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71.
Wang W Lohi H Skurat AV DePaoli-Roach AA Minassian BA Roach PJ 《Archives of biochemistry and biophysics》2007,457(2):264-269
Laforin, encoded by the EPM2A gene, by sequence is a member of the dual specificity protein phosphatase family. Mutations in the EPM2A gene account for around half of the cases of Lafora disease, an autosomal recessive neurodegenerative disorder, characterized by progressive myoclonus epilepsy. The hallmark of the disease is the presence of Lafora bodies, which contain polyglucosan, a poorly branched form of glycogen, in neurons, muscle and other tissues. Glycogen metabolizing enzymes were analyzed in a transgenic mouse over-expressing a dominant negative form of laforin that accumulates Lafora bodies in several tissues. Skeletal muscle glycogen was increased 2-fold as was the total glycogen synthase protein. However, the -/+glucose-6-P activity of glycogen synthase was decreased from 0.29 to 0.16. Branching enzyme activity was increased by 30%. Glycogen phosphorylase activity was unchanged. In whole brain, no differences in glycogen synthase or branching enzyme activities were found. Although there were significant differences in enzyme activities in muscle, the results do not support the hypothesis that Lafora body formation is caused by a major change in the balance between glycogen elongation and branching activities. 相似文献
72.
PD Dr. N. Wolf 《Medizinische Genetik》2007,19(4):414-417
Dental anomalies in children with neuropediatric disorders are easy to diagnose and can be essential in the diagnosis of different entities. They are present in well-known disorders as Incontinentia pigmenti, but also in rare diseases as in Kohlschütter-Tönz syndrome or the recently described ataxia, delayed dentition and hypomyelination. Anomalies of dental shape, enamel and in this case also teeth color, dental number and eruption are all encountered. Knowledge of these abnormalities is important for both clinical geneticist and child neurologist. 相似文献
73.
Because of their high prevalence, cases of coronary artery disease (CAD) and myocardial infarction (MI) are frequently found when asking for a patient’s family history. It is common knowledge that a positive familial history constitutes a risk factor for CAD in its own right, in addition to smoking, increased alcohol intake, diabetes, obesity, hypertension, and hyperlipidemia. Nevertheless, for correct risk assessment it is crucial to accurately distinguish between sporadic and true familial cases of CAD and MI. Familial disposition is present when at least one male first-grade relative under the age of 55 or one female first-grade relative under the age of 65 has/had been diagnosed with myocardial infarction or significant coronary artery disease. In the review presented here, we compile the relevant epidemiological and genetic studies that constitute the scientific basis of this risk assessment. Furthermore, a short overview of the state of the art of genetic CAD/MI research is given. 相似文献
74.
Frank R. Thompson III Melissa C. Roach Thomas W. Bonnot 《The Journal of wildlife management》2022,86(2):e22170
Chuck-will's-widow (Antrostomus carolinensis) and eastern whip-poor-will (Antrostomus vociferus) are nightjars in eastern North America that have declined 69% and 67%, respectively, in abundance since 1966, resulting in conservation concerns for these species. We investigated relationships between nightjar abundance and landscape composition, forest structure, and application of tree thinning and prescribed fire because of regional interest in woodland restoration and nightjar conservation. We conducted nocturnal nightjar surveys at 385 points in southern Missouri, USA, in 2014 and 2015 and related counts to pine (Pinus spp.) and hardwood basal area, canopy closure, percent forest cover, and percent of area thinned or burned within 500 m of survey points. We modeled abundance of chuck-will's-widow and eastern whip-poor-will using time-removal models that included a detection process and an abundance process within a hierarchical Bayesian framework. We detected 534 eastern whip-poor-will and 186 chuck-will's-widow during surveys. Our data supported global models that included all 6 vegetation and management variables for both species. Chuck-will's-widow abundance was negatively related to hardwood basal area and peaked at intermediate values of percent area burned and percent forest cover. Eastern whip-poor-will abundance was negatively related to hardwood basal area and canopy cover, positively related to percent forest cover and percent of area burned, and peaked at low to moderate levels of percent of area thinned. Relationships to forest structure and management activities generally supported the conclusion that woodland restoration benefits nightjars and that chuck-will's-widow select landscapes with less forest cover than eastern whip-poor-will. 相似文献
75.
