Publications

TitleAbstractYear
Filter
PMID(sorted ascending)
Filter
biophysical and immunological characterization and in vivo pharmacokinetics and toxicology in nonhuman primates of the anti-pd-1 antibody pembrolizumab.the programmed cell death 1 (pd-1) pathway represents a major immune checkpoint, which may be engaged by cells in the tumor microenvironment to overcome active t-cell immune surveillance. pembrolizumab (keytruda®, mk-3475) is a potent and highly selective humanized mab of the igg4/kappa isotype designed to directly block the interaction between pd-1 and its ligands, pd-l1 and pd-l2. this blockade enhances the functional activity of t cells to facilitate tumor regression and ultimately immune rej ...202032229606
excretion of the polymyxin derivative nab739 in murine urine.extremely multiresistant strains of enterobacteriaceae are emerging and spreading at a worrisome pace. polymyxins are used as the last-resort therapy against such strains, in spite of their nephrotoxicity. we have previously shown that novel polymyxin derivatives nab739 and nab815 are less nephrotoxic in cynomolgus monkeys than polymyxin b and are therapeutic in murine escherichia coli pyelonephritis at doses only one-tenth of that needed for polymyxin b. here we evaluated whether the increased ...202032230751
non-human primate models of dengue virus infection: a comparison of viremia levels and antibody responses during primary and secondary infection among old world and new world monkeys.due to the global burden of dengue disease, a vaccine is urgently needed. one of the key points in vaccine development is the development of a robust and reliable animal model of dengue virus infection. characteristics including the ability to sustain viral replication, demonstration of clinical signs, and immune response that resemble those of human dengue virus infection are vital in animal models. preclinical studies in vaccine development usually include parameters such as safety evaluation, ...202032230836
modeling variant creutzfeldt-jakob disease and its pathogenesis in non-human primates.in the early 90s', europe was shaken by the fear that the prions from "mad cow disease" (bovine spongiform encephalopathy) would transmit the disease to humans via beef products. in 1996, the first variant creutzfeldt-jakob (vcjd) patients were described, and the same year our bovine spongiform encephalopathy (bse) transmission studies to cynomolgus macaques demonstrated that the bse prion was highly infectious for primates, inducing brain lesions identical to those observed in vcjd patients. th ...201732231924
melengestrol acetate (veterinary medicinal products).food safety commission of japan (fscj) conducted a risk assessment of melengestrol acetate (mga, cas no. 2919-66-6), a synthetic hormone, based on results from various studies. mga was recognized to have no genotoxicity relevant to human health, and it enabled fscj to specify an acceptable daily intake (adi) in the assessment. in vitro studies using various human hormone-receptors showed that mga exerts biological action primarily as progestogens and secondarily as glucocorticoids. major adverse ...201732231940
group size experiences with enhanced pre- and postnatal development studies in the long-tailed macaque (macaca fascicularis).enhanced pre- and postnatal development (eppnd) studies have become the default developmental toxicity test for biopharmaceuticals if nonhuman primates represent the relevant species. spontaneous pregnancy losses and infant deaths can be significant in macaques such as long-tailed macaques. the international council for harmonisation of technical requirements for pharmaceuticals for human use (ich) guideline s6(r1) states that pregnancy outcome can be judged also by the normogram-based variabili ...202032232119
generation of transgenic cynomolgus monkeys overexpressing the gene for amyloid-β precursor protein.alzheimer's disease (ad) is the most common cause of dementia and understanding its pathogenesis should lead to improved therapeutic and diagnostic methods. although several groups have developed transgenic mouse models overexpressing the human amyloid-β precursor protein (app) gene with ad mutations, with and without presenilin mutations, as well as app gene knock-in mouse models, these animals display amyloid pathology but do not show neurofibrillary tangles or neuronal loss. this presumably i ...202032250299
interleukin-1β and tumor necrosis factor-α affect cytochrome p450 expression in cynomolgus macaque hepatocytes.the cynomolgus macaque, partly due to its evolutionary closeness to humans, is an important nonhuman primate species used in drug metabolism studies. in humans, expressions of cytochromes p450 (p450s), including the important drug-metabolizing enzyme p450 3a4, are affected by various cytokines. however, this phenomenon has not been fully investigated in cynomolgus macaques. in this study, the effects of cytokines on p450 expression were investigated using the quantitative polymerase chain reacti ...202032253084
preclinical studies on the toxicology, pharmacokinetics and safety of k1-70tm a human monoclonal autoantibody to the tsh receptor with tsh antagonist activity.the human monoclonal autoantibody k1-70™ binds to the tsh receptor (tshr) with high affinity and blocks tshr cyclic amp stimulation by tsh and thyroid stimulating autoantibodies.201932257067
reference values of hematological and biochemical parameters in young-adult cynomolgus monkey (macaca fascicularis) and rhesus monkey (macaca mulatta) anesthetized with ketamine hydrochloride.nonhuman primate models are valuable in biomedical research. however, reference data for clinical pathology parameters in cynomolgus and rhesus monkeys are limited. in the present study, we established hematologic and biochemical reference intervals for healthy cynomolgus and rhesus monkeys anesthetized with ketamine hydrochloride. a total of 142 cynomolgus monkeys (28 males and 114 females) and 42 rhesus monkeys (22 males and 20 females) were selected and analyzed in order to examine reference ...201932257895
islet transplantation to the anterior chamber of the eye-a future treatment option for insulin-deficient type-2 diabetics? a case report from a nonhuman type-2 diabetic primate.replacement of the insulin-secreting beta cells through transplantation of pancreatic islets to the liver is a promising treatment for type-1 diabetes. however, low oxygen tension, shear stress, and the induction of inflammation lead to significant islet dysfunction and loss. the anterior chamber of the eye (ace) has gained considerable interest and represents an alternative therapeutic islet transplantation site because of its accessibility, high oxygen tension, and immune-privileged milieu. we ...202032264703
transient mixed chimerism with nonmyeloablative conditioning does not induce liver allograft tolerance in nonhuman primates.although short-term outcomes for liver transplantation have improved, patient and graft survivals are limited by infection, cancer and other complications of immunosuppression. rapid induction of tolerance after liver transplantation would decrease these complications, improving survival and quality of life. tolerance to kidneys, but not thoracic organs or islets, has been achieved in nonhuman primates and humans through the induction of transient donor chimerism. since the liver is considered t ...202032265416
