Publications

Environmental Correlates of Physical Activity

No abstract is provided for this article.

IKKβ in postnatal perichondrium remotely controls endochondral ossification of the growth plate through downregulation of MCP-5

Age-Related Changes in Types and Contexts of Physical Activity in Middle School Girls

Background Because girls are less physically active than boys, it is important to understand the types of activities preferred by girls, and changes in those preferences over time, in order to design effective physical activity interventions. Purpose To describe developmental trends in participation in specific forms of physical activity in 6th- and 8th-grade girls. Methods Data for this study are from the Trial of Activity for Adolescent Girls. Self-reported physical activity, anthropometric, and demographic data were collected from random cross sections of 6th-grade girls in 36 middle schools in six U.S. communities. The same data were collected 2 years later from random cross sections of 8th-grade girls, as well as in previously measured 6th-grade girls who remained in the schools. Analyses were conducted with SAS using mixed-model ANOVAs to determine differences between 6th- and 8th-grade girls. Data were collected in 2002–2003 and 2004–2005 and analyzed in 2008–2009. Results The top physical activities reported by 6th- and 8th-grade girls were similar. Of the top 13 activities reported by 6th- or 8th-grade girls, 8th-grade girls reported participating in more 30-minute blocks for ten of the activities and were more likely to report participating as part of an organized program. Conclusions The activities reported by 6th- and 8th-grade girls were similar, but the way they participated in them changed from 6th to 8th grade. Eighth-grade girls were more likely to participate in activities that are often part of school-based team sports, and the time of participation in these activities was greater. Interventions to increase physical activity in adolescent girls should be informed by the factors that influence their participation in organized school sports programs and community-based activities that promote physical activity.

Abstract B14: Anti-miR-135b in colon cancer treatment

Abstract Background: MicroRNAs (miRs) are small non coding RNAs involved in cell homeostasis. miRs are deregulated in colorectal cancer (CRC). Our study aimed at identifying miRs with a driver role in carcinogenesis altered by similar mechanisms in both human and mouse CRC. Goal of the study was to use CRC mouse models for the pre-clinical development of anti-miRs as therapeutic drugs. Methods: Azoximetane (AOM)/Dextran-Sulfate (DSS) treated mice or CDX2Cre-APC f/wt mice were used to study inflammation-associated and sporadic APC-related CRC. Human Inflammatory Bowel Disease associated (n=30), and sporadic (n=90) CRC with their matched normal tissues were collected according to Good Clinical Practice recommendation and subjected to RNA extraction using Trizol. miR and gene expression profiling was assessed by nCounter technology (Nanostring Seattle). AntimiR-135b and scrambled probes for in vivo studies were synthesized by Girindus. Results: miRs profiling from AOM/DSS and CDX2Cre-APC f/wt CRC. revealed that miR-135b is one of the most up-regulated miRs in both models. In humans miR-135b over-expression was found in both IBD and sporadic CRC and was associated with reduced Progression Free Survival and Overall Survival in CRC patients. Molecular studies in Mouse Embryo Fibroblast and human CRC cell lines highlighted the role of two major pathways in the upstream activation of miR-135b: APC-β-Catenin and SRC-PI3K. MiR-135b up-regulation resulted in reduced apoptosis and increased invasion and metastasis due to the down-regulation of TGFRB2, DAPK1, APC and HIF1AN. Silencing of miR-135b in vivo reduced tumor multiplicity and tumor load in the AOM/DSS CRC model. Mice treated with anti-miR-135b showed well differentiated tumors and acinar pattern while tumors in the control groups showed low differentiation and adenomatous pattern. Conclusions: Our data suggest that miR-135b is a key molecule whose activation is downstream of oncogenes and oncosuppressor genes frequently altered in CRC. Our study defines specific pathways that converge on the activation of the same microrna. The “in vivo” silencing of miR-135 shows preclinical efficacy with low toxicity and represents the first in vivo study for the use of antimiRs in CRC treatment Note: This abstract was not presented at the conference because the presenter was unable to attend. Citation Format: Nicola Valeri, Roberta Gafa', Gerard Nuovo, Giovanni Lanza, Wendy Frankel, Peter K. Vogt, Joanna Groden, Michael Karin, Carlo M. Croce, Chiara Braconi, Pierluigi Gasparini, Sergei Grivennikov, Jonathan R. Hart, Alessio Paone, Francesca Lovat, Muller Fabbri. Anti-miR-135b in colon cancer treatment [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr B14.

