Location-specific nanoplasmonic sensing of biomolecular binding to lipid membranes with negative curvature

The biochemical processes of cell membranes are sensitive to the geometry of the lipid bilayer. We show how plasmonic "nanowells" provide label-free real-time analysis of molecules on membranes with detection of preferential binding at negative curvature. It is demonstrated that norovirus accumulate in invaginations due to multivalent interactions with glycosphingolipids

Ocorrência de Tripalea clavaria (Studer, 1878) na plataforma continental do Rio Grande do Sul

The occurrence and distribution of Tripalea clavaria (Studer, 1878) is discussed, in relation to Brazilian and Falklands currents convergence and water mass in the South-western Atlantic

A randomized controlled trial reporting functional outcomes of cognitive-behavioural therapy in medication‑treated adults with ADHD and comorbid psychopathology

Studies assessing psychological treatment of attention deficit hyperactivity disorder (ADHD) in adults are increasingly reported. However, functional outcomes are often neglected in favour of symptom outcomes. We investigated functional outcomes in 95 adults with ADHD who were already treated with medication and randomized to receive treatment as usual (TAU/MED) or psychological treatment (CBT/MED) using a cognitive–behavioural programme, R&R2ADHD, which employs both group and individual modalities. RATE-S functional outcomes associated with ADHD symptoms, social functioning, emotional control and antisocial behaviour were given at baseline, end of treatment and three-month follow-up. The Total composite score of these scales is associated with life satisfaction. In addition, independent evaluator ratings of clinicians who were blind to treatment arm were obtained on the Clinical Global Impression scale at each time point. CBT/MED showed overall (combined outcome at end of treatment and 3-month follow-up) significantly greater functional improvement on all scales. Post-group treatment effects were maintained at follow-up with the exception of emotional control and the Total composite scales, which continued to improve. The largest treatment effect was for the RATE-S Total composite scale, associated with life satisfaction. CGI significantly correlated with all outcomes except for social functioning scale at follow-up. The study provides further evidence for the effectiveness of R&R2ADHD and demonstrates the importance of measuring functional outcomes. The key mechanism associated with improved functional outcomes is likely to be behavioural control

Cognitive-behavioural therapy in medication-treated adults with attention-deficit/hyperactivity disorder and co-morbid psychopathology:a randomized controlled trial using multi-level analysis

Background. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by high rates of co-morbid psychopathology. Randomized controlled trials of multimodal interventions, combining pharmacological and psychological treatments, have shown a robust treatment effect for ADHD symptoms but outcomes for co-morbid symptoms have been mixed. This may be accounted for by the type of intervention selected and/or by methodological problems including lack of follow-up and low power. The current study addressed these limitations in a parallel-group randomized controlled trial conducted in Iceland.  Method. A total of 95 adult ADHD patients who were already being treated with medication (MED) were randomly assigned to receive treatment as usual (TAU/MED) or 15 sessions of cognitive-behavioural therapy (CBT/MED) using the R&R2ADHD intervention which employs both group and individual modalities. Primary measures of ADHD symptoms and severity of illness, and secondary measures of anxiety, depression and quality of life were given at baseline, end of treatment and 3-month follow-up. Primary outcomes were rated by clinicians blind to treatment condition assignment.  Results. CBT/MED showed overall (combined outcome at end of treatment and 3-month follow-up) significantly greater reduction in primary outcomes for clinician-rated and self-rated ADHD symptoms. Treatment effect of primary outcomes was maintained at follow-up, which suggests robust and lasting findings. In contrast to the primary outcomes, the secondary outcomes showed significant improvement over time.  Conclusions. The study provides evidence for the effectiveness of R&R2ADHD and demonstrates that there are differential effects over time for ADHD symptoms versus co-morbid problems, the latter taking longer to show positive effects

Genetical genomics: spotlight on QTL hotspots

No abstract available

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

JEPEGMIX2: improved gene-level joint analysis of eQTLs in cosmopolitan cohorts.

Motivation: To increase detection power, researchers use gene level analysis methods to aggregate weak marker signals. Due to gene expression controlling biological processes, researchers proposed aggregating signals for expression Quantitative Trait Loci (eQTL). Most gene-level eQTL methods make statistical inferences based on i) summary statistics from genome-wide association studies (GWAS) and ii) linkage disequilibrium (LD) patterns from a relevant reference panel. While most such tools assume homogeneous cohorts, our Gene-level Joint Analysis of functional SNPs in Cosmopolitan Cohorts (JEPEGMIX) method accommodates cosmopolitan cohorts by using heterogeneous panels. However, JEPGMIX relies on brain eQTLs from older gene expression studies and does not adjust for background enrichment in GWAS signals. Results: We propose JEPEGMIX2, an extension of JEPEGMIX. When compared to JPEGMIX, it uses i) cis-eQTL SNPs from the latest expression studies and ii) brains specific (sub)tissues and tissues other than brain. JEPEGMIX2 also i) avoids accumulating averagely enriched polygenic information by adjusting for background enrichment and ii), to avoid an increase in false positive rates for studies with numerous highly enriched (above the background) genes, it outputs gene q-values based on Holm adjustment of p-values. Supplementary information: Supplementary material is available at Bioinformatics online. Bioinformatics 2018; 34(2):286-28