Synthetic Mimic of Antimicrobial Peptide with Nonmembrane-Disrupting Antibacterial Properties

Proteolysis in dairy lactic acid bacteria has been studied in great detail by genetic, biochemical and ultrastructural methods. From these studies the picture emerges that the proteolytic systems of lactococci and lactobacilli are remarkably similar in their components and mode of action. The proteolytic system consists of an extracellularly located serine-proteinase, transport systems specific for di-tripeptides and oligopeptides (> 3 residues), and a multitude of intracellular peptidases. This review describes the properties and regulation of individual components as well as studies that have led to identification of their cellular localization. Targeted mutational techniques developed in recent years have made it possible to investigate the role of individual and combinations of enzymes in vivo. Based on these results as well as in vitro studies of the enzymes and transporters, a model for the proteolytic pathway is proposed. The main features are: (i) proteinases have a broad specificity and are capable of releasing a large number of different oligopeptides, of which a large fraction falls in the range of 4 to 8 amino acid residues; (ii) oligopeptide transport is the main route for nitrogen entry into the cell; (iii) all peptidases are located intracellularly and concerted action of peptidases is required for complete degradation of accumulated peptides.

Modelling credit spreads with time volatility, skewness, and kurtosis

This paper seeks to identify the macroeconomic and financial factors that drive credit spreads on bond indices in the US credit market. To overcome the idiosyncratic nature of credit spread data reflected in time varying volatility, skewness and thick tails, it proposes asymmetric GARCH models with alternative probability density functions. The results show that credit spread changes are mainly explained by the interest rate and interest rate volatility, the slope of the yield curve, stock market returns and volatility, the state of liquidity in the corporate bond market and, a heretofore overlooked variable, the foreign exchange rate. They also confirm that the asymmetric GARCH models and Student-t distributions are systematically superior to the conventional GARCH model and the normal distribution in in-sample and out-of-sample testing

Imaging of bronchial pathology in antibody deficiency: Data from the European Chest CT Group

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease

X-Shooting ULLYSES: Massive stars at low metallicity: I. Project description

Observations of individual massive stars, super-luminous supernovae, gamma-ray bursts, and gravitational wave events involving spectacular black hole mergers indicate that the low-metallicity Universe is fundamentally different from our own Galaxy. Many transient phenomena will remain enigmatic until we achieve a firm understanding of the physics and evolution of massive stars at low metallicity (Z). The Hubble Space Telescope has devoted 500 orbits to observing ∼250 massive stars at low Z in the ultraviolet (UV) with the COS and STIS spectrographs under the ULLYSES programme. The complementary X-Shooting ULLYSES (XShootU) project provides an enhanced legacy value with high-quality optical and near-infrared spectra obtained with the wide-wavelength coverage X-shooter spectrograph at ESOa's Very Large Telescope. We present an overview of the XShootU project, showing that combining ULLYSES UV and XShootU optical spectra is critical for the uniform determination of stellar parameters such as effective temperature, surface gravity, luminosity, and abundances, as well as wind properties such as mass-loss rates as a function of Z. As uncertainties in stellar and wind parameters percolate into many adjacent areas of astrophysics, the data and modelling of the XShootU project is expected to be a game changer for our physical understanding of massive stars at low Z. To be able to confidently interpret James Webb Space Telescope spectra of the first stellar generations, the individual spectra of low-Z stars need to be understood, which is exactly where XShootU can deliver

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

Direct and indirect costs of immunoglobulin replacement therapy in patients with common variable immunodeficiency (CVID) and X-Linked agammaglobulinemia (XLA) in Italy

In Italy, there is scarce evidence on the epidemiological and economic burden induced by primary antibody deficiencies

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe