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The regulation of jun family genes and AP1 activity during the course of differentiation of F9 embryonal carcinoma stem cells was investigated. The induction of differentiation by retinoic acid (RA) leads to an accumulation of c-jun mRNA caused by increased c-jun transcription. This induction is an indirect response to RA and requires a functional AP1 binding site within the c-jun promoter. Expression of jun-B mRNA, however, is transiently induced but at a later time point is repressed by RA. The third member of the family, jun-D, is already active in undifferentiated cells and is only slightly induced after differentiation. Differentiation also converts c-jun from being refractory to phorbol esters to a highly inducible state. The development of this response is correlated with increased AP1 activity in RA-treated cells. By contrast, the induction of c-fos by phorbol esters or cAMP is greatly diminished after RA treatment. Transfection experiments indicate that, in the absence of c-Fos, only c-Jun is an effective transactivator. Hence, the major increase in AP1 activity is due to elevated c-jun expression and probably involves positive autoregulation by the c-Jun protein. Furthermore, these results demonstrate that AP1 activity can be stimulated by phorbol ester without concomitant c-fos induction. Forced expression of c-Jun and v-Jun results in activation of at least two differentiation marker genes, EndoB and tissue plasminogen activator, whose regulatory regions contain AP1 binding sites. Thus, the induction of c-jun transcription by RA, although indirect, can have an important role in the differentiation process.
The present study examined correlates of bicycle ownership and bicycling frequency, and projected increases in cycling if perceived safety from cars was improved.Participants were 1780 adults aged 20-65 recruited from the Seattle, Washington and Baltimore, Maryland regions (48% female; 25% ethnic/racial minority) and studied in 2002-2005. Bicycling outcomes were assessed by survey. Multivariable models were conducted to examine demographic and built environment correlates of bicycling outcomes.About 71% of the sample owned bicycles, but 60% of those did not report cycling. Among bicycle owners, frequency of riding was greater among young, male, White, educated, and lean subgroups. Neighborhood walkability measures within 1 km were not consistently related to bicycling. For the whole sample, bicycling at least once per week was projected to increase from 9% to 39% if bicycling was safe from cars. Ethnic-racial minority groups and those in the least safe neighborhoods for bicycling had greater projected increases in cycling if safety from traffic was improved.Implementing measures to improve bicyclists' safety from cars would primarily benefit racial-ethnic groups who cycle less but have higher rates of chronic diseases, as well as those who currently feel least safe bicycling.
Modernisation and urbanisation have led to lifestyle changes and increasing risks for chronic diseases in China. Physical activity and sedentary behaviours among rural populations need to be better understood, as the rural areas are undergoing rapid transitions. This study assessed levels of physical activity and sedentary behaviours of farming and non-farming adults in rural Suixi, described activity differences between farming and non-farming seasons, and examined correlates of leisure-time physical activity (LTPA) and TV viewing. A random sample of rural adults (n = 287) in Suixi County, Guangdong, China were surveyed in 2009 by trained interviewers. Questionnaires assessed multiple physical activities and sedentary behaviours, and their correlates. Analysis of covariance compared activity patterns across occupations, and multiple logistic regressions assessed correlates of LTPA and TV viewing. Quantitative data analyses were followed by community consultation for validation and interpretation of findings. Activity patterns differed by occupation. Farmers were more active through their work than other occupations, but were less active and more sedentary during the non-farming season than the farming season. Rural adults in Suixi generally had a low level of LTPA and a high level of TV viewing. Marital status, household size, social modelling for LTPA and owning sports equipment were significantly associated with LTPA but not with TV time. Most findings were validated through community consultation. For chronic disease prevention, attention should be paid to the currently decreasing occupational physical activity and increasing sedentary behaviours in rural China. Community and socially-based initiatives provide opportunities to promote LTPA and prevent further increase in sedentary behaviours.
Incubation of cultured human cells with interleukin 1 leads to increased expression of the human metallothionein-IIA gene. Recently, metallothionein has been shown to be an efficient free radical scavenger, and induction by interleukin 1 may be part of a protective response to minimize damage by hydroxyl radicals.
Inflammation is an essential defense mechanism in which innate immune cells are coordinately activated on encounter of harmful stimuli, including pathogens, tissue injury, and toxic compounds and metabolites to neutralize and eliminate the instigator and initiate healing and regeneration. Properly terminated inflammation is vital to health, but uncontrolled runaway inflammation that becomes chronic begets a variety of inflammatory and metabolic diseases and increases cancer risk. Making damaged tissues behave as "wounds that do not heal" and sustaining the production of growth factors whose physiologic function is tissue healing, chronic inflammation accelerates cancer emergence from premalignant lesions. In 1863, Rudolf Virchow, a leading German pathologist, suggested a possible association between inflammation and tumor formation, but it took another 140 years to fully elucidate and appreciate the tumorigenic role of inflammation. Key findings outlined molecular events in the inflammatory cascade that promote cancer onset and progression and enabled a better appreciation of when and where inflammation should be inhibited. These efforts triggered ongoing research work to discover and develop inflammation-reducing chemopreventive strategies for decreasing cancer risk and incidence.
