Structural characterization and evaluation of the antioxidant activities of polysaccharides extracted from Qingzhuan brick tea.

PubMed

Yang, Xinhe; Huang, Mingjun; Qin, Caiqin; Lv, Bangyu; Mao, Qingli; Liu, Zhonghua

2017-08-01

The crude tea polysaccharides (CTPS) from Qingzhuan brick tea(QZBT) were extracted and fractionated to afford two fractions, namely TPS-1 and TPS-2. Analyses were conducted concerning the structural characterization and antioxidant activities of these samples. Component analysis revealed that the carbohydrate, uronic acid, protein and polyphenol contents of these samples differed significantly. Fourier transform infrared analysis showed that these samples showed similar characteristic absorption peaks for polysaccharides. Ultraviolet-visible spectroscopy, circular dichroism, scanning electron microscopy and thermogravimetric analyses indicated that there were considerable differences in the presence of protein, surface features, conformational characteristics and thermodynamic behaviors. For antioxidant activities in vitro, CTPS, TPS-1 and TPS-2 exhibited concentration-dependent antioxidant activities, with TPS-2 showing significantly higher antioxidant activity than CTPS and TPS-1. These results provide a scientific and strong foundation for the use of tea polysaccharides(TPS) from QZBT and further research towards the relationships between the characteristics and antioxidant activities of TPS. Copyright © 2017 Elsevier B.V. All rights reserved.

Self-efficacy and pain acceptance as mediators of the relationship between pain and performance of valued life activities in women and men with rheumatoid arthritis.

PubMed

Ahlstrand, Inger; Vaz, Sharmila; Falkmer, Torbjörn; Thyberg, Ingrid; Björk, Mathilda

2017-06-01

To study whether personal factors (self-efficacy and pain acceptance) mediate the relationship between pain and performance of valued life activities in persons with rheumatoid arthritis. Persons with rheumatoid arthritis for at least four years ( n = 737; 73% women) answered a questionnaire measuring self-efficacy, pain acceptance, performance of valued life activities, and self-rated pain. Relationships among these constructs were explored using univariate and multivariate analyses. Structural equation modelling was then used to examine the mediational role of personal factors on the relationship between pain and performance of valued life activities. A direct negative association between pain and performance of valued life activities was identified ( Beta = .34, P < .001). This suggests that people with rheumatoid arthritis who had higher levels of pain has increased difficulties in performing valued life activities. Self-efficacy and activity engagement component of pain acceptance mediated the relationship between pain and performance of valued life activities, however the pain willingness component of pain acceptance did not influence participation in valued life activities. These findings highlight the importance of considering personal factors, such as pain acceptance and self-efficacy, in facilitating participation in valued life activities.

Social Relationships, Leisure Activity, and Health in Older Adults

PubMed Central

Chang, Po-Ju; Wray, Linda; Lin, Yeqiang

2015-01-01

Objective Although the link between enhanced social relationships and better health has generally been well established, few studies have examined the role of leisure activity in this link. This study examined how leisure influences the link between social relationships and health in older age. Methods Using data from the 2006 and 2010 waves of the nationally representative U.S. Health and Retirement Study and structural equation modelling analyses, we examined data on 2,965 older participants to determine if leisure activities mediated the link between social relationships and health in 2010, controlling for race, education level, and health in 2006. Results The results demonstrated that leisure activities mediate the link between social relationships and health in these age groups. Perceptions of positive social relationships were associated with greater involvement in leisure activities, and greater involvement in leisure activities was associated with better health in older age. Discussion & Conclusions The contribution of leisure to health in these age groups is receiving increasing attention, and the results of this study add to the literature on this topic, by identifying the mediating effect of leisure activity on the link between social relationships and health. Future studies aimed at increasing leisure activity may contribute to improved health outcomes in older adults. PMID:24884905

Social relationships, leisure activity, and health in older adults.

PubMed

Chang, Po-Ju; Wray, Linda; Lin, Yeqiang

2014-06-01

Although the link between enhanced social relationships and better health has generally been well established, few studies have examined the role of leisure activity in this link. This study examined how leisure influences the link between social relationships and health in older age. Using data from the 2006 and 2010 waves of the nationally representative U.S. Health and Retirement Study and structural equation modeling analyses, we examined data on 2,965 older participants to determine if leisure activities mediated the link between social relationships and health in 2010, controlling for race, education level, and health in 2006. The results demonstrated that leisure activities mediate the link between social relationships and health in these age groups. Perceptions of positive social relationships were associated with greater involvement in leisure activities, and greater involvement in leisure activities was associated with better health in older age. The contribution of leisure to health in these age groups is receiving increasing attention, and the results of this study add to the literature on this topic, by identifying the mediating effect of leisure activity on the link between social relationships and health. Future studies aimed at increasing leisure activity may contribute to improved health outcomes in older adults. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Detailed Structural Analyses of KOH Activated Carbon from Waste Coffee Beans

NASA Astrophysics Data System (ADS)

Takahata, Tomokazu; Toda, Ikumi; Ono, Hiroki; Ohshio, Shigeo; Akasaka, Hiroki; Himeno, Syuji; Kokubu, Toshinori; Saitoh, Hidetoshi

2009-11-01

The relationship of the detailed structural change of KOH activated carbon and hydrogen storage ability was investigated in activated carbon materials fabricated from waste coffee beans. The specific surface area of porous carbon materials calculated from N2 adsorption isotherms stood at 2070 m2/g when the weight ratio of KOH to carbon materials was 5:1, and pore size was in the range of approximately 0.6 to 1.1 nm as micropores. In the structural analysis, X-ray diffraction analysis and Raman spectroscopy indicated structural change in these carbon materials through KOH activation. The order of the graphite structure changed to a smaller scale with this activation. It is theorized that specific surface area increased using micropores provided by carbon materials developed from the descent of the graphite structure. Hydrogen storage ability improved with these structural changes, and reached 0.6 wt % at 2070 m2/g. These results suggest that hydrogen storage ability is conferred by the chemical effect on graphite of carbon materials.

Computer-assisted determination of minimum energy conformations. 7: A pharmacophore model of the active region of the alpha2-adrenoceptor

NASA Astrophysics Data System (ADS)

Ashman, William P.; Mickiewicz, A. P.; Nelson, Todd M.

1992-09-01

Molecular modeling and computational chemistry techniques are used to analyze compounds in developing pharmacophores of biological receptors to use as templates in structure activity relationship studies and to design new chemicals having physiological activity of interest. In this study, the results of x-ray crystal analyses and PM3 semi-empirical molecular orbital conformational analyses are used to determine the three-dimensional representations of selected adrenergic compounds known to be agonists with the alpha2-adrenoceptor in achieving optimized geometries and electrostatic parameters. The alpha2-adrenergic agonists interact with the adrenergic system receptors to produce various increases or decreases in hemodynamic responses (i.e., hypertension, hypotension, and bradycardia) and sedation. A pharmacophore model of the active region of the alpha2-adrenoceptor is described based on the superimposition of common structural, electrostatic, and physicochemical features of the compounds. Using the model to predict compound adrenergic activity and to design alpha2-adrenergic compounds is discussed.

RELATIONSHIPS OF QUANTITATIVE STRUCTURE-ACTIVITY TO COMPARATIVE TOXICITY OF SELECTED PHENOLS IN THE 'PIMEPHALES PROMELAS' AND 'TETRAHYMENA PYRIFORMIS' TEST SYSTEMS

EPA Science Inventory

The relative toxic response of 27 selected phenols in the 96-hr acute flowthrough Pimephales promelas (fathead minnow) and the 48- to 60-hr chronic static Tetrahymena pyriformis (ciliate protozoan) test systems was evaluated. Log Kow-dependent linear regression analyses revealed ...

Comparison of fate profiles of PAHs in soil, sediments and mangrove leaves after oil spills by QSAR and QSPR.

PubMed

Tansel, Berrin; Lee, Mengshan; Tansel, Derya Z

2013-08-15

First order removal rates for 15 polyaromatic hydrocarbons (PAHs) in soil, sediments and mangrove leaves were compared in relation to the parameters used in fate transport analyses (i.e., octanol-water partition coefficient, organic carbon-water partition coefficient, solubility, diffusivity in water, HOMO-LUMO gap, molecular size, molecular aspect ratio). The quantitative structure activity relationships (QSAR) and quantitative structure property relationships (QSPR) showed that the rate of disappearance of PAHs is correlated with their diffusivities in water as well as molecular volumes in different media. Strong correlations for the rate of disappearance of PAHs in sediments could not be obtained in relation to most of the parameters evaluated. The analyses showed that the QSAR and QSPR correlations developed for removal rates of PAHs in soils would not be adequate for sediments and plant tissues. Copyright © 2013 Elsevier Ltd. All rights reserved.

Quantitative structure-activity relationship and molecular docking of artemisinin derivatives to vascular endothelial growth factor receptor 1.

PubMed

Saeed, Mohamed E M; Kadioglu, Onat; Seo, Ean-Jeong; Greten, Henry Johannes; Brenk, Ruth; Efferth, Thomas

2015-04-01

The antimalarial drug artemisinin has been shown to exert anticancer activity through anti-angiogenic effects. For further drug development, it may be useful to have derivatives with improved anti-angiogenic properties. We performed molecular docking of 52 artemisinin derivatives to vascular endothelial growth factor receptors (VEGFR1, VEGFR2), and VEGFA ligand using Autodock4 and AutodockTools-1.5.7.rc1 using the Lamarckian genetic algorithm. Quantitative structure-activity relationship (QSAR) analyses of the compounds prepared by Corina Molecular Networks were performed using the Molecular Operating Environment MOE 2012.10. A statistically significant inverse relationship was obtained between in silico binding energies to VEGFR1 and anti-angiogenic activity in vivo of a test-set of artemisinin derivatives (R=-0.843; p=0.035). This served as a control experiment to validate molecular docking predicting anti-angiogenc effects. Furthermore, 52 artemisinin derivatives were docked to VEGFR1 and in selected examples also to VEGFR2 and VEGFA. Higher binding affinities were calculated for receptors than for the ligand. The best binding affinities to VEGFR1 were found for an artemisinin dimer, 10-dihydroartemisinyl-2-propylpentanoate, and dihydroartemisinin α-hemisuccinate sodium salt. QSAR analyses revealed significant relationships between VEGFR1 binding energies and defined molecular descriptors of 35 artemisinins assigned to the training set (R=0.0848, p<0.0001) and 17 derivatives assigned to the test set (R=0.761, p<0.001). Molecular docking and QSAR calculations can be used to identify novel artemisinin derivatives with anti-angiogenic effects. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Molecular mechanics and dynamics characterization of an in silico mutated protein: a stand-alone lab module or support activity for in vivo and in vitro analyses of targeted proteins.

PubMed

Chiang, Harry; Robinson, Lucy C; Brame, Cynthia J; Messina, Troy C

2013-01-01

Over the past 20 years, the biological sciences have increasingly incorporated chemistry, physics, computer science, and mathematics to aid in the development and use of mathematical models. Such combined approaches have been used to address problems from protein structure-function relationships to the workings of complex biological systems. Computer simulations of molecular events can now be accomplished quickly and with standard computer technology. Also, simulation software is freely available for most computing platforms, and online support for the novice user is ample. We have therefore created a molecular dynamics laboratory module to enhance undergraduate student understanding of molecular events underlying organismal phenotype. This module builds on a previously described project in which students use site-directed mutagenesis to investigate functions of conserved sequence features in members of a eukaryotic protein kinase family. In this report, we detail the laboratory activities of a MD module that provide a complement to phenotypic outcomes by providing a hypothesis-driven and quantifiable measure of predicted structural changes caused by targeted mutations. We also present examples of analyses students may perform. These laboratory activities can be integrated with genetics or biochemistry experiments as described, but could also be used independently in any course that would benefit from a quantitative approach to protein structure-function relationships. Copyright © 2013 Wiley Periodicals, Inc.

Insight into the structural requirements of aminopyrimidine derivatives for good potency against both purified enzyme and whole cells of M. tuberculosis: combination of HQSAR, CoMSIA, and MD simulation studies.

PubMed

Punkvang, Auradee; Hannongbua, Supa; Saparpakorn, Patchreenart; Pungpo, Pornpan

2016-05-01

The Mycobacterium tuberculosis protein kinase B (PknB) is critical for growth and survival of M. tuberculosis within the host. The series of aminopyrimidine derivatives show impressive activity against PknB (IC50 < .5 μM). However, most of them show weak or no cellular activity against M. tuberculosis (MIC > 63 μM). Consequently, the key structural features related to activity against of both PknB and M. tuberculosis need to be investigated. Here, two- and three-dimensional quantitative structure-activity relationship (2D and 3D QSAR) analyses combined with molecular dynamics (MD) simulations were employed with the aim to evaluate these key structural features of aminopyrimidine derivatives. Hologram quantitative structure-activity relationship (HQSAR) and CoMSIA models constructed from IC50 and MIC values of aminopyrimidine compounds could establish the structural requirements for better activity against of both PknB and M. tuberculosis. The NH linker and the R1 substituent of the template compound are not only crucial for the biological activity against PknB but also for the biological activity against M. tuberculosis. Moreover, the results obtained from MD simulations show that these moieties are the key fragments for binding of aminopyrimidine compounds in PknB. The combination of QSAR analysis and MD simulations helps us to provide a structural concept that could guide future design of PknB inhibitors with improved potency against both the purified enzyme and whole M. tuberculosis cells.

The importance of forest structure to biodiversity–productivity relationships

PubMed Central

Huth, Andreas

2017-01-01

While various relationships between productivity and biodiversity are found in forests, the processes underlying these relationships remain unclear and theory struggles to coherently explain them. In this work, we analyse diversity–productivity relationships through an examination of forest structure (described by basal area and tree height heterogeneity). We use a new modelling approach, called ‘forest factory’, which generates various forest stands and calculates their annual productivity (above-ground wood increment). Analysing approximately 300 000 forest stands, we find that mean forest productivity does not increase with species diversity. Instead forest structure emerges as the key variable. Similar patterns can be observed by analysing 5054 forest plots of the German National Forest Inventory. Furthermore, we group the forest stands into nine forest structure classes, in which we find increasing, decreasing, invariant and even bell-shaped relationships between productivity and diversity. In addition, we introduce a new index, called optimal species distribution, which describes the ratio of realized to the maximal possible productivity (by shuffling species identities). The optimal species distribution and forest structure indices explain the obtained productivity values quite well (R2 between 0.7 and 0.95), whereby the influence of these attributes varies within the nine forest structure classes. PMID:28280550

Interhemispheric Plasticity following Intermittent Theta Burst Stimulation in Chronic Poststroke Aphasia

PubMed Central

Griffis, Joseph C.; Nenert, Rodolphe; Allendorfer, Jane B.; Szaflarski, Jerzy P.

2016-01-01

The effects of noninvasive neurostimulation on brain structure and function in chronic poststroke aphasia are poorly understood. We investigated the effects of intermittent theta burst stimulation (iTBS) applied to residual language-responsive cortex in chronic patients using functional and anatomical MRI data acquired before and after iTBS. Lateralization index (LI) analyses, along with comparisons of inferior frontal gyrus (IFG) activation and connectivity during covert verb generation, were used to assess changes in cortical language function. Voxel-based morphometry (VBM) was used to assess effects on regional grey matter (GM). LI analyses revealed a leftward shift in IFG activity after treatment. While left IFG activation increased, right IFG activation decreased. Changes in right to left IFG connectivity during covert verb generation also decreased after iTBS. Behavioral correlations revealed a negative relationship between changes in right IFG activation and improvements in fluency. While anatomical analyses did not reveal statistically significant changes in grey matter volume, the fMRI results provide evidence for changes in right and left IFG function after iTBS. The negative relationship between post-iTBS changes in right IFG activity during covert verb generation and improvements in fluency suggests that iTBS applied to residual left-hemispheric language areas may reduce contralateral responses related to language production and facilitate recruitment of residual language areas after stroke. PMID:26881111

Interhemispheric Plasticity following Intermittent Theta Burst Stimulation in Chronic Poststroke Aphasia.

PubMed

Griffis, Joseph C; Nenert, Rodolphe; Allendorfer, Jane B; Szaflarski, Jerzy P

2016-01-01

The effects of noninvasive neurostimulation on brain structure and function in chronic poststroke aphasia are poorly understood. We investigated the effects of intermittent theta burst stimulation (iTBS) applied to residual language-responsive cortex in chronic patients using functional and anatomical MRI data acquired before and after iTBS. Lateralization index (LI) analyses, along with comparisons of inferior frontal gyrus (IFG) activation and connectivity during covert verb generation, were used to assess changes in cortical language function. Voxel-based morphometry (VBM) was used to assess effects on regional grey matter (GM). LI analyses revealed a leftward shift in IFG activity after treatment. While left IFG activation increased, right IFG activation decreased. Changes in right to left IFG connectivity during covert verb generation also decreased after iTBS. Behavioral correlations revealed a negative relationship between changes in right IFG activation and improvements in fluency. While anatomical analyses did not reveal statistically significant changes in grey matter volume, the fMRI results provide evidence for changes in right and left IFG function after iTBS. The negative relationship between post-iTBS changes in right IFG activity during covert verb generation and improvements in fluency suggests that iTBS applied to residual left-hemispheric language areas may reduce contralateral responses related to language production and facilitate recruitment of residual language areas after stroke.

The effects of physically active leisure on stress-health relationships.

PubMed

Iwasaki, Y; Zuzanek, J; Mannell, R C

2001-01-01

In this article, the effects of physically active leisure on the relationships between stress and health are examined using structural equation modeling (SEM). The analyses are based on data from Canada's 1994 National Population Health Survey (n = 17,626). Overall, physically active leisure was found to directly contribute to higher levels of physical health and wellbeing, and lower levels of mental ill-health among Canadians. When the respondents experienced higher levels of chronic stress, life event stress, and/or work stress, involvement in physically active leisure appeared to help them maintain good health and wellbeing. Also, higher levels of participation in physically active leisure helped paid workers suppress levels of work stress. Agencies involved in health promotion and lifestyle intervention should give greater consideration to physically active leisure. As a significant component of an active lifestyle, physically active leisure can contribute to better health, and provide a valuable resource for coping with stress.

Identification of PGC-1α activating constituents in Zingiberaceous crude drugs.

PubMed

Nishidono, Yuto; Fujita, Takashi; Kawanami, Akira; Nishizawa, Mikio; Tanaka, Ken

2017-10-01

The activity of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) as an index of thermogenesis induced by four Indonesian Zingiberaceous crude drugs, Boesenbergia rotunda, Curcuma longa, Kaempferia galanga, Zingiber montanum, was examined, and GC-MS analyses of extracts of these drugs were performed. The results showed that activation of PGC-1α by K. galanga was high, whereas no activation was shown for the other drugs. Ethyl p-methoxycinnamate and ethyl cinnamate were identified as the PGC-1α activating compounds of K. galanga. Furthermore, study on the structure-activity relationship revealed that ethyl p-methoxycinnamate has the strongest activity among the cinnamic acid derivatives. This suggests that the ester structure and the methoxy group are important factors responsible for the PGC-1α activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Modelling the effect of structural QSAR parameters on skin penetration using genetic programming

NASA Astrophysics Data System (ADS)

Chung, K. K.; Do, D. Q.

2010-09-01

In order to model relationships between chemical structures and biological effects in quantitative structure-activity relationship (QSAR) data, an alternative technique of artificial intelligence computing—genetic programming (GP)—was investigated and compared to the traditional method—statistical. GP, with the primary advantage of generating mathematical equations, was employed to model QSAR data and to define the most important molecular descriptions in QSAR data. The models predicted by GP agreed with the statistical results, and the most predictive models of GP were significantly improved when compared to the statistical models using ANOVA. Recently, artificial intelligence techniques have been applied widely to analyse QSAR data. With the capability of generating mathematical equations, GP can be considered as an effective and efficient method for modelling QSAR data.

Representation of molecular structure using quantum topology with inductive logic programming in structure-activity relationships.

PubMed

Buttingsrud, Bård; Ryeng, Einar; King, Ross D; Alsberg, Bjørn K

2006-06-01

The requirement of aligning each individual molecule in a data set severely limits the type of molecules which can be analysed with traditional structure activity relationship (SAR) methods. A method which solves this problem by using relations between objects is inductive logic programming (ILP). Another advantage of this methodology is its ability to include background knowledge as 1st-order logic. However, previous molecular ILP representations have not been effective in describing the electronic structure of molecules. We present a more unified and comprehensive representation based on Richard Bader's quantum topological atoms in molecules (AIM) theory where critical points in the electron density are connected through a network. AIM theory provides a wealth of chemical information about individual atoms and their bond connections enabling a more flexible and chemically relevant representation. To obtain even more relevant rules with higher coverage, we apply manual postprocessing and interpretation of ILP rules. We have tested the usefulness of the new representation in SAR modelling on classifying compounds of low/high mutagenicity and on a set of factor Xa inhibitors of high and low affinity.

Evaluation of analgesic and anti-inflammatory activities of Rubia cordifolia L. by spectrum-effect relationships.

PubMed

Shen, Cai-Hong; Liu, Cui-Ting; Song, Xiao-Juan; Zeng, Wei-Ya; Lu, Xiao-Ying; Zheng, Zuo-Liang; Jie-Pan; Zhan, Ruo-Ting; Ping-Yan

2018-07-15

The objective of the current work was to evaluate the spectrum-effect relationships between high-performance liquid chromatography fingerprints and analgesic and anti-inflammatory effects of Rubia cordifolia L. extract (RCE), and to identify active components of RCE. Chemical fingerprints of ten batches of RC from various sources were obtained by HPLC, and similarity and hierarchical clustering analyses were carried out. Pharmacodynamic assays were performed in adjuvant-induced arthritis rat model to assess the analgesic and anti-inflammatory properties of RCE. The spectrum-effect relationships between chemical fingerprints and the analgesic and anti-inflammatory effects of RCE were established by gray correlation analysis. UPLC-ESI-MS was used to identify the structures of potential active components, by reference standards comparison. The results showed that a close correlation existed between chemical fingerprints with analgesic and anti-inflammatory activities, and alizarin, 6-hydroxyrubiadin, purpurin and rubiadin might be the active constituents of RCE. In addition, RCE attenuated pathological changes in adjuvant-induced arthritis. The current findings provide a strong basis for combining chemical fingerprints with analgesic and anti-inflammatory activities in assessing the spectrum-effect relationships of RCE. Copyright © 2018. Published by Elsevier B.V.

STRUCTURE-ACTIVITY RELATIONSHIP STUIDES AND THEIR ROLE IN PREDICTING AND INVESTIGATING CHEMICAL TOXICITY

EPA Science Inventory

Structure-Activity Relationship Studies and their Role in Predicting and Investigating Chemical Toxicity

Structure-activity relationships (SAR) represent attempts to generalize chemical information relative to biological activity for the twin purposes of generating insigh...

CONSIDERATION OF REACTION INTERMEDIATES IN STRUCTURE-ACTIVITY RELATIONSHIPS: A KEY TO UNDERSTANDING AND PREDICTION

EPA Science Inventory

Consideration of Reaction Intermediates in Structure- Activity Relationships: A Key to Understanding and Prediction

A structure-activity relationship (SAR) represents an empirical means for generalizing chemical information relative to biological activity, and is frequent...

Ecological Structure Activity Relationships

EPA Science Inventory

Ecological Structure Activity Relationships, v1.00a, February 2009
ECOSAR (Ecological Structure Activity Relationships) is a personal computer software program that is used to estimate the toxicity of chemicals used in industry and discharged into water. The program predicts...

G Protein-Coupled Estrogen Receptor (GPER) Agonist Dual Binding Mode Analyses toward Understanding of its Activation Mechanism: A Comparative Homology Modeling Approach.

PubMed

Arnatt, Christopher K; Zhang, Yan

2013-07-01

G protein-coupled estrogen receptor (GPER) has been shown to be important in several disease states such as estrogen sensitive cancers. While several selective ligands have been identified for the receptor, little is known about how they interact with GPER and how their structures influence their activity. Specifically, within one series of ligands, whose structure varied only at one position, the replacement of a hydrogen atom with an acetyl group changed a potent antagonist into a potent agonist. In this study, two GPER homology models were constructed based on the x-ray crystal structures of both the active and inactive β 2 -adrenergic receptors (β 2 AR) in an effort to characterize the differences of binding modes between agonists and antagonists to the receptor, and to understand their activity in relation to their structures. The knowledge attained in this study is expected to provide valuable information on GPER ligands structure activity relationship to benefit future rational design of potent agonists and antagonists of the receptor for potential therapeutic applications.

G Protein-Coupled Estrogen Receptor (GPER) Agonist Dual Binding Mode Analyses toward Understanding of its Activation Mechanism: A Comparative Homology Modeling Approach

PubMed Central

Arnatt, Christopher K.; Zhang, Yan

2015-01-01

G protein-coupled estrogen receptor (GPER) has been shown to be important in several disease states such as estrogen sensitive cancers. While several selective ligands have been identified for the receptor, little is known about how they interact with GPER and how their structures influence their activity. Specifically, within one series of ligands, whose structure varied only at one position, the replacement of a hydrogen atom with an acetyl group changed a potent antagonist into a potent agonist. In this study, two GPER homology models were constructed based on the x-ray crystal structures of both the active and inactive β2-adrenergic receptors (β2AR) in an effort to characterize the differences of binding modes between agonists and antagonists to the receptor, and to understand their activity in relation to their structures. The knowledge attained in this study is expected to provide valuable information on GPER ligands structure activity relationship to benefit future rational design of potent agonists and antagonists of the receptor for potential therapeutic applications. PMID:26229572

Multidimensional Predictors of Fatigue among Octogenarians and Centenarians

PubMed Central

Cho, Jinmyoung; Martin, Peter; Margrett, Jennifer; MacDonald, Maurice; Johnson, Mary Ann; Poon, Leonard W.

2012-01-01

Background Fatigue is a common and frequently observed complaint among older adults. However, knowledge about the nature and correlates of fatigue in old age is very limited. Objective: This study examined the relationship of functional indicators, psychological and situational factors and fatigue for 210 octogenarians and centenarians from the Georgia Centenarian Study. Methods Three indicators of functional capacity (self-rated health, instrumental activities of daily living, physical activities of daily living), two indicators of psychological well-being (positive and negative affect), two indicators of situational factors (social network and social support), and a multidimensional fatigue scale were used. Blocked multiple regression analyses were computed to examine significant factors related to fatigue. In addition, multi-group analysis in structural equation modeling was used to investigate residential differences (i.e., long-term care facilities vs. private homes) in the relationship between significant factors and fatigue. Results Blocked multiple regression analyses indicated that two indicators of functional capacity, self-rated health and instrumental activities of daily living, both positive and negative affect, and social support were significant predictors of fatigue among oldest-old adults. The multiple group analysis in structural equation modeling revealed a significant difference among oldest-old adults based on residential status. Conclusion The results suggest that we should not consider fatigue as merely an unpleasant physical symptom, but rather adopt a perspective that different factors such as psychosocial aspects can influence fatigue in advanced later life. PMID:22094445

Multidimensional predictors of fatigue among octogenarians and centenarians.

PubMed

Cho, Jinmyoung; Martin, Peter; Margrett, Jennifer; MacDonald, Maurice; Johnson, Mary Ann; Poon, Leonard W; Jazwinski, S M; Green, R C; Gearing, M; Woodard, J L; Tenover, J S; Siegler, I C; Rott, C; Rodgers, W L; Hausman, D; Arnold, J; Davey, A

2012-01-01

Fatigue is a common and frequently observed complaint among older adults. However, knowledge about the nature and correlates of fatigue in old age is very limited. This study examined the relationship of functional indicators, psychological and situational factors and fatigue for 210 octogenarians and centenarians from the Georgia Centenarian Study. Three indicators of functional capacity (self-rated health, instrumental activities of daily living, physical activities of daily living), two indicators of psychological well-being (positive and negative affect), two indicators of situational factors (social network and social support), and a multidimensional fatigue scale were used. Blocked multiple regression analyses were computed to examine significant factors related to fatigue. In addition, multi-group analysis in structural equation modeling was used to investigate residential differences (i.e., long-term care facilities vs. private homes) in the relationship between significant factors and fatigue. Blocked multiple regression analyses indicated that two indicators of functional capacity, self-rated health and instrumental activities of daily living, both positive and negative affect, and social support were significant predictors of fatigue among oldest-old adults. The multiple group analysis in structural equation modeling revealed a significant difference among oldest-old adults based on residential status. The results suggest that we should not consider fatigue as merely an unpleasant physical symptom, but rather adopt a perspective that different factors such as psychosocial aspects can influence fatigue in advanced later life. Copyright © 2011 S. Karger AG, Basel.

Cobalt Oxide Nanoclusters on Rutile Titania as Bifunctional Units for Water Oxidation Catalysis and Visible Light Absorption: Understanding the Structure-Activity Relationship.

PubMed

Maeda, Kazuhiko; Ishimaki, Koki; Okazaki, Megumi; Kanazawa, Tomoki; Lu, Daling; Nozawa, Shunsuke; Kato, Hideki; Kakihana, Masato

2017-02-22

The structure of cobalt oxide (CoO x ) nanoparticles dispersed on rutile TiO 2 (R-TiO 2 ) was characterized by X-ray diffraction, UV-vis-NIR diffuse reflectance spectroscopy, high-resolution transmission electron microscopy, X-ray absorption fine-structure spectroscopy, and X-ray photoelectron spectroscopy. The CoO x nanoparticles were loaded onto R-TiO 2 by an impregnation method from an aqueous solution containing Co(NO 3 ) 2 ·6H 2 O followed by heating in air. Modification of the R-TiO 2 with 2.0 wt % Co followed by heating at 423 K for 1 h resulted in the highest photocatalytic activity with good reproducibility. Structural analyses revealed that the activity of this photocatalyst depended strongly on the generation of Co 3 O 4 nanoclusters with an optimal distribution. These nanoclusters are thought to interact with the R-TiO 2 surface, resulting in visible light absorption and active sites for water oxidation.

An examination on the influence of small and medium enterprise (SME) stakeholder on green supply chain management practices

NASA Astrophysics Data System (ADS)

Shahlan, M. Z.; Sidek, A. A.; Suffian, S. A.; Hazza, M. H. F. A.; Daud, M. R. C.

2018-01-01

In this paper, climate change and global warming are the biggest current issues in the industrial sectors. The green supply chain managements (GSCM) is one of the crucial input to these issues. Effective GSCM can potentially secure the organization’s competitive advantage and improve the environmental performance of the network activities. In this study, the aim is to investigate and examine how a small and medium enterprises (SMEs) stakeholder pressure and top management influence green supply chain management practices. The study is further advance green supply chain management research in Malaysia focusing on SMEs manufacturing sector using structural equation modelling. Structural equation modelling is a multivariate statistical analysis technique used to examine structural relationship. It is the combination of factor analysis and multi regression analysis and used to analyse structural relationship between measure variable and latent factor. This research found that top management support and stakeholder pressure is the major influence for SMEs to adopt green supply chain management. The research also found that top management is fully mediate with the relationship between stakeholder pressure and monitoring supplier environmental performance.

An examination of the structure of posttraumatic stress disorder in relation to the anxiety and depressive disorders.

PubMed

Forbes, David; Lockwood, Emma; Elhai, Jon D; Creamer, Mark; O'Donnell, Meaghan; Bryant, Richard; McFarlane, Alexander; Silove, Derrick

2011-07-01

The nature and structure of posttraumatic stress disorder (PTSD) has been the subject of much interest in recent times. This research has been represented by two streams, the first representing a substantive body of work which focuses specifically on the factor structure of PTSD and the second exploring PTSD's relationship with other mood and anxiety disorders. The present study attempted to bring these two streams together by examining structural models of PTSD and their relationship with dimensions underlying other mood and anxiety disorders. PTSD, anxiety and mood disorder data from 989 injury survivors interviewed 3-months following their injury were analyzed using a series of confirmatory factor analyses (CFA) to identify the optimal structural model. CFA analyses indicated that the best fitting model included PTSD's re-experiencing (B1-5), active avoidance (C1-2), and hypervigilance and startle (D4-5) loading onto a Fear factor (represented by panic disorder, agoraphobia and social phobia) and the PTSD dysphoria symptoms (numbing symptoms C3-7 and hyperarousal symptoms D1-3) loading onto an Anxious Misery/Distress factor (represented by depression, generalized anxiety disorder and obsessive compulsive disorder). The findings have implications for informing potential revisions to the structure of the diagnosis of PTSD and the diagnostic algorithm to be applied, with the aim of enhancing diagnostic specificity. Copyright © 2011 Elsevier B.V. All rights reserved.

Data Sets Representative of the Structures and Experimental Properties of FDA-Approved Drugs.

PubMed

Douguet, Dominique

2018-03-08

Presented here are several data sets that gather information collected from the labels of the FDA approved drugs: their molecular structures and those of the described active metabolites, their associated pharmacokinetics and pharmacodynamics data, and the history of their marketing authorization by the FDA. To date, 1852 chemical structures have been identified with a molecular weight less than 2000 of which 492 are or have active metabolites. To promote the sharing of data, the original web server was upgraded for browsing the database and downloading the data sets (http://chemoinfo.ipmc.cnrs.fr/edrug3d). It is believed that the multidimensional chemistry-oriented collections are an essential resource for a thorough analysis of the current drug chemical space. The data sets are envisioned as being used in a wide range of endeavors that include drug repurposing, drug design, privileged structures analyses, structure-activity relationship studies, and improving of absorption, distribution, metabolism, and elimination predictive models.

Structural diversity in the dandelion (Taraxacum officinale) polyphenol oxidase family results in different responses to model substrates.

PubMed

Dirks-Hofmeister, Mareike E; Singh, Ratna; Leufken, Christine M; Inlow, Jennifer K; Moerschbacher, Bruno M

2014-01-01

Polyphenol oxidases (PPOs) are ubiquitous type-3 copper enzymes that catalyze the oxygen-dependent conversion of o-diphenols to the corresponding quinones. In most plants, PPOs are present as multiple isoenzymes that probably serve distinct functions, although the precise relationship between sequence, structure and function has not been addressed in detail. We therefore compared the characteristics and activities of recombinant dandelion PPOs to gain insight into the structure-function relationships within the plant PPO family. Phylogenetic analysis resolved the 11 isoenzymes of dandelion into two evolutionary groups. More detailed in silico and in vitro analyses of four representative PPOs covering both phylogenetic groups were performed. Molecular modeling and docking predicted differences in enzyme-substrate interactions, providing a structure-based explanation for grouping. One amino acid side chain positioned at the entrance to the active site (position HB2+1) potentially acts as a "selector" for substrate binding. In vitro activity measurements with the recombinant, purified enzymes also revealed group-specific differences in kinetic parameters when the selected PPOs were presented with five model substrates. The combination of our enzyme kinetic measurements and the in silico docking studies therefore indicate that the physiological functions of individual PPOs might be defined by their specific interactions with different natural substrates.

