Publications

Checklist of Health Promotion Environments at Worksites (CHEW): Development and Measurement Characteristics

Intercellular telomere transfer extends T cell lifespan

The common view is that T-lymphocytes activate telomerase, a DNA polymerase that extends telomeres at chromosome ends, to delay senescence. We show that independently of telomerase, T cells elongate telomeres by acquiring telomere vesicles from antigen-presenting cells (APCs). Upon contact with T cells, APCs degraded shelterin to donate telomeres, which were cleaved by TZAP, and then transferred in extracellular vesicles (EVs) at the immunological synapse. Telomere vesicles retained the Rad51 recombination factor that enabled them to fuse with T cell chromosomal ends causing an average lengthening of ∼3000 base pairs. Thus, we identify a previously unknown telomere transfer program that supports T cell lifespan.

MEK kinase 1 is critically required for c-Jun N-terminal kinase activation by proinflammatory stimuli and growth factor-induced cell migration

Exposure of eukaryotic cells to extracellular stimuli results in activation of mitogen-activated protein kinase (MAPK) cascades composed of MAPKs, MAPK kinases (MAP2Ks), and MAPK kinase kinases (MAP3Ks). Mammals possess a large number of MAP3Ks, many of which can activate the c-Jun N-terminal kinase (JNK) MAPK cascade when overexpressed, but whose biological function is poorly understood. We examined the function of the MAP3K MEK kinase 1 (MEKK1) in proinflammatory signaling. Using MEKK1-deficient embryonic stem cells prepared by gene targeting, we find that, in addition to its function in JNK activation by growth factors, MEKK1 is required for JNK activation by diverse proinflammatory stimuli, including tumor necrosis factor alpha, IL-1, double-stranded RNA, and lipopolysaccharide. MEKK1 is also essential for induction of embryonic stem cell migration by serum factors, but is not required for activation of other MAPKs or the IkappaB kinase signaling cascade.

Building evidence to reduce inequities in youth physical activity and obesity: Introduction to the Physical Activity Research Center (PARC) Special Section

This guest editorial introduces the rationale and goals of the Physical Activity Research Center. It provides an overview of the five papers in this Special Section plus six commissioned studies intended to inform advocacy efforts.

Role of Inflammation in Metastatic Progression

A link between chronic inflammation and cancer has been suspected since the nineteenth century, when Rudolf Virchow first noted that malignant tumors arise at regions of chronic inflammation and contain inflammatory infiltrates [1–5]. However, the sources of inflammation in tumors that are not associated with a chronic inflammation remain incompletely understood. Recently, it became apparent that inflammation can be evoked not only by extrinsic mediators but also by intrinsic mediators (endogenous molecules) (Figure 14.1). For instance, it has been established that necrotic cell death results in the release of molecules normally stored within cells, such as high-mobility group box 1 (HMGB1) and interleukin (IL)-1α, that act as potent inflammatory mediators [6, 7]. Such molecules may responsible for the triggering of tumor-associated inflammation [7].

Author Correction: A central role for JNK in obesity and insulin resistance

Indoor tanning facility density in eighty U.S. cities.

The purpose of this study was to examine the number of tanning facilities in select U.S. cities. The twenty most populated cities from each of 4 U.S. regio

Determinants of Exercise Behavior

No abstract is provided for this article.

Family Exercise: Designing a Program To Fit Everyone

'The family that plays together stays together' is not just a cliché. Family exercise is a good way to spend time together, and the resulting mutual support helps people make a long-term commitment to fitness.

Induction of Human Growth Hormone Promoter Activity by the Adenosine 3′,5′-Monophosphate Pathway Involves a Novel Responsive Element

Regulation of GH gene expression by GRF involves cAMP as a second messenger. We have demonstrated that a 500-basepair fragment of the human GH (hGH) gene 5' flanking region can confer cAMP inducibility upon the chloramphenicol acetyltransferase transcription unit in transient transfections of rat pituitary tumor cells treated with forskolin, an activator of adenyl cyclase. The same hGH construct is not induced by forskolin in nonpituitary-derived cells. Experiments with hGH deletion constructs reveal that binding sites for transcription factor AP-2 and the pituitary-specific factor GHF-1 are not required for forskolin stimulation, but that GHF-1 may potentiate the effect. RNA analyses reveal that forskolin also stimulates accumulation of transcripts initiated at the hGH promoter. Other agents that elevate cAMP levels also stimulate hGH expression. Since the hGH 5' flanking region contains no sequences homologous to the cAMP-responsive element of the somatostatin gene, and the AP-2 sites do not appear to be required for the forskolin response, these results suggest that a novel cAMP-responsive element exists within 82 basepairs upstream from the transcriptional start of the hGH gene and that hGH regulation by GRF may involve interaction between a tissue-specific element and a cAMP-inducible element.