prima subretinal wireless photovoltaic microchip implantation in non-human primate and feline models.to evaluate the surgical technique for subretinal implantation of two sizes of prima photovoltaic wireless microchip in two animal models, and refine these surgical procedures for human trials.202032267845
multilocus sequence typing of enterocytozoon bieneusi in crab-eating macaques (macaca fascicularis) in hainan, china.enterocytozoon bieneusi is one of common intestinal pathogens in humans and animals including non-human primates (nhps). many zoonotic pathogens including e. bieneusi have been found in these animals. however, there are few studies on the population structure of e. bieneusi in nhps. to infer the gene diversity and population genetics of e. bieneusi, we selected 88 e. bieneusi-positive samples from crab-eating macaques for multilocus characterizations in this study.202032268912
mecp2 duplication causes aberrant gaba pathways, circuits and behaviors in transgenic monkeys: neural mappings to patients with autism.mecp2 gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where mecp2 mutation affects the monkey brain and whether/how it relates to autism pathology remain unknown. here we report a combination of gene-circuit-behavior analyses including mecp2 coexpression network, locomotive and cognitive behaviors, and eeg and fmri findings in 5 mecp2 overexpressed monkeys (macaca fascicularis; 3 females) and 20 wild-type monke ...202032269107
cav-2-mediated gfp and lrrk2g2019s expression in the macaca fascicularis brain.parkinson's disease is characterized by motor and nonmotor symptoms that gradually appear as a consequence of the selective loss of dopaminergic neurons in the substantia nigra pars compacta. currently, no treatment can slow parkinson's disease progression. inasmuch, there is a need to develop animal models that can be used to understand the pathophysiological mechanisms underlying dopaminergic neuron death. the initial goal of this study was to determine if canine adenovirus type 2 (cav-2) vect ...202032269512
divergent strategies in faeces avoidance between two cercopithecoid primates.parasites constitute a major selective pressure which has shaped animal behaviour through evolutionary time. one adaption to parasites consists of recognizing and avoiding substrates or cues that indicate their presence. among substrates harbouring infectious agents, faeces are known to elicit avoidance behaviour in numerous animal species. however, the function and mechanisms of faeces avoidance in non-human primates has been largely overlooked by scientists. in this study, we used an experimen ...202032269806
quantitative magnetic susceptibility assessed by 7t magnetic resonance imaging in alzheimer's disease caused by streptozotocin administration.streptozotocin treatment has emerged as an alternative model of sporadic alzheimer's disease (sad). streptozotocin-induced alterations in iron and calcium levels reflect magnetic susceptibility changes, while susceptibility distribution in the cerebral regions has not been reported yet. this study aimed to investigate susceptibility distribution in the limbic system after streptozotocin administration to cynomolgus monkeys for exploring informative sad biomarkers. quantitative susceptibility map ...202032269937
target arm affinities determine preclinical efficacy and safety of anti-her2/cd3 bispecific antibody.systemic cytokine release and on-target/off-tumor toxicity to normal tissues are the main adverse effects limiting the clinical utility of t cell-redirecting therapies. this study was designed to determine how binding affinity for cd3 and tumor target her2 impact the efficacy and nonclinical safety of anti-her2/cd3 t cell-dependent antibodies (tdbs). affinity was found to be a major determinant for the overall tolerability. higher affinity for cd3 associated with rapidly elevated peripheral cyto ...202032271166
low replicative fitness of neuraminidase inhibitor-resistant h7n9 avian influenza a virus with r292k substitution in neuraminidase in cynomolgus macaques compared with i222t substitution.human cases of h7n9 influenza a virus infection have been increasing since 2013. the first choice of treatment for influenza is neuraminidase (na) inhibitors (nais), but there is a concern that nai-resistant viruses are selected in the presence of nais. in our previous study, an h7n9 virus carrying aa substitution of threonine (t) for isoleucine (i) at residue 222 in na (na222t, n2 numbering) and an h7n9 virus carrying aa substitution of lysine (k) for arginine (r) at residue 292 in na (na292k, ...202032272175
potent and rapid reversal of the von willebrand factor inhibitor aptamer bt200.bt200, a pegylated form of the aptamer bt100, inhibits binding of von willebrand factor (vwf) to platelet glycoprotein gpib, preventing arterial thrombosis in cynomolgus monkeys. it is being developed for secondary prevention of arterial thrombosis such as stroke or myocardial infarction. inhibition of thrombogenesis by bt200 is expected to provide a therapeutic benefit. however, there may be unexpected bleeding (eg, incidental trauma) in which a reversal agent is required. to address this need, ...202032275107
a single lentivector dna based immunization contains a late heterologous sivmac251 mucosal challenge infection.variety of conventional vaccine strategies tested against hiv-1 have failed to induce protection against hiv acquisition or durable control of viremia. therefore, innovative strategies that can induce long lasting protective immunity against hiv chronic infection are needed. recently, we developed an integration-defective hiv lentidna vaccine that undergoes a single cycle of replication in target cells in which most viral antigens are produced. a single immunization with such lentidna induced lo ...202032278522
efficacy of neuraminidase inhibitors against h5n6 highly pathogenic avian influenza virus in a nonhuman primate model.attention has been paid to h5n6 highly pathogenic avian influenza virus (hpaiv) because of its heavy burden on the poultry industry and human mortality. since an influenza a virus carrying n6 neuraminidase (na) has never spread in humans, the potential for h5n6 hpaiv to cause disease in humans and the efficacy of antiviral drugs against the virus need to be urgently assessed. we used nonhuman primates to elucidate the pathogenesis of h5n6 hpaiv as well as to determine the efficacy of antiviral d ...202032284377
a novel therapeutic and prophylactic vaccine (hvj-envelope / hsp65 dna + il-12 dna) against tuberculosis using the cynomolgus monkey model.we have developed a novel tuberculosis (tb) vaccine; a combination of the dna vaccines expressing mycobacterial heat shock protein 65 (hsp65) and interleukin 12 (il-12) delivered by the hemagglutinating virus of japan (hvj)-envelope and -liposome (hsp65 + il-12/hvj). an il-12 expression vector (il-12dna) encoding single-chain il-12 proteins comprised of p40 and p35 subunits were constructed. this vaccine provided remarkable protective efficacy in mouse and guinea pig models compared to the bcg v ...201032288910
