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Yongjun Sui, George K Lewis, Yichuan Wang, Kurt Berckmueller, Blake Frey, Amiran Dzutsev, Diego Vargas-Inchaustegui, Venkatramanan Mohanram, Thomas Musich, Xiaoying Shen, Anthony DeVico, Timothy Fouts, David Venzon, James Kirk, Robert C Waters, James Talton, Dennis Klinman, John Clements, Georgia D Tomaras, Genoveffa Franchini, Marjorie Robert-Guroff, Giorgio Trinchieri, Robert C Gallo, Jay A Berzofsky
It is widely believed that protection against acquisition of HIV or SIV infection requires anti-envelope (anti-Env) antibodies, and that cellular immunity may affect viral loads but not acquisition, except in special cases. Here we provide evidence to the contrary. Mucosal immunization may enhance HIV vaccine efficacy by eliciting protective responses at portals of exposure. Accordingly, we vaccinated macaques mucosally with HIV/SIV peptides, modified vaccinia Ankara-SIV (MVA-SIV), and HIV-gp120-CD4 fusion protein plus adjuvants, which consistently reduced infection risk against heterologous intrarectal SHIVSF162P4 challenge, both high dose and repeated low dose...
February 18, 2019: Journal of Clinical Investigation
Hannah Weinberg-Wolf, Steve W C Chang
Primates must balance the need to monitor other conspecifics to gain social information while not losing other resource opportunities. We consolidate evidence across the fields of primatology, psychology, and neuroscience to examine individual, population, and species differences in how primates, particularly macaques, monitor conspecifics. We particularly consider the role of serotonin in mediating social competency via social attention, aggression, and dominance behaviors. Finally, we consider how the evolution of variation in social tolerance, aggression, and social monitoring might be explained by differences in serotonergic function in macaques...
February 18, 2019: Wiley Interdisciplinary Reviews. Cognitive Science
Michael D Ward, Ernst E Brueggemann, Tara Kenny, Raven E Reitstetter, Christopher R Mahone, Sylvia Trevino, Kelly Wetzel, Ginger C Donnelly, Cary Retterer, Robert B Norgren, Rekha G Panchal, Travis K Warren, Sina Bavari, Lisa H Cazares
Background: In-depth examination of the plasma proteomic response to infection with a wide variety of pathogens can assist in the development of new diagnostic paradigms, while providing insight into the interdependent pathogenic processes which encompass a host's immunological and physiological responses. Ebola virus (EBOV) causes a highly lethal infection termed Ebola virus disease (EVD) in primates and humans. The Gram negative non-spore forming bacillus Burkholderia pseudomallei ( Bp ) causes melioidosis in primates and humans, characterized by severe pneumonia with high mortality...
2019: Clinical Proteomics
Misako Komatsu, Takaaki Kaneko, Hideyuki Okano, Noritaka Ichinohe
Electrocorticography (ECoG) allows the monitoring of electrical field potentials from the cerebral cortex with high spatiotemporal resolution. Recent development of thin, flexible ECoG electrodes has enabled conduction of stable recordings of large-scale cortical activity. We have developed a whole-cortical ECoG array for the common marmoset. The array continuously covers almost the entire lateral surface of cortical hemisphere, from the occipital pole to the temporal and frontal poles, and it captures whole-cortical neural activity in one shot...
February 1, 2019: Journal of Visualized Experiments: JoVE
Shamina M Rangwala, Katharine D'Aquino, Yue-Mei Zhang, Lindsay Bader, Wilson Edwards, Songmao Zheng, Annette Eckardt, Ann Lacombe, Rebecca Pick, Veronica Moreno, Lijuan Kang, Wenying Jian, Eric Arnoult, Martin Case, Celia Jenkinson, Ellen Chi, Ronald V Swanson, Paul Kievit, Kevin Grove, Mark Macielag, Mark D Erion, Ranabir SinhaRoy, James N Leonard
The gut hormone PYY3-36 reduces food intake in humans and exhibits at least additive efficacy in combination with GLP-1. However, the utility of PYY analogs as anti-obesity agents has been severely limited by emesis and rapid proteolysis, a profile similarly observed with native PYY3-36 in obese rhesus macaques. Here, we found that antibody conjugation of a cyclized PYY3-36 analog achieved high NPY2R selectivity, unprecedented in vivo stability, and gradual infusion-like exposure. These properties permitted profound reduction of food intake when administered to macaques for 23 days without a single emetic event in any animal...
