Publications

preclinical efficacy and safety assessment of an antibody-drug conjugate targeting the c-ret proto-oncogene for breast carcinoma.	the ret proto-oncogene has been implicated in breast cancer, and the studies herein describe the preclinical and safety assessment of an anti-ret antibody-drug conjugate (adc) being developed for the treatment of breast cancer.	2015	26240273
impact of the cryopreservation technique and vascular bed on ovarian tissue transplantation in cynomolgus monkeys.	the aim of this study was to determine the best combination in terms of cryopreservation techniques and vascular bed preparation before grafting in order to obtain functional ovarian tissue after transplantation.	2015	26238388
discovery and structure-guided optimization of tert-butyl 6-(phenoxymethyl)-3-(trifluoromethyl)benzoates as liver x receptor agonists.	to obtain potent liver x receptor (lxr) agonists, a structure-activity relationship study was performed on a series of tert-butyl benzoate analogs. as the crystal structure analysis suggested applicable interactions between the lxr ligand-binding domain and the ligands, two key functional groups were introduced. the introduction of the hydroxyl group on the c6-position of the benzoate part enhanced the agonistic activity in a cell-based assay, and the carboxyl group in terminal improved the phar ...	2015	26238323
evidence for a role of the reticulospinal system in recovery of skilled reaching after cortical stroke: initial results from a model of ischemic cortical injury.	the purposes of this pilot study were to create a model of focal cortical ischemia in macaca fascicularis and to explore contributions of the reticulospinal system in recovery of reaching. endothelin-1 was used to create a focal lesion in the shoulder/elbow representation of left primary motor cortex (m1) of two adult female macaques. repetitive microstimulation was used to map upper limb motor outputs from right and left cortical motor areas and from the pontomedullary reticular formation (pmrf ...	2015	26231990
integrated pharmacokinetic, pharmacodynamic and immunogenicity profiling of an anti-ccl21 monoclonal antibody in cynomolgus monkeys.	qbp359 is an igg1 human monoclonal antibody that binds with high affinity to human ccl21, a chemokine hypothesized to play a role in inflammatory disease conditions through activation of resident ccr7-expressing fibroblasts/myofibroblasts. the pharmacokinetics (pk) and pharmacodynamics (pd) of qbp359 in non-human primates were characterized through an integrated approach, combining pk, pd, immunogenicity, immunohistochemistry (ihc) and tissue profiling data from single- and multiple-dose experim ...	2015	26230385
characterization of a cynomolgus macaque model of pneumonic plague for evaluation of vaccine efficacy.	the efficacy of a recombinant plague vaccine (rf1v) was evaluated in cynomolgus macaques (cms) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of yersinia pestis strain colorado 92. cms were vaccinated with a range of rf1v doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. the humoral immune response following vaccination was evaluated with anti-rf1, anti-rv, and anti-rf1 ...	2015	26224691
a2e and lipofuscin distributions in macaque retinal pigment epithelium are similar to human.	the accumulation of lipofuscin, an autofluorescent aging marker, in the retinal pigment epithelium (rpe) has been implicated in the development of age-related macular degeneration (amd). lipofuscin contains several visual cycle byproducts, most notably the bisretinoid n-retinylidene-n-retinylethanolamine (a2e). previous studies with human donor eyes have shown a significant mismatch between lipofuscin autofluorescence (af) and a2e distributions. the goal of the current project was to examine thi ...	2015	26223373
identification of skin immune cells in non-human primates.	the skin is a valuable target for vaccine delivery because it contains many immune cell populations, notably antigen presenting cells. skin immune cells have been extensively described in mice and humans but not in non-human primates, which are pertinent models for immunological research in vaccination. the aim of this work was to describe immune cell populations in the epidermis, dermis and skin draining lymph nodes in cynomolgus macaques by a single 12-parameter flow cytometry protocol. given ...	2015	26219836
quantitative analysis of the myelin g-ratio from electron microscopy images of the macaque corpus callosum.	we provide a detailed morphometric analysis of eight transmission electron micrographs (tems) obtained from the corpus callosum of one cynomolgus macaque. the raw tem images are included in the article, along with the distributions of the axon caliber and the myelin g-ratio in each image. the distributions are analyzed to determine the relationship between axon caliber and g-ratio, and compared against the aggregate metrics (myelin volume fraction, fiber volume fraction, and the aggregate g-rati ...	2015	26217818
enhanced immunogenicity of a respiratory syncytial virus (rsv) f subunit vaccine formulated with the adjuvant gla-se in cynomolgus macaques.	respiratory syncytial virus (rsv) causes significant disease in elderly adults, but an effective vaccine is not yet available. we have previously reported that vaccines consisting of engineered respiratory syncytial virus soluble fusion protein (rsv sf) adjuvanted with glucopyranosyl lipid a (gla) in an oil-in-water emulsion (stable emulsion [se]) induce rsv f-specific t and b cell responses in mice and rats that protect from viral challenge. here, we evaluated the immunogenicity of gla-se adjuv ...	2015	26206269
an enhanced pre- and postnatal development study in cynomolgus monkeys with tabalumab: a human igg4 monoclonal antibody.	tabalumab, a human igg4 monoclonal antibody (mab) with neutralizing activity against both soluble and membrane b-cell activating factor (baff), has been under development for the treatment of autoimmune diseases. the purpose of this study was to determine the potential adverse effects of maternal tabalumab exposure on pregnancy, parturition, and lactation of the mothers and on the growth, viability, and development of the offspring through postnatal day (pnd) 204. tabalumab was administered by s ...	2015	26195230
the role of vp1 amino acid residue 145 of enterovirus 71 in viral fitness and pathogenesis in a cynomolgus monkey model.	enterovirus 71 (ev71), a major causative agent of hand, foot, and mouth disease, occasionally causes severe neurological symptoms. we identified p-selectin glycoprotein ligand-1 (psgl-1) as an ev71 receptor and found that an amino acid residue 145 in the capsid protein vp1 (vp1-145) defined psgl-1-binding (pb) and psgl-1-nonbinding (non-pb) phenotypes of ev71. however, the role of psgl-1-dependent ev71 replication in neuropathogenesis remains poorly understood. in this study, we investigated vir ...	2015	26181772
preclinical development of an anti-5t4 antibody-drug conjugate: pharmacokinetics in mice, rats, and nhp and tumor/tissue distribution in mice.	the pharmacokinetics of an antibody (hua1)-drug (auristatin microtubule disrupting mmaf) conjugate, targeting 5t4-expressing cells, were characterized during the discovery and development phases in female nu/nu mice and cynomolgus monkeys after a single dose and in s-d rats and cynomolgus monkeys from multidose toxicity studies. plasma/serum samples were analyzed using an elisa-based method for antibody and conjugate (adc) as well as for the released payload using an lc-ms/ms method. in addition ...	2015	26180901