a novel therapeutic and prophylactic vaccine against tuberculosis using the cynomolgus monkey model and mouse model.we have developed a novel tuberculosis (tb) vaccine; a combination of the dna vaccines expressing mycobacterial heat shock protein 65 (hsp65) and interleukin 12 (il-12) delivered by the hemagglutinating virus of japan (hvj)-envelope and -liposome (hsp65 + il-12/hvj). this vaccine provided remarkable protective efficacy in mouse model compared to the bcg. this vaccine also provided therapeutic efficacy against multi-drug resistant tb (mdr-tb) and extremely drug resistant tb (xdr-tb) in murine mod ...201132288912
comparison of the inducibility of cyp mrna exposed to typical inducers in fresh and cryopreserved cynomolgus monkey hepatocytes.herein, we evaluated cyps and their nuclear receptor mrna induction by exposure to typical inducers, omeprazole, rifampicin, and phenobarbital in cynomolgus monkey hepatocytes. six freshly-isolated hepatocytes and 6 cryopreserved hepatocytes from cynomolgus monkey liver were prepared for a 14-day monolayer culture, 28-day co-culture with feeder cells, and 28-day 3d spheroid culture with feeder cells. omeprazole and rifampicin respectively induced cyp1a1 and cyp3a8 mrnas, while phenobarbital indu ...202032303457
comparative pathogenesis of covid-19, mers, and sars in a nonhuman primate model.the current pandemic coronavirus, severe acute respiratory syndrome-coronavirus 2 (sars-cov-2), was recently identified in patients with an acute respiratory syndrome, coronavirus disease 2019 (covid-19). to compare its pathogenesis with that of previously emerging coronaviruses, we inoculated cynomolgus macaques with sars-cov-2 or middle east respiratory syndrome (mers)-cov and compared the pathology and virology with historical reports of sars-cov infections. in sars-cov-2-infected macaques, v ...202032303590
design and characterization of novel oxyntomodulin derivatives with potent dual glp-1/glucagon receptor activation and prolonged antidiabetic effects.to investigate the combination of dimerization and pegylation to enhance the receptor activation and in vivo stability of oxyntomodulin (oxm).202032304764
barusiban, a selective oxytocin receptor antagonist: placental transfer in rabbit, monkey, and human†.the use of drugs in pregnancy always raises concerns regarding potential fetal exposure and possible adverse effects through their accumulation in fetal tissues and organs. barusiban is an oxytocin antagonist under development for potential use as tocolytic in preterm-labor patients. it displays greater affinity for the oxytocin receptor compared to vasopressin v1a receptor and would thus not interfere with vasopressin-induced effects of the v1a receptor. barusiban placental transfer was determi ...202032307542
induction of diabetes in cynomolgus monkey with one shot of analytical grade streptozotocin.streptozotocin (stz)- induced diabetic monkey is a wide used preclinical animal model for the investigation of diabetes such as islet transplantation and development of diabetic drugs. there are serious side effects of this method, including nausea, emesis, weight loss, liver damage, renal failure, and metabolic acidosis. in order to reduce the side effects, diabetic monkeys were induced using clinical-grade stz. however, clinical-grade stz is not available in china. here, we establised a method ...202032318663
establishment of macaque trophoblast stem cell lines derived from cynomolgus monkey blastocysts.the placenta forms a maternal-fetal junction that supports many physiological functions such as the supply of nutrition and exchange of gases and wastes. establishing an in vitro culture model of human and non-human primate trophoblast stem/progenitor cells is important for investigating the process of early placental development and trophoblast differentiation. in this study, we have established five trophoblast stem cell (tsc) lines from cynomolgus monkey blastocysts, named mactsc #1-5. fibrob ...202032321940
first radiolabeling of a ganglioside with a positron emitting radionuclide: in vivo pet demonstrates low exposure of radiofluorinated gm1 in non-human primate brain.gangliosides are biologically important glycolipids widely distributed in vertebrate cells. an important member of the ganglioside family is the monosialylganglioside gm1, which has been suggested as a potential therapeutic for parkinson's disease. in the current study, a late-stage radiofluorination protocol was developed, in which fluorine-18 was introduced by substitution of a terminal tosyl group in the fatty acid backbone of gm1. the radiofluorination procedure was remarkably simple and fur ...202032324990
immune complex disease in a chronic monkey study with a humanised, therapeutic antibody against ccl20 is associated with complement-containing drug aggregates.despite the potential for the chemokine class as therapeutic targets in immune mediated disease, success has been limited. many chemokines can bind to multiple receptors and many receptors have multiple ligands, with few exceptions. one of those exceptions is ccl20, which exclusively pairs to ccr6 and is associated with several immunologic conditions, thus providing a promising therapeutic target. following successful evaluation in a single dose, first time in human clinical study, gsk3050002-a ...202032325480
genetic variants of n-acetyltransferases 1 and 2 (nat1 and nat2) in cynomolgus and rhesus macaques.in humans, polymorphic n-acetyltransferases nat1 and nat2 are important enzymes that metabolize endogenous and exogenous compounds, including drugs. these enzymes exhibit considerable inter-individual variability in humans. the cynomolgus macaque is a nonhuman primate species that is widely used in drug metabolism studies. nat1/2 in these macaques have molecular and enzymatic similarities to their human orthologs; however, genetic polymorphisms in nat1/2 have not been fully investigated in this ...202032339492
cell atlas of aqueous humor outflow pathways in eyes of humans and four model species provides insight into glaucoma pathogenesis.increased intraocular pressure (iop) represents a major risk factor for glaucoma, a prevalent eye disease characterized by death of retinal ganglion cells; lowering iop is the only proven treatment strategy to delay disease progression. the main determinant of iop is the equilibrium between production and drainage of aqueous humor, with compromised drainage generally viewed as the primary contributor to dangerous iop elevations. drainage occurs through two pathways in the anterior segment of the ...202032341164
a strategy for personalized treatment of ips-retinal immune rejections assessed in cynomolgus monkey models.recently, we successfully transplanted an autograft, or major histocompatibility complex (mhc)-matched allografts, from induced-pluripotent-stem-cell-derived retinal pigment epithelial (ipsc-rpe) cells in patients with age-related macular degeneration. however, there was an issue regarding immune rejection after transplantation. in this study, we established a preoperational in vitro "drug-lymphocytes-grafts immune reaction (drug-lgir)" test to determine the medication for immune rejection using ...202032349277
identification and analysis of components in yizhi granule and cynomolgus monkey plasma after oral administration by uplc/esi-q-tof ms and their protective effects on pc12 cells.yizhi granule (yzg) is a health food containing six traditional chinese medicines (tcms). it improves memory barriers in rat experiments. here, we describe the first fast and sensitive ultraperformance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (uplc/esi-q-tof ms) method for analyzing yzg in plasma. we used this technique for studies in cynomolgus monkey plasma. by comparing retention time, ms, and ms/ms data of reference compounds, 70 compounds wer ...202032351755