February 11, 2019: Cell Metabolism
Amarender R Bogadhi, Anil Bollimunta, David A Leopold, Richard J Krauzlis
Spatial neglect is a common clinical syndrome involving disruption of the brain's attention-related circuitry, including the dorsocaudal temporal cortex. In macaques, the attention deficits associated with neglect can be readily modeled, but the absence of evidence for temporal cortex involvement has suggested a fundamental difference from humans. To map the neurological expression of neglect-like attention deficits in macaques, we measured attention-related fMRI activity across the cerebral cortex during experimental induction of neglect through reversible inactivation of the superior colliculus and frontal eye fields...
February 9, 2019: Current Biology: CB
Paula Alonso-Guallart, Jonah S Zitsman, Jeffrey Stern, Sigal B Kofman, David Woodland, Siu-Hong Ho, Hugo P Sondermeijer, Leo Bühler, Adam Griesemer, Megan Sykes, Raimon Duran-Struuck
Reliable in vitro expansion protocols of regulatory T cells (Tregs) are needed for clinical use. We studied the biology of Mauritian Cynomolgus macaque (MCM) Tregs and developed four in vitro Treg expansion protocols for translational studies. Tregs expanded three-thousand-fold when artificial APCs (aAPCs) expressing human CD80, CD58 and CD32 were used throughout the culture. When donor PBMCs were used as the single source of APCs followed by aAPCs, Tregs expanded 2,000-fold. Tregs from all protocols suppressed the proliferation of anti-CD2CD3CD28 bead-stimulated autologous PBMCs albeit with different potencies, varying from 1:2-1:4 Treg:PBMC ratios, up to >1:32...
February 15, 2019: American Journal of Transplantation
Davide Folloni, Lennart Verhagen, Rogier B Mars, Elsa Fouragnan, Charlotte Constans, Jean-François Aubry, Matthew F S Rushworth, Jérôme Sallet
The causal role of an area within a neural network can be determined by interfering with its activity and measuring the impact. Many current reversible manipulation techniques have limitations preventing their application, particularly in deep areas of the primate brain. Here, we demonstrate that a focused transcranial ultrasound stimulation (TUS) protocol impacts activity even in deep brain areas: a subcortical brain structure, the amygdala (experiment 1), and a deep cortical region, the anterior cingulate cortex (ACC, experiment 2), in macaques...
February 7, 2019: Neuron
Pinyi Wang, Dingxin Wang, Jialu Zhang, Ruiliang Bai, Meizhen Qian, Yi Sun, Yi Lu, Xiaotong Zhang
OBJECTIVE: The purpose of the present study was to achieve submillimeter-level diffusion tensor imaging (DTI) of the macaque brain by using diffusion weighted (DW) readout-segmented echo planar imaging (rsEPI) with an optimized protocol at 7T MRI. METHODS: Three anesthetized macaques were included in this study. Under different scan settings, we compared signal-to-noise ratio (SNR) and geometric distortion of DW images, implemented an optimized protocol for submillimeter-level DTI acquisition, and evaluated its performance...
February 13, 2019: IEEE Transactions on Bio-medical Engineering
Alison R Weiss, Jessica White, Rebecca Richardson, Jocelyne Bachevalier
Previous research indicated that monkeys with neonatal perirhinal lesions (Neo-PRh) were impaired on working memory (WM) tasks that generated proactive interference, but performed normally on WM tasks devoid of interference (Weiss et al., 2016). This finding suggested that the early lesions disrupted cognitive processes important for resolving proactive interference, such as behavioral inhibition and cognitive flexibility. To distinguish between these possibilities, the same Neo-PRh monkeys and their controls were tested using the Intradimensional/Extradimensional attentional set-shifting task (Roberts et al...
