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https://www.readbyqxmd.com/read/28727150/generalized-convulsive-seizures-are-associated-with-ketamine-anesthesia-in-a-rhesus-macaque-macaca-mulatta-undergoing-urodynamic-studies-and-transcutaneous-spinal-cord-stimulation
#1
Parag N Gad, Gregory W Salyards, Laura M Garzel, Kari L Christe, V Reggie Edgerton, Leif A Havton
A female rhesus macaque developed two episodes of generalized convulsions during transcutaneous spinal cord stimulation (TSCS) and urodynamic studies under ketamine anesthesia. The seizures took place in the absence of active TSCS and bladder pressure elevation. Ketamine anesthesia remains the primary risk factor for the convulsions during these experimental procedures.
July 20, 2017: Journal of Medical Primatology
https://www.readbyqxmd.com/read/28726496/a-preclinical-study-in-rhesus-macaques-for-cystic-fibrosis-to-assess-gene-transfer-and-transduction-by-aav1-and-aav5-with-a-dual-luciferase-reporter-system
#2
William Guggino, Janet Benson, JeanClare Seagrave, Ziying Yan, John F Engelhardt, Guangping Gao, Thomas J Conlon, Liudmila Cebotaru
Cystic fibrosis (CF) is an autosomal recessive disease that is potentially treatable by gene therapy. Since the identification of the gene encoding CFTR, a number of preclinical and clinical trials have been conducted using the first generation of adeno-associated virus, AAV2. All these studies showed that AAV gene therapy for CF is safe, but clinical benefit was not clearly demonstrated. Thus, a new generation of AAV Vectors based on other serotypes is needed to move the field forward. Here we have tested two AAV serotypes (AAV1 and AAV5), using a dual-luciferase reporter system with firefly and Renilla luciferase genes packaged into AAV1 or AAV5, respectively...
July 20, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28725019/high-dose-sertraline-monotherapy-fails-to-protect-rhesus-macaques-from-lethal-challenge-with-ebola-virus-makona
#3
Anna N Honko, Joshua C Johnson, Jonathan S Marchand, Louis Huzella, Ricky D Adams, Nicholas Oberlander, Lisa M Torzewski, Richard S Bennett, Lisa E Hensley, Peter B Jahrling, Gene G Olinger
The recent epidemic of Ebola virus disease in West Africa resulted in an unprecedented number of cases and deaths. Due to the scope of the outbreak combined with the lack of available approved treatment options, there was strong motivation to investigate any potential drug which had existing data reporting anti-Ebola activity. Drugs with demonstrated antiviral activity in the nonhuman primate models already approved for another indication or for which there was existing safety data were considered to be priorities for evaluation by the World Health Organization...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724494/pharmacokinetics-of-a-novel-transdermal-fentanyl-solution-in-rhesus-macaques-macaca-mulatta
#4
Gregory W Salyards, Marie-Josee Lemoy, Heather K Knych, Ashley E Hill, Kari L Christe
Rhesus macaques (Macaca mulatta) are the most commonly used NHP biomedical model and experience both research and clinical procedures requiring analgesia. Opioids are a mainstay of analgesic therapy. A novel, transdermal fentanyl solution (TFS) has been developed as a long-acting, single-administration topical opioid and was reported to provide at least 4 d of effective plasma concentrations in beagles (Canis familiaris). To evaluate the pharmacokinetic profile of TFS in healthy adult rhesus macaques, we used a 2-period, 2-treatment crossover study of a single topical administration of 1...
July 1, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28724489/population-genetic-structure-of-the-cayo-santiago-colony-of-rhesus-macaques-macaca-mulatta
#5
Sreetharan Kanthaswamy, Robert F Oldt, Jillian Ng, Angelina V Ruiz-Lambides, Elizabeth Maldonado, Melween I Martínez, Carlos A Sariol
The rhesus macaque population at Cayo Santiago increases annually and is in urgent need of control. In-depth assessments of the colony's population genetic and pedigree structures provide a starting point for improving the colony's long-term management program. We evaluated the degree of genetic variation and coefficients of inbreeding and kinship of the Cayo Santiago colony by using pedigree and short tandem repeat (STR) data from 4738 rhesus macaques, which represent 7 extant social groups and a group of migrant males...
