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Selected AbstractsCath6, a bHLH atonal family proneural gene, negatively regulates neuronal differentiation in the retinaDEVELOPMENTAL DYNAMICS, Issue 9 2010Fumi Kubo Abstract Basic helix,loop,helix (bHLH) transcription factors play important roles in cell type specification and differentiation during the development of the nervous system. In this study, we identified a chicken homolog of Atonal 8/ath6 (Cath6) and examined its role in the developing retina. Unlike other Atonal-family proneural genes that induce neuronal differentiation, Cath6 was expressed in stem cell-like progenitor cells in the marginal region of the retina, and its overexpression inhibited neuronal differentiation. A Cath6 fused with a VP16 transactivation domain recapitulated the inhibitory effect of Cath6 on neuronal differentiation, indicating that Cath6 functions as a transcription activator. These results demonstrate that Cath6 constitutes a unique member of the Atonal-family of genes in that it acts as a negative regulator of neuronal differentiation. Developmental Dynamics 239:2492,2500, 2010. © 2010 Wiley-Liss, Inc. [source] The presence of active Cdk5 associated with p35 in astrocytes and its important role in process elongation of scratched astrocyteGLIA, Issue 6 2007Yi He Abstract Cyclin-dependent kinase 5 (Cdk5) is a unique member of the Cdk family; its kinase activity requires association with its activator, p35 or p39. p35 is the strongest and best characterized activator. Previous studies showed that p35 is a neuron-specific protein that restricts Cdk5 activity in neurons. However, a high expression level of Cdk5 is found in astrocytes, which raises the possibility that astrocytic Cdk5 is functional. Here we show the presence of functional Cdk5 associated with p35 in astrocytes and demonstrate its important role in process elongation of scratched astrocytes. We found that p35 and glial fibrillary acidic protein (GFAP) were co-localized in primary cultured and acute isolated brain cells. Cdk5 could form an immunocomplex with p35 and its activity was shown in pure primary cultured astrocytes. p35 was upregulated in astrocytes injured by scratching, concomitantly with upregulation of Cdk5 kinase activity. Pretreatment of the scratched astrocytes with a Cdk5 inhibitor, roscovitine, could delay wound healing by inhibiting the reorganization of tubulin, GFAP, and the extension of hypertrophic processes. Moreover, overexpression of dominant negative Cdk5 could shorten the length of extending protrusion of reactive astrocytes. Thus, our findings demonstrated that functional Cdk5, associated with p35, was expressed in astrocytes and its activity could be upregulated in reactive astrocytes, a new role of Cdk5 that has never been reported in the nervous system. The present study may provide new insight for understanding the multifunctional protein complex Cdk5/p35 in the nervous system. © 2007 Wiley-Liss, Inc. [source] Structure of the G225P/G226P mutant of mouse 3(17),-hydroxysteroid dehydrogenase (AKR1C21) ternary complex: implications for the binding of inhibitor and substrateACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2009Urmi Dhagat 3(17),-Hydroxysteroid dehydrogenase (AKR1C21) is a unique member of the aldo-keto reductase (AKR) superfamily owing to its ability to reduce 17-ketosteroids to 17,-hydroxysteroids, as opposed to other members of the AKR family, which can only produce 17,-hydroxysteroids. In this paper, the crystal structure of a double mutant (G225P/G226P) of AKR1C21 in complex with the coenzyme NADP+ and the inhibitor hexoestrol refined at 2.1,Å resolution is presented. Kinetic analysis and molecular-modelling studies of 17,- and 17,-hydroxysteroid substrates in the active site of AKR1C21 suggested that Gly225 and Gly226 play an important role in determining the substrate stereospecificity of the enzyme. Additionally, the G225P/G226P mutation of the enzyme reduced the affinity (Km) for both 3,- and 17,-hydroxysteroid substrates by up to 160-fold, indicating that these residues are critical for the binding of substrates. [source] Pediatric hospital medicine core competencies: Development and methodologyJOURNAL OF HOSPITAL MEDICINE, Issue S2 2010Erin R. Stucky MD Abstract Background: Pediatric hospital medicine is the most rapidly growing site-based pediatric specialty. There are over 2500 unique members in the three core societies in which pediatric hospitalists are members: the American Academy of Pediatrics (AAP), the Academic Pediatric Association (APA) and the Society of Hospital Medicine (SHM). Pediatric hospitalists are fulfilling both clinical and system improvement roles within varied hospital systems. Defined expectations and competencies for pediatric hospitalists are needed. Methods: In 2005, SHM's Pediatric Core Curriculum Task Force initiated the project and formed the editorial board. Over the subsequent four years, multiple pediatric hospitalists belonging to the AAP, APA, or SHM contributed to the content of and guided the development of the project. Editors and collaborators created a framework for identifying appropriate competency content areas. Content experts from both within and outside of pediatric hospital medicine participated as contributors. A number of selected national organizations and societies provided valuable feedback on chapters. The final product was validated by formal review from the AAP, APA, and SHM. Results: The Pediatric Hospital Medicine Core Competencies were created. They include 54 chapters divided into four sections: Common Clinical Diagnoses and Conditions, Core Skills, Specialized Clinical Services, and Healthcare Systems: Supporting and Advancing Child Health. Each chapter can be used independently of the others. Chapters follow the knowledge, skills, and attitudes educational curriculum format, and have an additional section on systems organization and improvement to reflect the pediatric hospitalist's responsibility to advance systems of care. Conclusion: These competencies provide a foundation for the creation of pediatric hospital medicine curricula and serve to standardize and improve inpatient training practices. Journal of Hospital Medicine 2010;5(4)(Suppl 2):82,86. © 2010 Society of Hospital Medicine. [source] | ||||||||||