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941.
Phosphatidylinositol 3-phosphate [PtdIns3P] is generated at the plasma membrane by an inositol polyphosphate 5-phosphatase: endogenous PtdIns3P can promote GLUT4 translocation to the plasma membrane
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Kong AM Horan KA Sriratana A Bailey CG Collyer LJ Nandurkar HH Shisheva A Layton MJ Rasko JE Rowe T Mitchell CA 《Molecular and cellular biology》2006,26(16):6065-6081
Exogenous delivery of carrier-linked phosphatidylinositol 3-phosphate [PtdIns(3)P] to adipocytes promotes the trafficking, but not the insertion, of the glucose transporter GLUT4 into the plasma membrane. However, it is yet to be demonstrated if endogenous PtdIns(3)P regulates GLUT4 trafficking and, in addition, the metabolic pathways mediating plasma membrane PtdIns(3)P synthesis are uncharacterized. In unstimulated 3T3-L1 adipocytes, conditions under which PtdIns(3,4,5)P3 was not synthesized, ectopic expression of wild-type, but not catalytically inactive 72-kDa inositol polyphosphate 5-phosphatase (72-5ptase), generated PtdIns(3)P at the plasma membrane. Immunoprecipitated 72-5ptase from adipocytes hydrolyzed PtdIns(3,5)P2, forming PtdIns(3)P. Overexpression of the 72-5ptase was used to functionally dissect the role of endogenous PtdIns(3)P in GLUT4 translocation and/or plasma membrane insertion. In unstimulated adipocytes wild type, but not catalytically inactive, 72-5ptase, promoted GLUT4 translocation and insertion into the plasma membrane but not glucose uptake. Overexpression of FLAG-2xFYVE/Hrs, which binds and sequesters PtdIns(3)P, blocked 72-5ptase-induced GLUT4 translocation. Actin monomer binding, using latrunculin A treatment, also blocked 72-5ptase-stimulated GLUT4 translocation. 72-5ptase expression promoted GLUT4 trafficking via a Rab11-dependent pathway but not by Rab5-mediated endocytosis. Therefore, endogenous PtdIns(3)P at the plasma membrane promotes GLUT4 translocation. 相似文献
942.
Madsen PP Kibaek M Roca X Sachidanandam R Krainer AR Christensen E Steiner RD Gibson KM Corydon TJ Knudsen I Wanders RJ Ruiter JP Gregersen N Andresen BS 《Human genetics》2006,118(6):680-690
Short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) is an autosomal recessive disorder of l-isoleucine catabolism. Little is known about the clinical presentation associated with this enzyme defect, as it has been
reported in only a limited number of patients. Because the presence of C5-carnitine in blood may indicate SBCADD, the disorder
may be detected by MS/MS-based routine newborn screening. It is, therefore, important to gain more knowledge about the clinical
presentation and the mutational spectrum of SBCADD. In the present study, we have studied two unrelated families with SBCADD,
both with seizures and psychomotor delay as the main clinical features. One family illustrates the fact that affected individuals
may also remain asymptomatic. In addition, the normal level of newborn blood spot C5-acylcarnitine in one patient underscores
the fact that newborn screening by MS/MS currently lacks sensitivity in detecting SBCADD. Until now, seven mutations in the SBCAD gene have been reported, but only three have been tested experimentally. Here, we identify and characterize an IVS3+3A>G
mutation (c.303+3A>G) in the SBCAD gene, and provide evidence that this mutation is disease-causing in both families. Using a minigene approach, we show that
the IVS3+3A>G mutation causes exon 3 skipping, despite the fact that it does not appear to disrupt the consensus sequence
of the 5′ splice site. Based on these results and numerous literature examples, we suggest that this type of mutation (IVS+3A>G)
induces missplicing only when in the context of non-consensus (weak) 5′ splice sites. Statistical analysis of the sequences
shows that the wild-type versions of 5′ splice sites in which +3A>G mutations cause exon skipping and disease are weaker on
average than a random set of 5′ splice sites. This finding is relevant to the interpretation of the functional consequences
of this type of mutation in other disease genes. 相似文献
943.
944.
von Korff M Wang H Léon J Pillen K 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2006,112(7):1221-1231
The objective of the present study was to identify favourable exotic Quantitative Trait Locus (QTL) alleles for the improvement
of agronomic traits in the BC2DH population S42 derived from a cross between the spring barley cultivar Scarlett and the wild barley accession ISR42-8 (Hordeum vulgare ssp. spontaneum). QTLs were detected as a marker main effect and/or a marker × environment interaction effect (M × E) in a three-factorial ANOVA. Using field data of up to eight environments and genotype data of 98 SSR loci, we detected 86
QTLs for nine agronomic traits. At 60 QTLs the marker main effect, at five QTLs the M × E interaction effect, and at 21 QTLs both the effects were significant. The majority of the M × E interaction effects were due to changes in magnitude and are, therefore, still valuable for marker assisted selection across
environments. The exotic alleles improved performance in 31 (36.0%) of 86 QTLs detected for agronomic traits. The exotic alleles
had favourable effects on all analysed quantitative traits. These favourable exotic alleles were detected, in particular on
the short arm of chromosome 2H and the long arm of chromosome 4H. The exotic allele on 4HL, for example, improved yield by
7.1%. Furthermore, the presence of the exotic allele on 2HS increased the yield component traits ears per m2 and thousand grain weight by 16.4% and 3.2%, respectively. The present study, hence, demonstrated that wild barley does harbour
valuable alleles, which can enrich the genetic basis of cultivated barley and improve quantitative agronomic traits. 相似文献
945.
