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https://www.readbyqxmd.com/read/28538724/applying-systems-level-spectral-imaging-and-analysis-to-reveal-the-organelle-interactome
#1
Alex M Valm, Sarah Cohen, Wesley R Legant, Justin Melunis, Uri Hershberg, Eric Wait, Andrew R Cohen, Michael W Davidson, Eric Betzig, Jennifer Lippincott-Schwartz
The organization of the eukaryotic cell into discrete membrane-bound organelles allows for the separation of incompatible biochemical processes, but the activities of these organelles must be coordinated. For example, lipid metabolism is distributed between the endoplasmic reticulum for lipid synthesis, lipid droplets for storage and transport, mitochondria and peroxisomes for β-oxidation, and lysosomes for lipid hydrolysis and recycling. It is increasingly recognized that organelle contacts have a vital role in diverse cellular functions...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28534450/population-estimate-and-morphometry-of-ovarian-preantral-follicles-from-three-recently-recognized-squirrel-monkey-species-a-comparative-study
#2
Gerson P Lopes, Regiane R Santos, Débora V Almeida, Adriel B Brito, Helder L Queiroz, Sheyla F S Domingues
We describe morphological and morphometrical characteristics of preantral ovarian follicles from three recently recognized Saimiri species: S. macrodon, S. cassiquiarensis and S. vanzolinii; the last one a threatened species. Ovaries from four adult monkeys were evaluated: one pair from a pregnant S. macrodon, two ovarian pairs from S. cassiquiarensis females (one of them pregnant), and one left ovary from a senile S. vanzolinii, applying classical histology. Follicular preantral population was quantified and morphology and morphometry of primordial, primary and secondary follicles were evaluated...
May 23, 2017: Zygote: the Biology of Gametes and Early Embryos
https://www.readbyqxmd.com/read/28533468/vacuolation-activity-and-intracellular-trafficking-of-artb-the-binding-subunit-of-an-ab5-toxin-produced-by-salmonella-enterica-serovar-typhi
#3
Brock P Herdman, James C Paton, Hui Wang, Travis Beddoe, Adrienne W Paton
Various Salmonella enterica serovars, including S Typhi, encode an AB5 toxin (ArtAB), the A subunit of which is an ADP-ribosyltransferase related to the S1 subunit of pertussis toxin. However, although the A subunit is able to catalyse ADP-ribosylation of host G proteins, a cytotoxic phenotype has yet to be identified for the holotoxin. Here we show that its B subunit pentamer (ArtB) binds to receptors on the surface of Vero (African green monkey kidney), CHO (Chinese hamster ovary), U937 (human monocyte) and HBMEC (human brain microvascular endothelial) cell lines...
May 22, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28533288/apparent-affinity-estimates-and-reversal-of-the-effects-of-synthetic-cannabinoids-am-2201-cp-47-497-jwh-122-and-jwh-250-by-rimonabant-in-rhesus-monkeys
#4
Lenka Hruba, Lance R McMahon
Synthetic cannabinoids have been prohibited due to abuse liability and toxicity. Four such synthetic cannabinoids, AM-2201, CP-47,497, JWH-122, and JWH-250, were tested for their capacity to produce CB1 receptor-mediated discriminative stimulus effects in two groups of rhesus monkeys. One group (n=4) discriminated ∆9-THC (0.1 mg/kg i.v.) and a second group (n=4) discriminated the cannabinoid antagonist rimonabant (1 mg/kg i.v.) while receiving 1 mg/kg/12 h of ∆9-THC. AM-2201, JWH-122, CP-47,497, JWH-250, and ∆9-THC increased ∆9-THC-lever responding...
