Virtual-pion and two-photon production in pp scattering

Two-photon production in pp scattering is proposed as a means of studying virtual-pion emission. Such a process is complementary to real-pion emission in pp scattering. The virtual-pion signal is embedded in a background of double-photon bremsstrahlung. We have developed a model to describe this background process and show that in certain parts of phase space the virtual-pion signal gives significant contribution. In addition, through interference with the two-photon bremsstrahlung background, one can determine the relative phase of the virtual-pion process

Cellular Notch responsiveness is defined by phosphoinositide 3-kinase-dependent signals

<p>Abstract</p> <p>Background</p> <p>Notch plays a wide-ranging role in controlling cell fate, differentiation and development. The PI3K-Akt pathway is a similarly conserved signalling pathway which regulates processes such as differentiation, proliferation and survival. Mice with disrupted Notch and PI3K signalling show phenotypic similarities during haematopoietic cell development, suggesting functional interaction between these pathways.</p> <p>Results</p> <p>We show that cellular responsiveness to Notch signals depends on the activity of the PI3K-Akt pathway in cells as diverse as CHO cells, primary T-cells and hippocampal neurons. Induction of the endogenous PI3K-Akt pathway in CHO cells (by the insulin pathway), in T-cells (via TCR activation) or in neurons (via TrKB activation) potentiates Notch-dependent responses. We propose that the PI3K-Akt pathway exerts its influence on Notch primarily via inhibition of GSK3-beta, a kinase known to phosphorylate and regulate Notch signals.</p> <p>Conclusion</p> <p>The PI3K-Akt pathway acts as a "gain control" for Notch signal responses. Since physiological levels of intracellular Notch are often low, coincidence with PI3K-activation may be crucial for induction of Notch-dependent responses.</p

A Network Analysis of the Human T-Cell Activation Gene Network Identifies Jagged1 as a Therapeutic Target for Autoimmune Diseases

Understanding complex diseases will benefit the recognition of the properties of the gene networks that control biological functions. Here, we set out to model the gene network that controls T-cell activation in humans, which is critical for the development of autoimmune diseases such as Multiple Sclerosis (MS). The network was established on the basis of the quantitative expression from 104 individuals of 20 genes of the immune system, as well as on biological information from the Ingenuity database and Bayesian inference. Of the 31 links (gene interactions) identified in the network, 18 were identified in the Ingenuity database and 13 were new and we validated 7 of 8 interactions experimentally. In the MS patients network, we found an increase in the weight of gene interactions related to Th1 function and a decrease in those related to Treg and Th2 function. Indeed, we found that IFN-ß therapy induces changes in gene interactions related to T cell proliferation and adhesion, although these gene interactions were not restored to levels similar to controls. Finally, we identify JAG1 as a new therapeutic target whose differential behaviour in the MS network was not modified by immunomodulatory therapy. In vitro treatment with a Jagged1 agonist peptide modulated the T-cell activation network in PBMCs from patients with MS. Moreover, treatment of mice with experimental autoimmune encephalomyelitis with the Jagged1 agonist ameliorated the disease course, and modulated Th2, Th1 and Treg function. This study illustrates how network analysis can predict therapeutic targets for immune intervention and identified the immunomodulatory properties of Jagged1 making it a new therapeutic target for MS and other autoimmune diseases

Intraspecific Variation and Interspecific Differences in the Bacterial and Fungal Assemblages of Blue Tit (Cyanistes caeruleus) and Great Tit (Parus major) Nests