July 1, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28724484/echocardiographic-parameters-of-clinically-normal-geriatric-rhesus-macaques-macacamulatta
#6
Yu Ueda, Catherine T Gunther-Harrington, Christina L Cruzen, Jeffrey A Roberts, Joshua A Stern
The goal of this study was to generate reference intervals for echocardiographic variables in a population of clinically normal geriatric rhesus macaques (Macaca mulatta). To do this, we studied 51 animals (age, 18-29 y; weight, 5.24-17.04 kg). The normal values for cardiac indices, including geometry and systolic and diastolic function, were determined by 2D, M-mode, spectral Doppler, and tissue Doppler echocardiography under ketamine hydrochloride sedation. Statistical correlations between the echocardiographic parameters and age, body weight, sex, and heart rate were investigated...
July 1, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28722685/neural-control-of-finger-movement-via-intracortical-brain-machine-interface
#7
Zachary T Irwin, Karen E Schroeder, Philip P Vu, Autumn J Bullard, Derek M Tat, Chrono S Nu, Alex Vaskov, Samuel R Nason, David E Thompson, Nicole Bentley, Parag G Patil, Cynthia A Chestek
OBJECTIVE: Intracortical brain-machine interfaces (BMIs) are a promising source of prosthesis control signals for individuals with severe motor disabilities. Previous BMI studies have primarily focused on predicting and controlling whole-arm movements; precise control of hand kinematics, however, has not been fully demonstrated. Here, we investigate the continuous decoding of precise finger movements in rhesus macaques. APPROACH: In order to elicit precise and repeatable finger movements, we have developed a novel behavioral task paradigm which requires the subject to acquire virtual fingertip position targets...
July 19, 2017: Journal of Neural Engineering
https://www.readbyqxmd.com/read/28720462/a-novel-trivalent-hpv-16-18-58-vaccine-with-anti-hpv-16-and-18-neutralizing-antibody-responses-comparable-to-those-induced-by-the-gardasil-quadrivalent-vaccine-in-rhesus-macaque-model
#8
Fei Yin, Yajun Wang, Na Chen, Dunquan Jiang, Yefeng Qiu, Yan Wang, Mei Yan, Jianping Chen, Haijiang Zhang, Yongjiang Liu
Persistent infection with human papillomavirus (HPV) is a key factor in the development of precancerous lesions and invasive cervical cancer. Prophylactic vaccines to immunize against HPV are an effective approach to reducing HPV related disease burden. In this study, we investigated the immunogenicity and dosage effect of a trivalent HPV 16/18/58 vaccine (3vHPV) produced in Escherichia coli (E.coli), with Gardasil quadrivalent vaccine (4vHPV, Merck & Co.) as a positive control. Sera collected from rhesus macaques vaccinated with three dosage formulations of 3vHPV (termed low-, mid-, and high-dosage formulations, respectively), and the 4vHPV vaccine were analyzed by both Pseudovirus-Based Neutralization Assay (PBNA) and Enzyme-Linked Immunosorbent Assay (ELISA)...
June 2017: Papillomavirus Research
https://www.readbyqxmd.com/read/28719653/isolation-of-a-monoclonal-antibody-from-a-phage-display-library-binding-the-rhesus-macaque-mhc-class-i-allomorph-mamu-a1-001
#9
Nathan Holman, Jason T Weinfurter, Trevor R Harsla, Roger W Wiseman, Aaron J Belli, Anthony J Michaels, Keith A Reimann, Robert I DeMars, Matthew R Reynolds
Monoclonal antibodies that bind to human leukocyte antigen (HLA) are useful tools for HLA-typing, tracking donor-recipient chimerisms after bone marrow transplants, and characterizing specific major histocompatibility complexes (MHC) on cell surfaces. Unfortunately, equivalent reagents are not available for rhesus macaques, which are commonly used animal as models in organ transplant and infectious disease research. To address this deficiency, we isolated an antibody that recognizes the common Indian rhesus macaque MHC class I molecule, Mamu-A1*001...