engineered antibody domains with significantly increased transcytosis and half-life in macaques mediated by fcrn.	engineered antibody domains (eads) are promising candidate therapeutics but their half-life is relatively short partly due to weak or absent binding to the neonatal fc receptor (fcrn). we developed a novel approach to increase the ead binding to fcrn based on a combination of structure-based design, computational modeling and phage display methodologies. by using this approach, we identified 2 igg1 ch2-derived eads fused to a short fcrn-binding motif derived from igg1 ch3 that exhibited greatly ...	2015	26179052
expansion of simian immunodeficiency virus (siv)-specific cd8 t cell lines from siv-naive mauritian cynomolgus macaques for adoptive transfer.	cd8 t cells play a crucial role in the control of human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv). however, the specific qualities and characteristics of an effective cd8 t cell response remain unclear. although targeting breadth, cross-reactivity, polyfunctionality, avidity, and specificity are correlated with hiv control, further investigation is needed to determine the precise contributions of these various attributes to cd8 t cell efficacy. we developed protocols f ...	2015	26178985
longitudinal studies of cardiac troponin i concentrations in serum from male cynomolgus monkeys: resting values and effects of oral and intravenous dosing on biologic variability.	there is a paucity of information regarding cardiac troponin (ctn) concentrations in peripheral blood of nonhuman primates (nhp). even less is known regarding ctn concentrations in monkeys that are restrained for oral or intravenous (iv) dosing.	2015	26175009
measurement of crystalline lens volume during accommodation in a lens stretcher.	to determine if the lens volume changes during accommodation.	2015	26161985
site-dependent degradation of a non-cleavable auristatin-based linker-payload in rodent plasma and its effect on adc efficacy.	the efficacy of an antibody-drug conjugate (adc) is dependent on the properties of its linker-payload which must remain stable while in systemic circulation but undergo efficient processing upon internalization into target cells. here, we examine the stability of a non-cleavable amino-peg6-based linker bearing the monomethyl auristatin d (mmad) payload site-specifically conjugated at multiple positions on an antibody. enzymatic conjugation with transglutaminase allows us to create a stable amide ...	2015	26161543
predictive and comparative analysis of ebolavirus proteins.	ebolavirus is the pathogen for ebola hemorrhagic fever (ehf). this disease exhibits a high fatality rate and has recently reached a historically epidemic proportion in west africa. out of the 5 known ebolavirus species, only reston ebolavirus has lost human pathogenicity, while retaining the ability to cause ehf in long-tailed macaque. significant efforts have been spent to determine the three-dimensional (3d) structures of ebolavirus proteins, to study their interaction with host proteins, and ...	2015	26158395
preclinical development of an anti-napi2b (slc34a2) antibody-drug conjugate as a therapeutic for non-small cell lung and ovarian cancers.	antibody-drug conjugates (adc) selectively deliver a cytotoxic drug to cells expressing an accessible antigenic target. here, we have appended monomethyl auristatin e (mmae) to an antibody recognizing the slc34a2 gene product napi2b, the type ii sodium-phosphate cotransporter, which is highly expressed on tumor surfaces of the lung, ovary, and thyroid as well as on normal lung pneumocytes. this study evaluated its efficacy and safety in preclinical studies.	2015	26156394
contrasted patterns of variation and evolutionary convergence at the antiviral oas1 gene in old world primates.	the oligoadenylate synthetase 1 (oas1) enzyme acts as an innate sensor of viral infection and plays a major role in the defense against a wide diversity of viruses. polymorphisms at oas1 have been shown to correlate with differential susceptibility to several infections of great public health significance, including hepatitis c virus, sars coronavirus, and west nile virus. population genetics analyses in hominoids have revealed interesting evolutionary patterns. in central african chimpanzee, oa ...	2015	26156123
cross-species differences in the preclinical pharmacokinetics of ct7758, an α4β1/α4β7 integrin antagonist.	ct7758, a carboxylate containing α4β1/α4/β7 integrin antagonist, was characterized for its pharmacokinetic profile in various in vitro and in vivo assays in support of clinical development. the oral bioavailability of ct7758 was 4% in mice, 2% in rats, 7-55% in dogs, and 0.2% in cynomolgus monkeys. the low bioavailability in rodents and monkey results from low intestinal absorption as evidenced by a low fraction absorbed in the rat portal vein model (3%), low-to-medium permeability in caco-2 cel ...	2015	26153275
late-stage cancer patients remain highly responsive to immune activation by the selective tlr8 agonist motolimod (vtx-2337).	immunotherapy as a treatment for cancer holds the promise of complete and durable tumor remission, yet the immunosuppressive environment created by many tumors, advanced patient age, and previous treatments with cytotoxic agents may limit the approach. the activity of motolimod (vtx-2337), a potent and selective toll-like receptor 8 (tlr8) agonist, was therefore assessed in the context of advanced, late-stage cancer patients.	2015	26152744
loss of marginal zone b-cells in shivsf162p4 challenged rhesus macaques despite control of viremia to low or undetectable levels in chronic infection.	marginal zone (mz) b cells generate t-independent antibody responses to pathogens before t-dependent antibodies arise in germinal centers. they have been identified in cynomolgus monkeys and monitored during acute siv infection, yet have not been well-studied in rhesus macaques. here we characterized rhesus macaque mz b cells, present in secondary lymphoid tissue but not peripheral blood, as cd19(+), cd20(+), cd21(hi), igm(+), cd22(+), cd38(+), btla(+), cd40(+), ccr6(+) and bcl-2(+). compared to ...	2015	26151223
increased oligomerization and phosphorylation of α-synuclein are associated with decreased activity of glucocerebrosidase and protein phosphatase 2a in aging monkey brains.	aging is associated with an increased risk for parkinson's disease and dementia with lewy bodies, in which α-synuclein (α-syn) oligomerization plays key pathogenic roles. here, we show that oligomeric α-syn levels increase with age in the brain of cynomolgus monkeys and are accompanied by a decrease in the expression and activity of glucocerebrosidase (gcase), a lysosomal enzyme whose dysfunction is linked to accumulation of oligomeric α-syn. besides, levels of α-syn phosphorylated at serine 129 ...	2015	26149921
