Feature selection environment for genomic applications

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Dhvar5 antimicrobial peptide (AMP) chemoselective covalent immobilization results on higher antiadherence effect than simple physical adsorption

Bacterial colonization and subsequent biofilm formation is still one of the major problems associated with medical devices. Antimicrobial peptides (AMP) immobilization onto biomaterials surface is a promising strategy to avoid bacterial colonization. However, a correct peptide orientation and exposure from the surface is essential to maintain AMP antimicrobial activity. This work aims to evaluate the effect of the immobilization on antibacterial activity of Dhvar5 (LLLFLLKKRKKRKY), an AMP with a head-to-tail amphipathicity. Dhvar5 was linked to thin chitosan coatings in i) a controlled orientation and exposure, testing covalent immobilization of its N- or C-terminus and using spacers with different lengths and flexibilities or in ii) a random orientation by physical adsorption. Chitosan coating was chosen due to its antimicrobial properties and readiness to be functionalized. Surface characterization demonstrated the chemoselective immobilization of the peptide with different spacers in a similar concentration (∼2 ng/cm2). Efficacy assays demonstrated that covalent immobilization of Dhvar5 exposing its cationic end, improves the chitosan coating antimicrobial effect by decreasing Methicillin-resistant Staphylococcus aureus (MRSA) colonization. This effect was enhanced when longer spacers were used independently of their flexibility. In opposite, immobilized Dhvar5 exposing its hydrophobic end has no effect on bacterial adhesion to chitosan, and when adsorbed in a random orientation even induces bacterial adhesion to chitosan coating.This work was financed by FEDER funds through the Programa Operacional Factores de Competitividade (COMPETE) and by Portuguese funds through FCT (Fundacao para a Ciencia e a Tecnologia) in the framework of the projects: PTDC/CTM/101484/2008; PEst-C/SAU/LA0002/2013; Pest-C/QUI/UI0081/2013. Fabiola Costa acknowledges FCT for the PhD grant SFRH/BD/72471/2010

Symptom appraisal and help-seeking in men with symptoms of possible prostate cancer: a qualitative study with an ethnically diverse sample in London

This is the final version. Available on open access from the Royal College of General Practitioners via the DOI in this recordBACKGROUND: Prostate cancer mortality in Black males is disproportionately high. This problem may be overcome by reducing delays in the pathway to diagnosis, particularly those occurring before initial medical help seeking. A greater understanding of symptom appraisal and help seeking could support the development of targeted interventions for improving early presentation among Black males. AIM: To provide an in-depth understanding of males' pre-consultation experiences following the onset of symptoms of possible prostate cancer, identifying both general trends as well as potential differences that may exist between Black and White males. DESIGN AND SETTING: Qualitative study of 18 males (nine Black, nine White) in London, UK, who had recently seen their GP with urinary symptoms, erectile dysfunction, or haematuria. METHOD: Semi-structured interviews from a previous multi-methods study of primary care use by males with symptoms of possible prostate cancer were analysed using thematic framework analysis. RESULTS: Symptoms were often interpreted by patients as unimportant. Most delays occurred due to the absence of reasons to seek help, which, in Black males, often stemmed from poor awareness of prostate cancer. This lack of awareness could have been a consequence of their reluctance to seek health information and discuss health issues with others in their social network. Friends and relatives played an important role in symptom appraisal and help seeking. CONCLUSION: Cognitive biases, cultural stigmas, and everyday interpersonal interactions should be important areas at which to target strategies seeking to reduce delays and improve early presentation in males with possible prostate cancer, particularly Black males.Cancer Research UKNational Institute for Health and Care Research (NIHR

Genome analysis of DNA repair genes in the alpha proteobacterium Caulobacter crescentus

BACKGROUND: The integrity of DNA molecules is fundamental for maintaining life. The DNA repair proteins protect organisms against genetic damage, by removal of DNA lesions or helping to tolerate them. DNA repair genes are best known from the gamma-proteobacterium Escherichia coli, which is the most understood bacterial model. However, genome sequencing raises questions regarding uniformity and ubiquity of these DNA repair genes and pathways, reinforcing the need for identifying genes and proteins, which may respond to DNA damage in other bacteria. RESULTS: In this study, we employed a bioinformatic approach, to analyse and describe the open reading frames potentially related to DNA repair from the genome of the alpha-proteobacterium Caulobacter crescentus. This was performed by comparison with known DNA repair related genes found in public databases. As expected, although C. crescentus and E. coli bacteria belong to separate phylogenetic groups, many of their DNA repair genes are very similar. However, some important DNA repair genes are absent in the C. crescentus genome and other interesting functionally related gene duplications are present, which do not occur in E. coli. These include DNA ligases, exonuclease III (xthA), endonuclease III (nth), O(6)-methylguanine-DNA methyltransferase (ada gene), photolyase-like genes, and uracil-DNA-glycosylases. On the other hand, the genes imuA and imuB, which are involved in DNA damage induced mutagenesis, have recently been described in C. crescentus, but are absent in E. coli. Particularly interesting are the potential atypical phylogeny of one of the photolyase genes in alpha-proteobacteria, indicating an origin by horizontal transfer, and the duplication of the Ada orthologs, which have diverse structural configurations, including one that is still unique for C. crescentus. CONCLUSION: The absence and the presence of certain genes are discussed and predictions are made considering the particular aspects of the C. crescentus among other known DNA repair pathways. The observed differences enlarge what is known for DNA repair in the Bacterial world, and provide a useful framework for further experimental studies in this organism