2017: PloS One
https://www.readbyqxmd.com/read/28715405/identification-and-pathological-characterization-of-persistent-asymptomatic-ebola-virus-infection-in-rhesus-monkeys
#10
Xiankun Zeng, Candace D Blancett, Keith A Koistinen, Christopher W Schellhase, Jeremy J Bearss, Sheli R Radoshitzky, Shelley P Honnold, Taylor B Chance, Travis K Warren, Jeffrey W Froude, Kathleen A Cashman, John M Dye, Sina Bavari, Gustavo Palacios, Jens H Kuhn, Mei G Sun
Ebola virus (EBOV) persistence in asymptomatic humans and Ebola virus disease (EVD) sequelae have emerged as significant public health concerns since the 2013-2016 EVD outbreak in Western Africa. Until now, studying how EBOV disseminates into and persists in immune-privileged sites was impossible due to the absence of a suitable animal model. Here, we detect persistent EBOV replication coinciding with systematic inflammatory responses in otherwise asymptomatic rhesus monkeys that had survived infection in the absence of or after treatment with candidate medical countermeasures...
July 17, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28712672/noise-induced-cochlear-synaptopathy-in-rhesus-monkeys-macaca-mulatta
#11
M D Valero, J A Burton, S N Hauser, T A Hackett, R Ramachandran, M C Liberman
Cochlear synaptopathy can result from various insults, including acoustic trauma, aging, ototoxicity, or chronic conductive hearing loss. For example, moderate noise exposure in mice can destroy up to ∼50% of synapses between auditory nerve fibers (ANFs) and inner hair cells (IHCs) without affecting outer hair cells (OHCs) or thresholds, because the synaptopathy occurs first in high-threshold ANFs. However, the fiber loss likely impairs temporal processing and hearing-in-noise, a classic complaint of those with sensorineural hearing loss...
July 8, 2017: Hearing Research
https://www.readbyqxmd.com/read/28712361/plasmodium-knowlesi-a-superb-in-vivo-nonhuman-primate-model-of-antigenic-variation-in-malaria
#12
M R Galinski, S A Lapp, M S Peterson, F Ay, C J Joyner, K G LE Roch, L L Fonseca, E O Voit
Antigenic variation in malaria was discovered in Plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (M. mulatta). The variant proteins, known as the P. knowlesi Schizont Infected Cell Agglutination (SICA) antigens and the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) antigens, expressed by the SICAvar and var multigene families, respectively, have been studied for over 30 years. Expression of the SICA antigens in P. knowlesi requires a splenic component, and specific antibodies are necessary for variant antigen switch events in vivo...
July 17, 2017: Parasitology
https://www.readbyqxmd.com/read/28709963/animal-models-of-biliary-injury-and-altered-bile-acid-metabolism
#13
REVIEW
Valeria Mariotti, Mario Strazzabosco, Luca Fabris, Diego F Calvisi
In the last 25years, a number of animal models, mainly rodents, have been generated with the goal to mimic cholestatic liver injuries and, thus, to provide in vivo tools to investigate the mechanisms of biliary repair and, eventually, to test the efficacy of innovative treatments. Despite fundamental limitations applying to these models, such as the distinct immune system and the different metabolism regulating liver homeostasis in rodents when compared to humans, multiple approaches, such as surgery (bile duct ligation), chemical-induced (3,5-diethoxycarbonyl-1,4-dihydrocollidine, DDC, α-naphthylisothiocyanate, ANIT), viral infections (Rhesus rotavirustype A, RRV-A), and genetic manipulation (Mdr2, Cftr, Pkd1, Pkd2, Prkcsh, Sec63, Pkhd1) have been developed...
