52 research outputs found

    Evaluation of Candidate Stromal Epithelial Cross-Talk Genes Identifies Association between Risk of Serous Ovarian Cancer and TERT, a Cancer Susceptibility “Hot-Spot”

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    We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs) in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC). In the discovery stage, cases with epithelial ovarian cancer (n = 675) and controls (n = 1,162) were genotyped at 1,536 SNPs using an Illumina GoldenGate assay. Based on Positive Predictive Value estimates, three SNPs—PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616—were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with Pper-allele<0.05 in the discovery stage were selected for replication in a subset of five OCAC studies (n = 1,233 serous invasive cases; n = 3,364 controls). The discovery stage associations in PODXL, ITGA6, and MMP3 were attenuated in the larger replication set (adj. Pper-allele≄0.5). However genotypes at TERT rs7726159 were associated with ovarian cancer risk in the smaller, five-study replication study (Pper-allele = 0.03). Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. ORper-allele 1.14 (1.04–1.24) p = 0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∌99% of the euchromatic genome and is accurate to an error rate of ∌1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Empowered victims? Women’s contradictory positions in the discourse of violence prevention

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    Violence against women is a salient outcome of systemic gender inequality across the globe. In the US, the societal discourse of violence prevention simultaneously frames women in positions of victimhood and of empowerment. This study investigates the ways women draw upon these contradictory constructions in their meaning-making and practices related to violence prevention. Twenty women aged 18–62 discussed their experiences of risk and safety around an urban university campus in an in-depth interview. Women’s selective appropriation of victim and empowerment scripts produced multiple and tension-filled constructions of risk, in ways inflected by gender, ‘race,’ class, sexuality, and age. Themes included the endorsement of a “safety checklist” that functioned to construct women’s risk as unmanageable and victimhood as inevitable; complex generational differences in women’s willingness to identify fears of gendered bodily harm as legitimate and in the ways they did so; and the creation and maintenance of imagined communities of safety and danger, implicitly inflected by ‘race’ and class

    Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

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    INTRODUCTION: Immunological memory is the basis for durable protective immunity after infections or vaccinations. Duration of immunological memory after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 is unclear. Immunological memory can consist of memory B cells, antibodies, memory CD4+ T cells, and/or memory CD8+ T cells. Knowledge of the kinetics and interrelationships among those four types of memory in humans is limited. Understanding immune memory to SARS-CoV-2 has implications for understanding protective immunity against COVID-19 and assessing the likely future course of the COVID-19 pandemic. RATIONALE: Assessing virus-specific immune memory over at least a 6-month period is likely necessary to ascertain the durability of immune memory to SARS-CoV-2. Given the evidence that antibodies, CD4+ T cells, and CD8+ T cells can all participate in protective immunity to SARS-CoV-2, we measured antigen-specific antibodies, memory B cells, CD4+ T cells, and CD8+ T cells in the blood from subjects who recovered from COVID-19, up to 8 months after infection. RESULTS: The study involved 254 samples from 188 COVID-19 cases, including 43 samples at 6 to 8 months after infection. Fifty-one subjects in the study provided longitudinal blood samples, allowing for both cross-sectional and longitudinal analyses of SARS-CoV-2–specific immune memory. Antibodies against SARS-CoV-2 spike and receptor binding domain (RBD) declined moderately over 8 months, comparable to several other reports. Memory B cells against SARS-CoV-2 spike actually increased between 1 month and 8 months after infection. Memory CD8+ T cells and memory CD4+ T cells declined with an initial half-life of 3 to 5 months. This is the largest antigen-specific study to date of the four major types of immune memory for any viral infection. Among the antibody responses, spike immunoglobulin G (IgG), RBD IgG, and neutralizing antibody titers exhibited similar kinetics. Spike IgA was still present in the large majority of subjects at 6 to 8 months after infection. Among the memory B cell responses, IgG was the dominant isotype, with a minor population of IgA memory B cells. IgM memory B cells appeared to be short-lived. CD8+ T cell and CD4+ T cell memory was measured for all SARS-CoV-2 proteins. Although ~70% of individuals possessed detectable CD8+ T cell memory at 1 month after infection, that proportion declined to ~50% by 6 to 8 months after infection. For CD4+ T cell memory, 93% of subjects had detectable SARS-CoV-2 memory at 1 month after infection, and the proportion of subjects positive for CD4+ T cells (92%) remained high at 6 to 8 months after infection. SARS-CoV-2 spike-specific memory CD4+ T cells with the specialized capacity to help B cells [T follicular helper (TFH) cells] were also maintained. The different types of immune memory each had distinct kinetics, resulting in complex interrelationships between the abundance of T cell, B cell, and antibody immune memory over time. Additionally, substantially heterogeneity in memory to SARS-CoV-2 was observed. CONCLUSION: Substantial immune memory is generated after COVID-19, involving all four major types of immune memory. About 95% of subjects retained immune memory at ~6 months after infection. Circulating antibody titers were not predictive of T cell memory. Thus, simple serological tests for SARS-CoV-2 antibodies do not reflect the richness and durability of immune memory to SARS-CoV-2. This work expands our understanding of immune memory in humans. These results have implications for protective immunity against SARS-CoV-2 and recurrent COVID-19

    Family involvement for children with disruptive behaviors: The role of parenting stress and motivational beliefs

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    Children with disruptive behaviors are at risk for adverse outcomes. Family involvement is a significant predictor of positive child behavior outcomes; however, little research has investigated parent psychological variables that influence family involvement for children with disruptive behaviors. This study investigated the role of parental motivational beliefs (i.e., role construction and efficacy) as a potential mechanism by which parenting stress impacts family involvement for families of children with disruptive behaviors. Results indicated that parent role construction mediated the relation between parenting stress and all aspects of family involvement examined (i.e., home-based involvement, school-based involvement, and home–school communication). Parent efficacy mediated the relation between parenting stress and home-based involvement only. Parents of children with disruptive behaviors reporting stress may experience negative beliefs about their role and efficacy to support their child’s education, which may thereby negatively influence their actual involvement. Therefore, parent motivational beliefs may serve as an important point for intervention to support involvement of families of children with disruptive behavior
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