Motives and activities for continuing professional development: An exploration of their relationships by integrating literature and interview data.

PubMed

Pool, Inge A; Poell, Rob F; Berings, Marjolein G M C; Ten Cate, Olle

2016-03-01

To effectively enhance professional development, it is important to understand the motivational factors behind nurses' engagement in particular types of learning activities. Nurses have various motives for professional development and utilise different learning activities. Not much is known about how these relate. The aim of this study was to explore the relationship between nurses' motives and activities for continuing professional development, by examining in which types of learning activities nurses engage, with which motives, and whether certain motives are associated with certain learning activities. A qualitative study using semi-structured interviews. Twenty-one nurses in academic and general Dutch hospitals participated. Interview data on nurses' learning biographies were analysed using a literature-based framework on motives and learning activities for continuing professional development. As recent classifications of nurses' motives for professional development were absent, the literature was reviewed for motives, using three databases. The interview transcripts were analysed for motives, learning activities and their relationships. Nine motives and four categories of learning activities for continuing professional development were delineated. Increasing competence was the primary motive that stimulated nurses to engage in self-directed learning during work, and in formal learning activities. To comply with requirements, they engaged in mandatory courses. To deepen knowledge, they registered for conferences. To develop their careers, they enrolled in postgraduate education. Five other motives were not mentioned as frequently. Specific motives were found to be related to engagement in particular learning activities. Nurses could use these findings to increase their awareness of why and how they develop professionally, and managers and human resource development professionals could develop approaches that would better suit nurses' needs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of pyrrolo[2,3-d]pyrimidines as potent HCK and FLT3-ITD dual inhibitors.

PubMed

Koda, Yasuko; Kikuzato, Ko; Mikuni, Junko; Tanaka, Akiko; Yuki, Hitomi; Honma, Teruki; Tomabechi, Yuri; Kukimoto-Niino, Mutsuko; Shirouzu, Mikako; Shirai, Fumiyuki; Koyama, Hiroo

2017-11-15

A series of novel pyrrolo[2,3-d]pyrimidines were synthesized by introducing 15 different amino acids to 7-cyclohexyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine-4-amine. Compounds with potent activities against HCK and FLT3-ITD were evaluated in viability studies with acute myeloid leukemia cell line MV4-11. Our structure activity relationship analyses lead to the identification of compound 31, which exhibited potent HCK and FLT3-ITD inhibition and activity against the MV4-11 cell line. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Comparative Study on Selective PPAR Modulators through Quantitative Structure-activity Relationship, Pharmacophore and Docking Analyses.

PubMed

Nandy, Ashis; Roy, Kunal; Saha, Achintya

2018-01-01

Metabolic syndrome is a matrix of different metabolic disorders which are the leading cause of death in human beings. Peroxysome proliferated activated receptor (PPAR) is a nuclear receptor involved in metabolism of fats and glucose. In order to explore structural requirements for selective PPAR modulators to control lipid and carbohydrate metabolism, the multi-cheminformatics studies have been performed. In silico modeling studies have been performed on a diverse set of PPAR modulators through quantitative structure-activity relationship (QSAR), pharmacophore mapping and docking studies. It is observed that the presence of an amide fragment (-CONHRPh) has a detrimental effect while an aliphatic ether linkage has a beneficial effect on PPARα modulation. On the other hand, the presence of an amide fragment has a positive effect on PPARδ modulation, but the aliphatic ether linkage and substituted aromatic ring in the molecular scaffold are very much essential for imparting potent and selective PPARγ modulation. Negative ionizable features (i.e. polar fragments) must be present in PPARδ and α modulators, but a hydrophobic feature is the prime requirement for PPARγ modulation. Here, the essential structural features have been explored for selective modulation of each subtype of PPAR in order to design new modulators with improved activity/selectivity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Five Thousand American Families--Patterns of Economic Progress. Volume III: Analyses of the First Six Years of the Panel Study of Income Dynamics.

ERIC Educational Resources Information Center

Duncan, Greg J., Ed.; Morgan, James N., Ed.

This volume focuses on the main issues to which the Panel Study of Income Dynamics was directed--the determinants of the changing economic fortunes of black and white families. The economic status of the families studied, patterns of transition, and changes in the structure of the families and their relationship to changes in economic activity are…

Molecular Mechanics and Dynamics Characterization of an "in silico" Mutated Protein: A Stand-Alone Lab Module or Support Activity for "in vivo" and "in vitro" Analyses of Targeted Proteins

ERIC Educational Resources Information Center

Chiang, Harry; Robinson, Lucy C.; Brame, Cynthia J.; Messina, Troy C.

2013-01-01

Over the past 20 years, the biological sciences have increasingly incorporated chemistry, physics, computer science, and mathematics to aid in the development and use of mathematical models. Such combined approaches have been used to address problems from protein structure-function relationships to the workings of complex biological systems.…

Physical activity and the mediating effect of fear, depression, anxiety, and catastrophizing on pain related disability in people with chronic low back pain.

PubMed

Marshall, Paul W M; Schabrun, Siobhan; Knox, Michael F

2017-01-01

Chronic low back pain is a worldwide burden that is not being abated with our current knowledge and treatment of the condition. The fear-avoidance model is used to explain the relationship between pain and disability in patients with chronic low back pain. However there are gaps in empirical support for pathways proposed within this model, and no evidence exists as to whether physical activity moderates these pathways. This was a cross-sectional study of 218 people with chronic low back pain. Multiple mediation analyses were conducted to determine the role of fear, catastrophizing, depression, and anxiety in the relationship between pain and disability. Separate analyses were performed with physical activity as the moderator. Individuals were classified as performing regular structured physical activity if they described on average once per week for > 30-minutes an activity classified at least moderate intensity (≥ 4-6 METs), activity prescribed by an allied health professional for their back pain, leisure time sport or recreation, or self-directed physical activity such as resistance exercise. Fear, catastrophizing, and depression significantly mediated the relationship between pain and disability (p<0.001). However the mediating effect of catastrophizing was conditional upon weekly physical activity. That is, the indirect effect for catastrophizing mediating the relationship between pain and disability was only significant for individuals reporting weekly physical activity (B = 1.31, 95% CI 0.44 to 2.23), compared to individuals reporting no weekly physical activity (B = 0.21, 95% CI -0.50 to 0.97). Catastrophizing also mediated the relationship between pain and fear (B = 0.37, 95% CI 0.15 to 0.62), with higher scores explaining 53% of the total effect of pain on fear. These results support previous findings about the importance of fear and depression as factors that should be targeted in low back pain patients to reduce back pain related disability. We have also extended understanding for the mediating effect of catastrophizing on back pain related disability. Back pain patients engaged with regular physical activity may require counselling with regards to negative pain perceptions.

Physical activity and the mediating effect of fear, depression, anxiety, and catastrophizing on pain related disability in people with chronic low back pain

PubMed Central

Marshall, Paul W. M.; Schabrun, Siobhan; Knox, Michael F.

2017-01-01

Background Chronic low back pain is a worldwide burden that is not being abated with our current knowledge and treatment of the condition. The fear-avoidance model is used to explain the relationship between pain and disability in patients with chronic low back pain. However there are gaps in empirical support for pathways proposed within this model, and no evidence exists as to whether physical activity moderates these pathways. Methods This was a cross-sectional study of 218 people with chronic low back pain. Multiple mediation analyses were conducted to determine the role of fear, catastrophizing, depression, and anxiety in the relationship between pain and disability. Separate analyses were performed with physical activity as the moderator. Individuals were classified as performing regular structured physical activity if they described on average once per week for > 30-minutes an activity classified at least moderate intensity (≥ 4–6 METs), activity prescribed by an allied health professional for their back pain, leisure time sport or recreation, or self-directed physical activity such as resistance exercise. Results Fear, catastrophizing, and depression significantly mediated the relationship between pain and disability (p<0.001). However the mediating effect of catastrophizing was conditional upon weekly physical activity. That is, the indirect effect for catastrophizing mediating the relationship between pain and disability was only significant for individuals reporting weekly physical activity (B = 1.31, 95% CI 0.44 to 2.23), compared to individuals reporting no weekly physical activity (B = 0.21, 95% CI -0.50 to 0.97). Catastrophizing also mediated the relationship between pain and fear (B = 0.37, 95% CI 0.15 to 0.62), with higher scores explaining 53% of the total effect of pain on fear. Conclusions These results support previous findings about the importance of fear and depression as factors that should be targeted in low back pain patients to reduce back pain related disability. We have also extended understanding for the mediating effect of catastrophizing on back pain related disability. Back pain patients engaged with regular physical activity may require counselling with regards to negative pain perceptions. PMID:28686644

Internal and external relationships of the Cnidaria: implications of primary and predicted secondary structure of the 5'-end of the 23S-like rDNA.

PubMed Central

Odorico, D M; Miller, D J

1997-01-01

Since both internal (class-level) and external relationships of the Cnidaria remain unclear on the basis of analyses of 18S and (partial) 16S rDNA sequence data, we examined the informativeness of the 5'-end of the 23S-like rDNA. Here we describe analyses of both primary and predicted secondary structure data for this region from the ctenophore Bolinopsis sp., the placozoan Trichoplax adhaerens, the sponge Hymeniacidon heliophila, and representatives of all four cnidarian classes. Primary sequence analyses clearly resolved the Cnidaria from other lower Metazoa, supported sister group relationships between the Scyphozoa and Cubozoa and between the Ctenophora and the Placozoa, and confirmed the basal status of the Anthozoa within the Cnidaria. Additionally, in the ctenophore, placozoan and sponge, non-canonical base pairing is required to maintain the secondary structure of the B12 region, whereas amongst the Cnidaria this is not the case. Although the phylogenetic significance of this molecular character is unclear, our analyses do not support the close relationship between Cnidaria and Placozoa suggested by previous studies. PMID:9061962

Interaction Analysis of FABP4 Inhibitors by X-ray Crystallography and Fragment Molecular Orbital Analysis.

PubMed

Tagami, Uno; Takahashi, Kazutoshi; Igarashi, Shunsuke; Ejima, Chieko; Yoshida, Tomomi; Takeshita, Sen; Miyanaga, Wataru; Sugiki, Masayuki; Tokumasu, Munetaka; Hatanaka, Toshihiro; Kashiwagi, Tatsuki; Ishikawa, Kohki; Miyano, Hiroshi; Mizukoshi, Toshimi

2016-04-14

X-ray crystal structural determination of FABP4 in complex with four inhibitors revealed the complex binding modes, and the resulting observations led to improvement of the inhibitory potency of FABP4 inhibitors. However, the detailed structure-activity relationship (SAR) could not be explained from these structural observations. For a more detailed understanding of the interactions between FABP4 and inhibitors, fragment molecular orbital analyses were performed. These analyses revealed that the total interfragment interaction energies of FABP4 and each inhibitor correlated with the ranking of the K i value for the four inhibitors. Furthermore, interactions between each inhibitor and amino acid residues in FABP4 were identified. The oxygen atom of Lys58 in FABP4 was found to be very important for strong interactions with FABP4. These results might provide useful information for the development of novel potent FABP4 inhibitors.

The Relationship between Bureaucratic School Structures and Teacher Self-Efficacy

ERIC Educational Resources Information Center

Kilinç, Ali Çagatay; Kosar, Serkan; Er, Emre; Ögdem, Zeki

2016-01-01

The purpose of this study was to examine the relationship between bureaucratic school structures and teachers' self-efficacy. Participants included 252 teachers from 15 primary schools in Ankara, Turkey. Mean, standard deviation, correlation, and regression analyses were conducted. Results indicated that bureaucratic school structures and teacher…

Chemical construction and structural permutation of neurotoxic natural product, antillatoxin: importance of the three-dimensional structure of the bulky side chain

PubMed Central

INOUE, Masayuki

2014-01-01

Antillatoxin 1 is a unique natural product that displays potent neurotoxic and neuritogenic activities through activation of voltage-gated sodium channels. The peptidic macrocycle of 1 was attached to a side chain with an exceptionally high degree of methylation. In this review, we discuss the total synthesis and biological evaluation of 1 and its analogues. First we describe an efficient synthetic route to 1. This strategy enabled the unified preparation of nine side chain analogues. Structure-activity relationship studies of these analogues revealed that subtle side chain modification leads to dramatic changes in activity, and detailed structural analyses indicated the importance of the overall size and three dimensional shape of the side chain. Based on these data, we designed and synthesized a photoresponsive analogue, proving that the activity of 1 was modulated via a photochemical reaction. The knowledge accumulated through these studies will be useful for the rational design of new tailor-made molecules to control the function and behavior of ion channels. PMID:24522155

2D-QSAR and 3D-QSAR Analyses for EGFR Inhibitors

PubMed Central

Zhao, Manman; Zheng, Linfeng; Qiu, Chun

2017-01-01

Epidermal growth factor receptor (EGFR) is an important target for cancer therapy. In this study, EGFR inhibitors were investigated to build a two-dimensional quantitative structure-activity relationship (2D-QSAR) model and a three-dimensional quantitative structure-activity relationship (3D-QSAR) model. In the 2D-QSAR model, the support vector machine (SVM) classifier combined with the feature selection method was applied to predict whether a compound was an EGFR inhibitor. As a result, the prediction accuracy of the 2D-QSAR model was 98.99% by using tenfold cross-validation test and 97.67% by using independent set test. Then, in the 3D-QSAR model, the model with q2 = 0.565 (cross-validated correlation coefficient) and r2 = 0.888 (non-cross-validated correlation coefficient) was built to predict the activity of EGFR inhibitors. The mean absolute error (MAE) of the training set and test set was 0.308 log units and 0.526 log units, respectively. In addition, molecular docking was also employed to investigate the interaction between EGFR inhibitors and EGFR. PMID:28630865

Physical activity and cardiac function in the oldest old.

PubMed

Stessman-Lande, Irit; Jacobs, Jeremy M; Gilon, Dan; Leibowitz, David

2012-02-01

The relationship of physical activity (PA) and cardiac function in the oldest old remains unclear. The objective of this study was to evaluate the relationship between PA and cardiac structure and function, in the oldest old. Subjects were recruited from the Jerusalem Longitudinal Cohort Study that was initiated in 1990 and has followed an age homogeneous cohort of Jerusalem residents born in 1920-1921. A total of 496 of the subjects from the most recent set of data collection in 2005-2006 underwent echocardiography at their place of residence in addition to structured interviews and physical examination. Standard echocardiographic assessment of cardiac structure and function including ejection fraction (EF) and diastolic function as assessed by E:E' measurements was performed. PA was defined as a dichotomous (≥4 hr of light exercise weekly) and as a categorical variable (<4 hr weekly/4 hours weekly/at least 1 hr daily/sport at least twice weekly). On bivariate analysis, mean EF was lower among sedentary versus active women (55.5%±8.5% vs. 58.4%±8.3, p=0.021). No other significant differences were observed between sedentary and active subjects, for either systolic or diastolic function. After adjusting for sex, education, diabetes, ischemic heart disease, hypertension, dependence in activities of daily living, and body mass index (BMI), no significant associations were found between systolic or diastolic function, or left ventricular structure and PA. Gender-specific analyses yielded similar findings. Our study of the oldest old did not demonstrate an association between PA and cardiac structure or function.

Brain structure correlates of component reading processes: implications for reading disability.

PubMed

Phinney, Erin; Pennington, Bruce F; Olson, Richard; Filley, Christopher M; Filipek, Pauline A

2007-08-01

Brain structures implicated in developmental dyslexia (reading disability - RD) vary greatly across structural magnetic resonance imaging (MRI) studies due to methodological differences regarding the definition of RD and the exact measurements of a specific brain structure. The current study attempts to resolve some of those methodological concerns by examining brain volume as it relates to components of proposed RD subtypes. We performed individual regression analyses on total cerebral volume, neocortical volume, subcortical volume, 9 neo-cortical structures and 2 sub-cortical structures. These analyses used three dimensions of reading, phonemic ability (PA), orthographic ability, and rapid naming (RN) ability, while accounting for total cerebral volume, age, and performance IQ (PIQ). Primary analyses included membership to a group (poor reader vs. good reader) in the analysis. The result was a significant interaction between PA and reading ability as it predicts total cerebral volume. Analyses revealed that poor readers lacked a relationship between PA and brain size, but that good readers had a significant positive relationship. This pattern of interaction was not present for the other two reading component factors. These findings bring into question the general belief that individuals with RD are at the low end of a reading ability distribution and do not have a unique disorder. Additional analyses revealed only a few significant relationships between brain size and task performance, most notably a positive correlation between orthographic ability and the angular gyrus (AG), as well as a negative correlation between RN ability and the parietal operculum (PO).

THE USE OF STRUCTURE-ACTIVITY RELATIONSHIPS IN INTEGRATING THE CHEMISTRY AND TOXICOLOGY OF ENDOCRINE DISRUPTING CHEMICALS

EPA Science Inventory

Structure activity relationships (SARs) are based on the principle that structurally similar chemicals should have similar biological activity. SARs relate specifically-defined toxicological activity of chemicals to their molecular structure and physico-chemical properties. To de...

Development of an in Silico Model of DPPH• Free Radical Scavenging Capacity: Prediction of Antioxidant Activity of Coumarin Type Compounds.

PubMed

Goya Jorge, Elizabeth; Rayar, Anita Maria; Barigye, Stephen J; Jorge Rodríguez, María Elisa; Sylla-Iyarreta Veitía, Maité

2016-06-07

A quantitative structure-activity relationship (QSAR) study of the 2,2-diphenyl-l-picrylhydrazyl (DPPH•) radical scavenging ability of 1373 chemical compounds, using DRAGON molecular descriptors (MD) and the neural network technique, a technique based on the multilayer multilayer perceptron (MLP), was developed. The built model demonstrated a satisfactory performance for the training ( R 2 = 0.713 ) and test set ( Q ext 2 = 0.654 ) , respectively. To gain greater insight on the relevance of the MD contained in the MLP model, sensitivity and principal component analyses were performed. Moreover, structural and mechanistic interpretation was carried out to comprehend the relationship of the variables in the model with the modeled property. The constructed MLP model was employed to predict the radical scavenging ability for a group of coumarin-type compounds. Finally, in order to validate the model's predictions, an in vitro assay for one of the compounds (4-hydroxycoumarin) was performed, showing a satisfactory proximity between the experimental and predicted pIC50 values.

Crystal Structures of Phd-Doc, HigA, and YeeU Establish Multiple Evolutionary Links between Microbial Growth-Regulating Toxin-Antitoxin Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arbing, Mark A.; Handelman, Samuel K.; Kuzin, Alexandre P.

2010-09-27

Bacterial toxin-antitoxin (TA) systems serve a variety of physiological functions including regulation of cell growth and maintenance of foreign genetic elements. Sequence analyses suggest that TA families are linked by complex evolutionary relationships reflecting likely swapping of functional domains between different TA families. Our crystal structures of Phd-Doc from bacteriophage P1, the HigA antitoxin from Escherichia coli CFT073, and YeeU of the YeeUWV systems from E. coli K12 and Shigella flexneri confirm this inference and reveal additional, unanticipated structural relationships. The growth-regulating Doc toxin exhibits structural similarity to secreted virulence factors that are toxic for eukaryotic target cells. The Phdmore » antitoxin possesses the same fold as both the YefM and NE2111 antitoxins that inhibit structurally unrelated toxins. YeeU, which has an antitoxin-like activity that represses toxin expression, is structurally similar to the ribosome-interacting toxins YoeB and RelE. These observations suggest extensive functional exchanges have occurred between TA systems during bacterial evolution.« less

An information driven strategy to support multidisciplinary design

NASA Technical Reports Server (NTRS)

Rangan, Ravi M.; Fulton, Robert E.

1990-01-01

The design of complex engineering systems such as aircraft, automobiles, and computers is primarily a cooperative multidisciplinary design process involving interactions between several design agents. The common thread underlying this multidisciplinary design activity is the information exchange between the various groups and disciplines. The integrating component in such environments is the common data and the dependencies that exist between such data. This may be contrasted to classical multidisciplinary analyses problems where there is coupling between distinct design parameters. For example, they may be expressed as mathematically coupled relationships between aerodynamic and structural interactions in aircraft structures, between thermal and structural interactions in nuclear plants, and between control considerations and structural interactions in flexible robots. These relationships provide analytical based frameworks leading to optimization problem formulations. However, in multidisciplinary design problems, information based interactions become more critical. Many times, the relationships between different design parameters are not amenable to analytical characterization. Under such circumstances, information based interactions will provide the best integration paradigm, i.e., there is a need to model the data entities and their dependencies between design parameters originating from different design agents. The modeling of such data interactions and dependencies forms the basis for integrating the various design agents.

Cell wall integrity, genotoxic injury and PCD dynamics in alfalfa saponin-treated white poplar cells highlight a complex link between molecule structure and activity.

PubMed

Paparella, Stefania; Tava, Aldo; Avato, Pinarosa; Biazzi, Elisa; Macovei, Anca; Biggiogera, Marco; Carbonera, Daniela; Balestrazzi, Alma

2015-03-01

In the present work, eleven saponins and three sapogenins purified from Medicago sativa were tested for their cytotoxicity against highly proliferating white poplar (Populus alba L.) cell suspension cultures. After preliminary screening, four saponins with different structural features in terms of aglycone moieties and sugar chains (saponin 3, a bidesmoside of hederagenin; saponins 4 and 5, monodesmoside and bidesmoside of medicagenic acid respectively, and saponin 10, a bidesmoside of zanhic acid) and different cytotoxicity were selected and used for further investigation on their structure-activity relationship. Transmission Electron Microscopy (TEM) analyses provided for the first time evidence of the effects exerted by saponins on plant cell wall integrity. Exposure to saponin 3 and saponin 10 resulted into disorganization of the outer wall layer and the effect was even more pronounced in white poplar cells treated with the two medicagenic acid derivatives, saponins 4 and 5. Oxidative burst and nitric oxide accumulation were common hallmarks of the response of white poplar cells to saponins. When DNA damage accumulation and DNA repair profiles were evaluated by Single Cell Gel Electrophoresis, induction of single and double strand breaks followed by effective repair was observed within 24h. The reported data are discussed in view of the current issues dealing with saponin structure-activity relationship. Copyright © 2015 Elsevier Ltd. All rights reserved.

Study on the activity of non-purine xanthine oxidase inhibitor by 3D-QSAR modeling and molecular docking

NASA Astrophysics Data System (ADS)

Li, Peizhen; Tian, Yueli; Zhai, Honglin; Deng, Fangfang; Xie, Meihong; Zhang, Xiaoyun

2013-11-01

Non-purine derivatives have been shown to be promising novel drug candidates as xanthine oxidase inhibitors. Based on three-dimensional quantitative structure-activity relationship (3D-QSAR) methods including comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), two 3D-QSAR models for a series of non-purine xanthine oxidase (XO) inhibitors were established, and their reliability was supported by statistical parameters. Combined 3D-QSAR modeling and the results of molecular docking between non-purine xanthine oxidase inhibitors and XO, the main factors that influenced activity of inhibitors were investigated, and the obtained results could explain known experimental facts. Furthermore, several new potential inhibitors with higher activity predicted were designed, which based on our analyses, and were supported by the simulation of molecular docking. This study provided some useful information for the development of non-purine xanthine oxidase inhibitors with novel structures.

Structural Diversity in the Dandelion (Taraxacum officinale) Polyphenol Oxidase Family Results in Different Responses to Model Substrates

PubMed Central

Dirks-Hofmeister, Mareike E.; Singh, Ratna; Leufken, Christine M.; Inlow, Jennifer K.; Moerschbacher, Bruno M.

2014-01-01

Polyphenol oxidases (PPOs) are ubiquitous type-3 copper enzymes that catalyze the oxygen-dependent conversion of o-diphenols to the corresponding quinones. In most plants, PPOs are present as multiple isoenzymes that probably serve distinct functions, although the precise relationship between sequence, structure and function has not been addressed in detail. We therefore compared the characteristics and activities of recombinant dandelion PPOs to gain insight into the structure–function relationships within the plant PPO family. Phylogenetic analysis resolved the 11 isoenzymes of dandelion into two evolutionary groups. More detailed in silico and in vitro analyses of four representative PPOs covering both phylogenetic groups were performed. Molecular modeling and docking predicted differences in enzyme-substrate interactions, providing a structure-based explanation for grouping. One amino acid side chain positioned at the entrance to the active site (position HB2+1) potentially acts as a “selector” for substrate binding. In vitro activity measurements with the recombinant, purified enzymes also revealed group-specific differences in kinetic parameters when the selected PPOs were presented with five model substrates. The combination of our enzyme kinetic measurements and the in silico docking studies therefore indicate that the physiological functions of individual PPOs might be defined by their specific interactions with different natural substrates. PMID:24918587

The discovery of novel histone lysine methyltransferase G9a inhibitors (part 1): molecular design based on a series of substituted 2,4-diamino-7- aminoalkoxyquinazoline by molecular-docking-guided 3D quantitative structure-activity relationship studies.

PubMed

Feng, Taotao; Wang, Hai; Zhang, Xiaojin; Sun, Haopeng; You, Qidong

2014-06-01

Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is overexpressed in human cancers. This suggests that small molecular inhibitors of G9a might be attractive antitumor agents. Herein we report our efforts on the design of novel G9a inhibitor based on the 3D quantitative structure-activity relationship (3D-QSAR) analysis of a series of 2,4-diamino-7-aminoalkoxyquinazolineas G9a inhibitors. The 3D-QSAR model was generated from 47 compounds using docking based molecular alignment. The best predictions were obtained with CoMFA standard model (q2 =0.700, r2 = 0.952) and CoMSIA model combined with steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor fields (q2 = 0.724, r2 =0.960). The structural requirements for substituted 2,4-diamino-7-aminoalkoxyquinazoline for G9a inhibitory activity can be obtained by analysing the COMSIA plots. Based on the information, six novel follow-up analogs were designed.

Analysis of bacterial populations in the environment using two-dimensional gel electrophoresis of genomic DNA and complementary DNA.

PubMed

Liu, Guo-Hua; Nakamura, Tatsuo; Amemiya, Takashi; Rajendran, Narasimmalu; Itoh, Kiminori

2011-01-01

Two-dimensional gel electrophoresis (2-DGE) mapping of genomic DNA and complementary DNA (cDNA) amplicons was attempted to analyze total and active bacterial populations within soil and activated sludge samples. Distinct differences in the number and species of bacterial populations and those that were metabolically active at the time of sampling were visually observed especially for the soil community. Statistical analyses and sequencing based on the 2-DGE data further revealed the relationships between total and active bacterial populations within each community. This high-resolution technique would be useful for obtaining a better understanding of bacterial population structures in the environment.

Prevalence and Psychosocial Correlates of After-School Activities among Chinese Adolescents in Hong Kong

PubMed Central

Ma, Cecilia M. S.; Shek, Daniel Tan Lei

2014-01-01

Using a cross-sectional design, this study (a) explores the prevalence of after-school activities among Chinese early adolescents and (b) assesses the relationships between participation in after-school activities, personal well-being, and family functioning. A total of 3,328 Grade 7 students (mean age = 12.59 years, SD = 0.74) completed a self-administered questionnaire. Results showed that the majority of adolescents returned home under adult supervision. Further analyses showed the associations between after-school activities, positive youth development qualities, academic and school competence, family functioning, and risky behavior. Implications regarding efforts aimed at designing high quality and structured after-school youth programs are discussed. PMID:25309895

Synthesis and structure-activity relationships of novel cationic lipids with anti-inflammatory and antimicrobial activities.

PubMed

Myint, Melissa; Bucki, Robert; Janmey, Paul A; Diamond, Scott L

2015-07-15

Certain membrane-active cationic steroids are known to also possess both anti-inflammatory and antimicrobial properties. This combined functionality is particularly relevant for potential therapies of infections associated with elevated tissue damage, for example, cystic fibrosis airway disease, a condition characterized by chronic bacterial infections and ongoing inflammation. In this study, six novel cationic glucocorticoids were synthesized using beclomethasone, budesonide, and flumethasone. Products were either monosubstituted or disubstituted, containing one or two steroidal groups, respectively. In vitro evaluation of biological activities demonstrated dual anti-inflammatory and antimicrobial properties with limited cytotoxicity for all synthesized compounds. Budesonide-derived compounds showed the highest degree of both glucocorticoid and antimicrobial properties within their respective mono- and disubstituted categories. Structure-activity analyses revealed that activity was generally related to the potency of the parent glucocorticoid. Taken together, these data indicate that these types of dual acting cationic lipids can be synthesized with the appropriate starting steroid to tailor activities as desired. Copyright © 2015 Elsevier Ltd. All rights reserved.

Function-Oriented Synthesis of Marine Phidianidine Derivatives as Potential PTP1B Inhibitors with Specific Selectivity.

PubMed

Liu, Jin; Chen, Yu; Li, Jing-Ya; Luo, Cheng; Li, Jia; Chen, Kai-Xian; Li, Xu-Wen; Guo, Yue-Wei

2018-03-20

Phidianidines A and B are two novel marine indole alkaloids bearing an uncommon 1,2,4-oxadiazole ring and exhibiting various biological activities. Our previous research showed that the synthesized phidianidine analogs had the potential to inhibit the activity of protein tyrosine phosphatase 1B (PTP1B), a validated target for Type II diabetes, which indicates that these analogs are worth further structural modification. Therefore, in this paper, a series of phidianidine derivatives were designed and rapidly synthesized with a function-oriented synthesis (FOS) strategy. Their inhibitory effects on PTP1B and T-cell protein tyrosine phosphatase (TCPTP) were evaluated, and several compounds displayed significant inhibitory potency and specific selectivity over PTP1B. The structure-activity relationship (SAR) and molecular docking analyses are also described.

Multimodal assessment of hemispheric lateralization for language and its relevance for behavior.

PubMed

Piervincenzi, C; Petrilli, A; Marini, A; Caulo, M; Committeri, G; Sestieri, C

2016-11-15

Although different MRI-based techniques have been proposed to assess the hemispheric lateralization for language (HLL), the agreement across methods, and its relationship with language abilities, are still a matter of debate. In the present study we obtained measures of HLL using both task-evoked activity during the execution of three different protocols and task-free methods of functional [resting state functional connectivity (rs-FC)] and anatomical [diffusion tensor imaging (DTI) tractography] connectivity. Regional analyses focusing on the perisylvian language network were conducted to assess the consistency of HLL across techniques. In addition, following a multimodal approach, we identified macro-factors of lateralization and examined their relationship with language performance. Our findings indicate the existence of a negative relationship between the structural asymmetry of the direct segment of the arcuate fasciculus (AF) and the inter-hemispheric rs-FC of key nodes of the perisylvian network. Instead, despite all the language tasks exhibited a leftward pattern of asymmetry, measures of HLL derived from task-evoked activity did not show a direct relationship with those obtained with the two task-free methods. Furthermore, a robust brain-behavioral relationship was observed only with a specific macro-factor that combined HLL measures derived from all MRI techniques. In particular, general language performance was positively related to more symmetrical structural organization, stronger inter-hemispheric communication at rest but more lateralized activation of Wernicke's territory during production tasks. Our findings, while not supporting the existence of a direct relationship between indices of hemispheric lateralization for language derived from different MRI techniques, indicate that general language performance can be indexed using combined MRI measures. The same approach might prove successful for likewise complex human behaviours. Copyright © 2016 Elsevier Inc. All rights reserved.

Research data management and libraries: relationships, activities, drivers and influences.

PubMed

Pinfield, Stephen; Cox, Andrew M; Smith, Jen

2014-01-01

The management of research data is now a major challenge for research organisations. Vast quantities of born-digital data are being produced in a wide variety of forms at a rapid rate in universities. This paper analyses the contribution of academic libraries to research data management (RDM) in the wider institutional context. In particular it: examines the roles and relationships involved in RDM, identifies the main components of an RDM programme, evaluates the major drivers for RDM activities, and analyses the key factors influencing the shape of RDM developments. The study is written from the perspective of library professionals, analysing data from 26 semi-structured interviews of library staff from different UK institutions. This is an early qualitative contribution to the topic complementing existing quantitative and case study approaches. Results show that although libraries are playing a significant role in RDM, there is uncertainty and variation in the relationship with other stakeholders such as IT services and research support offices. Current emphases in RDM programmes are on developments of policies and guidelines, with some early work on technology infrastructures and support services. Drivers for developments include storage, security, quality, compliance, preservation, and sharing with libraries associated most closely with the last three. The paper also highlights a 'jurisdictional' driver in which libraries are claiming a role in this space. A wide range of factors, including governance, resourcing and skills, are identified as influencing ongoing developments. From the analysis, a model is constructed designed to capture the main aspects of an institutional RDM programme. This model helps to clarify the different issues involved in RDM, identifying layers of activity, multiple stakeholders and drivers, and a large number of factors influencing the implementation of any initiative. Institutions may usefully benchmark their activities against the data and model in order to inform ongoing RDM activity.

