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https://www.readbyqxmd.com/read/28646272/rhesus-cochlear-and-vestibular-functions-are-preserved-after-inner-ear-injection-of-saline-volume-sufficient-for-gene-therapy-delivery
#1
Chenkai Dai, Mohamed Lehar, Daniel Q Sun, Lani Swarthout Rvt, John P Carey, Tim MacLachlan, Doug Brough, Hinrich Staecker, Alexandra M Della Santina, Timothy E Hullar, Charles C Della Santina
Sensorineural losses of hearing and vestibular sensation due to hair cell dysfunction are among the most common disabilities. Recent preclinical research demonstrates that treatment of the inner ear with a variety of compounds, including gene therapy agents, may elicit regeneration and/or repair of hair cells in animals exposed to ototoxic medications or other insults to the inner ear. Delivery of gene therapy may also offer a means for treatment of hereditary hearing loss. However, injection of a fluid volume sufficient to deliver an adequate dose of a pharmacologic agent could, in theory, cause inner ear trauma that compromises functional outcome...
June 23, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28646234/electroporation-as-a-vaccine-delivery-system-and-a-natural-adjuvant-to-intradermal-administration-of-plasmid-dna-in-macaques
#2
Biliana Todorova, Lucille Adam, Slobodan Culina, Raphaël Boisgard, Frédéric Martinon, Antonio Cosma, Mart Ustav, Thierry Kortulewski, Roger Le Grand, Catherine Chapon
In vivo electroporation (EP) is used to enhance the uptake of nucleic acids and its association with DNA vaccination greatly stimulates immune responses to vaccine antigens delivered through the skin. However, the effect of EP on cutaneous cell behavior, the dynamics of immune cell recruitment and local inflammatory factors, have not been fully described. Here, we show that intradermal DNA vaccination combined with EP extends antigen expression to the epidermis and the subcutaneous skin muscle in non-human primates...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645244/evolution-of-the-vertebrate-insulin-receptor-substrate-irs-gene-family
#3
Ahmad Al-Salam, David M Irwin
BACKGROUND: Insulin receptor substrate (Irs) proteins are essential for insulin signaling as they allow downstream effectors to dock with, and be activated by, the insulin receptor. A family of four Irs proteins have been identified in mice, however the gene for one of these, IRS3, has been pseudogenized in humans. While it is known that the Irs gene family originated in vertebrates, it is not known when it originated and which members are most closely related to each other. A better understanding of the evolution of Irs genes and proteins should provide insight into the regulation of metabolism by insulin...
June 23, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28643203/nonhuman-primate-models-of-ebola-virus-disease
#4
Richard S Bennett, Louis M Huzella, Peter B Jahrling, Laura Bollinger, Gene G Olinger, Lisa E Hensley
Ebola virus disease (EVD) in humans is associated with four ebolaviruses: Ebola virus (EBOV), Sudan virus (SUDV), Bundibugyo virus (BDBV), and Taï Forest virus. To date, no documented cases of human disease have been associated with Reston virus. Here, we describe the nonhuman primate (NHP) models that currently serve as gold standards for testing ebolavirus vaccines and therapeutic agents and elucidating underlying mechanisms of pathogenesis. Although multiple models have been explored over the past 50 years, the predominance of published work has been performed in macaque models...
June 23, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28642691/mri-overestimates-excitotoxic-amygdala-lesion-damage-in-rhesus-monkeys
#5
Benjamin M Basile, Chloe L Karaskiewicz, Emily C Fiuzat, Ludise Malkova, Elisabeth A Murray
Selective, fiber-sparing excitotoxic lesions are a state-of-the-art tool for determining the causal contributions of different brain areas to behavior. For nonhuman primates especially, it is advantageous to keep subjects with high-quality lesions alive and contributing to science for many years. However, this requires the ability to estimate lesion extent accurately. Previous research has shown that in vivo T2-weighted magnetic resonance imaging (MRI) accurately estimates damage following selective ibotenic acid lesions of the hippocampus...
