Designed Azolopyridinium Salts Block Protective Antigen Pores In Vitro and Protect Cells from Anthrax Toxin

Background:Several intracellular acting bacterial protein toxins of the AB-type, which are known to enter cells by endocytosis, are shown to produce channels. This holds true for protective antigen (PA), the binding component of the tripartite anthrax-toxin of Bacillus anthracis. Evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric PA63 binding/translocation component are related phenomena. Chloroquine and some 4-aminoquinolones, known as potent drugs against Plasmodium falciparium infection of humans, block efficiently the PA63-channel in a dose dependent way.Methodology/Principal Findings:Here we demonstrate that related positively charged heterocyclic azolopyridinium salts block the PA63-channel in the μM range, when both, inhibitor and PA63 are added to the same side of the membrane, the cis-side, which corresponds to the lumen of acidified endosomal vesicles of target cells. Noise-analysis allowed the study of the kinetics of the plug formation by the heterocycles. In vivo experiments using J774A.1 macrophages demonstrated that the inhibitors of PA63-channel function also efficiently block intoxication of the cells by the combination lethal factor and PA63 in the same concentration range as they block the channels in vitro.Conclusions/Significance:These results strongly argue in favor of a transport of lethal factor through the PA63-channel and suggest that the heterocycles used in this study could represent attractive candidates for development of novel therapeutic strategies against anthrax. © 2013 Beitzinger et al

Electrically driven thermal light emission from individual single-walled carbon nanotubes

Light emission from nanostructures exhibits rich quantum effects and has broad applications. Single-walled carbon nanotubes (SWNTs) are one-dimensional (1D) metals or semiconductors, in which large number of electronic states in a narrow range of energies, known as van Hove singularities, can lead to strong spectral transitions. Photoluminescence and electroluminescence involving interband transitions and excitons have been observed in semiconducting SWNTs, but are not expected in metallic tubes due to non-radiative relaxations. Here, we show that in the negative differential conductance regime, a suspended quasi-metallic SWNT (QM-SWNT) emits light due to joule-heating, displaying strong peaks in the visible and infrared corresponding to interband transitions. This is a result of thermal light emission in 1D, in stark contrast with featureless blackbody-like emission observed in large bundles of SWNTs or multi-walled nanotubes. This allows for probing of the electronic temperature and non-equilibrium hot optical phonons in joule-heated QM-SWNTs

Enhancing medical students' communication skills: development and evaluation of an undergraduate training program

<p>Abstract</p> <p>Background</p> <p>There is a relative lack of current research on the effects of specific communication training offered at the beginning of the medical degree program. The newly developed communication training "Basics and Practice in Communication Skills" was pilot tested in 2008 and expanded in the following year at the University Medical Centre Hamburg-Eppendorf in Germany. The goal was to promote and improve the communicative skills of participants and show the usefulness of an early offered intervention on patient-physician communication within the medical curriculum.</p> <p>Methods</p> <p>The students participating in the project and a comparison group of students from the standard degree program were surveyed at the beginning and end of the courses. The survey consisted of a self-assessment of their skills as well as a standardised expert rating and an evaluation of the modules by means of a questionnaire.</p> <p>Results</p> <p>Students who attended the communication skills course exhibited a considerable increase of communication skills in this newly developed training. It was also observed that students in the intervention group had a greater degree of self-assessed competence following training than the medical students in the comparison group. This finding is also reflected in the results from a standardised objective measure.</p> <p>Conclusions</p> <p>The empirical results of the study showed that the training enabled students to acquire specialised competence in communication through the course of a newly developed training program. These findings will be used to establish new communication training at the University Medical Centre Hamburg-Eppendorf.</p

Specific Gene Expression Responses to Parasite Genotypes Reveal Redundancy of Innate Immunity in Vertebrates