Research Data Management and Libraries: Relationships, Activities, Drivers and Influences

PubMed Central

Pinfield, Stephen; Cox, Andrew M.; Smith, Jen

2014-01-01

The management of research data is now a major challenge for research organisations. Vast quantities of born-digital data are being produced in a wide variety of forms at a rapid rate in universities. This paper analyses the contribution of academic libraries to research data management (RDM) in the wider institutional context. In particular it: examines the roles and relationships involved in RDM, identifies the main components of an RDM programme, evaluates the major drivers for RDM activities, and analyses the key factors influencing the shape of RDM developments. The study is written from the perspective of library professionals, analysing data from 26 semi-structured interviews of library staff from different UK institutions. This is an early qualitative contribution to the topic complementing existing quantitative and case study approaches. Results show that although libraries are playing a significant role in RDM, there is uncertainty and variation in the relationship with other stakeholders such as IT services and research support offices. Current emphases in RDM programmes are on developments of policies and guidelines, with some early work on technology infrastructures and support services. Drivers for developments include storage, security, quality, compliance, preservation, and sharing with libraries associated most closely with the last three. The paper also highlights a ‘jurisdictional’ driver in which libraries are claiming a role in this space. A wide range of factors, including governance, resourcing and skills, are identified as influencing ongoing developments. From the analysis, a model is constructed designed to capture the main aspects of an institutional RDM programme. This model helps to clarify the different issues involved in RDM, identifying layers of activity, multiple stakeholders and drivers, and a large number of factors influencing the implementation of any initiative. Institutions may usefully benchmark their activities against the data and model in order to inform ongoing RDM activity. PMID:25485539

Quantitative structure carcinogenicity relationship for detecting structural alerts in nitroso-compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helguera, Aliuska Morales; Molecular Simulation and Drug Design, Chemical Bioactive Center, Central University of Las Villas, Santa Clara, 54830, Villa Clara; Department of Chemistry, Central University of Las Villas, Santa Clara, 54830, Villa Clara

2008-09-01

In this work, Quantitative Structure-Activity Relationship (QSAR) modelling was used as a tool for predicting the carcinogenic potency of a set of 39 nitroso-compounds, which have been bioassayed in male rats by using the oral route of administration. The optimum QSAR model provided evidence of good fit and performance of predicitivity from training set. It was able to account for about 84% of the variance in the experimental activity and exhibited high values of the determination coefficients of cross validations, leave one out and bootstrapping (q{sup 2}{sub LOO} = 78.53 and q{sup 2}{sub Boot} = 74.97). Such a model wasmore » based on spectral moments weighted with Gasteiger-Marsilli atomic charges, polarizability and hydrophobicity, as well as with Abraham indexes, specifically the summation solute hydrogen bond basicity and the combined dipolarity/polarizability. This is the first study to have explored the possibility of combining Abraham solute descriptors with spectral moments. A reasonable interpretation of these molecular descriptors from a toxicological point of view was achieved by means of taking into account bond contributions. The set of relationships so derived revealed the importance of the length of the alkyl chains for determining carcinogenic potential of the chemicals analysed, and were able to explain the difference between mono-substituted and di-substituted nitrosoureas as well as to discriminate between isomeric structures with hydroxyl-alkyl and alkyl substituents in different positions. Moreover, they allowed the recognition of structural alerts in classical structures of two potent nitrosamines, consistent with their biotransformation. These results indicate that this new approach has the potential for improving carcinogenicity predictions based on the identification of structural alerts.« less

Geo-Chip analysis reveals reduced functional diversity of the bacterial community at a dumping site for dredged Elbe sediment.

PubMed

Störmer, Rebecca; Wichels, Antje; Gerdts, Gunnar

2013-12-15

The dumping of dredged sediments represents a major stressor for coastal ecosystems. The impact on the ecosystem function is determined by its complexity not easy to assess. In the present study, we evaluated the potential of bacterial community analyses to act as ecological indicators in environmental monitoring programmes. We investigated the functional structure of bacterial communities, applying functional gene arrays (GeoChip4.2). The relationship between functional genes and environmental factors was analysed using distance-based multivariate multiple regression. Apparently, both the function and structure of the bacterial communities are impacted by dumping activities. The bacterial community at the dumping centre displayed a significant reduction of its entire functional diversity compared with that found at a reference site. DDX compounds separated bacterial communities of the dumping site from those of un-impacted sites. Thus, bacterial community analyses show great potential as ecological indicators in environmental monitoring. Copyright © 2013 Elsevier Ltd. All rights reserved.

Quantitative structure-antifungal activity relationships of some benzohydrazides against Botrytis cinerea.

PubMed

Reino, José L; Saiz-Urra, Liane; Hernandez-Galan, Rosario; Aran, Vicente J; Hitchcock, Peter B; Hanson, James R; Gonzalez, Maykel Perez; Collado, Isidro G

2007-06-27

Fourteen benzohydrazides have been synthesized and evaluated for their in vitro antifungal activity against the phytopathogenic fungus Botrytis cinerea. The best antifungal activity was observed for the N',N'-dibenzylbenzohydrazides 3b-d and for the N-aminoisoindoline-derived benzohydrazide 5. A quantitative structure-activity relationship (QSAR) study has been developed using a topological substructural molecular design (TOPS-MODE) approach to interpret the antifungal activity of these synthetic compounds. The model described 98.3% of the experimental variance, with a standard deviation of 4.02. The influence of an ortho substituent on the conformation of the benzohydrazides was investigated by X-ray crystallography and supported by QSAR study. Several aspects of the structure-activity relationships are discussed in terms of the contribution of different bonds to the antifungal activity, thereby making the relationships between structure and biological activity more transparent.

Design and synthesis of positional isomers of 5 and 6-bromo-1-[(phenyl)sulfonyl]-2-[(4-nitrophenoxy)methyl]-1H-benzimidazoles as possible antimicrobial and antitubercular agents.

PubMed

Ranjith, P Karuvalam; Rajeesh, P; Haridas, Karickal R; Susanta, Nayak K; Row, Tayur N Guru; Rishikesan, R; Kumari, N Suchetha

2013-09-15

In this Letter, we report the structure-activity relationship (SAR) studies on series of positional isomers of 5(6)-bromo-1-[(phenyl)sulfonyl]-2-[(4-nitrophenoxy)methyl]-1H-benzimidazoles derivatives 7(a-j) and 8(a-j) synthesized in good yields and characterized by (1)H NMR, (13)C NMR and mass spectral analyses. The crystal structure of 7a was evidenced by X-ray diffraction study. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, (Gram-positive), Escherichia coli and Klebsiella pneumoniae (Gram-negative), antifungal activity against Candida albicans, Aspergillus flavus and Rhizopus sp. and antitubercular activity against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis, Mycobacterium fortuitum and MDR-TB strains. The synthesized compounds displayed interesting antimicrobial activity. The compounds 7b, 7e and 7h displayed significant activity against Mycobacterium tuberculosis H37Rv strain. Copyright © 2013 Elsevier Ltd. All rights reserved.

History of the magmatic feeding system of the Campi Flegrei caldera (Italy)

NASA Astrophysics Data System (ADS)

Civetta, L.; Arienzo, I.; D'Antonio, M.; di Renzo, V.; di Vito, M. A.; Orsi, G.

2007-05-01

The definition of the magmatic feeding system of active volcanoes in terms of architecture, composition, crystallization time-scale, relationships between composition of the erupted magmas and structural position of the vents, and magma processes, is of paramount importance for volcanic hazards evaluation. Investigations aimed at defining the Campi Flegeri magmatic system, include detailed mineralogical, geochemical and isotopic analyses (Sr, Nd, Pb, Th,U). The magmatic feeding system of the Campi Flegrei caldera is characterized by deep and shallow magma reservoirs. In the deep reservoirs (20-10 km depth) mantle- derived magmas differentiated and were contaminated by continental crust. In the shallow reservoirs isotopically distinct magmas, further differentiated, contaminated, and mixed and mingled before eruptions. These processes generated isotopically distinct components, variably interacting with the different structural elements of the Campi Flegrei caldera through time. The relationships between the structural position of the eruption vents, during the last 15 ka of activity, and the isotopic composition of the magmas erupted at the Campi Flegrei caldera allow us to reconstruct the architecture of the magmatic feeding system and to infer the chemical and isotopic composition of the magma feeding a future eruption, according to vent position.

Chemical Structure-Biological Activity Models for Pharmacophores’ 3D-Interactions

PubMed Central

Putz, Mihai V.; Duda-Seiman, Corina; Duda-Seiman, Daniel; Putz, Ana-Maria; Alexandrescu, Iulia; Mernea, Maria; Avram, Speranta

2016-01-01

Within medicinal chemistry nowadays, the so-called pharmaco-dynamics seeks for qualitative (for understanding) and quantitative (for predicting) mechanisms/models by which given chemical structure or series of congeners actively act on biological sites either by focused interaction/therapy or by diffuse/hazardous influence. To this aim, the present review exposes three of the fertile directions in approaching the biological activity by chemical structural causes: the special computing trace of the algebraic structure-activity relationship (SPECTRAL-SAR) offering the full analytical counterpart for multi-variate computational regression, the minimal topological difference (MTD) as the revived precursor for comparative molecular field analyses (CoMFA) and comparative molecular similarity indices analysis (CoMSIA); all of these methods and algorithms were presented, discussed and exemplified on relevant chemical medicinal systems as proton pump inhibitors belonging to the 4-indolyl,2-guanidinothiazole class of derivatives blocking the acid secretion from parietal cells in the stomach, the 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)thymine congeners’ (HEPT ligands) antiviral activity against Human Immunodeficiency Virus of first type (HIV-1) and new pharmacophores in treating severe genetic disorders (like depression and psychosis), respectively, all involving 3D pharmacophore interactions. PMID:27399692

Structural and functional social network attributes moderate the association of self-rated health with mental health in midlife and older adults.

PubMed

Windsor, Tim D; Rioseco, Pilar; Fiori, Katherine L; Curtis, Rachel G; Booth, Heather

2016-01-01

Social relationships are multifaceted, and different social network components can operate via different processes to influence well-being. This study examined associations of social network structure and relationship quality (positive and negative social exchanges) with mental health in midlife and older adults. The focus was on both direct associations of network structure and relationship quality with mental health, and whether these social network attributes moderated the association of self-rated health (SRH) with mental health. Analyses were based on survey data provided by 2001 (Mean age = 65, SD = 8.07) midlife and older adults. We used Latent Class Analysis (LCA) to classify participants into network types based on network structure (partner status, network size, contact frequency, and activity engagement), and used continuous measures of positive and negative social exchanges to operationalize relationship quality. Regression analysis was used to test moderation. LCA revealed network types generally consistent with those reported in previous studies. Participants in more diverse networks reported better mental health than those categorized into a restricted network type after adjustment for age, sex, education, and employment status. Analysis of moderation indicated that those with poorer SRH were less likely to report poorer mental health if they were classified into more diverse networks. A similar moderation effect was also evident for positive exchanges. The findings suggest that both quantity and quality of social relationships can play a role in buffering against the negative implications of physical health decline for mental health.

Does Adolescent Family Structure Predict Military Enlistment? A Comparison of Post-High School Activities

PubMed Central

Spence, Naomi J.; Henderson, Kathryn A.; Elder, Glen H.

2013-01-01

This paper investigates the link between adolescent family structure and the likelihood of military enlistment in young adulthood, as compared to alternative post-high school activities. We use data from the National Longitudinal Study of Adolescent Health and multinomial logistic regression analyses to compare the odds of military enlistment with college attendance or labor force involvement. We find that alternative family structures predict enlistment relative to college attendance. Living in a single-parent household during adolescence increased odds of military enlistment, but the effect is accounted for by socioeconomic status and early feelings of social isolation. Living with a stepparent or with neither biological parent more than doubles the odds of enlistment, independent of socioeconomic status, characteristics of parent-child relationships, or feelings of social isolation. Although college attendance is widely promoted as a valued post-high school activity, military service may offer a route to independence and a greater sense of belonging. PMID:24000268

X-ray diffraction studies of enkephalins. Crystal structure of [(4'-bromo) Phe4,Leu5]enkephalin.

PubMed Central

Ishida, T; Kenmotsu, M; Mino, Y; Inoue, M; Fujiwara, T; Tomita, K; Kimura, T; Sakakibara, S

1984-01-01

In order to investigate the structure-activity relationship of [Leu5]- and [Met5]enkephalins, [(4'-bromo)Phe4, Leu5]-, [(4'-bromo)Phe4, Met5]- and [Met5] enkephalins were synthesized and crystallized. The crystal structure of [(4'-bromo) Phe4, Leu5]- enkephalin was determined by X-ray diffraction method using the heavy atom method and refined to R = 0.092 by the least-squares method. The molecule in this crystal took essentially the same type I' beta-turn conformation found in [Leu5]enkephalin [Smith & Griffin (1978) Science 199, 1214-1216). On the other hand, the preliminary three-dimensional Patterson analyses showed that the most probable conformations of [(4'-bromo)Phe4,Met5]- and [Met5]enkephalins are both the dimeric extended forms. Based on these insights, the biologically active conformation of enkephalin was discussed in relation to the mu- and delta-receptors. PMID:6721829

Sustainability of physical activity promoting environments and influences on sustainability following a structural intervention in residential children's homes.

PubMed

Dominick, Gregory M; Tudose, Alina; Pohlig, Ryan T; Saunders, Ruth P

2016-04-01

Research examining sustainability of health promotion programs within organizational settings is limited. The Environmental Interventions in Residential Children's Homes (ENRICH) was a structural intervention that trained Wellness Teams (WTs) within residential children's homes (RCH) to target environmental changes that promote physical activity (PA) among residential youth. This study examines the sustainability of PA promoting environments and influences on sustainability within RCHs. A sustainability survey was administered to 14 RCHs 2 years after receiving ENRICH. Variables included sustainability of PA promoting environments, Organizational Influences, perceived organizational and individual benefits, and implementation of PA and general (i.e. Global) wellness activities. Activities reported as sustained and barriers were used descriptively to inform sustainability. Path analyses explained the relationship between sustainability influences and sustainability of PA promoting environments. Sustainability was found in 8 of 14 (57%) RCHs. Sustained activities reflected greater Global versus PA implementation. Global implementation mediated the relationship between Organizational Influences and sustainability, which may have been more easily achieved since Global activities were most likely controlled by WTs and did not require extensive organizational support from RCH administrators. Results highlight the importance of defining and assessing different implementation types when measuring sustainability and influences on sustainability within RCHs organizations. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Use of QSARs in international decision-making frameworks to predict health effects of chemical substances.

PubMed Central

Cronin, Mark T D; Jaworska, Joanna S; Walker, John D; Comber, Michael H I; Watts, Christopher D; Worth, Andrew P

2003-01-01

This article is a review of the use of quantitative (and qualitative) structure-activity relationships (QSARs and SARs) by regulatory agencies and authorities to predict acute toxicity, mutagenicity, carcinogenicity, and other health effects. A number of SAR and QSAR applications, by regulatory agencies and authorities, are reviewed. These include the use of simple QSAR analyses, as well as the use of multivariate QSARs, and a number of different expert system approaches. PMID:12896862

3D-quantitative structure-activity relationship study for the design of novel enterovirus A71 3C protease inhibitors.

PubMed

Nie, Quandeng; Xu, Xiaoyi; Zhang, Qi; Ma, Yuying; Yin, Zheng; Shang, Luqing

2018-06-07

A three-dimensional quantitative structure-activity relationships model of enterovirus A71 3C protease inhibitors was constructed in this study. The protein-ligand interaction fingerprint was analyzed to generate a pharmacophore model. A predictive and reliable three-dimensional quantitative structure-activity relationships model was built based on the Flexible Alignment of AutoGPA. Moreover, three novel compounds (I-III) were designed and evaluated for their biochemical activity against 3C protease and anti-enterovirus A71 activity in vitro. III exhibited excellent inhibitory activity (IC 50 =0.031 ± 0.005 μM, EC 50 =0.036 ± 0.007 μM). Thus, this study provides a useful quantitative structure-activity relationships model to develop potent inhibitors for enterovirus A71 3C protease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Interaction Analysis of FABP4 Inhibitors by X-ray Crystallography and Fragment Molecular Orbital Analysis

PubMed Central

2016-01-01

X-ray crystal structural determination of FABP4 in complex with four inhibitors revealed the complex binding modes, and the resulting observations led to improvement of the inhibitory potency of FABP4 inhibitors. However, the detailed structure–activity relationship (SAR) could not be explained from these structural observations. For a more detailed understanding of the interactions between FABP4 and inhibitors, fragment molecular orbital analyses were performed. These analyses revealed that the total interfragment interaction energies of FABP4 and each inhibitor correlated with the ranking of the Ki value for the four inhibitors. Furthermore, interactions between each inhibitor and amino acid residues in FABP4 were identified. The oxygen atom of Lys58 in FABP4 was found to be very important for strong interactions with FABP4. These results might provide useful information for the development of novel potent FABP4 inhibitors. PMID:27096055

The Interactions of Relationships, Interest, and Self-Efficacy in Undergraduate Physics

NASA Astrophysics Data System (ADS)

Dou, Remy

This collected papers dissertation explores students' academic interactions in an active learning, introductory physics settings as they relate to the development of physics self-efficacy and interest. The motivation for this work extends from the national call to increase participation of students in the pursuit of science, technology, engineering, and mathematics (STEM) careers. Self-efficacy and interest are factors that play prominent roles in popular, evidence-based, career theories, including the Social cognitive career theory (SCCT) and the identity framework. Understanding how these constructs develop in light of the most pervasive characteristic of the active learning introductory physics classroom (i.e., peer-to-peer interactions) has implications on how students learn in a variety of introductory STEM classrooms and settings structured after constructivist and sociocultural learning theories. I collected data related to students' in-class interactions using the tools of social network analysis (SNA). Social network analysis has recently been shown to be an effective and useful way to examine the structure of student relationships that develop in and out of STEM classrooms. This set of studies furthers the implementation of SNA as a tool to examine self-efficacy and interest formation in the active learning physics classroom. Here I represent a variety of statistical applications of SNA, including bootstrapped linear regression (Chapter 2), structural equation modeling (Chapter 3), and hierarchical linear modeling for longitudinal analyses (Chapter 4). Self-efficacy data were collected using the Sources of Self-Efficacy for Science Courses - Physics survey (SOSESC-P), and interest data were collected using the physics identity survey. Data for these studies came from the Modeling Instruction sections of Introductory Physics with Calculus offered at Florida International University in the fall of 2014 and 2015. Analyses support the idea that students' perceptions of one another impact the development of their social network centrality, which in turn affects their self-efficacy building experiences and their overall self-efficacy. It was shown that unlike career theories that emphasize causal relationships between the development of self-efficacy and the subsequent growth of student interest, in this context student interest takes precedence before the development of student self-efficacy. This outcome also has various implications for career theories.

Synthesis and in vivo anticonvulsant activity of 2-methyl-2-[3-(5-piperazin-1-yl-[1,3,4]oxadiazol-2-yl)-phenyl]-propionitrile derivatives.

PubMed

Harish, Kikkeri P; Mohana, Kikkeri N; Mallesha, Lingappa; Veeresh, Bantal

2014-04-01

A series of new 2-methyl-2-[3-(5-piperazin-1-yl-[1,3,4]oxadiazol-2-yl)-phenyl]-propionitrile derivatives 8a-o, 9a-c, 10a-d, and 11a-d were synthesized to meet the structural requirements essential for anticonvulsant property. The structures of all the synthesized compounds were confirmed by means of (1)H NMR, (13)C NMR, and mass spectral studies. The purity of the novel compounds was confirmed by elemental analyses. All the compounds were screened for their anticonvulsant activity against maximal electroshock (MES) seizure method and their neurotoxic effects were determined by rotorod test. Compounds 8d, 8e, and 8f were found to be the most potent of this series. The same compounds showed no neurotoxicity at the maximum dose administered (100 mg/kg). The efforts were also made to establish the structure-activity relationships among the synthesized compounds. The pharmacophore model was used to validate the anticonvulsant activity of the synthesized molecules. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biochemical evaluation of interactions between synergistic molecules and phase I enzymes involved in insecticide resistance in B- and Q-type Bemisia tabaci (Hemiptera: Aleyrodidae).

PubMed

Panini, Michela; Tozzi, Francesco; Zimmer, Christoph T; Bass, Chris; Field, Linda; Borzatta, Valerio; Mazzoni, Emanuele; Moores, Graham

2017-09-01

Metabolic resistance is an important consideration in the whitefly Bemisia tabaci, where an esterase-based mechanism has been attributed to pyrethroid resistance and over-expression of the cytochrome P450, CYP6CM1, has been correlated to resistance to imidacloprid and other neonicotinoids. In vitro interactions between putative synergists and CYP6CM1, B and Q-type esterases were investigated, and structure-activity relationship analyses allowed the identification of chemical structures capable of acting as inhibitors of esterase and oxidase activities. Specifically, methylenedioxyphenyl (MDP) moieties with a polyether chain were preferable for optimum inhibition of B-type esterase, whilst corresponding dihydrobenzofuran structures were potent for the Q-esterase variation. Potent inhibition of CYP6CM1 resulted from structures which contained an alkynyl chain with a terminal methyl group. Synergist candidates could be considered for field control of B. tabaci, especially to abrogate neonicotinoid resistance. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

It's like balancing on a slackline - A description of how adults with congenital heart disease describe themselves in relation to physical activity.

PubMed

Bay, Annika; Lämås, Kristina; Berghammer, Malin; Sandberg, Camilla; Johansson, Bengt

2018-05-12

To illuminate how adults with CHD describe themselves in relation to physical activity. Several studies have shown that adults with congenital heart disease (CHD) have reduced exercise capacity and do not reach the recommended daily level of physical activity. With this in view, it is of immense importance to investigate how this population experiences physical activity. Qualitative study with semi-structured interviews analysed with qualitative content analysis. Semi-structured interviews were individually performed with fourteen adults (women=7, age 19-68 years) with complex CHD. Patients were purposively recruited from the clinic waiting list, based on a scheduled follow-up and diagnosis. The overall theme, It's like balancing on a slackline, illustrates how adults with CHD described themselves in relation to physical activity. This overall theme consisted of four subthemes: (1) Being an adventurer- enjoying the challenges of physical activity; (2) Being a realist- adapting to physical ability; (3) Being a non-doer- lacking prerequisites for physical activity; and (4) Being an outsider- feeling excluded depending on physical ability. Adults with CHD seem to have a diverse relationship to physical activity and it involves various aspects throughout the lifespan. The findings point out factors that might constitute as obstacles for being physically active, specific for people with chronic conditions like CHD. This highlights the importance of further exploring the hindering and facilitating factors for being physically active in order to get a deeper understanding of how to support adults with CHD to be physically active. Given the diverse relationship to physical activity, nurses have to further investigate the patients' relationship to physical activity, in order to support a healthy lifestyle. Nurses and allied health professionals should offer individualized exercise prescriptions and education about suitable physical activities in relation to physical ability. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Quantitative structure activity relationship studies of mushroom tyrosinase inhibitors

NASA Astrophysics Data System (ADS)

Xue, Chao-Bin; Luo, Wan-Chun; Ding, Qi; Liu, Shou-Zhu; Gao, Xing-Xiang

2008-05-01

Here, we report our results from quantitative structure-activity relationship studies on tyrosinase inhibitors. Interactions between benzoic acid derivatives and tyrosinase active sites were also studied using a molecular docking method. These studies indicated that one possible mechanism for the interaction between benzoic acid derivatives and the tyrosinase active site is the formation of a hydrogen-bond between the hydroxyl (aOH) and carbonyl oxygen atoms of Tyr98, which stabilized the position of Tyr98 and prevented Tyr98 from participating in the interaction between tyrosinase and ORF378. Tyrosinase, also known as phenoloxidase, is a key enzyme in animals, plants and insects that is responsible for catalyzing the hydroxylation of tyrosine into o-diphenols and the oxidation of o-diphenols into o-quinones. In the present study, the bioactivities of 48 derivatives of benzaldehyde, benzoic acid, and cinnamic acid compounds were used to construct three-dimensional quantitative structure-activity relationship (3D-QSAR) models using comparative molecular field (CoMFA) and comparative molecular similarity indices (CoMSIA) analyses. After superimposition using common substructure-based alignments, robust and predictive 3D-QSAR models were obtained from CoMFA ( q 2 = 0.855, r 2 = 0.978) and CoMSIA ( q 2 = 0.841, r 2 = 0.946), with 6 optimum components. Chemical descriptors, including electronic (Hammett σ), hydrophobic (π), and steric (MR) parameters, hydrogen bond acceptor (H-acc), and indicator variable ( I), were used to construct a 2D-QSAR model. The results of this QSAR indicated that π, MR, and H-acc account for 34.9, 31.6, and 26.7% of the calculated biological variance, respectively. The molecular interactions between ligand and target were studied using a flexible docking method (FlexX). The best scored candidates were docked flexibly, and the interaction between the benzoic acid derivatives and the tyrosinase active site was elucidated in detail. We believe that the QSAR models built here provide important information necessary for the design of novel tyrosinase inhibitors.

Assessing impacts of unconventional natural gas extraction on microbial communities in headwater stream ecosystems in Northwestern Pennsylvania

PubMed Central

Trexler, Ryan; Solomon, Caroline; Brislawn, Colin J.; Wright, Justin R.; Rosenberger, Abigail; McClure, Erin E.; Grube, Alyssa M.; Peterson, Mark P.; Keddache, Mehdi; Mason, Olivia U.; Hazen, Terry C.; Grant, Christopher J.; Lamendella, Regina

2014-01-01

Hydraulic fracturing and horizontal drilling have increased dramatically in Pennsylvania Marcellus shale formations, however the potential for major environmental impacts are still incompletely understood. High-throughput sequencing of the 16S rRNA gene was performed to characterize the microbial community structure of water, sediment, bryophyte, and biofilm samples from 26 headwater stream sites in northwestern Pennsylvania with different histories of fracking activity within Marcellus shale formations. Further, we describe the relationship between microbial community structure and environmental parameters measured. Approximately 3.2 million 16S rRNA gene sequences were retrieved from a total of 58 samples. Microbial community analyses showed significant reductions in species richness as well as evenness in sites with Marcellus shale activity. Beta diversity analyses revealed distinct microbial community structure between sites with and without Marcellus shale activity. For example, operational taxonomic units (OTUs) within the Acetobacteracea, Methylocystaceae, Acidobacteriaceae, and Phenylobacterium were greater than three log-fold more abundant in MSA+ sites as compared to MSA− sites. Further, several of these OTUs were strongly negatively correlated with pH and positively correlated with the number of wellpads in a watershed. It should be noted that many of the OTUs enriched in MSA+ sites are putative acidophilic and/or methanotrophic populations. This study revealed apparent shifts in the autochthonous microbial communities and highlighted potential members that could be responding to changing stream conditions as a result of nascent industrial activity in these aquatic ecosystems. PMID:25408683

Role strain in couples with and without a child with a chronic illness: associations with marital satisfaction, intimacy, and daily mood.

PubMed

Quittner, A L; Opipari, L C; Espelage, D L; Carter, B; Eid, N; Eigen, H

1998-03-01

This study examined marital role strain in 33 couples caring for a child with cystic fibrosis (CF) and 33 couples with a healthy child. The relationship between role strain, marital satisfaction, and psychological distress was tested. Couples completed a structured interview, questionnaires, a card sort procedure, and 4 daily diaries assessing activities and mood. Couples in the CF versus comparison group reported greater role strain on measures of role conflict, child-care tasks, and exchanges of affection. They also spent less time in recreational activities, but no reliable group differences were found in marital satisfaction or depression. Regression analyses indicated that role strain was related to marital satisfaction and depression and that recreation time accounted for additional variance. Path analysis suggested that recreation mediated the negative relationship between role strain and distress. The importance of using a contextual, process-oriented approach is discussed.

The Design and Development of Potent Small Molecules as Anticancer Agents Targeting EGFR TK and Tubulin Polymerization

PubMed Central

Ihmaid, Saleh; Ahmed, Hany E. A.; Zayed, Mohamed F.

2018-01-01

Some novel anthranilate diamides derivatives 4a–e, 6a–c and 9a–d were designed and synthesized to be evaluated for their in vitro anticancer activity. Structures of all newly synthesized compounds were confirmed by infra-red (IR), high-resolution mass (HR-MS) spectra, 1H nuclear magnetic resonance (NMR) and 13C nuclear magnetic resonance (NMR) analyses. Cytotoxic screening was performed according to (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium (MTT) assay method using erlotinib as a reference drug against two different types of breast cancer cells. The molecular docking study was performed for representative compounds against two targets, epidermal growth factor receptor (EGFR) and tubulin in colchicine binding site to assess their binding affinities in order to rationalize their anticancer activity in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticancer activity for these newly synthesized compounds. Biological data for most of the anthranilate diamide showed excellent activity with nanomolar or sub nanomolar half maximal inhibitory concentration (IC50) values against tumor cells. EGFR tyrosine kinase (TK) inhibition assay, tubulin inhibition assay and apoptosis analysis were performed for selected compounds to get more details about their mechanism of action. Extensive structure activity relationship (SAR) analyses were also carried out. PMID:29385728

Structure-reactivity relationships between fluorescent chromophores and antioxidant activity of grain and sweet sorghum seeds

USDA-ARS?s Scientific Manuscript database

Polyphenolic structures, such as tannins, are the putative cause of a variety of seed functions including bird/insect resistance and antioxidant activity. Structure-reactivity relationships are necessary to understand the influence of polyphenolic chromophore structures on the tannin content and fr...

PREDICTING TOXICOLOGICAL ENDPOINTS OF CHEMICALS USING QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSARS)

EPA Science Inventory

Quantitative structure-activity relationships (QSARs) are being developed to predict the toxicological endpoints for untested chemicals similar in structure to chemicals that have known experimental toxicological data. Based on a very large number of predetermined descriptors, a...

Riccardin C derivatives as anti-MRSA agents: structure-activity relationship of a series of hydroxylated bis(bibenzyl)s.

PubMed

Sawada, Hiromi; Okazaki, Miki; Morita, Daichi; Kuroda, Teruo; Matsuno, Kenji; Hashimoto, Yuichi; Miyachi, Hiroyuki

2012-12-15

Members of a series of macrocyclic bis(bibenzyl) riccardin-class derivatives were found to exhibit antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Structure-activity relationship (SAR) studies were conducted, focusing on the number and position of the hydroxyl groups. The minimum essential structure for anti-MRSA activity was also investigated. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sesquiterpenes from the essential oil of Curcuma wenyujin and their inhibitory effects on nitric oxide production.

PubMed

Xia, Guiyang; Zhou, Li; Ma, Jianghao; Wang, Ying; Ding, Liqin; Zhao, Feng; Chen, Lixia; Qiu, Feng

2015-06-01

Three new sesquiterpenes including a new elemane-type sesquiterpene, 5βH-elem-1,3,7,8-tetraen-8,12-olide (1), and two new carabrane-type sesquiterpenes, 7α,11-epoxy-6α-methoxy-carabrane-4,8-dione (2) and 8,11-epidioxy-8-hydroxy-4-oxo-6-carabren (3), together with eight known sesquiterpenes (4-11) were isolated from Curcuma wenyujin Y. H. Chen et C. Ling. Their structures were elucidated based on extensive spectroscopic analyses. A possible biogenetic scheme for the related compounds was postulated. All of the isolated compounds were tested for inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages. Meanwhile, preliminary structure-activity relationships for these compounds are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Multimodal Study of the Speciations and Activities of Supported Pd Catalysts During the Hydrogenation of Ethylene

DOE PAGES

Zhao, Shen; Li, Yuanyuan; Liu, Deyu; ...

2017-08-07

In this paper we describe a multimodal exploration of the atomic structure and chemical state of silica-supported palladium nanocluster catalysts during the hydrogenation of ethylene in operando conditions that variously transform the metallic phases between hydride and carbide speciations. The work exploits a microreactor that allows combined multiprobe investigations by high-resolution transmission electron microscopy (HR-TEM), X-ray absorption fine structure (XAFS), and microbeam IR (μ-IR) analyses on the catalyst under operando conditions. The work specifically explores the reaction processes that mediate the interconversion of hydride and carbide phases of the Pd clusters in consequence to changes made in the composition ofmore » the gas-phase reactant feeds, their stability against coarsening, the reversibility of structural/compositional transformations, and the role that oligomeric/waxy byproducts (here forming under hydrogen-limited reactant compositions) might play in modifying activity. The results provide new insights into structural features of the chemistry/mechanisms of Pd catalysis during the selective hydrogenation of acetylene in ethylene—a process simplified here in the use of binary ethylene/hydrogen mixtures. Finally, these explorations, performed in operando conditions, provide new understandings of structure–activity relationships for Pd catalysis in regimes that actively transmute important attributes of electronic and atomic structures.« less

Multimodal Study of the Speciations and Activities of Supported Pd Catalysts During the Hydrogenation of Ethylene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Shen; Li, Yuanyuan; Liu, Deyu

In this paper we describe a multimodal exploration of the atomic structure and chemical state of silica-supported palladium nanocluster catalysts during the hydrogenation of ethylene in operando conditions that variously transform the metallic phases between hydride and carbide speciations. The work exploits a microreactor that allows combined multiprobe investigations by high-resolution transmission electron microscopy (HR-TEM), X-ray absorption fine structure (XAFS), and microbeam IR (μ-IR) analyses on the catalyst under operando conditions. The work specifically explores the reaction processes that mediate the interconversion of hydride and carbide phases of the Pd clusters in consequence to changes made in the composition ofmore » the gas-phase reactant feeds, their stability against coarsening, the reversibility of structural/compositional transformations, and the role that oligomeric/waxy byproducts (here forming under hydrogen-limited reactant compositions) might play in modifying activity. The results provide new insights into structural features of the chemistry/mechanisms of Pd catalysis during the selective hydrogenation of acetylene in ethylene—a process simplified here in the use of binary ethylene/hydrogen mixtures. Finally, these explorations, performed in operando conditions, provide new understandings of structure–activity relationships for Pd catalysis in regimes that actively transmute important attributes of electronic and atomic structures.« less

The social network-network: size is predicted by brain structure and function in the amygdala and paralimbic regions

PubMed Central

Von Der Heide, Rebecca; Vyas, Govinda

2014-01-01

The social brain hypothesis proposes that the large size of the primate neocortex evolved to support complex and demanding social interactions. Accordingly, recent studies have reported correlations between the size of an individual’s social network and the density of gray matter (GM) in regions of the brain implicated in social cognition. However, the reported relationships between GM density and social group size are somewhat inconsistent with studies reporting correlations in different brain regions. One factor that might account for these discrepancies is the use of different measures of social network size (SNS). This study used several measures of SNS to assess the relationships SNS and GM density. The second goal of this study was to test the relationship between social network measures and functional brain activity. Participants performed a social closeness task using photos of their friends and unknown people. Across the VBM and functional magnetic resonance imaging analyses, individual differences in SNS were consistently related to structural and functional differences in three regions: the left amygdala, right amygdala and the right entorhinal/ventral anterior temporal cortex. PMID:24493846

Forecasting the Environmental Impacts of New Energetic Materials

DTIC Science & Technology

2010-11-30

Quantitative structure- activity relationships for chemical reductions of organic contaminants. Environmental Toxicology and Chemistry 22(8): 1733-1742. QSARs ...activity relationships [ QSARs ]) and the use of these properties to predict the chemical?s fate with multimedia assessment models. SERDP has recently...has several parts, including the prediction of chemical properties (e.g., with quantitative structure-activity relationships [ QSARs ]) and the use of

Exercise self-efficacy in older adults: social, affective, and behavioral influences.

