Role of the central cations in the mechanical unfolding of DNA and RNA G-quadruplexes.

Cations are known to mediate diverse interactions in nucleic acids duplexes but they are critical in the arrangement of four-stranded structures. Here, we use all-atom molecular dynamics simulations with explicit solvent to analyse the mechanical unfolding of representative intramolecular G-quadruplex structures: a parallel, a hybrid and an antiparallel DNA and a parallel RNA, in the presence of stabilising cations. We confirm the stability of these conformations in the presence of [Formula: see text] central ions and observe distortions from the tetrad topology in their absence. Force-induced unfolding dynamics is then investigated. We show that the unfolding events in the force-extension curves are concomitant to the loss of coordination between the central ions and the guanines of the G-quadruplex. We found lower ruptures forces for the parallel configuration with respect to the antiparallel one, while the behaviour of the force pattern of the parallel RNA appears similar to the parallel DNA. We anticipate that our results will be essential to interpret the fine structure rupture profiles in stretching assays at high resolution and will shed light on the mechanochemical activity of G-quadruplex-binding machinery

The role of positive emotion and contributions of positive psychology in depression treatment: systematic review

The present study aims to conduct a systematic review of the literature by checking the impact of positive emotion in the treatment of depression and on the use of strategies of positive psychology which involves positive emotion to treat and reduce symptoms of depression. For this purpose, we conducted searches in databases ISI Web of Knowledge, PsycINFO and PubMed and found a total of 3400 studies. After inclusion application and exclusion criteria, 28 articles remained, presented and discussed in this study. The studies have important relations between humor and positive emotion as well as a significant improvement in signs and symptoms of depression using differents strategies of positive psychology. Another relevant aspect is the preventative character of the proposed interventions by positive psychology by the fact that increase well-being and produce elements such as resilience and coping resources that reduce the recurrent relapses in the treatment of depression. The strategies of positive psychology, such as increasing positive emotions, develop personal strengths: seeking direction, meaning and engagement for the day-to-day life of the patients, appear as potentially tools for the prophylaxis and treatment of depression, helping to reduce signs and symptoms as well as for prevention of relapses

Effects of chronic exercise on severity, quality of life and functionality in an elderly Parkinson’s disease patient: case report

Exercise produces potential influences on physical and mental capacity in patients with neuropsychiatric disor- ders, and can be made a viable form of therapy to treat Parkinson’s disease (PD). We report the chronic effects of a regu- lar physical exercise protocol on cognitive and motor functions, functional capacity, and symptoms in an elderly PD pa- tient without dementia. The patient participated of a program composed of proprioceptive, aerobic and flexibility exer- cises, during 1 hour, three days a week, for nine months. Patient used 600 mg of L-DOPA daily, and 1 hour prior to each exercise session. Assessment was conducted in three stages, 0-3, 3-6 and 6 to 9 months, using percentual variation to the scales Hoehn and Yahr, Mini-Mental State Examination (MMSE), Parkinson Activity Scale (PAS), Beck Depression In- ventory (BDI), and Unified Parkinson's Disease Rating Scale (UPDRS-III). Reassessment showed clear changes in clini- cal parameters for Hoehn and Yahr (4 to 2.5), MMSE (14 to 22), PAS (13 to 29), BDI (9 to 7) and UPDRS-III (39 to 27) at the end of 9 months. According to our data, exercise seems to be effective in promoting the functional capacity and the maintenance of cognitive and motor functions of PD patients. Regular exercise protocols can be implemented as an ad- junctive treatment for reducing the severity of PD

Physical activity interventions in schools for improving lifestyle in European countries

Background : In the last decades, children’s and adolescents’ obesity and overweight have increased in European Countries. Unhealthy eating habits and sedentary lifestyle have been recognized to determine such an epidemic. Schools represent an ideal setting to modify harmful behaviors, and physical activity could be regarded as a potential way to avoid the metabolic risks related to obesity. Methods : A systematic review of the literature was carried out to summarize the evidence of school-based interventions aimed to promote, enhance and implement physical activity in European schools. Only randomized controlled trials were included, carried out in Europe from January 2000 to April 2014, universally delivered and targeting pupils aged between 3 and 18 years old. Results : Forty-seven studies were retrieved based either on multicomponent interventions or solely physical activity programs. Most aimed to prevent obesity and cardiovascular risks among youths. While few studies showed a decrease in BMI, positive results were achieved on other outcomes, such as metabolic parameters and physical fitness. Conclusion : Physical activity in schools should be regarded as a simple, non-expensive and enjoyable way to reach all the children and adolescents with adequate doses of moderate to vigorous physical activity

