Relative Contribution of P5 and Hap Surface Proteins to Nontypable Haemophilus influenzae Interplay with the Host Upper and Lower Airways

Nontypable Haemophilus influenzae (NTHi) is a major cause of opportunistic respiratory tract disease, and initiates infection by colonizing the nasopharynx. Bacterial surface proteins play determining roles in the NTHi-airways interplay, but their specific and relative contribution to colonization and infection of the respiratory tract has not been addressed comprehensively. In this study, we focused on the ompP5 and hap genes, present in all H. influenzae genome sequenced isolates, and encoding the P5 and Hap surface proteins, respectively. We employed isogenic single and double mutants of the ompP5 and hap genes generated in the pathogenic strain NTHi375 to evaluate P5 and Hap contribution to biofilm growth under continuous flow, to NTHi adhesion, and invasion/phagocytosis on nasal, pharyngeal, bronchial, alveolar cultured epithelial cells and alveolar macrophages, and to NTHi murine pulmonary infection. We show that P5 is not required for bacterial biofilm growth, but it is involved in NTHi interplay with respiratory cells and in mouse lung infection. Mechanistically, P5NTHi375 is not a ligand for CEACAM1 or α5 integrin receptors. Hap involvement in NTHi375-host interaction was shown to be limited, despite promoting bacterial cell adhesion when expressed in H. influenzae RdKW20. We also show that Hap does not contribute to bacterial biofilm growth, and that its absence partially restores the deficiency in lung infection observed for the ΔompP5 mutant. Altogether, this work frames the relative importance of the P5 and Hap surface proteins in NTHi virulence.

Adjustment to inflammatory bowel disease: The relative influence of illness perceptions and coping

Background: The Common Sense Model (CSM) of illness representations was used in the current study to examine the relative contribution of illness perceptions and coping strategies in explaining adjustment to inflammatory bowel disease (IBD). Methods: Participants were 80 adults consecutively attending an outpatients' clinic with a diagnosis of either Crohn's disease or ulcerative colitis. Respondents completed and returned a questionnaire booklet that assessed illness perceptions, coping, and adjustment. Adjustment was measured from the perspectives of psychological distress, quality of life, and functional independence. Results: Illness perceptions (particularly perception of consequences of IBD) were uniformly the most consistent variables explaining adjustment to IBD. Coping did not significantly add to predicting adjustment once illness perceptions were controlled for and therefore did not mediate the relationship between illness perceptions and adjustment, as proposed in the CSM. Conclusions: The results suggest the importance of addressing illness perceptions in developing appropriate psychological interventions for IBD.

Relative contributions of lipooligosaccharide inner and outer core modifications to nontypeable Haemophilus influenzae pathogenesis

Nontypeable Haemophilus influenzae (NTHi) is a frequent commensal of the human nasopharynx that causes opportunistic infection in immunocompromised individuals. Existing evidence associates lipooligosaccharide (LOS) with disease, but the specific and relative contributions of NTHi LOS modifications to virulence properties of the bacterium have not been comprehensively addressed. Using NTHi strain 375, an isolate for which the detailed LOS structure has been determined, we compared systematically a set of isogenic mutant strains expressing sequentially truncated LOS. The relative contributions of 2-keto-3-deoxyoctulosonic acid, the triheptose inner core, oligosaccharide extensions on heptoses I and III, phosphorylcholine, digalactose, and sialic acid to NTHi resistance to antimicrobial peptides (AMP), self-aggregation, biofilm formation, cultured human respiratory epithelial infection, and murine pulmonary infection were assessed. We show that opsX, lgtF, lpsA, lic1, and lic2A contribute to bacterial resistance to AMP; lic1 is related to NTHi self-aggregation; lgtF, lic1, and siaB are involved in biofilm growth; opsX and lgtF participate in epithelial infection; and opsX, lgtF, and lpsA contribute to lung infection. Depending on the phenotype, the involvement of these LOS modifications occurs at different extents, independently or having an additive effect in combination. We discuss the relative contribution of LOS epitopes to NTHi virulence and frame a range of pathogenic traits in the context of infection.

Identifying the relative importance of stock characteristics

There is no consensus in the literature as to which stock characteristic best explains returns. In this study, we employ a novel econometric approach better suited than the traditional characteristic sorting method to answer this question for the UK market. We evaluate the relative explanatory power of market, size, momentum, volatility, liquidity and book-to-market factors in a semiparametric characteristic-based factor model which does not require constructing characteristic portfolios. We find that momentum is the most important factor and liquidity is the least important based on their relative contribution to the fit of the model and the proportion of sample months for which factor returns are significant. Overall, this study provides strong evidence to support that the momentum characteristic can best explain stock returns in the UK market. The econometric approach employed in this study is a novel way to assess relevant investment risk in international financial markets outside U.S. Moreover, multinational institutions and investors can use this approach to identify regional factors in order to diversify their portfolios.

