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https://www.readbyqxmd.com/read/28328310/developing-human-radiation-biodosimetry-models-testing-cross-species-conversion-approaches-using-an-ex-vivo-model-system
#1
Jin G Park, Sunirmal Paul, Natalia Briones, Jia Zeng, Kristin Gillis, Garrick Wallstrom, Joshua LaBaer, Sally A Amundson
In the event of a large-scale radiation exposure, accurate and quick assessment of radiation dose received would be critical for triage and medical treatment of large numbers of potentially exposed individuals. Current methods of biodosimetry, such as the dicentric chromosome assay, are time consuming and require sophisticated equipment and highly trained personnel. Therefore, scalable biodosimetry approaches, including gene expression profiles in peripheral blood cells, are being investigated. Due to the limited availability of appropriate human samples, biodosimetry development has relied heavily on mouse models, which are not directly applicable to human response...
March 22, 2017: Radiation Research
https://www.readbyqxmd.com/read/28321697/robust-gene-expression-changes-in-the-ganglia-following-subclinical-reactivation-in-rhesus-macaques-infected-with-simian-varicella-virus
#2
Nicole Arnold, Christine Meyer, Flora Engelmann, Ilhem Messaoudi
Varicella zoster virus (VZV) causes varicella during acute infection and establishes latency in the sensory ganglia. Reactivation of VZV results in herpes zoster, a debilitating and painful disease. It is believed that VZV reactivates due to a decline in cell-mediated immunity; however, the roles that CD4 versus CD8 T cells play in the prevention of herpes zoster remain poorly understood. To address this question, we used a well-characterized model of VZV infection where rhesus macaques are intrabronchially infected with the homologous simian varicella virus (SVV)...
March 20, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28319449/non-clinical-study-examining-aav8-tbg-hldlr-vector-associated-toxicity-in-chow-fed-wild-type-and-ldlr-rhesus-macaques
#3
Jenny A Greig, Maria P Limberis, Peter Bell, Shu-Jen Chen, Roberto Calcedo, Daniel J Rader, James M Wilson
Vectors based on adeno-associated virus serotype 8 (AAV8) have been evaluated in several clinical trials of gene therapy for hemophilia B with encouraging results. In preparation for a Phase 1 clinical trial of AAV8 gene therapy for the treatment of homozygous familial hypercholesterolemia (HoFH), the safety of the clinical candidate vector, AAV8.TBG.hLDLR, was evaluated in wild-type rhesus macaques and macaques heterozygous for a nonsense mutation in the low-density lipoprotein receptor (LDLR) gene (LDLR(+/-))...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28317062/interhemispheric-gene-expression-differences-in-the-cerebral-cortex-of-humans-and-macaque-monkeys
#4
Gerard Muntané, Gabriel Santpere, Andrey Verendeev, William W Seeley, Bob Jacobs, William D Hopkins, Arcadi Navarro, Chet C Sherwood
Handedness and language are two well-studied examples of asymmetrical brain function in humans. Approximately 90% of humans exhibit a right-hand preference, and the vast majority shows left-hemisphere dominance for language function. Although genetic models of human handedness and language have been proposed, the actual gene expression differences between cerebral hemispheres in humans remain to be fully defined. In the present study, gene expression profiles were examined in both hemispheres of three cortical regions involved in handedness and language in humans and their homologues in rhesus macaques: ventrolateral prefrontal cortex, posterior superior temporal cortex (STC), and primary motor cortex...
March 19, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28315649/comparison-of-saliva-collection-methods-for-the-determination-of-salivary-cortisol-levels-in-rhesus-macaques-macaca-mulatta-cynomolgus-macaques-macaca-fascicularis-and-african-green-monkeys-chlorocebus-aethiops
#5
Kamala J Rapp-Santos, Louis A Altamura, Sarah L Norris, Luis A Lugo-Roman, Pedro J Rico, Christian C Hofer
The ability to quickly and accurately determine cortisol as a biomarker for stress is a valuable tool in assessing the wellbeing of NHP. In this study, 2 methods of collecting saliva (a commercial collection device and passive drool) and the resulting free salivary cortisol levels were compared with total serum cortisol concentration in rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis) and African green monkeys (Chlorocebus aethiops) at 2 collection time points. Serum and salivary cortisol levels were determined using a competitive quantitative ELISA...