PubMed

McAuley, Edward; Jerome, Gerald J; Marquez, David X; Elavsky, Steriani; Blissmer, Bryan

2003-01-01

A 6-month randomized controlled trial examined the effect of walking and stretching/toning activity on changes in self-efficacy to overcome barriers and engage in incremental periods of activity in older, formerly sedentary adults (N = 174, M age = 65.5 years). Additionally, we were interested in the extent to which social, affective, and behavioral influences contributed to self-efficacy at the end of the 6-month program. Multiple sample latent growth curve analyses revealed a nonsignificant curvilinear growth pattern for barriers efficacy with increases in efficacy occurring from baseline to 2 months and then declining at 4 and 6 months. In the case of efficacy related to continued activity participation, there was a significant growth pattern demonstrating declines in efficacy over the 4 time points. Structural modeling analyses revealed significant direct effects of physical activity, affect experienced during activity, and exercise social support on both types of self-efficacy. These relationships were not significantly different between modes of activity. The findings are discussed in terms of the need to target sources of efficacy information prior to program end and the implications that such an approach might have for long-term maintenance of physical activity in older adults.

Molecular design and structure--activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664.

PubMed

Das, Jagabandhu; Kimball, S David; Hall, Steven E; Han, Wen Ching; Iwanowicz, Edwin; Lin, James; Moquin, Robert V; Reid, Joyce A; Sack, John S; Malley, Mary F; Chang, Chiehying Y; Chong, Saeho; Wang-Iverson, David B; Roberts, Daniel G M; Seiler, Steven M; Schumacher, William A; Ogletree, Martin L

2002-01-07

A series of structurally novel small molecule inhibitors of human alpha-thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha-thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models.

DEVELOPMENT OF STRUCTURE ACTIVITY RELATIONSHIPS FOR ASSESSING ECOLOGICAL RISKS

EPA Science Inventory

In the field of environmental toxicology, structure activity relationships (SARs) have developed as scientifically-credible tools for predicting the effects of chemicals when little or no empirical data are available.

On the relationship between the “default mode network” and the “social brain”

PubMed Central

Mars, Rogier B.; Neubert, Franz-Xaver; Noonan, MaryAnn P.; Sallet, Jerome; Toni, Ivan; Rushworth, Matthew F. S.

2012-01-01

The default mode network (DMN) of the brain consists of areas that are typically more active during rest than during active task performance. Recently however, this network has been shown to be activated by certain types of tasks. Social cognition, particularly higher-order tasks such as attributing mental states to others, has been suggested to activate a network of areas at least partly overlapping with the DMN. Here, we explore this claim, drawing on evidence from meta-analyses of functional MRI data and recent studies investigating the structural and functional connectivity of the social brain. In addition, we discuss recent evidence for the existence of a DMN in non-human primates. We conclude by discussing some of the implications of these observations. PMID:22737119

Assessment of biofilm changes and concentration-depth profiles during arsenopyrite oxidation by Acidithiobacillus thiooxidans.

PubMed

Ramírez-Aldaba, Hugo; Vazquez-Arenas, Jorge; Sosa-Rodríguez, Fabiola S; Valdez-Pérez, Donato; Ruiz-Baca, Estela; García-Meza, Jessica Viridiana; Trejo-Córdova, Gabriel; Lara, René H

2017-08-01

Biofilm formation and evolution are key factors to consider to better understand the kinetics of arsenopyrite biooxidation. Chemical and surface analyses were carried out using Raman spectroscopy, scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), glow discharge spectroscopy (GDS), and protein analysis (i.e., quantification) in order to evaluate the formation of intermediate secondary compounds and any significant changes arising in the biofilm structure of Acidithiobacillus thiooxidans during a 120-h period of biooxidation. Results show that the biofilm first evolves from a low cell density structure (1 to 12 h) into a formation of microcolonies (24 to 120 h) and then finally becomes enclosed by a secondary compound matrix that includes pyrite (FeS 2 )-like, S n 2- /S 0 , and As 2 S 3 compounds, as shown by Raman and SEM-EDS. GDS analyses (concentration-depth profiles, i.e., 12 h) indicate significant differences for depth speciation between abiotic control and biooxidized surfaces, thus providing a quantitative assessment of surface-bulk changes across samples (i.e. reactivity and /or structure-activity relationship). Respectively, quantitative protein analyses and CLSM analyses suggest variations in the type of extracellular protein expressed and changes in the biofilm structure from hydrophilic (i.e., exopolysaccharides) to hydrophobic (i.e., lipids) due to arsenopyrite and cell interactions during the 120-h period of biooxidation. We suggest feasible environmental and industrial implications for arsenopyrite biooxidation based on the findings of this study.

Structure-activity studies and therapeutic potential of host defense peptides of human thrombin.

PubMed

Kasetty, Gopinath; Papareddy, Praveen; Kalle, Martina; Rydengård, Victoria; Mörgelin, Matthias; Albiger, Barbara; Malmsten, Martin; Schmidtchen, Artur

2011-06-01

Peptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus, and the fungus Candida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length- and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (>12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock and P. aeruginosa sepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest.

How improving practice relationships among clinicians and nonclinicians can improve quality in primary care.

PubMed

Lanham, Holly J; McDaniel, Reuben R; Crabtree, Benjamin F; Miller, William L; Stange, Kurt C; Tallia, Alfred F; Nutting, Paula

2009-09-01

Understanding the role of relationships health care organizations (HCOs) offers opportunities for shaping health care delivery. When quality is treated as a property arising from the relationships within HCOs, then different contributors of quality can be investigated and more effective strategies for improvement can be developed. Data were drawn from four large National Institutes of Health (NIH)-funded studies, and an iterative analytic strategy and a grounded theory approach were used to understand the characteristics of relationships within primary care practices. This multimethod approach amassed rich and comparable data sets in all four studies, which were all aimed at primary care practice improvement. The broad range of data included direct observation of practices during work activities and of patient-clinician interactions, in-depth interviews with physicians and other key staff members, surveys, structured checklists of office environments, and chart reviews. Analyses focused on characteristics of relationships in practices that exhibited a range of success in achieving practice improvement. Complex adaptive systems theory informed these analyses. Trust, mindfulness, heedfulness, respectful interaction, diversity, social/task relatedness, and rich/lean communication were identified as important in practice improvement. A model of practice relationships was developed to describe how these characteristics work together and interact with reflection, sensemaking, and learning to influence practice-level quality outcomes. Although this model of practice relationships was developed from data collected in primary care practices, which differ from other HCOs in some important ways, the ideas that quality is emergent and that relationships influence quality of care are universally important for all HCOs and all medical specialties.

Design and prediction of new acetylcholinesterase inhibitor via quantitative structure activity relationship of huprines derivatives.

PubMed

Zhang, Shuqun; Hou, Bo; Yang, Huaiyu; Zuo, Zhili

2016-05-01

Acetylcholinesterase (AChE) is an important enzyme in the pathogenesis of Alzheimer's disease (AD). Comparative quantitative structure-activity relationship (QSAR) analyses on some huprines inhibitors against AChE were carried out using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and hologram QSAR (HQSAR) methods. Three highly predictive QSAR models were constructed successfully based on the training set. The CoMFA, CoMSIA, and HQSAR models have values of r (2) = 0.988, q (2) = 0.757, ONC = 6; r (2) = 0.966, q (2) = 0.645, ONC = 5; and r (2) = 0.957, q (2) = 0.736, ONC = 6. The predictabilities were validated using an external test sets, and the predictive r (2) values obtained by the three models were 0.984, 0.973, and 0.783, respectively. The analysis was performed by combining the CoMFA and CoMSIA field distributions with the active sites of the AChE to further understand the vital interactions between huprines and the protease. On the basis of the QSAR study, 14 new potent molecules have been designed and six of them are predicted to be more active than the best active compound 24 described in the literature. The final QSAR models could be helpful in design and development of novel active AChE inhibitors.

Relationships between species feeding traits and environmental conditions in fish communities: a three-matrix approach.

PubMed

Brind'Amour, Anik; Boisclair, Daniel; Dray, Stéphane; Legendre, Pierre

2011-03-01

Understanding the relationships between species biological traits and the environment is crucial to predicting the effect of habitat perturbations on fish communities. It is also an essential step in the assessment of the functional diversity. Using two complementary three-matrix approaches (fourth-corner and RLQ analyses), we tested the hypothesis that feeding-oriented traits determine the spatial distributions of littoral fish species by assessing the relationship between fish spatial distributions, fish species traits, and habitat characteristics in two Laurentian Shield lakes. Significant associations between the feeding-oriented traits and the environmental characteristics suggested that fish communities in small lakes (displaying low species richness) can be spatially structured. Three groups of traits, mainly categorized by the species spatial and temporal feeding activity, were identified. The water column may be divided in two sections, each of them corresponding to a group of traits related to the vertical distribution of the prey coupled with the position of the mouth. Lake areas of low structural complexity were inhabited by functional assemblages dominated by surface feeders while structurally more complex areas were occupied by mid-water and benthic feeders. A third group referring to the time of feeding activity was observed. Our work could serve as a guideline study to evaluate species traits x environment associations at multiple spatial scales. Our results indicate that three-matrix statistical approaches are powerful tools that can be used to study such relationships. These recent statistical approaches open up new research directions such as the study of spatially based biological functions in lakes. They also provide new analytical tools for determining, for example, the potential size of freshwater protected areas.

Modeling Age-Friendly Environment, Active Aging, and Social Connectedness in an Emerging Asian Economy.

PubMed

Lai, Ming-Ming; Lein, Shi-Ying; Lau, Siok-Hwa; Lai, Ming-Ling

2016-01-01

This paper empirically tested eight key features of WHO guidelines to age-friendly community by surveying 211 informal caregivers and 402 self-care adults (aged 45 to 85 and above) in Malaysia. We examined the associations of these eight features with active aging and social connectedness through exploratory and confirmatory factor analyses. A structural model with satisfactory goodness-of-fit indices (CMIN/df = 1.11, RMSEA = 0.02, NFI = 0.97, TLI = 1.00, CFI = 1.00, and GFI = 0.96) indicates that transportation and housing, community support and health services, and outdoor spaces and buildings are statistically significant in creating an age-friendly environment. We found a statistically significant positive relationship between an age-friendly environment and active aging. This relationship is mediated by social connectedness. The results indicate that built environments such as accessible public transportations and housing, affordable and accessible healthcare services, and elderly friendly outdoor spaces and buildings have to be put into place before social environment in building an age-friendly environment. Otherwise, the structural barriers would hinder social interactions for the aged. The removal of the environmental barriers and improved public transportation services provide short-term solutions to meet the varied and growing needs of the older population.

Modeling Age-Friendly Environment, Active Aging, and Social Connectedness in an Emerging Asian Economy

PubMed Central

Lai, Ming-Ming; Lein, Shi-Ying; Lau, Siok-Hwa; Lai, Ming-Ling

2016-01-01

This paper empirically tested eight key features of WHO guidelines to age-friendly community by surveying 211 informal caregivers and 402 self-care adults (aged 45 to 85 and above) in Malaysia. We examined the associations of these eight features with active aging and social connectedness through exploratory and confirmatory factor analyses. A structural model with satisfactory goodness-of-fit indices (CMIN/df = 1.11, RMSEA = 0.02, NFI = 0.97, TLI = 1.00, CFI = 1.00, and GFI = 0.96) indicates that transportation and housing, community support and health services, and outdoor spaces and buildings are statistically significant in creating an age-friendly environment. We found a statistically significant positive relationship between an age-friendly environment and active aging. This relationship is mediated by social connectedness. The results indicate that built environments such as accessible public transportations and housing, affordable and accessible healthcare services, and elderly friendly outdoor spaces and buildings have to be put into place before social environment in building an age-friendly environment. Otherwise, the structural barriers would hinder social interactions for the aged. The removal of the environmental barriers and improved public transportation services provide short-term solutions to meet the varied and growing needs of the older population. PMID:27293889

A Social Network Analysis of Teaching and Research Collaboration in a Teachers' Virtual Learning Community

ERIC Educational Resources Information Center

Lin, Xiaofan; Hu, Xiaoyong; Hu, Qintai; Liu, Zhichun

2016-01-01

Analysing the structure of a social network can help us understand the key factors influencing interaction and collaboration in a virtual learning community (VLC). Here, we describe the mechanisms used in social network analysis (SNA) to analyse the social network structure of a VLC for teachers and discuss the relationship between face-to-face…

Mixed-severity fire history at a forest-grassland ecotone in west central British Columbia, Canada.

PubMed

Harvey, Jill E; Smith, Dan J; Veblen, Thomas T

2017-09-01

This study examines spatially variable stand structure and fire-climate relationships at a low elevation forest-grassland ecotone in west central British Columbia, Canada. Fire history reconstructions were based on samples from 92 fire-scarred trees and stand demography from 27 plots collected over an area of about 7 km 2 . We documented historical chronologies of widespread fires and localized grassland fires between AD 1600 and 1900. Relationships between fire events, reconstructed values of the Palmer Drought Severity Index, and annual precipitation were examined using superposed epoch and bivariate event analyses. Widespread fires occurred during warm, dry years and were preceded by multiple anomalously dry, warm years. Localized fires that affected only grassland-proximal forests were more frequent than widespread fires. These localized fires showed a lagged, positive relationship with wetter conditions. The landscape pattern of forest structure provided further evidence of complex fire activity with multiple plots shown to have experienced low-, mixed-, and/or high-severity fires over the last four centuries. We concluded that this forest-grassland ecotone was characterized by fires of mixed severity, dominated by frequent, low-severity fires punctuated by widespread fires of moderate to high severity. This landscape-level variability in fire-climate relationships and patterns in forest structure has important implications for fire and grassland management in west central British Columbia and similar environments elsewhere. Forest restoration techniques such as prescribed fire and thinning are oftentimes applied at the forest-grassland ecotone on the basis that historically high frequency, low-severity fires defined the character of past fire activity. This study provides forest managers and policy makers with important information on mixed-severity fire activity at a low elevation forest-grassland ecotone, a crucial prerequisite for the effective management of these complex ecosystems. © 2017 by the Ecological Society of America.

The Quaternary Structure of a Glycoside Hydrolase Dictates Specificity toward β-Glucans*

PubMed Central

Lafond, Mickael; Sulzenbacher, Gerlind; Freyd, Thibaud; Henrissat, Bernard; Berrin, Jean-Guy; Garron, Marie-Line

2016-01-01

In the Carbohydrate-Active Enzyme (CAZy) database, glycoside hydrolase family 5 (GH5) is a large family with more than 6,000 sequences. Among the 51 described GH5 subfamilies, subfamily GH5_26 contains members that display either endo-β(1,4)-glucanase or β(1,3;1,4)-glucanase activities. In this study, we focused on the GH5_26 enzyme from Saccharophagus degradans (SdGluc5_26A), a marine bacterium known for its capacity to degrade a wide diversity of complex polysaccharides. SdGluc5_26A displays lichenase activity toward β(1,3;1,4)-glucans with a side cellobiohydrolase activity toward β(1,4)-glucans. The three-dimensional structure of SdGluc5_26A adopts a stable trimeric quaternary structure also observable in solution. The N-terminal region of SdGluc5_26A protrudes into the active site of an adjacent monomer. To understand whether this occupation of the active site could influence its activity, we conducted a comprehensive enzymatic characterization of SdGluc5_26A and of a mutant truncated at the N terminus. Ligand complex structures and kinetic analyses reveal that the N terminus governs the substrate specificity of SdGluc5_26A. Its deletion opens the enzyme cleft at the −3 subsite and turns the enzyme into an endo-β(1,4)-glucanase. This study demonstrates that experimental approaches can reveal structure-function relationships out of reach of current bioinformatic predictions. PMID:26755730

Hydrothermal fluids circulation and travertine deposition in an active tectonic setting: Insights from the Kamara geothermal area (western Anatolia, Turkey)

NASA Astrophysics Data System (ADS)

Brogi, Andrea; Alçiçek, M. Cihat; Yalçıner, Cahit Çağlar; Capezzuoli, Enrico; Liotta, Domenico; Meccheri, Marco; Rimondi, Valentina; Ruggieri, Giovanni; Gandin, Anna; Boschi, Chiara; Büyüksaraç, Aydin; Alçiçek, Hülya; Bülbül, Ali; Baykara, Mehmet Oruç; Shen, Chuan-Chou

2016-06-01

Coexistence of thermal springs, travertine deposits and tectonic activity is a recurring feature for most geothermal areas. Although such a certainty, their relationships are debated mainly addressing on the role of the tectonic activity in triggering and controlling fluids flow and travertine deposition. In this paper, we present the results of an integrated study carried out in a geothermal area located in western Anatolia (Turkey), nearby the well-known Pamukkale area (Denizli Basin). Our study focused on the relationships among hydrothermal fluids circulation, travertine deposition and tectonic activity, with particular emphasis on the role of faults in controlling fluids upwelling, thermal springs location and deposition of travertine masses. New field mapping and structural/kinematics analyses allowed us to recognize two main faults systems (NW- and NE-trending), framed in the Neogene-Quaternary extensional tectonic evolution of western Anatolia. A geo-radar (GPR) prospection was also provided in a key-area, permitting us to reconstruct a buried fault zone and its relationships with the development of a fissure-ridge travertine deposit (Kamara fissure-ridge). The integration among structural and geophysical studies, fluids inclusion, geochemical, isotopic data and 230 Th/238 U radiometric age determination on travertine deposits, depict the characteristics of the geothermal fluids and their pathway, up to the surface. Hydrological and seismological data have been also taken in account to investigate the relation between local seismicity and fluid upwelling. As a main conclusion we found strict relationships among tectonic activity, earthquakes occurrence, and variation of the physical/chemical features of the hydrothermal fluids, presently exploited at depth, or flowing out in thermal springs. In the same way, we underline the tectonic role in controlling the travertine deposition, making travertine (mainly banded travertine) a useful proxy to reconstruct the seismological history of an area, as well as the characteristics of the parent geothermal fluids, adding an effective tool for geothermal exploration tasks.

Clustering of 3D-Structure Similarity Based Network of Secondary Metabolites Reveals Their Relationships with Biological Activities.

PubMed

Ohtana, Yuki; Abdullah, Azian Azamimi; Altaf-Ul-Amin, Md; Huang, Ming; Ono, Naoaki; Sato, Tetsuo; Sugiura, Tadao; Horai, Hisayuki; Nakamura, Yukiko; Morita Hirai, Aki; Lange, Klaus W; Kibinge, Nelson K; Katsuragi, Tetsuo; Shirai, Tsuyoshi; Kanaya, Shigehiko

2014-12-01

Developing database systems connecting diverse species based on omics is the most important theme in big data biology. To attain this purpose, we have developed KNApSAcK Family Databases, which are utilized in a number of researches in metabolomics. In the present study, we have developed a network-based approach to analyze relationships between 3D structure and biological activity of metabolites consisting of four steps as follows: construction of a network of metabolites based on structural similarity (Step 1), classification of metabolites into structure groups (Step 2), assessment of statistically significant relations between structure groups and biological activities (Step 3), and 2-dimensional clustering of the constructed data matrix based on statistically significant relations between structure groups and biological activities (Step 4). Applying this method to a data set consisting of 2072 secondary metabolites and 140 biological activities reported in KNApSAcK Metabolite Activity DB, we obtained 983 statistically significant structure group-biological activity pairs. As a whole, we systematically analyzed the relationship between 3D-chemical structures of metabolites and biological activities. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conformational analysis of the anti-HIV Nikavir prodrug: comparisons with AZT and Thymidine, and establishment of structure-activity relationships/tendencies in other 6'-derivatives.

PubMed

El-Sayed, Ahmed A; Tamara Molina, A; Álvarez-Ros, M C; Alcolea Palafox, M

2015-01-01

A comprehensive theoretical conformational analysis of the anti-HIV Nikavir prodrug was carried out; this prodrug has noticeable advantage over the approved drug AZT. The whole conformational parameters (χ, α, β, γ, δ, ϕ, P and νmax) were analysed as well as the NBO natural atomic charges. The calculations were carried out by means of DFT/B3LYP and ab initio MP2 methods with full relaxation of all geometrical parameters. The search located at least 67 stable structures, 4 of which were within a 1 kcal/mol electronic energy range of the global minimum. By MP2 it corresponds to the calculated values of the exocyclic torsional angles χ=-108.0°, β=14.5°, γ=76.7° and ε=71.5°. The results obtained are in accordance to those found in related anti-HIV nucleoside analogues. Comparisons of the conformers with those determined in the common anti-HIV drug AZT were carried out. A detailed analysis of the lowest vibrations (<200 cm(-1)) in the best conformer of Nikavir was carried out. The most stable hydrated cluster of this conformer with 20 explicit water molecules was determined. Calculations in five of its 6'-derivatives were performed to identify structural trends that might correlate with the anti-HIV activity of these compounds. Ten structure-activity relationships/tendencies were established that can help for the design of new drugs. Several recommendations for this design were expressed.

In vitro anticancer activity, toxicity and structure-activity relationships of phyllostictine A, a natural oxazatricycloalkenone produced by the fungus Phyllosticta cirsii

DOE Office of Scientific and Technical Information (OSTI.GOV)

Le Calve, Benjamin; Lallemand, Benjamin; Perrone, Carmen

2011-07-01

The in vitro anticancer activity and toxicity of phyllostictine A, a novel oxazatricycloalkenone recently isolated from a plant-pathogenic fungus (Phyllosticta cirsii) was characterized in six normal and five cancer cell lines. Phyllostictine A displays in vitro growth-inhibitory activity both in normal and cancer cells without actual bioselectivity, while proliferating cells appear significantly more sensitive to phyllostictine A than non-proliferating ones. The main mechanism of action by which phyllostictine displays cytotoxic effects in cancer cells does not seem to relate to a direct activation of apoptosis. In the same manner, phyllostictine A seems not to bind or bond with DNA asmore » part of its mechanism of action. In contrast, phyllostictine A strongly reacts with GSH, which is a bionucleophile. The experimental data from the present study are in favor of a bonding process between GSH and phyllostictine A to form a complex though Michael attack at C=C bond at the acrylamide-like system. Considering the data obtained, two new hemisynthesized phyllostictine A derivatives together with three other natural phyllostictines (B, C and D) were also tested in vitro in five cancer cell lines. Compared to phyllostictine A, the two derivatives displayed a higher, phyllostictines B and D a lower, and phyllostictine C an almost equal, growth-inhibitory activity, respectively. These results led us to propose preliminary conclusions in terms of the structure-activity relationship (SAR) analyses for the anticancer activity of phyllostictine A and its related compounds, at least in vitro.« less

High-Throughput, Data-Rich Cellular RNA Device Engineering

PubMed Central

Townshend, Brent; Kennedy, Andrew B.; Xiang, Joy S.; Smolke, Christina D.

2015-01-01

Methods for rapidly assessing sequence-structure-function landscapes and developing conditional gene-regulatory devices are critical to our ability to manipulate and interface with biology. We describe a framework for engineering RNA devices from preexisting aptamers that exhibit ligand-responsive ribozyme tertiary interactions. Our methodology utilizes cell sorting, high-throughput sequencing, and statistical data analyses to enable parallel measurements of the activities of hundreds of thousands of sequences from RNA device libraries in the absence and presence of ligands. Our tertiary interaction RNA devices exhibit improved performance in terms of gene silencing, activation ratio, and ligand sensitivity as compared to optimized RNA devices that rely on secondary structure changes. We apply our method to building biosensors for diverse ligands and determine consensus sequences that enable ligand-responsive tertiary interactions. These methods advance our ability to develop broadly applicable genetic tools and to elucidate understanding of the underlying sequence-structure-function relationships that empower rational design of complex biomolecules. PMID:26258292

Development, synthesis and structure-activity-relationships of inhibitors of the macrophage infectivity potentiator (Mip) proteins of Legionella pneumophila and Burkholderia pseudomallei.

PubMed

Seufert, Florian; Kuhn, Maximilian; Hein, Michael; Weiwad, Matthias; Vivoli, Mirella; Norville, Isobel H; Sarkar-Tyson, Mitali; Marshall, Laura E; Schweimer, Kristian; Bruhn, Heike; Rösch, Paul; Harmer, Nicholas J; Sotriffer, Christoph A; Holzgrabe, Ulrike

2016-11-01

The bacteria Burkholderia pseudomallei and Legionella pneumophila cause severe diseases like melioidosis and Legionnaire's disease with high mortality rates despite antibiotic treatment. Due to increasing antibiotic resistances against these and other Gram-negative bacteria, alternative therapeutical strategies are in urgent demand. As a virulence factor, the macrophage infectivity potentiator (Mip) protein constitutes an attractive target. The Mip proteins of B. pseudomallei and L. pneumophila exhibit peptidyl-prolyl cis/trans isomerase (PPIase) activity and belong to the PPIase superfamily. In previous studies, the pipecolic acid moiety proved to be a valuable scaffold for inhibiting this PPIase activity. Thus, a library of pipecolic acid derivatives was established guided by structural information and computational analyses of the binding site and possible binding modes. Stability and toxicity considerations were taken into account in iterative extensions of the library. Synthesis and evaluation of the compounds in PPIase assays resulted in highly active inhibitors. The activities can be interpreted in terms of a common binding mode obtained by docking calculations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Uncovering psychosocial needs: perspectives of Australian child and family health nurses in a sustained home visiting trial.

PubMed

Kardamanidis, Katina; Kemp, Lynn; Schmied, Virginia

2009-08-01

The first Australian trial of sustained nurse home visiting provided an opportunity to explore nurses' understanding of the situations that support mothers of infants to disclose personal and sensitive psychosocial information. Using a qualitative descriptive design, semi-structured interviews were conducted and transcripts were analysed drawing upon aspects of Smith's interpretative phenomenological analysis. Five themes pertaining to the experience of relationship building to foster disclosure of sensitive information emerged: (1) building trust is an ongoing process of giving and giving in return, (2) being 'actively passive' to develop trust, (3) the client is in control of the trust-relationship, (4) the association between disclosure of sensitive issues and a trust-relationship, and (5) empowerment over disclosure. This study provides a deeper understanding of how child and family health nurses develop relationships that lead women to entrust the nurse with personal, sensitive information, and may inform the practice of psychosocial needs assessment in other contexts.

Spatial and temporal relationships of electrocorticographic alpha and gamma activity during auditory processing.

PubMed

Potes, Cristhian; Brunner, Peter; Gunduz, Aysegul; Knight, Robert T; Schalk, Gerwin

2014-08-15

Neuroimaging approaches have implicated multiple brain sites in musical perception, including the posterior part of the superior temporal gyrus and adjacent perisylvian areas. However, the detailed spatial and temporal relationship of neural signals that support auditory processing is largely unknown. In this study, we applied a novel inter-subject analysis approach to electrophysiological signals recorded from the surface of the brain (electrocorticography (ECoG)) in ten human subjects. This approach allowed us to reliably identify those ECoG features that were related to the processing of a complex auditory stimulus (i.e., continuous piece of music) and to investigate their spatial, temporal, and causal relationships. Our results identified stimulus-related modulations in the alpha (8-12 Hz) and high gamma (70-110 Hz) bands at neuroanatomical locations implicated in auditory processing. Specifically, we identified stimulus-related ECoG modulations in the alpha band in areas adjacent to primary auditory cortex, which are known to receive afferent auditory projections from the thalamus (80 of a total of 15,107 tested sites). In contrast, we identified stimulus-related ECoG modulations in the high gamma band not only in areas close to primary auditory cortex but also in other perisylvian areas known to be involved in higher-order auditory processing, and in superior premotor cortex (412/15,107 sites). Across all implicated areas, modulations in the high gamma band preceded those in the alpha band by 280 ms, and activity in the high gamma band causally predicted alpha activity, but not vice versa (Granger causality, p<1e(-8)). Additionally, detailed analyses using Granger causality identified causal relationships of high gamma activity between distinct locations in early auditory pathways within superior temporal gyrus (STG) and posterior STG, between posterior STG and inferior frontal cortex, and between STG and premotor cortex. Evidence suggests that these relationships reflect direct cortico-cortical connections rather than common driving input from subcortical structures such as the thalamus. In summary, our inter-subject analyses defined the spatial and temporal relationships between music-related brain activity in the alpha and high gamma bands. They provide experimental evidence supporting current theories about the putative mechanisms of alpha and gamma activity, i.e., reflections of thalamo-cortical interactions and local cortical neural activity, respectively, and the results are also in agreement with existing functional models of auditory processing. Copyright © 2014 Elsevier Inc. All rights reserved.

Structure-activity relationship of indoloquinoline analogs anti-MRSA.

PubMed

Zhao, Min; Kamada, Tomonori; Takeuchi, Aya; Nishioka, Hiromi; Kuroda, Teruo; Takeuchi, Yasuo

2015-12-01

Indolo[3,2-b]quinoline analogs (3a-3s), 4-(acridin-9-ylamino) phenol hydrochloride (4), benzofuro[3,2-b]quinoline (3t), indeno[1,2-b]quinolines (3u and 3v) have been synthesized. Those compounds were found to exhibit anti-bacterial activity towards Methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Structure-activity relationship studies were conducted that indoloquinoline ring, benzofuroquinoline ring and 4-aminophenol group are essential structure for anti-MRSA activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

A hydroxylated flavonol, fisetin inhibits the formation of a carcinogenic estrogen metabolite.

PubMed

Meng, Xin; Sun, Hui; Yang, Lianrong; Yin, Rui; Qi, Lehui

2017-03-01

Fisetin can be found in a wide variety of plants and possesses strong efficacy against many cancers. 17β-Estradiol (E2) is hydrolyzed to 4-hydroxy-E2 (4-OHE2) via cytochrome P450 (CYP) 1B1 in vivo. In estrogen target tissues including the mammary gland, ovaries, and uterus, CYP1B1 is highly expressed, and 4-OHE2 is predominantly formed in cancerous tissues. Herein, we investigated the inhibitory activity of fisetin and flavone against CYP1B1 using estrogen E2 as substrate in vitro to reveal structure-activity relationship between structure of flavonoids and inhibition. The results showed that fisetin possessed inhibitory effect on CYP1B1 activity. Compared with flavone, the inhibition of fisetin was stronger. The V max and K i values were 1.950±0.157pmol/μgprotein/min and 4.925±0.689nM for fisetin and 2.277±0.231pmol/μgprotein/min and 9.148±2.150nM for flavone, respectively. By kinetic analyses, both fisetin and flavone displayed mixed inhibition. Taken together the data suggested that fisetin is able to inhibit the formation of carcinogenic 4-OHE2 from E2, which reveals one of its anti-cancer mechanisms and helps to reveal the relationship between the structure of flavonoids and the inhibition CYP1B1 for discovering new drugs in cancer therapy and prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

Amygdala reactivity in healthy adults is correlated with prefrontal cortical thickness.

PubMed

Foland-Ross, Lara C; Altshuler, Lori L; Bookheimer, Susan Y; Lieberman, Matthew D; Townsend, Jennifer; Penfold, Conor; Moody, Teena; Ahlf, Kyle; Shen, Jim K; Madsen, Sarah K; Rasser, Paul E; Toga, Arthur W; Thompson, Paul M

2010-12-08

Recent evidence suggests that putting feelings into words activates the prefrontal cortex (PFC) and suppresses the response of the amygdala, potentially helping to alleviate emotional distress. To further elucidate the relationship between brain structure and function in these regions, structural and functional magnetic resonance imaging (MRI) data were collected from a sample of 20 healthy human subjects. Structural MRI data were processed using cortical pattern-matching algorithms to produce spatially normalized maps of cortical thickness. During functional scanning, subjects cognitively assessed an emotional target face by choosing one of two linguistic labels (label emotion condition) or matched geometric forms (control condition). Manually prescribed regions of interest for the left amygdala were used to extract percentage signal change in this region occurring during the contrast of label emotion versus match forms. A correlation analysis between left amygdala activation and cortical thickness was then performed along each point of the cortical surface, resulting in a color-coded r value at each cortical point. Correlation analyses revealed that gray matter thickness in left ventromedial PFC was inversely correlated with task-related activation in the amygdala. These data add support to a general role of the ventromedial PFC in regulating activity of the amygdala.

Structure-Thermodynamics-Antioxidant Activity Relationships of Selected Natural Phenolic Acids and Derivatives: An Experimental and Theoretical Evaluation

PubMed Central

Zheng, Jie; Liang, Guizhao

2015-01-01

Phenolic acids and derivatives have potential biological functions, however, little is known about the structure-activity relationships and the underlying action mechanisms of these phenolic acids to date. Herein we investigate the structure-thermodynamics-antioxidant relationships of 20 natural phenolic acids and derivatives using DPPH• scavenging assay, density functional theory calculations at the B3LYP/6-311++G(d,p) levels of theory, and quantitative structure-activity relationship (QSAR) modeling. Three main working mechanisms (HAT, SETPT and SPLET) are explored in four micro-environments (gas-phase, benzene, water and ethanol). Computed thermodynamics parameters (BDE, IP, PDE, PA and ETE) are compared with the experimental radical scavenging activities against DPPH•. Available theoretical and experimental investigations have demonstrated that the extended delocalization and intra-molecular hydrogen bonds are the two main contributions to the stability of the radicals. The C = O or C = C in COOH, COOR, C = CCOOH and C = CCOOR groups, and orthodiphenolic functionalities are shown to favorably stabilize the specific radical species to enhance the radical scavenging activities, while the presence of the single OH in the ortho position of the COOH group disfavors the activities. HAT is the thermodynamically preferred mechanism in the gas phase and benzene, whereas SPLET in water and ethanol. Furthermore, our QSAR models robustly represent the structure-activity relationships of these explored compounds in polar media. PMID:25803685

Structure-thermodynamics-antioxidant activity relationships of selected natural phenolic acids and derivatives: an experimental and theoretical evaluation.

