BosR (BB0647) Controls the RpoN-RpoS Regulatory Pathway and Virulence Expression in Borrelia burgdorferi by a Novel DNA-Binding Mechanism

In Borrelia burgdorferi (Bb), the Lyme disease spirochete, the alternative σ factor σ54 (RpoN) directly activates transcription of another alternative σ factor, σS (RpoS) which, in turn, controls the expression of virulence-associated membrane lipoproteins. As is customary in σ54-dependent gene control, a putative NtrC-like enhancer-binding protein, Rrp2, is required to activate the RpoN-RpoS pathway. However, recently it was found that rpoS transcription in Bb also requires another regulator, BosR, which was previously designated as a Fur or PerR homolog. Given this unexpected requirement for a second activator to promote σ54-dependent gene transcription, and the fact that regulatory mechanisms among similar species of pathogenic bacteria can be strain-specific, we sought to confirm the regulatory role of BosR in a second virulent strain (strain 297) of Bb. Indeed, BosR displayed the same influence over lipoprotein expression and mammalian infectivity for strain Bb 297 that were previously noted for Bb strain B31. We subsequently found that recombinant BosR (rBosR) bound to the rpoS gene at three distinct sites, and that binding occurred despite the absence of consensus Fur or Per boxes. This led to the identification of a novel direct repeat sequence (TAAATTAAAT) critical for rBosR binding in vitro. Mutations in the repeat sequence markedly inhibited or abolished rBosR binding. Taken together, our studies provide new mechanistic insights into how BosR likely acts directly on rpoS as a positive transcriptional activator. Additional novelty is engendered by the facts that, although BosR is a Fur or PerR homolog and it contains zinc (like Fur and PerR), it has other unique features that clearly set it apart from these other regulators. Our findings also have broader implications regarding a previously unappreciated layer of control that can be involved in σ54–dependent gene regulation in bacteria

Resveratrol Inhibits Protein Translation in Hepatic Cells

Resveratrol is a plant-derived polyphenol that extends lifespan and healthspan in model organism. Despite extensive investigation, the biological processes mediating resveratrol's effects have yet to be elucidated. Because repression of translation shares many of resveratrol's beneficial effects, we hypothesized that resveratrol was a modulator of protein synthesis. We studied the effect of the drug on the H4-II-E rat hepatoma cell line. Initial studies showed that resveratrol inhibited global protein synthesis. Given the role of the mammalian Target of Rapamycin (mTOR) in regulating protein synthesis, we examined the effect of resveratrol on mTOR signaling. Resveratrol inhibited mTOR self-phosphorylation and the phosphorylation of mTOR targets S6K1 and eIF4E-BP1. It attenuated the formation of the translation initiation complex eIF4F and increased the phosphorylation of eIF2α. The latter event, also a mechanism for translation inhibition, was not recapitulated by mTOR inhibitors. The effects on mTOR signaling were independent of effects on AMP-activated kinase or AKT. We conclude that resveratrol is an inhibitor of global protein synthesis, and that this effect is mediated through modulation of mTOR-dependent and independent signaling

Taking it personally: the effect of ethnic attachment on preferences for regionalism

This article presents three related findings on regional decentralization. We use an original dataset collected in Uganda to establish, for the first time in a developing country context, that individuals have meaningful preferences over the degree of regional decentralization they desire, ranging from centralism to secessionism. Second, multilevel models suggest that a small share of this variation is explained at the district and ethnic group levels. The preference for regional decentralization monotonically increases with an ethnic group or a district’s average ethnic attachment. However, the relationship with an ethnic group or district’s income is U-shaped: both the richest and the poorest groups desire more regionalism, reconciling interest-based and identity-based explanations for regionalism. Finally, we show that higher individual ethnic attachment increases preferences for regionalism using fixed effects and a new matching method

A pilot study evaluating a support programme for parents of young people with suicidal behaviour

<p>Abstract</p> <p>Background</p> <p>Deliberate self harm (DSH) is a major public health concern and has increased among young people in Ireland. While DSH is undoubtedly the result of interacting factors, studies have identified an association between DSH and family dysfunction as well as the protective role of positive family relationships. Following a focus group meeting held to identify the needs of parents and carers of young people with DSH, a support programme (SPACE) was developed. The aims of the current study are to evaluate the effectiveness of the SPACE programme in decreasing parental psychological distress, reducing parental report of young peoples' difficulties, increasing parental satisfaction and increasing parents' ratings of their own defined challenges and goals.</p> <p>Methods</p> <p>Participants were recruited from a Mental Health Service within a paediatric hospital, Community Child and Adolescent Mental Health Teams and family support services. All services were located within the greater Dublin area in Ireland. Forty-six parents of children who had engaged in or expressed thoughts of self harm attended the programme and participated in the evaluation study. The programme ran once a week over an 8-week period and included topics such as information on self harm in young people, parenting adolescents, communication and parental self-care. Seventy percent (N = 32) of the original sample at Time 1 completed measures at Time 2 (directly following the programme) and 37% (N = 17) of the original sample at Time 1 completed them at Time 3 (6 months following the programme).</p> <p>A repeated measures design was used to identify changes in parental wellbeing after attendance at the programme as well as changes in parental reports of their children's difficulties.</p> <p>Results</p> <p>Participants had lower levels of psychological distress, increased parental satisfaction, lower ratings of their own defined challenges and higher ratings of their goals directly after the programme. These changes were maintained at 6-month follow up in the 37% of participants who could be followed up. Furthermore the young people who had engaged in or expressed thoughts of self harm had lower levels of difficulties, as reported by their parents, following the programme.</p> <p>Conclusion</p> <p>These findings suggest that the SPACE programme is a promising development in supporting the parents of young people with suicidal behaviour. The programme may also reduce parental reports of their children's difficulties. Further evaluation using a randomized controlled trial is indicated.</p