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Sample records for physical functioning domain

  1. Correlations between physical activity and neurocognitive domain functions in patients with schizophrenia: a cross-sectional study.

    Science.gov (United States)

    Kurebayashi, Yusuke; Otaki, Junichi

    2017-01-05

    Neurocognitive dysfunction is a critical target symptom of schizophrenia treatment. A positive correlation between physical activity level and neurocognitive function has been reported in healthy individuals, but it is unclear whether such a correlation exists in patients with schizophrenia and whether the relationship is different according to inpatients or outpatients. This study aimed to examine the differences in the correlations between physical activity and multiple neurocognitive domains in inpatients and outpatients with schizophrenia and obtain suggestions for further study to facilitate this field. Twenty-nine patients with schizophrenia were examined (16 inpatients and 13 outpatients, 56.0 ± 11.4 years of age). Current symptoms were assessed using the Positive and Negative Symptom Scale and neurocognitive functions using Cognitrax, which yields a composite neurocognitive index (NCI) and 11 domain scores. After testing, participants wore an HJA-750C accelerometer for one week to measure physical activity levels and durations. Partial correlation analyses were performed between exercise and cognitive parameters. In the outpatient group, higher physical activity was associated with faster Motor and Psychomotor Speeds in outpatients. However, higher physical activity was associated with lower overall NCI, Attention score, and Memory scores in inpatients. Although higher physical activity was associated with better neurocognitive functions of outpatients, in inpatients with non-remitted schizophrenia, higher physical activity was associated with worsening of several cognitive domains. In a future study examining the relationship between physical activity and neurocognitive function for facilitating this research field, separation between inpatients and outpatients are needed because the relationship is different between inpatients and outpatients.

  2. PROMIS PF CAT Outperforms the ODI and SF-36 Physical Function Domain in Spine Patients.

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    Brodke, Darrel S; Goz, Vadim; Voss, Maren W; Lawrence, Brandon D; Spiker, William Ryan; Hung, Man

    2017-06-15

    The Oswestry Disability Index v2.0 (ODI), SF36 Physical Function Domain (SF-36 PFD), and PROMIS Physical Function CAT v1.2 (PF CAT) questionnaires were prospectively collected from 1607 patients complaining of back or leg pain, visiting a university-based spine clinic. All questionnaires were collected electronically, using a tablet computer. The aim of this study was to compare the psychometric properties of the PROMIS PF CAT with the ODI and SF36 Physical Function Domain in the same patient population. Evidence-based decision-making is improved by using high-quality patient-reported outcomes measures. Prior studies have revealed the shortcomings of the ODI and SF36, commonly used in spine patients. The PROMIS Network has developed measures with excellent psychometric properties. The Physical Function domain, delivered by Computerized Adaptive Testing (PF CAT), performs well in the spine patient population, though to-date direct comparisons with common measures have not been performed. Standard Rasch analysis was performed to directly compare the psychometrics of the PF CAT, ODI, and SF36 PFD. Spearman correlations were computed to examine the correlations of the three instruments. Time required for administration was also recorded. One thousand six hundred seven patients were administered all assessments. The time required to answer all items in the PF CAT, ODI, and SF-36 PFD was 44, 169, and 99 seconds. The ceiling and floor effects were excellent for the PF CAT (0.81%, 3.86%), while the ceiling effects were marginal and floor effects quite poor for the ODI (6.91% and 44.24%) and SF-36 PFD (5.97% and 23.65%). All instruments significantly correlated with each other. The PROMIS PF CAT outperforms the ODI and SF-36 PFD in the spine patient population and is highly correlated. It has better coverage, while taking less time to administer with fewer questions to answer. 2.

  3. Physical Activity Throughout the Adult Life Span and Domain-Specific Cognitive Function in Old Age: A Systematic Review of Cross-Sectional and Longitudinal Data.

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    Engeroff, Tobias; Ingmann, Tobias; Banzer, Winfried

    2018-06-01

    A growing body of literature suggests that physical activity might alleviate the age-related neurodegeneration and decline of cognitive function. However, most of this evidence is based on data investigating the association of exercise interventions or current physical activity behavior with cognitive function in elderly subjects. We performed a systematic review and hypothesize that physical activity during the adult life span is connected with maintained domain-specific cognitive functions during late adulthood defined as age 60+ years. We performed a systematic literature search up to November 2017 in PubMed, Web of Science, and Google Scholar without language limitations for studies analyzing the association of leisure physical activity during the adult life span (age 18+ years) and domain-specific cognitive functions in older adults (age 60+ years). The literature review yielded 14,294 articles and after applying inclusion and exclusion criteria, nine cross-sectional and 14 longitudinal studies were included. Moderate- and vigorous-intensity leisure physical activity was associated with global cognitive function and specific cognitive domains including executive functions and memory but not attention or working memory. Most studies assessed mid- to late-adulthood physical activity, thus information concerning the influence of young adult life-span physical activity is currently lacking. Observational evidence that moderate- and vigorous-intensity leisure physical activity is beneficially associated with maintained cognitive functions during old age is accumulating. Further studies are necessary to confirm a causal link by assessing objective physical activity data and the decline of cognitive functions at multiple time points during old age.

  4. Bile acids modulate signaling by functional perturbation of plasma membrane domains.

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    Zhou, Yong; Maxwell, Kelsey N; Sezgin, Erdinc; Lu, Maryia; Liang, Hong; Hancock, John F; Dial, Elizabeth J; Lichtenberger, Lenard M; Levental, Ilya

    2013-12-13

    Eukaryotic cell membranes are organized into functional lipid and protein domains, the most widely studied being membrane rafts. Although rafts have been associated with numerous plasma membrane functions, the mechanisms by which these domains themselves are regulated remain undefined. Bile acids (BAs), whose primary function is the solubilization of dietary lipids for digestion and absorption, can affect cells by interacting directly with membranes. To investigate whether these interactions affected domain organization in biological membranes, we assayed the effects of BAs on biomimetic synthetic liposomes, isolated plasma membranes, and live cells. At cytotoxic concentrations, BAs dissolved synthetic and cell-derived membranes and disrupted live cell plasma membranes, implicating plasma membrane damage as the mechanism for BA cellular toxicity. At subtoxic concentrations, BAs dramatically stabilized domain separation in Giant Plasma Membrane Vesicles without affecting protein partitioning between coexisting domains. Domain stabilization was the result of BA binding to and disordering the nonraft domain, thus promoting separation by enhancing domain immiscibility. Consistent with the physical changes observed in synthetic and isolated biological membranes, BAs reorganized intact cell membranes, as evaluated by the spatial distribution of membrane-anchored Ras isoforms. Nanoclustering of K-Ras, related to nonraft membrane domains, was enhanced in intact plasma membranes, whereas the organization of H-Ras was unaffected. BA-induced changes in Ras lateral segregation potentiated EGF-induced signaling through MAPK, confirming the ability of BAs to influence cell signal transduction by altering the physical properties of the plasma membrane. These observations suggest general, membrane-mediated mechanisms by which biological amphiphiles can produce their cellular effects.

  5. Charm physics with physical light and strange quarks using domain wall fermions

    CERN Document Server

    Boyle, Peter A; Garron, Nicolas; Khamseh, Ava; Marinkovic, Marina; Sanfilippo, Francesco; Tsang, Justus Tobias; Boyle, Peter A.

    2015-01-01

    We present a study of charm physics using RBC/UKQCD 2+1 flavour physical point domain wall fermion ensembles for the light quarks as well as for the valence charm quark. After a brief motivation of domain wall fermions as a suitable heavy quark discretisation we will show first results for masses and matrix elements.

  6. From function to form using physical reasoning

    DEFF Research Database (Denmark)

    Zavbi, R.; Hansen, Claus Thorp

    2002-01-01

    The goal of engineering design is to design a product, which fulfils a required function. The Domain theory and chaining of physical laws (way to synthesise solutions) offer a possibility to propose a framework of how to carry out functional reasoning. The proposed framework consists of mental ob...

  7. Different functional modes of BAR domain proteins in formation and plasticity of mammalian postsynapses.

    Science.gov (United States)

    Kessels, Michael M; Qualmann, Britta

    2015-09-01

    A plethora of cell biological processes involve modulations of cellular membranes. By using extended lipid-binding interfaces, some proteins have the power to shape membranes by attaching to them. Among such membrane shapers, the superfamily of Bin-Amphiphysin-Rvs (BAR) domain proteins has recently taken center stage. Extensive structural work on BAR domains has revealed a common curved fold that can serve as an extended membrane-binding interface to modulate membrane topologies and has allowed the grouping of the BAR domain superfamily into subfamilies with structurally slightly distinct BAR domain subtypes (N-BAR, BAR, F-BAR and I-BAR). Most BAR superfamily members are expressed in the mammalian nervous system. Neurons are elaborately shaped and highly compartmentalized cells. Therefore, analyses of synapse formation and of postsynaptic reorganization processes (synaptic plasticity) - a basis for learning and memory formation - has unveiled important physiological functions of BAR domain superfamily members. These recent advances, furthermore, have revealed that the functions of BAR domain proteins include different aspects. These functions are influenced by the often complex domain organization of BAR domain proteins. In this Commentary, we review these recent insights and propose to classify BAR domain protein functions into (1) membrane shaping, (2) physical integration, (3) action through signaling components, and (4) suppression of other BAR domain functions. © 2015. Published by The Company of Biologists Ltd.

  8. Structural and functional analysis of multi-interface domains.

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    Liang Zhao

    Full Text Available A multi-interface domain is a domain that can shape multiple and distinctive binding sites to contact with many other domains, forming a hub in domain-domain interaction networks. The functions played by the multiple interfaces are usually different, but there is no strict bijection between the functions and interfaces as some subsets of the interfaces play the same function. This work applies graph theory and algorithms to discover fingerprints for the multiple interfaces of a domain and to establish associations between the interfaces and functions, based on a huge set of multi-interface proteins from PDB. We found that about 40% of proteins have the multi-interface property, however the involved multi-interface domains account for only a tiny fraction (1.8% of the total number of domains. The interfaces of these domains are distinguishable in terms of their fingerprints, indicating the functional specificity of the multiple interfaces in a domain. Furthermore, we observed that both cooperative and distinctive structural patterns, which will be useful for protein engineering, exist in the multiple interfaces of a domain.

  9. Physics education students’ cognitive and affective domains toward ecological phenomena

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    Napitupulu, N. D.; Munandar, A.; Redjeki, S.; Tjasyono, B.

    2018-05-01

    Environmental education is become prominent in dealing with natural phenomena that occur nowadays. Studying environmental physics will lead students to have conceptual understanding which are importent in enhancing attitudes toward ecological phenomena that link directry to cognitive and affective domains. This research focused on the the relationship of cognitive and affective domains toward ecological phenomena. Thirty-seven Physics Education students participated in this study and validated sources of data were collected to eksplore students’ conceptual understanding as cognitive domain and to investigate students’ attitudes as affective domain. The percentage of cognitive outcome and affective outcome are explore. The features of such approaches to environmental learning are discussion through analysis of contribution of cognitive to develop the attitude ecological as affective outcome. The result shows that cognitive domains do not contribute significantly to affective domain toward ecological henomena as an issue trend in Central Sulawesi although students had passed Environmental Physics instruction for two semester. In fact, inferior knowledge in a way actually contributes to the attitude domain caused by the prior knowledge that students have as ombo as a Kaili local wisdom.

  10. Physical optics far field inverse scattering in the time domain

    International Nuclear Information System (INIS)

    Bleistein, N.

    1976-01-01

    The physical optics far field inverse scattering (POFFIS) identity relates the phase and range normalized far field back scattering amplitude to the spatial Fourier transform of the characteristic function of the scattering obstacle. The characteristic function is equal to unity in the region occupied by the obstacle and zero elsewhere. The original identity was derived by Bojarski for impulsive point sources. The result is extended to sources of arbitrary time dependence. One obtains an alternative form of Bojarski's POFFIS identity. One also derives a POFFIS identity in the time domain. Numerically synthesized checks on the method are provided

  11. The YARHG domain: an extracellular domain in search of a function.

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    Penny Coggill

    Full Text Available We have identified a new bacterial protein domain that we hypothesise binds to peptidoglycan. This domain is called the YARHG domain after the most highly conserved sequence-segment. The domain is found in the extracellular space and is likely to be composed of four alpha-helices. The domain is found associated with protein kinase domains, suggesting it is associated with signalling in some bacteria. The domain is also found associated with three different families of peptidases. The large number of different domains that are found associated with YARHG suggests that it is a useful functional module that nature has recombined multiple times.

  12. Exploring the relations among physical fitness, executive functioning, and low academic achievement.

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    de Bruijn, A G M; Hartman, E; Kostons, D; Visscher, C; Bosker, R J

    2018-03-01

    Physical fitness seems to be related to academic performance, at least when taking the role of executive functioning into account. This assumption is highly relevant for the vulnerable population of low academic achievers because their academic performance might benefit from enhanced physical fitness. The current study examined whether physical fitness and executive functioning are independent predictors of low mathematics and spelling achievement or whether the relation between physical fitness and low achievement is mediated by specific executive functions. In total, 477 students from second- and third-grade classes of 12 primary schools were classified as either low or average-to-high achievers in mathematics and spelling based on their scores on standardized achievement tests. Multilevel structural equation models were built with direct paths between physical fitness and academic achievement and added indirect paths via components of executive functioning: inhibition, verbal working memory, visuospatial working memory, and shifting. Physical fitness was only indirectly related to low achievement via specific executive functions, depending on the academic domain involved. Verbal working memory was a mediator between physical fitness and low achievement in both domains, whereas visuospatial working memory had a mediating role only in mathematics. Physical fitness interventions aiming to improve low academic achievement, thus, could potentially be successful. The mediating effect of executive functioning suggests that these improvements in academic achievement will be preceded by enhanced executive functions, either verbal working memory (in spelling) or both verbal and visuospatial working memory (in mathematics). Copyright © 2017 Elsevier Inc. All rights reserved.

  13. An information theory framework for dynamic functional domain connectivity.

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    Vergara, Victor M; Miller, Robyn; Calhoun, Vince

    2017-06-01

    Dynamic functional network connectivity (dFNC) analyzes time evolution of coherent activity in the brain. In this technique dynamic changes are considered for the whole brain. This paper proposes an information theory framework to measure information flowing among subsets of functional networks call functional domains. Our method aims at estimating bits of information contained and shared among domains. The succession of dynamic functional states is estimated at the domain level. Information quantity is based on the probabilities of observing each dynamic state. Mutual information measurement is then obtained from probabilities across domains. Thus, we named this value the cross domain mutual information (CDMI). Strong CDMIs were observed in relation to the subcortical domain. Domains related to sensorial input, motor control and cerebellum form another CDMI cluster. Information flow among other domains was seldom found. Other methods of dynamic connectivity focus on whole brain dFNC matrices. In the current framework, information theory is applied to states estimated from pairs of multi-network functional domains. In this context, we apply information theory to measure information flow across functional domains. Identified CDMI clusters point to known information pathways in the basal ganglia and also among areas of sensorial input, patterns found in static functional connectivity. In contrast, CDMI across brain areas of higher level cognitive processing follow a different pattern that indicates scarce information sharing. These findings show that employing information theory to formally measured information flow through brain domains reveals additional features of functional connectivity. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Clustering of physical inactivity in leisure, work, commuting and household domains among Brazilian adults.

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    Del Duca, G F; Nahas, M V; de Sousa, T F; Mota, J; Hallal, P C; Peres, K G

    2013-06-01

    To identify the clustering of physical inactivity in leisure, work, commuting and household contexts, and the sociodemographic factors associated with the clustering of inactive behaviour in different domains among Brazilian adults. Cross-sectional population-based study. The study was performed in Florianopolis, capital of Santa Catarina, one of the southern states of Brazil, from September 2009 to January 2010. Adults aged 20-59 years were interviewed. Physical inactivity in each domain was defined as non-participation in specific physical activities, using a validated Brazilian questionnaire. Clustering of physical inactivity was identified by the ratio between observed prevalence and expected prevalence of 16 different combinations. Multinomial logistic regression was used in the analysis of sociodemographic factors associated with clustering of physical inactivity. Of the 1720 interviewees, the greatest differences between the observed and expected proportions were observed in simultaneous physical inactivity in the leisure and household domains for men, and physical inactivity in the leisure domain alone for women (59% and 88%, respectively); these differences were higher than expected if the behaviours were independent. Physical inactivity in two or more domains was observed more frequently in men and in individuals with a higher per-capita family income. Ageing was associated with physical inactivity in three or four domains. Physical inactivity was observed in different domains according to gender. Men and older individuals with a higher per-capita family income were more likely to exhibit physical inactivity when all domains were considered together. Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  15. Effects of multi-domain interventions in (prefrail elderly on frailty, functional, and cognitive status: a systematic review

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    Dedeyne L

    2017-05-01

    Full Text Available Lenore Dedeyne,1 Mieke Deschodt,2–4 Sabine Verschueren,5 Jos Tournoy,1,3 Evelien Gielen1,3 1Department of Clinical and Experimental Medicine, 2Department of Public Health and Primary Care, KU Leuven – University of Leuven, Leuven, Belgium; 3Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium; 4Department of Public Health, Institute of Nursing Science, University of Basel, Basel, Switzerland; 5Department of Rehabilitation Sciences, KU Leuven – University of Leuven, Heverlee, Belgium Background: Frailty is an aging syndrome caused by exceeding a threshold of decline across multiple organ systems leading to a decreased resistance to stressors. Treatment for frailty focuses on multi-domain interventions to target multiple affected functions in order to decrease the adverse outcomes of frailty. No systematic reviews on the effectiveness of multi-domain interventions exist in a well-defined frail population. Objectives: This systematic review aimed to determine the effect of multi-domain compared to mono-domain interventions on frailty status and score, cognition, muscle mass, strength and power, functional and social outcomes in (prefrail elderly (≥65 years. It included interventions targeting two or more domains (physical exercise, nutritional, pharmacological, psychological, or social interventions in participants defined as (prefrail by an operationalized frailty definition. Methods: The databases PubMed, EMBASE, CINAHL, PEDro, CENTRAL, and the Cochrane Central register of Controlled Trials were searched from inception until September 14, 2016. Additional articles were searched by citation search, author search, and reference lists of relevant articles. The protocol for this review was registered on PROSPERO (CRD42016032905. Results: Twelve studies were included, reporting a large diversity of interventions in terms of content, duration, and follow-up period. Overall, multi-domain interventions tended to be more

  16. Accumulation of Domain-Specific Physical Inactivity and Presence of Hypertension in Brazilian Public Healthcare System.

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    Turi, Bruna Camilo; Codogno, Jamile S; Fernandes, Romulo A; Sui, Xuemei; Lavie, Carl J; Blair, Steven N; Monteiro, Henrique Luiz

    2015-11-01

    Hypertension is one of the most common noncommunicable diseases worldwide, and physical inactivity is a risk factor predisposing to its occurrence and complications. However, it is still unclear the association between physical inactivity domains and hypertension, especially in public healthcare systems. Thus, this study aimed to investigate the association between physical inactivity aggregation in different domains and prevalence of hypertension among users of Brazilian public health system. 963 participants composed the sample. Subjects were divided into quartiles groups according to 3 different domains of physical activity (occupational; physical exercises; and leisure-time and transportation). Hypertension was based on physician diagnosis. Physical inactivity in occupational domain was significantly associated with higher prevalence of hypertension (OR = 1.52 [1.05 to 2.21]). The same pattern occurred for physical inactivity in leisure-time (OR = 1.63 [1.11 to 2.39]) and aggregation of physical inactivity in 3 domains (OR = 2.46 [1.14 to 5.32]). However, the multivariate-adjusted model showed significant association between hypertension and physical inactivity in 3 domains (OR = 2.57 [1.14 to 5.79]). The results suggest an unequal prevalence of hypertension according to physical inactivity across different domains and increasing the promotion of physical activity in the healthcare system is needed.

  17. Functional modelling for integration of human-software-hardware in complex physical systems

    International Nuclear Information System (INIS)

    Modarres, M.

    1996-01-01

    A framework describing the properties of complex physical systems composed of human-software-hardware interactions in terms of their functions is described. It is argued that such a framework is domain-general, so that functional primitives present a language that is more general than most other modeling methods such as mathematical simulation. The characteristics and types of functional models are described. Examples of uses of the framework in modeling physical systems composed of human-software-hardware (hereby we refer to them as only physical systems) are presented. It is concluded that a function-centered model of a physical system provides a capability for generating a high-level simulation of the system for intelligent diagnostic, control or other similar applications

  18. Physical activity domains and cognitive function over three years in older adults with subjective memory complaints: Secondary analysis from the MAPT trial.

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    de Souto Barreto, Philipe; Andrieu, Sandrine; Rolland, Yves; Vellas, Bruno

    2018-01-01

    We aimed to examine the associations of physical activity (PA) domains (i.e., PA in leisure-time (LTPA), for housework (HPA), or for gardening (GPA)) with cognitive function in older adults with subjective memory complaints (no-dementia) and to investigate if those associations were dependent on the status of apolipoprotein E allele 4 (APOE4), omega-3 levels and mild cognitive impairment (MCI). Observational prospective secondary analysis using longitudinal data from a randomized controlled trial. Participants were 420 French community-dwelling people (aged 75.6±4.4; 66.4% women) randomized into the placebo group. They were assessed at baseline, 6-, 12-, 24- and 36-month using a battery of neuropsychological tests; a composite cognitive Z score was elaborated for all time points. Data on PA come from baseline and was obtained using a self-reported questionnaire. In time-adjusted analysis, LTPA significantly predicted cognitive function over three years for almost all tests and the composite Z score, with higher LTPA associated with better function; multivariate analysis showed a significant association only for verbal fluency. HPA was not associated to cognitive function, whereas GPA had mixed results. The magnitude of the PA-cognition associations was very weak, being the strongest for LTPA. Stratified analyses showed that the associations between PA and cognitive function were stronger for MCI, people with normal omega-3 index levels, and APOE4 non-carriers. PA domain is an important aspect to take into account when examining the associations between PA and cognitive function. Biomarkers of cognitive function may modulate the PA-cognition associations. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  19. Relationship between the physical environment and different domains of physical activity in European adults: a systematic review

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    Van Holle Veerle

    2012-09-01

    Full Text Available Abstract Background In the past decade, various reviews described the relationship between the physical environment and different physical activity (PA domains. Yet, the majority of the current review evidence relies on North American/Australian studies, while only a small proportion of findings refer to European studies. Given some clear environmental differences across continents, this raises questions about the applicability of those results in European settings. This systematic review aimed at summarizing Europe-specific evidence on the relationship between the physical environment and different PA domains in adults. Methods Seventy eligible papers were identified through systematic searches across six electronic databases. Included papers were observational studies assessing the relationship between several aspects of the physical environment and PA in European adults (18-65y. Summary scores were calculated to express the strength of the relationship between each environmental factor and different PA domains. Results Convincing evidence on positive relationships with several PA domains was found for following environmental factors: walkability, access to shops/services/work and the composite factor environmental quality. Convincing evidence considering urbanization degree showed contradictory results, dependent on the observed PA domain. Transportation PA was more frequently related to the physical environment than recreational PA. Possible evidence for a positive relationship with transportation PA emerged for walking/cycling facilities, while a negative relationship was found for hilliness. Some environmental factors, such as access to recreational facilities, aesthetics, traffic- and crime-related safety were unrelated to different PA domains in Europe. Conclusions Generally, findings from this review of European studies are in accordance with results from North American/Australian reviews and may contribute to a generalization of the

  20. Executive functions, physical fitness and mobility in well-functioning older adults.

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    Berryman, Nicolas; Bherer, Louis; Nadeau, Sylvie; Lauzière, Séléna; Lehr, Lora; Bobeuf, Florian; Kergoat, Marie Jeanne; Vu, Thien Tuong Minh; Bosquet, Laurent

    2013-12-01

    The objective of this study was to examine the relationships between executive functions, physical fitness and mobility in well-functioning older adults. Forty-eight well functioning older adults (70.5±5.3years old; 20 men, 28 women) were included in this study. Two median splits were conducted based on each individual's performance for the 10MWT and TUG. Comparisons between groups of slower and faster individuals were made with regard to executive functions and physical fitness parameters. A correlational approach was used to assess the association between variables. Between groups comparisons revealed that faster individuals in mobility tests demonstrate better performances in measures of cognitive flexibility (0.68domain, significant correlations were established between faster mobility tests and better cognitive flexibility (TUG: r=0.565; 10MWT: r=0.324). Between groups comparisons also revealed that faster individuals in mobility tests presented higher physical fitness levels (aerobic: 0.49physical fitness and better cognitive flexibility (strength: r=-0.380; VO2 peak: r=-0.325) even after including age, education, fat-free mass and gender as covariates. These results suggest that the TUG and the 10MWT could potentially help distinguish individuals with poor neuromuscular, aerobic and cognitive flexibility performances. © 2013.

  1. A Conceptual Foundation for Measures of Physical Function and Behavioral Health Function for Social Security Work Disability Evaluation

    Science.gov (United States)

    Marfeo, Elizabeth E.; Haley, Stephen M.; Jette, Alan M.; Eisen, Susan V.; Ni, Pengsheng; Bogusz, Kara; Meterko, Mark; McDonough, Christine M.; Chan, Leighton; Brandt, Diane E.; Rasch, Elizabeth K.

    2014-01-01

    Physical and mental impairments represent the two largest health condition categories for which workers receive Social Security disability benefits. Comprehensive assessment of physical and mental impairments should include aspects beyond medical conditions such as a person’s underlying capabilities as well as activity demands relevant to the context of work. The objective of this paper is to describe the initial conceptual stages of developing new measurement instruments of behavioral health and physical functioning relevant for Social Security work disability evaluation purposes. To outline a clear conceptualization of the constructs to be measured, two content models were developed using structured and informal qualitative approaches. We performed a structured literature review focusing on work disability and incorporating aspects of the International Classification of Functioning, Disability, and Health (ICF) as a unifying taxonomy for framework development. Expert interviews provided advice and consultation to enhance face validity of the resulting content models. The content model for work-related behavioral health function identifies five major domains (1) Behavior Control, (2) Basic Interactions, (3) Temperament and Personality, (4) Adaptability, and (5) Workplace Behaviors. The content model describing physical functioning includes three domains (1) Changing and Maintaining Body Position, (2) Whole Body Mobility, and (3) Carrying, Moving and Handling Objects. These content models informed subsequent measurement properties including item development, measurement scale construction, and provided conceptual coherence guiding future empirical inquiry. The proposed measurement approaches show promise to comprehensively and systematically assess physical and behavioral health functioning relevant to work. PMID:23548543

  2. Domains of bosonic functional integrals

    International Nuclear Information System (INIS)

    Botelho, Luiz C.L.; Para Univ., Belem, PA

    1998-07-01

    We propose a mathematical framework for bosonic Euclidean quantum field functional integrals based on the theory of integration on the dual algebraic vector space of classical field sources. We present a generalization of the Minlos-Dao Xing theorem and apply it to determine exactly the domain of integration associated to the functional integral representation of the two-dimensional quantum electrodynamics Schwinger generating functional. (author)

  3. Conceptual foundation for measures of physical function and behavioral health function for Social Security work disability evaluation.

    Science.gov (United States)

    Marfeo, Elizabeth E; Haley, Stephen M; Jette, Alan M; Eisen, Susan V; Ni, Pengsheng; Bogusz, Kara; Meterko, Mark; McDonough, Christine M; Chan, Leighton; Brandt, Diane E; Rasch, Elizabeth K

    2013-09-01

    Physical and mental impairments represent the 2 largest health condition categories for which workers receive Social Security disability benefits. Comprehensive assessment of physical and mental impairments should include aspects beyond medical conditions such as a person's underlying capabilities as well as activity demands relevant to the context of work. The objective of this article is to describe the initial conceptual stages of developing new measurement instruments of behavioral health and physical functioning relevant for Social Security work disability evaluation purposes. To outline a clear conceptualization of the constructs to be measured, 2 content models were developed using structured and informal qualitative approaches. We performed a structured literature review focusing on work disability and incorporating aspects of the International Classification of Functioning, Disability and Health as a unifying taxonomy for framework development. Expert interviews provided advice and consultation to enhance face validity of the resulting content models. The content model for work-related behavioral health function identifies 5 major domains: (1) behavior control, (2) basic interactions, (3) temperament and personality, (4) adaptability, and (5) workplace behaviors. The content model describing physical functioning includes 3 domains: (1) changing and maintaining body position, (2) whole-body mobility, and (3) carrying, moving, and handling objects. These content models informed subsequent measurement properties including item development and measurement scale construction, and provided conceptual coherence guiding future empirical inquiry. The proposed measurement approaches show promise to comprehensively and systematically assess physical and behavioral health functioning relevant to work. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  4. Recombinant spider silk genetically functionalized with affinity domains.

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    Jansson, Ronnie; Thatikonda, Naresh; Lindberg, Diana; Rising, Anna; Johansson, Jan; Nygren, Per-Åke; Hedhammar, My

    2014-05-12

    Functionalization of biocompatible materials for presentation of active protein domains is an area of growing interest. Herein, we describe a strategy for functionalization of recombinant spider silk via gene fusion to affinity domains of broad biotechnological use. Four affinity domains of different origin and structure; the IgG-binding domains Z and C2, the albumin-binding domain ABD, and the biotin-binding domain M4, were all successfully produced as soluble silk fusion proteins under nondenaturing purification conditions. Silk films and fibers produced from the fusion proteins were demonstrated to be chemically and thermally stable. Still, the bioactive domains are concluded to be folded and accessible, since their respective targets could be selectively captured from complex samples, including rabbit serum and human plasma. Interestingly, materials produced from mixtures of two different silk fusion proteins displayed combined binding properties, suggesting that tailor-made materials with desired stoichiometry and surface distributions of several binding domains can be produced. Further, use of the IgG binding ability as a general mean for presentation of desired biomolecules could be demonstrated for a human vascular endothelial growth factor (hVEGF) model system, via a first capture of anti-VEGF IgG to silk containing the Z-domain, followed by incubation with hVEGF. Taken together, this study demonstrates the potential of recombinant silk, genetically functionalized with affinity domains, for construction of biomaterials capable of presentation of almost any desired biomolecule.

  5. Physical activity and sexual function in middle-aged women

    Directory of Open Access Journals (Sweden)

    Patrícia Uchôa Leitão Cabral

    2014-02-01

    Full Text Available Objective To investigate the relationship between physical activity level and sexual function in middle-aged women. Methods A cross-sectional study with a sample of 370 middle-aged women (40-65 years old, treated at public health care facilities in a Brazilian city. A questionnaire was used containing enquiries on sociodemographic, clinical and behavioral characteristics: the International Physical Activity Questionnaire (IPAQ, short form, and the Female Sexual Function Index (FSFI. Results The average age of the women studied was 49.8 years (± 8.1, 67% of whom exhibited sexual dysfunction (FSFI ≤ 26.55. Sedentary women had a higher prevalence (78.9% of sexual dysfunction when compared to active (57.6% and moderately active (66.7% females (p = 0.002. Physically active women obtained higher score in all FSFI domains (desire, arousal, lubrication, orgasm, satisfaction and pain and total FSFI score (20.9, indicating better sexual function than their moderately active (18.8 and sedentary (15.6 counterparts (p <0.05. Conclusion Physical activity appears to influence sexual function positively in middle-aged women.

  6. COPRED: prediction of fold, GO molecular function and functional residues at the domain level.

    Science.gov (United States)

    López, Daniel; Pazos, Florencio

    2013-07-15

    Only recently the first resources devoted to the functional annotation of proteins at the domain level started to appear. The next step is to develop specific methodologies for predicting function at the domain level based on these resources, and to implement them in web servers to be used by the community. In this work, we present COPRED, a web server for the concomitant prediction of fold, molecular function and functional sites at the domain level, based on a methodology for domain molecular function prediction and a resource of domain functional annotations previously developed and benchmarked. COPRED can be freely accessed at http://csbg.cnb.csic.es/copred. The interface works in all standard web browsers. WebGL (natively supported by most browsers) is required for the in-line preview and manipulation of protein 3D structures. The website includes a detailed help section and usage examples. pazos@cnb.csic.es.

  7. Analysis of the Sequences, Structures, and Functions of Product-Releasing Enzyme Domains in Fungal Polyketide Synthases

    Directory of Open Access Journals (Sweden)

    Lu Liu

    2017-09-01

    Full Text Available Product-releasing enzyme (PRE domains in fungal non-reducing polyketide synthases (NR-PKSs play a crucial role in catalysis and editing during polyketide biosynthesis, especially accelerating final biosynthetic reactions accompanied with product offloading. However, up to date, the systematic knowledge about PRE domains is deficient. In the present study, the relationships between sequences, structures, and functions of PRE domains were analyzed with 574 NR-PKSs of eight groups (I–VIII. It was found that the PRE domains in NR-PKSs could be mainly classified into three types, thioesterase (TE, reductase (R, and metallo-β-lactamase-type TE (MβL-TE. The widely distributed TE or TE-like domains were involved in NR-PKSs of groups I–IV, VI, and VIII. The R domains appeared in NR-PKSs of groups IV and VII, while the physically discrete MβL-TE domains were employed by most NR-PKSs of group V. The changes of catalytic sites and structural characteristics resulted in PRE functional differentiations. The phylogeny revealed that the evolution of TE domains was accompanied by complex functional divergence. The diverse sequence lengths of TE lid-loops affected substrate specificity with different chain lengths. The volume diversification of TE catalytic pockets contributed to catalytic mechanisms with functional differentiations. The above findings may help to understand the crucial catalysis of fungal aromatic polyketide biosyntheses and govern recombination of NR-PKSs to obtain unnatural target products.

  8. Perceived correlates of domain-specific physical activity in rural adults in the Midwest.

    Science.gov (United States)

    Chrisman, Matthew; Nothwehr, Faryle; Yang, Jingzen; Oleson, Jacob

    2014-01-01

    In response to calls for more specificity when measuring physical activity, this study examined perceived correlates of this behavior in rural adults separately by the domain in which this behavior occurs (ie, home care, work, active living, and sport). A cross-sectional survey was completed by 407 adults from 2 rural towns in the Midwest. The questionnaire assessed the perceived social and physical environment, including neighborhood characteristics, as well as barriers to being active. The Kaiser Physical Activity Survey captured domain-specific activity levels. The response rate was 25%. Multiple regression analyses were conducted to examine the associations between social and physical environment factors and domain-specific physical activity. Having a favorable attitude toward using government funds for exercise and activity-friendly neighborhood characteristic were positively associated with active living. Friends encouraging exercise was positively associated with participation in sport. Barriers were inversely associated with active living and sport. Total physical activity was positively associated with workplace incentives for exercise, favorable policy attitudes toward supporting physical education in schools and supporting the use of government funds for biking trails, and it was inversely associated with barriers. There were no factors associated with physical activity in the domains of work or home care. Correlates of physical activity are unique to the domain in which this behavior occurs. Programs to increase physical activity in rural adults should target policy attitudes, neighborhood characteristics, and social support from friends while also working to decrease personal barriers to exercise. © 2014 National Rural Health Association.

  9. Multi-material micro-electromechanical fibers with bendable functional domains

    Science.gov (United States)

    Nguyen-Dang, Tung; Page, Alexis G.; Qu, Yunpeng; Volpi, Marco; Yan, Wei; Sorin, Fabien

    2017-04-01

    The integration of increasingly complex functionalities within thermally drawn multi-material fibers is heralding a novel path towards advanced soft electronics and smart fabrics. Fibers capable of electronic, optoelectronic, piezoelectric or energy harvesting functions are created by assembling new materials in intimate contact within increasingly complex architectures. Thus far, however, the opportunities associated with the integration of cantilever-like structures with freely moving functional domains within multi-material fibers have not been explored. Used extensively in the micro-electromechanical system (MEMS) technology, electro-mechanical transductance from moving and bendable domains is used in a myriad of applications. In this article we demonstrate the thermal drawing of micro-electromechanical fibers (MEMF) that can detect and localize pressure with high accuracy along their entire length. This ability results from an original cantilever-like design where a freestanding electrically conductive polymer composite film bends under an applied pressure. As it comes into contact with another conducting domain, placed at a prescribed position in the fiber cross-section, an electrical signal is generated. We show that by a judicious choice of materials and electrical connectivity, this signal can be uniquely related to a position along the fiber axis. We establish a model that predicts the position of a local touch from the measurement of currents generated in the 1D MEMF device, and demonstrate an excellent agreement with the experimental data. This ability to detect and localize touch over large areas, curved surfaces and textiles holds significant opportunities in robotics and prosthetics, flexible electronic interfaces, and medical textiles. , which features invited work from the best early-career researchers working within the scope of J. Phys. D. This project is part of the Journal of Physics series’ 50th anniversary celebrations in 2017. Fabien Sorin

  10. Same But Different: FIM Summary Scores May Mask Variability in Physical Functioning Profiles.

    Science.gov (United States)

    Fisher, Steve R; Middleton, Addie; Graham, James E; Ottenbacher, Kenneth J

    2018-02-08

    To examine how similar summary scores of physical functioning using the FIM can represent different patient clinical profiles. Retrospective cohort study. Inpatient rehabilitation facilities. Medicare fee-for-service beneficiaries (N=765,441) discharged from inpatient rehabilitation. Not applicable. We used patients' scores on items of the FIM to quantify their level of independence on both self-care and mobility domains. We then identified patients as requiring "no physical assistance" at discharge from inpatient rehabilitation by using a rule and score-based approach. In those patients with FIM self-care and mobility summary scores suggesting no physical assistance needed, we found that physical assistance was in fact needed frequently in bathroom-related activities (eg, continence, toilet and tub transfers, hygiene, clothes management) and with stairs. It was not uncommon for actual performance to be lower than what may be suggested by a summary score of those domains. Further research is needed to create clinically meaningful descriptions of summary scores from combined performances on individual items of physical functioning. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  11. Domain wall partition functions and KP

    International Nuclear Information System (INIS)

    Foda, O; Wheeler, M; Zuparic, M

    2009-01-01

    We observe that the partition function of the six-vertex model on a finite square lattice with domain wall boundary conditions is (a restriction of) a KP τ function and express it as an expectation value of charged free fermions (up to an overall normalization)

  12. Protein domain recurrence and order can enhance prediction of protein functions

    KAUST Repository

    Abdel Messih, Mario A.

    2012-09-07

    Motivation: Burgeoning sequencing technologies have generated massive amounts of genomic and proteomic data. Annotating the functions of proteins identified in this data has become a big and crucial problem. Various computational methods have been developed to infer the protein functions based on either the sequences or domains of proteins. The existing methods, however, ignore the recurrence and the order of the protein domains in this function inference. Results: We developed two new methods to infer protein functions based on protein domain recurrence and domain order. Our first method, DRDO, calculates the posterior probability of the Gene Ontology terms based on domain recurrence and domain order information, whereas our second method, DRDO-NB, relies on the nave Bayes methodology using the same domain architecture information. Our large-scale benchmark comparisons show strong improvements in the accuracy of the protein function inference achieved by our new methods, demonstrating that domain recurrence and order can provide important information for inference of protein functions. The Author(s) 2012. Published by Oxford University Press.

  13. Characterizing Functional Domains for TIM-Mediated Enveloped Virus Entry

    Science.gov (United States)

    Moller-Tank, Sven; Albritton, Lorraine M.; Rennert, Paul D.

    2014-01-01

    ABSTRACT T-cell immunoglobulin and mucin domain 1 (TIM-1) and other TIM family members were recently identified as phosphatidylserine (PtdSer)-mediated virus entry-enhancing receptors (PVEERs). These proteins enhance entry of Ebola virus (EBOV) and other viruses by binding PtdSer on the viral envelope, concentrating virus on the cell surface, and promoting subsequent internalization. The PtdSer-binding activity of the immunoglobulin-like variable (IgV) domain is essential for both virus binding and internalization by TIM-1. However, TIM-3, whose IgV domain also binds PtdSer, does not effectively enhance virus entry, indicating that other domains of TIM proteins are functionally important. Here, we investigate the domains supporting enhancement of enveloped virus entry, thereby defining the features necessary for a functional PVEER. Using a variety of chimeras and deletion mutants, we found that in addition to a functional PtdSer-binding domain PVEERs require a stalk domain of sufficient length, containing sequences that promote an extended structure. Neither the cytoplasmic nor the transmembrane domain of TIM-1 is essential for enhancing virus entry, provided the protein is still plasma membrane bound. Based on these defined characteristics, we generated a mimic lacking TIM sequences and composed of annexin V, the mucin-like domain of α-dystroglycan, and a glycophosphatidylinositol anchor that functioned as a PVEER to enhance transduction of virions displaying Ebola, Chikungunya, Ross River, or Sindbis virus glycoproteins. This identification of the key features necessary for PtdSer-mediated enhancement of virus entry provides a basis for more effective recognition of unknown PVEERs. IMPORTANCE T-cell immunoglobulin and mucin domain 1 (TIM-1) and other TIM family members are recently identified phosphatidylserine (PtdSer)-mediated virus entry-enhancing receptors (PVEERs). These proteins enhance virus entry by binding the phospholipid, PtdSer, present on the viral

  14. Intraindividual variability in cognitive performance in three groups of older adults: cross-domain links to physical status and self-perceived affect and beliefs.

    Science.gov (United States)

    Strauss, Esther; MacDonald, Stuart W S; Hunter, Michael; Moll, Alex; Hultsch, David F

    2002-11-01

    Intraindividual variability of physical status and affect/beliefs as well as their relations with cognition were examined in 3 groups of older adults: healthy elderly, individuals with a nonneurological health-related disturbance (arthritis) and people with neurological compromise (dementia). The findings showed that greater inconsistency in physical performance was observed in groups characterized by central nervous system dysfunction. By contrast, fluctuations in affect appeared to reflect other more transient sources, such as pain. In general, increased inconsistency in non-cognitive domains was associated with poorer cognitive function. There were cross-domain links between inconsistency in physical functioning and fluctuations in cognitive performance, although the nature of the links depended largely upon the neurological status of the individuals. Considered together, the result indicated that measures of cognitive as well as physical variability are important behavioral markers of neurological integrity.

  15. Some asymptotic properties of functions holomorphic in tubular domains

    International Nuclear Information System (INIS)

    Zavialov, B.I.

    1988-10-01

    For the function holomorphic in curved tubular domain the connection between asymptotic behaviour of real part of its boundary value at a given point of base manifold and asymptotic behaviour of the whole function from the inside of this domain is studied. (author). 3 refs

  16. Aperiodic topological order in the domain configurations of functional materials

    Science.gov (United States)

    Huang, Fei-Ting; Cheong, Sang-Wook

    2017-03-01

    In numerous functional materials, such as steels, ferroelectrics and magnets, new functionalities can be achieved through the engineering of the domain structures, which are associated with the ordering of certain parameters within the material. The recent progress in technologies that enable imaging at atomic-scale spatial resolution has transformed our understanding of domain topology, revealing that, along with simple stripe-like or irregularly shaped domains, intriguing vortex-type topological domain configurations also exist. In this Review, we present a new classification scheme of 'Zm Zn domains with Zl vortices' for 2D macroscopic domain structures with m directional variants and n translational antiphases. This classification, together with the concepts of topological protection and topological charge conservation, can be applied to a wide range of materials, such as multiferroics, improper ferroelectrics, layered transition metal dichalcogenides and magnetic superconductors, as we discuss using selected examples. The resulting topological considerations provide a new basis for the understanding of the formation, kinetics, manipulation and property optimization of domains and domain boundaries in functional materials.

  17. Functional diversity of potassium channel voltage-sensing domains.

    Science.gov (United States)

    Islas, León D

    2016-01-01

    Voltage-gated potassium channels or Kv's are membrane proteins with fundamental physiological roles. They are composed of 2 main functional protein domains, the pore domain, which regulates ion permeation, and the voltage-sensing domain, which is in charge of sensing voltage and undergoing a conformational change that is later transduced into pore opening. The voltage-sensing domain or VSD is a highly conserved structural motif found in all voltage-gated ion channels and can also exist as an independent feature, giving rise to voltage sensitive enzymes and also sustaining proton fluxes in proton-permeable channels. In spite of the structural conservation of VSDs in potassium channels, there are several differences in the details of VSD function found across variants of Kvs. These differences are mainly reflected in variations in the electrostatic energy needed to open different potassium channels. In turn, the differences in detailed VSD functioning among voltage-gated potassium channels might have physiological consequences that have not been explored and which might reflect evolutionary adaptations to the different roles played by Kv channels in cell physiology.

  18. Quantification of extra-cerebral and cerebral hemoglobin concentrations during physical exercise using time-domain near infrared spectroscopy

    OpenAIRE

    Auger, Héloïse; Bherer, Louis; Boucher, Étienne; Hoge, Richard; Lesage, Frédéric; Dehaes, Mathieu

    2016-01-01

    Fitness is known to have beneficial effects on brain anatomy and function. However, the understanding of mechanisms underlying immediate and long-term neurophysiological changes due to exercise is currently incomplete due to the lack of tools to investigate brain function during physical activity. In this study, we used time-domain near infrared spectroscopy (TD-NIRS) to quantify and discriminate extra-cerebral and cerebral hemoglobin concentrations and oxygen saturation (SO2) in young adults...

  19. The method of images and Green's function for spherical domains

    International Nuclear Information System (INIS)

    Gutkin, Eugene; Newton, Paul K

    2004-01-01

    Motivated by problems in electrostatics and vortex dynamics, we develop two general methods for constructing Green's function for simply connected domains on the surface of the unit sphere. We prove a Riemann mapping theorem showing that such domains can be conformally mapped to the upper hemisphere. We then categorize all domains on the sphere for which Green's function can be constructed by an extension of the classical method of images. We illustrate our methods by several examples, such as the upper hemisphere, geodesic triangles, and latitudinal rectangles. We describe the point vortex motion in these domains, which is governed by a Hamiltonian determined by the Dirichlet Green's function

  20. An objective measure of physical function of elderly outpatients. The Physical Performance Test.

    Science.gov (United States)

    Reuben, D B; Siu, A L

    1990-10-01

    Direct observation of physical function has the advantage of providing an objective, quantifiable measure of functional capabilities. We have developed the Physical Performance Test (PPT), which assesses multiple domains of physical function using observed performance of tasks that simulate activities of daily living of various degrees of difficulty. Two versions are presented: a nine-item scale that includes writing a sentence, simulated eating, turning 360 degrees, putting on and removing a jacket, lifting a book and putting it on a shelf, picking up a penny from the floor, a 50-foot walk test, and climbing stairs (scored as two items); and a seven-item scale that does not include stairs. The PPT can be completed in less than 10 minutes and requires only a few simple props. We then tested the validity of PPT using 183 subjects (mean age, 79 years) in six settings including four clinical practices (one of Parkinson's disease patients), a board-and-care home, and a senior citizens' apartment. The PPT was reliable (Cronbach's alpha = 0.87 and 0.79, interrater reliability = 0.99 and 0.93 for the nine-item and seven-item tests, respectively) and demonstrated concurrent validity with self-reported measures of physical function. Scores on the PPT for both scales were highly correlated (.50 to .80) with modified Rosow-Breslau, Instrumental and Basic Activities of Daily Living scales, and Tinetti gait score. Scores on the PPT were more moderately correlated with self-reported health status, cognitive status, and mental health (.24 to .47), and negatively with age (-.24 and -.18). Thus, the PPT also demonstrated construct validity. The PPT is a promising objective measurement of physical function, but its clinical and research value for screening, monitoring, and prediction will have to be determined.

  1. Preserving the positive functions of the public domain in science

    Directory of Open Access Journals (Sweden)

    Pamela Samuelson

    2003-11-01

    Full Text Available Science has advanced in part because data and scientific methodologies have traditionally not been subject to intellectual property protection. In recent years, intellectual property has played a greater role in scientific work. While intellectual property rights may have a positive role to play in some fields of science, so does the public domain. This paper will discuss some of the positive functions of the public domain and ways in which certain legal developments may negatively impact the public domain. It suggests some steps that scientists can take to preserve the positive functions of the public domain for science.

  2. Compactified webs and domain wall partition functions

    Energy Technology Data Exchange (ETDEWEB)

    Shabbir, Khurram [Government College University, Department of Mathematics, Lahore (Pakistan)

    2017-04-15

    In this paper we use the topological vertex formalism to calculate a generalization of the ''domain wall'' partition function of M-strings. This generalization allows calculation of partition function of certain compactified webs using a simple gluing algorithm similar to M-strings case. (orig.)

  3. Entanglement versus negative domains of Wigner functions

    DEFF Research Database (Denmark)

    Dahl, Jens Peder; Mack, H.; Wolf, A.

    2006-01-01

    We show that s waves, that is wave functions that only depend on a hyperradius, are entangled if and only if the corresponding Wigner functions exhibit negative domains. We illustrate this feature using a special class of s waves which allows us to perform the calculations analytically. This class...

  4. Physical activity in the elderly is associated with improved executive function and processing speed: the LADIS Study

    NARCIS (Netherlands)

    Frederiksen, K.S.; Verdelho, A.; Madureira, S.; Bazner, H.; O'Brien, J. T.; Fazekas, F.; Scheltens, P.; Schmidt, R.; Wallin, A.; Wahlund, L.O.; Erkinjunttii, T.; Poggesi, A.; Pantoni, L.; Inzitari, D.; Waldemar, G.

    2015-01-01

    Objectives Physical activity reduces the risk of cognitive decline but may affect cognitive domains differently. We examined whether physical activity modifies processing speed, executive function and memory in a population of non-dementia elderly subjects with age-related white matter changes

  5. Functional Implications of Domain Organization Within Prokaryotic Rhomboid Proteases.

    Science.gov (United States)

    Panigrahi, Rashmi; Lemieux, M Joanne

    2015-01-01

    Intramembrane proteases are membrane embedded enzymes that cleave transmembrane substrates. This interesting class of enzyme and its water mediated substrate cleavage mechanism occurring within the hydrophobic lipid bilayer has drawn the attention of researchers. Rhomboids are a family of ubiquitous serine intramembrane proteases. Bacterial forms of rhomboid proteases are mainly composed of six transmembrane helices that are preceded by a soluble N-terminal domain. Several crystal structures of the membrane domain of the E. coli rhomboid protease ecGlpG have been solved. Independently, the ecGlpG N-terminal cytoplasmic domain structure was solved using both NMR and protein crystallography. Despite these structures, we still do not know the structure of the full-length protein, nor do we know the functional role of these domains in the cell. This chapter will review the structural and functional roles of the different domains associated with prokaryotic rhomboid proteases. Lastly, we will address questions remaining in the field.

  6. Validity of the German Version of the Continuous-Scale Physical Functional Performance 10 Test

    Directory of Open Access Journals (Sweden)

    Irene Härdi

    2017-01-01

    Full Text Available Background. The Continuous-Scale Physical Functional Performance 10 Test (CS-PFP 10 quantitatively assesses physical functional performance in older adults who have a broad range of physical functional ability. This study assessed the validity and reliability of the CS-PFP 10 German version. Methods. Forward-translations and backtranslations as well as cultural adaptions of the test were conducted. Participants were German-speaking Swiss community-dwelling adults aged 64 and older. Concurrent validity was assessed using Pearson correlation coefficients between CS-PFP 10 and gait velocity, Timed Up and Go Test, hand grip strength, SF-36 physical function domain, and Freiburger Physical Activity Questionnaire. Internal consistency was calculated by Cronbach’s alpha. Results. Backtranslation and cultural adaptions were accepted by the CS-PFP 10 developer. CS-PFP 10 total score and subscores (upper body strength, upper body flexibility, lower body strength, balance and coordination, and endurance correlated significantly with all measures of physical function tested. Internal consistency was high (Cronbach’s alpha 0.95–0.98. Conclusion. The CS-PFP 10 German version is valid and reliable for measuring physical functional performance in German-speaking Swiss community-dwelling older adults. Quantifying physical function is essential for clinical practice and research and provides meaningful insight into physical functional performance of older adults. This trial is registered with ClinicalTrials.gov NCT01539200.

  7. Concomitant prediction of function and fold at the domain level with GO-based profiles.

    Science.gov (United States)

    Lopez, Daniel; Pazos, Florencio

    2013-01-01

    Predicting the function of newly sequenced proteins is crucial due to the pace at which these raw sequences are being obtained. Almost all resources for predicting protein function assign functional terms to whole chains, and do not distinguish which particular domain is responsible for the allocated function. This is not a limitation of the methodologies themselves but it is due to the fact that in the databases of functional annotations these methods use for transferring functional terms to new proteins, these annotations are done on a whole-chain basis. Nevertheless, domains are the basic evolutionary and often functional units of proteins. In many cases, the domains of a protein chain have distinct molecular functions, independent from each other. For that reason resources with functional annotations at the domain level, as well as methodologies for predicting function for individual domains adapted to these resources are required.We present a methodology for predicting the molecular function of individual domains, based on a previously developed database of functional annotations at the domain level. The approach, which we show outperforms a standard method based on sequence searches in assigning function, concomitantly predicts the structural fold of the domains and can give hints on the functionally important residues associated to the predicted function.

  8. Domain wall QCD with physical quark masses

    CERN Document Server

    Blum, T.; Christ, N.H.; Frison, J.; Garron, N.; Hudspith, R.J.; Izubuchi, T.; Janowski, T.; Jung, C.; Jüttner, A.; Kelly, C.; Kenway, R.D.; Lehner, C.; Marinkovic, M.; Mawhinney, R.D.; McGlynn, G.; Murphy, D.J.; Ohta, S.; Portelli, A.; Sachrajda, C.T.; Soni, A.

    2016-01-01

    We present results for several light hadronic quantities ($f_\\pi$, $f_K$, $B_K$, $m_{ud}$, $m_s$, $t_0^{1/2}$, $w_0$) obtained from simulations of 2+1 flavor domain wall lattice QCD with large physical volumes and nearly-physical pion masses at two lattice spacings. We perform a short, O(3)%, extrapolation in pion mass to the physical values by combining our new data in a simultaneous chiral/continuum `global fit' with a number of other ensembles with heavier pion masses. We use the physical values of $m_\\pi$, $m_K$ and $m_\\Omega$ to determine the two quark masses and the scale - all other quantities are outputs from our simulations. We obtain results with sub-percent statistical errors and negligible chiral and finite-volume systematics for these light hadronic quantities, including: $f_\\pi$ = 130.2(9) MeV; $f_K$ = 155.5(8) MeV; the average up/down quark mass and strange quark mass in the $\\bar {\\rm MS}$ scheme at 3 GeV, 2.997(49) and 81.64(1.17) MeV respectively; and the neutral kaon mixing parameter, $B_K$...

  9. Towards a minimal generic set of domains of functioning and health.

    Science.gov (United States)

    Cieza, Alarcos; Oberhauser, Cornelia; Bickenbach, Jerome; Chatterji, Somnath; Stucki, Gerold

    2014-03-03

    The World Health Organization (WHO) has argued that functioning, and, more concretely, functioning domains constitute the operationalization that best captures our intuitive notion of health. Functioning is, therefore, a major public-health goal. A great deal of data about functioning is already available. Nonetheless, it is not possible to compare and optimally utilize this information. One potential approach to address this challenge is to propose a generic and minimal set of functioning domains that captures the experience of individuals and populations with respect to functioning and health. The objective of this investigation was to identify a minimal generic set of ICF domains suitable for describing functioning in adults at both the individual and population levels. We performed a psychometric study using data from: 1) the German National Health Interview and Examination Survey 1998, 2) the United States National Health and Nutrition Examination Survey 2007/2008, and 3) the ICF Core Set studies. Random Forests and Group Lasso regression were applied using one self-reported general-health question as a dependent variable. The domains selected were compared to those of the World Health Survey (WHS) developed by the WHO. Seven domains of the International Classification of Functioning, Disability and Health (ICF) are proposed as a minimal generic set of functioning and health: energy and drive functions, emotional functions, sensation of pain, carrying out daily routine, walking, moving around, and remunerative employment. The WHS domains of self-care, cognition, interpersonal activities, and vision were not included in our selection. The minimal generic set proposed in this study is the starting point to address one of the most important challenges in health measurement--the comparability of data across studies and countries. It also represents the first step in developing a common metric of health to link information from the general population to information

  10. Implicit function with natural behavior over entire domain

    International Nuclear Information System (INIS)

    Itoh, Taku; Saitoh, Ayumu; Kamitani, Atsushi; Nakamura, Hiroaki

    2012-01-01

    To generate a smooth implicit function that behaves naturally over an entire domain, a method to smoothly combine an implicit function f(x) with a global support function g(x) has been proposed. The proposed method can be applied to large scattered point data, since the implicit function f(x) is generated by a partition-of-unity-based method. The global support function g(x) is generated by a radial basis function-based method or by the least-squares method. To ensure a smooth combination of f(x) and g(x), an appropriate weight function is employed. In numerical experiments, the proposed method is applied to large point data. The results illustrate that the proposed method can generate a smooth implicit function F(x) with natural behavior over the entire domain. In addition, on the given points, the accuracy of F(x) is exactly the same as that of f(x). Furthermore, the computational cost for generation of F(x) is almost the same as that of f(x). (author)

  11. Back and neck pain prevalence and their association with physical inactivity domains in adolescents.

    Science.gov (United States)

    Scarabottolo, Catarina Covolo; Pinto, R Z; Oliveira, C B; Zanuto, E F; Cardoso, J R; Christofaro, D G D

    2017-09-01

    Back pain affects people of all ages. This may be associated with physical inactivity, and in the case of physical activity in different domains, the relationship with back pain is not clear in the literature. The aim of this study was to estimate the prevalence of low back and neck pain and investigate their association in different domains of physical inactivity. 1011 randomly selected students participated in this study. Neck and back pain were assessed using the Nordic questionnaire, whereas the Baecke Physical Activity questionnaire was used to measure physical activity domains. Separate Binary Logistic Regression models were performed to investigate the association of physical activity domains with neck or back pain. 17.4% of the students reported cervical pain, while 18.0% reported low back pain. Older adolescents had a higher prevalence of cervical pain (24.4%) than younger adolescents (11.9%) (p value pain, being 25.1% in older adolescents and 12.4% in younger (p value pain in the cervical region [OR 0.67 (0.44-0.99)] or back pain [OR 0.60 (0.40-0.91)]. Being inactive in occupational activities was associated with cervical pain [OR 1.49 (1.06-2.10)]. Being inactive in the sports environment presented a marginal relationship with pain in the cervical region [OR 1.41 (0.99-2.02)]. The prevalence of neck and low back pain was higher in older adolescents and physical inactivity in the sporting context and occupational activities could be a risk factor to increase the chances of back pain.

  12. Reduced density matrix embedding. General formalism and inter-domain correlation functional.

    Science.gov (United States)

    Pernal, Katarzyna

    2016-08-03

    An embedding method for a one-electron reduced density matrix (1-RDM) is proposed. It is based on partitioning of 1-RDM into domains and describing each domain in the effective potential of the other ones. To assure N-representability of the total 1-RDM N-representability and strong-orthogonality conditions are imposed on the domains. The total energy is given as a sum of single-domain energies and domain-domain electron interaction contributions. Higher than two-body inter-domain interaction terms are neglected. The two-body correlation terms are approximated by deriving inter-domain correlation from couplings of density fluctuations of two domains at a time. Unlike in most density embedding methods kinetic energy is treated exactly and it is not required that densities pertaining to the domains are only weakly overlapping. We propose to treat each domain by a corrected perfect-pairing functional. On a few examples it is shown that the embedding reduced density matrix functional method (ERDMF) yields excellent results for molecules that are well described by a single Lewis structure even if strong static intra-domain or dynamic inter-domain correlation effects must be accounted for.

  13. Complex mode indication function and its applications to spatial domain parameter estimation

    Science.gov (United States)

    Shih, C. Y.; Tsuei, Y. G.; Allemang, R. J.; Brown, D. L.

    1988-10-01

    This paper introduces the concept of the Complex Mode Indication Function (CMIF) and its application in spatial domain parameter estimation. The concept of CMIF is developed by performing singular value decomposition (SVD) of the Frequency Response Function (FRF) matrix at each spectral line. The CMIF is defined as the eigenvalues, which are the square of the singular values, solved from the normal matrix formed from the FRF matrix, [ H( jω)] H[ H( jω)], at each spectral line. The CMIF appears to be a simple and efficient method for identifying the modes of the complex system. The CMIF identifies modes by showing the physical magnitude of each mode and the damped natural frequency for each root. Since multiple reference data is applied in CMIF, repeated roots can be detected. The CMIF also gives global modal parameters, such as damped natural frequencies, mode shapes and modal participation vectors. Since CMIF works in the spatial domain, uneven frequency spacing data such as data from spatial sine testing can be used. A second-stage procedure for accurate damped natural frequency and damping estimation as well as mode shape scaling is also discussed in this paper.

  14. Interdependence of the rad50 hook and globular domain functions.

    Science.gov (United States)

    Hohl, Marcel; Kochańczyk, Tomasz; Tous, Cristina; Aguilera, Andrés; Krężel, Artur; Petrini, John H J

    2015-02-05

    Rad50 contains a conserved Zn(2+) coordination domain (the Rad50 hook) that functions as a homodimerization interface. Hook ablation phenocopies Rad50 deficiency in all respects. Here, we focused on rad50 mutations flanking the Zn(2+)-coordinating hook cysteines. These mutants impaired hook-mediated dimerization, but recombination between sister chromatids was largely unaffected. This may reflect that cohesin-mediated sister chromatid interactions are sufficient for double-strand break repair. However, Mre11 complex functions specified by the globular domain, including Tel1 (ATM) activation, nonhomologous end joining, and DNA double-strand break end resection were affected, suggesting that dimerization exerts a broad influence on Mre11 complex function. These phenotypes were suppressed by mutations within the coiled-coil and globular ATPase domains, suggesting a model in which conformational changes in the hook and globular domains are transmitted via the extended coils of Rad50. We propose that transmission of spatial information in this manner underlies the regulation of Mre11 complex functions. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Assessing physical function and physical activity in patients with CKD.

    Science.gov (United States)

    Painter, Patricia; Marcus, Robin L

    2013-05-01

    Patients with CKD are characterized by low levels of physical functioning, which, along with low physical activity, predict poor outcomes in those treated with dialysis. The hallmark of clinical care in geriatric practice and geriatric research is the orientation to and assessment of physical function and functional limitations. Although there is increasing interest in physical function and physical activity in patients with CKD, the nephrology field has not focused on this aspect of care. This paper provides an in-depth review of the measurement of physical function and physical activity. It focuses on physiologic impairments and physical performance limitations (impaired mobility and functional limitations). The review is based on established frameworks of physical impairment and functional limitations that have guided research in physical function in the aging population. Definitions and measures for physiologic impairments, physical performance limitations, self-reported function, and physical activity are presented. On the basis of the information presented, recommendations for incorporating routine assessment of physical function and encouragement for physical activity in clinical care are provided.

  16. Clustering of Physical Inactivity in Leisure, Work, Commuting, and Household Domains: Data From 47,477 Industrial Workers in Brazil.

    Science.gov (United States)

    Del Duca, Giovâni F; Garcia, Leandro Martin Totaro; da Silva, Shana Ginar; da Silva, Kelly Samara; Oliveira, Elusa S; Barros, Mauro V; Nahas, Markus V

    2015-09-01

    Physical inactivity in each domain (leisure, work, commuting, and household) is not completely independent. This study aimed to describe the clustering of physical inactivity in different domains and its association with sociodemographic factors among Brazilian industrial workers. This was a cross-sectional, population-based study using data from 23 Brazilian states and the Federal District collected via questionnaires between 2006 and 2008. Physical inactivity in each domain was defined as nonparticipation in specific physical activities. Clustering of physical inactivity was identified using the ratio of the observed (O) and expected (E) percentages of each combination. Multinomial logistic regression was used to identify sociodemographic factors with the outcome. Among the 44,477 interviewees, most combinations exceeded expectations, particularly the clustering of physical inactivity in all domains among men (O/E = 1.37; 95% CI: 1.30; 1.44) and women (O/E = 1.47; 95% CI: 1.36; 1.60). Physical inactivity in 2 or more domains was observed more frequently in women, older age groups, individuals living without a partner, and those with higher education and income levels. Physical inactivity tends to be observed in clusters regardless of gender. Women and workers with higher income levels were the main factors associated with to be physically inactive in 2 or more domains.

  17. Novel functions of CCM1 delimit the relationship of PTB/PH domains.

    Science.gov (United States)

    Zhang, Jun; Dubey, Pallavi; Padarti, Akhil; Zhang, Aileen; Patel, Rinkal; Patel, Vipulkumar; Cistola, David; Badr, Ahmed

    2017-10-01

    Three NPXY motifs and one FERM domain in CCM1 makes it a versatile scaffold protein for tethering the signaling components together within the CCM signaling complex (CSC). The cellular role of CCM1 protein remains inadequately expounded. Both phosphotyrosine binding (PTB) and pleckstrin homology (PH) domains were recognized as structurally related but functionally distinct domains. By utilizing molecular cloning, protein binding assays and RT-qPCR to identify novel cellular partners of CCM1 and its cellular expression patterns; by screening candidate PTB/PH proteins and subsequently structurally simulation in combining with current X-ray crystallography and NMR data to defined the essential structure of PTB/PH domain for NPXY-binding and the relationship among PTB, PH and FERM domain(s). We identified a group of 28 novel cellular partners of CCM1, all of which contain either PTB or PH domain(s), and developed a novel classification system for these PTB/PH proteins based on their relationship with different NPXY motifs of CCM1. Our results demonstrated that CCM1 has a wide spectrum of binding to different PTB/PH proteins and perpetuates their specificity to interact with certain PTB/PH domains through selective combination of three NPXY motifs. We also demonstrated that CCM1 can be assembled into oligomers through intermolecular interaction between its F3 lobe in FERM domain and one of the three NPXY motifs. Despite being embedded in FERM domain as F3 lobe, F3 module acts as a fully functional PH domain to interact with NPXY motif. The most salient feature of the study was that both PTB and PH domains are structurally and functionally comparable, suggesting that PTB domain is likely evolved from PH domain with polymorphic structural additions at its N-terminus. A new β1A-strand of the PTB domain was discovered and new minimum structural requirement of PTB/PH domain for NPXY motif-binding was determined. Based on our data, a novel theory of structure, function and

  18. The application of AFS in high-energy physical domain

    International Nuclear Information System (INIS)

    Xu Dong; Cheng Yaodong; Chen Gang; Yang Dajian; Yang Yi

    2004-01-01

    With the development of high-energy physics, the characteristics of experiments in high-energy physical domain have changed greatly, especially the requirements of comprehensive file-sharing and high performance file transfering. On the other hand, the old management system is too scattered and uncultured to meet the needs of scientific research and international cooperation. According to these new changes, we analyzed the characteristics of experiments and proposed the solution of using some kinds of file systems synthetically, including Ext3, NFS and AFS etc. The solution offers a new method of user management and file management. (authors)

  19. Intellectual Growth in Children as a Function of Domain Specific and Domain General Working Memory Subgroups

    Science.gov (United States)

    Swanson, H. Lee

    2011-01-01

    This study examined whether children's growth on measures of fluid (Raven Colored Progressive Matrices) and crystallized (reading and math achievement) intelligence was attributable to domain-specific or domain-general functions of working memory (WM). A sample of 290 elementary school children was tested on measures of intelligence across three…

  20. Characterization of the Functional Domains of a Mammalian Voltage-Sensitive Phosphatase.

    Science.gov (United States)

    Rosasco, Mario G; Gordon, Sharona E; Bajjalieh, Sandra M

    2015-12-15

    Voltage-sensitive phosphatases (VSPs) are proteins that directly couple changes in membrane electrical potential to inositol lipid phosphatase activity. VSPs thus couple two signaling pathways that are critical for cellular functioning. Although a number of nonmammalian VSPs have been characterized biophysically, mammalian VSPs are less well understood at both the physiological and biophysical levels. In this study, we aimed to address this gap in knowledge by determining whether the VSP from mouse, Mm-VSP, is expressed in the brain and contains a functional voltage-sensing domain (VSD) and a phosphatase domain. We report that Mm-VSP is expressed in neurons and is developmentally regulated. To address whether the functions of the VSD and phosphatase domain are retained in Mm-VSP, we took advantage of the modular nature of these domains and expressed each independently as a chimeric protein in a heterologous expression system. We found that the Mm-VSP VSD, fused to a viral potassium channel, was able to drive voltage-dependent gating of the channel pore. The Mm-VSP phosphatase domain, fused to the VSD of a nonmammalian VSP, was also functional: activation resulted in PI(4,5)P2 depletion that was sufficient to inhibit the PI(4,5)P2-regulated KCNQ2/3 channels. While testing the functionality of the VSD and phosphatase domain, we observed slight differences between the activities of Mm-VSP-based chimeras and those of nonmammalian VSPs. Although the properties of VSP chimeras may not completely reflect the properties of native VSPs, the differences we observed in voltage-sensing and phosphatase activity provide a starting point for future experiments to investigate the function of Mm-VSP and other mammalian VSPs. In conclusion, our data reveal that both the VSD and the lipid phosphatase domain of Mm-VSP are functional, indicating that Mm-VSP likely plays an important role in mouse neurophysiology. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All

  1. Insights into Hox protein function from a large scale combinatorial analysis of protein domains.

    Directory of Open Access Journals (Sweden)

    Samir Merabet

    2011-10-01

    Full Text Available Protein function is encoded within protein sequence and protein domains. However, how protein domains cooperate within a protein to modulate overall activity and how this impacts functional diversification at the molecular and organism levels remains largely unaddressed. Focusing on three domains of the central class Drosophila Hox transcription factor AbdominalA (AbdA, we used combinatorial domain mutations and most known AbdA developmental functions as biological readouts to investigate how protein domains collectively shape protein activity. The results uncover redundancy, interactivity, and multifunctionality of protein domains as salient features underlying overall AbdA protein activity, providing means to apprehend functional diversity and accounting for the robustness of Hox-controlled developmental programs. Importantly, the results highlight context-dependency in protein domain usage and interaction, allowing major modifications in domains to be tolerated without general functional loss. The non-pleoitropic effect of domain mutation suggests that protein modification may contribute more broadly to molecular changes underlying morphological diversification during evolution, so far thought to rely largely on modification in gene cis-regulatory sequences.

