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Brittany L Daughtry, Shawn L Chavez
The use of time-lapse microscopic imaging has proven to be a powerful tool for the study of mitotic divisions and other cellular processes across diverse species and cell types. Although time-lapse monitoring (TLM) of human preimplantation development was first introduced to the in vitro fertilization (IVF) community several decades ago, it was not until relatively recently that TLM systems were commercialized for clinical embryology purposes. Traditionally, human IVF embryos are assessed by successful progression and morphology under a stereomicroscope at distinct time points prior to selection for transfer...
2018: Methods in Molecular Biology
Ryan A Kelley, Shannon M Conley, Rasha Makkia, Jamie N Watson, Zongchao Han, Mark J Cooper, Muna I Naash
Introduction: DNA nanoparticles (NPs) comprising polylysine conjugated to polyethylene glycol efficiently target murine photoreceptors and the retinal pigment epithelium (RPE) and lead to long-term phenotypic improvement in models of retinal degeneration. Advancing this technology requires testing in a large animal model, particularly with regard to safety. So, herein we evaluate NPs in non-human primates (baboon). Methods and results: NPs with plasmids carrying GFP and a ubiquitous, RPE-specific, or photoreceptor-specific promoter were delivered by either subretinal or intravitreal injection...
2018: International Journal of Nanomedicine
David Thybert, Maša Roller, Fábio C P Navarro, Ian Fiddes, Ian Streeter, Christine Feig, David Martin-Galvez, Mikhail Kolmogorov, Václav Janoušek, Wasiu Akanni, Bronwen Aken, Sarah Aldridge, Varshith Chakrapani, William Chow, Laura Clarke, Carla Cummins, Anthony Doran, Matthew Dunn, Leo Goodstadt, Kerstin Howe, Matthew Howell, Ambre-Aurore Josselin, Robert C Karn, Christina M Laukaitis, Lilue Jingtao, Fergal Martin, Matthieu Muffato, Stefanie Nachtweide, Michael A Quail, Cristina Sisu, Mario Stanke, Klara Stefflova, Cock Van Oosterhout, Frederic Veyrunes, Ben Ward, Fengtang Yang, Golbahar Yazdanifar, Amonida Zadissa, David J Adams, Alvis Brazma, Mark Gerstein, Benedict Paten, Son Pham, Thomas M Keane, Duncan T Odom, Paul Flicek
Understanding the mechanisms driving lineage-specific evolution in both primates and rodents has been hindered by the lack of sister clades with a similar phylogenetic structure having high-quality genome assemblies. Here, we have created chromosome-level assemblies of the Mus caroli and Mus pahari genomes. Together with the Mus musculus and Rattus norvegicus genomes, this set of rodent genomes is similar in divergence times to the Hominidae (human-chimpanzee-gorilla-orangutan). By comparing the evolutionary dynamics between the Muridae and Hominidae, we identified punctate events of chromosome reshuffling that shaped the ancestral karyotype of Mus musculus and Mus caroli between 3 and 6 million yr ago, but that are absent in the Hominidae...
March 21, 2018: Genome Research
Agne Taraseviciute, Victor Tkachev, Rafael Ponce, Cameron J Turtle, Jessica M Snyder, H Denny Liggitt, David Myerson, Luis Gonzalez-Cuyar, Audrey Baldessari, Chris English, Alison Yu, Hengqi Zheng, Scott N Furlan, Daniel J Hunt, Virginia Hoglund, Olivia Finney, Hannah Brakke, Bruce R Blazar, Carolina Berger, Stanley Riddell, Rebecca Gardner, Leslie S Kean, Michael C Jensen
Chimeric Antigen Receptor (CAR) T cell immunotherapy has revolutionised the treatment of refractory leukemias and lymphomas, but is associated with significant toxicities, namely cytokine release syndrome (CRS) and neurotoxicity. A major barrier to developing therapeutics to prevent CAR T cell-mediated neurotoxicity is the lack of clinically relevant models. Accordingly, we developed a rhesus macaque (RM) model of neurotoxicity via adoptive transfer of autologous CD20-specific CAR T cells. Following cyclophosphamide lymphodepletion, CD20 CAR T cells expand to 272-4450 cells/µl after 7-8 days and elicit CRS and neurotoxicity...
March 21, 2018: Cancer Discovery
Matthieu Komorowski, Mark R Campbell
No abstract text is available yet for this article.
April 1, 2018: Aerospace Medicine and Human Performance
Marlena M Westcott, Jason Smedberg, Matthew J Jorgensen, Shelby Puckett, Douglas S Lyles
Recombinant vesicular stomatitis virus (VSV) is a promising platform for vaccine development. M51R VSV, an attenuated, M protein mutant strain, is an effective inducer of Type I interferon and dendritic cell (DC) maturation, which are desirable properties to exploit for vaccine design. We have previously evaluated M51R VSV (M51R) and M51R VSV that produces flagellin (M51R-F) as vaccine vectors using murine models, and found that flagellin enhanced DC activation and VSV-specific antibody production after low-dose vaccination...
