Genomic Organization and Expression of Iron Metabolism Genes in the Emerging Pathogenic Mold

The ubiquitous mold is increasingly recognized as an emerging pathogen, especially among patients with underlying disorders such as immunodeficiency or cystic fibrosis (CF). Indeed, it ranks the second among the filamentous fungi colonizing the respiratory tract of CF patients. However, our knowledge about virulence factors of this fungus is still limited. The role of iron-uptake systems may be critical for establishment of infections, notably in the iron-rich environment of the CF lung. Two main strategies are employed by fungi to efficiently acquire iron from their host or from their ecological niche: siderophore production and reductive iron assimilation (RIA) systems. The aim of this study was to assess the existence of orthologous genes involved in iron metabolism in the recently sequenced genome of . At first, a tBLASTn analysis using iron-related proteins as query revealed orthologs of almost all relevant loci in the genome. Whereas the genes putatively involved in RIA were randomly distributed, siderophore biosynthesis and transport genes were organized in two clusters, each containing a non-ribosomal peptide synthetase (NRPS) whose orthologs in have been described to catalyze hydroxamate siderophore synthesis. Nevertheless, comparative genomic analysis of siderophore-related clusters showed greater similarity between and phylogenetically close molds than with species. The expression level of these genes was then evaluated by exposing conidia to iron starvation and iron excess. The expression of several orthologs of genes involved in siderophore-based iron uptake or RIA was significantly induced during iron starvation, and conversely repressed in iron excess conditions. Altogether, these results indicate that possesses the genetic information required for efficient and competitive iron uptake. They also suggest an important role of the siderophore production system in iron uptake by

Investigation of nosocomial pneumocystis infections: usefulness of longitudinal screening of epidemic and post-epidemic pneumocystis genotypes

BACKGROUND: Twenty-five patients, of whom 22 were renal transplant recipients, developed Pneumocystis jirovecii infections at the nephrology department of Reims University Hospital (France) from September 2008 to October 2009, whereas only four sporadic cases had been diagnosed in this department over the 14 previous years. AIM: This outbreak was investigated by analysing patient encounters and P. jirovecii types. METHODS: A transmission map was drawn up. P. jirovecii typing at DHPS, ITS and mtLSU rRNA sequences was performed in the patients of the cluster (18 patients with Pneumocystis pneumonia (PCP) and seven colonized patients), 10 unlinked control patients (six PCP patients and four colonized patients), as well as 23 other patients diagnosed with P. jirovecii (nine PCP patients and 14 colonized patients) in the same department over a three-year post-epidemic period. FINDINGS: Eleven encounters between patients harbouring the same types were observed. Three PCP patients and one colonized patient were considered as possible index cases. The most frequent types in the cluster group and the control group were identical. However, their frequency was significantly higher in the first than in the second group (P < 0.01). Identical types were also identified in the post-epidemic group, suggesting a second outbreak due to the same strain, contemporary to a disruption in prevention measures. CONCLUSIONS: These results provide additional data on the role of both PCP and colonized patients as infectious sources. Longitudinal screening of P. jirovecii types in infected patients, including colonized patients, is required in the investigation of the fungus\u27s circulation within hospitals

Glutathione is key to the synergistic enhancement of doxorubicin and etoposide by polyphenols in leukaemia cell lines

Recently published in Nature: Cell Death and Discovery, Mahbub et al.1 have demonstrated that polyphenols can synergistically enhance the action of the topoisomerase II inhibitors: doxorubicin and etoposide in leukaemia cells. A reduction of glutathione (GSH) was strongly associated with sensitising cells to the pro-apoptotic effects of polyphenols when used in combination with doxorubicin or etoposide. Importantly, when polyphenols and topoisomerase II inhibitors were combined, it was possible to induce a synergistic decrease in cell proliferation (measured as ATP levels), cell-cycle arrest and induction of apoptosis in leukaemia cell lines

Type IIn supernovae at z ~ 2 from archival data

Supernovae have been confirmed to redshift z ~ 1.7 for type Ia (thermonuclear detonation of a white dwarf) and to z ~ 0.7 for type II (collapse of the core of the star). The subclass type IIn supernovae are luminous core-collapse explosions of massive stars and, unlike other types, are very bright in the ultraviolet, which should enable them to be found optically at redshifts z ~ 2 and higher. In addition, the interaction of the ejecta with circumstellar material creates strong, long-lived emission lines that allow spectroscopic confirmation of many events of this type at z ~ 2 for 3 - 5 years after explosion. Here we report three spectroscopically confirmed type IIn supernovae, at redshifts z = 0.808, 2.013 and 2.357, detected in archival data using a method designed to exploit these properties at z ~ 2. Type IIn supernovae directly probe the formation of massive stars at high redshift. The number found to date is consistent with the expectations of a locally measured stellar initial mass function, but not with an evolving initial mass function proposed to explain independent observations at low and high redshift.Comment: 8 pages, 2 figures, includes supplementary informatio

The supernova CSS121015:004244+132827: a clue for understanding super-luminous supernovae

