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21.
Hamidi S Chen CR Mizutori-Sasai Y McLachlan SM Rapoport B 《Molecular endocrinology (Baltimore, Md.)》2011,25(1):184-194
The glycoprotein hormone receptor hinge region is the least conserved component and the most variable in size; the TSH receptor (TSHR) being the longest (152 amino acids; residues 261-412). The TSHR is also unique among the glycoprotein hormone receptor in undergoing in vivo intramolecular cleavage into disulfide-linked A- and B-subunits with removal of an intervening 'C-peptide' region. Experimentally, hinge region amino acids 317-366 (50 residues) can be deleted without alteration in receptor function. However, in vivo, more than 50 amino acids are deleted during TSHR intramolecular cleavage; furthermore, the boundaries of this deleted region are ragged and poorly defined. Studies to determine the extent to which hinge region deletions can be tolerated without affecting receptor function ('minimal hinge') are lacking. Using as a template the functionally normal TSHR with residues 317-366 deleted, progressive downstream extension of deletions revealed residue 371 to be the limit compatible with normal TSH binding and coupling with cAMP signal transduction. Based on the foregoing downstream limit, upstream deletion from residue 307 (307-371 deletion) was also tolerated without functional alteration, as was deletion of residues 303-366. Addressing a related issue regarding the functional role of the TSHR hinge region, we observed that downstream hinge residues 377-384 contribute to coupling ligand binding with cAMP signal transduction. In summary, we report the first evaluation of TSHR function in relation to proteolytic posttranslational hinge region modifications. Deletion of TSHR hinge amino acids 303-366 (64 residues) or 307-371 (65 residues) are the maximum hinge region deletions compatible with normal TSHR function. 相似文献
22.
Biology Bulletin - To evaluate the accumulation potential of zinc (Zn) and chromium (Cr) by Brassica oleracea L. plant, 15-day-old seedlings were exposed to different concentrations of Zn and Cr... 相似文献
23.
Benjamin R Strub Tony L Parkes Spencer T Mukai Sepehr Bahadorani Alistair B Coulthard Nichole Hall John P Phillips Arthur J Hilliker 《Génome》2008,51(6):409-420
Since some oxygen defense mutants of Drosophila melanogaster exhibit a crinkled wing phenotype, a screen was performed on strains bearing mutant alleles conferring a visible wing phenotype to determine whether any were hypersensitive to oxidative stress. One mutant, withered (whd), was found to be sensitive to both dietary paraquat and hyperoxia. New alleles of whd were induced on a defined genetic background and strains carrying these alleles were also found to be sensitive to oxidative stress. To identify the product of the whd gene we used a sequence-based positional candidate approach and by this method we determined that whd encodes carnitine palmitoyltransferase I (CPT I), an enzyme of the outer mitochondrial membrane that is required for the import of long-chain fatty acids into the mitochondria for beta-oxidation. Although this function is not vital under laboratory conditions, whd adults were found to be highly sensitive to starvation and to heavy metal toxicity relative to controls. This work uncovers a novel relationship between fatty acid metabolism and reactive oxygen metabolism. Further, these results in conjunction with past research on whd and on mammalian CPT I support the hypothesis that CPT I serves a vital function in the response to thymine supplementation. 相似文献
24.
Substantial evidence suggests that antioxidants may play a major role in delaying the progress of Huntington's disease (HD). Here we investigated the effects of superoxide dismutase (cytoplasmic Cu/ZnSOD and mitochondrial MnSOD) and supplementation with dietary antioxidants (alpha-tocopherol and coenzyme Q10) on survival to adulthood in a Drosophila melanogaster model of HD. Our results illustrate that neither overexpression of superoxide dismutase nor supplementation of dietary antioxidants can rescue the lethal phenotype of HD flies. We discuss these results in conjunction with other evidence that antioxidants may only avert the oxidative stress induced progression of HD. 相似文献
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26.