2017: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/28642489/post-exposure-treatment-of-non-human-primates-lethally-infected-with-ebola-virus-with-ebotab-a-purified-ovine-igg-product
#6
Stuart D Dowall, Frédéric Jacquot, John Landon, Emma Rayner, Graham Hall, Caroline Carbonnelle, Hervé Raoul, Delphine Pannetier, Ian Cameron, Ruth Coxon, Ibrahim Al Abdulla, Roger Hewson, Miles W Carroll
Despite sporadic outbreaks of Ebola virus (EBOV) over the last 4 decades and the recent public health emergency in West Africa, there are still no approved vaccines or therapeutics for the treatment of acute EBOV disease (EVD). In response to the 2014 outbreak, an ovine immunoglobulin therapy was developed, termed EBOTAb. After promising results in the guinea pig model of EBOV infection, EBOTAb was tested in the cynomolgus macaque non-human primate model of lethal EBOV infection. To ensure stringent therapeutic testing conditions to replicate likely clinical usage, EBOTAb was first delivered 1, 2 or 3 days post-challenge with a lethal dose of EBOV...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642013/identifying-mechanisms-driving-formation-of-granuloma-associated-fibrosis-during-mycobacterium-tuberculosis-infection
#7
Hayley C Warsinske, Robert M DiFazio, Jennifer J Linderman, JoAnne L Flynn, Denise E Kirschner
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a pulmonary pathogen of major global concern. A key feature of Mtb infection in primates is the formation of granulomas, dense cellular structures surrounding infected lung tissue. These structures serve as the main site of host-pathogen interaction in TB, and thus to effectively treat TB we must clarify mechanisms of granuloma formation and their function in disease. Fibrotic granulomas are associated with both good and bad disease outcomes...
June 19, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28641988/wavy-multistratified-amacrine-cells-in-the-monkey-retina-contain-immunoreactive-secretoneurin
#8
Andrea S Bordt, Ye Long, Nobuo Kouyama, Elizabeth S Yamada, Jens Hannibal, David W Marshak
The goals of this study were to describe the morphology, neurotransmitter content and synaptic connections of neurons in primate retinas that contain the neuropeptide secretoneurin. Amacrine cells were labeled with antibodies to secretoneurin in macaque and baboon retinas. Their processes formed three distinct plexuses in the inner plexiform layer: one in the outermost stratum, one in the center and one in the innermost stratum. In light microscopic double immunolabeling experiments, GABA was colocalized with secretoneurin in these cells, but glycine transporter 1 and Substance P were not...
June 19, 2017: Peptides
https://www.readbyqxmd.com/read/28641214/motor-system-dysfunction-in-the-schizophrenia-diathesis-neural-systems-to-neurotransmitters
#9
R Abboud, C Noronha, V A Diwadkar
Motor control is a ubiquitous aspect of human function, and from its earliest origins, abnormal motor control has been proposed as being central to schizophrenia. The neurobiological architecture of the motor system is well understood in primates and involves cortical and sub-cortical components including the primary motor cortex, supplementary motor area, dorsal anterior cingulate cortex, the prefrontal cortex, the basal ganglia, and cerebellum. Notably all of these regions are associated in some manner to the pathophysiology of schizophrenia...
