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51.
Leticia Labriola Maria G Peters Karin Krogh Iván Stigliano Letícia F Terra Cecilia Buchanan Marcel CC Machado Elisa Bal de Kier Joffé Lydia Puricelli Mari C Sogayar 《BMC cell biology》2009,10(1):49-16
Background
The in vitro culture of insulinomas provides an attractive tool to study cell proliferation and insulin synthesis and secretion. However, only a few human beta cell lines have been described, with long-term passage resulting in loss of insulin secretion. Therefore, we set out to establish and characterize human insulin-releasing cell lines. 相似文献52.
Vladimir Novitsky Rui Wang Lauren Margolin Jeannie Baca Lemme Kebaabetswe Raabya Rossenkhan Caitlin Bonney Michaela Herzig David Nkwe Sikhulile Moyo Rosemary Musonda Elias Woldegabriel Erik van Widenfelt Joseph Makhema Stephen Lagakos M. Essex 《PloS one》2009,4(11)
Background
Aiming to answer the broad question “When does mutation occur?” this study examined the time of appearance, dominance, and completeness of in vivo Gag mutations in primary HIV-1 subtype C infection.Methods
A primary HIV-1C infection cohort comprised of 8 acutely and 34 recently infected subjects were followed frequently up to 500 days post-seroconversion (p/s). Gag mutations were analyzed by employing single-genome amplification and direct sequencing. Gag mutations were determined in relation to the estimated time of seroconversion. Time of appearance, dominance, and completeness was compared for different types of in vivo Gag mutations.Results
Reverse mutations to the wild type appeared at a median (IQR) of 62 (44;139) days p/s, while escape mutations from the wild type appeared at 234 (169;326) days p/s (p<0.001). Within the subset of mutations that became dominant, reverse and escape mutations appeared at 54 (30;78) days p/s and 104 (47;198) days p/s, respectively (p<0.001). Among the mutations that reached completeness, reverse and escape mutations appeared at 54 (30;78) days p/s and 90 (44;196) days p/s, respectively (p = 0.006). Time of dominance for reverse mutations to and escape mutations from the wild type was 58 (44;105) days p/s and 219 (90;326) days p/s, respectively (p<0.001). Time of completeness for reverse and escape mutations was 152 (100;176) days p/s and 243 (101;370) days p/s, respectively (p = 0.001). Fitting a Cox proportional hazards model with frailties confirmed a significantly earlier time of appearance (hazard ratio (HR): 2.6; 95% CI: 2.3–3.0), dominance (4.8 (3.4–6.8)), and completeness (3.6 (2.3–5.5)) of reverse mutations to the wild type Gag than escape mutations from the wild type. Some complex mutational pathways in Gag included sequential series of reversions and escapes.Conclusions
The study identified the timing of different types of in vivo Gag mutations in primary HIV-1 subtype C infection in relation to the estimated time of seroconversion. Overall, the in vivo reverse mutations to the wild type occurred significantly earlier than escape mutations from the wild type. This shorter time to incidence of reverse mutations remained in the subsets of in vivo Gag mutations that reached dominance or completeness. 相似文献53.
CC van Diemen DS Postma M Siedlinski A Blokstra HA Smit HM Boezen 《Respiratory research》2011,12(1):57
Background
An imbalance in Matrix MetalloProteases (MMPs) and Tissue Inhibitors of MMPs (TIMPs) contributes to Chronic Obstructive Pulmonary Disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) in MMPs and TIMPs with respect to COPD development and lung function decline in the general population are lacking.Methods
We genotyped SNPs in MMP1 (G-1607GG), MMP2 (-1306 C/T), MMP9 (3 tagging SNPs), MMP12 (A-82G and Asn357Ser) and TIMP1 (Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV1 measurements from a prospective cohort study in the general population. FEV1 decline was analyzed using linear mixed effect models adjusted for confounders. Analyses of the X-chromosomal TIMP1 gene were stratified according to sex. All significant associations were repeated in an independent general population cohort (n = 1152).Results
MMP2 -1306 TT genotype carriers had excess FEV1 decline (-4.0 ml/yr, p = 0.03) compared to wild type carriers. TIMP1 Ile158Ile predicted significant excess FEV1 decline in both males and females. TIMP1 Phe124Phe predicted significant excess FEV1 decline in males only, which was replicated (p = 0.10) in the second cohort. The MMP2 and TIMP1 Ile158Ile associations were not replicated. Although power was limited, we did not find associations with COPD development.Conclusions
We for the first time show that TIMP1 Phe124Phe contributes to excess FEV1 decline in two independent prospective cohorts, albeit not quite reaching conventional statistical significance in the replication cohort. SNPs in MMPs evidently do not contribute to FEV1 decline in the general population. 相似文献54.