  2. Insulator function and topological domain border strength scale with architectural protein occupancy

    Science.gov (United States)

    2014-01-01

    Background Chromosome conformation capture studies suggest that eukaryotic genomes are organized into structures called topologically associating domains. The borders of these domains are highly enriched for architectural proteins with characterized roles in insulator function. However, a majority of architectural protein binding sites localize within topological domains, suggesting sites associated with domain borders represent a functionally different subclass of these regulatory elements. How topologically associating domains are established and what differentiates border-associated from non-border architectural protein binding sites remain unanswered questions. Results By mapping the genome-wide target sites for several Drosophila architectural proteins, including previously uncharacterized profiles for TFIIIC and SMC-containing condensin complexes, we uncover an extensive pattern of colocalization in which architectural proteins establish dense clusters at the borders of topological domains. Reporter-based enhancer-blocking insulator activity as well as endogenous domain border strength scale with the occupancy level of architectural protein binding sites, suggesting co-binding by architectural proteins underlies the functional potential of these loci. Analyses in mouse and human stem cells suggest that clustering of architectural proteins is a general feature of genome organization, and conserved architectural protein binding sites may underlie the tissue-invariant nature of topologically associating domains observed in mammals. Conclusions We identify a spectrum of architectural protein occupancy that scales with the topological structure of chromosomes and the regulatory potential of these elements. Whereas high occupancy architectural protein binding sites associate with robust partitioning of topologically associating domains and robust insulator function, low occupancy sites appear reserved for gene-specific regulation within topological domains. PMID

  3. Time-domain representation of frequency-dependent foundation impedance functions

    Science.gov (United States)

    Safak, E.

    2006-01-01

    Foundation impedance functions provide a simple means to account for soil-structure interaction (SSI) when studying seismic response of structures. Impedance functions represent the dynamic stiffness of the soil media surrounding the foundation. The fact that impedance functions are frequency dependent makes it difficult to incorporate SSI in standard time-history analysis software. This paper introduces a simple method to convert frequency-dependent impedance functions into time-domain filters. The method is based on the least-squares approximation of impedance functions by ratios of two complex polynomials. Such ratios are equivalent, in the time-domain, to discrete-time recursive filters, which are simple finite-difference equations giving the relationship between foundation forces and displacements. These filters can easily be incorporated into standard time-history analysis programs. Three examples are presented to show the applications of the method.

  4. Effects of physical activity on executive functions, attention and academic performance in preadolescent children: a meta-analysis.

    Science.gov (United States)

    de Greeff, Johannes W; Bosker, Roel J; Oosterlaan, Jaap; Visscher, Chris; Hartman, E

    2018-05-01

    The aim of this meta-analysis was to provide a systematic review of intervention studies that investigated the effects of physical activity on multiple domains of executive functions, attention and academic performance in preadolescent children (6-12 years of age). In addition, a systematic quantification of the effects of physical activity on these domains is provided. Systematic review and meta-analysis. Searches of electronic databases and examining relevant reviews between 2000 and April 2017 resulted in 31 intervention studies meeting the inclusion criteria. Four subdomains of executive functions (inhibition, working memory, cognitive flexibility and planning), three subdomains of attention (selective, divided and sustained) and three subdomains of academic performance (mathematics, spelling and reading) were distinguished. Effects for different study designs (acute physical activity or longitudinal physical activity programs), type of physical activity (aerobic or cognitively engaging) and duration of intervention were examined separately. Acute physical activity has a positive effect on attention (g=0.43; 95% CI=0.09, 0.77; 6 studies), while longitudinal physical activity programs has a positive effect on executive functions (g=0.24; 95% CI=0.09, 0.39; 12 studies), attention (g=0.90; 95% CI=0.56, 1.24; 1 study) and academic performance (g=0.26; 95% CI=0.02, 0.49; 3 studies). The effects did depend on the subdomain. Positive effects were found for physical activity on executive functions, attention and academic performance in preadolescent children. Largest effects are expected for interventions that aim for continuous regular physical activity over several weeks. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  5. Role of the different sexuality domains on the sexual function of women with premature ovarian failure.

    Science.gov (United States)

    Benetti-Pinto, Cristina Laguna; Soares, Patrícia Magda; Giraldo, Helena Patrícia Donovan; Yela, Daniela Angerame

    2015-03-01

    Women with premature ovarian failure (POF) often manifest complaints involving different aspects of sexual function (SF), regardless of using hormone therapy. SF involves a complex interaction between physical, psychological, and sociocultural aspects. There are doubts about the impact of different complaints on the global context of SF of women with POF. To evaluate the percentage of influence of each of the sexuality domains on the SF in women with POF. Cross-sectional study with 80 women with POF, matched by age to 80 women with normal gonadal function. We evaluated SF through the "Female Sexual Function Index" (FSFI), a comparison between the POF and control groups using the Mann-Whitney test. Component exploratory factor analysis was used to assess the proportional influence of each domain on the composition of the overall SF for women in the POF group. SF was evaluated using FSFI. Exploratory Factor Analysis for components was used to evaluate the role of each domain on the SF of women with POF. The FSFI score was significantly worse for women with POF, with a decrease in arousal, lubrication, orgasm, satisfaction, and dyspareunia. Exploratory factor analysis of SF showed that the domain with greater influence in the SF was arousal, followed by desire, together accounting for 41% of the FSFI. The domains with less influence were dyspareunia and lubrication, which together accounted for 25% of the FSFI. Women with POF have impaired SF, determined mainly by changes in arousal and desire. Aspects related to lubrication and dyspareunia complaints have lower determination coefficient in SF. These results are important in adapting the approach of sexual disorders in this group of women. © 2014 International Society for Sexual Medicine.

  6. Time-domain Green's Function Method for three-dimensional nonlinear subsonic flows

    Science.gov (United States)

    Tseng, K.; Morino, L.

    1978-01-01

    The Green's Function Method for linearized 3D unsteady potential flow (embedded in the computer code SOUSSA P) is extended to include the time-domain analysis as well as the nonlinear term retained in the transonic small disturbance equation. The differential-delay equations in time, as obtained by applying the Green's Function Method (in a generalized sense) and the finite-element technique to the transonic equation, are solved directly in the time domain. Comparisons are made with both linearized frequency-domain calculations and existing nonlinear results.

  7. Processes of fungal proteome evolution and gain of function: gene duplication and domain rearrangement

    International Nuclear Information System (INIS)

    Cohen-Gihon, Inbar; Nussinov, Ruth; Sharan, Roded

    2011-01-01

    During evolution, organisms have gained functional complexity mainly by modifying and improving existing functioning systems rather than creating new ones ab initio. Here we explore the interplay between two processes which during evolution have had major roles in the acquisition of new functions: gene duplication and protein domain rearrangements. We consider four possible evolutionary scenarios: gene families that have undergone none of these event types; only gene duplication; only domain rearrangement, or both events. We characterize each of the four evolutionary scenarios by functional attributes. Our analysis of ten fungal genomes indicates that at least for the fungi clade, species significantly appear to gain complexity by gene duplication accompanied by the expansion of existing domain architectures via rearrangements. We show that paralogs gaining new domain architectures via duplication tend to adopt new functions compared to paralogs that preserve their domain architectures. We conclude that evolution of protein families through gene duplication and domain rearrangement is correlated with their functional properties. We suggest that in general, new functions are acquired via the integration of gene duplication and domain rearrangements rather than each process acting independently

  8. Boundary regularity of Nevanlinna domains and univalent functions in model subspaces

    International Nuclear Information System (INIS)

    Baranov, Anton D; Fedorovskiy, Konstantin Yu

    2011-01-01

    In the paper we study boundary regularity of Nevanlinna domains, which have appeared in problems of uniform approximation by polyanalytic polynomials. A new method for constructing Nevanlinna domains with essentially irregular nonanalytic boundaries is suggested; this method is based on finding appropriate univalent functions in model subspaces, that is, in subspaces of the form K Θ =H 2 ominus ΘH 2 , where Θ is an inner function. To describe the irregularity of the boundaries of the domains obtained, recent results by Dolzhenko about boundary regularity of conformal mappings are used. Bibliography: 18 titles.

  9. Context-specific requirements of functional domains of the Spectraplakin Short stop in vivo.

    Science.gov (United States)

    Bottenberg, Wolfgang; Sanchez-Soriano, Natalia; Alves-Silva, Juliana; Hahn, Ines; Mende, Michael; Prokop, Andreas

    2009-07-01

    Spectraplakins are large multifunctional cytoskeletal interacting molecules implicated in various processes, including gastrulation, wound healing, skin blistering and neuronal degeneration. It has been speculated that the various functional domains and regions found in Spectraplakins are used in context-specific manners, a model which would provide a crucial explanation for the multifunctional nature of Spectraplakins. Here we tested this possibility by studying domain requirements of the Drosophila Spectraplakin Short stop (Shot) in three different cellular contexts in vivo: (1) neuronal growth, which requires dynamic actin-microtubule interaction; (2) formation and maintenance of tendon cells, which depends on highly stabilised arrays of actin filaments and microtubules, and (3) compartmentalisation in neurons, which is likely to involve cortical F-actin networks. Using these cellular contexts for rescue experiments with Shot deletion constructs in shot mutant background, a number of differential domain requirements were uncovered. First, binding of Shot to F-actin through the first Calponin domain is essential in neuronal contexts but dispensable in tendon cells. This finding is supported by our analyses of shot(kakP2) mutant embryos, which produce only endogenous isoforms lacking the first Calponin domain. Thus, our data demonstrate a functional relevance for these isoforms in vivo. Second, we provide the first functional role for the Plakin domain of Shot, which has a strong requirement for compartmentalisation in neurons and axonal growth, demonstrating that Plakin domains of long Spectraplakin isoforms are of functional relevance. Like the Calponin domain, also the Plakin domain is dispensable in tendon cells, and the currently assumed role of Shot as a linker of microtubules to the tendon cell surface may have to be reconsidered. Third, we demonstrate a function of Shot as an actin-microtubule linker in dendritic growth, thus shedding new light into

  10. Comparison of structure, function and regulation of plant cold shock domain proteins to bacterial and animal cold shock domain proteins.

    Science.gov (United States)

    Chaikam, Vijay; Karlson, Dale T

    2010-01-01

    The cold shock domain (CSD) is among the most ancient and well conserved nucleic acid binding domains from bacteria to higher animals and plants. The CSD facilitates binding to RNA, ssDNA and dsDNA and most functions attributed to cold shock domain proteins are mediated by this nucleic acid binding activity. In prokaryotes, cold shock domain proteins only contain a single CSD and are termed cold shock proteins (Csps). In animal model systems, various auxiliary domains are present in addition to the CSD and are commonly named Y-box proteins. Similar to animal CSPs, plant CSPs contain auxiliary C-terminal domains in addition to their N-terminal CSD. Cold shock domain proteins have been shown to play important roles in development and stress adaptation in wide variety of organisms. In this review, the structure, function and regulation of plant CSPs are compared and contrasted to the characteristics of bacterial and animal CSPs. [BMB reports 2010; 43(1): 1-8].

  11. Regularized Laplace-Fourier-Domain Full Waveform Inversion Using a Weighted l 2 Objective Function

    Science.gov (United States)

    Jun, Hyunggu; Kwon, Jungmin; Shin, Changsoo; Zhou, Hongbo; Cogan, Mike

    2017-03-01

    Full waveform inversion (FWI) can be applied to obtain an accurate velocity model that contains important geophysical and geological information. FWI suffers from the local minimum problem when the starting model is not sufficiently close to the true model. Therefore, an accurate macroscale velocity model is essential for successful FWI, and Laplace-Fourier-domain FWI is appropriate for obtaining such a velocity model. However, conventional Laplace-Fourier-domain FWI remains an ill-posed and ill-conditioned problem, meaning that small errors in the data can result in large differences in the inverted model. This approach also suffers from certain limitations related to the logarithmic objective function. To overcome the limitations of conventional Laplace-Fourier-domain FWI, we introduce a weighted l 2 objective function, instead of the logarithmic objective function, as the data-domain objective function, and we also introduce two different model-domain regularizations: first-order Tikhonov regularization and prior model regularization. The weighting matrix for the data-domain objective function is constructed to suitably enhance the far-offset information. Tikhonov regularization smoothes the gradient, and prior model regularization allows reliable prior information to be taken into account. Two hyperparameters are obtained through trial and error and used to control the trade-off and achieve an appropriate balance between the data-domain and model-domain gradients. The application of the proposed regularizations facilitates finding a unique solution via FWI, and the weighted l 2 objective function ensures a more reasonable residual, thereby improving the stability of the gradient calculation. Numerical tests performed using the Marmousi synthetic dataset show that the use of the weighted l 2 objective function and the model-domain regularizations significantly improves the Laplace-Fourier-domain FWI. Because the Laplace-Fourier-domain FWI is improved, the

  12. Physical activity in the elderly is associated with improved executive function and processing speed

    DEFF Research Database (Denmark)

    Frederiksen, Kristian Steen; Verdelho, Ana; Madureira, Sofia

    2015-01-01

    or dementia, were included. Multiple variable linear regression analysis with baseline MMSE, education, gender, age, stroke, diabetes and ARWMC rating as covariates revealed that physical activity was associated with better scores at baseline and 3-year follow-up for executive function (baseline: β: 0.39, 95......OBJECTIVES: Physical activity reduces the risk of cognitive decline but may affect cognitive domains differently. We examined whether physical activity modifies processing speed, executive function and memory in a population of non-dementia elderly subjects with age-related white matter changes......-year follow-up. Physical activity was assessed at baseline, and cognitive compound scores at baseline and 3-year assessment were used. RESULTS: Two-hundred-eighty-two subjects (age, y (mean (SD)): 73.1 (± 5.1); gender (f/m): 164/118); MMSE (mean (SD)): 28.3 (± 1.7)) who had not progressed to MCI...

  13. PROMIS Pain Interference and Physical Function Scores Correlate With the Foot and Ankle Ability Measure (FAAM) in Patients With Hallux Valgus.

    Science.gov (United States)

    Nixon, Devon C; McCormick, Jeremy J; Johnson, Jeffrey E; Klein, Sandra E

    2017-11-01

    Traditional patient-reported outcome instruments like the Foot and Ankle Ability Measure (FAAM) quantify patient disability but often are limited by responder burden and incomplete questionnaires. The Patient-Reported Outcome Measurement Information System (PROMIS) overcomes such obstacles through computer-adaptive technology and can capture outcome data from various domains including physical and psychosocial function. Prior work has compared the FAAM with PROMIS physical function; however, there is little evidence comparing the association between foot and ankle-specific tools like the FAAM with more general outcomes measures of PROMIS pain interference and depression in foot and ankle conditions. (1) We asked whether there was a relationship between FAAM Activities of Daily Living (ADL) scores with PROMIS physical function, pain interference, and depression in patients with hallux valgus. (2) Additionally, we asked if we could identify specific factors that are associated with variance in FAAM and PROMIS physical function scores in patients with hallux valgus. Eighty-five new patients with either a primary or secondary diagnosis of hallux valgus based on clinic billing codes from July 2015 to February 2016 were retrospectively identified. Patients completed FAAM ADL paper-based surveys and electronic PROMIS questionnaires for physical function, pain interference, and depression from new patient visits at a single time. Spearman rho correlations were performed between FAAM ADL and PROMIS scores. Analyses then were used to identify differences in FAAM ADL and PROMIS physical function measures based on demographic variables. Stepwise linear regressions then determined which demographic and/or outcome variable(s) accounted for the variance in FAAM ADL and PROMIS physical function scores. FAAM scores correlated strongly with PROMIS physical function (r = 0.70, p hallux valgus. PROMIS tools allow for more-efficient data collection across multiple domains and, moving

  14. Physical exercise and executive functions in preadolescent children, adolescents and young adults: a meta-analysis.

    Science.gov (United States)

    Verburgh, Lot; Königs, Marsh; Scherder, Erik J A; Oosterlaan, Jaap

    2014-06-01

    The goal of this meta-analysis was to aggregate available empirical studies on the effects of physical exercise on executive functions in preadolescent children (6-12 years of age), adolescents (13-17 years of age) and young adults (18-35 years of age). The electronic databases PubMed, EMBASE and SPORTDiscus were searched for relevant studies reporting on the effects of physical exercise on executive functions. Nineteen studies were selected. There was a significant overall effect of acute physical exercise on executive functions (d=0.52, 95% CI 0.29 to 0.76, pexercise (d=0.14, 95%CI -0.04 to 0.32, p=0.19) on executive functions (Q (1)=5.08, pexercise on the domain's inhibition/interference control (d=0.46, 95% CI 0.33 to 0.60, pexercise on planning (d=0.16, 95% CI 0.18 to 0.89, p=0.18). Results suggest that acute physical exercise enhances executive functioning. The number of studies on chronic physical exercise is limited and it should be investigated whether chronic physical exercise shows effects on executive functions comparable to acute physical exercise. This is highly relevant in preadolescent children and adolescents, given the importance of well-developed executive functions for daily life functioning and the current increase in sedentary behaviour in these age groups. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  15. Expectations Regarding Aging, Physical Activity, and Physical Function in Older Adults

    Science.gov (United States)

    Breda, Aili I.; Watts, Amber S.

    2017-01-01

    Objective: The present study examined how expectations regarding aging (ERA) influence physical activity participation and physical function. Method: We surveyed 148 older adults about their ERA (ERA-38), health-promoting lifestyles (HPLP-II), and self-rated health (RAND-36). We tested the mediating effect of physical activity on the relationships between ERA and physical function. Results: Positive expectations were associated with more engagement in physical activity (B = 0.016, p physical function (B = 0.521, p Physical activity mediated the relationship between ERA and physical function (B = 5.890, p physically active lifestyles in older adults and may influence health outcomes, such as physical function. Future research should evaluate whether attempts to increase physical activity are more successful when modifications to ERA are also targeted. PMID:28491915

  16. Functional diversity of Csk, Chk, and Src SH2 domains due to a single residue variation.

    Science.gov (United States)

    Ayrapetov, Marina K; Nam, Nguyen Hai; Ye, Guofeng; Kumar, Anil; Parang, Keykavous; Sun, Gongqin

    2005-07-08

    The C-terminal Src kinase (Csk) family of protein tyrosine kinases contains two members: Csk and Csk homologous kinase (Chk). Both phosphorylate and inactivate Src family kinases. Recent reports suggest that the Src homology (SH) 2 domains of Csk and Chk may bind to different phosphoproteins, which provides a basis for different cellular functions for Csk and Chk. To verify and characterize such a functional divergence, we compared the binding properties of the Csk, Chk, and Src SH2 domains and investigated the structural basis for the functional divergence. First, the study demonstrated striking functional differences between the Csk and Chk SH2 domains and revealed functional similarities between the Chk and Src SH2 domains. Second, structural analysis and mutagenic studies revealed that the functional differences among the three SH2 domains were largely controlled by one residue, Glu127 in Csk, Ile167 in Chk, and Lys200 in Src. Mutating these residues in the Csk or Chk SH2 domain to the Src counterpart resulted in dramatic gain of function similar to Src SH2 domain, whereas mutating Lys200 in Src SH2 domain to Glu (the Csk counterpart) resulted in loss of Src SH2 function. Third, a single point mutation of E127K rendered Csk responsive to activation by a Src SH2 domain ligand. Finally, the optimal phosphopeptide sequence for the Chk SH2 domain was determined. These results provide a compelling explanation for the functional differences between two homologous protein tyrosine kinases and reveal a new structure-function relationship for the SH2 domains.

  17. Contributions of individual domains to function of the HIV-1 Rev response element.

    Science.gov (United States)

    O'Carroll, Ina P; Thappeta, Yashna; Fan, Lixin; Ramirez-Valdez, Edric A; Smith, Sean; Wang, Yun-Xing; Rein, Alan

    2017-08-16

    The HIV-1 Rev response element (RRE) is a 351-base element in unspliced and partially spliced viral RNA; binding of the RRE by the viral Rev protein induces nuclear export of RRE-containing RNAs, as required for virus replication. It contains one long, imperfect double helix (domain I), one branched domain (domain II) containing a high-affinity Rev-binding site, and two or three additional domains. We previously reported that the RRE assumes an "A" shape in solution and suggested that the location of the Rev binding sites in domains I and II, opposite each other on the two legs of the A, is optimal for Rev binding and explains Rev's specificity for RRE-containing RNAs. Using SAXS and a quantitative functional assay, we have now analyzed a panel of RRE mutants. All the results support the essential role of the A shape for RRE function. Moreover, they suggest that the distal portion of domain I and the three crowning domains all contribute to the maintenance of the A shape. Domains I and II are necessary and sufficient for substantial RRE function, provided they are joined by a flexible linker that allows the two domains to face each other. IMPORTANCE Retroviral replication requires that some of the viral RNAs transcribed in the cell nucleus be exported to the cytoplasm without being spliced. To achieve this, HIV-1 encodes a protein, Rev, which binds to a complex, highly structured element within viral RNA, the Rev Response Element (RRE), and escorts RRE-containing RNAs from the nucleus. We previously reported that the RRE is "A"-shaped and suggested that this architecture, with the 2 legs opposite one another, can explain the specificity of Rev for the RRE. We have analyzed the functional contributions of individual RRE domains, and now report that several domains contribute, with some redundancy, to maintenance of the overall RRE shape. The data strongly support the hypothesis that the opposed placement of the 2 legs is essential for RRE function. Copyright © 2017

  18. Readability and Comprehension of the Geriatric Depression Scale and PROMIS® Physical Function Items in Older African Americans and Latinos.

    Science.gov (United States)

    Paz, Sylvia H; Jones, Loretta; Calderón, José L; Hays, Ron D

    2017-02-01

    Depression and physical function are particularly important health domains for the elderly. The Geriatric Depression Scale (GDS) and the Patient-Reported Outcomes Measurement Information System (PROMIS ® ) physical function item bank are two surveys commonly used to measure these domains. It is unclear if these two instruments adequately measure these aspects of health in minority elderly. The aim of this study was to estimate the readability of the GDS and PROMIS ® physical function items and to assess their comprehensibility using a sample of African American and Latino elderly. Readability was estimated using the Flesch-Kincaid and Flesch Reading Ease (FRE) formulae for English versions, and a Spanish adaptation of the FRE formula for the Spanish versions. Comprehension of the GDS and PROMIS ® items by minority elderly was evaluated with 30 cognitive interviews. Readability estimates of a number of items in English and Spanish of the GDS and PROMIS ® physical functioning items exceed the U.S. recommended 5th-grade threshold for vulnerable populations, or were rated as 'fairly difficult', 'difficult', or 'very difficult' to read. Cognitive interviews revealed that many participants felt that more than the two (yes/no) GDS response options were needed to answer the questions. Wording of several PROMIS ® items was considered confusing, and interpreting responses was problematic because they were based on using physical aids. Problems with item wording and response options of the GDS and PROMIS ® physical function items may reduce reliability and validity of measurement when used with minority elderly.

  19. Identification of the functional domains of ANT-1, a novel coactivator of the androgen receptor

    International Nuclear Information System (INIS)

    Fan Shuli; Goto, Kiminobu; Chen Guangchun; Morinaga, Hidetaka; Nomura, Masatoshi; Okabe, Taijiro; Nawata, Hajime; Yanase, Toshihiko

    2006-01-01

    Previously, we identified a transcriptional coactivator for the activation function-1 (AF-1) domain of the human androgen receptor (AR) and designated it androgen receptor N-terminal domain transactivating protein-1 (ANT-1). This coactivator, which contains multiple tetratricopeptide repeat (TPR) motifs from amino acid (aa) 294, is identical to a component of U5 small nuclear ribonucleoprotein particles and binds specifically to the AR or glucocorticoid receptor. Here, we identified four distinct functional domains. The AR-AF-1-binding domain, which bound to either aa 180-360 or 360-532 in AR-AF-1, clearly overlapped with TAU-1 and TAU-5. This domain and the subnuclear speckle formation domain in ANT-1 were assigned within the TPR motifs, while the transactivating and nuclear localization signal domains resided within the N-terminal sequence. The existence of these functional domains may further support the idea that ANT-1 can function as an AR-AF-1-specific coactivator while mediating a transcription-splicing coupling

  20. Nonlinear System Identification via Basis Functions Based Time Domain Volterra Model

    Directory of Open Access Journals (Sweden)

    Yazid Edwar

    2014-07-01

    Full Text Available This paper proposes basis functions based time domain Volterra model for nonlinear system identification. The Volterra kernels are expanded by using complex exponential basis functions and estimated via genetic algorithm (GA. The accuracy and practicability of the proposed method are then assessed experimentally from a scaled 1:100 model of a prototype truss spar platform. Identification results in time and frequency domain are presented and coherent functions are performed to check the quality of the identification results. It is shown that results between experimental data and proposed method are in good agreement.

  1. Objectively-determined intensity- and domain-specific physical activity and sedentary behavior in relation to percent body fat.

    Science.gov (United States)

    Scheers, Tineke; Philippaerts, Renaat; Lefevre, Johan

    2013-12-01

    This study examined the independent and joint associations of overall, intensity-specific and domain-specific physical activity and sedentary behavior with bioelectrical impedance-determined percent body fat. Physical activity was measured in 442 Flemish adults (41.4 ± 9.8 years) using the SenseWear Armband and an electronic diary. Two-way analyses of covariance investigated the interaction of physical activity and sedentary behavior with percent body fat. Multiple linear regression analyses, adjusted for potential confounders, examined the associations of intensity-specific and domain-specific physical activity and sedentary behavior with percent body fat. Results showed a significant main effect for physical activity in both genders and for sedentary behavior in women, but no interaction effects. Light activity was positively (β = 0.41 for men and 0.43 for women) and moderate (β = -0.64 and -0.41), vigorous (β = -0.21 and -0.24) and moderate-to-vigorous physical activity (MVPA) inversely associated with percent body fat, independent of sedentary time. Regarding domain-specific physical activity, significant associations were present for occupation, leisure time and household chores, irrespective of sedentary time. The positive associations between body fat and total and domain-specific sedentary behavior diminished after MVPA was controlled for. MVPA during leisure time, occupation and household chores may be essential to prevent fat gain. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  2. Motor function domains in alternating hemiplegia of childhood.

    Science.gov (United States)

    Masoud, Melanie; Gordon, Kelly; Hall, Amanda; Jasien, Joan; Lardinois, Kara; Uchitel, Julie; Mclean, Melissa; Prange, Lyndsey; Wuchich, Jeffrey; Mikati, Mohamad A

    2017-08-01

    To characterize motor function profiles in alternating hemiplegia of childhood, and to investigate interrelationships between these domains and with age. We studied a cohort of 23 patients (9 males, 14 females; mean age 9y 4mo, range 4mo-43y) who underwent standardized tests to assess gross motor, upper extremity motor control, motor speech, and dysphagia functions. Gross Motor Function Classification System (GMFCS), Gross Motor Function Measure-88 (GMFM-88), Manual Ability Classification System (MACS), and Revised Melbourne Assessment (MA2) scales manifested predominantly mild impairments; motor speech, moderate to severe; Modified Dysphagia Outcome and Severity Scale (M-DOSS), mild-to moderate deficits. GMFCS correlated with GMFM-88 scores (Pearson's correlation, p=0.002), MACS (p=0.038), and MA2 fluency (p=0.005) and accuracy (p=0.038) scores. GMFCS did not correlate with motor speech (p=0.399), MA2 dexterity (p=0.247), range of motion (p=0.063), or M-DOSS (p=0.856). Motor speech was more severely impaired than the GMFCS (p<0.013). There was no correlation between any of the assessment tools and age (p=0.210-0.798). Our data establish a detailed profile of motor function in alternating hemiplegia of childhood, argue against the presence of worse motor function in older patients, identify tools helpful in evaluating this population, and identify oropharyngeal function as the more severely affected domain, suggesting that brain areas controlling this function are more affected than others. © 2017 Mac Keith Press.

  3. Structure and function of the TIR domain from the grape NLR protein RPV1

    Directory of Open Access Journals (Sweden)

    Simon John Williams

    2016-12-01

    Full Text Available The N-terminal Toll/interleukin-1 receptor/resistance protein (TIR domain has been shown to be both necessary and sufficient for defence signalling in the model plants flax and Arabidopsis. In examples from these organisms, TIR domain self-association is required for signalling function, albeit through distinct interfaces. Here, we investigate these properties in the TIR domain containing resistance protein RPV1 from the wild grapevine Muscadinia rotundifolia. The RPV1 TIR domain, without additional flanking sequence present, is autoactive when transiently expressed in tobacco, demonstrating that the TIR domain alone is capable of cell-death signalling. We determined the crystal structure of the RPV1 TIR domain at 2.3 Å resolution. In the crystals, the RPV1 TIR domain forms a dimer, mediated predominantly through residues in the αA and αE helices (AE interface. This interface is shared with the interface discovered in the dimeric complex of the TIR domains from the Arabidopsis RPS4/RRS1 resistance protein pair. We show that surface-exposed residues in the AE interface that mediate the dimer interaction in the crystals are highly conserved among plant TIR domain-containing proteins. While we were unable to demonstrate self-association of the RPV1 TIR domain in solution or using yeast 2-hybrid, mutations of surface-exposed residues in the AE interface prevent the cell-death autoactive phenotype. In addition, mutation of residues known to be important in the cell-death signalling function of the flax L6 TIR domain were also shown to be required for RPV1 TIR domain mediated cell-death. Our data demonstrate that multiple TIR domain surfaces control the cell-death function of the RPV1 TIR domain and we suggest that the conserved AE interface may have a general function in TIR-NLR signalling.

  4. Functional significance of SRJ domain mutations in CITED2.

    Directory of Open Access Journals (Sweden)

    Chiann-mun Chen

    Full Text Available CITED2 is a transcriptional co-activator with 3 conserved domains shared with other CITED family members and a unique Serine-Glycine Rich Junction (SRJ that is highly conserved in placental mammals. Loss of Cited2 in mice results in cardiac and aortic arch malformations, adrenal agenesis, neural tube and placental defects, and partially penetrant defects in left-right patterning. By screening 1126 sporadic congenital heart disease (CHD cases and 1227 controls, we identified 19 variants, including 5 unique non-synonymous sequence variations (N62S, R92G, T166N, G180-A187del and A187T in patients. Many of the CHD-specific variants identified in this and previous studies cluster in the SRJ domain. Transient transfection experiments show that T166N mutation impairs TFAP2 co-activation function and ES cell proliferation. We find that CITED2 is phosphorylated by MAPK1 in vitro at T166, and that MAPK1 activation enhances the coactivation function of CITED2 but not of CITED2-T166N. In order to investigate the functional significance in vivo, we generated a T166N mutation of mouse Cited2. We also used PhiC31 integrase-mediated cassette exchange to generate a Cited2 knock-in allele replacing the mouse Cited2 coding sequence with human CITED2 and with a mutant form deleting the entire SRJ domain. Mouse embryos expressing only CITED2-T166N or CITED2-SRJ-deleted alleles surprisingly show no morphological abnormalities, and mice are viable and fertile. These results indicate that the SRJ domain is dispensable for these functions of CITED2 in mice and that mutations clustering in the SRJ region are unlikely to be the sole cause of the malformations observed in patients with sporadic CHD. Our results also suggest that coding sequence mutations observed in case-control studies need validation using in vivo models and that predictions based on structural conservation and in vitro functional assays, or even in vivo global loss of function models, may be

  5. DPP6 domains responsible for its localization and function.

    Science.gov (United States)

    Lin, Lin; Long, Laura K; Hatch, Michael M; Hoffman, Dax A

    2014-11-14

    Dipeptidyl peptidase-like protein 6 (DPP6) is an auxiliary subunit of the Kv4 family of voltage-gated K(+) channels known to enhance channel surface expression and potently accelerate their kinetics. DPP6 is a single transmembrane protein, which is structurally remarkable for its large extracellular domain. Included in this domain is a cysteine-rich motif, the function of which is unknown. Here we show that this cysteine-rich domain of DPP6 is required for its export from the ER and expression on the cell surface. Disulfide bridges formed at C349/C356 and C465/C468 of the cysteine-rich domain are necessary for the enhancement of Kv4.2 channel surface expression but not its interaction with Kv4.2 subunits. The short intracellular N-terminal and transmembrane domains of DPP6 associates with and accelerates the recovery from inactivation of Kv4.2, but the entire extracellular domain is necessary to enhance Kv4.2 surface expression and stabilization. Our findings show that the cysteine-rich domain of DPP6 plays an important role in protein folding of DPP6 that is required for transport of DPP6/Kv4.2 complexes out of the ER. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Comparing Domain-Specific Physical Activity Efficacy Level between Turkish Adolescent Girls and Boys

    Science.gov (United States)

    Çatikkas, Fatih

    2017-01-01

    The adolescence period is a very critical developmental period for personality, socializing and promotion of physical activity. In this regard, the aim of this study was to compare domain-specific physical activity efficacy level between adolescent boys and girls. A total of 219 girls (body weight: 57.50 ± 10.44 kg, height: 160.30 ± 7.40 cm, age…

  7. Physical exercise and cognitive function across the life span: Results of a nationwide population-based study.

    Science.gov (United States)

    Gaertner, Beate; Buttery, Amanda K; Finger, Jonas D; Wolfsgruber, Steffen; Wagner, Michael; Busch, Markus A

    2018-05-01

    To examine cross-sectional and longitudinal associations between physical exercise and cognitive function across different age groups in a nationwide population-based sample of adults aged 18-79 years in Germany. Cross-sectional/prospective. Cognitive function was assessed in the mental health module of the German Health Interview and Examination Survey for Adults (DEGS1-MH, 2009-2012, n=3535), using a comprehensive neuropsychological test battery. Cognitive domain scores for executive function and memory were derived from confirmatory factor analysis. Regular physical exercise in the last three months was assessed by self-report and defined as no exercise, function in cross-sectional (function and memory in cross-sectional and longitudinal analyses with no evidence for differential effects by age. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  8. Domain-Specific Self-Reported and Objectively Measured Physical Activity in Children

    Directory of Open Access Journals (Sweden)

    Ole Sprengeler

    2017-03-01

    Full Text Available Little is known about the extent that different domains contribute to total sedentary (SED, light (LPA and moderate-to-vigorous physical activity (MVPA. We aimed to identify domain-specific physical activity (PA patterns in school-aged children who were assessed by questionnaire and accelerometry. For the study, 298 German school children and adolescents aged 6–17 years wore an accelerometer for one week and completed a PA recall-questionnaire for the same period. Spearman coefficients (r were used to evaluate the agreement between self-reported and objectively measured PA in five domains (transport, school hours, physical education, leisure-time, organized sports activities. School hours mainly contributed to the total objectively measured SED, LPA and MVPA (55%, 53% and 46%, respectively, whilst sports activities contributed only 24% to total MVPA. Compared to accelerometry, the proportion of self-reported LPA and MVPA during school hours was substantially underestimated but overestimated during leisure-time. The agreement of self-reported and objectively measured PA was low for total LPA (r = 0.09, 95% CI (confidence interval: −0.03–0.20 and total MVPA (r = 0.21, 95% CI: 0.10–0.32, while moderate agreement was only found for total SED (r = 0.44, 95% CI: 0.34–0.53, LPA during transport (r = 0.59; 95% CI: 0.49–0.67 and MVPA during organized sports activities (r = 0.54; 95% CI: 0.38–0.67. Since school hours mainly contribute to total SED, LPA and MVPA and self-reported LPA and MVPA during school were importantly underestimated compared to objectively measured LPA and MVPA, the application of objective measurements is compulsory to characterize the entire activity pattern of school-aged children.

  9. Association between domains of physical activity and all-cause, cardiovascular and cancer mortality.

    Science.gov (United States)

    Autenrieth, Christine S; Baumert, Jens; Baumeister, Sebastian E; Fischer, Beate; Peters, Annette; Döring, Angela; Thorand, Barbara

    2011-02-01

    Few studies have investigated the independent effects of domain-specific physical activity on mortality. We sought to investigate the association of physical activity performed in different domains of daily living on all-cause, cardiovascular (CVD) and cancer mortality. Using a prospective cohort design, 4,672 men and women, aged 25-74 years, who participated in the baseline examination of the MONICA/KORA Augsburg Survey 1989/1990 were classified according to their activity level (no, light, moderate, vigorous). Domains of self-reported physical activity (work, transportation, household, leisure time) and total activity were assessed by the validated MOSPA (MONICA Optional Study on Physical Activity) questionnaire. After a median follow-up of 17.8 years, a total of 995 deaths occurred, with 452 from CVD and 326 from cancer. For all-cause mortality, hazard ratios and 95% confidence interval (HR, 95% CI) of the highly active versus the inactive reference group were 0.69 (0.48-1.00) for work, 0.48 (0.36-0.65) for leisure time, and 0.73 (0.59-0.90) for total activity after multivariable adjustments. Reduced risks of CVD mortality were observed for high levels of work (0.54, 0.31-0.93), household (0.80, 0.54-1.19), leisure time (0.50, 0.31-0.79) and total activity (0.75, 0.55-1.03). Leisure time (0.36, 0.23-0.59) and total activity (0.62, 0.43-0.88) were associated with reduced risks of cancer mortality. Light household activity was related to lower all-cause (0.82, 0.71-0.95) and CVD (0.72, 0.58-0.89) mortality. No clear effects were found for transportation activities. Our findings suggest that work, household, leisure time and total physical activity, but not transportation activity, may protect from premature mortality.

  10. Exploring end user adoption and maintenance of a telephone-based physical activity counseling service for individuals with physical disabilities using the Theoretical Domains Framework.

    Science.gov (United States)

    Tomasone, Jennifer R; Arbour-Nicitopoulos, Kelly P; Pila, Eva; Lamontagne, Marie-Eve; Cummings, Isabelle; Latimer-Cheung, Amy E; Routhier, François

    2017-06-01

    In Canada, two counseling services are offered to facilitate physical activity participation among persons with physical disabilities, yet both have encountered concerns related to the recruitment and retainment of clients. The purpose of this paper is to explore factors related to service adoption among nonusers, and the barriers and facilitators to maintaining service participation among adopters. Individuals who had never enrolled in the services (nonusers, n = 13) as well as current/previous service clients (adopters, n = 26) participated in interviews based on the Theoretical Domains Framework. Transcripts were subjected to deductive thematic analysis according to participant group. Fifteen themes relating to service adoption within 10 of the 12 theoretical domains were identified for nonusers, while 23 themes relating to maintenence of service participation were identified across all 12 theoretical domains for adopters. The findings provide strategies to improve recruitment, adoption, and retention of clients in counseling services and to enhance the experiences of targeted service users. Implications for Rehabiliation Peer support and education for equipment use should be built into physical activity programs to encourage participation among persons with physical disabilities. Programs that encourage physical activity among individuals with disabilities should be designed by practitioners to be responsive to a variety of needs, which are addressed in the program's advertisements and offerings. The Theoretical Domains Framework is a useful framework for providing valuable insight about clients' experiences of adoption and maintenance of a behavior change service, suggesting merit in other rehabilitation settings.

  11. Time domain functional NIRS imaging for human brain mapping.

    Science.gov (United States)

    Torricelli, Alessandro; Contini, Davide; Pifferi, Antonio; Caffini, Matteo; Re, Rebecca; Zucchelli, Lucia; Spinelli, Lorenzo

    2014-01-15

    This review is aimed at presenting the state-of-the-art of time domain (TD) functional near-infrared spectroscopy (fNIRS). We first introduce the physical principles, the basics of modeling and data analysis. Basic instrumentation components (light sources, detection techniques, and delivery and collection systems) of a TD fNIRS system are described. A survey of past, existing and next generation TD fNIRS systems used for research and clinical studies is presented. Performance assessment of TD fNIRS systems and standardization issues are also discussed. Main strengths and weakness of TD fNIRS are highlighted, also in comparison with continuous wave (CW) fNIRS. Issues like quantification of the hemodynamic response, penetration depth, depth selectivity, spatial resolution and contrast-to-noise ratio are critically examined, with the help of experimental results performed on phantoms or in vivo. Finally we give an account on the technological developments that would pave the way for a broader use of TD fNIRS in the neuroimaging community. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Structural-Functional Analysis Reveals a Specific Domain Organization in Family GH20 Hexosaminidases.

    Science.gov (United States)

    Val-Cid, Cristina; Biarnés, Xevi; Faijes, Magda; Planas, Antoni

    2015-01-01

    Hexosaminidases are involved in important biological processes catalyzing the hydrolysis of N-acetyl-hexosaminyl residues in glycosaminoglycans and glycoconjugates. The GH20 enzymes present diverse domain organizations for which we propose two minimal model architectures: Model A containing at least a non-catalytic GH20b domain and the catalytic one (GH20) always accompanied with an extra α-helix (GH20b-GH20-α), and Model B with only the catalytic GH20 domain. The large Bifidobacterium bifidum lacto-N-biosidase was used as a model protein to evaluate the minimal functional unit due to its interest and structural complexity. By expressing different truncated forms of this enzyme, we show that Model A architectures cannot be reduced to Model B. In particular, there are two structural requirements general to GH20 enzymes with Model A architecture. First, the non-catalytic domain GH20b at the N-terminus of the catalytic GH20 domain is required for expression and seems to stabilize it. Second, the substrate-binding cavity at the GH20 domain always involves a remote element provided by a long loop from the catalytic domain itself or, when this loop is short, by an element from another domain of the multidomain structure or from the dimeric partner. Particularly, the lacto-N-biosidase requires GH20b and the lectin-like domain at the N- and C-termini of the catalytic GH20 domain to be fully soluble and functional. The lectin domain provides this remote element to the active site. We demonstrate restoration of activity of the inactive GH20b-GH20-α construct (model A architecture) by a complementation assay with the lectin-like domain. The engineering of minimal functional units of multidomain GH20 enzymes must consider these structural requirements.

  13. The DIMA web resource--exploring the protein domain network.

    Science.gov (United States)

    Pagel, Philipp; Oesterheld, Matthias; Stümpflen, Volker; Frishman, Dmitrij

    2006-04-15

    Conserved domains represent essential building blocks of most known proteins. Owing to their role as modular components carrying out specific functions they form a network based both on functional relations and direct physical interactions. We have previously shown that domain interaction networks provide substantially novel information with respect to networks built on full-length protein chains. In this work we present a comprehensive web resource for exploring the Domain Interaction MAp (DIMA), interactively. The tool aims at integration of multiple data sources and prediction techniques, two of which have been implemented so far: domain phylogenetic profiling and experimentally demonstrated domain contacts from known three-dimensional structures. A powerful yet simple user interface enables the user to compute, visualize, navigate and download domain networks based on specific search criteria. http://mips.gsf.de/genre/proj/dima

  14. Is the relationship between increased knee muscle strength and improved physical function following exercise dependent on baseline physical function status?

    Science.gov (United States)

    Hall, Michelle; Hinman, Rana S; van der Esch, Martin; van der Leeden, Marike; Kasza, Jessica; Wrigley, Tim V; Metcalf, Ben R; Dobson, Fiona; Bennell, Kim L

    2017-12-08

    Clinical guidelines recommend knee muscle strengthening exercises to improve physical function. However, the amount of knee muscle strength increase needed for clinically relevant improvements in physical function is unclear. Understanding how much increase in knee muscle strength is associated with improved physical function could assist clinicians in providing appropriate strength gain targets for their patients in order to optimise outcomes from exercise. The aim of this study was to investigate whether an increase in knee muscle strength is associated with improved self-reported physical function following exercise; and whether the relationship differs according to physical function status at baseline. Data from 100 participants with medial knee osteoarthritis enrolled in a 12-week randomised controlled trial comparing neuromuscular exercise to quadriceps strengthening exercise were pooled. Participants were categorised as having mild, moderate or severe physical dysfunction at baseline using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Associations between 12-week changes in physical function (dependent variable) and peak isometric knee extensor and flexor strength (independent variables) were evaluated with and without accounting for baseline physical function status and covariates using linear regression models. In covariate-adjusted models without accounting for baseline physical function, every 1-unit (Nm/kg) increase in knee extensor strength was associated with physical function improvement of 17 WOMAC units (95% confidence interval (CI) -29 to -5). When accounting for baseline severity of physical function, every 1-unit increase in knee extensor strength was associated with physical function improvement of 24 WOMAC units (95% CI -42 to -7) in participants with severe physical dysfunction. There were no associations between change in strength and change in physical function in participants with mild or moderate physical

  15. C-terminal domains of bacterial proteases: structure, function and the biotechnological applications.

    Science.gov (United States)

    Huang, J; Wu, C; Liu, D; Yang, X; Wu, R; Zhang, J; Ma, C; He, H

    2017-01-01

    C-terminal domains widely exist in the C-terminal region of multidomain proteases. As a β-sandwich domain in multidomain protease, the C-terminal domain plays an important role in proteolysis including regulation of the secretory process, anchoring and swelling the substrate molecule, presenting as an inhibitor for the preprotease and adapting the protein structural flexibility and stability. In this review, the diversity, structural characteristics and biological function of C-terminal protease domains are described. Furthermore, the application prospects of C-terminal domains, including polycystic kidney disease, prepeptidase C-terminal and collagen-binding domain, in the area of medicine and biological artificial materials are also discussed. © 2016 The Society for Applied Microbiology.

  16. Patterns of physical activity in different domains and implications for intervention in a multi-ethnic Asian population: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Tai E Shyong

    2010-10-01

    Full Text Available Abstract Background The benefits of regular physical activity for quality of life and disease prevention have been well documented. Identification of low activity groups would facilitate interventional programs. Many studies have focussed on leisure time activity, which may not capture the spectrum of physical activity relevant to disease prevention. Furthermore, few studies have been conducted in urban Asian settings. Methods We evaluated physical activity in different domains (leisure time, occupational, household and transportation and its sociodemographic determinants in 4750 adult Chinese, Malay, and Asian Indian Singaporeans. Physical activity was assessed using locally validated questionnaires. Results Occupational and household activity contributed substantially more to total physical activity than leisure time or transportation activity. However, when only activity of at least moderate intensity was considered leisure time activity contributed most to total physical activity. Higher socio-economic status was associated with more leisure time activity, but less total physical activity due to reduced activity in the other domains. Chinese ethnicity was also associated with less total physical activity as a result of less activity in non-leisure time domains. Conclusions In assessing levels of physical activity and recommending changes, it is important to consider physical activity in different domains. Focus on leisure-time physical activity alone could identify the wrong groups for intervention and miss opportunities for increasing physical activity in populations.

  17. Better assessment of physical function: item improvement is neglected but essential.

    Science.gov (United States)

    Bruce, Bonnie; Fries, James F; Ambrosini, Debbie; Lingala, Bharathi; Gandek, Barbara; Rose, Matthias; Ware, John E

    2009-01-01

    Physical function is a key component of patient-reported outcome (PRO) assessment in rheumatology. Modern psychometric methods, such as Item Response Theory (IRT) and Computerized Adaptive Testing, can materially improve measurement precision at the item level. We present the qualitative and quantitative item-evaluation process for developing the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function item bank. The process was stepwise: we searched extensively to identify extant Physical Function items and then classified and selectively reduced the item pool. We evaluated retained items for content, clarity, relevance and comprehension, reading level, and translation ease by experts and patient surveys, focus groups, and cognitive interviews. We then assessed items by using classic test theory and IRT, used confirmatory factor analyses to estimate item parameters, and graded response modeling for parameter estimation. We retained the 20 Legacy (original) Health Assessment Questionnaire Disability Index (HAQ-DI) and the 10 SF-36's PF-10 items for comparison. Subjects were from rheumatoid arthritis, osteoarthritis, and healthy aging cohorts (n = 1,100) and a national Internet sample of 21,133 subjects. We identified 1,860 items. After qualitative and quantitative evaluation, 124 newly developed PROMIS items composed the PROMIS item bank, which included revised Legacy items with good fit that met IRT model assumptions. Results showed that the clearest and best-understood items were simple, in the present tense, and straightforward. Basic tasks (like dressing) were more relevant and important versus complex ones (like dancing). Revised HAQ-DI and PF-10 items with five response options had higher item-information content than did comparable original Legacy items with fewer response options. IRT analyses showed that the Physical Function domain satisfied general criteria for unidimensionality with one-, two-, three-, and four-factor models

  18. INVESTIGATING THE ROLE OF PDZ-DOMAIN INTERACTIONS FOR DOPAMINE TRANSPORTER FUNCTION

    DEFF Research Database (Denmark)

    Fog, Jacob; Vægter, Christian Bjerggaard; Gether, Ulrik

    canonical PDZ domain interactions with proteins such as PICK1. To clarify the actual role of PDZ domain interactions for DAT function we have expressed the wild type DAT and a number of C-terminal mutants either alone or together with PICK1 in HEK293, N2A neuroblastoma and PC12 cells. Data obtained from...

  19. The epigenetic regulator Smchd1 contains a functional GHKL-type ATPase domain.

    Science.gov (United States)

    Chen, Kelan; Dobson, Renwick C J; Lucet, Isabelle S; Young, Samuel N; Pearce, F Grant; Blewitt, Marnie E; Murphy, James M

    2016-06-15

    Structural maintenance of chromosomes flexible hinge domain containing 1 (Smchd1) is an epigenetic regulator that plays critical roles in gene regulation during development. Mutations in SMCHD1 were recently implicated in the pathogenesis of facioscapulohumeral muscular dystrophy (FSHD), although the mechanistic basis remains of outstanding interest. We have previously shown that Smchd1 associates with chromatin via its homodimeric C-terminal hinge domain, yet little is known about the function of the putative GHKL (gyrase, Hsp90, histidine kinase, MutL)-type ATPase domain at its N-terminus. To formally assess the structure and function of Smchd1's ATPase domain, we have generated recombinant proteins encompassing the predicted ATPase domain and the adjacent region. Here, we show that the Smchd1 N-terminal region exists as a monomer and adopts a conformation resembling that of monomeric full-length heat shock protein 90 (Hsp90) protein in solution, even though the two proteins share only ∼8% overall sequence identity. Despite being monomeric, the N-terminal region of Smchd1 exhibits ATPase activity, which can be antagonized by the reaction product, ADP, or the Hsp90 inhibitor, radicicol, at a nanomolar concentration. Interestingly, introduction of an analogous mutation to that identified in SMCHD1 of an FSHD patient compromised protein stability, suggesting a possible molecular basis for loss of protein function and pathogenesis. Together, these results reveal important structure-function characteristics of Smchd1 that may underpin its mechanistic action at the chromatin level. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  20. Analysis of water hammer in pipelines by partial fraction expansion of transfer function in frequency domain

    International Nuclear Information System (INIS)

    Lee, Jun Shin; Lee, Wook Ryun; Oh, Ki Yong; Kim, Bong Ki

    2010-01-01

    Understanding water hammer is very important to the prevention of excessive pressure build-up in pipelines. Many researchers have studied this phenomenon, drawing effective solutions through the time- and frequency-domain approaches. For the purposes of enhancing the advantages of the frequency-domain approach and, thereby, rendering investigations of the dynamic characteristics of pipelines more effective, we propose partial fraction expansion of the transfer function between the unsteady flow source and a given section. We simulate the proposed approach using a vibration element inserted into a simple pipeline, deducing much useful physical information pertaining to pipeline design. We conclude that locating the resonance of the vibration element between the first and second resonances of the pipeline can mitigate the excessive pressure build-up attendant on the occurrence of water hammer. Our method of partial fraction expansion is expected to be useful and effective in analyses of unsteady flows in pipelines

  1. Age-related functional changes in domain-specific medial temporal lobe pathways.

    Science.gov (United States)

    Berron, David; Neumann, Katja; Maass, Anne; Schütze, Hartmut; Fliessbach, Klaus; Kiven, Verena; Jessen, Frank; Sauvage, Magdalena; Kumaran, Dharshan; Düzel, Emrah

    2018-05-01

    There is now converging evidence from studies in animals and humans that the medial temporal lobes (MTLs) harbor anatomically distinct processing pathways for object and scene information. Recent functional magnetic resonance imaging studies in humans suggest that this domain-specific organization may be associated with a functional preference of the anterior-lateral part of the entorhinal cortex (alErC) for objects and the posterior-medial entorhinal cortex (pmErC) for scenes. As MTL subregions are differentially affected by aging and neurodegenerative diseases, the question was raised whether aging may affect the 2 pathways differentially. To address this possibility, we developed a paradigm that allows the investigation of object memory and scene memory in a mnemonic discrimination task. A group of young (n = 43) and healthy older subjects (n = 44) underwent functional magnetic resonance imaging recordings during this novel task, while they were asked to discriminate exact repetitions of object and scene stimuli from novel stimuli that were similar but modified versions of the original stimuli ("lures"). We used structural magnetic resonance images to manually segment anatomical components of the MTL including alErC and pmErC and used these segmented regions to analyze domain specificity of functional activity. Across the entire sample, object processing was associated with activation of the perirhinal cortex (PrC) and alErC, whereas for scene processing, activation was more predominant in the parahippocampal cortex and pmErC. Functional activity related to mnemonic discrimination of object and scene lures from exact repetitions was found to overlap between processing pathways and suggests that while the PrC-alErC pathway was more involved in object discrimination, both pathways were involved in the discrimination of similar scenes. Older adults were behaviorally less accurate than young adults in discriminating similar lures from exact repetitions, but this

  2. The insulin receptor substrate (IRS)-1 pleckstrin homology domain functions in downstream signaling.

    Science.gov (United States)

    Vainshtein, I; Kovacina, K S; Roth, R A

    2001-03-16

    The pleckstrin homology (PH) domain of the insulin receptor substrate-1 (IRS-1) plays a role in directing this molecule to the insulin receptor, thereby regulating its tyrosine phosphorylation. In this work, the role of the PH domain in subsequent signaling was studied by constructing constitutively active forms of IRS-1 in which the inter-SH2 domain of the p85 subunit of phosphatidylinositol 3-kinase was fused to portions of the IRS-1 molecule. Chimeric molecules containing the PH domain were found to activate the downstream response of stimulating the Ser/Thr kinase Akt. A chimera containing point mutations in the PH domain that abolished the ability of this domain to bind phosphatidylinositol 4,5-bisphosphate prevented these molecules from activating Akt. These mutations also decreased by about 70% the amount of the constructs present in a particulate fraction of the cells. These results indicate that the PH domain of IRS-1, in addition to directing this protein to the receptor for tyrosine phosphorylation, functions in the ability of this molecule to stimulate subsequent responses. Thus, compromising the function of the PH domain, e.g. in insulin-resistant states, could decrease both the ability of IRS-1 to be tyrosine phosphorylated by the insulin receptor and to link to subsequent downstream targets.

  3. Green’s functions in classical physics

    CERN Document Server

    Rother, Tom

    2017-01-01

    This book presents the Green’s function formalism in a basic way and demonstrates its usefulness for applications to several well-known problems in classical physics which are usually solved not by this formalism but other approaches. The book bridges the gap between applications of the Green’s function formalism in quantum physics and classical physics. This book is written as an introduction for graduate students and researchers who want to become more familiar with the Green’s function formalism. In 1828 George Green has published an essay that was unfortunately sunken into oblivion shortly after its publication. It was rediscovered only after several years by the later Lord Kelvin. But since this time, using Green’s functions for solving partial differential equations in physics has become an important mathematical tool. While the conceptual and epistemological importance of these functions were essentially discovered and discussed in modern physics - especially in quantum field theory and quantum...

  4. Dutch translation and cross-cultural adaptation of the PROMIS® physical function item bank and cognitive pre-test in Dutch arthritis patients.

    Science.gov (United States)

    Oude Voshaar, Martijn Ah; Ten Klooster, Peter M; Taal, Erik; Krishnan, Eswar; van de Laar, Mart Afj

    2012-03-05

    Patient-reported physical function is an established outcome domain in clinical studies in rheumatology. To overcome the limitations of the current generation of questionnaires, the Patient-Reported Outcomes Measurement Information System (PROMIS®) project in the USA has developed calibrated item banks for measuring several domains of health status in people with a wide range of chronic diseases. The aim of this study was to translate and cross-culturally adapt the PROMIS physical function item bank to the Dutch language and to pretest it in a sample of patients with arthritis. The items of the PROMIS physical function item bank were translated using rigorous forward-backward protocols and the translated version was subsequently cognitively pretested in a sample of Dutch patients with rheumatoid arthritis. Few issues were encountered in the forward-backward translation. Only 5 of the 124 items to be translated had to be rewritten because of culturally inappropriate content. Subsequent pretesting showed that overall, questions of the Dutch version were understood as they were intended, while only one item required rewriting. Results suggest that the translated version of the PROMIS physical function item bank is semantically and conceptually equivalent to the original. Future work will be directed at creating a Dutch-Flemish final version of the item bank to be used in research with Dutch speaking populations.

  5. Aerobic capacity explains physical functioning and participation in patients with multiple sclerosis-related fatigue.

    Science.gov (United States)

    Rosalie Driehuis, Emma; van den Akker, Lizanne Eva; de Groot, Vincent; Beckerman, Heleen

    2018-02-13

    To investigate whether aerobic capacity explains the level of self-reported physical activity, physical functioning, and participation and autonomy in daily living in persons with multiple sclerosis-related fatigue. A cross-sectional study. Sixty-two participants with multiple sclerosis-related fatigue. Aerobic capacity was measured with a leg ergometer and was expressed as maximal oxygen uptake (VO2max, in ml/kg/min). Physical activity was measured with the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD), physical functioning with the Short Form 36 - physical functioning (SF36-pf), and participation and autonomy in daily living with the Impact on Participation and Autonomy questionnaire (IPA). Multiple regression analyses were performed, adjusted for potential confounders (gender, age, body mass index, educational level, and employment status). Mean maximal oxygen uptake (VO2max) was 23.9 ml/kg/min (standard deviation (SD) 6.3 ml/kg/min). There was no significant relationship between VO2max and physical activity (PASIPD): β = 0.320, 95% confidence interval (95% CI) = -0.109 to 0.749, R2 = 10.8%. Higher VO2max correlated with better physical functioning (SF36-pf): β = 1.527, 95% CI = 0.820-2.234, R2 = 25.9%, and was significantly related to IPA domains "autonomy indoors" (β = -0.043, 95% CI = -0.067 to -0.020, R2 = 20.6%), "autonomy outdoors" (β = -0.037, 95% CI = -0.062 to -0.012, R2 = 18.2%) and "social life and relationships" (β=-0.033, 95% CI = -0.060 to -0.007, R2 = 21.3%). Maximum aerobic capacity was severely reduced in persons with multiple sclerosis-related fatigue. This partly explains the limited physical functioning and restrictions in participation and autonomy indoors, outdoors and in social life and relationships in these persons.

  6. Aerobic capacity explains physical functioning and participation in patients with multiple sclerosis-related fatigue

    Directory of Open Access Journals (Sweden)

    Emma Rosalie Driehuis

    2018-01-01

    Full Text Available Objective: To investigate whether aerobic capacity explains the level of self-reported physical activity, physical functioning, and participation and autonomy in daily living in persons with multiple sclerosis-related fatigue. Design: A cross-sectional study. Patients: Sixty-two participants with multiple sclerosis-related fatigue. Methods: Aerobic capacity was measured with a leg ergometer and was expressed as maximal oxygen uptake (VO2max, in ml/kg/min. Physical activity was measured with the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD, physical functioning with the Short Form 36 – physical functioning (SF36-pf, and participation and autonomy in daily living with the Impact on Participation and Autonomy questionnaire (IPA. Multiple regression analyses were performed, adjusted for potential confounders (gender, age, body mass index, educational level, and employment status. Results: Mean maximal oxygen uptake (VO2max was 23.9 ml/kg/min (standard deviation (SD 6.3 ml/kg/min. There was no significant relationship between VO2max and physical activity (PASIPD: β = 0.320, 95% confidence interval (95% CI = –0.109 to 0.749, R2 = 10.8%. Higher VO2max correlated with better physical functioning (SF36-pf: β = 1.527, 95% CI = 0.820–2.234, R2 = 25.9%, and was significantly related to IPA domains “autonomy indoors” (β = –0.043, 95% CI = –0.067 to –0.020, R2 = 20.6%, “autonomy outdoors” (β = –0.037, 95% CI = –0.062 to –0.012, R2 = 18.2% and “social life and relationships” (β=–0.033, 95% CI = –0.060 to –0.007, R2 = 21.3%. Conclusion: Maximum aerobic capacity was severely reduced in persons with multiple sclerosis-related fatigue. This partly explains the limited physical functioning and restrictions in participation and autonomy indoors, outdoors and in social life and relationships in these persons.

  7. Molecular Details of Olfactomedin Domains Provide Pathway to Structure-Function Studies.

    Directory of Open Access Journals (Sweden)

    Shannon E Hill

    Full Text Available Olfactomedin (OLF domains are found within extracellular, multidomain proteins in numerous tissues of multicellular organisms. Even though these proteins have been implicated in human disorders ranging from cancers to attention deficit disorder to glaucoma, little is known about their structure(s and function(s. Here we biophysically, biochemically, and structurally characterize OLF domains from H. sapiens olfactomedin-1 (npoh-OLF, also called noelin, pancortin, OLFM1, and hOlfA, and M. musculus gliomedin (glio-OLF, also called collomin, collmin, and CRG-L2, and compare them with available structures of myocilin (myoc-OLF recently reported by us and R. norvegicus glio-OLF and M. musculus latrophilin-3 (lat3-OLF by others. Although the five-bladed β-propeller architecture remains unchanged, numerous physicochemical characteristics differ among these OLF domains. First, npoh-OLF and glio-OLF exhibit prominent, yet distinct, positive surface charges and copurify with polynucleotides. Second, whereas npoh-OLF and myoc-OLF exhibit thermal stabilities typical of human proteins near 55°C, and most myoc-OLF variants are destabilized and highly prone to aggregation, glio-OLF is nearly 20°C more stable and significantly more resistant to chemical denaturation. Phylogenetically, glio-OLF is most similar to primitive OLFs, and structurally, glio-OLF is missing distinguishing features seen in OLFs such as the disulfide bond formed by N- and C- terminal cysteines, the sequestered Ca2+ ion within the propeller central hydrophilic cavity, and a key loop-stabilizing cation-π interaction on the top face of npoh-OLF and myoc-OLF. While deciphering the explicit biological functions, ligands, and binding partners for OLF domains will likely continue to be a challenging long-term experimental pursuit, we used structural insights gained here to generate a new antibody selective for myoc-OLF over npoh-OLF and glio-OLF as a first step in overcoming the impasse in

  8. Evolution of function in the "two dinucleotide binding domains" flavoproteins.

    Directory of Open Access Journals (Sweden)

    Sunil Ojha

    2007-07-01

    Full Text Available Structural and biochemical constraints force some segments of proteins to evolve more slowly than others, often allowing identification of conserved structural or sequence motifs that can be associated with substrate binding properties, chemical mechanisms, and molecular functions. We have assessed the functional and structural constraints imposed by cofactors on the evolution of new functions in a superfamily of flavoproteins characterized by two-dinucleotide binding domains, the "two dinucleotide binding domains" flavoproteins (tDBDF superfamily. Although these enzymes catalyze many different types of oxidation/reduction reactions, each is initiated by a stereospecific hydride transfer reaction between two cofactors, a pyridine nucleotide and flavin adenine dinucleotide (FAD. Sequence and structural analysis of more than 1,600 members of the superfamily reveals new members and identifies details of the evolutionary connections among them. Our analysis shows that in all of the highly divergent families within the superfamily, these cofactors adopt a conserved configuration optimal for stereospecific hydride transfer that is stabilized by specific interactions with amino acids from several motifs distributed among both dinucleotide binding domains. The conservation of cofactor configuration in the active site restricts the pyridine nucleotide to interact with FAD from the re-side, limiting the flow of electrons from the re-side to the si-side. This directionality of electron flow constrains interactions with the different partner proteins of different families to occur on the same face of the cofactor binding domains. As a result, superimposing the structures of tDBDFs aligns not only these interacting proteins, but also their constituent electron acceptors, including heme and iron-sulfur clusters. Thus, not only are specific aspects of the cofactor-directed chemical mechanism conserved across the superfamily, the constraints they impose are

  9. Physical Activity and Physical Function in Individuals Post-bariatric Surgery

    Science.gov (United States)

    Josbeno, Deborah A.; Kalarchian, Melissa; Sparto, Patrick J.; Otto, Amy D.; Jakicic, John M.