May 22, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28532815/attitudes-and-practices-of-irish-hospital-based-physicians-towards-hand-hygiene-and-handrubbing-using-alcohol-based-hand-rubs-a-comparison-between-2007-and-2015
#5
Liz M Kingston, Barbara L Slevin, Nuala H O'Connell, Colum P Dunne
BACKGROUND: Hand hygiene is the cornerstone of infection prevention and control practices and reduces healthcare-associated infections significantly. Yet, international evidence suggests that medical doctors demonstrate poor compliance. AIM: To explore and compare practices and attitudes towards hand hygiene, in particular handrubbing using alcohol-based hand rubs (ABHR), among hospital-based physicians in Ireland between 2007 and 2015. METHODS: In 2007, a random sample of doctors in a large teaching hospital was invited to complete a postal survey using a validated questionnaire...
May 19, 2017: Journal of Hospital Infection
https://www.readbyqxmd.com/read/28530802/discovery-of-n-5-fluoropyridin-2-yl-6-methyl-4-pyrimidin-5-yloxy-picolinamide-vu0424238-a-novel-negative-allosteric-modulator-of-metabotropic-glutamate-receptor-subtype-5-selected-for-clinical-evaluation
#6
Andrew S Felts, Alice L Rodriguez, Anna L Blobaum, Ryan D Morrison, Brittney S Bates, Analisa Thompson Gray, Jerri M Rook, Mohammed N Tantawy, Frank W Byers, Sichen Chang, Daryl F Venable, Vincent B Luscombe, Gilles D Tamagnan, Colleen M Niswender, J Scott Daniels, Carrie K Jones, P Jeffrey Conn, Craig W Lindsley, Kyle A Emmitte
Preclinical evidence in support of the potential utility of mGlu5 NAMs for the treatment of a variety of psychiatric and neurodegenerative disorders is extensive, and multiple such molecules have entered clinical trials. Despite some promising results from clinical studies, no small molecule mGlu5 NAM has yet to reach market. Here we present the discovery and evaluation of N-(5-fluoropyridin-2-yl)-6-methyl-4-(pyrimidin-5-yloxy)picolinamide (27, VU0424238), a compound selected for clinical evaluation. Compound 27 is more than 900-fold selective for mGlu5 versus the other mGlu receptors, and binding studies established a Ki value of 4...
May 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28529273/septicemic-invasive-klebsiella-pneumoniae-infection-in-a-cynomolgus-monkey-macaca-fascicularis-with-severe-diffused-suppurative-meningoencephalitis
#7
Kazufumi Kasuya, Kou Takayama, Makiko Bito, Natsumi Shimokubo, Ryosuke Kawashima, Tomoyuki Shibahara
A 2-year-old male cynomolgus monkey (Macaca fascicularis) showed neurological symptoms during quarantine for importation into Japan, and was euthanized due to poor prognosis. Gross anatomical examination revealed a hemorrhagic lesion around the lateral ventricle in the cerebrum. Histologically, severe diffused suppurative meningitis and ventriculitis were detected with numerous Gram-negative bacilli in the cerebrum. Immunohistochemically, the bacilli were positively stained with an antibody against Klebsiella pneumoniae...
May 22, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28529118/early-life-allergen-and-air-pollutant-exposures-alter-longitudinal-blood-immune-profiles-in-infant-rhesus-monkeys
#8
Candace M Crowley, Justin H Fontaine, Joan E Gerriets, Edward S Schelegle, Dallas M Hyde, Lisa A Miller
Early life is a critical period for the progressive establishment of immunity in response to environmental stimuli; the impact of airborne challenges on this process is not well defined. In a longitudinal fashion, we determined the effect of episodic house dust mite (HDM) aerosol and ozone inhalation, both separately and combined, on peripheral blood immune cell phenotypes and cytokine expression from 4 to 25weeks of age in an infant rhesus monkey model of childhood development. Immune profiles in peripheral blood were compared with lung lavage at 25weeks of age...
