1,993 publications from this institution
Sestrins are a family of stress-inducible proteins that can function as antioxidants and as inhibitors of target of rapamycin complex 1. In this research perspective, we discuss the possible roles of Sestrins in diverse stress-induced patho-physiological contexts that can result in premature aging and age-related diseases. We suggest that Sestrins provide critical feedback regulation that adjust metabolic and stress responses to different environmental cues and evolutionary constraints.
BCL3 is a candidate proto-oncogene involved in the recurring translocation t(14;19) found in some patients with chronic lymphocytic leukemia. BCL3 protein acts as an I kappa B in that it can specifically inhibit the DNA binding of NF-kappa B factors. Here, we demonstrate that BCL3 is predominantly a nuclear protein and provide evidence that its N terminus is necessary to direct the protein into the nucleus. In contrast to I kappa B alpha (MAD3), BCL3 does not cause NF-kappa B p50 to be retained in the cytoplasm; instead, in cotransfection assays, it alters the subnuclear localization of p50. The two proteins colocalize, suggesting that they interact in vivo. Further immunofluorescence experiments showed that a mutant p50, lacking a nuclear localization signal and restricted to the cytoplasm, is brought into the nucleus in the presence of BCL3. Correspondingly, a wild-type p50 directs into the nucleus a truncated BCL3, which, when transfected alone, is found in the cytoplasm. We tested whether BCL3 could overcome the cytoplasmic retention of p50 by I kappa B alpha. Results from triple cotransfection experiments with BCL3, I kappa B alpha, and p50 implied that BCL3 can successfully compete with I kappa B alpha and bring p50 into the nucleus; thus, localization of NF-kappa B factors may be affected by differential expression of I kappa B proteins. These novel properties of BCL3 protein further establish BCL3 as a distinctive member of the I kappa B family.
No abstract is provided for this article.
Background Americans are increasingly eating out, but nutrition environments in restaurants are poorly understood. An observational measure was developed to assess factors believed to contribute to food choices in restaurants, including availability of more healthy foods, facilitators and barriers to healthful eating, pricing, and signage/promotion of healthy and unhealthy foods. Methods Inter-rater and test–retest reliability were assessed in 217 sit-down and fast-food restaurants in four neighborhoods in 2004 and 2005. Results Inter-rater reliability was generally high, with most kappa values greater than 0.80 (range 0.27–0.97) and all percent-agreement values greater than 75% (77.6–99.5). Test–retest reliability was high, with most kappa values greater than 0.80 (0.46–1.0) and all percent-agreement values greater than 80% (80.4–100). There were several differences (p<0.05) between nutrition environment variables in sit-down versus fast-food restaurants, although neither restaurant type was consistently more healthful. Fast-food restaurants had greater healthy entrée and main-dish salad availability, but sit-down restaurants had a higher proportion of healthy main-dish salads and more healthy food and beverage items. Fast-food restaurants more often encouraged large portions, unhealthful eating, and overeating, and offered relative cost savings for combination meals, but were also more likely to provide nutrition information and highlight healthy options. Conclusions Testing hypotheses about food environment influences on obesity and eating patterns requires psychometrically sound measurement of nutrition environments. This Nutrition Environment Measures Study restaurant assessment (NEMS-R) has evidence of reliability, and can discriminate restaurant types. The NEMS-R can be used in research and practice to characterize restaurant environments.
Initiation of transcription by RNA polymerase II in eukaryotes is strongly increased by cis-acting genetic elements, known as activators or enhancers. Enhancers, first detected in simian virus 40 (SV40), were subsequently also found to control the expression of several cellular genes. The human metallothionein-IIA (hMT-IIA) gene, although inducible by heavy metals and glucocorticoids, is widely expressed in most cell types in the absence of inducers. Here we show that the high basal level of transcription of the hMT-IIA gene is due to the presence of an enhancer element within the hMT-IIA promoter region. The structural and functional organization of this cellular enhancer element in two direct repeats is strikingly similar to that of the enhancer element of SV40. This suggests a possible functional and evolutionary relationship between enhancers and upstream promoter elements.
Abstract Recognition of extracellular pathogenassociated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) results in activation of host defense signaling pathways. Some virulent microbes can attenuate and escape antimicrobial immunity by manipulating these signaling pathways. However, impairment of the primary innate response may potentiate the activation of secondary defense program, centered around Nucleotide-binding domain and Leucine-rich repeat containing Receptor (NLRs) for inflammasome formation and IL-1β production. This review analyzes the current knowledge regarding association of innate immune signaling pathways with inflammasome activation in response to bacterial infection.