Jong-Min Lee Kyung-Hee Kim Aram Shin Michael?J. Chao Kawther Abu?Elneel Tammy Gillis Jayalakshmi?Srinidhi Mysore Julia?A. Kaye Hengameh Zahed Ian?H. Kratter Aaron?C. Daub Steven Finkbeiner Hong Li Jared?C. Roach Nathan Goodman Leroy Hood Richard?H. Myers Marcy?E. MacDonald James?F. Gusella 《American journal of human genetics》2015,97(3):435-444
Huntington disease (HD) reflects the dominant consequences of a CAG-repeat expansion in HTT. Analysis of common SNP-based haplotypes has revealed that most European HD subjects have distinguishable HTT haplotypes on their normal and disease chromosomes and that ∼50% of the latter share the same major HD haplotype. We reasoned that sequence-level investigation of this founder haplotype could provide significant insights into the history of HD and valuable information for gene-targeting approaches. Consequently, we performed whole-genome sequencing of HD and control subjects from four independent families in whom the major European HD haplotype segregates with the disease. Analysis of the full-sequence-based HTT haplotype indicated that these four families share a common ancestor sufficiently distant to have permitted the accumulation of family-specific variants. Confirmation of new CAG-expansion mutations on this haplotype suggests that unlike most founders of human disease, the common ancestor of HD-affected families with the major haplotype most likely did not have HD. Further, availability of the full sequence data validated the use of SNP imputation to predict the optimal variants for capturing heterozygosity in personalized allele-specific gene-silencing approaches. As few as ten SNPs are capable of revealing heterozygosity in more than 97% of European HD subjects. Extension of allele-specific silencing strategies to the few remaining homozygous individuals is likely to be achievable through additional known SNPs and discovery of private variants by complete sequencing of HTT. These data suggest that the current development of gene-based targeting for HD could be extended to personalized allele-specific approaches in essentially all HD individuals of European ancestry. 相似文献
76.
77.
Hudson AR Higuchi RI Roach SL Adams ME Vassar A Syka PM Mais DE Miner JN Marschke KB Zhi L 《Bioorganic & medicinal chemistry letters》2011,21(6):1697-1700
A series of tetrahydroquinoline derivatives were synthesized and profiled for their ability to act as glucocorticoid receptor selective modulators. Structure-activity relationships of the tetrahydroquinoline B-ring lead to the discovery of orally available GR-selective agonists with high in vivo activity. 相似文献
78.
Hudson AR Higuchi RI Roach SL Valdez LJ Adams ME Vassar A Rungta D Syka PM Mais DE Marschke KB Zhi L 《Bioorganic & medicinal chemistry letters》2011,21(6):1654-1657
Continuing studies based on dihydroquinoline glucocorticoid receptor agonists lead to the discovery of a series of C4-oxime analogs. Representative compounds exhibited potent transrepression activity with minimal transactivation of phosphoenolpyruvate caboxykinase (PEPCK), a key protein in the gluconeogenesis pathway. These compounds represent promising leads in identifying GR agonists with high anti-inflammatory activity and attenuated potential for glucose elevation. 相似文献
79.
Bauman A Higdon R Rapson S Loiue B Hogan J Stacy R Napuli A Guo W van Voorhis W Roach J Lu V Landorf E Stewart E Kolker N Collart F Myler P van Belle G Kolker E 《Omics : a journal of integrative biology》2011,15(1-2):73-82
High-throughput (HTP) proteomics studies generate large amounts of data. Interpretation of these data requires effective approaches to distinguish noise from biological signal, particularly as instrument and computational capacity increase and studies become more complex. Resolving this issue requires validated and reproducible methods and models, which in turn requires complex experimental and computational standards. The absence of appropriate standards and data sets for validating experimental and computational workflows hinders the development of HTP proteomics methods. Most protein standards are simple mixtures of proteins or peptides, or undercharacterized reference standards in which the identity and concentration of the constituent proteins is unknown. The Seattle Children's 200 (SC-200) proposed proteomics standard mixture is the next step toward developing realistic, fully characterized HTP proteomics standards. The SC-200 exhibits a unique modular design to extend its functionality, and consists of 200 proteins of known identities and molar concentrations from 6 microbial genomes, distributed into 10 molar concentration tiers spanning a 1,000-fold range. We describe the SC-200's design, potential uses, and initial characterization. We identified 84% of SC-200 proteins with an LTQ-Orbitrap and 65% with an LTQ-Velos (false discovery rate?=?1% for both). There were obvious trends in success rate, sequence coverage, and spectral counts with protein concentration; however, protein identification, sequence coverage, and spectral counts vary greatly within concentration levels. 相似文献
80.
Regulation of yeast glycogen phosphorylase by the cyclin-dependent protein kinase Pho85p 总被引:3,自引:0,他引:3
Yeast accumulate glycogen in response to nutrient limitation. The key enzymes of glycogen synthesis and degradation, glycogen synthase, and phosphorylase, are regulated by reversible phosphorylation. Phosphorylation inactivates glycogen synthase but activates phosphorylase. The kinases and phosphatases that control glycogen synthase are well characterized whilst the enzymes modifying phosphorylase are poorly defined. Here, we show that the cyclin-dependent protein kinase, Pho85p, which we have previously found to regulate glycogen synthase also controls the phosphorylation state of phosphorylase. 相似文献