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61.
Deidre A. Winnier Marcel Fourcaudot Luke Norton Muhammad A. Abdul-Ghani Shirley L. Hu Vidya S. Farook Dawn K. Coletta Satish Kumar Sobha Puppala Geetha Chittoor Thomas D. Dyer Rector Arya Melanie Carless Donna M. Lehman Joanne E. Curran Douglas T. Cromack Devjit Tripathy John Blangero Ravindranath Duggirala Harald H. H. G?ring Ralph A. DeFronzo Christopher P. Jenkinson 《PloS one》2015,10(4)
Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect common patterns of gene regulation associated with obesity and insulin resistance. We used phenotypic and genotypic data from 308 Mexican American participants from the Veterans Administration Genetic Epidemiology Study (VAGES). Basal fasting RNA was extracted from adipose tissue biopsies from a subset of 75 unrelated individuals, and gene expression data generated on the Illumina BeadArray platform. The number of gene probes with significant expression above baseline was approximately 31,000. We performed multiple regression analysis of all probes with 15 metabolic traits. Adipose tissue had 3,012 genes significantly associated with the traits of interest (false discovery rate, FDR ≤ 0.05). The significance of gene expression changes was used to select 52 genes with significant (FDR ≤ 10-4) gene expression changes across multiple traits. Gene sets/Pathways analysis identified one gene, alcohol dehydrogenase 1B (ADH1B) that was significantly enriched (P < 10-60) as a prime candidate for involvement in multiple relevant metabolic pathways. Illumina BeadChip derived ADH1B expression data was consistent with quantitative real time PCR data. We observed significant inverse correlations with waist circumference (2.8 x 10-9), BMI (5.4 x 10-6), and fasting plasma insulin (P < 0.001). These findings are consistent with a central role for ADH1B in obesity and insulin resistance and provide evidence for a novel genetic regulatory mechanism for human metabolic diseases related to these traits. 相似文献
62.
Lantana (Lantana camara) poses a serious threat to the biodiversity of the dry rainforest vegetation at Forty Mile Scrub National Park, Queensland, Australia, by outcompeting native species and increasing vulnerability to fire. This pilot study tests the effectiveness of three weed control methods (hand pulling, a glyphosphate‐based foliar spray herbicide and a picloram‐ and triclopyr‐based basal bark herbicide) in removing lantana and their success in reducing lantana fuel loads. The foliar spray herbicide was the most effective in killing lantana, while manual pulling resulted in the largest decrease in fuel height. We suggest that foliar spraying will be most efficient for combating large infestations of lantana, while hand pulling techniques are recommended for creating firebreaks or when minimizing damage to native species is paramount. 相似文献
63.
Xiao-Ming Zhou Patricia Curran Jesse Baumgold Peter H. Fishman 《Journal of neurochemistry》1994,63(4):1361-1370
Abstract: Exposure of human SK-N-MC neurotumor cells to 4β-phorbol 12-myristate 13-acetate (PMA) increased isoproterenol stimulation of cyclic AMP levels by severalfold. This potentiation was blocked by inhibitors of protein kinase C (PKC) and did not occur in cells in which PKC had been down-regulated. PMA treatment also enhanced the stimulation by dopamine, cholera toxin, and forskolin. Thus, the effect of PMA on the adenylylcyclase system was postreceptor and involved either the guanine nucleotide binding regulatory (G) proteins or the cyclase itself. As PMA treatment did not impair the inhibition of isoproterenol stimulation by neuropeptide Y, an involvement of the inhibitory G protein Gi was unlikely. Cholate extracts of membranes from control and PMA-treated cells were equally effective in the reconstitution of adenylylcyclase activity in S49 cyc? membranes, which lack the stimulatory G protein subunit Gsα; thus, Gs did not appear to be the target of PMA action. Membranes from PMA-treated cells exhibited increased adenylylcyclase activity to all stimulators including Mn2+ and Mn2+ plus forskolin. In addition, activity was increased when control membranes were incubated with ATP and purified PKC from rat brain. This is consistent with a direct effect of PKC on the adenylylcyclase catalyst in SK-N-MC cells. PMA treatment also resulted in a shift to less sensitivity in the Kact for isoproterenol but not for dopamine or CGP-12177 (a β3-adrenergic agonist) stimulation. Thus, the β1 but not the D1 or β3 receptors were being desensitized by PKC activation. Analysis of SK-N-MC cells by western blotting with antibodies against different PKC isozymes revealed that both the α and ζ isozymes were present in these cells. Whereas PKC-α was activated and translocated from cytosol to membrane by phorbol esters, the ζ isozyme was not. Thus, PKC-α, which has been implicated in desensitization in other cell lines, also appears to potentiate adenylylcyclase activity. 相似文献
64.
Rooney B O'Donovan H Gaffney A Browne M Faherty N Curran SP Sadlier D Godson C Brazil DP Crean J 《FEBS letters》2011,(3):2967-538
We describe the activation of Wnt signalling in mesangial cells by CCN2. CCN2 stimulates phosphorylation of LRP6 and GSK-3β resulting in accumulation and nuclear localisation of β-catenin, TCF/LEF activity and expression of Wnt targets. This is coincident with decreased phosphorylation of β-catenin on Ser 33/37 and increased phosphorylation on Tyr142. DKK-1 and LRP6 siRNA reversed CCN2’s effects. Microarray analyses of diabetic patients identified differentially expressed Wnt components. β-Catenin is increased in type 1 diabetic and UUO mice and in in vitro models of hyperglycaemia and hypertension. These findings suggest that Wnt/CCN2 signalling plays a role in the pathogenesis of diabetic nephropathy. 相似文献
65.