March 19, 2018: Vaccines
Marco K Wittmann, Patricia L Lockwood, Matthew F S Rushworth
Activity in a network of areas spanning the superior temporal sulcus, dorsomedial frontal cortex, and anterior cingulate cortex is concerned with how nonhuman primates negotiate the social worlds in which they live. Central aspects of these circuits are retained in humans. Activity in these areas codes for primates' interactions with one another, their attempts to find out about one another, and their attempts to prevent others from finding out too much about themselves. Moreover, important features of the social world, such as dominance status, cooperation, and competition, modulate activity in these areas...
March 21, 2018: Annual Review of Neuroscience
Marta Florio, Michael Heide, Anneline Pinson, Holger Brandl, Mareike Albert, Sylke Winkler, Pauline Wimberger, Wieland B Huttner, Michael Hiller
Understanding the molecular basis that underlies the expansion of the neocortex during primate, and notably human, evolution requires the identification of genes that are particularly active in the neural stem and progenitor cells of the developing neocortex. Here, we have used existing transcriptome datasets to carry out a comprehensive screen for protein-coding genes preferentially expressed in progenitors of fetal human neocortex. We show that fifteen human-specific genes exhibit such expression, and many of them evolved distinct neural progenitor cell-type expression profiles and levels compared to their ancestral paralogs...
March 21, 2018: ELife
Hang Joon Jo, Kevin W McCairn, William S Gibson, Paola Testini, Cong Zhi Zhao, Krzysztof R Gorny, Joel P Felmlee, Kirk M Welker, Charles D Blaha, Bryan T Klassen, Hoon-Ki Min, Kendall H Lee
Background and objectives: Deep brain stimulation (DBS) of the thalamus is a promising therapeutic alternative for treating medically refractory Tourette syndrome (TS). However, few human studies have examined its mechanism of action. Therefore, the networks that mediate the therapeutic effects of thalamic DBS remain poorly understood. Methods: Five participants diagnosed with severe medically refractory TS underwent bilateral thalamic DBS stereotactic surgery. Intraoperative fMRI characterized the blood oxygen level-dependent (BOLD) response evoked by thalamic DBS and determined whether the therapeutic effectiveness of thalamic DBS, as assessed using the Modified Rush Video Rating Scale test, would correlate with evoked BOLD responses in motor and limbic cortical and subcortical regions...
2018: NeuroImage: Clinical
Cody J Steely, Jasmine N Baker, Jerilyn A Walker, Charles D Loupe, Mark A Batzer
Background: Alu elements are primate-specific retroposons that mobilize using the enzymatic machinery of L1 s. The recently completed baboon genome project found that the mobilization rate of Alu elements is higher than in the genome of any other primate studied thus far. However, the Alu subfamily structure present in and specific to baboons had not been examined yet. Results: Here we report 129 Alu subfamilies that are propagating in the genome of the olive baboon, with 127 of these subfamilies being new and specific to the baboon lineage...
2018: Mobile DNA
Yoshikazu Taketa, Kanta Horie, Tetsuya Goto, Etsuko Ohta, Kyoko Nakano-Ito, Kazuhiro Hayakawa, Yuki Seki, Aya Goto, Satoru Hosokawa
Mifepristone, which is an orally active synthetic steroid with antiprogesterone activity, is known as an ovarian toxicant. Because the available data regarding the histopathologic characteristics of ovarian toxicity in nonhuman primates are limited, the present study was undertaken in order to investigate detailed histopathologic changes accompanying mifepristone-induced ovarian toxicity and its relationship to changes in menstrual cycle and circulating sex steroid hormone. Twenty mg/kg of mifepristone was orally administered daily to 4 cynomolgus monkeys for 2 months...
January 1, 2018: Toxicologic Pathology
Alex C Stabell, Nicholas R Meyerson, Rebekah C Gullberg, Alison R Gilchrist, Kristofor J Webb, William M Old, Rushika Perera, Sara L Sawyer
Human dengue viruses emerged from primate reservoirs, yet paradoxically dengue does not reach high titers in primate models. This presents a unique opportunity to examine the genetics of spillover versus reservoir hosts. The dengue virus 2 (DENV2) - encoded protease cleaves human STING, reducing type I interferon production and boosting viral titers in humans. We find that both human and sylvatic (reservoir) dengue viruses universally cleave human STING, but not the STING of primates implicated as reservoir species...
March 20, 2018: ELife
Jeffrey R Powell
Although numerous viruses are transmitted by mosquitoes, four have caused the most human suffering over the centuries and continuing today. These are the viruses causing yellow fever, dengue, chikungunya, and Zika fevers. Africa is clearly the ancestral home of yellow fever, chikungunya, and Zika viruses and likely the dengue virus. Several species of mosquitoes, primarily in the genus Aedes , have been transmitting these viruses and their direct ancestors among African primates for millennia allowing for coadaptation among viruses, mosquitoes, and primates...