synthesis, f-18 radiolabeling, and micropet evaluation of 3-(2,4-dichlorophenyl)-n-alkyl-n-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amines as ligands of the corticotropin-releasing factor type-1 (crf1) receptor.	a series of 3-(2,4-dichlorophenyl)-n-alkyl-n-fluoroalkyl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-amines were synthesized and evaluated as potential positron emission tomography (pet) tracers for the corticotropin-releasing factor type-1 (crf1) receptor. compounds 27, 28, 29, and 30 all displayed high binding affinity (⩽1.2 nm) to the crf1 receptor when assessed by in vitro competition binding assays at 23 °c, whereas a decrease in affinity (⩾10-fold) was observed with compound 26. the logp7.4 val ...	2015	26145817
severe acquired idiopathic thrombocytopenia in a female cynomolgus macaque (macaca fascicularis).	a 4-y-old female cynomolgus macaque presented for veterinary evaluation prior to placement in a preclinical study showed markedly low platelet counts that continued to decrease over time. physical examination over the next several days showed areas of pale red discoloration in forelimbs, anterior thorax, and inguinal area and multifocal pinpoint areas of erythema or scabs. an area of dark red discoloration approximately 2 cm in diameter on the dorsal surface of the tongue was discovered on day 9 ...	2015	26141452
a comparison of the pathogenesis of marburg virus disease in humans and nonhuman primates and evaluation of the suitability of these animal models for predicting clinical efficacy under the 'animal rule'.	marburg virus outbreaks are sporadic, infrequent, brief, and relatively small in terms of numbers of subjects affected. in addition, outbreaks most likely will occur in remote regions where clinical trials are not feasible; therefore, definitive, well-controlled human efficacy studies to test the effectiveness of a drug or biologic product are not feasible. healthy human volunteers cannot ethically be deliberately exposed to a lethal agent such as marburg virus in order to test the efficacy of a ...	2015	26141449
a novel, blocking, fc-silent anti-cd40 monoclonal antibody prolongs nonhuman primate renal allograft survival in the absence of b cell depletion.	cd40-cd154 pathway blockade prolongs renal allograft survival in nonhuman primates (nhps). however, antibodies targeting cd154 were associated with an increased incidence of thromboembolic complications. antibodies targeting cd40 prolong renal allograft survival in nhps without thromboembolic events but with accompanying b cell depletion, raising the question of the relative contribution of b cell depletion to the efficacy of anti-cd40 blockade. here, we investigated whether fully silencing fc e ...	2015	26139432
single- and repeat-dose toxicity of idx14184, a nucleotide prodrug with antiviral activity for hepatitis c viral infection, in mice, rats, and monkeys.	the single- and repeat-dose toxicity profile of idx14184, a novel guanosine nucleotide prodrug with antiviral activity against hepatitis c viral infection, was characterized following once daily oral administration for durations up to 13, 26, and 32 weeks in mouse, rat, and cynomolgus monkey, respectively. the heart, liver, kidney, skeletal muscles, and lower gastrointestinal tract (cecum, colon, and/or rectum) were identified as the primary toxicity targets in these nonclinical species. the mou ...	2016	26138064
unexpected toxicology findings in rats dosed with an antihuman il-13 monoclonal antibody.	interleukin 13 (il-13) is a type 2 helper t cytokine involved in allergic inflammation and immune responses to parasites. cnto5825 is an antihuman il-13 monoclonal antibody that inhibits the pharmacological activity of human, cynomolgus monkey, and rat il-13. repeated dose toxicology studies of 1- to 6-month duration were conducted in both rats and monkeys at doses of 20 to 100 mg/kg/wk. a decrease in the t cell-dependent antibody response to keyhole limpet hemocyanin immunization was observed i ...	2015	26124191
transmission of scrapie prions to primate after an extended silent incubation period.	classical bovine spongiform encephalopathy (c-bse) is the only animal prion disease reputed to be zoonotic, causing variant creutzfeldt-jakob disease (vcjd) in humans and having guided protective measures for animal and human health against animal prion diseases. recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-bse. we here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly rel ...	2015	26123044
generation of cynomolgus monkey chimeric fetuses using embryonic stem cells.	because of their similarity to humans, non-human primates are important models for studying human disease and developing therapeutic strategies. establishment of chimeric animals using embryonic stem cells (escs) could help with these investigations, but has not so far been achieved. here, we show that cynomolgus monkey escs (cescs) grown in adjusted culture conditions are able to incorporate into host embryos and develop into chimeras with contribution in all three germ layers and in germ cell ...	2015	26119236
long term sertraline effects on neural structures in depressed and nondepressed adult female nonhuman primates.	selective serotonin reuptake inhibitors (ssris) are widely prescribed for mood and other disorders. however, their neural effects are difficult to study due to patient compliance and drug history variability, and rarely studied in those prescribed ssris for non-mood disorders. here we evaluated ssri effects on neural volumetrics in depressed and nondepressed monkeys.	2015	26116816
simultaneous pharmacokinetics evaluation of human cytochrome p450 probes, caffeine, warfarin, omeprazole, metoprolol and midazolam, in common marmosets (callithrix jacchus).	1. pharmacokinetics of human cytochrome p450 probes (caffeine, racemic warfarin, omeprazole, metoprolol and midazolam) composite, after single intravenous and oral administrations at doses of 0.20 and 1.0 mg kg(-1), respectively, to four male common marmosets were investigated. 2. the plasma concentrations of caffeine and warfarin decreased slowly in a monophasic manner but those of omeprazole, metoprolol and midazolam decreased extensively after intravenous and oral administrations, in a manner ...	2016	26114209
comparison of physiologic and pharmacologic parameters in asian and mauritius cynomolgus macaques.	this comparative study was conducted to assess background physiologic and pharmacologic parameters of cynomolgus macaques (macaca fascicularis) from cambodia, from a mixed asian source (cambodia, vietnam and indonesia), and from mauritius. this evaluation provides a comprehensive assessment of several of these parameters in a single study. ten male and 10 female captive-bred, age-matched macaques from each source were evaluated. criteria for evaluation included weight gain, assessment of drug me ...	2015	26111605
a 9-month toxicity and toxicokinetic assessment of subcutaneous pegylated human c-peptide (cbx129801) in cynomolgus monkeys.	c-peptide is formed in the biosynthesis of insulin and is therefore deficient in patients with type 1 diabetes mellitus. a pegylated form of human synthetic c-peptide (cbx129801) has been developed to extend the half-life of the native peptide and is undergoing clinical investigation as replacement therapy to treat diabetic peripheral neuropathy. this monkey study was conducted to evaluate the toxicity of cbx129801 with weekly subcutaneous dosing for 39 weeks at dose levels of 0 (vehicle), 0.4, ...	2015	26111539