PubMed

Chen, Yuzhen; Xiao, Huizhi; Zheng, Jie; Liang, Guizhao

2015-01-01

Phenolic acids and derivatives have potential biological functions, however, little is known about the structure-activity relationships and the underlying action mechanisms of these phenolic acids to date. Herein we investigate the structure-thermodynamics-antioxidant relationships of 20 natural phenolic acids and derivatives using DPPH• scavenging assay, density functional theory calculations at the B3LYP/6-311++G(d,p) levels of theory, and quantitative structure-activity relationship (QSAR) modeling. Three main working mechanisms (HAT, SETPT and SPLET) are explored in four micro-environments (gas-phase, benzene, water and ethanol). Computed thermodynamics parameters (BDE, IP, PDE, PA and ETE) are compared with the experimental radical scavenging activities against DPPH•. Available theoretical and experimental investigations have demonstrated that the extended delocalization and intra-molecular hydrogen bonds are the two main contributions to the stability of the radicals. The C = O or C = C in COOH, COOR, C = CCOOH and C = CCOOR groups, and orthodiphenolic functionalities are shown to favorably stabilize the specific radical species to enhance the radical scavenging activities, while the presence of the single OH in the ortho position of the COOH group disfavors the activities. HAT is the thermodynamically preferred mechanism in the gas phase and benzene, whereas SPLET in water and ethanol. Furthermore, our QSAR models robustly represent the structure-activity relationships of these explored compounds in polar media.

Large scale analysis of the mutational landscape in β-glucuronidase: A major player of mucopolysaccharidosis type VII.

PubMed

Khan, Faez Iqbal; Shahbaaz, Mohd; Bisetty, Krishna; Waheed, Abdul; Sly, William S; Ahmad, Faizan; Hassan, Md Imtaiyaz

2016-01-15

The lysosomal storage disorders are a group of 50 unique inherited diseases characterized by unseemly lipid storage in lysosomes. These malfunctions arise due to genetic mutations that result in deficiency or reduced activities of the lysosomal enzymes, which are responsible for catabolism of biological macromolecules. Sly syndrome or mucopolysaccharidosis type VII is a lysosomal storage disorder associated with the deficiency of β-glucuronidase (EC 3.2.1.31) that catalyzes the hydrolysis of β-D-glucuronic acid residues from the non-reducing terminal of glycosaminoglycan. The effects of the disease causing mutations on the framework of the sequences and structure of β-glucuronidase (GUSBp) were analyzed utilizing a variety of bioinformatic tools. These analyses showed that 211 mutations may result in alteration of the biological activity of GUSBp, including previously experimentally validated mutations. Finally, we refined 90 disease causing mutations, which presumably cause a significant impact on the structure, function, and stability of GUSBp. Stability analyses showed that mutations p.Phe208Pro, p.Phe539Gly, p.Leu622Gly, p.Ile499Gly and p.Ile586Gly caused the highest impact on GUSBp stability and function because of destabilization of the protein structure. Furthermore, structures of wild type and mutant GUSBp were subjected to molecular dynamics simulation to examine the relative structural behaviors in the explicit conditions of water. In a broader view, the use of in silico approaches provided a useful understanding of the effect of single point mutations on the structure-function relationship of GUSBp. Copyright © 2015 Elsevier B.V. All rights reserved.

The Activities, Roles, and Relationships of Successful First-Generation College Students

ERIC Educational Resources Information Center

Demetriou, Cynthia; Meece, Judith; Eaker-Rich, Deborah; Powell, Candice

2017-01-01

This qualitative study describes the experiences of 16 successful first-generation college students (FGCS) utilizing a theoretical lens, informed significantly by bioecological systems theory (Bronfenbrenner, 1979), which guided our qualitative analyses of interview transcripts to examine the activities, roles, and relationships of these students…

Physical activity, self-efficacy, and quality of life in older Czech adults.

PubMed

Mudrak, Jiri; Stochl, Jan; Slepicka, Pavel; Elavsky, Steriani

2016-03-01

Despite efforts to expand global physical activity (PA) surveillance data to include both low- and high-income countries worldwide, our understanding of the relationship between PA and quality of life (QOL) in older adults from culturally diverse backgrounds is limited. We tested McAuley's social-cognitive model of the PA-QOL relationship in the cultural context of the Czech Republic, a post-communist central European country. A total of 546 older Czech adults (mean age 68 years) completed a battery of questionnaires assessing indicators of PA, self-efficacy, health status, and global QOL. A structural equation model was used to test the relationship between PA and QOL. The model hypothesized an indirect relationship between PA and QOL: PA predicted self-efficacy, which in turn predicted global QOL through mental and physical health status. The analyses indicated an acceptable fit of the proposed model, albeit with different emphases than those of studies from Western countries. Above all, we observed a stronger effect of PA on self-efficacy and a weaker mediating effect of health status on the PA-QOL relationship. Our findings supported the validity of McAuley's PA-QOL social-cognitive model for a non-Western cultural context. However, it seems that self-efficacy and health status may influence the PA-QOL relationship in this population in a manner different from that proposed in McAuley's model.

Trypanocidal constituents in plants 6. 1) Minor withanolides from the aerial parts of Physalis angulata.

PubMed

Abe, Fumiko; Nagafuji, Shinya; Okawa, Masafumi; Kinjo, Junei

2006-08-01

Further study of the methanol extract of the aerial parts of Physalis angulata (Solanaceae) resulted in the isolation of new withanolides, designated physagulins L, M and N, together with known withanolide, physagulin D and flavonol glycoside, quercetin 3-O-rhamnosyl-(1-->6)-galactoside. The chemical structures of these new withanolides were elucidated by detailed spectroscopic analyses to be (20R,22R)-15alpha-acetoxy-5alpha,6beta,14beta,17beta,27-pentahydroxy-1-oxo-witha-2, 24-dienolide, (20S,22S)-15alpha-acetoxy-5alpha,6beta,14alpha,23beta-tetrahydroxy-1-oxo-witha-2,16,24-trienolide and (20S,22R)-15alpha-acetoxy-5beta,6beta-epoxy-14alpha-hydoxy-3beta-methoxy-1-oxo-witha-16,24-dienolide, respectively. All these compounds showed weak trypanocidal activity against trypomastigotes, an infectious form of Trypanosoma cruzi, the etiologic agent for Chagas' disease. Withanolides obtained in the previous paper showed considerable trypanocidal activity, suggesting the structure-activity relationships.

In Vivo Characterization of Traumatic Brain Injury Neuropathology with Structural and Functional Neuroimaging

PubMed Central

LEVINE, BRIAN; FUJIWARA, ESTHER; O’CONNOR, CHARLENE; RICHARD, NADINE; KOVACEVIC, NATASA; MANDIC, MARINA; RESTAGNO, ADRIANA; EASDON, CRAIG; ROBERTSON, IAN H.; GRAHAM, SIMON J.; CHEUNG, GORDON; GAO, FUQIANG; SCHWARTZ, MICHAEL L.; BLACK, SANDRA E.

2007-01-01

Quantitative neuroimaging is increasingly used to study the effects of traumatic brain injury (TBI) on brain structure and function. This paper reviews quantitative structural and functional neuroimaging studies of patients with TBI, with an emphasis on the effects of diffuse axonal injury (DAI), the primary neuropathology in TBI. Quantitative structural neuroimaging has evolved from simple planometric measurements through targeted region-of-interest analyses to whole-brain analysis of quantified tissue compartments. Recent studies converge to indicate widespread volume loss of both gray and white matter in patients with moderate-to-severe TBI. These changes can be documented even when patients with focal lesions are excluded. Broadly speaking, performance on standard neuropsychological tests of speeded information processing are related to these changes, but demonstration of specific brain-behavior relationships requires more refined experimental behavioral measures. The functional consequences of these structural changes can be imaged with activation functional neuroimaging. Although this line of research is at an early stage, results indicate that TBI causes a more widely dispersed activation in frontal and posterior cortices. Further progress in analysis of the consequences of TBI on neural structure and function will require control of variability in neuropathology and behavior. PMID:17020478

The structure-activity relationship of inhibitors of serotonin uptake and receptor binding

NASA Astrophysics Data System (ADS)

Hansch, Corwin; Caldwell, Jonathan

1991-10-01

An analysis of five different datasets of inhibitors of serotonin uptake has yielded quantitative structure/ activity relationships (QSARs) which delineate the role of steric and hydrophobic properties essential for inhibition by phenylethylamine-type analogues.

Essential Set of Molecular Descriptors for ADME Prediction in Drug and Environmental Chemical Space

EPA Science Inventory

Historically, the disciplines of pharmacology and toxicology have embraced quantitative structure-activity relationships (QSAR) and quantitative structure-property relationships (QSPR) to predict ADME properties or biological activities of untested chemicals. The question arises ...

Structural Elucidation of cis / trans Dicaffeoylquinic Acid Photoisomerization Using Ion Mobility Spectrometry-Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Xueyun; Renslow, Ryan S.; Makola, Mpho M.

Due to the recently uncovered health benefits and anti-HIV activities of dicaffeoylquinic acids (diCQAs), understanding their structures and functions is of great interest for drug discovery efforts. DiCQAs are analytically challenging to identify and quantify since they commonly exist as a diverse mixture of positional and geometric (cis/trans) isomers. In this work, we utilized ion mobility spectrometry coupled with mass spectrometry to separate the various isomers before and after UV irradiation. The experimental collision cross sections were then compared with theoretical structures to differentiate and identify the diCQA isomers. Our analyses found that naturally the diCQAs existed predominantly as trans/transmore » isomers, but after 3 h of UV irradiation, cis/cis, cis/trans, trans/cis, and trans/trans isomers were all present in the mixture. This is the first report of successful differentiation of cis/trans diCQA isomers individually, which shows the great promise of IMS coupled with theoretical calculations for determining the structure and activity relationships of different isomers in drug discovery studies.« less

Threading the biophysics of mammalian Slo1 channels onto structures of an invertebrate Slo1 channel

PubMed Central

2017-01-01

For those interested in the machinery of ion channel gating, the Ca2+ and voltage-activated BK K+ channel provides a compelling topic for investigation, by virtue of its dual allosteric regulation by both voltage and intracellular Ca2+ and because its large-single channel conductance facilitates detailed kinetic analysis. Over the years, biophysical analyses have illuminated details of the allosteric regulation of BK channels and revealed insights into the mechanism of BK gating, e.g., inner cavity size and accessibility and voltage sensor-pore coupling. Now the publication of two structures of an Aplysia californica BK channel—one liganded and one metal free—promises to reinvigorate functional studies and interpretation of biophysical results. The new structures confirm some of the previous functional inferences but also suggest new perspectives regarding cooperativity between Ca2+-binding sites and the relationship between voltage- and Ca2+-dependent gating. Here we consider the extent to which the two structures explain previous functional data on pore-domain properties, voltage-sensor motions, and divalent cation binding and activation of the channel. PMID:29025867

Assessing the relationship between quality of life and behavioral activation using the Japanese Behavioral Activation for Depression Scale-Short Form.

PubMed

Shudo, Yusuke; Yamamoto, Tatsuya

2017-01-01

Quality of life (QOL) is an important health-related concept. Identifying factors that affect QOL can help develop and improve health-promotion interventions. Previous studies suggest that behavioral activation fosters subjective QOL, including well-being. However, the mechanism by which behavioral activation improves QOL is not clear. Considering that QOL improves when depressive symptoms improve post-treatment and that behavioral activation is an effective treatment for depression, it is possible that behavioral activation affects QOL indirectly rather than directly. To clarify the mechanism of the influence of behavioral activation on QOL, it is necessary to examine the relationships between factors related to behavioral activation, depressive symptoms, and QOL. Therefore, we attempted to examine the relationship between these factors. Participants comprised 221 Japanese undergraduate students who completed questionnaires on behavioral activation, QOL, and depressive symptoms: the Japanese versions of the Behavioral Activation for Depression Scale-Short Form (BADS-SF), WHO Quality of Life-BREF (WHOQOL-26), and Center for Epidemiologic Studies Depression Scale (CES-D). The BADS-SF comprises two subscales, Activation and Avoidance, and the WHOQOL-26 measures overall QOL and four domains, Physical Health, Psychological Health, Social Relationships, and Environment. Mediation analyses were conducted with BADS-SF activation and avoidance as independent variables, CES-D as a mediator variable, and each WHO-QOL as an outcome variable. Results indicated that depression completely mediated the relationship between Avoidance and QOL, and partially mediated the relationship between Activation and QOL. In addition, analyses of each domain of QOL showed that Activation positively affected all aspects of QOL directly and indirectly, but Avoidance had a negative influence on only part of QOL mainly through depression. The present study provides behavioral activation strategies aimed at QOL enhancement.

Anatomy of a Visible Light Activated Photocatalyst for Water Splitting

DOE PAGES

Phivilay, Somphonh Peter; Roberts, Charles; Gamalski, Andrew; ...

2018-06-08

The supported mixed oxide (Rh 2-yCr yO 3)/(Ga 1-xZn x)(N 1-xO x) photocatalyst, highly active for splitting of H 2O, was extensively characterized for its bulk and surface properties with the objective of developing fundamental structure-photoactivity relationships. Raman and UV-vis spectroscopy revealed that the molecular and electronic structures, respectively, of the oxynitride (Ga 1-xZn x)(N 1-xO x) support are not perturbed by the deposition of the (Rh 2-yCr yO 3) NPs. Photoluminescence (PL) spectroscopy, however, showed that the oxynitride (Ga 1-xZn x)(N 1-xO x) support is the source of excited electrons/holes and the (Rh 2-yCr yO 3) NPs greatly reducemore » the undesirable recombination of photoexcited electron/holes by acting as efficient electron traps as well as increase the lifetimes of the excitons. High Resolution-XPS and High Sensitivity-LEIS surface analyses reveal that the surfaces of the (Rh 2-yCr yO 3) NPs consist of Rh +3 and Cr +3 mixed oxide species. In Situ AP-XPS help to reveal that the Rh+3 and surface N atoms are involved in water splitting. Dispersed RhOx species on the (Ga 1-xZn x)(N 1-xO x) support and on CrO x NPs were found to be the photocatalytic active sites for H 2 generation and N and Zn sites from the (Ga 1-xZn x)(N 1-xO x) support are the photocatalytic active site for O 2 generation. The current investigation establishes the fundamental structure-photoactivity relationships of these visible light activated photocatalysts.« less

Anatomy of a Visible Light Activated Photocatalyst for Water Splitting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phivilay, Somphonh Peter; Roberts, Charles; Gamalski, Andrew

The supported mixed oxide (Rh 2-yCr yO 3)/(Ga 1-xZn x)(N 1-xO x) photocatalyst, highly active for splitting of H 2O, was extensively characterized for its bulk and surface properties with the objective of developing fundamental structure-photoactivity relationships. Raman and UV-vis spectroscopy revealed that the molecular and electronic structures, respectively, of the oxynitride (Ga 1-xZn x)(N 1-xO x) support are not perturbed by the deposition of the (Rh 2-yCr yO 3) NPs. Photoluminescence (PL) spectroscopy, however, showed that the oxynitride (Ga 1-xZn x)(N 1-xO x) support is the source of excited electrons/holes and the (Rh 2-yCr yO 3) NPs greatly reducemore » the undesirable recombination of photoexcited electron/holes by acting as efficient electron traps as well as increase the lifetimes of the excitons. High Resolution-XPS and High Sensitivity-LEIS surface analyses reveal that the surfaces of the (Rh 2-yCr yO 3) NPs consist of Rh +3 and Cr +3 mixed oxide species. In Situ AP-XPS help to reveal that the Rh+3 and surface N atoms are involved in water splitting. Dispersed RhOx species on the (Ga 1-xZn x)(N 1-xO x) support and on CrO x NPs were found to be the photocatalytic active sites for H 2 generation and N and Zn sites from the (Ga 1-xZn x)(N 1-xO x) support are the photocatalytic active site for O 2 generation. The current investigation establishes the fundamental structure-photoactivity relationships of these visible light activated photocatalysts.« less

The relationship between oral and written narratives: A three-year longitudinal study of narrative cohesion, coherence, and structure.

PubMed

Pinto, Giuliana; Tarchi, Christian; Bigozzi, Lucia

2015-12-01

The relationship between oral language and the writing process at early acquisition stages and the ways the former can enhance or limit the latter has not been researched extensively. The predictive relationship between kindergarten oral narrative competence and the first- and second-grade written narrative competence was explored in a 3-year longitudinal study. Among the first and second graders, the relationship between orthographic competence and narrative competence in written productions was also analysed. One hundred and nine Italian children participated in this study. Kindergarteners produced an oral narrative, whereas the first and second graders produced a written narrative. The oral and written narratives were analysed in terms of cohesion, coherence, and structure. The first-grade orthographic competence was assessed via a dictation task. Multiple linear regression and mediational analyses were performed. Kindergarten oral narrative competence affected the first- and second-grade written narrative competence via a mediational effect of orthographic competence. The results suggest the importance of practicing oral narrative competence in kindergarten and first grade and the value of composition quality independent of orthographic text accuracy. © 2015 The British Psychological Society.

The Relationship between Perceived Health and Physical Activity Indoors, Outdoors in Built Environments, and Outdoors in Nature

PubMed Central

Pasanen, Tytti P; Tyrväinen, Liisa; Korpela, Kalevi M

2014-01-01

Background: A body of evidence shows that both physical activity and exposure to nature are connected to improved general and mental health. Experimental studies have consistently found short term positive effects of physical activity in nature compared with built environments. This study explores whether these benefits are also evident in everyday life, perceived over repeated contact with nature. The topic is important from the perspectives of city planning, individual well-being, and public health. Methods: National survey data (n = 2,070) from Finland was analysed using structural regression analyses. Perceived general health, emotional well-being, and sleep quality were regressed on the weekly frequency of physical activity indoors, outdoors in built environments, and in nature. Socioeconomic factors and other plausible confounders were controlled for. Results: Emotional well-being showed the most consistent positive connection to physical activity in nature, whereas general health was positively associated with physical activity in both built and natural outdoor settings. Better sleep quality was weakly connected to frequent physical activity in nature, but the connection was outweighed by other factors. Conclusion: The results indicate that nature provides an added value to the known benefits of physical activity. Repeated exercise in nature is, in particular, connected to better emotional well-being. PMID:25044598

Relationships between abstract features and methodological quality explained variations of social media activity derived from systematic reviews about psoriasis interventions.

PubMed

Ruano, J; Aguilar-Luque, M; Isla-Tejera, B; Alcalde-Mellado, P; Gay-Mimbrera, J; Hernandez-Romero, José Luis; Sanz-Cabanillas, J L; Maestre-López, B; González-Padilla, M; Carmona-Fernández, P J; Gómez-García, F; García-Nieto, A Vélez

2018-05-24

The aim of this study was to describe the relationship among abstract structure, readability, and completeness, and how these features may influence social media activity and bibliometric results, considering systematic reviews (SRs) about interventions in psoriasis classified by methodological quality. Systematic literature searches about psoriasis interventions were undertaken on relevant databases. For each review, methodological quality was evaluated using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool. Abstract extension, structure, readability, and quality and completeness of reporting were analyzed. Social media activity, which consider Twitter and Facebook mention counts, as well as Mendeley readers and Google scholar citations were obtained for each article. Analyses were conducted to describe any potential influence of abstract characteristics on review's social media diffusion. We classified 139 intervention SRs as displaying high/moderate/low methodological quality. We observed that abstract readability of SRs has been maintained high for last 20 years, although there are some differences based on their methodological quality. Free-format abstracts were most sensitive to the increase of text readability as compared with more structured abstracts (IMRAD or 8-headings), yielding opposite effects on their quality and completeness depending on the methodological quality: a worsening in low quality reviews and an improvement in those of high-quality. Both readability indices and PRISMA for Abstract total scores showed an inverse relationship with social media activity and bibliometric results in high methodological quality reviews but not in those of lower quality. Our results suggest that increasing abstract readability must be specially considered when writing free-format summaries of high-quality reviews, because this fact correlates with an improvement of their completeness and quality, and this may help to achieve broader social media visibility and article usage. Copyright © 2018 Elsevier Inc. All rights reserved.

The association between physical activity and eating self-regulation in overweight and obese women.

PubMed

Carraça, Eliana V; Silva, Marlene N; Coutinho, Sílvia R; Vieira, Paulo N; Minderico, Cláudia S; Sardinha, Luís B; Teixeira, Pedro J

2013-01-01

Successful weight management relies heavily on eating and exercise behaviors. However, little is known about the association between both on a psychosocial level. This study examined the relationship between exercise and eating regulation by exploring the mediating effects of negative body image investment and depressive mood, and their stability through time. Analyses were conducted at two different moments (12 and 36 months), involving a sample of 221 overweight/obese women (age: 37.6 ± 7 years; BMI: 31.6 ± 4.1 kg/m(2)) that participated in a behavioral weight control intervention. Bivariate correlations and mediation analyses using Preacher & Hayes resampling procedures were conducted. At 12 months, negative body image investment was the only significant mediator of the exercise-eating relationship. This variable explained larger portions of the indirect effects of structured rather than lifestyle exercise on eating. At 36 months, negative investment and to a lesser extent depressive mood partially explained the exercise-eating association. Our findings suggest that, besides physiological effects of exercise, psychological mechanisms related to body image and mood also explain the role of physical activity as a 'gateway behavior' for improved eating regulation in overweight women. These effects appear to be stable and may help understand the key role of exercise in long-term weight management.

The importance of the organization of partner knowledge in understanding perceptions of relationship quality and conflict resolution behavior in married couples.

PubMed

Campbell, Lorne; Butzer, Bethany; Wong, Joanne

2008-06-01

This research investigated how the organization of partner knowledge was related to global relationship evaluations and specific interpersonal behaviors in a sample of 107 married couples. Spouses first completed several questionnaires and later participated in a 12-min videotaped conflict resolution task. As expected, wives in older relationships exhibited greater marital quality (self-reported and observed) when they had (a) an integrative knowledge structure and used many negative traits to describe their spouse or (b) a compartmentalized knowledge structure and used few negative traits to describe their spouse. Greater marital quality, however, was found for husbands when they were (a) in older relationships and possessed an integrative structure or (b) in newer relationships and possessed a compartmentalized structure. Exploratory analyses suggested that in some circumstances people may have greater marital quality when they share an organizational style with their spouse.

Using Theoretical Descriptions in Structure Activity Relations. 3. Electronic Descriptors

DTIC Science & Technology

1988-08-01

Activity Relationships (QSAR) have been used successfully in the past to develop predictive equations for several biological and physical properties...Linear Free Energy Relationships (,FF.3) and is based on work by Hammet in which he derived electronic descriptors for the dissociation of substituted...structure of a compound and its activity in a system. Several different structural descriptors have been used in QSAR equations . These range from

Synthesis-atomic structure-properties relationships in metallic nanoparticles by total scattering experiments and 3D computer simulations: case of Pt-Ru nanoalloy catalysts

NASA Astrophysics Data System (ADS)

Prasai, Binay; Ren, Yang; Shan, Shiyao; Zhao, Yinguang; Cronk, Hannah; Luo, Jin; Zhong, Chuan-Jian; Petkov, Valeri

2015-04-01

An approach to determining the 3D atomic structure of metallic nanoparticles (NPs) in fine detail and using the unique knowledge obtained for rationalizing their synthesis and properties targeted for optimization is described and exemplified on Pt-Ru alloy NPs of importance to the development of devices for clean energy conversion such as fuel cells. In particular, PtxRu100-x alloy NPs, where x = 31, 49 and 75, are synthesized by wet chemistry and activated catalytically by a post-synthesis treatment involving heating under controlled N2-H2 atmosphere. So-activated NPs are evaluated as catalysts for gas-phase CO oxidation and ethanol electro-oxidation reactions taking place in fuel cells. Both as-synthesized and activated NPs are characterized structurally by total scattering experiments involving high-energy synchrotron X-ray diffraction coupled to atomic pair distribution functions (PDFs) analysis. 3D structure models both for as-synthesized and activated NPs are built by molecular dynamics simulations based on the archetypal for current theoretical modelling Sutton-Chen method. Models are refined against the experimental PDF data by reverse Monte Carlo simulations and analysed in terms of prime structural characteristics such as metal-to-metal bond lengths, bond angles and first coordination numbers for Pt and Ru atoms. Analysis indicates that, though of a similar type, the atomic structure of as-synthesized and respective activated NPs differ in several details of importance to NP catalytic properties. Structural characteristics of activated NPs and data for their catalytic activity are compared side by side and strong evidence found that electronic effects, indicated by significant changes in Pt-Pt and Ru-Ru metal bond lengths at NP surface, and practically unrecognized so far atomic ensemble effects, indicated by distinct stacking of atomic layers near NP surface and prevalence of particular configurations of Pt and Ru atoms in these layers, contribute to the observed enhancement of the catalytic activity of PtxRu100-x alloy NPs at x ~ 50. Implications of so-established relationships between the atomic structure and catalytic activity of Pt-Ru alloy NPs on efforts aimed at improving further the latter by tuning-up the former are discussed and the usefulness of detailed NP structure studies to advancing science and technology of metallic NPs - exemplified.An approach to determining the 3D atomic structure of metallic nanoparticles (NPs) in fine detail and using the unique knowledge obtained for rationalizing their synthesis and properties targeted for optimization is described and exemplified on Pt-Ru alloy NPs of importance to the development of devices for clean energy conversion such as fuel cells. In particular, PtxRu100-x alloy NPs, where x = 31, 49 and 75, are synthesized by wet chemistry and activated catalytically by a post-synthesis treatment involving heating under controlled N2-H2 atmosphere. So-activated NPs are evaluated as catalysts for gas-phase CO oxidation and ethanol electro-oxidation reactions taking place in fuel cells. Both as-synthesized and activated NPs are characterized structurally by total scattering experiments involving high-energy synchrotron X-ray diffraction coupled to atomic pair distribution functions (PDFs) analysis. 3D structure models both for as-synthesized and activated NPs are built by molecular dynamics simulations based on the archetypal for current theoretical modelling Sutton-Chen method. Models are refined against the experimental PDF data by reverse Monte Carlo simulations and analysed in terms of prime structural characteristics such as metal-to-metal bond lengths, bond angles and first coordination numbers for Pt and Ru atoms. Analysis indicates that, though of a similar type, the atomic structure of as-synthesized and respective activated NPs differ in several details of importance to NP catalytic properties. Structural characteristics of activated NPs and data for their catalytic activity are compared side by side and strong evidence found that electronic effects, indicated by significant changes in Pt-Pt and Ru-Ru metal bond lengths at NP surface, and practically unrecognized so far atomic ensemble effects, indicated by distinct stacking of atomic layers near NP surface and prevalence of particular configurations of Pt and Ru atoms in these layers, contribute to the observed enhancement of the catalytic activity of PtxRu100-x alloy NPs at x ~ 50. Implications of so-established relationships between the atomic structure and catalytic activity of Pt-Ru alloy NPs on efforts aimed at improving further the latter by tuning-up the former are discussed and the usefulness of detailed NP structure studies to advancing science and technology of metallic NPs - exemplified. Electronic supplementary information (ESI) available: XRD patterns, TEM and 3D structure modelling methodology. See DOI: 10.1039/c5nr00800j

MOLECULAR INTERACTION POTENTIALS FOR THE DEVELOPMENT OF STRUCTURE-ACTIVITY RELATIONSHIPS

EPA Science Inventory

Abstract
One reasonable approach to the analysis of the relationships between molecular structure and toxic activity is through the investigation of the forces and intermolecular interactions responsible for chemical toxicity. The interaction between the xenobiotic and the bio...

ESTIMATION OF CHEMICAL SPECIFIC PARAMETERS WITHIN PHYSIOLOGICALLY BASED PHARMACOKINETIC/PHARMACODYNAMIC MODELS

EPA Science Inventory

While relationships between chemical structure and observed properties or activities (QSAR - quantitative structure activity relationship) can be used to predict the behavior of unknown chemicals, this method is semiempirical in nature relying on high quality experimental data to...

Re-Examining the Dimensions of Obligatory Exercise

ERIC Educational Resources Information Center

Duncan, Lindsay R.; Hall, Craig R.; Fraser, Shawn N.; Rodgers, Wendy M.; Wilson, Philip M.; Loitz, Christina C.

2012-01-01

The authors examined the factor structure and psychometric properties of the Obligatory Exercise Questionnaire using exploratory factor analyses (Study 1), and confirmatory factor analyses (Study 2). The relationships between obligatory exercise and other psychological variables including: motivation, subjective well-being, physical self-concept,…

Does Physical Self-Concept Mediate the Relationship between Motor Abilities and Physical Activity in Adolescents and Young Adults?

PubMed Central

Jekauc, Darko; Wagner, Matthias Oliver; Herrmann, Christian; Hegazy, Khaled; Woll, Alexander

2017-01-01

The purpose of this study is to examine the reciprocal relationship between motor abilities and physical activity and the mediation effects of physical self-concept in this relationship using longitudinal data. We expect that the effects of motor abilities on physical activity are rather indirect via physical self-concept and that the effects of physical activity on motor abilities are rather direct without involvement of the motor ability self-concept. Data was obtained from the Motorik-Modul (MoMo) Longitudinal Study in which 335 boys and 363 girls aged 11–17 years old at Baseline were examined twice in a period of six years. Physical activity was assessed by the MoMo Physical Activity Questionnaire for adolescents, physical self-concept by Physical Self-Description Questionnaire and motor abilities by MoMo Motor Test which comprised of the dimensions strength, endurance, coordination and flexibility. Multiple regression analyses were used to analyse the direct and indirect effects. The results of the multiple regression analyses show that the effects of motor abilities on physical activity were only indirect for the dimensions strength, coordination, and flexibility. For the dimension endurance, neither direct nor indirect effects were significant. In the opposite direction, the effects of physical activity on motor abilities were partially mediated by the self-concept of strength. For the dimensions endurance, coordination and flexibility, only indirect were significant. The results of this study support the assumption that the relationship between motor abilities and physical activity is mediated by physical self-concept in both directions. Physical self-concept seems to be an important determinant of adolescents´ physical activity. PMID:28045914

Does Physical Self-Concept Mediate the Relationship between Motor Abilities and Physical Activity in Adolescents and Young Adults?

PubMed

Jekauc, Darko; Wagner, Matthias Oliver; Herrmann, Christian; Hegazy, Khaled; Woll, Alexander

2017-01-01

The purpose of this study is to examine the reciprocal relationship between motor abilities and physical activity and the mediation effects of physical self-concept in this relationship using longitudinal data. We expect that the effects of motor abilities on physical activity are rather indirect via physical self-concept and that the effects of physical activity on motor abilities are rather direct without involvement of the motor ability self-concept. Data was obtained from the Motorik-Modul (MoMo) Longitudinal Study in which 335 boys and 363 girls aged 11-17 years old at Baseline were examined twice in a period of six years. Physical activity was assessed by the MoMo Physical Activity Questionnaire for adolescents, physical self-concept by Physical Self-Description Questionnaire and motor abilities by MoMo Motor Test which comprised of the dimensions strength, endurance, coordination and flexibility. Multiple regression analyses were used to analyse the direct and indirect effects. The results of the multiple regression analyses show that the effects of motor abilities on physical activity were only indirect for the dimensions strength, coordination, and flexibility. For the dimension endurance, neither direct nor indirect effects were significant. In the opposite direction, the effects of physical activity on motor abilities were partially mediated by the self-concept of strength. For the dimensions endurance, coordination and flexibility, only indirect were significant. The results of this study support the assumption that the relationship between motor abilities and physical activity is mediated by physical self-concept in both directions. Physical self-concept seems to be an important determinant of adolescents´ physical activity.

The genetic structure of Arabidopsis thaliana in the south-western Mediterranean range reveals a shared history between North Africa and southern Europe

PubMed Central

2014-01-01

Background Deciphering the genetic structure of Arabidopsis thaliana diversity across its geographic range provides the bases for elucidating the demographic history of this model plant. Despite the unique A. thaliana genomic resources currently available, its history in North Africa, the extreme southern limit in the biodiversity hotspot of the Mediterranean Basin, remains virtually unknown. Results To approach A. thaliana evolutionary history in North Africa, we have analysed the genetic diversity and structure of 151 individuals collected from 20 populations distributed across Morocco. Genotyping of 249 genome-wide SNPs indicated that Morocco contains substantially lower diversity than most analyzed world regions. However, IBD, STRUCTURE and PCA clustering analyses showed that genetic variation is strongly geographically structured. We also determined the genetic relationships between Morocco and the closest European region, the Iberian Peninsula, by analyses of 201 populations from both regions genotyped with the same SNPs. These analyses detected four genetic groups, but all Moroccan accessions belonged to a common Iberian/Moroccan cluster that appeared highly differentiated from the remaining groups. Thus, we identified a genetic lineage with an isolated demographic history in the south-western Mediterranean region. The existence of this lineage was further supported by the study of several flowering genes and traits, which also found Moroccan accessions similar to the same Iberian group. Nevertheless, genetic diversity for neutral SNPs and flowering genes was higher in Moroccan than in Iberian populations of this lineage. Furthermore, we analyzed the genetic relationships between Morocco and other world regions by joint analyses of a worldwide collection of 337 accessions, which detected an additional weak relationship between North Africa and Asia. Conclusions The patterns of genetic diversity and structure of A. thaliana in Morocco show that North Africa is part of the species native range and support the occurrence of a glacial refugium in the Atlas Mountains. In addition, the identification of a genetic lineage specific of Morocco and the Iberian Peninsula indicates that the Strait of Gibraltar has been an A. thaliana migration route between Europe and Africa. Finally, the genetic relationship between Morocco and Asia suggests another migration route connecting north-western Africa and Asia. PMID:24411008

How Improving Practice Relationships Among Clinicians and Nonclinicians Can Improve Quality in Primary Care

PubMed Central

Lanham, Holly J.; McDaniel, Reuben R.; Crabtree, Benjamin F.; Miller, William L.; Stange, Kurt C.; Tallia, Alfred F.; Nutting, Paul A.

