporter. the aim of this study was to assess uptake and distribution characteristics of this pet probe.	2019	30250991
minimal physiologically-based pharmacokinetic model to investigate the effect of ph dependent fcrn affinity and the endothelial endocytosis on the pharmacokinetics of anti-vegf humanized igg1 antibody in cynomolgus monkey.	in this study, we developed a first minimal physiologically-based pharmacokinetic (mpbpk) model to investigate the complex interaction effects of endocytosis rate/fcrn binding affinity at both acidic/physiological ph on the pharmacokinetics (pk) of the anti-vegf igg1 antibodies. the data used in this study were the pk of the native igg and humanized anti-vegf igg1 antibodies with a wide range fcrn-binding at both acidic and physiological ph in the cynomolgus monkey. the basic structure of the de ...	2018	30248389
age-related nomograms of serum anti-mullerian hormone levels in female monkeys: comparison of rhesus (macaca mulatta) and cynomolgus (macaca fascicularis) monkeys.	amh is regarded as a promising predictor for ovarian reserve in humans and non-human primate, and widely used in human medicine to predict ovarian response to gonadotropin, menopause and premature ovarian failure. however, large data set on the range of amh levels in nonhuman primates is still scarce, which limited its applications largely. in this study, age-related amh nomograms of rhesus (macaca mulatta) and cynomolgus (macaca fascicularis) were produced and compared. 219 rhesus and 529 cynom ...	2018	30243886
development of a bite®-mediated cd8+ cytotoxic t-lymphocyte activity assay to assess immunomodulatory potential of drug candidates in cynomolgus macaque.	the immunotoxic potential of drug candidates is assessed through the examination of results from a variety of studies and endpoints. while the functional assessment of cd8+ cytotoxic t-lymphocytes (ctl) is well-characterized in the clinic, the lack of a robust macaque ctl functional assay has been an important hurdle in evaluating and accurately quantifying cell-mediated cd8+ t-cell effector responses in the nonclinical setting. this paper describes the development of an assay to measure ctl act ...	2018	30241454
preexisting simian immunodeficiency virus infection increases susceptibility to tuberculosis in mauritian cynomolgus macaques.	tuberculosis (tb), caused by mycobacterium tuberculosis, is the leading cause of death among human immunodeficiency virus (hiv)-positive patients. the precise mechanisms by which hiv impairs host resistance to a subsequent m. tuberculosis infection are unknown. we modeled this coinfection in mauritian cynomolgus macaques (mcm) using simian immunodeficiency virus (siv) as an hiv surrogate. we infected seven mcm with sivmac239 intrarectally and 6 months later coinfected them via bronchoscope with ...	2018	30224552
superior efficacy of hi-6 dimethanesulfonate over pralidoxime methylsulfate against russian vx poisoning in cynomolgus monkeys (macaca fascicularis).	organophosphorus nerve agents still represent a serious risk to human health. in the french armed forces, the current emergency treatment against op intoxications is a fully licensed wet-dry dual-chambered autoinjector (ineurope ®), that contains pralidoxime methylsulfate (2-pam) to reactivate inhibited acetylcholinesterase (ache), atropine sulfate (as) and avizafone chlorhydrate (avz). while this treatment is effective against several of the known nerve agents, it shows little efficacy against ...	2018	30218682
safety profile after prolonged c3 inhibition.	the central component of the complement cascade, c3, is involved in various biological functions, including opsonization of foreign bodies, clearance of waste material, activation of immune cells, and triggering of pathways controlling development. given its broad role in immune responses, particularly in phagocytosis and the clearance of microbes, a deficiency in complement c3 in humans is often associated with multiple bacterial infections. interestingly, an increased susceptibility to infecti ...	2018	30217791
functionally relevant genetic variants of glutathione s-transferase gstm5 in cynomolgus and rhesus macaques.	glutathione s-transferase (gst) is a family of enzymes important for conjugation with glutathione of endogenous and exogenous compounds. human gstm1 null allele is associated with toxicity and cancers. cynomolgus and rhesus macaques have molecular and enzymatic similarities of gsts to humans; however, genetic variants have not been investigated. in macaques, instead of pseudogenized gstm1, gstm5 is a predominant gstm isoform. in this study, re-sequencing of gstm5 in 64 cynomolgus and 31 rhesus m ...	2019	30216105
distinct biological phenotypes of marburg and ravn virus infection in macaques.	filoviruses are among the most pathogenic infectious agents known to human, with high destructive potential, as evidenced by the recent ebola virus epidemic in west africa. as members of the filovirus family, marburgviruses have caused similar devastating outbreaks, albeit with lower case numbers. in this study we compare the pathogenesis of ravn virus (ravv) and marburg virus (marv) strains angola, musoke, and ozolin in rhesus and cynomolgus macaques, the 2 nonhuman primate species most commonl ...	2018	30215737