local immunosuppression for vascularized composite allografts: application of topical fk506-tyrospheres in a non-human primate model.transplantation of vascularized composite allografts (vcas) provides a means of restoring complex anatomical and functional units following burns and other disfigurement otherwise not amenable to conventional autologous reconstructive surgery. while short- to intermediate-term vca survival is largely dependent on patient compliance with medication, the myriad of side effects resulting from lifelong systemic immunosuppression continue to pose a significant challenge. topical immunosuppression is ...202032352521
comprehensive analysis of cardiac function, blood biomarkers and histopathology for milrinone-induced cardiotoxicity in cynomolgus monkeys.the objective of this study was to elucidate the underlying cardiotoxic mechanism of milrinone, a camp phosphodiesterase 3 inhibitor, by evaluating cardiac functions, blood biomarkers including cardiac troponin i (ctni), micrornas (mir-1, mir-133a and mir-499a) and various endogenous metabolites, and histopathology in conscious cynomolgus monkeys. milrinone at doses of 0, 3 and 30 mg/kg were orally administered to monkeys (n = 3-4/group), and the endpoints were evaluated 1 to 24 h post-dosing. m ...202032353509
the effects of b1344, a novel fibroblast growth factor 21 analog, on nonalcoholic steatohepatitis in nonhuman primates.nonalcoholic steatohepatitis has emerged as a major cause of liver diseases with no effective therapies. here, we evaluate the efficacies and pharmacokinetics of b1344, a long-acting polyethylene glycolylated (pegylated) fibroblast growth factor 21 analog, in a nongenetically modified nonhuman primate species that underwent liver biopsy and demonstrate the potential for efficacies in humans. b1344 is sufficient to selectively activate signaling from the βklotho/fgfr1c receptor complex. in cynomo ...202032354858
tissue cross-reactivity studies of cpgj701 in humans, cynomolgus monkeys and sprague-dawley rats and correlation analysis with in vivo toxicity.cpgj701 is a recombinant humanized anti-human epidermal growth factor receptor-2 (her2) monoclonal antibody-derivative of the cytotoxic agent maytansine (dm1) conjugate for the treatment of her2-positive metastatic breast cancer. tissue cross-reactivity (tcr) studies of cpgj701 in a complete panel of normal human, cynomolgus monkey and sprague-dawley were performed to provide evidence for selecting animal species for use in preclinical toxicity studies and predicting primary target organs and cl ...202032355769
intra-csf aav9 and aavrh10 administration in nonhuman primates: promising routes and vectors for which neurological diseases?the identification of the most efficient method for whole central nervous system targeting that is translatable to humans and the safest route of adeno-associated virus (aav) administration is a major concern for future applications in clinics. additionally, as many aav serotypes were identified for gene introduction into the brain and the spinal cord, another key to human gene-therapy success is to determine the most efficient serotype. in this study, we compared lumbar intrathecal administrati ...202032355866
positron emission tomography imaging evaluation of a novel 18f-labeled sigma-1 receptor radioligand in cynomolgus monkeys.we report a convenient radiosynthesis and the first positron emission tomography (pet) imaging evaluation of [18f]fbfp as a potent sigma-1 (σ1) receptor radioligand with advantageous characteristics. [18f]fbfp was synthesized in one step from an iodonium ylide precursor. in cynomolgus monkeys, [18f]fbfp displayed high brain uptake and suitable tissue kinetics for quantitative analysis. it exhibited heterogeneous distribution with higher regional volume of distribution (vt) values in the amygdala ...202032356969
maternal-fetal disposition of domoic acid following repeated oral dosing during pregnancy in nonhuman primate.domoic acid (da) is a marine algal toxin that causes acute and chronic neurotoxicity in animals and humans. prenatal exposure to da has been associated with neuronal damage and cognitive and behavioral deficits in juvenile california sea lions, cynomolgus monkeys and rodents. yet, the toxicokinetics (tk) of da during pregnancy and the maternal-fetal disposition of da have not been fully elucidated. in this study, we investigated the tk before, during, and after pregnancy and the maternal-fetal d ...202032360744
a single-cell transcriptomic landscape of primate arterial aging.our understanding of how aging affects the cellular and molecular components of the vasculature and contributes to cardiovascular diseases is still limited. here we report a single-cell transcriptomic survey of aortas and coronary arteries in young and old cynomolgus monkeys. our data define the molecular signatures of specialized arteries and identify eight markers discriminating aortic and coronary vasculatures. gene network analyses characterize transcriptional landmarks that regulate vascula ...202032371953
fviii half-life extension by coadministration of a d'd3 albumin fusion protein in mice, rabbits, rats, and monkeys.a novel mechanism for extending the circulatory half-life of coagulation factor viii (fviii) has been established and evaluated preclinically. the fviii binding domain of von willebrand factor (d'd3) fused to human albumin (rd'd3-fp) dose dependently improved pharmacokinetics parameters of coadministered fviii in all animal species tested, from mouse to cynomolgus monkey, after iv injection. at higher doses, the half-life of recombinant fviii (rviii-singlechain) was calculated to be increased 2. ...202032374879
nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury.after cns trauma such as spinal cord injury, the ability of surviving neural elements to sprout axons, reorganize neural networks and support recovery of function is severely restricted, contributing to chronic neurological deficits. among limitations on neural recovery are myelin-associated inhibitors functioning as ligands for neuronal nogo receptor 1 (ngr1). a soluble decoy (ngr1-fc, axer-204) blocks these ligands and provides a means to promote recovery of function in multiple preclinical ro ...202032375169
the gut microbiome modulates gut-brain axis glycerophospholipid metabolism in a region-specific manner in a nonhuman primate model of depression.emerging research demonstrates that microbiota-gut-brain (mgb) axis changes are associated with depression onset, but the mechanisms underlying this observation remain largely unknown. the gut microbiome of nonhuman primates is highly similar to that of humans, and some subordinate monkeys naturally display depressive-like behaviors, making them an ideal model for studying these phenomena. here, we characterized microbial composition and function, and gut-brain metabolic signatures, in female cy ...202032376998
in vitro screening and transfection concentration optimization of cynomolgus monkey iκbα-sirna.to seek for a small interfering rna (sirna) sequence targeting a cynomolgus monkey inhibitor of nuclear factor kappa b α (iκbα) that can specifically and effectively suppress iκbα gene expression of cynomolgus monkey ciliary muscle (cm) cells and trabecular meshwork (tm) cells in vitro and screen for optimal sirna transfection concentration.202032377413