Vertebrate innate immunity is the first line of defense against an invading pathogen and has long been assumed to be largely unspecific with respect to parasite/pathogen species. However, recent phenotypic evidence suggests that immunogenetic variation, i.e. allelic variability in genes associated with the immune system, results in host-parasite genotype-by-genotype interactions and thus specific innate immune responses. Immunogenetic variation is common in all vertebrate taxa and this reflects an effective immunological function in complex environments. However, the underlying variability in host gene expression patterns as response of innate immunity to within-species genetic diversity of macroparasites in vertebrates is unknown. We hypothesized that intra-specific variation among parasite genotypes must be reflected in host gene expression patterns. Here we used high-throughput RNA-sequencing to examine the effect of parasite genotypes on gene expression patterns of a vertebrate host, the three-spined stickleback (Gasterosteus aculeatus). By infecting naïve fish with distinct trematode genotypes of the species Diplostomum pseudospathaceum we show that gene activity of innate immunity in three-spined sticklebacks depended on the identity of an infecting macroparasite genotype. In addition to a suite of genes indicative for a general response against the trematode we also find parasite-strain specific gene expression, in particular in the complement system genes, despite similar infection rates of single clone treatments. The observed discrepancy between infection rates and gene expression indicates the presence of alternative pathways which execute similar functions. This suggests that the innate immune system can induce redundant responses specific to parasite genotypes

Lifelong Reduction of LDL-Cholesterol Related to a Common Variant in the LDL-Receptor Gene Decreases the Risk of Coronary Artery Disease—A Mendelian Randomisation Study

Rare mutations of the low-density lipoprotein receptor gene (LDLR) cause familial hypercholesterolemia, which increases the risk for coronary artery disease (CAD). Less is known about the implications of common genetic variation in the LDLR gene regarding the variability of cholesterol levels and risk of CAD.Imputed genotype data at the LDLR locus on 1 644 individuals of a population-based sample were explored for association with LDL-C level. Replication of association with LDL-C level was sought for the most significant single nucleotide polymorphism (SNP) within the LDLR gene in three European samples comprising 6 642 adults and 533 children. Association of this SNP with CAD was examined in six case-control studies involving more than 15 000 individuals.Each copy of the minor T allele of SNP rs2228671 within LDLR (frequency 11%) was related to a decrease of LDL-C levels by 0.19 mmol/L (95% confidence interval (CI) [0.13-0.24] mmol/L, p = 1.5x10(-10)). This association with LDL-C was uniformly found in children, men, and women of all samples studied. In parallel, the T allele of rs2228671 was associated with a significantly lower risk of CAD (Odds Ratio per copy of the T allele: 0.82, 95% CI [0.76-0.89], p = 2.1x10(-7)). Adjustment for LDL-C levels by logistic regression or Mendelian Randomisation models abolished the significant association between rs2228671 with CAD completely, indicating a functional link between the genetic variant at the LDLR gene locus, change in LDL-C and risk of CAD.A common variant at the LDLR gene locus affects LDL-C levels and, thereby, the risk for CAD

Effect of diminazene aceturate Isometamidium Chloride and Trypanosoma Brucei on epididiymal and testicular sperm reserves of mice

No Abstract. Bulletin of Animal Health and Production in Africa Vol. 50 (2) 2002: pp. 76-8

Emotional coping differences among breast cancer patients from an online support group: A cross-sectional study

Contains fulltext : 124122.pdf (publisher's version ) (Open Access)Background: Due to mixed findings in research on the effect of online peer-to-peer support on psychological well-being, there is a need for studies explaining why and when online support communities are beneficial for cancer patients. Objective: Previous studies have typically not taken into account individual coping differences, despite the fact that patients have different strategies to cope with cancer-related emotions. In the current study, it was predicted that the effects of online support group participation would partly depend on patients' ability to cope with thoughts and emotions regarding the illness. Methods: For this study, 184 Dutch breast cancer patients filled out a questionnaire assessing activity within a peer-led online support community, coping with emotions and thoughts regarding the illness (cognitive avoidance, emotional processing, and expression) and psychological well-being (depression, breast cancer-related concerns, and emotional well-being). Of these, 163 patients were visiting an online peer-led support community. Results: Results showed interactions of the intensity of support group participation and coping style on psychological well-being. Specifically, we found an interaction of online activity and emotional expression on depression (beta=–.17, P=.030), a marginally significant interaction of online activity and emotional expression on emotional well-being (beta=.14, P=.089), and an interaction of online activity and cognitive avoidance on breast cancer–related concerns (beta=.15, P=.027). For patients who actively dealt with their emotions and thoughts, active online support group participation was positively related to psychological well-being. For patients high on avoidance of illness-related thoughts or low on emotional expression, active participation was negatively related to measures of well-being. Conclusions: The current study revealed the role of individual differences in coping in online support group participation. Results suggest that breast cancer patients' ability to cope with emotions and thoughts regarding the illness influence the relationship between online support group participation and psychological well-being