correction: ires-containing veev vaccine protects cynomolgus macaques from ie venezuelan equine encephalitis virus aerosol challenge.		2015	26107877
a surgical technique using the ovarian vein in non-human primate models of potential living-donor surgery of uterus transplantation.	living donor surgery in organ transplantation should be performed in a minimally invasive manner under conditions that are as safe as possible. the objective of this study is to examine whether the procedure for using the ovarian vein makes donor surgery less invasive in a cynomolgus monkey model of potential living-donor surgery of uterus transplantation.	2015	26095999
epitope characterization of the ada response directed against a targeted immunocytokine.	targeted immunocytokines (tics) display potent activity in selective tumor suppression. this class of multi domain biotherapeutics (mdbs) is composed of the three major domains fab, fc, and a cytokine which may induce a complex polyclonal anti-drug antibody (ada) response. however, classical ada assays usually are not suitable to specify adas and to identify the immunogenic domains of a tic. the purpose of the present study was to establish epitope characterization of ada responses in order to s ...	2015	26093509
sensitivity and specificity of the in vitro guinea pig papillary muscle action potential duration for the assessment of drug-induced torsades de pointes liability in humans.	the ich s7b document, which provides guidance for the preclinical cardiovascular evaluation of pharmaceutical new chemical entities (nce), is essentially focused on drug-induced qt lengthening, a biomarker for the proarrhythmic adverse drug reaction, torsades de pointes (tdp). in 2005, this guidance recommended the ikr assay and the in vivo qt telemetry study as mandatory assays for detecting potential torsades de pointes liability and relegated the cardiac action potential (ap) assay as a follo ...	2015	26091641
production of a high-affinity monoclonal antibody reactive with folate receptors alpha and beta.	folate receptors α (frα) and β (frβ) are two isoforms of the cell surface glycoprotein that binds folate. the expression of frα is rare in normal cells and elevated in cancer cells. thus, frα-based tumor-targeted therapy has been a focus area of laboratory research and clinical trials. recently, it was shown that a significant fraction of tumor-associated macrophages expresses frβ and that these cells can enhance tumor growth. although frα and frβ share 70% identity in their deduced amino acid s ...	2015	26090596
transplantation of macaca cynomolgus ips-derived hematopoietic cells in nsg immunodeficient mice.		2015	26088930
structural differences of amyloid-β fibrils revealed by antibodies from phage display.	beside neurofibrillary tangles, amyloid plaques are the major histological hallmarks of alzheimer's disease (ad) being composed of aggregated fibrils of β-amyloid (aβ). during the underlying fibrillogenic pathway, starting from a surplus of soluble aβ and leading to mature fibrils, multiple conformations of this peptide appear, including oligomers of various shapes and sizes. to further investigate the fibrillization of β-amyloid and to have tools at hand to monitor the distribution of aggregate ...	2015	26084577
macacine herpesvirus 1 in long-tailed macaques, malaysia, 2009-2011.	macacine herpesvirus 1 (mahv1; b virus) naturally infects macaques (macaca spp.) and can cause fatal encephalitis in humans. in peninsular malaysia, wild macaques are abundant, and translocation is used to mitigate human-macaque conflict. most adult macaques are infected with mahv1, although the risk for transmission to persons who handle them during capture and translocation is unknown. we investigated mahv1 shedding among 392 long-tailed macaques (m. fascicularis) after capture and translocati ...	2015	26080081
human plasma concentrations of cytochrome p450 probes extrapolated from pharmacokinetics in cynomolgus monkeys using physiologically based pharmacokinetic modeling.	1. cynomolgus monkeys are widely used in preclinical studies as non-human primate species. pharmacokinetics of human cytochrome p450 probes determined in cynomolgus monkeys after single oral or intravenous administrations were extrapolated to give human plasma concentrations. 2. plasma concentrations of slowly eliminated caffeine and r-/s-warfarin and rapidly eliminated omeprazole and midazolam previously observed in cynomolgus monkeys were scaled to human oral biomonitoring equivalents using kn ...	2015	26075833
using hidden markov models to determine changes in subject data over time, studying the immunoregulatory effect of mesenchymal stem cells.	a novel application of hidden markov models is used to help research intended to test the immunuregulatory effects of mesenchymal stem cells in a cynomolgus monkey model of islet transplantation. the hidden markov model, an unsupervised learning data mining technique, is used to automatically determine the postoperative day (pod) corresponding to a decrease of graft function, a possible sign of transplant rejection, on nonhuman primates after isolated islet cell transplant. currently, decrease o ...	2014	26075290
the highly-selective 5-ht(1a) agonist f15599 reduces l-dopa-induced dyskinesia without compromising anti-parkinsonian benefits in the mptp-lesioned macaque.	l-3,4-dihydroxyphenylalanine (l-dopa) is the most effective anti-parkinsonian agent available, but upon chronic administration, patients with parkinson's disease (pd) experience abnormal involuntary movements, dyskinesia. modulation of serotonin 1a (5-ht1a) receptors is regarded as an effective way to alleviate dyskinesia, yet this approach has been marred by a reduction of the therapeutic effectiveness of l-dopa. we hypothesised that highly-selective 5-ht1a stimulation might be a way to allevia ...	2015	26071982
using icr and scid mice as animal models for smallpox to assess antiviral drug efficacy.	the possibility of using immunocompetent icr mice and immunodeficient scid mice as model animals for smallpox to assess antiviral drug efficacy was investigated. clinical signs of the disease did not appear following intranasal (i.n.) challenge of mice with strain ind-3a of variola virus (varv), even when using the highest possible dose of the virus (5.2 log10 p.f.u.). the 50 % infective doses (id50) of varv, estimated by the virus presence or absence in the lungs 3 and 4 days post-infection, we ...	2015	26067292
a noncytolytic antibody-like extendin-4-igg4 fusion protein as a long-acting potential anti-diabetic agent.	glp-1 and its analogs have a variety of anti-diabetic effects. however, short half-life and rapid degraded by dpp-iv limits the therapeutic potential of the native glp-1. so, many dpp-iv-resistant and long-acting glp-1 analogs were developed. in this study, an antibody-like extendin-4-igg4 fusion protein was developed.	2015	26064256
drug-induced skin lesions in cynomolgus macaques treated with metabotropic glutamate receptor 5 (mglur5) negative allosteric modulators.	three orally administered metabotropic glutamate receptor 5 (mglur5) negative allosteric modulators caused skin lesions consistent with delayed type-iv hypersensitivity in cynomolgus macaques in 2- and 12-week toxicity studies. several monkeys developed macroscopic skin lesions in multiple locations after 8 to 9 days of dosing; the most prominent effects involved the genital region of males and generalized erythema occurred in both sexes. microscopic lesions occurred in both clinically affected ...	2015	26059827