liver extracellular volume fraction values obtained with magnetic resonance imaging can quantitatively stage liver fibrosis: a validation study in monkeys with nonalcoholic steatohepatitis.this study was to evaluate the diagnostic value of liver extracellular volume (lecv) for the staging of liver fibrosis in a cynomolgus monkey model of nonalcoholic steatohepatitis (nash).202032377814
inhibition of complement pathway activation with pozelimab, a fully human antibody to complement component c5.complement is a key component of the innate immune system. inappropriate complement activation underlies the pathophysiology of a variety of diseases. complement component 5 (c5) is a validated therapeutic target for complement-mediated diseases, but the development of new therapeutics has been limited by a paucity of preclinical models to evaluate the pharmacokinetic (pk) and pharmacodynamic (pd) properties of candidate therapies. the present report describes a novel humanized c5 mouse and its ...202032384086
recombination between high-risk human papillomaviruses and non-human primate papillomaviruses: evidence of ancient host switching among alphapapillomaviruses.we use all the currently known 405 papillomavirus (pv) sequences, 343 curated pv sequences from both humans and animals from the pave data base, to analyse the recombination dynamics of these viruses at the whole genome levels. after showing some evidence of human and non-human primate pv recombination, we report a comprehensive recombination analysis of all currently known 82 alphapapillomaviruses (alpha-pvs). we carried out an exploratory study and found novel recombination events between high ...202032385625
novel mono-pegylated dimeric glp-1 conjugate with enhanced receptor activation and prolonged anti-diabetes efficacies.to design and evaluate novel mono-pegylated dimeric glp-1 conjugate with enhanced glp-1 receptor activation and prolonged anti-diabetes efficacies.202032387412
multiplex precise base editing in cynomolgus monkeys.common polygenic diseases result from compounded risk contributed by multiple genetic variants, meaning that simultaneous correction or introduction of single nucleotide variants is required for disease modeling and gene therapy. here, we show precise, efficient, and simultaneous multiplex base editing of up to three target sites across 11 genes/loci in cynomolgus monkey embryos using crispr-based cytidine- and adenine-base editors. unbiased whole genome sequencing demonstrates high specificity ...202032393762
potential use of actigraphy to measure sleep in monkeys: comparison with behavioral analysis from videography.sleep is indispensable for human health, with sleep disorders initiating a cascade of negative consequences. as our closest phylogenetic relatives, non-human primates (nhps) are invaluable for comparative sleep studies and exhibit tremendous potential for improving our understanding of human sleep and related disorders. previous work on measuring sleep in nhps has mostly used electroencephalography or videography. in this study, simultaneous videography and actigraphy were applied to observe sle ...202032400976
preclinical characterization of an antibody-drug conjugate targeting cs-1 and the identification of uncharacterized populations of cs-1-positive cells.multiple myeloma is a hematologic cancer that disrupts normal bone marrow function and has multiple lines of therapeutic options, but is incurable as patients ultimately relapse. we developed a novel antibody-drug conjugate (adc) targeting cs-1, a protein that is highly expressed on multiple myeloma tumor cells. the anti-cs-1 mab specifically bound to cells expressing cs-1 and, when conjugated to a cytotoxic pyrrolobenzodiazepine payload, reduced the viability of multiple myeloma cell lines in v ...202032404408
enhanced normograms and pregnancy outcome analysis in nonhuman primate developmental toxicity studies.the incidence of spontaneous pregnancy/infant losses is highly variable in long-tailed macaques (cynomolgus monkey), making it potentially difficult to ascertain test item-related effects in developmental toxicity studies. therefore, pregnancy normograms had been developed by jarvis et al. [1] to aid in the distinction of normal (e.g. test facility background) versus non-normal pregnancy outcomes. these normograms were mostly derived from embryo-fetal development studies and from ppnd studies wi ...202032413491
pet imaging of [11c]mpc-6827, a microtubule-based radiotracer in non-human primate brains.dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and alzheimer's disease. imaging of microtubules in vivo using positron emission tomography (pet) could provide valuable information on their role in the development of disease pathogenesis and aid in improving therapeutic regimens. we developed [11c]mpc-6827, the first brain-penetrating pet radiotracer to image microtubules in vivo in the mouse brain. the aim of the pres ...202032414052
identification and classification of interstitial cells in the mouse renal pelvis.platelet-derived growth factor receptor-α (pdgfrα) is a novel biomarker along with smooth myosin heavy chain for the pacemaker cells (previously termed 'atypical' smooth muscle cells) in the murine and cynomolgus monkey pelvis-kidney junction. pdgfrα+ cells present in adventitial and urothelial layers of murine renal pelvis do not express smooth muscle myosin heavy chain (smmhc) but are in close apposition to nerve fibres. most c-kit+ cells in the renal pelvis are mast cells. mast cells (cd117+ ...202032415739
inferring functional patterns of tool use behavior from the temporal structure of object play sequences in a non-human primate species.inferring functional components of behavioral sequences is a crucial but challenging task. a systematic comparison of their temporal structure is a good starting point, based on the postulate that more functional traits are less structurally variable. we studied stone handling behavior (sh) in balinese long-tailed macaques, a versatile form of stone-directed play. we tested the hypothesis that stones are used by male monkeys to stimulate their genitals in a sexual context (i.e., "sex toy" hypoth ...202032417233
anatomical study of the incisivus labii superioris and inferioris muscles in non-human primates.the facial muscles have significant roles for vocalization, feeding, and facial expression in both human and non-human primates. of these, the anatomy of the incisivus labii superioris (ils) and incisivus labii inferioris (ili), which are considered as the accessory bundle of the orbicularis oris (oo) in humans, has rarely been documented in the literature. our current understanding of the function of the ils and ili is that they probably retract the upper and lower lips. also, there is no accou ...202032420698
cholecystokinin-1 receptor agonist induced pathological findings in the exocrine pancreas of non-human primates.cholecystokinin (cck) may potentially be used to treat obesity. however, it is well-known to induce acute pancreatitis and pancreas neoplasia in rodents, but not in primates. here we report the nonclinical safety profile of a long-acting cck-1 receptor (cck-1r) agonist, nn9056, in rats and monkeys to support a first-in-man clinical trial with nn9056.202032422327