Biphasic Increase in c-<i>jun</i> mRNA Is Required for Induction of AP-1-Mediated Gene Transcription: Differential Effects of Muscarinic and Thrombin Receptor Activation

Activation of either muscarinic cholinergic or thrombin receptors increases phosphoinositide turnover, Ca2+ mobilization, and redistribution of protein kinase C and induces rapid transient increases in c-fos mRNA and c-jun mRNA in 1321N1 cells. To determine whether the increases in c-fos and c-jun mRNA induced by carbachol and thrombin are sufficient to stimulate AP-1-mediated transactivation, 1321N1 cells were transfected with a reporter carrying two copies of the tetradecanoyl phorbol acetate response element and the firefly luciferase gene. Thrombin was significantly more effective than carbachol at stimulating AP-1-mediated transactivation. To identify the factors underlying the difference in AP-1 activity induced by carbachol and thrombin, members of the fos and jun families which encode components of AP-1 were examined. Carbachol and thrombin have similar effects on expression of c-fos, fosB, fra-2, junB, and junD, both acutely and over a 24-h time course. However, whereas carbachol leads only to transient induction of c-jun (maximal at 0.5 h), thrombin induces a biphasic increase in c-jun mRNA--an initial peak at 0.5 h and a second, more-prolonged increase at 12 h. Thrombin but not carbachol also induces a late increase in fra-1 mRNA, which peaks at 12 h. The secondary increase in c-jun mRNA is associated with marked increases in c-Jun protein levels and AP-1 DNA-binding activity. The late induction of c-jun and fra-1 mRNA can be prevented by adding the antagonist hirudin 30 min after thrombin, which results in loss of thrombin-stimulated increases in c-Jun protein, AP-1 DNA-binding activity, and AP-1-mediated transactivation. These findings suggest that rapid and transient conduction of c-fos and c-jun mRNA is insufficient to induce prominent changes in gene transcription, while the sustained increase in c-jun mRNA and perhaps the late induction of fra-1 mRNA are required for generation of AP-1 DNA-binding activity and transactivation through AP-1.

Supplementary figure 2 from Characterization of HCC Mouse Models: Towards an Etiology-Oriented Subtyping Approach

&lt;p&gt;non-tumorous murine livers&lt;/p&gt;

Environmental Assessment of Public Recreation Space--Shortened Version

Outcomes of a 12-Month Technology-Based Intervention to Promote Weight Loss in Adolescents at Risk for Type 2 Diabetes

Background: Obese adolescents are at risk for type 2 diabetes mellitus (T2DM). Obesity interventions delivered through media, such as the web and text messages [short message service (SMS)] may be beneficial when targeting obese adolescents. Methods: A randomized controlled trial, Pace-Internet for Diabetes Prevention Intervention (PACEi-DP), compared three forms of an obesity intervention to usual care (UC): (a) website only (W); (b) website, monthly group sessions, and follow-up calls (WG); and (c) website and SMS (WSMS). Participants were overweight or obese adolescents at risk for T2DM ( n = 101; age 12–16 years; mean body mass index (BMI) percentile = 97.6; 74.3% Hispanic). In addition to the website, WSMS participants received SMS supporting intervention goals and behavioral strategies and communicated via SMS with a case manager. WG participants had additional group activities related to weight loss and received follow-up calls from a health coach. UC participants were given printed materials and encouraged to attend three initial group sessions. Repeated measures mixed model regression analyses tested treatment effects for anthropometric, behavioral, and behavioral change strategy outcomes. Results: There were no treatment effects for BMI, adiposity, physical activity, or diet at 12 months. Treatment effects were observed for sedentary behavior, with the W arm having a greater decrease in sedentary behavior (4.9 to 2.8 h/day) than the UC arm ( p = .006). Conclusion: Although not sufficient to produce weight loss, the combination of web intervention and group sessions with telephone follow-up yielded improvements in sedentary behavior and in the use of behavior change strategies expected to lead to behavior change.

