Publications

Supplementary Figure 2 from c-Jun NH<sub>2</sub>-Terminal Kinase 1 Is a Critical Regulator for the Development of Gastric Cancer in Mice

Supplementary Figure 2 from c-Jun NH<sub>2</sub>-Terminal Kinase 1 Is a Critical Regulator for the Development of Gastric Cancer in Mice

Special Issue: Active Living Research - a six-year report.

No abstract is provided for this article.

JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension

MAP kinase (MAPK) cascades are composed of a MAPK, MAPK kinase (MAPKK), and a MAPKK kinase (MAPKKK). Despite the existence of numerous components and ample opportunities for crosstalk, most MAPKs are specifically and distinctly activated. We investigated the basis for specific activation of the JNK subgroup of MAPKs. The specificity of JNK activation is determined by the MAPKK JNKK1, which interacts with the MAPKKK MEKK1 and JNK through its amino-terminal extension. Inactive JNKK1 mutants can disrupt JNK activation by MEKK1 or tumor necrosis factor (TNF) in intact cells only if they contain an intact amino-terminal extension. Mutations in this region interfere with the ability of JNKK1 to respond to TNF but do not affect its activation by physical stressors. As JNK and MEKK1 compete for binding to JNKK1 and activation of JNKK1 prevents its binding to MEKK1, activation of this module is likely to occur through sequential MEKK1:JNKK1 and JNKK1:JNK interactions. These results underscore a role for the amino-terminal extension of MAPKKs in determination of response specificity.

Table of Contents

No abstract is provided for this article.

Specific members of the Jun protein family regulate collagenase expression in response to various extracellular stimuli.

The transcription factor AP1 which regulates expression of collagenase in response to various extracellular signals is a multimeric complex composed of members of the Jun- and Fos families. To examine the biological role of the various components in signal transduction we analyzed the expression of two of them (cJun, JunB) and collagenase in response to phorbol esters, cAMP and TGF-beta. While all three genes are induced by phorbol ester and TGF-beta only JunB is induced by cAMP. In contrast expression of cJun and collagenase is reduced by cAMP indicating that cJun and JunB are not coordinately regulated. In addition JunB is not an efficient activator of the cJun and collagenase promoters although both cJun and JunB exhibit similar DNA binding properties, indicating that the differences in biological activity is due to differences in their activation domains. Our results imply that enhanced expression of collagenase (and cJun) depends on the activation of cJun. Expression of cJun and collagenase is inhibited under certain conditions of high levels of JunB. This suggests a negative regulatory function of JunB which greatly expands the potential of the Jun protein family in changing the transcription of specific genes involved in triggering complex biological processes.

Aggregation of physical activity habits in Mexican-American and Anglo families

It is believed that families are important influences on the development of health habits, and the purpose of the present study was to examine the familial

Inflammation and cancer: the long reach of Ras

Process variables as predictors of risk factor changes in a family health behavior change program

The purpose of the present study was to determine the extent to which intervention process measures are useful in predicting changes in cardiovascular disease (CVD) risk factors among subjects exposed to interventions. Subjects were 99 adult and 105 children who participated in an 18 session, family-based diet and exercise change program. During the intervention, each participant self-monitonally, diet and exercise for 12 weeks. Additinally, attendance, session evaluation, confidence to achieve goals and goal achievement data were collected each week. The intervention was successful in changing diet, blood pressure and cholesterol levels, but did not produce significant changes in exercise or body mass index. Stepwise multiple regression analyses were conducted for each outcome variable at the 1 and 2 year follow-ups. Ethnicity and sex were first forced into each regression. None of the process measures consistently predicted multiple outcomes in adults and children. The pattern of results provides limited support for the hypothesis that intervention process variables such as attendance, adherence to self–monitoring, achievement of goals and attitude toward sessions partially mediate intervention effects. It is concluded that process measures should be collected in health behavior change programs so that process-outcome relation ships can be further explored.