    2016-01-01

    Background A better understanding of the physical activity behavior of individuals who undergo bariatric surgery will enable the development of effective post-surgical exercise guidelines and interventions to enhance weight loss outcomes. This study characterized the physical activity profile and physical function of 40 subjects 2–5 years post-bariatric surgery and examined the association between physical activity, physical function, and weight loss after surgery. Methods Moderate-to-vigorous intensity physical activity (MVPA) was assessed with the BodyMedia SenseWear® Pro (SWPro) armband, and physical function (PF) was measured using the physical function subscale of the 36-Item Short Form Health Survey instrument (SF-36PF). Height and weight were measured. Results Percent of excess weight loss (%EWL) was associated with MVPA (r = 0.44, p = 0.01) and PF (r = 0.38, p = 0.02); MVPA was not associated with PF (r = 0.24, p = 0.14). Regression analysis demonstrated that MVPA was associated with %EWL (β = 0.38, t = 2.43, p = 0.02). Subjects who participated in ≥150 min/week of MVPA had a greater %EWL (68.2 ± 19, p = 0.01) than those who participated in activities. However, the lack of an association between PF and MVPA suggests that a higher level of PF does not necessarily correspond to a higher level of MVPA participation. Thus, the barriers to adoption of a more physically active lifestyle may not be fully explained by the subjects’ physical limitations. Further understanding of this relationship is needed for the development of post-surgical weight loss guidelines and interventions. PMID:21153567

  10. Dutch translation and cross-cultural adaptation of the PROMIS® physical function item bank and cognitive pre-test in Dutch arthritis patients

    NARCIS (Netherlands)

    Oude Voshaar, Antonius H.; ten Klooster, Peter M.; Taal, Erik; Krishnan, Eswar; van de Laar, Mart A F J

    2012-01-01

    INTRODUCTION: Patient-reported physical function is an established outcome domain in clinical studies in rheumatology. To overcome the limitations of the current generation of questionnaires, the Patient-Reported Outcomes Measurement Information System (PROMIS®) project in the USA has developed

  11. A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies.

    Science.gov (United States)

    Zahn, Raphael; Osmanović, Dino; Ehret, Severin; Araya Callis, Carolina; Frey, Steffen; Stewart, Murray; You, Changjiang; Görlich, Dirk; Hoogenboom, Bart W; Richter, Ralf P

    2016-04-08

    The permeability barrier of nuclear pore complexes (NPCs) controls bulk nucleocytoplasmic exchange. It consists of nucleoporin domains rich in phenylalanine-glycine motifs (FG domains). As a bottom-up nanoscale model for the permeability barrier, we have used planar films produced with three different end-grafted FG domains, and quantitatively analyzed the binding of two different nuclear transport receptors (NTRs), NTF2 and Importin β, together with the concomitant film thickness changes. NTR binding caused only moderate changes in film thickness; the binding isotherms showed negative cooperativity and could all be mapped onto a single master curve. This universal NTR binding behavior - a key element for the transport selectivity of the NPC - was quantitatively reproduced by a physical model that treats FG domains as regular, flexible polymers, and NTRs as spherical colloids with a homogeneous surface, ignoring the detailed arrangement of interaction sites along FG domains and on the NTR surface.

  12. Intraindividual variability in physical and emotional functioning: comparison of adults with traumatic brain injuries and healthy adults.

    Science.gov (United States)

    Burton, Catherine L; Hultsch, David F; Strauss, Esther; Hunter, Michael A

    2002-08-01

    Recent research has shown that individuals with certain neurological conditions demonstrate greater intraindividual variability on cognitive tasks compared to healthy controls. The present study investigated intraindividual variability in the domains of physical functioning and affect/stress in three groups: adults with mild head injuries, adults with moderate/severe head injuries, and healthy adults. Participants were assessed on 10 occasions and results indicated that (a) individuals with head injuries demonstrated greater variability in dominant finger dexterity and right grip strength than the healthy controls; (b) increased variability tended to be associated with poorer performance/report both within and across tasks; and (c) increased variability on one task was associated with increased variability on other tasks. The findings suggest that increased variability in physical function, as well as cognitive function, represents an indicator of neurological compromise.

  13. The scavenger receptor SSc5D physically interacts with bacteria through the SRCR-containing N-terminal domain

    Directory of Open Access Journals (Sweden)

    Catarina Bessa-Pereira

    2016-10-01

    Full Text Available The scavenger receptor cysteine-rich (SRCR family comprises a group of membrane-attached or secreted proteins that contain one or more modules/domains structurally similar to the membrane distal domain of type I macrophage scavenger receptor. Although no all-inclusive biological function has been ascribed to the SRCR family, some of these receptors have been shown to recognize pathogen-associated molecular patterns (PAMP of bacteria, fungi or other microbes. SSc5D is a recently described soluble SRCR receptor produced by monocytes/macrophages and T lymphocytes, consisting of an N-terminal portion which contains five SRCR modules, and a large C-terminal mucin-like domain. Towards establishing a global common role for SRCR domains, we interrogated whether the set of five SRCR domains of SSc5D displayed pattern recognition receptor (PRR properties. For that purpose, we have expressed in a mammalian expression system the N-terminal SRCR-containing moiety of SSC5D (N-SSc5D, thus excluding the mucin-like domain likely by nature to bind microorganisms, and tested the capacity of the SRCR functional groups to physically interact with bacteria. Using conventional protein-bacteria binding assays, we showed that N-SSc5D had a superior capacity to bind to E. coli strains RS218 and IHE3034 compared with that of the extracellular domains of the SRCR proteins CD5 and CD6 (sCD5 and sCD6, respectively, and similar E. coli-binding properties as Spα, a proven PRR of the SRCR family. We have further designed a more sensitive, real-time and label-free surface plasmon resonance (SPR-based assay, and examined the capacity of N-SSc5D, Spα, sCD5 and sCD6 to bind to different bacteria. We demonstrated that the N-SSc5D compares with Spα in the capacity to bind to E. coli and L. monocytogenes, and further that it can distinguish between pathogenic E. coli RS218 and IHE3034 strains and the non-pathogenic laboratory E. coli strain BL21(DE3. Our work thus advocates the

  14. Functional neuroanatomy of intuitive physical inference.

    Science.gov (United States)

    Fischer, Jason; Mikhael, John G; Tenenbaum, Joshua B; Kanwisher, Nancy

    2016-08-23

    To engage with the world-to understand the scene in front of us, plan actions, and predict what will happen next-we must have an intuitive grasp of the world's physical structure and dynamics. How do the objects in front of us rest on and support each other, how much force would be required to move them, and how will they behave when they fall, roll, or collide? Despite the centrality of physical inferences in daily life, little is known about the brain mechanisms recruited to interpret the physical structure of a scene and predict how physical events will unfold. Here, in a series of fMRI experiments, we identified a set of cortical regions that are selectively engaged when people watch and predict the unfolding of physical events-a "physics engine" in the brain. These brain regions are selective to physical inferences relative to nonphysical but otherwise highly similar scenes and tasks. However, these regions are not exclusively engaged in physical inferences per se or, indeed, even in scene understanding; they overlap with the domain-general "multiple demand" system, especially the parts of that system involved in action planning and tool use, pointing to a close relationship between the cognitive and neural mechanisms involved in parsing the physical content of a scene and preparing an appropriate action.

  15. Functional Diversity of Tandem Substrate-Binding Domains in ABC Transporters from Pathogenic Bacteria

    NARCIS (Netherlands)

    Fulyani, Faizah; Schuurman-Wolters, Gea K.; Vujicic - Zagar, Andreja; Guskov, Albert; Slotboom, Dirk-Jan; Poolman, Bert

    2013-01-01

    The ATP-binding cassette (ABC) transporter GInPQ is an essential uptake system for amino acids in gram-positive pathogens and related nonpathogenic bacteria. The transporter has tandem substrate-binding domains (SBDs) fused to each transmembrane domain, giving rise to four SBDs per functional

  16. It is not just comfort: waterproof casting increases physical functioning in children with minimally angulated distal radius fractures.

    Science.gov (United States)

    Silva, Mauricio; Avoian, Tigran; Warnock, Robert Sean; Sadlik, Gal; Ebramzadeh, Edward

    2017-09-01

    Waterproof casting has been reported to increase patient comfort and satisfaction, and decrease skin irritation. There are no available data on the influence of waterproof casting materials on physical function in pediatric patients. Our aim was to determine whether the use of waterproof casting would result in faster recovery of physical function while maintaining similar clinical outcomes as those obtained with nonwaterproof materials. Twenty-six children with nonangulated or minimally angulated distal radius fractures were assigned randomly to initially receive a short-arm cast made of one of two optional materials: a hybrid mesh material with a waterproof lining or fiberglass with a nonwaterproof skin protector. Two weeks later, the initial cast was removed and replaced with a short-arm cast made of the alternative option. We compared the rate of fracture displacement, physical function, pain, skin changes, itchiness, and patient satisfaction. No evidence of displacement was found in either group. The mean Activities Scale for Kids - Performance (ASK-P) (physical function) score was 10% higher during the period of time when a waterproof cast was used (P=0.04). When a waterproof cast was used during the first 2 weeks of treatment, the mean total ASK-P scores were 23% higher than that when a nonwaterproof one was used during the same period of time (P=0.003). Patients who received a waterproof cast as the initial treatment reported lower functional scores overall and in almost every domain of the ASK-P once they were in a nonwaterproof one; similarly, those who received a nonwaterproof cast as the initial treatment reported higher functional scores overall and in every domain of the ASK-P once they were in a waterproof cast. Compared with a nonwaterproof cast, the use of waterproof casting resulted in comparable levels of pain, itchiness, skin irritability, and overall patient satisfaction. The results of this randomized, cross-over trial suggest that the use of

  17. Reconstruction of the domain orientation distribution function of polycrystalline PZT ceramics using vector piezoresponse force microscopy.

    Science.gov (United States)

    Kratzer, Markus; Lasnik, Michael; Röhrig, Sören; Teichert, Christian; Deluca, Marco

    2018-01-11

    Lead zirconate titanate (PZT) is one of the prominent materials used in polycrystalline piezoelectric devices. Since the ferroelectric domain orientation is the most important parameter affecting the electromechanical performance, analyzing the domain orientation distribution is of great importance for the development and understanding of improved piezoceramic devices. Here, vector piezoresponse force microscopy (vector-PFM) has been applied in order to reconstruct the ferroelectric domain orientation distribution function of polished sections of device-ready polycrystalline lead zirconate titanate (PZT) material. A measurement procedure and a computer program based on the software Mathematica have been developed to automatically evaluate the vector-PFM data for reconstructing the domain orientation function. The method is tested on differently in-plane and out-of-plane poled PZT samples, and the results reveal the expected domain patterns and allow determination of the polarization orientation distribution function at high accuracy.

  18. Cognitive and Physical Function in Relation to the Risk of Injurious Falls in Older Adults: A Population-Based Study.

    Science.gov (United States)

    Welmer, Anna-Karin; Rizzuto, Debora; Laukka, Erika J; Johnell, Kristina; Fratiglioni, Laura

    2017-05-01

    We aimed to quantify the independent effect of cognitive and physical deficits on the risk of injurious falls, to verify whether this risk is modified by global cognitive impairment, and to explore whether risk varies by follow-up time. Data on 2,495 participants (≥60 years) from the population-based Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) study were analyzed using flexible parametric survival models. Two cognitive domains (processing speed and executive function) were assessed with standard tests. Physical function tests included balance (one-leg-stands), walking speed, chair stands, and grip strength. Global cognition was assessed using the Mini-Mental State Examination. A total of 167 people experienced an injurious fall over 3 years of follow-up, 310 over 5 years, and 571 over 10 years. Each standard deviation worse balance, slower walking speed, and longer chair stand time increased the risk of injurious falls over 3 years by 43%, 38%, and 23%, respectively (p risk of injurious falls over 10 years (p falls only in people with cognitive impairment, whereas deficits in processing speed and executive function were associated with injurious falls only in people without cognitive impairment. Deficits in specific cognitive domains, such as processing speed and executive function, appear to predict injurious falls in the long term. Deficits in physical function predict falls in the short term, especially in people with global cognitive impairment. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. How Students' Epistemological Beliefs in the Domain of Physics and Their Conceptual Change Are Related?

    Science.gov (United States)

    Kaymak, Ercan; Ogan-Bekiroglu, Feral

    2013-01-01

    The purposes of this study were to determine high school students' epistemological beliefs in the domain of physics and to explore and explain the possible relationship between their beliefs and their conceptual change in physics by taking the students' learning strategies into account. A multi-case study design was used for the research…

  20. Improved functional immobilization of llama single-domain antibody fragments to polystyrene surfaces using small peptides

    NARCIS (Netherlands)

    Harmsen, M.M.; Fijten, H.P.D.

    2012-01-01

    We studied the effect of different fusion domains on the functional immobilization of three llama single-domain antibody fragments (VHHs) after passive adsorption to polystyrene in enzyme-linked immunosorbent assays (ELISA). Three VHHs produced without any fusion domain were efficiently adsorbed to

  1. Extrinsic functions of lectin domains in O-N-acetylgalactosamine glycan biosynthesis

    DEFF Research Database (Denmark)

    Lorenz, Virginia; Ditamo, Yanina; Cejas, Romina B

    2016-01-01

    during O-GalNAc glycan biosynthesis. The presence of lectin domain T3lec or T4lec during ppGalNAc-T2 and ppGalNAc-T3 catalytic reaction had a clear inhibitory effect on GalNAc-T activity. Interaction of T3lec or T4lec with ppGalNAc-T2 catalytic domain was not mediated by carbohydrate. T3lec, but not T2......Glycan biosynthesis occurs mainly in Golgi. Molecular organization and functional regulation of this process are not well understood. We evaluated the extrinsic effect of lectin domains (β-trefoil fold) of polypeptide GalNAc-transferases (ppGalNAc-Ts) on catalytic activity of glycosyltransferases...

  2. Discrete Green’s function diakoptics for stable FDTD interaction between multiply-connected domains

    NARCIS (Netherlands)

    Hon, de B.P.; Arnold, J.M.; Graglia, R.D.

    2007-01-01

    We have developed FDTD boundary conditions based on discrete Green's function diakoptics for arbitrary multiply-connected 2D domains. The associated Z-domain boundary operator is symmetric, with an imaginary part that can be proved to be positive semi-definite on the upper half of the unit circle in

  3. Associations among workplace environment, self-regulation, and domain-specific physical activities among white-collar workers: a multilevel longitudinal study.

    Science.gov (United States)

    Watanabe, Kazuhiro; Kawakami, Norito; Otsuka, Yasumasa; Inoue, Shigeru

    2018-05-31

    Psychological and environmental determinants have been discussed for promoting physical activity among workers. However, few studies have investigated effects of both workplace environment and psychological determinants on physical activity. It is also unknown which domains of physical activities are promoted by these determinants. This study aimed to investigate main and interaction effects of workplace environment and individual self-regulation for physical activity on domain-specific physical activities among white-collar workers. A multi-site longitudinal study was conducted at baseline and about 5-month follow-up. A total of 49 worksites and employees within the worksites were recruited. Inclusion criteria for the worksites (a) were located in the Kanto area, Japan and (b) employed two or more employees. Employee inclusion criteria were (a) employed by the worksites, (b) aged 18 years or older, and (c) white-collar workers. For outcomes, three domain-specific physical activities (occupational, transport-related, and leisure-time) at baseline and follow-up were measured. For independent variables, self-regulation for physical activity, workplace environments (parking/bike, signs/bulletin boards/advertisements, stairs/elevators, physical activity/fitness facilities, work rules, written policies, and health promotion programs), and covariates at baseline were measured. Hierarchical Linear Modeling was conducted to investigate multilevel associations. Of the recruited worksites, 23 worksites and 562 employees, and 22 worksites and 459 employees completed the baseline and the follow-up surveys. As results of Hierarchical Linear Modeling, stairs/elevator (γ=3.80 [SE=1.80], ppsychological approaches to increase effect sizes to promote overall physical activity.

  4. Domain-specific physical activity and health-related quality of life in university students.

    Science.gov (United States)

    Pedišić, Zeljko; Rakovac, Marija; Titze, Sylvia; Jurakić, Danijel; Oja, Pekka

    2014-01-01

    Information on the relationship between domain-specific physical activity (PA) and health-related quality of life (HRQoL) in the general population and specific groups is still scarce. The aim of this study was to determine the relationship between PA in work, transport, domestic and leisure-time domains and HRQoL among university students. PA and HRQoL were assessed in a random stratified sample of 1750 university students using the International Physical Activity Questionnaire - long form and 12-item Short Form Health Survey, respectively. The Spearman's rank correlations, adjusted for age, community size, personal monthly budget, body mass index, smoking habits and alcohol intake ranged from -0.11 to 0.18 in female students and -0.29 to 0.19 in male students. Leisure-time, domestic, transport-related PA and total PA were positively related to HRQoL. Inverse correlations with HRQoL were only found for work-related PA in male students. Multiple linear regression analysis showed that only leisure-time PA was related to the Physical Summary Component score (β = 0.08 for females and β = 0.10 for males, P leisure-time, transport and domestic PA with HRQoL can potentially be used to support evidence-based promotion of PA in a university setting, and as a hypothesis for future longitudinal studies on such potential causal relationships.

  5. Core outcome domains for clinical trials in non-specific low back pain.

    Science.gov (United States)

    Chiarotto, Alessandro; Deyo, Richard A; Terwee, Caroline B; Boers, Maarten; Buchbinder, Rachelle; Corbin, Terry P; Costa, Leonardo O P; Foster, Nadine E; Grotle, Margreth; Koes, Bart W; Kovacs, Francisco M; Lin, Chung-Wei Christine; Maher, Chris G; Pearson, Adam M; Peul, Wilco C; Schoene, Mark L; Turk, Dennis C; van Tulder, Maurits W; Ostelo, Raymond W

    2015-06-01

    Inconsistent reporting of outcomes in clinical trials of patients with non-specific low back pain (NSLBP) hinders comparison of findings and the reliability of systematic reviews. A core outcome set (COS) can address this issue as it defines a minimum set of outcomes that should be reported in all clinical trials. In 1998, Deyo et al. recommended a standardized set of outcomes for LBP clinical research. The aim of this study was to update these recommendations by determining which outcome domains should be included in a COS for clinical trials in NSLBP. An International Steering Committee established the methodology to develop this COS. The OMERACT Filter 2.0 framework was used to draw a list of potential core domains that were presented in a Delphi study. Researchers, care providers and patients were invited to participate in three Delphi rounds and were asked to judge which domains were core. A priori criteria for consensus were established before each round and were analysed together with arguments provided by panellists on importance, overlap, aggregation and/or addition of potential core domains. The Steering Committee discussed the final results and made final decisions. A set of 280 experts was invited to participate in the Delphi; response rates in the three rounds were 52, 50 and 45%. Of 41 potential core domains presented in the first round, 13 had sufficient support to be presented for rating in the third round. Overall consensus was reached for the inclusion of three domains in this COS: 'physical functioning', 'pain intensity' and 'health-related quality of life'. Consensus on 'physical functioning' and 'pain intensity' was consistent across all stakeholders, 'health-related quality of life' was not supported by the patients, and all the other domains were not supported by two or more groups of stakeholders. Weighting all possible argumentations, the Steering Committee decided to include in the COS the three domains that reached overall consensus and

  6. Physical Activity Predicts Higher Physical Function in Older Adults: The Osteoarthritis Initiative.

    Science.gov (United States)

    Batsis, John A; Germain, Cassandra M; Vásquez, Elizabeth; Zbehlik, Alicia J; Bartels, Stephen J

    2016-01-01

    Physical activity reduces mobility impairments in elders. We examined the association of physical activity on risk of subjective and objective physical function in adults with and at risk for osteoarthritis (OA). Adults aged ≥ 60 years from the longitudinal Osteoarthritis Initiative, a prospective observational study of knee OA, were classified by sex-specific quartiles of Physical Activity Score for the Elderly scores. Using linear mixed models, we assessed 6-year data on self-reported health, gait speed, Late-Life Function and Disability Index (LLFDI) and chair stand. Of 2252 subjects, mean age ranged from 66 to 70 years. Within each quartile, physical component (PCS) of the Short Form-12 and gait speed decreased from baseline to follow-up in both sexes (all P physical activity is associated with maintained physical function and is mediated by muscle strength, highlighting the importance of encouraging physical activity in older adults with and at risk for OA.

  7. Functional Properties at Domain Walls in BiFeO3: Electrical, Magnetic, and Structural investigations

    Science.gov (United States)

    He, Qing; Yang, C.-H.; Yu, P.; Gajek, M.; Seidel, J.; Ramesh, R.; Wang, F.; Chu, Y.-H.; Martin, L. W.; Spaldin, N.; Rother, A.

    2009-03-01

    BiFeO3 (BFO) is a widely studied robust ferroelectric, antiferromagnetic multiferroic. Conducting-atomic force microscopy studies reveal the presence of enhanced conductivity at certain types of domain walls in BFO. We have completed detailed TEM studies of the physical structure at these domain walls as well as in-depth DFT calculations of the evolution of electronic structure at these domain walls. These studies reveal two major contributions to the observed conduction: the formation of an electrostatic potential at the domain walls as well as a structurally-driven change in the electronic structure (i.e., a lower band gap locally) at the domain walls. We will discuss the use of optical characterization techniques as a way of probing this change in electronic structure at domain walls as well as detailed IV characterization both in atmospheric and UHV environments. Finally, the evolution of magnetism at these domain walls has been studied through the use of photoemission measurements. Initial findings point to a significant change in the magnetic order at these domain walls in BFO.

  8. AGN Accretion Physics in the Time Domain: Survey Cadences, Stochastic Analysis, and Physical Interpretations

    Science.gov (United States)

    Moreno, Jackeline; Vogeley, Michael S.; Richards, Gordon; O'Brien, John T.; Kasliwal, Vishal

    2018-01-01

    We present rigorous testing of survey cadences (K2, SDSS, CRTS, & Pan-STARRS) for quasar variability science using a magnetohydrodynamics synthetic lightcurve and the canonical lightcurve from Kepler, Zw 229.15. We explain where the state of the art is in regards to physical interpretations of stochastic models (CARMA) applied to AGN variability. Quasar variability offers a time domain approach of probing accretion physics at the SMBH scale. Evidence shows that the strongest amplitude changes in the brightness of AGN occur on long timescales ranging from months to hundreds of days. These global behaviors can be constrained by survey data despite low sampling resolution. CARMA processes provide a flexible family of models used to interpolate between data points, predict future observations and describe behaviors in a lightcurve. This is accomplished by decomposing a signal into rise and decay timescales, frequencies for cyclic behavior and shock amplitudes. Characteristic timescales may point to length-scales over which a physical process operates such as turbulent eddies, warping or hotspots due to local thermal instabilities. We present the distribution of SDSS Stripe 82 quasars in CARMA parameters space that pass our cadence tests and also explain how the Damped Harmonic Oscillator model, CARMA(2,1), reduces to the Damped Random Walk, CARMA(1,0), given the data in a specific region of the parameter space.

  9. Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains.

    Science.gov (United States)

    Vishwanath, Sneha; de Brevern, Alexandre G; Srinivasan, Narayanaswamy

    2018-02-01

    The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in

  10. Factors across home, work, and school domains influence nutrition and physical activity behaviors of nontraditional college students.

    Science.gov (United States)

    Quintiliani, Lisa M; Bishop, Hillary L; Greaney, Mary L; Whiteley, Jessica A

    2012-10-01

    Nontraditional college students (older, part-time, and/or working) have less healthful nutrition and physical activity behaviors compared to traditional students, yet few health promotion efforts focus on nontraditional students. The purpose of this study was to use qualitative methods to explore factors affecting nutrition and physical activity behaviors of nontraditional students. Fourteen semi-structured individual interviews were conducted with nontraditional undergraduate students attending a large university. The sample had a median age of 25 (range, 21-64), 57% were men, 43% were racial/ethnic minorities, and 57% were employed (mean 22 hours/week). Data were coded using a systematic team-based approach. Consistent themes (mentioned by 4+ students) were identified and categorized into three domains: home, work, and school. Home (themes: neighborhood characteristics, family, partners), work (theme: work environment), and school (themes: cafeteria, vending machines) factors consistently influenced positive nutrition behaviors. Similarly, home (themes: neighborhood including safety, friends from home, partner,), work (theme: work environment), and school (themes: not having a car, campus structure, campus gym, friends at school) factors consistently influenced positive physical activity. Financial resources and perceptions of autonomy had influence across domains. Results indicate consistent influences on nutrition and physical activity behaviors across home, work, and school domains for nontraditional college students. Study findings suggest possible, and sometimes unconventional, intervention strategies to promote healthful eating and physical activity. For example, when cafeteria meal plans are not offered and financial constraints limit eating at the cafeteria, encouraging healthful choices from vending machines could be preferable to not eating at all. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Physical activity and cognitive function in individuals over 60 years of age: a systematic review

    Directory of Open Access Journals (Sweden)

    Carvalho A

    2014-04-01

    which types of exercise have the greatest benefit on specific cognitive domains. Despite these caveats, the current evidence suggests that physical activity may help to improve cognitive function and, consequently, delay the progression of cognitive impairment in the elderly.Keywords: exercise, cognitive function, elderly

  12. Measurement of Function Post Hip Fracture: Testing a Comprehensive Measurement Model of Physical Function.

    Science.gov (United States)

    Resnick, Barbara; Gruber-Baldini, Ann L; Hicks, Gregory; Ostir, Glen; Klinedinst, N Jennifer; Orwig, Denise; Magaziner, Jay

    2016-07-01

    Measurement of physical function post hip fracture has been conceptualized using multiple different measures. This study tested a comprehensive measurement model of physical function. This was a descriptive secondary data analysis including 168 men and 171 women post hip fracture. Using structural equation modeling, a measurement model of physical function which included grip strength, activities of daily living, instrumental activities of daily living, and performance was tested for fit at 2 and 12 months post hip fracture, and among male and female participants. Validity of the measurement model of physical function was evaluated based on how well the model explained physical activity, exercise, and social activities post hip fracture. The measurement model of physical function fit the data. The amount of variance the model or individual factors of the model explained varied depending on the activity. Decisions about the ideal way in which to measure physical function should be based on outcomes considered and participants. The measurement model of physical function is a reliable and valid method to comprehensively measure physical function across the hip fracture recovery trajectory. © 2015 Association of Rehabilitation Nurses.

  13. Characterization of the functional domains of the natriuretic peptide receptor/guanylate cyclase by radiation inactivation

    International Nuclear Information System (INIS)

    Tremblay, J.; Huot, C.; Koch, C.; Potier, M.

    1991-01-01

    Radiation inactivation has been used to evaluate the molecular size of domains responsible for atrial natriuretic peptide (ANP)-binding and cyclase functions of the ANP receptor/guanylate cyclase. Two types of inactivation curves were observed for cyclase function in both adrenal cortex and aortic smooth muscle cells: (1) biphasic with enhanced guanylate cyclase activity after exposure to low radiation doses and (2) linear after preincubation of membrane proteins with 0.5 microM ANP or solubilization with Triton X-100. The existence of an inhibitory component was the simplest model that best explained the types of radiation curves obtained. Activation of guanylate cyclase by ANP or Triton X-100 could occur via the dissociation of this inhibitory component from the catalytic domain. On the other hand, the loss of ANP-binding activity was linear with increasing radiation exposures under basal, ANP treatment, and Triton X-100 solubilization conditions. Radiation inactivation sizes of about 30 kDa for cyclase function, 20 kDa for ANP-binding function, and 90 kDa for inhibitory function were calculated. These studies suggest that the ANP receptor/guanylate cyclase behaves as a multidomain protein. The results obtained by radiation inactivation of the various biological functions of this receptor are compatible with the hypothesis of an intramolecular inhibitory domain repressing the guanylate cyclase catalytic domain within its membrane environment

  14. Testosterone Replacement, Muscle Strength, and Physical Function

    Directory of Open Access Journals (Sweden)

    You-Seon Nam

    2018-05-01

    Full Text Available Muscle strength and physical function decrease in older men, as do testosterone levels. Nonetheless, the effects of testosterone replacement therapy on muscle strength and physical function remain inconclusive and equivocal. We conducted a rapid systematic review, the results of which showed that testosterone replacement does not affect muscle strength (measured by hand grip strength and leg muscle strength, although it may increase physical function (measured by the 6-minute walk test, Physical Activity Scale for the Elderly score, and other physical performance tests. However, most of the studies were conducted in the United States or Europe and did not include participants from Asian or other ethnic backgrounds; therefore, further studies are needed to evaluate the effects of testosterone replacement in a broader population.

  15. The Association between Belgian Older Adults' Physical Functioning and Physical Activity: What Is the Moderating Role of the Physical Environment?

    Science.gov (United States)

    Van Holle, Veerle; Van Cauwenberg, Jelle; Gheysen, Freja; Van Dyck, Delfien; Deforche, Benedicte; Van de Weghe, Nico; De Bourdeaudhuij, Ilse

    2016-01-01

    Better physical functioning in the elderly may be associated with higher physical activity levels. Since older adults spend a substantial part of the day in their residential neighborhood, the neighborhood physical environment may moderate associations between functioning and older adults' physical activity. The present study investigated the moderating role of the objective and perceived physical environment on associations between Belgian older adults' physical functioning and transport walking, recreational walking, and moderate-to-vigorous physical activity. Data from 438 older adults were included. Objective physical functioning was assessed using the Short Physical Performance Battery. Potential moderators included objective neighborhood walkability and perceptions of land use mix diversity, access to recreational facilities, access to services, street connectivity, physical barriers for walking, aesthetics, crime-related safety, traffic speeding-related safety, and walking infrastructure. Transport and recreational walking were self-reported, moderate-to-vigorous physical activity was assessed through accelerometers. Multi-level regression analyses were conducted using MLwiN to examine two-way interactions between functioning and the environment on both walking outcomes. Based on a previous study where environment x neighborhood income associations were found for Belgian older adults' moderate-to-vigorous physical activity, three-way functioning x environment x income interactions were examined for moderate-to-vigorous physical activity. Objectively-measured walkability moderated the association between functioning and transport walking; this positive association was only present in high-walkable neighborhoods. Moreover, a three-way interaction was observed for moderate-to-vigorous physical activity. Only in high-income, high-walkable neighborhoods, there was a positive association between functioning and moderate-to-vigorous physical activity. No

  16. Large ethnic variations in recommended physical activity according to activity domains in Amsterdam, the Netherlands

    NARCIS (Netherlands)

    de Munter, Jeroen S. L.; van Valkengoed, Irene G. M.; Agyemang, Charles; Kunst, Anton E.; Stronks, Karien

    2010-01-01

    ABSTRACT: Purpose: The level of recommended physical activity (PA) is met less frequently by people from some ethnic minorities than others. We explored whether these differences in recommended PA between ethnic minority groups and the general population varied by domain and type of

  17. Physical domains in plasma physics

    International Nuclear Information System (INIS)

    Liboff, R.L.

    1987-01-01

    Do the plasma in the sun's core and the electron-conduction plasma in a semiconductor behave in the same way? This question is both fundamental and practical, for plasma physics plays a role in a vast area of natural phenomena and in many engineering devices. Understanding the cosmos, or designing a computer chip or a thermonuclear fusion reactor, requires first of all a realization of equations of motion that are appropriate to the particular problem. Similar physical differences occur in engineered structures. The plasmas in most thermonuclear fusion devices are basically like the plasma in the core of the sun: weakly coupled and classical - that is, obeying Newton's laws and Maxwell's equations. The conduction electrons in a semiconductor, on the other hand, obey the laws of quantum mechanics

  18. Phylogenomic and functional domain analysis of polyketide synthases in Fusarium

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Daren W.; Butchko, Robert A.; Baker, Scott E.; Proctor, Robert H.

    2012-02-01

    Fusarium species are ubiquitous in nature, cause a range of plant diseases, and produce a variety of chemicals often referred to as secondary metabolites. Although some fungal secondary metabolites affect plant growth or protect plants from other fungi and bacteria, their presence in grain based food and feed is more often associated with a variety of diseases in plants and in animals. Many of these structurally diverse metabolites are derived from a family of related enzymes called polyketide synthases (PKSs). A search of genomic sequence of Fusarium verticillioides, F. graminearum, F. oxysporum and Nectria haematococca (anamorph F. solani) identified a total of 58 PKS genes. To gain insight into how this gene family evolved and to guide future studies, we conducted a phylogenomic and functional domain analysis. The resulting genealogy suggested that Fusarium PKSs represent 34 different groups responsible for synthesis of different core metabolites. The analyses indicate that variation in the Fusarium PKS gene family is due to gene duplication and loss events as well as enzyme gain-of-function due to the acquisition of new domains or of loss-of-function due to nucleotide mutations. Transcriptional analysis indicate that the 16 F. verticillioides PKS genes are expressed under a range of conditions, further evidence that they are functional genes that confer the ability to produce secondary metabolites.

  19. Gender Differences in the Domain-Specific Contributions to Moderate-to-Vigorous Physical Activity, Accessed by GPS

    DEFF Research Database (Denmark)

    Pizarro, Andreia Nogueira; Schipperijn, Jasper; Ribeiro, José Carlos

    2017-01-01

    time in school (37.0%) and leisure (24.9%) than girls (24.7% and 18.1, respectively).Conclusions:Interventions to increase transport behavior may be relevant for children?s MVPA. School is an important domain for boys PA, while for girls increasing the supportiveness of the school environment for PA...... children (201 girls; X=11.7y) wore an accelerometer and a GPS for 7 days. PALMS software combined data, categorized non-sedentary time and bouts of moderate-to-vigorous physical activity (MVPA). Geographical information system allocated activity into 4 domains: school, leisure, transport and home.......Results:Overall, a higher proportion of time in MVPA was found in the transport domain (45.5%), school (30.5%), leisure (21.3%) and home (2.7%). Gender differences were found for the proportion of time spent across domains. Girls (54.5%) had more MVPA than boys (35.2%) in the transport domain, whereas boys spent more MVPA...

  20. David Adler Lectureship Award in the Field of Materials Physics: Racetrack Memory - a high-performance, storage class memory using magnetic domain-walls manipulated by current

    Science.gov (United States)

    Parkin, Stuart

    2012-02-01

    Racetrack Memory is a novel high-performance, non-volatile storage-class memory in which magnetic domains are used to store information in a ``magnetic racetrack'' [1]. The magnetic racetrack promises a solid state memory with storage capacities and cost rivaling that of magnetic disk drives but with much improved performance and reliability: a ``hard disk on a chip''. The magnetic racetrack is comprised of a magnetic nanowire in which a series of magnetic domain walls are shifted to and fro along the wire using nanosecond-long pulses of spin polarized current [2]. We have demonstrated the underlying physics that makes Racetrack Memory possible [3,4] and all the basic functions - creation, and manipulation of a train of domain walls and their detection. The physics underlying the current induced dynamics of domain walls will also be discussed. In particular, we show that the domain walls respond as if they have mass, leading to significant inertial driven motion of the domain walls over long times after the current pulses are switched off [3]. We also demonstrate that in perpendicularly magnetized nanowires there are two independent current driving mechanisms: one derived from bulk spin-dependent scattering that drives the domain walls in the direction of electron flow, and a second interfacial mechanism that can drive the domain walls either along or against the electron flow, depending on subtle changes in the nanowire structure. Finally, we demonstrate thermally induced spin currents are large enough that they can be used to manipulate domain walls. [4pt] [1] S.S.P. Parkin, US Patent 6,834,005 (2004); S.S.P. Parkin et al., Science 320, 190 (2008); S.S.P. Parkin, Scientific American (June 2009). [0pt] [2] M. Hayashi, L. Thomas, R. Moriya, C. Rettner and S.S.P. Parkin, Science 320, 209 (2008). [0pt] [3] L. Thomas, R. Moriya, C. Rettner and S.S.P. Parkin, Science 330, 1810 (2010). [0pt] [4] X. Jiang et al. Nat. Comm. 1:25 (2010) and Nano Lett. 11, 96 (2011).

  1. The functions of mathematical physics

    CERN Document Server

    Hochstadt, Harry

    2012-01-01

    A modern classic, this clearly written, incisive textbook provides a comprehensive, detailed survey of the functions of mathematical physics, a field of study straddling the somewhat artificial boundary between pure and applied mathematics.In the 18th and 19th centuries, the theorists who devoted themselves to this field - pioneers such as Gauss, Euler, Fourier, Legendre, and Bessel - were searching for mathematical solutions to physical problems. Today, although most of the functions have practical applications, in areas ranging from the quantum-theoretical model of the atom to the vibrating

  2. Domains of Daily Physical Activity in Children with Mitochondrial Disease: A 3D Accelerometry Approach

    NARCIS (Netherlands)

    Koene, S.; Dirks, I.; Mierlo, E. van; Vries, P.R. de; Janssen, A.J.W.M.; Smeitink, J.; Bergsma, A.; Essers, H.; Meijer, K.; Groot, I.J.M. de

    2017-01-01

    Feasible, sensitive and clinically relevant outcome measures are of extreme importance when designing clinical trials. For paediatric mitochondrial disease, no robust end point has been described to date. The aim of this study was to select the domains of daily physical activity, which can be

  3. Pentameric ligand-gated ion channels exhibit distinct transmembrane domain archetypes for folding/expression and function.

    Science.gov (United States)

    Therien, J P Daniel; Baenziger, John E

    2017-03-27

    Although transmembrane helix-helix interactions must be strong enough to drive folding, they must still permit the inter-helix movements associated with conformational change. Interactions between the outermost M4 and adjacent M1 and M3 α-helices of pentameric ligand-gated ion channels have been implicated in folding and function. Here, we evaluate the role of different physical interactions at this interface in the function of two prokaryotic homologs, GLIC and ELIC. Strikingly, disruption of most interactions in GLIC lead to either a reduction or a complete loss of expression and/or function, while analogous disruptions in ELIC often lead to gains in function. Structural comparisons suggest that GLIC and ELIC represent distinct transmembrane domain archetypes. One archetype, exemplified by GLIC, the glycine and GABA receptors and the glutamate activated chloride channel, has extensive aromatic contacts that govern M4-M1/M3 interactions and that are essential for expression and function. The other archetype, exemplified by ELIC and both the nicotinic acetylcholine and serotonin receptors, has relatively few aromatic contacts that are detrimental to function. These archetypes likely have evolved different mechanisms to balance the need for strong M4 "binding" to M1/M3 to promote folding/expression, and the need for weaker interactions that allow for greater conformational flexibility.

  4. Long-Term Impact of Family Arguments and Physical Violence on Adult Functioning at Age 30 Years: Findings from the Simmons Longitudinal Study

    Science.gov (United States)

    Paradis, Angela D.; Reinherz, Helen Z.; Giaconia, Rose M.; Beardslee, William R.; Ward, Kirsten; Fitzmaurice, Garrett M.

    2009-01-01

    Family arguments by the age of 15 and family physical violence by the age of 18 is found to significantly compromise key domains of adult functioning at age 30. The findings are based on data from 346 participants whose psychosocial development has been followed since age 5.

  5. Infected cell protein 0 functional domains and their coordination in herpes simplex virus replication

    Science.gov (United States)

    Gu, Haidong

    2016-01-01

    Herpes simplex virus 1 (HSV-1) is a ubiquitous human pathogen that establishes latent infection in ganglia neurons. Its unique life cycle requires a balanced “conquer and compromise” strategy to deal with the host anti-viral defenses. One of HSV-1 α (immediate early) gene products, infected cell protein 0 (ICP0), is a multifunctional protein that interacts with and modulates a wide range of cellular defensive pathways. These pathways may locate in different cell compartments, which then migrate or exchange factors upon stimulation, for the purpose of a concerted and effective defense. ICP0 is able to simultaneously attack multiple host pathways by either degrading key restrictive factors or modifying repressive complexes. This is a viral protein that contains an E3 ubiquitin ligase, translocates among different cell compartments and interacts with major defensive complexes. The multiple functional domains of ICP0 can work independently and at the same time coordinate with each other. Dissecting the functional domains of ICP0 and delineating the coordination of these domains will help us understand HSV-1 pathogenicity as well as host defense mechanisms. This article focuses on describing individual ICP0 domains, their biochemical properties and their implication in HSV-1 infection. By putting individual domain functions back into the picture of host anti-viral defense network, this review seeks to elaborate the complex interactions between HSV-1 and its host. PMID:26870669

  6. Automation strategies in five domains - A comparison of levels of automation, function allocation and visualisation of automatic functions

    International Nuclear Information System (INIS)

    Andersson, J.

    2011-01-01

    This study was conducted as a field study where control room operators and engineers from the refinery, heat and power, aviation, shipping and nuclear domain were interviewed regarding use of automation and the visualisation of automatic functions. The purpose of the study was to collect experiences and best practices from the five studied domains on levels of automation, function allocation and visualisation of automatic functions. In total, nine different control room settings were visited. The studied settings were compared using a systemic approach based on a human-machine systems model. The results show that the 'left over principle' is still the most common applied approach for function allocation but in high risk settings the decision whether to automate or not is more carefully considered. Regarding the visualisation of automatic functions, it was found that as long as each display type (process based, functional oriented, situation oriented and task based) are applied so that they correspond to the same level of abstraction as the technical system the operators mental model will be supported. No single display type can however readily match all levels of abstraction at the same time - all display types are still needed and serve different purposes. (Author)

  7. Evaluating PROMIS Physical Function Measures in Older Adults at Risk for Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Curtis Tatsuoka PhD

    2016-09-01

    Full Text Available Activities of daily living can be affected by cognitive decline. Self-report measurement of functioning is attractive due to ease of data collection, low cost, and accessibility via technology-assisted means, and for understanding patient perspective. A concern is with reliability of such measurement as cognitive decline occurs. We compared a widely used, self-report “legacy” measure of functioning, Lawton and Brody’s Instrumental Activities of Daily Living Scale (IADLS, with a subset of physical functioning items from the Patient-Reported Outcomes Measurement Information System (PROMIS. The study sample consisted of 304 individuals of varying cognitive status: normal, mild cognitive impairment (MCI, or early dementia. An expert consensus method was used to select PROMIS functional items most relevant to neurocognitive disorder and to identify major functional sub-domains. Selected PROMIS functional subscales and the IADLS were then evaluated with respect to cognitive status. Few PROMIS functional items were useful in identifying MCI, while we reaffirmed the utility of the IADLS. Also, even mild depression levels were found to have negative effects on functioning according to both PROMIS and IADLS.

  8. Updating the Psoriatic Arthritis (PsA) Core Domain Set

    DEFF Research Database (Denmark)

    Orbai, Ana-Maria; de Wit, Maarten; Mease, Philip J

    2017-01-01

    OBJECTIVE: To include the patient perspective in accordance with the Outcome Measures in Rheumatology (OMERACT) Filter 2.0 in the updated Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials (RCT) and longitudinal observational studies (LOS). METHODS: At OMERACT 2016, research...... conducted to update the PsA Core Domain Set was presented and discussed in breakout groups. The updated PsA Core Domain Set was voted on and endorsed by OMERACT participants. RESULTS: We conducted a systematic literature review of domains measured in PsA RCT and LOS, and identified 24 domains. We conducted...... and breakout groups at OMERACT 2016 in which findings were presented and discussed. The updated PsA Core Domain Set endorsed with 90% agreement by OMERACT 2016 participants included musculoskeletal disease activity, skin disease activity, fatigue, pain, patient's global assessment, physical function, health...

  9. Purification of SOCS (Suppressor of Cytokine Signaling) SH2 Domains for Structural and Functional Studies.

    Science.gov (United States)

    Liau, Nicholas P D; Laktyushin, Artem; Babon, Jeffrey J

    2017-01-01

    Src Homology 2 (SH2) domains are protein domains which have a high binding affinity for specific amino acid sequences containing a phosphorylated tyrosine residue. The Suppressors of Cytokine Signaling (SOCS) proteins use an SH2 domain to bind to components of certain cytokine signaling pathways to downregulate the signaling cascade. The recombinantly produced SH2 domains of various SOCS proteins have been used to undertake structural and functional studies elucidating the method of how such targeting occurs. Here, we describe the protocol for the recombinant production and purification of SOCS SH2 domains, with an emphasis on SOCS3.

  10. Wall thickness dependence of the scaling law for ferroic stripe domains

    International Nuclear Information System (INIS)

    Catalan, G; Scott, J F; Schilling, A; Gregg, J M

    2007-01-01

    The periodicity of 180 0 stripe domains as a function of crystal thickness scales with the width of the domain walls, both for ferroelectric and for ferromagnetic materials. Here we derive an analytical expression for the generalized ferroic scaling factor and use this to calculate the domain wall thickness and gradient coefficients (exchange constants) in some ferroelectric and ferromagnetic materials. We then use these to discuss some of the wider implications for the physics of ferroelectric nanodevices and periodically poled photonic crystals. (fast track communication)

  11. Multiple functions of the von Willebrand Factor A domain in matrilins: secretion, assembly, and proteolysis

    Directory of Open Access Journals (Sweden)

    Kanbe Katsuaki

    2008-06-01

    Full Text Available Abstract The von Willebrand Factor A (vWF A domain is one of the most widely distributed structural modules in cell-matrix adhesive molecules such as intergrins and extracellular matrix proteins. Mutations in the vWF A domain of matrilin-3 cause multiple epiphyseal dysplasia (MED, however the pathological mechanism remains to be determined. Previously we showed that the vWF A domain in matrilin-1 mediates formation of a filamentous matrix network through metal-ion dependent adhesion sites in the domain. Here we show two new functions of the vWF A domain in cartilage-specific matrilins (1 and 3. First, vWF A domain regulates oligomerization of matrilins. Insertion of a vWF A domain into matrilin-3 converts the formation of a mixture of matrilin-3 tetramer, trimer, and dimer into a tetramer only, while deletion of a vWF A domain from matrilin-1 converts the formation of the native matrilin-1 trimer into a mixture of trimer and dimer. Second, the vWF A domain protects matrilin-1 from proteolysis. We identified a latent proteolytic site next to the vWF A2 domain in matrilin-1, which is sensitive to the inhibitors of matrix proteases. Deletion of the abutting vWF A domain results in degradation of matrilin-1, presumably by exposing the adjacent proteolytic site. In addition, we also confirmed the vWF A domain is vital for the secretion of matrilin-3. Secretion of the mutant matrilin-3 harbouring a point mutation within the vWF A domain, as occurred in MED patients, is markedly reduced and delayed, resulting from intracellular retention of the mutant matrilin-3. Taken together, our data suggest that different mutations/deletions of the vWF A domain in matrilins may lead to distinct pathological mechanisms due to the multiple functions of the vWF A domain.

  12. Structure and catalytic regulatory function of ubiquitin specific protease 11 N-terminal and ubiquitin-like domains.

    Science.gov (United States)

    Harper, Stephen; Gratton, Hayley E; Cornaciu, Irina; Oberer, Monika; Scott, David J; Emsley, Jonas; Dreveny, Ingrid

    2014-05-13

    The ubiquitin specific protease 11 (USP11) is implicated in DNA repair, viral RNA replication, and TGFβ signaling. We report the first characterization of the USP11 domain architecture and its role in regulating the enzymatic activity. USP11 consists of an N-terminal "domain present in USPs" (DUSP) and "ubiquitin-like" (UBL) domain, together referred to as DU domains, and the catalytic domain harboring a second UBL domain. Crystal structures of the DU domains show a tandem arrangement with a shortened β-hairpin at the two-domain interface and altered surface characteristics compared to the homologues USP4 and USP15. A conserved VEVY motif is a signature feature at the two-domain interface that shapes a potential protein interaction site. Small angle X-ray scattering and gel filtration experiments are consistent with the USP11DU domains and full-length USP11 being monomeric. Unexpectedly, we reveal, through kinetic assays of a series of deletion mutants, that the catalytic activity of USP11 is not regulated through intramolecular autoinhibition or activation by the N-terminal DU or UBL domains. Moreover, ubiquitin chain cleavage assays with all eight linkages reveal a preference for Lys(63)-, Lys(6)-, Lys(33)-, and Lys(11)-linked chains over Lys(27)-, Lys(29)-, and Lys(48)-linked and linear chains consistent with USP11's function in DNA repair pathways that is mediated by the protease domain. Our data support a model whereby USP11 domains outside the catalytic core domain serve as protein interaction or trafficking modules rather than a direct regulatory function of the proteolytic activity. This highlights the diversity of USPs in substrate recognition and regulation of ubiquitin deconjugation.

  13. Self-consistent field theory simulations of polymers on arbitrary domains

    Energy Technology Data Exchange (ETDEWEB)

    Ouaknin, Gaddiel, E-mail: gaddielouaknin@umail.ucsb.edu [Department of Mechanical Engineering, University of California, Santa Barbara, CA 93106-5070 (United States); Laachi, Nabil; Delaney, Kris [Materials Research Laboratory, University of California, Santa Barbara, CA 93106-5080 (United States); Fredrickson, Glenn H. [Materials Research Laboratory, University of California, Santa Barbara, CA 93106-5080 (United States); Department of Chemical Engineering, University of California, Santa Barbara, CA 93106-5080 (United States); Department of Materials, University of California, Santa Barbara, CA 93106-5050 (United States); Gibou, Frederic [Department of Mechanical Engineering, University of California, Santa Barbara, CA 93106-5070 (United States); Department of Computer Science, University of California, Santa Barbara, CA 93106-5110 (United States)

    2016-12-15

    We introduce a framework for simulating the mesoscale self-assembly of block copolymers in arbitrary confined geometries subject to Neumann boundary conditions. We employ a hybrid finite difference/volume approach to discretize the mean-field equations on an irregular domain represented implicitly by a level-set function. The numerical treatment of the Neumann boundary conditions is sharp, i.e. it avoids an artificial smearing in the irregular domain boundary. This strategy enables the study of self-assembly in confined domains and enables the computation of physically meaningful quantities at the domain interface. In addition, we employ adaptive grids encoded with Quad-/Oc-trees in parallel to automatically refine the grid where the statistical fields vary rapidly as well as at the boundary of the confined domain. This approach results in a significant reduction in the number of degrees of freedom and makes the simulations in arbitrary domains using effective boundary conditions computationally efficient in terms of both speed and memory requirement. Finally, in the case of regular periodic domains, where pseudo-spectral approaches are superior to finite differences in terms of CPU time and accuracy, we use the adaptive strategy to store chain propagators, reducing the memory footprint without loss of accuracy in computed physical observables.

  14. Feasibility and Domain Validation of Rheumatoid Arthritis (RA) Flare Core Domain Set

    DEFF Research Database (Denmark)

    Bartlett, Susan J; Bykerk, Vivian P; Cooksey, Roxanne

    2015-01-01

    , and stiffness scores averaged ≥ 2 times higher (2 of 11 points) in flaring individuals. Correlations between flare domains and corresponding legacy instruments were obtained: r = 0.46 to 0.93. A combined definition (patient report of flare and 28-joint Disease Activity Score increase) was evaluated in 2 other...... provided input for stiffness, self-management, contextual factors, and measurement considerations. RESULTS: Flare data from 501 patients in an observational study indicated 39% were in flare, with mean (SD) severity of 6.0 (2.6) and 55% lasting > 14 days. Pain, physical function, fatigue, participation...

  15. LWD lithostratigraphy, physical properties and correlations across tectonic domains at the NanTroSEIZE drilling transect, Nankai Trough subduction zone, Japan

    Science.gov (United States)

    Tudge, J.; Webb, S. I.; Tobin, H. J.

    2013-12-01

    Since 2007 the Nankai Trough Seismogenic Zone Experiment (NanTroSEIZE) has drilled a total of 15 sites across the Nankai Trough subduction zone, including two sites on the incoming sediments of the Philippine Sea plate (PSP). Logging-while-drilling (LWD) data was acquired at 11 of these sites encompassing the forearc Kumano Basin, upper accretionary prism, toe region and input sites. Each of these tectonic domains is investigated for changes in physical properties and LWD characteristics, and this work fully integrates a large data set acquired over multiple years and IODP expeditions, most recently Expedition 338. Using the available logging-while-drilling data, primarily consisting of gamma ray, resistivity and sonic velocity, a log-based lithostratigraphy is developed at each site and integrated with the core, across the entire NanTroSEIZE transect. In addition to simple LWD characterization, the use of Iterative Non-hierarchical Cluster Analysis (INCA) on the sites with the full suite of LWD data clearly differentiates the unaltered forearc and slope basin sediments from the deformed sediments of the accretionary prism, suggesting the LWD is susceptible to the subtle changes in the physical properties between the tectonic domains. This differentiation is used to guide the development of tectonic-domain specific physical properties relationships. One of the most important physical property relationships between is the p-wave velocity and porosity. To fully characterize the character and properties of each tectonic domain we develop new velocity-porosity relationships for each domain found across the NanTroSEIZE transect. This allows the porosity of each domain to be characterized on the seismic scale and the resulting implications for porosity and pore pressure estimates across the plate interface fault zone.

  16. Going outdoors and cognitive function among community-dwelling older adults: Moderating role of physical function.

    Science.gov (United States)

    Harada, Kazuhiro; Lee, Sangyoon; Park, Hyuntae; Shimada, Hiroyuki; Makizako, Hyuma; Doi, Takehiko; Yoshida, Daisuke; Tsutsumimoto, Kota; Anan, Yuya; Uemura, Kazuki; Suzuki, Takao

    2016-01-01

    Identifying the risk factors of cognitive impairment is essential for implementing effective prevention strategies for dementia. Previous studies have shown that the frequency of going outdoors is inversely associated with cognitive decline. Little research has examined whether the relationship between going outdoors and cognitive decline varies with physical functioning in older adults. The aim of the present study was to examine the relationship between going outdoors and cognitive function in older adults with and without physical function limitations. The present study analyzed the data of 4450 individuals (aged 65 years or older) who participated in the Obu Study of Health Promotion for the Elderly. The measures were the Mini-Mental State Examination (MMSE), going outdoors (at least once a week or not), self-reported physical function limitations (with or without), and demographic and health-related factors as potential confounders. Analysis of covariance and post-hoc comparisons showed that although going outdoors at least once a week was associated with higher MMSE scores among older adults with limited physical function, it was not significantly associated with the MMSE scores among older adults without limited physical function. Similarly, logistic regression analyses, stratified by physical function, showed a significant association between going outdoors and MMSE (older adults with limited physical function. The results show that going outdoors less than once a week is associated with decreased cognitive function among older adults with limited physical function, but it is not associated with cognitive function among older adults without limited physical function. © 2015 Japan Geriatrics Society.

  17. Alternative to domain wall fermions

    International Nuclear Information System (INIS)

    Neuberger, H.

    2002-01-01

    An alternative to commonly used domain wall fermions is presented. Some rigorous bounds on the condition number of the associated linear problem are derived. On the basis of these bounds and some experimentation it is argued that domain wall fermions will in general be associated with a condition number that is of the same order of magnitude as the product of the condition number of the linear problem in the physical dimensions by the inverse bare quark mass. Thus, the computational cost of implementing true domain wall fermions using a single conjugate gradient algorithm is of the same order of magnitude as that of implementing the overlap Dirac operator directly using two nested conjugate gradient algorithms. At a cost of about a factor of two in operation count it is possible to make the memory usage of direct implementations of the overlap Dirac operator independent of the accuracy of the approximation to the sign function and of the same order as that of standard Wilson fermions

  18. Change in economic difficulties and physical and mental functioning: Evidence from British and Finnish employee cohorts.

    Science.gov (United States)

    Lallukka, Tea; Ferrie, Jane E; Rahkonen, Ossi; Shipley, Martin J; Pietiläinen, Olli; Kivimäki, Mika; Marmot, Michael G; Lahelma, Eero

    2013-09-01

    The main aims of this longitudinal study were to (i) examine associations between changes in economic difficulties and health functioning among middle-aged employees and (ii) assess whether the associations remained after considering conventional domains of socioeconomic position. The associations were tested in two European welfare state occupational cohorts to strengthen the evidence base and improve generalizability. Data came from two cohorts: the Finnish Helsinki Health Study (baseline 2000-2002, follow-up 2007, N = 6328) and the British Whitehall II Study (baseline 1997-1999, follow-up 2003-2004, N = 4350). Responses to the survey item "finding it hard to afford adequate food and clothes and pay bills" repeated at baseline and follow-up were used to examine persistent, increasing, and decreasing economic difficulties. Poor physical and mental health functioning were denoted as being in the lowest quartile of the Short Form 36 physical and mental component summary. Logistic regression analyses were adjusted for sex, age, childhood economic difficulties, household income at baseline and follow-up, employment status at follow-up, and baseline health functioning. We observed strong sex- and age-adjusted associations between increasing [odds ratio (OR) range 1.69-2.96] and persistent (OR range 2.54-3.21) economic difficulties and poorer physical and mental health functioning in both British and Finnish occupational cohorts. These associations remained after full adjustments. Those reporting decreasing difficulties over follow-up also had poorer functioning (OR range 1.30-1.61) compared to those who did not have difficulties at baseline, possibly reflecting residual effects of economic difficulties at baseline. Changes in economic difficulties are associated with poorer physical and mental health functioning independent of income, employment status, and baseline health functioning.

  19. Automation strategies in five domains - A comparison of levels of automation, function allocation and visualisation of automatic functions

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, J. (Chalmers Univ. of Technology. Division Design and Human factors. Dept. of Product and Production Development, Goeteborg (Sweden))

    2011-01-15

    This study was conducted as a field study where control room operators and engineers from the refinery, heat and power, aviation, shipping and nuclear domain were interviewed regarding use of automation and the visualisation of automatic functions. The purpose of the study was to collect experiences and best practices from the five studied domains on levels of automation, function allocation and visualisation of automatic functions. In total, nine different control room settings were visited. The studied settings were compared using a systemic approach based on a human-machine systems model. The results show that the 'left over principle' is still the most common applied approach for function allocation but in high risk settings the decision whether to automate or not is more carefully considered. Regarding the visualisation of automatic functions, it was found that as long as each display type (process based, functional oriented, situation oriented and task based) are applied so that they correspond to the same level of abstraction as the technical system the operator's mental model will be supported. No single display type can however readily match all levels of abstraction at the same time - all display types are still needed and serve different purposes. (Author)

  20. Physical Activity, Aging, and Physiological Function.

    Science.gov (United States)

    Harridge, Stephen D R; Lazarus, Norman R

    2017-03-01

    Human evolution suggests that the default position for health is to be physically active. Inactivity, by contrast, has serious negative effects on health across the lifespan. Therefore, only in physically active people can the inherent aging process proceed unaffected by disuse complications. In such individuals, although the relationship between age and physiological function remains complex, function is generally superior with health, well being, and the aging process optimized. ©2017 Int. Union Physiol. Sci./Am. Physiol. Soc.

  1. Expanding the landscape of chromatin modification (CM-related functional domains and genes in human.

    Directory of Open Access Journals (Sweden)

    Shuye Pu

    2010-11-01

    Full Text Available Chromatin modification (CM plays a key role in regulating transcription, DNA replication, repair and recombination. However, our knowledge of these processes in humans remains very limited. Here we use computational approaches to study proteins and functional domains involved in CM in humans. We analyze the abundance and the pair-wise domain-domain co-occurrences of 25 well-documented CM domains in 5 model organisms: yeast, worm, fly, mouse and human. Results show that domains involved in histone methylation, DNA methylation, and histone variants are remarkably expanded in metazoan, reflecting the increased demand for cell type-specific gene regulation. We find that CM domains tend to co-occur with a limited number of partner domains and are hence not promiscuous. This property is exploited to identify 47 potentially novel CM domains, including 24 DNA-binding domains, whose role in CM has received little attention so far. Lastly, we use a consensus Machine Learning approach to predict 379 novel CM genes (coding for 329 proteins in humans based on domain compositions. Several of these predictions are supported by very recent experimental studies and others are slated for experimental verification. Identification of novel CM genes and domains in humans will aid our understanding of fundamental epigenetic processes that are important for stem cell differentiation and cancer biology. Information on all the candidate CM domains and genes reported here is publicly available.

  2. Hand-related physical function in rheumatic hand conditions

    DEFF Research Database (Denmark)

    Klokker, Louise; Terwee, Caroline B; Wæhrens, Eva Ejlersen

    2016-01-01

    as well as those items from the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) item bank that are relevant to patients with rheumatic hand conditions. Selection will be based on consensus among reviewers. Content validity of selected items will be established......INTRODUCTION: There is no consensus about what constitutes the most appropriate patient-reported outcome measurement (PROM) instrument for measuring physical function in patients with rheumatic hand conditions. Existing instruments lack psychometric testing and vary in feasibility...... and their psychometric qualities. We aim to develop a PROM instrument to assess hand-related physical function in rheumatic hand conditions. METHODS AND ANALYSIS: We will perform a systematic search to identify existing PROMs to rheumatic hand conditions, and select items relevant for hand-related physical function...

  3. Hand-related physical function in rheumatic hand conditions

    DEFF Research Database (Denmark)

    Klokker, Louise; Terwee, Caroline; Wæhrens, Eva Elisabet Ejlersen

    2016-01-01

    INTRODUCTION: There is no consensus about what constitutes the most appropriate patient-reported outcome measurement (PROM) instrument for measuring physical function in patients with rheumatic hand conditions. Existing instruments lack psychometric testing and vary in feasibility...... and their psychometric qualities. We aim to develop a PROM instrument to assess hand-related physical function in rheumatic hand conditions. METHODS AND ANALYSIS: We will perform a systematic search to identify existing PROMs to rheumatic hand conditions, and select items relevant for hand-related physical function...... as well as those items from the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) item bank that are relevant to patients with rheumatic hand conditions. Selection will be based on consensus among reviewers. Content validity of selected items will be established...

  4. [Detection of the functionally active domains in the molecule of the lethal factor of the anthrax exotoxin].

    Science.gov (United States)

    Noskov, A N; Kravchenko, T B; Noskova, V P

    1996-01-01

    Three functional domains were revealed in the molecule of the lethal factor of B. anthracis. They are located in the linear structure of the molecula as follows: the associative domain occupies the area from Lys39 to Met242, the stabilizing domain from Leu517 to Lys614, and the effector domain still further to the COOH-terminal Lys mino acid.

  5. Cardiovascular functioning, personality, and the social world: the domain of hierarchical power.

    Science.gov (United States)

    Newton, Tamara L

    2009-02-01

    The present paper considers connections between cardiovascular functioning (i.e., disease status and acute stress responses) and social dominance, and its counterpart, social submissiveness, both of which are part of the broader domain of "hierarchical power" [Bugental, D.B., 2000. Acquisition of the algorithms of social life: a domain-based approach. Psychological Bulletin 126, 187-219]. Empirical research on connections between dominance/submissiveness and cardiovascular morbidity and mortality in humans is reviewed, as is research on dominance/submissiveness and cardiovascular reactivity to, and recovery from, acute stressors. Three general conclusions are established. First, in both cross-sectional and longitudinal investigations, trait and behavioral indicators of dominance have been positively associated with cardiovascular disease severity, incidence, and progression, whereas preliminary evidence from two studies suggests that trait submissiveness may protect against poorer disease outcomes. Second, among men and women, trait dominance is associated with reactivity to and recovery from acute stressors, particularly social challenges. Third, linkages between dominance/submissiveness and cardiovascular functioning, especially cardiovascular reactivity, are characterized by gender-specific patterning, and this patterning emerges as a function of social context. Implications for the next generation of research concerning social dominance, gender, and cardiovascular functioning are discussed.

  6. Dialectical behavior therapy and domains of functioning over two years

    Science.gov (United States)

    Wilks, Chelsey R.; Korslund, Kathryn E.; Harned, Melanie; Linehan, Marsha M.

    2016-01-01

    Individuals diagnosed with borderline personality disorder (BPD) tend to have a significant degree of functional impairment across a range of social and occupational spheres including difficulty finding and maintaining satisfying employment, housing, or relationships. Understanding what factors are associated with functional impairment will enable treatment providers to move those diagnosed with BPD beyond symptomatic recovery and toward a life worth living. This paper investigated the trajectories and predictors of functional outcomes for suicidal women with BPD (N=99) during a treatment outcome study of Dialectical Behavior Therapy (DBT). Results revealed that participants had statistical and clinical improvements in functioning. Individuals with high emotion dysregulation displayed poorer psychosocial functioning at the subsequent assessment period and slower rates of change, which was also seen in reverse for one psychosocial functioning variable. Skills use was not related to individual trajectories in functioning. This study highlights the relationship of emotion dysregulation to functioning within a sample of suicidal women with BPD as well as the importance researching multiple domains in functioning. PMID:26764586

  7. Recursive evaluation of space-time lattice Green's functions

    NARCIS (Netherlands)

    Hon, de B.P.; Arnold, J.M.

    2012-01-01

    Up to a multiplicative constant, the lattice Green’s function (LGF) as defined in condensed matter physics and lattice statistical mechanics is equivalent to the Z- domain counterpart of the finite-difference time-domain Green’s function (GF) on a lattice. Expansion of a well-known integral

  8. Crystal Structure of the Human, FIC-Domain Containing Protein HYPE and Implications for Its Functions

    Science.gov (United States)

    Bunney, Tom D.; Cole, Ambrose R.; Broncel, Malgorzata; Esposito, Diego; Tate, Edward W.; Katan, Matilda

    2014-01-01

    Summary Protein AMPylation, the transfer of AMP from ATP to protein targets, has been recognized as a new mechanism of host-cell disruption by some bacterial effectors that typically contain a FIC-domain. Eukaryotic genomes also encode one FIC-domain protein, HYPE, which has remained poorly characterized. Here we describe the structure of human HYPE, solved by X-ray crystallography, representing the first structure of a eukaryotic FIC-domain protein. We demonstrate that HYPE forms stable dimers with structurally and functionally integrated FIC-domains and with TPR-motifs exposed for protein-protein interactions. As HYPE also uniquely possesses a transmembrane helix, dimerization is likely to affect its positioning and function in the membrane vicinity. The low rate of autoAMPylation of the wild-type HYPE could be due to autoinhibition, consistent with the mechanism proposed for a number of putative FIC AMPylators. Our findings also provide a basis to further consider possible alternative cofactors of HYPE and distinct modes of target-recognition. PMID:25435325

  9. Physical Activity Level and Physical Functionality in Nonagenarians Compared to Individuals Aged 60–74 Years

    Science.gov (United States)

    Frisard, Madlyn I.; Fabre, Jennifer M.; Russell, Ryan D.; King, Christina M.; DeLany, James P.; Wood, Robert H.; Ravussin, Eric

    2009-01-01

    Background Functional dependence and the risks of disability increase with age. The loss of independence is thought to be partially due to a decrease in physical activity. However, in populations, accurate measurement of physical activity is challenging and may not provide information on functional impairment. Methods This study therefore assessed physical functionality and physical activity level in a group of nonagenarians (11 men/11 women; 93 ± 1 years, 66.6 ± 2.4 kg, body mass index [BMI] = 24 ± 1 kg/m2) and a group of participants aged 60–74 years (17 men/15 women; 70 ± 1 years, 83.3 ± 3.0 kg, BMI = 29 ± 1 kg/m2) from the Louisiana Healthy Aging Study. Physical activity level was calculated from total energy expenditure (TEE) and resting metabolic rate (RMR). Physical functionality was assessed using the Reduced Continuous Scale Physical Functional Performance Test (CS-PFP10). Results Nonagenarians had lower absolute ( p < .001) and adjusted ( p < .007) TEE compared to participants aged 60–74 years which was attributed to a reduction in both RMR and physical activity level. Nonagenarians also had reduced functional performance ( p < .001) which was correlated with activity level (r = 0.68, p < .001). Conclusions When compared to individuals aged 60–74 years, 73% of the reduction in TEE in nonagenarians can be attributed to a reduction in physical activity level, the remaining being accounted for by a reduction in RMR. The reduced physical activity in nonagenarians is associated with less physical functionality. This study provides the first objective comparison of physical functionality and actual levels of physical activity in older individuals. PMID:17634327

  10. A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression

    Science.gov (United States)

    Syed, Salahuddin; Desler, Claus; Rasmussen, Lene J.; Schmidt, Kristina H.

    2016-01-01

    In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186–212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5-dependent error-free DNA damage bypass act as independent mechanisms on DNA lesions that arise when Rrm3 catalytic activity is disrupted whereas these mechanisms are dispensable for DNA damage tolerance when the replication function is disrupted, indicating that the DNA lesions generated by the loss of each Rrm3 function are distinct. Although both lesion types activate the DNA-damage checkpoint, we find that the resultant increase in nucleotide levels is not sufficient for continued DNA synthesis under replication stress. Together, our findings suggest a role of Rrm3, via its Orc5-binding domain, in restricting DNA synthesis that is genetically and physically separable from its established catalytic role in facilitating fork progression through replication blocks. PMID:27923055

  11. A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression.

    Science.gov (United States)

    Syed, Salahuddin; Desler, Claus; Rasmussen, Lene J; Schmidt, Kristina H

    2016-12-01

    In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186-212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5-dependent error-free DNA damage bypass act as independent mechanisms on DNA lesions that arise when Rrm3 catalytic activity is disrupted whereas these mechanisms are dispensable for DNA damage tolerance when the replication function is disrupted, indicating that the DNA lesions generated by the loss of each Rrm3 function are distinct. Although both lesion types activate the DNA-damage checkpoint, we find that the resultant increase in nucleotide levels is not sufficient for continued DNA synthesis under replication stress. Together, our findings suggest a role of Rrm3, via its Orc5-binding domain, in restricting DNA synthesis that is genetically and physically separable from its established catalytic role in facilitating fork progression through replication blocks.

