Structural insights into Helicobacter pylori oncoprotein CagA interaction with β1 integrin

Infection with the gastric pathogen Helicobacter pylori is a risk factor for the development of gastric cancer. Pathogenic strains of H. pylori carry a type IV secretion system (T4SS) responsible for the injection of the oncoprotein CagA into host cells. H. pylori and its cag-T4SS exploit α5β1 integrin as a receptor for CagA translocation. Injected CagA localizes to the inner leaflet of the host cell membrane, where it hijacks host cell signaling and induces cytoskeleton reorganization. Here we describe the crystal structure of the N-terminal ∼100-kDa subdomain of CagA at 3.6 Å that unveils a unique combination of folds. The core domain of the protein consists of an extended single-layer β-sheet stabilized by two independent helical subdomains. The core is followed by a long helix that forms a four-helix helical bundle with the C-terminal domain. Mapping of conserved regions in a set of CagA sequences identified four conserved surface-exposed patches (CSP1–4), which represent putative hot-spots for protein–protein interactions. The proximal part of the single-layer β-sheet, covering CSP4, is involved in specific binding of CagA to the β1 integrin, as determined by yeast two-hybrid and in vivo competition assays in H. pylori cell-culture infection studies. These data provide a structural basis for the first step of CagA internalization into host cells and suggest that CagA uses a previously undescribed mechanism to bind β1 integrin to mediate its own translocation.     

Liquid crystal self-assembly of random-sequence DNA oligomers

In biological systems and nanoscale assemblies, the self-association of DNA is typically studied and applied in the context of the evolved or directed design of base sequences that give complementary pairing, duplex formation, and specific structural motifs. Here we consider the collective behavior of DNA solutions in the distinctly different regime where DNA base sequences are chosen at random or with varying degrees of randomness. We show that in solutions of completely random sequences, corresponding to a remarkably large number of different molecules, e.g., approximately 10(12) for random 20-mers, complementary still emerges and, for a narrow range of oligomer lengths, produces a subtle hierarchical sequence of structured self-assembly and organization into liquid crystal (LC) phases. This ordering follows from the kinetic arrest of oligomer association into long-lived partially paired double helices, followed by reversible association of these pairs into linear aggregates that in turn condense into LC domains.     

Head and neck polypoid melanoma

Polypoid melanoma represents a rare clinical variant of nodular melanoma skin cancer in which the tumor is connected to the skin by a pedicle, characterized by exophytic growth, ulceration, and young age at onset (20-39 years) with a special predilection for the back and with a survival rate at 5 years ranging from 32% to 42% as compared with 57% 5-year survival for nodular subtype and 77% for the superficial subtype. We present a case of a deeply pigmented polypoid melanoma arising on the face of a 77-year-old man. We performed a literature review to clarify its surgical management and prognosis.     

Melanotic neuroectodermal tumor of infancy: a histopathological and immunohistochemical study

Melanotic neuroectodermal tumor of infancy is an uncommon neoplasm that normally occurs in the anterior maxilla of children less than 1 year of age. This is a tumor with controversial origin, although neural crest origin is proposed. This case report presents an analysis of histopathological and immunohistochemical findings in this rare tumor.     

Establishment and progress of the chest pain unit certification process in Germany and the local experiences of Mainz

The establishment of chest pain units (CPUs) in the USA and UK has led to improvements in the prognosis of patients with chest pain and myocardial infarction, optimizing access to specialized diagnostic and therapeutic facilities and reducing costs. To establish a uniform implementation of this type of service in Germany, the German Cardiac Society (DGK) founded a 'CPU task force' in 2007, which developed a set of standard requirements and a nationwide certification programme. The recommendations for minimum standard requirements were published in 2008. As of November 2011, 132 CPUs were certified and 36 units were in the certification process. The aim of the DGK is to certify as many as 250 centres (units) throughout Germany within the next 2 years, to provide nationwide coverage. Applications from Switzerland are also being filed. Public awareness campaigns in cooperation with national league soccer teams were organized to raise awareness of the importance for early diagnosis and treatment of cardiac diseases and to publicize the existence of these new facilities. The German model of CPU certification allows nationwide and prospectively European-wide standardization of patient care and to improve adherence to international guidelines. Coupled with awareness campaigns and with the launch of a German CPU Registry, this process is aimed at improving the education and treatment of patients with chest pain and to provide scientific information about the quality of patient care.