Modeling DNA Structure, Elasticity and Deformations at the Base-pair Level

We present a generic model for DNA at the base-pair level. We use a variant of the Gay-Berne potential to represent the stacking energy between neighboring base-pairs. The sugar-phosphate backbones are taken into account by semi-rigid harmonic springs with a non-zero spring length. The competition of these two interactions and the introduction of a simple geometrical constraint leads to a stacked right-handed B-DNA-like conformation. The mapping of the presented model to the Marko-Siggia and the Stack-of-Plates model enables us to optimize the free model parameters so as to reproduce the experimentally known observables such as persistence lengths, mean and mean squared base-pair step parameters. For the optimized model parameters we measured the critical force where the transition from B- to S-DNA occurs to be approximately $140{pN}$. We observe an overstretched S-DNA conformation with highly inclined bases that partially preserves the stacking of successive base-pairs.Comment: 15 pages, 25 figures. submitted to PR

Effects of eight neuropsychiatric copy number variants on human brain structure

peer reviewedMany copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions. © 2021, The Author(s)

Coping, adapting or self-managing - what is the difference? A concept review based on the neurological literature

AIM: The aim of this study was to report: (1) an analysis of the concepts of coping, adaptation and self-management in the context of managing a neurological condition; and (2) the overlap between the concepts. BACKGROUND: The three concepts are often confused or used interchangeably. Understanding similarities and differences between concepts will avoid misunderstandings in care. The varied and often unpredictable symptoms and degenerative nature of neurological conditions make this an ideal population in which to examine the concepts. DESIGN: Concept analysis. DATA SOURCES: Articles were extracted from a large literature review about living with a neurological condition. The original searches were conducted using SCOPUS, EMBASE, CINAHL and Psych INFO. Seventy-seven articles met the inclusion criteria of: (1) original article concerning coping, adaptation or self-management of a neurological condition; (2) written in English; and (3) published between 1999-2011. METHODS: The concepts were examined according to Morse's concept analysis method; structural elements were then compared. Results : Coping and adaptation to a neurological condition showed statistically significant overlap with a common focus on internal management. In contrast, self-management appears to focus on disease-controlling and health-related management strategies. Coping appears to be the most mature concept, whereas self-management is least coherent in definition and application. CONCLUSION: All three concepts are relevant for people with neurological conditions. Healthcare teams need to be cautious when using these terms to avoid miscommunication and to ensure clients have access to all needed interventions. Viewing the three concepts as a complex whole may be more aligned with client experience

A systematic review of the effectiveness of stroke self-management programs for improving function and participation outcomes: self-management programs for stroke survivors

Item does not contain fulltextPURPOSE: A systematic review of stroke self-management programs was conducted to: (i) identify how many and what self-management support strategies were included in stroke self-management interventions and (ii) describe whether self-management programs effectively improved outcomes, focusing specifically on function and participation outcomes. METHODS: Twelve databases were searched for the years 1986-2012 to identify self-management programs for stroke survivors. Pre-post, quasi-experimental and randomized controlled trial study designs were included. Descriptive information about the intervention was scrutinized to identify what self-management support strategies were present in the intervention and comparisons were made between programs using a group versus a one-to-one format. All outcomes were included and categorized. RESULTS: The most prominent strategies identified in our review were goal setting and follow-up, and an individualized approach using structured information and professional support. There are indications that self-management programs can significantly increase participation and functional ability. However, the high level of clinical heterogeneity in program delivery, outcomes and level of stroke severity made it impossible to conduct a meta-analysis. Further examination of individual self-management support strategies, such as linking rehabilitation goal setting to post-acute self-management programs, the inclusion of family members and the contribution of peer-support is warranted. Implications for Rehabilitation Self-management programs for stroke survivors: Linking post-acute self-management programs to rehabilitation goal setting could improve outcomes. Involving family members in self-management programs may benefit stroke survivors

Managing everyday life: Self-management strategies people use to live well with neurological conditions

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