2019: Frontiers in Systems Neuroscience
Qingbo Liu, Yen-Ting Lai, Peng Zhang, Mark K Louder, Amarendra Pegu, Reda Rawi, Mangaiarkarasi Asokan, Xuejun Chen, Chen-Hsiang Shen, Gwo-Yu Chuang, Eun Sung Yang, Huiyi Miao, Yuge Wang, Anthony S Fauci, Peter D Kwong, John R Mascola, Paolo Lusso
Broadly neutralizing antibodies (bNAbs) represent a promising alternative to antiretroviral drugs for HIV-1 prevention and treatment. Selected antibodies to the CD4-binding site bolster envelope trimer binding via quaternary contacts. Here, we rationally engraft a new paratope, i.e., the extended heavy-chain framework region 3 (FR3) loop of VRC03, which mediates quaternary interaction, onto several potent bNAbs, enabling them to reach an adjacent gp120 protomer. The interactive quaternary surface is delineated by solving the crystal structure of two FR3 loop-chimeric antibodies...
February 13, 2019: Nature Communications
Mingkui Zhou, Michael Humbert, Muhammad M Mukhtar, Hanna B Scinto, Hemant K Vyas, Samir K Lakhashe, Siddappa N Byrareddy, Gregor Maurer, Swati Thorat, Joshua Owuor, Zhao Lai, Yidong Chen, Anthony Griffiths, Agnès-Laurence Chenine, Sanjeev Gumber, François Villinger, David Montefiori, Ruth M Ruprecht
Simian-human immunodeficiency virus (SHIV) infection in rhesus macaques (RMs) resembles human immunodeficiency virus type 1 (HIV-1) infection in humans and serves as a tool to evaluate candidate AIDS vaccines. HIV-1 clade A (HIV-A) predominates in parts of Africa. We constructed an R5 clade A SHIV (SHIV-A; strain SHIV-KNH1144) carrying env from a Kenyan HIV-A. SHIV-A underwent rapid serial passage through six RMs. To allow unbridled replication without adaptive immunity, we simultaneously ablated CD8+ and B cells with cytotoxic monoclonal antibodies in the next RM, resulting in extremely high viremia and CD4+ T-cell loss...
February 13, 2019: Journal of Virology
Laura P Hale, Gowrisankar Rajam, George M Carlone, Chen Jiang, Kouros Owzar, Greg Dugan, David Caudell, Nelson Chao, J Mark Cline, Thomas C Register, Gregory D Sempowski
While exposure to radiation can be lifesaving in certain settings, it can also potentially result in long-lasting adverse effects, particularly to hematopoietic and immune cells. This study investigated hematopoietic recovery and immune function in rhesus macaques Cross-sectionally (at a single time point) 2 to 5 years after exposure to a single large dose (6.5 to 8.4 Gray) of total body radiation (TBI) derived from linear accelerator-derived photons (2 MeV, 80 cGy/minute) or Cobalt 60-derived gamma irradiation (60 cGy/min)...
2019: PloS One
Andrew J Zimnik, Antonio H Lara, Mark M Churchland
The contribution of the supplementary motor area (SMA) to movement initiation remains unclear. SMA exhibits pre-movement activity across a variety of contexts, including externally cued and self-initiated movements. Yet SMA lesions impair initiation primarily for self-initiated movements. Does SMA influence initiation across contexts or does it play a more specialized role, perhaps contributing only when initiation is less dependent on external cues? To address this question, we perturbed SMA activity via microstimulation at variable times before movement onset...
February 12, 2019: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jonathan Q Purnell, Henryk F Urbanski, Paul Kievit, Charles T Roberts, Cynthia L Bethea
Whether hormone replacement therapy has beneficial metabolic effects in postmenopausal women remains controversial due to between-study differences in menopausal duration, estrogen formulations, and diet. Additionally, animal studies have not reflected the typical human obesogenic, Western-Style Diet (WSD). In this study, we determined the effects of immediate E (ImE) or delayed E treatment on weight and metabolism parameters in old ovo-hysterectomized rhesus macaques consuming a WSD over a 30-month period...