  12. Insights into function of PSI domains from structure of the Met receptor PSI domain

    International Nuclear Information System (INIS)

    Kozlov, Guennadi; Perreault, Audrey; Schrag, Joseph D.; Park, Morag; Cygler, Miroslaw; Gehring, Kalle; Ekiel, Irena

    2004-01-01

    PSI domains are cysteine-rich modules found in extracellular fragments of hundreds of signaling proteins, including plexins, semaphorins, integrins, and attractins. Here, we report the solution structure of the PSI domain from the human Met receptor, a receptor tyrosine kinase critical for proliferation, motility, and differentiation. The structure represents a cysteine knot with short regions of secondary structure including a three-stranded antiparallel β-sheet and two α-helices. All eight cysteines are involved in disulfide bonds with the pattern consistent with that for the PSI domain from Sema4D. Comparison with the Sema4D structure identifies a structurally conserved core comprising the N-terminal half of the PSI domain. Interestingly, this part links adjacent SEMA and immunoglobulin domains in the Sema4D structure, suggesting that the PSI domain serves as a wedge between propeller and immunoglobulin domains and is responsible for the correct positioning of the ligand-binding site of the receptor

  13. Distinct ubiquitin binding modes exhibited by SH3 domains: molecular determinants and functional implications.

    Directory of Open Access Journals (Sweden)

    Jose L Ortega Roldan

    Full Text Available SH3 domains constitute a new type of ubiquitin-binding domains. We previously showed that the third SH3 domain (SH3-C of CD2AP binds ubiquitin in an alternative orientation. We have determined the structure of the complex between first CD2AP SH3 domain and ubiquitin and performed a structural and mutational analysis to decipher the determinants of the SH3-C binding mode to ubiquitin. We found that the Phe-to-Tyr mutation in CD2AP and in the homologous CIN85 SH3-C domain does not abrogate ubiquitin binding, in contrast to previous hypothesis and our findings for the first two CD2AP SH3 domains. The similar alternative binding mode of the SH3-C domains of these related adaptor proteins is characterised by a higher affinity to C-terminal extended ubiquitin molecules. We conclude that CD2AP/CIN85 SH3-C domain interaction with ubiquitin constitutes a new ubiquitin-binding mode involved in a different cellular function and thus changes the previously established mechanism of EGF-dependent CD2AP/CIN85 mono-ubiquitination.

  14. CD80 and CD86 IgC domains are important for quaternary structure, receptor binding and co-signaling function.

    Science.gov (United States)

    Girard, Tanya; Gaucher, Denis; El-Far, Mohamed; Breton, Gaëlle; Sékaly, Rafick-Pierre

    2014-09-01

    CD86 and CD80, the ligands for the co-stimulatory molecules CD28 and CTLA-4, are members of the Ig superfamily. Their structure includes Ig variable-like (IgV) domains, Ig constant-like (IgC) domains and intracellular domains. Although crystallographic studies have clearly identified the IgV domain to be responsible for receptor interactions, earlier studies suggested that both Ig domains are required for full co-signaling function. Herein, we have used deletion and chimeric human CD80 and CD86 molecules in co-stimulation assays to study the impact of the multimeric state of IgV and IgC domains on receptor binding properties and on co-stimulatory function in a peptide-specific T cell activation model. We report for the first time the presence of CD80 dimers and CD86 monomers in living cells. Moreover, we show that the IgC domain of both molecules inhibits multimer formation and greatly affects binding to the co-receptors CD28 and CTLA-4. Finally, both IgC and intracellular domains are required for full co-signaling function. These findings reveal the distinct but complementary roles of CD80 and CD86 IgV and IgC domains in T cell activation. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. The Mental Health Impact of Physical Appearance Concerns in the Context of Other Life Domains Among Australian Gay Men.

    Science.gov (United States)

    Hosking, Warwick; Lyons, Anthony; van der Rest, Brittany

    2017-07-01

    Previous studies have identified gay men as a high-risk population for body image disturbances. However, little research has examined the mental health impact of gay men's physical appearance concerns in the context of other major life domains. The present study addressed this gap by investigating how mental health outcomes (satisfaction with life, self-esteem, positive well-being, and psychological distress) were associated with satisfaction with and importance of physical appearance, work, family relationships, friendships, health and fitness, and sex life among Australian gay men aged 18-39. The possible moderating role of intimate relationship status was also examined. Results from an online survey revealed that greater satisfaction with physical appearance, work, family, and friendships all had similar positive associations with mental health. However, more importance placed on physical appearance was more consistently associated with poorer mental health compared with the subjective importance of other domains. Findings also indicated the associations between physical appearance satisfaction and life satisfaction, and between physical appearance importance and positive well-being, were weaker for those in relationships. Thus, physical appearance matters in gay men's lives, but was only one factor when considered in the broader context of other life areas that contributed to overall well-being. These findings suggest the need for a nuanced and contextualized understanding of how physical appearance concerns fit into gay men's lives.

  16. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity

    Directory of Open Access Journals (Sweden)

    Alexander Tallner

    2015-07-01

    Full Text Available Multiple sclerosis (MS patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36, and Beck Depression Inventory (BDI. We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL. Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients.

  17. Functional interchangeability of late domains, late domain cofactors and ubiquitin in viral budding.

    Directory of Open Access Journals (Sweden)

    Maria Zhadina

    2010-10-01

    Full Text Available The membrane scission event that separates nascent enveloped virions from host cell membranes often requires the ESCRT pathway, which can be engaged through the action of peptide motifs, termed late (L- domains, in viral proteins. Viral PTAP and YPDL-like L-domains bind directly to the ESCRT-I and ALIX components of the ESCRT pathway, while PPxY motifs bind Nedd4-like, HECT-domain containing, ubiquitin ligases (e.g. WWP1. It has been unclear precisely how ubiquitin ligase recruitment ultimately leads to particle release. Here, using a lysine-free viral Gag protein derived from the prototypic foamy virus (PFV, where attachment of ubiquitin to Gag can be controlled, we show that several different HECT domains can replace the WWP1 HECT domain in chimeric ubiquitin ligases and drive budding. Moreover, artificial recruitment of isolated HECT domains to Gag is sufficient to stimulate budding. Conversely, the HECT domain becomes dispensable if the other domains of WWP1 are directly fused to an ESCRT-1 protein. In each case where budding is driven by a HECT domain, its catalytic activity is essential, but Gag ubiquitination is dispensable, suggesting that ubiquitin ligation to trans-acting proteins drives budding. Paradoxically, however, we also demonstrate that direct fusion of a ubiquitin moiety to the C-terminus of PFV Gag can also promote budding, suggesting that ubiquitination of Gag can substitute for ubiquitination of trans-acting proteins. Depletion of Tsg101 and ALIX inhibits budding that is dependent on ubiquitin that is fused to Gag, or ligated to trans-acting proteins through the action of a PPxY motif. These studies underscore the flexibility in the ways that the ESCRT pathway can be engaged, and suggest a model in which the identity of the protein to which ubiquitin is attached is not critical for subsequent recruitment of ubiquitin-binding components of the ESCRT pathway and viral budding to proceed.

  18. Correlating structure and function during the evolution of fibrinogen-related domains

    Science.gov (United States)

    Doolittle, Russell F; McNamara, Kyle; Lin, Kevin

    2012-01-01

    Fibrinogen-related domains (FReDs) are found in a variety of animal proteins with widely different functions, ranging from non-self recognition to clot formation. All appear to have a common surface where binding of one sort or other occurs. An examination of 19 completed animal genomes—including a sponge and sea anemone, six protostomes, and 11 deuterostomes—has allowed phylogenies to be constructed that show where various types of FReP (proteins containing FReDs) first made their appearance. Comparisons of sequences and structures also reveal particular features that correlate with function, including the influence of neighbor-domains. A particular set of insertions in the carboxyl-terminal subdomain was involved in the transition from structures known to bind sugars to those known to bind amino-terminal peptides. Perhaps not unexpectedly, FReDs with different functions have changed at different rates, with ficolins by far the fastest changing group. Significantly, the greatest amount of change in ficolin FReDs occurs in the third subdomain (“P domain”), the very opposite of the situation in most other vertebrate FReDs. The unbalanced style of change was also observed in FReDs from non-chordates, many of which have been implicated in innate immunity. PMID:23076991

  19. PREFACE: Domain wall dynamics in nanostructures Domain wall dynamics in nanostructures

    Science.gov (United States)

    Marrows, C. H.; Meier, G.

    2012-01-01

    Domain structures in magnetic materials are ubiquitous and have been studied for decades. The walls that separate them are topological defects in the magnetic order parameter and have a wide variety of complex forms. In general, their investigation is difficult in bulk materials since only the domain structure on the surface of a specimen is visible. Cutting the sample to reveal the interior causes a rearrangement of the domains into a new form. As with many other areas of magnetism, the study of domain wall physics has been revitalised by the advent of nanotechnology. The ability to fabricate nanoscale structures has permitted the formation of simplified and controlled domain patterns; the development of advanced microscopy methods has permitted them to be imaged and then modelled; subjecting them to ultrashort field and current pulses has permitted their dynamics to be explored. The latest results from all of these advances are described in this special issue. Not only has this led to results of great scientific beauty, but also to concepts of great applicability to future information technologies. In this issue the reader will find the latest results for these domain wall dynamics and the high-speed processes of topological structures such as domain walls and magnetic vortices. These dynamics can be driven by the application of magnetic fields, or by flowing currents through spintronic devices using the novel physics of spin-transfer torque. This complexity has been studied using a wide variety of experimental techniques at the edge of the spatial and temporal resolution currently available, and can be described using sophisticated analytical theory and computational modelling. As a result, the dynamics can be engineered to give rise to finely controlled memory and logic devices with new functionality. Moreover, the field is moving to study not only the conventional transition metal ferromagnets, but also complex heterostructures, novel magnets and even other

  20. Correlation of six-minute walking performance with quality of life is domain- and gender-specific in healthy older adults.

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    Andrey Jorge Serra

    Full Text Available We analyzed the relationship between performance on the 6-min walk test (6MWT and health-related quality of life (HRQoL in older subjects. Our secondary aim was to determine the distance to be completed on the 6MWT for the subject to achieve a score of 50 on the Short Form (36 Health Survey (SF-36. Associations were tested using linear correlation and multivariate linear regression. Participants were 130 healthy older individuals. The predictive performance of the 6MWT based on an SF-36 score of 50 was assessed using a receiver operating characteristic curve and its area under curve (AUC. Associations were observed between physical functioning, role-emotional, social functioning, vitality, general health score, and 6MWT performance in women, after adjusting for confounding variables (coefficients: 0.57, 0.38, 0.40, and 0.46, respectively; p < 0.05. No association was found for men. The distance for the 6MWT to predict an SF-36 score of 50 was 481 m for men in the physical functioning (AUC: 0.79 and role-physical (AUC: 0.84 domains, and 420 m for women in role-emotional (AUC: 0.75, role-physical (AUC: 0.80, and general health (AUC: 0.80 domains. Our results indicate that superior 6MWT performance may be associated with better HRQoL in several domains in only healthy older women. No association between 6MWT performance and role-emotional, mental health, or vitality domains was found. We suggest that a score of 50 is represented by a 6MWT distance of 481 m for men and 420 m for women, at least in the role-physical domain.

  1. Hours spent and energy expended in physical activity domains: Results from The Tomorrow Project cohort in Alberta, Canada

    Science.gov (United States)

    2011-01-01

    Background Knowledge of adult activity patterns across domains of physical activity is essential for the planning of population-based strategies that will increase overall energy expenditure and reduce the risk of obesity and related chronic diseases. We describe domain-specific hours of activity and energy expended among participants in a prospective cohort in Alberta, Canada. Methods The Past Year Total Physical Activity Questionnaire was completed by 15,591 Tomorrow Project® participants, between 2001 and 2005 detailing physical activity type, duration, frequency and intensity. Domain-specific hours of activity and activity-related energy expenditure, expressed as a percent of total energy expenditure (TEE) (Mean (SD); Median (IQR)) are reported across inactive (<1.4), low active (1.4 to 1.59), active (1.6 to 1.89) and very active (≥ 1.9) Physical Activity Level (PAL = TEE:REE) categories. Results In very active women and amongst all men except those classified as inactive, activity-related energy expenditure comprised primarily occupational activity. Amongst inactive men and women in active, low active and inactive groups, activity-related energy expenditure from household activity was comparable to, or exceeded that for occupational activity. Leisure-time activity-related energy expenditure decreased with decreasing PAL categories; however, even amongst the most active men and women it accounted for less than 10 percent of TEE. When stratified by employment status, leisure-time activity-related energy expenditure was greatest for retired men [mean (SD): 10.8 (8.5) percent of TEE], compared with those who were fully employed, employed part-time or not employed. Transportation-related activity was negligible across all categories of PAL and employment status. Conclusion For the inactive portion of this population, active non-leisure activities, specifically in the transportation and occupational domains, need to be considered for inclusion in daily routines

  2. Barriers and facilitators to the implementation of a school-based physical activity policy in Canada: application of the theoretical domains framework.

    Science.gov (United States)

    Weatherson, Katie A; McKay, Rhyann; Gainforth, Heather L; Jung, Mary E

    2017-10-23

    In British Columbia Canada, a Daily Physical Activity (DPA) policy was mandated that requires elementary school teachers to provide students with opportunities to achieve 30 min of physical activity during the school day. However, the implementation of school-based physical activity policies is influenced by many factors. A theoretical examination of the factors that impede and enhance teachers' implementation of physical activity policies is necessary in order to develop strategies to improve policy practice and achieve desired outcomes. This study used the Theoretical Domains Framework (TDF) to understand teachers' barriers and facilitators to the implementation of the DPA policy in one school district. Additionally, barriers and facilitators were examined and compared according to how the teacher implemented the DPA policy during the instructional school day. Interviews were conducted with thirteen teachers and transcribed verbatim. One researcher performed barrier and facilitator extraction, with double extraction occurring across a third of the interview transcripts by a second researcher. A deductive and inductive analytical approach in a two-stage process was employed whereby barriers and facilitators were deductively coded using TDF domains (content analysis) and analyzed for sub-themes within each domain. Two researchers performed coding. A total of 832 items were extracted from the interview transcripts. Some items were coded into multiple TDF domains, resulting in a total of 1422 observations. The most commonly coded TDF domains accounting for 75% of the total were Environmental context and resources (ECR; n = 250), Beliefs about consequences (n = 225), Social influences (n = 193), Knowledge (n = 100), and Intentions (n = 88). Teachers who implemented DPA during instructional time differed from those who relied on non-instructional time in relation to Goals, Behavioural regulation, Social/professional role and identity, Beliefs about

  3. Barriers and facilitators to the implementation of a school-based physical activity policy in Canada: application of the theoretical domains framework

    Directory of Open Access Journals (Sweden)

    Katie A. Weatherson

    2017-10-01

    Full Text Available Abstract Background In British Columbia Canada, a Daily Physical Activity (DPA policy was mandated that requires elementary school teachers to provide students with opportunities to achieve 30 min of physical activity during the school day. However, the implementation of school-based physical activity policies is influenced by many factors. A theoretical examination of the factors that impede and enhance teachers’ implementation of physical activity policies is necessary in order to develop strategies to improve policy practice and achieve desired outcomes. This study used the Theoretical Domains Framework (TDF to understand teachers’ barriers and facilitators to the implementation of the DPA policy in one school district. Additionally, barriers and facilitators were examined and compared according to how the teacher implemented the DPA policy during the instructional school day. Methods Interviews were conducted with thirteen teachers and transcribed verbatim. One researcher performed barrier and facilitator extraction, with double extraction occurring across a third of the interview transcripts by a second researcher. A deductive and inductive analytical approach in a two-stage process was employed whereby barriers and facilitators were deductively coded using TDF domains (content analysis and analyzed for sub-themes within each domain. Two researchers performed coding. Results A total of 832 items were extracted from the interview transcripts. Some items were coded into multiple TDF domains, resulting in a total of 1422 observations. The most commonly coded TDF domains accounting for 75% of the total were Environmental context and resources (ECR; n = 250, Beliefs about consequences (n = 225, Social influences (n = 193, Knowledge (n = 100, and Intentions (n = 88. Teachers who implemented DPA during instructional time differed from those who relied on non-instructional time in relation to Goals, Behavioural regulation, Social

  4. Changes in leisure-time physical activity and physical and mental health functioning: a follow-up study.

    Science.gov (United States)

    Holstila, A; Mänty, M; Rahkonen, O; Lahelma, E; Lahti, J

    2017-12-01

    Functioning will be an increasingly important issue in Finland over the coming decades as the proportion of the population aged 65 and older is growing significantly. However, the associations between changes in physical activity and subsequent health functioning are poorly understood. The aim of this study was to examine how changes in physical activity relate to concurrent and prospective levels of health functioning. Cohort data from the Helsinki Health Study were used. Phase 1 (n = 8960, response rate 67%, 80% women) was conducted among 40- to 60-year-old employees of the City of Helsinki in 2000-2002, phase 2 in 2007 (n = 7332, response rate 83%), and phase 3 in 2012 (n = 6814, response rate 79%). Linear mixed models were used as the main statistical method. Increasing physical activity was associated with higher concurrent and prospective levels of physical health functioning, whereas decreasing activity was associated with lower levels of physical health functioning. The associations were stronger with physical than with mental health functioning. Promoting physical activity among aging people may help to maintain their level of health functioning. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Identification of the functional domains of the telomere protein Rap1 in Schizosaccharomyces pombe.

    Directory of Open Access Journals (Sweden)

    Ikumi Fujita

    Full Text Available The telomere at the end of a linear chromosome plays crucial roles in genome stability. In the fission yeast Schizosaccharomyces pombe, the Rap1 protein, one of the central players at the telomeres, associates with multiple proteins to regulate various telomere functions, such as the maintenance of telomere DNA length, telomere end protection, maintenance of telomere heterochromatin, and telomere clustering in meiosis. The molecular bases of the interactions between Rap1 and its partners, however, remain largely unknown. Here, we describe the identification of the interaction domains of Rap1 with its partners. The Bqt1/Bqt2 complex, which is required for normal meiotic progression, Poz1, which is required for telomere length control, and Taz1, which is required for the recruitment of Rap1 to telomeres, bind to distinct domains in the C-terminal half of Rap1. Intriguingly, analyses of a series of deletion mutants for rap1(+ have revealed that the long N-terminal region (1-456 a.a. [amino acids] of Rap1 (full length: 693 a.a. is not required for telomere DNA length control, telomere end protection, and telomere gene silencing, whereas the C-terminal region (457-693 a.a. containing Poz1- and Taz1-binding domains plays important roles in those functions. Furthermore, the Bqt1/Bqt2- and Taz1-binding domains are essential for normal spore formation after meiosis. Our results suggest that the C-terminal half of Rap1 is critical for the primary telomere functions, whereas the N-terminal region containing the BRCT (BRCA1 C-terminus and Myb domains, which are evolutionally conserved among the Rap1 family proteins, does not play a major role at the telomeres.

  6. Characterization of the TRBP domain required for Dicer interaction and function in RNA interference

    Directory of Open Access Journals (Sweden)

    El Far Mohamed

    2009-05-01

    Full Text Available Abstract Background Dicer, Ago2 and TRBP are the minimum components of the human RNA-induced silencing complex (RISC. While Dicer and Ago2 are RNases, TRBP is the double-stranded RNA binding protein (dsRBP that loads small interfering RNA into the RISC. TRBP binds directly to Dicer through its C-terminal domain. Results We show that the TRBP binding site in Dicer is a 165 amino acid (aa region located between the ATPase and the helicase domains. The binding site in TRBP is a 69 aa domain, called C4, located at the C-terminal end of TRBP. The TRBP1 and TRBP2 isoforms, but not TRBPs lacking the C4 site (TRBPsΔC4, co-immunoprecipitated with Dicer. The C4 domain is therefore necessary to bind Dicer, irrespective of the presence of RNA. Immunofluorescence shows that while full-length TRBPs colocalize with Dicer, TRBPsΔC4 do not. tarbp2-/- cells, which do not express TRBP, do not support RNA interference (RNAi mediated by short hairpin or micro RNAs against EGFP. Both TRBPs, but not TRBPsΔC4, were able to rescue RNAi function. In human cells with low RNAi activity, addition of TRBP1 or 2, but not TRBPsΔC4, rescued RNAi function. Conclusion The mapping of the interaction sites between TRBP and Dicer show unique domains that are required for their binding. Since TRBPsΔC4 do not interact or colocalize with Dicer, we suggest that TRBP and Dicer, both dsRBPs, do not interact through bound dsRNA. TRBPs, but not TRBPsΔC4, rescue RNAi activity in RNAi-compromised cells, indicating that the binding of Dicer to TRBP is critical for RNAi function.

  7. Differential Item Functioning of the Psychological Domain of the Menopause Rating Scale

    Science.gov (United States)

    Portela-Buelvas, Katherin; Oviedo, Heidi C.; Herazo, Edwin; Campo-Arias, Adalberto

    2016-01-01

    Introduction. Quality of life could be quantified with the Menopause Rating Scale (MRS), which evaluates the severity of somatic, psychological, and urogenital symptoms in menopause. However, differential item functioning (DIF) analysis has not been applied previously. Objective. To establish the DIF of the psychological domain of the MRS in Colombian women. Methods. 4,009 women aged between 40 and 59 years, who participated in the CAVIMEC (Calidad de Vida en la Menopausia y Etnias Colombianas) project, were included. Average age was 49.0 ± 5.9 years. Women were classified in mestizo, Afro-Colombian, and indigenous. The results were presented as averages and standard deviation (X ± SD). A p value <0.001 was considered statistically significant. Results. In mestizo women, the highest X ± SD were obtained in physical and mental exhaustion (PME) (0.86 ± 0.93) and the lowest ones in anxiety (0.44 ± 0.79). In Afro-Colombian women, an average score of 0.99 ± 1.07 for PME and 0.63 ± 0.88 for anxiety was gotten. Indigenous women obtained an increased average score for PME (1.33 ± 0.93). The lowest score was evidenced in depressive mood (0.50 ± 0.81), which is different from other Colombian women (p < 0.001). Conclusions. The psychological items of the MRS show differential functioning according to the ethnic group, which may induce systematic error in the measurement of the construct. PMID:27847825

  8. Differential Item Functioning of the Psychological Domain of the Menopause Rating Scale.

    Science.gov (United States)

    Monterrosa-Castro, Alvaro; Portela-Buelvas, Katherin; Oviedo, Heidi C; Herazo, Edwin; Campo-Arias, Adalberto

    2016-01-01

    Introduction. Quality of life could be quantified with the Menopause Rating Scale (MRS), which evaluates the severity of somatic, psychological, and urogenital symptoms in menopause. However, differential item functioning (DIF) analysis has not been applied previously. Objective . To establish the DIF of the psychological domain of the MRS in Colombian women. Methods . 4,009 women aged between 40 and 59 years, who participated in the CAVIMEC (Calidad de Vida en la Menopausia y Etnias Colombianas) project, were included. Average age was 49.0 ± 5.9 years. Women were classified in mestizo, Afro-Colombian, and indigenous. The results were presented as averages and standard deviation ( X ± SD). A p value <0.001 was considered statistically significant. Results . In mestizo women, the highest X ± SD were obtained in physical and mental exhaustion (PME) (0.86 ± 0.93) and the lowest ones in anxiety (0.44 ± 0.79). In Afro-Colombian women, an average score of 0.99 ± 1.07 for PME and 0.63 ± 0.88 for anxiety was gotten. Indigenous women obtained an increased average score for PME (1.33 ± 0.93). The lowest score was evidenced in depressive mood (0.50 ± 0.81), which is different from other Colombian women ( p < 0.001). Conclusions . The psychological items of the MRS show differential functioning according to the ethnic group, which may induce systematic error in the measurement of the construct.

  9. Functional Independence and Interdependence of the Src Homology Domains of Phospholipase C-γ1 in B-Cell Receptor Signal Transduction

    Science.gov (United States)

    DeBell, Karen E.; Stoica, Bogdan A.; Verí, Maria-Concetta; Di Baldassarre, Angela; Miscia, Sebastiano; Graham, Laurie J.; Rellahan, Barbara L.; Ishiai, Masamichi; Kurosaki, Tomohiro; Bonvini, Ezio

    1999-01-01

    B-cell receptor (BCR)-induced activation of phospholipase C-γ1 (PLCγ1) and PLCγ2 is crucial for B-cell function. While several signaling molecules have been implicated in PLCγ activation, the mechanism coupling PLCγ to the BCR remains undefined. The role of PLCγ1 SH2 and SH3 domains at different steps of BCR-induced PLCγ1 activation was examined by reconstitution in a PLCγ-negative B-cell line. PLCγ1 membrane translocation required a functional SH2 N-terminal [SH2(N)] domain, was decreased by mutation of the SH3 domain, but was unaffected by mutation of the SH2(C) domain. Tyrosine phosphorylation did not require the SH2(C) or SH3 domains but depended exclusively on a functional SH2(N) domain, which mediated the association of PLCγ1 with the adapter protein, BLNK. Forcing PLCγ1 to the membrane via a myristoylation signal did not bypass the SH2(N) domain requirement for phosphorylation, indicating that the phosphorylation mediated by this domain is not due to membrane anchoring alone. Mutation of the SH2(N) or the SH2(C) domain abrogated BCR-stimulated phosphoinositide hydrolysis and signaling events, while mutation of the SH3 domain partially decreased signaling. PLCγ1 SH domains, therefore, have interrelated but distinct roles in BCR-induced PLCγ1 activation. PMID:10523627

  10. Asymmetric functional contributions of acidic and aromatic side chains in sodium channel voltage-sensor domains

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Elstone, Fisal D; Niciforovic, Ana P

    2014-01-01

    largely enigmatic. To this end, natural and unnatural side chain substitutions were made in the S2 hydrophobic core (HC), the extracellular negative charge cluster (ENC), and the intracellular negative charge cluster (INC) of the four VSDs of the skeletal muscle sodium channel isoform (NaV1......Voltage-gated sodium (NaV) channels mediate electrical excitability in animals. Despite strong sequence conservation among the voltage-sensor domains (VSDs) of closely related voltage-gated potassium (KV) and NaV channels, the functional contributions of individual side chains in Nav VSDs remain.......4). The results show that the highly conserved aromatic side chain constituting the S2 HC makes distinct functional contributions in each of the four NaV domains. No obvious cation-pi interaction exists with nearby S4 charges in any domain, and natural and unnatural mutations at these aromatic sites produce...

  11. Initial report of the cancer Patient-Reported Outcomes Measurement Information System (PROMIS) sexual function committee: review of sexual function measures and domains used in oncology.

    Science.gov (United States)

    Jeffery, Diana D; Tzeng, Janice P; Keefe, Francis J; Porter, Laura S; Hahn, Elizabeth A; Flynn, Kathryn E; Reeve, Bryce B; Weinfurt, Kevin P

    2009-03-15

    For this report, the authors described the initial activities of the Cancer Patient-Reported Outcomes Measurement Information System (PROMIS)-Sexual Function domain group, which is part of the National Institutes of Health Roadmap Initiative to develop brief questionnaires or individually tailored assessments of quality-of-life domains. Presented are a literature review of sexual function measures used in cancer populations and descriptions of the domains found in those measures. By using a consensus-driven approach, an electronic bibliographic search was conducted for articles that were published from 1991 to 2007, and 486 articles were identified for in-depth review. In total, 257 articles reported the administration of a psychometrically evaluated sexual function measure to individuals who were diagnosed with cancer. Apart from the University of California-Los Angeles Prostate Cancer Index, the International Index of Erectile Function, and the Female Sexual Function Index, the 31 identified measures have not been tested widely in cancer populations. Most measures were multidimensional and included domains related to the sexual response cycle and to general sexual satisfaction. The current review supports the need for a flexible, psychometrically robust measure of sexual function for use in oncology settings and strongly justifies the development of the PROMIS-Sexual Function instrument. When the PROMIS-Sexual Function instrument is available publicly, cancer clinicians and researchers will have another measure with which to assess patient-reported sexual function outcomes in addition to the few legacy measures that were identified through this review. Copyright (c) 2009 American Cancer Society.

  12. Green's functions in quantum physics

    CERN Document Server

    Economou, Eleftherios N

    2006-01-01

    The main part of this book is devoted to the simplest kind of Green's functions, namely the solutions of linear differential equations with a -function source. It is shown that these familiar Green's functions are a powerful tool for obtaining relatively simple and general solutions of basic problems such as scattering and bound-level information. The bound-level treatment gives a clear physical understanding of "difficult" questions such as superconductivity, the Kondo effect, and, to a lesser degree, disorder-induced localization. The more advanced subject of many-body Green's functions is presented in the last part of the book.

  13. Changes in Physical Activity Domains During the Transition Out of High School: Psychosocial and Environmental Correlates.

    Science.gov (United States)

    Molina-García, Javier; Queralt, Ana; Castillo, Isabel; Sallis, James F

    2015-10-01

    This study examined changes in multiple physical activity domains during the transition out of high school and psychosocial and environmental determinants of these changes. A 1-year prospective study was designed. The baseline sample was composed of 244 last-year high school students (58.6% female) from Valencia, Spain. Follow-up rate was 46%. Physical activity and potential determinants were measured by the Global Physical Activity Questionnaire and other evaluated scales in 2 waves. Total physical activity and active commuting (AC) decreased, respectively, by 21% and 36%, only in males. At time 1, access to car/motorbike (inverse), planning/psychosocial barriers (inverse), street connectivity (positive) and parental education (inverse) were significantly associated with AC (P genders, there was a decrease in leisure-time physical activity (LTPA; -35% in males, -43% in females). At time 1, self-efficacy and social support were positive correlates of LTPA (P physical activity change were identified, and these are promising targets for interventions.

  14. Cellulase linkers are optimized based on domain type and function: insights from sequence analysis, biophysical measurements, and molecular simulation.

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    Deanne W Sammond

    Full Text Available Cellulase enzymes deconstruct cellulose to glucose, and are often comprised of glycosylated linkers connecting glycoside hydrolases (GHs to carbohydrate-binding modules (CBMs. Although linker modifications can alter cellulase activity, the functional role of linkers beyond domain connectivity remains unknown. Here we investigate cellulase linkers connecting GH Family 6 or 7 catalytic domains to Family 1 or 2 CBMs, from both bacterial and eukaryotic cellulases to identify conserved characteristics potentially related to function. Sequence analysis suggests that the linker lengths between structured domains are optimized based on the GH domain and CBM type, such that linker length may be important for activity. Longer linkers are observed in eukaryotic GH Family 6 cellulases compared to GH Family 7 cellulases. Bacterial GH Family 6 cellulases are found with structured domains in either N to C terminal order, and similar linker lengths suggest there is no effect of domain order on length. O-glycosylation is uniformly distributed across linkers, suggesting that glycans are required along entire linker lengths for proteolysis protection and, as suggested by simulation, for extension. Sequence comparisons show that proline content for bacterial linkers is more than double that observed in eukaryotic linkers, but with fewer putative O-glycan sites, suggesting alternative methods for extension. Conversely, near linker termini where linkers connect to structured domains, O-glycosylation sites are observed less frequently, whereas glycines are more prevalent, suggesting the need for flexibility to achieve proper domain orientations. Putative N-glycosylation sites are quite rare in cellulase linkers, while an N-P motif, which strongly disfavors the attachment of N-glycans, is commonly observed. These results suggest that linkers exhibit features that are likely tailored for optimal function, despite possessing low sequence identity. This study suggests

  15. Comparative kinomics of human and chimpanzee reveal unique kinship and functional diversity generated by new domain combinations

    Directory of Open Access Journals (Sweden)

    Martin Juliette

    2008-12-01

    Full Text Available Abstract Background Phosphorylation by protein kinases is a common event in many cellular processes. Further, many kinases perform specialized roles and are regulated by non-kinase domains tethered to kinase domain. Perturbation in the regulation of kinases leads to malignancy. We have identified and analysed putative protein kinases encoded in the genome of chimpanzee which is a close evolutionary relative of human. Result The shared core biology between chimpanzee and human is characterized by many orthologous protein kinases which are involved in conserved pathways. Domain architectures specific to chimp/human kinases have been observed. Chimp kinases with unique domain architectures are characterized by deletion of one or more non-kinase domains in the human kinases. Interestingly, counterparts of some of the multi-domain human kinases in chimp are characterized by identical domain architectures but with kinase-like non-kinase domain. Remarkably, out of 587 chimpanzee kinases no human orthologue with greater than 95% sequence identity could be identified for 160 kinases. Variations in chimpanzee kinases compared to human kinases are brought about also by differences in functions of domains tethered to the catalytic kinase domain. For example, the heterodimer forming PB1 domain related to the fold of ubiquitin/Ras-binding domain is seen uniquely tethered to PKC-like chimpanzee kinase. Conclusion Though the chimpanzee and human are evolutionary very close, there are chimpanzee kinases with no close counterpart in the human suggesting differences in their functions. This analysis provides a direction for experimental analysis of human and chimpanzee protein kinases in order to enhance our understanding on their specific biological roles.

  16. Physically unclonable functions constructions, properties and applications

    CERN Document Server

    Maes, Roel

    2013-01-01

    Physically unclonable functions (PUFs) are innovative physical security primitives that produce unclonable and inherent instance-specific measurements of physical objects; in many ways they are the inanimate equivalent of biometrics for human beings. Since they are able to securely generate and store secrets, they allow us to bootstrap the physical implementation of an information security system. In this book the author discusses PUFs in all their facets: the multitude of their physical constructions, the algorithmic and physical properties which describe them, and the techniques required to

  17. Quantum readout of physical unclonable functions

    NARCIS (Netherlands)

    Skoric, B.

    2012-01-01

    Physical unclonable functions (PUFs) are physical structures that are hard to clone and have a unique challenge-response behavior. The term PUF was coined by Pappu et al. in 2001. That work triggered a lot of interest, and since then a substantial number of papers has been written about the use of a

  18. Evolutionary rates at codon sites may be used to align sequences and infer protein domain function

    Directory of Open Access Journals (Sweden)

    Hazelhurst Scott

    2010-03-01

    Full Text Available Abstract Background Sequence alignments form part of many investigations in molecular biology, including the determination of phylogenetic relationships, the prediction of protein structure and function, and the measurement of evolutionary rates. However, to obtain meaningful results, a significant degree of sequence similarity is required to ensure that the alignments are accurate and the inferences correct. Limitations arise when sequence similarity is low, which is particularly problematic when working with fast-evolving genes, evolutionary distant taxa, genomes with nucleotide biases, and cases of convergent evolution. Results A novel approach was conceptualized to address the "low sequence similarity" alignment problem. We developed an alignment algorithm termed FIRE (Functional Inference using the Rates of Evolution, which aligns sequences using the evolutionary rate at codon sites, as measured by the dN/dS ratio, rather than nucleotide or amino acid residues. FIRE was used to test the hypotheses that evolutionary rates can be used to align sequences and that the alignments may be used to infer protein domain function. Using a range of test data, we found that aligning domains based on evolutionary rates was possible even when sequence similarity was very low (for example, antibody variable regions. Furthermore, the alignment has the potential to infer protein domain function, indicating that domains with similar functions are subject to similar evolutionary constraints. These data suggest that an evolutionary rate-based approach to sequence analysis (particularly when combined with structural data may be used to study cases of convergent evolution or when sequences have very low similarity. However, when aligning homologous gene sets with sequence similarity, FIRE did not perform as well as the best traditional alignment algorithms indicating that the conventional approach of aligning residues as opposed to evolutionary rates remains the

  19. Domain architecture conservation in orthologs

    Science.gov (United States)

    2011-01-01

    Background As orthologous proteins are expected to retain function more often than other homologs, they are often used for functional annotation transfer between species. However, ortholog identification methods do not take into account changes in domain architecture, which are likely to modify a protein's function. By domain architecture we refer to the sequential arrangement of domains along a protein sequence. To assess the level of domain architecture conservation among orthologs, we carried out a large-scale study of such events between human and 40 other species spanning the entire evolutionary range. We designed a score to measure domain architecture similarity and used it to analyze differences in domain architecture conservation between orthologs and paralogs relative to the conservation of primary sequence. We also statistically characterized the extents of different types of domain swapping events across pairs of orthologs and paralogs. Results The analysis shows that orthologs exhibit greater domain architecture conservation than paralogous homologs, even when differences in average sequence divergence are compensated for, for homologs that have diverged beyond a certain threshold. We interpret this as an indication of a stronger selective pressure on orthologs than paralogs to retain the domain architecture required for the proteins to perform a specific function. In general, orthologs as well as the closest paralogous homologs have very similar domain architectures, even at large evolutionary separation. The most common domain architecture changes observed in both ortholog and paralog pairs involved insertion/deletion of new domains, while domain shuffling and segment duplication/deletion were very infrequent. Conclusions On the whole, our results support the hypothesis that function conservation between orthologs demands higher domain architecture conservation than other types of homologs, relative to primary sequence conservation. This supports the

  20. The development of a short measure of physical function for hip OA HOOS-Physical Function Shortform (HOOS-PS)

    DEFF Research Database (Denmark)

    Davis, A M; Perruccio, A V; Canizares, M

    2008-01-01

    : The daily activity and sports and recreational items of the HOOS were reduced to five items achieving a feasible, short measure of physical function with interval level properties. This tool has potential for use as the function component of an OA severity scoring system. Further testing of this measure......OBJECTIVE: To derive a cross-culturally valid, short measure of physical function using function subscales (daily living and sports and recreation) of the Hip disability and Osteoarthritis Outcome Score (HOOS). METHODS: Rasch analysis was conducted on data from individuals from multiple countries...... who had hip osteoarthritis (OA). Fit of the data to the Rasch model was evaluated by model chi(2) and item fit statistics (chi(2), size of residual, and F-test). Differential item functioning was evaluated by gender, age and country. Unidimensionality was evaluated by factor analysis of residuals...

  1. Self-reported domain-specific and accelerometer-based physical activity and sedentary behaviour in relation to psychological distress among an urban Asian population.

    Science.gov (United States)

    Chu, A H Y; van Dam, R M; Biddle, S J H; Tan, C S; Koh, D; Müller-Riemenschneider, F

    2018-04-05

    The interpretation of previous studies on the association of physical activity and sedentary behaviour with psychological health is limited by the use of mostly self-reported physical activity and sedentary behaviour, and a focus on Western populations. We aimed to explore the association of self-reported and devise-based measures of physical activity and sedentary behaviour domains on psychological distress in an urban multi-ethnic Asian population. From a population-based cross-sectional study of adults aged 18-79 years, data were used from an overall sample (n = 2653) with complete self-reported total physical activity/sedentary behaviour and domain-specific physical activity data, and a subsample (n = 703) with self-reported domain-specific sedentary behaviour and accelerometry data. Physical activity and sedentary behaviour data were collected using the Global Physical Activity Questionnaire (GPAQ), a domain-specific sedentary behaviour questionnaire and accelerometers. The Kessler Screening Scale (K6) and General Health Questionnaire (GHQ-12) were used to assess psychological distress. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals, adjusted for socio-demographic and lifestyle characteristics. The sample comprised 45.0% men (median age = 45.0 years). The prevalence of psychological distress based on the K6 and GHQ-12 was 8.4% and 21.7%, respectively. In the adjusted model, higher levels of self-reported moderate-to-vigorous physical activity (MVPA) were associated with significantly higher odds for K6 (OR = 1.47 [1.03-2.10]; p-trend = 0.03) but not GHQ-12 (OR = 0.97 [0.77-1.23]; p-trend = 0.79), when comparing the highest with the lowest tertile. Accelerometry-assessed MVPA was not significantly associated with K6 (p-trend = 0.50) nor GHQ-12 (p-trend = 0.74). The highest tertile of leisure-time physical activity, but not work- or transport-domain activity, was associated

  2. An Amphipathic Helix Directs Cellular Membrane Curvature Sensing and Function of the BAR Domain Protein PICK1.

    Science.gov (United States)

    Herlo, Rasmus; Lund, Viktor K; Lycas, Matthew D; Jansen, Anna M; Khelashvili, George; Andersen, Rita C; Bhatia, Vikram; Pedersen, Thomas S; Albornoz, Pedro B C; Johner, Niklaus; Ammendrup-Johnsen, Ina; Christensen, Nikolaj R; Erlendsson, Simon; Stoklund, Mikkel; Larsen, Jannik B; Weinstein, Harel; Kjærulff, Ole; Stamou, Dimitrios; Gether, Ulrik; Madsen, Kenneth L

    2018-05-15

    BAR domains are dimeric protein modules that sense, induce, and stabilize lipid membrane curvature. Here, we show that membrane curvature sensing (MCS) directs cellular localization and function of the BAR domain protein PICK1. In PICK1, and the homologous proteins ICA69 and arfaptin2, we identify an amphipathic helix N-terminal to the BAR domain that mediates MCS. Mutational disruption of the helix in PICK1 impaired MCS without affecting membrane binding per se. In insulin-producing INS-1E cells, super-resolution microscopy revealed that disruption of the helix selectively compromised PICK1 density on insulin granules of high curvature during their maturation. This was accompanied by reduced hormone storage in the INS-1E cells. In Drosophila, disruption of the helix compromised growth regulation. By demonstrating size-dependent binding on insulin granules, our finding highlights the function of MCS for BAR domain proteins in a biological context distinct from their function, e.g., at the plasma membrane during endocytosis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Association Between Perceived Physical Activity and Cognitive Function in Older Adults.

    Science.gov (United States)

    Loprinzi, Paul D; Frith, Emily

    2018-01-01

    There is irrefutable evidence that regular participation in physical activity is favorably associated with numerous positive health outcomes, including cognitive function. Emerging work suggests that perceived physical activity, independent of actual physical activity behavior, is inversely associated with mortality risk. In this study, we evaluate whether perceived physical activity, independent of actual physical activity, is associated with cognitive function, a robust indicator of mortality risk. Data from the cross-sectional 1999-2002 National Health and Nutrition Examination Survey were employed ( N = 2352; 60+ years of age). Actual physical activity was assessed via a validated survey. Perceived physical activity was assessed using the following question: "Compared with others of the same age, would you say that you are: more active, less active, or about the same?" Cognitive function was assessed from the Digit Symbol Substitution Test. When examined in separate models, both actual and perceived physical activity were positively and statistically significantly associated with cognitive function. However, when considered in the same model, actual physical activity was no longer statistically significantly associated with cognitive function, but perceived physical activity was. Perceived physical activity, independent of actual physical activity, is independently associated with cognitive function. If these findings are replicated, future work should consider evaluating perceived physical activity when examining the effects of actual physical activity behavior on cognitive function.

  4. Generalized multiscale finite element methods for problems in perforated heterogeneous domains

    KAUST Repository

    Chung, Eric T.

    2015-06-08

    Complex processes in perforated domains occur in many real-world applications. These problems are typically characterized by physical processes in domains with multiple scales. Moreover, these problems are intrinsically multiscale and their discretizations can yield very large linear or nonlinear systems. In this paper, we investigate multiscale approaches that attempt to solve such problems on a coarse grid by constructing multiscale basis functions in each coarse grid, where the coarse grid can contain many perforations. In particular, we are interested in cases when there is no scale separation and the perforations can have different sizes. In this regard, we mention some earlier pioneering works, where the authors develop multiscale finite element methods. In our paper, we follow Generalized Multiscale Finite Element Method (GMsFEM) and develop a multiscale procedure where we identify multiscale basis functions in each coarse block using snapshot space and local spectral problems. We show that with a few basis functions in each coarse block, one can approximate the solution, where each coarse block can contain many small inclusions. We apply our general concept to (1) Laplace equation in perforated domains; (2) elasticity equation in perforated domains; and (3) Stokes equations in perforated domains. Numerical results are presented for these problems using two types of heterogeneous perforated domains. The analysis of the proposed methods will be presented elsewhere. © 2015 Taylor & Francis

  5. Large ethnic variations in recommended physical activity according to activity domains in amsterdam, the netherlands

    Directory of Open Access Journals (Sweden)

    Kunst Anton E

    2010-11-01

    Full Text Available Abstract Purpose The level of recommended physical activity (PA is met less frequently by people from some ethnic minorities than others. We explored whether these differences in recommended PA between ethnic minority groups and the general population varied by domain and type of culturally-specific activity. Methods Participants were sampled from the population based SUNSET study and were from ethnic Dutch (n = 567, Hindustani-Surinamese (n = 370 and African-Surinamese (n = 689 descent. The validated SQUASH-questionnaire measured PA for the following domains: commuting, occupation, household, leisure time. Culturally-specific activities were added as extra question within the leisure time domain. The effect of each domain on ethnic differences in recommended PA prevalence was examined by odds-ratio (OR analysis through recalculating recommended PA, while, in turn, excluding the contribution of each domain. Results In the ethnic Dutch population, more vigorous PA in commuting and leisure time was reported compared to the Surinamese groups. The Hindustani-Surinamese and African-Surinamese reported more walking as commuting activity, while the Dutch group reported cycling more frequently. Ethnic differences in recommended PA became smaller in both Surinamese groups compared with the Dutch after removing commuting activity, for example, in Hindustani-Surinamese men (OR = 0.92, 95%CI: 0.62-1.37 vs. OR = 1.33, 0.89-2.00 and women (OR = 1.61, 1.12-2.32 vs. OR = 2.03, 1.41-2.92. Removing occupational activity resulted in larger ethnic differences in both groups compared with the Dutch. Smaller effects were found for yoga and dancing, leisure time and household activities. Conclusion This study shows that differences in PA between ethnic minority groups and the general population vary according to the activity domain. The results indicate that including all relevant domains and activities is essential for assessment of ethnic differences in recommended

  6. Distinct Functional Domains of Ubc9 Dictate Cell Survival and Resistance to Genotoxic Stress

    Science.gov (United States)

    van Waardenburg, Robert C. A. M.; Duda, David M.; Lancaster, Cynthia S.; Schulman, Brenda A.; Bjornsti, Mary-Ann

    2006-01-01

    Covalent modification with SUMO alters protein function, intracellular localization, or protein-protein interactions. Target recognition is determined, in part, by the SUMO E2 enzyme, Ubc9, while Siz/Pias E3 ligases may facilitate select interactions by acting as substrate adaptors. A yeast conditional Ubc9P123L mutant was viable at 36°C yet exhibited enhanced sensitivity to DNA damage. To define functional domains in Ubc9 that dictate cellular responses to genotoxic stress versus those necessary for cell viability, a 1.75-Å structure of yeast Ubc9 that demonstrated considerable conservation of backbone architecture with human Ubc9 was solved. Nevertheless, differences in side chain geometry/charge guided the design of human/yeast chimeras, where swapping domains implicated in (i) binding residues within substrates that flank canonical SUMOylation sites, (ii) interactions with the RanBP2 E3 ligase, and (iii) binding of the heterodimeric E1 and SUMO had distinct effects on cell growth and resistance to DNA-damaging agents. Our findings establish a functional interaction between N-terminal and substrate-binding domains of Ubc9 and distinguish the activities of E3 ligases Siz1 and Siz2 in regulating cellular responses to genotoxic stress. PMID:16782883

  7. Allostery Is an Intrinsic Property of the Protease Domain of DegS Implications for Enzyme Function and Evolution

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Jungsan; Grant, Robert A.; Sauer, Robert T. (MIT)

    2010-12-02

    DegS is a periplasmic Escherichia coli protease, which functions as a trimer to catalyze the initial rate-limiting step in a proteolytic cascade that ultimately activates transcription of stress response genes in the cytoplasm. Each DegS subunit consists of a protease domain and a PDZ domain. During protein folding stress, DegS is allosterically activated by peptides exposed in misfolded outer membrane porins, which bind to the PDZ domain and stabilize the active protease. It is not known whether allostery is conferred by the PDZ domains or is an intrinsic feature of the trimeric protease domain. Here, we demonstrate that free DegS{sup {Delta}PDZ} equilibrates between active and inactive trimers with the latter species predominating. Substrate binding stabilizes active DegS{sup {Delta}PDZ} in a positively cooperative fashion. Mutations can also stabilize active DegS{sup {Delta}PDZ} and produce an enzyme that displays hyperbolic kinetics and degrades substrate with a maximal velocity within error of that for fully activated, intact DegS. Crystal structures of multiple DegS{sup {Delta}PDZ} variants, in functional and non-functional conformations, support a two-state model in which allosteric switching is mediated by changes in specific elements of tertiary structure in the context of an invariant trimeric base. Overall, our results indicate that protein substrates must bind sufficiently tightly and specifically to the functional conformation of DegS{sup {Delta}PDZ} to assist their own degradation. Thus, substrate binding alone may have regulated the activities of ancestral DegS trimers with subsequent fusion of the protease domain to a PDZ domain, resulting in ligand-mediated regulation.

  8. Core domain and outcome measurement sets for shoulder pain trials are needed: Systematic review of physical therapy trials

    NARCIS (Netherlands)

    M.J. Page (Matthew J.); J.E. McKenzie (Joanne E.); S.E. Green (Sally E.); D.E. Beaton (Dorcas E.); N.B. Jain (Nitin B.); M. Lenza (Mario); A.P. Verhagen (Arianne); S. Surace (Stephen); J. Deitch (Jessica); R. Buchbinder (Rachelle)

    2015-01-01

    textabstractObjectives To explore the outcome domains and measurement instruments reported in published randomized controlled trials of physical therapy interventions for shoulder pain (rotator cuff disease, adhesive capsulitis, or nonspecific shoulder pain). Study Design and Setting We included

  9. Vitamin D, surface electromyography and physical function in uraemic patients

    DEFF Research Database (Denmark)

    Heaf, J.G.; Mølsted, Stig; Harrison, Adrian Paul

    2010-01-01

    EMG signal peak-peak amplitude, frequency and RMS were positively correlated to the quality of life scales Physical Function, Role Physical, General Health, Vitality, Social Function, Mental Health, and Physical Component Scale (p ... was to investigate the association between 25-OHD and muscle function as well as physical function in chronic kidney disease (CKD) and peritoneal dialysis (PD) patients. Methods: In this cross-sectional study, 21 adult patients with CKD stage 3-5 and 21 patients treated with PD were included. Standard biochemistry......) under voluntary contractions. Physical function was determined using a 30-second Chair Stand Test and the Short Form 36 quality of life questionnaire. Clinical characteristics were collected from the patient records. Results: Moderate vitamin 25-OHD deficiency (

  10. Functional hierarchy of two L domains in porcine endogenous retrovirus (PERV) that influence release and infectivity

    International Nuclear Information System (INIS)

    Marcucci, Katherine T.; Martina, Yuri; Harrison, Frank; Wilson, Carolyn A.; Salomon, Daniel R.

    2008-01-01

    The porcine endogenous retrovirus (PERV) Gag protein contains two late (L) domain motifs, PPPY and P(F/S)AP. Using viral release assays we demonstrate that PPPY is the dominant L domain involved in PERV release. PFAP represents a novel retroviral L domain variant and is defined by abnormal viral assembly phenotypes visualized by electron microscopy and attenuation of early PERV release as measured by viral genomes. PSAP is functionally dominant over PFAP in early PERV release. PSAP virions are 3.5-fold more infectious in vitro by TCID 50 and in vivo results in more RNA positive tissues and higher levels of proviral DNA using our human PERV-A receptor (HuPAR-2) transgenic mouse model [Martina, Y., Marcucci, K.T., Cherqui, S., Szabo, A., Drysdale, T., Srinivisan, U., Wilson, C.A., Patience, C., Salomon, D.R., 2006. Mice transgenic for a human porcine endogenous retrovirus receptor are susceptible to productive viral infection. J. Virol. 80 (7), 3135-3146]. The functional hierarchies displayed by PERV L domains, demonstrates that L domain selection in viral evolution exists to promote efficient viral assembly, release and infectivity in the virus-host context

  11. Quantification of extra-cerebral and cerebral hemoglobin concentrations during physical exercise using time-domain near infrared spectroscopy.

    Science.gov (United States)

    Auger, Héloïse; Bherer, Louis; Boucher, Étienne; Hoge, Richard; Lesage, Frédéric; Dehaes, Mathieu

    2016-10-01

    Fitness is known to have beneficial effects on brain anatomy and function. However, the understanding of mechanisms underlying immediate and long-term neurophysiological changes due to exercise is currently incomplete due to the lack of tools to investigate brain function during physical activity. In this study, we used time-domain near infrared spectroscopy (TD-NIRS) to quantify and discriminate extra-cerebral and cerebral hemoglobin concentrations and oxygen saturation ( SO 2 ) in young adults at rest and during incremental intensity exercise. In extra-cerebral tissue, an increase in deoxy-hemoglobin ( HbR ) and a decrease in SO 2 were observed while only cerebral HbR increased at high intensity exercise. Results in extra-cerebral tissue are consistent with thermoregulatory mechanisms to dissipate excess heat through skin blood flow, while cerebral changes are in agreement with cerebral blood flow ( CBF ) redistribution mechanisms to meet oxygen demand in activated regions during exercise. No significant difference was observed in oxy- ( HbO 2 ) and total hemoglobin ( HbT ). In addition HbO 2 , HbR and HbT increased with subject's peak power output (equivalent to the maximum oxygen volume consumption; VO 2 peak) supporting previous observations of increased total mass of red blood cells in trained individuals. Our results also revealed known gender differences with higher hemoglobin in men. Our approach in quantifying both extra-cerebral and cerebral absolute hemoglobin during exercise may help to better interpret past and future continuous-wave NIRS studies that are prone to extra-cerebral contamination and allow a better understanding of acute cerebral changes due to physical exercise.

  12. Protein domain organisation: adding order.

    Science.gov (United States)

    Kummerfeld, Sarah K; Teichmann, Sarah A

    2009-01-29

    Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected degree of clustering and more domain pairs in forward and

  13. Protein domain organisation: adding order

    Directory of Open Access Journals (Sweden)

    Kummerfeld Sarah K

    2009-01-01

    Full Text Available Abstract Background Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. Results We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Conclusion Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected

  14. Domain duplication, divergence, and loss events in vertebrate Msx paralogs reveal phylogenomically informed disease markers.

    Science.gov (United States)

    Finnerty, John R; Mazza, Maureen E; Jezewski, Peter A

    2009-01-20

    Msx originated early in animal evolution and is implicated in human genetic disorders. To reconstruct the functional evolution of Msx and inform the study of human mutations, we analyzed the phylogeny and synteny of 46 metazoan Msx proteins and tracked the duplication, diversification and loss of conserved motifs. Vertebrate Msx sequences sort into distinct Msx1, Msx2 and Msx3 clades. The sister-group relationship between MSX1 and MSX2 reflects their derivation from the 4p/5q chromosomal paralogon, a derivative of the original "MetaHox" cluster. We demonstrate physical linkage between Msx and other MetaHox genes (Hmx, NK1, Emx) in a cnidarian. Seven conserved domains, including two Groucho repression domains (N- and C-terminal), were present in the ancestral Msx. In cnidarians, the Groucho domains are highly similar. In vertebrate Msx1, the N-terminal Groucho domain is conserved, while the C-terminal domain diverged substantially, implying a novel function. In vertebrate Msx2 and Msx3, the C-terminal domain was lost. MSX1 mutations associated with ectodermal dysplasia or orofacial clefting disorders map to conserved domains in a non-random fashion. Msx originated from a MetaHox ancestor that also gave rise to Tlx, Demox, NK, and possibly EHGbox, Hox and ParaHox genes. Duplication, divergence or loss of domains played a central role in the functional evolution of Msx. Duplicated domains allow pleiotropically expressed proteins to evolve new functions without disrupting existing interaction networks. Human missense sequence variants reside within evolutionarily conserved domains, likely disrupting protein function. This phylogenomic evaluation of candidate disease markers will inform clinical and functional studies.

  15. Domain duplication, divergence, and loss events in vertebrate Msx paralogs reveal phylogenomically informed disease markers

    Directory of Open Access Journals (Sweden)

    Finnerty John R

    2009-01-01

    Full Text Available Abstract Background Msx originated early in animal evolution and is implicated in human genetic disorders. To reconstruct the functional evolution of Msx and inform the study of human mutations, we analyzed the phylogeny and synteny of 46 metazoan Msx proteins and tracked the duplication, diversification and loss of conserved motifs. Results Vertebrate Msx sequences sort into distinct Msx1, Msx2 and Msx3 clades. The sister-group relationship between MSX1 and MSX2 reflects their derivation from the 4p/5q chromosomal paralogon, a derivative of the original "MetaHox" cluster. We demonstrate physical linkage between Msx and other MetaHox genes (Hmx, NK1, Emx in a cnidarian. Seven conserved domains, including two Groucho repression domains (N- and C-terminal, were present in the ancestral Msx. In cnidarians, the Groucho domains are highly similar. In vertebrate Msx1, the N-terminal Groucho domain is conserved, while the C-terminal domain diverged substantially, implying a novel function. In vertebrate Msx2 and Msx3, the C-terminal domain was lost. MSX1 mutations associated with ectodermal dysplasia or orofacial clefting disorders map to conserved domains in a non-random fashion. Conclusion Msx originated from a MetaHox ancestor that also gave rise to Tlx, Demox, NK, and possibly EHGbox, Hox and ParaHox genes. Duplication, divergence or loss of domains played a central role in the functional evolution of Msx. Duplicated domains allow pleiotropically expressed proteins to evolve new functions without disrupting existing interaction networks. Human missense sequence variants reside within evolutionarily conserved domains, likely disrupting protein function. This phylogenomic evaluation of candidate disease markers will inform clinical and functional studies.

  16. Upper extremity function in stroke subjects: relationships between the international classification of functioning, disability, and health domains.

    Science.gov (United States)

    Faria-Fortini, Iza; Michaelsen, Stella Maris; Cassiano, Janine Gomes; Teixeira-Salmela, Luci Fuscaldi

    2011-01-01

    Upper limb (UL) impairments are the most common disabling deficits after stroke and have complex relationships with activity and participation domains. However, relatively few studies have applied the ICF model to identify the contributions of specific UL impairments, such as muscular weakness, pain, and sensory loss, as predictors of activity and participation. The purposes of this predictive study were to evaluate the relationships between UL variables related to body functions/structures, activity, and participation domains and to determine which would best explain activity and participation with 55 subjects with chronic stroke. Body functions/structures were assessed by measures of grip, pinch, and UL strength, finger tactile sensations, shoulder pain, and cognition (MMSE); activity domain by measures of observed performance (BBT, NHPT, and TEMPA); and participation by measures of quality of life (SSQOL). Upper-limb and grip strength were related to all activity measures (0.52

  17. PTSD is negatively associated with physical performance and physical function in older overweight military veterans

    OpenAIRE

    Hall, Katherine S.; Beckham, Jean C.; Bosworth, Hayden B.; Sloane, Richard; Pieper, Carl F.; Morey, Miriam C.

    2014-01-01

    This study examines the effect of posttraumatic stress disorder (PTSD) on function and physical performance in older overweight military Veterans with comorbid conditions. This is a secondary data analysis of older Veterans (mean age = 62.9 yr) participating in a physical activity counseling trial. Study participants with PTSD (n = 67) and without PTSD (n = 235) were identified. Self-reported physical function (36-item Short Form Health Survey) and directly measured physical performance (mobi...

  18. Investigating the Role of Large-Scale Domain Dynamics in Protein-Protein Interactions.

    Science.gov (United States)

    Delaforge, Elise; Milles, Sigrid; Huang, Jie-Rong; Bouvier, Denis; Jensen, Malene Ringkjøbing; Sattler, Michael; Hart, Darren J; Blackledge, Martin

    2016-01-01

    Intrinsically disordered linkers provide multi-domain proteins with degrees of conformational freedom that are often essential for function. These highly dynamic assemblies represent a significant fraction of all proteomes, and deciphering the physical basis of their interactions represents a considerable challenge. Here we describe the difficulties associated with mapping the large-scale domain dynamics and describe two recent examples where solution state methods, in particular NMR spectroscopy, are used to investigate conformational exchange on very different timescales.

  19. Yeast Fex1p Is a Constitutively Expressed Fluoride Channel with Functional Asymmetry of Its Two Homologous Domains*

    Science.gov (United States)

    Smith, Kathryn D.; Gordon, Patricia B.; Rivetta, Alberto; Allen, Kenneth E.; Berbasova, Tetyana; Slayman, Clifford; Strobel, Scott A.

    2015-01-01

    Fluoride is a ubiquitous environmental toxin with which all biological species must cope. A recently discovered family of fluoride export (FEX) proteins protects organisms from fluoride toxicity by removing it from the cell. We show here that FEX proteins in Saccharomyces cerevisiae function as ion channels that are selective for fluoride over chloride and that these proteins are constitutively expressed at the yeast plasma membrane. Continuous expression is in contrast to many other toxin exporters in yeast, and this, along with the fact that two nearly duplicate proteins are encoded in the yeast genome, suggests that the threat posed by fluoride ions is frequent and detrimental. Structurally, eukaryotic FEX proteins consist of two homologous four-transmembrane helix domains folded into an antiparallel dimer, where the orientation of the two domains is fixed by a single transmembrane linker helix. Using phylogenetic sequence conservation as a guide, we have identified several functionally important residues. There is substantial functional asymmetry in the effect of mutation at corresponding sites in the two domains. Specifically, mutations to residues in the C-terminal domain proved significantly more detrimental to function than did similar mutations in the N-terminal domain. Our data suggest particular residues that may be important to anion specificity, most notably the necessity of a positive charge near the end of TMH1 in the C-terminal domain. It is possible that a cationic charge at this location may create an electrostatic well for fluoride ions entering the channel from the cytoplasm. PMID:26055717

  20. Development of a computer-adaptive physical function instrument for Social Security Administration disability determination.

    Science.gov (United States)

    Ni, Pengsheng; McDonough, Christine M; Jette, Alan M; Bogusz, Kara; Marfeo, Elizabeth E; Rasch, Elizabeth K; Brandt, Diane E; Meterko, Mark; Haley, Stephen M; Chan, Leighton

    2013-09-01

    To develop and test an instrument to assess physical function for Social Security Administration (SSA) disability programs, the SSA-Physical Function (SSA-PF) instrument. Item response theory (IRT) analyses were used to (1) create a calibrated item bank for each of the factors identified in prior factor analyses, (2) assess the fit of the items within each scale, (3) develop separate computer-adaptive testing (CAT) instruments for each scale, and (4) conduct initial psychometric testing. Cross-sectional data collection; IRT analyses; CAT simulation. Telephone and Internet survey. Two samples: SSA claimants (n=1017) and adults from the U.S. general population (n=999). None. Model fit statistics, correlation, and reliability coefficients. IRT analyses resulted in 5 unidimensional SSA-PF scales: Changing & Maintaining Body Position, Whole Body Mobility, Upper Body Function, Upper Extremity Fine Motor, and Wheelchair Mobility for a total of 102 items. High CAT accuracy was demonstrated by strong correlations between simulated CAT scores and those from the full item banks. On comparing the simulated CATs with the full item banks, very little loss of reliability or precision was noted, except at the lower and upper ranges of each scale. No difference in response patterns by age or sex was noted. The distributions of claimant scores were shifted to the lower end of each scale compared with those of a sample of U.S. adults. The SSA-PF instrument contributes important new methodology for measuring the physical function of adults applying to the SSA disability programs. Initial evaluation revealed that the SSA-PF instrument achieved considerable breadth of coverage in each content domain and demonstrated noteworthy psychometric properties. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  1. Generating Dynamic Persistence in the Time Domain

    Science.gov (United States)

    Guerrero, A.; Smith, L. A.; Smith, L. A.; Kaplan, D. T.

    2001-12-01

    Many dynamical systems present long-range correlations. Physically, these systems vary from biological to economical, including geological or urban systems. Important geophysical candidates for this type of behaviour include weather (or climate) and earthquake sequences. Persistence is characterised by slowly decaying correlation function; that, in theory, never dies out. The Persistence exponent reflects the degree of memory in the system and much effort has been expended creating and analysing methods that successfully estimate this parameter and model data that exhibits persistence. The most widely used methods for generating long correlated time series are not dynamical systems in the time domain, but instead are derived from a given spectral density. Little attention has been drawn to modelling persistence in the time domain. The time domain approach has the advantage that an observation at certain time can be calculated using previous observations which is particularly suitable when investigating the predictability of a long memory process. We will describe two of these methods in the time domain. One is a traditional approach using fractional ARIMA (autoregressive and moving average) models; the second uses a novel approach to extending a given series using random Fourier basis functions. The statistical quality of the two methods is compared, and they are contrasted with weather data which shows, reportedly, persistence. The suitability of this approach both for estimating predictability and for making predictions is discussed.

  2. Combining protein sequence, structure, and dynamics: A novel approach for functional evolution analysis of PAS domain superfamily.

    Science.gov (United States)

    Dong, Zheng; Zhou, Hongyu; Tao, Peng

    2018-02-01

    PAS domains are widespread in archaea, bacteria, and eukaryota, and play important roles in various functions. In this study, we aim to explore functional evolutionary relationship among proteins in the PAS domain superfamily in view of the sequence-structure-dynamics-function relationship. We collected protein sequences and crystal structure data from RCSB Protein Data Bank of the PAS domain superfamily belonging to three biological functions (nucleotide binding, photoreceptor activity, and transferase activity). Protein sequences were aligned and then used to select sequence-conserved residues and build phylogenetic tree. Three-dimensional structure alignment was also applied to obtain structure-conserved residues. The protein dynamics were analyzed using elastic network model (ENM) and validated by molecular dynamics (MD) simulation. The result showed that the proteins with same function could be grouped by sequence similarity, and proteins in different functional groups displayed statistically significant difference in their vibrational patterns. Interestingly, in all three functional groups, conserved amino acid residues identified by sequence and structure conservation analysis generally have a lower fluctuation than other residues. In addition, the fluctuation of conserved residues in each biological function group was strongly correlated with the corresponding biological function. This research suggested a direct connection in which the protein sequences were related to various functions through structural dynamics. This is a new attempt to delineate functional evolution of proteins using the integrated information of sequence, structure, and dynamics. © 2017 The Protein Society.

  3. Stability of a pinned magnetic domain wall as a function of its internal configuration

    Energy Technology Data Exchange (ETDEWEB)

    Montaigne, F.; Duluard, A.; Briones, J.; Lacour, D.; Hehn, M. [Institut Jean Lamour, Université de Lorraine, CNRS, BP 70239, F-54506 Vandoeuvre lès Nancy (France); Childress, J. R. [HGST San Jose Research Center, 3403 Yerba Buena Rd, San Jose, California 95135 (United States)

    2015-01-14

    It is shown that there are many stable configurations for a domain wall pinned by a notch along a magnetic stripe. The stability of several of these configurations is investigated numerically as a function of the thickness of the magnetic film. The depinning mechanism depends on the structure of the domain wall and on the thickness of the magnetic film. In the case of a spin-valve structure, it appears that the stray fields emerging from the hard layer at the notch location influence the stability of the micromagnetic configuration. Different depinning mechanisms are thus observed for the same film thickness depending on the magnetization orientation of the propagating domain. This conclusion qualitatively explains experimental magnetoresistance measurements.