discovery of indoximod prodrugs and characterization of clinical candidate nlg802.a series of different prodrugs of indoximod, including estesrs and peptide amides were synthesized with the aim of improving its oral bioavailability in humans. the pharmacokinetics of prodrugs that were stable in buffers, plasma and simulated gastric and intestinal fluids was first assessed in rats after oral dosing in solution or in capsule formulation. two prodrugs that produced the highest exposure to indoximod in rats were further tested in cynomolgus monkeys, a species in which indoximod h ...202032422549
sars-cov-2 causes covid-19-like disease in cynomolgus macaques. 202032424314
method development and validation of lc-ms/ms-based assay for the simultaneous quantitation of trastuzumab and pertuzumab in cynomolgus monkey serum and its application in pharmacokinetic study.we present a simple and robust lc-ms/ms assay for the simultaneous quantitation of an antibody cocktail of trastuzumab and pertuzumab in monkey serum. the lc-ms/ms method saved costs, decreased the analysis time, and reduced quantitative times relative to the traditional ligand-binding assays. the serum samples were digested with trypsin at 50°c for 60 min after methanol precipitation, ammonium bicarbonate denaturation, dithiothreitol reduction, and iodoacetamide alkylation. the tryptic peptides ...202032428305
a non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs.stroke is a devastating disease. endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. in this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood-brain barrier disruption and reperfusion damage. ...202032428423
in vitro and in vivo interspecies chimera assay using early pig embryos.chimeric pigs harboring organs derived from human stem cells are promising for patient-specific regenerative therapies. induced pluripotent stem cells (ipscs) can contribute to all cell types of the fetus, including germline after injection into embryos. however, ethical concerns prohibit testing human ipscs in chimera assays. here, we evaluated porcine embryos as hosts for an interspecies chimera assay using ipscs from either cynomolgus monkeys (cyipscs) or mouse (mipscs). to establish an in vi ...202032429746
diazoxide preconditioning of nonhuman primate pancreas improves islet isolation outcomes by mitochondrial protection.previously, we showed that diazoxide (dz), an effective ischemic preconditioning agent, protected rodent pancreas against ischemia-reperfusion injury. here, we further investigate whether dz supplementation to university of wisconsin (uw) solution during pancreas procurement and islet isolation has similar cytoprotection in a preclinical nonhuman primate model.202032433410
mait cells are functionally impaired in a mauritian cynomolgus macaque model of siv and mtb co-infection.mucosal-associated invariant t (mait) cells can recognize and respond to some bacterially infected cells. several in vitro and in vivo models of mycobacterium tuberculosis (mtb) infection suggest that mait cells can contribute to control of mtb, but these studies are often cross-sectional and use peripheral blood cells. whether mait cells are recruited to mtb-affected granulomas and lymph nodes (lns) during early mtb infection and what purpose they might serve there is less well understood. furt ...202032433713
assessment of parp-1 distribution in tissues of cynomolgus monkeys.the poly(adp-ribose) polymerase 1 (parp-1) enzyme has received much attention in the last decade due to its promising role in cancer therapeutics. despite the expanding use of parp inhibitors in cancer therapy, little is known about parp-1 tissue distribution. our study provides a detailed survey of parp-1 tissue and cellular distribution using well-preserved cynomolgus monkey organs and a well-characterized, highly specific monoclonal parp-1 antibody. overall, parp-1 was detected in most organs ...202032436762
characterization of tumour-infiltrating lymphocytes in a tumour rejection cynomolgus macaque model.immunotherapy has emerged as a promising and effective treatment for cancer, yet the clinical benefit is still variable, in part due to insufficient accumulation of immune effector cells in the tumour microenvironment. better understanding of tumour-infiltrating lymphocytes (tils) from nonhuman primate tumours could provide insights into improving effector cell accumulation in tumour tissues during immunotherapy. here, we characterize tils in a cynomolgus macaque tumour model in which the tumour ...202032439888
anti-vascular endothelial growth factor antibody limits vascular leakage and decreases subretinal fibrosis in a cynomolgus monkey choroidal neovascularization model.this study was conducted to evaluate the effects of anti-vascular endothelial growth factor (vegf) antibody (bevacizumab) on vascular leakage and fibrosis in a monkey choroidal neovascularization (cnv) model. the relationship between fibrotic tissue and subretinal hyper-reflective material (shrm) in optical coherence tomography (oct) images was also investigated.202032445455
development of cdx-527: a bispecific antibody combining pd-1 blockade and cd27 costimulation for cancer immunotherapy.cd27 is a costimulatory molecule that provides a complementary target to the pd-1/pd-l1 checkpoint axis on t cells. combining a cd27 agonist antibody with pd-1/pd-l1 blockade has shown synergistic antitumor activity in preclinical models, which led to clinical studies of the combination in cancer patients. we theorized that coupling cd27 costimulation with pd-1/pd-l1 blockade in a bispecific antibody (bsab) may provide greater immune activating properties than combining the individual mabs due t ...202032451681
distinct spatiotemporal mechanisms underlie extra-classical receptive field modulation in macaque v1 microcircuits.complex scene perception depends upon the interaction between signals from the classical receptive field (crf) and the extra-classical receptive field (ecrf) in primary visual cortex (v1) neurons. although much is known about v1 ecrf properties, we do not yet know how the underlying mechanisms map onto the cortical microcircuit. we probed the spatio-temporal dynamics of ecrf modulation using a reverse correlation paradigm, and found three principal ecrf mechanisms: tuned-facilitation, untuned-su ...202032458798
combining in vivo and organotypic in vitro approaches to assess the human relevance of basimglurant (rg7090), a potential car activator.basimglurant (rg7090), a small molecule under development to treat certain forms of depression, demonstrated foci of altered hepatocytes in a long-term rodent-toxicity study. additional evidence pointed toward the activation of the constitutive androstane receptor (car), an established promoter of nongenotoxic and rodent-specific hepatic tumors. this mode of action and the potential human relevance was explored in vivo using rodent and cynomolgus monkey models and in vitro using murine and human ...202032458970
