Publications

TitleAbstractYear
Filter
PMID(sorted descending)
Filter
major histocompatibility complex-matched arteries have similar patency to autologous arteries in a mauritian cynomolgus macaque major histocompatibility complex-defined transplant model.background arterial bypass and interposition grafts are used routinely across multiple surgical subspecialties. current options include both autologous and synthetic materials; however, each graft presents specific limitations. engineering artificial small-diameter arteries with vascular cells derived from induced pluripotent stem cells could provide a useful therapeutic solution. banking induced pluripotent stem cells from rare individuals who are homozygous for human leukocyte antigen alleles ...201931313646
establishment of a new formula for qt interval correction using a large colony of cynomolgus monkeys.the demand for monkeys for medical research is increasing, because their ionic mechanism of repolarization is similar to that of humans. the qt interval is the distance between the q wave and t wave, but this interval is affected by heart rate. therefore, qt correction methods are commonly used in clinical settings. however, an accurate correction formula for the qt interval in cynomolgus monkeys has not been reported. we assessed snapshot electrocardiograms (ecgs) of 353 ketamine-immobilized mo ...202031308302
cryptosporidium parvum and cryptosporidium hominis subtypes in crab-eating macaques.non-human primates are often infected with human-pathogenic cryptosporidium hominis subtypes, but rarely with cryptosporidium parvum. in this study, 1452 fecal specimens were collected from farmed crab-eating macaques (macaca fascicularis) in hainan, china during the period april 2016 to january 2018. these specimens were analyzed for cryptosporidium species and subtypes by using pcr and sequence analysis of the 18s rrna and 60 kda glycoprotein (gp60) genes, respectively.201931307508
performance evaluation of a high-resolution nonhuman primate pet/ct system.the lfer 150 pet/ct device (large-field-of-view extreme-resolution portable research imager) is a system for nonhuman primate (nhp) imaging. the objective of this study was to evaluate the performance of the system using the national electrical manufacturers association nu 4-2008 standard protocol. as a preliminary in vivo evaluation of the system, a pet measurement in an nhp was also performed. methods: resolution, sensitivity, image quality, and noise-equivalent count rate (necr) were measured ...201931302634
preparation of hybrid porcine thymus containing non-human primate thymic epithelial cells in miniature swine.we have achieved greater than a 6-month survival of a life-supporting kidney co-transplanted with a vascularized thymic graft into non-human primates (nhps). although we have achieved pig-specific unresponsiveness in vitro, immunosuppression was not able to be fully weaned. studies in mice and humanized mice suggest that a hybrid pig thymus (hyb-thy)-containing host thymic epithelial cells (tecs) can optimize intra-thymic selection, achieving xenograft tolerance with improved reconstitution of t ...201931293016
whole genome sequencing of amplified plasmodium knowlesi dna from unprocessed blood reveals genetic exchange events between malaysian peninsular and borneo subpopulations.the zoonotic plasmodium knowlesi parasite is the most common cause of human malaria in malaysia. genetic analysis has shown that the parasites are divided into three subpopulations according to their geographic origin (peninsular or borneo) and, in borneo, their macaque host (macaca fascicularis or m. nemestrina). whilst evidence suggests that genetic exchange events have occurred between the two borneo subpopulations, the picture is unclear in less studied peninsular strains. one difficulty is ...201931285495
imaging mass cytometry and single-cell genomics reveal differential depletion and repletion of b-cell populations following ofatumumab treatment in cynomolgus monkeys.ofatumumab is the first, fully human, anti-cd20 monoclonal antibody in phase 3 development for multiple sclerosis (ms). the study focused on changes in lymphocyte subsets in blood and lymphoid tissues and on potential novel biomarkers as a result of anti-cd20 antibody action in cynomolgus monkeys treated with human equivalent doses of subcutaneous (s.c.) ofatumumab on days 0, 7, and 14. axillary lymph nodes (lns) and blood samples were collected at various time points until day 90. lymphocyte su ...201931281311
genetic diversity of plasmodium knowlesi among human and long-tailed macaque populations in peninsular malaysia: the utility of microsatellite markers.it has been discovered that plasmodium knowlesi (p. knowlesi) is transmitted from macaque to man. thus, the aim of the present study was to determine p. knowlesi genetic diversity in both human (n = 147) and long-tailed macaque (n = 26) samples from high- and low-endemicity localities. genotyping was performed using seven neutral microsatellite loci markers. the size of the alleles, multiplicity of infection (moi), mean number of alleles (na), expected heterozygosity (he), linkage disequilibrium ...201931279818
neuronal loss without amyloid-β deposits in the thalamus and hippocampus in the late period after middle cerebral artery occlusion in cynomolgus monkeys.conflicting evidence exists regarding whether focal cerebral infarction contributes to cerebral amyloid-β (aβ) deposition, as observed in alzheimer's disease. in this study, we aimed to evaluate the presence of aβ deposits in the ipsilateral thalamus and hippocampus 12 months post-stroke in non-human primates, whose brains are structurally and functionally similar to that of humans. four young male cynomolgus monkeys were subjected to unilateral permanent middle cerebral artery occlusion (mcao), ...202031278793
evaluation and use of an anti-cynomolgus monkey cd79b surrogate antibody-drug conjugate to enable clinical development of polatuzumab vedotin.polatuzumab vedotin is an antibody-drug conjugate (adc) being developed for non-hodgkin's lymphoma. it contains a humanized anti-cd79b igg1 monoclonal antibody linked to monomethyl auristatin e (mmae), an anti-mitotic agent. polatuzumab vedotin binds to human cd79b only. therefore, a surrogate adc that binds to cynomolgus monkey cd79b was used to determine cd79b-mediated pharmacological effects in the monkey and to enable first-in-human clinical trials.201931270798
natural infection of captive cynomolgus monkeys (macaca fascicularis) with hepatitis e virus genotype 4.data on natural hev infection of infection in monkeys are limited. we report a case of hepatitis e virus genotype 4 infection in captive non-human primates (cynomolgus monkeys) imported from vietnam. phylogenetic analysis demonstrated that hev infection was not the result of spillover from single source of infection, but rather the persistent circulation of hev-4 among cynomolgus monkeys or multiple infections by related strains from a human or swine reservoir.201931270608
autophagy of sensory neurons in the trigeminal and dorsal root ganglia of cynomolgus monkeys (macaca fascicularis).although necrosis and apoptosis are uncommon, autophagy of sensory neurons (asn) in trigeminal and dorsal root ganglia is a very common, spontaneous finding in cynomolgus monkeys (macaca fascicularis). data from one author's (butt) laboratory showed 12 of 22 studies (year range 2017 to 2019) that included the evaluation of sensory ganglia from cynomolgus monkeys had at least one control animal with asn. autophagy of sensory neurons is characterized by a distinct cell membrane, cytoplasm filled w ...202031269872