Jennifer A. Danielewski Suzanne M. Garland Jenny McCloskey Richard J. Hillman Sepehr N. Tabrizi 《PloS one》2013,8(5)
Genetic variation of 49 human papillomavirus (HPV) 6 and 22 HPV11 isolates from recurrent respiratory papillomatosis (RRP) (n = 17), genital warts (n = 43), anal cancer (n = 6) and cervical neoplasia cells (n = 5), was determined by sequencing the long control region (LCR) and the E6 and E7 genes. Comparative analysis of genetic variability was examined to determine whether different disease states resulting from HPV6 or HPV11 infection cluster into distinct variant groups. Sequence variation analysis of HPV6 revealed that isolates cluster into variants within previously described HPV6 lineages, with the majority (65%) clustering to HPV6 sublineage B1 across the three genomic regions examined. Overall 72 HPV6 and 25 HPV11 single nucleotide variations, insertions and deletions were observed within samples examined. In addition, missense alterations were observed in the E6/E7 genes for 6 HPV6 and 5 HPV11 variants. No nucleotide variations were identified in any isolates at the four E2 binding sites for HPV6 or HPV11, nor were any isolates found to be identical to the HPV6 lineage A or HPV11 sublineage A1 reference genomes. Overall, a high degree of sequence conservation was observed between isolates across each of the regions investigated for both HPV6 and HPV11. Genetic variants identified a slight association with HPV6 and anogenital lesions (p = 0.04). This study provides important information on the genetic diversity of circulating HPV 6 and HPV11 variants within the Australian population and supports the observation that the majority of HPV6 isolates cluster to the HPV6 sublineage B1 with anogenital lesions demonstrating an association with this sublineage (p = 0.02). Comparative analysis of Australian isolates for both HPV6 and HPV11 to those from other geographical regions based on the LCR revealed a high degree of sequence similarity throughout the world, confirming previous observations that there are no geographically specific variants for these HPV types. 相似文献
27.
Jason J. Ong Tim R. H. Read Lenka A. Vodstrcil Sandra Walker Marcus Chen Catriona S. Bradshaw Suzanne M. Garland Sepehr N. Tabrizi Alyssa Cornall Andrew Grulich Jane Hocking Christopher K. Fairley 《PloS one》2014,9(7)
Background
Human papillomavirus (HPV) is a causative agent in oropharyngeal squamous cell carcinoma. The natural history of oral HPV in HIV-positive men who have sex with men (MSM) is unclear.Methods
Detection of oral human papillomavirus in 173 HIV-positive MSM using oral rinse samples 3 years apart was investigated. HPV DNA was detected by polymerase chain reaction, and genotyped by Roche Linear Array.Results
Of 173 men tested in 2010, 30 had at least one HPV genotype (17%, 95% CI: 12–23), 15 at least one hr-HPV (9%, 95% CI: 5–14) and 8 had HPV 16 (5%, 95% CI: 2–9) detected. In 2013, 33 had at least one HPV genotype (19%, 95% CI: 14–26), 20 had at least one hr-HPV (12%, 95% CI: 7–17) and 7 had HPV 16 (4%, 95% CI: 2–8) detected. Of 30 men at baseline (2010) with any HPV detected, 14 (47%, 95% CI: 28–66) had at least one persistent genotype. Of the 15 men in 2010 with high risk (hr-) HPV, 6 men (40%, 95% CI: 16–68) had at least one persistent hr-HPV genotype. The incidence rate of detection of at least one new HPV genotype was 4.8 per 100 person years (95% CI: 3.1–7.0), of at least one hr-HPV genotype was 3.2 per 100 person years (95% CI: 1.8–5.1) and of HPV 16 was 0.8 per 100 person years (95% CI: 0.2–2.0). The clearance rate was 14.9 per 100 person years (95% CI: 8.2–24.2) for any HPV, 18.2 per 100 person years (95% CI: 8.2–32.7) for hr-HPV and 17.4 per 100 person years (95% CI: 5.0–38.8) for HPV-16. Persistent HPV detection was associated with duration of HIV (OR 1.13 (per additional year), 95% CI: 1.00–1.26) and tonsillectomy (OR 8.17, 95% CI: 1.30–51.40).Conclusion
The same oral HPV genotype was detected again after 3 years in nearly half of HIV-positive men who have sex with men. 相似文献28.
