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Daisuke Furutama Noriyuki Morita Riya Takano Yukiko Sekine Tetsushi Sadakata Yo Shinoda Kanehiro Hayashi Yuriko Mishima Katsuhiko Mikoshiba Richard Hawkes Teiichi Furuichi 《Journal of neuroscience research》2010,88(13):2810-2825
The cerebellar Purkinje cell monolayer is organized into heterogeneous Purkinje cell compartments that have different molecular compositions. Here we describe a transgenic mouse line, 1NM13, that shows heterogeneous transgene expression in parasagittal Purkinje cell arrays. The transgene consists of a nuclear localization signal (nls) fused to the β‐galactosidase (lacZ) composite gene driven by the type 1 inositol 1,4,5‐trisphosphate receptor (IP3R1) gene promoter. IP3R1‐nls‐lacZ transgene expression was detected at a single Purkinje cell level over the surface of a whole‐mount X‐gal‐stained cerebellum because of nuclear accumulation of the nls‐lacZ activity. Developing cerebella of 1NM13 mice showed stripe‐like X‐gal staining patterns of parasagittal Purkinje cell subsets. The X‐gal stripe pattern was likely determined by an intrinsic property as early as E15 and showed increasing complexity with cerebellar development. The X‐gal stripe pattern was reminiscent of, but not identical to, the stripe pattern of zebrin II immunoreactivity. We designated the symmetrical X‐gal‐positive (transgene‐positive, Tg+) Purkinje cell stripes about the midline as vermal Tg1+, Tg2(a, b)+ and Tg3(a, b)+ stripes and hemispheric Tg4(a, b)+, Tg5(a, b)+, Tg6(a, b, c)+, and Tg7(a, b)+ stripes, where a, b, and c indicate substripes. We also assigned three parafloccular substripes Tg8(a, b, c)+. The boundaries of X‐gal stripes at P5 were consistent with raphes in the Purkinje cell layer through which granule cells migrate, suggesting a possible association of the X‐gal stripes with raphe formation. Our results indicate that 1NM13 is a good mouse model with a reproducible and clear marker for the compartmentalization of Purkinje cell arrays. © 2010 Wiley‐Liss, Inc. 相似文献
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Felder Jennifer N. Mirchandaney Riya Dimidjian Sona 《Archives of women's mental health》2022,25(6):1149-1153
Archives of Women's Mental Health - Perinatal depression is the most common complication of pregnancy and childbirth, and it is associated with adverse consequences. The United States... 相似文献
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Rengasamy Palanivel Riya Ganguly Subat Turdi Aimin Xu Gary Sweeney 《Metabolism: clinical and experimental》2014
Objective
Adiponectin is known to confer its cardioprotective effects in obesity and type 2 diabetes, mainly by regulating glucose and fatty acid metabolism in cardiomyocytes. Dynamic actin cytoskeleton remodeling is involved in regulation of multiple biological functions, including glucose uptake. Here we investigated in neonatal cardiomyocytes whether adiponectin induced actin cytoskeleton remodeling and if this played a role in adiponectin-stimulated glucose uptake.Materials/methods
Primary cardiomyocytes were treated with full-length and globular adiponectin (fAd and gAd, respectively).Results
Both fAd and gAd increased RhoA activity, phosphorylation of the Rho/ROCK signaling target cofilin and actin polymerization to form filamentous actin as determined by rhodamine–phallodin immunofluorescence and quantitative analysis of filamentous to globular actin ratio. Scanning electron microscopy also demonstrated structural remodeling. Adiponectin stimulated glucose uptake, was significantly abrogated in the presence of inhibitors of actin cytoskeleton remodeling (cytochalasin D) and Rho/ROCK signaling (C3 transferase, Y27632). We showed that adiponectin increased colocalization of actin and APPL1 and that actin remodeling, phosphorylation of AMPK, p38MAPK and cofilin, glucose uptake and oxidation were all attenuated after siRNA-mediated knockdown of APPL1.Conclusion
We show that adiponectin mediates Rho/ROCK-dependent actin cytoskeleton remodeling to increase glucose uptake and metabolism via APPL1 signaling. 相似文献45.
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Gong Inna Y. Yazdan-Ashoori Payam Jimenez-Juan Laura Tan Nigel S. Angaran Paul Chacko Binita Riya Al-Mousawy Saif Singh Sheldon M. Shalmon Tamar Folador Luciano Mangat Iqwal Deva Djeven P. Yan Andrew T. 《The international journal of cardiovascular imaging》2021,37(7):2259-2267
The International Journal of Cardiovascular Imaging - Left atrial (LA) volume and function (LA ejection fraction, LAEF) have demonstrated prognostic value in various cardiovascular diseases. We... 相似文献
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蒙医学基础理论实验教学现状与发展思路 总被引:2,自引:0,他引:2
阐述蒙医学基础理论实验课从起步到现在开展的实验项目及发展过程,初步研究和探讨蒙医学基础理论实验教学的思路、方法、手段,为蒙医药现代化精品教学而努力。 相似文献
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Joelle I. Rosser Nadine Nagy Riya Goel Gernot Kaber Sally Demirdjian Jamie Saxena Jennifer B. Bollyky Adam R. Frymoyer Ana E. Pacheco-Navarro Elizabeth B. Burgener Jayakumar Rajadas Zhe Wang Olga Arbach Colleen E. Dunn Anissa Kalinowski Carlos E. Milla Paul L. Bollyky 《The Journal of clinical investigation》2022,132(9)
BACKGROUNDHyaluronan (HA), an extracellular matrix glycosaminoglycan, has been implicated in the pathophysiology of COVID-19 infection, pulmonary hypertension, pulmonary fibrosis, and other diseases, but is not targeted by any approved drugs. We asked whether hymecromone (4-methylumbelliferone [4-MU]), an oral drug approved in Europe for biliary spasm treatment that also inhibits HA in vitro and in animal models, could be repurposed as an inhibitor of HA synthesis in humans.METHODSWe conducted an open-label, single-center, dose-response study of hymecromone in healthy adults. Subjects received hymecromone at 1200 (n = 8), 2400 (n = 9), or 3600 (n = 9) mg/d divided into 3 doses daily, administered orally for 4 days. We assessed safety and tolerability of hymecromone and analyzed HA, 4-MU, and 4-methylumbelliferyl glucuronide (4-MUG; the main metabolite of 4-MU) concentrations in sputum and serum.RESULTSHymecromone was well tolerated up to doses of 3600 mg/d. Both sputum and serum drug concentrations increased in a dose-dependent manner, indicating that higher doses lead to greater exposures. Across all dose arms combined, we observed a significant decrease in sputum HA from baseline after 4 days of treatment. We also observed a decrease in serum HA. Additionally, higher baseline sputum HA levels were associated with a greater decrease in sputum HA.CONCLUSIONAfter 4 days of exposure to oral hymecromone, healthy human subjects experienced a significant reduction in sputum HA levels, indicating this oral therapy may have potential in pulmonary diseases where HA is implicated in pathogenesis.TRIAL REGISTRATIONClinicalTrials.gov .FUNDINGStanford Medicine Catalyst, Stanford SPARK, Stanford Innovative Medicines Accelerator program, NIH training grants 5T32AI052073-14 and T32HL129970. NCT02780752相似文献