synthesis and biological evaluation of [18f]fluorovinpocetine, a potential pet radioligand for tspo imaging.despite of various pet radioligands targeting the translocator protein tspo 18-kda are used for the investigations of neuroinflammatory conditions associated with neurological disorders, development of new tspo radiotracers is still an active area of the researches with a major focus on the 18f-labelled radiotracers. here, we report the radiochemical synthesis of [18f]vinpocetine, fluorinated analogue of previously reported tspo radioligand, [11c]vinpocetine. radiolabeling was achieved by [18f]f ...201931257082
exposure-response analysis of drug-induced qt interval prolongation in telemetered monkeys for translational prediction to human.the preclinical in vivo assay for qt prolongation is critical for predicting torsadogenic risk, but still difficult to extrapolate to humans. this study ran preclinical tests in cynomolgus monkeys on seven qt reference drugs containing the drugs used in the iq-csrc clinical trial and applied exposure-response (er) analysis to the data to investigate the potential for translational information on the qt effect.202031255745
the influence of masseter and temporalis sarcomere length operating ranges as determined by laser diffraction on architectural estimates of muscle force and excursion in macaques (macaca fascicularis and macaca mulatta).determine sarcomere length (ls) operating ranges of the superficial masseter and temporalis in vitro in a macaque model and examine the impact of position-dependent variation on ls and architectural estimates of muscle function (i.e., fiber length, pcsa) before and after ls-normalization.201931254839
identification and characterization of an octameric peg-protein conjugate system for intravitreal long-acting delivery to the back of the eye.innovative protein engineering and chemical conjugation technologies have yielded an impressive number of drug candidates in clinical development including >80 antibody drug conjugates, >60 bispecific antibodies, >35 fc-fusion proteins and >10 immuno-cytokines. despite these innovations, technological advances are needed to address unmet medical needs with new pharmacological mechanisms. age-related eye diseases are among the most common causes of blindness and poor vision in the world. many suc ...201931251757
determination of il-23 pharmacokinetics by highly sensitive accelerator mass spectrometry and subsequent modeling to project il-23 suppression in psoriasis patients treated with anti-il-23 antibodies.the pro-inflammatory cytokine interleukin (il)-23 is a key modulator of the immune response, making it an attractive target for the treatment of autoimmune disease. correspondingly, several monoclonal antibodies against il-23 are either in development or approved for autoimmune indications such as psoriasis. despite being a clinical validated target, il-23 pharmacokinetics (e.g., il-23 synthesis and elimination rates) and the degree of target suppression (i.e., decrease in free "active" il-23) a ...201931250228
dynamics of vaginal and rectal microbiota over several menstrual cycles in female cynomolgus macaques.the composition of the microbiota in cynomolgus macaques is only partially characterized, although this animal model is often used to study pathogenesis and preventive strategies against infections. we thus performed, for the first time, a longitudinal characterization of the vaginal and rectal microbiota of five cycling female cynomolgus macaques. samples were collected weekly for 15 weeks and the v3/v4 regions of the16s rrna gene sequenced. sequences were analyzed with qiime for otu detection ...201931249812
electrophysiological characterization of sleep/wake, activity and the response to caffeine in adult cynomolgus macaques.most preclinical sleep studies are conducted in nocturnal rodents that have fragmented sleep in comparison to humans who are primarily diurnal, typically with a consolidated sleep period. consequently, we sought to define basal sleep characteristics, sleep/wake architecture and electroencephalographic (eeg) activity in a diurnal non-human primate (nhp) to evaluate the utility of this species for pharmacological manipulation of the sleep/wake cycle. adult, 9-11 y.o. male cynomolgus macaques (n = ...201931236518
protective effects of the francisella tularensis δpdpc mutant against its virulent parental strain schu p9 in cynomolgus macaques.tularemia is a severe infectious zoonotic disease caused by francisella tularensis. although f. tularensis is considered to be a potential biological weapon due to its high infectivity and mortality rate, no vaccine has been currently licensed. recently, we reported that f. tularensis schu p9 derived δpdpc strain lacking the pathogenicity determinant protein c gene conferred stable and good protection in a mouse lethal model. in this study, the protective effect of δpdpc was evaluated using a mo ...201931235714
transcon cnp, a sustained-release c-type natriuretic peptide prodrug, a potentially safe and efficacious new therapeutic modality for the treatment of comorbidities associated with fibroblast growth factor receptor 3-related skeletal dysplasias.transcon cnp is a c-type natriuretic peptide (cnp-38) conjugated via a cleavable linker to a polyethylene glycol carrier molecule, designed to provide sustained systemic cnp levels upon weekly subcutaneous administration. transcon cnp is in clinical development for the treatment of comorbidities associated with achondroplasia. in both mice and cynomolgus monkeys, sustained exposure to cnp via transcon cnp was more efficacious in stimulating bone growth than intermittent cnp exposure. transcon cn ...201931235532
in vitro culture of embryos from the cynomolgus macaque (macaca fascicularis).the cynomolgus macaque (macaca fascicularis) has contributed significantly as an animal model in a variety of biological systems including reproductive biology. the first reported delivery of a cynomolgus infant born through ivf was in 1984, and since then the use of assisted reproductive technologies (arts) in the cynomolgus macaque for modeling primate early embryonic development has evolved to include studies on gene editing in primate embryos and embryonic stem cell chimerism. the significan ...201931230290
preclinical studies of a death receptor 5 fusion protein that ameliorates acute liver failure.acute liver failure (alf) is a life-threatening disease with a high mortality rate. there is an urgent need to develop new drugs with high efficacy and low toxicity. in this study, we produced a pharmaceutical-grade soluble death receptor 5 (sdr5)-fc fusion protein for treating alf and evaluated the pharmacology, safety, pharmacokinetics, efficacy, and mechanisms of sdr5-fc in mice, rats, and cynomolgus monkeys. sdr5-fc bound with high affinity to both human and monkey tumor necrosis factor-rela ...201931230087
characterization and population dynamics of germ cells in adult macaque testicular cultures.from a biological and clinical perspective, it is imperative to establish primate spermatogonial cultures. due to limited availability of human testicular tissues, the macaque (macaca fascicularis) was employed as non-human primate model. the aim of this study was to characterize the expression of somatic as well as germ cell markers in testicular tissues and to establish macaque testicular primary cell cultures.201931226129
