Genes Differentially Expressed in Conidia and Hyphae of Aspergillus fumigatus upon Exposure to Human Neutrophils

Aspergillus fumigatus is the most common etiologic agent of invasive aspergillosis in immunocompromised patients. Several studies have addressed the mechanism involved in host defense but only few have investigated the pathogen's response to attack by the host cells. To our knowledge, this is the first study that investigates the genes differentially expressed in conidia vs hyphae of A. fumigatus in response to neutrophils from healthy donors as well as from those with chronic granulomatous disease (CGD) which are defective in the production of reactive oxygen species.Transcriptional profiles of conidia and hyphae exposed to neutrophils, either from normal donors or from CGD patients, were obtained by using the genome-wide microarray. Upon exposure to either normal or CGD neutrophils, 244 genes were up-regulated in conidia but not in hyphae. Several of these genes are involved in the degradation of fatty acids, peroxisome function and the glyoxylate cycle which suggests that conidia exposed to neutrophils reprogram their metabolism to adjust to the host environment. In addition, the mRNA levels of four genes encoding proteins putatively involved in iron/copper assimilation were found to be higher in conidia and hyphae exposed to normal neutrophils compared to those exposed to CGD neutrophils. Deletants in several of the differentially expressed genes showed phenotypes related to the proposed functions, i.e. deletants of genes involved in fatty acid catabolism showed defective growth on fatty acids and the deletants of iron/copper assimilation showed higher sensitivity to the oxidative agent menadione. None of these deletants, however, showed reduced resistance to neutrophil attack.This work reveals the complex response of the fungus to leukocytes, one of the major host factors involved in antifungal defense, and identifies fungal genes that may be involved in establishing or prolonging infections in humans

Antenatal treatment in two Dutch families with pyridoxine-dependent seizures

Contains fulltext : 88199.pdf (publisher's version ) (Closed access)Incidental reports suggest that antenatal treatment of pyridoxine dependent seizures (PDS) may improve neurodevelopmental outcome of affected patients. Two families with PDS are reported, both with two affected siblings. Antenatal treatment with pyridoxine was instituted during the second pregnancy in each family (50 and 60 mg daily from 3 and 10 weeks of gestation, respectively). Perinatal characteristics and neurodevelopmental outcome at 4 (Family A) and 12 (Family B) years of age were compared between the untreated and treated child within each family. Meconium-stained amniotic fluid was present in both first pregnancies and abnormal foetal movements were noticed in one. In the treated infants, pregnancy and birth were uncomplicated. In family A, postnatal pyridoxine supplementation prevented neonatal seizures. Both children in family A were hypotonic and started walking after 2 years of age; both had white matter changes on MRI, and the first child was treated for squint. IQ was 73 and 98 in the antenatally untreated and treated child, respectively. The second child in family B developed seizures on the seventh day, because pyridoxine maintenance therapy had not been instituted after birth. Seizures responded rapidly to pyridoxine supplementation. MRI showed large ventricles and a mega cisterna magna. IQ was 80 and 106 in the antenatally untreated and treated child respectively. Both children had normal motor development. These results suggest that antenatal pyridoxine supplementation may be effective in preventing intrauterine seizures, decreasing the risk of complicated birth and improving neurodevelopmental outcome in PDS.1 maart 201

A Network-Based Approach to Prioritize Results from Genome-Wide Association Studies

Genome-wide association studies (GWAS) are a valuable approach to understanding the genetic basis of complex traits. One of the challenges of GWAS is the translation of genetic association results into biological hypotheses suitable for further investigation in the laboratory. To address this challenge, we introduce Network Interface Miner for Multigenic Interactions (NIMMI), a network-based method that combines GWAS data with human protein-protein interaction data (PPI). NIMMI builds biological networks weighted by connectivity, which is estimated by use of a modification of the Google PageRank algorithm. These weights are then combined with genetic association p-values derived from GWAS, producing what we call ‘trait prioritized sub-networks.’ As a proof of principle, NIMMI was tested on three GWAS datasets previously analyzed for height, a classical polygenic trait. Despite differences in sample size and ancestry, NIMMI captured 95% of the known height associated genes within the top 20% of ranked sub-networks, far better than what could be achieved by a single-locus approach. The top 2% of NIMMI height-prioritized sub-networks were significantly enriched for genes involved in transcription, signal transduction, transport, and gene expression, as well as nucleic acid, phosphate, protein, and zinc metabolism. All of these sub-networks were ranked near the top across all three height GWAS datasets we tested. We also tested NIMMI on a categorical phenotype, Crohn’s disease. NIMMI prioritized sub-networks involved in B- and T-cell receptor, chemokine, interleukin, and other pathways consistent with the known autoimmune nature of Crohn’s disease. NIMMI is a simple, user-friendly, open-source software tool that efficiently combines genetic association data with biological networks, translating GWAS findings into biological hypotheses

First measurement of coherent ρ0 photoproduction in ultra-peripheral Xe–Xe collisions at √sNN = 5.44 TeV

