Proteomic profile of cystic fibrosis sputum cells in adults chronically infected with Pseudomonas aeruginosa

Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF), and involves chronic infection and perturbed immune responses. Tissue damage is mediated mostly by extracellular proteases, but other cellular proteins may also contribute to damage through their effect on cell activities and/or release into sputum fluid by means of active secretion or cell death.We employed MudPIT (multidimensional protein identification technology) to identify sputum cellular proteins with consistently altered abundance in adults with CF, chronically infected with Pseudomonas aeruginosa, compared with healthy controls. Ingenuity Pathway Analysis, Gene Ontology, protein abundance and correlation with lung function were used to infer their potential clinical significance.Differentially abundant proteins relate to Rho family small GTPase activity, immune cell movement/activation, generation of reactive oxygen species, and dysregulation of cell death and proliferation. Compositional breakdown identified high abundance of proteins previously associated with neutrophil extracellular traps. Furthermore, negative correlations with lung function were detected for 17 proteins, many of which have previously been associated with lung injury.These findings expand our current understanding of the mechanisms driving CF lung disease and identify sputum cellular proteins with potential for use as indicators of disease status/prognosis, stratification determinants for treatment prescription or therapeutic targets

2-methylbutyryl-CoA dehydrogenase deficiency associated with autism and mental retardation: a case report

<p>Abstract</p> <p>Background</p> <p>2-methylbutyryl-CoA dehydrogenase deficiency or short/branched chain acyl-CoA dehydrogenase deficiency (SBCADD) is caused by a defect in the degradation pathway of the amino acid L-isoleucine.</p> <p>Methods</p> <p>We report a four-year-old mentally retarded Somali boy with autism and a history of seizures, who was found to excrete increased amounts of 2-methylbutyryl glycine in the urine. The SBCAD gene was examined with sequence analysis. His development was assessed with psychometric testing before and after a trial with low protein diet.</p> <p>Results</p> <p>We found homozygosity for A > G changing the +3 position of intron 3 (c.303+3A > G) in the SBCAD gene. Psychometric testing showed moderate mental retardation and behavioral scores within the autistic spectrum. No beneficial effect was detected after 5 months with a low protein diet.</p> <p>Conclusion</p> <p>This mutation was also found in two previously reported cases with SBCADD, both originating from Somalia and Eritrea, indicating that it is relatively prevalent in this population. Autism has not previously been described with mutations in this gene, thus expanding the clinical spectrum of SBCADD.</p

Reagentless Affimer- and antibody-based impedimetric biosensors for CEA-detection using a novel non-conducting polymer

Polyoctopamine (POct), an amine-functionalised non-conducting polymer, as the transducer layer in an electrochemical biosensor, is presented. This polymer offers versatile covalent coupling either through thiol linker conjugation, carboxyl or aldehyde functional groups without the requirement of pre- or post-surface activation. The colorectal cancer biomarker carcinoembryonic antigen (CEA) was selected as the target analyte, whilst an antibody and a synthetic binding protein, an Affimer, were used as distinct bioreceptors to demonstrate the versatility of polyoctopamine as a transducer polymer layer for oriented immobilisation of the bioreceptors. The electrodeposited polymer layer was characterised using cyclic voltammetry, electrochemical impedance spectroscopy, and on-sensor chemiluminescent blotting. The performance of optimised POct-based biosensors were tested in spiked human serum. Results showed that the electropolymerisation of octopamine on screen printed gold electrode generates a thin polymer film with low resistance. Close proximity of the immobilised bioreceptors to the transducer layer greatly enhanced the sensitivity detection. The sensitivity of the smaller monomeric bioreceptor (Affimer, 12.6 kDa) to detect CEA was comparable to the dimeric antibody (150 kDa) with limit of detection at 11.76 fM which is significantly lower than the basal clinical levels of 25 pM. However, the Affimer-based sensor had a narrower dynamic range compared to the immunosensor (1–100 fM vs. 1 fM – 100 nM, respectively). All electrochemical measurements were done in less than 5 min with small sample volumes (10 μl). Hence, polyoctopamine features a simple fabrication of impedimetric biosensors using amine-functionalisation technique, provides rapid response time with enhanced sensitivity and label-free detection

Flux line lattice structure and behavior in antiphase boundary free vicinal YBa2Cu3O7-delta thin films

