Seroprevalence and risk factors for Helicobacter pylori infection in Greenlanders

BACKGROUND: In contrast to most populations worldwide, the incidence of gastric cancer increases among Inuit in Greenland. Contributing factors to this increase are unknown, but Helicobacter pylori may be involved. However, little is known regarding the epidemiology of H. pylori in Arctic communities. With the aim of determining age-specific prevalence, risk factors, and association with clinical conditions of H. pylori infection, we carried out a population-based study of H. pylori in Sisimiut, the second biggest town of Greenland. MATERIALS AND METHODS: A population-based sample of 685 persons had serum drawn that was analyzed for H. pylori IgG antibodies using enzyme-linked immunosorbent assay (ELISA). Risk factors analyses were carried out using multivariate logistic regression models. RESULTS: The seroprevalence was lowest among children aged 0-4 years (6%), but increased rapidly thereafter. In persons aged 15-87 years the seroprevalence had stabilized around 58%. Total number of children in household, number of older, but not younger, siblings and narrow age gap to closest older sibling were associated with H. pylori seropositivity. In contrast, number of adults in household and socioeconomic status did not influence serostatus. CONCLUSIONS: The age-specific prevalence pattern in Greenland is intermediate between that of developing and developed countries. The risk factor pattern indicates crowding and older siblings in particular to be key elements in risk of infection.     

Second intermediate host land snails and definitive host animals of Brachylaima cribbi in southern Australia

This study of infection of southern Australian land snails with Brachylaima cribbi metacercariae has shown that all commonly encountered native and introduced snails are susceptible second intermediate hosts. The range of infected snails is extensive with metacercariae-infected snails being present in all districts across southern Australia. C. virgata has the highest average natural metacercarial infection intensity of 6.1 metacercariae per infected snail. The susceptibility of birds, mammals and reptiles to B. cribbi infection was studied in South Australia by capturing, dissecting and examining the intestinal tract contents of animals which commonly eat land snails as a food source. Indigenous Australian little ravens (Corvus mellori), which are a common scavenger bird, and two other passeriform birds, the black bird (Turdus merula) and the starling (Sturnus vulgaris), which are both introduced European birds, were found to have the highest infection rates of all animals examined. Other birds found infected with B. cribbi were an emu (Dromaius novaehollandiae), chickens (Gallus gallus) and a pigeon (Columba livia). Natural infections were also detected in field mice (Mus domesticus) and shingleback lizards (Tiliqua rugosa) although the intensity of infection was lower than that observed in birds. Susceptibility studies of laboratory mice, rats and ducks showed that mice developed patent infections which persisted for several weeks, rats developed a short-lived infection of three weeks' duration and ducks did not support infection. This study has shown for the first time that a brachylaimid can infect a wide host range of birds, mammals and reptiles in nature.     

Histone-like protein HU from Deinococcus radiodurans binds preferentially to four-way DNA junctions

The histone-like protein HU from Escherichia coli is involved in DNA compaction and in processes such as DNA repair and recombination. Its participation in these events is reflected in its ability to bend DNA and in its preferred binding to DNA junctions and DNA with single-strand breaks. Deinococcus radiodurans is unique in its ability to reconstitute its genome from double strand breaks incurred after exposure to ionizing radiation. Using electrophoretic mobility shift assays (EMSA), we show that D.radiodurans HU (DrHU) binds preferentially only to DNA junctions, with half-maximal saturation of 18 nM. In distinct contrast to E.coli HU, DrHU does not exhibit a marked preference for DNA with nicks or gaps compared to perfect duplex DNA, nor is it able to mediate circularization of linear duplex DNA. These unexpected properties identify DrHU as the first member of the HU protein family not to serve an architectural role and point to its potential participation in DNA recombination events. Our data also point to a mechanism whereby differential target site selection by HU proteins is achieved and suggest that the substrate specificity of HU proteins should be expected to vary as a consequence of their individual capacity for inducing the required DNA bend.     

Quantitative investigation of antigen and immune response in nervous and lymphoid tissues of Atlantic halibut (Hippoglossus hippoglossus) challenged with nodavirus

