No abstract is provided for this article.
Sestrins are highly conserved, stress-inducible proteins that inhibit target of rapamycin complex 1 (TORC1) signaling. After their transcriptional induction, both vertebrate and invertebrate Sestrins turn on the adenosine monophosphate (AMP)-activated protein kinase (AMPK), which activates the tuberous sclerosis complex (TSC), a key inhibitor of TORC1 activation. However, Sestrin overexpression, on occasion, can result in TORC1 inhibition even in AMPK-deficient cells. This effect has been attributed to Sestrin's ability to bind the TORC1-regulating GATOR2 protein complex, which was postulated to control trafficking of TORC1 to lysosomes. How the binding of Sestrins to GATOR2 is regulated and how it contributes to TORC1 inhibition are unknown. New findings suggest that the amino acid leucine specifically disrupts the association of Sestrin2 with GATOR2, thus explaining how leucine and related amino acids stimulate TORC1 activity. We discuss whether and how these findings fit what has already been learned about Sestrin-mediated TORC1 inhibition from genetic studies conducted in fruit flies and mammals.
: This study examined ethnic and gender differences in frequency of use and request for low‐fat or non‐fat foods in bag lunches, while controlling for socioeconomic status. Questionnaires were completed by 1,678 middle school students and their parents (72% response). Ethnic distribution included White (51%), Latino (17%), Asian (11%), Multi‐ethnic (11%), and African American (8%). Forty‐five percent of students (N = 712, 59% female) brought lunch to school a mean of 3.6 (SD = 1.5) days per week. Boys brought lunch more often (M = 3.8 days/week vs. 3.4, respectively), yet requested less low‐fat foods than girls. Whites brought lunches with the most low/non‐fat items. Ethnic differences also were found in the use of seven specific bag lunch foods and whether these items were regular or low‐fat. Because of ethnic and gender differences, different strategies for reducing fat in bag lunches are needed for different groups.
In the present study, the authors extend previous cross-sectional findings by using a prospective design to determine whether physical and social environmental characteristics predict physical activity over 6 months.Inactive adults were recruited to the Activity Counseling Trial, a multicenter, randomized, controlled trial of physical activity intervention in primary care. Participants were 387 women and 474 men aged 35-75 years in 3 regions; 1/3 were minorities; 56% had some college education. Baseline perceived environmental variables were used to predict physical activity at 6 months, adjusting for experimental condition and other potential moderators.The validated 7-day physical activity recall interview was used to estimate minutes of moderate to vigorous physical activity. A standardized survey was used to measure social and physical environmental variables around the home and neighborhood.Women reporting no unattended dogs and low crime in their neighborhoods and men reporting frequently seeing people being active in their neighborhoods did 50-75 more minutes of physical activity per week than did those with different environmental characteristics. Interactions of environmental variables with age group suggested that older adults may be more affected by environmental variables than are younger adults.Self-reported social and physical environmental variables were significantly related to moderate to vigorous physical activity among a diverse sample of adults living in 3 regions of the United States. These prospective findings strengthen the conclusion from previous cross-sectional studies that environmental variables are important correlates of physical activity.
Background: This study investigated whether reported neighborhood variables explained variance in time spent walking, exercising, and being sedentary, in addition to mental health and demographic variables among Ugandan outpatients with mental illness. Methods: Ninety-nine outpatients (78 men; 31.1 [8.6] y) of the Butabika National Referral Hospital in Uganda completed the Neighborhood Environment Walkability Scale for Africa, the Simple Physical Activity Questionnaire, and the Brief Symptoms Inventory-18. Multiple regression analyses were performed. Results: Seven percent of the variance in walking time was explained by the variance in anxiety/depression and an additional 13% by the variance in perceived mixed land use and the availability of roads and walking paths. Eight percent of the variance in exercise time was explained by variance in age and an additional 6% by the variance anxiety/depression. The availability of recreational space added 8%. Six percent of variance in time spent sedentary was explained by family income, while availability of roads and walking paths added another 6%. Conclusions: This study shows the relevance of availability of roads and walking paths and recreational space for more physical activity and less sedentary behavior in people with mental illness. This is particularly relevant in low-income countries where a rapid urbanization is taking place.
Protein kinases that regulate the activity of specific transcription factors in response to extracellular stimuli not only are the subject of intense research but also are being chased as potential targets for development of new drugs for treatment of various human diseases. One such protein kinase is IKK, the IκB kinase that activates nuclear factor κB (NF-κB) through phosphorylation of IκB inhibitory proteins. In this review, we summarize the discovery of IKK and recent knowledge about its composition, regulation, and physiological functions. NF-κB transcription factors regulate the expression of a large number of genes that are necessary for proper functioning of the immune system and are key mediators of inflammatory responses to pathogens (2, 4, 5). NF-κB is also associated with cellular transformation and oncogenesis, and one of its most important, but lately discovered functions, is the activation of an antiapoptotic gene expression program (6, 29, 36, 38, 39, 42). As a transcription factor that orchestrates the inflammatory response, NF-κB is rapidly activated, independently of new protein synthesis, in response to signals produced during infection (e.g., bacterial endotoxins and viral double-stranded RNA) (for a review, see reference 3). NF-κB activation is also a transient response; this is of importance because many of the genes that are activated by NF-κB encode potentially toxic products such as tumor necrosis factor (TNF). The key to NF-κB regulation is the inhibitory κB (IκB) proteins which retain NF-κB in the cytoplasm (reviewed in reference 37). In response to diverse stimuli, IκBs are rapidly degraded and the freed NF-κB dimers translocate to the nucleus. Several years ago, it was established that the critical event which triggers the polyubiquitination and degradation of IκBs via the 26S proteasome is their stimulus-dependent phosphorylation at two serine residues (residues 32 and 36 in IκBα) that are located within their conserved N-terminal regulatory region (1, 10–12, 18, 20, 34, 40). The protein kinase that phosphorylates these regulatory sites remained elusive, and without detailed knowledge about its molecular identity, there was little progress towards a full understanding of the signaling pathways that control NF-κB activity. The initial hunt for such a protein kinase yielded many false candidates, such as protein kinase C, casein kinase II, and ribosomal S6 kinase (pp90rsk) (reviewed in reference 43). Although most of these kinases phosphorylate IκB proteins in the test tube on different serine, threonine, or tyrosine residues, none of them was found to phosphorylate the two regulatory sites that trigger the degradation of IκBs in a stimulus-dependent manner. A large-molecular-mass (700-kDa) protein kinase activity that phosphorylates IκBα on S32 and S36 in a ubiquitin-dependent manner was also detected in extracts of nonstimulated HeLa cells (13, 25). However, this activity was not reported to be stimulus dependent, and to date, its components and molecular identity are unknown. A careful consideration of IκB phosphorylation indicated that the physiological IκB kinase had to fulfill several criteria. Its activity should be stimulated by inducers of NF-κB with kinetics that are consistent with those of NF-κB activation, and it should phosphorylate both S32 and S36 in the N terminus of IκBα and both S19 and S23 in the N terminus of IκBβ. In addition, since substitution of threonines for these serines results in IκB mutants that are resistant to degradation, the physiological IκB kinase should be serine specific (18).
No abstract is provided for this article.