novel recombinant coxsackievirus b3 with genetically inserted basic peptide elicits robust antitumor activity against lung cancer.cancer therapy that utilizes oncolytic virus may offer an exciting alternative, and coxsackievirus b3 (cvb3) is a potent oncolytic virus. this study was to assess the oncolytic activities of novel recombinant cvb3 with genetically inserted basic peptides in lung cancer. recombinant cvb3 was produced in vero cells, with or without genetically inserted basic peptides. in vitro and in vivo experiments with nude mouse models bearing human lung carcinoma xenografts were performed to examine the antit ...202032459400
brain delivery of therapeutic proteins using an fc fragment blood-brain barrier transport vehicle in mice and monkeys.effective delivery of protein therapeutics to the central nervous system (cns) has been greatly restricted by the blood-brain barrier (bbb). we describe the development of a bbb transport vehicle (tv) comprising an engineered fc fragment that exploits receptor-mediated transcytosis for cns delivery of biotherapeutics by binding a highly expressed brain endothelial cell target. tvs were engineered using directed evolution to bind the apical domain of the human transferrin receptor (htfr) without ...202032461332
sedative and physiological effects of alfaxalone intramuscular administration in cynomolgus monkeys (macaca fascicularis).to evaluate the sedative and physiological effects of alfaxalone intramuscular (im) administration, 12 healthy cynomolgus monkeys were administered single im doses of alfaxalone at 0.625 mg/kg (alfx0.625), 1.25 mg/kg (alfx1.25), 2.5 mg/kg (alfx2.5), 5 mg/kg (alfx5), 7.5 mg/kg (alfx7.5), or 10 mg/kg (alfx10); saline was used as the control (cont). the sedative effects were subjectively evaluated using a composite measure scoring system in six animals. changes in respiratory rate, pulse rate, non- ...202032461537
correlations of serum biochemistry profile with ultrasonic histogram of liver, gallbladder, and kidneys and morphometry of rescued long-tailed macaques (macaca fascicularis).serum biochemistry and ultrasonography can be useful diagnostic tools in evaluating the general health condition of long-tailed macaques in rescue and rehabilitation centers.202032463113
cs1003, a novel human and mouse cross-reactive pd-1 monoclonal antibody for cancer therapy.the programmed cell death protein 1 (pd-1) is an immune-checkpoint that negatively regulates the immune system and a key mechanism that tumors utilize to escape from immune surveillance. pd-1 antibodies can block the interaction of pd-1 with its ligands (pd-l1 and pd-l2), restore t cells activation, and elicit antitumor activity. in this paper, we reported a novel pd-1 monoclonal antibody (mab) cs1003, which is a humanized igg4 pd-1 mab generated by conventional hybridoma technology, and current ...202032467569
everestmab, a novel long-acting glp-1/anti glp-1r nanobody fusion protein, exerts potent anti-diabetic effects.in the present study, a novel single domain antibody (sdab) fusion protein, named everestmab, composing of a mutated glp-1(a8g) fused to the tandem bispecific humanized glp-1r-targeting and albumin-binding nanobodies was designed and characterized for the therapies for type 2 diabetes mellitus (t2dm). surface plasmon resonance (spr) measurements demonstrated everestmab associates with serum albumins of rat and monkey species with high affinity, and tends to be cross-reactive with rat and monkey ...202032468873
generation of cynomolgus monkey fetuses with intracytoplasmic sperm injection based on the mii-stage oocytes acquired by personalized superovulation protocol.mature oocytes at the metaphase ii status (mii-stage oocytes) played an important role in assisted reproductive technology in non-human primates.202032476321
toward a macaque model of hiv-1 infection: roadblocks, progress, and future strategies.the human-specific tropism of human immunodeficiency virus type 1 (hiv-1) has complicated the development of a macaque model of hiv-1 infection/aids that is suitable for preclinical evaluation of vaccines and novel treatment strategies. several innate retroviral restriction factors, such as apobec3 family of proteins, trim5α, bst2, and samhd1, that prevent hiv-1 replication have been identified in macaque cells. accessory proteins expressed by simian immunodeficiency virus (siv) such as viral in ...202032477302
evaluation of il-1 blockade as an adjunct to linezolid therapy for tuberculosis in mice and macaques.in 2017 over 550,000 estimated new cases of multi-drug/rifampicin resistant tuberculosis (mdr/rr-tb) occurred, emphasizing a need for new treatment strategies. linezolid (lzd) is a potent antibiotic for drug-resistant gram-positive infections and is an effective treatment for tb. however, extended lzd use can lead to lzd-associated host toxicities, most commonly bone marrow suppression. lzd toxicities may be mediated by il-1, an inflammatory pathway important for early immunity during m. tubercu ...202032477361
major depression accompanied with inflammation and multiple cytokines alterations: evidences from clinical patients to macaca fascicularis and lps-induced depressive mice model.inflammation progress has been consistently implicated in the pathophysiology of major depressive disorder (mdd). however, the underlying mechanism of inflammation and depressive symptoms still far from being fully elucidated. in addition, studies on emotional disorders could also benefit from model of the non-human primates. to explore the difference of serum multi-cytokines levels among the mdd patients and depressed macaca fascicularis as well as lps-treated mice, thus may find the reliable p ...202032479325
remdesivir (gs-5734) is efficacious in cynomolgus macaques infected with marburg virus.marburg virus (marv) is a filovirus with documented human case-fatality rates of up to 90%. here, we evaluated the therapeutic efficacy of remdesivir (gs-5734) in nonhuman primates experimentally infected with marv. beginning 4 or 5 days post inoculation, cynomolgus macaques were treated once daily for 12 days with vehicle, 5 mg/kg remdesivir, or a 10-mg/kg loading dose followed by 5 mg/kg remdesivir. all vehicle-control animals died, whereas 83% of animals receiving a 10-mg/kg loading dose of r ...202032479636
absorption and disposition of coproporphyrin i (cpi) in cynomolgus monkeys and mice: pharmacokinetic evidence to support the use of cpi to inform the potential for organic anion-transporting polypeptide inhibition.despite a recent expansion in the recognition of the potential utility of coproporphyrin (cp) as an endogenous biomarker of organic anion-transporting polypeptide (oatp) 1b activity, there have been few detailed studies of cp's pharmacokinetic behavior and an overall poor understanding of its pharmacokinetic fate from tissues and excretion. here, we describe the pharmacokinetics of octadeuterium-labeled coproporphyrin i (cpi-d8) in cynomolgus monkeys following oral and intravenous administration ...202032482623
natural history of aerosol induced lassa fever in non‑human primates.lassa virus (lasv), an arenavirus causing lassa fever, is endemic to west africa with up to 300,000 cases and between 5000 and 10,000 deaths per year. rarely seen in the united states, lassa virus is a cdc category a biological agent inasmuch deliberate aerosol exposure can have high mortality rates compared to naturally acquired infection. with the need for an animal model, specific countermeasures remain elusive as there is no fda-approved vaccine. this natural history of aerosolized lassa vir ...202032485952
