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Sabine Oligschläger, Ting Xu, Blazej M Baczkowski, Marcel Falkiewicz, Arnaud Falchier, Gary Linn, Daniel S Margulies
Cortical connectivity conforms to a series of organizing principles that are common across species. Spatial proximity, similar cortical type, and similar connectional profile all constitute factors for determining the connectivity between cortical regions. We previously demonstrated another principle of connectivity that is closely related to the spatial layout of the cerebral cortex. Using functional connectivity from resting-state fMRI in the human cortex, we found that the further a region is located from primary cortex, the more distant are its functional connections with the other areas of the cortex...
December 13, 2018: Brain Structure & Function
Jenny A Greig, Roberto Calcedo, Leticia Kuri-Cervantes, Jayme M L Nordin, Jessica Albrecht, Erin Bote, Tamara Goode, Edward A Chroscinski, Peter Bell, Laura K Richman, Michael R Betts, James M Wilson
Systemic delivery of adeno-associated viral (AAV) vectors has been evaluated for the treatment of several liver diseases, including homozygous familial hypercholesterolemia, ornithine transcarbamylase deficiency, and hemophilia. Here, we evaluated this approach for the treatment of Crigler-Najjar syndrome. We administered wild-type rhesus macaques with 1.0 × 1013 or 2.5 × 1013 genome copies/kg of an AAV serotype 8 vector expressing a codon-optimized version of human uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) from a liver-specific promoter...
December 14, 2018: Molecular Therapy. Methods & Clinical Development
Idalia M Yabe, Lauren L Truitt, Diego A Espinoza, Chuanfeng Wu, Samson Koelle, Sandhya Panch, Marcus A F Corat, Thomas Winkler, Kyung-Rok Yu, So Gun Hong, Aylin Bonifacino, Allen Krouse, Mark Metzger, Robert E Donahue, Cynthia E Dunbar
Gene therapies using integrating retrovirus vectors to modify hematopoietic stem and progenitor cells have shown great promise for the treatment of immune system and hematologic diseases. However, activation of proto-oncogenes via insertional mutagenesis has resulted in the development of leukemia. We have utilized cellular bar coding to investigate the impact of different vector designs on the clonal behavior of hematopoietic stem and progenitor cells (HSPCs) during in vivo expansion, as a quantitative surrogate assay for genotoxicity in a non-human primate model with high relevance for human biology...
December 14, 2018: Molecular Therapy. Methods & Clinical Development
Craig A Taswell, Vincent D Costa, Elisabeth A Murray, Bruno B Averbeck
Adaptive behavior requires animals to learn from experience. Ideally, learning should both promote choices that lead to rewards and reduce choices that lead to losses. Because the ventral striatum (VS) contains neurons that respond to aversive stimuli and aversive stimuli can drive dopamine release in the VS, it is possible that the VS contributes to learning about aversive outcomes, including losses. However, other work suggests that the VS may play a specific role in learning to choose among rewards, with other systems mediating learning from aversive outcomes...
December 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ying Zhu, André M M Sousa, Tianliuyun Gao, Mario Skarica, Mingfeng Li, Gabriel Santpere, Paula Esteller-Cucala, David Juan, Luis Ferrández-Peral, Forrest O Gulden, Mo Yang, Daniel J Miller, Tomas Marques-Bonet, Yuka Imamura Kawasawa, Hongyu Zhao, Nenad Sestan
Human nervous system development is an intricate and protracted process that requires precise spatiotemporal transcriptional regulation. We generated tissue-level and single-cell transcriptomic data from up to 16 brain regions covering prenatal and postnatal rhesus macaque development. Integrative analysis with complementary human data revealed that global intraspecies (ontogenetic) and interspecies (phylogenetic) regional transcriptomic differences exhibit concerted cup-shaped patterns, with a late fetal-to-infancy (perinatal) convergence...