May 18, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28528459/on-the-contribution-of-overt-tactile-expectations-to-visuo-tactile-interactions-within-the-peripersonal-space
#9
Manasa Kandula, Nathan Van der Stoep, Dennis Hofman, H C Dijkerman
Since the discovery of neural regions in the monkey brain that respond preferentially to multisensory stimuli presented in proximal space, researchers have been studying this specialised spatial representation in humans. It has been demonstrated that approaching auditory or visual stimuli modulate tactile processing, while they are within the peripersonal space (PPS). The aim of the current study is to investigate the additional effects of tactile expectation on the PPS-related multisensory interactions. Based on the output of a computational simulation, we expected that as tactile expectation increases rapidly during the course of the motion of the visual stimulus, the outcome RT curves would mask the multisensory contribution of PPS...
May 20, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28528082/discovery-of-bi-135585-an-in-vivo-efficacious-oxazinanone-based-11%C3%AE-hydroxysteroid-dehydrogenase-type-1-inhibitor
#10
Linghang Zhuang, Colin M Tice, Zhenrong Xu, Wei Zhao, Salvacion Cacatian, Yuan-Jie Ye, Suresh B Singh, Peter Lindblom, Brian M McKeever, Paula M Krosky, Yi Zhao, Deepak Lala, Barbara A Kruk, Shi Meng, Lamont Howard, Judith A Johnson, Yuri Bukhtiyarov, Reshma Panemangalore, Joan Guo, Rong Guo, Frank Himmelsbach, Bradford Hamilton, Annette Schuler-Metz, Heike Schauerte, Richard Gregg, Gerard M McGeehan, Katerina Leftheris, David A Claremon
A potent, in vivo efficacious 11β hydroxysteroid dehydrogenase type 1 (11β HSD1) inhibitor (11j) has been identified. Compound 11j inhibited 11β HSD1 activity in human adipocytes with an IC50 of 4.3nM and in primary human adipose tissue with an IC80 of 53nM. Oral administration of 11j to cynomolgus monkey inhibited 11β HSD1 activity in adipose tissue. Compound 11j exhibited >1000× selectivity over other hydroxysteroid dehydrogenases, displays desirable pharmacodynamic properties and entered human clinical trials in 2011...
April 29, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28526067/the-chimeric-monoclonal-antibody-mhcsz-123-against-human-von-willebrand-factor-a3-domain-inhibits-high-shear-arterial-thrombosis-in-a-rhesus-monkey-model
#11
Shundong Ji, Miao Jiang, Bin Yan, Fei Shen, Yang He, Aini Wan, Lijun Xia, Changgeng Ruan, Yiming Zhao
BACKGROUND: SZ-123, a murine monoclonal antibody that targets the human von Willebrand factor (VWF) A3 domain and blocks the binding of collagen, is a powerful antithrombotic. In a Rhesus monkey model of thrombosis, SZ-123 had no side effects, such as bleeding or thrombocytopenia. METHODS: The mouse/human chimeric version of SZ-123, MHCSZ-123, was developed and maintained inhibitory capacities in vitro and ex vivo after injection into monkeys. CHO-S cells were selected for stable expression of MHCSZ-123...