  4. MIT domain of Vps4 is a Ca2+-dependent phosphoinositide-binding domain.

    Science.gov (United States)

    Iwaya, Naoko; Takasu, Hirotoshi; Goda, Natsuko; Shirakawa, Masahiro; Tanaka, Toshiki; Hamada, Daizo; Hiroaki, Hidekazu

    2013-05-01

    The microtubule interacting and trafficking (MIT) domain is a small protein module that is conserved in proteins of diverged function, such as Vps4, spastin and sorting nexin 15 (SNX15). The molecular function of the MIT domain is protein-protein interaction, in which the domain recognizes peptides containing MIT-interacting motifs. Recently, we identified an evolutionarily related domain, 'variant' MIT domain at the N-terminal region of the microtubule severing enzyme katanin p60. We found that the domain was responsible for binding to microtubules and Ca(2+). Here, we have examined whether the authentic MIT domains also bind Ca(2+). We found that the loop between the first and second α-helices of the MIT domain binds a Ca(2+) ion. Furthermore, the MIT domains derived from Vps4b and SNX15a showed phosphoinositide-binding activities in a Ca(2+)-dependent manner. We propose that the MIT domain is a novel membrane-associating domain involved in endosomal trafficking.

  5. Functional Domains of the Quechua Language in Peru: Issues of Status Planning.

    Science.gov (United States)

    Coronel-Molina, Serafin M.

    1999-01-01

    Examines the status of Quechua in Peru and how it has affected language maintenance efforts; discusses the functional domains served by Quechua, relating them to Peruvian language policies; notes the lack of grassroots efforts by indigenous people in Peru; and suggests possible measures to improve its status, noting predictions of the future of…

  6. Roles of the SH2 and SH3 domains in the regulation of neuronal Src kinase functions.

    Science.gov (United States)

    Groveman, Bradley R; Xue, Sheng; Marin, Vedrana; Xu, Jindong; Ali, Mohammad K; Bienkiewicz, Ewa A; Yu, Xian-Min

    2011-02-01

    Previous studies demonstrated that intra-domain interactions between Src family kinases (SFKs), stabilized by binding of the phosphorylated C-terminus to the SH2 domain and/or binding of the SH2 kinase linker to the SH3 domain, lock the molecules in a closed conformation, disrupt the kinase active site, and inactivate SFKs. Here we report that the up-regulation of N-methyl-D-aspartate receptors (NMDARs) induced by expression of constitutively active neuronal Src (n-Src), in which the C-terminus tyrosine is mutated to phenylalanine (n-Src/Y535F), is significantly reduced by dysfunctions of the SH2 and/or SH3 domains of the protein. Furthermore, we found that dysfunctions of SH2 and/or SH3 domains reduce auto-phosphorylation of the kinase activation loop, depress kinase activity, and decrease NMDAR phosphorylation. The SH2 domain plays a greater regulatory role than the SH3 domain. Our data also show that n-Src binds directly to the C-terminus of the NMDAR NR2A subunit in vitro, with a K(D) of 108.2 ± 13.3 nM. This binding is not Src kinase activity-dependent, and dysfunctions of the SH2 and/or SH3 domains do not significantly affect the binding. These data indicate that the SH2 and SH3 domains may function to promote the catalytic activity of active n-Src, which is important in the regulation of NMDAR functions. © 2010 The Authors Journal compilation © 2010 FEBS.

  7. Screen time by different devices in adolescents: association with physical inactivity domains and eating habits.

    Science.gov (United States)

    Delfino, Leandro D; Dos Santos Silva, Diego A; Tebar, William R; Zanuto, Edner F; Codogno, Jamile S; Fernandes, Rômulo A; Christofaro, Diego G

    2018-03-01

    Sedentary behaviors in adolescents are associated with using screen devices, analyzed as the total daily time in television viewing, using the computer and video game. However, an independent and clustered analysis of devices allows greater understanding of associations with physical inactivity domains and eating habits in adolescents. Sample of adolescents aged 10-17 years (N.=1011) from public and private schools, randomly selected. The use of screen devices was measured by hours per week spent in each device: TV, computer, videogames and mobile phone/tablet. Physical inactivity domains (school, leisure and sports), eating habits (weekly food consumption frequency) and socioeconomic status were assessed by questionnaire. The prevalence of high use of mobile phone/tablet was 70% among adolescents, 63% showed high use of TV or computer and 24% reported high use of videogames. High use of videogames was greater among boys and high use of mobile phone/tablet was higher among girls. Significant associations of high use of TV (OR=1.43, 95% CI: 1.04-1.99), computer (OR=1.44, 95% CI: 1.03-2.02), videogames (OR=1.65, 95% CI: 1.13-2.69) and consumption of snacks were observed. High use of computer was associated with fried foods consumption (OR=1.32, 95% CI: 1.01-1.75) and physical inactivity (OR=1.41, 95% CI: 1.03-1.95). Mobile phone was associated with consumption of sweets (OR=1.33, 95% CI: 1.00-1.80). Cluster using screen devices showed associations with high consumption of snacks, fried foods and sweets, even after controlling for confounding variables. The high use of screen devices was associated with high consumption of snacks, fried foods, sweets and physical inactivity in adolescents.

  8. Use of Heuristics to Facilitate Scientific Discovery Learning in a Simulation Learning Environment in a Physics Domain

    Science.gov (United States)

    Veermans, Koen; van Joolingen, Wouter; de Jong, Ton

    2006-01-01

    This article describes a study into the role of heuristic support in facilitating discovery learning through simulation-based learning. The study compares the use of two such learning environments in the physics domain of collisions. In one learning environment (implicit heuristics) heuristics are only used to provide the learner with guidance…

  9. Trajectory of change in pain, depression, and physical functioning after physical activity adoption in fibromyalgia.

    Science.gov (United States)

    Steiner, Jennifer L; Bigatti, Silvia M; Ang, Dennis C

    2015-07-01

    Fibromyalgia is associated with widespread pain, depression, and declines in physical functioning. The purpose of this study was to examine the trajectory of these symptoms over time related to physical activity adoption and maintenance via motivational interviewing versus education, to increase physical activity. There were no treatment group differences; we divided the sample (n = 184) based on changes in physical activity. Repeated measures analyses demonstrated differential patterns in depression, pain, and physical functioning at 24 and 36 weeks. Findings suggest increased physical activity may serve as a multiple-target intervention that provides moderate to large, long-lasting benefits for individuals with fibromyalgia. © The Author(s) 2013.

  10. A physics-motivated Centroidal Voronoi Particle domain decomposition method

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Lin, E-mail: lin.fu@tum.de; Hu, Xiangyu Y., E-mail: xiangyu.hu@tum.de; Adams, Nikolaus A., E-mail: nikolaus.adams@tum.de

    2017-04-15

    In this paper, we propose a novel domain decomposition method for large-scale simulations in continuum mechanics by merging the concepts of Centroidal Voronoi Tessellation (CVT) and Voronoi Particle dynamics (VP). The CVT is introduced to achieve a high-level compactness of the partitioning subdomains by the Lloyd algorithm which monotonically decreases the CVT energy. The number of computational elements between neighboring partitioning subdomains, which scales the communication effort for parallel simulations, is optimized implicitly as the generated partitioning subdomains are convex and simply connected with small aspect-ratios. Moreover, Voronoi Particle dynamics employing physical analogy with a tailored equation of state is developed, which relaxes the particle system towards the target partition with good load balance. Since the equilibrium is computed by an iterative approach, the partitioning subdomains exhibit locality and the incremental property. Numerical experiments reveal that the proposed Centroidal Voronoi Particle (CVP) based algorithm produces high-quality partitioning with high efficiency, independently of computational-element types. Thus it can be used for a wide range of applications in computational science and engineering.

  11. Functional and topological characteristics of mammalian regulatory domains

    Science.gov (United States)

    Symmons, Orsolya; Uslu, Veli Vural; Tsujimura, Taro; Ruf, Sandra; Nassari, Sonya; Schwarzer, Wibke; Ettwiller, Laurence; Spitz, François

    2014-01-01

    Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles. PMID:24398455

  12. Uncertainty Analysis via Failure Domain Characterization: Unrestricted Requirement Functions

    Science.gov (United States)

    Crespo, Luis G.; Kenny, Sean P.; Giesy, Daniel P.

    2011-01-01

    This paper proposes an uncertainty analysis framework based on the characterization of the uncertain parameter space. This characterization enables the identification of worst-case uncertainty combinations and the approximation of the failure and safe domains with a high level of accuracy. Because these approximations are comprised of subsets of readily computable probability, they enable the calculation of arbitrarily tight upper and lower bounds to the failure probability. The methods developed herein, which are based on nonlinear constrained optimization, are applicable to requirement functions whose functional dependency on the uncertainty is arbitrary and whose explicit form may even be unknown. Some of the most prominent features of the methodology are the substantial desensitization of the calculations from the assumed uncertainty model (i.e., the probability distribution describing the uncertainty) as well as the accommodation for changes in such a model with a practically insignificant amount of computational effort.

  13. Investigating the Role of Large-Scale Domain Dynamics in Protein-Protein Interactions

    Directory of Open Access Journals (Sweden)

    Elise Delaforge

    2016-09-01

    Full Text Available Intrinsically disordered linkers provide multi-domain proteins with degrees of conformational freedom that are often essential for function. These highly dynamic assemblies represent a significant fraction of all proteomes, and deciphering the physical basis of their interactions represents a considerable challenge. Here we describe the difficulties associated with mapping the large-scale domain dynamics and describe two recent examples where solution state methods, in particular NMR spectroscopy, are used to investigate conformational exchange on very different timescales.

  14. The phospholipase PNPLA7 functions as a lysophosphatidylcholine hydrolase and interacts with lipid droplets through its catalytic domain.

    Science.gov (United States)

    Heier, Christoph; Kien, Benedikt; Huang, Feifei; Eichmann, Thomas O; Xie, Hao; Zechner, Rudolf; Chang, Ping-An

    2017-11-17

    Mammalian patatin-like phospholipase domain-containing proteins (PNPLAs) are lipid-metabolizing enzymes with essential roles in energy metabolism, skin barrier development, and brain function. A detailed annotation of enzymatic activities and structure-function relationships remains an important prerequisite to understand PNPLA functions in (patho-)physiology, for example, in disorders such as neutral lipid storage disease, non-alcoholic fatty liver disease, and neurodegenerative syndromes. In this study, we characterized the structural features controlling the subcellular localization and enzymatic activity of PNPLA7, a poorly annotated phospholipase linked to insulin signaling and energy metabolism. We show that PNPLA7 is an endoplasmic reticulum (ER) transmembrane protein that specifically promotes hydrolysis of lysophosphatidylcholine in mammalian cells. We found that transmembrane and regulatory domains in the PNPLA7 N-terminal region cooperate to regulate ER targeting but are dispensable for substrate hydrolysis. Enzymatic activity is instead mediated by the C-terminal domain, which maintains full catalytic competence even in the absence of N-terminal regions. Upon elevated fatty acid flux, the catalytic domain targets cellular lipid droplets and promotes interactions of PNPLA7 with these organelles in response to increased cAMP levels. We conclude that PNPLA7 acts as an ER-anchored lysophosphatidylcholine hydrolase that is composed of specific functional domains mediating catalytic activity, subcellular positioning, and interactions with cellular organelles. Our study provides critical structural insights into an evolutionarily conserved class of phospholipid-metabolizing enzymes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Pathogenic Parkinson's disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation.

    Science.gov (United States)

    Manzoni, Claudia; Mamais, Adamantios; Dihanich, Sybille; McGoldrick, Phillip; Devine, Michael J; Zerle, Julia; Kara, Eleanna; Taanman, Jan-Willem; Healy, Daniel G; Marti-Masso, Jose-Felix; Schapira, Anthony H; Plun-Favreau, Helene; Tooze, Sharon; Hardy, John; Bandopadhyay, Rina; Lewis, Patrick A

    2013-11-29

    LRRK2 is one of the most important genetic contributors to Parkinson's disease (PD). Point mutations in this gene cause an autosomal dominant form of PD, but to date no cellular phenotype has been consistently linked with mutations in each of the functional domains (ROC, COR and Kinase) of the protein product of this gene. In this study, primary fibroblasts from individuals carrying pathogenic mutations in the three central domains of LRRK2 were assessed for alterations in the autophagy/lysosomal pathway using a combination of biochemical and cellular approaches. Mutations in all three domains resulted in alterations in markers for autophagy/lysosomal function compared to wild type cells. These data highlight the autophagy and lysosomal pathways as read outs for pathogenic LRRK2 function and as a marker for disease, and provide insight into the mechanisms linking LRRK2 function and mutations. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Diverse Supramolecular Nanofiber Networks Assembled by Functional Low-Complexity Domains.

    Science.gov (United States)

    An, Bolin; Wang, Xinyu; Cui, Mengkui; Gui, Xinrui; Mao, Xiuhai; Liu, Yan; Li, Ke; Chu, Cenfeng; Pu, Jiahua; Ren, Susu; Wang, Yanyi; Zhong, Guisheng; Lu, Timothy K; Liu, Cong; Zhong, Chao

    2017-07-25

    Self-assembling supramolecular nanofibers, common in the natural world, are of fundamental interest and technical importance to both nanotechnology and materials science. Despite important advances, synthetic nanofibers still lack the structural and functional diversity of biological molecules, and the controlled assembly of one type of molecule into a variety of fibrous structures with wide-ranging functional attributes remains challenging. Here, we harness the low-complexity (LC) sequence domain of fused in sarcoma (FUS) protein, an essential cellular nuclear protein with slow kinetics of amyloid fiber assembly, to construct random copolymer-like, multiblock, and self-sorted supramolecular fibrous networks with distinct structural features and fluorescent functionalities. We demonstrate the utilities of these networks in the templated, spatially controlled assembly of ligand-decorated gold nanoparticles, quantum dots, nanorods, DNA origami, and hybrid structures. Owing to the distinguishable nanoarchitectures of these nanofibers, this assembly is structure-dependent. By coupling a modular genetic strategy with kinetically controlled complex supramolecular self-assembly, we demonstrate that a single type of protein molecule can be used to engineer diverse one-dimensional supramolecular nanostructures with distinct functionalities.

  17. Nanoscale diffusive memristor crossbars as physical unclonable functions.

    Science.gov (United States)

    Zhang, R; Jiang, H; Wang, Z R; Lin, P; Zhuo, Y; Holcomb, D; Zhang, D H; Yang, J J; Xia, Q

    2018-02-08

    Physical unclonable functions have emerged as promising hardware security primitives for device authentication and key generation in the era of the Internet of Things. Herein, we report novel physical unclonable functions built upon the crossbars of nanoscale diffusive memristors that translate the stochastic distribution of Ag clusters in a SiO 2 matrix into a random binary bitmap that serves as a device fingerprint. The random dispersion of Ag led to an uneven number of clusters at each cross-point, which in turn resulted in a stochastic ability to switch in the Ag:SiO 2 diffusive memristors in an array. The randomness of the dispersion was a barrier to fingerprint cloning and the unique fingerprints of each device were persistent after fabrication. Using an optimized fabrication procedure, we maximized the randomness and achieved an inter-class Hamming distance of 50.68%. We also discovered that the bits were not flipping after over 10 4 s at 400 K, suggesting superior reliability of our physical unclonable functions. In addition, our diffusive memristor-based physical unclonable functions were easy to fabricate and did not require complicated post-processing for digitization and thus, provide new opportunities in hardware security applications.

  18. The Kunitz-protease inhibitor domain in amyloid precursor protein reduces cellular mitochondrial enzymes expression and function.

    Science.gov (United States)

    Chua, Li-Min; Lim, Mei-Li; Wong, Boon-Seng

    2013-08-09

    Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD) and this can be contributed by aberrant metabolic enzyme function. But, the mechanism causing this enzymatic impairment is unclear. Amyloid precursor protein (APP) is known to be alternatively spliced to produce three major isoforms in the brain (APP695, APP751, APP770). Both APP770 and APP751 contain the Kunitz Protease Inhibitory (KPI) domain, but the former also contain an extra OX-2 domain. APP695 on the other hand, lacks both domains. In AD, up-regulation of the KPI-containing APP isoforms has been reported. But the functional contribution of this elevation is unclear. In the present study, we have expressed and compared the effect of the non-KPI containing APP695 and the KPI-containing APP751 on mitochondrial function. We found that the KPI-containing APP751 significantly decreased the expression of three major mitochondrial metabolic enzymes; citrate synthase, succinate dehydrogenase and cytochrome c oxidase (COX IV). This reduction lowers the NAD(+)/NADH ratio, COX IV activity and mitochondrial membrane potential. Overall, this study demonstrated that up-regulation of the KPI-containing APP isoforms is likely to contribute to the impairment of metabolic enzymes and mitochondrial function in AD. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Are total, intensity- and domain-specific physical activity levels associated with life satisfaction among university students?

    Science.gov (United States)

    Pedišić, Željko; Greblo, Zrinka; Phongsavan, Philayrath; Milton, Karen; Bauman, Adrian E

    2015-01-01

    Thorough information about the relationship between physical activity (PA) and life satisfaction is still lacking. Therefore, this study examined the cross-sectional relationships between life satisfaction and meeting the World Health Organization (WHO) moderate to vigorous-intensity PA recommendations, total volume and duration of PA, intensity-specific PA (walking, moderate- and vigorous-intensity), domain-specific PA (work, transport-related, domestic, and leisure-time), and 11 domain and intensity-specific PA types among university students. Additionally, we examined the associations between life satisfaction and gender, age, disposable income, community size, smoking, alcohol intake, body mass index (BMI), and self-rated health. The study included a random sample of 1750 university students in Zagreb, Croatia (response rate = 71.7%; 62.4% females; mean age 21.5 ± 1.8 years), using the International Physical Activity Questionnaire-long form and the Satisfaction with Life Scale. Higher life satisfaction was associated with female gender (β = 0.13; p = leisure-time vigorous-intensity PA was significantly associated with life satisfaction after adjustments for socio-demographic characteristics, lifestyle and self-rated general health (β = 0.06; p = 0.045). This study indicated a weak positive relationship between leisure-time vigorous-intensity PA and life satisfaction, whilst no such association was found for other PA variables. These findings underscore the importance of analyzing domain and intensity-specific PA levels in future studies among university students, as drawing conclusions about the relationship between PA and life satisfaction based on total PA levels only may be misleading.

  20. Domain structures and temperature-dependent spin reorientation transitions in c-axis oriented Co-Cr thin films

    International Nuclear Information System (INIS)

    Kusinski, Greg J.; Krishnan, Kannan M.; Thomas, Gareth; Nelson, E. C.

    2000-01-01

    Highly c-axis oriented Co 95 Cr 5 films with perpendicular anisotropy were grown epitaxially on Si (111), using an Ag seed layer, by physical vapor deposition. Films were characterized by x-ray diffraction, transmission electron microscopy (TEM), selected area electron diffraction, and Lorentz microscopy in a TEM. The following epitaxial relationship was confirmed: (111) Si (parallel sign)(111) Ag (parallel sign)(0001) CoCr ;[2(bar sign)20] Si (parallel sign)[2(bar sign)20] Ag (parallel sign)[1(bar sign)100] CoCr . Magnetic domain structures of these films were observed as a function of thickness; t, in the range, 200 Aa c ≅300 Aa, the magnetization was found to be effectively in-plane of the film, and above t c a regular, stripe-like domain pattern with a significant, alternating in sign, perpendicular component was observed. The spin reorientation transitions of the stripe domains to the in-plane magnetization were studied dynamically by observing the domains as a function of temperature by in situ heating up to 350 degree sign C. The critical transition thickness, t c , which is a function of K u and magnetostatic energy, was found to increase with increasing temperature. The stripe-domain period, L observed at room temperature was found to increase gradually with thickness; L=90 nm at t=300 Aa, and L=110 nm at t=700 Aa. (c) 2000 American Institute of Physics

  1. Handgrip performance in relation to self-perceived fatigue, physical functioning and circulating IL-6 in elderly persons without inflammation

    Directory of Open Access Journals (Sweden)

    Gorus Ellen

    2007-03-01

    Full Text Available Abstract Background Low grip strength is recognized as one of the characteristics of frailty, as are systemic inflammation and the sensation of fatigue. Contrary to maximal grip strength, the physical resistance of the muscles to fatigue is not often included in the clinical evaluation of elderly patients. The aim of this study was to investigate if the grip strength and the resistance of the handgrip muscles to fatigue are related to self-perceived fatigue, physical functioning and circulating IL-6 in independently living elderly persons. Methods Forty elderly subjects (15 female and 25 male, mean age 75 ± 5 years were assessed for maximal grip strength, as well as for fatigue resistance and grip work (respectively time and work delivered until grip strength drops to 50% of its maximum during sustained contraction, self perceived fatigue (VAS-Fatigue, Mob-Tiredness scale and the energy & fatigue items of the WHOQOL-100, self rated physical functioning (domain of physical functioning on the MOS short-form and circulating IL-6. Relationships between handgrip performance and the other outcome measures were assessed. Results In the male participants, fatigue resistance was negatively related to actual sensation of fatigue (VAS-F, p Conclusion Well functioning elderly subjects presenting less handmuscle fatigue resistance and weaker grip strength are more fatigued, experience more tiredness during daily activities and are more bothered by fatigue sensations. Body weight seems to play an important role in the relation of muscle performance to fatigue perception. Elderly patients complaining from fatigue should be physically assessed, both evaluating maximal grip strength and fatigue resistance, allowing the calculation of grip work, which integrates both parameters. Grip work might best reflect the functional capacity resulting from the development of a certain strength level in relation to the time it can be maintained.

  2. Domain-orientation dependence of levitation force in seeded melt grown single-domain YBa2Cu3Ox

    International Nuclear Information System (INIS)

    Shi, D.; Qu, D.; Sagar, S.; Lahiri, K.

    1997-01-01

    Domain-orientation dependence of levitation force has been determined for single-domain YBa 2 Cu 3 O x . The single-domain material is obtained from a seeded melt growth process. The levitation force has been found to reach a maximum as the c axis of the domain is parallel to the direction of the force. The levitation force decreases in a cosine law fashion as the angle θ (the angle between the direction of the force and the c axis) increases from 0 degree to 60 degree. A maximum anisotropy of levitation force of 2.29 has been found. A physical model is proposed to explain the observed orientation dependence. copyright 1997 American Institute of Physics

  3. Effects of functional physical activity on the maintenance of motor function in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Laís Fajersztajn

    Full Text Available Abstract It is widely known that older adults, even frail individuals, can improve their physical function using appropriately targeted exercise. Nevertheless, older adults with Alzheimer's disease (AD have been excluded from the majority of studies on exercise. The functional-task physical activity program is based on activities of daily living, and may be suited for elderly people with AD because it focuses on the maintenance and stimulation of preserved abilities. In addition, session costs are substantially reduced by adopting a group approach. Furthermore, the group approach may improve the social interaction of the demented patient. Objectives: To determine whether a functional-task physical activity program in groups can maintain motor function in elderly with AD. Methods: 10 elderly diagnosed with mild or moderate AD were assigned into one of two groups: subjects with and without intervention. The intervention consisted of a 12-week function-task physical activity program in groups. Measurements: activities of daily living (Katz and Lawton & Brody questionnaires, mobility (Timed Up and Go Test, Timed Up and Go manual Test and Timed Up and Go Cognitive Test, cognition (Mini-Mental State Examination, behavioral disturbances (Neuropsychiatric Inventory I-brief and functional balance (Berg Balance Scale. Results: A statistically significant difference between the two groups was found regarding the functional balance mean change measured by Berg scale score (p=0.046. A significant improvement of 1.60 points (95%CI[0.22;2.98] was observed in the intervention group on this scale, while the non-intervention group showed -0.40 points (95%CI[-1.78;0.98], no change. Conclusions: It is possible to treat mild and moderate Alzheimer's patients using a group approach. The functional task physical activity program was efficient in functional balance improvement and also appeared to prevent mobility decline.

  4. Increased Physical Fitness Is Associated with Higher Executive Functioning in People with Dementia

    Directory of Open Access Journals (Sweden)

    Alice Hollamby

    2017-12-01

    Full Text Available Physical fitness (PF has been associated with improved cognition in older age, but less is known about its effects on different cognitive domains in individuals diagnosed with dementia. We explored the associations between PF and cognitive performance in 40 healthy elderly and 30 individuals with dementia. Participants completed a battery of standardized cognitive tests (Mini-Mental State Exam, Verbal Fluency, Prospective and Retrospective Memory Questionnaire, Clock Drawing, and California Verbal Learning Test and were classified into high versus low levels of PF based on their score on the Physical Fitness Questionnaire. Analyses took into account age, gender, education, occupation, head injury, Internet use, brain training, and past levels of exercise and revealed overall benefits of PF, in particular for the people with dementia. Discriminant analysis showed high accuracy of reclassification, with most errors being due to the misclassification of dementia cases as healthy when they had high PF. The first discriminant function accounted for 83% of the variance. Using individual estimates of this function, which reflected global cognitive performance, confirmed the beneficial role of PF in dementia, even when taking into account age, past level of exercise, and the number of years since the dementia diagnosis. Finally, univariate analyses confirmed the differential sensitivity of the cognitive tests, with MMSE and clock drawing showing reliable interaction effects. This work shows that PF is associated with a reduced level of cognitive deterioration expected with dementia, especially in executive functioning and provides empirical support for the cognitive benefits of interventions promoting PF for individuals with dementia.

  5. Physical Activity to Improve Erectile Function

    DEFF Research Database (Denmark)

    Gerbild, Helle; Larsen, Camilla Marie; Graugaard, Christian

    2018-01-01

    , and metabolic syndrome. Physical activity (PA) has proved to be a protective factor against erectile problems, and it has been shown to improve erectile function for men affected by vascular ED. This systematic review estimated the levels of PA needed to decrease ED for men with physical inactivity, obesity......, hypertension, metabolic syndrome, and/or manifest cardiovascular diseases. Aim To provide recommendations of levels of PA needed to decrease ED for men with physical inactivity, obesity, hypertension, metabolic syndrome, and/or cardiovascular diseases. Methods In accord with the Preferred Reporting Items...... intensity 4 times per week. Overall, weekly exercise of 160 minutes for 6 months contributes to decreasing erectile problems in men with ED caused by physical inactivity, obesity, hypertension, metabolic syndrome, and/or cardiovascular diseases....

  6. Uncertainty Analysis via Failure Domain Characterization: Polynomial Requirement Functions

    Science.gov (United States)

    Crespo, Luis G.; Munoz, Cesar A.; Narkawicz, Anthony J.; Kenny, Sean P.; Giesy, Daniel P.

    2011-01-01

    This paper proposes an uncertainty analysis framework based on the characterization of the uncertain parameter space. This characterization enables the identification of worst-case uncertainty combinations and the approximation of the failure and safe domains with a high level of accuracy. Because these approximations are comprised of subsets of readily computable probability, they enable the calculation of arbitrarily tight upper and lower bounds to the failure probability. A Bernstein expansion approach is used to size hyper-rectangular subsets while a sum of squares programming approach is used to size quasi-ellipsoidal subsets. These methods are applicable to requirement functions whose functional dependency on the uncertainty is a known polynomial. Some of the most prominent features of the methodology are the substantial desensitization of the calculations from the uncertainty model assumed (i.e., the probability distribution describing the uncertainty) as well as the accommodation for changes in such a model with a practically insignificant amount of computational effort.

  7. PANDA: Protein function prediction using domain architecture and affinity propagation.

    Science.gov (United States)

    Wang, Zheng; Zhao, Chenguang; Wang, Yiheng; Sun, Zheng; Wang, Nan

    2018-02-22

    We developed PANDA (Propagation of Affinity and Domain Architecture) to predict protein functions in the format of Gene Ontology (GO) terms. PANDA at first executes profile-profile alignment algorithm to search against PfamA, KOG, COG, and SwissProt databases, and then launches PSI-BLAST against UniProt for homologue search. PANDA integrates a domain architecture inference algorithm based on the Bayesian statistics that calculates the probability of having a GO term. All the candidate GO terms are pooled and filtered based on Z-score. After that, the remaining GO terms are clustered using an affinity propagation algorithm based on the GO directed acyclic graph, followed by a second round of filtering on the clusters of GO terms. We benchmarked the performance of all the baseline predictors PANDA integrates and also for every pooling and filtering step of PANDA. It can be found that PANDA achieves better performances in terms of area under the curve for precision and recall compared to the baseline predictors. PANDA can be accessed from http://dna.cs.miami.edu/PANDA/ .

  8. Functional domains of plant chimeric calcium/calmodulin-dependent protein kinase: regulation by autoinhibitory and visinin-like domains

    Science.gov (United States)

    Ramachandiran, S.; Takezawa, D.; Wang, W.; Poovaiah, B. W.

    1997-01-01

    A novel calcium-binding calcium/calmodulin-dependent protein kinase (CCaMK) with a catalytic domain, calmodulin-binding domain, and a neural visinin-like domain was cloned and characterized from plants [Patil et al., (1995) Proc. Natl. Acad. Sci. USA 92, 4797-4801; Takezawa et al. (1996) J. Biol. Chem. 271, 8126-8132]. The mechanisms of CCaMK activation by calcium and calcium/calmodulin were investigated using various deletion mutants. The use of deletion mutants of CCaMK lacking either one, two, or all three calcium-binding EF hands indicated that all three calcium-binding sites in the visinin-like domain were crucial for the full calcium/calmodulin-dependent kinase activity. As each calcium-binding EF hand was deleted, there was a gradual reduction in calcium/calmodulin-dependent kinase activity from 100 to 4%. Another mutant (amino acids 1-322) which lacks both the visinin-like domain containing three EF hands and the calmodulin-binding domain was constitutively active, indicating the presence of an autoinhibitory domain around the calmodulin-binding domain. By using various synthetic peptides and the constitutively active mutant, we have shown that CCaMK contains an autoinhibitory domain within the residues 322-340 which overlaps its calmodulin-binding domain. Kinetic studies with both ATP and the GS peptide substrate suggest that the autoinhibitory domain of CCaMK interacts only with the peptide substrate binding motif of the catalytic domain, but not with the ATP-binding motif.

  9. Functional Pathways of Social Support for Mental Health in Work and Family Domains Among Chinese Scientific and Technological Professionals.

    Science.gov (United States)

    Gan, Yiqun; Gan, Tingting; Chen, Zhiyan; Miao, Miao; Zhang, Kan

    2015-10-01

    This study investigated the role of social support in the complex pattern of associations among stressors, work-family interferences and depression in the domains of work and family. A questionnaire was administered to a nationwide sample of 11,419 Chinese science and technology professionals. Several structural equation models were specified to determine whether social support functioned as a predictor or a mediator. Using Mplus 5.0, we compared the moderation model, the independence model, the antecedent model and the mediation model. The results revealed that the relationship between work-family interference and social support was domain specific. The independence model fit the data best in the work domain. Both the moderation model and the antecedent model fit the family domain data equally well. The current study was conducted to answer the need for comprehensive investigations of cultural uniqueness in the antecedents of work-family interference. The domain specificity, i.e. the multiple channels of the functions of support in the family domain and not in the work domain, ensures that this study is unique and culturally specific. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Functional Domain Driven Design

    OpenAIRE

    Herrera Guzmán, Sergio

    2016-01-01

    Las tecnologías están en constante expansión y evolución, diseñando nuevas técnicas para cumplir con su fin. En el desarrollo de software, las herramientas y pautas para la elaboración de productos software constituyen una pieza en constante evolución, necesarias para la toma de decisiones sobre los proyectos a realizar. Uno de los arquetipos para el desarrollo de software es el denominado Domain Driven Design, donde es importante conocer ampliamente el negocio que se desea modelar en form...

  11. Domain decomposition method for solving elliptic problems in unbounded domains

    International Nuclear Information System (INIS)

    Khoromskij, B.N.; Mazurkevich, G.E.; Zhidkov, E.P.

    1991-01-01

    Computational aspects of the box domain decomposition (DD) method for solving boundary value problems in an unbounded domain are discussed. A new variant of the DD-method for elliptic problems in unbounded domains is suggested. It is based on the partitioning of an unbounded domain adapted to the given asymptotic decay of an unknown function at infinity. The comparison of computational expenditures is given for boundary integral method and the suggested DD-algorithm. 29 refs.; 2 figs.; 2 tabs

  12. Physical and mental health-related correlates of physical function in community dwelling older adults: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Burbank Patricia A

    2010-02-01

    Full Text Available Abstract Background Physical function is the ability to perform both basic and instrumental activities of daily living, and the ability of older adults to reside in the community depends to a large extent on their level of physical function. Multiple physical and health-related variables may differentially affect physical function, but they have not been well characterized. The purpose of this investigation was to identify and examine physical and mental health-related correlates of physical function in a sample of community-dwelling older adults. Methods Nine hundred and four community dwelling older men (n = 263 and women (n = 641 with a mean (95% Confidence Interval age of 76.6 (76.1, 77.1 years underwent tests of physical function (Timed Up and Go; TUG, Body Mass Index (BMI was calculated from measured height and weight, and data were collected on self-reported health quality of life (SF-36, falls during the past 6 months, number of medications per day, depression (Geriatric Depression Scale; GDS, social support, and sociodemographic variables. Results Subjects completed the TUG in 8.7 (8.2, 9.2 seconds and expended 6,976 (6,669, 7,284 Kcal.wk-1 in physical activity. The older persons had a mean BMI of 27. 6 (27.2, 28.0, 62% took 3 or more medications per day, and14.4% had fallen one or more times over the last 6 months. Mean scores on the Mental Component Summary (MCS was 50.6 (50.2, 51,0 and the Physical Component Summary (PCS was 41.3 (40.8, 41.8. Multiple sequential regression analysis showed that, after adjustment for TUG floor surface correlates of physical function included age, sex, education, physical activity (weekly energy expenditure, general health, bodily pain, number of medications taken per day, depression and Body Mass Index. Further, there is a dose response relationship such that greater degree of physical function impairment is associated with poorer scores on physical health-related variables. Conclusions Physical

  13. The ER stress sensor PERK luminal domain functions as a molecular chaperone to interact with misfolded proteins

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Peng; Li, Jingzhi; Sha, Bingdong

    2016-11-29

    PERK is one of the major sensor proteins which can detect the protein-folding imbalance generated by endoplasmic reticulum (ER) stress. It remains unclear how the sensor protein PERK is activated by ER stress. It has been demonstrated that the PERK luminal domain can recognize and selectively interact with misfolded proteins but not native proteins. Moreover, the PERK luminal domain may function as a molecular chaperone to directly bind to and suppress the aggregation of a number of misfolded model proteins. The data strongly support the hypothesis that the PERK luminal domain can interact directly with misfolded proteins to induce ER stress signaling. To illustrate the mechanism by which the PERK luminal domain interacts with misfolded proteins, the crystal structure of the human PERK luminal domain was determined to 3.2 Å resolution. Two dimers of the PERK luminal domain constitute a tetramer in the asymmetric unit. Superimposition of the PERK luminal domain molecules indicated that the β-sandwich domain could adopt multiple conformations. It is hypothesized that the PERK luminal domain may utilize its flexible β-sandwich domain to recognize and interact with a broad range of misfolded proteins.

  14. Residues 240-250 in the C-terminus of the Pirh2 protein complement the function of the RING domain in self-ubiquitination of the Pirh2 protein.

    Directory of Open Access Journals (Sweden)

    Rami Abou Zeinab

    Full Text Available Pirh2 is a p53 inducible gene that encodes a RING-H2 domain and is proposed to be a main regulator of p53 protein, thus fine tuning the DNA damage response. Pirh2 interacts physically with p53 and promotes its MDM2-independent ubiquitination and subsequent degradation as well as participates in an auto-regulatory feedback loop that controls p53 function. Pirh2 also self-ubiquitinates. Interestingly, Pirh2 is overexpressed in a wide range of human tumors. In this study, we investigated the domains and residues essential for Pirh2 self-ubiquitination. Deletions were made in each of the three major domains of Pirh2: the N-terminal domain (NTD, Ring domain (RING, and C-terminal domain (CTD. The effects of these deletions on Pirh2 self-ubiquitination were then assessed using in vitro ubiquitination assays. Our results demonstrate that the RING domain is essential, but not sufficient, for Pirh2 self-ubiquitination and that residues 240-250 of the C-terminal domain are also essential. Our results demonstrate that Pirh2 mediated p53 polyubiquitination occurs mainly through the K48 residue of ubiquitin in vitro. Our data further our understanding of the mechanism of Pirh2 self-ubiquitination and may help identify valuable therapeutic targets that play roles in reducing the effects of the overexpression of Pirh2, thus maximizing p53's response to DNA damage.

  15. Item response theory, computerized adaptive testing, and PROMIS: assessment of physical function.

    Science.gov (United States)

    Fries, James F; Witter, James; Rose, Matthias; Cella, David; Khanna, Dinesh; Morgan-DeWitt, Esi

    2014-01-01

    Patient-reported outcome (PRO) questionnaires record health information directly from research participants because observers may not accurately represent the patient perspective. Patient-reported Outcomes Measurement Information System (PROMIS) is a US National Institutes of Health cooperative group charged with bringing PRO to a new level of precision and standardization across diseases by item development and use of item response theory (IRT). With IRT methods, improved items are calibrated on an underlying concept to form an item bank for a "domain" such as physical function (PF). The most informative items can be combined to construct efficient "instruments" such as 10-item or 20-item PF static forms. Each item is calibrated on the basis of the probability that a given person will respond at a given level, and the ability of the item to discriminate people from one another. Tailored forms may cover any desired level of the domain being measured. Computerized adaptive testing (CAT) selects the best items to sharpen the estimate of a person's functional ability, based on prior responses to earlier questions. PROMIS item banks have been improved with experience from several thousand items, and are calibrated on over 21,000 respondents. In areas tested to date, PROMIS PF instruments are superior or equal to Health Assessment Questionnaire and Medical Outcome Study Short Form-36 Survey legacy instruments in clarity, translatability, patient importance, reliability, and sensitivity to change. Precise measures, such as PROMIS, efficiently incorporate patient self-report of health into research, potentially reducing research cost by lowering sample size requirements. The advent of routine IRT applications has the potential to transform PRO measurement.

  16. Improving the performance of DomainDiscovery of protein domain boundary assignment using inter-domain linker index

    Directory of Open Access Journals (Sweden)

    Zomaya Albert Y

    2006-12-01

    Full Text Available Abstract Background Knowledge of protein domain boundaries is critical for the characterisation and understanding of protein function. The ability to identify domains without the knowledge of the structure – by using sequence information only – is an essential step in many types of protein analyses. In this present study, we demonstrate that the performance of DomainDiscovery is improved significantly by including the inter-domain linker index value for domain identification from sequence-based information. Improved DomainDiscovery uses a Support Vector Machine (SVM approach and a unique training dataset built on the principle of consensus among experts in defining domains in protein structure. The SVM was trained using a PSSM (Position Specific Scoring Matrix, secondary structure, solvent accessibility information and inter-domain linker index to detect possible domain boundaries for a target sequence. Results Improved DomainDiscovery is compared with other methods by benchmarking against a structurally non-redundant dataset and also CASP5 targets. Improved DomainDiscovery achieves 70% accuracy for domain boundary identification in multi-domains proteins. Conclusion Improved DomainDiscovery compares favourably to the performance of other methods and excels in the identification of domain boundaries for multi-domain proteins as a result of introducing support vector machine with benchmark_2 dataset.

  17. Ligand binding by PDZ domains

    DEFF Research Database (Denmark)

    Chi, Celestine N.; Bach, Anders; Strømgaard, Kristian

    2012-01-01

    , for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well...... as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context....

  18. Functional interactions at the interface between voltage-sensing and pore domains in the Shaker K(v) channel.

    Science.gov (United States)

    Soler-Llavina, Gilberto J; Chang, Tsg-Hui; Swartz, Kenton J

    2006-11-22

    Voltage-activated potassium (K(v)) channels contain a central pore domain that is partially surrounded by four voltage-sensing domains. Recent X-ray structures suggest that the two domains lack extensive protein-protein contacts within presumed transmembrane regions, but whether this is the case for functional channels embedded in lipid membranes remains to be tested. We investigated domain interactions in the Shaker K(v) channel by systematically mutating the pore domain and assessing tolerance by examining channel maturation, S4 gating charge movement, and channel opening. When mapped onto the X-ray structure of the K(v)1.2 channel the large number of permissive mutations support the notion of relatively independent domains, consistent with crystallographic studies. Inspection of the maps also identifies portions of the interface where residues are sensitive to mutation, an external cluster where mutations hinder voltage sensor activation, and an internal cluster where domain interactions between S4 and S5 helices from adjacent subunits appear crucial for the concerted opening transition.

  19. Physical Activity to Improve Erectile Function

    DEFF Research Database (Denmark)

    Gerbild, Helle; Larsen, Camilla Marie; Graugaard, Christian

    2018-01-01

    , and metabolic syndrome. Physical activity (PA) has proved to be a protective factor against erectile problems, and it has been shown to improve erectile function for men affected by vascular ED. This systematic review estimated the levels of PA needed to decrease ED for men with physical inactivity, obesity...... for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was performed of research articles specifically investigating PA as a possible treatment of ED. The review included research on ED from physical inactivity, obesity, hypertension, metabolic syndrome, and/or cardiovascular diseases......Introduction The leading cause of erectile dysfunction (ED) is arterial dysfunction, with cardiovascular disease as the most common comorbidity. Therefore, ED is typically linked to a web of closely interrelated cardiovascular risk factors such as physical inactivity, obesity, hypertension...

  20. Vigorous physical activity predicts higher heart rate variability among younger adults.

    Science.gov (United States)

    May, Richard; McBerty, Victoria; Zaky, Adam; Gianotti, Melino

    2017-06-14

    Baseline heart rate variability (HRV) is linked to prospective cardiovascular health. We tested intensity and duration of weekly physical activity as predictors of heart rate variability in young adults. Time and frequency domain indices of HRV were calculated based on 5-min resting electrocardiograms collected from 82 undergraduate students. Hours per week of both moderate and vigorous activity were estimated using the International Physical Activity Questionnaire. In regression analyses, hours of vigorous physical activity, but not moderate activity, significantly predicted greater time domain and frequency domain indices of heart rate variability. Adjusted for weekly frequency, greater daily duration of vigorous activity failed to predict HRV indices. Future studies should test direct measurements of vigorous activity patterns as predictors of autonomic function in young adulthood.

  1. Context Influences on the Subjective Experience of Aging: The Impact of Culture and Domains of Functioning.

    Science.gov (United States)

    O'Brien, Erica L; Hess, Thomas M; Kornadt, Anna E; Rothermund, Klaus; Fung, Helene; Voss, Peggy

    2017-08-01

    Attitudes about aging influence how people feel about their aging and affect psychological and health outcomes in later life. Given cross-cultural variability in such attitudes, the subjective experience of aging (e.g., subjective age [SA]) may also vary, potentially accounting for culture-specific patterns of aging-related outcomes. Our study explored cultural variation in SA and its determinants. American (N = 569), Chinese (N = 492), and German (N = 827) adults aged 30-95 years completed a questionnaire that included instruments measuring basic demographic information, SA, beliefs about thresholds of old age, control over life changes, and age dependency of changes in eight different life domains (i.e., family, work). Analyses revealed consistency across cultures in the domain-specificity of SA, but differences in the amount of shared variance across domains (e.g., Chinese adults exhibited greater homogeneity across domains than did Americans and Germans). Cultural differences were also observed in levels of SA in some domains, which were attenuated by domain-specific beliefs (e.g., control). Interestingly, beliefs about aging accounted for more cultural variation in SA than did sociodemographic factors (e.g., education). Our results demonstrate that subjective perceptions of aging and everyday functioning may be best understood from a perspective focused on context (i.e., culture, life domain). Given its important relation to functioning, examination of cross-cultural differences in the subjective experience of aging may highlight factors that determine variations in aging-related outcomes that then could serve as targets of culture-specific interventions promoting well-being in later life. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Context influences on the relationship between views of aging and subjective age: The moderating role of culture and domain of functioning.

    Science.gov (United States)

    Hess, Thomas M; O'Brien, Erica L; Voss, Peggy; Kornadt, Anna E; Rothermund, Klaus; Fung, Helene H; Popham, Lauren E

    2017-08-01

    Subjective age has been shown to reliably predict a variety of psychological and physical health outcomes, yet our understanding of its determinants is still quite limited. Using data from the Aging as Future project, the authors examined the degree to which views of aging influence subjective age and how this influence varies across cultures and domains of everyday functioning. Using data from 1,877 adults aged from 30 to 95 years of age collected in China, Germany, and the United States, they assessed how general attitudes about aging and perceptions of oneself as an older adult influenced subjective age estimates in 8 different domains of functioning. More positive attitudes about aging were associated with older subjective ages, whereas more positive views of self in old age were associated with younger subjective age. It is hypothesized that these effects are reflective of social-comparison processes and self-protective mechanisms. These influences varied considerably over contexts, with views of aging having a greater impact in domains associated with stronger negative stereotypes of aging (e.g., health) compared to those with more positive ones (e.g., family). Culture also moderated the impact of aging views in terms of the strength of prediction, direction of effect, and age of greatest influence, presumably due to cultural differences in the salience and strength of aging-related belief systems across contexts. The results illustrate the contextual sensitivity of subjective age and highlight the role played by an individual's views of old age-both in general and regarding oneself-in determining their own experience of aging. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  3. Physical Activity and Cognitive Functioning of Children: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Ilona Bidzan-Bluma

    2018-04-01

    Full Text Available Childhood is an important and sensitive period for cognitive development. There is limited published research regarding the relationship between sports and cognitive functions in children. We present studies that demonstrate the influence of physical activity on health, especially a positive correlation between sports and cognitive functions. The keywords “children, cognition, cognitive function, physical activity, and brain” were searched for using PsycInfo, Medline, and Google Scholar, with publication dates ranging from January 2000 to November 2017. Of the 617 results, 58 articles strictly connected to the main topics of physical activity and cognitive functioning were then reviewed. The areas of attention, thinking, language, learning, and memory were analyzed relative to sports and childhood. Results suggest that engaging in sports in late childhood positively influences cognitive and emotional functions. There is a paucity of publications that investigate the impact of sports on pre-adolescents’ cognitive functions, or explore which cognitive functions are developed by which sporting disciplines. Such knowledge would be useful in developing training programs for pre-adolescents, aimed at improving cognitive functions that may guide both researchers and practitioners relative to the wide range of benefits that result from physical activity.

  4. The pilus usher controls protein interactions via domain masking and is functional as an oligomer.

    Science.gov (United States)

    Werneburg, Glenn T; Henderson, Nadine S; Portnoy, Erica B; Sarowar, Samema; Hultgren, Scott J; Li, Huilin; Thanassi, David G

    2015-07-01

    The chaperone-usher (CU) pathway assembles organelles termed pili or fimbriae in Gram-negative bacteria. Type 1 pili expressed by uropathogenic Escherichia coli are prototypical structures assembled by the CU pathway. Biogenesis of pili by the CU pathway requires a periplasmic chaperone and an outer-membrane protein termed the usher (FimD). We show that the FimD C-terminal domains provide the high-affinity substrate-binding site but that these domains are masked in the resting usher. Domain masking requires the FimD plug domain, which serves as a switch controlling usher activation. We demonstrate that usher molecules can act in trans for pilus biogenesis, providing conclusive evidence for a functional usher oligomer. These results reveal mechanisms by which molecular machines such as the usher regulate and harness protein-protein interactions and suggest that ushers may interact in a cooperative manner during pilus assembly in bacteria.

  5. Physical Environmental Correlates of Domain-Specific Sedentary Behaviours across Five European Regions (the SPOTLIGHT Project).

    Science.gov (United States)

    Compernolle, Sofie; De Cocker, Katrien; Roda, Célina; Oppert, Jean-Michel; Mackenbach, Joreintje D; Lakerveld, Jeroen; Glonti, Ketevan; Bardos, Helga; Rutter, Harry; Cardon, Greet; De Bourdeaudhuij, Ilse

    2016-01-01

    The relation between neighbourhood environmental factors and domain-specific sedentary behaviours among adults remains unclear. This study firstly aims to examine the association of perceived and objectively measured neighbourhood safety, aesthetics, destinations and functionality with transport-related, work-related and leisure-time sedentary behaviour. Secondly, the study aims to assess whether these associations are moderated by age, gender or educational level. In 60 randomly sampled neighbourhoods from 5 urban regions in Europe (Ghent and suburbs, Paris and inner suburbs, Budapest and suburbs, the Randstad, and Greater London), a virtual audit with Google Street View was performed to assess environmental characteristics. A total of 5,205 adult inhabitants of these neighbourhoods reported socio-demographic characteristics, sedentary behaviours, and neighbourhood perceptions in an online survey. Generalized linear mixed models were conducted to examine associations between physical environmental neighbourhood factors and sedentary behaviours. Interaction terms were added to test the moderating role of individual-level socio-demographic variables. Lower levels of leisure-time sedentary behaviour (i.e. all leisure activities except television viewing and computer use) were observed among adults who perceived greater numbers of destinations such as supermarkets, recreational facilities, or restaurants in their neighbourhood, and among adults who lived in a neighbourhood with more objectively measured aesthetic features, such as trees, water areas or public parks. Lower levels of work-related sedentary behaviour were observed among adults who perceived less aesthetic features in their neighbourhood, and among adults who lived in a neighbourhood with less objectively measured destinations. Both age, gender and educational level moderated the associations between neighbourhood environmental factors and sedentary behaviours. Preliminary evidence was found for

  6. Physical Environmental Correlates of Domain-Specific Sedentary Behaviours across Five European Regions (the SPOTLIGHT Project.

    Directory of Open Access Journals (Sweden)

    Sofie Compernolle

    Full Text Available The relation between neighbourhood environmental factors and domain-specific sedentary behaviours among adults remains unclear. This study firstly aims to examine the association of perceived and objectively measured neighbourhood safety, aesthetics, destinations and functionality with transport-related, work-related and leisure-time sedentary behaviour. Secondly, the study aims to assess whether these associations are moderated by age, gender or educational level.In 60 randomly sampled neighbourhoods from 5 urban regions in Europe (Ghent and suburbs, Paris and inner suburbs, Budapest and suburbs, the Randstad, and Greater London, a virtual audit with Google Street View was performed to assess environmental characteristics. A total of 5,205 adult inhabitants of these neighbourhoods reported socio-demographic characteristics, sedentary behaviours, and neighbourhood perceptions in an online survey. Generalized linear mixed models were conducted to examine associations between physical environmental neighbourhood factors and sedentary behaviours. Interaction terms were added to test the moderating role of individual-level socio-demographic variables.Lower levels of leisure-time sedentary behaviour (i.e. all leisure activities except television viewing and computer use were observed among adults who perceived greater numbers of destinations such as supermarkets, recreational facilities, or restaurants in their neighbourhood, and among adults who lived in a neighbourhood with more objectively measured aesthetic features, such as trees, water areas or public parks. Lower levels of work-related sedentary behaviour were observed among adults who perceived less aesthetic features in their neighbourhood, and among adults who lived in a neighbourhood with less objectively measured destinations. Both age, gender and educational level moderated the associations between neighbourhood environmental factors and sedentary behaviours.Preliminary evidence was

  7. Structural domains required for channel function of the mouse transient receptor potential protein homologue TRP1beta.

    Science.gov (United States)

    Engelke, Michael; Friedrich, Olaf; Budde, Petra; Schäfer, Christina; Niemann, Ursula; Zitt, Christof; Jüngling, Eberhard; Rocks, Oliver; Lückhoff, Andreas; Frey, Jürgen

    2002-07-17

    Transient receptor potential proteins (TRP) are supposed to participate in the formation of store-operated Ca(2+) influx channels by co-assembly. However, little is known which domains facilitate the interaction of subunits. Contribution of the N-terminal coiled-coil domain and ankyrin-like repeats and the putative pore region of the mouse TRP1beta (mTRP1beta) variant to the formation of functional cation channels were analyzed following overexpression in HEK293 (human embryonic kidney) cells. MTRP1beta expressing cells exhibited enhanced Ca(2+) influx and enhanced whole-cell membrane currents compared to mTRP1beta deletion mutants. Using a yeast two-hybrid assay only the coiled-coil domain facilitated homodimerization of the N-terminus. These results suggest that the N-terminus of mTRP1beta is required for structural organization thus forming functional channels.

  8. Physical function, pain, quality of life and life satisfaction of amputees from the 2008 Sichuan earthquake: A prospective cohort study.

    Science.gov (United States)

    Li, Ling; Reinhardt, Jan D; Zhang, Xia; Pennycott, Andrew; Zhao, Zhengen; Zeng, Xianmen; Li, Jianan

    2015-05-01

    To examine the development and determinants of long-term outcomes for earthquake victims with amputations, including physical function, pain, quality of life and life satisfaction. Prospective cohort study with 2-3 measurement points. A total of 72 people who underwent amputations following the 2008 Sichuan Earthquake and resided in Mianzhu County, Sichuan Province, China were enrolled in the study. Of these, 27 people were lost to follow-up. Data on pain (visual analogue scale) and physical function (Barthel Index) were collected at 3 measurement points (2009, 2010 and 2012), and data on quality of life (Medical Outcomes Short-Form 36) and life satisfaction (Life Satisfaction Questionnaire-11) were collected at 2 measurement points (2010 and 2012). Data were analysed with mixed effects regression. Pain severity declined significantly and physical function increased by 2012. Quality of life and life satisfaction remained relatively stable between 2010 and 2012, while quality of life was significantly lower than reference values from the general population. Illiteracy and lower extremity amputations were associated with lower quality of life and life satisfaction in several domains. While amputees' functioning and pain were improved over time, quality of life and life satisfaction did not change. Illiterate earthquake survivors and those with lower extremity amputations are at particular risk of low quality of life and life satisfaction, and may require additional attention in future earthquake rehabilitation programs.

  9. Green's functions in quantum physics. 3. ed.

    International Nuclear Information System (INIS)

    Economou, E.N.

    2006-01-01

    The new edition of a standard reference will be of interest to advanced students wishing to become familiar with the method of Green's functions for obtaining simple and general solutions to basic problems in quantum physics. The main part is devoted to the simplest kind of Green's functions, namely the solutions of linear differential equations with a -function source. It is shown that these familiar Green's functions are a powerful tool for obtaining relatively simple and general solutions of basic problems such as scattering and bound level information. The bound-level treatment gives a clear physical understanding of ''difficult'' questions such as superconductivity, the Kondo effect, and, to a lesser degree, disorder-induced localization. The more advanced subject of many-body Green's functions is presented in the last part of the book. This third edition is 50% longer than the previous and offers end-of-chapter problems and solutions (40% are solved) and additional appendices to help it is to serve as an effective self-tutorial and self-sufficient reference. Throughout, it demonstrates the powerful and unifying formalism of Green's functions across many applications, including transport properties, carbon nanotubes, and photonics and photonic crystals. (orig.)

  10. Elderly’s Physical-Functional Fitness and Perceived Functional Capacity and Health after Participation in a Hydrotherapy Program

    Directory of Open Access Journals (Sweden)

    Elsa Cristina Sacramento Pereira

    2014-06-01

    Full Text Available Several studies have demonstrated how physical activity in older people benefits their physical fitness, health and well-being. The relation between physical activity and perceived functional capacity and health is yet to be considered. This study is a quantitative research design that investigated the improvement of the physical-functional fitness and the perception of the functional capacity and health of an elderly group participating in a waterbased exercise program (hydrotherapy. The data was collected in three different moments of the exercise program through a battery of tests of physical-functional fitness established by Batista and Sardinha (2005 and a questionnaire adapted from SABE project (Lebrão and Duarte, 2003. Twenty-six elderly persons (23 women and 3 men aged between 60 and 84 years old participated in a 31-week hydrotherapy program (twice a week; 45 minutes by session. Friedman test was used for assessing statistical differences between the physical-functional fitness and the questionnaire responses in each of the three evaluation moments. Results revealed that this program was enough to improve the physical-functional fitness of the elderly, as well as the perception they had about their health and ability to perform activities of daily living.

  11. Seventh Graders' Academic Achievement, Creativity, and Ability to Construct a Cross-Domain Concept Map--A Brain Function Perspective

    Science.gov (United States)

    Yeh, Yu-Chu

    2004-01-01

    This study proposes an interactive model of "cross-domain" concept mapping with an emphasis on brain functions, and it further investigates the relationships between academic achievement, creative thinking, and cross-domain concept mapping. Sixty-nine seventh graders participated in this study which employed two 50-minute instructional…

  12. The BRCT domain is a phospho-protein binding domain.

    Science.gov (United States)

    Yu, Xiaochun; Chini, Claudia Christiano Silva; He, Miao; Mer, Georges; Chen, Junjie

    2003-10-24

    The carboxyl-terminal domain (BRCT) of the Breast Cancer Gene 1 (BRCA1) protein is an evolutionarily conserved module that exists in a large number of proteins from prokaryotes to eukaryotes. Although most BRCT domain-containing proteins participate in DNA-damage checkpoint or DNA-repair pathways, or both, the function of the BRCT domain is not fully understood. We show that the BRCA1 BRCT domain directly interacts with phosphorylated BRCA1-Associated Carboxyl-terminal Helicase (BACH1). This specific interaction between BRCA1 and phosphorylated BACH1 is cell cycle regulated and is required for DNA damage-induced checkpoint control during the transition from G2 to M phase of the cell cycle. Further, we show that two other BRCT domains interact with their respective physiological partners in a phosphorylation-dependent manner. Thirteen additional BRCT domains also preferentially bind phospho-peptides rather than nonphosphorylated control peptides. These data imply that the BRCT domain is a phospho-protein binding domain involved in cell cycle control.

  13. Impact of different physical activities on executive functioning

    Directory of Open Access Journals (Sweden)

    Sneidere K.

    2018-01-01

    Full Text Available The aging of the Western society has become one of the key issues in research. Lately research has shown relationship between improvement in cognitive functioning and involvement in physical activities. The aim of the study was to examine the impact of different types of physical activities on executive functioning. Overall 30 seniors aged from 65 participated in a two-day study. They were divided into three groups per their life-style – aerobic activity, strength training and sedentary. Results indicated differences between the groups in cognitive efficiency (F = 6.791, p < 0.01 and working memory (F = 6.179, p < 0.01 as well as the inhibition of attention (F = 4.311, p < 0.01. The mean scores were higher in the aerobic group. The results indicate that involvement in aerobic physical activity might lessen the decline in executive functioning in seniors.

  14. Preschoolers’ Technology-Assessed Physical Activity and Cognitive Function: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Minghui Quan

    2018-05-01

    Full Text Available Early childhood is a critical period for development of cognitive function, but research on the association between physical activity and cognitive function in preschool children is limited and inconclusive. This study aimed to examine the association between technology-assessed physical activity and cognitive function in preschool children. A cross-sectional analysis of baseline data from the Physical Activity and Cognitive Development Study was conducted in Shanghai, China. Physical activity was measured with accelerometers for 7 consecutive days, and cognitive functions were assessed using the Chinese version of Wechsler Young Children Scale of Intelligence (C-WYCSI. Linear regression analyses were used to assess the association between physical activity and cognitive function. A total of 260 preschool children (boys, 144; girls, 116; mean age: 57.2 ± 5.4 months were included in analyses for this study. After adjusting for confounding factors, we found that Verbal Intelligence Quotient, Performance Intelligence Quotient, and Full Intelligence Quotient were significantly correlated with light physical activity, not moderate to vigorous physical activity, in boys. Standardized coefficients were 0.211, 0.218, and 0.242 (all p < 0.05 in three different models, respectively. However, the correlation between physical activity and cognitive functions were not significant in girls (p > 0.05. These findings suggest that cognitive function is apparently associated with light physical activity in boys. Further studies are required to clarify the sex-specific effect on physical activity and cognitive functions.

  15. Different Binding Properties and Function of CXXC Zinc Finger Domains in Dnmt1 and Tet1

    Science.gov (United States)

    Meilinger, Daniela; Bultmann, Sebastian; Fellinger, Karin; Hasenöder, Stefan; Wang, Mengxi; Qin, Weihua; Söding, Johannes; Spada, Fabio; Leonhardt, Heinrich

    2011-01-01

    Several mammalian proteins involved in chromatin and DNA modification contain CXXC zinc finger domains. We compared the structure and function of the CXXC domains in the DNA methyltransferase Dnmt1 and the methylcytosine dioxygenase Tet1. Sequence alignment showed that both CXXC domains have a very similar framework but differ in the central tip region. Based on the known structure of a similar MLL1 domain we developed homology models and designed expression constructs for the isolated CXXC domains of Dnmt1 and Tet1 accordingly. We show that the CXXC domain of Tet1 has no DNA binding activity and is dispensable for catalytic activity in vivo. In contrast, the CXXC domain of Dnmt1 selectively binds DNA substrates containing unmethylated CpG sites. Surprisingly, a Dnmt1 mutant construct lacking the CXXC domain formed covalent complexes with cytosine bases both in vitro and in vivo and rescued DNA methylation patterns in dnmt1−/− embryonic stem cells (ESCs) just as efficiently as wild type Dnmt1. Interestingly, neither wild type nor ΔCXXC Dnmt1 re-methylated imprinted CpG sites of the H19a promoter in dnmt1−/− ESCs, arguing against a role of the CXXC domain in restraining Dnmt1 methyltransferase activity on unmethylated CpG sites. PMID:21311766

  16. Different binding properties and function of CXXC zinc finger domains in Dnmt1 and Tet1.

    Directory of Open Access Journals (Sweden)

    Carina Frauer

    2011-02-01

    Full Text Available Several mammalian proteins involved in chromatin and DNA modification contain CXXC zinc finger domains. We compared the structure and function of the CXXC domains in the DNA methyltransferase Dnmt1 and the methylcytosine dioxygenase Tet1. Sequence alignment showed that both CXXC domains have a very similar framework but differ in the central tip region. Based on the known structure of a similar MLL1 domain we developed homology models and designed expression constructs for the isolated CXXC domains of Dnmt1 and Tet1 accordingly. We show that the CXXC domain of Tet1 has no DNA binding activity and is dispensable for catalytic activity in vivo. In contrast, the CXXC domain of Dnmt1 selectively binds DNA substrates containing unmethylated CpG sites. Surprisingly, a Dnmt1 mutant construct lacking the CXXC domain formed covalent complexes with cytosine bases both in vitro and in vivo and rescued DNA methylation patterns in dnmt1⁻/⁻ embryonic stem cells (ESCs just as efficiently as wild type Dnmt1. Interestingly, neither wild type nor ΔCXXC Dnmt1 re-methylated imprinted CpG sites of the H19a promoter in dnmt1⁻/⁻ ESCs, arguing against a role of the CXXC domain in restraining Dnmt1 methyltransferase activity on unmethylated CpG sites.

  17. Functional interactions of the AF-2 activation domain core region of the human androgen receptor with the amino-terminal domain and with the transcriptional coactivator TIF2 (transcriptional intermediary factor2)

    NARCIS (Netherlands)

    C.A. Berrevoets (Cor); P. Doesburg (Paul); K. Steketee (Karine); J. Trapman (Jan); A.O. Brinkmann (Albert)

    1998-01-01

    textabstractPrevious studies in yeast and mammalian cells showed a functional interaction between the amino-terminal domain and the carboxy-terminal, ligand-binding domain (LBD) of the human androgen receptor (AR). In the present study, the AR subdomains involved in

  18. Upper extremity function and quality of life in patients with breast cancer related lymphedema

    Directory of Open Access Journals (Sweden)

    Bojinović-Rodić Dragana

    2016-01-01

    Full Text Available Background/Aim. Upper limb lymphedema is one of the most frequent chronic complications after breast cancer treatment with a significant impact on the upper extremity function and quality of life (QoL. The aim of this study was to estimate health-related quality of life (HRQoL in patients with breast-cancer-related lymphedema and its correlation with upper limb function and the size of edema. Methods. The cross-sectional study included 54 breast-cancer-related lymphedema patients. The quality of life was evaluated by the Short Form 36-Item Health Survey (SF-36. Upper limb function was assessed by the Quick Disability of the Arm, Shoulder and Hand questionnaire (Quick DASH. The size of lymphedema was determined by the arm circumference. Results. The higher HRQoL score was assessed for mental health (47.0 ± 12.2 than for physical one (42.2 ± 7.5. The highest values of SF-36 were found in the domains of Mental Health (67.7 ± 22.9 and Social Function (70.1 ± 23.1. The lowest scores were registered in the domains of Role Physical (46.9 ± 39.1 and General Health (49.3 ± 20.1. Upper extremity function statistically significantly correlated with the domains Role Physical, Bodily Pain and Physical Composite Summary and also, with the domain Role Emotional (p 0.05. Conclusions. Physical disability in patients with breast cancer-related lymphedema influences quality of life more than mental health. Upper limb function has a significant impact on quality of life, not only on the physical, but also on the mental component. The presence of breast-cancer-related lymphedema certainly affects upper limb function and quality of life, but in this study no significant correlation between the size of edema and quality of life was found.

  19. Relationship between Physical Activity and Age on the Main Categories of Cognitive Processes

    OpenAIRE

    Perrot , Alexandra; Maillot , Pauline; Gagnon , Christine; Bertsch , Jean

    2011-01-01

    Many transversal studies show a positive relationship between physical activity and a large panel of cognitive functions. However, the majority of studies in this domain separately investigated categories of cognitive functions (e.g., attention, executive functions, visuospatial abilities). Studies simultaneously addressing the main categories of cognitive functions are rare. Moreover, assessment methods to measure physical activity are diverse (i.e., direct method with VO2max or indirect met...

  20. Physical activity in the elderly is associated with improved executive function and processing speed: the LADIS Study.

    Science.gov (United States)

    Frederiksen, Kristian Steen; Verdelho, Ana; Madureira, Sofia; Bäzner, Hansjörg; O'Brien, John T; Fazekas, Franz; Scheltens, Philip; Schmidt, Reinhold; Wallin, Anders; Wahlund, Lars-Olof; Erkinjunttii, Timo; Poggesi, Anna; Pantoni, Leonardo; Inzitari, Domenico; Waldemar, Gunhild

    2015-07-01

    Physical activity reduces the risk of cognitive decline but may affect cognitive domains differently. We examined whether physical activity modifies processing speed, executive function and memory in a population of non-dementia elderly subjects with age-related white matter changes (ARWMC). Data from the Leukoaraiosis And DISability (LADIS) study, a multicenter, European prospective cohort study aimed at examining the role of ARWMC in transition to disability, was used. Subjects in the LADIS study were clinically assessed yearly for 3 years including MRI at baseline and 3-year follow-up. Physical activity was assessed at baseline, and cognitive compound scores at baseline and 3-year assessment were used. Two-hundred-eighty-two subjects (age, y (mean (SD)): 73.1 (± 5.1); gender (f/m): 164/118); MMSE (mean (SD)): 28.3 (± 1.7)) who had not progressed to MCI or dementia, were included. Multiple variable linear regression analysis with baseline MMSE, education, gender, age, stroke, diabetes and ARWMC rating as covariates revealed that physical activity was associated with better scores at baseline and 3-year follow-up for executive function (baseline: β: 0.39, 95% CI: 0.13-0.90, p = 0.008; follow-up: β: 0.24, 95% CI: 0.10-0.38, p = 0.001) and processing speed (baseline: β: 0.48, 95% CI: 0.14-0.89, p = 0.005; follow-up: β: 0.15, 95% CI: 0.02-0.29, p = 0.02) but not memory. When including baseline cognitive score as a covariate in the analysis of 3-year follow-up scores, executive function remained significant (β: 0.11, 95% CI: 0-0.22, p = 0.04). Our findings confirm previous findings of a positive effect of physical activity on cognitive functions in elderly subjects, and further extends these by showing that the association is also present in patients with ARWMC. Copyright © 2014 John Wiley & Sons, Ltd.

  1. Image-domain full waveform inversion

    KAUST Repository

    Zhang, Sanzong

    2013-08-20

    The main difficulty with the data-domain full waveform inversion (FWI) is that it tends to get stuck in the local minima associated with the waveform misfit function. This is because the waveform misfit function is highly nonlinear with respect to changes in velocity model. To reduce this nonlinearity, we define the image-domain objective function to minimize the difference of the suboffset-domain common image gathers (CIGs) obtained by migrating the observed data and the calculated data. The derivation shows that the gradient of this new objective function is the combination of the gradient of the conventional FWI and the image-domain differential semblance optimization (DSO). Compared to the conventional FWI, the imagedomain FWI is immune to cycle skipping problems by smearing the nonzero suboffset images along wavepath. It also can avoid the edge effects and the gradient artifacts that are inherent in DSO due to the falsely over-penalized focused images. This is achieved by subtracting the focused image associated with the calculated data from the unfocused image associated with the observed data in the image-domain misfit function. The numerical results of the Marmousi model show that image-domain FWI is less sensitive the initial model than the conventional FWI. © 2013 SEG.