Tim R. H. Read Jane S. Hocking Lenka A. Vodstrcil Sepehr N. Tabrizi Michael J. McCullough Andrew E. Grulich Suzanne M. Garland Catriona S. Bradshaw Marcus Y. Chen Christopher K. Fairley 《PloS one》2012,7(11)
Background
Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma is becoming more common. We examined prevalence and risk factors for oral HPV among men who have sex with men (MSM) and compared sampling and transport methods.Methods
In 2010, 500 MSM (249 HIV-positive) attending Melbourne Sexual Health Centre answered a questionnaire, swabbed their mouth and throat and collected a gargled oral rinse sample. Half the oral rinse was transported absorbed in a tampon (to enable postage). HPV was detected by polymerase chain reaction, and genotyped by Roche Linear Array®. Men with HPV 16 or 18 were retested after six months.Results
Any HPV genotype was detected in 19% (95% confidence intervals (CI) 15–25%) of HIV-infected men and 7% (95% CI 4–11%) of HIV-negative men (p<0.001), and HPV 16 was detected in 4.4% (95% CI 2–8%) of HIV-infected men and 0.8% (0.1–2.8%) of HIV-negative men. Oral HPV was associated with: current smoking (adjusted odds ratio (aOR) 2.2 (95%CI: 1.2–3.9)), time since tooth-brushing (aOR per hour 0.87, 95%CI: 0.8–0.96) and number of lifetime tongue-kissing partners aOR 3.2 95%CI: (1.2–8.4) for 26–100 partners and 4.9 95%CI: (1.9–12.5) for>100 partners. Lifetime oral-penile sex partner numbers were significantly associated in a separate model: aOR 2.8(1.2–6.3) for 26–100 partners and 3.2(1.4–7.2) for>100 partners. HPV 16 and 18 persisted in 10 of 12 men after a median six months. Sensitivities of sampling methods compared to all methods combined were: oral rinse 97%, tampon-absorbed oral rinse 69%, swab 32%.Conclusions
Oral HPV was associated with HIV infection, smoking, recent tooth-brushing, and more lifetime tongue-kissing and oral sex partners. The liquid oral rinse sample was more sensitive than a tampon-absorbed oral rinse or a self-collected swab. 相似文献29.
Fethers K Twin J Fairley CK Fowkes FJ Garland SM Fehler G Morton AM Hocking JS Tabrizi SN Bradshaw CS 《PloS one》2012,7(2):e30633
Background
In recent years several new fastidious bacteria have been identified that display a high specificity for BV; however no previous studies have comprehensively assessed the behavioural risk associations of these bacterial vaginosis-candidate organisms (BV-COs).Methods
We examined the associations between 8 key previously described BV-COs and BV status established by Nugent''s score (NS). We also examined the sexual practices associated with each BV-CO. We incorporated 2 study populations: 193 from a sexually-inexperienced university population and 146 from a highly sexually-active clinic population. Detailed behavioural data was collected by questionnaire and vaginal smears were scored by the Nugent method. Stored samples were tested by quantitative PCR assays for the 8 BV-COs: Atopobium vaginae, Gardnerella vaginalis, Leptotrichia spp., Megasphaera type I, Sneathia spp., and the Clostridia-like bacteria BVAB1, BVAB2 and BVAB3. Associations between BV-COs and BV and behaviours were examined by univariate and multivariable analyses.Results
On univariate analysis, all BV-COs were more common in BV compared to normal flora. However, only Megasphaera type I, BVAB2, A. vaginae and G. vaginalis were significantly independently associated with BV by multivariable analysis. Six of the eight BV-COs (Megasphaera type I, BVAB2, BVAB3, Sneathia, Leptotrichia and G. vaginalis) were rare or absent in sexually-unexposed women, and demonstrated increasing odds of detection with increasing levels of sexual activity and/or numbers of lifetime sexual partners. Only G. vaginalis and A. vaginae were commonly detected in sexually-unexposed women. Megasphaera type I was independently associated with women-who-have-sex-with women (WSW) and lifetime sexual partner numbers, while unprotected penile-vaginal-sex was associated with BVAB2 detection by multivariate analysis.Conclusions
Four of eight key BV-COs were significantly associated with BV after adjusting for the presence of other BV-COs. The majority of BV-COs were absent or rare in sexually-unexposed women, and associated with increasing sexual exposure, suggesting potential sexual transmission of BV-COs. 相似文献30.
Shakeri R Kamangar F Nasrollahzadeh D Nouraie M Khademi H Etemadi A Islami F Marjani H Fahimi S Sepehr A Rahmati A Abnet CC Dawsey SM Brennan P Boffetta P Malekzadeh R Majdzadeh R 《PloS one》2012,7(3):e32711