May 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28525759/modeling-rett-syndrome-using-talen-edited-mecp2-mutant-cynomolgus-monkeys
#12
Yongchang Chen, Juehua Yu, Yuyu Niu, Dongdong Qin, Hailiang Liu, Gang Li, Yingzhou Hu, Jiaojian Wang, Yi Lu, Yu Kang, Yong Jiang, Kunhua Wu, Siguang Li, Jingkuan Wei, Jing He, Junbang Wang, Xiaojing Liu, Yuping Luo, Chenyang Si, Raoxian Bai, Kunshan Zhang, Jie Liu, Shaoyong Huang, Zhenzhen Chen, Shuang Wang, Xiaoying Chen, Xinhua Bao, Qingping Zhang, Fuxing Li, Rui Geng, Aibin Liang, Dinggang Shen, Tianzi Jiang, Xintian Hu, Yuanye Ma, Weizhi Ji, Yi Eve Sun
Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here, we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss-of-function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination with brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525647/evaluation-of-the-effects-of-tanezumab-a-monoclonal-antibody-against-nerve-growth-factor-on-the-sympathetic-nervous-system-in-adult-cynomolgus-monkeys-macaca-fascicularis-a-stereologic-histomorphologic-and-cardiofunctional-assessment
#13
Patrice Belanger, Paul Butler, Mark Butt, Siddhartha Bhatt, Stephen Foote, David Shelton, Mark Evans, Rosalinda Arends, Susan Hurst, Carlin Okerberg, Thomas Cummings, David Potter, Jill Steidl-Nichols, Mark Zorbas
Tanezumab, a humanized monoclonal antibody against nerve growth factor is in development for treatment of chronic pain. Three nonclinical studies assessed effects of clinically relevant and supratherapeutic doses of tanezumab on the sympathetic nervous system (SNS) of adult nonhuman primates. Study 1 evaluated potential effects of subcutaneous (SC) tanezumab (1.2 mg/kg every 8 weeks [Q8W]) on SNS in cynomolgus monkeys for 3 or 6 months and reversibility or persistence of any effects through a non-dosing/recovery period...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28524166/homology-mediated-end-joining-based-targeted-integration-using-crispr-cas9
#14
Xuan Yao, Xing Wang, Xinde Hu, Zhen Liu, Junlai Liu, Haibo Zhou, Xiaowen Shen, Yu Wei, Zijian Huang, Wenqin Ying, Yan Wang, Yan-Hong Nie, Chen-Chen Zhang, Sanlan Li, Leping Cheng, Qifang Wang, Yan Wu, Pengyu Huang, Qiang Sun, Linyu Shi, Hui Yang
Targeted integration of transgenes can be achieved by strategies based on homologous recombination (HR), microhomology-mediated end joining (MMEJ) or non-homologous end joining (NHEJ). The more generally used HR is inefficient for achieving gene integration in animal embryos and tissues, because it occurs only during cell division, although MMEJ and NHEJ can elevate the efficiency in some systems. Here we devise a homology-mediated end joining (HMEJ)-based strategy, using CRISPR/Cas9-mediated cleavage of both transgene donor vector that contains guide RNA target sites and ∼800 bp of homology arms, and the targeted genome...
May 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28523853/radiographic-evaluation-of-cardiac-silhouette-using-vertebral-heart-size-method-in-squirrel-monkey-saimiri-sciureus
#15
L N Coutinho, Mbs Brito, A A Imbeloni, Acc Lacreta, F Rech, M P Souto, Ira Ataíde
BACKGROUND: The Saimiri sciureus represents a valuable resource for biomedical research, due to its large number on primate centers and similarity to human anatomy and physiology. The aim of this study was to apply the method proposed by Buchanan & Bücheler in healthy squirrel monkeys (S. sciureus) and determine by radiographic examination, the average value of the vertebral heart size (VHS) for the specie. METHOD: Laterolateral left (LLL), laterolateral right (LLR), ventrodorsal (VD), and dorsoventral (DV) projections were used for radiographic examinations to evaluate the heart silhouette of S...