April 25, 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28641108/high-speed-and-scalable-whole-brain-imaging-in-rodents-and-primates
#10
Kaoru Seiriki, Atsushi Kasai, Takeshi Hashimoto, Wiebke Schulze, Misaki Niu, Shun Yamaguchi, Takanobu Nakazawa, Ken-Ichi Inoue, Shiori Uezono, Masahiko Takada, Yuichiro Naka, Hisato Igarashi, Masato Tanuma, James A Waschek, Yukio Ago, Kenji F Tanaka, Atsuko Hayata-Takano, Kazuki Nagayasu, Norihito Shintani, Ryota Hashimoto, Yasuto Kunii, Mizuki Hino, Junya Matsumoto, Hirooki Yabe, Takeharu Nagai, Katsumasa Fujita, Toshio Matsuda, Kazuhiro Takuma, Akemichi Baba, Hitoshi Hashimoto
Subcellular resolution imaging of the whole brain and subsequent image analysis are prerequisites for understanding anatomical and functional brain networks. Here, we have developed a very high-speed serial-sectioning imaging system named FAST (block-face serial microscopy tomography), which acquires high-resolution images of a whole mouse brain in a speed range comparable to that of light-sheet fluorescence microscopy. FAST enables complete visualization of the brain at a resolution sufficient to resolve all cells and their subcellular structures...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28640911/evolution-of-microrna-in-primates
#11
Jennifer C McCreight, Sean E Schneider, Damien B Wilburn, Willie J Swanson
MicroRNA play an important role in post-transcriptional regulation of most transcripts in the human genome, but their evolution across the primate lineage is largely uncharacterized. A particular miRNA can have one to thousands of messenger RNA targets, establishing the potential for a small change in sequence or overall miRNA structure to have profound phenotypic effects. However, the majority of non-human primate miRNA is predicted solely by homology to the human genome and lacks experimental validation. In the present study, we sequenced thirteen species representing a wide range of the primate phylogeny...
2017: PloS One
https://www.readbyqxmd.com/read/28640816/topographic-independent-component-analysis-reveals-random-scrambling-of-orientation-in-visual-space
#12
Marina Martinez-Garcia, Luis M Martinez, Jesús Malo
Neurons at primary visual cortex (V1) in humans and other species are edge filters organized in orientation maps. In these maps, neurons with similar orientation preference are clustered together in iso-orientation domains. These maps have two fundamental properties: (1) retinotopy, i.e. correspondence between displacements at the image space and displacements at the cortical surface, and (2) a trade-off between good coverage of the visual field with all orientations and continuity of iso-orientation domains in the cortical space...
2017: PloS One
https://www.readbyqxmd.com/read/28639977/topical-delivery-of-immunosuppression-to-prolong-xenogeneic-and-allogeneic-split-thickness-skin-graft-survival
#13
Melissa Mastroianni, Zhi Yang Ng, Ritu Goyal, Christopher Mallard, Evan A Farkash, David A Leonard, Alexander Albritton, Kumaran Shanmugarajah, Josef M Kurtz, David H Sachs, Lauren K Macri, Joachim Kohn, Curtis L Cetrulo
Cadaveric skin allograft is the current standard of treatment for temporary coverage of large burn wounds. Porcine xenografts are viable alternatives but undergo α-1,3-galactose (Gal)-mediated hyperacute rejection and are lost by POD 3 because of naturally occurring antibodies to Gal in primate recipients. Using baboons, we previously demonstrated that xenografts from GalT-KO swine (lacking Gal) provided wound coverage comparable with allografts with systemic immunosuppression. In this study, we investigate topical immunosuppression as an alternative to prolong xenograft survival...
June 7, 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/28639374/snp-based-genetic-characterization-of-the-tulane-national-primate-research-center-s-conventional-and-specific-pathogen-free-rhesus-macaque-macaca-mulatta-populations
#14
Sree Kanthaswamy, Jillian Ng, Robert F Oldt, Kathrine Phillippi-Falkenstein, H Michael Kubisch
BACKGROUND: The rhesus macaque is an important biomedical model organism, and the Tulane National Primate Research Center (TNPRC) has one of the largest rhesus macaque breeding colonies in the United States. METHODS: SNP profiles from 3266 rhesus macaques were used to examine the TNPRC colony genetic composition over time and across conventional or SPF animals of Chinese and Indian ancestry. RESULTS: Chinese origin animals were the least genetically diverse and the most inbred; however, since their derivation from their conventional forebearers, neither the Chinese nor the Indian SPF animals exhibit any significant loss of genetic diversity or differentiation...
June 21, 2017: Journal of Medical Primatology
https://www.readbyqxmd.com/read/28638896/a-scalable-cyberinfrastructure-for-interactive-visualization-of-terascale-microscopy-data
#15
A Venkat, C Christensen, A Gyulassy, B Summa, F Federer, A Angelucci, V Pascucci
The goal of the recently emerged field of connectomics is to generate a wiring diagram of the brain at different scales. To identify brain circuitry, neuroscientists use specialized microscopes to perform multichannel imaging of labeled neurons at a very high resolution. CLARITY tissue clearing allows imaging labeled circuits through entire tissue blocks, without the need for tissue sectioning and section-to-section alignment. Imaging the large and complex non-human primate brain with sufficient resolution to identify and disambiguate between axons, in particular, produces massive data, creating great computational challenges to the study of neural circuits...
