Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions

BACKGROUND: Mycobacteria inhabit diverse niches and display high metabolic versatility. They can colonise both humans and animals and are also able to survive in the environment. In order to succeed, response to environmental cues via transcriptional regulation is required. In this study we focused on the TetR family of transcriptional regulators (TFTRs) in mycobacteria. RESULTS: We used InterPro to classify the entire complement of transcriptional regulators in 10 mycobacterial species and these analyses showed that TFTRs are the most abundant family of regulators in all species. We identified those TFTRs that are conserved across all species analysed and those that are unique to the pathogens included in the analysis. We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes. Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps. TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs. The C-terminal ligand binding domain from the TFTR complement in M. tuberculosis showed great diversity in amino acid sequence but with an overall architecture common to other TFTRs. CONCLUSION: This study suggests that mycobacteria depend on TFTRs for the transcriptional control of a number of metabolic functions yet the physiological role of the majority of these regulators remain unknown. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1696-9) contains supplementary material, which is available to authorized users

Cognitive and behavioral predictors of light therapy use

Objective: Although light therapy is effective in the treatment of seasonal affective disorder (SAD) and other mood disorders, only 53-79% of individuals with SAD meet remission criteria after light therapy. Perhaps more importantly, only 12-41% of individuals with SAD continue to use the treatment even after a previous winter of successful treatment. Method: Participants completed surveys regarding (1) social, cognitive, and behavioral variables used to evaluate treatment adherence for other health-related issues, expectations and credibility of light therapy, (2) a depression symptoms scale, and (3) self-reported light therapy use. Results: Individuals age 18 or older responded (n = 40), all reporting having been diagnosed with a mood disorder for which light therapy is indicated. Social support and self-efficacy scores were predictive of light therapy use (p's<.05). Conclusion: The findings suggest that testing social support and self-efficacy in a diagnosed patient population may identify factors related to the decision to use light therapy. Treatments that impact social support and self-efficacy may improve treatment response to light therapy in SAD. © 2012 Roecklein et al

Regulation of the co-evolved HrpR and HrpS AAA+ proteins required for Pseudomonas syringae pathogenicity.

Published versio

A Sustained Dietary Change Increases Epigenetic Variation in Isogenic Mice

Epigenetic changes can be induced by adverse environmental exposures, such as nutritional imbalance, but little is known about the nature or extent of these changes. Here we have explored the epigenomic effects of a sustained nutritional change, excess dietary methyl donors, by assessing genomic CpG methylation patterns in isogenic mice exposed for one or six generations. We find stochastic variation in methylation levels at many loci; exposure to methyl donors increases the magnitude of this variation and the number of variable loci. Several gene ontology categories are significantly overrepresented in genes proximal to these methylation-variable loci, suggesting that certain pathways are susceptible to environmental influence on their epigenetic states. Long-term exposure to the diet (six generations) results in a larger number of loci exhibiting epigenetic variability, suggesting that some of the induced changes are heritable. This finding presents the possibility that epigenetic variation within populations can be induced by environmental change, providing a vehicle for disease predisposition and possibly a substrate for natural selection

Contrastive prosody and the subsequent mention of alternatives during discourse processing

Linguistic research has long viewed prosody as an important indicator of information structure in intonationally rich languages like English. Correspondingly, numerous psycholinguistic studies have shown significant effects of prosody, particularly with respect to the immediate processing of a prosodically prominent phrase. Although co-reference resolution is known to be influenced by information structure, it has been less clear whether prosodic prominence can affect decisions about next mention in a discourse, and if so, how. We present results from an open-ended story continuation task, conducted as part of a series of experiments that examine how prosody influences the anticipation and resolution of co-reference. Overall results from the project suggest that prosodic prominence can increase or decrease reference to a saliently pitch-accented phrase, depending on additional circumstances of the referential decision. We argue that an adequate account of prosody’s role in co-reference requires consideration of how the processing system interfaces with multiple levels of linguistic representation

Protein Pattern Formation

Protein pattern formation is essential for the spatial organization of many intracellular processes like cell division, flagellum positioning, and chemotaxis. A prominent example of intracellular patterns are the oscillatory pole-to-pole oscillations of Min proteins in \textit{E. coli} whose biological function is to ensure precise cell division. Cell polarization, a prerequisite for processes such as stem cell differentiation and cell polarity in yeast, is also mediated by a diffusion-reaction process. More generally, these functional modules of cells serve as model systems for self-organization, one of the core principles of life. Under which conditions spatio-temporal patterns emerge, and how these patterns are regulated by biochemical and geometrical factors are major aspects of current research. Here we review recent theoretical and experimental advances in the field of intracellular pattern formation, focusing on general design principles and fundamental physical mechanisms.Comment: 17 pages, 14 figures, review articl