Neuropsychological Assessment of Children With Reading Disabilities From 8 to 10 Years Old: An Exploratory Portuguese Study

Abstract Reading disabilities are one of the most significant causes of school failure and may result from different causes and cognitive processes. A comprehensive battery of neuropsychological tests was applied to a control group of 102 children (46 girls, 56 boys) with no history of learning disabilities and 32 children (13 girls, 19 boys) with poor reading achievement (PRA) to characterize their cognitive profile. A principal component analysis of the cognitive measures was undertaken to identify cognitive domains. Age-adjusted normative data were computed from controls for verbal and visuospatial abilities, psychomotor skills, executive functions, and a total score. Significant differences were found between the 2 groups. Although single tests could not identify children with PRA, measures of oral and written language, immediate and working memory, calculation, and verbal learning discriminated the 2 groups. A logistic regression model using these factors allowed us to identify 91.2% of healthy children and 96.9% of children with PRA. PRA may result from different patterns of cognitive difficulties, and it is more common in children with oral language and working-memory deficits. Wide-range cognitive testing is necessary to identify strong and weak areas to plan personalized intervention program

Direct and Inverse Variational Problems on Time Scales: A Survey

We deal with direct and inverse problems of the calculus of variations on arbitrary time scales. Firstly, using the Euler-Lagrange equation and the strengthened Legendre condition, we give a general form for a variational functional to attain a local minimum at a given point of the vector space. Furthermore, we provide a necessary condition for a dynamic integro-differential equation to be an Euler-Lagrange equation (Helmholtz's problem of the calculus of variations on time scales). New and interesting results for the discrete and quantum settings are obtained as particular cases. Finally, we consider very general problems of the calculus of variations given by the composition of a certain scalar function with delta and nabla integrals of a vector valued field.Comment: This is a preprint of a paper whose final and definite form will be published in the Springer Volume 'Modeling, Dynamics, Optimization and Bioeconomics II', Edited by A. A. Pinto and D. Zilberman (Eds.), Springer Proceedings in Mathematics & Statistics. Submitted 03/Sept/2014; Accepted, after a revision, 19/Jan/201

Transcatheter closure of a fenestration in intracardiac Fontan circulation

We present a case of tricuspid atresia and the treatment that was used in a child now aged 12. The malformation was corrected at the age of five through intracardiac Fontan circulation. Later, the child developed a right-to-left shunt due to dehiscence in the intra-atrial conduit, causing significant desaturation. This was treated by transcatheter closure with a 10 mm Amplatzer device at 8 years of age. Currently the child is asymptomatic with no residual shunts, and the position of the device is normal. The percutaneous closure of Fontan fenestrations using the Amplatzer device is a therapeutic approach that provides good results. It results in normal oxygen saturation and has low morbidity. The technique is simple, available to most cardiac catheterization laboratories, safe, and offers a reasonable cost-benefit ratio. In addition, the design of the device is suitable for this type of defect

Histological changes and impairment of liver mitochondrial bioenergetics after long-term treatment with alpha-naphthyl-isothiocyanate (ANIT)

This study was designed to evaluate the effects of long-term treatment with alpha-naphthyl-isothiocyanate (ANIT) on liver histology and at the mitochondrial bioenergetic level. Since, ANIT has been used as a cholestatic agent and it has been pointed out that an impairment of mitochondrial function is a cause of hepatocyte dysfunction leading to cholestatic liver injury, serum markers of liver injury were measured and liver sections were analyzed in ANIT-treated rats (i.p. 80 mg/kg/week x 16 weeks). Mitochondrial parameters such as transmembrane potential, respiration, calcium capacity, alterations in permeability transition susceptibility and ATPase activity were monitored. Histologically, the most important features were the marked ductular proliferation, proliferation of mast cells and the presence of iron deposits in ANIT-treated liver. Mitochondria isolated from ANIT-treated rats showed no alterations in state 4 respiration, respiratory control ratio and ADP/O ratio, while state 3 respiration was significantly decreased. No changes were observed on transmembrane potential, but the repolarization rate was decreased in treated rats. Consistently with these data, there was a significant decrease in the ATPase activity of treated mitochondria. Associated with these parameters, mitochondria from treated animals exhibited increased susceptibility to mitochondrial permeability transition pore opening (lower calcium capacity). Since, human cholestatic liver disease progress slowly overtime, these data provide further insight into the role of mitochondrial dysfunction in the process