March 1, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28315640/effects-of-human-management-events-on-conspecific-aggression-in-captive-rhesus-macaques-macaca-mulatta
#6
Jacob H Theil, Brianne A Beisner, Ashley E Hill, Brenda McCowan
Conspecific aggression in outdoor-housed rhesus macaques (Macaca mulatta) at primate research facilities is a leading source of trauma and can potentially influence animal wellbeing and research quality. Although aggression between macaques is a normal part of daily social interactions, human presence might affect the frequency of various behaviors and instigate increases in conspecific aggression. We sought to determine how and which human management events affect conspecific aggression both immediately after an event and throughout the course of a day...
March 1, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28314593/25-hydroxycholesterol-protects-host-against-zika-virus-infection-and-its-associated-microcephaly-in-a-mouse-model
#7
Chunfeng Li, Yong-Qiang Deng, Shuo Wang, Feng Ma, Roghiyh Aliyari, Xing-Yao Huang, Na-Na Zhang, Momoko Watanabe, Hao-Long Dong, Ping Liu, Xiao-Feng Li, Qing Ye, Min Tian, Shuai Hong, Junwan Fan, Hui Zhao, Lili Li, Neda Vishlaghi, Jessie E Buth, Connie Au, Ying Liu, Ning Lu, Peishuang Du, F Xiao-Feng Qin, Bo Zhang, Danyang Gong, Xinghong Dai, Ren Sun, Bennett G Novitch, Zhiheng Xu, Cheng-Feng Qin, Genhong Cheng
Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28304255/neurocysticercosis-in-a-rhesus-macaque-macaca-mulatta
#8
Jessica M Johnston, Cecilia D Dyer, Susan Madison-Antenucci, Kimberly Am Mergen, Christin L Veeder, Angela K Brice
An 8-y-old, intact, male rhesus macaque (Macaca mulatta) was sedated to undergo MRI in preparation for the implantation of cranial hardware. During imaging, 9 focal lesions were noted in the brain and musculature of the head. The lesions were hyperechoic with hypoechoic rims. The animal was deemed inappropriate for neuroscience research, and euthanasia was elected. Gross examination revealed multiple round, thick-walled, fluid-filled cysts (diameter, approximately 0.5 cm) in multiple tissues: one each in the left caudal lung lobe, left masseter muscle, and the dura overlying the brain and 8 throughout the gray and white matter of the brain parenchyma...
December 1, 2016: Comparative Medicine
https://www.readbyqxmd.com/read/28304253/ventricular-parasystole-in-a-neonatal-rhesus-macaque-macaca-mulatta
#9
Dalis E Collins, Brandy L Dozier, Jeffrey J Stanton, Lois Ma Colgin, Rhonda MacAllister
A 6-d-old Indian-origin female rhesus macaque (Macaca mulatta) presented with bradycardia shortly after sedation with ketamine. No other cardiac abnormalities were apparent. Approximately 2 wk after the initial presentation, the macaque was again bradycardic and exhibited a regularly irregular arrhythmia on a prestudy examination. ECG, echocardiography, blood pressure measurement, SpO2 assessment, and a CBC analysis were performed. The echocardiogram and bloodwork were normal, but the infant was hypotensive at the time of echocardiogram...
December 1, 2016: Comparative Medicine
https://www.readbyqxmd.com/read/28304251/using-hematology-data-from-malaria-vaccine-research-trials-in-humans-and-rhesus-macaques-macaca-mulatta-to-guide-volume-limits-for-blood-withdrawal
#10
Sara R Hegge, Bradley W Hickey, Shannon M Mcgrath, V Ann Stewart
Guidelines on safe volume limits for blood collection from research participants in both humans and laboratory animals vary widely between institutions. The main adverse event that may be encountered in large blood volume withdrawal is iron-deficiency anemia. Monitoring various parameters in a standard blood panel may help to prevent this outcome. To this end, we analyzed the Hgb and MCV values from 43 humans and 46 macaques in malaria vaccine research trials. Although the percentage of blood volume removed was greater for macaques than humans, macaques demonstrated an overall increase of MCV over time, indicating the ability to respond appropriately to frequent volume withdrawals...
December 1, 2016: Comparative Medicine
https://www.readbyqxmd.com/read/28302457/mucosal-vaccination-with-heterologous-viral-vectored-vaccine-targeting-subdominant-siv-accessory-antigens-strongly-inhibits-early-viral-replication
#11
Huanbin Xu, Anne-Marie Andersson, Emeline Ragonnaud, Ditte Boilesen, Anders Tolver, Benjamin Anderschou Holbech Jensen, James L Blanchard, Alfredo Nicosia, Antonella Folgori, Stefano Colloca, Riccardo Cortese, Allan Randrup Thomsen, Jan Pravsgaard Christensen, Ronald S Veazey, Peter Johannes Holst
Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat, vif, rev and vpr antigens fused to the MHC class II associated invariant chain. Immunizations induced broad T cell responses in all vaccinees. Following up to 10 repeated low-dose intrarectal challenges, vaccinees suppressed early viral replication (P=0...