2010-01-01

Background Understanding the role of relationships in health care organizations (HCOs) offers opportunities for shaping health care delivery. When quality is treated as a property arising from the relationships within HCOs, then different contributors of quality can be investigated and more effective strategies for improvement can be developed. Methods Data were drawn from four large National Institutes of Health (NIH)–funded studies, and an iterative analytic strategy and a grounded theory approach were used to understand the characteristics of relationships within primary care practices. This multimethod approach amassed rich and comparable data sets in all four studies, which were all aimed at primary care practice improvement. The broad range of data included direct observation of practices during work activities and of patient-clinician interactions, in-depth interviews with physicians and other key staff members, surveys, structured checklists of office environments, and chart reviews. Analyses focused on characteristics of relationships in practices that exhibited a range of success in achieving practice improvement. Complex adaptive systems theory informed these analyses. Findings Trust, mindfulness, heedfulness, respectful interaction, diversity, social/task relatedness, and rich/lean communication were identified as important in practice improvement. A model of practice relationships was developed to describe how these characteristics work together and interact with reflection, sensemaking, and learning to influence practice-level quality outcomes. Discussion Although this model of practice relationships was developed from data collected in primary care practices, which differ from other HCOs in some important ways, the ideas that quality is emergent and that relationships influence quality of care are universally important for all HCOs and all medical specialties. PMID:19769206

Use of Information and Communication Technologies in Clinical Practice Related to the Treatment of Pain. Influence on the Professional Activity and the Doctor-Patient Relationship.

PubMed

Fernandez, Jorge Muriel; Cenador, Maria Begoña García; Manuel López Millan, J; Méndez, Juan Antonio Juanes; Ledesma, María José Sánchez

2017-05-01

The increasing relevance of Information and Communication Technologies (ICTs) in medical care is indisputable. This evidence makes it necessary to start studies that analyse the scope these new forms of access to information and understanding of medicine have on the professional activity of the physician, on the attitude and on the knowledge of patients or, on the doctor-patient relationship. The purpose of this study is to explore some of these aspects in a group of physicians whose clinical activity is related to one of the greatest social impact health problems which is the treatment of chronic pain. Starting with the completion of a questionnaire, in the study group it is observed that the interaction between social structure, increase of information flows and ICTs generate transformations in social practices and behaviour of the actors of the health system. Internet is confirmed as an information space on the subject, but is shown as an underutilized space of interaction between the doctor and his patient.

Relationship between the structure of SET/TAF-Ibeta/INHAT and its histone chaperone activity.

PubMed

Muto, Shinsuke; Senda, Miki; Akai, Yusuke; Sato, Lui; Suzuki, Toru; Nagai, Ryozo; Senda, Toshiya; Horikoshi, Masami

2007-03-13

Histone chaperones assemble and disassemble nucleosomes in an ATP-independent manner and thus regulate the most fundamental step in the alteration of chromatin structure. The molecular mechanisms underlying histone chaperone activity remain unclear. To gain insights into these mechanisms, we solved the crystal structure of the functional domain of SET/TAF-Ibeta/INHAT at a resolution of 2.3 A. We found that SET/TAF-Ibeta/INHAT formed a dimer that assumed a "headphone"-like structure. Each subunit of the SET/TAF-Ibeta/INHAT dimer consisted of an N terminus, a backbone helix, and an "earmuff" domain. It resembles the structure of the related protein NAP-1. Comparison of the crystal structures of SET/TAF-Ibeta/INHAT and NAP-1 revealed that the two proteins were folded similarly except for an inserted helix. However, their backbone helices were shaped differently, and the relative dispositions of the backbone helix and the earmuff domain between the two proteins differed by approximately 40 degrees . Our biochemical analyses of mutants revealed that the region of SET/TAF-Ibeta/INHAT that is engaged in histone chaperone activity is the bottom surface of the earmuff domain, because this surface bound both core histones and double-stranded DNA. This overlap or closeness of the activity surface and the binding surfaces suggests that the specific association among SET/TAF-Ibeta/INHAT, core histones, and double-stranded DNA is requisite for histone chaperone activity. These findings provide insights into the possible mechanisms by which histone chaperones assemble and disassemble nucleosome structures.

A population study of 5 to 15 year olds: full time maternal employment not associated with high BMI. The importance of screen-based activity, reading for pleasure and sleep duration in children's BMI.

PubMed

Taylor, Anne W; Winefield, Helen; Kettler, Lisa; Roberts, Rachel; Gill, Tiffany K

2012-04-01

To describe the relationship between maternal full time employment and health-related and demographic variables associated with children aged 5-15 years, and the factors associated with child overweight/obesity. Data from a chronic disease and risk factor surveillance system were limited to children aged 5-15 years whose mothers responded on their behalf (n = 641). Univariate/multivariate analyses described the differences between mothers who did and did not work full time. The same data were analysed comparing children who are overweight/obese against those with a normal BMI. The children of mothers who worked full time are more likely to be older, live in a household with a higher household income, be an only child or have one sibling or other child in the household, have a sole mother family structure and not spend any time reading for pleasure. No relationship was found between maternal employment and BMI. Compared with children of normal weight, those who were overweight/obese were more likely to spend no time studying, spend more than 2 h per day in screen-based activity and sleep less than 10 h per night. Child BMI status was not related to maternal employment. Although this analysis included eight diet related variables none proved to be significant in the final models.This study has shown that mothers' working status is not related to children's BMI. The relationship between overweight/obesity of children and high levels of screen-based activity, low levels of studying, and short sleep duration suggests a need for better knowledge and understanding of sedentary behaviours of children.

Prediction of Environmental Impact of High-Energy Materials with Atomistic Computer Simulations

DTIC Science & Technology

2010-11-01

from a training set of compounds. Other methods include Quantitative Struc- ture-Activity Relationship ( QSAR ) and Quantitative Structure-Property...26 28 the development of QSPR/ QSAR models, in contrast to boiling points and critical parameters derived from empirical correlations, to improve...Quadratic Configuration Interaction Singles Doubles QSAR Quantitative Structure-Activity Relationship QSPR Quantitative Structure-Property

Quantitative Structure--Activity Relationship Modeling of Rat Acute Toxicity by Oral Exposure

EPA Science Inventory

Background: Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. Objective: In this study, a combinatorial QSAR approach has been employed for the creation of robust and predictive models of acute toxi...

STRUCTURE-ACTIVITY RELATIONSHIPS (SARS) AMONG MUTAGENS AND CARCINOGENS: A REVIEW

EPA Science Inventory

The review is an introduction to methods for evaluating structure-activity relationships (SARs), and, in particular, to those methods that have been applied to study mutagenicity and carcinogenicity. A brief history and some background material on the earliest attempts to correla...

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS FOR CHEMICAL REDUCTIONS OF ORGANIC CONTAMINANTS

EPA Science Inventory

Sufficient kinetic data on abiotic reduction reactions involving organic contaminants are now available that quantitative structure-activity relationships (QSARs) for these reactions can be developed. Over 50 QSARs have been reported, most in just the last few years, and they ar...

The temporal structure of resting-state brain activity in the medial prefrontal cortex predicts self-consciousness.

PubMed

Huang, Zirui; Obara, Natsuho; Davis, Henry Hap; Pokorny, Johanna; Northoff, Georg

2016-02-01

Recent studies have demonstrated an overlap between the neural substrate of resting-state activity and self-related processing in the cortical midline structures (CMS). However, the neural and psychological mechanisms mediating this so-called "rest-self overlap" remain unclear. To investigate the neural mechanisms, we estimated the temporal structure of spontaneous/resting-state activity, e.g. its long-range temporal correlations or self-affinity across time as indexed by the power-law exponent (PLE). The PLE was obtained in resting-state activity in the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in 47 healthy subjects by functional magnetic resonance imaging (fMRI). We performed correlation analyses of the PLE and Revised Self-Consciousness Scale (SCSR) scores, which enabled us to access different dimensions of self-consciousness and specified rest-self overlap in a psychological regard. The PLE in the MPFC's resting-state activity correlated with private self-consciousness scores from the SCSR. Conversely, we found no correlation between the PLE and the other subscales of the SCSR (public, social) or between other resting-state measures, including functional connectivity, and the SCSR subscales. This is the first evidence for the association between the scale-free dynamics of resting-state activity in the CMS and the private dimension of self-consciousness. This finding implies the relationship of especially the private dimension of self with the temporal structure of resting-state activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Contribution of the Cholinergic System to Verbal Memory Performance in Mild Cognitive Impairment.

PubMed

Peter, Jessica; Lahr, Jacob; Minkova, Lora; Lauer, Eliza; Grothe, Michel J; Teipel, Stefan; Köstering, Lena; Kaller, Christoph P; Heimbach, Bernhard; Hüll, Michael; Normann, Claus; Nissen, Christoph; Reis, Janine; Klöppel, Stefan

2016-06-18

Acetylcholine is critically involved in modulating learning and memory function, which both decline in neurodegeneration. It remains unclear to what extent structural and functional changes in the cholinergic system contribute to episodic memory dysfunction in mild cognitive impairment (MCI), in addition to hippocampal degeneration. A better understanding is critical, given that the cholinergic system is the main target of current symptomatic treatment in mild to moderate Alzheimer's disease. We simultaneously assessed the structural and functional integrity of the cholinergic system in 20 patients with MCI and 20 matched healthy controls and examined their effect on verbal episodic memory via multivariate regression analyses. Mediating effects of either cholinergic function or hippocampal volume on the relationship between cholinergic structure and episodic memory were computed. In MCI, a less intact structure and function of the cholinergic system was found. A smaller cholinergic structure was significantly correlated with a functionally more active cholinergic system in patients, but not in controls. This association was not modulated by age or disease severity, arguing against compensational processes. Further analyses indicated that neither functional nor structural changes in the cholinergic system influence verbal episodic memory at the MCI stage. In fact, those associations were fully mediated by hippocampal volume. Although the cholinergic system is structurally and functionally altered in MCI, episodic memory dysfunction results primarily from hippocampal neurodegeneration, which may explain the inefficiency of cholinergic treatment at this disease stage.

Intrinsic Brain Activity in Altered States of Consciousness

PubMed Central

Boly, M.; Phillips, C.; Tshibanda, L.; Vanhaudenhuyse, A.; Schabus, M.; Dang-Vu, T.T.; Moonen, G.; Hustinx, R.; Maquet, P.; Laureys, S.

2010-01-01

Spontaneous brain activity has recently received increasing interest in the neuroimaging community. However, the value of resting-state studies to a better understanding of brain–behavior relationships has been challenged. That altered states of consciousness are a privileged way to study the relationships between spontaneous brain activity and behavior is proposed, and common resting-state brain activity features observed in various states of altered consciousness are reviewed. Early positron emission tomography studies showed that states of extremely low or high brain activity are often associated with unconsciousness. However, this relationship is not absolute, and the precise link between global brain metabolism and awareness remains yet difficult to assert. In contrast, voxel-based analyses identified a systematic impairment of associative frontoparieto–cingulate areas in altered states of consciousness, such as sleep, anesthesia, coma, vegetative state, epileptic loss of consciousness, and somnambulism. In parallel, recent functional magnetic resonance imaging studies have identified structured patterns of slow neuronal oscillations in the resting human brain. Similar coherent blood oxygen level–dependent (BOLD) systemwide patterns can also be found, in particular in the default-mode network, in several states of unconsciousness, such as coma, anesthesia, and slow-wave sleep. The latter results suggest that slow coherent spontaneous BOLD fluctuations cannot be exclusively a reflection of conscious mental activity, but may reflect default brain connectivity shaping brain areas of most likely interactions in a way that transcends levels of consciousness, and whose functional significance remains largely in the dark. PMID:18591474

Students' Relationships with Mathematics: Affect and Identity

ERIC Educational Resources Information Center

Ingram, Naomi

2015-01-01

In this paper, an examination of students' relationships with mathematics is informed by affective research into internal mathematical structures and identity research into students' narratives. By analysing the perceptions of a class of 31 adolescents, five interacting elements emerged: students' views, feelings, mathematical knowledge,…

Comments on the use of network structures to analyse commercial companies’ evolution and their impact on economic behaviour

NASA Astrophysics Data System (ADS)

Costea, Carmen

2006-10-01

Network analysis studies the development of the social structure of relationships around a group or an institutional body, and how it affects beliefs and behaviours. Causal constraints require a special and deeper attention to the social structure. The purpose of this paper is to give a new approach to the idea that this reality should be primarily conceived and investigated from the perspective of the properties of relations between and within units, instead of the properties of these units themselves. The relationship may refer to the exchange of products, labour, information and money. By mapping these relationships, network analysis can help to uncover the emergent and informal communication patterns of commercial companies that may be compared to the formal communication structures. These emergent patterns can be used to explain institutional and individuals’ behaviours. Network analysis techniques focus on the communication structure of an organization that can be subdivided and handled with different approaches. Structural features that can be analysed through the use of network analysis techniques are, for example, the (formal and informal) communication patterns in an organization or the identification of specific groups within an organization. Special attention may be given to specific aspects of communication patterns.

Extraction of Multilayered Social Networks from Activity Data

PubMed Central

Bródka, Piotr; Kazienko, Przemysław; Gaworecki, Jarosław

2014-01-01

The data gathered in all kinds of web-based systems, which enable users to interact with each other, provides an opportunity to extract social networks that consist of people and relationships between them. The emerging structures are very complex due to the number and type of discovered connections. In web-based systems, the characteristic element of each interaction between users is that there is always an object that serves as a communication medium. This can be, for example, an e-mail sent from one user to another or post at the forum authored by one user and commented on by others. Based on these objects and activities that users perform towards them, different kinds of relationships can be identified and extracted. Additional challenge arises from the fact that hierarchies can exist between objects; for example, a forum consists of one or more groups of topics, and each of them contains topics that finally include posts. In this paper, we propose a new method for creation of multilayered social network based on the data about users activities towards different types of objects between which the hierarchy exists. Due to the flattening, preprocessing procedure of new layers and new relationships in the multilayered social network can be identified and analysed. PMID:25105159

Structural Relationships between Social Activities and Longitudinal Trajectories of Depression among Older Adults

ERIC Educational Resources Information Center

Hong, Song-Iee; Hasche, Leslie; Bowland, Sharon

2009-01-01

Purpose: This study examines the structural relationships between social activities and trajectories of late-life depression. Design and Methods: Latent class analysis was used with a nationally representative sample of older adults (N = 5,294) from the Longitudinal Study on Aging II to classify patterns of social activities. A latent growth curve…

Genetic structure and domestication of carrot (Daucus carota subsp. sativus L.) (Apiaceae)

USDA-ARS?s Scientific Manuscript database

Analyses of genetic structure and phylogenetic relationships illuminate the origin and domestication of modern crops. Despite being an important world-wide vegetable, the genetic structure and domestication of carrot (Daucus carota L.) is poorly understood. We provide the first such study using a la...

New SIRT1 activator from alkaline hydrolysate of total saponins in the stems-leaves of Panax ginseng.

PubMed

Ma, Li-Yuan; Zhou, Qi-Le; Yang, Xiu-Wei

2015-11-15

Two new dammarane-type triterpenes, namely ginsenoslaloside-I [3β,12β,24S-trihydroxy-dammara-20(22)E,25-diene-3-O-β-D-glucopyranoside, 1] and 20(S)-ginsenoside-Rh1-6'-acetate (2), together with twelve known compounds (3-14) were isolated from the alkaline hydrolysate of total saponins of the stems-leaves of Panax ginseng C.A. Meyer. Their chemical structures were elucidated by extensive spectroscopic analyses and comparison with the reported data. All 14 compounds were evaluated for their anti-proliferative activities against two human cancer cell lines (HL-60 and Hep-G2) and promotion activities of SIRT1. Compound 6 exhibited significant inhibitory activity in a concentration-dependent manner against HL-60 and Hep-G2 with the IC50 values of 10.32 and 24.33μM, respectively, and had comparable IC50 values with those of vinorelbine, a positive control agent. Meanwhile, compounds 1 and 6 were found to be a potential activator of SIRT1. The preliminary structure-activity relationship was also discussed based on the experimental data obtained. Copyright © 2015 Elsevier Ltd. All rights reserved.

Physical Activity, Physical Fitness and Academic Achievement in Adolescents: A Self-Organizing Maps Approach

ERIC Educational Resources Information Center

Pellicer-Chenoll, Maite; Garcia-Massó, Xavier; Morales, Jose; Serra-Añó, Pilar; Solana-Tramunt, Mònica; González, Luis-Millán; Toca-Herrera, José-Luis

2015-01-01

The relationship among physical activity, physical fitness and academic achievement in adolescents has been widely studied; however, controversy concerning this topic persists. The methods used thus far to analyse the relationship between these variables have included mostly traditional lineal analysis according to the available literature. The…

No association between hair cortisol or cortisone and brain morphology in children.

PubMed

Chen, Ruoqing; Muetzel, Ryan L; El Marroun, Hanan; Noppe, Gerard; van Rossum, Elisabeth F C; Jaddoe, Vincent W; Verhulst, Frank C; White, Tonya; Fang, Fang; Tiemeier, Henning

2016-12-01

Little is known about the relationship between the long-term hypothalamic-pituitary-adrenal (HPA) axis functioning and brain structure in children. Glucocorticoid in hair has emerged as an important biomarker of HPA activity. In this study, we investigated the associations of hair cortisol and cortisone concentrations with brain morphology in young children. We included 219 children aged 6-10 years from the Generation R Study in Rotterdam, the Netherlands. We examined cortisol and cortisone concentrations by hair analysis using liquid chromatography-tandem mass spectrometry, and assessed brain morphometric measures with structural magnetic resonance imaging. The relationships of hair cortisol and cortisone concentrations with brain volumetrics, cortical thickness, cortical surface area and gyrification were analyzed separately after adjustment for several potential confounding factors. We observed a positive association between cortisol concentrations and cortical surface area in the parietal lobe, positive associations of cortisone concentrations with thalamus volume, occipital lobe volume and cortical surface area in the parietal lobe, and a negative association between cortisone concentrations and cortical surface area in the temporal lobe in the regions of interest analyses. A negative association between cortisol or cortisone concentrations and hippocampal volume was observed in children with behavioral problems. The whole brain vertex-wise analyses did however not show any association between cortisol or cortisone concentration and brain morphometric measures after correction for multiple testing. Although some associations are noted in region of interest analyses, we do not observe clear association of hair cortisol or cortisone with brain morphometric measures in typically developing young children. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hierarchical structure of the Sicilian goats revealed by Bayesian analyses of microsatellite information.

PubMed

Siwek, M; Finocchiaro, R; Curik, I; Portolano, B

2011-02-01

Genetic structure and relationship amongst the main goat populations in Sicily (Girgentana, Derivata di Siria, Maltese and Messinese) were analysed using information from 19 microsatellite markers genotyped on 173 individuals. A posterior Bayesian approach implemented in the program STRUCTURE revealed a hierarchical structure with two clusters at the first level (Girgentana vs. Messinese, Derivata di Siria and Maltese), explaining 4.8% of variation (amovaФ(ST) estimate). Seven clusters nested within these first two clusters (further differentiations of Girgentana, Derivata di Siria and Maltese), explaining 8.5% of variation (amovaФ(SC) estimate). The analyses and methods applied in this study indicate their power to detect subtle population structure. © 2010 The Authors, Animal Genetics © 2010 Stichting International Foundation for Animal Genetics.

Social relationships and cognitive decline: a systematic review and meta-analysis of longitudinal cohort studies.

PubMed

Kuiper, Jisca S; Zuidersma, Marij; Zuidema, Sytse U; Burgerhof, Johannes Gm; Stolk, Ronald P; Oude Voshaar, Richard C; Smidt, Nynke

2016-08-01

Although poor social relationships are assumed to contribute to cognitive decline, meta-analytic approaches have not been applied. Individual study results are mixed and difficult to interpret due to heterogeneity in measures of social relationships. We conducted a systematic review and meta-analysis to investigate the relation between poor social relationships and cognitive decline. MEDLINE, Embase and PsycINFO were searched for longitudinal cohort studies examining various aspects of social relationships and cognitive decline in the general population. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random effects meta-analysis. Sources of heterogeneity were explored and likelihood of publication bias was assessed. We stratified analyses according to three aspects of social relationships: structural, functional and a combination of these. We identified 43 articles. Poor social relationships predicted cognitive decline; for structural (19 studies): pooled OR: 1.08 (95% CI: 1.05-1.11); functional (8 studies): pooled OR: 1.15 (95% CI: 1.00-1.32); and combined measures (7 studies): pooled OR: 1.12 (95% CI: 1.01-1.24). Meta-regression and subgroup analyses showed that the heterogeneity could be explained by the type of social relationship measurement and methodological quality of included studies. Despite heterogeneity in study design and measures, our meta-analyses show that multiple aspects of social relationships are associated with cognitive decline. As evidence for publication bias was found, the association might be overestimated and should therefore be interpreted with caution. Future studies are needed to better define the mechanisms underlying these associations. Potential causality of this prognostic association should be examined in future randomized controlled studies. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Moderators, mediators, and bidirectional relationships in the International Classification of Functioning, Disability and Health (ICF) framework: An empirical investigation using a longitudinal design and Structural Equation Modeling (SEM).

PubMed

Rouquette, Alexandra; Badley, Elizabeth M; Falissard, Bruno; Dub, Timothée; Leplege, Alain; Coste, Joël

2015-06-01

The International Classification of Functioning, Disability and Health (ICF) published in 2001 describes the consequences of health conditions with three components of impairments in body structures or functions, activity limitations and participation restrictions. Two of the new features of the conceptual model were the possibility of feedback effects between each ICF component and the introduction of contextual factors conceptualized as moderators of the relationship between the components. The aim of this longitudinal study is to provide empirical evidence of these two kinds of effect. Structural equation modeling was used to analyze data from a French population-based cohort of 548 patients with knee osteoarthritis recruited between April 2007 and March 2009 and followed for three years. Indicators of the body structure and function, activity and participation components of the ICF were derived from self-administered standardized instruments. The measurement model revealed four separate factors for body structures impairments, body functions impairments, activity limitations and participation restrictions. The classic sequence from body impairments to participation restrictions through activity limitations was found at each assessment time. Longitudinal study of the ICF component relationships showed a feedback pathway indicating that the level of participation restrictions at baseline was predictive of activity limitations three years later. Finally, the moderating role of personal (age, sex, mental health, etc.) and environmental factors (family relationships, mobility device use, etc.) was investigated. Three contextual factors (sex, family relationships and walking stick use) were found to be moderators for the relationship between the body impairments and the activity limitations components. Mental health was found to be a mediating factor of the effect of activity limitations on participation restrictions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Objective and subjective measures of neighborhood environment (NE): relationships with transportation physical activity among older persons.

PubMed

Nyunt, Ma Shwe Zin; Shuvo, Faysal Kabir; Eng, Jia Yen; Yap, Keng Bee; Scherer, Samuel; Hee, Li Min; Chan, Siew Pang; Ng, Tze Pin

2015-09-15

This study examined the associations of subjective and objective measures of the neighbourhood environment with the transportation physical activity of community-dwelling older persons in Singapore. A modified version of the Neighborhood Environment Walkability Scale (NEWS) and Geographical Information System (GIS) measures of the built environment characteristics were related to the frequency of walking for transportation purpose in a study sample of older persons living in high-density apartment blocks within a public housing estate in Singapore. Relevant measured variables to assess the complex relationships among built environment measures and transportation physical activity were examined using structural equation modelling and multiple regression analyses. The subjective measures of residential density, street connectivity, land use mix diversity and aesthetic environment and the objective GIS measure of Accessibility Index have positively significant independent associations with transportation physical activity, after adjusting for demographics, socio-economic and health status. Subjective and objective measures are non-overlapping measures complementing each other in providing information on built environment characteristics. For elderly living in a high-density urban neighborhood, well connected street, diversity of land use mix, close proximity to amenities and facilities, and aesthetic environment were associated with higher frequency of walking for transportation purposes.

Associations of work-family conflicts with food habits and physical activity.

PubMed

Roos, Eva; Sarlio-Lähteenkorva, Sirpa; Lallukka, Tea; Lahelma, Eero

2007-03-01

This study examines the relationship between family-work conflicts with food habits and physical activity, and whether the relationship is dependent on family structure and work-related factors. Cross-sectional postal surveys were carried out in 2001 and 2002 among employees of the City of Helsinki, Finland, aged 40-60 years (n = 5346, response rate 66%; for women 70% and for men 60%). Dependent variables in logistic regression analyses were nationally recommended food habits and physical activity. Independent variables were work-family conflicts and family-work conflicts. Covariates included age, marital status, number of children, occupational class, working hours, time travelling to work, and physical and mental work load. Women reporting strong work-family conflicts were more likely to follow recommended food habits (odds ratio (OR) and 95% confidence intervals 1.49 (1.19-1.86)), but this relationship weakened when adjusting for work-related factors (OR 1.20 (0.93-1.55)). Women and men with strong family-work conflicts were less likely to report recommended food habits after adjusting for family structure and work-related factors (women OR 0.75 (0.61-0.92), men OR 0.57 (0.34-0.96)). Women and men with strong work-family conflicts were less likely to follow the recommended amount of physical activity (women OR 0.76 (0.60-0.96), men OR 0.54 (0.34-0.87)). Additionally, women with strong family-work conflicts were less likely to follow the recommended amount of physical activity (OR 0.77 (0.63-0.94)). Adjusting for family and work-related factors did not affect these associations. Conflicts between paid work and family life are likely to constitute barriers for a physically active lifestyle and possibly also for healthy food habits. Improving the balance between work and family may provide a route for promoting health-related behaviours.

Use of Zarit Burden Interview in analysis of family caregivers' perception among Taiwanese caring with hospitalized relatives.

PubMed

Yeh, Pi-Ming; Chang, Yuanmay

2015-10-01

This study was conducted to examine the relationships between family caregivers' perception of caregiving and its influencing factors among Taiwanese with hospitalized relatives. The study used a cross-sectional and descriptive correlational design. A convenience sample of 200 primary caregivers of hospitalized patients diagnosed with cancer, stroke and chronic illness was recruited in a Taiwanese Medical Center; this focus was chosen because cancer, stroke and chronic illness generally require long term care. Data were collected by structured questionnaires. Pearson product-moment correlation and stepwise multiple regression analyses were used to analyse the results of this study. Family caregivers who lacked family support and whose patients' ADL (activities of daily living) dependency was increasing experienced a greater caregiving burden. Family caregivers who had better psychological well-being, better quality of relationship and more caregiving knowledge experienced a lower caregiving burden. Quality of relationship, lack of family support and patients' ADL dependency accounted for 43% of the Zarit Burden Interview variance. The results indicated that family caregivers' perception of caregiving included sacrifice, strain, embarrassment, anger and loss of control. It is vital for nurses to understand these caregiving perceptions and their related factors to provide a holistic care plan. © 2014 Wiley Publishing Asia Pty Ltd.

[Molecular phylogeny and systematics of flowering plants of the family Crassulaceae DC].

PubMed

Goncharova, S B; Goncharov, A A

2009-01-01

Crassulaceae is the most species rich (ca. 1400) family in the order Saxifragales. Most members of the family are succulent plants. Phenotypic diversity and a large number of species complicate systematics of the family and reconstruction of relationship within it. Phylogenetic analyses based on morphological and molecular markers placed Crassulaceae as one of the crown clades of Saxifragales. In this contribution a review of phylogenetic studies of the family Crassulaceae, based on DNA nucleotide sequence comparisons is presented; major clades established in the family are characterised; their structure and polyphylesis of some genera related to it are discussed. It was shown that the traditional taxonomic structure of Crassulaceae contradicts pattern of phylogenetic relationships between its members. We critically analysed recent taxonomic systems of the family and stress that homoplasy of morphological characters does not allow to use them to reconstruct relationships between crassulacean taxa even at the low taxonomic levels.

Early Life Stress and the Anxious Brain: Evidence for A Neural Mechanism Linking Childhood Emotional Maltreatment to Anxiety in Adulthood

PubMed Central

Fonzo, Gregory A.; Ramsawh, Holly J.; Flagan, Taru M.; Simmons, Alan N.; Sullivan, Sarah G.; Allard, Carolyn B.; Paulus, Martin P.; Stein, Murray B.

2016-01-01

Background Childhood emotional maltreatment (CEM) increases likelihood of developing an anxiety disorder in adulthood, but the neural processes underlying conferment of this risk have not been established. Here, we test the potential for neuroimaging the adult brain to inform understanding of the mechanism linking CEM to adult anxiety symptoms. Methods One hundred eighty-two adults (148 females, 34 males) with a normal-to-clinical range of anxiety symptoms underwent structural and functional magnetic resonance imaging while completing an emotion-processing paradigm with facial expressions of fear, anger, and happiness. Participants completed self-report measures of CEM and current anxiety symptoms. Voxelwise mediation analyses on gray matter volumes and activation to each emotion condition were used to identify candidate brain mechanisms relating CEM to anxiety in adulthood. Results During processing of fear and anger faces, greater amygdala and less right dorsolateral prefrontal (dlPFC) activation partially mediated the positive relationship between CEM and anxiety symptoms. Greater right posterior insula activation to fear also partially mediated this relationship, as did greater ventral anterior cingulate (ACC) and less dorsal ACC activation to anger. Responses to happy faces in these regions did not mediate the CEM-anxiety relationship. Smaller right dlPFC gray matter volumes also partially mediated the CEM-anxiety relationship. Conclusions Activation patterns of the adult brain demonstrate the potential to inform mechanistic accounts of the CEM conferment of anxiety symptoms. Results support the hypothesis that exaggerated limbic activation to negative valence facial emotions links CEM to anxiety symptoms, which may be consequent to a breakdown of cortical regulatory processes. PMID:26670947

Activation characteristics of candidate structural materials for a near-term Indian fusion reactor and the impact of their impurities on design considerations

NASA Astrophysics Data System (ADS)

H, L. SWAMI; C, DANANI; A, K. SHAW

2018-06-01

Activation analyses play a vital role in nuclear reactor design. Activation analyses, along with nuclear analyses, provide important information for nuclear safety and maintenance strategies. Activation analyses also help in the selection of materials for a nuclear reactor, by providing the radioactivity and dose rate levels after irradiation. This information is important to help define maintenance activity for different parts of the reactor, and to plan decommissioning and radioactive waste disposal strategies. The study of activation analyses of candidate structural materials for near-term fusion reactors or ITER is equally essential, due to the presence of a high-energy neutron environment which makes decisive demands on material selection. This study comprises two parts; in the first part the activation characteristics, in a fusion radiation environment, of several elements which are widely present in structural materials, are studied. It reveals that the presence of a few specific elements in a material can diminish its feasibility for use in the nuclear environment. The second part of the study concentrates on activation analyses of candidate structural materials for near-term fusion reactors and their comparison in fusion radiation conditions. The structural materials selected for this study, i.e. India-specific Reduced Activation Ferritic‑Martensitic steel (IN-RAFMS), P91-grade steel, stainless steel 316LN ITER-grade (SS-316LN-IG), stainless steel 316L and stainless steel 304, are candidates for use in ITER either in vessel components or test blanket systems. Tungsten is also included in this study because of its use for ITER plasma-facing components. The study is carried out using the reference parameters of the ITER fusion reactor. The activation characteristics of the materials are assessed considering the irradiation at an ITER equatorial port. The presence of elements like Nb, Mo, Co and Ta in a structural material enhance the activity level as well as the dose level, which has an impact on design considerations. IN-RAFMS was shown to be a more effective low-activation material than SS-316LN-IG.

Molecular Modeling on Berberine Derivatives toward BuChE: An Integrated Study with Quantitative Structure-Activity Relationships Models, Molecular Docking, and Molecular Dynamics Simulations.

PubMed

Fang, Jiansong; Pang, Xiaocong; Wu, Ping; Yan, Rong; Gao, Li; Li, Chao; Lian, Wenwen; Wang, Qi; Liu, Ai-lin; Du, Guan-hua

2016-05-01

A dataset of 67 berberine derivatives for the inhibition of butyrylcholinesterase (BuChE) was studied based on the combination of quantitative structure-activity relationships models, molecular docking, and molecular dynamics methods. First, a series of berberine derivatives were reported, and their inhibitory activities toward butyrylcholinesterase (BuChE) were evaluated. By 2D- quantitative structure-activity relationships studies, the best model built by partial least-square had a conventional correlation coefficient of the training set (R(2)) of 0.883, a cross-validation correlation coefficient (Qcv2) of 0.777, and a conventional correlation coefficient of the test set (Rpred2) of 0.775. The model was also confirmed by Y-randomization examination. In addition, the molecular docking and molecular dynamics simulation were performed to better elucidate the inhibitory mechanism of three typical berberine derivatives (berberine, C2, and C55) toward BuChE. The predicted binding free energy results were consistent with the experimental data and showed that the van der Waals energy term (ΔEvdw) difference played the most important role in differentiating the activity among the three inhibitors (berberine, C2, and C55). The developed quantitative structure-activity relationships models provide details on the fine relationship linking structure and activity and offer clues for structural modifications, and the molecular simulation helps to understand the inhibitory mechanism of the three typical inhibitors. In conclusion, the results of this study provide useful clues for new drug design and discovery of BuChE inhibitors from berberine derivatives. © 2015 John Wiley & Sons A/S.

Testing Theory of Planned Behavior and Neo-Socioanalytic Theory models of trait activity, industriousness, exercise social cognitions, exercise intentions, and physical activity in a representative U.S. sample.

PubMed

Vo, Phuong T; Bogg, Tim

2015-01-01

Prior research identified assorted relations between trait and social cognition models of personality and engagement in physical activity. Using a representative U.S. sample (N = 957), the goal of the present study was to test two alternative structural models of the relationships among the extraversion-related facet of activity, the conscientiousness-related facet of industriousness, social cognitions from the Theory of Planned Behavior (perceived behavioral control, affective attitudes, subjective norms, intentions), Social Cognitive Theory (self-efficacy, outcome expectancies), and the Transtheoretical Model (behavioral processes of change), and engagement in physical activity. Path analyses with bootstrapping procedures were used to model direct and indirect effects of trait and social cognition constructs on physical activity through two distinct frameworks - the Theory of Planned Behavior and Neo-Socioanalytic Theory. While both models showed good internal fit, comparative model information criteria showed the Theory-of-Planned-Behavior-informed model provided a better fit. In the model, social cognitions fully mediated the relationships from the activity facet and industriousness to intentions for and engagement in physical activity, such that the relationships were primarily maintained by positive affective evaluations, positive expected outcomes, and confidence in overcoming barriers related to physical activity engagement. The resultant model - termed the Disposition-Belief-Motivation model- is proposed as a useful framework for organizing and integrating personality trait facets and social cognitions from various theoretical perspectives to investigate the expression of health-related behaviors, such as physical activity. Moreover, the results are discussed in terms of extending the application of the Disposition-Belief-Motivation model to longitudinal and intervention designs for physical activity engagement.

Testing Theory of Planned Behavior and Neo-Socioanalytic Theory models of trait activity, industriousness, exercise social cognitions, exercise intentions, and physical activity in a representative U.S. sample

PubMed Central

Vo, Phuong T.; Bogg, Tim

2015-01-01

Prior research identified assorted relations between trait and social cognition models of personality and engagement in physical activity. Using a representative U.S. sample (N = 957), the goal of the present study was to test two alternative structural models of the relationships among the extraversion-related facet of activity, the conscientiousness-related facet of industriousness, social cognitions from the Theory of Planned Behavior (perceived behavioral control, affective attitudes, subjective norms, intentions), Social Cognitive Theory (self-efficacy, outcome expectancies), and the Transtheoretical Model (behavioral processes of change), and engagement in physical activity. Path analyses with bootstrapping procedures were used to model direct and indirect effects of trait and social cognition constructs on physical activity through two distinct frameworks – the Theory of Planned Behavior and Neo-Socioanalytic Theory. While both models showed good internal fit, comparative model information criteria showed the Theory-of-Planned-Behavior-informed model provided a better fit. In the model, social cognitions fully mediated the relationships from the activity facet and industriousness to intentions for and engagement in physical activity, such that the relationships were primarily maintained by positive affective evaluations, positive expected outcomes, and confidence in overcoming barriers related to physical activity engagement. The resultant model – termed the Disposition-Belief-Motivation model– is proposed as a useful framework for organizing and integrating personality trait facets and social cognitions from various theoretical perspectives to investigate the expression of health-related behaviors, such as physical activity. Moreover, the results are discussed in terms of extending the application of the Disposition-Belief-Motivation model to longitudinal and intervention designs for physical activity engagement. PMID:26300811

Facial EMG responses to emotional expressions are related to emotion perception ability.

PubMed

Künecke, Janina; Hildebrandt, Andrea; Recio, Guillermo; Sommer, Werner; Wilhelm, Oliver

2014-01-01

Although most people can identify facial expressions of emotions well, they still differ in this ability. According to embodied simulation theories understanding emotions of others is fostered by involuntarily mimicking the perceived expressions, causing a "reactivation" of the corresponding mental state. Some studies suggest automatic facial mimicry during expression viewing; however, findings on the relationship between mimicry and emotion perception abilities are equivocal. The present study investigated individual differences in emotion perception and its relationship to facial muscle responses - recorded with electromyogram (EMG)--in response to emotional facial expressions. N° = °269 participants completed multiple tasks measuring face and emotion perception. EMG recordings were taken from a subsample (N° = °110) in an independent emotion classification task of short videos displaying six emotions. Confirmatory factor analyses of the m. corrugator supercilii in response to angry, happy, sad, and neutral expressions showed that individual differences in corrugator activity can be separated into a general response to all faces and an emotion-related response. Structural equation modeling revealed a substantial relationship between the emotion-related response and emotion perception ability, providing evidence for the role of facial muscle activation in emotion perception from an individual differences perspective.

Facial EMG Responses to Emotional Expressions Are Related to Emotion Perception Ability

PubMed Central

Künecke, Janina; Hildebrandt, Andrea; Recio, Guillermo; Sommer, Werner; Wilhelm, Oliver

2014-01-01

Although most people can identify facial expressions of emotions well, they still differ in this ability. According to embodied simulation theories understanding emotions of others is fostered by involuntarily mimicking the perceived expressions, causing a “reactivation” of the corresponding mental state. Some studies suggest automatic facial mimicry during expression viewing; however, findings on the relationship between mimicry and emotion perception abilities are equivocal. The present study investigated individual differences in emotion perception and its relationship to facial muscle responses - recorded with electromyogram (EMG) - in response to emotional facial expressions. N° = °269 participants completed multiple tasks measuring face and emotion perception. EMG recordings were taken from a subsample (N° = °110) in an independent emotion classification task of short videos displaying six emotions. Confirmatory factor analyses of the m. corrugator supercilii in response to angry, happy, sad, and neutral expressions showed that individual differences in corrugator activity can be separated into a general response to all faces and an emotion-related response. Structural equation modeling revealed a substantial relationship between the emotion-related response and emotion perception ability, providing evidence for the role of facial muscle activation in emotion perception from an individual differences perspective. PMID:24489647

Phyto-fungicides: Structure activity relationships of the thymol derivatives against Rhizoctonia solani

USDA-ARS?s Scientific Manuscript database

Thymol, the key component of thyme oil and its derivatives were evaluated for their structure activity relationship as fungicide against Rhizoctonia solani. Since plant based chemicals are considered as “Generally Recognized as Safe” (GRAS) chemicals, there is a great potential to use phytochemicals...

ESTIMATION OF MICROBIAL REDUCTIVE TRANSFORMATION RATES FOR CHLORINATED BENZENES AND PHENOLS USING A QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP APPROACH

EPA Science Inventory

A set of literature data was used to derive several quantitative structure-activity relationships (QSARs) to predict the rate constants for the microbial reductive dehalogenation of chlorinated aromatics. Dechlorination rate constants for 25 chloroaromatics were corrected for th...

Toxicity challenges in environmental chemicals: Prediction of human plasma protein binding through quantitative structure-activity relationship (QSAR) models

EPA Science Inventory

The present study explores the merit of utilizing available pharmaceutical data to construct a quantitative structure-activity relationship (QSAR) for prediction of the fraction of a chemical unbound to plasma protein (Fub) in environmentally relevant compounds. Independent model...

An Exploration of Teachers' Agency and Social Relationships within Dyslexia-Support Provision in an English Secondary School

ERIC Educational Resources Information Center

Ross, Helen

2017-01-01

This article explores teachers' experiences of dyslexia and classroom interventions via lesson observations and semi-structured interviews. These experiences were analysed through a Bourdieusien lens, based on Jenkins's "levels of interaction", to delineate power relationships inherent in classroom interactions, teachers' interactions…

In silico study of in vitro GPCR assays by QSAR modeling ...

EPA Pesticide Factsheets

The U.S. EPA is screening thousands of chemicals of environmental interest in hundreds of in vitro high-throughput screening (HTS) assays (the ToxCast program). One goal is to prioritize chemicals for more detailed analyses based on activity in molecular initiating events (MIE) of adverse outcome pathways (AOPs). However, the chemical space of interest for environmental exposure is much wider than this set of chemicals. Thus, there is a need to fill data gaps with in silico methods, and quantitative structure-activity relationships (QSARs) are a proven and cost effective approach to predict biological activity. ToxCast in turn provides relatively large datasets that are ideal for training and testing QSAR models. The overall goal of the study described here was to develop QSAR models to fill the data gaps in a larger environmental database of ~32k structures. The specific aim of the current work was to build QSAR models for 18 G-Protein Coupled Receptor (GPCR) assays, part of the aminergic category. Two QSAR modeling strategies were adopted: classification models were developed to separate chemicals into active/non-active classes, and then regression models were built to predict the potency values of the bioassays for the active chemicals. Multiple software programs were used to calculate constitutional, topological and substructural molecular descriptors from two-dimensional (2D) chemical structures. Model-fitting methods included PLSDA (partial least squares d

Adult-Supplied Structure and Children's Activity Levels.

ERIC Educational Resources Information Center

Carpenter, C. J.; And Others

This study investigated the relationship between preschool children's participation in play activities structured by adults and the level of motor activity children exhibited while in those activities, to test the hypothesis that children's motor activity levels vary according to the level of structure imposed on activities by adults. Subjects…

Function-Oriented Synthesis of Marine Phidianidine Derivatives as Potential PTP1B Inhibitors with Specific Selectivity

PubMed Central

Liu, Jin; Chen, Yu; Li, Jing-Ya; Luo, Cheng; Li, Jia; Chen, Kai-Xian; Li, Xu-Wen

2018-01-01

Phidianidines A and B are two novel marine indole alkaloids bearing an uncommon 1,2,4-oxadiazole ring and exhibiting various biological activities. Our previous research showed that the synthesized phidianidine analogs had the potential to inhibit the activity of protein tyrosine phosphatase 1B (PTP1B), a validated target for Type II diabetes, which indicates that these analogs are worth further structural modification. Therefore, in this paper, a series of phidianidine derivatives were designed and rapidly synthesized with a function-oriented synthesis (FOS) strategy. Their inhibitory effects on PTP1B and T-cell protein tyrosine phosphatase (TCPTP) were evaluated, and several compounds displayed significant inhibitory potency and specific selectivity over PTP1B. The structure–activity relationship (SAR) and molecular docking analyses are also described. PMID:29558377

Discovery and structure-activity relationships of a series of pyroglutamic acid amide antagonists of the P2X7 receptor.

PubMed

Abdi, Muna H; Beswick, Paul J; Billinton, Andy; Chambers, Laura J; Charlton, Andrew; Collins, Sue D; Collis, Katharine L; Dean, David K; Fonfria, Elena; Gleave, Robert J; Lejeune, Clarisse L; Livermore, David G; Medhurst, Stephen J; Michel, Anton D; Moses, Andrew P; Page, Lee; Patel, Sadhana; Roman, Shilina A; Senger, Stefan; Slingsby, Brian; Steadman, Jon G A; Stevens, Alexander J; Walter, Daryl S

2010-09-01

A computational lead-hopping exercise identified compound 4 as a structurally distinct P2X(7) receptor antagonist. Structure-activity relationships (SAR) of a series of pyroglutamic acid amide analogues of 4 were investigated and compound 31 was identified as a potent P2X(7) antagonist with excellent in vivo activity in animal models of pain, and a profile suitable for progression to clinical studies. Copyright 2010 Elsevier Ltd. All rights reserved.

Redefining ADHD Using an Adult Population: Should Inattention be Viewed as a Separate Dimension From Cognitive and Physiological Activity Level?

PubMed

Miller, Nathan; Prevatt, Frances

2017-10-01

The purpose of this study was to reexamine the latent structure of ADHD and sluggish cognitive tempo (SCT) due to issues with construct validity. Two proposed changes to the construct include viewing hyperactivity and sluggishness (hypoactivity) as a single continuum of activity level, and viewing inattention as a separate dimension from activity level. Data were collected from 1,398 adults using Amazon's MTurk. A new scale measuring activity level was developed, and scores of Inattention were regressed onto scores of Activity Level using curvilinear regression. The Activity Level scale showed acceptable levels of internal consistency, normality, and unimodality. Curvilinear regression indicates that a quadratic (curvilinear) model accurately explains a small but significant portion of the variance in levels of inattention. Hyperactivity and hypoactivity may be viewed as a continuum, rather than separate disorders. Inattention may have a U-shaped relationship with activity level. Linear analyses may be insufficient and inaccurate for studying ADHD.

Marine sediment-derived Streptomyces bacteria from British Columbia, Canada are a promising microbiota resource for the discovery of antimicrobial natural products.

PubMed

Dalisay, Doralyn S; Williams, David E; Wang, Xiao Ling; Centko, Ryan; Chen, Jessie; Andersen, Raymond J

2013-01-01

Representatives of the genus Streptomyces from terrestrial sources have been the focus of intensive research for the last four decades because of their prolific production of chemically diverse and biologically important compounds. However, metabolite research from this ecological niche had declined significantly in the past years because of the rediscovery of the same bioactive compounds and redundancy of the sample strains. More recently, a new picture has begun to emerge in which marine-derived Streptomyces bacteria have become the latest hot spot as new source for unique and biologically active compounds. Here, we investigated the marine sediments collected in the temperate cold waters from British Columbia, Canada as a valuable source for new groups of marine-derived Streptomyces with antimicrobial activities. We performed culture dependent isolation from 49 marine sediments samples and obtained 186 Streptomyces isolates, 47 of which exhibited antimicrobial activities. Phylogenetic analyses of the active isolates resulted in the identification of four different clusters of bioactive Streptomyces including a cluster with isolates that appear to represent novel species. Moreover, we explored whether these marine-derived Streptomyces produce new secondary metabolites with antimicrobial properties. Chemical analyses revealed structurally diverse secondary metabolites, including four new antibacterial novobiocin analogues. We conducted structure-activity relationships (SAR) studies of these novobiocin analogues against methicillin-resistant Staphylococcus aureus (MRSA). In this study, we revealed the importance of carbamoyl and OMe moieties at positions 3" and 4" of novobiose as well as the hydrogen substituent at position 5 of hydroxybenzoate ring for the anti-MRSA activity. Changes in the substituents at these positions dramatically impede or completely eliminate the inhibitory activity of novobiocins against MRSA.

Antiproliferative activity of flavonoids: influence of the sequential methoxylation state of the flavonoid structure.

PubMed

Moghaddam, Ghazaal; Ebrahimi, Soltan Ahmad; Rahbar-Roshandel, Nahid; Foroumadi, Alireza

2012-07-01

Dracocephalum kotschyi Boiss. has been used as part of an ethnobotanical remedy against many forms of human cancer in Iran. It has been demonstrated that a flavonoid named xanthomicrol from D. kotschyi contributes to its preferential antiproliferative activity against malignant cells. In the present study, the antiproliferative activity of its flavonoid fraction was further characterized. Using liquid-liquid extraction and a semi-preparative reversed-phase HPLC method, eight flavonoid aglycones were isolated from the aerial parts of the plant and their identities were confirmed through MS and NMR analyses as luteolin, naringenin, apigenin, isokaempferide, cirsimaritin, penduletin, xanthomicrol and calycopterin. The in vitro antiproliferative activity of each compound was evaluated against a panel of established normal and malignant cell lines using the MTT assay and some structure-activity relationships were observed. The hydroxyflavones (luteolin, apigenin and isokaempferide) exerted comparable antiproliferative activities against malignant and normal cells, while the methoxylated hydroxyflavones (cirsimaritin, penduletin, xanthomicrol and calycopterin) showed preferential activities against tumor cells. This activity may be of value in treating tumors as it would exert few side effects in normal tissues. Xanthomicrol selectively inhibited the growth of human gastric adenocarcinoma, while calycopterin selectively prevented human acute promyelocytic leukemia and human colon carcinoma cells proliferation. Copyright © 2011 John Wiley & Sons, Ltd.

Searching for “Environmentally-Benign” Antifouling Biocides

PubMed Central

Cui, Yan Ting; Teo, Serena L. M.; Leong, Wai; Chai, Christina L. L.

2014-01-01

As the result of the ecological impacts from the use of tributyltins (TBT) in shipping, environmental legislation for the registration of chemicals for use in the environment has grown to a monumental challenge requiring product dossiers to include information on the environmental fate and behavior of any chemicals. Specifically, persistence, bioaccumulation and toxicity, collectively known as PBT, are properties of concern in the assessment of chemicals. However, existing measurements of PBT properties are a cumbersome and expensive process, and thus not applied in the early stages of the product discovery and development. Inexpensive methods for preliminary PBT screening would minimize risks arising with the subsequent registration of products. In this article, we evaluated the PBT properties of compounds reported to possess anti-fouling properties using QSAR (quantitative structure-activity relationship) prediction programs such as BIOWIN™ (a biodegradation probability program), KOWWIN™ (log octanol-water partition coefficient calculation program) and ECOSAR™ (Ecological Structure Activity Relationship Programme). The analyses identified some small (Mr < 400) synthetic and natural products as potential candidates for environmentally benign biocides. We aim to demonstrate that while these methods of estimation have limitations, when applied with discretion, they are powerful tools useful in the early stages of research for compound selection for further development as anti-foulants. PMID:24865489

Alcohol Use and Crime: Findings from a Longitudinal Sample of U.S. Adolescents and Young Adults

PubMed Central

Popovici, Ioana; Homer, Jenny F.; Fang, Hai; French, Michael T.

2011-01-01

Background A positive relationship between alcohol use and criminal activity has been well documented among adults, but fewer studies explore this relationship among adolescents. Methods Using data from four waves of the National Longitudinal Study of Adolescent Health (Add Health), we examine alcohol use patterns and criminal activity from adolescence to young adulthood. Fixed-effects models partially address the potential endogeneity of alcohol use, and, because numerous studies indicate that males are more likely than females to engage in drinking and criminal activity, the analyses are segmented by gender. Results We find a strong positive relationship between alcohol consumption, the commission of crimes, and criminal victimization for both genders. Various sensitivity analyses and robustness checks support this core finding. Conclusions Our results have important policy implications, as public policy tools that aim to reduce drinking among adolescents could also reduce criminal activity. Moreover, effective alcohol abuse treatment may indirectly reduce delinquency and thus have greater long-term economic benefits than previously estimated. PMID:22168924

Alcohol use and crime: findings from a longitudinal sample of U.S. adolescents and young adults.

PubMed

Popovici, Ioana; Homer, Jenny F; Fang, Hai; French, Michael T

2012-03-01

A positive relationship between alcohol use and criminal activity has been well documented among adults, but fewer studies explore this relationship among adolescents. Using data from 4 waves of the National Longitudinal Study of Adolescent Health (Add Health), we examine alcohol use patterns and criminal activity from adolescence to young adulthood. Fixed-effects models partially address the potential endogeneity of alcohol use, and, because numerous studies indicate that males are more likely than females to engage in drinking and criminal activity, the analyses are segmented by gender. We find a strong positive relationship between alcohol consumption, the commission of crimes, and criminal victimization for both genders. Various sensitivity analyses and robustness checks support this core finding. Our results have important policy implications, as public policy tools that aim to reduce drinking among adolescents could also reduce criminal activity. Moreover, effective alcohol abuse treatment may indirectly reduce delinquency and thus have greater long-term economic benefits than previously estimated. Copyright © 2011 by the Research Society on Alcoholism.

Activation mechanism of a noncanonical RNA-dependent RNA polymerase.

PubMed

Garriga, Damià; Navarro, Aitor; Querol-Audí, Jordi; Abaitua, Fernando; Rodríguez, José F; Verdaguer, Núria

2007-12-18

Two lineages of viral RNA-dependent RNA polymerases (RDRPs) differing in the organization (canonical vs. noncanonical) of the palm subdomain have been identified. Phylogenetic analyses indicate that both lineages diverged at a very early stage of the evolution of the enzyme [Gorbalenya AE, Pringle FM, Zeddam JL, Luke BT, Cameron CE, Kalmakoff J, Hanzlik TN, Gordon KH, Ward VK (2002) J Mol Biol 324:47-62]. Here, we report the x-ray structure of a noncanonical birnaviral RDRP, named VP1, in its free form, bound to Mg(2+) ions, and bound to a peptide representing the polymerase-binding motif of the regulatory viral protein VP3. The structure of VP1 reveals that the noncanonical connectivity of the palm subdomain maintains the geometry of the catalytic residues found in canonical polymerases but results in a partial blocking of the active site cavity. The VP1-VP3 peptide complex shows a mode of polymerase activation in which VP3 binding promotes a conformational change that removes the steric blockade of the VP1 active site, facilitating the accommodation of the template and incoming nucleotides for catalysis. The striking structural similarities between birnavirus (dsRNA) and the positive-stranded RNA picornavirus and calicivirus RDRPs provide evidence supporting the existence of functional and evolutionary relationships between these two virus groups.

Space-time evolution of a growth fold (Betic Cordillera, Spain). Evidences from 3D geometrical modelling

NASA Astrophysics Data System (ADS)

Martin-Rojas, Ivan; Alfaro, Pedro; Estévez, Antonio

2014-05-01

We present a study that encompasses several software tools (iGIS©, ArcGIS©, Autocad©, etc.) and data (geological mapping, high resolution digital topographic data, high resolution aerial photographs, etc.) to create a detailed 3D geometric model of an active fault propagation growth fold. This 3D model clearly shows structural features of the analysed fold, as well as growth relationships and sedimentary patterns. The results obtained permit us to discuss the kinematics and structural evolution of the fold and the fault in time and space. The study fault propagation fold is the Crevillente syncline. This fold represents the northern limit of the Bajo Segura Basin, an intermontane basin in the Eastern Betic Cordillera (SE Spain) developed from upper Miocene on. 3D features of the Crevillente syncline, including growth pattern, indicate that limb rotation and, consequently, fault activity was higher during Messinian than during Tortonian; consequently, fault activity was also higher. From Pliocene on our data point that limb rotation and fault activity steadies or probably decreases. This in time evolution of the Crevillente syncline is not the same all along the structure; actually the 3D geometric model indicates that observed lateral heterogeneity is related to along strike variation of fault displacement.

What is the effect of physical activity on the knee joint? A systematic review.

PubMed

Urquhart, Donna M; Tobing, Jephtah F L; Hanna, Fahad S; Berry, Patricia; Wluka, Anita E; Ding, Changhai; Cicuttini, Flavia M

2011-03-01

Although several studies have examined the relationship between physical activity and knee osteoarthritis, the effect of physical activity on knee joint health is unclear. The aim of this systematic review was to examine the relationships between physical activity and individual joint structures at the knee. Computer-aided searches were conducted up until November 2008, and the reference lists of key articles were examined. The methodological quality of selected studies was assessed based on established criteria, and a best-evidence synthesis was used to summarize the results. We found that the relationships between physical activity and individual joint structures at the knee differ. There was strong evidence for a positive association between physical activity and tibiofemoral osteophytes. However, we also found strong evidence for the absence of a relationship between physical activity and joint space narrowing, a surrogate method of assessing cartilage. Moreover, there was limited evidence from magnetic resonance imaging studies for a positive relationship between physical activity and cartilage volume and strong evidence for an inverse relationship between physical activity and cartilage defects. This systematic review found that knee structures are affected differently by physical activity. Although physical activity is associated with an increase in radiographic osteophytes, there was no related increase in joint space narrowing, rather emerging evidence of an associated increase in cartilage volume and decrease in cartilage defects on magnetic resonance imaging. Given that optimizing cartilage health is important in preventing osteoarthritis, these findings indicate that physical activity is beneficial, rather than detrimental, to joint health.

Cognitive predictors of a common multitasking ability: Contributions from working memory, attention control, and fluid intelligence.

PubMed

Redick, Thomas S; Shipstead, Zach; Meier, Matthew E; Montroy, Janelle J; Hicks, Kenny L; Unsworth, Nash; Kane, Michael J; Hambrick, D Zachary; Engle, Randall W

2016-11-01

Previous research has identified several cognitive abilities that are important for multitasking, but few studies have attempted to measure a general multitasking ability using a diverse set of multitasks. In the final dataset, 534 young adult subjects completed measures of working memory (WM), attention control, fluid intelligence, and multitasking. Correlations, hierarchical regression analyses, confirmatory factor analyses, structural equation models, and relative weight analyses revealed several key findings. First, although the complex tasks used to assess multitasking differed greatly in their task characteristics and demands, a coherent construct specific to multitasking ability was identified. Second, the cognitive ability predictors accounted for substantial variance in the general multitasking construct, with WM and fluid intelligence accounting for the most multitasking variance compared to attention control. Third, the magnitude of the relationships among the cognitive abilities and multitasking varied as a function of the complexity and structure of the various multitasks assessed. Finally, structural equation models based on a multifaceted model of WM indicated that attention control and capacity fully mediated the WM and multitasking relationship. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Impulsivity and the Modular Organization of Resting-State Neural Networks

PubMed Central

Davis, F. Caroline; Knodt, Annchen R.; Sporns, Olaf; Lahey, Benjamin B.; Zald, David H.; Brigidi, Bart D.; Hariri, Ahmad R.

2013-01-01

Impulsivity is a complex trait associated with a range of maladaptive behaviors, including many forms of psychopathology. Previous research has implicated multiple neural circuits and neurotransmitter systems in impulsive behavior, but the relationship between impulsivity and organization of whole-brain networks has not yet been explored. Using graph theory analyses, we characterized the relationship between impulsivity and the functional segregation (“modularity”) of the whole-brain network architecture derived from resting-state functional magnetic resonance imaging (fMRI) data. These analyses revealed remarkable differences in network organization across the impulsivity spectrum. Specifically, in highly impulsive individuals, regulatory structures including medial and lateral regions of the prefrontal cortex were isolated from subcortical structures associated with appetitive drive, whereas these brain areas clustered together within the same module in less impulsive individuals. Further exploration of the modular organization of whole-brain networks revealed novel shifts in the functional connectivity between visual, sensorimotor, cortical, and subcortical structures across the impulsivity spectrum. The current findings highlight the utility of graph theory analyses of resting-state fMRI data in furthering our understanding of the neurobiological architecture of complex behaviors. PMID:22645253

Structure-Activity Relationship in TLR4 Mutations: Atomistic Molecular Dynamics Simulations and Residue Interaction Network Analysis

NASA Astrophysics Data System (ADS)

Anwar, Muhammad Ayaz; Choi, Sangdun

2017-03-01

Toll-like receptor 4 (TLR4), a vital innate immune receptor present on cell surfaces, initiates a signaling cascade during danger and bacterial intrusion. TLR4 needs to form a stable hexamer complex, which is necessary to dimerize the cytoplasmic domain. However, D299G and T399I polymorphism may abrogate the stability of the complex, leading to compromised TLR4 signaling. Crystallography provides valuable insights into the structural aspects of the TLR4 ectodomain; however, the dynamic behavior of polymorphic TLR4 is still unclear. Here, we employed molecular dynamics simulations (MDS), as well as principal component and residue network analyses, to decipher the structural aspects and signaling propagation associated with mutations in TLR4. The mutated complexes were less cohesive, displayed local and global variation in the secondary structure, and anomalous decay in rotational correlation function. Principal component analysis indicated that the mutated complexes also exhibited distinct low-frequency motions, which may be correlated to the differential behaviors of these TLR4 variants. Moreover, residue interaction networks (RIN) revealed that the mutated TLR4/myeloid differentiation factor (MD) 2 complex may perpetuate abnormal signaling pathways. Cumulatively, the MDS and RIN analyses elucidated the mutant-specific conformational alterations, which may help in deciphering the mechanism of loss-of-function mutations.

Receptor-based 3D-QSAR in Drug Design: Methods and Applications in Kinase Studies.

PubMed

Fang, Cheng; Xiao, Zhiyan

2016-01-01

Receptor-based 3D-QSAR strategy represents a superior integration of structure-based drug design (SBDD) and three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis. It combines the accurate prediction of ligand poses by the SBDD approach with the good predictability and interpretability of statistical models derived from the 3D-QSAR approach. Extensive efforts have been devoted to the development of receptor-based 3D-QSAR methods and two alternative approaches have been exploited. One associates with computing the binding interactions between a receptor and a ligand to generate structure-based descriptors for QSAR analyses. The other concerns the application of various docking protocols to generate optimal ligand poses so as to provide reliable molecular alignments for the conventional 3D-QSAR operations. This review highlights new concepts and methodologies recently developed in the field of receptorbased 3D-QSAR, and in particular, covers its application in kinase studies.

Collagenolytic Matrix Metalloproteinase Structure-Function Relationships: Insights From Molecular Dynamics Studies.

PubMed

Karabencheva-Christova, Tatyana G; Christov, Christo Z; Fields, Gregg B

2017-01-01

Several members of the zinc-dependent matrix metalloproteinase (MMP) family catalyze collagen degradation. Experimental data reveal a collaboration between different MMP domains in order to achieve efficient collagenolysis. Molecular dynamics (MD) simulations have been utilized to provide atomistic details of the collagenolytic process. The triple-helical structure of collagen exhibits local regions of flexibility, with modulation of interchain salt bridges and water bridges contributing to accessibility of individual chains by the enzyme. In turn, the hemopexin-like (HPX) domain of the MMP initially binds the triple helix and facilitates the presentation of individual strands to active site in the catalytic (CAT) domain. Extensive positive and negative correlated motions are observed between the CAT and HPX domains when collagen is bound. Ultimately, the MD simulation studies have complemented structural (NMR spectroscopy, X-ray crystallography) and kinetic analyses to provide a more detailed mechanistic view of MMP-catalyzed collagenolysis. © 2017 Elsevier Inc. All rights reserved.

An Exploration of Jamaican Mothers’ Perceptions of Closeness and Intimacy in the Mother–Child Relationship during Middle Childhood

PubMed Central

Burke, Taniesha; Kuczynski, Leon; Perren, Sonja

2017-01-01

Research on Jamaican mother–child relationships has had a limited focus on authoritarian parenting styles and selected discipline practices such as corporal punishment. This study examined Jamaican mothers’ experiences of closeness and connectedness with their children to provide a holistic perspective on Jamaican-parent–child relationships. Thirty mothers (17 middle class and 13 lower class) living in Kingston and St. Andrew, Jamaica, participated in a 1-h to 1.5-h semi-structured, open-ended interview regarding their 8- to 12-year-old children. Thematic analyses indicated that mothers experienced closeness through intimate interactions (e.g., shared projects, shared physical affection, mutuality, and child self-disclosure) and parent–child nurturance. Both mothers and children were active in creating contexts for closeness. Mothers also reported experiences that temporarily damaged their connection with their children. The findings suggest that the construct of parent–child intimacy may be useful in teasing out the psychological meanings and interpersonal processes of parent–child relatedness in cultural research. PMID:29312035

Body size phenology in a regional bee fauna: a temporal extension of Bergmann's rule.

PubMed

Osorio-Canadas, Sergio; Arnan, Xavier; Rodrigo, Anselm; Torné-Noguera, Anna; Molowny, Roberto; Bosch, Jordi

2016-12-01

Bergmann's rule originally described a positive relationship between body size and latitude in warm-blooded animals. Larger animals, with a smaller surface/volume ratio, are better enabled to conserve heat in cooler climates (thermoregulatory hypothesis). Studies on endothermic vertebrates have provided support for Bergmann's rule, whereas studies on ectotherms have yielded conflicting results. If the thermoregulatory hypothesis is correct, negative relationships between body size and temperature should occur in temporal in addition to geographical gradients. To explore this possibility, we analysed seasonal activity patterns in a bee fauna comprising 245 species. In agreement with our hypothesis of a different relationship for large (endothermic) and small (ectothermic) species, we found that species larger than 27.81 mg (dry weight) followed Bergmann's rule, whereas species below this threshold did not. Our results represent a temporal extension of Bergmann's rule and indicate that body size and thermal physiology play an important role in structuring community phenology. © 2016 John Wiley & Sons Ltd/CNRS.

An Exploration of Jamaican Mothers' Perceptions of Closeness and Intimacy in the Mother-Child Relationship during Middle Childhood.

PubMed

Burke, Taniesha; Kuczynski, Leon; Perren, Sonja

2017-01-01

Research on Jamaican mother-child relationships has had a limited focus on authoritarian parenting styles and selected discipline practices such as corporal punishment. This study examined Jamaican mothers' experiences of closeness and connectedness with their children to provide a holistic perspective on Jamaican-parent-child relationships. Thirty mothers (17 middle class and 13 lower class) living in Kingston and St. Andrew, Jamaica, participated in a 1-h to 1.5-h semi-structured, open-ended interview regarding their 8- to 12-year-old children. Thematic analyses indicated that mothers experienced closeness through intimate interactions (e.g., shared projects, shared physical affection, mutuality, and child self-disclosure) and parent-child nurturance. Both mothers and children were active in creating contexts for closeness. Mothers also reported experiences that temporarily damaged their connection with their children. The findings suggest that the construct of parent-child intimacy may be useful in teasing out the psychological meanings and interpersonal processes of parent-child relatedness in cultural research.

Specific sulfation and glycosylation—a structural combination for the anticoagulation of marine carbohydrates

PubMed Central

Pomin, Vitor H.; Mourão, Paulo A. S.

2014-01-01

Based on considered achievements of the last 25 years, specific combinations of sulfation patterns and glycosylation types have been proved to be key structural players for the anticoagulant activity of certain marine glycans. These conclusions were obtained from comparative and systematic analyses on the structure-anticoagulation relationships of chemically well-defined sulfated polysaccharides of marine invertebrates and red algae. These sulfated polysaccharides are known as sulfated fucans (SFs), sulfated galactans (SGs) and glycosaminoglycans (GAGs). The structural combinations necessary for the anticoagulant activities are the 2-sulfation in α-L-SGs, the 2,4-di-sulfation in α-L-fucopyranosyl units found as composing units of certain sea-urchin and sea-cucumber linear SFs, or as branching units of the fucosylated chondroitin sulfate, a unique GAG from sea-cucumbers. Another unique GAG type from marine organisms is the dermatan sulfate isolated from ascidians. The high levels of 4-sulfation at the galactosamine units combined with certain levels of 2-sulfation at the iduronic acid units is the anticoagulant structural requirements of these GAGs. When the backbones of red algal SGs are homogeneous, the anticoagulation is proportionally dependent of their sulfation content. Finally, 4-sulfation was observed to be the structural motif required to enhance the inhibition of thrombin via heparin cofactor-II by invertebrate SFs. PMID:24639954

The relationship between perceived health and physical activity indoors, outdoors in built environments, and outdoors in nature.

PubMed

Pasanen, Tytti P; Tyrväinen, Liisa; Korpela, Kalevi M

2014-11-01

A body of evidence shows that both physical activity and exposure to nature are connected to improved general and mental health. Experimental studies have consistently found short term positive effects of physical activity in nature compared with built environments. This study explores whether these benefits are also evident in everyday life, perceived over repeated contact with nature. The topic is important from the perspectives of city planning, individual well-being, and public health. National survey data (n = 2,070) from Finland was analysed using structural regression analyses. Perceived general health, emotional well-being, and sleep quality were regressed on the weekly frequency of physical activity indoors, outdoors in built environments, and in nature. Socioeconomic factors and other plausible confounders were controlled for. Emotional well-being showed the most consistent positive connection to physical activity in nature, whereas general health was positively associated with physical activity in both built and natural outdoor settings. Better sleep quality was weakly connected to frequent physical activity in nature, but the connection was outweighed by other factors. The results indicate that nature provides an added value to the known benefits of physical activity. Repeated exercise in nature is, in particular, connected to better emotional well-being. © 2014 The Authors. Applied Psychology: Health and Well-Being published by John Wiley & Sons Ltd on behalf of The International Association of Applied Psychology.

Independent and joint associations between multiple measures of the built and social environment and physical activity in a multi-ethnic urban community.