February 7, 2019: Endocrinology
Yasushi Hattori, Kazunobu Aoyama, Jun Maeda, Naoto Arimura, Yasuko Takahashi, Masako Sasaki, Masayuki Fujinaga, Chie Seki, Yuji Nagai, Kazunori Kawamura, Tomoteru Yamasaki, Ming-Rong Zhang, Makoto Higuchi, Tatsuki Koike
Monoacylglycerol lipase (MAGL) is a cytosolic serine hydrolase involved in endocannabinoid and inflammatory signaling. Positron-emission tomography (PET) imaging of MAGL serves to validate target engagement of therapeutic MAGL inhibitors as well as to investigate MAGL levels under normal and disease conditions. However, PET radioligands with reversible binding kinetics for MAGL, which allow quantitative assessment of MAGL, are hitherto unavailable. In this study, we designed and synthesized fluoro-containing PET probes starting from a recently identified piperazinyl pyrrolidine-2-one derivative with reversible binding to MAGL...
February 12, 2019: Journal of Medicinal Chemistry
David A Welsh, Tekeda Ferguson, Katherine P Theall, Liz Simon, Angela Amedee, Robert W Siggins, Steve Nelson, Meghan Brashear, Donald Mercante, Patricia E Molina
BACKGROUND: Alcohol use disorders (AUDs) are highly prevalent in persons living with HIV (PLWH) and are associated with increased HIV risk behaviors, suboptimal treatment adherence, potential interaction with medication pharmacodynamics, and greater risk for disease progression. Preclinical studies show that chronic binge alcohol administration accelerates disease progression and aggravates pathogenesis in the simian immunodeficiency virus (SIV)-infected rhesus macaque model despite viral suppression by antiretroviral therapy...
February 12, 2019: Alcoholism, Clinical and Experimental Research
Lennart Verhagen, Cécile Gallea, Davide Folloni, Charlotte Constans, Daria Ea Jensen, Harry Ahnine, Léa Roumazeilles, Mathieu Santin, Bashir Ahmed, Stéphane Lehericy, Miriam C Klein-Flügge, Kristine Krug, Rogier B Mars, Matthew Fs Rushworth, Pierre Pouget, Jean-François Aubry, Jerome Sallet
To understand brain circuits it is necessary both to record and manipulate their activity. Transcranial ultrasound stimulation (TUS) is a promising non-invasive brain stimulation technique. To date, investigations report short-lived neuromodulatory effects, but to deliver on its full potential for research and therapy, ultrasound protocols are required that induce longer-lasting 'offline' changes. Here, we present a TUS protocol that modulates brain activation in macaques for more than one hour after 40 s of stimulation, while circumventing auditory confounds...
February 12, 2019: ELife
Michael J Raboin, John Letaw, Asia D Mitchell, David Toffey, Jessica McKelvey, Charles T Roberts, Joanne E Curran, Amanda Vinson
OBJECTIVE: Whereas the metabolic consequences of obesity have been studied extensively in the rhesus macaque, corollary genetic studies of obesity are nonexistent. This study assessed genetic contributions to spontaneous adiposity in this species. METHODS: Phenotypic variation by age class and sex for BMI, waist to height ratio, waist to thigh ratio, and waist circumference was assessed in 583 macaques. Total and sex-specific heritability for all traits was estimated, including waist to thigh ratio adjusted for BMI, as well as genotypic and phenotypic correlations...
February 11, 2019: Obesity
Michael A Schillaci, Jessica Lintlop, Monika Sumra, Mark Pizarro, Lisa Jones-Engel
RATIONALE: Prolonged exposure to the stress hormone cortisol can precipitate a catabolic state in animals resulting in a negative nitrogen balance and increased excreted nitrogen, possibly affecting stable nitrogen and carbon isotope ratios in animal tissues. Here we test the hypothesis that stress, as measured by hair cortisol, is a significant contributor to variation in δ15 N and δ13 C values in hair. The results of the present study have important implications for the use of stable carbon and nitrogen isotope ratios measured in animal and human tissues to make inferences regarding feeding ecology and diet...
February 11, 2019: Rapid Communications in Mass Spectrometry: RCM
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