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11.
Locus Heterogeneity for Waardenburg Syndrome is Predictive of Clinical Subtypes 总被引:1,自引:4,他引:1 下载免费PDF全文
Lindsay A. Farrer Kathleen S. Arnos James H. Asher Clinton T. Baldwin Scott R. Diehl Thomas B. Friedman Jacquie Greenberg Kenneth M. Grundfast Christopher Hoth Anil K. Lalwani Barbara Landa Kate Leverton Aubrey Milunsky Robert Morell Walter E. Nance Valerie Newton Rajkumar Ramesar Valluri S. Rao Jennifer E. Reynolds Theresa B. San Agustin Edward R. Wilcox Ingrid Winship Andrew P. Read 《American journal of human genetics》1994,55(4):728-737
Waardenburg syndrome (WS) is a dominantly inherited and clinically variable syndrome of deafness, pigmentary changes, and distinctive facial features. Clinically, WS type I (WS1) is differentiated from WS type II (WS2) by the high frequency of dystopia canthorum in the family. In some families, WS is caused by mutations in the PAX3 gene on chromosome 2q. We have typed microsatellite markers within and flanking PAX3 in 41 WS1 kindreds and 26 WS2 kindreds in order to estimate the proportion of families with probable mutations in PAX3 and to study the relationship between phenotypic and genotypic heterogeneity. Evaluation of heterogeneity in location scores obtained by multilocus analysis indicated that WS is linked to PAX3 in 60% of all WS families and in 100% of WS1 families. None of the WS2 families were linked. In those families in which equivocal lod scores (between −2 and +1) were found, PAX3 mutations have been identified in 5 of the 15 WS1 families but in none of the 4 WS2 families. Although preliminary studies do not suggest any association between the phenotype and the molecular pathology in 20 families with known PAX3 mutations and in four patients with chromosomal abnormalities in the vicinity of PAX3, the presence of dystopia in multiple family members is a reliable indicator for identifying families likely to have a defect in PAX3. 相似文献
12.
Zhou H Li W Wang SP Mendoza V Rosa R Hubert J Herath K McLaughlin T Rohm RJ Lassman ME Wong KK Johns DG Previs SF Hubbard BK Roddy TP 《Journal of lipid research》2012,53(6):1223-1231
Stable isotope tracer studies of apoprotein flux in rodent models present difficulties as they require working with small volumes of plasma. We demonstrate the ability to measure apoprotein flux by administering either (2)H- or (18)O-labeled water to mice and then subjecting samples to LC-MS/MS analyses; we were able to simultaneously determine the labeling of several proteolytic peptides representing multiple apoproteins. Consistent with relative differences reported in the literature regarding apoprotein flux in humans, we found that the fractional synthetic rate of apoB is greater than apoA1 in mice. In addition, the method is suitable for quantifying acute changes in protein flux: we observed a stimulation of apoB production in mice following an intravenous injection of Intralipid and a decrease in apoB production in mice treated with an inhibitor of microsomal triglyceride transfer protein. In summary, we demonstrate a high-throughput method for studying apoprotein kinetics in rodent models. Although notable differences exist between lipoprotein profiles that are observed in rodents and humans, we expect that the method reported here has merit in studies of dyslipidemia as i) rodent models can be used to probe target engagement in cases where one aims to modulate apoprotein production and ii) the approach should be adaptable to studies in humans. 相似文献
13.
Martha S. Petrovick Frances E. Nargi Theresa Towle Kristine Hogan Marie Bohane Deborah J. Wright Thomas H. MacRae Malcolm Potts Richard F. Helm 《Biotechnology and bioengineering》2010,106(3):474-481
The unique properties of mammalian cells make them valuable for a variety of applications in medicine, industry, and diagnostics. However, the utility of such cells is restricted due to the difficulty in storing them non‐frozen for an extended time and still maintaining their stability and responsiveness. In order to extend the active life span of a mammalian biosensor cell line at room and refrigerated temperatures, we have over expressed genes that are reported to provide protection from apoptosis, stress, or oxidation. We demonstrated that over expression of genes from the extremophile, Artemia franciscana, as well as GADD45β, extends room‐temperature storage of fully active cells 3.5‐fold, while over production of several anti‐apoptotic proteins extended 4°C storage 2‐ to 3‐fold. Methodologies like these that improve the stability of mammalian‐cell‐based technologies in the absence of freezers may enable widespread use of these tools in applications that have been considered impractical based solely on limited storage characteristics. Biotechnol. Bioeng. 2010; 106: 474–481. © 2010 Wiley Periodicals, Inc. 相似文献
14.
