40 research outputs found

    Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency

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    Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5-yr-old child with severe pulmonary influenza at 2 yr. She is homozygous for a loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not IFN-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-α2b. The transcriptome induced by IFN-α2b in the patient's cells is much narrower than that of control cells; however, induction of a subset of IFN-stimulated gene transcripts remains detectable. In vitro, the patient's cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV). These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV

    Targeting Protein-Protein Interactions for Parasite Control

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    Finding new drug targets for pathogenic infections would be of great utility for humanity, as there is a large need to develop new drugs to fight infections due to the developing resistance and side effects of current treatments. Current drug targets for pathogen infections involve only a single protein. However, proteins rarely act in isolation, and the majority of biological processes occur via interactions with other proteins, so protein-protein interactions (PPIs) offer a realm of unexplored potential drug targets and are thought to be the next-generation of drug targets. Parasitic worms were chosen for this study because they have deleterious effects on human health, livestock, and plants, costing society billions of dollars annually and many sequenced genomes are available. In this study, we present a computational approach that utilizes whole genomes of 6 parasitic and 1 free-living worm species and 2 hosts. The species were placed in orthologous groups, then binned in species-specific ortholgous groups. Proteins that are essential and conserved among species that span a phyla are of greatest value, as they provide foundations for developing broad-control strategies. Two PPI databases were used to find PPIs within the species specific bins. PPIs with unique helminth proteins and helminth proteins with unique features relative to the host, such as indels, were prioritized as drug targets. The PPIs were scored based on RNAi phenotype and homology to the PDB (Protein DataBank). EST data for the various life stages, GO annotation, and druggability were also taken into consideration. Several PPIs emerged from this study as potential drug targets. A few interactions were supported by co-localization of expression in M. incognita (plant parasite) and B. malayi (H. sapiens parasite), which have extremely different modes of parasitism. As more genomes of pathogens are sequenced and PPI databases expanded, this methodology will become increasingly applicable

    ESKIMO1 Disruption in Arabidopsis Alters Vascular Tissue and Impairs Water Transport

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    Water economy in agricultural practices is an issue that is being addressed through studies aimed at understanding both plant water-use efficiency (WUE), i.e. biomass produced per water consumed, and responses to water shortage. In the model species Arabidopsis thaliana, the ESKIMO1 (ESK1) gene has been described as involved in freezing, cold and salt tolerance as well as in water economy: esk1 mutants have very low evapo-transpiration rates and high water-use efficiency. In order to establish ESK1 function, detailed characterization of esk1 mutants has been carried out. The stress hormone ABA (abscisic acid) was present at high levels in esk1 compared to wild type, nevertheless, the weak water loss of esk1 was independent of stomata closure through ABA biosynthesis, as combining mutant in this pathway with esk1 led to additive phenotypes. Measurement of root hydraulic conductivity suggests that the esk1 vegetative apparatus suffers water deficit due to a defect in water transport. ESK1 promoter-driven reporter gene expression was observed in xylem and fibers, the vascular tissue responsible for the transport of water and mineral nutrients from the soil to the shoots, via the roots. Moreover, in cross sections of hypocotyls, roots and stems, esk1 xylem vessels were collapsed. Finally, using Fourier-Transform Infrared (FTIR) spectroscopy, severe chemical modifications of xylem cell wall composition were highlighted in the esk1 mutants. Taken together our findings show that ESK1 is necessary for the production of functional xylem vessels, through its implication in the laying down of secondary cell wall components

    Un modÚle neuronal pour la simulation opérationnelle des radiances observées par l'interféromÚtre spatial à haute résolution spectrale IASI

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    PARIS-BIUSJ-ThĂšses (751052125) / SudocPARIS-BIUSJ-Sci.Terre recherche (751052114) / SudocSudocFranceF

    Remote sensing of the vertical distribution of atmospheric water vapor from the TOVS observations: Method and validation

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    International audienceThis paper presents a method to remotely sense the vertical distribution of atmospheric water vapor using spaceborne measurements from the TOVS instrument aboard the NOAA polar satellite series. It describes a new approach to the water vapor retrieval scheme in the improved initialization inversion (3I) method. The technique is based on a neural network scheme, which is analyzed theoretically. Cross‐comparisons of its results with a wide variety of independent observations (in situ measurements or other global data sets, e.g., the special sensor microwave/imager (SSM/I) retrievals, analyses) are then carried out to fully evaluate the method. It is shown that the mean of the differences between total water vapor contents obtained from each data set represents less than 20% of the global mean value of the water vapor content. Different behaviors between TOVS and SSM/I in tropical situations are also highlighted. Concerning the vertical profile, the standard deviation between water vapor content retrieved by 3I and measured by radiosondes varies from 20% in the 1000–850 hPa layer to less than 40% in the 500–300 hPa layer. The vertical increase of the error is linked to the difficulty of measuring weak values by radiosonde instruments, radiometers, or analyses

    Relationship between sea surface temperature, vertical dynamics, and the vertical distribution of atmospheric water vapor inferred from TOVS observations

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    International audienceWith the aim of better understanding the respective role of sea surface temperature (SST) and vertical dynamics on the vertical distribution of atmospheric water vapor, particularly in the tropics, global scale observations from NOAA 10, covering a 31−month period, have been processed using the improved initialization inversion ((3I) [ ChĂ©din and Scott , 1984]) retrieval method and interpreted in terms of tropospheric layered water vapor contents. The method of analysis uses the power law, which expresses the specific humidity q at pressure p as a function of their values at the surface, q 0 and p 0 ; q = q 0 ( p / p 0 ) λ . This description is applied independently to three layers giving three values of λ: λ 1 for surface‐700 hPa, λ 2 for 700–500 hPa, and λ 3 for 500–300 hPa. It is shown that λ 2 is a good indicator of the large‐scale vertical dynamics and gives results equivalent to those obtained using the vertical velocity at 500 hPa issued from a model. Consequently, the role of enhanced upward motion with increased SST for the “super greenhouse effect” situations is confirmed as well as the contribution of externally forced subsidence on the suppression of the deep convection for cases where SSTs exceed about 303 K. In addition, the influence of SST on the vertical distribution of water vapor is analyzed together with the large‐scale vertical dynamics contribution. The results show that the rate of change of water vapor content in the 700‐ to 500‐hPa and 500‐ to 300‐hPa layers with respect to SST increases with decreasing rate of change of λ 2 with respect to SST, that is, with increasing rate of change of upward vertical dynamics with respect to SST
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