Abstract The majority of sporadic human colorectal cancer is initiated by genetic loss or inactivation of tumor suppressor APC (Absent in Polyposis Coli). In addition to activation of beta-catenin signaling, we found that loss of APC results in upregulation of IL-6 signal transducer (IL6/gp130), thereby leading to activation of STAT3 and YAP, two transcription factors that make important contributions to colorectal tumorigenesis. In addition, APC loss results in deterioration of the intestinal epithelial barrier and immune homeostasis, barrier loss due to downregulation of genes encoding tight junction proteins, and suppression of mucin production. Together, such changes promote the invasion of inflammation-inducing colitogenic bacteria and their products. Loss of immune homeostasis is due to defective luminal transport of IgA dimers caused by loss of polyimmunoglobin receptor (PIgR) and CCL28, a chemokine responsible for recruitment of IgA-producing plasma cells. Defective luminal transport of IgA results in dysbiosis and over-representation of inflammation-causing bacteria that can accelerate colorectal tumor genesis through upregulation of IL-17 production. Citation Format: Michael Karin. Tumor-elicited inflammation in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY19-01. doi:10.1158/1538-7445.AM2017-SY19-01
Background: For research on physical activity interventions to progress systematically, the mechanisms of action must be studied. In doing so, the research methods and their associated concepts and terminology become more complex. It is particularly important to clearly distinguish among determinants, correlates, mediators, moderators, and confounder variables used in physical activity research. This article examines the factors that are correlated with and that may have a causal relationship to physical activity. Methods and Results: We propose that the term “correlate” be used, instead of “determinant,” to describe statistical associations or correlations between measured variables and physical activity. Studies of the correlates of physical activity are reviewed. The findings of these studies can help to critique existing theories of health behavior change and can provide hypotheses to be tested in intervention studies from which it is possible to draw causal inferences. Mediator, moderator, and confounder variables can act to influence measured changes in physical activity. Intervening causal variables that are necessary to complete a cause-effect pathway between an intervention and physical activity are termed “mediators.” The relationship between an intervention and physical activity behaviors may vary for different groups; the strata by which they vary are levels of “moderators” of the relationship. Other factors may distort or affect the observed relationships between program exposure and physical activity, and are known as “confounders.” Conclusions: Consistent use of terms and additional research on mediators and moderators of intervention effects will improve our ability to understand and influence physical activity.
Purpose: The strength of the relationship of environment to physical activity may differ by age group. Older adults were expected to be more affected by environmental attributes than younger adults. The present study examined age-related differences in associations between perceived neighborhood environment and physical activity. Methods: Participants were 1623 adults aged 20 to 97 yr divided into five groups: ages 20-39, 40-49, 50-65, 66-75, and 76+. They were recruited from King County/Seattle, WA, neighborhoods selected to vary in land use and median income. Participants completed questionnaires about neighborhood environment attributes and walking for transportation and for leisure purposes. Neighborhood environment, within a 15- to 20-min walk from home, was measured on nine attributes with the validated Neighborhood Environment Walkability Scale questionnaire: residential density, proximity to nonresidential land uses, ease of access to nonresidential uses, street connectivity, walking/cycling facilities, esthetics, pedestrian traffic safety, crime safety, and proximity to recreation facilities. Participants reported frequency and duration of walking using the validated International Physical Activity Questionnaire and the Community Healthy Activities Model Program for Seniors. Partial correlations were computed, adjusting for demographics. Results: Walking for transportation was significantly related to multiple perceived neighborhood attributes in all age groups, although walking for leisure was not. Walking for transportation was significantly related to almost all neighborhood environment variables in the youngest age group. In contrast, only two environmental attributes, proximity to nonresidential uses (like shops) and recreation facilities, were moderately correlated with walking for transportation in the two oldest groups. Conclusion: Communities need to be designed with many favorable environmental attributes to support walking for transportation among younger adults. Having nonresidential destinations and recreation facilities within walking distance may be among the most important attributes to support older adults' physical activity.
In brief Promoting physical activity among patients is an essential role for physicians. Project PACE (Physician-based Assessment and Counseling for Exercise) is a practical system of matching physician counseling with patient readiness for physical activity. The PACE counseling approach will help physicians attain national goals for health promotion for the year 2000.