Conditional ablation of Ikkb inhibits melanoma tumor development in mice

Several lines of evidence suggest that tumor cells show elevated activity of the NF-kappaB transcription factor, a phenomenon often resulting from constitutive activity of IkappaB kinase beta (IKKbeta). However, others have found that loss of NF-kappaB activity or IKKbeta is tumor promoting. The role of NF-kappaB in tumor progression is therefore controversial and varies with tumor type. We sought to more extensively investigate the role IKKbeta in melanoma tumor development by specifically disrupting Ikkb in melanocytes in an established mouse model of spontaneous melanoma, whereby HRasV12 is expressed in a melanocyte-specific, doxycycline-inducible manner in mice null for the gene encoding the tumor suppressor inhibitor cyclin-dependent kinase 4/alternative reading frame (Ink4a/Arf). Our results show that Ink4a/Arf-/- mice with melanocyte-specific deletion of Ikkb were protected from HRasV12-initiated melanoma only when p53 was expressed. This protection was accompanied by cell cycle arrest, with reduced cyclin-dependent kinase 2 (Cdk2), Cdk4, Aurora kinase A, and Aurora kinase B expression. Increased p53-mediated apoptosis was also observed, with decreased expression of the antiapoptotic proteins Bcl2 and survivin. Enhanced stabilization of p53 involved increased phosphorylation at Ser15 and reduced phosphorylation of double minute 2 (Mdm2) at Ser166. Together, our findings provide genetic and mechanistic evidence that mutant HRas initiation of tumorigenesis requires Ikkbeta-mediated NF-kappaB activity.

AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update

HomeCirculationVol. 106, No. 3AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update

Review of Behavioral Research for Cardiopulmonary Health: Emphasis on Youth, Gender, and Ethnicity

(1995). Review of Behavioral Research for Cardiopulmonary Health: Emphasis on Youth, Gender, and Ethnicity. Journal of Health Education: Vol. 26, Cardiopulmonary Health Behavior Research: Focus on Youth, Gender, and Ethnicity, pp. S9-S17.

"Neighbourhood walkability, neighbourhood SES, physical activity, sedentary behaviour and overweight in Belgian adults : results from the Belgian Environmental physical Activity Study.

No abstract is provided for this article.

The relative importance of self reported psychological, social and environmental influences in explaining leisure-time physical activity

No abstract is provided for this article.

JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction

Inflammation is thought to underlie the pathogenesis of many chronic diseases. It is now established that obesity results in a state of chronic low-grade inflammation thought to contribute to several metabolic disorders, including insulin resistance and pancreatic islet dysfunction. The protein kinases JNK1 and IKKbeta have been found to serve as critical molecular links between obesity, metabolic inflammation, and disorders of glucose homeostasis. The precise mechanisms of these linkages are still being investigated. However, as we discuss here, JNK1 and IKKbeta are activated by almost all forms of metabolic stress that have been implicated in insulin resistance or islet dysfunction. Furthermore, both JNK1 and IKKbeta are critically involved in the promotion of diet-induced obesity, metabolic inflammation, insulin resistance, and beta-cell dysfunction. Understanding the molecular mechanisms by which JNK1 and IKKbeta mediate obesity-induced metabolic stress is likely to be of importance for the development of new treatments for a variety of obesity-associated diseases.

CMHC awareness: Effects on utilization in an underserved population

Utilization of a community mental health center was found to be extremely low in a “high risk” segment of its catchment area. To test the hypot

Objectively measured access to recreational destinations and leisure-time physical activity: Associations and demographic moderators in a six-country study

Within the growing body of research linking neighbourhood environmental attributes with physical activity, associations between recreational destinations and non-walking leisure-time physical activity (LTPA) are rarely studied, and to date, not across multiple cities. We examined six potential associations of objectively-measured access to private recreational facilities (e.g., fitness centres, swimming pools) and parks with adults’ non-walking LTPA (e.g., swimming, cycling, tennis), using data gathered with consistent methods from adults living in international cities with a range of environment attributes. The potential effects of socio-demographic moderators and between-city variations were also examined. Data from 6725 adults from 10 cities (6 countries) were gathered. Adults were more likely to engage in non-walking LTPA if they had a greater number of private recreational facilities within 0.5 or 1 km of the home, particularly in women, and if they lived closer to a park. The amount of non-zero LTPA was only associated (positively) with the number of recreational facilities within 1 km. Relationships between amount of LTPA and park proximity appear complex, with likely contextual and cultural differences. Improving access to private recreational facilities could promote non-walking LTPA, especially in women.

