Search results for "being"

Intercalation of daunomycin into stacked DNA base pairs. DFT study of an anticancer drug

2008

We have computationally studied the intercalation of the antitumor drug daunomycin into six stacks of Watson-Crick DNA base pairs i.e., AT-AT, AT-TA, GC-AT, CG-TA, GC-GC, GC-CG) using density functional theory (DFT). The proton affinity of the DNA intercalater daunomycin in water was computed to be 159.2 kcal/mol at BP86/TZ2P, which is in line with the experimental observation that daunomycin is protonated under physiological conditions. The intercalation interaction of protonated daunomycin with two stacked DNA base pairs was studied through a hybrid approach in which intercalation is treated at LDA/TZP while the molecular structure of daunomycin and hydrogen-bonded Watson-Crick pairs is c…

Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops

2014

AbstractHypervariable loops of HIV-1 Env protein gp120 are speculated to play roles in the conformational transition of Env to the receptor binding-induced metastable state. Structural analysis of full-length Env-based immunogens, containing the entire V2 loop, displayed tighter association between gp120 subunits, resulting in a smaller trimeric diameter than constructs lacking V2. A prominent basal quaternary location of V2 and V3′ that challenges previous reports would facilitate gp41-independent gp120-gp120 interactions and suggests a quaternary mechanism of epitope occlusion facilitated by hypervariable loops. Deletion of V2 resulted in dramatic exposure of basal, membrane-proximal gp41…

Lipid profiling following intake of the Omega 3 fatty acid DHA identifies the peroxidized metabolites F-4-Neuroprostanes as the best predictors of at…

2014

International audience; The anti-atherogenic effects of omega 3 fatty acids, namely eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) are well recognized but the impact of dietary intake on bioactive lipid mediat or profiles remains unclear. Such a profiling effort may offer novel targets for future studies into the mechanism of action of omega 3 fatty acids. The present study aimed to determine the impact of DHA supplementation on the profiles of polyunsaturated fatty acids (PUFA) oxygenated metabolites and to investigate their contribution to therosclerosis prevention. A special emphasis was given to the non-enzymatic metabolites knowing the high susceptibility of DHA to free radical…

2021

Background and objectives Choir singing has been associated with better mood and quality of life (QOL) in healthy older adults, but little is known about its potential cognitive benefits in aging. In this study, our aim was to compare the subjective (self-reported) and objective (test-based) cognitive functioning of senior choir singers and matched control subjects, coupled with assessment of mood, QOL, and social functioning. Research design and methods We performed a cross-sectional questionnaire study in 162 healthy older (age ≥ 60 years) adults (106 choir singers, 56 controls), including measures of cognition, mood, social engagement, QOL, and role of music in daily life. The choir sin…

Perceived Reciprocity and Well-Being at Work in Non-Professional Employees: Fairness or Self-Interest?

2012

This article assesses the links between non-professional employees' perceptions of reciprocity in their relationships with their supervisors and the positive and negative sides of employees' well-being at work: burnout and engagement. Two hypotheses were explored. First, the fairness hypothesis assumes a curvilinear relationship where balanced reciprocity (when the person perceives that there is equilibrium between his/her efforts and the benefits he/she receives) presents the highest level of well-being. Second, the self-interest hypothesis proposes a linear pattern where over-benefitted situations for employees (when the person perceives that he/she is receiving more than he/she deserves)…

Personal goal appraisals vary across both individuals and goal contents

2009

Abstract This study examined personal goals as a multilevel construct. After investigating to what extent goal appraisals were characteristics of an individual as compared to the extent to which they vary across different goals, both individual-level and goal-level predictors of goal appraisals were examined. To examine these research questions 477 undergraduates filled in the Personal Project Analysis and Beck’s Depression inventory. Multilevel modeling showed that, although goal appraisals varied between individuals, they differed to greater extent across the different goals a particular person reported. At the individual level, a high amount of depressive symptoms was associated with a l…

Theory-based digital intervention to promote weight loss and weight loss maintenance (Choosing Health)

2020

IntroductionDigital behavioural weight loss interventions have the potential to improve public health; however, these interventions are often not adequately tailored to the needs of the participants. This is the protocol for a trial that aims to determine the effectiveness and cost-effectiveness of the Choosing Health programme as a means to promote weight loss and weight loss maintenance among overweight/obese adults.Methods and analysisThe proposed study is a two-group randomised controlled trial with a nested interrupted time series (ITS) within-person design. Participants (n=285) will be randomly assigned to either the Choosing Health digital intervention or a control group. For interve…

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: Further evidence and meta-analysis

2013

NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our stron…

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

2018

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generat…

A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol

2011

Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ∼25% of the heritability of the phenotypes. To date, no unbiased screen for gene–environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on …