a mucin 16 bispecific t cell-engaging antibody for the treatment of ovarian cancer.advanced ovarian cancer is frequently treated with combination chemotherapy, but high recurrence rates show the need for therapies that can produce durable responses and extend overall survival. bispecific antibodies that interact with tumor antigens on cancer cells and activating receptors on immune cells offer an innovative immunotherapy approach. here, we describe a human bispecific antibody (regn4018) that binds both mucin 16 (muc16), a glycoprotein that is highly expressed on ovarian cancer ...201931217340
antibody fc engineering for enhanced neonatal fc receptor binding and prolonged circulation half-life.the neonatal fc receptor (fcrn) promotes antibody recycling through rescue from normal lysosomal degradation. the binding interaction is ph-dependent with high affinity at low ph, but not under physiological ph conditions. here, we combined rational design and saturation mutagenesis to generate novel antibody variants with prolonged half-life and acceptable development profiles. first, a panel of saturation point mutations was created at 11 key fcrn-interacting sites on the fc region of an antib ...201931216930
evidences of hev genotype 3 persistence and reactivity in liver parenchyma from experimentally infected cynomolgus monkeys (macaca fascicularis).hepatitis e virus genotype 3 (hev-3) is an emerging zoonotic pathogen, responsible for sporadic cases of acute hepatitis e worldwide. primate models have proven to be an essential tool for the study of hev pathogenesis. here we describe the outcomes of hev infection in macaca fascicularis (cynomolgus) inoculated experimentally with genotype 3. eight adult cynomolgus macaques were inoculated intravenously with hev-3 viral particles isolated from swine and human samples. liver, spleen, duodenum, g ...201931211801
bioanalytical assays in support of tanezumab developmental and reproductive toxicity studies: challenges and learnings.bioanalytical challenges were encountered during developmental and reproductive toxicity studies of tanezumab in cynomolgus monkeys. possible changes in breast milk composition over the postpartum period potentially complicated assessment of tanezumab concentration in this matrix, requiring validation of the quantification assay across different time intervals. immunogenicity assessment in maternal serum was complicated by apparent increases in the incidence of antidrug antibody-positive results ...201931204868
comparison of contrast sensitivity in macaque monkeys and humans.contrast sensitivity functions reveal information about a subject's overall visual ability and have been investigated in several species of nonhuman primates (nhps) with experimentally induced amblyopia and glaucoma. however, there are no published studies comparing contrast sensitivity functions across these species of normal nhps. the purpose of this investigation was to compare contrast sensitivity across these primates to determine whether they are similar. ten normal humans and eight normal ...201931199217
the impact of pre-existing immunity on the non-clinical pharmacodynamics of aav5-based gene therapy.adeno-associated virus (aav)-based vectors are widely used for gene therapy, but the effect of pre-existing antibodies resulting from exposure to wild-type aav is unclear. in addition, other poorly defined plasma factors could inhibit aav vector transduction where antibodies are not detected. to better define the relationship between various forms of pre-existing aav immunity and gene transfer, we studied valoctocogene roxaparvovec (bmn 270) in cynomolgus monkeys with varying pre-dose levels of ...201931193016
determining overweight and underweight with a new weight-for-height index in captive group-housed macaques.housing primates in naturalistic groups provides social benefits relative to solitary housing. however, food intake may vary across individuals, possibly resulting in overweight and underweight individuals. information on relative adiposity (the amount of fat tissue relative to body weight) is needed to monitor overweight and underweight of group-housed individuals. however, the upper and lower relative adiposity boundaries are currently only known for macaques living solitarily in small cages. ...201931192494
atypical behaviour and connectivity in shank3-mutant macaques.mutation or disruption of the sh3 and ankyrin repeat domains 3 (shank3) gene represents a highly penetrant, monogenic risk factor for autism spectrum disorder, and is a cause of phelan-mcdermid syndrome. recent advances in gene editing have enabled the creation of genetically engineered non-human-primate models, which might better approximate the behavioural and neural phenotypes of autism spectrum disorder than do rodent models, and may lead to more effective treatments. here we report crispr-c ...201931189958
discovery of novel genic-ssr markers from transcriptome dataset of an important non-human primate, macaca fascicularis.macaca fascicularis, also known as the cynomolgus macaque, is an important non-human primate animal model used in biomedical research. it is an old-world primate widely distributed in southeast asia and is one of the most abundant macaque species in malaysia. however, the genetic structure of wild cynomolgus macaque populations in malaysia has not been thoroughly elucidated. in this study, we developed genic-simple sequence repeat (genic-ssr) markers from an in-house transcriptome dataset genera ...201931186469
dissection of the trigeminal ganglion of nonrodent species used in toxicology studies.the ganglion of the trigeminal (v cranial) nerve is generally sampled at necropsy in nonrodent toxicology studies only when somatic or autonomic peripheral nervous system toxicity is suspected. the ganglion is far more difficult to locate in nonrodents than in rats and mice, and suitable methods to dissect it have been described only for swine. the trigeminal nerve caudal to the ganglion passes through a canal, roofed by bone in dogs and rabbits and by a tough layer of dura mater in swine and no ...202031181996
development of tibulizumab, a tetravalent bispecific antibody targeting baff and il-17a for the treatment of autoimmune disease.we describe a bispecific dual-antagonist antibody against human b cell activating factor (baff) and interleukin 17a (il-17). an anti-il-17 single-chain variable fragment (scfv) derived from ixekizumab (taltz®) was fused via a glycine-rich linker to anti-baff tabalumab. the igg-scfv bound both baff and il-17 simultaneously with identical stoichiometry as the parental mabs. stability studies of the initial igg-scfv revealed chemical degradation and aggregation not observed in either parental antib ...202031181988
comparison of mrna expression profiles of drug-metabolizing enzymes and transporters in fresh and cryopreserved cynomolgus monkey hepatocytes.in this study, freshly isolated and cryopreserved cynomolgus monkey hepatocytes were seeded on cell-able® plates with feeder cells to form spheroids and were cultured for 28 days. as a control, hepatocytes were also cultured with or without feeder cells on collagen-coated plates. we verified the mrna expression levels of drug-metabolizing enzyme-related genes and the leakage of enzymes (ast, alt, ldh, and γ-gtp) as indicators of cell survival. as a result, the patterns of target mrna expression ...201931174977
development of an intravaginal ring delivering simultaneously anastrozole and levonorgestrel: a pharmacokinetic perspective.intravaginal rings (ivrs) are an option for continuous administration of drugs in women. as an attractive approach for the treatment of endometriosis-associated pelvic pain, ivrs delivering a combination of the aromatase inhibitor anastrozole (atz) and the progestin levonorgestrel (lng) have been developed. this article describes the developmental pharmacokinetic (pk) aspects covering the characterization of in vitro release, preclinical ivr pk investigations in monkeys, and clinical pk consider ...201931174438