Intermittent hypoxia and hypercapnia induces inhibitor of nuclear factor-κB kinase subunit β-dependent atherosclerosis in pulmonary arteries

Clinical studies have shown that obstructive sleep apnea (OSA) increases atherosclerosis risk. The inflammation, especially mediated by the macrophages via nuclear factor-κB (NF-κB), has been speculated to contribute to atherogenicity in OSA patients. Inhibitor of NF-κB kinase-β (IKKβ) is an essential element of the NF-κB pathway and is linked to atherosclerosis. We previously reported that atherosclerosis was accelerated in pulmonary artery (PA) but not in aorta when low-density lipoprotein receptor knockout (<i>Ldlr^-/-</i>) mice were exposed to intermittent hypoxia/hypercapnia (IHH), a surrogate for recurrent upper-airway obstruction. Therefore, we hypothesized that IKKβ-dependent NF-κB activation in monocytes and macrophages plays a role in IHH-induced PA atherosclerosis. To test this hypothesis, myeloid restricted IKKβ deletion (<i>Ikkβ^ΔMye</i>) or control (<i>Ikkβ^F/F</i>) mice were crossed with <i>Ldlr^-/-</i> mice to generate double-knockout mice. Then, the mice were exposed to IHH or room air (Air) on high-fat diet for 8 or 16 wk. Lesions of PA and aorta were examined in <i>Ikkβ^ΔMye</i>;<i>Ldlr^-/-</i> and <i>Ikkβ^F/F</i>;<i>Ldlr^-/-</i> male mice under IHH vs. Air. The results revealed that IKKβ deletion abolished IHH-induced PA atherosclerosis after 8-wk exposure but not after 16-wk exposure (8 wk: <i>Ikkβ^F/F</i>;<i>Ldlr^-/-</i>, IHH 13.5 ± 1.4 vs. Air 5.7 ± 0.7%, <i>P</i> < 0.01; <i>Ikkβ^ΔMye</i>;<i>Ldlr^-/-</i>, IHH 7.4 ± 1.9% vs. Air 4.6 ± 1.3%, <i>P</i> = 0.24). Both IKKβ deletion and IHH had no effects on atherosclerosis in the aorta. Our findings demonstrate that IKKβ-dependent NF-κB activity in myeloid-lineage cells plays a critical role in IHH-induced PA atherosclerosis at the early stage.

Evaluation of a Two-Year Middle-School Physical Education Intervention: M-SPAN

MCKENZIE, T. L., J. F. SALLIS, J. J. PROCHASKA, T. L. CONWAY, S. J. MARSHALL, and P. ROSENGARD. Evaluation of a Two-Year Middle-School Physical Education Intervention: M-SPAN. Med. Sci. Sports Exerc., Vol. 36, No. 8, pp. 1382–1388, 2004. Purpose: School physical education (PE) is highly recommended as a means of promoting physical activity, and randomized studies of health-related PE interventions in middle schools have not been reported. We developed, implemented, and assessed an intervention to increase physical activity during middle-school PE classes. Methods: Twenty-four middle schools (approximately 25,000 students, 45% nonwhite) in Southern California participated in a randomized trial. Schools were assigned to intervention (N = 12) or control (N = 12) conditions, and school was the unit of analysis. A major component of the intervention was a 2-yr PE program, which consisted of curricular materials, staff development, and on-site follow-up. Control schools continued usual programs. Student activity and lesson context were observed in 1849 PE lessons using a validated instrument during baseline and intervention years 1 and 2. Results: The intervention significantly (P = 0.02) improved student moderate to vigorous physical activity (MVPA) in PE, by approximately 3 min per lesson. Effects were cumulative; by year 2 intervention schools increased MVPA by 18%. Effect sizes were greater for boys (d = 0.98; large) than girls (d = 0.68; medium). Conclusions: A standardized program increased MVPA in middle schools without requiring an increase in frequency or duration of PE lessons. Program components were well received by teachers and have the potential for generalization to other schools. Additional strategies may be needed for girls.