Search results for "SoMe"
showing 10 items of 5114 documents
Elimination of a bacterial pore-forming toxin by sequential endocytosis and exocytosis
2008
Staphylococcus aureus alpha-toxin is the archetype of bacterial pore forming toxins and a key virulence factor secreted by the majority of clinical isolates of S. aureus. Toxin monomers bind to target cells and oligomerize to form small beta-barrel pores in the plasma membrane. Many nucleated cells are able to repair a limited number of lesions by unknown, calcium-independent mechanisms. Here we show that cells can internalize alpha-toxin, that uptake is essential for cellular survival, and that pore-complexes are not proteolytically degraded, but returned to the extracellular milieu in the context of exosome-like structures, which we term toxosomes.
Lipid and phase specificity of α-toxin from S. aureus
2013
AbstractThe pore forming toxin Hla (α-toxin) from Staphylococcus aureus is an important pathogenic factor of the bacterium S. aureus and also a model system for the process of membrane-induced protein oligomerisation and pore formation. It has been shown that binding to lipid membranes at neutral or basic pH requires the presence of a phosphocholine-headgroup. Thus, sphingomyelin and phosphatidylcholine may serve as interaction partners in cellular membranes. Based on earlier studies it has been suggested that rafts of sphingomyelin are particularly efficient in toxin binding. In this study we compared the oligomerisation of Hla on liposomes of various lipid compositions in order to identif…
A subunit of eukaryotic translation initiation factor 2α-phosphatase (CreP/PPP1R15B) regulates membrane traffic.
2012
The constitutive reverter of eIF2α phosphorylation (CReP)/PPP1r15B targets the catalytic subunit of protein phosphatase 1 (PP1c) to phosphorylated eIF2α (p-eIF2α) to promote its dephosphorylation and translation initiation. Here, we report a novel role and mode of action of CReP. We found that CReP regulates uptake of the pore-forming Staphylococcus aureus α-toxin by epithelial cells. This function was independent of PP1c and translation, although p-eIF2α was involved. The latter accumulated at sites of toxin attack and appeared conjointly with α-toxin in early endosomes. CReP localized to membranes, interacted with phosphomimetic eIF2α, and, upon overexpression, induced and decorated a pop…
Musket: a multistage k-mer spectrum-based error corrector for Illumina sequence data
2012
Abstract Motivation: The imperfect sequence data produced by next-generation sequencing technologies have motivated the development of a number of short-read error correctors in recent years. The majority of methods focus on the correction of substitution errors, which are the dominant error source in data produced by Illumina sequencing technology. Existing tools either score high in terms of recall or precision but not consistently high in terms of both measures. Results: In this article, we present Musket, an efficient multistage k-mer-based corrector for Illumina short-read data. We use the k-mer spectrum approach and introduce three correction techniques in a multistage workflow: two-s…
On the function of modified nucleosides in the RNA world.
1998
Presumably ribosome and transfer RNA (tRNA) evolved from a pre-existing function in the RNA stage of life and were secondarily adapted for protein synthesis. Various possible initial functions of the primitive ribosome (protoribosome) have been suggested. The initial function of the primitive ribosome and primitive genetic translation would have been quite similar. It is possible that, initially, both functions coexisted in the protoribosome. Given that the three-dimensional structure of ribosomal RNAs shows only minor variations throughout time, it is, then, most likely that present ribosomes can still recall (remember) the most important parts of the mechanism of their initial function. A…
SeqEditor: an application for primer design and sequence analysis with or without GTF/GFF files
2021
[Motivation]: Sequence analyses oriented to investigate specific features, patterns and functions of protein and DNA/RNA sequences usually require tools based on graphic interfaces whose main characteristic is their intuitiveness and interactivity with the user’s expertise, especially when curation or primer design tasks are required. However, interface-based tools usually pose certain computational limitations when managing large sequences or complex datasets, such as genome and transcriptome assemblies. Having these requirments in mind we have developed SeqEditor an interactive software tool for nucleotide and protein sequences’ analysis.
A non-linear optimization procedure to estimate distances and instantaneous substitution rate matrices under the GTR model.
2006
Abstract Motivation: The general-time-reversible (GTR) model is one of the most popular models of nucleotide substitution because it constitutes a good trade-off between mathematical tractability and biological reality. However, when it is applied for inferring evolutionary distances and/or instantaneous rate matrices, the GTR model seems more prone to inapplicability than more restrictive time-reversible models. Although it has been previously noted that the causes for intractability are caused by the impossibility of computing the logarithm of a matrix characterised by negative eigenvalues, the issue has not been investigated further. Results: Here, we formally characterize the mathematic…
Long read alignment based on maximal exact match seeds
2012
Abstract Motivation: The explosive growth of next-generation sequencing datasets poses a challenge to the mapping of reads to reference genomes in terms of alignment quality and execution speed. With the continuing progress of high-throughput sequencing technologies, read length is constantly increasing and many existing aligners are becoming inefficient as generated reads grow larger. Results: We present CUSHAW2, a parallelized, accurate, and memory-efficient long read aligner. Our aligner is based on the seed-and-extend approach and uses maximal exact matches as seeds to find gapped alignments. We have evaluated and compared CUSHAW2 to the three other long read aligners BWA-SW, Bowtie2 an…
Conformationally Locked Pyramidality Explains the Diastereoselectivity in the Methylation of trans-Fused Butyrolactones
2020
A stereoselectivity model inspired by the total synthesis of stemona alkaloids is developed to explain why enolate-derived 3,4-fused butyrolactones are methylated with a preference for syn alkylation. The model shows how conformational locking present in nonplanar enolate structures favors syn over anti methylation, due to less significant structural distortions in the syn pathway. The developed model was also successfully used to rationalize selectivities of previously documented methylation reactions. peerReviewed
Regioselectivity of the OH Radical Addition to Uracil in Nucleic Acids. A Theoretical Approach Based on QM/MM Simulations.
2017
Oxidation of nucleic acids is ubiquitous in living beings under metabolic impairments and/or exposed to external agents such as radiation, pollutants, or drugs, playing a central role in the development of many diseases mediated by DNA/RNA degeneration. Great efforts have been devoted to unveil the molecular mechanisms behind the OH radical additions to the double bonds of nucleobases; however, the specific role of the biological environment remains relatively unexplored. The present contribution tackles the study of the OH radical addition to uracil from the gas phase to a full RNA macromolecule by means of quantum-chemistry methods combined with molecular dynamics simulations. It is shown…