conjugation of dm1 to anti-cd30 antibody has potential antitumor activity in cd30-positive hematological malignancies with lower systemic toxicity.an anti-cd30 antibody-drug conjugate incorporating the antimitotic agent dm1 and a stable smcc linker, anti-cd30-mcc-dm1, was generated as a new antitumor drug candidate for cd30-positive hematological malignancies. here, the in vitro and in vivo pharmacologic activities of anti-cd30-mcc-dm1 (also known as f0002-adc) were evaluated and compared with adcetris (brentuximab vedotin). pharmacokinetics (pk) and the safety profiles in cynomolgus monkeys were assessed. anti-cd30-mcc-dm1 was effective i ...202031161871
evaluation of fecal microbiomes associated with obesity in captive cynomolgus monkeys (macaca fascicularis).microorganisms play important roles in obesity; however, the role of the gut microbiomes in obesity is controversial because of the inconsistent findings. this study investigated the gut microbiome communities in obese and lean groups of captive healthy cynomolgus monkeys reared under strict identical environmental conditions, including their diet. no significant differences in the relative abundance of firmicutes, bacteroidetes and prevotella were observed between the obese and lean groups, but ...201931161737
half-life extension and non-human primate pharmacokinetic safety studies of i-body ad-114 targeting human cxcr4.single domain antibodies that combine antigen specificity with high tissue penetration are an attractive alternative to conventional antibodies. however, rapid clearance from the bloodstream owing to their small size can be a limitation of therapeutic single domain antibodies. here, we describe and evaluate the conjugation of a single domain i-body, ad-114, which targets cxcr4, to a panel of half-life extension technologies including a human serum albumin-binding peptide, linear and branched peg ...201931156041
application of ultrasound-guided cholecystocentesis to the evaluation of the metabolite profiling in bile of dogs and cynomolgus monkeys.in this study, we describe a novel approach for collecting bile from dogs and cynomolgus monkeys for metabolite profiling, ultrasound-guided cholecystocentesis (ucc). sampling bile by ucc twice within 24 hours was well tolerated by dogs and monkeys. in studies with atorvastatin (atv) the metabolite profiles were similar in bile obtained through ucc and from bile duct-cannulated (bdc) dogs. similar results were observed in ucc and bdc monkeys as well. in both monkey and dog, the primary metabolic ...201931149343
hepatic hemangiosarcoma in a cynomolgus macaque (macaca fascicularis).an experimentally naïve, 9-y-old, intact male cynomolgus macaque was reported for bleeding from an unidentified site. sedated physical examination indicated mild gingival separation from the lingual aspect of the upper right canine tooth as the source of the hemorrhage. physical exam revealed a firm mass adhered to the left zygomatic arch, 2 subcutaneous nodules on the chest, and a large mass in the cranial abdomen. radiographs revealed a large soft-tissue mass in the cranial abdomen and multifo ...201931142400
cynomolgus macaque il37 polymorphism and control of siv infection.the association between gene polymorphisms and plasma virus load at the set point (sp-pvl) was investigated in mauritian macaques inoculated with siv. among 44 macaques inoculated with 50 aid50, six individuals were selected: three with sp-pvl among the highest and three with sp-pvl among the lowest. the exons of 390 candidate genes of these six animals were sequenced. twelve non-synonymous single nucleotide polymorphisms (ns-snps) lying in nine genes potentially associated with pvl were genotyp ...201931138840
antiviral innate responses induced by vsv-ebov vaccination contribute to rapid protection.ebola virus (ebov) is a single-stranded rna virus that causes ebola virus disease (evd), characterized by excessive inflammation, lymphocyte apoptosis, hemorrhage, and coagulation defects leading to multiorgan failure and shock. recombinant vesicular stomatitis virus expressing the ebov glycoprotein (vsv-ebov), which is highly efficacious against lethal challenge in nonhuman primates, is the only vaccine that successfully completed a phase iii clinical trial. additional studies showed vsv-ebov p ...201931138743
tumor-localized costimulatory t-cell engagement by the 4-1bb/her2 bispecific antibody-anticalin fusion prs-343.4-1bb (cd137) is a key costimulatory immunoreceptor and promising therapeutic target in cancer. to overcome limitations of current 4-1bb-targeting antibodies, we have developed prs-343, a 4-1bb/her2 bispecific molecule. prs-343 is designed to facilitate t-cell costimulation by tumor-localized, her2-dependent 4-1bb clustering and activation.201931138587
serological evidence and experimental infection of cynomolgus macaques with pteropine orthoreovirus reveal monkeys as potential hosts for transmission to humans.pteropine orthoreoviruses (prv) are emerging bat-borne viruses with proven zoonotic transmission. we recently demonstrated human exposure to prv in singapore, which together with previous reports from malaysia and vietnam suggest that human infection of prv may occur periodically in the region. this raises the question whether bats are the only sources of human infection. in this study, we screened 517 cynomolgus macaques caught in singapore for evidence of exposure to prv3m (also known as melak ...201931132935
human plasma-derived butyrylcholinesterase is behaviorally safe and effective in cynomolgus macaques (macaca fascicularis) challenged with soman.organophosphorus compounds (op) pose a significant threat. administration of human butyrylcholinesterase (hubche) may reduce or prevent op toxicity. thus, we evaluated the safety and efficacy of hubche in monkeys using sensitive neurobehavioral tests while concurrently characterizing absorption and elimination in the presence and absence of high-dose soman exposure to predict time course and degree of protection. eight young adult male cynomolgus macaques were trained on two distinct automated t ...201931129133
exploiting orthology and de novo transcriptome assembly to refine target sequence information.the ability to generate recombinant drug target proteins is important for drug discovery research as it facilitates the investigation of drug-target-interactions in vitro. to accomplish this, the target's exact protein sequence is required. public databases, such as ensembl, uniprot and refseq, are extensive protein and nucleotide sequence repositories. however, many sequences for non-human organisms are predicted by computational pipelines and may thus be incomplete or incorrect. this could lea ...201931122257
metabonomics reveals peripheral and central short-chain fatty acid and amino acid dysfunction in a naturally occurring depressive model of macaques.depression is a complex psychiatric disorder. various depressive rodent models are usually constructed based on different pathogenesis hypotheses.201931118641
genotypes and public health potential of enterocytozoon bieneusi and giardia duodenalis in crab-eating macaques.enterocytozoon bieneusi and giardia duodenalis are common human and animal pathogens. studies have increasingly shown that non-human primates (nhps) are common hosts of these two zoonotic parasites. however, few studies have explored the genetic diversity and public health potential of these pathogens in laboratory monkeys. in this study, we examined the genetic diversity of the two pathogens in crab-eating macaques (macaca fascicularis) in a commercial facility in hainan, china.201931118092