March 19, 2018: American Journal of Tropical Medicine and Hygiene
Anthony J Mannion, Heather R Martin, Zeli Shen, Ellen M Buckley, JoAnn L Dzink-Fox, Alexis Garcia, Robert P Marini, Mary M Patterson, James G Fox
Non-human primates (NHPs) for biomedical research are commonly infected with Shigella spp. that can cause acute dysentery or chronic episodic diarrhea. These animals are often prophylactically and clinically treated with quinolone antibiotics to eradicate these possible infections. However, chromosomally- and plasmid-mediated antibiotic resistance has become an emerging concern for species in the family Enterobacteriaceae . In this study, five individual isolates of multi-drug resistant Shigella flexneri were isolated from the feces of three macaques...
2018: Frontiers in Microbiology
Tokiko Watanabe, Kiyoko Iwatsuki-Horimoto, Maki Kiso, Noriko Nakajima, Kenta Takahashi, Tiago Jose da Silva Lopes, Mutsumi Ito, Satoshi Fukuyama, Hideki Hasegawa, Yoshihiro Kawaoka
Several animal models are used to study influenza viruses. Intranasal inoculation of animals with a liquid inoculum is one of the main methods used to experimentally infect animals with influenza virus; however, this method does not reflect the natural infection with influenza virus by contact or aerosol route. Aerosol inhalation methods have been established with several influenza viruses for mouse and ferret models, but few studies have evaluated inoculation routes in a nonhuman primates (NHP) model. Here, we performed the experimental infection of NHPs with a highly pathogenic H5N1 influenza virus via the aerosol route and demonstrated that aerosol infection had no effect on clinical outcome, but caused broader infection throughout all of the lobes of the lung compared with a non-aerosolized approach...
March 19, 2018: Scientific Reports
Jacob D Estes, Scott W Wong, Jason M Brenchley
Humans have a close phylogenetic relationship with nonhuman primates (NHPs) and share many physiological parallels, such as highly similar immune systems, with them. Importantly, NHPs can be infected with many human or related simian viruses. In many cases, viruses replicate in the same cell types as in humans, and infections are often associated with the same pathologies. In addition, many reagents that are used to study the human immune response cross-react with NHP molecules. As such, NHPs are often used as models to study viral vaccine efficacy and antiviral therapeutic safety and efficacy and to understand aspects of viral pathogenesis...
March 19, 2018: Nature Reviews. Immunology
Hsin-Hao Yu, Nafiseh Atapour, Tristan A Chaplin, Katrina H Worthy, Marcello G P Rosa
Lesions of striate cortex (V1) trigger massive retrograde degeneration of neurons in the lateral geniculate nucleus (LGN). In primates, these lesions also lead to scotomas within which conscious vision is abolished. Mediation of residual visual capacity within these regions (blindsight) has been traditionally attributed to an indirect visual pathway to the extrastriate cortex, which involves the superior colliculus and pulvinar complex. However, recent studies have suggested that preservation of the LGN is critical for behavioral evidence of blindsight, raising the question of what type of visual information is channeled by remaining neurons in this structure...
March 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Guadalupe Miró, Amelia Troyano, Ana Montoya, Fernando Fariñas, Ma Luisa Fermín, Luís Flores, Carlos Rojo, Rocío Checa, Rosa Gálvez, Valentina Marino, Cristina Fragío, Eva Martínez-Nevado
BACKGROUND: Some wild animals have been recognized as potential reservoirs of Leishmania infantum infection (e.g. carnivores, lagomorphs, rodents, etc.). Leishmania infantum was also identified infecting humans and lagomorphs (i.e. hares and rabbits) over the period of 2009-2016, with the latter acting as the main reservoirs involved in the human leishmaniosis outbreak in Madrid. RESULTS: Two cases of clinical leishmaniosis are reported in orangutans (Pongo pygmaeus pygmaeus) housed at two different centres in Madrid...
March 20, 2018: Parasites & Vectors
Maria José Costa, Jyothirmayee Kudaravalli, Wen-Hui Liu, Jeffrey Stock, Sophanna Kong, Shu-Hui Liu
The development of therapeutic monoclonal antibodies through mouse immunization often originates drug candidates that are not cross-reactive to the mouse ortholog. In such cases, and particularly in oncology, drug efficacy studies are performed on human tumor xenografts or with "surrogate" anti-mouse ortholog antibodies if targeting tumor host cells. Safety assessment of drug candidate(s) is performed at a later development stage in healthy non-human primates. While the latter remains necessary before a drug advances into human subjects, it precludes evaluation of safety in disease conditions and drug de-risking during early development...
2018: PloS One
Sho Kurihara, Masato Fujioka, Tomohiko Yoshida, Makoto Koizumi, Kaoru Ogawa, Hiromi Kojima, Hirotaka James Okano
Hearing research has long been facilitated by rodent models, although in some diseases, human symptoms cannot be recapitulated. The common marmoset (Callithrix jacchus) is a small, easy-to-handle New World monkey which has a similar anatomy of the temporal bone, including the middle ear ossicular chains and inner ear to humans, than in comparison with that of rodents. Here, we report a reproducible, safe, and rational surgical approach to the cochlear round window niche for the drug delivery to the inner ear of the common marmoset...
February 27, 2018: Journal of Visualized Experiments: JoVE
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