Genbank accession #: AF 135190 总被引:1,自引:0,他引:1
Plant Molecular Biology - 相似文献
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Age-stiffening of ocular tissues is statistically linked to glaucoma in the elderly. In this study, the effects of age-stiffening on the lamina cribrosa, the primary site of glaucomatous nerve damages, were modeled using computational finite element analysis. We showed that glaucomatous nerve damages and peripheral vision loss behavior can be phenomenologically modeled by shear-based damage criterion. Using this damage criterion, the potential vision loss for 30 years old with mild hypertension of 25mmHg intraocular pressure (IOP) was estimated to be 4%. When the IOP was elevated to 35mmHg, the potential vision loss rose to 45%; and age-stiffening from 35 to 60 years old increased the potential vision loss to 52%. These results showed that while IOP plays a central role in glaucomatous damages, age-stiffening facilitates glaucomatous damages and may be the principal factor that resulted in a higher rate of glaucoma in the elderly than the general population. 相似文献
58.
Molecular Epidemiology of Human Immunodeficiency Virus Type 1 Transmission in a Heterosexual Cohort of Discordant Couples in Zambia
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Stanley A. Trask Cynthia A. Derdeyn Ulgen Fideli Yalu Chen Sreelatha Meleth Francis Kasolo Rosemary Musonda Eric Hunter Feng Gao Susan Allen Beatrice H. Hahn 《Journal of virology》2002,76(1):397-405
Most human immunodeficiency virus type 1 (HIV-1) transmissions in sub-Saharan Africa are believed to occur between married adults who are discordant for their HIV-1 infection status; however, no studies to date have investigated the molecular epidemiology of such transmission events. Here we report the genetic characterization of HIV-1 strains from 149 transmission pairs that were identified prospectively in a cohort of discordant couples in Lusaka, Zambia. Subgenomic gag, gp120, gp41, and/or long terminal repeat regions were amplified by PCR analysis of uncultured blood samples from both partners and sequenced without interim cloning. Pairwise genetic distances were calculated for the regions analyzed and compared to those of subtype-specific reference sequences as well as local controls. Sequence relationships were also examined by phylogenetic tree analysis. By these approaches, epidemiological linkage was established for the majority of transmission pairs. Viruses from 129 of the 149 couples (87%) were very closely related and clustered together in phylogenetic trees in a statistically highly significant manner. In contrast, viruses from 20 of the 149 couples (13%) were only distantly related in two independent genomic regions, thus ruling out transmission between the two partners. The great majority (95%) of transmitted viruses were of subtype C origin, although representatives of subtypes A, D, G, and J were also identified. There was no evidence for extensive transmission networks within the cohort, although two phylogenetic subclusters of viruses infecting two couples each were identified. Taken together, these data indicate that molecular epidemiological analyses of presumed transmission pairs are both feasible and required to determine behavioral, virological, and immunological correlates of heterosexual transmission in sub-Saharan Africa with a high level of accuracy. 相似文献
59.
Masemola AM Mashishi TN Khoury G Bredell H Paximadis M Mathebula T Barkhan D Puren A Vardas E Colvin M Zijenah L Katzenstein D Musonda R Allen S Kumwenda N Taha T Gray G McIntyre J Karim SA Sheppard HW Gray CM;HIVNET Study Team 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(7):4607-4617
Characterization of optimal CTL epitopes in Gag can provide crucial information for evaluation of candidate vaccines in populations at the epicenter of the HIV-1 epidemic. We screened 38 individuals with recent subtype C HIV-1 infection using overlapping consensus C Gag peptides and hypothesized that unique HLA-restricting alleles in the southern African population would determine novel epitope identity. Seventy-four percent of individuals recognized at least one Gag peptide pool. Ten epitopic regions were identified across p17, p24, and p2p7p1p6, and greater than two-thirds of targeted regions were directed at: TGTEELRSLYNTVATLY (p17, 35%); GPKEPFRDYVDRFFKTLRAEQATQDV (p24, 19%); and RGGKLDKWEKIRLRPGGKKHYMLKHL (p17, 15%). After alignment of these epitopic regions with consensus M and a consensus subtype C sequence from the cohort, it was evident that the regions targeted were highly conserved. Fine epitope mapping revealed that five of nine identified optimal Gag epitopes were novel: HLVWASREL, LVWASRELERF, LYNTVATLY, PFRDYVDRFF, and TLRAEQATQD, and were restricted by unique HLA-Cw*08, HLA-A*30/B*57, HLA-A*29/B*44, and HLA-Cw*03 alleles, respectively. Notably, three of the mapped epitopes were restricted by more than one HLA allele. Although these epitopes were novel and restricted by unique HLA, they overlapped or were embedded within previously described CTL epitopes from subtype B HIV-1 infection. These data emphasize the promiscuous nature of epitope binding and support our hypothesis that HLA diversity between populations can shape fine epitope identity, but may not represent a constraint for universal recognition of Gag in highly conserved domains. 相似文献
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Elisangela F Silva Mariana Orsi ?ngela L Andrade Rosana Z Domingues Breno M Silva Helena RC de Araújo Paulo FP Pimenta Michael S Diamond Eliseu SO Rocha Erna G Kroon Luiz CC Malaquias Luiz FL Coelho 《Journal of nanobiotechnology》2012,10(1):1-5