March 8, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28298605/cxcr5-dependent-entry-of-cd8-t-cells-into-rhesus-macaque-b-cell-follicles-achieved-through-t-cell-engineering
#12
Victor I Ayala, Claire Deleage, Matthew T Trivett, Sumiti Jain, Lori V Coren, Matthew W Breed, Joshua A Kramer, James A Thomas, Jacob D Estes, Jeffrey D Lifson, David E Ott
Follicular helper CD4 T cells, TFH, residing in B-cell follicles within secondary lymphoid tissues, are readily infected by AIDS viruses and are a major source of persistent virus despite relative control of viral replication. This persistence is due at least in part to a relative exclusion of effective antiviral CD8 T cells from B-cell follicles. To determine whether CD8 T cells could be engineered to enter B-cell follicles, we genetically modified unselected CD8 T cells to express CXCR5, the chemokine receptor implicated in cellular entry into B-cell follicles...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28298421/mimicry-of-an-hiv-broadly-neutralizing-antibody-epitope-with-a-synthetic-glycopeptide
#13
S Munir Alam, Baptiste Aussedat, Yusuf Vohra, R Ryan Meyerhoff, Evan M Cale, William E Walkowicz, Nathan A Radakovich, Kara Anasti, Lawrence Armand, Robert Parks, Laura Sutherland, Richard Scearce, M Gordon Joyce, Marie Pancera, Aliaksandr Druz, Ivelin S Georgiev, Tarra Von Holle, Amanda Eaton, Christopher Fox, Steven G Reed, Mark Louder, Robert T Bailer, Lynn Morris, Salim S Abdool-Karim, Myron Cohen, Hua-Xin Liao, David C Montefiori, Peter K Park, Alberto Fernández-Tejada, Kevin Wiehe, Sampa Santra, Thomas B Kepler, Kevin O Saunders, Joseph Sodroski, Peter D Kwong, John R Mascola, Mattia Bonsignori, M Anthony Moody, Samuel Danishefsky, Barton F Haynes
A goal for an HIV-1 vaccine is to overcome virus variability by inducing broadly neutralizing antibodies (bnAbs). One key target of bnAbs is the glycan-polypeptide at the base of the envelope (Env) third variable loop (V3). We have designed and synthesized a homogeneous minimal immunogen with high-mannose glycans reflective of a native Env V3-glycan bnAb epitope (Man9-V3). V3-glycan bnAbs bound to Man9-V3 glycopeptide and native-like gp140 trimers with similar affinities. Fluorophore-labeled Man9-V3 glycopeptides bound to bnAb memory B cells and were able to be used to isolate a V3-glycan bnAb from an HIV-1-infected individual...
March 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28295315/a-comparative-analysis-of-the-physiological-properties-of-neurons-in-the-anterolateral-bed-nucleus-of-the-stria-terminalis-in-the-mus-musculus-rattus-norvegicus-and-macaca-mulatta
#14
Sarah E Daniel, Jidong Guo, Donald G Rainnie
The anterolateral group of the bed nucleus of the stria terminalis (BNSTALG ) is a critical modulator of a variety of rodent and primate behaviors spanning anxiety behavior and drug addiction. Three distinct neuronal cell types have been previously defined in the rat BNSTALG based on differences in the voltage-response to hyperpolarizing and depolarizing current injection. Differences in genetic expression profile between these three cell types suggest electrophysiological cell type may be an indicator for functional differences in the circuit of the rat BNSTALG ...
March 13, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28292762/gpr40-reduces-food-intake-and-body-weight-through-glp-1
#15
Judith N Gorski, Michele J Pachanski, Joel Mane, Christopher W Plummer, Sarah Souza, Brande S Thomas-Fowlkes, Aimie M Ogawa, Adam B Weinglass, Jerry Di Salvo, Boonlert Cheewatrakoolpong, Andrew D Howard, Steven L Colletti, Maria E Trujillo
GPR40 partial agonists lower glucose through the potentiation of glucose-stimulated insulin secretion, which is believed to provide significant glucose lowering without the weight gain or hypoglycemic risk associated with exogenous insulin or glucose independent insulin secretagogues. The class of small molecule GPR40 modulators, known as AgoPAMs (agonist also capable of acting as positive allosteric modulators), differentiate from partial agonists, binding to a distinct site and functioning as full agonists to stimulate the secretion of both insulin and GLP-1 (17)...
