731 research outputs found

    The Psychological Effects of Short-Term Fasting in Healthy Women.

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    OBJECTIVE: The study aimed to investigate affective responses to 18-h fasting in healthy controls. In particular, the study focused on self-reported mood, irritability, sense of achievement, reward, pride, and control. METHOD: Participants were a non-clinical sample of 52 women with a mean age of 25. A repeated-measures design was used, whereby participants provided diary measures of psychological variables throughout both 18-h fasting and non-fasting periods. RESULTS: Fasting led to increased irritability, and also to positive affective experiences of increased sense of achievement, reward, pride, and control. DISCUSSION: Even short-term fasting in healthy controls can lead to positive psychological experiences. This lends support to cognitive-behavioral and cognitive-interpersonal models of ANR, which suggest that dietary restriction is maintained through positive reinforcement

    The relationship between amyloid structure and cytotoxicity

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    Self-assembly of proteins and peptides into amyloid structures has been the subject of intense and focused research due to their association with neurodegenerative, age-related human diseases and transmissible prion diseases in humans and mammals. Of the disease associated amyloid assemblies, a diverse array of species, ranging from small oligomeric assembly intermediates to fibrillar structures, have been shown to have toxic potential. Equally, a range of species formed by the same disease associated amyloid sequences have been found to be relatively benign under comparable monomer equivalent concentrations and conditions. In recent years, an increasing number of functional amyloid systems have also been found. These developments show that not all amyloid structures are generically toxic to cells. Given these observations, it is important to understand why amyloid structures may encode such varied toxic potential despite sharing a common core molecular architecture. Here, we discuss possible links between different aspects of amyloidogenic structures and assembly mechanisms with their varied functional effects. We propose testable hypotheses for the relationship between amyloid structure and its toxic potential in the context of recent reports on amyloid sequence, structure, and toxicity relationships

    Improving the post-meal experience of hospitalised patients with eating disorders using visuospatial, verbal and somatic activities

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    BACKGROUND: This study compares the effects of different cognitive tasks on post-meal negative affect, positive affect, intrusive thoughts and intrusive images of hospitalised patients with eating disorders. METHODS: Twenty-five participants were recruited from an eating disorder service. Using a within-subjects design, participants performed one of the following tasks for 15 min: the game 'Tetris' (visuospatial), a general knowledge 'Quiz' (verbal), 'Braille' translation (somatic) and 'Sitting Quietly' (control). In total, participants completed each task on three occasions. RESULTS: The visuospatial, verbal and somatic tasks had beneficial effects on all positive and negative indicators, when compared with 'Sitting Quietly'. Visuospatial and somatic tasks were more effective at reducing intrusive imagery than the verbal task. CONCLUSIONS: The results suggest that certain engaging activities can help hospitalised patients with eating disorders manage the difficult post-meal period

    Self-adaptation of mutation operator and probability for permutation representations in genetic algorithms

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    The choice of mutation rate is a vital factor in the success of any genetic algorithm (GA), and for permutation representations this is compounded by the availability of several alternative mutation operators. It is now well understood that there is no one "optimal choice"; rather, the situation changes per problem instance and during evolution. This paper examines whether this choice can be left to the processes of evolution via selfadaptation, thus removing this nontrivial task fromtheGAuser and reducing the risk of poor performance arising from (inadvertent) inappropriate decisions. Self-adaptation has been proven successful for mutation step sizes in the continuous domain, and for the probability of applying bitwise mutation to binary encodings; here we examine whether this can translate to the choice and parameterisation of mutation operators for permutation encodings. We examine one method for adapting the choice of operator during runtime, and several different methods for adapting the rate at which the chosen operator is applied. In order to evaluate these algorithms, we have used a range of benchmark TSP problems. Of course this paper is not intended to present a state of the art in TSP solvers; rather, we use this well known problem as typical of many that require a permutation encoding, where our results indicate that self-adaptation can prove beneficial. The results show that GAs using appropriate methods to self-adapt their mutation operator and mutation rate find solutions of comparable or lower cost than algorithms with "static" operators, even when the latter have been extensively pretuned. Although the adaptive GAs tend to need longer to run, we show that is a price well worth paying as the time spent finding the optimal mutation operator and rate for the nonadaptive versions can be considerable. Finally, we evaluate the sensitivity of the self-adaptive methods to changes in the implementation, and to the choice of other genetic operators and population models. The results show that the methods presented are robust, in the sense that the performance benefits can be obtained in a wide range of host algorithms. © 2010 by the Massachusetts Institute of Technology

    Amyloidogenicity and toxicity of the reverse and scrambled variants of amyloid-β 1-42