effects of the glp-1 receptor agonist dulaglutide on the structure of the exocrine pancreas of cynomolgus monkeys.	clinical and nonclinical studies have implicated glucagon-like peptide-1 (glp-1) receptor agonist therapy as a risk factor for acute pancreatitis in patients with type 2 diabetes. therefore, it is critical to understand the effect that dulaglutide, an approved glp-1 receptor agonist, has on the exocrine pancreas. dulaglutide 8.15 mg/kg (approximately 500 times the maximum recommended human dose based on plasma exposure) was administered twice weekly for 12 months to cynomolgus monkeys. serum amy ...	2015	26059826
emergence of h7n9 influenza a virus resistant to neuraminidase inhibitors in nonhuman primates.	the number of patients infected with h7n9 influenza virus has been increasing since 2013. we examined the efficacy of neuraminidase (na) inhibitors and the efficacy of a vaccine against an h7n9 influenza virus, a/anhui/1/2013 (h7n9), isolated from a patient in a cynomolgus macaque model. na inhibitors (oseltamivir and peramivir) barely reduced the total virus amount because of the emergence of resistant variants with r289k or i219t in na [residues 289 and 219 in n9 of a/anhui/1/2013 (h7n9) corre ...	2015	26055368
widespread gene transfer in the central nervous system of cynomolgus macaques following delivery of aav9 into the cisterna magna.	adeno-associated virus serotype 9 (aav9) vectors have recently been shown to transduce cells throughout the central nervous system of nonhuman primates when injected into the cerebrospinal fluid (csf), a finding which could lead to a minimally invasive approach to treat genetic and acquired diseases affecting the entire cns. we characterized the transduction efficiency of two routes of vector administration into the csf of cynomolgus macaques-lumbar puncture, which is typically used in clinical ...	2014	26052519
neonatal exposure to sevoflurane may not cause learning and memory deficits and behavioral abnormality in the childhood of cynomolgus monkeys.	results of animal studies have raised a significant concern that commonly used general anesthetics may induce neurotoxicity in children. it may be difficult to resolve this concern with human studies because randomizing children only for testing anesthetic toxicity may not be feasible. we randomized 6-day old male cynomolgus monkeys to receive or not to receive sevoflurane anesthesia at surgical plane for 5 h. sevoflurane is the most commonly used general anesthetic in children in the u.s.a. her ...	2015	26046459
comparison of methods for determining abo blood type in cynomolgus macaques (macaca fascicularis).	thorough examination of abo blood type in cynomolgus monkeys is an essential experimental step to prevent humoral rejection during transplantation research. in the present study, we evaluated current methods of abo blood-antigen typing in cynomolgus monkeys by comparing the outcomes obtained by reverse hemagglutination, single-nucleotide polymorphism (snp) analysis, and buccal mucosal immunohistochemistry. among 21 animals, 5 were type a regardless of the method. however, of 8 serologically type ...	2015	26045449
effect of new training technique on affinity of cynomolgus monkeys for animal care personnel.	to confirm our hypothesis that the sex and age of cynomolgus monkeys influences the effect of training, we employed a new training technique designed to increase the animal's affinity for animal care personnel. during 151 days of training, monkeys aged 2 to 10 years accepted each 3 raisins/3 times/day, and communicated with animal care personnel (5 times/day). behavior was scored using integers between -1 and 5. before training, 35 of the 61 monkeys refused raisins offered directly by animal car ...	2015	26041546
pathobiology of hepatitis e: lessons learned from primate models.	like the other hepatitis viruses, hepatitis e virus (hev) has been difficult to study because of limitations in cell culture systems and small animal models. much of what we know has come from epidemiological studies in developing countries and, more recently, in industrialized countries. however, the epidemiology is very different in these two settings: hepatitis e in developing countries is epidemic as well as sporadic, principally water-borne, most likely to cause disease in older children an ...	2013	26038457
a novel hplc-ms/ms method for the simultaneous determination of astemizole and its major metabolite in dog or monkey plasma and application to pharmacokinetics.	astemizole (ast), a second-generation antihistamine, is metabolized to desmethyl astemizole (dea), and although it has been removed from the market for inducing qt interval prolongation, it has reemerged as a potential anticancer and antimalarial agent. this report describes a novel high-performance liquid chromatography-tandem mass spectrometry (hplc-ms/ms) method for simultaneously determining the concentrations of ast and dea in beagle dog and cynomolgus monkey plasma with simple preparation ...	2015	26037160
serum biomarkers of burkholderia mallei infection elucidated by proteomic imaging of skin and lung abscesses.	the bacterium burkholderia mallei is the etiological agent of glanders, a highly contagious, often fatal zoonotic infectious disease that is also a biodefense concern. clinical laboratory assays that analyze blood or other biological fluids are the highest priority because these specimens can be collected with minimal risk to the patient. however, progress in developing sensitive assays for monitoring b. mallei infection is hampered by a shortage of useful biomarkers.	2015	26034464
non-clinical safety evaluation of repeated intramuscular administration of the as15 immunostimulant combined with various antigens in rabbits and cynomolgus monkeys.	combination of tumor antigens with immunostimulants is a promising approach in cancer immunotherapy. we assessed animal model toxicity of as15 combined with various tumor antigens: wt1 (rabbits), or p501, dher2 and recprame (cynomolgus monkeys), administered in seven or 20 dose regimens versus a saline control. clinical and ophthalmological examinations, followed by extensive post-mortem pathological examinations, were performed on all animals. blood hematology and biochemistry parameters were a ...	2015	26032931
preclinical safety and efficacy studies with an affinity-enhanced epithelial junction opener and pegylated liposomal doxorubicin.	a central treatment resistance mechanism in solid tumors is the maintenance of epithelial junctions between malignant cells that prevent drug penetration into the tumor. we have developed a small recombinant protein (jo-1) that triggers the transient opening of intercellular junctions and thus increases the efficacy of monoclonal antibodies and chemotherapeutic drugs without causing toxicity in mouse tumor models. here, we provide data toward the clinical translation of an affinity-enhanced vers ...	2015	26029716