  2. Image-domain full waveform inversion

    KAUST Repository

    Zhang, Sanzong; Schuster, Gerard T.

    2013-01-01

    The main difficulty with the data-domain full waveform inversion (FWI) is that it tends to get stuck in the local minima associated with the waveform misfit function. This is because the waveform misfit function is highly nonlinear with respect to changes in velocity model. To reduce this nonlinearity, we define the image-domain objective function to minimize the difference of the suboffset-domain common image gathers (CIGs) obtained by migrating the observed data and the calculated data. The derivation shows that the gradient of this new objective function is the combination of the gradient of the conventional FWI and the image-domain differential semblance optimization (DSO). Compared to the conventional FWI, the imagedomain FWI is immune to cycle skipping problems by smearing the nonzero suboffset images along wavepath. It also can avoid the edge effects and the gradient artifacts that are inherent in DSO due to the falsely over-penalized focused images. This is achieved by subtracting the focused image associated with the calculated data from the unfocused image associated with the observed data in the image-domain misfit function. The numerical results of the Marmousi model show that image-domain FWI is less sensitive the initial model than the conventional FWI. © 2013 SEG.

  3. Physical and functional interactions between SH2 and SH3 domains of the Src family protein tyrosine kinase p59fyn

    NARCIS (Netherlands)

    Panchamoorthy, G.; Fukazawa, T.; Stolz, L.; Payne, G.; Reedquist, K.; Shoelson, S.; Songyang, Z.; Cantley, L.; Walsh, C.; Band, H.

    1994-01-01

    The Src family protein tyrosine kinases participate in signalling through cell surface receptors that lack intrinsic tyrosine kinase domains. All nine members of this family possess adjacent Src homology (SH2 and SH3) domains, both of which are essential for repression of the enzymatic activity. The

  4. Social class differences in physical functions in middle-aged men and women

    DEFF Research Database (Denmark)

    Hansen, Åse Marie; Andersen, Lars Louis; Skotte, Jørgen

    2014-01-01

    The objective of the present study is to analyze gender differences and social class gradients in physical functions; and to study whether the social class gradients in physical functions in midlife differed between men and women.......The objective of the present study is to analyze gender differences and social class gradients in physical functions; and to study whether the social class gradients in physical functions in midlife differed between men and women....

  5. Domain fusion analysis by applying relational algebra to protein sequence and domain databases.

    Science.gov (United States)

    Truong, Kevin; Ikura, Mitsuhiko

    2003-05-06

    Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at http://calcium.uhnres.utoronto.ca/pi. As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time.

  6. Virtual rehabilitation via Nintendo Wii® and conventional physical therapy effectively treat post-stroke hemiparetic patients.

    Science.gov (United States)

    da Silva Ribeiro, Nildo Manoel; Ferraz, Daniel Dominguez; Pedreira, Érika; Pinheiro, Ígor; da Silva Pinto, Ana Cláudia; Neto, Mansueto Gomes; Dos Santos, Luan Rafael Aguiar; Pozzato, Michele Gea Guimarães; Pinho, Ricardo Silva; Masruha, Marcelo Rodrigues

    2015-08-01

    The Nintendo® Wii is a simple and affordable virtual therapy alternative. It may be used at home, and it is a motivating recreational activity that provides continuous feedback. However, studies comparing the use of the Nintendo® Wii to conventional physical therapy are needed. To compare the effect of a rehabilitation treatment using the Nintendo® Wii (NW) with conventional physical therapy (CPT) to improve the sensorimotor function and quality of life for post-stroke hemiparetic patients. The present study applied a randomized, blind, and controlled clinical trial. In total, 30 patients with post-stroke hemiparesis were evaluated. A total of 15 patients were randomly assigned to each group. The SF-36 quality of life and Fugl-Meyer scales were used to evaluate the patients. After treatment, the only variable that differed between the groups was the physical functioning domain of the SF-36 in the group that received conventional physical therapy. A significant difference was observed between both groups before and after treatment in terms of the following Fugl-Meyer scale items: passive movement and pain, motor function of the upper limbs (ULs), and balance. The CPT group also showed a significant difference with regard to their UL and lower limb (LL) coordination. The SF-36 scale analysis revealed a significant difference within both groups with regard to the following domains: physical functioning, role limitation due to physical aspects, vitality, and role limitation due to emotional aspects. The NW group also exhibited a significant difference in the mental health domain. The results indicate that both approaches improved the patients' performance in a similar manner. Virtual rehabilitation using the Nintendo Wii® and CPT both effectively treat post-stroke hemiparetic patients by improving passive movement and pain scores, motor function of the upper limb, balance, physical functioning, vitality, and the physical and emotional aspects of role functioning.

  7. Effects of interactive physical-activity video-game training on physical and cognitive function in older adults.

    Science.gov (United States)

    Maillot, Pauline; Perrot, Alexandra; Hartley, Alan

    2012-09-01

    The purpose of the present study was to assess the potential of exergame training based on physically simulated sport play as a mode of physical activity that could have cognitive benefits for older adults. If exergame play has the cognitive benefits of conventional physical activity and also has the intrinsic attractiveness of video games, then it might be a very effective way to induce desirable lifestyle changes in older adults. To examine this issue, the authors developed an active video game training program using a pretest-training-posttest design comparing an experimental group (24 × 1 hr of training) with a control group without treatment. Participants completed a battery of neuropsychological tests, assessing executive control, visuospatial functions, and processing speed, to measure the cognitive impact of the program. They were also given a battery of functional fitness tests to measure the physical impact of the program. The trainees improved significantly in measures of game performance. They also improved significantly more than the control participants in measures of physical function and cognitive measures of executive control and processing speed, but not on visuospatial measures. It was encouraging to observe that, engagement in physically simulated sport games yielded benefits to cognitive and physical skills that are directly involved in functional abilities older adults need in everyday living (e.g., Hultsch, Hertzog, Small, & Dixon, 1999).

  8. Decaying quasi-two-dimensional viscous flow on a square domain

    DEFF Research Database (Denmark)

    Konijnenberg, J.A. van de; Flor, J.B.; Heijst, G.J.F. van

    1998-01-01

    A comparison is made between experimental, numerical and analytical results for the two-dimensional flow on a square domain. The experiments concern the flow at the interface of a two-layer stratified fluid, evoked by either stirring the fluid with a rake, or by injecting additional fluid...... at the interface. Two numerical simulations were performed with initial conditions and boundary conditions that correspond approximately with those met in the experiments. The analytical results concern the calculation of the lowest modes of a decaying Stokes flow on a square domain. At late times...... relationship between vorticity and stream function in the experiments and the simulations. (C) 1998 American Institute of Physics....

  9. Functional Interaction Map of Lyssavirus Phosphoprotein: Identification of the Minimal Transcription Domains

    Science.gov (United States)

    Jacob, Yves; Real, Eléonore; Tordo, Noël

    2001-01-01

    Lyssaviruses, the causative agents of rabies encephalitis, are distributed in seven genotypes. The phylogenetically distant rabies virus (PV strain, genotype 1) and Mokola virus (genotype 3) were used to develop a strategy to identify functional homologous interactive domains from two proteins (P and N) which participate in the viral ribonucleoprotein (RNP) transcription-replication complex. This strategy combined two-hybrid and green fluorescent protein–reverse two-hybrid assays in Saccharomyces cerevisiae to analyze protein-protein interactions and a reverse genetic assay in mammalian cells to study the transcriptional activity of the reconstituted RNP complex. Lyssavirus P proteins contain two N-binding domains (N-BDs), a strong one encompassing amino acid (aa) 176 to the C terminus and a weak one in the 189 N-terminal aa. The N-terminal portion of P (aa 52 to 189) also contains a homomultimerization site. Here we demonstrate that N-P interactions, although weaker, are maintained between proteins of the different genotypes. A minimal transcriptional module of the P protein was obtained by fusing the first 60 N-terminal aa containing the L protein binding site to the C-terminal strong N-BD. Random mutation of the strong N-BD on P protein identified three highly conserved K residues crucial for N-P interaction. Their mutagenesis in full-length P induced a transcriptionally defective RNP. The analysis of homologous interactive domains presented here and previously reported dissections of the P protein allowed us to propose a model of the functional interaction network of the lyssavirus P protein. This model underscores the central role of P at the interface between L protein and N-RNA template. PMID:11559793

  10. Multiscale Seismic Inversion in the Data and Image Domains

    KAUST Repository

    Zhang, Sanzong

    2015-12-01

    with both synthetic data and field records reveal both the benefits and limitations of WT. • Generalized Differental Semblance Optimization in the Image Domain (GDSO): We now extend the multiscale physics approach to differential semblance optimization (DSO) in the image domain. That is, we identify the space-lag offset H(x, z, h) in the subsurface-offset domain as an implicit function of velocity. It describes the smoothly varying moveout H(x, z, h) of the migration image m(x, z, h) in the subsurface-offset domain, which is analogous to the smoothly varying traveltime residual ∆τ(x) of a reflection event in a shot gather. The velocity model is found that minimizes the objective function ∑x,z,h H(x, z, h)2m(x, z, h)2, where coherent noise is eliminated everywhere except along the picked curve H(x, z, h). This method is denoted as generalized DSO (GDSO) and mitigates the coherent noise problem with DSO. Numerical examples are presented that empirically demonstrate its effectiveness in providing more accurate velocity models compared to conventional DSO.

  11. Using Common Spatial Distributions of Atoms to Relate Functionally Divergent Influenza Virus N10 and N11 Protein Structures to Functionally Characterized Neuraminidase Structures, Toxin Cell Entry Domains, and Non-Influenza Virus Cell Entry Domains

    Science.gov (United States)

    Weininger, Arthur; Weininger, Susan

    2015-01-01

    The ability to identify the functional correlates of structural and sequence variation in proteins is a critical capability. We related structures of influenza A N10 and N11 proteins that have no established function to structures of proteins with known function by identifying spatially conserved atoms. We identified atoms with common distributed spatial occupancy in PDB structures of N10 protein, N11 protein, an influenza A neuraminidase, an influenza B neuraminidase, and a bacterial neuraminidase. By superposing these spatially conserved atoms, we aligned the structures and associated molecules. We report spatially and sequence invariant residues in the aligned structures. Spatially invariant residues in the N6 and influenza B neuraminidase active sites were found in previously unidentified spatially equivalent sites in the N10 and N11 proteins. We found the corresponding secondary and tertiary structures of the aligned proteins to be largely identical despite significant sequence divergence. We found structural precedent in known non-neuraminidase structures for residues exhibiting structural and sequence divergence in the aligned structures. In N10 protein, we identified staphylococcal enterotoxin I-like domains. In N11 protein, we identified hepatitis E E2S-like domains, SARS spike protein-like domains, and toxin components shared by alpha-bungarotoxin, staphylococcal enterotoxin I, anthrax lethal factor, clostridium botulinum neurotoxin, and clostridium tetanus toxin. The presence of active site components common to the N6, influenza B, and S. pneumoniae neuraminidases in the N10 and N11 proteins, combined with the absence of apparent neuraminidase function, suggests that the role of neuraminidases in H17N10 and H18N11 emerging influenza A viruses may have changed. The presentation of E2S-like, SARS spike protein-like, or toxin-like domains by the N10 and N11 proteins in these emerging viruses may indicate that H17N10 and H18N11 sialidase-facilitated cell

  12. Protein domain analysis of genomic sequence data reveals regulation of LRR related domains in plant transpiration in Ficus.

    Science.gov (United States)

    Lang, Tiange; Yin, Kangquan; Liu, Jinyu; Cao, Kunfang; Cannon, Charles H; Du, Fang K

    2014-01-01

    Predicting protein domains is essential for understanding a protein's function at the molecular level. However, up till now, there has been no direct and straightforward method for predicting protein domains in species without a reference genome sequence. In this study, we developed a functionality with a set of programs that can predict protein domains directly from genomic sequence data without a reference genome. Using whole genome sequence data, the programming functionality mainly comprised DNA assembly in combination with next-generation sequencing (NGS) assembly methods and traditional methods, peptide prediction and protein domain prediction. The proposed new functionality avoids problems associated with de novo assembly due to micro reads and small single repeats. Furthermore, we applied our functionality for the prediction of leucine rich repeat (LRR) domains in four species of Ficus with no reference genome, based on NGS genomic data. We found that the LRRNT_2 and LRR_8 domains are related to plant transpiration efficiency, as indicated by the stomata index, in the four species of Ficus. The programming functionality established in this study provides new insights for protein domain prediction, which is particularly timely in the current age of NGS data expansion.

  13. The insulin and IGF1 receptor kinase domains are functional dimers in the activated state

    Science.gov (United States)

    Cabail, M. Zulema; Li, Shiqing; Lemmon, Eric; Bowen, Mark E.; Hubbard, Stevan R.; Miller, W. Todd

    2015-03-01

    The insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R) are highly related receptor tyrosine kinases with a disulfide-linked homodimeric architecture. Ligand binding to the receptor ectodomain triggers tyrosine autophosphorylation of the cytoplasmic domains, which stimulates catalytic activity and creates recruitment sites for downstream signalling proteins. Whether the two phosphorylated tyrosine kinase domains within the receptor dimer function independently or cooperatively to phosphorylate protein substrates is not known. Here we provide crystallographic, biophysical and biochemical evidence demonstrating that the phosphorylated kinase domains of IR and IGF1R form a specific dimeric arrangement involving an exchange of the juxtamembrane region proximal to the kinase domain. In this dimer, the active position of α-helix C in the kinase N lobe is stabilized, which promotes downstream substrate phosphorylation. These studies afford a novel strategy for the design of small-molecule IR agonists as potential therapeutic agents for type 2 diabetes.

  14. Single-domain versus two-domain configuration in thin ferromagnetic prisms

    International Nuclear Information System (INIS)

    Pini, Maria Gloria; Politi, Paolo

    2007-01-01

    Thin ferromagnetic elements in the form of rectangular prisms are theoretically investigated in order to study the transition from single-domain to two-domain state, with changing the in-plane aspect ratio p. We address two main questions: first, how general is the transition; second, how the critical value p c depends on the physical parameters. We use two complementary methods: discrete-lattice calculations and a micromagnetic continuum approach. Ultrathin films do not appear to split in two domains. Instead, thicker films may undergo the above transition. We have used the continuum approach to analyze recent magnetic force microscopy observations in 30nm-thick patterned permalloy elements, finding a good agreement for p c

  15. A novel PKD2L1 C-terminal domain critical for trimerization and channel function.

    Science.gov (United States)

    Zheng, Wang; Hussein, Shaimaa; Yang, JungWoo; Huang, Jun; Zhang, Fan; Hernandez-Anzaldo, Samuel; Fernandez-Patron, Carlos; Cao, Ying; Zeng, Hongbo; Tang, Jingfeng; Chen, Xing-Zhen

    2015-03-30

    As a transient receptor potential (TRP) superfamily member, polycystic kidney disease 2-like-1 (PKD2L1) is also called TRPP3 and has similar membrane topology as voltage-gated cation channels. PKD2L1 is involved in hedgehog signaling, intestinal development, and sour tasting. PKD2L1 and PKD1L3 form heterotetramers with 3:1 stoichiometry. C-terminal coiled-coil-2 (CC2) domain (G699-W743) of PKD2L1 was reported to be important for its trimerization but independent studies showed that CC2 does not affect PKD2L1 channel function. It thus remains unclear how PKD2L1 proteins oligomerize into a functional channel. By SDS-PAGE, blue native PAGE and mutagenesis we here identified a novel C-terminal domain called C1 (K575-T622) involved in stronger homotrimerization than the non-overlapping CC2, and found that the PKD2L1 N-terminus is critical for dimerization. By electrophysiology and Xenopus oocyte expression, we found that C1, but not CC2, is critical for PKD2L1 channel function. Our co-immunoprecipitation and dynamic light scattering experiments further supported involvement of C1 in trimerization. Further, C1 acted as a blocking peptide that inhibits PKD2L1 trimerization as well as PKD2L1 and PKD2L1/PKD1L3 channel function. Thus, our study identified C1 as the first PKD2L1 domain essential for both PKD2L1 trimerization and channel function, and suggest that PKD2L1 and PKD2L1/PKD1L3 channels share the PKD2L1 trimerization process.

  16. Influence of temple headache frequency on physical functioning and emotional functioning in subjects with temporomandibular disorder pain.

    Science.gov (United States)

    List, Thomas; John, Mike T; Ohrbach, Richard; Schiffman, Eric L; Truelove, Edmond L; Anderson, Gary C

    2012-01-01

    To investigate the relationship of headache frequency with patient-reported physical functioning and emotional functioning in temporomandibular disorder (TMD) subjects with concurrent temple headache. The Research Diagnostic Criteria for TMD (RDC/TMD) Validation Project identified, as a subset of 614 TMD cases and 91 controls (n = 705), 309 subjects with concurrent TMD pain diagnoses (RDC/TMD) and temple headache. The temple headaches were subdivided into infrequent, frequent, and chronic headache according to the International Classification of Headache Disorders, second edition (ICHD-II). Study variables included self-report measures of physical functioning (Jaw Function Limitation Scale [JFLS], Graded Chronic Pain Scale [GCPS], Short Form-12 [SF-12]) and emotional functioning (depression and anxiety as measured by the Symptom Checklist-90R/SCL-90R). Differences among the three headache subgroups were characterized by increasing headache frequency. The relationship between ordered headache frequency and physical as well as emotional functioning was analyzed using linear regression and trend tests for proportions. Physical functioning, as assessed with the JFLS (P headache frequency. Emotional functioning, reflected in depression and anxiety, was also associated with increased frequency of headache (both P Headache frequency was substantially correlated with reduced physical functioning and emotional functioning in subjects with TMD and concurrent temple headaches. A secondary finding was that headache was precipitated by jaw activities more often in subjects with more frequent temple headaches.

  17. Arabidopsis thaliana FLA4 functions as a glycan-stabilized soluble factor via its carboxy-proximal Fasciclin 1 domain.

    Science.gov (United States)

    Xue, Hui; Veit, Christiane; Abas, Lindy; Tryfona, Theodora; Maresch, Daniel; Ricardi, Martiniano M; Estevez, José Manuel; Strasser, Richard; Seifert, Georg J

    2017-08-01

    Fasciclin-like arabinogalactan proteins (FLAs) are involved in numerous important functions in plants but the relevance of their complex structure to physiological function and cellular fate is unresolved. Using a fully functional fluorescent version of Arabidopsis thaliana FLA4 we show that this protein is localized at the plasma membrane as well as in endosomes and soluble in the apoplast. FLA4 is likely to be GPI-anchored, is highly N-glycosylated and carries two O-glycan epitopes previously associated with arabinogalactan proteins. The activity of FLA4 was resistant against deletion of the amino-proximal fasciclin 1 domain and was unaffected by removal of the GPI-modification signal, a highly conserved N-glycan or the deletion of predicted O-glycosylation sites. Nonetheless these structural changes dramatically decreased endoplasmic reticulum (ER)-exit and plasma membrane localization of FLA4, with N-glycosylation acting at the level of ER-exit and O-glycosylation influencing post-secretory fate. We show that FLA4 acts predominantly by molecular interactions involving its carboxy-proximal fasciclin 1 domain and that its amino-proximal fasciclin 1 domain is required for stabilization of plasma membrane localization. FLA4 functions as a soluble glycoprotein via its carboxy-proximal Fas1 domain and its normal cellular trafficking depends on N- and O-glycosylation. © 2017 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

  18. Functional roles of the amino terminal domain in determining biophysical properties of Cx50 gap junction channels

    Directory of Open Access Journals (Sweden)

    Li eXin

    2013-12-01

    Full Text Available Communication through gap junction channels is essential for synchronized and coordinated cellular activities. The gap junction channel pore size, its switch control for opening/closing, and the modulations by chemicals can be different depending on the connexin subtypes that compose the channel. Recent structural and functional studies provide compelling evidence that the amino terminal (NT domains of several connexins line the pore of gap junction channels and play an important role in single channel conductance (γj and transjunctional voltage-dependent gating (Vj-gating. This article reviews recent studies conducted on a series of mutations/chimeras in the NT domain of connexin50 (Cx50. Functional examination of the gap junction channels formed by these mutants/chimeras shows the net charge number at the NT domain to be an important factor in γj and in Vj-gating. Furthermore, with an increase in the net negative charge at the NT domain, we observed an increase in the γj, as well as changes in the parameters of the Boltzmann fit of the normalized steady-state conductance and Vj relationship. Our data are consistent with a structural model where the NT domain of Cx50 lines the gap junction pore and plays an important role in sensing Vj and in the subsequent conformational changes leading to gating, as well as in limiting the rate of ion permeation.

  19. Going from microscopic to macroscopic on nonuniform growing domains.

    Science.gov (United States)

    Yates, Christian A; Baker, Ruth E; Erban, Radek; Maini, Philip K

    2012-08-01

    Throughout development, chemical cues are employed to guide the functional specification of underlying tissues while the spatiotemporal distributions of such chemicals can be influenced by the growth of the tissue itself. These chemicals, termed morphogens, are often modeled using partial differential equations (PDEs). The connection between discrete stochastic and deterministic continuum models of particle migration on growing domains was elucidated by Baker, Yates, and Erban [Bull. Math. Biol. 72, 719 (2010)] in which the migration of individual particles was modeled as an on-lattice position-jump process. We build on this work by incorporating a more physically reasonable description of domain growth. Instead of allowing underlying lattice elements to instantaneously double in size and divide, we allow incremental element growth and splitting upon reaching a predefined threshold size. Such a description of domain growth necessitates a nonuniform partition of the domain. We first demonstrate that an individual-based stochastic model for particle diffusion on such a nonuniform domain partition is equivalent to a PDE model of the same phenomenon on a nongrowing domain, providing the transition rates (which we derive) are chosen correctly and we partition the domain in the correct manner. We extend this analysis to the case where the domain is allowed to change in size, altering the transition rates as necessary. Through application of the master equation formalism we derive a PDE for particle density on this growing domain and corroborate our findings with numerical simulations.

  20. Perceived difficulty, importance, and satisfaction with physical function in COPD patients

    Directory of Open Access Journals (Sweden)

    Berry Michael J

    2004-03-01

    Full Text Available Abstract Background Research suggests that patients' satisfaction with their physical functioning (SPF is a critical component of HRQL. This study was designed to examine the extent to which perceptions of physical function and the value placed on physical function are related to satisfaction ratings. The sample consisted of older adults suffering from a progressively debilitating disease, chronic obstructive pulmonary disease (COPD. Methods During baseline assessments, COPD patients participating in a randomized controlled physical activity trial completed measures of SPF, perceived difficulty, and perceived importance. Results An ANCOVA controlling for age and gender indicated that perceived difficulty, perceived importance, and their interaction accounted for 43% of the variance in SPF. Additionally, participants were most satisfied with important tasks that they performed with little difficulty. Participants were least satisfied with important tasks that they perceived as highly difficult. Conclusion The results of the present study indicate that not being able to perform valued tasks produces discontent that is reflected in lower rating of satisfaction with physical functioning. Clearly, the significance of loss in function to individual patients is related to the importance of the functional activities that may be compromised. These data have implications for the scope of patient assessment in clinical care and for the conceptual basis of future research in the area of physical functioning.

  1. Are Total, Intensity- and Domain-Specific Physical Activity Levels Associated with Life Satisfaction among University Students?

    Science.gov (United States)

    Pedišić, Željko; Greblo, Zrinka; Phongsavan, Philayrath; Milton, Karen; Bauman, Adrian E.

    2015-01-01

    Background Thorough information about the relationship between physical activity (PA) and life satisfaction is still lacking. Therefore, this study examined the cross-sectional relationships between life satisfaction and meeting the World Health Organization (WHO) moderate to vigorous-intensity PA recommendations, total volume and duration of PA, intensity-specific PA (walking, moderate- and vigorous-intensity), domain-specific PA (work, transport-related, domestic, and leisure-time), and 11 domain and intensity-specific PA types among university students. Additionally, we examined the associations between life satisfaction and gender, age, disposable income, community size, smoking, alcohol intake, body mass index (BMI), and self-rated health. Methods The study included a random sample of 1750 university students in Zagreb, Croatia (response rate = 71.7%; 62.4% females; mean age 21.5 ± 1.8 years), using the International Physical Activity Questionnaire — long form and the Satisfaction with Life Scale. Results Higher life satisfaction was associated with female gender (β = 0.13; p = life satisfaction and size of community (p = 0.567), smoking status (p = 0.056), alcohol consumption (p = 0.058), or BMI (p = 0.508). Among all PA variables, only leisure-time vigorous-intensity PA was significantly associated with life satisfaction after adjustments for socio-demographic characteristics, lifestyle and self-rated general health (β = 0.06; p = 0.045). Conclusions This study indicated a weak positive relationship between leisure-time vigorous-intensity PA and life satisfaction, whilst no such association was found for other PA variables. These findings underscore the importance of analyzing domain and intensity-specific PA levels in future studies among university students, as drawing conclusions about the relationship between PA and life satisfaction based on total PA levels only may be misleading. PMID:25695492

  2. Refolding and characterization of the functional ligand-binding domain of human lectin-like oxidized LDL receptor.

    Science.gov (United States)

    Xie, Qiuhong; Matsunaga, Shigeru; Shi, Xiaohua; Ogawa, Setsuko; Niimi, Setsuko; Wen, Zhesheng; Tokuyasu, Ken; Machida, Sachiko

    2003-11-01

    Lectin-like oxidized low-density lipoprotein receptor (LOX-1), a type II membrane protein that can recognize a variety of structurally unrelated macromolecules, plays an important role in host defense and is implicated in atherogenesis. To understand the interaction between human LOX-1 and its ligands, in this study the functional C-type lectin-like domain (CTLD) of LOX-1 was reconstituted at high efficiency from inactive aggregates in Escherichia coli using a refolding technique based on an artificial chaperone. The CD spectra of the purified domain suggested that the domain has alpha-helical structure and the blue shift of Trp residues was observed on refolding of the domain. Like wild-type hLOX-1, the refolded CTLD domain was able to bind modified LDL. Thus, even though CTLD contains six Cys residues that form disulfide bonds, it recovered its specific binding ability on refolding. This suggests that the correct disulfide bonds in CTLD were formed by the artificial chaperone technique. Although the domain lacked N-glycosylation, it showed high affinity for its ligand in surface plasmon resonance experiments. Thus, unglycosylated CTLD is sufficient for binding modified LDL.

  3. Physical Heterogeneity and Aquatic Community Function in ...

    Science.gov (United States)

    The geomorphological character of a river network provides the template upon which evolution acts to create unique biological communities. Deciphering commonly observed patterns and processes within riverine landscapes resulting from the interplay between physical and biological components is a central tenet for the interdisciplinary field of river science. Relationships between the physical heterogeneity and food web character of functional process zones (FPZs) – large tracts of river with a similar geomorphic character - in the Kanawha River (West Virginia, USA) are examined in this study. Food web character was measured as food chain length (FCL), which reflects ecological community structure and ecosystem function. Our results show the same basal resources were present throughout the Kanawha River but their assimilation into the aquatic food web by primary consumers differed between FPZs. Differences in the trophic position of secondary consumers – fish - were also recorded between FPZs. Overall, both the morphological heterogeneity and heterogeneity of the river bed sediment of FPZs were significantly correlated with FCL. Specifically, FCL increases with greater FPZ physical heterogeneity, supporting tenet 8 of the river ecosystem synthesis. In previous research efforts, we delineated the functional process zones (FPZs) of the Kanawha River. In this study, we examined the relationship between the hydrogeomorphically-derived zones with food webs.

  4. The E-domain region of mechano-growth factor inhibits cellular apoptosis and preserves cardiac function during myocardial infarction.

    Science.gov (United States)

    Mavrommatis, Evangelos; Shioura, Krystyna M; Los, Tamara; Goldspink, Paul H

    2013-09-01

    Insulin-like growth factor-1 (IGF-1) isoforms are expressed via alternative splicing. Expression of the minor isoform IGF-1Eb [also known as mechano-growth factor (MGF)] is responsive to cell stress. Since IGF-1 isoforms differ in their E-domain regions, we are interested in determining the biological function of the MGF E-domain. To do so, a synthetic peptide analog was used to gain mechanistic insight into the actions of the E-domain. Treatment of H9c2 cells indicated a rapid cellular uptake mechanism that did not involve IGF-1 receptor activation but resulted in a nuclear localization. Peptide treatment inhibited the intrinsic apoptotic pathway in H9c2 cells subjected to cell stress with sorbitol by preventing the collapse of the mitochondrial membrane potential and inhibition of caspase-3 activation. Therefore, we administered the peptide at the time of myocardial infarction (MI) in mice. At 2 weeks post-MI cardiac function, gene expression and cell death were assayed. A significant decline in both systolic and diastolic function was evident in untreated mice based on PV loop analysis. Delivery of the E-peptide ameliorated the decline in function and resulted in significant preservation of cardiac contractility. Associated with these changes were an inhibition of pathologic hypertrophy and significantly fewer apoptotic nuclei in the viable myocardium of E-peptide-treated mice post-MI. We conclude that administration of the MGF E-domain peptide may provide a means of modulating local tissue IGF-1 autocrine/paracrine actions to preserve cardiac function, prevent cell death, and pathologic remodeling in the heart.

  5. Domain wall partition function of the eight-vertex model with a non-diagonal reflecting end

    International Nuclear Information System (INIS)

    Yang Wenli; Chen Xi; Feng Jun; Hao Kun; Shi Kangjie; Sun Chengyi; Yang Zhanying; Zhang Yaozhong

    2011-01-01

    With the help of the Drinfeld twist or factorizing F-matrix for the eight-vertex SOS model, we derive the recursion relations of the partition function for the eight-vertex model with a generic non-diagonal reflecting end and domain wall boundary condition. Solving the recursion relations, we obtain the explicit determinant expression of the partition function. Our result shows that, contrary to the eight-vertex model without a reflecting end, the partition function can be expressed as a single determinant.

  6. Green's Kernels and meso-scale approximations in perforated domains

    CERN Document Server

    Maz'ya, Vladimir; Nieves, Michael

    2013-01-01

    There are a wide range of applications in physics and structural mechanics involving domains with singular perturbations of the boundary. Examples include perforated domains and bodies with defects of different types. The accurate direct numerical treatment of such problems remains a challenge. Asymptotic approximations offer an alternative, efficient solution. Green’s function is considered here as the main object of study rather than a tool for generating solutions of specific boundary value problems. The uniformity of the asymptotic approximations is the principal point of attention. We also show substantial links between Green’s functions and solutions of boundary value problems for meso-scale structures. Such systems involve a large number of small inclusions, so that a small parameter, the relative size of an inclusion, may compete with a large parameter, represented as an overall number of inclusions. The main focus of the present text is on two topics: (a) asymptotics of Green’s kernels in domai...

  7. HMMerThread: detecting remote, functional conserved domains in entire genomes by combining relaxed sequence-database searches with fold recognition.

    Directory of Open Access Journals (Sweden)

    Charles Richard Bradshaw

    Full Text Available Conserved domains in proteins are one of the major sources of functional information for experimental design and genome-level annotation. Though search tools for conserved domain databases such as Hidden Markov Models (HMMs are sensitive in detecting conserved domains in proteins when they share sufficient sequence similarity, they tend to miss more divergent family members, as they lack a reliable statistical framework for the detection of low sequence similarity. We have developed a greatly improved HMMerThread algorithm that can detect remotely conserved domains in highly divergent sequences. HMMerThread combines relaxed conserved domain searches with fold recognition to eliminate false positive, sequence-based identifications. With an accuracy of 90%, our software is able to automatically predict highly divergent members of conserved domain families with an associated 3-dimensional structure. We give additional confidence to our predictions by validation across species. We have run HMMerThread searches on eight proteomes including human and present a rich resource of remotely conserved domains, which adds significantly to the functional annotation of entire proteomes. We find ∼4500 cross-species validated, remotely conserved domain predictions in the human proteome alone. As an example, we find a DNA-binding domain in the C-terminal part of the A-kinase anchor protein 10 (AKAP10, a PKA adaptor that has been implicated in cardiac arrhythmias and premature cardiac death, which upon stress likely translocates from mitochondria to the nucleus/nucleolus. Based on our prediction, we propose that with this HLH-domain, AKAP10 is involved in the transcriptional control of stress response. Further remotely conserved domains we discuss are examples from areas such as sporulation, chromosome segregation and signalling during immune response. The HMMerThread algorithm is able to automatically detect the presence of remotely conserved domains in

  8. A novel heavy domain antibody library with functionally optimized complementarity determining regions.

    Directory of Open Access Journals (Sweden)

    Ole Aalund Mandrup

    Full Text Available Today a number of synthetic antibody libraries of different formats have been created and used for the selection of a large number of recombinant antibodies. One of the determining factors for successful isolation of recombinant antibodies from libraries lies in the quality of the libraries i.e. the number of correctly folded, functional antibodies contained in the library. Here, we describe the construction of a novel, high quality, synthetic single domain antibody library dubbed Predator. The library is based on the HEL4 domain antibody with the addition of recently reported mutations concerning the amino acid composition at positions critical for the folding characteristics and aggregation propensities of domain antibodies. As a unique feature, the CDR3 of the library was designed to mimic the natural human immune response by designating amino acids known to be prevalent in functional antibodies to the diversity in CDR3. CDR randomizations were performed using trinucleotide synthesis to avoid the presence of stop codons. Furthermore a novel cycle free elongation method was used for the conversion of the synthesized single stranded DNA containing the randomized CDRs into double stranded DNA of the library. In addition a modular approach has been adopted for the scaffold in which each CDR region is flanked by unique restrictions sites, allowing easy affinity maturation of selected clones by CDR shuffling. To validate the quality of the library, one round phage display selections were performed on purified antigens and highly complex antigen mixtures such as cultured eukaryotic cells resulting in several specific binders. The further characterization of some of the selected clones, however, indicates a reduction in thermodynamic stability caused by the inclusion the additional mutations to the HEL4 scaffold.

  9. The SHOCT domain: a widespread domain under-represented in model organisms.

    Directory of Open Access Journals (Sweden)

    Ruth Y Eberhardt

    Full Text Available We have identified a new protein domain, which we have named the SHOCT domain (Short C-terminal domain. This domain is widespread in bacteria with over a thousand examples. But we found it is missing from the most commonly studied model organisms, despite being present in closely related species. It's predominantly C-terminal location, co-occurrence with numerous other domains and short size is reminiscent of the Gram-positive anchor motif, however it is present in a much wider range of species. We suggest several hypotheses about the function of SHOCT, including oligomerisation and nucleic acid binding. Our initial experiments do not support its role as an oligomerisation domain.

  10. A snapshot of the physical and functional wiring of the Eps15 homology domain network in the nematode

    DEFF Research Database (Denmark)

    Tsushima, Hanako; Malabarba, Maria Grazia; Confalonieri, Stefano

    2013-01-01

    Protein interaction modules coordinate the connections within and the activity of intracellular signaling networks. The Eps15 Homology (EH) module, a protein-protein interaction domain that is a key feature of the EH-network, was originally identified in a few proteins involved in endocytosis and...

  11. The effect of pain on physical functioning after breast cancer treatment

    DEFF Research Database (Denmark)

    Andersen, Kenneth Geving; Christensen, Karl Bang; Kehlet, Henrik

    2014-01-01

    OBJECTIVES:: Persistent postsurgical pain, musculoskeletal pain, sensory disturbances and lymphedema are major clinical problems after treatment for breast cancer. However, there is little evidence on how these sequelae affects physical function. The aim was to develop and validate a procedure...... specific tool for assessing the impact of pain and other sequelae on physical function after breast cancer treatment. METHODS:: Literature review, patient and expert interviews were used to identify dimensions of physical function and sequelae. A questionnaire was developed and tested using cognitive......, lymphedema and other causes. Convergent validity was assessed using the "Quick-disability of arm, shoulder and hand" scale (Q-DASH). RESULTS:: About half of the patients reported decreased physical function. All 5 scales displayed good fit, unidimensionality, monotonicity, local independence, and lack...

  12. Conformational entropic maps of functional coupling domains in GPCR activation: A case study with beta2 adrenergic receptor

    Science.gov (United States)

    Liu, Fan; Abrol, Ravinder; Goddard, William, III; Dougherty, Dennis

    2014-03-01

    Entropic effect in GPCR activation is poorly understood. Based on the recent solved structures, researchers in the GPCR structural biology field have proposed several ``local activating switches'' that consisted of a few number of conserved residues, but have long ignored the collective dynamical effect (conformational entropy) of a domain comprised of an ensemble of residues. A new paradigm has been proposed recently that a GPCR can be viewed as a composition of several functional coupling domains, each of which undergoes order-to-disorder or disorder-to-order transitions upon activation. Here we identified and studied these functional coupling domains by comparing the local entropy changes of each residue between the inactive and active states of the β2 adrenergic receptor from computational simulation. We found that agonist and G-protein binding increases the heterogeneity of the entropy distribution in the receptor. This new activation paradigm and computational entropy analysis scheme provides novel ways to design functionally modified mutant and identify new allosteric sites for GPCRs. The authors thank NIH and Sanofi for funding this project.

  13. Functional interaction between the N- and C-terminal domains of murine leukemia virus surface envelope protein

    International Nuclear Information System (INIS)

    Lu, C.-W.; Roth, Monica J.

    2003-01-01

    A series of murine leukemia viruses (MuLVs) with chimeric envelope proteins (Env) was generated to map functional interactions between the N- and the C-terminal domains of surface proteins (SU). All these chimeras have the 4070A amphotropic receptor-binding region flanked by various lengths of Moloney ecotropic N- and C-terminal Env. A charged residue, E49 (E16 on the mature protein), was identified at the N-terminals of Moloney MuLV SU that is important for the interaction with the C-terminal domain of the SU. The region that interacts with E49 was localized between junction 4 (R265 of M-MuLV Env) and junction 6 (L374 of M-MuLV Env) of SU. Sequencing the viable chimeric Env virus populations identified residues within the SU protein that improved the replication kinetics of the input chimeric Env viruses. Mutations in the C-domain of SU (G387E/R, L435I, L442P) were found to improve chimera IV4, which displayed a delayed onset of replication. The replication of AE6, containing a chimeric junction in the SU C-terminus, was improved by mutations in the N-domain (N40H, E80K), the proline-rich region (Q252R), or the transmembrane protein (L538N). Altogether, these observations provide insights into the structural elements required for Env function

  14. [The relationship between executive functions, physical and functional capability in people over 60 years old].

    Science.gov (United States)

    Rajtar-Zembaty, Anna; Sałakowski, Andrzej; Rajtar-Zembaty, Jakub

    Nowadays it is believed that cognitive decline may contribute to the formation of gait disturbance and increased risk of falls. Currently the importance of executive functions to maintain proper control of gait is emphasized. The aim of the study was to assess the relationship between the level of executive function, functional and physical capability in patients over 60 years of age. The study included 300 patients (199 women and 101 men) aged 60-88 years. In order to screening for cognitive function Mini-Mental State Examination (MMSE) was used. The following researchers tools were used to conduct functional assessment: a) Short Physical Performance Battery (SPPB), b) Timed “Up and Go” (TUG) and c) Fast Walking Test. To assess executive fucntion Trail Making Test (TMT) was selected. The relationship between the speed of information processing (part A, TMT), executive functions (Part B, TMT), level of functional and physical capability was observed. The strongest positive correlation was noted between the time of TUG test and TMT part B (r=0.32; pphysical capability in patients over 60 years of age. Cognitive processes play an important role in the control of motor functions therefore it is important to incorporate examination of cognitive functions in the early geriatric diagnosis.

  15. Axonal Membranes and Their Domains: Assembly and Function of the Axon Initial Segment and Node of Ranvier

    Directory of Open Access Journals (Sweden)

    Andrew D. Nelson

    2017-05-01

    Full Text Available Neurons are highly specialized cells of the nervous system that receive, process and transmit electrical signals critical for normal brain function. Here, we review the intricate organization of axonal membrane domains that facilitate rapid action potential conduction underlying communication between complex neuronal circuits. Two critical excitable domains of vertebrate axons are the axon initial segment (AIS and the nodes of Ranvier, which are characterized by the high concentrations of voltage-gated ion channels, cell adhesion molecules and specialized cytoskeletal networks. The AIS is located at the proximal region of the axon and serves as the site of action potential initiation, while nodes of Ranvier, gaps between adjacent myelin sheaths, allow rapid propagation of the action potential through saltatory conduction. The AIS and nodes of Ranvier are assembled by ankyrins, spectrins and their associated binding partners through the clustering of membrane proteins and connection to the underlying cytoskeleton network. Although the AIS and nodes of Ranvier share similar protein composition, their mechanisms of assembly are strikingly different. Here we will cover the mechanisms of formation and maintenance of these axonal excitable membrane domains, specifically highlighting the similarities and differences between them. We will also discuss recent advances in super resolution fluorescence imaging which have elucidated the arrangement of the submembranous axonal cytoskeleton revealing a surprising structural organization necessary to maintain axonal organization and function. Finally, human mutations in axonal domain components have been associated with a growing number of neurological disorders including severe cognitive dysfunction, epilepsy, autism, neurodegenerative diseases and psychiatric disorders. Overall, this review highlights the assembly, maintenance and function of axonal excitable domains, particularly the AIS and nodes of

  16. Conformational Dynamics of the Focal Adhesion Targeting Domain Control Specific Functions of Focal Adhesion Kinase in Cells

    KAUST Repository

    Kadaré, Gress

    2015-01-02

    Focal adhesion (FA) kinase (FAK) regulates cell survival and motility by transducing signals from membrane receptors. The C-terminal FA targeting (FAT) domain of FAK fulfils multiple functions, including recruitment to FAs through paxillin binding. Phosphorylation of FAT on Tyr925 facilitates FA disassembly and connects to the MAPK pathway through Grb2 association, but requires dissociation of the first helix (H1) of the four-helix bundle of FAT. We investigated the importance of H1 opening in cells by comparing the properties of FAK molecules containing wild-type or mutated FAT with impaired or facilitated H1 openings. These mutations did not alter the activation of FAK, but selectively affected its cellular functions, including self-association, Tyr925 phosphorylation, paxillin binding, and FA targeting and turnover. Phosphorylation of Tyr861, located between the kinase and FAT domains, was also enhanced by the mutation that opened the FAT bundle. Similarly phosphorylation of Ser910 by ERK in response to bombesin was increased by FAT opening. Although FAK molecules with the mutation favoring FAT opening were poorly recruited at FAs, they efficiently restored FA turnover and cell shape in FAK-deficient cells. In contrast, the mutation preventing H1 opening markedly impaired FAK function. Our data support the biological importance of conformational dynamics of the FAT domain and its functional interactions with other parts of the molecule.

  17. Multi-functional roles for the polypeptide transport associated domains of Toc75 in chloroplast protein import

    Science.gov (United States)

    Paila, Yamuna D; Richardson, Lynn GL; Inoue, Hitoshi; Parks, Elizabeth S; McMahon, James; Inoue, Kentaro; Schnell, Danny J

    2016-01-01

    Toc75 plays a central role in chloroplast biogenesis in plants as the membrane channel of the protein import translocon at the outer envelope of chloroplasts (TOC). Toc75 is a member of the Omp85 family of bacterial and organellar membrane insertases, characterized by N-terminal POTRA (polypeptide-transport associated) domains and C-terminal membrane-integrated β-barrels. We demonstrate that the Toc75 POTRA domains are essential for protein import and contribute to interactions with TOC receptors, thereby coupling preprotein recognition at the chloroplast surface with membrane translocation. The POTRA domains also interact with preproteins and mediate the recruitment of molecular chaperones in the intermembrane space to facilitate membrane transport. Our studies are consistent with the multi-functional roles of POTRA domains observed in other Omp85 family members and demonstrate that the domains of Toc75 have evolved unique properties specific to the acquisition of protein import during endosymbiotic evolution of the TOC system in plastids. DOI: http://dx.doi.org/10.7554/eLife.12631.001 PMID:26999824

  18. Self-reported Physical Activity Predicts Pain Inhibitory and Facilitatory Function

    Science.gov (United States)

    Naugle, Kelly M.; Riley, Joseph L.

    2013-01-01

    Considerable evidence suggests regular physical activity can reduce chronic pain symptoms. Dysfunction of endogenous facilitatory and inhibitory systems has been implicated in multiple chronic pain conditions. However, few studies have investigated the relationship between levels of physical activity and descending pain modulatory function. Purpose This study’s purpose was to determine whether self-reported levels of physical activity in healthy adults predicted 1) pain sensitivity to heat and cold stimuli, 2) pain facilitatory function as tested by temporal summation of pain (TS), and 3) pain inhibitory function as tested by conditioned pain modulation (CPM) and offset analgesia. Methods Forty-eight healthy adults (age range 18–76) completed the International Physical Activity Questionnaire (IPAQ) and the following pain tests: heat pain thresholds (HPT), heat pain suprathresholds, cold pressor pain (CPP), temporal summation of heat pain, conditioned pain modulation, and offset analgesia. The IPAQ measured levels of walking, moderate, vigorous and total physical activity over the past seven days. Hierarchical linear regressions were conducted to determine the relationship between each pain test and self-reported levels of physical activity, while controlling for age, sex and psychological variables. Results Self-reported total and vigorous physical activity predicted TS and CPM (p’s pain and greater CPM. The IPAQ measures did not predict any of the other pain measures. Conclusion Thus, these results suggest that healthy older and younger adults who self-report greater levels of vigorous and total physical activity exhibit enhanced descending pain modulatory function. Improved descending pain modulation may be a mechanism through which exercise reduces or prevents chronic pain symptoms. PMID:23899890

  19. Functional analysis of the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jung Hwan; Choi, Yoo Jin; Choi, Won Suk; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang, E-mail: wonsang@catholic.ac.kr

    2013-11-01

    Highlights: •NH{sub 2}-terminal and BRICHOS domain of GKN1 inhibited tumor cell growth. •NH{sub 2}-terminal and BRICHOS domain of GKN1 regulated cell cycle. •NH{sub 2}-terminal and BRICHOS domain of GKN1 inhibited epigenetic regulators. -- Abstract: Gastrokine 1 (GKN1) protects the gastric antral mucosa and promotes healing by facilitating restitution and proliferation after injury. GKN1 is down-regulated in Helicobacter pylori-infected gastric epithelial cells and loss of GKN1 expression is tightly associated with gastric carcinogenesis. However, the underlying mechanisms as a tumor suppressor are largely unknown. Presently, the hydrophobic region and BRICHOS domain of GKN1, pGKN1{sup D13N}, pGKN1{sup Δ68–199}, and pGKN1{sup Δ1–67,165–199} were shown to suppress gastric cancer cell growth and recapitulate GKN1 functions. As well, the hydrophobic region and BRICHOS domain of GKN1 had a synergistic anti-cancer effect with 5-FU on tumor cell growth, implying that the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1 are sufficient for tumor suppression, thereby suggesting a therapeutic intervention for gastric cancer. Also, its domain inducing endogenous miR-185 directly targeted the epigenetic effectors DNMT1 and EZH2 in gastric cancer cells. Our results suggest that the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1 are sufficient for its tumor suppressor activities.

  20. Effects of physical exercise programs on cognitive function in Parkinson's disease patients: A systematic review of randomized controlled trials of the last 10 years.

    Science.gov (United States)

    da Silva, Franciele Cascaes; Iop, Rodrigo da Rosa; de Oliveira, Laiana Cândido; Boll, Alice Mathea; de Alvarenga, José Gustavo Souza; Gutierres Filho, Paulo José Barbosa; de Melo, Lídia Mara Aguiar Bezerra; Xavier, André Junqueira; da Silva, Rudney

    2018-01-01

    Given the relative importance of cognitive impairment, there was considerable interest in identifying the cognitive profile of PD patients, in order to ensure specific and appropriate therapeutic interventions. To determine the effects of physical exercise programs on cognitive function in PD patients, compared with the control group. Medline, Cochrane, Scopus, PEDro and Web of Science (last searched in September 2016). Randomized clinical trials examining the effects of physical exercise programs and cognitive function in PD patients. Nine studies fulfilled the selection criteria and were included in this review. Characteristics of the publication, characteristics of the participants, test used for cognitive screening, cognitive domain assessed, tools used to assess cognitive function, characteristics of the experimental intervention, characteristics of the control group, mean results and standard deviation of function cognitive. The PEDro score was used to evaluate methodological quality. Most eligible studies showed good methodological quality based on the PEDro scale. Studies have shown that adapted tango for PD patients, cognitive training combined with motor training, and treadmill training promote the preservation or improvement of cognitive function in PD patients. The diversity of cognitive tests used to assess cognitive function and the high heterogeneity identified between the physical exercise programs. Physical exercise programs promote positive and significant effects on global cognitive function, processing speed, sustained attention and mental flexibility in PD patients, at a mild to moderate stage for patients with a 6-year clinical diagnosis of PD. However, treadmill training performed 3 times a week for about 60 minutes and for a period of 24 weeks produced larger improvements in cognition.

  1. Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in Azospirillum brasilense Sp7.

    Science.gov (United States)

    Gullett, Jessica M; Bible, Amber; Alexandre, Gladys

    2017-07-01

    Chemotaxis is the movement of cells in response to gradients of diverse chemical cues. Motile bacteria utilize a conserved chemotaxis signal transduction system to bias their motility and navigate through a gradient. A central regulator of chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with membrane-bound receptors, which assemble into large polar arrays, to propagate the signal. In the alphaproteobacterium Azospirillum brasilense , Che1 controls transient increases in swimming speed during chemotaxis, but it also biases the cell length at division. However, the exact underlying molecular mechanisms for Che1-dependent control of multiple cellular behaviors are not known. Here, we identify specific domains of the CheA1 histidine kinase implicated in modulating each of these functions. We show that CheA1 is produced in two isoforms: a membrane-anchored isoform produced as a fusion with a conserved seven-transmembrane domain of unknown function (TMX) at the N terminus and a soluble isoform similar to prototypical CheA. Site-directed and deletion mutagenesis combined with behavioral assays confirm the role of CheA1 in chemotaxis and implicate the TMX domain in mediating changes in cell length. Fluorescence microscopy further reveals that the membrane-anchored isoform is distributed around the cell surface while the soluble isoform localizes at the cell poles. Together, the data provide a mechanism for the role of Che1 in controlling multiple unrelated cellular behaviors via acquisition of a new domain in CheA1 and production of distinct functional isoforms. IMPORTANCE Chemotaxis provides a significant competitive advantage to bacteria in the environment, and this function has been transferred laterally multiple times, with evidence of functional divergence in different genomic contexts. The molecular principles that underlie functional diversification of chemotaxis in various genomic contexts are unknown. Here, we provide a molecular

  2. Roland-Morris Disability Questionnaire and Oswestry Disability Index: Which Has Better Measurement Properties for Measuring Physical Functioning in Nonspecific Low Back Pain? Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Chiarotto, Alessandro; Maxwell, Lara J; Terwee, Caroline B; Wells, George A; Tugwell, Peter; Ostelo, Raymond W

    2016-10-01

    Physical functioning is a core outcome domain to be measured in nonspecific low back pain (NSLBP). A panel of experts recommended the Roland-Morris Disability Questionnaire (RMDQ) and Oswestry Disability Index (ODI) to measure this domain. The original 24-item RMDQ and ODI 2.1a are recommended by their developers. The purpose of this study was to evaluate whether the 24-item RMDQ or the ODI 2.1a has better measurement properties than the other to measure physical functioning in adult patients with NSLBP. Bibliographic databases (MEDLINE, Embase, CINAHL, SportDiscus, PsycINFO, and Google Scholar), references of existing reviews, and citation tracking were the data sources. Two reviewers selected studies performing a head-to-head comparison of measurement properties (reliability, validity, and responsiveness) of the 2 questionnaires. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to assess the methodological quality of these studies. The studies' characteristics and results were extracted by 2 reviewers. A meta-analysis was conducted when there was sufficient clinical and methodological homogeneity among studies. Nine articles were included, for a total of 11 studies assessing 5 measurement properties. All studies were classified as having poor or fair methodological quality. The ODI displayed better test-retest reliability and smaller measurement error, whereas the RMDQ presented better construct validity as a measure of physical functioning. There was conflicting evidence for both instruments regarding responsiveness and inconclusive evidence for internal consistency. The results of this review are not generalizable to all available versions of these questionnaires or to patients with specific causes for their LBP. Based on existing head-to-head comparison studies, there are no strong reasons to prefer 1 of these 2 instruments to measure physical functioning in patients with NSLBP, but studies of higher

  3. Associating Physical Activity Levels with Motor Performance and Physical Function in Childhood Survivors of Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Hung, Stanley H; Rankin, Anne; Virji-Babul, Naznin; Pritchard, Sheila; Fryer, Christopher; Campbell, Kristin L

    2017-01-01

    Purpose: This cross-sectional, observational study investigated whether physical activity (PA) levels are associated with motor performance and physical function in children after treatment for acute lymphoblastic leukemia (ALL). Method: Participants aged 8-13 years who had completed treatment for ALL (3-36 months post-treatment) were tested at their oncology long-term follow-up appointment at the British Columbia Children's Hospital. PA level was measured using the Physical Activity Questionnaire for Older Children (PAQ-C). Motor performance was measured using the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, Short Form (BOT-2 SF), and physical function was measured using the 6-minute walk test (6MWT). Results: Thirteen children completed testing. PAQ-C scores were not associated with BOT-2 SF or 6MWT performance. Eleven children (85%) performed below the norm for the 6MWT. Children with elevated body mass index had poorer 6MWT but similar PAQ-C scores. Conclusion: PA was not found to be associated with motor performance and physical function. Participants who were overweight or obese had poorer 6MWT performance, which may indicate the need for closer monitoring of post-treatment weight status and physical function in the oncology follow-up setting.

  4. Characterisation of Physical Frailty and Associated Physical and Functional Impairments in Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Ma Shwe Zin Nyunt

    2017-12-01

    Full Text Available ObjectiveTo characterize the physical frailty phenotype and its associated physical and functional impairments in mild cognitive impairment (MCI.MethodParticipants with MCI (N = 119, normal low cognition (NLC, N = 138, and normal high cognition (NHC, N = 1,681 in the Singapore Longitudinal Ageing Studies (SLAS-2 were compared on the prevalence of physical frailty, low lean body mass, weakness, slow gait, exhaustion and low physical activity, and POMA balance and gait impairment and fall risk.ResultsThere were significantly higher prevalence of frailty in MCI (18.5%, than in NLC (8.0% and NHC (3.9%, and pre-frailty in MCI (54.6%, NLC (52.9% than in NHC (48.0%. Age, sex, and ethnicity-adjusted OR (95% CI of association with MCI (versus NHC for frailty were 4.65 (2.40–9.04 and for pre-frailty, 1.67 (1.07–2.61. Similar significantly elevated prevalence and adjusted ORs of association with MCI were observed for frailty-associated physical and functional impairments. Further adjustment for education, marital status, living status, comorbidities, and GDS significantly reduced the OR estimates. However, the OR estimates remained elevated for frailty: 3.86 (1.83–8.17, low body mass: 1.70 (1.08–2.67, slow gait: 1.84 (1.17–2.89, impaired gait: 4.17 (1.98–8.81, and elevated fall risk 3.42 (1.22–9.53.ConclusionTwo-thirds of MCI were physically frail or pre-frail, most uniquely due to low lean muscle mass, slow gait speed, or balance and gait impairment. The close associations of frailty and physical and functional impairment with MCI have important implications for improving diagnostic acuity of MCI and targetting interventions among cognitively frail individuals to prevent dementia and disability.

  5. Role of the transmembrane domain of FXYD7 in structural and functional interactions with Na,K-ATPase.

    Science.gov (United States)

    Li, Ciming; Crambert, Gilles; Thuillard, Delphine; Roy, Sophie; Schaer, Danièle; Geering, Käthi

    2005-12-30

    Members of the FXYD family are tissue-specific regulators of the Na,K-ATPase. Here, we have investigated the contribution of amino acids in the transmembrane (TM) domain of FXYD7 to the interaction with Na,K-ATPase. Twenty amino acids of the TM domain were replaced individually by tryptophan, and combined mutations and alanine insertion mutants were constructed. Wild type and mutant FXYD7 were expressed in Xenopus oocytes with Na,K-ATPase. Mutational effects on the stable association with Na,K-ATPase and on the functional regulation of Na,K-ATPase were determined by co-immunoprecipitation and two-electrode voltage clamp techniques, respectively. Most residues important for the structural and functional interaction of FXYD7 are clustered in a face of the TM helix containing the two conserved glycine residues, but others are scattered over two-thirds of the FXYD TM helix. Ile-35, Ile-43, and Ile-44 are only involved in the stable association with Na,K-ATPase. Glu-26, Met-30, and Ile-44 are important for the functional effect and/or the efficient association of FXYD7 with Na,K-ATPase, consistent with the prediction that these amino acids contact TM domain 9 of the alpha subunit (Li, C., Grosdidier, A., Crambert, G., Horisberger, J.-D., Michielin, O., and Geering, K. (2004) J. Biol. Chem. 279, 38895-38902). Several amino acids that are not implicated in the efficient association of FXYD7 with the Na,K-ATPase are specifically involved in the functional effect of FXYD7. Leu-32 and Phe-37 influence the apparent affinity for external K+, whereas Val-28 and Ile-42 are implicated in the apparent affinity for both external K+ and external Na+. These amino acids act in a synergistic way. These results highlight the important structural and functional role of the TM domain of FXYD7 and delineate the determinants that mediate the complex interactions of FXYD7 with Na,K-ATPase.

  6. Functional Equivalence of Retroviral MA Domains in Facilitating Psi RNA Binding Specificity by Gag

    Directory of Open Access Journals (Sweden)

    Tiffiny Rye-McCurdy

    2016-09-01

    Full Text Available Retroviruses specifically package full-length, dimeric genomic RNA (gRNA even in the presence of a vast excess of cellular RNA. The “psi” (Ψ element within the 5′-untranslated region (5′UTR of gRNA is critical for packaging through interaction with the nucleocapsid (NC domain of Gag. However, in vitro Gag binding affinity for Ψ versus non-Ψ RNAs is not significantly different. Previous salt-titration binding assays revealed that human immunodeficiency virus type 1 (HIV-1 Gag bound to Ψ RNA with high specificity and relatively few charge interactions, whereas binding to non-Ψ RNA was less specific and involved more electrostatic interactions. The NC domain was critical for specific Ψ binding, but surprisingly, a Gag mutant lacking the matrix (MA domain was less effective at discriminating Ψ from non-Ψ RNA. We now find that Rous sarcoma virus (RSV Gag also effectively discriminates RSV Ψ from non-Ψ RNA in a MA-dependent manner. Interestingly, Gag chimeras, wherein the HIV-1 and RSV MA domains were swapped, maintained high binding specificity to cognate Ψ RNAs. Using Ψ RNA mutant constructs, determinants responsible for promoting high Gag binding specificity were identified in both systems. Taken together, these studies reveal the functional equivalence of HIV-1 and RSV MA domains in facilitating Ψ RNA selectivity by Gag, as well as Ψ elements that promote this selectivity.

  7. Changes in working conditions and physical health functioning among midlife and ageing employees.

    Science.gov (United States)

    Mänty, Minna; Kouvonen, Anne; Lallukka, Tea; Lahti, Jouni; Lahelma, Eero; Rahkonen, Ossi

    2015-11-01

    The aim this study was to examine the effect of changes in physical and psychosocial working conditions on physical health functioning among ageing municipal employees. Follow-up survey data were collected from midlife employees of the City of Helsinki, Finland, at three time points: wave 1 (2000-2002), wave 2 (2007), and wave 3 (2012). Changes in physical and psychosocial working conditions were assessed between waves 1 and 2. Physical health functioning was measured by the physical component summary (PCS) of the Short-Form 36 questionnaire at each of the three waves. In total, 2784 respondents (83% women) who remained employed over the follow-up were available for the analyses. Linear mixed-effect models were used to assess the associations and adjust for key covariates (age, gender, obesity, chronic diseases, and health behaviors). Repeated and increased exposure to adverse physical working conditions was associated with greater decline in physical health functioning over time. In contrast, decrease in exposures reduced the decline. Of the psychosocial working conditions, changes in job demands had no effects on physical health functioning. However, decreased job control was associated with greater decline and repeated high or increased job control reduced the decline in physical health functioning over time. Adverse changes in physical working conditions and job control were associated with greater decline in physical health functioning over time, whereas favorable changes in these exposures reduced the decline. Preventing deterioration and promoting improvement of working conditions are likely to help maintain better physical health functioning among ageing employees.

  8. Structure-function analysis of the OB and latch domains of chlorella virus DNA ligase.

    Science.gov (United States)

    Samai, Poulami; Shuman, Stewart

    2011-06-24

    Chlorella virus DNA ligase (ChVLig) is a minimized eukaryal ATP-dependent DNA sealing enzyme with an intrinsic nick-sensing function. ChVLig consists of three structural domains, nucleotidyltransferase (NTase), OB-fold, and latch, that envelop the nicked DNA as a C-shaped protein clamp. The OB domain engages the DNA minor groove on the face of the duplex behind the nick, and it makes contacts to amino acids in the NTase domain surrounding the ligase active site. The latch module occupies the DNA major groove flanking the nick. Residues at the tip of the latch contact the NTase domain to close the ligase clamp. Here we performed a structure-guided mutational analysis of the OB and latch domains. Alanine scanning defined seven individual amino acids as essential in vivo (Lys-274, Arg-285, Phe-286, and Val-288 in the OB domain; Asn-214, Phe-215, and Tyr-217 in the latch), after which structure-activity relations were clarified by conservative substitutions. Biochemical tests of the composite nick sealing reaction and of each of the three chemical steps of the ligation pathway highlighted the importance of Arg-285 and Phe-286 in the catalysis of the DNA adenylylation and phosphodiester synthesis reactions. Phe-286 interacts with the nick 5'-phosphate nucleotide and the 3'-OH base pair and distorts the DNA helical conformation at the nick. Arg-285 is a key component of the OB-NTase interface, where it forms a salt bridge to the essential Asp-29 side chain, which is imputed to coordinate divalent metal catalysts during the nick sealing steps.

  9. Structure-Function Analysis of the OB and Latch Domains of Chlorella Virus DNA Ligase*

    Science.gov (United States)

    Samai, Poulami; Shuman, Stewart

    2011-01-01

    Chlorella virus DNA ligase (ChVLig) is a minimized eukaryal ATP-dependent DNA sealing enzyme with an intrinsic nick-sensing function. ChVLig consists of three structural domains, nucleotidyltransferase (NTase), OB-fold, and latch, that envelop the nicked DNA as a C-shaped protein clamp. The OB domain engages the DNA minor groove on the face of the duplex behind the nick, and it makes contacts to amino acids in the NTase domain surrounding the ligase active site. The latch module occupies the DNA major groove flanking the nick. Residues at the tip of the latch contact the NTase domain to close the ligase clamp. Here we performed a structure-guided mutational analysis of the OB and latch domains. Alanine scanning defined seven individual amino acids as essential in vivo (Lys-274, Arg-285, Phe-286, and Val-288 in the OB domain; Asn-214, Phe-215, and Tyr-217 in the latch), after which structure-activity relations were clarified by conservative substitutions. Biochemical tests of the composite nick sealing reaction and of each of the three chemical steps of the ligation pathway highlighted the importance of Arg-285 and Phe-286 in the catalysis of the DNA adenylylation and phosphodiester synthesis reactions. Phe-286 interacts with the nick 5′-phosphate nucleotide and the 3′-OH base pair and distorts the DNA helical conformation at the nick. Arg-285 is a key component of the OB-NTase interface, where it forms a salt bridge to the essential Asp-29 side chain, which is imputed to coordinate divalent metal catalysts during the nick sealing steps. PMID:21527793

  10. Psychometric properties of the PROMIS Physical Function item bank in patients receiving physical therapy.

    Directory of Open Access Journals (Sweden)

    Martine H P Crins

    Full Text Available The Patient-Reported Outcomes Measurement Information System (PROMIS is a universally applicable set of instruments, including item banks, short forms and computer adaptive tests (CATs, measuring patient-reported health across different patient populations. PROMIS CATs are highly efficient and the use in practice is considered feasible with little administration time, offering standardized and routine patient monitoring. Before an item bank can be used as CAT, the psychometric properties of the item bank have to be examined. Therefore, the objective was to assess the psychometric properties of the Dutch-Flemish PROMIS Physical Function item bank (DF-PROMIS-PF in Dutch patients receiving physical therapy.Cross-sectional study.805 patients >18 years, who received any kind of physical therapy in primary care in the past year, completed the full DF-PROMIS-PF (121 items.Unidimensionality was examined by Confirmatory Factor Analysis and local dependence and monotonicity were evaluated. A Graded Response Model was fitted. Construct validity was examined with correlations between DF-PROMIS-PF T-scores and scores on two legacy instruments (SF-36 Health Survey Physical Functioning scale [SF36-PF10] and the Health Assessment Questionnaire Disability-Index [HAQ-DI]. Reliability (standard errors of theta was assessed.The results for unidimensionality were mixed (scaled CFI = 0.924, TLI = 0.923, RMSEA = 0.045, 1th factor explained 61.5% of variance. Some local dependence was found (8.2% of item pairs. The item bank showed a broad coverage of the physical function construct (threshold-parameters range: -4.28-2.33 and good construct validity (correlation with SF36-PF10 = 0.84 and HAQ-DI = -0.85. Furthermore, the DF-PROMIS-PF showed greater reliability over a broader score-range than the SF36-PF10 and HAQ-DI.The psychometric properties of the DF-PROMIS-PF item bank are sufficient. The DF-PROMIS-PF can now be used as short forms or CAT to measure the level of

  11. Magnetic hysteresis at the domain scale of a multi-scale material model for magneto-elastic behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Vanoost, D., E-mail: dries.vanoost@kuleuven-kulak.be [KU Leuven Technology Campus Ostend, ReMI Research Group, Oostende B-8400 (Belgium); KU Leuven Kulak, Wave Propagation and Signal Processing Research Group, Kortrijk B-8500 (Belgium); Steentjes, S. [Institute of Electrical Machines, RWTH Aachen University, Aachen D-52062 (Germany); Peuteman, J. [KU Leuven Technology Campus Ostend, ReMI Research Group, Oostende B-8400 (Belgium); KU Leuven, Department of Electrical Engineering, Electrical Energy and Computer Architecture, Heverlee B-3001 (Belgium); Gielen, G. [KU Leuven, Department of Electrical Engineering, Microelectronics and Sensors, Heverlee B-3001 (Belgium); De Gersem, H. [KU Leuven Kulak, Wave Propagation and Signal Processing Research Group, Kortrijk B-8500 (Belgium); TU Darmstadt, Institut für Theorie Elektromagnetischer Felder, Darmstadt D-64289 (Germany); Pissoort, D. [KU Leuven Technology Campus Ostend, ReMI Research Group, Oostende B-8400 (Belgium); KU Leuven, Department of Electrical Engineering, Microelectronics and Sensors, Heverlee B-3001 (Belgium); Hameyer, K. [Institute of Electrical Machines, RWTH Aachen University, Aachen D-52062 (Germany)

    2016-09-15

    This paper proposes a multi-scale energy-based material model for poly-crystalline materials. Describing the behaviour of poly-crystalline materials at three spatial scales of dominating physical mechanisms allows accounting for the heterogeneity and multi-axiality of the material behaviour. The three spatial scales are the poly-crystalline, grain and domain scale. Together with appropriate scale transitions rules and models for local magnetic behaviour at each scale, the model is able to describe the magneto-elastic behaviour (magnetostriction and hysteresis) at the macroscale, although the data input is merely based on a set of physical constants. Introducing a new energy density function that describes the demagnetisation field, the anhysteretic multi-scale energy-based material model is extended to the hysteretic case. The hysteresis behaviour is included at the domain scale according to the micro-magnetic domain theory while preserving a valid description for the magneto-elastic coupling. The model is verified using existing measurement data for different mechanical stress levels. - Highlights: • A ferromagnetic hysteretic energy-based multi-scale material model is proposed. • The hysteresis is obtained by new proposed hysteresis energy density function. • Avoids tedious parameter identification.