July 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28708886/kir3dl01-upregulation-on-gut-natural-killer-cells-in-response-to-siv-infection-of-kir-and-mhc-class-i-defined-rhesus-macaques
#14
Moritz Ries, Matthew R Reynolds, Ksenia Bashkueva, Kristin Crosno, Saverio Capuano, Trent M Prall, Roger Wiseman, David H O'Connor, Eva G Rakasz, Hajime Uno, Jeffrey D Lifson, David T Evans
Natural killer cells provide an important early defense against viral pathogens and are regulated in part by interactions between highly polymorphic killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their MHC class I ligands on target cells. We previously identified MHC class I ligands for two rhesus macaque KIRs: KIR3DL01 recognizes Mamu-Bw4 molecules and KIR3DL05 recognizes Mamu-A1*002. To determine how these interactions influence NK cell responses, we infected KIR3DL01+ and KIR3DL05+ macaques with and without defined ligands for these receptors with SIVmac239, and monitored NK cell responses in peripheral blood and lymphoid tissues...
July 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28705990/systemic-pan-ampk-activator-mk-8722-improves-glucose-homeostasis-but-induces-cardiac-hypertrophy
#15
Robert W Myers, Hong-Ping Guan, Juliann Ehrhart, Aleksandr Petrov, Srinivasa Prahalada, Effie Tozzo, Xiaodong Yang, Marc M Kurtz, Maria Trujillo, Dinko Gonzalez Trotter, Danqing Feng, Shiyao Xu, George Eiermann, Marie A Holahan, Daniel Rubins, Stacey Conarello, Xiaoda Niu, Sandra C Souza, Corin Miller, Jinqi Liu, Ku Lu, Wen Feng, Ying Li, Ronald E Painter, James A Milligan, Huaibing He, Franklin Liu, Aimie Ogawa, Douglas Wisniewski, Rory J Rohm, Liyang Wang, Michelle Bunzel, Ying Qian, Wei Zhu, Hongwu Wang, Bindu Bennet, Lisa LaFranco Scheuch, Guillermo E Fernandez, Cai Li, Michael Klimas, Gaochao Zhou, Margaret van Heek, Tesfaye Biftu, Ann Weber, David E Kelley, Nancy Thornberry, Mark D Erion, Daniel M Kemp, Iyassu K Sebhat
5'-Adenosine monophosphate-activated protein kinase (AMPK) is a master regulator of energy homeostasis in eukaryotes. Despite investigations over three decades, the biological roles of AMPK and its potential as a drug target remain incompletely understood, due largely to the lack of optimized pharmacological tools. We now report MK-8722, a potent, direct, allosteric activator of all twelve mammalian AMPK complexes. In rodents and rhesus monkeys, MK-8722-mediated AMPK activation in skeletal muscle induces robust, durable, insulin-independent glucose uptake and glycogen synthesis, with resultant improvements in glycemia and no evidence of hypoglycemia...
July 13, 2017: Science
https://www.readbyqxmd.com/read/28704181/the-impact-of-hyperglycemia-on-vegf-secretion-in-retinal-endothelial-cells
#16
Martin Caprnda, Peter Kubatka, Sandeep Saxena, Jela Valaskova, Jana Stefanickova, Nazarii Kobyliak, Anthony Zulli, Peter Kruzliak
BACKGROUND: Diabetic retinopathy is a serious sight-threatening complication which is manifested by excessive angiogenesis in diabetic patients. AIM: We hypothesize that cultured Rhesus monkey retinal endothelial cells (RhRECs) respond to high glucose with a change in cell proliferation and vascular endothelial growth factor (VEGF) secretion. MATERIALS AND METHODS: In our study, 20 000 cells per well were treated without glucose or with 5...
