ATP-dependent chromatosome remodeling

Chromatin serves to package, protect and organize the complex eukaryotic genomes to assure their stable inheritance over many cell generations. At the same time, chromatin must be dynamic to allow continued use of DNA during a cell's lifetime. One important principle that endows chromatin with flexibility involves ATP-dependent `remodeling' factors, which alter DNA-histone interactions to form, disrupt or move nucleosomes. Remodeling is well documented at the nucleosomal level, but little is known about the action of remodeling factors in a more physiological chromatin environment. Recent findings suggest that some remodeling machines can reorganize even folded chromatin fibers containing the linker histone H1, extending the potential scope of remodeling reactions to the bulk of euchromatin

Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in mycobacterium tuberculosis–infected individuals

Copyright © 2009 by the American Thoracic Society.Rationale: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care. Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. Methods: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. Patients were assessed clinically and had blood samples drawn for immunological analysis over a 52-week period after vaccination with MVA85A. Thoracic computed tomography scans were performed at baseline and at 10 weeks after vaccination. Safety of MVA85A was assessed by clinical, radiological, and inflammatory markers. The immunogenicity of MVA85A was assessed by IFNγ and IL-2 ELISpot assays and FACS. Measurements and Main Results: MVA85A was safe in subjects with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic computed tomography scans after vaccination. MVA85A induced a strong antigen-specific IFN-γ and IL-2 response that was durable for 52 weeks. The magnitude of IFN-γ response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin–vaccinated individuals. Antigen 85A–specific polyfunctional CD4+ T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination. Conclusions: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas.Oxford Biomedical Research Centre, Wellcome Trust, and AFTBVAC

Aspects of Nucleon Compton Scattering

We consider the spin-averaged nucleon forward Compton scattering amplitude in heavy baryon chiral perturbation theory including all terms to order ${\cal O} (q^4)$. The chiral prediction for the spin-averaged forward Compton scattering amplitude is in good agreement with the data for photon energies $\omega \le 110$ MeV. We also evaluate the nucleon electric and magnetic Compton polarizabilities to this order and discuss the uncertainties of the various counter terms entering the chiral expansion of these quantities.Comment: 17 pp, TeX, 7 figures available from the authors, preprint CRN-93/5

Enter exitrons

Staiger D, Simpson GG. Enter exitrons. Genome Biology. 2015;16(1): 136.Exitrons are exon-like introns located within protein-coding exons. Removal or retention of exitrons through alternative splicing increases proteome complexity and thus adds to phenotypic diversity

Why Social Enterprises Are Asking to Be Multi-stakeholder and Deliberative: An Explanation around the Costs of Exclusion.

The study of multi-stakeholdership (and multi-stakeholder social enterprises in particular) is only at the start. Entrepreneurial choices which have emerged spontaneously, as well as the first legal frameworks approved in this direction, lack an adequate theoretical support. The debate itself is underdeveloped, as the existing understanding of organisations and their aims resist an inclusive, public interest view of enterprise. Our contribution aims at enriching the thin theoretical reflections on multi-stakeholdership, in a context where they are already established, i.e. that of social and personal services. The aim is to provide an economic justification on why the governance structure and decision-making praxis of the firm needs to account for multiple stakeholders. In particular with our analysis we want: a) to consider production and the role of firms in the context of the “public interest” which may or may not coincide with the non-profit objective; b) to ground the explanation of firm governance and processes upon the nature of production and the interconnections between demand and supply side; c) to explain that the costs associated with multi-stakeholder governance and deliberation in decision-making can increase internal efficiency and be “productive” since they lower internal costs and utilise resources that otherwise would go astray. The key insight of this work is that, differently from major interpretations, property costs should be compared with a more comprehensive range of costs, such as the social costs that emerge when the supply of social and personal services is insufficient or when the identification of aims and means is not shared amongst stakeholders. Our model highlights that when social costs derived from exclusion are high, even an enterprise with costly decisional processes, such as the multistakeholder, can be the most efficient solution amongst other possible alternatives