Canakinumab relieves symptoms of acute flares and improves health-related quality of life in patients with difficult-to-treat Gouty Arthritis by suppressing inflammation: results of a randomized, dose-ranging study

INTRODUCTION: We report the impact of canakinumab, a fully human anti-interleukin-1β monoclonal antibody, on inflammation and health-related quality of life (HRQoL) in patients with difficult-to-treat Gouty Arthritis. METHODS: In this eight-week, single-blind, double-dummy, dose-ranging study, patients with acute Gouty Arthritis flares who were unresponsive or intolerant to--or had contraindications for--non-steroidal anti-inflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg) (N = 143) or an intramuscular dose of triamcinolone acetonide 40 mg (N = 57). Patients assessed pain using a Likert scale, physicians assessed clinical signs of joint inflammation, and HRQoL was measured using the 36-item Short-Form Health Survey (SF-36) (acute version). RESULTS: At baseline, 98% of patients were suffering from moderate-to-extreme pain. The percentage of patients with no or mild pain was numerically greater in most canakinumab groups compared with triamcinolone acetonide from 24 to 72 hours post-dose; the difference was statistically significant for canakinumab 150 mg at these time points (P &lt; 0.05). Treatment with canakinumab 150 mg was associated with statistically significant lower Likert scores for tenderness (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.27 to 7.89; P = 0.014) and swelling (OR, 2.7; 95% CI, 1.09 to 6.50, P = 0.032) at 72 hours compared with triamcinolone acetonide. Median C-reactive protein and serum amyloid A levels were normalized by seven days post-dose in most canakinumab groups, but remained elevated in the triamcinolone acetonide group. Improvements in physical health were observed at seven days post-dose in all treatment groups; increases in scores were highest for canakinumab 150 mg. In this group, the mean SF-36 physical component summary score increased by 12.0 points from baseline to 48.3 at seven days post-dose. SF-36 scores for physical functioning and bodily pain for the canakinumab 150 mg group approached those for the US general population by seven days post-dose and reached norm values by eight weeks post-dose. CONCLUSIONS: Canakinumab 150 mg provided significantly greater and more rapid reduction in pain and signs and symptoms of inflammation compared with triamcinolone acetonide 40 mg. Improvements in HRQoL were seen in both treatment groups with a faster onset with canakinumab 150 mg compared with triamcinolone acetonide 40 mg. TRIAL REGISTRATION: clinicaltrials.gov: NCT00798369

Cigarette smoking, health status, socio-economic status and access to health care in diabetes mellitus: a cross-sectional survey

BACKGROUND: In diabetes mellitus, cigarette smoking is associated with increased risk of cardiovascular mortality and microvascular complications. We evaluated cigarette smoking in people with diabetes mellitus in a socio-economically deprived area. METHODS: We carried out a cross-sectional survey of people registered with diabetes mellitus at 29 general practices in inner London. Responses were analysed for 1,899 (64%) respondents out of 2,983 eligible. RESULTS: There were 1,899 respondents of whom 968 (51%) had never smoked, 296 (16%) were current smokers and 582 (31%) were ex-smokers. Smoking was more frequent in white Europeans (men 22%, women 20%), than in African Caribbeans (men 15%, women 10%) or Africans (men 8%, women 2%). Smoking prevalence decreased with age. Smokers were more likely to be living in rented accommodation (odds ratio, OR 2.02, 95% confidence interval 1.48 to 2.74). After adjusting for confounding, current smokers had lower SF-36 scores than subjects who had never smoked (mean difference in physical functioning score -5.6, 95% confidence interval -10.0 to -1.2; general health -6.1, -9.7 to -2.5). Current smokers were less likely to have attended a hospital diabetic clinic in the last year (OR 0.59, 0.44 to 0.79), and their hypertension was less likely to be treated (OR 0.47, 0.30 to 0.74). CONCLUSIONS: Compared with non-smokers, smokers had lower socio-economic status and worse health status, but were less likely to be referred to hospital or treated for their hypertension. People with diabetes who smoke can be regarded as a vulnerable group who need more intensive support and treatment