We present optical photometry and spectra of the super luminous type II/IIn supernova CSS121015:004244+132827 (z=0.2868) spanning epochs from -30 days (rest frame) to more than 200 days after maximum. CSS121015 is one of the more luminous supernova ever found and one of the best observed. The photometric evolution is characterized by a relatively fast rise to maximum (~40 days in the SN rest frame), and by a linear post-maximum decline. The light curve shows no sign of a break to an exponential tail. A broad Halpha is first detected at ~ +40 days (rest-frame). Narrow, barely-resolved Balmer and [O III] 5007 A lines, with decreasing strength, are visible along the entire spectral evolution. The spectra are very similar to other super luminous supernovae (SLSNe) with hydrogen in their spectrum, and also to SN 2005gj, sometimes considered a type Ia interacting with H-rich CSM. The spectra are also similar to a subsample of H-deficient SLSNe. We propose that the properties of CSS121015 are consistent with the interaction of the ejecta with a massive, extended, opaque shell, lost by the progenitor decades before the final explosion, although a magnetar powered model cannot be excluded. Based on the similarity of CSS121015 with other SLSNe (with and without H), we suggest that the shocked-shell scenario should be seriously considered as a plausible model for both types of SLSN.Comment: 17 pages, 10 figures and 5 tables. In press to MNRAS. This version matches the accepted one. Main conclusions are unchange

Type Ia Supernovae Rates and Galaxy Clustering from the CFHT Supernova Legacy Survey

The Canada-France-Hawaii Telescope Supernova Legacy Survey (SNLS) has created a large homogeneous database of intermediate redshift (0.2 < z < 1.0) type Ia supernovae (SNe Ia). The SNLS team has shown that correlations exist between SN Ia rates, properties, and host galaxy star formation rates. The SNLS SN Ia database has now been combined with a photometric redshift galaxy catalog and an optical galaxy cluster catalog to investigate the possible influence of galaxy clustering on the SN Ia rate, over and above the expected effect due to the dependence of SFR on clustering through the morphology-density relation. We identify three cluster SNe Ia, plus three additional possible cluster SNe Ia, and find the SN Ia rate per unit mass in clusters at intermediate redshifts is consistent with the rate per unit mass in field early-type galaxies and the SN Ia cluster rate from low redshift cluster targeted surveys. We also find the number of SNe Ia in cluster environments to be within a factor of two of expectations from the two component SNIa rate model.Comment: 21 pages, 2 figures, 6 tables, accepted for publication in A

Hubble Space Telescope studies of low-redshift Type Ia supernovae: Evolution with redshift and ultraviolet spectral trends

We present an analysis of the maximum light, near ultraviolet (NUV; 2900-5500 A) spectra of 32 low redshift (0.001<z<0.08) Type Ia supernovae (SNe Ia), obtained with the Hubble Space Telescope (HST). We combine this spectroscopic sample with high-quality gri light curves obtained with robotic telescopes to measure photometric parameters, such as stretch, optical colour, and brightness. By comparing our data to a comparable sample of SNe Ia at intermediate-z (0.4<z<0.9), we detect modest spectral evolution (3-sigma), in the sense that our mean low-z NUV spectrum has a depressed flux compared to its intermediate-z counterpart. We also see a strongly increased dispersion about the mean with decreasing wavelength, confirming the results of earlier surveys. These trends are consistent with changes in metallicity as predicted by contemporary SN Ia spectral models. We also examine the properties of various NUV spectral diagnostics in the individual spectra. We find a general correlation between stretch and the velocity (or position) of many NUV spectral features. In particular, we observe that higher stretch SNe have larger Ca II H&K velocities, that also correlate with host galaxy stellar mass. This latter trend is probably driven by the well-established correlation between stretch and stellar mass. We find no trends between UV spectral features and optical colour. Mean spectra constructed according to whether the SN has a positive or negative Hubble residual show very little difference at NUV wavelengths, indicating that the NUV evolution and variation we identify do not directly correlate with Hubble residuals. Our work confirms and strengthens earlier conclusions regarding the complex behaviour of SNe Ia in the NUV spectral region, but suggests the correlations we find are more useful in constraining progenitor models than improving the use of SNe Ia as cosmological probes.Comment: 22 pages, 14 figures, accepted in MNRAS with minor changes - Spectra are available on WISeREP, http://www.weizmann.ac.il/astrophysics/wiserep

Influence of through-flow on linear pattern formation properties in binary mixture convection

We investigate how a horizontal plane Poiseuille shear flow changes linear convection properties in binary fluid layers heated from below. The full linear field equations are solved with a shooting method for realistic top and bottom boundary conditions. Through-flow induced changes of the bifurcation thresholds (stability boundaries) for different types of convective solutions are deter- mined in the control parameter space spanned by Rayleigh number, Soret coupling (positive as well as negative), and through-flow Reynolds number. We elucidate the through-flow induced lifting of the Hopf symmetry degeneracy of left and right traveling waves in mixtures with negative Soret coupling. Finally we determine with a saddle point analysis of the complex dispersion relation of the field equations over the complex wave number plane the borders between absolute and convective instabilities for different types of perturbations in comparison with the appropriate Ginzburg-Landau amplitude equation approximation. PACS:47.20.-k,47.20.Bp, 47.15.-x,47.54.+rComment: 19 pages, 15 Postscript figure