  12. Adiposity, physical activity, and muscle quality are independently related to physical function performance in middle-aged postmenopausal women.

    Science.gov (United States)

    Ward-Ritacco, Christie L; Adrian, Amanda L; Johnson, Mary Ann; Rogers, Laura Q; Evans, Ellen M

    2014-10-01

    Poor physical function performance is associated with risks for disability in late life; however, determinants of physical function are not well characterized in middle-aged women. The aim of this cross-sectional study was to examine the contributions of body composition, physical activity, muscle capacity, and muscle quality to physical function performance. Postmenopausal women (N = 64; mean [SD] age, 58.6 [3.6] y) were assessed for body composition via dual-energy x-ray absorptiometry, for physical activity via accelerometer (steps per day), and for physical function via Timed Up and Go, 30-second chair stand, and 6-minute walk. Leg strength was assessed using isokinetic dynamometry at 60° second. Leg power was assessed with the Nottingham Leg Extensor Power Rig. Muscle quality was calculated as (1) the ratio of leg strength at 60° second to upper leg lean mass and (2) the ratio of leg power to total lower body lean mass. Regression analyses revealed the following: (1) age and muscle quality calculated with leg power are independently related to Timed Up and Go, explaining 12% and 11% of the variance, respectively (P quality calculated with leg strength are independently related to 30-second chair stand, explaining 12% and 10% of the variance, respectively (P quality calculated with leg strength, steps per day, and adiposity are independent predictors of 6-minute walk, collectively explaining 51% of the variance. In postmenopausal women, a more optimal body composition (including lower adiposity and higher lean mass) and higher levels of physical activity are associated with better physical function performance at midlife.

  13. Influence of diabetes on physical function among the elderly persons

    Directory of Open Access Journals (Sweden)

    Farzana Tabassum

    2009-07-01

    Full Text Available There is growing recognition that the complications associated with type-2 diabetes may translate into functional impairments in older people.This cross sectional study was conducted between January and June 2008 to determine the influence of diabetes on physical functions in an elderly (³55 years population. Fifty-five elderly diabetics attending the out-patient department of a diabetic centre were selected by convenient sampling and compared with fifty-five non-diabetic elderly persons of the near-by community. Their physical functions were assessed by Barthel Index, SF-36 Health Survey and Modified Physical Performance test. Diabetic elderly persons, on average, obtained lower scores in all these three tests. After removing the effect of socio-demographic variables, influence of diabetes on level of independence measured by Barthel Index did not persist. However, the difference in SF-36 health survey and Modified Physical Performance test scores between diabetics and non-diabetics remained significant after controlling for socio-demographic variables. The current study showed influence of diabetes on physical functions in the elderly. People should be motivated and guided properly to practice a healthy lifestyle in order to prevent and control diabetes and thus avoid complications of diabetes mellitus and disabilities in later life. Ibrahim Med. Coll. J. 2009; 3(2: 45-49

  14. Structure determination of the functional domain interaction of a chimeric nonribosomal peptide synthetase from a challenging crystal with noncrystallographic translational symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Sundlov, Jesse A.; Gulick, Andrew M., E-mail: gulick@hwi.buffalo.edu [University at Buffalo, 700 Ellicott Street, Buffalo, NY 14203 (United States)

    2013-08-01

    The structure of the functional interaction of NRPS adenylation and carrier protein domains, trapped with a mechanism-based inhibitor, is described. Crystals exhibit translational non-crystallographic symmetry, which challenged structure determination and refinement. The nonribosomal peptide synthetases (NRPSs) are a family of modular proteins that contain multiple catalytic domains joined in a single protein. Together, these domains work to produce chemically diverse peptides, including compounds with antibiotic activity or that play a role in iron acquisition. Understanding the structural mechanisms that govern the domain interactions has been a long-standing goal. During NRPS synthesis, amino-acid substrates are loaded onto integrated carrier protein domains through the activity of NRPS adenylation domains. The structures of two adenylation domain–carrier protein domain complexes have recently been determined in an effort that required the use of a mechanism-based inhibitor to trap the domain interaction. Here, the continued analysis of these proteins is presented, including a higher resolution structure of an engineered di-domain protein containing the EntE adenylation domain fused with the carrier protein domain of its partner EntB. The protein crystallized in a novel space group in which molecular replacement and refinement were challenged by noncrystallographic pseudo-translational symmetry. The structure determination and how the molecular packing impacted the diffraction intensities are reported. Importantly, the structure illustrates that in this new crystal form the functional interface between the adenylation domain and the carrier protein domain remains the same as that observed previously. At a resolution that allows inclusion of water molecules, additional interactions are observed between the two protein domains and between the protein and its ligands. In particular, a highly solvated region that surrounds the carrier protein cofactor is described.

  15. Structure determination of the functional domain interaction of a chimeric nonribosomal peptide synthetase from a challenging crystal with noncrystallographic translational symmetry

    International Nuclear Information System (INIS)

    Sundlov, Jesse A.; Gulick, Andrew M.

    2013-01-01

    The structure of the functional interaction of NRPS adenylation and carrier protein domains, trapped with a mechanism-based inhibitor, is described. Crystals exhibit translational non-crystallographic symmetry, which challenged structure determination and refinement. The nonribosomal peptide synthetases (NRPSs) are a family of modular proteins that contain multiple catalytic domains joined in a single protein. Together, these domains work to produce chemically diverse peptides, including compounds with antibiotic activity or that play a role in iron acquisition. Understanding the structural mechanisms that govern the domain interactions has been a long-standing goal. During NRPS synthesis, amino-acid substrates are loaded onto integrated carrier protein domains through the activity of NRPS adenylation domains. The structures of two adenylation domain–carrier protein domain complexes have recently been determined in an effort that required the use of a mechanism-based inhibitor to trap the domain interaction. Here, the continued analysis of these proteins is presented, including a higher resolution structure of an engineered di-domain protein containing the EntE adenylation domain fused with the carrier protein domain of its partner EntB. The protein crystallized in a novel space group in which molecular replacement and refinement were challenged by noncrystallographic pseudo-translational symmetry. The structure determination and how the molecular packing impacted the diffraction intensities are reported. Importantly, the structure illustrates that in this new crystal form the functional interface between the adenylation domain and the carrier protein domain remains the same as that observed previously. At a resolution that allows inclusion of water molecules, additional interactions are observed between the two protein domains and between the protein and its ligands. In particular, a highly solvated region that surrounds the carrier protein cofactor is described

  16. BLUES function method in computational physics

    Science.gov (United States)

    Indekeu, Joseph O.; Müller-Nedebock, Kristian K.

    2018-04-01

    We introduce a computational method in physics that goes ‘beyond linear use of equation superposition’ (BLUES). A BLUES function is defined as a solution of a nonlinear differential equation (DE) with a delta source that is at the same time a Green’s function for a related linear DE. For an arbitrary source, the BLUES function can be used to construct an exact solution to the nonlinear DE with a different, but related source. Alternatively, the BLUES function can be used to construct an approximate piecewise analytical solution to the nonlinear DE with an arbitrary source. For this alternative use the related linear DE need not be known. The method is illustrated in a few examples using analytical calculations and numerical computations. Areas for further applications are suggested.

  17. Multifunctional G-rich and RRM-containing domains of TbRGG2 perform separate yet essential functions in trypanosome RNA editing.

    Science.gov (United States)

    Foda, Bardees M; Downey, Kurtis M; Fisk, John C; Read, Laurie K

    2012-09-01

    Efficient editing of Trypanosoma brucei mitochondrial RNAs involves the actions of multiple accessory factors. T. brucei RGG2 (TbRGG2) is an essential protein crucial for initiation and 3'-to-5' progression of editing. TbRGG2 comprises an N-terminal G-rich region containing GWG and RG repeats and a C-terminal RNA recognition motif (RRM)-containing domain. Here, we perform in vitro and in vivo separation-of-function studies to interrogate the mechanism of TbRGG2 action in RNA editing. TbRGG2 preferentially binds preedited mRNA in vitro with high affinity attributable to its G-rich region. RNA-annealing and -melting activities are separable, carried out primarily by the G-rich and RRM domains, respectively. In vivo, the G-rich domain partially complements TbRGG2 knockdown, but the RRM domain is also required. Notably, TbRGG2's RNA-melting activity is dispensable for RNA editing in vivo. Interactions between TbRGG2 and MRB1 complex proteins are mediated by both G-rich and RRM-containing domains, depending on the binding partner. Overall, our results are consistent with a model in which the high-affinity RNA binding and RNA-annealing activities of the G-rich domain are essential for RNA editing in vivo. The RRM domain may have key functions involving interactions with the MRB1 complex and/or regulation of the activities of the G-rich domain.

  18. Structure of a Novel DNA-binding Domain of Helicase-like Transcription Factor (HLTF) and Its Functional Implication in DNA Damage Tolerance.

    Science.gov (United States)

    Hishiki, Asami; Hara, Kodai; Ikegaya, Yuzu; Yokoyama, Hideshi; Shimizu, Toshiyuki; Sato, Mamoru; Hashimoto, Hiroshi

    2015-05-22

    HLTF (helicase-like transcription factor) is a yeast RAD5 homolog found in mammals. HLTF has E3 ubiquitin ligase and DNA helicase activities, and plays a pivotal role in the template-switching pathway of DNA damage tolerance. HLTF has an N-terminal domain that has been designated the HIRAN (HIP116 and RAD5 N-terminal) domain. The HIRAN domain has been hypothesized to play a role in DNA binding; however, the structural basis of, and functional evidence for, the HIRAN domain in DNA binding has remained unclear. Here we show for the first time the crystal structure of the HIRAN domain of human HLTF in complex with DNA. The HIRAN domain is composed of six β-strands and two α-helices, forming an OB-fold structure frequently found in ssDNA-binding proteins, including in replication factor A (RPA). Interestingly, this study reveals that the HIRAN domain interacts with not only with a single-stranded DNA but also with a duplex DNA. Furthermore, the structure unexpectedly clarifies that the HIRAN domain specifically recognizes the 3'-end of DNA. These results suggest that the HIRAN domain functions as a sensor to the 3'-end of the primer strand at the stalled replication fork and that the domain facilitates fork regression. HLTF is recruited to a damaged site through the HIRAN domain at the stalled replication fork. Furthermore, our results have implications for the mechanism of template switching. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Regular growth of systems of functions and systems of non-homogeneous convolution equations in convex domains of the complex plane

    International Nuclear Information System (INIS)

    Krivosheev, A S

    2000-01-01

    In this paper we introduce the notion of regular growth for a system of entire functions of finite order and type. This is a direct and natural generalization of the classical completely regular growth of an entire function. We obtain sufficient and necessary conditions for the solubility of a system of non-homogeneous convolution equations in convex domains of the complex plane. These conditions depend on whether the system of Laplace transforms of the analytic functionals that generate the convolution equations has regular growth. In the case of smooth convex domains, these solubility conditions form a criterion

  20. Domains within domains and walls within walls: Evidence for polar domains in cryogenic SrTiO.sub.3./sub..

    Czech Academy of Sciences Publication Activity Database

    Salje, E.K.H.; Aktas, O.; Carpenter, M.A.; Laguta, Valentyn; Scott, J.F.

    2013-01-01

    Roč. 111, č. 24 (2013), "247603-1"-"247603-5" ISSN 0031-9007 Institutional support: RVO:68378271 Keywords : ferroelectric domains * SrTiO 3 * phase transition Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 7.728, year: 2013

  1. Effects of group exercise on functional abilities: Differences between physically active and physically inactive women.

    Science.gov (United States)

    Cokorilo, Nebojsa; Mikalacki, Milena; Satara, Goran; Cvetkovic, Milan; Marinkovic, Dragan; Zvekic-Svorcan, Jelena; Obradovic, Borislav

    2018-03-30

    Aerobic exercises to music can have a positive effect on functional and motor skills of an exerciser, their health, as well as an aesthetic and socio-psychological component. The objective of this study was to determine the effects of reactive exercising in a group on functional capabilities in physically active and physically inactive women. A prospective study included 64 healthy women aged 40-60 years. The sample was divided into the experimental group (n= 36), i.e. physically active women who have been engaged in recreational group exercises at the Faculty of Sport and Physical Education, University of Novi Sad, Serbia, and the control group (n= 28), which consisted of physically inactive women. All the participants were monitored using the same protocol before and after the implementation of the research. All women had their height, weight, body mass index measured as well as spiroergometric parameters determined according to the Bruce protocol. A univariate analysis of variance has shown that there is a statistically significant difference between the experimental group and the control group in maximum speed, the total duration of the test, relative oxygen consumption, absolute oxygen consumption and ventilation during the final measurement. After the training intervention, the experimental group showed improvements in all the parameters analyzed compared with pretest values. The recreational group exercise model significantly improves aerobic capacity and functioning of the cardiovascular system. Therefore, it is essential for women to be involved more in any form of recreational group exercising in order to improve functional capacity and health.

  2. Multiple functional self-association interfaces in plant TIR domains

    NARCIS (Netherlands)

    Zhang, Xiaoxiao; Bernoux, Maud; Bentham, Adam R; Newman, Toby E; Ve, Thomas; Casey, Lachlan W; Raaymakers, Tom M; Hu, Jian; Croll, Tristan I; Schreiber, Karl J; Staskawicz, Brian J; Anderson, Peter A; Sohn, Kee Hoon; Williams, Simon J; Dodds, Peter N; Kobe, Bostjan

    2017-01-01

    The self-association of Toll/interleukin-1 receptor/resistance protein (TIR) domains has been implicated in signaling in plant and animal immunity receptors. Structure-based studies identified different TIR-domain dimerization interfaces required for signaling of the plant nucleotide-binding

  3. Functional importance of conserved domains in the flowering-time gene CONSTANS demonstrated by analysis of mutant alleles and transgenic plants.

    Science.gov (United States)

    Robson, F; Costa, M M; Hepworth, S R; Vizir, I; Piñeiro, M; Reeves, P H; Putterill, J; Coupland, G

    2001-12-01

    CONSTANS promotes flowering of Arabidopsis in response to long-day conditions. We show that CONSTANS is a member of an Arabidopsis gene family that comprises 16 other members. The CO-Like proteins encoded by these genes contain two segments of homology: a zinc finger containing region near their amino terminus and a CCT (CO, CO-Like, TOC1) domain near their carboxy terminus. Analysis of seven classical co mutant alleles demonstrated that the mutations all occur within either the zinc finger region or the CCT domain, confirming that the two regions of homology are important for CO function. The zinc fingers are most similar to those of B-boxes, which act as protein-protein interaction domains in several transcription factors described in animals. Segments of CO protein containing the CCT domain localize GFP to the nucleus, but one mutation that affects the CCT domain delays flowering without affecting the nuclear localization function, suggesting that this domain has additional functions. All eight co alleles, including one recovered by pollen irradiation in which DNA encoding both B-boxes is deleted, are shown to be semidominant. This dominance appears to be largely due to a reduction in CO dosage in the heterozygous plants. However, some alleles may also actively delay flowering, because overexpression from the CaMV 35S promoter of the co-3 allele, that has a mutation in the second B-box, delayed flowering of wild-type plants. The significance of these observations for the role of CO in the control of flowering time is discussed.

  4. Inferring domain-domain interactions from protein-protein interactions with formal concept analysis.

    Directory of Open Access Journals (Sweden)

    Susan Khor

    Full Text Available Identifying reliable domain-domain interactions will increase our ability to predict novel protein-protein interactions, to unravel interactions in protein complexes, and thus gain more information about the function and behavior of genes. One of the challenges of identifying reliable domain-domain interactions is domain promiscuity. Promiscuous domains are domains that can occur in many domain architectures and are therefore found in many proteins. This becomes a problem for a method where the score of a domain-pair is the ratio between observed and expected frequencies because the protein-protein interaction network is sparse. As such, many protein-pairs will be non-interacting and domain-pairs with promiscuous domains will be penalized. This domain promiscuity challenge to the problem of inferring reliable domain-domain interactions from protein-protein interactions has been recognized, and a number of work-arounds have been proposed. This paper reports on an application of Formal Concept Analysis to this problem. It is found that the relationship between formal concepts provides a natural way for rare domains to elevate the rank of promiscuous domain-pairs and enrich highly ranked domain-pairs with reliable domain-domain interactions. This piggybacking of promiscuous domain-pairs onto less promiscuous domain-pairs is possible only with concept lattices whose attribute-labels are not reduced and is enhanced by the presence of proteins that comprise both promiscuous and rare domains.

  5. Inferring Domain-Domain Interactions from Protein-Protein Interactions with Formal Concept Analysis

    Science.gov (United States)

    Khor, Susan

    2014-01-01

    Identifying reliable domain-domain interactions will increase our ability to predict novel protein-protein interactions, to unravel interactions in protein complexes, and thus gain more information about the function and behavior of genes. One of the challenges of identifying reliable domain-domain interactions is domain promiscuity. Promiscuous domains are domains that can occur in many domain architectures and are therefore found in many proteins. This becomes a problem for a method where the score of a domain-pair is the ratio between observed and expected frequencies because the protein-protein interaction network is sparse. As such, many protein-pairs will be non-interacting and domain-pairs with promiscuous domains will be penalized. This domain promiscuity challenge to the problem of inferring reliable domain-domain interactions from protein-protein interactions has been recognized, and a number of work-arounds have been proposed. This paper reports on an application of Formal Concept Analysis to this problem. It is found that the relationship between formal concepts provides a natural way for rare domains to elevate the rank of promiscuous domain-pairs and enrich highly ranked domain-pairs with reliable domain-domain interactions. This piggybacking of promiscuous domain-pairs onto less promiscuous domain-pairs is possible only with concept lattices whose attribute-labels are not reduced and is enhanced by the presence of proteins that comprise both promiscuous and rare domains. PMID:24586450

  6. THEORETICAL RESEARCH ON HYDRODYNAMICS OF A GEOMETRIC SPAR IN FREQUENCY- AND TIME-DOMAINS

    Institute of Scientific and Technical Information of China (English)

    WANG Ying; YANG Jian-min; HU Zhi-qiang; XIAO Long-fei

    2008-01-01

    Considering the coupling effects of the vessel and its riser and mooring system, hydrodynamic analyses of a geometric spar were performed both in frequency- and time-domains. Based on the boundary element method, the 3-D panel model of the geometric spar and the related free water surface model were established, and the first-order and second-order difference-frequency wave loads and other hydrodynamic coefficients were calculated. Frequency domain analysis of the motion Response Amplitude Operators (RAO) and Quadratic Transfer Functions (QTF) and time domain analysis of the response series and spectra in an extreme wave condition were conducted for the coupled system with the mooring lines and risers involved. These analyses were further validated by the physical model test results.

  7. Switching of the positive feedback for RAS activation by a concerted function of SOS membrane association domains.

    Science.gov (United States)

    Nakamura, Yuki; Hibino, Kayo; Yanagida, Toshio; Sako, Yasushi

    2016-01-01

    Son of sevenless (SOS) is a guanine nucleotide exchange factor that regulates cell behavior by activating the small GTPase RAS. Recent in vitro studies have suggested that an interaction between SOS and the GTP-bound active form of RAS generates a positive feedback loop that propagates RAS activation. However, it remains unclear how the multiple domains of SOS contribute to the regulation of the feedback loop in living cells. Here, we observed single molecules of SOS in living cells to analyze the kinetics and dynamics of SOS behavior. The results indicate that the histone fold and Grb2-binding domains of SOS concertedly produce an intermediate state of SOS on the cell surface. The fraction of the intermediated state was reduced in positive feedback mutants, suggesting that the feedback loop functions during the intermediate state. Translocation of RAF, recognizing the active form of RAS, to the cell surface was almost abolished in the positive feedback mutants. Thus, the concerted functions of multiple membrane-associating domains of SOS governed the positive feedback loop, which is crucial for cell fate decision regulated by RAS.

  8. Rumors of transcendence in physics

    International Nuclear Information System (INIS)

    Pollard, W.G.

    1984-01-01

    There are several hints in physics of a domain of external reality transcendent to three-dimensional space and time. This paper calls attention to several of these intimations of a real world beyond the natural order. Examples are the complex state functions in configuration space of quantum mechanics, the singularity at the birth of the universe, the anthropic principle, the role of chance in evolution, and the unaccountable fruitfulness of mathematics for physics. None of these examples touch on the existence or activity of God, but they do suggest that external reality may be much richer than the natural world which it is the task of physics to describe

  9. Physical Performance Is Associated with Executive Functioning in Older African American Women

    Directory of Open Access Journals (Sweden)

    Brooke C. Schneider

    2011-01-01

    Full Text Available An older adult's ability to perform physical tasks is predictive of disability onset and is associated with declines in cognition. Risk factors for physical performance declines among African Americans, a group with the highest rates of disability, remain understudied. This study sought to identify demographic, health, and cognitive factors associated with lower-extremity physical performance in a sample of 106 African American women ages 56 to 91. After controlling for global cognitive functioning (Mini Mental State Exam, physical performance was associated with executive functioning (Stroop Color/Word, but not visuospatial construction (WASI Block Design or processing speed (Trail Making Test, Part A. Executive functioning remained associated with physical performance after entry of demographic variables, exercise, depression, disease burden, and body mass index (BMI. Age, and BMI were also significant in this model. Executive functioning, age and BMI are associated with lower-extremity physical performance among older African American women.

  10. Physical Fitness and Serum Vitamin D and Cognition in Elderly Koreans.

    Science.gov (United States)

    Ahn, Jeong-Deok; Kang, Hyunsik

    2015-12-01

    Poor physical fitness and low serum vitamin D are known to be modifiable risk factors for cognitive declines with normal aging. We investigated the association of physical fitness and serum vitamin D levels with global cognitive function in older adults. In this cross-sectional study, a total of 412 older Korean adults (108 men aged 74.4 ± 6.0 years and 304 women aged 73.1 ± 5.4 years) completed the Korean version of Mini-Mental State Examination (MMSE) to assess global cognitive performance and the senior fitness test to assess strength, flexibility, agility, and endurance domains of physical fitness. Body mass index, percent body fat, serum vitamin D, geriatric depression scale (GDS), level of education, smoking, and history of cardiovascular or cerebrovascular disease were also assessed as covariates. Age, sex, GDS, and body fatness were negatively associated with MMSE-based cognitive performance. Serum vitamin D and physical fitness were positively associated with MMSE-based cognitive performance. Multivariate linear regression showed that agility (partial R(2) = -0.184, p = 0.029) and endurance (partial R(2) = 0.191, p = 0.022) domains of physical fitness along with serum vitamin D (partial R(2) = 0.210, p = 0.012) were significant predictors for global cognitive performance after controlling for covariates (i.e., age, sex, education, GDS, body fatness, and comorbidity index). The current findings of the study suggest that promotion of physical fitness and vitamin D supplementation should be key components of interventions to prevent cognitive decline with normal aging. Key pointsCognitive declines are associated with normal aging as well as modifiable lifestyle risk factors, and there is an increasing need to identify the modifiable risk factors for the onset of cognitive declines and to provide evidence-based strategies for healthy and successful aging.In Korea, little is known about the relationships of physical fitness and serum vitamin D with cognitive

  11. Effect of Moderate to Vigorous Physical Activity Intervention on Improving Dementia Family Caregiver Physical Function: A Randomized Controlled Trial

    Science.gov (United States)

    Farran, Carol J; Etkin, Caryn D; Eisenstein, Amy; Paun, Olimpia; Rajan, Kumar B; Sweet, Cynthia M Castro; McCann, Judith J; Barnes, Lisa L; Shah, Raj C; Evans, Denis A

    2017-01-01

    Objective Alzheimer’s disease and related dementias (ADRD) affect more than five million Americans and their family caregivers. Caregiving creates challenges, may contribute to decreased caregiver health and is associated with $9.7 billion of caregiver health care costs. The purpose of this 12 month randomized clinical trial (RCT) was to examine if the Enhancing Physical Activity Intervention (EPAI), a moderate to vigorous physical activity (MVPA) treatment group, versus the Caregiver Skill Building Intervention (CSBI) control, would have greater: (1) MVPA adherence; and (2) physical function. Methods Caregivers were randomly assigned to EPAI or CSBI (N=211). MVPA was assessed using a self-report measure; and physical function was objectively assessed using two measures. Intention-to-treat analyses used descriptive, categorical and generalized estimating equations (GEE), with an exchangeable working correlation matrix and a log link, to examine main effects and interactions in change of MVPA and physical function over time. Results At 12 months, EPAI significantly increased MVPA (p=caregiving hours and use of formal services; while CSBI increased hours of caregiving (p=caregivers had difficulties completing physical function tests. Conclusion The EPAI had a stronger 12 month effect on caregiver MVPA and physical function, as well as maintaining stability of caregiving hours and formal service use; while CSBI increased caregiving hours and use of formal services. A study limitation included greater EPAI versus CSBI attrition. Future directions are proposed for dementia family caregiver physical activity research. PMID:28752016

  12. Cognitive function and the agreement between self-reported and accelerometer-accessed physical activity.

    Science.gov (United States)

    Herbolsheimer, Florian; Riepe, Matthias W; Peter, Richard

    2018-02-21

    Numerous studies have reported weak or moderate correlations between self-reported and accelerometer-assessed physical activity. One explanation is that self-reported physical activity might be biased by demographic, cognitive or other factors. Cognitive function is one factor that could be associated with either overreporting or underreporting of daily physical activity. Difficulties in remembering past physical activities might result in recall bias. Thus, the current study examines whether the cognitive function is associated with differences between self-reported and accelerometer-assessed physical activity. Cross-sectional data from the population-based Activity and Function in the Elderly in Ulm study (ActiFE) were used. A total of 1172 community-dwelling older adults (aged 65-90 years) wore a uniaxial accelerometer (activPAL unit) for a week. Additionally, self-reported physical activity was assessed using the LASA Physical Activity Questionnaire (LAPAQ). Cognitive function was measured with four items (immediate memory, delayed memory, recognition memory, and semantic fluency) from the Consortium to Establish a Registry for Alzheimer's Disease Total Score (CERAD-TS). Mean differences of self-reported and accelerometer-assessed physical activity (MPA) were associated with cognitive function in men (r s  = -.12, p = .002) but not in women. Sex-stratified multiple linear regression analyses showed that MPA declined with high cognitive function in men (β = -.13; p = .015). Results suggest that self-reported physical activity should be interpreted with caution in older populations, as cognitive function was one factor that explained the differences between objective and subjective physical activity measurements.

  13. Identification of functional domains of the IR2 protein of equine herpesvirus 1 required for inhibition of viral gene expression and replication

    International Nuclear Information System (INIS)

    Kim, Seong K.; Kim, Seongman; Dai Gan; Zhang Yunfei; Ahn, Byung C.; O'Callaghan, Dennis J.

    2011-01-01

    The equine herpesvirus 1 (EHV-1) negative regulatory IR2 protein (IR2P), an early 1,165-amino acid (aa) truncated form of the 1487-aa immediate-early protein (IEP), lacks the trans-activation domain essential for IEP activation functions but retains domains for binding DNA, TFIIB, and TBP and the nuclear localization signal. IR2P mutants of the N-terminal region which lack either DNA-binding activity or TFIIB-binding activity were unable to down-regulate EHV-1 promoters. In EHV-1-infected cells expressing full-length IR2P, transcription and protein expression of viral regulatory IE, early EICP0, IR4, and UL5, and late ETIF genes were dramatically inhibited. Viral DNA levels were reduced to 2.1% of control infected cells, but were vey weakly affected in cells that express the N-terminal 706 residues of IR2P. These results suggest that IR2P function requires the two N-terminal domains for binding DNA and TFIIB as well as the C-terminal residues 707 to 1116 containing the TBP-binding domain. - Highlights: → We examine the functional domains of IR2P that mediates negative regulation. → IR2P inhibits at the transcriptional level. → DNA-binding mutant or TFIIB-binding mutant fails to inhibit. → C-terminal aa 707 to 1116 are required for full inhibition. → Inhibition requires the DNA-binding domain, TFIIB-binding domain, and C-terminus.

  14. Simplicity and Specificity in Language: Domain-General Biases Have Domain-Specific Effects

    Science.gov (United States)

    Culbertson, Jennifer; Kirby, Simon

    2016-01-01

    The extent to which the linguistic system—its architecture, the representations it operates on, the constraints it is subject to—is specific to language has broad implications for cognitive science and its relation to evolutionary biology. Importantly, a given property of the linguistic system can be “specific” to the domain of language in several ways. For example, if the property evolved by natural selection under the pressure of the linguistic function it serves then the property is domain-specific in the sense that its design is tailored for language. Equally though, if that property evolved to serve a different function or if that property is domain-general, it may nevertheless interact with the linguistic system in a way that is unique. This gives a second sense in which a property can be thought of as specific to language. An evolutionary approach to the language faculty might at first blush appear to favor domain-specificity in the first sense, with individual properties of the language faculty being specifically linguistic adaptations. However, we argue that interactions between learning, culture, and biological evolution mean any domain-specific adaptations that evolve will take the form of weak biases rather than hard constraints. Turning to the latter sense of domain-specificity, we highlight a very general bias, simplicity, which operates widely in cognition and yet interacts with linguistic representations in domain-specific ways. PMID:26793132

  15. A Highly Accurate Regular Domain Collocation Method for Solving Potential Problems in the Irregular Doubly Connected Domains

    Directory of Open Access Journals (Sweden)

    Zhao-Qing Wang

    2014-01-01

    Full Text Available Embedding the irregular doubly connected domain into an annular regular region, the unknown functions can be approximated by the barycentric Lagrange interpolation in the regular region. A highly accurate regular domain collocation method is proposed for solving potential problems on the irregular doubly connected domain in polar coordinate system. The formulations of regular domain collocation method are constructed by using barycentric Lagrange interpolation collocation method on the regular domain in polar coordinate system. The boundary conditions are discretized by barycentric Lagrange interpolation within the regular domain. An additional method is used to impose the boundary conditions. The least square method can be used to solve the overconstrained equations. The function values of points in the irregular doubly connected domain can be calculated by barycentric Lagrange interpolation within the regular domain. Some numerical examples demonstrate the effectiveness and accuracy of the presented method.

  16. Functional analysis of the global repressor Tup1 for maltose metabolism in Saccharomyces cerevisiae: different roles of the functional domains.

    Science.gov (United States)

    Lin, Xue; Yu, Ai-Qun; Zhang, Cui-Ying; Pi, Li; Bai, Xiao-Wen; Xiao, Dong-Guang

    2017-11-09

    Tup1 is a general transcriptional repressor of diverse gene families coordinately controlled by glucose repression, mating type, and other mechanisms in Saccharomyces cerevisiae. Several functional domains of Tup1 have been identified, each of which has differing effects on transcriptional repression. In this study, we aim to investigate the role of Tup1 and its domains in maltose metabolism of industrial baker's yeast. To this end, a battery of in-frame truncations in the TUP1 gene coding region were performed in the industrial baker's yeasts with different genetic background, and the maltose metabolism, leavening ability, MAL gene expression levels, and growth characteristics were investigated. The results suggest that the TUP1 gene is essential to maltose metabolism in industrial baker's yeast. Importantly, different domains of Tup1 play different roles in glucose repression and maltose metabolism of industrial baker's yeast cells. The Ssn6 interaction, N-terminal repression and C-terminal repression domains might play roles in the regulation of MAL transcription by Tup1 for maltose metabolism of baker's yeast. The WD region lacking the first repeat could influence the regulation of maltose metabolism directly, rather than indirectly through glucose repression. These findings lay a foundation for the optimization of industrial baker's yeast strains for accelerated maltose metabolism and facilitate future research on glucose repression in other sugar metabolism.

  17. Direct time-domain techniques for transient radiation and scattering

    International Nuclear Information System (INIS)

    Miller, E.K.; Landt, J.A.

    1976-01-01

    A tutorial introduction to transient electromagnetics, focusing on direct time-domain techniques, is presented. Physical, mathematical, numerical, and experimental aspects of time-domain methods, with emphasis on wire objects excited as antennas or scatters are examined. Numerous computed examples illustrate the characteristics of direct time-domain procedures, especially where they may offer advantages over procedures in the more familiar frequency domain. These advantages include greater solution efficiency for many types of problems, the ability to handle nonlinearities, improved physical insight and interpretability, availability of wide-band information from a single calculation, and the possibility of isolating interactions among various parts of an object using time-range gating

  18. Are total, intensity- and domain-specific physical activity levels associated with life satisfaction among university students?

    Directory of Open Access Journals (Sweden)

    Željko Pedišić

    Full Text Available Thorough information about the relationship between physical activity (PA and life satisfaction is still lacking. Therefore, this study examined the cross-sectional relationships between life satisfaction and meeting the World Health Organization (WHO moderate to vigorous-intensity PA recommendations, total volume and duration of PA, intensity-specific PA (walking, moderate- and vigorous-intensity, domain-specific PA (work, transport-related, domestic, and leisure-time, and 11 domain and intensity-specific PA types among university students. Additionally, we examined the associations between life satisfaction and gender, age, disposable income, community size, smoking, alcohol intake, body mass index (BMI, and self-rated health.The study included a random sample of 1750 university students in Zagreb, Croatia (response rate = 71.7%; 62.4% females; mean age 21.5 ± 1.8 years, using the International Physical Activity Questionnaire-long form and the Satisfaction with Life Scale.Higher life satisfaction was associated with female gender (β = 0.13; p = <0.001, younger age (β = -0.07; p = 0.024, higher disposable income (β = 0.10; p = 0.001, and better self-rated health (β = 0.30; p = <0.001. No significant association was found between life satisfaction and size of community (p = 0.567, smoking status (p = 0.056, alcohol consumption (p = 0.058, or BMI (p = 0.508. Among all PA variables, only leisure-time vigorous-intensity PA was significantly associated with life satisfaction after adjustments for socio-demographic characteristics, lifestyle and self-rated general health (β = 0.06; p = 0.045.This study indicated a weak positive relationship between leisure-time vigorous-intensity PA and life satisfaction, whilst no such association was found for other PA variables. These findings underscore the importance of analyzing domain and intensity-specific PA levels in future studies among university students, as drawing conclusions about the

  19. The conservation pattern of short linear motifs is highly correlated with the function of interacting protein domains

    Directory of Open Access Journals (Sweden)

    Wang Yiguo

    2008-10-01

    Full Text Available Abstract Background Many well-represented domains recognize primary sequences usually less than 10 amino acids in length, called Short Linear Motifs (SLiMs. Accurate prediction of SLiMs has been difficult because they are short (often Results Our combined approach revealed that SLiMs are highly conserved in proteins from functional classes that are known to interact with a specific domain, but that they are not conserved in most other protein groups. We found that SLiMs recognized by SH2 domains were highly conserved in receptor kinases/phosphatases, adaptor molecules, and tyrosine kinases/phosphatases, that SLiMs recognized by SH3 domains were highly conserved in cytoskeletal and cytoskeletal-associated proteins, that SLiMs recognized by PDZ domains were highly conserved in membrane proteins such as channels and receptors, and that SLiMs recognized by S/T kinase domains were highly conserved in adaptor molecules, S/T kinases/phosphatases, and proteins involved in transcription or cell cycle control. We studied Tyr-SLiMs recognized by SH2 domains in more detail, and found that SH2-recognized Tyr-SLiMs on the cytoplasmic side of membrane proteins are more highly conserved than those on the extra-cellular side. Also, we found that SH2-recognized Tyr-SLiMs that are associated with SH3 motifs and a tyrosine kinase phosphorylation motif are more highly conserved. Conclusion The interactome of protein domains is reflected by the evolutionary conservation of SLiMs recognized by these domains. Combining scoring matrixes derived from peptide libraries and conservation analysis, we would be able to find those protein groups that are more likely to interact with specific domains.

  20. Leisure-Time and Occupational Physical Activity in Early and Late Adulthood in Relation to Later Life Physical Functioning.

    Science.gov (United States)

    Kulmala, Jenni; Ngandu, Tiia; Pajala, Satu; Lehtisalo, Jenni; Levälahti, Esko; Antikainen, Riitta; Laatikainen, Tiina; Oksa, Heikki; Peltonen, Markku; Rauramaa, Rainer; Soininen, Hilkka; Strandberg, Timo; Tuomilehto, Jaakko; Kivipelto, Miia

    2016-10-01

    Physical activity (PA) has beneficial effects on older age physical functioning, but longitudinal studies with follow-ups extending up to decades are few. We investigated the association between leisure-time PA (LTPA) and occupational PA (OPA) from early to late adulthood in relation to later life performance-based physical functioning. The study involved 1260 people aged 60 to 79 years who took part in assessments of physical functioning (Short Physical Performance Battery [SPPB] test, 10-m maximal walking test, and grip strength test). Participants' data on earlier life LTPA/OPA (age range 25 to 74 years) were received from the previous studies (average follow-up 13.4 years). Logistic, linear, and censored regression models were used to assess the associations between LTPA/OPA earlier in life and subsequent physical functioning. A high level of LTPA earlier in life was associated with a lower risk of having difficulties on the SPPB test (odds ratio [OR]: 0.37; 95% confidence interval [CI], 0.24-0.58) and especially on the chair rise test (OR: 0.42; 95% CI, 0.27-0.64) in old age. Heavy manual work predicted difficulties on SPPB (OR: 1.91; 95% CI, 1.22-2.98) and the chair rise test (OR: 1.75; 95% CI, 1.14-2.69) and poorer walking speed (β = .10, P = .005). This study highlights the importance of LTPA on later life functioning, but also indicates the inverse effects that may be caused by heavy manual work.

  1. Structure, functional characterization, and evolution of the dihydroorotase domain of human CAD.

    Science.gov (United States)

    Grande-García, Araceli; Lallous, Nada; Díaz-Tejada, Celsa; Ramón-Maiques, Santiago

    2014-02-04

    Upregulation of CAD, the multifunctional protein that initiates and controls the de novo biosynthesis of pyrimidines in animals, is essential for cell proliferation. Deciphering the architecture and functioning of CAD is of interest for its potential usage as an antitumoral target. However, there is no detailed structural information about CAD other than that it self-assembles into hexamers of ∼1.5 MDa. Here we report the crystal structure and functional characterization of the dihydroorotase domain of human CAD. Contradicting all assumptions, the structure reveals an active site enclosed by a flexible loop with two Zn²⁺ ions bridged by a carboxylated lysine and a third Zn coordinating a rare histidinate ion. Site-directed mutagenesis and functional assays prove the involvement of the Zn and flexible loop in catalysis. Comparison with homologous bacterial enzymes supports a reclassification of the DHOase family and provides strong evidence against current models of the architecture of CAD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. fMRI reveals reciprocal inhibition between social and physical cognitive domains

    Science.gov (United States)

    Jack, Anthony I.; Dawson, Abigail; Begany, Katelyn; Leckie, Regina L.; Barry, Kevin; Ciccia, Angela; Snyder, Abraham

    2012-01-01

    Two lines of evidence indicate that there exists a reciprocal inhibitory relationship between opposed brain networks. First, most attention-demanding cognitive tasks activate a stereotypical set of brain areas, known as the task-positive network and simultaneously deactivate a different set of brain regions, commonly referred to as the task negative or default mode network. Second, functional connectivity analyses show that these same opposed networks are anti-correlated in the resting state. We hypothesize that these reciprocally inhibitory effects reflect two incompatible cognitive modes, each of which is directed towards understanding the external world. Thus, engaging one mode activates one set of regions and suppresses activity in the other. We test this hypothesis by identifying two types of problem-solving task which, on the basis of prior work, have been consistently associated with the task positive and task negative regions: tasks requiring social cognition, i.e., reasoning about the mental states of other persons, and tasks requiring physical cognition, i.e., reasoning about the causal/mechanical properties of inanimate objects. Social and mechanical reasoning tasks were presented to neurologically normal participants during fMRI. Each task type was presented using both text and video clips. Regardless of presentation modality, we observed clear evidence of reciprocal suppression: social tasks deactivated regions associated with mechanical reasoning and mechanical tasks deactivated regions associated with social reasoning. These findings are not explained by self-referential processes, task engagement, mental simulation, mental time travel or external vs. internal attention, all factors previously hypothesized to explain default mode network activity. Analyses of resting state data revealed a close match between the regions our tasks identified as reciprocally inhibitory and regions of maximal anti-correlation in the resting state. These results indicate

  3. fMRI reveals reciprocal inhibition between social and physical cognitive domains.

    Science.gov (United States)

    Jack, Anthony I; Dawson, Abigail J; Begany, Katelyn L; Leckie, Regina L; Barry, Kevin P; Ciccia, Angela H; Snyder, Abraham Z

    2013-02-01

    Two lines of evidence indicate that there exists a reciprocal inhibitory relationship between opposed brain networks. First, most attention-demanding cognitive tasks activate a stereotypical set of brain areas, known as the task-positive network and simultaneously deactivate a different set of brain regions, commonly referred to as the task negative or default mode network. Second, functional connectivity analyses show that these same opposed networks are anti-correlated in the resting state. We hypothesize that these reciprocally inhibitory effects reflect two incompatible cognitive modes, each of which may be directed towards understanding the external world. Thus, engaging one mode activates one set of regions and suppresses activity in the other. We test this hypothesis by identifying two types of problem-solving task which, on the basis of prior work, have been consistently associated with the task positive and task negative regions: tasks requiring social cognition, i.e., reasoning about the mental states of other persons, and tasks requiring physical cognition, i.e., reasoning about the causal/mechanical properties of inanimate objects. Social and mechanical reasoning tasks were presented to neurologically normal participants during fMRI. Each task type was presented using both text and video clips. Regardless of presentation modality, we observed clear evidence of reciprocal suppression: social tasks deactivated regions associated with mechanical reasoning and mechanical tasks deactivated regions associated with social reasoning. These findings are not explained by self-referential processes, task engagement, mental simulation, mental time travel or external vs. internal attention, all factors previously hypothesized to explain default mode network activity. Analyses of resting state data revealed a close match between the regions our tasks identified as reciprocally inhibitory and regions of maximal anti-correlation in the resting state. These results

  4. Problem-Matched Basis Functions for Microstrip Coupled Slot Antennas based on Transmission Line Greens Functions

    NARCIS (Netherlands)

    Bruni, S.; Llombart Juan, N.; Neto, A.; Gerini, G.; Maci, S.

    2004-01-01

    A general algorithm for the analysis of microstrip coupled leaky wave slot antennas was discussed. The method was based on the construction of physically appealing entire domain Methods of Moments (MoM) basis function that allowed a consistent reduction of the number of unknowns and of total

  5. Between-Domain Relations of Students’ Academic Emotions and Their Judgments of School Domain Similarity

    Directory of Open Access Journals (Sweden)

    Thomas eGoetz

    2014-10-01

    Full Text Available With the aim to deepen our understanding of the between-domain relations of academic emotions, a series of three studies was conducted. We theorized that between-domain relations of trait (i.e., habitual emotions reflected students’ judgments of domain similarities, whereas between-domain relations of state (i.e., momentary emotions did not. This supposition was based on the accessibility model of emotional self-report, according to which individuals’ beliefs tend to strongly impact trait, but not state emotions. The aim of Study 1 (interviews; N = 40; 8th and 11th graders was to gather salient characteristics of academic domains from students’ perspective. In Study 2 (N=1709; 8th and 11th graders the 13 characteristics identified in Study 1 were assessed along with academic emotions in four different domains (mathematics, physics, German, and English using a questionnaire-based trait assessment. With respect to the same domains, state emotions were assessed in Study 3 (N = 121; 8th and 11th graders by employing an experience sampling approach. In line with our initial assumptions, between-domain relations of trait but not state academic emotions reflected between-domain relations of domain characteristics. Implications for research and practice are discussed.

  6. Between-domain relations of students' academic emotions and their judgments of school domain similarity

    Science.gov (United States)

    Goetz, Thomas; Haag, Ludwig; Lipnevich, Anastasiya A.; Keller, Melanie M.; Frenzel, Anne C.; Collier, Antonie P. M.

    2014-01-01

    With the aim to deepen our understanding of the between-domain relations of academic emotions, a series of three studies was conducted. We theorized that between-domain relations of trait (i.e., habitual) emotions reflected students' judgments of domain similarities, whereas between-domain relations of state (i.e., momentary) emotions did not. This supposition was based on the accessibility model of emotional self-report, according to which individuals' beliefs tend to strongly impact trait, but not state emotions. The aim of Study 1 (interviews; N = 40; 8th and 11th graders) was to gather salient characteristics of academic domains from students' perspective. In Study 2 (N = 1709; 8th and 11th graders) the 13 characteristics identified in Study 1 were assessed along with academic emotions in four different domains (mathematics, physics, German, and English) using a questionnaire-based trait assessment. With respect to the same domains, state emotions were assessed in Study 3 (N = 121; 8th and 11th graders) by employing an experience sampling approach. In line with our initial assumptions, between-domain relations of trait but not state academic emotions reflected between-domain relations of domain characteristics. Implications for research and practice are discussed. PMID:25374547

  7. Test-retest reliability of a questionnaire to assess physical environmental factors pertaining to physical activity

    Directory of Open Access Journals (Sweden)

    McGinn Aileen P

    2005-06-01

    Full Text Available Abstract Background Despite the documented benefits of physical activity, many adults do not obtain the recommended amounts. Barriers to physical activity occur at multiple levels, including at the individual, interpersonal, and environmental levels. Only until more recently has there been a concerted focus on how the physical environment might affect physical activity behavior. With this new area of study, self-report measures should be psychometrically tested before use in research studies. Therefore the objective of this study was to document the test-retest reliability of a questionnaire designed to assess physical environmental factors that might be associated with physical activity in a diverse adult population. Methods Test and retest surveys were conducted over the telephone with 106 African American and White women and men living in either Forsyth County, North Carolina or Jackson, Mississippi. Reliability of self-reported environmental factors across four domains (e.g., access to facilities and destinations, functionality and safety, aesthetics, natural environment was determined using intraclass correlation coefficients (ICC overall and separately by gender and race. Results Generally items displayed moderate and sometimes substantial reliability (ICC between 0.4 to 0.8, with a few differences by gender or race, across each of the domains. Conclusion This study provides some psychometric evidence for the use of many of these questions in studies examining the effect of self-reported physical environmental measures on physical activity behaviors, among African American and White women and men.

  8. Long-Term Effects of Individually Tailored Physical Training and Activity on Physical Function, Well-Being and Cognition in Scandinavian Nursing Home Residents

    DEFF Research Database (Denmark)

    Frändin, Kerstin; Grönstedt, Helena; Helbostad, Jorunn L

    2016-01-01

    . Objective: To evaluate the long-term effects on ADL, balance function, physical activity level, physical performance, falls-related self-efficacy, well-being and cognitive function 3 months after the completion of our intervention in nursing home residents. Methods: The study was a multicenter randomized...... and 66 from Denmark. Of these, 241 [129 intervention group (IG), 112 control group (CG)] were eligible for the 6-month follow-up tests. The level of dependence in ADL, physical activity level, several dimensions of physical function, well-being, falls-related self-efficacy and cognitive function were......Background: The preservation of physical functions such as muscle strength, balance and mobility is fundamental to maintaining independence in activities of daily living (ADL). The physical activity level of most nursing home residents is very low, which implies that they are often subject...

  9. Physical Activity of Croatian Population: Cross-sectional Study Using International Physical Activity Questionnaire

    OpenAIRE

    Jurakić, Danijel; Pedišić, Željko; Andrijašević, Mirna

    2009-01-01

    Aim To determine the physical activity level of the Croatian population in different domains of everyday life. Methods A random stratified sample of 1032 Croatians aged 15 years and older was interviewed using the official Croatian long version of the International Physical Activity Questionnaire (IPAQ). Total physical activity and physical activity in each of the 4 life domains – work, transport, domestic and garden, and leisure-time – were estimated. Physical activit...

  10. Physical function was related to mortality in patients with chronic kidney disease and dialysis.

    Science.gov (United States)

    Morishita, Shinichiro; Tsubaki, Atsuhiro; Shirai, Nobuyuki

    2017-10-01

    Previous studies have shown that exercise improves aerobic capacity, muscular functioning, cardiovascular function, walking capacity, and health-related quality of life (QOL) in patients with chronic kidney disease (CKD) and dialysis. Recently, additional studies have shown that higher physical activity contributes to survival and decreased mortality as well as physical function and QOL in patients with CKD and dialysis. Herein, we review the evidence that physical function and physical activity play an important role in mortality for patients with CKD and dialysis. During November 2016, Medline and Web of Science databases were searched for published English medical reports (without a time limit) using the terms "CKD" or "dialysis" and "mortality" in conjunction with "exercise capacity," "muscle strength," "activities of daily living (ADL)," "physical activity," and "exercise." Numerous studies suggest that higher exercise capacity, muscle strength, ADL, and physical activity contribute to lower mortality in patients with CKD and dialysis. Physical function is associated with mortality in patients with CKD and dialysis. Increasing physical function may decrease the mortality rate of patients with CKD and dialysis. Physicians and medical staff should recognize the importance of physical function in CKD and dialysis. In addition, exercise is associated with reduced mortality among patients with CKD and dialysis. © 2017 International Society for Hemodialysis.

  11. [Effect of physical activity on functional performance].

    Science.gov (United States)

    Nikolaus, T

    2001-02-01

    Epidemiological studies clearly show a connection between physical activity and the occurrence of disabilities in old age. Physical exercise is possible and useful at every age. Numerous intervention trials have shown that training of endurance, strength and coordination has positive effects on the cardiovascular system, the lung, the musculo-skeletal system, metabolism and the immune system in elderly people. Even very frail elderly people can increase their muscle strength and functional capabilities by strength training. Group sessions may improve social interactions and additionally increase the quality of life.

  12. Stability of a Jensen Type Logarithmic Functional Equation on Restricted Domains and Its Asymptotic Behaviors

    Directory of Open Access Journals (Sweden)

    Chung Jae-Young

    2010-01-01

    Full Text Available Let be the set of positive real numbers, a Banach space, and , with . We prove the Hyers-Ulam stability of the Jensen type logarithmic functional inequality in restricted domains of the form for fixed with or and . As consequences of the results we obtain asymptotic behaviors of the inequality as .

  13. Direct Binding between Pre-S1 and TRP-like Domains in TRPP Channels Mediates Gating and Functional Regulation by PIP2

    OpenAIRE

    Wang Zheng; Ruiqi Cai; Laura Hofmann; Vasyl Nesin; Qiaolin Hu; Wentong Long; Mohammad Fatehi; Xiong Liu; Shaimaa Hussein; Tim Kong; Jingru Li; Peter E. Light; Jingfeng Tang; Veit Flockerzi; Leonidas Tsiokas

    2018-01-01

    Transient receptor potential (TRP) channels are regulated by diverse stimuli comprising thermal, chemical, and mechanical modalities. They are also commonly regulated by phosphatidylinositol-4,5-bisphosphate (PIP2), with underlying mechanisms largely unknown. We here revealed an intramolecular interaction of the TRPP3 N and C termini (N-C) that is functionally essential. The interaction was mediated by aromatic Trp81 in pre-S1 domain and cationic Lys568 in TRP-like domain. Structure-function ...

  14. Physical practice is associated with less functional disability in medical students with migraine

    Directory of Open Access Journals (Sweden)

    Renan B. Domingues

    2011-02-01

    Full Text Available The aim of this study was to investigate possible association between migraine and physical practice among 480 medical students who were submitted to a questionnaire about headaches and physical practices. Migraine diagnosis was assessed by ID-Migraine and functional disability was evaluated with MIDAS. The type (aerobic or strength training, the weekly frequency and the intensity of physical practice and body mass index (BMI were assessed. There was a reduction in functional disability of migraine in students reporting physical practice (no physical practice - MIDAS=8.81±1.40, physical practice - MIDAS=15.49±1.78; P=0.03. Frequency, intensity, and type of physical practices were not associated with functional impact of migraine. BMI did not correlate with migraine impact (normal weight - MIDAS=12.34±1.33, overweight or obese - MIDAS=17.45±3.86; P=0.33. These results were confirmed by multivariate analysis. Our data suggest that physical practice is inversely related with functional disability of migraine in university students regardless of BMI.

  15. The dimer interface of the membrane type 1 matrix metalloproteinase hemopexin domain: crystal structure and biological functions.

    Science.gov (United States)

    Tochowicz, Anna; Goettig, Peter; Evans, Richard; Visse, Robert; Shitomi, Yasuyuki; Palmisano, Ralf; Ito, Noriko; Richter, Klaus; Maskos, Klaus; Franke, Daniel; Svergun, Dmitri; Nagase, Hideaki; Bode, Wolfram; Itoh, Yoshifumi

    2011-03-04

    Homodimerization is an essential step for membrane type 1 matrix metalloproteinase (MT1-MMP) to activate proMMP-2 and to degrade collagen on the cell surface. To uncover the molecular basis of the hemopexin (Hpx) domain-driven dimerization of MT1-MMP, a crystal structure of the Hpx domain was solved at 1.7 Å resolution. Two interactions were identified as potential biological dimer interfaces in the crystal structure, and mutagenesis studies revealed that the biological dimer possesses a symmetrical interaction where blades II and III of molecule A interact with blades III and II of molecule B. The mutations of amino acids involved in the interaction weakened the dimer interaction of Hpx domains in solution, and incorporation of these mutations into the full-length enzyme significantly inhibited dimer-dependent functions on the cell surface, including proMMP-2 activation, collagen degradation, and invasion into the three-dimensional collagen matrix, whereas dimer-independent functions, including gelatin film degradation and two-dimensional cell migration, were not affected. These results shed light on the structural basis of MT1-MMP dimerization that is crucial to promote cellular invasion.

  16. Self-reported fatigue and physical function in late mid-life

    DEFF Research Database (Denmark)

    Boter, Han; Mänty, Minna; Hansen, Åse Marie

    2014-01-01

    Objective: To determine the association between the 5 subscales of the Multidimensional Fatigue Inventory (MFI-20) and physical function in late mid-life. Design: Cross-sectional study. Subjects: A population-based sample of adults who participated in the Copenhagen Aging and Midlife Biobank...... population cohort (n = 4,964; age 49-63 years). Methods: Self-reported fatigue was measured using the MFI-20 comprising: general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. Handgrip strength and chair rise tests were used as measures of physical function. Multiple...... logistic regression analyses were used to determine the associations between handgrip strength and the chair rise test with the MFI-20 subscales, adjusted for potential confounders. Results: After adjustments for potential confounders, handgrip strength was associated with physical fatigue (adjusted odds...

  17. Genetic and environmental links between cognitive and physical functions in old age

    DEFF Research Database (Denmark)

    Johnson, Wendy; Deary, Ian J; McGue, Matt

    2009-01-01

    of twins from the Longitudinal Study of Aging Danish Twins. Cognitive function was measured using forward and backward digit span, immediate and delayed memory, and fluency tasks. Physical function was measured using self-report of ability to carry out physical activities including walking, running......In old age, cognitive and physical functions are correlated. Knowing the correlations between genetic and environmental influences underlying this correlation can help to clarify the reasons for the observable (phenotypic) correlation. We estimated these correlations in a sample of 1,053 pairs...

  18. A randomised controlled trial of adjunctive yoga and adjunctive physical exercise training for cognitive dysfunction in schizophrenia.

    Science.gov (United States)

    Bhatia, Triptish; Mazumdar, Sati; Wood, Joel; He, Fanyin; Gur, Raquel E; Gur, Ruben C; Nimgaonkar, Vishwajit L; Deshpande, Smita N

    2017-04-01

    Yoga and physical exercise have been used as adjunctive intervention for cognitive dysfunction in schizophrenia (SZ), but controlled comparisons are lacking. Aims A single-blind randomised controlled trial was designed to evaluate whether yoga training or physical exercise training enhance cognitive functions in SZ, based on a prior pilot study. Consenting, clinically stable, adult outpatients with SZ (n=286) completed baseline assessments and were randomised to treatment as usual (TAU), supervised yoga training with TAU (YT) or supervised physical exercise training with TAU (PE). Based on the pilot study, the primary outcome measure was speed index for the cognitive domain of 'attention' in the Penn computerised neurocognitive battery. Using mixed models and contrasts, cognitive functions at baseline, 21 days (end of training), 3 and 6 months post-training were evaluated with intention-to-treat paradigm. Speed index of attention domain in the YT group showed greater improvement than PE at 6 months follow-up (pattention domain showed greater improvement than TAU alone at 6-month follow-up (pattention and additional cognitive domains well past the training period, supporting our prior reported beneficial effect of YT on speed index of attention domain. As adjuncts, YT or PE can benefit individuals with SZ.

  19. The Control of Anisotropic Transport in Manganites by Stripy Domains

    Science.gov (United States)

    Ju, Changcheng; Lu, Xiaomei; Chu, Yinghao

    2014-03-01

    Epitaxial thin film acts as a significant tool to investigate novel phenomena of complex oxide systems. Extrinsic constraint1 of uniform or certain designed buffer layer strain could be easily implanted to these materials. However, the strain distribution might be quite complicated by involving micro- or nano-lattice distortions which could partially relax the strain and determine the complex phase diagrams of thin film, meanwhile introducing structural and physical inhomogeneities. In this work , we report 71° striped ferroelectric domains created in BFO can also epitaxially lock the perovskite manganites leading to the emerge of ordered structural domain. LSMO/BFO hetero-epitaxial samples are deposited by PLD. The 71° periodic striped domains and coherent growth are demonstrated by PFM and X-ray analysis. Plan-view TEM and X-ray RSM have been used to confirm the epitaxial relationships of the functional layers and IP lattice constant. Both the simulation and structural analysis demonstrate we can create a periodic ordered stripe structural domain in LSMO. And this will leave an anisotropic distribution of structural domain walls which makes it possible to capture the anisotropic tunneling for strong electron-lattice coupling in manganites. Temperature-dependent resistivity measurements reveal a substantial anisotropic resistivities and a remarkable shift of the MI transition between the perpendicular and parallel to the stripe domain directions.

  20. Domain Walls and Matter-Antimatter Domains in the Early Universe

    Directory of Open Access Journals (Sweden)

    Dolgov A.D.

    2017-01-01

    Full Text Available We suggest a scenario of spontaneous (or dynamical C and CP violation according to which it is possible to generate domains of matter and antimatter separated by cosmologically large distances. Such C(CP violation existed only in the early universe and later it disappeared with the only trace of generated matter and antimatter domains. So this scenario does not suffer from the problem of domain walls. According to this scenario the width of the domain wall should grow exponentially to prevent annihilation at the domain boundaries. Though there is a classical result obtained by Basu and Vilenkin that the width of the wall tends to the one of the stationary solution (constant physical width. That is why we considered thick domain walls in a de Sitter universe following paper by Basu and Vilenkin. However, we were interested not only in stationary solutions found therein, but also investigated the general case of domain wall evolution with time. When the wall thickness parameter, δ0 , is smaller than H−1/2 where H is the Hubble parameter in de Sitter space-time, then the stationary solutions exist, and initial field configurations tend with time to the stationary ones. However, there are no stationary solutions for δ0>H−1/2 We have calculated numerically the rate of the wall expansion in this case and have found that the width of the wall grows exponentially fast for δ0≫H−1 An explanation for the critical value δ0c=H−1/2 is also proposed.

  1. Domain-to-domain coupling in voltage-sensing phosphatase.

    Science.gov (United States)

    Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi

    2017-01-01

    Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain.

  2. Long-term Associations Between Physical Frailty and Performance in Specific Cognitive Domains.

    Science.gov (United States)

    Bunce, David; Batterham, Philip J; Mackinnon, Andrew J

    2018-02-01

    No longitudinal epidemiological research has reported associations between physical frailty and performance in specific cognitive domains. Our aim was to investigate whether such associations existed in the absence of accompanying neurodegenerative disorders such as mild cognitive impairment (MCI) and dementia. We addressed this issue in a population-based sample of 896 adults aged 70 years and older over 4 waves of data covering a 12-year period. Physical frailty was assessed and a cognitive battery included measures of processing speed, verbal fluency, face and word recognition, episodic memory and simple and choice reaction time (RT). Latent growth models showed frailty was associated with poorer baseline performance in processing speed, verbal fluency, simple and choice RT, and choice intraindividual RT variability. However, no significant effects of frailty on slopes of cognition were observed, suggesting that frailty was not associated with cognitive decline. Importantly, when the models took possible dementia into account, significant effects were retained suggesting that differences were not associated with dementia-related neurodegenerative disorders. The findings suggest that frailty-related cognitive deficits may exist independently of mechanisms underpinning neurodegenerative disorders such as MCI and dementia. If confirmed, this finding suggests a new avenue for preventative and therapeutic interventions in clinical and public health contexts for older adults. © The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. The role of neuropsychological performance in the relationship between chronic pain and functional physical impairment.

    Science.gov (United States)

    Pulles, Wiesje L J A; Oosterman, Joukje M

    2011-12-01

      In this study, the relationship between pain intensity, neuropsychological, and physical function in adult chronic pain patients was examined.   Thirty participants with chronic pain completed neuropsychological tests tapping mental processing speed, memory, and executive function. Pain intensity was measured with three visual analog scales and the Pain Rating Index of the McGill Pain Questionnaire. A grip strength test, the 6-minute walk test, the Unipedal Stance Test and the Lifting Low Test were administered in order to obtain a performance-based measure of physical capacity. Self-reported physical ability was assessed with the Disability Rating Index and the Short Form-36 Physical Functioning, and Role Physical scales. Psychosocial function was examined using the Mental Health and Role Emotional subscales of the Short Form-36.   The study was set in two outpatient physical therapy clinics in The Netherlands.   The analysis showed that a lower mental processing speed was related to a higher level of pain, as well as to a lower performance-based and self-reported physical functioning. In addition, both performance-based and self-reported physical function revealed an inverse correlation with pain intensity. Psychosocial function turned out to be an important mediator of the relationship between pain and self-reported, but not performance-based, physical function. Mental processing speed, on the other hand, was found to mediate the relationship between pain and performance-based physical functioning.   The results suggest that in chronic pain patients, mental processing speed mediates the relationship between pain and physical function. Wiley Periodicals, Inc.

  4. Polymer physics of nuclear organization and function

    Energy Technology Data Exchange (ETDEWEB)

    Amitai, A. [Department of Chemical Engineering, Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Holcman, D., E-mail: david.holcman@ens.fr [Department of Applied Mathematics and Theoretical Physics (DAMTP), University of Cambridge, Churchill College, CB30DS, Cambridge (United Kingdom); Ecole Normale Superieure, Paris (France)

    2017-03-23

    We review here recent progress to link the nuclear organization to its function, based on elementary physical processes such as diffusion, polymer dynamics of DNA, chromatin and the search mechanism for a small target by double-stranded DNA (dsDNA) break. These physical models and their analysis make it possible to compute critical rates involved in cell reorganization timing, which depend on many parameters. In the framework of polymer models, various empirical observations are interpreted as anomalous diffusion of chromatin at various time scales. The reviewed theoretical approaches offer a framework for extracting features, biophysical parameters, predictions, and so on, based on a large variety of experimental data, such as chromosomal capture data, single particle trajectories, and more. Combining theoretical approaches with live cell microscopy data should unveil some of the still unexplained behavior of the nucleus in carrying out some of its key function involved in survival, DNA repair or gene activation.

  5. Compensating for Incomplete Domain Knowledge

    National Research Council Canada - National Science Library

    Scott, Lynn M; Drezner, Steve; Rue, Rachel; Reyes, Jesse

    2007-01-01

    .... First, many senior leader positions require experience in more than one functional or operational domain, but it is difficult to develop a corps of senior leaders with all the required combinations of domain knowledge...

  6. The structure function of the death domain of human IRAK-M.

    Science.gov (United States)

    Du, Jiangfeng; Nicolaes, Gerry Af; Kruijswijk, Danielle; Versloot, Miranda; van der Poll, Tom; van 't Veer, Cornelis

    2014-12-07

    IRAK-M is an inhibitor of Toll-like receptor signaling that acts by re-directing IRAK-4 activity to TAK1 independent NF-κB activation and by inhibition of IRAK-1/IRAK-2 activity. IRAK-M is expressed in monocytes/macrophages and lung epithelial cells. Lack of IRAK-M in mice greatly improves the resistance to nosocomial pneumonia and lung tumors, which entices IRAK-M as a potential therapeutic target. IRAK-M consists of an N-terminal death domain (DD), a dysfunctional kinase domain and unstructured C-terminal domain. Little is known however on IRAK-M's structure-function relationships. Since death domains provide the important interactions of IRAK-1, IRAK-2 and IRAK-4 molecules, we generated a 3D structure model of the human IRAK-M-DD (residues C5-G119) to guide mutagenesis studies and predict protein-protein interaction points. First we identified the DD residues involved in the endogenous capacity of IRAK-M to activate NF-κB that is displayed upon overexpression in 293T cells. W74 and R97, at distinct interfaces of the IRAK-M-DD, were crucial for this endogenous NF-κB activating capacity, as well as the C-terminal domain (S445-E596) of IRAK-M. Resulting anti-inflammatory A20 and pro-inflammatory IL-8 transcription in 293T cells was W74 dependent, while IL-8 protein expression was dependent on R97 and the TRAF6 binding motif at P478. The IRAK-M-DD W74 and R97 binding interfaces are predicted to interact with opposite sides of IRAK-4-DD's. Secondly we identified DD residues important for the inhibitory action of IRAK-M by stable overexpression of mutants in THP-1 macrophages and H292 lung epithelial cells. IRAK-M inhibited TLR2/4-mediated cytokine production in macrophages in a manner that is largely dependent on W74. R97 was not involved in inhibition of TNF production but was engaged in IL-6 down-regulation by IRAK-M. Protein-interactive residues D19-A23, located in between W74 and R97, were also observed to be crucial for inhibition of TLR2/4 mediated cytokine

  7. Organization of functional domains in the docking protein p130Cas

    International Nuclear Information System (INIS)

    Nasertorabi, Fariborz; Garcia-Guzman, Miguel; Briknarova, Klara; Larsen, Elise; Havert, Marnie L.; Vuori, Kristiina; Ely, Kathryn R.

    2004-01-01

    The docking protein p130Cas becomes phosphorylated upon cell adhesion to extracellular matrix proteins, and is thought to play an essential role in cell transformation. Cas transmits signals through interactions with the Src-homology 3 (SH3) and Src-homology 2 domains of FAK or v-Crk signaling molecules, or with 14-3-3 protein, as well as phosphatases PTP1B and PTP-PEST. The large (130 kDa), multi-domain Cas molecule contains an SH3 domain, a Src-binding domain, a serine-rich protein interaction region, and a C-terminal region that participates in protein interactions implicated in antiestrogen resistance in breast cancer. In this study, as part of a long-term goal to examine the protein interactions of Cas by X-ray crystallography and nuclear magnetic resonance spectroscopy, molecular constructs were designed to express two adjacent domains, the serine-rich domain and the Src-binding domain, that each participate in intermolecular contacts dependent on protein phosphorylation. The protein products are soluble, homogeneous, monodisperse, and highly suitable for structural studies to define the role of Cas in integrin-mediated cell signaling

  8. System Identification A Frequency Domain Approach

    CERN Document Server

    Pintelon, Rik

    2012-01-01

    System identification is a general term used to describe mathematical tools and algorithms that build dynamical models from measured data. Used for prediction, control, physical interpretation, and the designing of any electrical systems, they are vital in the fields of electrical, mechanical, civil, and chemical engineering. Focusing mainly on frequency domain techniques, System Identification: A Frequency Domain Approach, Second Edition also studies in detail the similarities and differences with the classical time domain approach. It high??lights many of the important steps in the identi

  9. Resolution of unsteady Maxwell equations with charges in non convex domains

    International Nuclear Information System (INIS)

    Garcia, Emmanuelle

    2002-01-01

    This research thesis deals with the modelling and numerical resolution of problems related to plasma physics. The interaction of charged particles (electrons and ions) with electromagnetic fields is modelled with the system of unsteady Vlasov-Maxwell coupled equations (the Vlasov system describes the transport of charged particles and the Maxwell equations describe the wave propagation). The author presents definitions related to singular domains, establishes a Helmholtz decomposition in a space of electro-magnetostatic solutions. He reports a mathematical analysis of decompositions into a regular and a singular part of general functional spaces intervening in the investigation of the Maxwell system in complex geometries. The method is then implemented for bi-dimensional domains. A last part addressed the study and the numerical resolution of three-dimensional problems

  10. Domains of cognitive function in early old age: which ones are predicted by pre-retirement psychosocial work characteristics?