Although interest in the relationship between birds and microorganisms is increasing, few studies have compared nest microbial assemblages in wild passerines to determine variation within and between species. Culturing microorganisms from blue tit (Cyanistes caeruleus) and great tit (Parus major) nests from the same study site demonstrated diverse microbial communities with 32 bacterial and 13 fungal species being isolated. Dominant bacteria were Pseudomonas fluorescens, Pseudomonas putida, and Staphylococcus hyicus. Also common in the nests were the keratinolytic bacteria Pseudomonas stutzeri and Bacillus subtilis. Dominant fungi were Cladosporium herbarum and Epicoccum purpurascens. Aspergillus flavous, Microsporum gallinae, and Candida albicans (causative agents of avian aspergillosis, favus, and candidiasis, respectively) were present in 30%, 25%, and 10% of nests, respectively. Although there were no differences in nest mass or materials, bacterial (but not fungal) loads were significantly higher in blue tit nests. Microbial species also differed interspecifically. As regards potential pathogens, the prevalence of Enterobacter cloacae was higher in blue tit nests, while Pseudomonas aeruginosa—present in 30% of blue tit nests—was absent from great tit nests. The allergenic fungus Cladosporium cladosporioides was both more prevalent and abundant in great tit nests. Using discriminant function analysis (DFA), nests were classified to avian species with 100% accuracy using the complete microbial community. Partial DFA models were created using a reduced number of variables and compared using Akaike’s information criterion on the basis of model fit and parsimony. The best models classified unknown nests with 72.5–95% accuracy using a small subset of microbes (n = 1–8), which always included Pseudomonas agarici. This suggests that despite substantial intraspecific variation in nest microflora, there are significant interspecific differences—both in terms of individual microbes and the overall microbial community—even when host species are closely related, ecologically similar, sympatric, and construct very similar nests

Differences in Culturable Microbial Communities in Bird Nestboxes According to Orientation and Influences on Offspring Quality in Great Tits (Parus major)

Although bird–microbial interactions have become a topic of increasing research, the influence of nest-site characteristics, such as cavity orientation, on nest microbial communities in free-living passerines has not, to our knowledge, been investigated. This is despite the possibility of microbial differences explaining non-random patterns in nest-site selection and offspring quality, such as those exhibited by great tits (Parus major). We swabbed great tit nestboxes that faced either south–southwest (180–269°) or north–northeast (0–89°). Overall, 28 bacterial species and 11 fungal species were isolated, but the culturable microbial community differed substantially between different orientations—indeed nestboxes could be classified to their orientation group with high accuracy using microbial data. Nestboxes facing south–southwest had a significantly higher fungal load (typically double) than those facing north–northeast due to a higher abundance of two species, Epicoccum purpurascens and Cladosporium cladosporioides. There was no relationship between total bacterial load and orientation, although the abundance of one species, Pseudomonas veronii, was significantly lower in south–southwest boxes. The abundance of the allergen E. purpurascens explained almost 20% of the variation in offspring quality, being significantly and inversely related to chick size (high loads associated with small, poor quality, chicks). Our results provide empirical evidence for a correlation between nestbox orientation and culturable microbial load and a further correlation between abundance of one species, E. purpurascens, and offspring quality. Thus, microbial load, which is itself influenced by nest cavity parameters, could be the proximate factor that influences nest-site choice through its effect on offspring quality (and thus, overall fecundity)

Characterization of AmpC-Mediated Resistance in Clinical Salmonella Isolates Recovered from Humans during the Period 1992 to 2003 in England and Wales

The increase in AmpC-mediated resistance in salmonellae constitutes a serious public health concern, since these enzymes confer resistance to a wide range of β-lactams. One hundred six isolates were selected from 278,308 Salmonella isolates based on resistance to ampicillin and cephalosporins and were subjected to further characterization. Nine isolates had a cefoxitin inhibition diameter ≤17 mm and were proven to be AmpC positive by multiplex PCR. Sequence analysis revealed the presence of bla(DHA-1), bla(CMY-2), and bla(CMY-4) genes. All nine isolates presented different pulsed-field gel electrophoresis restriction profiles. The AmpC genetic determinants were present in transferable plasmids of around 11, 42, 70, 98, and 99 MDa. A combination of size and restriction fragment length polymorphism (RFLP) analysis showed that all the bla(CMY) plasmids investigated in our study were different, which suggests that bla(CMY) may be located in different plasmid environments. Some United Kingdom isolates linked to foreign travel showed RFLP plasmid patterns consistent with plasmids previously seen in the United States, which suggests that bla(CMY-2) has also been disseminated through plasmid transfer. The fact that two of the domestically acquired United Kingdom isolates presented previously unseen RFLP plasmid patterns could indicate that these strains have followed routes different from those prevalent in North America or other parts of the world. This study represents the first report of bla(CMY) genes in Salmonella isolates in the United Kingdom and the first report of CMY-4 in Salmonella enterica serotype Senftenberg worldwide