Gap junctions of some vertebrates are capable of passing the elongate molecule, calmodulin, with a molecular weight 8-17 times greater than the previously recognized size limits. Fluorescently labeled calmodulin (FCaM) (17.34 kDa) microinjected into oocytes of ovarian follicles from an amphibian, Xenopus laevis, and from two species of teleost fish, Danio rerio (Zebrafish) and Oryzias latipes (Medaka), is shown to transit their gap junctions and enter the surrounding epithelial cells. Passage of FCaM was terminated when follicles were first treated with 1 mM octanol, a molecule known to down-regulate gap junctions. There was no FCaM detected in the surrounding medium, nor did epithelial cells become fluorescent when follicles were incubated in medium containing dye. Calmodulin is well known to modulate many cytoplasmic reactions; thus, its passage through gap junctions opens possibilities of additional means by which cells may be supplied with this signaling molecule, and by which their supply may be regulated. 相似文献
66.
Formation of Tellurium Nanocrystals during Anaerobic Growth of Bacteria That Use Te Oxyanions as Respiratory Electron Acceptors 总被引:2,自引:1,他引:1 下载免费PDF全文
Shaun M. Baesman Thomas D. Bullen James Dewald Donghui Zhang Seamus Curran Farhana S. Islam Terry J. Beveridge Ronald S. Oremland 《Applied microbiology》2007,73(7):2135-2143
Certain toxic elements support the metabolism of diverse prokaryotes by serving as respiratory electron acceptors for growth. Here, we demonstrate that two anaerobes previously shown to be capable of respiring oxyanions of selenium also achieve growth by reduction of either tellurate [Te(VI)] or tellurite [Te(IV)] to elemental tellurium [Te(0)]. This reduction achieves a sizeable stable-Te-isotopic fractionation (isotopic enrichment factor [] = −0.4 to −1.0 per ml per atomic mass unit) and results in the formation of unique crystalline Te(0) nanoarchitectures as end products. The Te(0) crystals occur internally within but mainly externally from the cells, and each microorganism forms a distinctly different structure. Those formed by Bacillus selenitireducens initially are nanorods (~10-nm diameter by 200-nm length), which cluster together, forming larger (~1,000-nm) rosettes composed of numerous individual shards (~100-nm width by 1,000-nm length). In contrast, Sulfurospirillum barnesii forms extremely small, irregularly shaped nanospheres (diameter < 50 nm) that coalesce into larger composite aggregates. Energy-dispersive X-ray spectroscopy and selected area electron diffraction indicate that both biominerals are composed entirely of Te and are crystalline, while Raman spectroscopy confirms that they are in the elemental state. These Te biominerals have specific spectral signatures (UV-visible light, Raman) that also provide clues to their internal structures. The use of microorganisms to generate Te nanomaterials may be an alternative for bench-scale syntheses. Additionally, they may also generate products with unique properties unattainable by conventional physical/chemical methods. 相似文献
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69.
Garabed Gary Demerjian Anothony Benjamin Sims Brendan Curran Stack 《Bioinformation》2011,5(7):282-284
The temporomandibular joint (TMJ) articulates the mandible with the maxilla. Temporomandibular joint disorders (TMD) are dysfunctions of this joint,
which range from acute to chronic inflammation, trauma and dislocations, developmental anomalies and neoplasia. TMD manifest as signs and symptoms
that involve the surrounding muscles, ligaments, bones, synovial capsule, connective tissue, teeth and innervations proximal and distal to this joint. TMD
induce proximal and distal, chronic and acute, dull or intense pain and discomfort, muscle spasm, clicking/popping sounds upon opening and closing of
the mouth, and chewing or speaking difficulties. The trigeminal cranial nerve V, and its branches provide the primary sensory innervation to the TMJ. Our
clinical work suggests that the auriculotemporal (AT) nerve, a branch of the mandibular nerve, the largest of the three divisions of the trigeminal nerve,
plays a critical role in TMD sequelae. The AT nerve provides the somatosensory fibers that supply the joint, the middle ear, and the temporal region. By
projecting fibers toward the otic ganglion, the AT nerve establishes an important bridge to the sympathetic system. As it courses posteriorly to the
condylar head of the TMJ, compression, injury or irritation of the AT nerve can lead to significant neurologic and neuro-muscular disorders, including
Tourette''s syndrome,Torticolli, gait or balance disorders and Parkinson’s disease. Here, we propose that a proteomic signature of TMD can be obtained by
assessing certain biomarkers in local (e.g., synovial fluid at the joint) and distal body fluids (e.g., saliva, cerebrospinal fluid), which can aid TMD
diagnosis and prognosis. 相似文献
70.
Sarkar G Curran GL Mahlum E Decklever T Wengenack TM Blahnik A Hoesley B Lowe VJ Poduslo JF Jenkins RB 《PloS one》2011,6(12):e28881