Papillomavirus E6 proteins

AbstractThe papillomaviruses are small DNA viruses that encode approximately eight genes, and require the host cell DNA replication machinery for their viral DNA replication. Thus papillomaviruses have evolved strategies to induce host cell DNA synthesis balanced with strategies to protect the cell from unscheduled replication. While the papillomavirus E1 and E2 genes are directly involved in viral replication by binding to and unwinding the origin of replication, the E6 and E7 proteins have auxillary functions that promote proliferation. As a consequence of disrupting the normal checkpoints that regulate cell cycle entry and progression, the E6 and E7 proteins play a key role in the oncogenic properties of human papillomaviruses with a high risk of causing anogenital cancers (HR HPVs). As a consequence, E6 and E7 of HR HPVs are invariably expressed in cervical cancers. This article will focus on the E6 protein and its numerous activities including inactivating p53, blocking apoptosis, activating telomerase, disrupting cell adhesion, polarity and epithelial differentiation, altering transcription and reducing immune recognition

Retrospective Reports of Child Feeding Practices, Current Eating Behaviors, and BMI in College Students

Research concerning child feeding practices has focused on children and adolescents, and little is known about how feeding practices used in childhood relate to eating behaviors and weight status in early adulthood. We assessed college students’ and their parents’ retrospective reports of child feeding practices used when the students were in middle childhood. We also assessed the college students’ current reports of their eating behaviors using the Dutch Eating Behavior Questionnaire (DEBQ) and the Intuitive Eating Scale (IES), and measured their current BMI. Results showed that college students’ and their parents’ reports about previous parental use of child feeding practices were not correlated. Parent reports of their own use of child feeding practices were more related to students’ eating behaviors and BMI than were students’ recollections about feeding practices used by their parents. An analysis of gender effects showed that there were positive correlations between parental child feeding practices, BMI, and emotional eating for female students. These relationships did not exist for male students. The results suggest that child feeding practices recollected by parents are linked to the development of emotional eating and weight status of women in early adulthood

MuTrack: a genome analysis system for large-scale mutagenesis in the mouse

BACKGROUND: Modern biological research makes possible the comprehensive study and development of heritable mutations in the mouse model at high-throughput. Using techniques spanning genetics, molecular biology, histology, and behavioral science, researchers may examine, with varying degrees of granularity, numerous phenotypic aspects of mutant mouse strains directly pertinent to human disease states. Success of these and other genome-wide endeavors relies on a well-structured bioinformatics core that brings together investigators from widely dispersed institutions and enables them to seamlessly integrate data, observations and discussions. DESCRIPTION: MuTrack was developed as the bioinformatics core for a large mouse phenotype screening effort. It is a comprehensive collection of on-line computational tools and tracks thousands of mutagenized mice from birth through senescence and death. It identifies the physical location of mice during an intensive phenotype screening process at several locations throughout the state of Tennessee and collects raw and processed experimental data from each domain. MuTrack's statistical package allows researchers to access a real-time analysis of mouse pedigrees for aberrant behavior, and subsequent recirculation and retesting. The end result is the classification of potential and actual heritable mutant mouse strains that become immediately available to outside researchers who have expressed interest in the mutant phenotype. CONCLUSION: MuTrack demonstrates the effectiveness of using bioinformatics techniques in data collection, integration and analysis to identify unique result sets that are beyond the capacity of a solitary laboratory. By employing the research expertise of investigators at several institutions for a broad-ranging study, the TMGC has amplified the effectiveness of any one consortium member. The bioinformatics strategy presented here lends future collaborative efforts a template for a comprehensive approach to large-scale analysis

c-Myc Accelerates S-Phase and Requires WRN to Avoid Replication Stress

c-Myc interacts with components of the pre-replication complex and directly regulates DNA replication [1]. However the consequences of this novel c-Myc function on cell cycle dynamics and replication-associated damage are unknown. Here, we show that c-Myc overexpression in primary human fibroblasts markedly accelerates S-phase while c-Myc deficient fibroblasts exhibit a prolonged S-phase. We also show that the Werner DNA helicase protein (WRN) plays a critical role in supporting c-Myc-driven S-phase, as depletion of WRN in c-Myc overexpressing cells increases DNA damage specifically at sites of DNA synthesis. This excess DNA damage activates a “replication stress” pathway involving ATR, CHK1, CHK2, and p53, leading to rapid senescence of WRN deficient c-Myc overexpressing cells. Indeed, depletion of p53 rescues this senescence response. We propose that WRN functions to repair abnormal replication structures caused by the acceleration of DNA replication by c-Myc. This work provides an additional mechanistic explanation for c-Myc-induced DNA damage and senescence, and reveals a vulnerability of c-Myc overexpressing cells that could potentially be exploited in cancer therapy

Predicting Ideal Body Mass Index: What Does Clothing Size Have To Do With It?