prediction of human pharmacokinetics of antibody-drug conjugates from nonclinical data.prediction of human pharmacokinetics (pk) based on preclinical information for antibody-drug conjugates (adcs) provide important insight into first-in-human (fih) study design. this retrospective analysis was conducted to identify an appropriate scaling method to predict human pk for adcs from animal pk data in the linear range. different methods for projecting human clearance (cl) from animal pk data for 11 adcs exhibiting linear pk over the tested dose ranges were examined: multiple species al ...201931115997
skeletal muscle mitochondrial respiration is elevated in female cynomolgus macaques fed a western compared with a mediterranean diet.western diets are associated with increased incidences of obesity, hypertension, diabetes, and hypercholesterolemia, whereas mediterranean diets, richer in polyphenols, monounsaturated fats, fruits, vegetables, poultry, and fish, appear to have cardiometabolic health benefits. previous work has included population-based studies with limited evidence for causation or animal studies focused on single macro- or micronutrients; therefore, primate animal models provide an opportunity to determine pot ...201931112997
hbb-deficient macaca fascicularis monkey presents with human β-thalassemia. 201931111443
chronic mild stress leads to aberrant glucose energy metabolism in depressed macaca fascicularis models.major depressive disorder (mdd) is a pathophysiologically uncharacterized mental illness with complex etiology and clinical manifestations. rodent depression-like models have been widely used to mimic the morbid state of depression. however, research on emotional disorders can also benefit from the use of models in non-human primates, which share a wide range of genetic and social similarities with humans.201931108306
mhc-mismatched allotransplantation of induced pluripotent stem cell-derived cardiomyocyte sheets to improve cardiac function in a primate ischemic cardiomyopathy model.although allogeneic-induced pluripotent stem cell (ipsc)-derived cardiomyocytes (cms) exhibit potential in cardiomyogenesis for heart failure, whether major histocompatibility complex (mhc)-matched allogenic ipsc implantation (mmai) minimizes immune rejection for cell survival or functional recovery remains unknown. we herein explored whether mmai with an ipsc-cm sheet is stable for a longer period and therapeutically more effective than mhc-mismatched ai in a primate ischemic cardiomyopathy mod ...201931107828
therapeutic effect of transplanted umbilical cord mesenchymal stem cells in a cynomolgus monkey model of multiple sclerosis.multiple sclerosis (ms) is a demyelinating disease affecting 2.5 million young people worldwide because of its immune-mediated pathological mechanisms. recent studies have shown that stem cell transplantation is a new potential therapy for ms. there has been renewed interest in cell therapy to improve quality of life for ms patients. in this study, the experimental autoimmune encephalomyelitis (eae) model, which is the most commonly model to mimic ms, was successfully established in cynomolgus m ...201931105859
molecular and functional characterization of cytosolic sulfotransferases in cynomolgus macaque.cytosolic sulfotransferases (sults), drug-metabolizing enzymes essential for the metabolism of endogenous biochemicals and foreign compounds, have been characterized in humans, but remain to be investigated in cynomolgus macaques, important species in drug metabolism studies. in this study, based on the genome data, cynomolgus sult1a1, sult1a3, sult1b1, sult1c2v1, sult1c2v2, sult1c4, sult1e1, and sult2a1 cdnas were isolated and characterized. among these, cynomolgus sult1c2v2 was highly homologo ...201931100221
highly efficient induction of primate ips cells by combining rna transfection and chemical compounds.induced pluripotent stem (ips) cells hold great promise for regenerative medicine and the treatment of various diseases. before proceeding to clinical trials, it is important to test the efficacy and safety of ips cell-based treatments using experimental animals. the common marmoset is a new world monkey widely used in biomedical studies. however, efficient methods that could generate ips cells from a variety of cells have not been established. here, we report that marmoset cells are efficiently ...201931099158
tracking and clarifying differential traits of classical- and atypical l-type bovine spongiform encephalopathy prions after transmission from cattle to cynomolgus monkeys.classical- (c-) and atypical l-type bovine spongiform encephalopathy (bse) prions cause different pathological phenotypes in cattle brains, and the disease-associated forms of each prion protein (prpsc) has a dissimilar biochemical signature. bovine c-bse prions are the causative agent of variant creutzfeldt-jakob disease. to date, human infection with l-bse prions has not been reported, but they can be transmitted experimentally from cows to cynomolgus monkeys (macaca fascicularis), a non-human ...201931095605
cd8β depletion does not prevent control of viral replication or protection from challenge in macaques chronically infected with a live attenuated simian immunodeficiency virus.we evaluated the contribution of cd8αβ+ t cells to control of live-attenuated simian immunodeficiency virus (lasiv) replication during chronic infection and subsequent protection from pathogenic siv challenge. unlike previous reports with a cd8α-specific depleting monoclonal antibody (mab), the cd8β-specific mab cd8β255r1 selectively depleted cd8αβ+ t cells without also depleting non-cd8+ t cell populations that express cd8α, such as natural killer (nk) cells and γδ t cells. following infusion w ...201931092584
myocarditis in cynomolgus monkeys following treatment with immune checkpoint inhibitors.immune checkpoint inhibitors (ici) targeting pd1, pdl1, or ctla4 are associated with immune-related adverse events (irae) in multiple organ systems including myocarditis. the pathogenesis and early diagnostic markers for ici-induced myocarditis are poorly understood, and there is currently a lack of laboratory animal model to enhance our understanding. we aimed to develop such a model using cynomolgus monkeys.201931085720
a reduction in b, t, and natural killer cells expressing cd38 by tak-079 inhibits the induction and progression of collagen-induced arthritis in cynomolgus monkeys.ectoenzyme cd38 is increased on lymphocytes in response to an antigenic challenge and it is hypothesized that targeting these activated lymphocytes could ameliorate pathologic activities in autoimmune diseases. the cynomolgus monkey is an appropriate model for assessing potential effects of targeting cd38 in humans because these species exhibit similar expression profiles. tak-079 is a human monoclonal antibody (igg1λ ) that binds to cd38 and lyses bound cells by complement-dependent cytotoxicit ...201931085699
nonclinical safety evaluation of erenumab, a cgrp receptor inhibitor for the prevention of migraine.calcitonin gene-related peptide (cgrp) and its receptor have been implicated as a key mediator in the pathophysiology of migraine. thus, erenumab, a monoclonal antibody antagonist of the cgrp receptor, administered as a once monthly dose of 70 or 140 mg has been approved for the preventive treatment of migraine in adults. due to the species specificity of erenumab, the cynomolgus monkey was used in the pharmacology, pharmacokinetics, and toxicology studies to support the clinical program. there ...201931085251