December 14, 2018: Science
Connor Buechler, Matthew Semler, David A Baker, Christina Newman, Joseph P Cornish, Deborah Chavez, Bernadette Guerra, Robert Lanford, Kathy Brasky, Jens H Kuhn, Reed F Johnson, David H O'Connor, Adam L Bailey
Simarteriviruses ( Arteriviridae : Simarterivirinae ) are commonly found at high titers in the blood of African monkeys but do not cause overt disease in these hosts. In contrast, simarteriviruses cause severe disease in Asian macaques upon accidental or experimental transmission. Here, we sought to better understand the host-dependent drivers of simarterivirus pathogenesis by infecting olive baboons (n = 4) and rhesus monkeys (n = 4) with the simarterivirus Southwest baboon virus 1 (SWBV-1). Surprisingly, none of the animals in our study showed signs of disease following SWBV-1 inoculation...
December 10, 2018: Viruses
Lisa A Ostrin, Christianne E Strang, Kevin Chang, Ashutosh Jnawali, Li-Fang Hung, Baskar Arumugam, Laura J Frishman, Earl L Smith, Paul D Gamlin
Purpose: Intrinsically photosensitive retinal ganglion cells (ipRGCs) contain the photopigment melanopsin, and are primarily involved in non-image forming functions, such as the pupillary light reflex and circadian rhythm entrainment. The goal of this study was to develop and validate a targeted ipRGC immunotoxin to ultimately examine the role of ipRGCs in macaque monkeys. Methods: An immunotoxin for the macaque melanopsin gene ( OPN4 ), consisting of a saporin-conjugated antibody directed at the N-terminus, was prepared in solutions of 0...
2018: Frontiers in Neurology
Taeko K Naruse, Hirofumi Akari, Tetsuro Matano, Akinori Kimura
Non-human primates such as rhesus macaque and cynomolgus macaque are important animals for medical research. These species are classified as Old-World monkeys (Cercopithecidae), in which the immune-related genome structure is characterized by gene duplications. In the present study, we investigated polymorphisms in two genes for ULBP5 encoding ligands for NKG2D. We found 18 and 11 ULBP5.1 alleles and 11 and 13 ULBP5.2 alleles in rhesus macaques and cynomolgus macaques, respectively. In addition, phylogenetic analyses revealed that ULBP5...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
Jacqueline R Hembrook-Short, Vanessa L Mock, W Martin Usrey, Farran Briggs
Attention is a critical component of visual perception, however the mechanisms of attention at the granular level are poorly understood. One possible mechanism by which attention modulates neuronal activity is to control the efficacy of communication between connected neurons, however it is unclear whether attention alters communication efficacy across a variety of neuronal circuits. In parallel, attentional modulation of neuronal firing rate is not uniform, but depends upon the match between neuronal feature selectivity and the feature required for successful task completion...
December 12, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Mauricio A Martins, Lucas Gonzalez-Nieto, Young C Shin, Aline Domingues, Martin J Gutman, Helen S Maxwell, Diogo M Magnani, Michael J Ricciardi, Núria Pedreño-Lopez, Varian K Bailey, John D Altman, Christopher L Parks, David B Allison, Keisuke Ejima, Eva G Rakasz, Saverio Capuano, Ronald C Desrosiers, Jeffrey D Lifson, David I Watkins
Approximately 50% of rhesus macaques (RMs) expressing the major histocompatibility complex class I (MHC-I) allele Mamu-B*08 spontaneously control chronic phase viremia after infection with the pathogenic simian immunodeficiency virus (SIV)mac239 clone. CD8+ T-cell responses in these animals are focused on immunodominant Mamu-B*08-restricted SIV epitopes in Vif and Nef, and prophylactic vaccination with these epitopes increases the incidence of elite control in SIVmac239-infected Mamu-B*08+ RMs. Here we evaluated if robust vaccine-elicited CD8+ T-cell responses against Vif and Nef can prevent systemic infection in Mamu-B*08+ RMs following mucosal SIV challenges...