a novel wireless recording and stimulating multichannel epicortical grid for supplementing or enhancing the sensory-motor functions in monkey (macaca fascicularis).	artificial brain-machine interfaces (bmis) represent a prospective step forward supporting or replacing faulty brain functions. so far, several obstacles, such as the energy supply, the portability and the biocompatibility, have been limiting their effective translation in advanced experimental or clinical applications. in this work, a novel 16 channel chronically implantable epicortical grid has been proposed. it provides wireless transmission of cortical recordings and stimulations, with induc ...	2015	26029061
no assembly required: full-length mhc class i allele discovery by pacbio circular consensus sequencing.	single-molecule real-time (smrt) sequencing technology with the pacific biosciences (pacbio) rs ii platform offers the potential to obtain full-length coding regions (∼1100-bp) from mhc class i cdnas. despite the relatively high error rate associated with smrt technology, high quality sequences can be obtained by circular consensus sequencing (ccs) due to the random nature of the error profile. in the present study we first validated the ability of smrt-ccs to accurately identify class i transcr ...	2015	26028281
rat, mouse, and primate models of chronic glaucoma show sustained elevation of extracellular atp and altered purinergic signaling in the posterior eye.	the cellular mechanisms linking elevated iop with glaucomatous damage remain unresolved. mechanical strains and short-term increases in iop can trigger atp release from retinal neurons and astrocytes, but the response to chronic iop elevation is unknown. as excess extracellular atp can increase inflammation and damage neurons, we asked if sustained iop elevation was associated with a sustained increase in extracellular atp in the posterior eye.	2015	26024091
admixture in humans of two divergent plasmodium knowlesi populations associated with different macaque host species.	human malaria parasite species were originally acquired from other primate hosts and subsequently became endemic, then spread throughout large parts of the world. a major zoonosis is now occurring with plasmodium knowlesi from macaques in southeast asia, with a recent acceleration in numbers of reported cases particularly in malaysia. to investigate the parasite population genetics, we developed sensitive and species-specific microsatellite genotyping protocols and applied these to analysis of s ...	2015	26020959
glucagon receptor blockade with a human antibody normalizes blood glucose in diabetic mice and monkeys.	antagonizing glucagon action represents an attractive therapeutic option for reducing hepatic glucose production in settings of hyperglycemia where glucagon excess plays a key pathophysiological role. we therefore generated regn1193, a fully human monoclonal antibody that binds and inhibits glucagon receptor (gcgr) signaling in vitro. regn1193 administration to diabetic ob/ob and diet-induced obese mice lowered blood glucose to levels observed in gcgr-deficient mice. in diet-induced obese mice, ...	2015	26020795
ires-containing veev vaccine protects cynomolgus macaques from ie venezuelan equine encephalitis virus aerosol challenge.	venezuelan equine encephalitis virus (veev) is an arbovirus endemic to the americas that is responsible for severe, sometimes fatal, disease in humans and horses. we previously described an ires-based vee vaccine candidate based up the ie serotype that offers complete protection against a lethal subtype ie veev challenge in mice. here we demonstrate the ires-based vaccine's ability to protect against febrile disease in cynomolgus macaques. vaccination was well tolerated and elicited robust neutr ...	2015	26020513
a cd3xcd123 bispecific dart for redirecting host t cells to myelogenous leukemia: preclinical activity and safety in nonhuman primates.	current therapies for acute myeloid leukemia (aml) are largely ineffective, and aml patients may benefit from targeted immunotherapy approaches. mgd006 is a bispecific cd3xcd123 dual-affinity re-targeting (dart) molecule that binds t lymphocytes and cells expressing cd123, an antigen up-regulated in several hematological malignancies including aml. mgd006 mediates blast killing in aml samples, together with concomitant activation and expansion of residual t cells. mgd006 is designed to be rapidl ...	2015	26019218
a novel immunoassay to measure total serum lymphotoxin-α levels in the presence of an anti-ltα therapeutic antibody.	during drug development, measurement of suitable pharmacodynamic biomarkers is key to establishing in vivo drug activity. binding of monoclonal antibody (mab) therapeutics to soluble target proteins often results in elevated serum levels of their target antigen, and measuring total (free and bound) concentration of the target antigen can be an important means of demonstrating that the mab has reached its specific target. however, accurately measuring soluble circulating antigen in preclinical or ...	2015	26009247
animal models for ebolavirus countermeasures discovery: what defines a useful model?	ebolaviruses are highly pathogenic filoviruses, which cause disease in humans and nonhuman primates (nhp) in africa. the zaire ebolavirus outbreak in 2014, which continues to greatly affect western africa and other countries to which the hemorrhagic fever was exported due to travel of unsymptomatic yet infected individuals, was complicated by the lack of available licensed vaccines or therapeutics to combat infection. after almost a year of research at an increased pace to find and test vaccines ...	2015	26004783
in vivo histology of the myelin g-ratio with magnetic resonance imaging.	the myelin g-ratio, defined as the ratio between the inner and the outer diameter of the myelin sheath, is a fundamental property of white matter that can be computed from a simple formula relating the myelin volume fraction to the fiber volume fraction or the axon volume fraction. in this paper, a unique combination of magnetization transfer, diffusion imaging and histology is presented, providing a novel method for in vivo magnetic resonance imaging of the axon volume fraction and the myelin g ...	2015	26004502
a quantitative approach to developing parkinsonian monkeys (macaca fascicularis) with intracerebroventricular 1-methyl-4-phenylpyridinium injections.	non-human primate parkinson's disease (pd) models are essential for pd research. the most extensively used pd monkey models are induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp). however, the modeling processes of developing pd monkeys cannot be quantitatively controlled with mptp. therefore, a new approach to quantitatively develop chronic pd monkey models will help to advance the goals of "reduction, replacement and refinement" in animal experiments.	2015	26003862
codon-optimized filovirus dna vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal ebola and marburg virus challenges.	cynomolgus macaques were vaccinated by intramuscular electroporation with dna plasmids expressing codon-optimized glycoprotein (gp) genes of ebola virus (ebov) or marburg virus (marv) or a combination of codon-optimized gp dna vaccines for ebov, marv, sudan virus and ravn virus. when measured by elisa, the individual vaccines elicited slightly higher igg responses to ebov or marv than did the combination vaccines. no significant differences in immune responses of macaques given the individual or ...	0	25996997