tanshinoneⅱa phenanthroimidazole derivative polarizes macrophage to improve metabolic homeostasis.macrophages infiltrated in adipose tissue play a key role in obesity. some traditional pharmaceutical compounds may shift the polarization of recruited macrophages to improve metabolic homeostasis. tanshinoneⅱa (tan2a) is a major active component of salvia miltiorrhiza, a traditional anti-inflammatory cardiovascular medicine. in our study, we firstly constructed a phenanthroimidazole derivative of tan2a named tan20 by chemical synthesis, then identified its structure by chromatography and hydrog ...201931084927
fecal microbiota dysbiosis in macaques and humans within a shared environment.traditional zoonotic disease research focuses on detection of recognized pathogens and may miss opportunities to understand broader microbial transmission dynamics between humans, animals, and the environment. we studied human-macaque microbiome overlap in kosum phisai district, maha sarakham province, thailand, where a growing population of long-tailed macaques (macaca fascicularis) in kosumpee forest park interact with humans from an adjacent village. we surveyed workers in or near the park wi ...201931083685
mandibular vertical growth deficiency after botulinum-induced hypotrophy of masticatory closing muscles in juvenile nonhuman primates.the purpose of this study was to investigate the relationship between masticatory muscular hypotrophy and mandibular growth in juvenile nonhuman primates (cynolmolgus monkeys, macaca fasicularis). we hypothesized that botulinum toxin (btx)-induced neuro-muscular junctional block and its resultant hypotrophy of masticatory muscles would produce mandibular growth disturbances in size and shape. ten male cynomolgus monkeys were divided into three groups: group i (control; n = 3), group ii (unilater ...201931080418
tridimensional mapping of phox2b expressing neurons in the brainstem of adult macaca fascicularis and identification of the retrotrapezoid nucleus.chemosensitivity is a key mechanism for the regulation of breathing in vertebrates. the retrotrapezoid nucleus is a crucial hub for respiratory chemoreception within the brainstem. it integrates chemosensory information that are both peripheral from the carotid bodies (via the nucleus of the solitary tract) and central through the direct sensing of extracellular protons. to date, the location of a genetically defined rtn has only been ascertained in rodents. we first demonstrated that phox2b, a ...201931071232
immunogenicity of a protective intradermal dna vaccine against lassa virus in cynomolgus macaques.lassa virus (lasv) is a hemorrhagic fever virus of the arenaviridae family with high rates of mortality and co-morbidities, including chronic seizures and permanent bilateral or unilateral deafness. lasv is endemic in west africa and lassa fever accounts for 10-16% of hospitalizations annually in parts of sierra leone and liberia according to the cdc. an ongoing outbreak in nigeria has resulted in 144 deaths in 568 cases confirmed as lasv as of november 2018, with many more suspected, highlighti ...201931071008
relationships between cytokine levels and disease parameters during the development of a collagen-induced arthritis model in cynomolgus macaques (macaca fascicularis).in rheumatoid arthritis research, nhp models of collagen-induced arthritis are important because these species share many immunologic and pathologic features with humans. in addition, serum levels of various cytokines in patients with rheumatoid arthritis have been studied as immune markers for disease prediction, early diagnosis, and effective therapeutic management. the purpose of this study was to identify changes in cytokine levels that occur during the development of collagen-induced arthri ...201931068244
revised recommendations for health monitoring of non-human primate colonies (2018): felasa working group report.the genetic and biological similarity between non-human primates and humans has ensured the continued use of primates in biomedical research where other species cannot be used. health-monitoring programmes for non-human primates provide an approach to monitor and control both endemic and incoming agents that may cause zoonotic and anthroponotic disease or interfere with research outcomes. in 1999 felasa recommendations were published which aimed to provide a harmonized approach to health monitor ...201931068070
color perception in protanomalous female macaca fascicularis.protanomalous females with x chromosome-linked color vision deficiency exhibit mild abnormalities, whereas dichromats show a distinct deficiency in discriminating certain color pairs. dichromats have an advantage in detecting a textured target when it is camouflaged by red-green colors, owing to their insensitivity to these colors. however, it is not certain whether protanomalous females possess a similar advantage in breaking camouflage. here, we introduce an animal model of dichromatic macaque ...202031066374
type ii diabetes mellitus accelerates age-dependent aβ pathology in cynomolgus monkey brain.accumulating evidence suggests that diabetes mellitus (dm) is one of the strongest risk factors for developing alzheimer's disease (ad). however, it remains unclear how dm accelerates ad pathology in the brain. cynomolgus monkey (macaca fascicularis) is one of the nonhuman primates used for biomedical research, and we can observe spontaneous formation of ad pathology, such as senile plaques (sps) and neurofibrillary tangles (nfts), with the advance of aging. furthermore, obesity is occasionally ...201931062328
[comparative study of hydrolase activity in skin with liver and intestine, and its aging relation of carboxylesterase expression in cynomolgus monkey and beagle dog].the hydrolysis activity and expression level of carboxylesterase (ces) in skin were compared with liver and intestine in the same individual of beagle dog and cynomolgus monkey, and their aging effects were studied. ces1 isozymes were mainly present in skin of both animals. the dermal hydrolysis activity was about 10 and 40% of hepatic activity in beagle dog and cynomolgus monkey, respectively. in beagle dog, the hydrolysis activity and the expression level of ces isozyme in liver and skin were ...201931061351
transcriptional profiling of non-human primate lymphoid organ responses to total-body irradiation.the global threat of exposure to radiation and its subsequent outcomes require the development of effective strategies to mitigate immune cell injury. in this study we explored transcriptional and immunophenotypic characteristics of lymphoid organs of a non-human primate model after total-body irradiation (tbi). fifteen middle-aged adult, ovariectomized, female cynomolgus macaques received a single dose of 0, 2 or 5 gy gamma radiation. thymus, spleen and lymph node from three controls and 2 gy ( ...201931059377
immunogenicity and efficacy of a measles virus-vectored chikungunya vaccine in nonhuman primates.chikungunya virus (chikv) infection can result in chikungunya fever (chikf), a self-limited acute febrile illness that can progress to chronic arthralgic sequelae in a large percentage of patients. a new measles virus-vectored vaccine was developed to prevent chikf, and we tested it for immunogenicity and efficacy in a nonhuman primate model.201931053842
