Small but Crucial: The Novel Small Heat Shock Protein Hsp21 Mediates Stress Adaptation and Virulence in \u3ci\u3eCandida albicans\u3c/i\u3e

Small heat shock proteins (sHsps) have multiple cellular functions. However, the biological function of sHsps in pathogenic microorganisms is largely unknown. In the present study we identified and characterized the novel sHsp Hsp21 of the human fungal pathogen Candida albicans. Using a reverse genetics approach we demonstrate the importance of Hsp21 for resistance of C. albicans to specific stresses, including thermal and oxidative stress. Furthermore, a hsp21∆/∆ mutant was defective in invasive growth and formed significantly shorter filaments compared to the wild type under various filamentinducing conditions. Although adhesion to and invasion into human-derived endothelial and oral epithelial cells was unaltered, the hsp21∆/∆ mutant exhibited a strongly reduced capacity to damage both cell lines. Furthermore, Hsp21 was required for resisting killing by human neutrophils. Measurements of intracellular levels of stress protective molecules demonstrated that Hsp21 is involved in both glycerol and glycogen regulation and plays a major role in trehalose homeostasis in response to elevated temperatures. Mutants defective in trehalose and, to a lesser extent, glycerol synthesis phenocopied HSP21 deletion in terms of increased susceptibility to environmental stress, strongly impaired capacity to damage epithelial cells and increased sensitivity to the killing activities of human primary neutrophils. Via systematic analysis of the three main C. albicans stress-responsive kinases (Mkc1, Cek1, Hog1) under a range of stressors, we demonstrate Hsp21-dependent phosphorylation of Cek1 in response to elevated temperatures. Finally, the hsp21∆/∆mutant displayed strongly attenuated virulence in two in vivo infection models. Taken together, Hsp21 mediates adaptation to specific stresses via fine-tuning homeostasis of compatible solutes and activation of the Cek1 pathway, and is crucial for multiple stages of C. albicans pathogenicity. Hsp21 therefore represents the first reported example of a small heat shock protein functioning as a virulence factor in a eukaryotic pathogen

Mécanique et thermique des aimants pour champs magnétiques intenses

Les aimants pour champs magnétiques intenses (c'est à dire au delà des champs fournis par les aimants supraconducteurs) sont réalisés à partir de bobinages d'alliage de cuivre soumis à des contraintes mécaniques et thermiques extrêmes. Ces structures mécaniques travaillent à des contraintes proches de leur limite élastique et les flux de chaleur surfacique à évacuer atteignent 500 W par cm2. Nous présentons les développements en cours pour la conception et la réalisation de ces échangeurs thermiques aux caractéristiques très particulières

Analysis of temperature-dependant current-voltage characteristics and extraction of series resistance in Pd/ZnO Schottky barrier diodes

We report on the analysis of current voltage (I-V) measurements performed on Pd/ZnO Schottky barrier diodes (SBDs) in the 80-320 K temperature range. Assuming thermionic emission (TE) theory, the forward bias I-V characteristics were analysed to extract Pd/ZnO Schottky diode parameters. Comparing Cheung’s method in the extraction of the series resistance with Ohm’s law, it was observed that at lower temperatures (T<180 K) the series resistance decreased with increasing temperature, the absolute minimum was reached near 180 K and increases linearly with temperature at high temperatures (T>200 K). The barrier height and the ideality factor decreased and increased, respectively, with decrease in temperature, attributed to the existence of barrier height inhomogeneity. Such inhomogeneity was explained based on TE with the assumption of Gaussian distribution of barrier heights with a mean barrier height of 0.99 eV and a standard deviation of 0.02 eV. A mean barrier height of 0.11 eV and Richardson constant value of 37 A cm-2 K-2 were determined from the modified Richardson plot that considers the Gaussian distribution of barrier heights.South Africa National Research Foundation (NRF) and the University of Pretoria.http://www.journals.elsevier.com/physica-b-condensed-matter2017-01-31hb2016Physic

Ar plasma induced deep levels in epitaxial n-GaAs

Ar plasma etching of n-type (Si doped) GaAs introduces several electron traps (Ec - 0.04 eV, Ec - 0.07 eV, Ec - 0.19 eV, Ec - 0.31 eV, Ec - 0.53 eV, and Ec - 0.61 eV). The trap, Ec - 0.04 eV, labelled E10 and having a trap signature similar to irradiation induced defect E1, appears to be metastable. Ec - 0.31 eV and Ec - 0.61 eV are metastable too and they are similar to the M3/M4 defect configuration present in hydrogen plasma exposed n-GaAs.South African National Research Foundationhttp://jap.aip.org/nf201

Burden and risk factors for Pseudomonas aeruginosa community-acquired pneumonia:a Multinational Point Prevalence Study of Hospitalised Patients

Pseudornonas aeruginosa is a challenging bacterium to treat due to its intrinsic resistance to the antibiotics used most frequently in patients with community-acquired pneumonia (CAP). Data about the global burden and risk factors associated with P. aeruginosa-CAP are limited. We assessed the multinational burden and specific risk factors associated with P. aeruginosa-CAP. We enrolled 3193 patients in 54 countries with confirmed diagnosis of CAP who underwent microbiological testing at admission. Prevalence was calculated according to the identification of P. aeruginosa. Logistic regression analysis was used to identify risk factors for antibiotic-susceptible and antibiotic-resistant P. aeruginosa-CAP. The prevalence of P. aeruginosa and antibiotic-resistant P. aeruginosa-CAP was 4.2% and 2.0%, respectively. The rate of P. aeruginosa CAP in patients with prior infection/colonisation due to P. aeruginosa and at least one of the three independently associated chronic lung diseases (i.e. tracheostomy, bronchiectasis and/or very severe chronic obstructive pulmonary disease) was 67%. In contrast, the rate of P. aeruginosa-CAP was 2% in patients without prior P. aeruginosa infection/colonisation and none of the selected chronic lung diseases. The multinational prevalence of P. aeruginosa-CAP is low. The risk factors identified in this study may guide healthcare professionals in deciding empirical antibiotic coverage for CAP patients

Measurement of the Tau Lepton Polarisation at LEP2

A first measurement of the average polarisation P_tau of tau leptons produced in e+e- annihilation at energies significantly above the Z resonance is presented. The polarisation is determined from the kinematic spectra of tau hadronic decays. The measured value P_tau = -0.164 +/- 0.125 is consistent with the Standard Model prediction for the mean LEP energy of 197 GeV.A first measurement of the average polarisation Pτ of tau leptons produced in e + e − annihilation at energies significantly above the Z resonance is presented. The polarisation is determined from the kinematic spectra of tau hadronic decays. The measured value Pτ=−0.164±0.125 is consistent with the Standard Model prediction for the mean LEP energy of 197 GeV.A first measurement of the average polarisation P_tau of tau leptons produced in e+e- annihilation at energies significantly above the Z resonance is presented. The polarisation is determined from the kinematic spectra of tau hadronic decays. The measured value P_tau = -0.164 +/- 0.125 is consistent with the Standard Model prediction for the mean LEP energy of 197 GeV

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity