The trans-activation domain of the sporulation response regulator Spo0A revealed by X-ray crystallography

Sporulation in Bacillus involves the induction of scores of genes in a temporally and spatially co-ordinated programme of cell development. Its initiation is under the control of an expanded two-component signal transduction system termed a phosphorelay. The master control element in the decision to sporulate is the response regulator, Spo0A, which comprises a receiver or phosphoacceptor domain and an effector or transcription activation domain. The receiver domain of Spo0A shares sequence similarity with numerous response regulators, and its structure has been determined in phosphorylated and unphosphorylated forms. However, the effector domain (C-Spo0A) has no detectable sequence similarity to any other protein, and this lack of structural information is an obstacle to understanding how DNA binding and transcription activation are controlled by phosphorylation in Spo0A. Here, we report the crystal structure of C-Spo0A from Bacillus stearothermophilus revealing a single alpha -helical domain comprising six alpha -helices in an unprecedented fold. The structure contains a helix-turn-helix as part of a three alpha -helical bundle reminiscent of the catabolite gene activator protein (CAP), suggesting a mechanism for DNA binding. The residues implicated in forming the sigma (A)-activating region clearly cluster in a flexible segment of the polypeptide on the opposite side of the structure from that predicted to interact with DNA. The structural results are discussed in the context of the rich array of existing mutational data

Older Workers and Care-Giving in England: the Policy Context for Older Workers’ Employment Patterns

This article considers recent changes in the incidence of caring among people aged 50-64 in England and the policy context in which these have occurred. After introducing the topic, research questions addressed and methods used, it outlines findings from other research on how older workers experience and manage caring roles. It then sets out relevant public policy developments since carers were first accorded rights to recognition and services in 1995, focusing on workplace support, local services and financial help for people who reduce or quit their paid work to care. The article presents new analyses of the population censuses conducted in England in 2001 and 2011, focusing on people aged 50-64 and especially on those aged 60-64, the group in which the largest changes were seen. Theses show growth in caring at higher levels of intensity for older workers, and increases in the incidence of caring alongside paid work. To deepen understanding of these changes, the analysis also draws on data from a government survey of carers conducted in 2009-10. The concluding discussion argues that although the modest policy changes implemented since 1995 have provided some support to older workers managing work and care, more policy attention needs to be given following the sharp increase in the incidence of caring seen among people aged 50-64 in England between 2001 and 2011

Fluctuation Dominated Josephson Tunneling with a Scanning Tunneling Microscope

We demonstrate Josephson tunneling in vacuum tunnel junctions formed between a superconducting scanning tunneling microscope tip and a Pb film, for junction resistances in the range 50-300 k$\Omega$. We show that the superconducting phase dynamics is dominated by thermal fluctuations, and that the Josephson current appears as a peak centered at small finite voltages. In the presence of microwave fields (f=15.0 GHz) the peak decreases in magnitude and shifts to higher voltages with increasing rf power, in agreement with theory.Comment: 4 pages, REVTeX, submitted to PR

Comparing a Modified Dry By-product to Dry Distillers Grains with Solubles in Growing Calf Diets

A growing trial was conducted to contrast a new by-product, Dakota Bran Cake (DBRAN), against dry distillers grains with solubles (DDGS) and evaluate the two by-products at two dietary inclusion levels on steer calf performance measurements. Diet treatments included 15% DBRAN, 30% DBRAN, 15% DDGS, and 30% DDGS, replacing a blend (70:30 ratio) of brome grass hay and alfalfa haylage (DM basis). Final BW, ADG, and DMI increased, while F:G decreased as the inclusion level for both of these by-products increased from 15 to 30% DM. DDGS significantly improved ADG and F:G compared to feeding DBRAN at both inclusion levels. Feeding DBRAN and DDGS in growing diets to steer calves improved performance at higher dietary inclusion levels, while DDGS tended to improve performance over DBRAN

Effects of Isoproterenol on Histamine Release Induced from Monodispersed Guinea-Pig Lung Cells by Different Secretagogues1 2

ABSTRACT The effects of isoproterenol on histamine release induced by specific antige

The Politics of Commerce : The Congress of Chambers of Commerce of the Empire, 1886-1914

Peer reviewedPublisher PD

Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: a nested case-control study

OBJECTIVE: The aim of this study was to investigate omega-3 fatty acid (FA) supplement use and omega-3 FAs in erythrocyte membranes [omega-3 FA % in erythrocyte membranes (RBC)] and their association with anti-CCP autoantibodies in a population without RA, but who are at genetic risk for RA. METHODS: The multicentre Studies of the Etiology of RA (SERA) cohort includes RA-free subjects who are first-degree relatives of RA probands or are enriched with the HLA-DR4 allele. In a nested case-control study, 30 SERA cases were identified who were anti-CCP2 antibody positive. We further identified 47 autoantibody negative controls, frequency matched to cases on age at study visit, sex, race and study site. Anti-CCP2 status, self-reported omega-3 FA supplement use and omega-3 FA % in RBCs were obtained from a single visit. RESULTS: Anti-CCP2 positive cases were less likely than controls to report omega-3 FA supplement use (odds ratio: 0.14; 95% CI 0.03, 0.68). In addition, the likelihood of anti-CCP2 positivity was inversely associated with total omega-3 FA % in RBCs (odds ratio: 0.47; 95% CI 0.24, 0.92, for a s.d. increase). CONCLUSION: The inverse association between anti-CCP2 positivity and self-reported omega-3 FA supplement use and omega-3 FA % in RBCs suggests that omega-3 FAs may protect against the development of RA-related autoimmunity in pre-clinical RA