sym021, a promising anti-pd1 clinical candidate antibody derived from a new chicken antibody discovery platform.discovery of therapeutic antibodies is a field of intense development, where immunization of rodents remains a major source of antibody candidates. however, high orthologue protein sequence homology between human and rodent species disfavors generation of antibodies against functionally conserved binding epitopes. chickens are phylogenetically distant from mammals. since chickens generate antibodies from a restricted set of germline genes, the possibility of adapting the symplex antibody discove ...202031046547
molecular prevalence and subtyping of cryptosporidium hominis among captive long-tailed macaques (macaca fascicularis) and rhesus macaques (macaca mulatta) from hainan island, southern china.cryptosporidium is an important zoonotic parasite that is commonly found in non-human primates (nhps). consequently, there is the potential for transmission of this pathogen from nhps to humans. however, molecular characterization of the isolates of cryptosporidium from nhps remains relatively poor. the aim of the present work was to (i) determine the prevalence; and (ii) perform a genetic characterization of the cryptosporidium isolated from captive macaca fascicularis and m. mulatta on hainan ...201931039801
dissecting the contribution of oatp1b1 to hepatic uptake of statins using the oatp1b1 selective inhibitor estropipate.identification of a selective inhibitor of organic anion transporting polypeptide (oatp) 1b1 is critical in order to determine the contribution of oatp1b1-mediated uptake of investigational drugs into human hepatocytes for successful in vitro-to-in vivo extrapolation (ivive) of hepatic uptake and drug-drug interaction (ddi). the following study examined the inhibitory effects of estropipate (epp) on major sinusoidal drug uptake transporters and explored its utility regarding ivive of statin hepa ...201931039308
an anti-plvap antibody suppresses laser-induced choroidal neovascularization in monkeys.plasmalemma vesicle-associated protein (plvap, also called pv-1) is the only protein that forms endothelial diaphragms. plvap expression is very low in the normal blood-retinal barrier; however, pathological factors such as high glucose and vascular endothelial growth factor (vegf) induce its expression, leading to the exacerbation of cellular permeability. because the new blood vessels are fragile and leaky, plvap could possibly be considered a therapeutic target against retinovascular diseases ...201931026444
a highly effective and ultra-long-acting anti-glaucoma drug, with a novel periorbital delivery method.purpose: two features define the future of glaucoma therapeutics: (1) greatly improved ocular hypotensive efficacy and (2) a delivery method that improves patient convenience and compliance. a highly efficacious and extraordinarily long-acting ocular hypotensive agent pgn 9856-isopropyl ester represents a potential next-generation anti-glaucoma drug. a new periorbital drug delivery route was also investigated. methods: pgn 9856-isopropyl ester pharmacology was determined by employing human cells ...201931025909
comparison of gene expression in cynomolgus monkeys with preclinical type ii diabetes induced by different high energy diets.cynomolgus disease models that are similar to the preclinical stage of human type 2 diabetes mellitus (t2dm) were established by feeding middle-aged cynomolgus monkeys different high energy diets to study the differential expression of diabetes-related genes.201931016286
first molecular characterization of balantioides coli (malmsten, 1857) isolates maintained in vitro culture and from feces of captive animals, rio de janeiro, brazil.ciliate protozoa of the genus balantioides can parasitize a variety of animals. the morphology of the evolutionary forms of the parasite and the host species affected have long been the only characteristics used to taxonomically identify the species of these protozoa, but these variables are not very precise. to confirm species identity, molecular biology tools are currently used. in this context, this study aimed to analyze protozoan isolates maintained in culture medium and from fecal samples ...201731014580
plasmodium knowlesi and other malaria parasites in long-tailed macaques from the philippines.macaca fascicularis (long-tailed macaque) is the most widespread species of macaque in southeast asia and the only species of monkey found naturally in the philippines. the species is the natural host for the zoonotic malaria species, plasmodium knowlesi and plasmodium cynomolgi and for the potentially zoonotic species, plasmodium inui. moreover, other plasmodium species such as plasmodium coatneyi and plasmodium fieldi are also natural parasites of m. fascicularis. the aims of this study were t ...201931014342
depressed female cynomolgus monkeys (macaca fascicularis) display a higher second-to-fourth (2d:4d) digit ratio.this research aimed to provide evidence of a relationship between digit ratio and depression status in the cynomolgus monkey (macaca fascicularis). in stable cynomolgus monkey social groups, we selected 15 depressed monkeys based on depressive-like behavioral criteria and 16 normal control monkeys. all animals were video recorded for two weeks, with the duration and frequency of the core depressive behaviors and 58 other behaviors in 12 behavioral categories then evaluated via behavioral analysi ...201931011132
evaluation of analgesic patches in cynomolgus macaques (macaca fascicularis).opioids are widely used in veterinary and human medicine to manage pain. however, there is a paucity of information in the literature regarding the pharmacokinetics of opioid transdermal patches (tdp) in nhp. therefore, to determine whether opioid tdp attain therapeutic concentrations in nhp, the pharmacokinetics of fentanyl (25 μg/h) and buprenorphine (10 and 20 μg/h) tdp were evaluated in naïve, adult, male cynomolgus macaques (n = 4) in a crossover study. plasma opioid levels were determined ...201931010456
generation of an oct3/4 reporter cynomolgus monkey es cell line using crispr/cas9.cynomolgus monkey es (cyn es) cells can be generated in a similar manner as human es cells. however, cyn es cells are difficult to maintain in an undifferentiated state by untrained researchers. for easier culture, we generated an oct3/4-p2a tdtomato ires zeocinr cyn es cell line using crispr/cas9 genome editing technology. the stop codon of the endogenous oct3/4 locus was replaced with the p2a tdtomato ires zeocinr pa cassette by homologous recombination. this cell line enables us to isolate pl ...201931005787
a normalization circuit underlying coding of spatial attention in primate lateral prefrontal cortex.lateral prefrontal cortex (lpfc) neurons signal the allocation of voluntary attention; however, the neural computations underlying this function remain unknown. to investigate this, we recorded from neuronal ensembles in the lpfc of two macaca fascicularis performing a visuospatial attention task. lpfc neural responses to a single stimulus were normalized when additional stimuli/distracters appeared across the visual field and were well-characterized by an averaging computation. deploying attent ...202031001577
generation of macrophages from cynomolgus-monkey bone marrow as a model to evaluate effects of drugs on innate immunity.macrophages are innate immune cells that play important roles in various physiological and pathological processes. evaluation of pro-inflammatory effects of drugs on macrophages has become commonplace in preclinical drug development prior to human clinical trials. despite their body-wide distribution, tissue macrophages are often difficult to collect from large animals and humans in a noninvasive manner. therefore, in vitro-differentiated macrophages are important tools to facilitate cross-speci ...201930982234