Allender MC Mitchell MA Phillips CA Gruszynski K Beasley VR 《Journal of wildlife diseases》2006,42(1):107-114
During the 2004 field season, blood was collected from Eastern massasauga rattlesnakes (Sistrurus catenatus catenatus) in the Carlyle Lake (Carlyle, Illinois, USA) and Allerton Park (Monticello, Illinois, USA) populations to derive baseline complete blood count and plasma biochemistry data and to assess the prevalence of antibodies to West Nile virus (WNV) and ophidian paramyxovirus (OPMV). Massasaugas were located for sampling through visual encounter surveys. Body weight, snout-vent length, total protein, globulins, sodium, and potassium were normally distributed among the survey population. Aspartate aminotransferase, creatine kinase, albumin, calcium, uric acid, white blood cell count, heterophils, lymphocytes, monocytes, eosinophils, and basophils were non-normally distributed within these animals. Female snakes had significantly shorter tail lengths; lower blood glucose, packed cell volumes, and absolute azurophil counts; and higher plasma calcium and phosphorus concentrations than did males. None of the snakes tested (n=21) were seropositive for WNV, whereas all (n=20) were seropositive for OPMV. 相似文献
946.
947.
FSH directly regulates bone mass 总被引:21,自引:0,他引:21
Sun L Peng Y Sharrow AC Iqbal J Zhang Z Papachristou DJ Zaidi S Zhu LL Yaroslavskiy BB Zhou H Zallone A Sairam MR Kumar TR Bo W Braun J Cardoso-Landa L Schaffler MB Moonga BS Blair HC Zaidi M 《Cell》2006,125(2):247-260
Postmenopausal osteoporosis, a global public health problem, has for decades been attributed solely to declining estrogen levels. Although FSH levels rise sharply in parallel, a direct effect of FSH on the skeleton has never been explored. We show that FSH is required for hypogonadal bone loss. Neither FSHbeta nor FSH receptor (FSHR) null mice have bone loss despite severe hypogonadism. Bone mass is increased and osteoclastic resorption is decreased in haploinsufficient FSHbeta+/- mice with normal ovarian function, suggesting that the skeletal action of FSH is estrogen independent. Osteoclasts and their precursors possess G(i2alpha)-coupled FSHRs that activate MEK/Erk, NF-kappaB, and Akt to result in enhanced osteoclast formation and function. We suggest that high circulating FSH causes hypogonadal bone loss. 相似文献
948.
Biodeterioration of archaeological sites and historic buildings is a major concern for conservators, archaeologists, and scientists
involved in preservation of the world's cultural heritage. The Maya archaeological sites in southern Mexico, some of the most
important cultural artifacts in the Western Hemisphere, are constructed of limestone. High temperature and humidity have resulted
in substantial microbial growth on stone surfaces at many of the sites. Despite the porous natureof limestone and the common
occurrence of endolithic microorganisms in many habitats, little is known about the microbial flora living inside the stone.
We found a large endolithic bacterial community in limestone from the interior of the Maya archaeological site Ek' Balam.
Analysis of 16S rDNA clones demonstrated disparate communities (endolithic: >80% Actinobacteria, Acidobacteria, and Low GC
Firmicutes; epilithic: >50% Proteobacteria). The presence of differing epilithic and endolithic bacterial communities may
be a significant factor for conservation of stone cultural heritage materials and quantitative prediction of carbonate weathering. 相似文献
949.
Hybridization increases measures of innate and cell-mediated immunity in an endangered bird species 总被引:3,自引:0,他引:3
1. Given the increasing threat of 'emerging infectious diseases' (EIDs), and the vulnerability of small inbred populations to such novel challenges (at least partly through compromised immunity), a degree of interspecific hybridization may improve the viability of endangered species by enriching depauperate gene pools. 2. To investigate this hypothesis, we quantified indicators of the strength of both innate and cell-mediated immunity in wild populations of hybridizing parakeets on the Chatham Islands, New Zealand. 3. We show that both measures of immune function are markedly higher in the cosmopolitan red-crowned parakeet Cyanoramphus novaezelandiae than in the island endemic Forbes' parakeet C. forbesi, as is to be expected when comparing relatively outbred vs. relatively inbred species. 4. In addition, we show that both measures of immune function are higher in Forbes'x red-crowned parakeet hybrids than in the Forbes' parakeet. Even those individuals with few red-crowned characteristics, suggesting they are the products of matings between hybrids and Forbes' parakeets, have significantly higher measures of immune function. 5. As at least one of the immune indicators measured correlates directly with both survivorship and the viability of small bird populations, this study reveals a potential management option for hybridizing species of conservation concern, where an increase in resilience to novel disease challenges could outweigh some loss of genetic integrity. 相似文献
950.