the preclinical pharmacology of the high affinity anti-il-6r nanobody® alx-0061 supports its clinical development in rheumatoid arthritis.	the pleiotropic cytokine interleukin-6 (il-6) plays an important role in the pathogenesis of different diseases, including rheumatoid arthritis (ra). alx-0061 is a bispecific nanobody® with a high affinity and potency for il-6 receptor (il-6r), combined with an extended half-life by targeting human serum albumin. we describe here the relevant aspects of its in vitro and in vivo pharmacology.	2015	25994180
a method for estimating the glomerular filtration rate in conscious monkeys.	to establish a method for estimating the glomerular filtration rate (gfr) in conscious monkeys, the radiographic contrast medium iodixanol and the standard agent inulin were coadministered as tracers to male cynomolgus monkeys (macaca fascicularis) as a bolus injection; blood was collected after 60, 90 and 120 min. an equation based on a single-blood-sample method derived from jacobsson's formula was prepared using the data from healthy and saline- and gentamicin-treated monkeys by a multisample ...	2016	25994107
using immunoglobulin y as an alternative antibody for the detection of hepatitis a virus in frozen liver sections.	an increasing amount of research has been conducted on immunoglobulin y (igy) because the use of igy offers several advantages with respect to diagnostic testing, including its easy accessibility, low cost and translatability to large-scale production, in addition to the fact that it can be ethically produced. in a previous work, immunoglobulin was produced and purified from egg yolks (igy) reactive to hepatitis a virus (hav) antigens. in the present work, this anti-hav-specific igy was used in ...	2015	25993400
dehydroepiandrosterone sulfate, a useful endogenous probe for evaluation of drug-drug interaction on hepatic organic anion transporting polypeptide (oatp) in cynomolgus monkeys.	since drug-drug interaction (ddi) can affect organic anion-transporting polypeptide (oatp) and cause clinical events, prediction of such ddi is important in early clinical development. although statins are useful probes for oatp-mediated ddi, endogenous probes would be more practical for predicting such ddi. in this study, we investigate the possible use of dehydroepiandrosterone sulfate (dheas), an endogenous oatp substrate, in predicting oatp-mediated ddi in cynomolgus monkeys as a first step ...	2015	25989893
effects of group housing on ecg assessment in conscious cynomolgus monkeys.	assessing the cardiovascular safety of new chemical or biological entities is important during pre-clinical development. electrocardiogram (ecg) assessments in non-human primate (nhp) toxicology studies are often made using non-invasive telemetry systems. we investigated whether ecg recording was feasible during group housing of nhps, rather than the usual single housed arrangement, and whether it would impact the data collected or affect the ability to detect drug-induced changes in qtc interva ...	2015	25979821
prefrontal cortex afferents to the anterior temporal lobe in the macaca fascicularis monkey.	the anatomical organization of the lateral prefrontal cortex (lpfc) afferents to the anterior part of the temporal lobe (atl) remains to be clarified. the lpfc has two subdivisions, dorsal (dlpfc) and ventral (vlpfc), which have been linked to cognitive processes. the atl includes several different cortical areas, namely, the temporal polar cortex and rostral parts of the perirhinal, inferotemporal, and anterior tip of the superior temporal gyrus cortices. multiple sensory modalities converge in ...	2015	25975699
correction: examining the species-specificity of rhesus macaque cytomegalovirus (rhcmv) in cynomolgus macaques.		2015	25973867
microrna profiling in ethylene glycol monomethyl ether-induced monkey testicular toxicity model.	to establish and characterize ethylene glycol monomethyl ether (egme)-induced testicular toxicity model in cynomolgus monkeys, egme at 0 or 300 mg/kg was administered orally to sexually mature male cynomolgus monkeys (n = 3/group) for 4 consecutive days. circulating and testicular microrna (mirna) profiles in this model were investigated using mirna microarray or real-time quantitative reverse transcription-pcr methods. egme at 300 mg/kg induced testicular toxicity in all the monkeys, which was ...	2015	25972197
detection of cyclospora in captive chimpanzees and macaques by a quantitative pcr-based mutation scanning approach.	cyclospora is a protistan parasite that causes enteritis in several species of animals including humans. the aim of this study was to investigate the presence of cyclospora in captive non-human primates.	2015	25972100
anti-cd20/cd3 t cell-dependent bispecific antibody for the treatment of b cell malignancies.	bispecific antibodies and antibody fragments in various formats have been explored as a means to recruit cytolytic t cells to kill tumor cells. encouraging clinical data have been reported with molecules such as the anti-cd19/cd3 bispecific t cell engager (bite) blinatumomab. however, the clinical use of many reported t cell-recruiting bispecific modalities is limited by liabilities including unfavorable pharmacokinetics, potential immunogenicity, and manufacturing challenges. we describe a b ce ...	2015	25972002
there is more than one way to crack an oyster: identifying variation in burmese long-tailed macaque (macaca fascicularis aurea) stone-tool use.	we explored variation in patterns of percussive stone-tool use on coastal foods by burmese long-tailed macaques (macaca fascicularis aurea) from two islands in laem son national park, ranong, thailand. we catalogued variation into three hammering classes and 17 action patterns, after examining 638 tool-use bouts across 90 individuals. hammering class was based on the stone surface used for striking food, being face, point, and edge hammering. action patterns were discriminated by tool material, ...	2015	25970286
cholinergic neurons intrinsic to the primate external pallidum.	we report the presence of a small population of cholinergic neurons closely intermingled with external pallidal neurons in cynomolgus monkeys (macaca fascicularis). the majority of these cholinergic pallidal neurons are devoid of nerve growth factor receptor (ngfr), which sets them apart from the population of corticopetal ngfr-rich neurons of the nucleus basalis of meynert and its ectopic elements that impinge dorsally upon the pallidum via the medullary laminae.	2015	25967898
a temperature-monitoring vaginal ring for measuring adherence.	product adherence is a pivotal issue in the development of effective vaginal microbicides to reduce sexual transmission of hiv. to date, the six phase iii studies of vaginal gel products have relied primarily on self-reporting of adherence. accurate and reliable methods for monitoring user adherence to microbicide-releasing vaginal rings have yet to be established.	2015	25965956
