Synthesis of human amyloid restricted to liver results in an Alzheimer disease-like neurodegenerative phenotype.

Several lines of study suggest that peripheral metabolism of amyloid beta (Aß) is associated with risk for Alzheimer disease (AD). In blood, greater than 90% of Aß is complexed as an apolipoprotein, raising the possibility of a lipoprotein-mediated axis for AD risk. In this study, we report that genetic modification of C57BL/6J mice engineered to synthesise human Aß only in liver (hepatocyte-specific human amyloid (HSHA) strain) has marked neurodegeneration concomitant with capillary dysfunction, parenchymal extravasation of lipoprotein-Aß, and neurovascular inflammation.

Role of the Transporter-Like Sensor Kinase CbrA in Histidine Uptake and Signal Transduction.

Unlabelled: CbrA is an atypical sensor kinase found in Pseudomonas. The autokinase domain is connected to a putative transporter of the sodium/solute symporter family (SSSF). CbrA functions together with its cognate response regulator, CbrB, and plays an important role in nutrient acquisition, including regulation of hut genes for the utilization of histidine and its derivative, urocanate.

Phase-variable restriction/modification systems are required for Helicobacter pylori colonization.

Background: One mechanism utilized by bacterial pathogens for host adaptation and immune evasion is the generation of phenotypic diversity by the phasevarion that results from the differential expression of a suite of genes regulated by the activity of a phase-variable methyltransferase within a restriction modification (RM) system. Phasevarions are active in Helicobacter pylori, however there have been no studies investigating the significance of phase-variable RM systems on host colonization.

Methods: Two mutant types incapable of phase variation were constructed; a clean deletion mutant ('DEL') and a mutant ('ON') where the homopolymeric repeat was replaced with a non-repeat synonymous sequence, resulting in expression of the full-length protein.

Xer-cise in Helicobacter pylori: one-step transformation for the construction of markerless gene deletions.

Background: Xer-cise is an efficient selectable marker removal technique that was first applied in Bacillus subtilis and Escherichia coli for the construction of markerless gene deletions. Xer-cise marker excision takes advantage of the presence of site-specific Xer recombination in most bacterial species for the resolution of chromosome dimers at the dif site during replication. The identification and functional characterization of the difH/XerH recombination system enabled the development of Xer-cise in Helicobacter pylori.

Xer recombinase and genome integrity in Helicobacter pylori, a pathogen without topoisomerase IV.

In the model organism E. coli, recombination mediated by the related XerC and XerD recombinases complexed with the FtsK translocase at specialized dif sites, resolves dimeric chromosomes into free monomers to allow efficient chromosome segregation at cell division. Computational genome analysis of Helicobacter pylori, a slow growing gastric pathogen, identified just one chromosomal xer gene (xerH) and its cognate dif site (difH).

Variation in transport explains polymorphism of histidine and urocanate utilization in a natural Pseudomonas population.

Phenotypic variation is a fundamental requirement for evolution by natural selection. While evidence of phenotypic variation in natural populations abounds, its genetic basis is rarely understood. Here we report variation in the ability of plant-colonizing Pseudomonas to utilize histidine, and its derivative, urocanate, as sole sources of carbon and nitrogen.

Molecular analysis of BcrR, a membrane-bound bacitracin sensor and DNA-binding protein from Enterococcus faecalis.

BcrR has been identified as a novel regulatory protein of high level bacitracin resistance encoded by the bcrABD operon in Enterococcus faecalis. The N-terminal domain of BcrR has similarity to the helix-turn-helix motif of DNA-binding proteins, and topological modeling predicts that the C-terminal domain contains four transmembrane alpha-helices. These data have led to the hypothesis that BcrR functions as both a membrane-bound sensor and transducer of bacitracin availability to regulate bcrABD expression.