August 2016: N Y Sci Data Summit NYSDS
https://www.readbyqxmd.com/read/28637812/sensitivity-of-neurons-in-the-middle-temporal-area-of-marmoset-monkeys-to-random-dot-motion
#16
Tristan A Chaplin, Benjamin J Allitt, Maureen A Hagan, Nicholas Sc Price, Ramesh Rajan, Marcello G P Rosa, Leo L Lui
Neurons in the Middle Temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of "neurometric" thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide anesthetized marmoset monkeys, a species which has attracted considerable recent interest as an animal model for vision research...
June 21, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28637387/immunopathology-of-chikungunya-virus-infection-lessons-learned-from-patients-and-animal-models
#17
Lisa F P Ng
Chikungunya virus (CHIKV) is an arthropod-borne alphavirus that causes acute and chronic arthritis. The virus reemerged in the Indian Ocean islands in 2005-2006 and is responsible for outbreaks in the Caribbean islands and the Americas since late 2013. Despite the wealth of research over the past 10 years, there are no commercially available antiviral drugs or vaccines. Treatment usually involves analgesics, anti-inflammatory drugs, and supportive care. Most studies have been focused on understanding the pathogenesis of CHIKV infection through clinical observation and with animal models...
June 21, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28637327/effect-of-simvastatin-on-baboon-endometriosis
#18
Hugh S Taylor, Myles Alderman, Thomas M D'Hooghe, Asgerally T Fazleabas, Duleba J Antoni
Endometriosis, a common disorder affecting women of reproductive age is characterized by ectopic growth of the endometrial tissues, altered steroid hormone response and inflammation. Previous studies revealed that statins, selective inhibitors of the key step of mevalonate pathway, inhibit growth of endometrial stromal cells in vitro and reduce endometriotic lesions in murine models of endometriosis. This study evaluated the effects of simvastatin on the development of endometriosis in a baboon model of this disease...
June 16, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28637190/evolution-of-the-sperm-methylome-of-primates-is-associated-with-retrotransposon-insertions-and-genome-instability
#19
Kei Fukuda, Yukihiro Inoguchi, Kenji Ichiyanagi, Tomoko Ichiyanagi, Yasuhiro Go, Masashi Nagano, Yojiro Yanagawa, Noboru Takaesu, Yasuyuki Ohkawa, Hiroo Imai, Hiroyuki Sasaki
Changes in gene expression resulting from epigenetic and/or genetic changes play an important role in the evolutionary divergence of phenotypes. To explore how epigenetic and genetic changes are linked during primate evolution, we have compared the genome-wide DNA methylation profiles (methylomes) of humans and chimpanzees, which have a 1.2% DNA sequence divergence, of sperm, the frontal cortices, B cells, and neutrophils. We revealed that species-specific differentially methylated regions (S-DMRs), ranging from several hundred bp to several kb, were frequently associated with sequence changes in transcription factor binding sites and insertions of Alu and SVA retrotransposons...
June 20, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28637171/representation-of-rapid-image-sequences-in-v4-networks
#20
Jose A Fernandez-Leon, Bryan J Hansen, Valentin Dragoi
Natural viewing often consists of sequences of brief fixations to image patches of different structure. Whether and how briefly presented sequential stimuli are encoded in a temporal-position manner is poorly understood. Here, we performed multiple-electrode recordings in the visual cortex (area V4) of nonhuman primates (Macaca mulatta) viewing a sequence of 7 briefly flashed natural images, and measured correlations between the cue-triggered population response in the presence and absence of the stimulus. Surprisingly, we found significant correlations for images occurring at the beginning and the end of a sequence, but not for those in the middle...
June 20, 2017: Cerebral Cortex
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