Shiga toxin (Stx), the unique virulence factor released by enterohemorrhagic Escherichia coli (EHEC), associated with gastrointestinal infection and in severe cases hemolytic uremic syndrome (HUS). Up until now, no effective therapies have been developed to control disease progression. In this thesis, four novel treatment strategies have been investigated targeting different aspects of EHEC pathog

Accelerated economic change in developing countries is rapidly transforming cities; existing urban systems and land-use patterns are poorly adapted to the scale of growth and the spatial restructuring of economic activity. Within this context, the paper assesses the challenges in educating planners in the knowledge and skills needed to deal with these trends. The paper argues for a review of plann

Structural adjustment (SA) — or macroeconomic reform — has become a dominant characteristic especially in developing countries, where national economies are being reshaped to a common discipline regardless of local circumstances. Within this context, the paper examines the impact of structural adjustment on disaster vulnerability in the urban sector, through examining some structural consideration

The interplay between international policies and the interests and internal pressures of the state is examined in the context of project‐based community participation in urban shelter provision in Egypt. Three contrasting upgrading projects are used. Using the concept of interest mediation, the paper argues that, whilst the state may be receptive to external pressure for community participation, t

Linking macro level political economy perspectives with micro level project-based analysis, the paper examines the impact of foreign technical assistance on urban sector projects in Egypt. The paper demonstrates how large aid flows into this sector, following Egypt's Western orientation after 1973, failed to achieve intended results. Three case studies, focusing on community development and partic

OBJECTIVE: The objectives of this study was to establish a sensitive and reproducible method to map the cartilage and subchondral bone proteomes in quantitative terms, and mine the proteomes for proteins of particular interest in the pathogenesis of osteoarthritis (OA). The horse was used as a model animal.DESIGN: Protein was extracted from articular cartilage and subchondral bone samples from thr

Hepatic failure is an important risk factor for poor outcome in septic patients. Using a chemical tagging workflow and high-resolution mass spectrometry, we demonstrate that rapid proteome remodeling of the vascular surfaces precedes hepatic damage in a murine model of Staphylococcus aureus sepsis. These early changes include vascular deposition of neutrophil-derived proteins, shedding of vascular

Many antibiotics inhibit bacterial growth by binding to the ribosome and interfering with protein biosynthesis. Macrolides represent one of the most successful classes of ribosome-targeting antibiotics. The main clinically relevant mechanism of resistance to macrolides is dimethylation of the 23S rRNA nucleotide A2058, located in the drug-binding site, a reaction catalyzed by Erm-type rRNA methylt

Gram-negative bacteria have evolved numerous pathways to secrete proteins across their complex cell envelopes. Here, we describe a protein secretion system that uses a holin membrane protein in tandem with a cell wall-editing enzyme to mediate the secretion of substrate proteins from the periplasm to the cell exterior. The identity of the cell wall-editing enzymes involved was found to vary across

SUMMARY: Analysis of conservation of gene neighbourhoods over different evolutionary levels is important for understanding operon and gene cluster evolution, and predicting functional associations. Our tool FlaGs (standing for Flanking Genes) takes a list of NCBI protein accessions as input, clusters neighbourhood-encoded proteins into homologous groups using sensitive sequence searching, and outp

The type VI nanomachine is critical for Vibrio cholerae to establish infections and to thrive in niches co-occupied by competing bacteria. The genes for the type VI structural proteins are encoded in one large and two small auxiliary gene clusters. VCA0117 (VasH) - a σ54 -transcriptional activator - is strictly required for functionality of the type VI secretion system since it controls production

BACKGROUND: The ribosome translates mRNA to protein with the aid of a number of accessory protein factors. Translational GTPases (trGTPases) are an integral part of the 'core set' of essential translational factors, and are some of the most conserved proteins across life. This study takes advantage of the wealth of available genomic data, along with novel functional information that has come to li

Background: Allergic contact dermatitis from glucose sensors may interfere with their ongoing application. Objective: To evaluate a series of Spanish patients with contact dermatitis to glucose sensors regarding former sources of contact allergens, patch test results, and outcomes from the ongoing use of the device. Methods: A series of patients with contact dermatitis from glucose sensors was inv

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