Comparative mesocosm study of biostimulation efficiency in two different oil-amended sub-antarctic soils

Biological treatment has become increasingly popular as a remediation method for soils and groundwater contaminated with petroleum hydrocarbon, chlorinated solvents, and pesticides. Bioremediation has been considered for application in cold regions such as Arctic and sub-Arctic climates and Antarctica. Studies to date suggest that indigenous microbes suitable for bioremediation exist in soils in these regions. This paper reports on two case studies at the sub-Antarctic Kerguelen Island, in which indigenous bacteria were found that were capable of mineralizing petroleum hydrocarbons in soil contaminated with crude oil and diesel fuel. All results demonstrate a serious influence of the soil properties on the biostimulation efficiency. Both temperature elevation and fertilizer addition have a more significant impact on the microbial assemblages in the mineral soil than in the organic one. Analysis of the hydrocarbons remaining at the end of the experiments confirmed the bacterial observations. Optimum temperature seems to be around 10°C in organic soil while it was higher in mineral soil. The benefit of adding nutrient was much stronger in mineral than in the organic soil. Overall, this study suggests on the basis of microbiological and physicochemical parameters, that biostimulation treatments were driven by soil properties and that ex-situ bioremediation for treatment of cold contaminated soils will allow greater control over soil temperature, a limiting factor in cold climates.French Polar Institute (IPEV) and EU project FaceiT (Fast Advanced Cellular and Ecosystems Information Technologies [STREP grant no 018391 (COGE)

Fear of hypoglycaemia in parents of young children with type 1 diabetes : a systematic review

Background Many children with type 1 diabetes have poor glycaemic control. Since the Diabetes Control and Complications Trial (DCCT) showed that tighter control reduces complication rates, there has been more emphasis on intensified insulin therapy. We know that patients and families are afraid of hypoglycaemia. We hypothesised that fear of hypoglycaemia might take precedence over concern about long-term complications, and that behaviour to avoid hypoglycaemia might be at the cost of poorer control, and aimed to evaluate the effectiveness of any interventions designed to prevent that. The objective of this review was to systematically review studies concerning the extent and consequences of fear of hypoglycaemia in parents of children under 12 years of age with type 1 diabetes, and interventions to reduce it. Methods Data Sources: MEDLINE, EMBASE, PsycINFO, The Cochrane Library, Web of Science, meeting abstracts of EASD, ADA and Diabetes UK, Current Controlled Trials, ClinicalTrials.gov, UK CRN, scrutiny of bibliographies of retrieved papers and contact with experts in the field. Inclusions: Relevant studies of any design of parents of children under 12 years of age with Type 1 diabetes were included. The key outcomes were the extent and impact of fear, hypoglycaemia avoidance behaviour in parents due to parental fear of hypoglycaemia in their children, the effect on diabetes control, and the impact of interventions to reduce this fear and hypoglycaemia avoidance behaviour. Results Eight articles from six studies met the inclusion criteria. All were cross sectional studies and most were of good quality. Parental fear of hypoglycaemia, anxiety and depression were reported to be common. There was a paucity of evidence on behaviour to avoid hypoglycaemia, but there were some suggestions that higher than desirable blood glucose levels might be permitted in order to avoid hypoglycaemia. No studies reporting interventions to reduce parental fear of hypoglycaemia were found. Conclusions The evidence base was limited. Parents of children with Type 1 diabetes reported considerable parental fear of hypoglycaemia, affecting both parental health and quality of life. There is some suggestion that hypoglycaemia avoidance behaviours by parents might adversely affect glycaemic control. Trials of interventions to reduce parental anxiety and hypoglycaemia avoidance behaviour are needed. We suggest that there should be a trial of structured education for parents of young children with Type 1 diabetes