December 12, 2018: Journal of Virology
Maria Dennis, Joshua Eudailey, Justin Pollara, Arthur S McMillan, Kenneth D Cronin, Pooja T Saha, Alan D Curtis, Michael G Hudgens, Genevieve G Fouda, Guido Ferrari, Munir Alam, Koen K A Van Rompay, Kristina De Paris, Sallie Permar, Xiaoying Shen
Prevention of mother to child transmission (MTCT) is an indispensable component of the combat against the global AIDS epidemic. A combination of passive broadly neutralizing antibody (bnAb) infusion and active vaccination promises to provide protection of infants against MTCT from birth through the breastfeeding period, and could prime the immune system for life-long immunity. In this study, we investigate the impact of a single infusion of CD4 binding site (CD4bs) bnAb administered at birth on de novo antibody responses elicited by concurrent active HIV envelope vaccination...
December 12, 2018: Journal of Virology
Lynette S Chea, Linda S Wyatt, Sailaja Gangadhara, Bernard Moss, Rama R Amara
Modified vaccinia Ankara (MVA), an attenuated poxvirus, has been developed as a potential vaccine vector for use against cancer and multiple infectious diseases including HIV. MVA is highly immunogenic and elicits strong cellular and humoral responses in pre-clinical models and humans. However, there is potential to further enhance the immunogenicity of MVA as MVA-infected cells undergo rapid apoptosis leading to faster clearance of recombinant antigens and potentially blunting a greater response. Here, we generated MVA-B13R by replacing the fragmented 181R/182R genes of MVA with a functional anti-apoptotic gene B13R and confirmed its anti-apoptotic function against chemically induced apoptosis in vitro In addition, MVA-B13R showed a significant delay in induction of apoptosis in muscle cells derived from mice and humans as well as pDCs and CD141+ DCs from rhesus macaques compared to MVA infected cells...
December 12, 2018: Journal of Virology
Rebecca A Tarantelli, Finja Schweitzer, Marc A Simon, Rebecca R Vanderpool, Ian Christman, Emily Rayens, Heather M Kling, ToniAnn Zullo, Jonathan P Carney, Brian J Lopresti, Thomas Bertero, Stephen Y Chan, Karen A Norris
Pulmonary arterial hypertension (PAH) is a life-threatening disease with higher incidence in HIV-infected compared withnoninfected patients. SIV-infected NHP develop clinical manifestations of HIV infection, including PAH. To understand thepathogenesis of PAH and determine the relationship between hemodynamic changes and clinical characteristics associatedwith SIV infection, we performed right heart catheterization and echocardiographic imaging of 21 rhesus macaques before andafter SIV infection. Between 6 and 12 mo after infection, 11 of the 21 animals had elevated mean pulmonary arterial pressure(mPAP; greater than 25 mm Hg)...
December 12, 2018: Comparative Medicine
Julianne Skinner, Antimo Buonocore, Ziad M Hafed
Two main types of small eye movements occur during gaze fixation: microsaccades and slow ocular drifts. While microsaccade generation has been relatively well-studied, ocular drift control mechanisms are unknown. Here we explored the degree to which monkey smooth eye movements, on the velocity scale of slow ocular drifts, can be generated systematically. Two male rhesus macaque monkeys tracked a spot moving sinusoidally, but slowly, along the horizontal or vertical directions. Maximum target displacement in the motion trajectory was 30 min arc (0...
December 12, 2018: Journal of Neurophysiology
Vanessa L Mock, Kimberly L Luke, Jacqueline R Hembrook-Short, Farran Briggs
The local field potential (LFP) contains rich information about activity in local neuronal populations. However, it has been challenging to establish direct links between LFP modulations and task-relevant behavior or cognitive processes, such as attention. We sought to determine whether LFP amplitude or phase modulations were predictive of the allocation of visual spatial attention. LFPs were recorded simultaneously in multiple early visual brain structures of alert macaque monkeys performing attention-demanding detection and discrimination tasks...