Differentiation of Lactotrope Precursor GHFT Cells in Response to Fibroblast Growth Factor-2

The mechanisms that control the emergence of different anterior pituitary cells from a common stem cell population are largely unknown. The immortalized GHFT cells derived from targeted expression of SV40 T antigen to mouse pituitary display characteristics of somatolactotropic progenitors in that they express the transcription factor GHF-1 (Pit-1) but not growth hormone (GH) or prolactin (PRL). We searched for factors capable of inducing lactotropic differentiation of GHFT cells. PRL gene expression was not observed in cells subjected to a variety of stimuli, which induce PRL gene expression in mature lactotropes. Only fibroblast growth factor-2 (FGF-2) was able to initiate the transcription, synthesis, and release of PRL in GHFT cells. However, induction of PRL expression was incomplete in FGF-2-treated cells, suggesting that additional factors are necessary to attain high levels of PRL transcription in fully differentiated lactotropes. We also show that the FGF-2 response element is located in the proximal PRL promoter. Stimulation of PRL expression by FGF-2 requires endogenous Ets factors and these factors as well as GHF-1 are expressed at low levels in the committed precursor, suggesting that these low levels are limiting for full PRL expression. Moreover, FGF-2 effect on lactotrope differentiation is mediated, at least partially, by stimulation of the Ras-signaling pathway. Our results suggest that, indeed, GHFT cells represent a valid model for studying lactotropic differentiation and that FGF-2 could play a key role both in initiating lactotrope differentiation and maintaining PRL expression.

Phorbol ester induces the transcriptional stimulatory activity of the SV40 enhancer

Activation of IKK by thymosin α1 requires the TRAF6 signalling pathway

Physical Activity 2016: Progress and Challenges Progress in physical activity over the Olympic quadrennium

The Active Living Research 2014 Conference: “Niche to norm”

No abstract is provided for this article.

Ethnic and Gender Differences in Request For and Use of Low/Non‐Fat Foods in Bag Lunches

: 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.

Sestrin regulation of TORC1: Is Sestrin a leucine sensor?

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.

Perceived environmental predictors of physical activity over 6 months in adults: Activity Counseling Trial.

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.

Erratum: Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity

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NF-κB-p62-NRF2 survival signaling is associated with high ROR1 expression in chronic lymphocytic leukemia

Associations of the Built Environment With Physical Activity and Sedentary Time in Ugandan Outpatients With Mental Health Problems

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.

An ecosystem service perspective on urban nature, physical activity, and health

Nature underpins human well-being in critical ways, especially in health. Nature provides pollination of nutritious crops, purification of drinking water, protection from floods, and climate security, among other well-studied health benefits. A crucial, yet challenging, research frontier is clarifying how nature promotes physical activity for its many mental and physical health benefits, particularly in densely populated cities with scarce and dwindling access to nature. Here we frame this frontier by conceptually developing a spatial decision-support tool that shows where, how, and for whom urban nature promotes physical activity, to inform urban greening efforts and broader health assessments. We synthesize what is known, present a model framework, and detail the model steps and data needs that can yield generalizable spatial models and an effective tool for assessing the urban nature–physical activity relationship. Current knowledge supports an initial model that can distinguish broad trends and enrich urban planning, spatial policy, and public health decisions. New, iterative research and application will reveal the importance of different types of urban nature, the different subpopulations who will benefit from it, and nature’s potential contribution to creating more equitable, green, livable cities with active inhabitants.

Bridging the Gap: Composition, Regulation, and Physiological Function of the IκB Kinase Complex

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).