Cognitive Behavior Therapy for Anxious Adolescents: Developmental Influences on Treatment Design and Delivery

Anxiety disorders in adolescence are common and disruptive, pointing to a need for effective treatments for this age group. Cognitive behavior therapy (CBT) is one of the most popular interventions for adolescent anxiety, and there is empirical support for its application. However, a significant proportion of adolescent clients continue to report anxiety symptoms post-treatment. This paper underscores the need to attend to the unique developmental characteristics of the adolescent period when designing and delivering treatment, in an effort to enhance treatment effectiveness. Informed by the literature from developmental psychology, developmental psychopathology, and clinical child and adolescent psychology, we review the ‘why’ and the ‘how’ of developmentally appropriate CBT for anxious adolescents. ‘Why’ it is important to consider developmental factors in designing and delivering CBT for anxious adolescents is addressed by examining the age-related findings of treatment outcome studies and exploring the influence of developmental factors, including cognitive capacities, on engagement in CBT. ‘How’ clinicians can developmentally tailor CBT for anxious adolescents in six key domains of treatment design and delivery is illustrated with suggestions drawn from both clinically and research-oriented literature. Finally, recommendations are made for research into developmentally appropriate CBT for anxious adolescents

Chromosomal macrodomains and associated proteins : implications for DNA organization and replication in gram negative bacteria

The Escherichia coli chromosome is organized into four macrodomains, the function and organisation of which are poorly understood. In this review we focus on the MatP, SeqA, and SlmA proteins that have recently been identified as the first examples of factors with macrodomain-specific DNA-binding properties. In particular, we review the evidence that these factors contribute towards the control of chromosome replication and segregation by specifically targeting subregions of the genome and contributing towards their unique properties. Genome sequence analysis of multiple related bacteria, including pathogenic species, reveals that macrodomain-specific distribution of SeqA, SlmA, and MatP is conserved, suggesting common principles of chromosome organisation in these organisms. This discovery of proteins with macrodomain-specific binding properties hints that there are other proteins with similar specificity yet to be unveiled. We discuss the roles of the proteins identified to date as well as strategies that may be employed to discover new factors

Scanning a DNA molecule for bound proteins using hybrid magnetic and optical tweezers

The functional state of the genome is determined by its interactions with proteins that bind, modify, and move along the DNA. To determine the positions and binding strength of proteins localized on DNA we have developed a combined magnetic and optical tweezers apparatus that allows for both sensitive and label-free detection. A DNA loop, that acts as a scanning probe, is created by looping an optically trapped DNA tether around a DNA molecule that is held with magnetic tweezers. Upon scanning the loop along the ?-DNA molecule, EcoRI proteins were detected with ?17 nm spatial resolution. An offset of 33±5 nm for the detected protein positions was found between back and forwards scans, corresponding to the size of the DNA loop and in agreement with theoretical estimates. At higher applied stretching forces, the scanning loop was able to remove bound proteins from the DNA, showing that the method is in principle also capable of measuring the binding strength of proteins to DNA with a force resolution of 0.1 pN/[Formula: see text]. The use of magnetic tweezers in this assay allows the facile preparation of many single-molecule tethers, which can be scanned one after the other, while it also allows for direct control of the supercoiling state of the DNA molecule, making it uniquely suitable to address the effects of torque on protein-DNA interactions.BN/BionanoscienceApplied Science

STED nanoscopy combined with optical tweezers reveals protein dynamics on densely covered DNA

Dense coverage of DNA by proteins is a ubiquitous feature of cellular processes such as DNA organization, replication and repair. We present a single-molecule approach capable of visualizing individual DNA-binding proteins on densely covered DNA and in the presence of high protein concentrations. Our approach combines optical tweezers with multicolor confocal and stimulated emission depletion (STED) fluorescence microscopy. Proteins on DNA are visualized at a resolution of 50 nm, a sixfold resolution improvement over that of confocal microscopy. High temporal resolution (<50 ms) is ensured by fast one-dimensional beam scanning. Individual trajectories of proteins translocating on DNA can thus be distinguished and tracked with high precision. We demonstrate our multimodal approach by visualizing the assembly of dense nucleoprotein filaments with unprecedented spatial resolution in real time. Experimental access to the force-dependent kinetics and motility of DNA-associating proteins at biologically relevant protein densities is essential for linking idealized in vitro experiments with the in vivo situation. © 2013 Nature America, Inc. All rights reserved

Laminar flow cells for single-molecule studies of DNA-protein interactions

Microfluidic flow cells are used in single-molecule experiments, enabling measurements to be made with high spatial and temporal resolution. We discuss the fundamental processes affecting flow cell operation and describe the flow cells in use at present for studying the interaction of optically trapped or mechanically isolated, single DNA molecules with proteins. To assist the experimentalist in flow cell selection, we review the construction techniques and materials used to fabricate both single-and multiple-channel flow cells and the advantages of each design for different experiments