December 12, 2018: Journal of Neurophysiology
Nobuo Masataka, Hiroki Koda, Takeshi Atsumi, Madoka Satoh, Ottmar V Lipp
In humans, attentional biases have been shown to negative (dangerous animals, physical threat) and positive (high caloric food, alcohol) stimuli. However, it is not clear whether these attentional biases reflect on stimulus driven, bottom up, or goal driven, top down, attentional processes. Here we show that, like humans, Japanese macaques show an attentional bias to snakes in a dot probe task (Experiment 1). Moreover, this attentional bias reflects on bottom up driven, preferential engagement of attention by snake images (Experiment 2a), a finding that was replicated in a study that used the same methodology in humans (Experiment 2b)...
December 11, 2018: Scientific Reports
Enzhuo Yang, Rui Yang, Ming Guo, Dan Huang, Wandang Wang, Zhuoran Zhang, Crystal Chen, Feifei Wang, Wenzhe Ho, Ling Shen, Heping Xiao, Zheng W Chen, Hongbo Shen
Tuberculosis (TB) has become the most deadly infectious diseases due to epidemics of HIV/AIDS and multidrug-resistant/extensively drug-resistant TB (MDR-/XDR-TB). Although person-to-person transmission contributes to MDR-TB, it remains unknown whether infection with MDR strains resembles infection with drug-sensitive (DS) TB strains, manipulating limited or broad immune responses. To address these questions, macaques were infected with MDR strain V791 and a drug-sensitive Erdman strain of TB. MDR bacilli burdens in the airway were significantly higher than those of the Erdman control after pulmonary exposure...
December 12, 2018: Emerging Microbes & Infections
Noah Snyder-Mackler, Joaquín Sanz, Jordan N Kohn, Tawni Voyles, Roger Pique-Regi, Mark E Wilson, Luis B Barreiro, Jenny Tung
Low social status is an important predictor of disease susceptibility and mortality risk in humans and other social mammals. These effects are thought to stem in part from dysregulation of the glucocorticoid (GC)-mediated stress response. However, the molecular mechanisms that connect low social status and GC dysregulation to downstream health outcomes remain elusive. Here, we used an in vitro GC challenge to investigate the consequences of experimentally manipulated social status (i.e., dominance rank) for immune cell gene regulation in female rhesus macaques, using paired control and GC-treated peripheral blood mononuclear cell samples...
December 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Amanda J Lea, Mercy Y Akinyi, Ruth Nyakundi, Peter Mareri, Fred Nyundo, Thomas Kariuki, Susan C Alberts, Elizabeth A Archie, Jenny Tung
In humans and other hierarchical species, social status is tightly linked to variation in health and fitness-related traits. Experimental manipulations of social status in female rhesus macaques suggest that this relationship is partially explained by status effects on immune gene regulation. However, social hierarchies are established and maintained in different ways across species: While some are based on kin-directed nepotism, others emerge from direct physical competition. We investigated how this variation influences the relationship between social status and immune gene regulation in wild baboons, where hierarchies in males are based on fighting ability but female hierarchies are nepotistic...
December 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Vassilis Papadourakis, Vassilis Raos
We identified neurons in dorsal premotor cortex (PMd) of the macaque brain that respond during execution and observation of reaching-to-grasp actions, thus fulfilling the mirror neuron (MirN) criterion. During observation, the percentage of grip-selective MirNs in PMd and area F5 were comparable, and the selectivity indices in the two areas were similar. During execution, F5-MirNs were more selective than PMd-MirNs for grip, which was reflected in the higher selectivity indices in F5 than in PMd. PMd displayed grip-related information earlier than F5 during both conditions...
December 7, 2018: Cerebral Cortex
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