angptl3 blockade with a human monoclonal antibody reduces plasma lipids in dyslipidemic mice and monkeys.	angiopoietin-like protein 3 (angptl3) is a circulating protein synthesized exclusively in the liver that inhibits lpl and endothelial lipase (el), enzymes that hydrolyze tgs and phospholipids in plasma lipoproteins. here we describe the development and testing of a fully human monoclonal antibody (regn1500) that binds angptl3 with high affinity. regn1500 reversed angptl3-induced inhibition of lpl activity in vitro. intravenous administration of regn1500 to normolipidemic c57bl/6 mice increased l ...	2015	25964512
monitoring gene expression in muscle tissue of macaca fascicularis under the influence of testosterone and sarm.	the focus of this study was to evaluate data on the gene expression profiles induced by testosterone and a selective androgen receptor modulator (sarm, tap pharmaceutical products inc., lake forest, il, usa) in androgen sensitive muscle tissue to obtain a better understanding on the molecular mechanisms of action and to identify biomarkers for sarm function in primate organs. a total of 24 male cyomolgus monkeys were divided into four groups: testosterone group, sarm1 group, sarm10 group, and co ...	2010	25961973
no costly prosociality among related long-tailed macaques (macaca fascicularis).	altruism, benefiting another at a cost to the donor, may be achieved through prosocial behavior. studies of nonhuman animals typically investigate prosocial behavior with paradigms in which the donor can choose to give a recipient a food item, and the choice does not affect the donor's reward (which is either present or absent). in such tasks, long-tailed macaques (macaca fascicularis) show prosocial behavior, especially toward kin. here, we tested captive long-tailed macaques with related recip ...	2015	25961651
telemetric assessment of social and single housing: evaluation of electrocardiographic intervals in jacketed cynomolgus monkeys.	proactive efforts to socially house laboratory animals are a contemporary, important focus for enhancing animal welfare. jacketing cynomolgus monkeys has been traditionally considered an exclusionary criterion for social housing based on unsubstantiated concerns that study conduct or telemetry equipment might be compromised. our objective was to evaluate the effects of jacketing naïve, adolescent cynomolgus monkeys in different single and social housing types based on parallel comparisons of hea ...	2015	25959881
immune response to marburg virus angola infection in nonhuman primates.	the 2005 outbreak of marburg virus (marv) infection in angola was the most lethal marv infection outbreak in history, with a case-fatality rate (90%) similar to that for zaire ebolavirus (ebov) infection. however, very little is known about the pathogenicity of marv angola, as few studies have been conducted to date. therefore, the immune response was examined in marv angola-infected nonhuman primates.	2015	25957966
adenovirus-vectored vaccine provides postexposure protection to ebola virus-infected nonhuman primates.	ebola virus (ebov) causes lethal disease in up to 90% of ebov-infected humans. among vaccines, only the vesicular stomatitis virus platform has been successful in providing postexposure protection in nonhuman primates. here, we show that an adjuvanted human adenovirus serotype 5 (ad5)-vectored vaccine (ad5-zaire ebov glycoprotein) protected 67% (6 of 9) and 25% (1 of 4) of cynomolgus macaques when administered 30 minutes and 24 hours following ebov challenge, respectively. the treatment also pro ...	2015	25957963
comprehensive evaluation for substrate selectivity of cynomolgus monkey cytochrome p450 2c9, a new efavirenz oxidase.	cynomolgus monkeys are widely used as primate models in preclinical studies, because of their evolutionary closeness to humans. in humans, the cytochrome p450 (p450) 2c enzymes are important drug-metabolizing enzymes and highly expressed in livers. the cyp2c enzymes, including cyp2c9, are also expressed abundantly in cynomolgus monkey liver and metabolize some endogenous and exogenous substances like testosterone, s-mephenytoin, and diclofenac. however, comprehensive evaluation regarding substra ...	2015	25948712
pandemic swine-origin h1n1 influenza virus replicates to higher levels and induces more fever and acute inflammatory cytokines in cynomolgus versus rhesus monkeys and can replicate in common marmosets.	the close immunological and physiological resemblance with humans makes non-human primates a valuable model for studying influenza virus pathogenesis and immunity and vaccine efficacy against infection. although both cynomolgus and rhesus macaques are frequently used in influenza virus research, a direct comparison of susceptibility to infection and disease has not yet been performed. in the current study a head-to-head comparison was made between these species, by using a recently described swi ...	2015	25946071
a combination of alfaxalone and medetomidine followed by an alfaxalone continuous rate infusion in cynomolgus monkeys (macaca fascicularis) undergoing pharmacomrs.		2015	25943584
b-1 lymphocytes in mice and nonhuman primates.	b-1 cells comprise subpopulations of b lymphocytes in mice that display developmental, phenotypic, and functional characteristics that are distinct from those of conventional b cell populations (b-2 cells). despite the known importance of murine b-1a (cd5(+) ) and b-1b (cd5(-) ) cells in the production of natural antibodies and rapid antigen-specific humoral responses to infection, evidence for b-1 cells in primates, including humans, is very limited. identifying these cells in humans proves cha ...	2015	25930711
monkeys and rats are not susceptible to ferret hepatitis e virus infection.	ferret hepatitis e virus (hev), a novel hepatitis e-like virus, has been identified in ferrets in the netherlands, japan, and the us. to determine whether ferret hev transmits to other animals, we inoculated laboratory rats (wistar), nude rats (long-evans-rnu/rnu), and cynomolgus monkeys with ferret hev (f4351) by intravenous injection. none of the animals demonstrated a positive sign for virus replication, indicating that rats and monkeys are not susceptible to ferret hev.	2015	25925280
relationship between estradiol and progesterone concentrations and cognitive performance in normally cycling female cynomolgus monkeys.	preclinical research has demonstrated that cognitive function may be influenced by estradiol (e2) and progesterone (p4) concentrations, although few cognition studies involve normally cycling females. the present study examined cognitive performance in normally cycling female cynomolgus macaques (n = 14), a species with similarities to humans in brain organization and a nearly identical menstrual cycle to women. initial assessments compared cognitive measures to circulating concentrations of e2 ...	2015	25921587
effects of chronic manganese exposure on attention and working memory in non-human primates.	manganese (mn) is essential for a variety of physiological processes, but at elevated levels, can be neurotoxic. while cognitive dysfunction has been recently appreciated to occur as a result of chronic mn exposures, it is still unclear as to which cognitive domains are most susceptible to disruption by mn exposure. we previously described early appearing mn-induced changes in performance on a paired associate learning task in monkeys chronically exposed to mn and suggested that performance of t ...	2015	25917687