June 1, 2017: Folia Medica
https://www.readbyqxmd.com/read/28701795/terahertz-spectroscopic-diagnosis-of-myelin-deficit-brain-in-mice-and-rhesus-monkey-with-chemometric-techniques
#17
Yi Zou, Jiang Li, Yiyuan Cui, Peiren Tang, Lianghui Du, Tunan Chen, Kun Meng, Qiao Liu, Hua Feng, Jianheng Zhao, Mina Chen, Li-Guo Zhu
While myelin deficit of the central nervous system leads to several severe diseases, the definitive diagnostic means are lacking. We proposed and performed terahertz time-domain spectroscopy (THz-TDS) combined with chemometric techniques to discriminate and evaluate the severity of myelin deficit in mouse and rhesus monkey brains. The THz refractive index and absorption coefficient of paraffin-embedded brain tissues from both normal and mutant dysmyelinating mice are shown. Principal component analysis of time-domain THz signal (PCA-tdTHz) and absorption-refractive index relation of THz spectrum identified myelin deficit without exogenous labeling or any pretreatment...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701536/spatially-tuned-normalization-explains-attention-modulation-variance-within-neurons
#18
Amy M Ni, John H R Maunsell
Spatial attention improves perception of attended parts of a scene, a behavioral enhancement accompanied by modulations of neuronal firing rates. These modulations vary in size across neurons in the same brain area. Models of normalization explain much of this variance in attention modulation with differences in tuned normalization across neurons (Lee and Maunsell 2009; Ni et al. 2012). However, recent studies suggest that normalization tuning varies with spatial location both across and within neurons (Ruff et al...
July 12, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28701402/increased-durable-b-cell-and-adcc-responses-associated-with-t-helper-responses-to-hiv-1-envelope-in-macaques-vaccinated-with-gp140-occluded-at-the-cd4-receptor-binding-site
#19
Willy M J M Bogers, Susan W Barnett, Herman Oostermeijer, Ivonne G Nieuwenhuis, Niels Beenhakker, Daniella Mortier, Petra Mooij, Gerrit Koopman, Edmund Remarque, Gregoire Martin, Rachel Pei-Jen Lai, Antu K Dey, Yide Sun, Brian Burke, Guido Ferrari, David Montefiori, Loic Martin, David Davis, Indresh Srivastava, Jonathan L Heeney
Strategies are needed to improve the immunogenicity of HIV-1 envelope (Env) antigens for more long lived, efficacious HIV-1 vaccine induced B-cell responses. HIV-1 Env gp140 (native or un-cleaved molecules) or gp120 monomeric proteins elicit relatively poor B-cell responses which are short-lived. We hypothesized that Env engagement of the CD4 receptor on T-helper cells may result in anergic effects on T-cell recruitment and consequently a lack of strong robust and durable B-memory responses. To test this hypothesis we occluded the CD4 binding site (CD4bs) of gp140 by stable cross-linking with a 3kD CD4 miniprotein mimetic serving to block ligation of gp140 on CD4+T-cells while preserving CD4 inducible (CDi) neutralizing and epitopes targeted by antibody dependent cellular cytotoxic (ADCC) effector responses...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28701394/single-particle-detection-of-transcription-following-rotavirus-entry
#20
Eric N Salgado, Srigokul Upadhyayula, Stephen C Harrison
Infectious rotavirus particles are triple-layered, icosahedral assemblies. The outer layer proteins, VP4 (cleaved to VP8* and VP5*) and VP7, surround a transcriptionally competent, double-layer particle (DLP), which they deliver into the cytosol. During entry of rhesus rotavirus, VP8* interacts with cell-surface gangliosides, allowing engulfment into a membrane vesicle by a clathrin-independent process. Escape into the cytosol and outer-layer shedding depend on interaction of a hydrophobic surface on VP5* with the membrane bilayer and on a large-scale conformational change...
July 12, 2017: Journal of Virology
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