March 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28290002/plasma-and-cerebrospinal-fluid-pharmacokinetics-of-select-chemotherapeutic-agents-following-intranasal-delivery-in-a-non-human-primate-model
#16
James C League-Pascual, Cynthia M Lester-McCully, Shaefali Shandilya, Lukas Ronner, Louis Rodgers, Rafael Cruz, Cody J Peer, William D Figg, Katherine E Warren
The blood-brain barrier (BBB) limits entry of most chemotherapeutic agents into the CNS, resulting in inadequate exposure within CNS tumor tissue. Intranasal administration is a proposed means of delivery that can bypass the BBB, potentially resulting in more effective chemotherapeutic exposure at the tumor site. The objective of this study was to evaluate the feasibility and pharmacokinetics (plasma and CSF) of intranasal delivery using select chemotherapeutic agents in a non-human primate (NHP) model. Three chemotherapeutic agents with known differences in CNS penetration were selected for intranasal administration in a NHP model to determine proof of principle of CNS delivery, assess tolerability and feasibility, and to evaluate whether certain drug characteristics were associated with increased CNS exposure...
March 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28289281/oxytocin-by-intranasal-and-intravenous-routes-reaches-the-cerebrospinal-fluid-in-rhesus-macaques-determination-using-a-novel-oxytocin-assay
#17
M R Lee, K B Scheidweiler, X X Diao, F Akhlaghi, A Cummins, M A Huestis, L Leggio, B B Averbeck
Oxytocin (OT) is a potential treatment for multiple neuropsychiatric disorders. As OT is a peptide, delivery by the intranasal (IN) route is the preferred method in clinical studies. Although studies have shown increased cerebrospinal fluid (CSF) OT levels following IN administration, this does not unequivocably demonstrate that the peripherally administered OT is entering the CSF. For example, it has been suggested that peripheral delivery of OT could lead to central release of endogenous OT. It is also unknown whether the IN route provides for more efficient entry of the peptide into the CSF compared to the intravenous (IV) route, which requires blood-brain barrier penetration...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28288899/kisspeptin-10-treatment-generated-specific-gnrh-expression-in-cells-differentiated-from-rhesus-monkey-derived-lyon-nscs
#18
Tanzeel Huma, Xintian Hu, Yuanye Ma, Andrew Willden, Joshua Rizak, Muhammad Shahab, Zhengbo Wang
Embryonic stem cells (ESCs) have enormous potential as novel cell-based therapies, but their effectiveness depends on stem cell differentiation and specific signaling regulators, which remain poorly understood. In this study, a kisspeptin peptide (KP-10) was used at different dosages to determine whether rhesus macaque derived tau GFP-Lyon ES cells underwent kisspeptin specific neuronal differentiation. It was found that KP-10 exhibited an anti-proliferative effect on the cells and led to morphological changes and cellular differentiation consistent with neuronal stem cell (NSC) development...
March 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28288639/rhesus-macaque-and-mouse-models-for-down-selecting-circumsporozoite-protein-based-malaria-vaccines-differ-significantly-in-immunogenicity-and-functional-outcomes
#19
Timothy W Phares, Anthony D May, Christopher J Genito, Nathan A Hoyt, Farhat A Khan, Michael D Porter, Margot DeBot, Norman C Waters, Philippe Saudan, Sheetij Dutta
BACKGROUND: Non-human primates, such as the rhesus macaques, are the preferred model for down-selecting human malaria vaccine formulations, but the rhesus model is expensive and does not allow for direct efficacy testing of human malaria vaccines. Transgenic rodent parasites expressing genes of human Plasmodium are now routinely used for efficacy studies of human malaria vaccines. Mice have however rarely predicted success in human malaria trials and there is scepticism whether mouse studies alone are sufficient to move a vaccine candidate into the clinic...
March 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28286579/brain-xanthophyll-content-and-exploratory-gene-expression-analysis-subspecies-differences-in-rhesus-macaque
#20
Emily S Mohn, John W Erdman, Martha Neuringer, Matthew J Kuchan, Elizabeth J Johnson
BACKGROUND: The dietary xanthophylls, lutein and zeaxanthin, accumulate in primate retina and brain, and emerging evidence indicates neural lutein content may be beneficial for cognition. Neural xanthophyll content in primates varies greatly among individuals, and genetic factors are likely to be significant contributors. Subspecies of rhesus macaques originating from different geographic locations are known to differ genetically, but the effect of origin on gene expression and carotenoid status has not been determined...
2017: Genes & Nutrition
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