Use of A192621 to provide evidence for involvement of endothelin ET(B)-receptors in endothelin-1-mediated cardiomyocyte hypertrophy.

Increased plasma levels of endothelin-1 correlate with the severity of left ventricular hypertrophy in vivo. The aim of the study was to determine the relative contribution of stimulation of endothelin ETA and endothelin ETB receptors, and the associated activation of protein kinase C, to the hypertrophic response initiated by endothelin-1 in adult rat ventricular cardiomyocytes maintained in culture (24 h). Endothelin-1 (10-7 M) increased the total mass of protein and the incorporation of [14C] phenylalanine into protein to 26% and 25% greater (P

Tracing nitrate and sulfate in river basins using isotope techniques

The objective of this paper is to outline how stable isotope techniques can contribute to the elucidation of the sources and the fate of riverine nitrate and sulphate in watershed studies. The example used is the Oldman River Basin (OMRB), located in southern Alberta (Canada). Increasing sulphate concentrations and decreasing d34S values along the flowpath of the Oldman River indicate that oxidation of pyrite in tills is a major source of riverine sulphate in the agriculturally used portion of the OMRB. Chemical and isotopic data showed that manure-derived nitrogen contributes significantly to the increase in nitrate concentrations in the Oldman River and its tributaries draining agricultural land. It is suggested that hydrological conditions control agricultural return flows to the surface water bodies in southern Alberta and impart significant seasonal variations on concentrations and isotopic compositions of riverine nitrate. Combining isotopic, chemical, and hydrometric data permitted us to estimate the relative contribution of major sources to the total solute fluxes. Hence, we submit that isotopic measurements can make an important contribution to the identification of nutrient and pollutant sources and to river basin management.

Globally synchronous climate change 2800 years ago: Proxy data from peat in South America

Initial findings from high-latitude ice-cores implied a relatively unvarying Holocene climate, in contrast to the major climate swings in the preceding late-Pleistocene. However, several climate archives from low latitudes imply a less than equable Holocene climate, as do recent studies on peat bogs in mainland north-west Europe, which indicate an abrupt climate cooling 2800 years ago, with parallels claimed in a range of climate archives elsewhere. A hypothesis that this claimed climate shift was global, and caused by reduced solar activity, has recently been disputed. Until now, no directly comparable data were available from the southern hemisphere to help resolve the dispute. Building on investigations of the vegetation history of an extensive mire in the Valle de Andorra, Tierra del Fuego, we took a further peat core from the bog to generate a high-resolution climate history through the use of determination of peat hurnification and quantitative leaf-count plant macrofossil analysis. Here, we present the new proxy-climate data from the bog in South America. The data are directly comparable with those in Europe, as they were produced using identical laboratory methods. They show that there was a major climate perturbation at the same time as in northwest European bogs. Its timinia, nature and apparent global synchronicity lend support to the notion of solar forcing of past climate change, amplified by oceanic circulation. This finding of a similar response simultaneously in both hemispheres may help validate and improve global climate models. That reduced solar activity might cause a global climatic change suggests that attention be paid also to consideration of any global climate response to increases in solar activity. This has implications for interpreting the relative contribution of climate drivers of recent 'global warming'. (c) 2006 Elsevier B.V. All rights reserved.

Arteriolar involvement in the microvascular lesions of diabetic retinopathy: Implications for pathogenesis

Diabetic retinopathy (DR) is the most widespread complication of diabetes mellitus and a major cause of blindness in the working population of developed countries. The clinicopathology of the diabetic retina has been extensively studied, although the relative contribution of the various biochemical and molecular sequelae of hyperglycemia remains ill defined. Many neural and microvascular abnormalities occur in the retina of short-term diabetic animals but it remains uncertain how closely these acute changes relate to chronic human disease. It is important to determine the relationship between alterations observed within the first weeks or months in short-term aminal models, and human disease, where clinically manifest retinopathy occurs only after durations of diabetes measured in years. This review is focused on the retinal microvasculature, although it should be appreciated that pathological changes in this system often occur in parallel with abnormalities in the neural parenchyma that may be derivative or even causal. Nevertheless, it is useful to reevaluate the microvascular lesions that are manifest in the retina during diabetes in humans and long-term animal models, since in addition to providing useful clues to the pathogenic basis of DR as a disease entity, it is in the deterrence of such changes that the efficacy of any novel treatment regimes will be measured. In particular, an emphasis will be placed on the relatively unappreciated role of arteriolar dysfunction in the clinical manifestations and pathology of this disease.

Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration

Distinct cell populations with regenerative capacity have been reported to contribute to myofibres after skeletal muscle injury, including non-satellite cells as well as myogenic satellite cells. However, the relative contribution of these distinct cell types to skeletal muscle repair and homeostasis and the identity of adult muscle stem cells remain unknown. We generated a model for the conditional depletion of satellite cells by expressing a human diphtheria toxin receptor under control of the murine Pax7 locus. Intramuscular injection of diphtheria toxin during muscle homeostasis, or combined with muscle injury caused by myotoxins or exercise, led to a marked loss of muscle tissue and failure to regenerate skeletal muscle. Moreover, the muscle tissue became infiltrated by inflammatory cells and adipocytes. This localised loss of satellite cells was not compensated for endogenously by other cell types, but muscle regeneration was rescued after transplantation of adult Pax7(+) satellite cells alone. These findings indicate that other cell types with regenerative potential depend on the presence of the satellite cell population, and these observations have important implications for myopathic conditions and stem cell-based therapeutic approaches.

The effect of month of birth on the attainments of primary and secondary school pupils

Background: Previous research has produced conflicting results regarding the effects of season of birth and age-position on cognitive attainments. In Northern Ireland the school year divides the summer season into two providing an opportunity to evaluate the relative contribution of season of birth and age-position effects. Aims: To investigate the relationship between attainment in literacy skills and month of birth for primary and secondary school pupils and to determine the relationship between motor skills and month of birth in primary school pupils. Sample: One thousand one hundred and twenty four primary school pupils participated, and results for key stage 3 (KS3) English and GCSE English Language, for 3,493 Year 10 and 3,697 Year 12 secondary school pupils, respectively, were obtained. Method: Primary school pupils were individually assessed using standardised reading and spelling tests, as well as tests of motor skill. They were also assessed using a standardised group reading test in their class groups. For the secondary school pupils, the results for two year cohorts, in KS3 English and GCSE English language, respectively, were analysed. Results: For the primary school pupils there was evidence of both a season of birth and an age-position effect on all of the cognitive measures, particularly in the early years of schooling. There was, also, evidence of a significant age-position effect at both KS3 and GCSE in favour of the older pupils. For the younger primary school pupils there was evidence of significant age-position effects on both motor measures. Conclusions: The findings from the present study suggest that month of birth may be related to both season of birth and age-position effects. These effects may be compounded, particularly in the early years of primary school, when summer born children are youngest in their year, as in England. In Northern Ireland, age-position effects are also evident in secondary school public examination results, which may have implications for long-term life choices. © 2009 The British Psychological Society.

Agricultural intensification and biodiversity partitioning in European landscapes comparing plants, carabids, and birds

Effects of agricultural intensification (AI) on biodiversity are often assessed on the plot scale, although processes determining diversity also operate on larger spatial scales. Here, we analyzed the diversity of vascular plants, carabid beetles, and birds in agricultural landscapes in cereal crop fields at the field (n = 1350), farm (n = 270), and European-region (n = 9) scale. We partitioned diversity into its additive components alpha, beta, and gamma, and assessed the relative contribution of beta diversity to total species richness at each spatial scale. AI was determined using pesticide and fertilizer inputs, as well as tillage operations and categorized into low, medium, and high levels. As AI was not significantly related to landscape complexity, we could disentangle potential AI effects on local vs. landscape community homogenization. AI negatively affected the species richness of plants and birds, but not carabid beetles, at all spatial scales. Hence, local AI was closely correlated to beta diversity on larger scales up to the farm and region level, and thereby was an indicator of farm-and region-wide biodiversity losses. At the scale of farms (12.83-20.52%) and regions (68.34-80.18%), beta diversity accounted for the major part of the total species richness for all three taxa, indicating great dissimilarity in environmental conditions on larger spatial scales. For plants, relative importance of alpha diversity decreased with AI, while relative importance of beta diversity on the farm scale increased with AI for carabids and birds. Hence, and in contrast to our expectations, AI does not necessarily homogenize local communities, presumably due to the heterogeneity of farming practices. In conclusion, a more detailed understanding of AI effects on diversity patterns of various taxa and at multiple spatial scales would contribute to more efficient agri-environmental schemes in agroecosystems.