Transactivation by NF-IL6/LAP is enhanced by phosphorylation of its activation domain

Health Behavior Change at the Worksite: Cardiovascular Risk Reduction

No abstract is provided for this article.

Elevated A20 promotes TNF-induced and RIPK1-dependent intestinal epithelial cell death

Intestinal epithelial cell (IEC) death is a common feature of inflammatory bowel disease (IBD) that triggers inflammation by compromising barrier integrity. In many patients with IBD, epithelial damage and inflammation are TNF-dependent. Elevated TNF production in IBD is accompanied by increased expression of the <i>TNFAIP3</i> gene, which encodes A20, a negative feedback regulator of NF-κB. A20 in intestinal epithelium from patients with IBD coincided with the presence of cleaved caspase-3, and A20 transgenic (Tg) mice, in which A20 is expressed from an IEC-specific promoter, were highly susceptible to TNF-induced IEC death, intestinal damage, and shock. A20-expressing intestinal organoids were also susceptible to TNF-induced death, demonstrating that enhanced TNF-induced apoptosis was a cell-autonomous property of A20. This effect was dependent on Receptor Interacting Protein Kinase 1 (RIPK1) activity, and A20 was found to associate with the Ripoptosome complex, potentiating its ability to activate caspase-8. A20-potentiated RIPK1-dependent apoptosis did not require the A20 deubiquitinase (DUB) domain and zinc finger 4 (ZnF4), which mediate NF-κB inhibition in fibroblasts, but was strictly dependent on ZnF7 and A20 dimerization. We suggest that A20 dimers bind linear ubiquitin to stabilize the Ripoptosome and potentiate its apoptosis-inducing activity.

The TROLLEY Study: assessing travel, health, and equity impacts of a new light rail transit investment during the COVID-19 pandemic

Background The COVID-19 pandemic disrupted life in extraordinary ways impacting health and daily mobility. Public transit provides a strategy to improve individual and population health through increased active travel and reduced vehicle dependency, while ensuring equitable access to jobs, healthcare, education, and mitigating climate change. However, health safety concerns during the COVID-19 pandemic eroded ridership, which could have longstanding negative consequences. Research is needed to understand how mobility and health change as the pandemic recedes and how transit investments impact health and equity outcomes. Methods The TROLLEY (TRansit Opportunities for HeaLth, Livability, Exercise and EquitY) study will prospectively investigate a diverse cohort of university employees after the opening of a new light rail transit (LRT) line and the easing of campus COVID-19 restrictions. Participants are current staff who live either &lt; 1 mile, 1–2 miles, or &gt; 2 miles from LRT, with equal distribution across economic and racial/ethnic strata. The primary aim is to assess change in physical activity, travel mode, and vehicle miles travelled using accelerometer and GPS devices. Equity outcomes include household transportation and health-related expenditures. Change in health outcomes, including depressive symptoms, stress, quality of life, body mass index and behavior change constructs related to transit use will be assessed via self-report. Pre-pandemic variables will be retrospectively collected. Participants will be measured at 3 times over 2 years of follow up. Longitudinal changes in outcomes will be assessed using multilevel mixed effects models. Analyses will evaluate whether proximity to LRT, sociodemographic, and environmental factors modify change in outcomes over time. Discussion The TROLLEY study will utilize rigorous methods to advance our understanding of health, well-being, and equity-oriented outcomes of new LRT infrastructure through the COVID-19 recovery period, in a sample of demographically diverse adult workers whose employment location is accessed by new transit. Results will inform land use, transportation and health investments, and workplace interventions. Findings have the potential to elevate LRT as a public health priority and provide insight on how to ensure public transit meets the needs of vulnerable users and is more resilient in the face of future health pandemics. Trial registration The TROLLEY study was registered at ClinicalTrials.gov ( NCT04940481 ) June 17, 2021, and OSF Registries ( https://doi.org/10.17605/OSF.IO/PGEHU ) June 24, 2021, prior to participant enrollment.