Ammonium Metabolism Enzymes Aid Helicobacter pylori Acid Resistance

The gastric pathogen Helicobacter pylori possesses a highly active urease to support acid tolerance. Urea hydrolysis occurs inside the cytoplasm, resulting in the production of NH₃ that is immediately protonated to form NH₄⁺. This ammonium must be metabolized or effluxed because its presence within the cell is counterproductive to the goal of raising pH while maintaining a viable proton motive force (PMF). Two compatible hypotheses for mitigating intracellular ammonium toxicity include (i) the exit of protonated ammonium outward via the UreI permease, which was shown to facilitate diffusion of both urea and ammonium, and/or (ii) the assimilation of this ammonium, which is supported by evidence that H. pylori assimilates urea nitrogen into its amino acid pools. We investigated the second hypothesis by constructing strains with altered expression of the ammonium-assimilating enzymes glutamine synthetase (GS) and glutamate dehydrogenase (GDH) and the ammonium-evolving periplasmic enzymes glutaminase (Ggt) and asparaginase (AsnB). H. pylori strains expressing elevated levels of either GS or GDH are more acid tolerant than the wild type, exhibit enhanced ammonium production, and are able to alkalize the medium faster than the wild type. Strains lacking the genes for either Ggt or AsnB are acid sensitive, have 8-fold-lower urea-dependent ammonium production, and are more acid sensitive than the parent. Additionally, we found that purified H. pylori GS produces glutamine in the presence of Mg²⁺ at a rate similar to that of unadenylated Escherichia coli GS. These data reveal that all four enzymes contribute to whole-cell acid resistance in H. pylori and are likely important for assimilation and/or efflux of urea-derived ammonium.     

Amyloid-β Peptide-specific DARPins as a Novel Class of Potential Therapeutics for Alzheimer Disease

Passive immunization with anti-amyloid-β peptide (Aβ) antibodies is effective in animal models of Alzheimer disease. With the advent of efficient in vitro selection technologies, the novel class of designed ankyrin repeat proteins (DARPins) presents an attractive alternative to the immunoglobulin scaffold. DARPins are small and highly stable proteins with a compact modular architecture ideal for high affinity protein-protein interactions. In this report, we describe the selection, binding profile, and epitope analysis of Aβ-specific DARPins. We further showed their ability to delay Aβ aggregation and prevent Aβ-mediated neurotoxicity in vitro. To demonstrate their therapeutic potential in vivo, mono- and trivalent Aβ-specific DARPins (D23 and 3×D23) were infused intracerebroventricularly into the brains of 11-month-old Tg2576 mice over 4 weeks. Both D23 and 3×D23 treatments were shown to result in improved cognitive performance and reduced soluble Aβ levels. These findings demonstrate the therapeutic potential of Aβ-specific DARPins for the treatment of Alzheimer disease.     

Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate cancer associated SNPs for familial disease

Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case–control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p ≤ 1E ^?3) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may contribute risk to aggressive disease.     

Vegetation patterns of floodplain meadows along the climatic gradient at the Middle Elbe River

Central European floodplain meadows are characterised by flooding mainly in winter/spring and dry conditions over the summer. They harbour many rare and endangered plant species. We studied the vegetation of floodplain meadows along the regional climatic gradient of the Middle Elbe River. This gradient exhibits rather continental conditions in the south-east and oceanic conditions in the north-west. We aimed at detecting the influence of climate on the vegetation of floodplain meadows along this gradient.     

Improved appreciation of the functioning and importance of biological soil crusts in Europe: the Soil Crust International Project (SCIN)

Here we report details of the European research initiative “Soil Crust International” (SCIN) focusing on the biodiversity of biological soil crusts (BSC, composed of bacteria, algae, lichens, and bryophytes) and on functional aspects in their specific environment. Known as the so-called “colored soil lichen community” (Bunte Erdflechtengesellschaft), these BSCs occur all over Europe, extending into subtropical and arid regions. Our goal is to study the uniqueness of these BSCs on the regional scale and investigate how this community can cope with large macroclimatic differences. One of the major aims of this project is to develop biodiversity conservation and sustainable management strategies for European BSCs. To achieve this, we established a latitudinal transect from the Great Alvar of Öland, Sweden in the north over Gössenheim, Central Germany and Hochtor in the Hohe Tauern National Park, Austria down to the badlands of Tabernas, Spain in the south. The transect stretches over 20° latitude and 2,300 m in altitude, including natural (Hochtor, Tabernas) and semi-natural sites that require maintenance such as by grazing activities (Öland, Gössenheim). At all four sites BSC coverage exceeded 30 % of the referring landscape, with the alpine site (Hochtor) reaching the highest cyanobacterial cover and the two semi-natural sites (Öland, Gössenheim) the highest bryophyte cover. Although BSCs of the four European sites share a common set of bacteria, algae (including cyanobacteria) lichens and bryophytes, first results indicate not only climate specific additions of species, but also genetic/phenotypic uniqueness of species between the four sites. While macroclimatic conditions are rather different, microclimatic conditions and partly soil properties seem fairly homogeneous between the four sites, with the exception of water availability. Continuous activity monitoring of photosystem II revealed the BSCs of the Spanish site as the least active in terms of photosynthetic active periods.     

Emotional Reactions of Mothers Facing Premature Births: Study of 100 Mother-Infant Dyads 32 Gestational Weeks

Objectives

This current study has been conducted to clarify the relationship between the mother''s post-traumatic reaction triggered by premature birth and the mother-infant interactions. In this article, the precocious maternal feelings are described.

Methods

A multicenter prospective study was performed in three French hospitals. 100 dyads with 100 very premature infants and their mothers were recruited. Mothers completed, at two different times self-questionnaires of depression/anxiety, trauma and social support. The quality of interactions in the dyads was evaluated.

Results

Thirty-nine percent of the mothers obtained a score at HADS suggesting a high risk of depression at the first visit and approximately one-third at visit two. Seventy-five percent of the mothers were at risk of suffering from an anxiety disorder at visit one and half remained so at visit two. A “depressed” score at visits one and two correlated with a hospitalization for a threatened premature labor. We noted a high risk of trauma for 35% of the mothers and high interactional synchrony was observed for approximately two-thirds of the dyads. The mothers'' psychological reactions such as depression and anxiety or postnatal depression correlate strongly with the presence of an initial trauma. At visit one and visit two, a high score of satisfaction concerning social support correlates negatively with presence of a trauma. A maternal risk of trauma is more frequent with a C-section delivery.

Conclusions

Mothers'' psychological reactions such as depression and anxiety correlate greatly with the presence of an initial trauma. The maternal traumatic reaction linked to premature birth does not correlate with the term at birth, but rather with the weight of the baby. Social support perceived by the mother is correlated with the absence of maternal trauma before returning home, and also seems to inhibit from depressive symptoms from the time of the infant''s premature birth.