The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations ...in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study’s conclusion of selection in African Americans before admixture is also subject to doubt. This is because the FST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas.
FlyBase (http://flybase.bio.indiana.edu/) provides an integrated view of the fundamental genomic and genetic data on the major genetic model Drosophila melanogaster and related species. FlyBase has ...primary responsibility for the continual reannotation of the D. melanogaster genome. The ultimate goal of the reannotation effort is to decorate the euchromatic sequence of the genome with as much biological information as is available from the community and from the major genome project centers. A complete revision of the annotations of the now-finished euchromatic genomic sequence has been completed. There are many points of entry to the genome within FlyBase, most notably through maps, gene products and ontologies, structured phenotypic and gene expression data, and anatomy.
Metalloproteinases and their inhibitors are known to play an important role in the extracellular matrix remodeling associated with preinvasive lesions and invasive carcinomas; however, little is ...known about their role in early lung carcinoma. Immunohistochemical studies were made of the reactivity of bronchial squamous preneoplastic lesions from cigarette smokers, including basal cell hyperplasia, squamous metaplasia, dysplasia, carcinoma in situ, and invasive squamous cell carcinoma for matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and type IV collagen in 13 patients. Staining for type IV collagen disclosed discontinuities in basement membranes from basal cell hyperplasia to dysplasia, progressing to destruction in carcinoma in situ and invasive carcinoma. Reactivity for MMP-9 was mild in basal cell hyperplasia and squamous metaplasia, increasing in carcinoma in situ and invasive carcinoma. In contrast, reactivity for MMP-1 was strong in basal cell hyperplasia and squamous metaplasia, decreasing in carcinoma in situ and invasive carcinoma. Some neoplastic cells in carcinoma in situ and invasive carcinoma were MMP-3 positive. Staining for MMP-2 and TIMP-1 was moderate to strong in all squamous preinvasive lesions. Confocal microscopy showed MMP-9-positive cells passing through fragmented basement membranes in which type IV collagen and MMP-9 were colocalized. Type IV collagen colocalized with MMP-2 in all lesions and with TIMP-1 in basal cell hyperplasia and squamous metaplasia. The inverse relationships between the reactivity for MMP-1 and MMP-9 with progression of bronchial squamous preinvasive lesions suggest important roles for these MMPs in basement membrane remodeling in these lesions.
Loss of heterozygosity (LOH) at the long arm of chromosome 16 occurs in at least half of all breast tumors and is considered to target one or more tumor suppressor genes. Despite extensive studies by ...us and by others, a clear consensus of the boundaries of the smallest region of overlap (SRO) could not be identified. To find more solid evidence for SROs, we tested a large series of 712 breast tumors for LOH at 16q using a dense map of polymorphic markers. Strict criteria for LOH and retention were applied, and results that did not meet these criteria were excluded from the analysis. We compared LOH results obtained from samples with different DNA isolation methods, ie., from microdissected tissue versus total tissue blocks. In the latter group, 16% of the cases were excluded because of noninterpretable LOH results. The selection of polymorphic markers is clearly influencing the LOH pattern because a chromosomal region seems more frequently involved in LOH when many markers from this region are used. The LOH detection method, i.e., radioactive versus fluorescence detection, has no marked effect on the results. Increasing the threshold window for retention of heterozygosity resulted in significantly more cases with complex LOH, i.e., several alternating regions of loss and retention, than seen in tumors with a small window for retention. Tumors with complex LOH do not provide evidence for clear-cut SROs that are repeatedly found in other samples. On disregarding these complex cases, we could identify three different SROs, two at band 16q24.3 and one at 16q22.1. In all three tumor series, we found cases with single LOH regions that designated the distal region at 16q24.3 and the region at 16q22.1. Comparing histological data on these tumors did not result in the identification of a particular subtype with LOH at 16q or a specific region involved in LOH. Only the rare mucinous tumors had no 16q LOH at all. Furthermore, a positive estrogen content is prevalent in tumors with 16q LOH, but not in tumors with LOH at 16q24.3 only.
Predictors of relapse to drinking were examined in a clinical sample of 122 individuals seeking outpatient treatment for alcohol problems. Drinking status and a variety of predictor variables were ...measured every two months for one year following presentation for treatment. In addition to pretreatment characteristics, potential antecedents of relapse were assessed at each point within five domains: (1) the occurrence of negative life events; (2) cognitive appraisal variables including self‐efficacy, alcohol expectancies, and motivation for change; (3) client coping resources; (4) craving experiences; and (5) affective/mood status. Although the occurrence of adverse life events did not predict 6‐month relapse, all other domains singly accounted for significant variance in drinking outcomes. Proximal antecedents (from the prior 2‐month interval) significantly and substantially improved predictive power over that achieved from pretreatment characteristics alone. When analyzed jointly, these predictors accounted for a majority of variance in 6‐month relapse status. A prospective test supported Marlatt's developmental model of relapse, pointing to two client factors as optimally predictive of resumed drinking: lack of coping skills and belief in the disease model of alcoholism.
Over the last several years, national programs to lower the content of industrially produced (IP) C18:1 and C18:2 trans fatty acids in foods have been implemented, but whether this has resulted in ...lower blood trans fatty acid levels is unknown. Likewise, an increased perception of the health benefits of fish oils rich in EPA and DHA may have resulted in an increase in consumption and blood levels of these fatty acids. To explore these issues, we analyzed the changes in RBC fatty acid composition between the 7th (1998–2001) and 8th (2005–2007) examination cycles in a random sample of the Framingham Offspring cohort. This was a retrospective cohort study of 291 participants from whom blood was drawn at both examinations and for whom complete covariate data were available. Overall, the proportion of trans fatty acids in RBC changed by -23% (95% CI: -26 to -21%). RBC EPA+DHA proportions increased by 41% (95% CI: 31 to 52%) in 38 individuals who were taking fish oil supplements at examination 8, but in 253 participants not taking fish oil, the proportion of RBC EPA+DHA did not change. In conclusion, in a random subsample of Framingham Offspring participants with serial observations over 6.7 y, the proportion of trans fatty acids in RBC decreased. Those of EPA+DHA increased in people taking fish oil supplements. These changes could potentially translate into a lower risk for cardiovascular disease.
Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this ...uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.
We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).
In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.
In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.
The study was conducted within a training and demonstration center for teachers from several different school districts. The teachers staffing the center were employees of the host school district ...who volunteered to serve in the center. Unfortunately, these volunteers did not always use the program materials appropriately and therefore did not always provide clear models for visiting teachers. In particular, four of the volunteer teachers did not always instruct their students from the appropriate reading text, even when encouraged to do so by the principal of the school in which the center was located. Various procedures were employed to alter this situation. The experimenter, (associate director of the training and demonstration center) provided instructions, feedback, and praise regarding use of the appropriate reading text. These procedures had clear effects with only one teacher. Then, merit or bonus payments were provided for teachers who used the appropriate reading text for criterion periods of time; a procedure that was very effective with all four teachers. The problem worked on in this study is typical of those faced by workers in public institutions where change cannot be brought about by the researcher's authority. All teachers in the present study had the necessary skills to demonstrate accurately the prescribed program procedures, but they did not always do so until the bonus payment was used. Although the bonus payment procedure might be inappropriate in some school situations, the procedure could easily be adjusted to accommodate the established practices of many schools. For example, establishment of explicit performance criterion and use of in‐service stipends for meeting criterion performance during school hours, rather than attendance at meetings after school, might well be comparably effective.
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