This study examined demographic and anthropometric variables as predictors of ideal body mass index (BMI) from cross-sectional, archival, self-reported data from the Psychology of Size Survey of 4014 U.S. residents collected in 2007. As hypothesized, ideal BMI can be predicted by a within gender hierarchical multiple regression analysis with the predictor variables of age, number of clothing sizes from ideal size, and current BMI; these variables account for 54.1% of variance in women’s ideal BMI and 65.5% of variance in men’s ideal BMI. Findings also demonstrated a logarithmic relationship between current BMI and ideal BMI, with increasing variance in ideal BMI for individuals with high current BMIs. These ?ndings evidence the strong role of current body characteristics in the formation of ideals. Understanding how individuals conceptualize body ideals can inform researchers and practitioners alike, as this evidence has important implications related to both medical and psychological health

Recollections of pressure to eat during childhood, but not picky eating, predict young adult eating behavior

Picky eating is a childhood behavior that vexes many parents and is a symptom in the newer diagnosis of Avoidant/Restrictive Food Intake Disorder (ARFID) in adults. Pressure to eat, a parental controlling feeding practice aimed at encouraging a child to eat more, is associated with picky eating and a number of other childhood eating concerns. Low intuitive eating, an insensitivity to internal hunger and satiety cues, is also associated with a number of problem eating behaviors in adulthood. Whether picky eating and pressure to eat are predictive of young adult eating behavior is relatively unstudied. Current adult intuitive eating and disordered eating behaviors were self-reported by 170 college students, along with childhood picky eating and pressure through retrospective self- and parent reports. Hierarchical regression analyses revealed that childhood parental pressure to eat, but not picky eating, predicted intuitive eating and disordered eating symptoms in college students. These findings suggest that parental pressure in childhood is associated with problematic eating patterns in young adulthood. Additional research is needed to understand the extent to which parental pressure is a reaction to or perhaps compounds the development of problematic eating behavior

Characterization of IgA response among women with incident HPV 16 infection

AbstractPrevious studies have characterized the prevalence and duration of serum IgG antibodies to human papillomavirus type 16 (HPV 16) in a well-studied cohort of college women, using viruslike particle- (VLP) based ELISAs. In this study IgA antibodies in cervical secretions and sera were examined using a newly developed capsomer-based ELISA and the patterns observed for serum IgG, serum IgA, and cervical IgA antibodies were compared. The median time to antibody detection from the first detection of HPV 16 DNA was 10.5 months for IgA in cervical secretions and 19.1 months for serum IgA. Serum IgA antibody conversion was observed less frequently and occurred later than IgA conversion in cervical secretions (P = 0.011) or serum IgG conversion (P = 0.051). The median time to antibody reversion, following seroconversion, was 12.0 months for IgA in cervical secretions and 13.6 months for serum IgA, whereas approximately 20% of women with serum IgG antibodies reverted within 36 months. Thus, the duration of IgA in cervical secretions and sera was shorter than the duration of serum IgG (P = 0.007 and 0.001)

Prior human polyomavirus and papillomavirus infection and incident lung cancer: a nested case–control study

Purpose—To test whether infection with select human polyomaviruses (HPyV) and human papillomaviruses (HPV) is associated with incident lung cancer. Methods—We performed a nested case-control study, testing serum from the Carotene and Retinol Efficacy Trial CARET), conducted 1985–2005, for antibodies to Merkel cell (MCV), KI (KIV), and WU (WUV) HPyVs as well as to six high-risk and two low-risk HPV types. Incident lung cancer cases (n=200) were frequency-matched with controls (n=200) on age, enrollment and blood draw dates, intervention arm assignment, and the number of serum freeze / thaw cycles. Sera were tested using multiplex liquid bead microarray antibody assays. We used logistic regression to assess the association between HPyV and HPV antibodies and lung cancer. Results—There was no evidence of a positive association between levels of MCV, KIV, or WUV antibodies and incident lung cancer (P-corrected>0.10 for all trend tests; odds ratio (OR) range 0.72 to 1.09, P-corrected>0.10 for all). There was also no evidence for a positive association between HPV 16 or 18 infection and incident lung cancer (P-corrected≥0.10 for all trend tests; OR range 0.25 to 2.54, P>0.05 for all OR>1), but the number of persons with serologic evidence of these infections was small. Conclusions—Prior infection with any of several types of HPyV or HPV was not associated with subsequent diagnosis of lung cancer. Infection with these viruses likely does not influence a person’s risk of lung cancer in Western smoking populations