BAR domains as sensors of membrane curvature:the amphiphysin BAR structure

The BAR (Bin/amphiphysin/Rvs) domain is the most conserved feature in amphiphysins from yeast to human and is also found in endophilins and nadrins. We solved the structure of the Drosophila amphiphysin BAR domain. It is a crescent-shaped dimer that binds preferentially to highly curved negatively charged membranes. With its N-terminal amphipathic helix and BAR domain (N-BAR), amphiphysin can drive membrane curvature in vitro and in vivo. The structure is similar to that of arfaptin2, which we find also binds and tubulates membranes. From this, we predict that BAR domains are in many protein families, including sorting nexins, centaurins, and oligophrenins. The universal and minimal BAR domain is a dimerization, membrane-binding, and curvature-sensing module.

Membrane fission is promoted by insertion of amphipathic helices and is restricted by crescent BAR domains

Shallow hydrophobic insertions and crescent-shaped BAR scaffolds promote membrane curvature. Here, we investigate membrane fission by shallow hydrophobic insertions quantitatively and mechanistically. We provide evidence that membrane insertion of the ENTH domain of epsin leads to liposome vesiculation, and that epsin is required for clathrin-coated vesicle budding in cells. We also show that BAR-domain scaffolds from endophilin, amphiphysin, GRAF, and β2-centaurin limit membrane fission driven by hydrophobic insertions. A quantitative assay for vesiculation reveals an antagonistic relationship between amphipathic helices and scaffolds of N-BAR domains in fission. The extent of vesiculation by these proteins and vesicle size depend on the number and length of amphipathic helices per BAR domain, in accord with theoretical considerations. This fission mechanism gives a new framework for understanding membrane scission in the absence of mechanoenzymes such as dynamin and suggests how Arf and Sar proteins work in vesicle scission.

Establishing the Evidence Bar for Molecular Diagnostics in Personalised Cancer Care

While personalised cancer medicine holds great promise, targeting therapies to the biological characteristics of patients is limited by the number of validated biomarkers currently available. The implementation of biomarkers has undergone many challenges with few biomarkers reaching cancer patients in the clinic. There have been many biomarkers that have been published and claimed to be therapeutically useful, but few become part of the clinical decision-making process due to technical, validation and market access issues. To reduce this attrition rate, there is a significant need for policy makers and reimbursement agencies to define specific evidence requirements for the introduction of biomarkers into clinical practice. Once these requirements are more clearly defined, in an analogous manner to pharmaceuticals, researchers and diagnostic companies can better focus their biomarker research and development on meeting these specific requirements, which should lead to the more rapid introduction of new molecular oncology tests for patient benefit.

MEMOIR OF THE LIFE, CHARACTER, AND PUBLIC SERVICES OF THE LATE HON. HENRY WM. DE SAUSSURE, PREPARED AND READ ON THE 15th FEBRUARY, 1841, AT THE CIRCULAR CHURCH, CHARLESTON, BY APPOINTMENT OF THE SOUTH CAROLINA BAR ASSOCIATION.

A special meeting of the Association was held as it was resolved that Chancellor Harper was requested to prepare a memoir of the late Chancellor De Saussure.

Making way for change at the Bar: The practical implications of the new Bar Standards Board Handbook

The Legal Services Act 2007 caused a need to change professional conduct rules for lawyers in England and Wales. The Bar Standards Board Handbook brings substantial changes to the way barristers are regulated. Changes include litigation rights, reporting of professional misconduct, an increased focus on chambers, and expansion to include employees of chambers and barristers without practicing certificates (unregistered or non-practicing barristers). The approach to enforcement and supervision moves to include elements of outcome focused, principle based and risk based approaches. These changes have the potential to change the practice of different groups of barristers and the dynamics between them.

Plano de negócios para a reestruturação da subsecção de bar da Cooperativa Agrícola de Vila do Conde, CRL

Projeto apresentado ao Instituto Politécnico do Porto para obtenção do Grau de Mestre em Gestão das Organizações, Ramo de Gestão de Empresas Orientação Científica: Professor Doutor Eduardo de Sá e Silva | Doutora Fátima Monteiro Orientação Técnica: Dr. Paulo Costa

(Arrêt de parlement qui condamne Jean Massard de La Cressonnière, curé de Ville-sur-Arce à faire amende honorable au bailliage de Bar-sur-Seine, à 3 ans de bannissement du ressort et à 100 livres d'amende, 10 livres d'aumône et mille livres de dommages et interêts.)

[Acte. 1752-06-17. Paris]

Archives mensuelles d'obstétrique et de gynécologie / dirigées par Paul Bar et Jean-Louis Faure...

1912/01 (A17,T1)-1912/06.

Archives mensuelles d'obstétrique et de gynécologie / dirigées par Paul Bar et Jean-Louis Faure...

1913/01 (T3,A18)-1913/06.

Archives mensuelles d'obstétrique et de gynécologie / dirigées par Paul Bar et Jean-Louis Faure...

1912/07 (A17,T2)-1912/12.