Field angle dependent critical current, magneto-optical microscopy and high resolution electron microscopy studies have been performed on YBa2Cu3O7-delta thin films grown on miscut substrates. High resolution electron microscopy images show that the films studied exhibited clean epitaxial growth with a low density of antiphase boundaries and stacking faults. Any antiphase boundaries (APBs) formed near the film substrate interface rapidly healed rather than extending through the thickness of the film. Unlike vicinal films grown on annealed substrates, which contain a high density of antiphase boundaries, magneto-optical imaging showed no filamentary flux penetration in the films studied. The flux penetration is, however, asymmetric. This is associated with intrinsic pinning of flux strings by the tilted a-b planes and the dependence of the pinning force on the angle between the local field and the a-b planes. Field angle dependent critical current measurements exhibited the striking vortex channeling effect previously reported in vicinal films. By combining the results of three complementary characterization techniques it is shown that extended APB free films exhibit markedly different critical current behavior compared to APB rich films. This is attributed to the role of APB sites as strong pinning centers for Josephson string vortices between the a-b planes. (C) 2003 American Institute of Physics

Environmental differences between sites control the diet and nutrition of the carnivorous plant Drosera rotundifolia

Background and aims: Carnivorous plants are sensitive to small changes in resource availability, but few previous studies have examined how differences in nutrient and prey availability affect investment in and the benefit of carnivory. We studied the impact of site-level differences in resource availability on ecophysiological traits of carnivory for Drosera rotundifolia L. Methods: We measured prey availability, investment in carnivory (leaf stickiness), prey capture and diet of plants growing in two bogs with differences in N deposition and plant available N: Cors Fochno (0.62 g m−2 yr.−1, 353 μg l−1), Whixall Moss (1.37 g m−2 yr.−1, 1505 μg l−1). The total N amount per plant and the contributions of prey/root N to the plants’ N budget were calculated using a single isotope natural abundance method. Results: Plants at Whixall Moss invested less in carnivory, were less likely to capture prey, and were less reliant on prey-derived N (25.5% compared with 49.4%). Actual prey capture did not differ between sites. Diet composition differed – Cors Fochno plants captured 62% greater proportions of Diptera. Conclusions: Our results show site-level differences in plant diet and nutrition consistent with differences in resource availability. Similarity in actual prey capture may be explained by differences in leaf stickiness and prey abundance

Genetics of callous-unemotional behavior in children

Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase ‘missing heritability’ was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU

Cracking in asphalt materials

This chapter provides a comprehensive review of both laboratory characterization and modelling of bulk material fracture in asphalt mixtures. For the purpose of organization, this chapter is divided into a section on laboratory tests and a section on models. The laboratory characterization section is further subdivided on the basis of predominant loading conditions (monotonic vs. cyclic). The section on constitutive models is subdivided into two sections, the first one containing fracture mechanics based models for crack initiation and propagation that do not include material degradation due to cyclic loading conditions. The second section discusses phenomenological models that have been developed for crack growth through the use of dissipated energy and damage accumulation concepts. These latter models have the capability to simulate degradation of material capacity upon exceeding a threshold number of loading cycles.Peer ReviewedPostprint (author's final draft

Personal values and involvement in problem behaviors among Bahamian early adolescents: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Few studies, particularly in developing countries, have explored the relationship between adolescents and parental values with adolescent problem behaviors. The objectives of the study are to (1) describe adolescents' personal values, their problem behaviors, and the relationships thereof according to gender and (2) examine the relationship between parental values, adolescent values, and adolescents' problem behaviors among sixth-grade students and one of their parents.</p> <p>Methods</p> <p>The data used in these analyses were from the baseline assessment of a school-based HIV risk reduction intervention being conducted and evaluated among sixth grade students and one of their parents across 9 elementary schools in The Bahamas. Personal values were measured by the Portrait Values Questionnaire (PVQ). Seven reported problem behaviors were queried from the students, which included physical fight with a friend, drank alcohol, beer, or wine, smoked a cigarette, pushed or carried any drugs, carried a gun, knife, screwdriver or cutlass to use as a weapon, had sex and used marijuana or other illicit drugs over the past 6 months. Multilevel modeling for binary data was performed to estimate the associations between adolescent and parental values and adolescent problem behaviors.</p> <p>Results</p> <p>Among 785 students, 47% of the students reported at least one problem behavior. More boys (54%) reported having one or more problem behaviors than girls (41%, p < 0.01). Boys compared to girls expressed a higher level of self-enhancement (means score: 36.5 vs. 35.1; p = 0.03), while girls expressed a higher level of self-transcendence (42.3 vs. 40.7; p = 0.03). The results of multilevel modeling indicates that boys with a higher level of self-enhancement and girls with a higher level of openness to change and a lower level of conservation were more likely to report engagement in problem behaviors. Only two parental values (self-transcendence and conservation) were low or modestly correlated with youth' values (openness to change and self-enhancement). Parental-reported values documented limited association on adolescents' reported values and behaviors.</p> <p>Conclusion</p> <p>In designing interventions for reducing adolescents' problem behaviors, it may be important to understand the values associated with specific problem behaviors. Further exploration regarding lack of association between adolescent and parental values and problem behaviors is needed.</p