71 research outputs found
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Feasibility of High-Throughput Genome-Wide Genotyping using DNA from Stored Buccal Cell Samples
It is unclear if buccal cell samples contain sufficient human DNA with adequately sized fragments for high throughput genetic bioassays. Yet buccal cell sample collection is an attractive alternative to gathering blood samples for genetic epidemiologists engaged in large-scale genetic biomarker studies. We assessed the genotyping efficiency (GE) and genotyping concordance (GC) of buccal cell DNA samples compared to corresponding blood DNA samples, from 32 Nurses’ Health Study (NHS) participants using the Illumina Infinium 660W-Quad platform. We also assessed how GE and GC accuracy varied as a function of DNA concentration using serial dilutions of buccal DNA samples. Finally we determined the nature and genomic distribution of discordant genotypes in buccal DNA samples. The mean GE of undiluted buccal cell DNA samples was high (99.32%), as was the GC between the paired buccal and blood samples (99.29%). GC between the dilutions versus the undiluted buccal DNA was also very high (greater than 97%), though both GE and GC notably declined at DNA concentrations less than 5 ng/μl. Most (greater than 95%) genotype determinations in buccal cell samples were of the “missing call” variety (as opposed to the “alternative genotype call” variety) across the spectrum of buccal DNA concentrations studied. Finally, for buccal DNA concentration above 1.7 ng/ul, discordant genotyping calls did not cluster in any particular chromosome. Buccal cell-derived DNA represents a viable alternative to blood DNA for genotyping on a high-density platform
The evolutionary legacy of size-selective harvesting extends from genes to populations
Size-selective harvesting is assumed to alter life histories of exploited fish populations, thereby negatively affecting population productivity, recovery, and yield. However, demonstrating that fisheries-induced phenotypic changes in the wild are at least partly genetically determined has proved notoriously difficult. Moreover, the population-level consequences of fisheries-induced evolution are still being controversially discussed. Using an experimental approach, we found that five generations of size-selective harvesting altered the life histories and behavior, but not the metabolic rate, of wild-origin zebrafish (Danio rerio). Fish adapted to high positively size selective fishing pressure invested more in reproduction, reached a smaller adult body size, and were less explorative and bold. Phenotypic changes seemed subtle but were accompanied by genetic changes in functional loci. Thus, our results provided unambiguous evidence for rapid, harvest-induced phenotypic and evolutionary change when harvesting is intensive and size selective. According to a life-history model, the observed life-history changes elevated population growth rate in harvested conditions, but slowed population recovery under a simulated moratorium. Hence, the evolutionary legacy of size-selective harvesting includes populations that are productive under exploited conditions, but selectively disadvantaged to cope with natural selection pressures that often favor large body size.Peer reviewe
Graphene matrices as carriers for metal ions against antibiotic susceptible and resistant bacterial pathogens
Due to the ever-increasing burden of antimicrobial-resistant (AMR) bacteria, the development of novel antimicrobial agents and biomaterials to act as carriers and/or potentiate antimicrobial activity is essential. This study assessed the antimicrobial efficacy of the following ionic metals, silver, gold, palladium, platinum, zinc, and gallium alone and in combination with graphene matrices (which were coated via a drop casting coating method). The graphene foam was utilized as a carrier for the ionic metals against both, antibiotic susceptible and resistant bacterial strains of Acinetobac-ter baumannii, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa. Ionic gold, palladium and platinum demonstrated the greatest antimicrobial activity against the susceptible and resistant strains. Scanning electron microscopy (SEM) visualized cellular ultrastructure damage, when the bacteria were incubated upon the graphene foam alone. This study suggests that specific metal ions applied in combination with graphene foam could present a potential therapeutic option to treat AMR bacterial infections. The application of the graphene foam as a potential carrier could promote antimicrobial activity, provide a sustained release approach and reduce possible resistance acquisition. In light of this study, the graphene foam and ionic metal combinations could potentially be further developed as part of a wound dressing
TU Tau B: The Peculiar 'Eclipse' of a possible proto-Barium Giant
TU Tau (= HD 38218 = HIP 27135) is a binary system consisting of a C-N carbon
star primary and an A-type secondary. We report on new photometry and
spectroscopy which tracked the recent disappearance of the A-star secondary.
The dimming of the A-star was gradual and irregular, with one or more brief
brightenings, implying the presence of nonhomogeneities in the carbon star
outflow. We also present evidence that the A-star is actively accreting
s-process enriched material from the carbon star and suggest that it will
therefore eventually evolve into a Barium giant. This is an important system as
well because the A-type star can serve as a probe of the outer atmosphere of
the carbon star.Comment: 9 pages, 9 figures, 4 tables, a number of amateur observatories made
significant contributions to this research. Paper accepted for publication in
The Astronomical Journa
Revisiting Estimates of CTL Killing Rates In Vivo
Recent experimental advances have allowed the estimation of the in vivo rates of killing of infected target cells by cytotoxic T lymphocytes (CTL). We present several refinements to a method applied previously to quantify killing of targets in the spleen using a dynamical model. We reanalyse data previously used to estimate killing rates of CTL specific for two epitopes of lymphocytic choriomeningitis virus (LCMV) in mice and show that, contrary to previous estimates the “killing rate” of effector CTL is approximately twice that of memory CTL. Further, our method allows the fits to be visualized, and reveals one potentially interesting discrepancy between fits and data. We discuss extensions to the basic CTL killing model to explain this discrepancy and propose experimental tests to distinguish between them
Variability of Ice Supersaturation, Nucleation, and Cirrus in TTL Vertical Layers
No abstract availabl
Genetic variance in fitness indicates rapid contemporary adaptive evolution in wild animals
Funding: Hoge Veluwe great tits: the NIOO-KNAW, ERC, and numerous funding agencies; Wytham great tits: Biotechnology and Biological Sciences Research Council, ERC, and the UK Natural Environment Research Council (NERC).The rate of adaptive evolution, the contribution of selection to genetic changes that increase mean fitness, is determined by the additive genetic variance in individual relative fitness. To date, there are few robust estimates of this parameter for natural populations, and it is therefore unclear whether adaptive evolution can play a meaningful role in short-term population dynamics. We developed and applied quantitative genetic methods to long-term datasets from 19 wild bird and mammal populations and found that, while estimates vary between populations, additive genetic variance in relative fitness is often substantial and, on average, twice that of previous estimates. We show that these rates of contemporary adaptive evolution can affect population dynamics and hence that natural selection has the potential to partly mitigate effects of current environmental change.PostprintPeer reviewe
Shared genetics underlying epidemiological association between endometriosis and ovarian cancer
Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.Other Research Uni
Common variants at theCHEK2gene locus and risk of epithelial ovarian cancer
Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.Other Research Uni
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Consortium analysis of 7 candidate SNPs for ovarian cancer
The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5′ flanking CDKN2A, rs523349 in the 3′ UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach
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