187 research outputs found
Assimilation of atmospheric methane products into the MACC-II system: From SCIAMACHY to TANSO and IASI
The Monitoring Atmospheric Composition and Climate Interim Implementation
(MACC-II) delayed-mode (DM) system has been producing an atmospheric methane
(CH4) analysis 6 months behind real time since June 2009. This analysis
used to rely on the assimilation of the CH4 product from the SCanning
Imaging Absorption spectroMeter for Atmospheric CHartographY (SCIAMACHY)
instrument onboard Envisat. Recently the Laboratoire de
Météorologie Dynamique (LMD) CH4 products from the Infrared
Atmospheric Sounding Interferometer (IASI) and the SRON Netherlands Institute
for Space Research CH4 products from the Thermal And Near-infrared Sensor
for carbon Observation (TANSO) were added to the DM system. With the loss of
Envisat in April 2012, the DM system now has to rely on the assimilation of
methane data from TANSO and IASI. This paper documents the impact of this
change in the observing system on the methane tropospheric analysis. It is
based on four experiments: one free run and three analyses from respectively
the assimilation of SCIAMACHY, TANSO and a combination of TANSO and IASI
CH4 products in the MACC-II system. The period between December 2010 and
April 2012 is studied. The SCIAMACHY experiment globally underestimates the
tropospheric methane by 35 part per billion (ppb) compared to the HIAPER
Pole-to-Pole Observations (HIPPO) data and by 28 ppb compared the Total
Carbon Column Observing Network (TCCON) data, while the free run presents an
underestimation of 5 ppb and 1 ppb against the same HIPPO and
TCCON data, respectively. The assimilated TANSO product changed in October
2011 from version v.1 to version v.2.0. The analysis of version v.1 globally
underestimates the tropospheric methane by 18 ppb compared to the
HIPPO data and by 15 ppb compared to the TCCON data. In contrast, the
analysis of version v.2.0 globally overestimates the column by 3 ppb.
When the high density IASI data are added in the tropical region between
30° N and 30° S, their impact is mainly positive but more
pronounced and effective when combined with version v.2.0 of the TANSO
products. The resulting analysis globally underestimates the column-averaged
dry-air mole fractions of methane (xCH4) just under 1 ppb on
average compared to the TCCON data, whereas in the tropics it overestimates
xCH4 by about 3 ppb. The random error is estimated to be less
than 7 ppb when compared to TCCON data
Een staatssteunkader voor het VLIZ voor diensten ten behoeve van de blauwe economie: Finaal Rapport
Methionine sulfoxide reductase B from Corynebacterium diphtheriae catalyzes sulfoxide reduction via an intramolecular disulfide cascade
Corynebacterium diphtheriae is a human pathogen that causes diphtheria. In response to immune systemâinduced oxidative stress, C. diphtheriae expresses antioxidant enzymes, among which are methionine sulfoxide reductase (Msr) enzymes, which are critical for bacterial survival in the face of oxidative stress. Although some aspects of the catalytic mechanism of the Msr enzymes have been reported, several details still await full elucidation. Here, we solved the solution structure of C. diphtheriae MsrB (Cd-MsrB) and unraveled its catalytic and oxidation-protection mechanisms. Cd-MsrB catalyzes methionine sulfoxide reduction involving three redox-active cysteines. Using NMR heteronuclear single-quantum coherence (HSQC) spectra, kinetics, biochemical assays, and MS analyses, we show that the conserved nucleophilic residue Cys122 is S-sulfenylated after substrate reduction, which is then resolved by a conserved cysteine, Cys66, or by the non-conserved residue Cys127. We noted that the overall structural changes during the disulfide cascade expose the Cys122âCys66 disulfide to recycling through thioredoxin (Trx). In the presence of hydrogen peroxide, Cd-MsrB formed reversible intra- and intermolecular disulfides without losing its Cys-coordinated Zn2+, and only the non-conserved Cys127 reacted with the low-molecular-weight (LMW) thiol mycothiol, protecting it from overoxidation. In summary, our structureâfunction analyses reveal critical details of the Cd-MsrB catalytic mechanism, including a major structural rearrangement that primes the Cys122âCys66 disulfide for Trx reduction and a reversible protection against excessive oxidation of the catalytic cysteines in Cd-MsrB through intra- and intermolecular disulfide formation and S-mycothiolation
What traits are carried on mobile genetic elements, and why?
Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes
Saccharomyces boulardii Improves Intestinal Cell Restitution through Activation of the α2ÎČ1 Integrin Collagen Receptor
Intestinal epithelial cell damage is frequently seen in the mucosal lesions of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. Complete remission of these diseases requires both the cessation of inflammation and the migration of enterocytes to repair the damaged epithelium. Lyophilized Saccharomyces boulardii (Sb, Biocodex) is a nonpathogenic yeast widely used as a therapeutic agent for the treatment and prevention of diarrhea and other gastrointestinal disorders. In this study, we determined whether Sb could accelerate enterocyte migration. Cell migration was determined in Sb force-fed C57BL6J mice and in an in vitro wound model. The impact on α2ÎČ1 integrin activity was assessed using adhesion assays and the analysis of α2ÎČ1 mediated signaling pathways both in vitro and in vivo. We demonstrated that Sb secretes compounds that enhance the migration of enterocytes independently of cell proliferation. This enhanced migration was associated with the ability of Sb to favor cell-extracellular matrix interaction. Indeed, the yeast activates α2ÎČ1 integrin collagen receptors. This leads to an increase in tyrosine phosphorylation of cytoplasmic molecules, including focal adhesion kinase and paxillin, involved in the integrin signaling pathway. These changes are associated with the reorganization of focal adhesion structures. In conclusion Sb secretes motogenic factors that enhance cell restitution through the dynamic regulation of α2ÎČ1 integrin activity. This could be of major importance in the development of novel therapies targeting diseases characterized by severe mucosal injury, such as inflammatory and infectious bowel diseases
Capric Acid Secreted by S. boulardii Inhibits C. albicans Filamentous Growth, Adhesion and Biofilm Formation
Candidiasis are life-threatening systemic fungal diseases, especially of gastro intestinal track, skin and mucous membranes lining various body cavities like the nostrils, the mouth, the lips, the eyelids, the ears or the genital area. Due to increasing resistance of candidiasis to existing drugs, it is very important to look for new strategies helping the treatment of such fungal diseases. One promising strategy is the use of the probiotic microorganisms, which when administered in adequate amounts confer a health benefit. Such a probiotic microorganism is yeast Saccharomyces boulardii, a close relative of baker yeast. Saccharomyces boulardii cells and their extract affect the virulence factors of the important human fungal pathogen C. albicans, its hyphae formation, adhesion and biofilm development. Extract prepared from S. boulardii culture filtrate was fractionated and GC-MS analysis showed that the active fraction contained, apart from 2-phenylethanol, caproic, caprylic and capric acid whose presence was confirmed by ESI-MS analysis. Biological activity was tested on C. albicans using extract and pure identified compounds. Our study demonstrated that this probiotic yeast secretes into the medium active compounds reducing candidal virulence factors. The chief compound inhibiting filamentous C. albicans growth comparably to S. boulardii extract was capric acid, which is thus responsible for inhibition of hyphae formation. It also reduced candidal adhesion and biofilm formation, though three times less than the extract, which thus contains other factors suppressing C. albicans adherence. The expression profile of selected genes associated with C. albicans virulence by real-time PCR showed a reduced expression of HWP1, INO1 and CSH1 genes in C. albicans cells treated with capric acid and S. boulardii extract. Hence capric acid secreted by S. boulardii is responsible for inhibition of C. albicans filamentation and partially also adhesion and biofilm formation
Characterization of the Interaction and Cross-Regulation of Three Mycobacterium tuberculosis RelBE Modules
RelBE represents a typical bacterial toxin-antitoxin (TA) system. Mycobacterium tuberculosis H37Rv, the pathogen responsible for human tuberculosis, contains three RelBE-like modules, RelBE, RelFG, and RelJK, which are at least partly expressed in human macrophages during infection. RelBE modules appear to be autoregulated in an atypical manner compared to other TA systems; however, the molecular mechanisms and potential interactions between different RelBE modules remain to be elucidated. In the present study, we characterized the interaction and cross-regulation of these Rel toxin-antitoxin modules from this unique pathogen. The physical interactions between the three pairs of RelBE proteins were confirmed and the DNA-binding domain recognized by three RelBE-like pairs and domain structure characteristics were described. The three RelE-like proteins physically interacted with the same RelB-like protein, and could conditionally regulate its binding with promoter DNA. The RelBE-like modules exerted complex cross-regulation effects on mycobacterial growth. The relB antitoxin gene could replace relF in cross-neutralizing the relG toxin gene. Conversely, relF enhanced the toxicity of the relE toxin gene, while relB increased the toxicity of relK. This is the first report of interactions between different pairs of RelBE modules of M. tuberculosis
Interactions of KidâKis toxinâantitoxin complexes with the parD operator-promoter region of plasmid R1 are piloted by the Kis antitoxin and tuned by the stoichiometry of KidâKis oligomers
The parD operon of Escherichia coli plasmid R1 encodes a toxinâantitoxin system, which is involved in plasmid stabilization. The toxin Kid inhibits cell growth by RNA degradation and its action is neutralized by the formation of a tight complex with the antitoxin Kis. A fascinating but poorly understood aspect of the kidâkis system is its autoregulation at the transcriptional level. Using macromolecular (tandem) mass spectrometry and DNA binding assays, we here demonstrate that Kis pilots the interaction of the KidâKis complex in the parD regulatory region and that two discrete Kis-binding regions are present on parD. The data clearly show that only when the Kis concentration equals or exceeds the Kid concentration a strong cooperative effect exists between strong DNA binding and Kid(2)âKis(2)âKid(2)âKis(2) complex formation. We propose a model in which transcriptional repression of the parD operon is tuned by the relative molar ratio of the antitoxin and toxin proteins in solution. When the concentration of the toxin exceeds that of the antitoxin tight Kid(2)âKis(2)âKid(2) complexes are formed, which only neutralize the lethal activity of Kid. Upon increasing the Kis concentration, (Kid(2)âKis(2))(n) complexes repress the kidâkis operon
Rapid Probing of Biological Surfaces with a Sparse-Matrix Peptide Library
Finding unique peptides to target specific biological surfaces is crucial to basic research and technology development, though methods based on biological arrays or large libraries limit the speed and ease with which these necessary compounds can be found. We reasoned that because biological surfaces, such as cell surfaces, mineralized tissues, and various extracellular matrices have unique molecular compositions, they present unique physicochemical signatures to the surrounding medium which could be probed by peptides with appropriately corresponding physicochemical properties. To test this hypothesis, a naĂŻve pilot library of 36 peptides, varying in their hydrophobicity and charge, was arranged in a two-dimensional matrix and screened against various biological surfaces. While the number of peptides in the matrix library was very small, we obtained âhitsâ against all biological surfaces probed. Sequence refinement of the âhitsâ led to peptides with markedly higher specificity and binding activity against screened biological surfaces. Genetic studies revealed that peptide binding to bacteria was mediated, at least in some cases, by specific cell-surface molecules, while examination of human tooth sections showed that this method can be used to derive peptides with highly specific binding to human tissue
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