    Science.gov (United States)

    Sabbath, Erika; Andel, Ross; Zins, Marie; Goldberg, Marcel; Berr, Claudine

    2016-01-01

    Background Psychosocial work characteristics may predict cognitive functioning after retirement. However, little research has explored specific cognitive domains associated with psychosocial work environments. Our study tested whether exposure to job demands, job control, and their combination during working life predicted post-retirement performance on eight cognitive tests. Methods We used data from French GAZEL cohort members who had undergone post-retirement cognitive testing (n=2,149). Psychosocial job characteristics were measured on average four years before retirement using Karasek’s Job Content Questionnaire (job demands, job control, demand-control combinations). We tested associations between these exposures and post-retirement performance on tests of executive function, visual-motor speed, psycho-motor speed, verbal memory, and verbal fluency using OLS regression. Results Low job control during working life was negatively associated with executive function, psychomotor speed, phonemic fluency, and semantic fluency after retirement (p’scognitive domains. In addition to work stress, associations between passive work and subsequent cognitive function may implicate lack of cognitive engagement at work as a risk factor for future cognitive difficulties. PMID:27188277

  11. Physical activity as intervention for age-related loss of muscle mass and function

    DEFF Research Database (Denmark)

    Eriksen, Christian Skou; Garde, Ellen; Reislev, Nina Linde

    2016-01-01

    insights into training-induced promotion of functional ability and independency after retirement and will help to formulate national recommendations regarding physical activity schemes for the growing population of older individuals in western societies. Results will be published in scientific peer......INTRODUCTION: Physical and cognitive function decline with age, accelerating during the 6th decade. Loss of muscle power (force×velocity product) is a dominant physical determinant for loss of functional ability, especially if the lower extremities are affected. Muscle strength training is known...... to maintain or even improve muscle power as well as physical function in older adults, but the optimal type of training for beneficial long-term training effects over several years is unknown. Moreover, the impact of muscle strength training on cognitive function and brain structure remains speculative...

  12. Functional Elements on SIRPα IgV domain Mediate Cell Surface Binding to CD47

    OpenAIRE

    Liu, Yuan; Tong, Qiao; Zhou, Yubin; Lee, Hsiau-Wei; Yang, Jenny J.; Bühring, Hans-Jörg; Chen, Yi-Tien; Ha, Binh; Chen, Celia X-J.; Zen, Ke

    2006-01-01

    SIRPα and SIRPβ1, the two major isoforms of the signal regulatory protein (SIRP) family, are co-expressed in human leukocytes but mediate distinct extracellular binding interactions and divergent cell signaling responses. Previous studies have demonstrated that binding of SIRPα with CD47, another important cell surface molecule, through the extracellular IgV domain regulates important leukocyte functions including macrophage recognition, leukocyte adhesion and transmigration. Although SIRPβ1 ...

  13. Structural Conservation and Functional Diversity of the Poxvirus Immune Evasion (PIE) Domain Superfamily.

    Science.gov (United States)

    Nelson, Christopher A; Epperson, Megan L; Singh, Sukrit; Elliott, Jabari I; Fremont, Daved H

    2015-08-28

    Poxviruses encode a broad array of proteins that serve to undermine host immune defenses. Structural analysis of four of these seemingly unrelated proteins revealed the recurrent use of a conserved beta-sandwich fold that has not been observed in any eukaryotic or prokaryotic protein. Herein we propose to call this unique structural scaffolding the PIE (Poxvirus Immune Evasion) domain. PIE domain containing proteins are abundant in chordopoxvirinae, with our analysis identifying 20 likely PIE subfamilies among 33 representative genomes spanning 7 genera. For example, cowpox strain Brighton Red appears to encode 10 different PIEs: vCCI, A41, C8, M2, T4 (CPVX203), and the SECRET proteins CrmB, CrmD, SCP-1, SCP-2, and SCP-3. Characterized PIE proteins all appear to be nonessential for virus replication, and all contain signal peptides for targeting to the secretory pathway. The PIE subfamilies differ primarily in the number, size, and location of structural embellishments to the beta-sandwich core that confer unique functional specificities. Reported ligands include chemokines, GM-CSF, IL-2, MHC class I, and glycosaminoglycans. We expect that the list of ligands and receptors engaged by the PIE domain will grow as we come to better understand how this versatile structural architecture can be tailored to manipulate host responses to infection.

  14. Structural considerations for functional anti-EGFR × anti-CD3 bispecific diabodies in light of domain order and binding affinity.

    Science.gov (United States)

    Asano, Ryutaro; Nagai, Keisuke; Makabe, Koki; Takahashi, Kento; Kumagai, Takashi; Kawaguchi, Hiroko; Ogata, Hiromi; Arai, Kyoko; Umetsu, Mitsuo; Kumagai, Izumi

    2018-03-02

    We previously reported a functional humanized bispecific diabody (bsDb) that targeted EGFR and CD3 (hEx3-Db) and enhancement of its cytotoxicity by rearranging the domain order in the V domain. Here, we further dissected the effect of domain order in bsDbs on their cross-linking ability and binding kinetics to elucidate general rules regarding the design of functional bsDbs. Using Ex3-Db as a model system, we first classified the four possible domain orders as anti-parallel (where both chimeric single-chain components are variable heavy domain (VH)-variable light domain (VL) or VL-VH order) and parallel types (both chimeric single-chain components are mixed with VH-VL and VL-VH order). Although anti-parallel Ex3-Dbs could cross-link the soluble target antigens, their cross-linking ability between soluble targets had no correlation with their growth inhibitory effects. In contrast, the binding affinity of one of the two constructs with a parallel-arrangement V domain was particularly low, and structural modeling supported this phenomenon. Similar results were observed with E2x3-Dbs, in which the V region of the anti-EGFR antibody clone in hEx3 was replaced with that of another anti-EGFR clone. Only anti-parallel types showed affinity-dependent cancer inhibitory effects in each molecule, and E2x3-LH (both components in VL-VH order) showed the most intense anti-tumor activity in vitro and in vivo . Our results showed that, in addition to rearranging the domain order of bsDbs, increasing their binding affinity may be an ideal strategy for enhancing the cytotoxicity of anti-parallel constructs and that E2x3-LH is particularly attractive as a candidate next-generation anti-cancer drug.

  15. Effects of dance on depression, physical function, and disability in underserved adults.

    Science.gov (United States)

    Murrock, Carolyn J; Graor, Christine Heifner

    2014-07-01

    This study documented the feasibility and immediate effects of a dance intervention two times per week for 12 weeks on depression, physical function, and disability in older, underserved adults. The one-group, pretest-posttest study had a convenience sample of 40 participants recruited from a federally subsidized apartment complex located in an economically depressed, inner-city neighborhood. Depression, physical function, and disability were measured at baseline and 12 weeks. Average age was 63 years (SD = 7.9), 92% were female, and 75% were African American. At baseline, participants reported increased depression (M = 20.0, SD = 12.4), decreased physical function (M = 56.6, SD = 10.9), and increased disability limitations (M = 65.7, SD = 14.9). At posttest, paired t tests showed that the dance intervention significantly decreased depression, t = 6.11, p dance intervention may be an effective adjunct therapy to improve depression, disability, and physical function in underserved adults.

  16. A Priority-aware Frequency Domain Polling MAC Protocol for OFDMA-based Networks in Cyber-physical Systems

    Institute of Scientific and Technical Information of China (English)

    Meng Zheng; Junru Lin; Wei Liang; Haibin Yu

    2015-01-01

    Wireless networking in cyber-physical systems(CPSs) is characteristically different from traditional wireless systems due to the harsh radio frequency environment and applications that impose high real-time and reliability constraints.One of the fundamental considerations for enabling CPS networks is the medium access control protocol. To this end, this paper proposes a novel priority-aware frequency domain polling medium access control(MAC) protocol, which takes advantage of an orthogonal frequency-division multiple access(OFDMA)physical layer to achieve instantaneous priority-aware polling.Based on the polling result, the proposed work then optimizes the resource allocation of the OFDMA network to further improve the data reliability. Due to the non-polynomial-complete nature of the OFDMA resource allocation, we propose two heuristic rules,based on which an efficient solution algorithm to the OFDMA resource allocation problem is designed. Simulation results show that the reliability performance of CPS networks is significantly improved because of this work.

  17. Cross-Genome Comparisons of Newly Identified Domains in Mycoplasma gallisepticum and Domain Architectures with Other Mycoplasma species

    Directory of Open Access Journals (Sweden)

    Chandra Sekhar Reddy Chilamakuri

    2011-01-01

    Full Text Available Accurate functional annotation of protein sequences is hampered by important factors such as the failure of sequence search methods to identify relationships and the inherent diversity in function of proteins related at low sequence similarities. Earlier, we had employed intermediate sequence search approach to establish new domain relationships in the unassigned regions of gene products at the whole genome level by taking Mycoplasma gallisepticum as a specific example and established new domain relationships. In this paper, we report a detailed comparison of the conservation status of the domain and domain architectures of the gene products that bear our newly predicted domains amongst 14 other Mycoplasma genomes and reported the probable implications for the organisms. Some of the domain associations, observed in Mycoplasma that afflict humans and other non-human primates, are involved in regulation of solute transport and DNA binding suggesting specific modes of host-pathogen interactions.

  18. Objectively-measured outdoor time and physical and psychological function among older adults.

    Science.gov (United States)

    Harada, Kazuhiro; Lee, Sangyoon; Lee, Sungchul; Bae, Seongryu; Harada, Kenji; Suzuki, Takao; Shimada, Hiroyuki

    2017-10-01

    Objective measurements of outdoor time are essential to establishing evidence about the health benefits of going outdoors among older adults. To better understanding the health benefits of going outdoors, clarification of potential mediators to connect going outdoors with health benefits is necessary. The present study aimed to investigate associations of objectively-measured outdoor time with older adults' physical and psychological function, and examine the mediating role of physical activity on these associations. Baseline data from a randomized control trial of physical activity among older adults with global cognitive impairment was used. Data from 192 participants were analyzed. Measures included steps-per-day, objectively-measured outdoor time per day using global positioning systems, physical function (cardiorespiratory fitness, lower-extremity strength), psychological function (depression, well-being) and basic factors. Path analysis showed that outdoor time was significantly associated with steps-per-day (path coefficient = 0.23) and depression (path coefficient = -0.16). Outdoor time was not directly associated with cardiorespiratory fitness, lower-extremity strength and well-being. However, steps-per-day was associated with cardiorespiratory fitness (path coefficient = 0.18), lower-extremity strength (path coefficient = -0.22) and well-being (path coefficient = 0.14). We found that objectively-measured outdoor time was indirectly associated with physical function, and both directly and indirectly with psychological function through physical activity among older adults. This finding indicates that going outdoors influences older adults' health outcomes, and is mainly mediated by physical activity. Geriatr Gerontol Int 2017; 17: 1455-1462. © 2016 Japan Geriatrics Society.

  19. Cardiorespiratory fitness and physical function in children with cancer from diagnosis throughout treatment

    DEFF Research Database (Denmark)

    Thorsteinsson, Troels; Larsen, Hanne Bækgaard; Schmiegelow, Kjeld

    2017-01-01

    Background: Children with cancer experience severe reductions in physical fitness and functionality during and following intensive treatment. This may negatively impact their quality of life. Purpose: To describe the physical capacity and functionality of children with cancer during and after...... treatment as well as the feasibility of physical activity intervention in the Rehabilitation including Social and Physical activity and Education in Children and Teenagers with Cancer study. Patients and methods: The study included children diagnosed from January 2013 to April 2016 with paediatric cancer...... or Langerhans cell histiocytosis, all treated with chemotherapy. Seventy-five of 78 consecutively eligible children (96.2%) were included. Median age was 11 years (range 6‒18). The physical capacity and function were assessed based on testing of physical strength, balance and cardiorespiratory fitness. Children...

  20. Sex-specific relationships of physical activity, body composition, and muscle quality with lower-extremity physical function in older men and women.

    Science.gov (United States)

    Straight, Chad R; Brady, Anne O; Evans, Ellen

    2015-03-01

    This study aims to determine the sex-specific relationships of physical activity, body composition, and muscle quality with lower-extremity physical function in older men and women. Seventy-nine community-dwelling men (n = 39; mean [SD] age, 76.1 [6.2] y; mean [SD] body mass index, 27.3 [3.8] kg/m(2)) and women (n = 40; mean [SD] age, 75.8 [5.5] y; mean [SD] body mass index, 27.0 [3.8] kg/m(2)) were assessed for physical activity via questionnaire, body composition via dual-energy x-ray absorptiometry scanning, leg extension power using the Nottingham power rig, and muscle quality (W/kg; the ratio of leg extension power [W] to lower-body mineral-free lean mass [kg]). A composite measure of physical function was obtained by summing Z scores from the 6-minute walk, 8-ft up-and-go test, and 30-second chair-stand test. As expected, men had significantly greater levels of physical activity, lower adiposity, greater lean mass, higher leg extension power, and greater muscle quality compared with women (all P physical activity were the strongest predictors of lower-extremity physical function in men and independently explained 42% and 29% of the variance, respectively. In women, muscle quality (16%) and percent body fat (12%) were independent predictors after adjustment for covariates. Muscle quality is the strongest predictor of lower-extremity physical function in men and women, but sex impacts the importance of physical activity and adiposity. These findings suggest that older men and women may benefit from different intervention strategies for preventing physical disability and also highlight the importance of weight management for older women to preserve physical function.

  1. Waggawagga-CLI: A command-line tool for predicting stable single α-helices (SAH-domains, and the SAH-domain distribution across eukaryotes.

    Directory of Open Access Journals (Sweden)

    Dominic Simm

    Full Text Available Stable single-alpha helices (SAH-domains function as rigid connectors and constant force springs between structural domains, and can provide contact surfaces for protein-protein and protein-RNA interactions. SAH-domains mainly consist of charged amino acids and are monomeric and stable in polar solutions, characteristics which distinguish them from coiled-coil domains and intrinsically disordered regions. Although the number of reported SAH-domains is steadily increasing, genome-wide analyses of SAH-domains in eukaryotic genomes are still missing. Here, we present Waggawagga-CLI, a command-line tool for predicting and analysing SAH-domains in protein sequence datasets. Using Waggawagga-CLI we predicted SAH-domains in 24 datasets from eukaryotes across the tree of life. SAH-domains were predicted in 0.5 to 3.5% of the protein-coding content per species. SAH-domains are particularly present in longer proteins supporting their function as structural building block in multi-domain proteins. In human, SAH-domains are mainly used as alternative building blocks not being present in all transcripts of a gene. Gene ontology analysis showed that yeast proteins with SAH-domains are particular enriched in macromolecular complex subunit organization, cellular component biogenesis and RNA metabolic processes, and that they have a strong nuclear and ribonucleoprotein complex localization and function in ribosome and nucleic acid binding. Human proteins with SAH-domains have roles in all types of RNA processing and cytoskeleton organization, and are predicted to function in RNA binding, protein binding involved in cell and cell-cell adhesion, and cytoskeletal protein binding. Waggawagga-CLI allows the user to adjust the stabilizing and destabilizing contribution of amino acid interactions in i,i+3 and i,i+4 spacings, and provides extensive flexibility for user-designed analyses.

  2. Work-related measures of physical and behavioral health function: Test-retest reliability.

    Science.gov (United States)

    Marino, Molly Elizabeth; Meterko, Mark; Marfeo, Elizabeth E; McDonough, Christine M; Jette, Alan M; Ni, Pengsheng; Bogusz, Kara; Rasch, Elizabeth K; Brandt, Diane E; Chan, Leighton

    2015-10-01

    The Work Disability Functional Assessment Battery (WD-FAB), developed for potential use by the US Social Security Administration to assess work-related function, currently consists of five multi-item scales assessing physical function and four multi-item scales assessing behavioral health function; the WD-FAB scales are administered as Computerized Adaptive Tests (CATs). The goal of this study was to evaluate the test-retest reliability of the WD-FAB Physical Function and Behavioral Health CATs. We administered the WD-FAB scales twice, 7-10 days apart, to a sample of 376 working age adults and 316 adults with work-disability. Intraclass correlation coefficients were calculated to measure the consistency of the scores between the two administrations. Standard error of measurement (SEM) and minimal detectable change (MDC90) were also calculated to measure the scales precision and sensitivity. For the Physical Function CAT scales, the ICCs ranged from 0.76 to 0.89 in the working age adult sample, and 0.77-0.86 in the sample of adults with work-disability. ICCs for the Behavioral Health CAT scales ranged from 0.66 to 0.70 in the working age adult sample, and 0.77-0.80 in the adults with work-disability. The SEM ranged from 3.25 to 4.55 for the Physical Function scales and 5.27-6.97 for the Behavioral Health function scales. For all scales in both samples, the MDC90 ranged from 7.58 to 16.27. Both the Physical Function and Behavioral Health CATs of the WD-FAB demonstrated good test-retest reliability in adults with work-disability and general adult samples, a critical requirement for assessing work related functioning in disability applicants and in other contexts. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Successful Aging: Advancing the Science of Physical Independence in Older Adults

    Science.gov (United States)

    Anton, Stephen D.; Woods, Adam J.; Ashizawa, Tetso; Barb, Diana; Buford, Thomas W.; Carter, Christy S.; Clark, David J.; Cohen, Ronald A.; Corbett, Duane B.; Cruz-Almeida, Yenisel; Dotson, Vonetta; Ebner, Natalie; Efron, Philip A.; Fillingim, Roger B.; Foster, Thomas C.; Gundermann, David M.; Joseph, Anna-Maria; Karabetian, Christy; Leeuwenburgh, Christiaan; Manini, Todd M.; Marsiske, Michael; Mankowski, Robert T.; Mutchie, Heather L.; Perri, Michael G.; Ranka, Sanjay; Rashidi, Parisa; Sandesara, Bhanuprasad; Scarpace, Philip J.; Sibille, Kimberly T.; Solberg, Laurence M.; Someya, Shinichi; Uphold, Connie; Wohlgemuth, Stephanie; Wu, Samuel Shangwu; Pahor, Marco

    2015-01-01

    The concept of ‘Successful Aging’ has long intrigued the scientific community. Despite this long-standing interest, a consensus definition has proven to be a difficult task, due to the inherent challenge involved in defining such a complex, multi-dimensional phenomenon. The lack of a clear set of defining characteristics for the construct of successful aging has made comparison of findings across studies difficult and has limited advances in aging research. The domain in which consensus on markers of successful aging is furthest developed is the domain of physical functioning. For example, walking speed appears to be an excellent surrogate marker of overall health and predicts the maintenance of physical independence, a cornerstone of successful aging. The purpose of the present article is to provide an overview and discussion of specific health conditions, behavioral factors, and biological mechanisms that mark declining mobility and physical function and promising interventions to counter these effects. With life expectancy continuing to increase in the United States and developed countries throughout the world, there is an increasing public health focus on the maintenance of physical independence among all older adults. PMID:26462882

  4. General quadratic gauge theory: constraint structure, symmetries and physical functions

    Energy Technology Data Exchange (ETDEWEB)

    Gitman, D M [Institute of Physics, University of Sao Paulo (Brazil); Tyutin, I V [Lebedev Physics Institute, Moscow (Russian Federation)

    2005-06-17

    How can we relate the constraint structure and constraint dynamics of the general gauge theory in the Hamiltonian formulation to specific features of the theory in the Lagrangian formulation, especially relate the constraint structure to the gauge transformation structure of the Lagrangian action? How can we construct the general expression for the gauge charge if the constraint structure in the Hamiltonian formulation is known? Whether we can identify the physical functions defined as commuting with first-class constraints in the Hamiltonian formulation and the physical functions defined as gauge invariant functions in the Lagrangian formulation? The aim of the present paper is to consider the general quadratic gauge theory and to answer the above questions for such a theory in terms of strict assertions. To fulfil such a programme, we demonstrate the existence of the so-called superspecial phase-space variables in terms of which the quadratic Hamiltonian action takes a simple canonical form. On the basis of such a representation, we analyse a functional arbitrariness in the solutions of the equations of motion of the quadratic gauge theory and derive the general structure of symmetries by analysing a symmetry equation. We then use these results to identify the two definitions of physical functions and thus prove the Dirac conjecture.

  5. Perspective: Fifty years of density-functional theory in chemical physics

    International Nuclear Information System (INIS)

    Becke, Axel D.

    2014-01-01

    Since its formal inception in 1964–1965, Kohn-Sham density-functional theory (KS-DFT) has become the most popular electronic structure method in computational physics and chemistry. Its popularity stems from its beautifully simple conceptual framework and computational elegance. The rise of KS-DFT in chemical physics began in earnest in the mid 1980s, when crucial developments in its exchange-correlation term gave the theory predictive power competitive with well-developed wave-function methods. Today KS-DFT finds itself under increasing pressure to deliver higher and higher accuracy and to adapt to ever more challenging problems. If we are not mindful, however, these pressures may submerge the theory in the wave-function sea. KS-DFT might be lost. I am hopeful the Kohn-Sham philosophical, theoretical, and computational framework can be preserved. This Perspective outlines the history, basic concepts, and present status of KS-DFT in chemical physics, and offers suggestions for its future development

  6. Perspective: Fifty years of density-functional theory in chemical physics

    Energy Technology Data Exchange (ETDEWEB)

    Becke, Axel D., E-mail: axel.becke@dal.ca [Department of Chemistry, Dalhousie University, 6274 Coburg Rd., P.O. Box 15000, Halifax, Nova Scotia B3H 4R2 (Canada)

    2014-05-14

    Since its formal inception in 1964–1965, Kohn-Sham density-functional theory (KS-DFT) has become the most popular electronic structure method in computational physics and chemistry. Its popularity stems from its beautifully simple conceptual framework and computational elegance. The rise of KS-DFT in chemical physics began in earnest in the mid 1980s, when crucial developments in its exchange-correlation term gave the theory predictive power competitive with well-developed wave-function methods. Today KS-DFT finds itself under increasing pressure to deliver higher and higher accuracy and to adapt to ever more challenging problems. If we are not mindful, however, these pressures may submerge the theory in the wave-function sea. KS-DFT might be lost. I am hopeful the Kohn-Sham philosophical, theoretical, and computational framework can be preserved. This Perspective outlines the history, basic concepts, and present status of KS-DFT in chemical physics, and offers suggestions for its future development.

  7. Building a patchwork - The yeast plasma membrane as model to study lateral domain formation.

    Science.gov (United States)

    Schuberth, Christian; Wedlich-Söldner, Roland

    2015-04-01

    The plasma membrane (PM) has to fulfill a wide range of biological functions including selective uptake of substances, signal transduction and modulation of cell polarity and cell shape. To allow efficient regulation of these processes many resident proteins and lipids of the PM are laterally segregated into different functional domains. A particularly striking example of lateral segregation has been described for the budding yeast PM, where integral membrane proteins as well as lipids exhibit very slow translational mobility and form a patchwork of many overlapping micron-sized domains. Here we discuss the molecular and physical mechanisms contributing to the formation of a multi-domain membrane and review our current understanding of yeast PM organization. Many of the fundamental principles underlying membrane self-assembly and organization identified in yeast are expected to equally hold true in other organisms, even for the more transient and elusive organization of the PM in mammalian cells. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Measurement of multi-bunch transfer functions using time-domain data and Fourier analysis

    International Nuclear Information System (INIS)

    Hindi, H.; Sapozhnikov, L.; Fox, J.; Prabhakar, S.; Oxoby, G.; Linscott, I.; Drago, A.

    1993-12-01

    Multi-bunch transfer functions are principal ingredients in understanding both the behavior of high-current storage rings as well as control of their instabilities. The measurement of transfer functions on a bunch-by-bunch basis is particularly important in the design of active feedback systems. Traditional methods of network analysis that work well in the single bunch case become difficult to implement for many bunches. We have developed a method for obtaining empirical estimates of the multi-bunch longitudinal transfer functions from the time-domain measurements of the bunches' phase oscillations. This method involves recording the response of the bunch of interest to a white-noise excitation. The transfer function can then be computed as the ratio of the fast Fourier transforms (FFTs) of the response and excitation sequences, averaged over several excitations. The calculation is performed off-line on bunch-phase data and is well-suited to the multi-bunch case. A description of this method and an analysis of its performance is presented with results obtained using the longitudinal quick prototype feedback system developed at SLAC

  9. Criteria, indicators and levels of formed professional functional competences of future teachers of physical culture

    Directory of Open Access Journals (Sweden)

    Samsutina N.M.

    2012-09-01

    Full Text Available It is shown the structural components of the functional competence of professional teachers of physical education: motivational, cognitive and action-practical. We used the following methods of scientific knowledge, as the analysis of psychological, educational and methodological literature, synthesis, comparison, generalization, specification, classification, ordering Criteria and levels of occupational functional competence of future teachers of physical education. It is determined that the high level of professional formation of the functional competence of future teachers of physical culture is characterized by the motivation to perform professional functions of a teacher of physical culture, fundamental knowledge required to perform professional functions of a teacher of physical culture, a high level of general physical fitness, pronounced specific motor abilities and skills.

  10. Physical function and muscle strength in sporadic inclusion body myositis

    DEFF Research Database (Denmark)

    Jørgensen, Anders N; Aagaard, Per; Nielsen, Jakob L

    2017-01-01

    INTRODUCTION: In this study, self-reported physical function, functional capacity, and isolated muscle function were investigated in sporadic inclusion body myositis (sIBM) patients. METHODS: The 36-item Short Form (SF-36) Health Survey and 2-min walk test (2MWT), timed up & go test (TUG), and 30-s...

  11. Adherence to physical activity guidelines and functional fitness of elderly women, using objective measurement.

    Science.gov (United States)

    Nawrocka, Agnieszka; Mynarski, Władysław; Cholewa, Jarosław

    2017-12-23

    Physical activity is an important factor in maintaining the health and functional fitness of elderly people. The aim of the study was to determine the number of senior women meeting the physical activity guidelines, and their level of functional fitness in comparison to women who are not sufficiently physically active. The study involved 61 women, aged 60-75. Physical activity was monitored on seven consecutive days of the week, using a triaxial accelerometer ActiGraph GT3X. Results of the assessment of physical activity were verified against the Global Recommendations of Physical Activity for Health. The Senior Fitness Test (Fullerton Test) was used to evaluate functional fitness. In the studied group, 36.1% achieved the recommended level of physical activity. All those examined mainly undertook physical activity of low intensity. Vigorous physical activity during the week was noted in only 6 seniors. Women who met the recommendations of physical activity achieved significantly better results in test trials, e.g. Chair Stands, Up and Go, Six Minute Step Test. Adherence to physical activity guidelines was associated with better functional fitness of older women. However, less than half of the examined seniors met the Global Recommendations on Physical Activity for Health.

  12. Functional role of the cytoplasmic tail domain of the major envelope fusion protein of group II baculoviruses

    NARCIS (Netherlands)

    Long, G.; Pan, M.; Westenberg, M.; Vlak, J.M.

    2006-01-01

    F proteins from baculovirus nucleopolyhedrovirus (NPV) group II members are the major budded virus (BV) viral envelope fusion proteins. They undergo furin-like proteolysis processing in order to be functional. F proteins from different baculovirus species have a long cytoplasmic tail domain (CTD),

  13. Association between physical activity and kidney function: National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Hawkins, Marquis S; Sevick, Mary Ann; Richardson, Caroline R; Fried, Linda F; Arena, Vincent C; Kriska, Andrea M

    2011-08-01

    Chronic kidney disease is a condition characterized by the deterioration of the kidney's ability to remove waste products from the body. Although treatments to slow the progression of the disease are available, chronic kidney disease may eventually lead to a complete loss of kidney function. Previous studies have shown that physical activities of moderate intensity may have renal benefits. Few studies have examined the effects of total movement on kidney function. The purpose of this study was to determine the association between time spent at all levels of physical activity intensity and sedentary behavior and kidney function. Data were obtained from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Survey, a cross-sectional study of a complex, multistage probability sample of the US population. Physical activity was assessed using an accelerometer and questionnaire. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease study formula. To assess linear associations between levels of physical activity and sedentary behavior with log-transformed estimated GFR (eGFR), linear regression was used. In general, physical activity (light and total) was related to log eGFR in females and males. For females, the association between light and total physical activity with log eGFR was consistent regardless of diabetes status. For males, the association between light and total physical activity and log eGFR was only significant in males without diabetes. When examining the association between physical activity, measured objectively with an accelerometer, and kidney function, total and light physical activities were found to be positively associated with kidney function.

  14. Optimizing the benefits of exercise on physical function in older adults.

    Science.gov (United States)

    Buford, Thomas W; Anton, Stephen D; Clark, David J; Higgins, Torrance J; Cooke, Matthew B

    2014-06-01

    As the number of older adults continues to rise worldwide, the prevention of physical disability among seniors is an increasingly important public health priority. Physical exercise is among the best known methods of preventing disability, but accumulating evidence indicates that considerable variability exists in the responsiveness of older adults to standard training regimens. Accordingly, a need exists to develop tailored interventions to optimize the beneficial effects of exercise on the physical function of older adults at risk for becoming disabled. The present review summarizes the available literature related to the use of adjuvant or alternative strategies intended to enhance the efficacy of exercise in improving the physical function of older adults. Within this work, we also discuss potential future research directions in this area. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  15. A conserved tryptophan within the WRDPLVDID domain of yeast Pah1 phosphatidate phosphatase is required for its in vivo function in lipid metabolism.

    Science.gov (United States)

    Park, Yeonhee; Han, Gil-Soo; Carman, George M

    2017-12-01

    PAH1 -encoded phosphatidate phosphatase, which catalyzes the dephosphorylation of phosphatidate to produce diacylglycerol at the endoplasmic reticulum membrane, plays a major role in controlling the utilization of phosphatidate for the synthesis of triacylglycerol or membrane phospholipids. The conserved N-LIP and haloacid dehalogenase-like domains of Pah1 are required for phosphatidate phosphatase activity and the in vivo function of the enzyme. Its non-conserved regions, which are located between the conserved domains and at the C terminus, contain sites for phosphorylation by multiple protein kinases. Truncation analyses of the non-conserved regions showed that they are not essential for the catalytic activity of Pah1 and its physiological functions ( e.g. triacylglycerol synthesis). This analysis also revealed that the C-terminal region contains a previously unrecognized WRDPLVDID domain (residues 637-645) that is conserved in yeast, mice, and humans. The deletion of this domain had no effect on the catalytic activity of Pah1 but caused the loss of its in vivo function. Site-specific mutational analyses of the conserved residues within WRDPLVDID indicated that Trp-637 plays a crucial role in Pah1 function. This work also demonstrated that the catalytic activity of Pah1 is required but is not sufficient for its in vivo functions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Frequency-domain Green's functions for radar waves in heterogeneous 2.5D media

    Science.gov (United States)

    Ellefsen, K.J.; Croize, D.; Mazzella, A.T.; McKenna, J.R.

    2009-01-01

    Green's functions for radar waves propagating in heterogeneous 2.5D media might be calculated in the frequency domain using a hybrid method. The model is defined in the Cartesian coordinate system, and its electromagnetic properties might vary in the x- and z-directions, but not in the y-direction. Wave propagation in the x- and z-directions is simulated with the finite-difference method, and wave propagation in the y-direction is simulated with an analytic function. The absorbing boundaries on the finite-difference grid are perfectly matched layers that have been modified to make them compatible with the hybrid method. The accuracy of these numerical Greens functions is assessed by comparing them with independently calculated Green's functions. For a homogeneous model, the magnitude errors range from -4.16% through 0.44%, and the phase errors range from -0.06% through 4.86%. For a layered model, the magnitude errors range from -2.60% through 2.06%, and the phase errors range from -0.49% through 2.73%. These numerical Green's functions might be used for forward modeling and full waveform inversion. ?? 2009 Society of Exploration Geophysicists. All rights reserved.

  17. Exploring quality of life of children with cerebral palsy and intellectual disability: What are the important domains of life?

    Science.gov (United States)

    Davis, E; Reddihough, D; Murphy, N; Epstein, A; Reid, S M; Whitehouse, A; Williams, K; Leonard, H; Downs, J

    2017-11-01

    Although it is estimated that half of all children with cerebral palsy also have comorbid intellectual disability, the domains of quality of life (QOL) important for these children are not well understood. The aim of this study was to identify important domains of QOL for these children and adolescents. Due to the children's communication impairments, qualitative semi-structured interviews were conducted with 18 parents. The children (9 males) had a median age of 12 (range 7 to 17) years at interview and nearly two thirds were classified as Gross Motor Function Classification System IV or V. A grounded theory approach was used to identify domains of QOL. The 11 domains identified as important to QOL were physical health, body comfort, behaviour and emotion, communication, predictability and routine, movement and physical activity, nature and outdoors, variety of activity, independence and autonomy, social connectedness, and access to services. The domains of QOL that emerged from this study will be useful for professionals who support children with cerebral palsy and their families. They will also be important for developing a QOL instrument essential for informing the development of interventions and their monitoring and evaluation. © 2017 John Wiley & Sons Ltd.

  18. Relationships of self-reported physical activity domains with accelerometry recordings in French adults.

    Science.gov (United States)

    Jacobi, David; Charles, Marie-Aline; Tafflet, Muriel; Lommez, Agnès; Borys, Jean-Michel; Oppert, Jean-Michel

    2009-01-01

    The objective was to examine the relationships of self-reported physical activity (PA) by domain (leisure, occupational, other) with PA and sedentary time as measured objectively by accelerometry. Subjects were adults with low habitual PA levels from a community in northern France. Among subjects in the lowest tertile of a PA score from a screening questionnaire, 160 (37% males, age: 41.0 +/- 10.8 years, BMI: 25.1 +/- 4.1 kg/m(2), mean +/- SD) completed a detailed instrument (Modifiable Activity Questionnaire), and wore an accelerometer (Actigraph) for seven consecutive days. Relationships between questionnaire domains (occupational, leisure, and "non-occupational non-leisure") and accelerometry measures (total activity and sedentary time) were assessed using Spearman correlation coefficients. In this population, the highest contributor to total reported PA (h/week) was occupational PA. Time spent in non-occupational non-leisure PA ranked second in women and third in men. The most frequent non-occupational non-leisure PA were shopping and household chores. In women, non-occupational non-leisure PA contributed more than occupational or leisure-time PA to total PA energy expenditure (median: 18.0, 9.1, and 4.9 MET-h/week, respectively). Total PA by accelerometry (count/day) was correlated to leisure-time PA in women (r = 0.22, P time (h/day) and non-occupational non-leisure PA (MET-h/week, r = -0.30, P importance of assessing non-occupational non-leisure PA for a better understanding of how individuals partition their time between active or sedentary occupations.

  19. Physical and mental decline and yet rather happy?

    DEFF Research Database (Denmark)

    Vestergaard, Sonja; Thinggaard, Mikael; Jeune, Bernard

    2015-01-01

    Objectives: Little is known about whether the feeling of happiness follows the age-related decline in physical and mental functioning. The objective of this study was to analyze differences with age in physical and mental functions and in the feeling of happiness among Danes aged 45 years and older......-reported mobility, a cognitive composite score, and a depression symptomatology score including a question about happiness were assessed. T-score metric was used to compare across domains and age groups. Results: Overall, successively older age groups performed worse than the youngest age group (45-49 years.......9), and the total depression symptomatology score (men: 15.5, women: 17.4). Conversely, the T-score difference in happiness was small (men: 5.6, women: 6.0). Conclusion: Despite markedly poorer physical and mental functions with increasing age, in this Danish sample age did not seem to affect happiness...

  20. Functional Elements on SIRPα IgV domain Mediate Cell Surface Binding to CD47

    Science.gov (United States)

    Liu, Yuan; Tong, Qiao; Zhou, Yubin; Lee, Hsiau-Wei; Yang, Jenny J.; Bühring, Hans-Jörg; Chen, Yi-Tien; Ha, Binh; Chen, Celia X-J.; Zen, Ke

    2007-01-01

    Summary SIRPα and SIRPβ1, the two major isoforms of the signal regulatory protein (SIRP) family, are co-expressed in human leukocytes but mediate distinct extracellular binding interactions and divergent cell signaling responses. Previous studies have demonstrated that binding of SIRPα with CD47, another important cell surface molecule, through the extracellular IgV domain regulates important leukocyte functions including macrophage recognition, leukocyte adhesion and transmigration. Although SIRPβ1 shares highly homologous extracellular IgV structure with SIRPα, it does not bind to CD47. In this study, we defined key amino acid residues exclusively expressing in the IgV domain of SIRPα, but not SIRPβ1, which determine the extracellular binding interaction of SIRPα to CD47. These key residues include Gln67, a small hydrophobic amino acid (Ala or Val) at the 57th position and Met102. We found that Gln67 and Ala/Val57 are critical. Mutation of either of these residues abates SIRPα directly binding to CD47. Functional cell adhesion and leukocyte transmigration assays further demonstrated central roles of Gln67 and Ala/Val57 in SIRPα extracellular binding mediated cell interactions and cell migration. Another SIRPα-specific residue, Met102, appears to assist SIRPα IgV binding through Gln67 and Ala/Val57. An essential role of these amino acids in SIRPα binding to CD47 was further confirmed by introducing these residues into the SIRPβ1 IgV domain, which dramatically converts SIRPβ1 into a CD47-binding molecule. Our results thus revealed the molecular basis by which SIRPα selectively binds to CD47 and shed new light into the structural mechanisms of SIRP isoform mediated distinctive extracellular interactions and cellular responses. PMID:17070842

  1. Functional elements on SIRPalpha IgV domain mediate cell surface binding to CD47.

    Science.gov (United States)

    Liu, Yuan; Tong, Qiao; Zhou, Yubin; Lee, Hsiau-Wei; Yang, Jenny J; Bühring, Hans-Jörg; Chen, Yi-Tien; Ha, Binh; Chen, Celia X-J; Yang, Yang; Zen, Ke

    2007-01-19

    SIRPalpha and SIRPbeta1, the two major isoforms of the signal regulatory protein (SIRP) family, are co-expressed in human leukocytes but mediate distinct extracellular binding interactions and divergent cell signaling responses. Previous studies have demonstrated that binding of SIRPalpha with CD47, another important cell surface molecule, through the extracellular IgV domain regulates important leukocyte functions including macrophage recognition, leukocyte adhesion and transmigration. Although SIRPbeta1 shares highly homologous extracellular IgV structure with SIRPalpha, it does not bind to CD47. Here, we defined key amino acid residues exclusively expressing in the IgV domain of SIRPalpha, but not SIRPbeta1, which determine the extracellular binding interaction of SIRPalpha to CD47. These key residues include Gln67, a small hydrophobic amino acid (Ala or Val) at the 57th position and Met102. We found that Gln67 and Ala/Val57 are critical. Mutation of either of these residues abates SIRPalpha directly binding to CD47. Functional cell adhesion and leukocyte transmigration assays further demonstrated central roles of Gln67 and Ala/Val57 in SIRPalpha extracellular binding mediated cell interactions and cell migration. Another SIRPalpha-specific residue, Met102, appears to assist SIRPalpha IgV binding through Gln67 and Ala/Val57. An essential role of these amino acid residues in SIRPalpha binding to CD47 was further confirmed by introducing these residues into the SIRPbeta1 IgV domain, which dramatically converts SIRPbeta1 into a CD47-binding molecule. Our results thus revealed the molecular basis by which SIRPalpha binds to CD47 and shed new light into the structural mechanisms of SIRP isoform mediated distinctive extracellular interactions and cellular responses.

  2. Physical exercise and osteoporosis: effects of different types of exercises on bone and physical function of postmenopausal women.

    Science.gov (United States)

    Moreira, Linda Denise Fernandes; Oliveira, Mônica Longo de; Lirani-Galvão, Ana Paula; Marin-Mio, Rosângela Villa; Santos, Rodrigo Nolasco dos; Lazaretti-Castro, Marise

    2014-07-01

    Physical exercise is an important stimulus for osteoporosis prevention and treatment. However, it is not clear yet which modality would be better to stimulate bone metabolism and enhance physical function of postmenopausal women. This review paper aims to summarize and update present knowledge on the effects of different kinds of aquatic and ground physical exercises on bone metabolism and physical function of postmenopausal women. Moderate to intense exercises, performed in a high speed during short intervals of time, in water or on the ground, can be part of a program to prevent and treat postmenopausal osteoporosis. Mechanical vibration has proven to be beneficial for bone microarchitecture, improving bone density and bone strength, as well as increasing physical function. Although impact exercises are recognized as beneficial for the stimulation of bone tissue, other variables such as muscle strength, type of muscle contraction, duration and intensity of exercises are also determinants to induce changes in bone metabolism of postmenopausal women. Not only osteoanabolic exercises should be recommended; activities aimed to develop muscle strength and body balance and improve the proprioception should be encouraged to prevent falls and fractures.

  3. Stochastic lattice model of synaptic membrane protein domains.

    Science.gov (United States)

    Li, Yiwei; Kahraman, Osman; Haselwandter, Christoph A

    2017-05-01

    Neurotransmitter receptor molecules, concentrated in synaptic membrane domains along with scaffolds and other kinds of proteins, are crucial for signal transmission across chemical synapses. In common with other membrane protein domains, synaptic domains are characterized by low protein copy numbers and protein crowding, with rapid stochastic turnover of individual molecules. We study here in detail a stochastic lattice model of the receptor-scaffold reaction-diffusion dynamics at synaptic domains that was found previously to capture, at the mean-field level, the self-assembly, stability, and characteristic size of synaptic domains observed in experiments. We show that our stochastic lattice model yields quantitative agreement with mean-field models of nonlinear diffusion in crowded membranes. Through a combination of analytic and numerical solutions of the master equation governing the reaction dynamics at synaptic domains, together with kinetic Monte Carlo simulations, we find substantial discrepancies between mean-field and stochastic models for the reaction dynamics at synaptic domains. Based on the reaction and diffusion properties of synaptic receptors and scaffolds suggested by previous experiments and mean-field calculations, we show that the stochastic reaction-diffusion dynamics of synaptic receptors and scaffolds provide a simple physical mechanism for collective fluctuations in synaptic domains, the molecular turnover observed at synaptic domains, key features of the observed single-molecule trajectories, and spatial heterogeneity in the effective rates at which receptors and scaffolds are recycled at the cell membrane. Our work sheds light on the physical mechanisms and principles linking the collective properties of membrane protein domains to the stochastic dynamics that rule their molecular components.

  4. The Arabidopsis thaliana proteome harbors undiscovered multi-domain molecules with functional guanylyl cyclase catalytic centers

    KAUST Repository

    Wong, Aloysius Tze

    2013-07-08

    Background: Second messengers link external cues to complex physiological responses. One such messenger, 3\\',5\\'-cyclic guanosine monophosphate (cGMP), has been shown to play a key role in many physiological responses in plants. However, in higher plants, guanylyl cyclases (GCs), enzymes that generate cGMP from guanosine-5\\'-triphosphate (GTP) have remained elusive until recently. GC search motifs constructed from the alignment of known GCs catalytic centers form vertebrates and lower eukaryotes have led to the identification of a number of plant GCs that have been characterized in vitro and in vivo.Presentation of the hypothesis.Recently characterized GCs in Arabidopsis thaliana contributed to the development of search parameters that can identify novel candidate GCs in plants. We hypothesize that there are still a substantial number (> 40) of multi-domain molecules with potentially functional GC catalytic centers in plants that remain to be discovered and characterized. Testing the hypothesis. The hypothesis can be tested, firstly, by computational methods constructing 3D models of selected GC candidates using available crystal structures as templates. Homology modeling must include substrate docking that can provide support for the structural feasibility of the GC catalytic centers in those candidates. Secondly, recombinant peptides containing the GC domain need to be tested in in vitro GC assays such as the enzyme-linked immune-sorbent assay (ELISA) and/or in mass spectrometry based cGMP assays. In addition, quantification of in vivo cGMP transients with fluorescent cGMP-reporter assays in wild-type or selected mutants will help to elucidate the biological role of novel GCs.Implications of the hypothesis.If it turns out that plants do harbor a large number of functional GC domains as part of multi-domain enzymes, then major new insights will be gained into the complex signal transduction pathways that link cGMP to fundamental processes such as ion transport

  5. Predictive value of different conventional and non-conventional MRI-parameters for specific domains of cognitive function in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Daniela Pinter

    2015-01-01

    Conclusions: The predictive value of distinct MRI-parameters differs for specific domains of cognitive function, with a greater impact of cortical volume, focal and diffuse white matter abnormalities on overall cognitive function, an additional role of basal ganglia iron deposition on cognitive efficiency, and thalamic and hippocampal volume on memory function. This suggests the usefulness of using multiparametric MRI to assess (microstructural correlates of different cognitive constructs.

  6. Optimizing the Benefits of Exercise on Physical Function in Older Adults

    Science.gov (United States)

    Buford, Thomas W.; Anton, Stephen D.; Clark, David J.; Higgins, Torrance J.; Cooke, Matthew B.

    2014-01-01

    As the number of older adults continues to rise worldwide, the prevention of physical disability among seniors is an increasingly important public health priority. Physical exercise is among the best known methods of preventing disability, but accumulating evidence indicates that considerable variability exists in the responsiveness of older adults to standard training regimens. Accordingly, a need exists to develop tailored interventions to optimize the beneficial effects of exercise on the physical function of older adults at risk for becoming disabled. The present review summarizes the available literature related to the use of adjuvant or alternative strategies intended to enhance the efficacy of exercise in improving the physical function of older adults. Within this work, we also discuss potential future research directions in this area. PMID:24361365

  7. Multiple functional roles of the accessory I-domain of bacteriophage P22 coat protein revealed by NMR structure and CryoEM modeling.

    Science.gov (United States)

    Rizzo, Alessandro A; Suhanovsky, Margaret M; Baker, Matthew L; Fraser, LaTasha C R; Jones, Lisa M; Rempel, Don L; Gross, Michael L; Chiu, Wah; Alexandrescu, Andrei T; Teschke, Carolyn M

    2014-06-10

    Some capsid proteins built on the ubiquitous HK97-fold have accessory domains imparting specific functions. Bacteriophage P22 coat protein has a unique insertion domain (I-domain). Two prior I-domain models from subnanometer cryoelectron microscopy (cryoEM) reconstructions differed substantially. Therefore, the I-domain's nuclear magnetic resonance structure was determined and also used to improve cryoEM models of coat protein. The I-domain has an antiparallel six-stranded β-barrel fold, not previously observed in HK97-fold accessory domains. The D-loop, which is dynamic in the isolated I-domain and intact monomeric coat protein, forms stabilizing salt bridges between adjacent capsomers in procapsids. The S-loop is important for capsid size determination, likely through intrasubunit interactions. Ten of 18 coat protein temperature-sensitive-folding substitutions are in the I-domain, indicating its importance in folding and stability. Several are found on a positively charged face of the β-barrel that anchors the I-domain to a negatively charged surface of the coat protein HK97-core. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. The Relationship Between Emotion Regulation, Executive Functioning, and Aggressive Behaviors.

    Science.gov (United States)

    Holley, Sarah R; Ewing, Scott T; Stiver, Jordan T; Bloch, Lian

    2015-06-30

    Emotion regulation deficits and executive functioning deficits have independently been shown to increase vulnerability toward engaging in aggressive behaviors. The effects of these risk factors, however, have not been evaluated in relation to one another. This study evaluated the degree to which each was associated with aggressive behaviors in a sample of 168 undergraduate students. Executive functioning (cognitive inhibition and mental flexibility) was assessed with a Stroop-like neuropsychological task. Emotion regulation and aggressive behaviors were assessed via self-report inventories. Results showed main effects for both emotion regulation and executive functioning, as well as a significant interaction, indicating that those who scored lowest in both domains reported engaging in aggressive behaviors the most frequently. When different types of aggression were examined, this interaction was only significant for acts of physical aggression, not for acts of verbal aggression. Therefore, for physical aggression, emotion regulation and executive functioning exerted a moderating effect on one another. The implications are that, at least for acts of physical aggression, relatively strong capabilities in either domain may buffer against tendencies to engage in aggressive behaviors. Thus, both emotion regulation skills and executive functioning abilities may be valuable targets for interventions aiming to reduce aggressive behaviors. © The Author(s) 2015.

  9. Symbolic Computation, Number Theory, Special Functions, Physics and Combinatorics

    CERN Document Server

    Ismail, Mourad

    2001-01-01

    These are the proceedings of the conference "Symbolic Computation, Number Theory, Special Functions, Physics and Combinatorics" held at the Department of Mathematics, University of Florida, Gainesville, from November 11 to 13, 1999. The main emphasis of the conference was Com­ puter Algebra (i. e. symbolic computation) and how it related to the fields of Number Theory, Special Functions, Physics and Combinatorics. A subject that is common to all of these fields is q-series. We brought together those who do symbolic computation with q-series and those who need q-series in­ cluding workers in Physics and Combinatorics. The goal of the conference was to inform mathematicians and physicists who use q-series of the latest developments in the field of q-series and especially how symbolic computa­ tion has aided these developments. Over 60 people were invited to participate in the conference. We ended up having 45 participants at the conference, including six one hour plenary speakers and 28 half hour speakers. T...

  10. PHYSICAL CULTURE AND HEALTH CULTURE – INNOVATIONAL CULTUROLOGICAL APPROACH

    Directory of Open Access Journals (Sweden)

    Grujo Bjeković

    2008-08-01

    Full Text Available Inaugural discusses of metatheoretical innovatinal forming of upgrading the cultural health and pedagogical technology of children’s and youth’s health progress and protection systems in the system of generally educational and health-school organizations. Establishment of a dynamical cumulative knowledge exchange and cooperative harmonization of the pedagogues of teaching obligations in the constitution of knowledge management educational space on rising health culture, physicality, and enriching sport and recreative lifestyle. Working out of con ceptual structural-functional scheme of health management measures in school and of evaluation of psychophysical and functional potentials, from the aspect of personalorientation. Establishment of complex system monitoring for physical development and physical capabilities and achieved results in domain of self-organized sport and sport-recreative selected activities.

  11. A Heparin Binding Motif Rich in Arginine and Lysine is the Functional Domain of YKL-40

    Directory of Open Access Journals (Sweden)

    Nipaporn Ngernyuang

    2018-02-01

    Full Text Available The heparin-binding glycoprotein YKL-40 (CHI3L1 is intimately associated with microvascularization in multiple human diseases including cancer and inflammation. However, the heparin-binding domain(s pertinent to the angiogenic activity have yet been identified. YKL-40 harbors a consensus heparin-binding motif that consists of positively charged arginine (R and lysine (K (RRDK; residues 144–147; but they don't bind to heparin. Intriguingly, we identified a separate KR-rich domain (residues 334–345 that does display strong heparin binding affinity. A short synthetic peptide spanning this KR-rich domain successfully competed with YKL-40 and blocked its ability to bind heparin. Three individual point mutations, where alanine (A substituted for K or R (K337A, K342A, R344A, led to remarkable decreases in heparin-binding ability and angiogenic activity. In addition, a neutralizing anti-YKL-40 antibody that targets these residues and prevents heparin binding impeded angiogenesis in vitro. MDA-MB-231 breast cancer cells engineered to express ectopic K337A, K342A or R344A mutants displayed reduced tumor development and compromised tumor vessel formation in mice relative to control cells expressing wild-type YKL-40. These data reveal that the KR-rich heparin-binding motif is the functional heparin-binding domain of YKL-40. Our findings shed light on novel molecular mechanisms underlying endothelial cell angiogenesis promoted by YKL-40 in a variety of diseases.

  12. Image reconstruction by domain-transform manifold learning

    Science.gov (United States)

    Zhu, Bo; Liu, Jeremiah Z.; Cauley, Stephen F.; Rosen, Bruce R.; Rosen, Matthew S.

    2018-03-01

    Image reconstruction is essential for imaging applications across the physical and life sciences, including optical and radar systems, magnetic resonance imaging, X-ray computed tomography, positron emission tomography, ultrasound imaging and radio astronomy. During image acquisition, the sensor encodes an intermediate representation of an object in the sensor domain, which is subsequently reconstructed into an image by an inversion of the encoding function. Image reconstruction is challenging because analytic knowledge of the exact inverse transform may not exist a priori, especially in the presence of sensor non-idealities and noise. Thus, the standard reconstruction approach involves approximating the inverse function with multiple ad hoc stages in a signal processing chain, the composition of which depends on the details of each acquisition strategy, and often requires expert parameter tuning to optimize reconstruction performance. Here we present a unified framework for image reconstruction—automated transform by manifold approximation (AUTOMAP)—which recasts image reconstruction as a data-driven supervised learning task that allows a mapping between the sensor and the image domain to emerge from an appropriate corpus of training data. We implement AUTOMAP with a deep neural network and exhibit its flexibility in learning reconstruction transforms for various magnetic resonance imaging acquisition strategies, using the same network architecture and hyperparameters. We further demonstrate that manifold learning during training results in sparse representations of domain transforms along low-dimensional data manifolds, and observe superior immunity to noise and a reduction in reconstruction artefacts compared with conventional handcrafted reconstruction methods. In addition to improving the reconstruction performance of existing acquisition methodologies, we anticipate that AUTOMAP and other learned reconstruction approaches will accelerate the development

  13. Relationship between physical activity and cognitive function in apparently healthy young to middle-aged adults: A systematic review.

    Science.gov (United States)

    Cox, Eka Peng; O'Dwyer, Nicholas; Cook, Rebecca; Vetter, Melanie; Cheng, Hoi Lun; Rooney, Kieron; O'Connor, Helen

    2016-08-01

    There is increasing evidence that physical activity (PA) positively affects cognitive function (CF). Existing research has focussed on this association in children and the elderly, with less research available in young to middle-aged adults who constitute a substantial proportion of the population. A systematic review investigating the relationship between habitual PA (≥12 months) and CF in young to middle-aged adults (18-50 years). A search was conducted using AMED, CINAHL, MEDLINE, PsychINFO, AUSPORT MED and SPORTDiscus databases. Eligible studies had to report descriptive statistics for CF and PA levels in healthy participants 18-50 years. Effect sizes (ES) (Hedges g) were calculated where possible. The initial search netted 26,988 potentially relevant manuscripts, with four more identified through hand searching. Fourteen were included for review. A range of validated platforms assessed CF across three domains: executive function (12 studies), memory (four studies) and processing speed (seven studies). Habitual PA was assessed via questionnaire/self-report methods (n=13, 8 validated) or accelerometers (n=1). In studies of executive function, five found a significant ES in favour of higher PA, ranging from small to large. Although three of four studies in the memory domain reported a significant benefit of higher PA, there was only one significant ES, which favoured low PA. Only one study examining processing speed had a significant ES, favouring higher PA. A limited body of evidence supports a positive effect of PA on CF in young to middle-aged adults. Further research into this relationship at this age stage is warranted. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  14. Relationship between physical function and biomechanical gait patterns in boys with haemophilia.

    Science.gov (United States)

    Stephensen, D; Taylor, S; Bladen, M; Drechsler, W I

    2016-11-01

    The World Federation of Haemophilia recommends joint and muscle health is evaluated using X-ray and magnetic resonance imaging, together with clinical examination scores. To date, inclusion of performance-based functional activities to monitor children with the condition has received little attention. To evaluate test-retest repeatability of physical function tests and quantify relationships between physical function, lower limb muscle strength and gait patterns in young boys with haemophilia. Timed 6-minute walk, timed up and down stairs, timed single leg stance, muscle strength of the knee extensors, ankle dorsi and plantar flexors, together with joint biomechanics during level walking were collected from 21 boys aged 6-12 years with severe haemophilia. Measures of physical function and recording of muscle strength with a hand-held myometer were repeatable (ICC > 0.78). Distances walked in six minutes, time taken to go up and down a flight of stairs and lower limb muscle strength correlated closely with ankle range of motion, together with peak knee flexion and ankle dorsi and plantarflexion moments during walking (P biomechanical joint function, and hence might serve as a basis for the clinical monitoring of physical function outcomes in children with haemophilia. © 2016 John Wiley & Sons Ltd.

  15. Ligand binding reduces SUMOylation of the peroxisome proliferator-activated receptor γ (PPARγ activation function 1 (AF1 domain.

    Directory of Open Access Journals (Sweden)

    Rolf Diezko

    Full Text Available Peroxisome proliferator-activated receptor gamma (PPARγ is a ligand-activated nuclear receptor regulating adipogenesis, glucose homeostasis and inflammatory responses. The activity of PPARγ is controlled by post-translational modifications including SUMOylation and phosphorylation that affects its biological and molecular functions. Several important aspects of PPARγ SUMOylation including SUMO isoform-specificity and the impact of ligand binding on SUMOylation remain unresolved or contradictory. Here, we present a comprehensive study of PPARγ1 SUMOylation. We show that PPARγ1 can be modified by SUMO1 and SUMO2. Mutational analyses revealed that SUMOylation occurs exclusively within the N-terminal activation function 1 (AF1 domain predominantly at lysines 33 and 77. Ligand binding to the C-terminal ligand-binding domain (LBD of PPARγ1 reduces SUMOylation of lysine 33 but not of lysine 77. SUMOylation of lysine 33 and lysine 77 represses basal and ligand-induced activation by PPARγ1. We further show that lysine 365 within the LBD is not a target for SUMOylation as suggested in a previous report, but it is essential for full LBD activity. Our results suggest that PPARγ ligands negatively affect SUMOylation by interdomain communication between the C-terminal LBD and the N-terminal AF1 domain. The ability of the LBD to regulate the AF1 domain may have important implications for the evaluation and mechanism of action of therapeutic ligands that bind PPARγ.

  16. PROMIS®-29 v2.0 profile physical and mental health summary scores.

    Science.gov (United States)

    Hays, Ron D; Spritzer, Karen L; Schalet, Benjamin D; Cella, David

    2018-03-22

    The PROMIS-29 v2.0 profile assesses pain intensity using a single 0-10 numeric rating item and seven health domains (physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance) using four items per domain. This paper describes the development of physical and mental health summary scores for the PROMIS-29 v2.0. We conducted factor analyses of PROMIS-29 scales on data collected from two internet panels (n = 3000 and 2000). Confirmatory factor analyses provided support for a physical health factor defined by physical function, pain (interference and intensity), and ability to participate in social roles and activities, and a mental health factor defined primarily by emotional distress (anxiety and depressive symptoms). Reliabilities for these two summary scores were 0.98 (physical health) and 0.97 (mental health). Correlations of the PROMIS-29 v2.0 physical and mental health summary scores with chronic conditions and other health-related quality of life measures were consistent with a priori hypotheses. This study develops and provides preliminary evidence supporting the reliability and validity of PROMIS-29 v2.0 physical and mental health summary scores that can be used in future studies to assess impacts of health care interventions and track changes in health over time. Further evaluation of these and alternative summary measures is recommended.

  17. Function of the ATR N-terminal domain revealed by an ATM/ATR chimera

    International Nuclear Information System (INIS)

    Chen Xinping; Zhao Runxiang; Glick, Gloria G.; Cortez, David

    2007-01-01

    The ATM and ATR kinases function at the apex of checkpoint signaling pathways. These kinases share significant sequence similarity, phosphorylate many of the same substrates, and have overlapping roles in initiating cell cycle checkpoints. However, they sense DNA damage through distinct mechanisms. ATR primarily senses single stranded DNA (ssDNA) through its interaction with ATRIP, and ATM senses double strand breaks through its interaction with Nbs1. We determined that the N-terminus of ATR contains a domain that binds ATRIP. Attaching this domain to ATM allowed the fusion protein (ATM*) to bind ATRIP and associate with RPA-coated ssDNA. ATM* also gained the ability to localize efficiently to stalled replication forks as well as double strand breaks. Despite having normal kinase activity when tested in vitro and being phosphorylated on S1981 in vivo, ATM* is defective in checkpoint signaling and does not complement cellular deficiencies in either ATM or ATR. These data indicate that the N-terminus of ATR is sufficient to bind ATRIP and to promote localization to sites of replication stress

  18. REPRESENTATION OF PHYSICAL ACTIVITY DOMAINS AND ...

    African Journals Online (AJOL)

    Autor

    the need to analyse elementary and middle school curricula to include educational activities ..... The Statistical Package for the Social Sciences (IBM, 2014), ..... A comparison of Web and print media for physical activity promotion among.

  19. Are a Healthy Diet and Physical Activity Synergistically Associated with Cognitive Functioning in Older Adults?

    Science.gov (United States)

    Nijholt, W; Jager-Wittenaar, H; Visser, M; van der Schans, C P; Hobbelen, J S M

    2016-01-01

    Previous research has demonstrated that being both physically active and adhering a healthy diet is associated with improved cognitive functioning; however, it remains unclear whether these factors act synergistically. We investigated the synergistic association of a healthy diet and being physically active with cognitive functioning. Cross-sectional study. Data from the Longitudinal Aging Study Amsterdam (LASA) were used. We analyzed data from 2,165 community dwelling adults who were aged 55-85 years, 56% of whom were female. Cognitive functioning was assessed by the Mini-Mental State Examination (MMSE), an MMSE score of >26 indicates good cognitive functioning. Physical activity was assessed by the LASA Physical Activity Questionnaire and was considered sufficient if the person engaged in moderately intense physical activity ≥ 20 min/day. A healthy diet score was based on the intake of fruit, vegetables and fish. Each of the food groups was assigned a score that ranged from 1 (well below the Dutch guideline for a healthy diet) to 4 (well above the Dutch guideline for a healthy diet), and the scores were aggregated to determine a healthy diet (healthy ≥ 9 points). Multiple logistic and linear regression analyses were used to examine the (synergistic) association among physical activity, a healthy diet and cognitive functioning. All analyses were adjusted for potential chronic diseases and lifestyle confounders. Of all of the participants, 25% were diagnosed with a cognitive impairment (MMSE ≤26), 80% were physically active and 41% had a healthy diet. Sixty three percent of the participants both adhered to a healthy diet and were physically active. Sufficient daily physical activity (OR=2.545 phealthy diet (OR=1.766 p=.002) were associated with good cognitive functioning. After adjusting for confounding factors, sufficient physical activity was not significantly related to cognitive functioning (p=.163); however adherence to a healthy diet remained

  20. Structural and functional characterization of the CAP domain of pathogen-related yeast 1 (Pry1) protein

    Science.gov (United States)

    Darwiche, Rabih; Kelleher, Alan; Hudspeth, Elissa M.; Schneiter, Roger; Asojo, Oluwatoyin A.

    2016-06-01

    The production, crystal structure, and functional characterization of the C-terminal cysteine-rich secretory protein/antigen 5/pathogenesis related-1 (CAP) domain of pathogen-related yeast protein-1 (Pry1) from Saccharomyces cerevisiae is presented. The CAP domain of Pry1 (Pry1CAP) is functional in vivo as its expression restores cholesterol export to yeast mutants lacking endogenous Pry1 and Pry2. Recombinant Pry1CAP forms dimers in solution, is sufficient for in vitro cholesterol binding, and has comparable binding properties as full-length Pry1. Two crystal structures of Pry1CAP are reported, one with Mg2+ coordinated to the conserved CAP tetrad (His208, Glu215, Glu233 and His250) in spacegroup I41 and the other without divalent cations in spacegroup P6122. The latter structure contains four 1,4-dioxane molecules from the crystallization solution, one of which sits in the cholesterol binding site. Both structures reveal that the divalent cation and cholesterol binding sites are connected upon dimerization, providing a structural basis for the observed Mg2+-dependent sterol binding by Pry1.

  1. E pluribus unum: Harmonization of physical functioning across intervention studies of middle-aged and older adults.

    Directory of Open Access Journals (Sweden)

    Nicole M Armstrong

    Full Text Available Common scales for physical functioning are not directly comparable without harmonization techniques, complicating attempts to pool data across studies. Our aim was to provide a standardized metric for physical functioning in adults based on basic and instrumental activities of daily living scaled to NIH PROMIS norms. We provide an item bank to compare the difficulty of various physical functioning activities. We used item response theory methods to place 232 basic and instrumental activities of daily living questions, administered across eight intervention studies of middle-aged and older adults (N = 2,556, on a common metric. We compared the scale's precision to an average z-score of items and evaluated criterion validity based on objective measures of physical functioning and Fried's frailty criteria. Model-estimated item thresholds were widely distributed across the range of physical functioning. From test information plots, the lowest precision in each dataset was 0.80. Using power calculations, the sample size needed to detect 25% physical functional decline with 80% power based on the physical functioning factor was less than half of what would be needed using an average z-score. The physical functioning factor correlated in expected directions with objective measurements from the Timed Up and Go task, tandem balance, gait speed, chair stands, grip strength, and frailty status. Item-level harmonization enables direct comparison of physical functioning measures across existing and potentially future studies and across levels of function using a nationally representative metric. We identified key thresholds of physical functioning items in an item bank to facilitate clinical and epidemiologic decision-making.

  2. Domain switching in single-phase multiferroics

    Science.gov (United States)

    Jia, Tingting; Cheng, Zhenxiang; Zhao, Hongyang; Kimura, Hideo

    2018-06-01

    Multiferroics are a time-honoured research subject by reason for their tremendous application potential in the information industry, such as in multi-state information storage devices and new types of sensors. An outburst of studies on multiferroicity has been witnessed in the 21st century, although this field has a long research history since the 19th century. Multiferroicity has now become one of the hottest research topics in condensed matter physics and materials science. Numerous efforts have been made to investigate the cross-coupling phenomena among ferroic orders such as ferroelectricity, (anti-)ferromagnetism, and ferroelasticity, especially the coupling between electric and magnetic orderings that would account for the magnetoelectric (ME) effect in multiferroic materials. The magnetoelectric properties and coupling behavior of single phase multiferroics are dominated by their domain structures. It was also noted that, however, the multiferroic materials exhibit very complicated domain structures. Studies on domain structure characterization and domain switching are a crucial step in the exploration of approaches to the control and manipulation of magnetic (electric) properties using an electric (magnetic) field or other means. In this review, following a concise outline of our current basic knowledge on the magnetoelectric (ME) effect, we summarize some important research activities on domain switching in single-phase multiferroic materials in the form of single crystals and thin films, especially domain switching behavior involving strain and the related physics in the last decade. We also introduce recent developments in characterization techniques for domain structures of ferroelectric or multiferroic materials, which have significantly advanced our understanding of domain switching dynamics and interactions. The effects of a series of issues such as electric field, magnetic field, and stress effects on domain switching are been discussed as well. It

  3. Comparison of SH3 and SH2 domain dynamics when expressed alone or in an SH(3+2) construct: the role of protein dynamics in functional regulation.

    Science.gov (United States)

    Engen, J R; Smithgall, T E; Gmeiner, W H; Smith, D L

    1999-04-02

    Protein dynamics play an important role in protein function and regulation of enzymatic activity. To determine how additional interactions with surrounding structure affects local protein dynamics, we have used hydrogen exchange and mass spectrometry to investigate the SH2 and SH3 domains of the protein tyrosine kinase Hck. Exchange rates of isolated Hck SH3 and SH2 domains were compared with rates for the sam