Maintaining and breaking symmetry in homomeric coiled-coil assemblies

Higher order coiled coils with five or more helices can form α-helical barrels. Here the authors show that placing β-branched aliphatic residues along the lumen yields stable and open α-helical barrels, which is of interest for the rational design of functional proteins; whereas, the absence of β-branched side chains leads to unusual low-symmetry α-helical bundles

Antitumor Effect of Malaria Parasite Infection in a Murine Lewis Lung Cancer Model through Induction of Innate and Adaptive Immunity

BACKGROUND: Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL) staining and decreased Ki-67 expression in tumors. Through natural killer (NK) cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+) T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. CONCLUSIONS/SIGNIFICANCE: Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria parasite may provide a novel strategy or therapeutic vaccine vector for anti-lung cancer immune-based therapy

The Staphylococcus aureus Response to Unsaturated Long Chain Free Fatty Acids: Survival Mechanisms and Virulence Implications

Staphylococcus aureus is an important human commensal and opportunistic pathogen responsible for a wide range of infections. Long chain unsaturated free fatty acids represent a barrier to colonisation and infection by S. aureus and act as an antimicrobial component of the innate immune system where they are found on epithelial surfaces and in abscesses. Despite many contradictory reports, the precise anti-staphylococcal mode of action of free fatty acids remains undetermined. In this study, transcriptional (microarrays and qRT-PCR) and translational (proteomics) analyses were applied to ascertain the response of S. aureus to a range of free fatty acids. An increase in expression of the σB and CtsR stress response regulons was observed. This included increased expression of genes associated with staphyloxanthin synthesis, which has been linked to membrane stabilisation. Similarly, up-regulation of genes involved in capsule formation was recorded as were significant changes in the expression of genes associated with peptidoglycan synthesis and regulation. Overall, alterations were recorded predominantly in pathways involved in cellular energetics. In addition, sensitivity to linoleic acid of a range of defined (sigB, arcA, sasF, sarA, agr, crtM) and transposon-derived mutants (vraE, SAR2632) was determined. Taken together, these data indicate a common mode of action for long chain unsaturated fatty acids that involves disruption of the cell membrane, leading to interference with energy production within the bacterial cell. Contrary to data reported for other strains, the clinically important EMRSA-16 strain MRSA252 used in this study showed an increase in expression of the important virulence regulator RNAIII following all of the treatment conditions tested. An adaptive response by S. aureus of reducing cell surface hydrophobicity was also observed. Two fatty acid sensitive mutants created during this study were also shown to diplay altered pathogenesis as assessed by a murine arthritis model. Differences in the prevalence and clinical importance of S. aureus strains might partly be explained by their responses to antimicrobial fatty acids

9. Steinfurter Bioenergiefachtagung - Wärmewende im ländlichen Raum

Die Hälfte des Endenergiebedarfs in Deutschland wird zur Deckung des Wärmebedarfs der Wirtschaft und der privaten Haushalte benötigt; überwiegend erzeugt durch Erdgas und Heizöl. Gerade die energetisch nur unzureichend sanierten Einfamilienhausbestände des ländlichen Raumes bergen ein hohes Potenzial für Energieeinsparungs- und Effizienzsstrategien, um zum einen den Klimaschutz zu fördern und zum anderen eine nachhaltige wirtschaftliche Entwicklung des ländlichen Raumes anzustoßen. Die 9. Steinfurter Bioenergiefachtagung zeigt Strategien und Maßnahmen auf, die zeigen, wie eine "Wärmewende im ländlichen Raum" aussehen kann, welche Chancen und Möglichkeiten sie bietet und warum eine "Wärmewende" strategisch unabdingbar für das Gelingen des Generationenprojektes "Energiewende" insgesamt ist. Die Veranstaltung zeichnet den Pfad von konzeptionellen Ideen über Beispiele aus der Praxis bis hin zu zukunftsweisenden technologischen Ansätzen: Wärmekataster Kreis Steinfurt KWK-Modellkommune Saerbeck Wege zum Bioenergiedorf - Praxisbeispiele Technische Voraussetzungen und Möglichkeiten für effiziente Wärmenetze im ländlichen Raum Finanzierungs- und Fördermodelle für eine gelungene Wärmewend

Imaging of Lamb Waves in Plates for Quantitative Determination of Anisotropy Using Photorefractive Dynamic Holography

Anisotropic properties of sheet materials can be determined by measuring the propagation of Lamb waves in different directions. Electromagnetic acoustic transduction and laser ultrasonic methods provide noncontacting approaches that are often desired for application to industrial and processing environments. This paper describes a laser imaging approach utilizing the adaptive property of photorefractive materials to produce a real-time measurement of the antisymmetric Lamb wave mode in all directions simultaneously. Continuous excitation is employed enabling the data to be recorded and displayed by a CCD camera. Analysis of the image produces a direct quantitative determination of the phase velocity in all directions showing plate anisotropy in the plane