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4 result(s) for "March, Oliver P."
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Arginine‐ but not alanine‐rich carboxy‐termini trigger nuclear translocation of mutant keratin 10 in ichthyosis with confetti
Ichthyosis with confetti (IWC) is a genodermatosis associated with dominant‐negative variants in keratin 10 (KRT10) or keratin 1 (KRT1). These frameshift variants result in extended aberrant proteins, localized to the nucleus rather than the cytoplasm. This mislocalization is thought to occur as a result of the altered carboxy (C)‐terminus, from poly‐glycine to either a poly‐arginine or ‐alanine tail. Previous studies on the type of C‐terminus and subcellular localization of the respective mutant protein are divergent. In order to fully elucidate the pathomechanism of IWC, a greater understanding is critical. This study aimed to establish the consequences for localization and intermediate filament formation of altered keratin 10 (K10) C‐termini. To achieve this, plasmids expressing distinct KRT10 variants were generated. Sequences encoded all possible reading frames of the K10 C‐terminus as well as a nonsense variant. A keratinocyte line was transfected with these plasmids. Additionally, gene editing was utilized to introduce frameshift variants in exon 6 and exon 7 at the endogenous KRT10 locus. Cellular localization of aberrant K10 was observed via immunofluorescence using various antibodies. In each setting, immunofluorescence analysis demonstrated aberrant nuclear localization of K10 featuring an arginine‐rich C‐terminus. However, this was not observed with K10 featuring an alanine‐rich C‐terminus. Instead, the protein displayed cytoplasmic localization, consistent with wild‐type and truncated forms of K10. This study demonstrates that, of the various 3′ frameshift variants of KRT10, exclusively arginine‐rich C‐termini lead to nuclear localization of K10.
Logging cuts the functional importance of invertebrates in tropical rainforest
Invertebrates are dominant species in primary tropical rainforests, where their abundance and diversity contributes to the functioning and resilience of these globally important ecosystems. However, more than one-third of tropical forests have been logged, with dramatic impacts on rainforest biodiversity that may disrupt key ecosystem processes. We find that the contribution of invertebrates to three ecosystem processes operating at three trophic levels (litter decomposition, seed predation and removal, and invertebrate predation) is reduced by up to one-half following logging. These changes are associated with decreased abundance of key functional groups of termites, ants, beetles and earthworms, and an increase in the abundance of small mammals, amphibians and insectivorous birds in logged relative to primary forest. Our results suggest that ecosystem processes themselves have considerable resilience to logging, but the consistent decline of invertebrate functional importance is indicative of a human-induced shift in how these ecological processes operate in tropical rainforests. Invertebrates are key components in the ecological functioning of tropical forests. Here, Ewers et al . show that, compared to primary forest, logging halves the contribution of invertebrate species to several key ecosystem processes, including litter decomposition.
Readiness of the ATLAS Spanish Federated Tier-2 for the Physics Analysis of the early collision events at the LHC
In this contribution an evaluation of the readiness parameters for the Spanish ATLAS Federated Tier-2 is presented, regarding the ATLAS data taking which is expected to start by the end of the year 2009. Special attention will be paid to the Physics Analysis from different points of view: Data Management, Simulated events Production and Distributed Analysis Tests. Several use cases of Distributed Analysis in GRID infrastructures and local interactive analysis in non-Grid farms, are provided, in order to evaluate the interoperability between both environments, and to compare the different performances. The prototypes for local computing infrastructures for data analysis are described. Moreover, information about a local analysis facilities, called Tier-3, is given.
The Herschel Multi-Tiered Extragalactic Survey: Source Extraction and Cross-Identifications in Confusion-Dominated SPIRE Images
We present the cross-identification and source photometry techniques used to process Herschel SPIRE imaging taken as part of the Herschel Multi-Tiered Extragalactic Survey (HerMES). Cross-identifications are performed in map-space so as to minimise source blending effects. We make use of a combination of linear inversion and model selection techniques to produce reliable cross-identification catalogues based on Spitzer MIPS 24 micron source positions. Testing on simulations and real Herschel observations show that this approach gives robust results for even the faintest sources S250~10 mJy. We apply our new technique to HerMES SPIRE observations taken as part of the science demostration phase of Herschel. For our real SPIRE observations we show that, for bright unconfused sources, our flux density estimates are in good agreement with those produced via more traditional point source detection methods (SussExtractor; Savage & Oliver et al. 2006) by Smith et al. 2010. When compared to the measured number density of sources in the SPIRE bands, we show that our method allows the recovery of a larger fraction of faint sources than these traditional methods. However this completeness is heavily dependant on the relative depth of the existing 24 micron catalogues and SPIRE imaging. Using our deepest multi-wavelength dataset in GOODS-N, we estimate that the use of shallow 24 micron in our other fields introduces an incompleteness at faint levels of between 20-40 per cent at 250 micron.