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161.
Njajou OT Blackburn EH Pawlikowska L Mangino M Damcott CM Kwok PY Spector TD Newman AB Harris TB Cummings SR Cawthon RM Shuldiner AR Valdes AM Hsueh WC 《PloS one》2010,5(9):e13048
Background
Telomeres shorten as cells divide. This shortening is compensated by the enzyme telomerase. We evaluated the effect of common variants in the telomerase RNA component (TERC) gene on telomere length (TL) in the population-based Health Aging and Body Composition (Health ABC) Study and in two replication samples (the TwinsUK Study and the Amish Family Osteoporosis Study, AFOS).Methodology
Five variants were identified in the TERC region by sequence analysis and only one SNP was common (rs2293607, G/A). The frequency of the G allele was 0.26 and 0.07 in white and black, respectively. Testing for association between TL and rs2293607 was performed using linear regression models or variance component analysis conditioning on relatedness among subjects.Results
The adjusted mean TL was significantly shorter in 665 white carriers of the G allele compared to 887 non-carriers from the Health ABC Study (4.69±0.05 kbp vs. 4.86±0.04 kbp, measured by quantitative PCR, p = 0.005). This association was replicated in another white sample from the TwinsUK Study (6.90±0.03 kbp in 301 carriers compared to 7.06±0.03 kbp in 395 non-carriers, measured by Southern blots, p = 0.009). A similar pattern of association was observed in whites from the family-based AFOS and blacks from the Health ABC cohort, although not statistically significant, possibly due to the lower allele frequency in these populations. Combined analysis using 2,953 white subjects from 3 studies showed a significant association between TL and rs2293607 (β = −0.19±0.04 kbp, p = 0.001).Conclusion
Our study shows a significant association between a common variant in TERC and TL in humans, suggesting that TERC may play a role in telomere homeostasis. 相似文献162.
Wong Mark Lawrence Zhang Jinxiao Wing Yun Kwok Lau Esther Yuet Ying 《Sleep and biological rhythms》2017,15(1):21-30
Sleep and Biological Rhythms - Neuroticism has been found to predispose individuals to depression, but the underlying mechanism is not well studied. The current study sought to delineate the... 相似文献
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164.
James EA DeVoti JA Rosenthal DW Hatam LJ Steinberg BM Abramson AL Kwok WW Bonagura VR 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(11):6633-6640
Recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus type 6 (HPV-6) or HPV-11. Specific HLA-DR haplotypes DRB1*01:02 and DRB1*03:01 are associated with the development of RRP, disease severity, and Th2-like responses to HPV early proteins. Th1-like responses to HPV proteins have been shown to be protective in animal models. Therefore, we investigated the hypothesis that RRP patients have dysfunctional Th1-like, HPV-specific T cell responses. Using MHC class II tetramers, we identified immunogenic peptides within HPV-11 early proteins. Two distinct peptides (E6(113-132) and E2(1-20)) contained DRB1*01:02- or DRB1*03:01-restricted epitopes, respectively. An additional peptide (E2(281-300)) contained an epitope presented by both alleles. Peptide binding, tetramer, and proliferation assays identified minimal epitopes within these peptides. These epitopes elicited E2/E6-specific CD4(+) T cell responses in RRP patients and healthy control subjects, allowing the isolation of HPV-specific T cell lines using tetramers. The cytokine profiles and STAT signaling of these tetramer-positive T cells were measured to compare the polarization and responsiveness of HPV-specific T cells from patients with RRP and healthy subjects. HPV-specific IFN-γ secretion was substantially lower in T cells from RRP patients. HPV-specific IL-13 secretion was seen at modest levels in T cells from RRP patients and was absent in T cells from healthy control subjects. HPV-specific T cells from RRP patients exhibited reduced STAT-5 phosphorylation and reduced IL-2 secretion, suggesting anergy. Levels of STAT-5 phosphorylation and IFN-γ secretion could be improved through addition of IL-2 to HPV-specific T cell lines from RRP patients. Therapeutic vaccination or interventions aimed at restoring Th1-like cytokine responses to HPV proteins and reversing anergy could improve clinical outcomes for RRP patients. 相似文献
165.
Victoria Kasprowicz Julian Schulze zur Wiesch Thomas Kuntzen Brian E. Nolan Steven Longworth Andrew Berical Jenna Blum Cory McMahon Laura L. Reyor Nahel Elias William W. Kwok Barbara G. McGovern Gordon Freeman Raymond T. Chung Paul Klenerman Lia Lewis-Ximenez Bruce D. Walker Todd M. Allen Arthur Y. Kim Georg M. Lauer 《Journal of virology》2011,85(9):4633
166.
Kerfeld CA Sawaya MR Brahmandam V Cascio D Ho KK Trevithick-Sutton CC Krogmann DW Yeates TO 《Structure (London, England : 1993)》2003,11(1):55-65
Carotenoids undergo a wide range of photochemical reactions in animal, plant, and microbial systems. In photosynthetic organisms, in addition to light harvesting, they perform an essential role in protecting against light-induced damage by quenching singlet oxygen, superoxide anion radicals, or triplet-state chlorophyll. We have determined the crystal structure of a water-soluble orange carotenoid protein (OCP) isolated from the cyanobacterium Arthrospira maxima at a resolution of 2.1 A. OCP forms a homodimer with one carotenoid molecule per monomer. The carotenoid binding site is lined by a striking number of methionine residues. The structure reveals several possible ways in which the protein environment influences the spectral properties of the pigment and provides insight into how the OCP carries out its putative functions in photoprotection. 相似文献
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Marco O. Bertelli Luis Salvador‐Carulla Daniela Scuticchio Niccolò Varrucciu Rafael Martinez‐Leal Sally‐Ann Cooper Rune J. Simeonsson Shoumitro Deb Germain Weber Rex Jung Kerim Munir Colleen Adnams Leyla Akoury‐Dirani Satish Chandra Girimaji Gregorio Katz Henry Kwok Carolyn Walsh 《World psychiatry》2014,13(1):93-94