May 19, 2017: Journal of Medical Primatology
https://www.readbyqxmd.com/read/28523098/incb24360-epacadostat-a-highly-potent-and-selective-indoleamine-2-3-dioxygenase-1-ido1-inhibitor-for-immuno-oncology
#16
Eddy W Yue, Richard Sparks, Padmaja Polam, Dilip Modi, Brent Douty, Brian Wayland, Brian Glass, Amy Takvorian, Joseph Glenn, Wenyu Zhu, Michael Bower, Xiangdong Liu, Lynn Leffet, Qian Wang, Kevin J Bowman, Michael J Hansbury, Min Wei, Yanlong Li, Richard Wynn, Timothy C Burn, Holly K Koblish, Jordan S Fridman, Tom Emm, Peggy A Scherle, Brian Metcalf, Andrew P Combs
A data-centric medicinal chemistry approach led to the invention of a potent and selective IDO1 inhibitor 4f, INCB24360 (epacadostat). The molecular structure of INCB24360 contains several previously unknown or underutilized functional groups in drug substances, including a hydroxyamidine, furazan, bromide, and sulfamide. These moieties taken together in a single structure afford a compound that falls outside of "drug-like" space. Nevertheless, the in vitro ADME data is consistent with the good cell permeability and oral bioavailability observed in all species (rat, dog, monkey) tested...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28522533/a-dedicated-network-for-social-interaction-processing-in-the-primate-brain
#17
J Sliwa, W A Freiwald
Primate cognition requires interaction processing. Interactions can reveal otherwise hidden properties of intentional agents, such as thoughts and feelings, and of inanimate objects, such as mass and material. Where and how interaction analyses are implemented in the brain is unknown. Using whole-brain functional magnetic resonance imaging in macaque monkeys, we discovered a network centered in the medial and ventrolateral prefrontal cortex that is exclusively engaged in social interaction analysis. Exclusivity of specialization was found for no other function anywhere in the brain...
May 19, 2017: Science
https://www.readbyqxmd.com/read/28521874/sirna-mediated-inhibition-of-srebp-cleavage-activating-protein-reduces-dyslipidemia-in-spontaneously-dysmetabolic-rhesus-monkeys
#18
Beth Ann Murphy, Marija Tadin-Strapps, Kristian Jensen, Robin Mogg, Andy Liaw, Kithsiri Herath, Gowri Bhat, David G McLaren, Stephen F Previs, Shirly Pinto
BACKGROUND: SREBP cleavage-activating protein (SCAP) is a cholesterol binding endoplasmic reticulum (ER) membrane protein that is required to activate SREBP transcription factors. SREBPs regulate genes involved in lipid biosynthesis. They also influence lipid clearance by modulating the expression of LDL receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Inhibiting SCAP decreases circulating PCSK9, triglycerides (TG), and LDL-cholesterol (LDL-C), both in vitro and in vivo...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28521247/cognitive-performance-of-juvenile-monkeys-after-chronic-fluoxetine-treatment
#19
Mari S Golub, Edward P Hackett, Casey E Hogrefe, Csaba Leranth, John D Elsworth, Robert H Roth
Potential long term effects on brain development are a concern when drugs are used to treat depression and anxiety in childhood. In this study, male juvenile rhesus monkeys (three-four years of age) were dosed with fluoxetine or vehicle (N=16/group) for two years. Histomorphometric examination of cortical dendritic spines conducted after euthanasia at one year postdosing (N=8/group) suggested a trend toward greater dendritic spine synapse density in prefrontal cortex of the fluoxetine-treated monkeys. During dosing, subjects were trained for automated cognitive testing, and evaluated with a test of sustained attention...
May 1, 2017: Developmental Cognitive Neuroscience
https://www.readbyqxmd.com/read/28516852/effects-of-olanexidine-gluconate-on-preoperative-skin-preparation-an-experimental-study-in-cynomolgus-monkeys
#20
Hikaru Nakata, Yoshie Tsubotani, Takuya Nii, Akifumi Hagi, Yasuhide Inoue, Tadashi Imamura
PURPOSE: To determine the bactericidal efficacy of a new topical antiseptic for preoperative skin preparation, olanexidine gluconate (development code: OPB-2045G), against transient or resident bacterial flora on the skin of cynomolgus monkeys. METHODOLOGY: After measuring baseline bacterial counts on test sites marked on the abdomens, we applied olanexidine, chlorhexidine or povidone-iodine. After 10 min (fast-acting effect) and 6 h (long-lasting effect), bacterial counts were measured again and log10 reductions were calculated...
May 2017: Journal of Medical Microbiology
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