Kristen L.G. Jones M. Katharine Holloway Hua-Poo Su Steven S. Carroll Christine Burlein Sinoeun Touch Daniel J. DiStefano Rosa I. Sanchez Theresa M. Williams Joseph P. Vacca Craig A. Coburn 《Bioorganic & medicinal chemistry letters》2010,20(14):4065-4068
A series of HIV-1 protease inhibitors containing an epsilon substituted lysinol backbone was synthesized. Two novel synthetic routes using N-boc-l-glutamic acid alpha-benzyl ester and 2,6-diaminopimelic acid were developed. Incorporation of this epsilon substituent enabled access to the S2 pocket of the enzyme, affording high potency inhibitors. Modeling studies and synthetic efforts suggest the potency increase is due to both conformational bias and van der Waals interactions with the S2 pocket. 相似文献
15.
Abderrahman El Maarouf Damali Moyo-Lee Yaw Theresa Lindhout Damien D. Pearse Warren Wakarchuk Urs Rutishauser 《The Journal of biological chemistry》2012,287(39):32770-32779
In vertebrates, polysialic acid (PSA) is typically added to the neural cell adhesion molecule (NCAM) in the Golgi by PST or STX polysialyltransferase. PSA promotes plasticity, and its enhanced expression by viral delivery of the PST or STX gene has been shown to promote cellular processes that are useful for repair of the injured adult nervous system. Here we demonstrate a new strategy for PSA induction on cells involving addition of a purified polysialyltransferase from Neisseria meningitidis (PSTNm) to the extracellular environment. In the presence of its donor substrate (CMP-Neu5Ac), PSTNm synthesized PSA directly on surfaces of various cell types in culture, including Chinese hamster ovary cells, chicken DF1 fibroblasts, primary rat Schwann cells, and mouse embryonic stem cells. Similarly, injection of PSTNm and donor in vivo was able to produce PSA in different adult brain regions, including the cerebral cortex, striatum, and spinal cord. PSA synthesis by PSTNm requires the presence of the donor CMP-Neu5Ac, and the product could be degraded by the PSA-specific endoneuraminidase-N. Although PSTNm was able to add PSA to NCAM, most of its product was attached to other cell surface proteins. Nevertheless, the PSTNm-induced PSA displayed the ability to attenuate cell adhesion, promote neurite outgrowth, and enhance cell migration as has been reported for endogenous PSA-NCAM. Polysialylation by PSTNm occurred in vivo in less than 2.5 h, persisted in tissues, and then decreased within a few weeks. Together these characteristics suggest that a PSTNm-based approach may provide a valuable alternative to PST gene therapy. 相似文献
16.
Nguyen DN Stump CA Walsh ES Fernandes C Davide JP Ellis-Hutchings M Robinson RG Williams TM Lobell RB Huber HE Buser CA 《Bioorganic & medicinal chemistry letters》2002,12(9):1269-1273
Compound 1 has been shown to be a dual prenylation inhibitor with FPTase (IC50=2 nM) and GGPTase-I (IC50=95 nM). Analogues of 1, which replaced the cyanophenyl group with various biaryls, led to the discovery of highly potent dual FPTase/GGPTase-I inhibitors. 4-trifluoromethylphenyl, trifluoropentynyl, and trifluoropentyl were identified as good p-cyano replacements. 相似文献
17.
Acute temperature preference tests were conducted with American eels, Anguilla rostrata, collected from Maryland's eastern shore. Eels were acclimated to temperatures of 6, 12, 18, 24 and 30°C. Final temperature preferendum was 16.7°C. Data differ from the temperature responses of the majority of fishes tested to date in that acclimation temperature did not influence selected temperatures. Similar results were obtained for various other fishes (Oncorhynchus, Salmo, Salvelinus) by other investigators. Behavioral responses at various acclimation temperatures were observed. 相似文献
18.
Katja Paul Minli Wang Emil Mladenov Alena Bencsik-Theilen Theresa Bednar Wenqi Wu Hiroshi Arakawa George Iliakis 《PloS one》2013,8(3)
Biochemical and genetic studies suggest that vertebrates remove double-strand breaks (DSBs) from their genomes predominantly by two non-homologous end joining (NHEJ) pathways. While canonical NHEJ depends on the well characterized activities of DNA-dependent protein kinase (DNA-PK) and LIG4/XRCC4/XLF complexes, the activities and the mechanisms of the alternative, backup NHEJ are less well characterized. Notably, the contribution of LIG1 to alternative NHEJ remains conjectural and although biochemical, cytogenetic and genetic experiments implicate LIG3, this contribution has not been formally demonstrated. Here, we take advantage of the powerful genetics of the DT40 chicken B-cell system to delineate the roles of LIG1 and LIG3 in alternative NHEJ. Our results expand the functions of LIG1 to alternative NHEJ and demonstrate a remarkable ability for LIG3 to backup DSB repair by NHEJ in addition to its essential function in the mitochondria. Together with results on DNA replication, these observations uncover a remarkable and previously unappreciated functional flexibility and interchangeability between LIG1 and LIG3. 相似文献
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