Persistent negative effects of pesticides on biodiversity and biological control potential on European farmland

During the last 50 years, agricultural intensification has caused many wild plant and animal species to go extinct regionally or nationally and has profoundly changed the functioning of agro-ecosystems. Agricultural intensification has many components, such as loss of landscape elements, enlarged farm and field sizes and larger inputs of fertilizer and pesticides. However, very little is known about the relative contribution of these variables to the large-scale negative effects on biodiversity. In this study, we disentangled the impacts of various components of agricultural intensification on species diversity of wild plants, carabids and ground-nesting farmland birds and on the biological control of aphids.

Skin langerin+ dendritic cells transport intradermally injected anti-DEC-205 antibodies but are not essential for subsequent cytotoxic CD8+ T cell responses

Incorporation of Ags by dendritic cells (DCs) increases when Ags are targeted to endocytic receptors by mAbs. We have previously demonstrated in the mouse that mAbs against C-type lectins administered intradermally are taken up by epidermal Langerhans cells (LCs), dermal Langerin(neg) DCs, and dermal Langerin(+) DCs in situ. However, the relative contribution of these skin DC subsets to the induction of immune responses after Ag targeting has not been addressed in vivo. We show in this study that murine epidermal LCs and dermal DCs transport intradermally injected mAbs against the lectin receptor DEC-205/CD205 in vivo. Skin DCs targeted in situ with mAbs migrated through lymphatic vessels in steady state and inflammation. In the skin-draining lymph nodes, targeting mAbs were found in resident CD8a(+) DCs and in migrating skin DCs. More than 70% of targeted DCs expressed Langerin, including dermal Langerin(+) DCs and LCs. Numbers of targeted skin DCs in the nodes increased 2-3-fold when skin was topically inflamed by the TLR7 agonist imiquimod. Complete removal of the site where OVA-coupled anti-DEC-205 had been injected decreased endogenous cytotoxic responses against OVA peptide-loaded target cells by 40-50%. Surprisingly, selective ablation of all Langerin(+) skin DCs in Langerin-DTR knock-in mice did not affect such responses independently of the adjuvant chosen. Thus, in cutaneous immunization strategies where Ag is targeted to DCs, Langerin(+) skin DCs play a major role in transport of anti-DEC-205 mAb, although Langerin(neg) dermal DCs and CD8a(+) DCs are sufficient to subsequent CD8(+) T cell responses.

Peer tutoring in reading: The effects of role and organization on two dimensions of self-esteem

Background. Paired reading (PR) is an application of peer tutoring. It has been extensively researched, and its efficacy across a range of outcomes has been established. Benefits include improvements in key reading skills, and also in affective aspects of learning. Several studies have shown gains in self-esteem, although measurement methods have varied, and the model of self-esteem has rarely been clearly articulated.
Aims. To investigate the changes in self-esteem of children participating in a randomized trial of PR over a 15-week treatment period. To investigate the relative contribution of self-worth and self-competence to any gains in self-esteem. To investigate whether the pattern of change differs in children who take on different roles in the PR process.
Participants. The participants comprised a subset of a large-scale randomized trial of peer learning (The Fife Peer Learning Project). Four schools were randomly selected from schools allocated to the same-age PR condition, and four schools from those allocated to the cross-age PR condition. The same-age group consisted of 87 primary 6 children (10–11 years old). The cross-age group consisted of 81 primary 6 children. The controls, from schools randomly selected from a neighbouring authority, consisted of 92 primary 6 children.
Method. A pre–post design employing self-report measures of self-esteem. Rosenberg’s Self-Esteem Scale was used, with scores analysed for worth and competence. The treatment period was 15 weeks, with the participants following a prescribed PR process.
Results. Significant pre–post gains were noted in self-esteem, driven predominantly by improved beliefs about competence, in both same-age and cross-age conditions, but not for controls. Gains were also seen in self-worth in the cross-age condition. Further analyses of the influence of organizational condition (same-age or cross-age) and role played (tutor vs. tutee) showed significant differences between same-age tutors and cross-age tutors in relation to self-worth. Effect sizes were generally small or moderate.
Conclusions. The findings provide further support for the belief that PR can enhance self-esteem. Importantly, the use of a two-dimensional model provides extra information about self-perceptions in PR contexts: first, the central role of self- competence; and second, the gains in self-worth which are associated with tutoring younger children (but not same-age peers). This new information has educational significance for schools considering the potential of peer tutoring and the benefits of different organizational conditions.