sting agonists activate latently infected cells and enhance siv-specific responses ex vivo in naturally siv controlled cynomolgus macaques.to achieve a functional cure for hiv, treatment regimens that eradicate latently hiv-infected cells must be established. for this, many groups have attempted to reactivate latently-infected cells to induce cytopathic effects and/or elicit cytotoxic t lymphocyte (ctl)/nk cell-mediated immune responses to kill these cells. we believe that not only the reactivation of latently-infected cells, but also the induction of strong ctl responses, would be required for this. here, we used typical immune ac ...201930976083
determination of a no observable effect level for endotoxin following a single intravitreal administration to cynomolgus monkeys.purpose: to characterize the inflammatory response and determine the no-observable-effect level (noel) in cynomolgus monkey eyes after intravitreal (itv) injection of endotoxin. methods: the inflammatory response to endotoxin was assessed in a single-dose study in monkeys at doses of 0.01 to 0.51 endotoxin units (eu)/eye. tolerability was assessed by clinical ophthalmic examinations, intraocular pressure measurements, fundus color photography, optical coherence tomography, and anatomic pathology ...201930964386
discovery of a novel egfr-targeting antibody-drug conjugate, shr-a1307, for the treatment of solid tumors resistant or refractory to anti-egfr therapies.although inhibiting egfr-mediated signaling proved to be effective in treating certain types of cancers, a quickly evolved mechanism that either restores the egfr signaling or activates an alternative pathway for driving the proliferation and survival of malignant cells limits the efficacy and utility of the approach via suppressing the egfr functionality. given the fact that overexpression of egfr is commonly seen in many cancers, an egfr-targeting antibody-drug conjugate (adc) can selectively ...201930962319
trace amine-associated receptor 1 agonism promotes wakefulness without impairment of cognition in cynomolgus macaques.trace amine-associated receptor 1 (taar1) is a g-protein coupled receptor with affinity for the trace amines. taar1 agonists have pro-cognitive, antidepressant-, and antipsychotic-like properties in both rodents and non-human primates (nhps). taar1 agonism also increases wakefulness and suppresses rapid-eye movement (rem) sleep in mice and rats and reduces cataplexy in two mouse models of narcolepsy. we investigated the effects of taar1 agonism in cynomolgus macaques, a diurnal species that exhi ...201930954024
associations between sounds and actions in early auditory cortex of nonhuman primates.an individual may need to take different actions to the same stimulus in different situations to achieve a given goal. the selection of the appropriate action hinges on the previously learned associations between stimuli, actions, and outcomes in the situations. here, using a go/no-go paradigm and a symmetrical reward, we show that early auditory cortex of nonhuman primates represents such associations, in both the spiking activity and the local field potentials. sound-evoked neuronal responses ...201930946010
adverse event following live attenuated chikungunya vaccine in a cynomolgus macaque with pre-existing chronic hydrocephalus.a cynomolgus macaque (macaca fascicularis) with a pre-existing, undiagnosed, subclinical but severe cerebral hydrocephalus was enrolled in a study of long-term immunogenicity of the ires/chik vaccine. the animal began showing signs of neurological dysfunction post-vaccination, which progressed and ultimately resulted in euthanasia. the underlying brain abnormality was revealed at necropsy and was subsequently investigated with gross and microscopic examination. this becomes the first reported ca ...201930945306
capacitation of human naïve pluripotent stem cells for multi-lineage differentiation.human naïve pluripotent stem cells (pscs) share features with the pre-implantation epiblast. they therefore provide an unmatched opportunity for characterising the developmental programme of pluripotency in homo sapiens here, we confirm that naïve pscs do not respond directly to germ layer induction, but must first acquire competence. capacitation for multi-lineage differentiation occurs without exogenous growth factor stimulation and is facilitated by inhibition of wnt signalling. whole-transcr ...201930944104
probucol induces the generation of lipid peroxidation products in erythrocytes and plasma of male cynomolgus macaques.we previously reported that probucol, a lipid lowering agent, protected mice from malaria infection via depletion in plasma α-tocopherol. the antioxidant α-tocopherol in host circulation is necessary for the malaria parasites to protect themselves from oxidative stress in erythrocytes where high amounts of reactive oxygen species are generated. to assess the potential for the clinical application of probucol as an anti-malarial therapy, it was necessary to determine the effects of probucol by us ...201930936625
visualization of early events in mrna vaccine delivery in non-human primates via pet-ct and near-infrared imaging.visualization of the spatio-temporal trafficking of vaccines after their delivery would help evaluate the efficacy of candidate formulations and aid their rational design for preclinical and translational studies. here, we show that a dual radionuclide-near-infrared probe allows for quantitative, longitudinal and non-invasive monitoring, via positron emission tomography-computed tomography and near-infrared imaging of cynomolgus macaques, of the trafficking dynamics to draining lymph nodes of a ...201930936432
estimating the amount of chronic wasting disease infectivity passing through abattoirs and field slaughter.chronic wasting disease (cwd) is a highly infectious, naturally occurring, transmissible spongiform encephalopathy (tse, or prion disease) affecting many cervid species. cwd has been widely circulating in north america since it was first reported in 1967. in 2016, the first european case of prion disease in deer was reported and confirmed in norway. there have since been several confirmed several cases in reindeer and moose and in one red deer in norway, and recently in a moose in finland. there ...201930935503
mycoplasma ocular infection in subretinal graft transplantation of ips cells-derived retinal pigment epithelial cells.to report occurrence of acute severe inflammation after surgical implantation of mycoplasma-infected induced pluripotent stem cell-derived rpe (ips-rpe) cells into the eyes of healthy primates, and determine the immunopathological mechanisms of the inflammation.201930933257
effects of cervical rotatory manipulation on internal carotid artery in hemodynamics using an animal model of carotid atherosclerosis: a safety study.background spinal manipulation, particularly in cervical rotatory manipulation (crm), has become increasingly popular in physical therapies, with satisfying effect. however, it is still unclear whether crm affects internal carotid arteries (ica) with mild carotid atherosclerosis (cas), especially in hemodynamics. material and methods nine cynomolgus monkeys were randomly divided into 3 groups: the cas-crm, the cas, and the blank control groups. cas models were developed in the left ica in the ca ...201930928990
Displaying items 601 - 700 of 11313