The present study reports the quantitative analysis of the spatio-temporal development of nodavirus infection and corresponding immune response in juvenile Atlantic halibut (Hippoglossus hippoglossus) challenged by intramuscular injection of nodavirus. Novel quantitative real-time RT-PCR protocols were applied to evaluate the absolute copy numbers of nodavirus RNA2 (RNA2) and secretory-IgM mRNA (sec-igmicro) in the eye, brain, mid/posterior kidney and spleen sampled over a period of 81 days. In the eye and brain, levels of both RNA2 and sec-igmicro increased significantly early in the infection. In the spleen and mid/posterior kidney, both RNA2 and sec-igmicro were detected but the levels remained unchanged during the experimental period. The levels of RNA2 and sec-igmicro in the eye and brain were strongly correlated (P<0.0001). Nodavirus antigen was demonstrated by immunohistochemistry (IHC) in the retina of eyes from a relatively few fish from day 34 post challenge (brain not examined), but not at any time in the spleen and anterior kidney. By IHC, IgM+ cells were observed in conjunction with nodavirus positive IHC labelling in the retina. In both the spleen and anterior kidney, the number of IgM+ cells increased from day 3 post challenge. By conventional real-time RT-PCR, RNA2 was only sporadically demonstrated in the posterior intestine, heart and gills. ELISA analysis revealed a nodavirus specific antibody response in serum that was significant from day 18 post challenge. No clinical signs or mortality related to nodavirus infection were observed in the challenged halibut. The results suggest that the nodavirus infection induced a significant antibody response through activation of B-cells in the kidney and spleen, and involved a substantial migration of antibody-secreting cells to infected peripheral tissues.     

Stimulation of the Streptococcus pneumoniae RecA protein-promoted three-strand exchange reaction by the competence-specific SsbB protein

The effect of the transformational competence-specific Streptococcus pneumoniae single-stranded DNA binding protein, SpSsbB, on the ATP-dependent three-strand exchange activity of the SpRecA protein was investigated. Although SpRecA exhibited only a trace level of strand exchange activity in the absence of SpSsbB, an extensive strand exchange reaction was observed when SpSsbB was added to the reaction solution after SpRecA. A more limited strand exchange reaction was observed, however, when SpSsbB was added to the reaction solution before SpRecA. This dependence on the order of addition, together with additional DNA-dependent ATP hydrolysis experiments, indicated that the mechanism of stimulation may involve the postsynaptic binding of SpSsbB to the displaced linear single-stranded DNA reaction product. When dATP was provided in place of ATP as the nucleotide cofactor (to suppress a potentially inhibitory effect of SpSsbB on the interaction of SpRecA with the circular ssDNA reaction substrate), the stimulatory effect of SpSsbB on the strand exchange reaction was apparent regardless of the order in which it was added to the reaction solution. These findings suggest that SpSsbB may be able to facilitate SpRecA-promoted DNA recombination reactions during natural transformation in S. pneumoniae.     

Metal Binding at the Deinococcus radiodurans Dps-1 N-Terminal Metal Site Controls Dodecameric Assembly and DNA Binding

The prokaryotic DNA protection during starvation (Dps) proteins typically protect macromolecules against damaging agents via physical association with DNA and by oxidizing and sequestering iron. However, Deinococcus radiodurans Dps-1, which binds DNA with high affinity, fails to protect DNA against hydroxyl radicals due to iron leakage from the core, raising the question of how (?)OH-mediated damage to Dps-1-bound DNA is avoided. As shown here, Mn(II) inhibits ferroxidase activity, suggesting that ferroxidation may be prevented in vivo as D. radiodurans accumulates a high ratio of Mn:Fe. Dps-1 has an N-terminal extension with a unique metal-binding site, an extension that has been proposed to be important for DNA binding and dodecameric assembly. Electrophoretic mobility shift assays show that Mn(II) restores DNA binding to bipyridyl-treated Dps-1, whereas Fe(II) fails to do so in the presence of H(2)O(2), thus preventing DNA binding under conditions of ongoing ferroxidase activity. We also show that disruption of the N-terminal metal site leads to a significant reduction in DNA binding and to compromised oligomeric assembly, with the mutant protein assembling into a hexamer in the presence of divalent metal. We propose that securing the N-terminal loop by metal binding is required to initiate dodecameric assembly by contacting the neighboring dimer and that the absence of such optimal contacts results in formation of a hexameric assembly intermediate in which three dimers associate about one of the 3-fold axes. Once dodecameric Dps-1 is assembled, metal binding no longer affects oligomeric state; instead, differential metal binding controls DNA interaction under conditions of oxidative stress.     

New materials from proteins and peptides

In this review we highlight recent accomplishments in the design of materials from proteins and peptides. Examples include hydrogels made from aggregating designed β-hairpin peptides, whose physical properties respond to small changes in the amino acid composition of the peptide; materials that combine different segments of natural elastomeric proteins - such as elastin, resilin, silk fibroin whose bulk properties are dictated in unanticipated ways by their composition; and hydrogels formed by strings or arrays of protein modules, which are cross-linked by multivalent versions of their peptide ligands, and which may exhibit exquisite stimuli-responsive behavior. The suitability of the unique properties of such new materials for practical applications is also considered.