Operator theory and function theory in Drury-Arveson space and its quotients

The Drury-Arveson space $H^2_d$, also known as symmetric Fock space or the $d$-shift space, is a Hilbert function space that has a natural $d$-tuple of operators acting on it, which gives it the structure of a Hilbert module. This survey aims to introduce the Drury-Arveson space, to give a panoramic view of the main operator theoretic and function theoretic aspects of this space, and to describe the universal role that it plays in multivariable operator theory and in Pick interpolation theory.Comment: Final version (to appear in Handbook of Operator Theory); 42 page

Orientation of the Calcium Channel β Relative to the α12.2 Subunit Is Critical for Its Regulation of Channel Activity

BACKGROUND: The Ca(v)beta subunits of high voltage-activated Ca(2+) channels control the trafficking and biophysical properties of the alpha(1) subunit. The Ca(v)beta-alpha(1) interaction site has been mapped by crystallographic studies. Nevertheless, how this interaction leads to channel regulation has not been determined. One hypothesis is that betas regulate channel gating by modulating movements of IS6. A key requirement for this direct-coupling model is that the linker connecting IS6 to the alpha-interaction domain (AID) be a rigid structure. METHODOLOGY/PRINCIPAL FINDINGS: The present study tests this hypothesis by altering the flexibility and orientation of this region in alpha(1)2.2, then testing for Ca(v)beta regulation using whole cell patch clamp electrophysiology. Flexibility was induced by replacement of the middle six amino acids of the IS6-AID linker with glycine (PG6). This mutation abolished beta2a and beta3 subunits ability to shift the voltage dependence of activation and inactivation, and the ability of beta2a to produce non-inactivating currents. Orientation of Ca(v)beta with respect to alpha(1)2.2 was altered by deletion of 1, 2, or 3 amino acids from the IS6-AID linker (Bdel1, Bdel2, Bdel3, respectively). Again, the ability of Ca(v)beta subunits to regulate these biophysical properties were totally abolished in the Bdel1 and Bdel3 mutants. Functional regulation by Ca(v)beta subunits was rescued in the Bdel2 mutant, indicating that this part of the linker forms beta-sheet. The orientation of beta with respect to alpha was confirmed by the bimolecular fluorescence complementation assay. CONCLUSIONS/SIGNIFICANCE: These results show that the orientation of the Ca(v)beta subunit relative to the alpha(1)2.2 subunit is critical, and suggests additional points of contact between these subunits are required for Ca(v)beta to regulate channel activity

From evolutionary computation to the evolution of things

Evolution has provided a source of inspiration for algorithm designers since the birth of computers. The resulting field, evolutionary computation, has been successful in solving engineering tasks ranging in outlook from the molecular to the astronomical. Today, the field is entering a new phase as evolutionary algorithms that take place in hardware are developed, opening up new avenues towards autonomous machines that can adapt to their environment. We discuss how evolutionary computation compares with natural evolution and what its benefits are relative to other computing approaches, and we introduce the emerging area of artificial evolution in physical systems

Mesoscopic model for DNA G-quadruplex unfolding

[EN] Genomes contain rare guanine-rich sequences capable of assembling into four-stranded helical structures, termed G-quadruplexes, with potential roles in gene regulation and chromosome stability. Their mechanical unfolding has only been reported to date by all-atom simulations, which cannot dissect the major physical interactions responsible for their cohesion. Here, we propose a mesoscopic model to describe both the mechanical and thermal stability of DNA G-quadruplexes, where each nucleotide of the structure, as well as each central cation located at the inner channel, is mapped onto a single bead. In this framework we are able to simulate loading rates similar to the experimental ones, which are not reachable in simulations with atomistic resolution. In this regard, we present single-molecule force-induced unfolding experiments by a high-resolution optical tweezers on a DNA telomeric sequence capable of adopting a G-quadruplex conformation. 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