influence of physiochemical properties on the subcutaneous absorption and bioavailability of monoclonal antibodies.many therapeutic monoclonal antibodies (mabs) were initially developed for intravenous (iv) administration. as a means to improve mab drug-ability and the patient experience, subcutaneous (sc) administration is an increasingly important delivery route for mabs. unlike iv administration, bioavailability limitations for antibodies have been reported following sc injection and can dictate whether a mab is administered via this parenteral route. the sc bioavailability of antibodies has been difficul ...202032486889
nonclinical characterization of the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat, a novel treatment of anemia of chronic kidney disease.anemia of chronic kidney disease (ckd) is a multifactorial disorder caused by impaired erythropoietin (epo) production and altered iron homeostasis associated with inflammation. hypoxia-inducible factor (hif) is a transcription factor that stimulates erythropoiesis via a coordinated response involving increased epo production and enhanced iron availability for hb synthesis. hif degradation is regulated by hif-prolyl hydroxylase (hif-ph) enzymes. we hypothesized that roxadustat, an orally availab ...202032487538
in vivo analysis of the effects of intravenously as well as orally administered moxifloxacin on the pharmacokinetic and electrocardiographic variables along with its torsadogenic action in the chronic atrioventricular block cynomolgus monkeys.we analyzed the effects of intravenously as well as orally administered moxifloxacin on the pharmacokinetic and electrocardiographic variables along with its torsadogenic action using the chronic atrioventricular block cynomolgus monkeys with a cross-over design. initially, moxifloxacin was intravenously administered in doses of 60 mg/kg/2 h, 60 mg/kg/1 h and 105 mg/kg/1.75 h with an interval of >1 week (n = 3), which provided cmax of 19.7, 25.4 and 37.8 μg/ml, and induced torsade de pointes in ...202032499095
a single mutation in the actr8 gene associated with lineage-specific expression in primates.alternative splicing (as) generates various transcripts from a single gene and thus plays a significant role in transcriptomic diversity and proteomic complexity. alu elements are primate-specific transposable elements (tes) and can provide a donor or acceptor site for as. in a study on te-mediated as, we recently identified a novel alusz6-exonized actr8 transcript of the crab-eating monkey (macaca fascicularis). in the present study, we sought to determine the molecular mechanism of alusz6 exon ...202032503430
characteristic and quantifiable covid-19-like abnormalities in ct- and pet/ct-imaged lungs of sars-cov-2-infected crab-eating macaques (macaca fascicularis).severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is causing an exponentially increasing number of coronavirus disease 19 (covid-19) cases globally. prioritization of medical countermeasures for evaluation in randomized clinical trials is critically hindered by the lack of covid-19 animal models that enable accurate, quantifiable, and reproducible measurement of covid-19 pulmonary disease free from observer bias. we first used serial computed tomography (ct) to demonstrate that bilate ...202032511338
habitat use by a primate community in a lowland dipterocarp forest in danum valley, borneo.knowledge of niche partitioning with respect to habitat is indispensable to understand the mechanism of coexistence of multiple species. among primates, however, data are still deficient because repeated survey for a sufficiently long time, covering seasonal changes over a large area, is the only way to clarify habitat segregation within a seasonally fluctuating environment. southeast asia is particularly interesting because of the supra-annual, highly unpredictable seasonality in fruiting known ...202032515849
characterization of a novel flt3 bite molecule for the treatment of acute myeloid leukemia.despite advances in the treatment of acute myeloid leukemia (aml), novel therapies are needed to induce deeper and more durable clinical response. bispecific t-cell engager (bite) molecules, which redirect patient t cells to lyse tumor cells, are a clinically validated modality for hematologic malignancies. due to broad aml expression and limited normal tissue expression, fms-related tyrosine kinase 3 (flt3) is proposed to be an optimal bite molecule target. expression profiling of flt3 was perf ...202032518207
tetravalent dengue dna vaccine is not immunogenic when delivered by retrograde infusion into salivary glands.a tetravalent dna vaccine for dengue virus is under development but has not yet achieved optimal immunogenicity. salivary glands vaccination has been reported efficacious in rodents and dogs. we report on a pilot study testing the salivary gland as a platform for a dengue dna vaccine in a non-human primate model.202032518668
evaluation of canine teeth crown reduction technique in macaques.the reduction of canine teeth in adult males in whom permanent canine teeth eruption occurs should be considered due to the safety of humans or other monkeys. the objective of this study was to evaluate the complications of canine teeth reduction in macaques. case presentation: canine teeth reductions were performed in 8 rhesus and 2 cynomolgus macaques. complications related to canine teeth reduction were evaluated at one to three week intervals during the experimental period by gross examinati ...202032518764
innate and adaptive anti-siv responses in macaque semen: implications for infectivity and risk of transmission.hiv-1 infection is transmitted primarily by sexual exposure, with semen being the principal contaminated fluid. however, hiv-specific immune response in semen has been understudied. we investigated specific parameters of the innate, cellular, and humoral immune response that may affect semen infectivity in macaques infected with sivmac251. serial semen levels of cytokines and chemokines, siv-specific antibodies, neutralization, and fcγr-mediated functions and siv-specific t-cell responses were a ...202032528466
discovery of 3-pyridyl isoindolin-1-one derivatives as potent, selective, and orally active aldosterone synthase (cyp11b2) inhibitors.aldosterone synthase (cyp11b2) inhibitors have been explored in recent years as an alternative therapeutic option to mineralocorticoid receptor (mr) antagonists to reduce elevated aldosterone levels, which are associated with deleterious effects on various organ systems including the heart, vasculature, kidney, and central nervous system (cns). a benzamide pyridine hit derived from a focused screen was successfully developed into a series of potent and selective 3-pyridyl isoindolin-1-ones cyp11 ...202032530624
cooperation with closely bonded individuals reduces cortisol levels in long-tailed macaques.many animal species cooperate with conspecifics in various social contexts. while ultimate causes of cooperation are being studied extensively, its proximate causes, particularly endocrine mechanisms, have received comparatively little attention. here, we present a study investigating the link between the hormone cortisol, cooperation and social bonds in long-tailed macaques (macaca fascicularis). we tested 14 macaques in a dyadic cooperation task (loose-string paradigm), each with two partners ...202032537186
Refresh
firstprev
...111112113114
nextlast
Displaying items 11001 - 11100 of 11313