The first measurement of the coherent photoproduction of ρ0 vector mesons in ultra-peripheral Xe–Xe collisions at sNN=5.44 TeV is presented. This result, together with previous HERA γp data and γ–Pb measurements from ALICE, describes the atomic number (A) dependence of this process, which is particularly sensitive to nuclear shadowing effects and to the approach to the black-disc limit of QCD at a semi-hard scale. The cross section of the Xe+Xe→ρ0+Xe+Xe process, measured at midrapidity through the decay channel ρ0→π+π−, is found to be dσ/dy=131.5±5.6(stat.)−16.9+17.5(syst.) mb. The ratio of the continuum to resonant contributions for the production of pion pairs is also measured. In addition, the fraction of events accompanied by electromagnetic dissociation of either one or both colliding nuclei is reported. The dependence on A of cross section for the coherent ρ0 photoproduction at a centre-of-mass energy per nucleon of the γA system of WγA,n=65 GeV is found to be consistent with a power-law behaviour σ(γA→ρ0A)∝Aα with a slope α=0.96±0.02(syst.). This slope signals important shadowing effects, but it is still far from the behaviour expected in the black-disc limit.publishedVersio

A(c)(+) Production and Baryon-to-Meson Ratios in pp and p-Pb Collisions at root S-NN=5.02 TeV at the LHC

The prompt production of the charm baryon \u39bc+ and the \u39bc+/D0 production ratios were measured at midrapidity with the ALICE detector in pp and p-Pb collisions at sNN=5.02 TeV. These new measurements show a clear decrease of the \u39bc+/D0 ratio with increasing transverse momentum (pT) in both collision systems in the range 2<12 GeV/c, exhibiting similarities with the light-flavor baryon-to-meson ratios p/\u3c0 and \u39b/KS0. At low pT, predictions that include additional color-reconnection mechanisms beyond the leading-color approximation, assume the existence of additional higher-mass charm-baryon states, or include hadronization via coalescence can describe the data, while predictions driven by charm-quark fragmentation processes measured in e+e- and e-p collisions significantly underestimate the data. The results presented in this Letter provide significant evidence that the established assumption of universality (colliding-system independence) of parton-to-hadron fragmentation is not sufficient to describe charm-baryon production in hadronic collisions at LHC energies

A(c)(+) Production and Baryon-to-Meson Ratios in pp and p-Pb Collisions at root S-NN=5.02 TeV at the LHC

The prompt production of the charm baryon Λ_{c}^{+} and the Λ_{c}^{+}/D^{0} production ratios were measured at midrapidity with the ALICE detector in pp and p-Pb collisions at sqrt[s_{NN}]=5.02  TeV. These new measurements show a clear decrease of the Λ_{c}^{+}/D^{0} ratio with increasing transverse momentum (p_{T}) in both collision systems in the range 2<p_{T}<12  GeV/c, exhibiting similarities with the light-flavor baryon-to-meson ratios p/π and Λ/K_{S}^{0}. At low p_{T}, predictions that include additional color-reconnection mechanisms beyond the leading-color approximation, assume the existence of additional higher-mass charm-baryon states, or include hadronization via coalescence can describe the data, while predictions driven by charm-quark fragmentation processes measured in e^{+}e^{-} and e^{-}p collisions significantly underestimate the data. The results presented in this Letter provide significant evidence that the established assumption of universality (colliding-system independence) of parton-to-hadron fragmentation is not sufficient to describe charm-baryon production in hadronic collisions at LHC energies

The Mosaic Genome of Anaeromyxobacter dehalogenans Strain 2CP-C Suggests an Aerobic Common Ancestor to the Delta-Proteobacteria

©2008 Thomas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.doi:10.1371/journal.pone.0002103Anaeromyxobacter dehalogenans strain 2CP-C is a versaphilic delta-Proteobacterium distributed throughout many diverse soil and sediment environments. 16S rRNA gene phylogenetic analysis groups A. dehalogenans together with the myxobacteria, which have distinguishing characteristics including strictly aerobic metabolism, sporulation, fruiting body formation, and surface motility. Analysis of the 5.01 Mb strain 2CP-C genome substantiated that this organism is a myxobacterium but shares genotypic traits with the anaerobic majority of the delta-Proteobacteria (i.e., the Desulfuromonadales). Reflective of its respiratory versatility, strain 2CP-C possesses 68 genes coding for putative c-type cytochromes, including one gene with 40 heme binding motifs. Consistent with its relatedness to the myxobacteria, surface motility was observed in strain 2CP-C and multiple types of motility genes are present, including 28 genes for gliding, adventurous (A-) motility and 17 genes for type IV pilus-based motility (i.e., social (S-) motility) that all have homologs in Myxococcus xanthus. Although A. dehalogenans shares many metabolic traits with the anaerobic majority of the delta- Proteobacteria, strain 2CP-C grows under microaerophilic conditions and possesses detoxification systems for reactive oxygen species. Accordingly, two gene clusters coding for NADH dehydrogenase subunits and two cytochrome oxidase gene clusters in strain 2CP-C are similar to those in M. xanthus. Remarkably, strain 2CP-C possesses a third NADH dehydrogenase gene cluster and a cytochrome cbb3 oxidase gene cluster, apparently acquired through ancient horizontal gene transfer from a strictly anaerobic green sulfur bacterium. The mosaic nature of the A. dehalogenans strain 2CP-C genome suggests that the metabolically versatile, anaerobic members of the delta-Proteobacteria may have descended from aerobic ancestors with complex lifestyles