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Translation arrest directed by nascent peptides and small cofactors controls expression of important bacterial and eukaryotic genes, including antibiotic resistance genes, activated by binding of macrolide drugs to the ribosome. Previous studies suggested that specific interactions between the nascent peptide and the antibiotic in the ribosomal exit tunnel play a central role in triggering ribosom
Bacterial ribosomes stall on polyproline stretches and require the elongation factor P (EF-P) to relieve the arrest. Yet it remains unclear why evolution has favored the development of EF-P rather than selecting against the occurrence of polyproline stretches in proteins. We have discovered that only a single polyproline stretch is invariant across all domains of life, namely a proline triplet in
Ribosomes are the protein synthesizing factories of the cell, polymerizing polypeptide chains from their constituent amino acids. However, distinct combinations of amino acids, such as polyproline stretches, cannot be efficiently polymerized by ribosomes, leading to translational stalling. The stalled ribosomes are rescued by the translational elongation factor P (EF-P), which by stimulating pepti
The cfr gene encodes the Cfr methyltransferase that primarily methylates C-8 in A2503 of 23S rRNA in the peptidyl transferase region of bacterial ribosomes. The methylation provides resistance to six classes of antibiotics of clinical and veterinary importance. The rlmN gene encodes the RlmN methyltransferase that methylates C-2 in A2503 in 23S rRNA and A37 in tRNA, but RlmN does not significantly
The polymerization of amino acids into proteins occurs on ribosomes, with the rate influenced by the amino acids being polymerized. The imino acid proline is a poor donor and acceptor for peptide-bond formation, such that translational stalling occurs when three or more consecutive prolines (PPP) are encountered by the ribosome. In bacteria, stalling at PPP motifs is rescued by the elongation fact
Lys34 of the conserved translation elongation factor P (EF-P) is post-translationally lysinylated by YjeK and YjeA--a modification that is critical for bacterial virulence. Here we show that the currently accepted Escherichia coli EF-P modification pathway is incomplete and lacks a final hydroxylation step mediated by YfcM, an enzyme distinct from deoxyhypusine hydroxylase that catalyzes the final
Analyses of multiple sequence alignments generally focus on well-defined conserved sequence blocks, while the rest of the alignment is largely ignored or discarded. This is especially true in phylogenomics, where large multigene datasets are produced through automated pipelines. However, some of the most powerful phylogenetic markers have been found in the variable length regions of multiple align
Protein synthesis elongation factor G (EF-G) is an essential protein with central roles in both the elongation and ribosome recycling phases of protein synthesis. Although EF-G evolution is predicted to be conservative, recent reports suggest otherwise. We have characterized EF-G in terms of its molecular phylogeny, genomic context, and patterns of amino acid substitution. We find that most bacter
Virtual clinical trials (VCTs) can be used to evaluate and optimise medical imaging systems. VCTs are based on computer simulations of human anatomy, imaging modalities and image interpretation. OpenVCT is an open-source framework for conducting VCTs of medical imaging, with a particular focus on breast imaging. The aim of this paper was to evaluate the OpenVCT framework in two tasks involving dig
Twenty-first-century politics have been defined by celebrity leaders such as Tony Blair, Gerhard Schröder, and Barack Obama. How have ‘traditional’ politicians like ‘Mutti Merkel’, who embody the opposite of star status, still managed to compete with these celebrity politicians in an attention economy in which politicians continuously vie for media exposure? Scholarship on concepts such as ‘mediat
The nanowire geometry is favorable for the growth of ternary semiconductor materials, because the composition and properties can be tuned freely without substrate lattice matching. To achieve precise control of the composition in ternary semiconductor nanowires, a deeper understanding of the growth is required. One unknown aspect of seeded nanowire growth is how the composition of the catalyst nan
Background: To examine the effects of different stages of visual field loss (VFL) from advanced glaucoma on performance in a driving simulator. Methods: Data on performance and safety from a traffic simulator test for 104 participants with withdrawn driver’s licences due to visual field loss from advanced glaucoma were compared with data from 83 individuals without visual deficits in a cross-secti
A new hard-shelled sea turtle (Pan-Cheloniidae) with vestigial soft tissues from the lower Eocene (Ypresian) Fur Formation of Denmark is described and illustrated. The fossil (DK 807) comprises a partial, yet fully articulated carapace (estimated original length ∼50 cm) where the individual bones mostly are preserved in three dimensions, together with an intact sacrum, a consecutive series of arti
A rare fossiliferous site in Willacy County, Texas, contains a mass concentration of fossil Giant Gopher Tortoises (Gopherus hexagonatus). The site southeast of Raymondville was exposed in the late 1980s during archaeological surveys for drainage canal improvements. Numerous large adults with complete shells were recovered along with partial limb, cranial, and vertebral elements. Especially remark
