Indirect DNA Readout by an H-NS Related Protein: Structure of the DNA Complex of the C-Terminal Domain of Ler

Ler, a member of the H-NS protein family, is the master regulator of the LEE pathogenicity island in virulent Escherichia coli strains. Here, we determined the structure of a complex between the DNA-binding domain of Ler (CT-Ler) and a 15-mer DNA duplex. CT-Ler recognizes a preexisting structural pattern in the DNA minor groove formed by two consecutive regions which are narrower and wider, respectively, compared with standard B-DNA. The compressed region, associated with an AT-tract, is sensed by the side chain of Arg90, whose mutation abolishes the capacity of Ler to bind DNA. The expanded groove allows the approach of the loop in which Arg90 is located. This is the first report of an experimental structure of a DNA complex that includes a protein belonging to the H-NS family. The indirect readout mechanism not only explains the capacity of H-NS and other H-NS family members to modulate the expression of a large number of genes but also the origin of the specificity displayed by Ler. Our results point to a general mechanism by which horizontally acquired genes may be specifically recognized by members of the H-NS family

Analysis of ancestral and functionally relevant CD5 variants in systemic lupus erythematosus patients

OBJECTIVE: CD5 plays a crucial role in autoimmunity and is a well-established genetic risk factor of developing RA. Recently, evidence of positive selection has been provided for the CD5 Pro224-Val471 haplotype in East Asian populations. The aim of the present work was to further analyze the functional relevance of non-synonymous CD5 polymorphisms conforming the ancestral and the newly derived haplotypes (Pro224-Ala471 and Pro224-Val471, respectively) as well as to investigate the potential role of CD5 on the development of SLE and/or SLE nephritis. METHODS: The CD5 SNPs rs2241002 (C/T; Pro224Leu) and rs2229177 (C/T; Ala471Val) were genotyped using TaqMan allelic discrimination assays in a total of 1,324 controls and 681 SLE patients of Spanish origin. In vitro analysis of CD3-mediated T cell proliferative and cytokine response profiles of healthy volunteers homozygous for the above mentioned CD5 haplotypes were also analyzed. RESULTS: T-cell proliferation and cytokine release were significantly increased showing a bias towards to a Th2 profile after CD3 cross-linking of peripheral mononuclear cells from healthy individuals homozygous for the ancestral Pro224-Ala471 (CC) haplotype, compared to the more recently derived Pro224-Val471 (CT). The same allelic combination was statistically associated with Lupus nephritis. CONCLUSION: The ancestral Ala471 CD5 allele confers lymphocyte hyper-responsiveness to TCR/CD3 cross-linking and is associated with nephritis in SLE patients

Differences in daily objective physical activity and sedentary time between women with self-reported fibromyalgia and controls: results from the Canadian health measures survey

Introduction Physical activity and sedentary behaviors are important modifiable factors that influence health and quality of life in women with fibromyalgia. The purpose of this study was to compare objectively assessed physical activity and sedentary time in women self-reporting fibromyalgia with a control group. Method Data were drawn from the Canadian Health Measures Survey cycle 1, 2 and 3 conducted by Statistics Canada. We included women aged 18 to 79 years with complete accelerometer data. We performed one-way analyses of covariance (adjusted-for socio-demographic and health factors) to determine mean differences in physical activity and sedentary variables (minutes per day of moderate and vigorous physical activity, light physical activity, sedentary and daily steps) between women with and without fibromyalgia. Results In total, 4132 participants were included. A cross-sectional weighted analysis indicated that 3,1% of participants self-reported a diagnosis of fibromyalgia. Participants with fibromyalgia spent less time than controls engaged in moderate and vigorous physical activity (M = 19.2 min/d (SE=0.7) vs M = 9.1 min/d (SE=1.2), p = 0.03, η2= 0.01). No significant differences were found for daily time spent in light physical activity, sedentary activities and number of steps. Conclusion Women participants with self-reported fibromyalgia spent significantly less time in moderate and vigorous physical activity than control. Physical activity promotion interventions for women with self-reported fibromyalgia should, as a priority, target physical activities with moderate to vigorous intensity

Study protocol: effects of the THAO-child health intervention program on the prevention of childhood obesity - the POIBC study

BACKGROUND: The speeding increase and the high prevalence of childhood obesity is a serious problem for Public Health. Community Based Interventions has been developed to combat against the childhood obesity epidemic. However little is known on the efficacy of these programs. Therefore, there is an urgent need to determine the effect of community based intervention on changes in lifestyle and surrogate measures of adiposity. METHODS/DESIGN: Parallel intervention study including two thousand 2249 children aged 8 to 10 years ( 4th and 5th grade of elementary school) from 4 Spanish towns. The THAO-Child Health Program, a community based intervention, were implemented in 2 towns. Body weight, height, and waist circumferences were measured. Children recorded their dietary intake on a computer-based 24h recall. All children also completed validated computer based questionnaires to estimate physical activity, diet quality, eating behaviors, and quality of life and sleep. Additionally, parental diet quality and physical activity were assessed by validated questionnaires. DISCUSSION: This study will provide insight in the efficacy of the THAO-Child Health Program to promote a healthy lifestyle. Additionally it will evaluate if lifestyle changes are accompanied by favorable weight management. TRIAL REGISTRATION: Trial Registration Number ISRCTN68403446.This work was supported by grants from Instituto de Salud Carlos III FEDER, (PI11/01900) and by a joint contract (CES09/030) with the Instituto de Salud Carlos III and the Health Department of the Catalan Government (Generalitat de Catalunya