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    β-amyloid 1-42 (Aβ1-42) is a self-assembling peptide that goes through many conformational and morphological changes before forming the fibrils that are deposited in extracellular plaques characteristic of Alzheimer's disease. The link between Aβ1-42 structure and toxicity is of major interest, in particular, the neurotoxic potential of oligomeric species. Many studies utilise reversed (Aβ42-1) and scrambled (AβS) forms of amyloid-β as control peptides. Here, using circular dichroism, thioflavin T fluorescence and transmission electron microscopy, we reveal that both control peptides self-assemble to form fibres within 24 h. However, oligomeric Aβ reduces cell survival of hippocampal neurons, while Aβ42-1 and Aβs have reduced effect on cellular health, which may arise from their ability to assemble rapidly to form protofibrils and fibrils

    How Does Fasting Affect Cognition? An Updated Systematic Review (2013–2020)

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    Purpose of Review: The goal of this review was to provide an update on the literature examining how voluntary, temporary abstention from eating impacts cognitive function. / Recent Findings: We evaluated peer-reviewed articles published between August 2013 and January 2021 that assessed adults, included a measure of cognitive functioning with neutral stimuli, and compared individuals in a fasted state to individuals in a fed state (either within- or between-subject designs). Nineteen articles (21 studies) met inclusion criteria. Sample sizes, fasting methods, and tasks varied across studies. Review of studies indicated that fasting was associated with deficits in cognitive functioning; few studies indicated a benefit in cognitive functioning following a single voluntary fast. / Summary: The heterogeneity and rarity of available studies limits the conclusions that can be drawn. Several crucial psychosocial and sociodemographic moderators remain unexplored. Recommendations for future work are discussed

    The diversity and utility of amyloid fibrils formed by short amyloidogenic peptides

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    Amyloidogenic peptides are well known for their involvement in diseases such as type 2 diabetes and Alzheimer's disease. However, more recently, amyloid fibrils have been shown to provide scaffolding and protection as functional materials in a range of organisms from bacteria to humans. These roles highlight the incredible tensile strength of the cross-β amyloid architecture. Many amino acid sequences are able to self-assemble to form amyloid with a cross-β core. Here we describe our recent advances in understanding how sequence contributes to amyloidogenicity and structure. For example, we describe penta- and hexapeptides that assemble to form different morphologies; a 12mer peptide that forms fibrous crystals; and an eight-residue peptide originating from α-synuclein that has the ability to form nanotubes. This work provides a wide range of peptides that may be exploited as fibrous bionanomaterials. These fibrils provide a scaffold upon which functional groups may be added, or templated assembly may be performed

    The molecular basis for apolipoprotein E4 as the major risk factor for late onset Alzheimer's disease

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    Apolipoprotein E4 (ApoE4) is one of three (E2, E3 and E4) human isoforms of an -helical, 299-amino acid protein. Homozygosity for the ε4 allele is the major risk factor for developing late onset Alzheimer’s disease (AD). ApoE2, ApoE3 and ApoE4 differ at amino acid positions 112 and 158 and these sequence variations may confer conformational differences that underlie their participation in the risk of developing AD. Here, we compared the shape, oligomerisation state, conformation and stability of ApoE isoforms using a range of complementary biophysical methods including small angle X-ray scattering, analytical ultracentrifugation, circular dichroism, X-ray fibre diffraction and transmission electron microscopy We provide an in-depth and definitive study demonstrating that all three proteins are similar in stability and conformation. However, we show that ApoE4 has a propensity to polymerise to form wavy filaments which do not share the characteristics of cross- amyloid fibrils. Moreover, we provide evidence for the inhibition of ApoE4 fibril formation by ApoE3. This study shows that recombinant ApoE isoforms show no significant differences at the structural or conformational level. However, self-assembly of the ApoE4 isoform may play a role in pathogenesis and these results open opportunities for uncovering new triggers for AD onset

    Oxidative Stress Conditions Result in Trapping of PHF-Core Tau (297–391) Intermediates

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    Funding: This work was supported by funding from Alzheimer’s Society [345 (AS-PG-16b-010)] awarded to L.C.S. and funding M.B.M. Y.K.A.-H. is supported by WisTa Laboratories Ltd. (PAR1596). The work was supported by ARUK South Coast Network. G.B. was supported by European Molecular Biology Organisation (EMBO) Short-Term Fellowship award (EMBO-STF 7674). LCS is supported by BBSRC [BB/S003657/1]. Acknowledgments: TEM work was performed at the University of Sussex’s Electron microscopy imaging centre (EMC), funded by the School of Life Sciences, the Wellcome Trust (095605/Z/11/A, 208348/Z/17/Z) and the RM Phillips Trust. The authors thank Pascale Schellenberger for valuable support.Peer reviewedPublisher PD
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