PubMed

Schulz, Amy; Mentz, Graciela; Johnson-Lawrence, Vicki; Israel, Barbara A; Max, Paul; Zenk, Shannon N; Wineman, Jean; Marans, Robert W

2013-10-01

Physical activity is associated with reduced risk of a number of health outcomes, yet fewer than half of adults in the United States report recommended levels of physical activity. Analyses of structural characteristics of the built environment as correlates of physical activity have yielded mixed results. We examine associations between multiple aspects of urban neighborhood environments and physical activity in order to understand their independent and joint effects, with a focus on the extent to which the condition of the built environment and indicators of the social environment modify associations between structural characteristics and physical activity. We use data from a stratified, multi-stage proportional probability sample of 919 non-Hispanic Black, non-Hispanic White, and Hispanic adults in an urban community, observational data from their residential neighborhoods, and census data to examine independent and joint associations of structural characteristics (e.g., street network connectivity), their condition (e.g., sidewalk condition), and social environments (e.g., territoriality) with physical activity. Our findings suggest that sidewalk condition is associated with physical activity, above and beyond structural characteristics of the built environment. Associations between some structural characteristics of the built environment and physical activity were conditional upon street condition, physical deterioration, and the proportion of parks and playgrounds in good condition. We found modest support for the hypothesis that associations between structural characteristics and physical activity are modified by aspects of the social environment. Results presented here point to the value of and need for understanding and addressing the complexity of factors that contribute to the relationships between the built and social environments and physical activity, and in turn, obesity and co-morbidities. Bringing together urban planners, public health practitioners and policy makers to understand and address aspects of urban environment associated with health outcomes is critical to promoting health and health equity.

Structure-activity relationships of selected phenazines against Mycobacterium leprae in vitro.

PubMed Central

Franzblau, S G; O'Sullivan, J F

1988-01-01

Structure-activity relationships of phenazines against Mycobacterium leprae were investigated by using an in vitro radiorespirometric assay. In general, activity in ascending order was observed in compounds containing no chlorine atoms, a monochlorinated phenazine nucleus, and chlorines in the para positions of both the anilino and phenyl rings. The most active compounds contained a 2,2,6,6-tetramethylpiperidine substitution at the imino nitrogen. Most of these chlorinated phenazines were considerably more active in vitro than clofazimine (B663). PMID:3056241

Comparative Analysis of Predictive Models for Liver Toxicity Using ToxCast Assays and Quantitative Structure-Activity Relationships (MCBIOS)

EPA Science Inventory

Comparative Analysis of Predictive Models for Liver Toxicity Using ToxCast Assays and Quantitative Structure-Activity Relationships Jie Liu1,2, Richard Judson1, Matthew T. Martin1, Huixiao Hong3, Imran Shah1 1National Center for Computational Toxicology (NCCT), US EPA, RTP, NC...

[Volunteer satisfaction: Internal structure and relationship with permanence in organizations].

PubMed

Vecina Jiménez, M L; Chacón Fuertes, Fernando; Sueiro Abad, Manuel J

2009-02-01

Volunteer satisfaction: Internal structure and relationship with permanence in organizations. The concept of satisfaction is considered theoretically relevant in practically all the studies that have investigated the factors that influence the permanence of volunteer participation in organizations. However, the practical results are not conclusive, perhaps due to the wide range of ways in which the concept is understood and measured. The object of this study is: to analyse the internal structure of satisfaction and to verify its relationship with volunteer duration in organizations. The results of the factor analysis yield a three-factor structure: Satisfaction with the management of the organization, Satisfaction with the tasks, Satisfaction of motivations. The three factors allow us to differentiate between individuals who remain in the organization for a period of 12 consecutive months, and those who leave earlier. The results of structural equation model analysis show that the relationship between satisfaction and the length of time that volunteers stay with the organization is affected by the intention to remain.

The Association between Physical Activity and Eating Self-Regulation in Overweight and Obese Women

PubMed Central

Carraça, Eliana V.; Silva, Marlene N.; Coutinho, Sílvia R.; Vieira, Paulo N.; Minderico, Cláudia S.; Sardinha, Luís B.; Teixeira, Pedro J.

2013-01-01

Objective Successful weight management relies heavily on eating and exercise behaviors. However, little is known about the association between both on a psychosocial level. This study examined the relationship between exercise and eating regulation by exploring the mediating effects of negative body image investment and depressive mood, and their stability through time. Methods Analyses were conducted at two different moments (12 and 36 months), involving a sample of 221 overweight/obese women (age: 37.6 ± 7 years; BMI: 31.6 ± 4.1 kg/m2) that participated in a behavioral weight control intervention. Bivariate correlations and mediation analyses using Preacher & Hayes resampling procedures were conducted. Results At 12 months, negative body image investment was the only significant mediator of the exercise-eating relationship. This variable explained larger portions of the indirect effects of structured rather than lifestyle exercise on eating. At 36 months, negative investment and to a lesser extent depressive mood partially explained the exercise-eating association. Conclusions Our findings suggest that, besides physiological effects of exercise, psychological mechanisms related to body image and mood also explain the role of physical activity as a ‘gateway behavior’ for improved eating regulation in overweight women. These effects appear to be stable and may help understand the key role of exercise in long-term weight management. PMID:24217426

Partitioning and lipophilicity in quantitative structure-activity relationships.

PubMed Central

Dearden, J C

1985-01-01

The history of the relationship of biological activity to partition coefficient and related properties is briefly reviewed. The dominance of partition coefficient in quantitation of structure-activity relationships is emphasized, although the importance of other factors is also demonstrated. Various mathematical models of in vivo transport and binding are discussed; most of these involve partitioning as the primary mechanism of transport. The models describe observed quantitative structure-activity relationships (QSARs) well on the whole, confirming that partitioning is of key importance in in vivo behavior of a xenobiotic. The partition coefficient is shown to correlate with numerous other parameters representing bulk, such as molecular weight, volume and surface area, parachor and calculated indices such as molecular connectivity; this is especially so for apolar molecules, because for polar molecules lipophilicity factors into both bulk and polar or hydrogen bonding components. The relationship of partition coefficient to chromatographic parameters is discussed, and it is shown that such parameters, which are often readily obtainable experimentally, can successfully supplant partition coefficient in QSARs. The relationship of aqueous solubility with partition coefficient is examined in detail. Correlations are observed, even with solid compounds, and these can be used to predict solubility. The additive/constitutive nature of partition coefficient is discussed extensively, as are the available schemes for the calculation of partition coefficient. Finally the use of partition coefficient to provide structural information is considered. It is shown that partition coefficient can be a valuable structural tool, especially if the enthalpy and entropy of partitioning are available. PMID:3905374

Evaluating a Model of Youth Physical Activity

ERIC Educational Resources Information Center

Heitzler, Carrie D.; Lytle, Leslie A.; Erickson, Darin J.; Barr-Anderson, Daheia; Sirard, John R.; Story, Mary

2010-01-01

Objective: To explore the relationship between social influences, self-efficacy, enjoyment, and barriers and physical activity. Methods: Structural equation modeling examined relationships between parent and peer support, parent physical activity, individual perceptions, and objectively measured physical activity using accelerometers among a…

Development of Novel Repellents Using Structure - Activity Modeling of Compounds in the USDA Archival Database

DTIC Science & Technology

2011-01-01

used in efforts to develop QSAR models. Measurement of Repellent Efficacy Screening for Repellency of Compounds with Unknown Toxicology In screening...CPT) were used to develop Quantitative Structure Activity Relationship ( QSAR ) models to predict repellency. Successful prediction of novel...acylpiperidine QSAR models employed 4 descriptors to describe the relationship between structure and repellent duration. The ANN model of the carboxamides did not

Hot and Spicy versus Cool and Minty as an Example of Organic Structure-Activity Relationships

NASA Astrophysics Data System (ADS)

Kimbrough, Doris R.

1997-07-01

There are two classes of substances that activate neural receptors that are involved in temperature perception. Structures of substances found in spices and food that we normally associate with "hot" (or spicy) and "cool" (or minty) flavors are presented and discussed. Functional group similarities within the two groups provide an interesting example of the relationship between molecular structure and molecular function in organic chemistry.

Toll-like receptor 4-related immunostimulatory polysaccharides: Primary structure, activity relationships, and possible interaction models.

PubMed

Zhang, Xiaorui; Qi, Chunhui; Guo, Yan; Zhou, Wenxia; Zhang, Yongxiang

2016-09-20

Toll-like receptor (TLR) 4 is an important polysaccharide receptor; however, the relationships between the structures and biological activities of TLR4 and polysaccharides remain unknown. Many recent findings have revealed the primary structure of TLR4/MD-2-related polysaccharides, and several three-dimensional structure models of polysaccharide-binding proteins have been reported; and these models provide insights into the mechanisms through which polysaccharides interact with TLR4. In this review, we first discuss the origins of polysaccharides related to TLR4, including polysaccharides from higher plants, fungi, bacteria, algae, and animals. We then briefly describe the glucosidic bond types of TLR4-related heteroglycans and homoglycans and describe the typical molecular weights of TLR4-related polysaccharides. The primary structures and activity relationships of polysaccharides with TLR4/MD-2 are also discussed. Finally, based on the existing interaction models of LPS with TLR4/MD-2 and linear polysaccharides with proteins, we provide insights into the possible interaction models of polysaccharide ligands with TLR4/MD-2. To our knowledge, this review is the first to summarize the primary structures and activity relationships of TLR4-related polysaccharides and the possible mechanisms of interaction for TLR4 and TLR4-related polysaccharides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Burnout and connectedness in the job demands-resources model: studying palliative care volunteers and their families.

PubMed

Huynh, Jasmine-Yan; Winefield, Anthony H; Xanthopoulou, Despoina; Metzer, Jacques C

2012-09-01

This study examined the role of burnout and connectedness in the job demands-resources (JD-R) model among palliative care volunteers. It was hypothesized that (a) exhaustion mediates the relationship between demands and depression, and between demands and retention; (b) cynicism mediates the relationship between resources and retention; and (c) connectedness mediates the relationship between resources and retention. Hypotheses were tested in 2 separate analyses: structural equation modeling (SEM) and path analyses. The first was based on volunteer self-reports (N = 204), while the second analysis concerned matched data from volunteers and their family members (N = 99). While strong support was found for cynicism and connectedness as mediators in both types of analyses, this was not altogether the case for exhaustion. Implications of these findings for the JD-R model and volunteer organizations are discussed.

Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells.

PubMed Central

Takeuchi, M; Inoue, N; Strickland, T W; Kubota, M; Wada, M; Shimizu, R; Hoshi, S; Kozutsumi, H; Takasaki, S; Kobata, A

1989-01-01

Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). In contrast, EPO-tetra showed both in vivo and in vitro activities comparable to those of the standard EPO. EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. PMID:2813359

Structural and functional hallmarks of amyotrophic lateral sclerosis progression in motor- and memory-related brain regions

PubMed Central

Stoppel, Christian Michael; Vielhaber, Stefan; Eckart, Cindy; Machts, Judith; Kaufmann, Jörn; Heinze, Hans-Jochen; Kollewe, Katja; Petri, Susanne; Dengler, Reinhard; Hopf, Jens-Max; Schoenfeld, Mircea Ariel

2014-01-01

Previous studies have shown that in amyotrophic lateral sclerosis (ALS) multiple motor and extra-motor regions display structural and functional alterations. However, their temporal dynamics during disease-progression are unknown. To address this question we employed a longitudinal design assessing motor- and novelty-related brain activity in two fMRI sessions separated by a 3-month interval. In each session, patients and controls executed a Go/NoGo-task, in which additional presentation of novel stimuli served to elicit hippocampal activity. We observed a decline in the patients' movement-related activity during the 3-month interval. Importantly, in comparison to controls, the patients' motor activations were higher during the initial measurement. Thus, the relative decrease seems to reflect a breakdown of compensatory mechanisms due to progressive neural loss within the motor-system. In contrast, the patients' novelty-evoked hippocampal activity increased across 3 months, most likely reflecting the build-up of compensatory processes typically observed at the beginning of lesions. Consistent with a stage-dependent emergence of hippocampal and motor-system lesions, we observed a positive correlation between the ALSFRS-R or MRC-Megascores and the decline in motor activity, but a negative one with the hippocampal activation-increase. Finally, to determine whether the observed functional changes co-occur with structural alterations, we performed voxel-based volumetric analyses on magnetization transfer images in a separate patient cohort studied cross-sectionally at another scanning site. Therein, we observed a close overlap between the structural changes in this cohort, and the functional alterations in the other. Thus, our results provide important insights into the temporal dynamics of functional alterations during disease-progression, and provide support for an anatomical relationship between functional and structural cerebral changes in ALS. PMID:25161894

The third wheel: the impact of Twitter use on relationship infidelity and divorce.

PubMed

Clayton, Russell B

2014-07-01

The purpose of this study was to examine how social networking site (SNS) use, specifically Twitter use, influences negative interpersonal relationship outcomes. This study specifically examined the mediational effect of Twitter-related conflict on the relationship between active Twitter use and negative relationship outcomes, and how this mechanism may be contingent on the length of the romantic relationship. A total of 581 Twitter users aged 18 to 67 years (Mage=29, SDage=8.9) completed an online survey questionnaire. Moderation-mediation regression analyses using bootstrapping methods indicated that Twitter-related conflict mediated the relationship between active Twitter use and negative relationship outcomes. The length of the romantic relationship, however, did not moderate the indirect effect on the relationship between active Twitter use and negative relationship outcomes. The results from this study suggest that active Twitter use leads to greater amounts of Twitter-related conflict among romantic partners, which in turn leads to infidelity, breakup, and divorce. This indirect effect is not contingent on the length of the romantic relationship. The current study adds to the growing body of literature investigating SNS use and romantic relationship outcomes.

The influence of self-efficacy and outcome expectations on the relationship between perceived environment and physical activity in the workplace

PubMed Central

Prodaniuk, Tricia R; Plotnikoff, Ronald C; Spence, John C; Wilson, Phillip M

2004-01-01

Background Recent research and commentary contends that ecological approaches may be particularly useful for understanding and promoting physical activity participation in various settings including the workplace. Yet within the physical activity domain there is a lack of understanding of how ecological environment factors influence behaviour. Thus, the purpose of this study was to examine the relationships between perceived environment, social-cognitive variables, and physical activity behaviour. Methods Participants (N = 897) were employees from three large worksites who completed self-report inventories containing measures of self-efficacy, outcome expectations, perceptions of the workplace environment (PWES), and physical activity behaviour during both leisure-time and incorporated throughout the workday. Results Results of both bivariate and multiple regression analyses indicated the global PWES scores had a limited association with leisure-time physical activity (R2adj =.01). Sequential regression analyses supported a weak association between physical activity incorporated in the workplace and PWES (R2adj = .04) and the partial mediation of self-efficacy on the relationship between PWES and workplace physical activity (variance accounted for reduced to R2adj = .02 when self-efficacy was controlled). Conclusion Overall, the results of the present investigation indicate that self-efficacy acted as a partial mediator of the relationship between perceived environment and workplace physical activity participation. Implications of the findings for physical activity promotion using ecological-based approaches, and future directions for research from this perspective in worksite settings are discussed. PMID:15169560

The Consequences of Perfectionism Scale: Factorial Structure and Relationships with Perfectionism, Performance Perfectionism, Affect, and Depressive Symptoms

ERIC Educational Resources Information Center

Stoeber, Joachim; Hoyle, Azina; Last, Freyja

2013-01-01

This study investigated the Consequences of Perfectionism Scale (COPS) and its relationships with perfectionism, performance perfectionism, affect, and depressive symptoms in 202 university students using confirmatory factor analysis, correlations, and regression analyses. Results suggest that the COPS is a reliable and valid measure of positive…

Cultivating Relationships with School Placement Stakeholders: The Perspective of the Cooperating Teacher

ERIC Educational Resources Information Center

Young, Ann-Marie; MacPhail, Ann

2016-01-01

The aim of this paper is to analyse Irish school placement cooperating teachers' supervisory experiences when involved in various structures of communities and explore factors which enabled or challenged them in cultivating relationships with school placement stakeholders where there is no formal system of supervision established in schools in the…

Happy Spouses, Happy Parents? Family Relationships among Finnish and Dutch Dual Earners

ERIC Educational Resources Information Center

Malinen, Kaisa; Kinnunen, Ulla; Tolvanen, Asko; Ronka, Anna; Wierda-Boer, Hilde; Gerris, Jan

2010-01-01

In this study links between spousal and parent-child relationships among Finnish (n = 157 couples) and Dutch (n = 276 couples) dual earners with young children were examined using paired questionnaire data. Variable-oriented analyses (structural equation modeling with a multigroup procedure) supported the spillover hypothesis, as higher levels of…

Re-inscribing Gender in New Modes of Medical Expertise: The Investigator–Coordinator Relationship in the Clinical Trials Industry

PubMed Central

Fisher, Jill A.

2011-01-01

This article analyses the ways in which research coordinators forge professional identities in the highly gendered organizational context of the clinic. Drawing upon qualitative research on the organization of the clinical trials industry (that is, the private sector, for profit auxiliary companies that support pharmaceutical drug studies), this article explores the relationships between predominantly male physician-investigators and female research coordinators and the constitution of medical expertise in pharmaceutical drug development. One finding is that coordinators actively seek to establish relationships with investigators that mirror traditional doctor–nurse relationships, in which the feminized role is subordinated and devalued. Another finding is that the coordinators do, in fact, have profound research expertise that is frequently greater than that of the investigators. The coordinators develop expertise on pharmaceutical products and diseases through their observations of the patterns that occur in patient–participants’ responses to investigational drugs. The article argues, however, that the nature of the relationships between coordinators and investigators renders invisible the coordinators’ expertise. In this context, gender acts as a persistent social structure shaping both coordinators’ and investigators’ perceptions of who can be recognized as having authority and power in the workplace. PMID:21394219

Molecular design of new aggrecanases-2 inhibitors.

PubMed

Shan, Zhi Jie; Zhai, Hong Lin; Huang, Xiao Yan; Li, Li Na; Zhang, Xiao Yun

2013-10-01

Aggrecanases-2 is a very important potential drug target for the treatment of osteoarthritis. In this study, a series of known aggrecanases-2 inhibitors was analyzed by the technologies of three-dimensional quantitative structure-activity relationships (3D-QSAR) and molecular docking. Two 3D-QSAR models, which based on comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) methods, were established. Molecular docking was employed to explore the details of the interaction between inhibitors and aggrecanases-2 protein. According to the analyses for these models, several new potential inhibitors with higher activity predicted were designed, and were supported by the simulation of molecular docking. This work propose the fast and effective approach to design and prediction for new potential inhibitors, and the study of the interaction mechanism provide a better understanding for the inhibitors binding into the target protein, which will be useful for the structure-based drug design and modifications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Family instability and early initiation of sexual activity in Western Kenya.

PubMed

Goldberg, Rachel E

2013-04-01

Epidemiological, economic, and social forces have produced high levels of volatility in family and household structure for young people growing up in sub-Saharan Africa in recent decades. However, scholarship on the family to date has not examined the influence of this family instability on young people's well-being. The current study employs unique life history calendar data from Western Kenya to investigate the relationship between instability in caregiving and early initiation of sexual activity. It draws on a body of work on parental union instability in the United States, and examines new dimensions of family change. Analyses reveal a positive association between transitions in primary caregiver and the likelihood of early sexual debut that is rapidly manifested following caregiver change and persists for a short period. The association is strongest at early ages, and there is a cumulative effect of multiple caregiver changes. The results highlight the importance of studying family stability in sub-Saharan Africa, as distinct from family structure, and for attention to dimensions such as age and recency.

Defining the molecular structure of teixobactin analogues and understanding their role in antibacterial activities.

PubMed

Parmar, Anish; Prior, Stephen H; Iyer, Abhishek; Vincent, Charlotte S; Van Lysebetten, Dorien; Breukink, Eefjan; Madder, Annemieke; Taylor, Edward J; Singh, Ishwar

2017-02-07

The discovery of the highly potent antibiotic teixobactin, which kills the bacteria without any detectable resistance, has stimulated interest in its structure-activity relationship. However, a molecular structure-activity relationship has not been established so far for teixobactin. Moreover, the importance of the individual amino acids in terms of their l/d configuration and their contribution to the molecular structure and biological activity are still unknown. For the first time, we have defined the molecular structure of seven teixobactin analogues through the variation of the d/l configuration of its key residues, namely N-Me-d-Phe, d-Gln, d-allo-Ile and d-Thr. Furthermore, we have established the role of the individual d amino acids and correlated this with the molecular structure and biological activity. Through extensive NMR and structural calculations, including molecular dynamics simulations, we have revealed the residues for maintaining a reasonably unstructured teixobactin which is imperative for biological activity.

Structural complexities in the active layers of organic electronics.

PubMed

Lee, Stephanie S; Loo, Yueh-Lin

2010-01-01

The field of organic electronics has progressed rapidly in recent years. However, understanding the direct structure-function relationships between the morphology in electrically active layers and the performance of devices composed of these materials has proven difficult. The morphology of active layers in organic electronics is inherently complex, with heterogeneities existing across multiple length scales, from subnanometer to micron and millimeter range. A major challenge still facing the organic electronics community is understanding how the morphology across all of the length scales in active layers collectively determines the device performance of organic electronics. In this review we highlight experiments that have contributed to the elucidation of structure-function relationships in organic electronics and also point to areas in which knowledge of such relationships is still lacking. Such knowledge will lead to the ability to select active materials on the basis of their inherent properties for the fabrication of devices with prespecified characteristics.

Structure-activity relationship of karrikin germination stimulants.

PubMed

Flematti, Gavin R; Scaffidi, Adrian; Goddard-Borger, Ethan D; Heath, Charles H; Nelson, David C; Commander, Lucy E; Stick, Robert V; Dixon, Kingsley W; Smith, Steven M; Ghisalberti, Emilio L

2010-08-11

Karrikins (2H-furo[2,3-c]pyran-2-ones) are potent smoke-derived germination promoters for a diverse range of plant species but, to date, their mode of action remains unknown. This paper reports the structure-activity relationship of numerous karrikin analogues to increase understanding of the key structural features of the molecule that are required for biological activity. The results demonstrate that modification at the C5 position is preferred over modification at the C3, C4, or C7 positions for retaining the highest bioactivity.

Computational modeling approaches to quantitative structure-binding kinetics relationships in drug discovery.

PubMed

De Benedetti, Pier G; Fanelli, Francesca

2018-03-21

Simple comparative correlation analyses and quantitative structure-kinetics relationship (QSKR) models highlight the interplay of kinetic rates and binding affinity as an essential feature in drug design and discovery. The choice of the molecular series, and their structural variations, used in QSKR modeling is fundamental to understanding the mechanistic implications of ligand and/or drug-target binding and/or unbinding processes. Here, we discuss the implications of linear correlations between kinetic rates and binding affinity constants and the relevance of the computational approaches to QSKR modeling. Copyright © 2018 Elsevier Ltd. All rights reserved.

Aquatic toxicity of acrylates and methacrylates: quantitative structure-activity relationships based on Kow and LC50

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reinert, K.H.

1987-12-01

Recent EPA scrutiny of acrylate and methacrylate monomers has resulted in restrictive consent orders and Significant New Use Rules under the Toxic Substances Control Act, based on structure-activity relationships using mouse skin painting studies. The concern is centered on human health issues regarding worker and consumer exposure. Environmental issues, such as aquatic toxicity, are still of concern. Understanding the relationships and environmental risks to aquatic organisms may improve the understanding of the potential risks to human health. This study evaluates the quantitative structure-activity relationships from measured log Kow's and log LC50's for Pimephales promelas (fathead minnow) and Carassius auratus (goldfish).more » Scientific support of the current regulations is also addressed. Two monomer classes were designated: acrylates and methacrylates. Spearman rank correlation and linear regression were run. Based on this study, an ecotoxicological difference exists between acrylates and methacrylates. Regulatory activities and scientific study should reflect this difference.« less

Functional Evolution of PLP-dependent Enzymes based on Active-Site Structural Similarities

PubMed Central

Catazaro, Jonathan; Caprez, Adam; Guru, Ashu; Swanson, David; Powers, Robert

2014-01-01

Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5’-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the Comparison of Protein Active Site Structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS. PMID:24920327

Functional evolution of PLP-dependent enzymes based on active-site structural similarities.

PubMed

Catazaro, Jonathan; Caprez, Adam; Guru, Ashu; Swanson, David; Powers, Robert

2014-10-01

Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5'-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the comparison of protein active site structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional-fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS. © 2014 Wiley Periodicals, Inc.

Prediction of enzyme activity with neural network models based on electronic and geometrical features of substrates.

PubMed

Szaleniec, Maciej

2012-01-01

Artificial Neural Networks (ANNs) are introduced as robust and versatile tools in quantitative structure-activity relationship (QSAR) modeling. Their application to the modeling of enzyme reactivity is discussed, along with methodological issues. Methods of input variable selection, optimization of network internal structure, data set division and model validation are discussed. The application of ANNs in the modeling of enzyme activity over the last 20 years is briefly recounted. The discussed methodology is exemplified by the case of ethylbenzene dehydrogenase (EBDH). Intelligent Problem Solver and genetic algorithms are applied for input vector selection, whereas k-means clustering is used to partition the data into training and test cases. The obtained models exhibit high correlation between the predicted and experimental values (R(2) > 0.9). Sensitivity analyses and study of the response curves are used as tools for the physicochemical interpretation of the models in terms of the EBDH reaction mechanism. Neural networks are shown to be a versatile tool for the construction of robust QSAR models that can be applied to a range of aspects important in drug design and the prediction of biological activity.

Beyond Warmth and Conflict: The Developmental Utility of a Boundary Conceptualization of Sibling Relationship Processes

PubMed Central

Bascoe, Sonnette M.; Davies, Patrick T.; Cummings, E. Mark

2012-01-01

Translating relationship boundaries conceptualizations to the study of sibling relationships, this study examined the utility of sibling enmeshment and disengagement in predicting child adjustment difficulties in a sample of 282 mothers and adolescents (Mean age = 12.7 years). Mothers completed a semi-structured interview at the first measurement occasion to assess sibling interaction patterns. Adolescents, mothers, and teachers reported on children’s adjustment problems across two annual waves of assessment. Supporting the incremental utility of a boundary conceptualization of sibling relationships, results of latent difference score analyses indicated that coder ratings of sibling enmeshment and disengagement uniquely predicted greater adolescent adjustment difficulties even after taking into account standard indices of sibling relationship quality (i.e., warmth, conflict) and sibling structural characteristics (e.g., sex). PMID:22862542

Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange.

PubMed

Burns, Michael C; Sun, Qi; Daniels, R Nathan; Camper, DeMarco; Kennedy, J Phillip; Phan, Jason; Olejniczak, Edward T; Lee, Taekyu; Waterson, Alex G; Rossanese, Olivia W; Fesik, Stephen W

2014-03-04

Aberrant activation of the small GTPase Ras by oncogenic mutation or constitutively active upstream receptor tyrosine kinases results in the deregulation of cellular signals governing growth and survival in ∼30% of all human cancers. However, the discovery of potent inhibitors of Ras has been difficult to achieve. Here, we report the identification of small molecules that bind to a unique pocket on the Ras:Son of Sevenless (SOS):Ras complex, increase the rate of SOS-catalyzed nucleotide exchange in vitro, and modulate Ras signaling pathways in cells. X-ray crystallography of Ras:SOS:Ras in complex with these molecules reveals that the compounds bind in a hydrophobic pocket in the CDC25 domain of SOS adjacent to the Switch II region of Ras. The structure-activity relationships exhibited by these compounds can be rationalized on the basis of multiple X-ray cocrystal structures. Mutational analyses confirmed the functional relevance of this binding site and showed it to be essential for compound activity. These molecules increase Ras-GTP levels and disrupt MAPK and PI3K signaling in cells at low micromolar concentrations. These small molecules represent tools to study the acute activation of Ras and highlight a pocket on SOS that may be exploited to modulate Ras signaling.

Higher Media Multi-Tasking Activity Is Associated with Smaller Gray-Matter Density in the Anterior Cingulate Cortex

PubMed Central

Loh, Kep Kee; Kanai, Ryota

2014-01-01

Media multitasking, or the concurrent consumption of multiple media forms, is increasingly prevalent in today’s society and has been associated with negative psychosocial and cognitive impacts. Individuals who engage in heavier media-multitasking are found to perform worse on cognitive control tasks and exhibit more socio-emotional difficulties. However, the neural processes associated with media multi-tasking remain unexplored. The present study investigated relationships between media multitasking activity and brain structure. Research has demonstrated that brain structure can be altered upon prolonged exposure to novel environments and experience. Thus, we expected differential engagements in media multitasking to correlate with brain structure variability. This was confirmed via Voxel-Based Morphometry (VBM) analyses: Individuals with higher Media Multitasking Index (MMI) scores had smaller gray matter density in the anterior cingulate cortex (ACC). Functional connectivity between this ACC region and the precuneus was negatively associated with MMI. Our findings suggest a possible structural correlate for the observed decreased cognitive control performance and socio-emotional regulation in heavy media-multitaskers. While the cross-sectional nature of our study does not allow us to specify the direction of causality, our results brought to light novel associations between individual media multitasking behaviors and ACC structure differences. PMID:25250778

Life Satisfaction and Family Structure among Adolescents in Hong Kong

ERIC Educational Resources Information Center

Kwan, Ying-Keung

2008-01-01

Relationships between family structure and perceived life satisfaction in overall life and five domains of the Brief Multidimensional Students' Life Satisfaction Scale, family life, friendships, school experience, myself, and where I live were examined among 4,502 Chinese adolescent secondary school students in Hong Kong. Bivariate analyses showed…

Multiplicity Control in Structural Equation Modeling: Incorporating Parameter Dependencies

ERIC Educational Resources Information Center

Smith, Carrie E.; Cribbie, Robert A.

2013-01-01

When structural equation modeling (SEM) analyses are conducted, significance tests for all important model relationships (parameters including factor loadings, covariances, etc.) are typically conducted at a specified nominal Type I error rate ([alpha]). Despite the fact that many significance tests are often conducted in SEM, rarely is…

Distributed Structure Searchable Toxicity

EPA Pesticide Factsheets

The Distributed Structure Searchable Toxicity (DSSTox) online resource provides high quality chemical structures and annotations in association with toxicity data. It helps to build a data foundation for improved structure-activity relationships and predictive toxicology. DSSTox publishes summarized chemical activity representations for structure-activity modeling and provides a structure browser. This tool also houses the chemical inventories for the ToxCast and Tox21 projects.

Molecular Modeling Studies of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors through Receptor-Based 3D-QSAR and Molecular Dynamics Simulations.

PubMed

Qian, Haiyan; Chen, Jiongjiong; Pan, Youlu; Chen, Jianzhong

2016-09-19

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a potential target for the treatment of numerous human disorders, such as diabetes, obesity, and metabolic syndrome. In this work, molecular modeling studies combining molecular docking, 3D-QSAR, MESP, MD simulations and free energy calculations were performed on pyridine amides and 1,2,4-triazolopyridines as 11β-HSD1 inhibitors to explore structure-activity relationships and structural requirement for the inhibitory activity. 3D-QSAR models, including CoMFA and CoMSIA, were developed from the conformations obtained by docking strategy. The derived pharmacophoric features were further supported by MESP and Mulliken charge analyses using density functional theory. In addition, MD simulations and free energy calculations were employed to determine the detailed binding process and to compare the binding modes of inhibitors with different bioactivities. The binding free energies calculated by MM/PBSA showed a good correlation with the experimental biological activities. Free energy analyses and per-residue energy decomposition indicated the van der Waals interaction would be the major driving force for the interactions between an inhibitor and 11β-HSD1. These unified results may provide that hydrogen bond interactions with Ser170 and Tyr183 are favorable for enhancing activity. Thr124, Ser170, Tyr177, Tyr183, Val227, and Val231 are the key amino acid residues in the binding pocket. The obtained results are expected to be valuable for the rational design of novel potent 11β-HSD1 inhibitors.

Reliability, Factor Structure, and Associations With Measures of Problem Relationship and Behavior of the Personality Inventory for DSM-5 in a Sample of Italian Community-Dwelling Adolescents.

PubMed

Somma, Antonella; Borroni, Serena; Maffei, Cesare; Giarolli, Laura E; Markon, Kristian E; Krueger, Robert F; Fossati, Andrea

2017-10-01

In order to assess the reliability, factorial validity, and criterion validity of the Personality Inventory for DSM-5 (PID-5) among adolescents, 1,264 Italian high school students were administered the PID-5. Participants were also administered the Questionnaire on Relationships and Substance Use as a criterion measure. In the full sample, McDonald's ω values were adequate for the PID-5 scales (median ω = .85, SD = .06), except for Suspiciousness. However, all PID-5 scales showed average inter-item correlation values in the .20-.55 range. Exploratory structural equation modeling analyses provided moderate support for the a priori model of PID-5 trait scales. Ordinal logistic regression analyses showed that selected PID-5 trait scales predicted a significant, albeit moderate (Cox & Snell R 2 values ranged from .08 to .15, all ps < .001) amount of variance in Questionnaire on Relationships and Substance Use variables.

Structural dynamics and activity of nanocatalysts inside fuel cells by in operando atomic pair distribution studies.

PubMed

Petkov, Valeri; Prasai, Binay; Shan, Shiyao; Ren, Yang; Wu, Jinfang; Cronk, Hannah; Luo, Jin; Zhong, Chuan-Jian

2016-05-19

Here we present the results from a study aimed at clarifying the relationship between the atomic structure and activity of nanocatalysts for chemical reactions driving fuel cells, such as the oxygen reduction reaction (ORR). In particular, using in operando high-energy X-ray diffraction (HE-XRD) we tracked the evolution of the atomic structure and activity of noble metal-transition metal (NM-TM) nanocatalysts for ORR as they function at the cathode of a fully operational proton exchange membrane fuel cell (PEMFC). Experimental HE-XRD data were analysed in terms of atomic pair distribution functions (PDFs) and compared to the current output of the PEMFC, which was also recorded during the experiments. The comparison revealed that under actual operating conditions, NM-TM nanocatalysts can undergo structural changes that differ significantly in both length-scale and dynamics and so can suffer losses in their ORR activity that differ significantly in both character and magnitude. Therefore we argue that strategies for reducing ORR activity losses should implement steps for achieving control not only over the length but also over the time-scale of the structural changes of NM-TM NPs that indeed occur during PEMFC operation. Moreover, we demonstrate how such a control can be achieved and thereby the performance of PEMFCs improved considerably. Last but not least, we argue that the unique capabilities of in operando HE-XRD coupled to atomic PDF analysis to characterize active nanocatalysts inside operating fuel cells both in a time-resolved manner and with atomic level resolution, i.e. in 4D, can serve well the ongoing search for nanocatalysts that deliver more with less platinum.

Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors.

PubMed

Imramovský, Aleš; Pejchal, Vladimír; Štěpánková, Šárka; Vorčáková, Katarína; Jampílek, Josef; Vančo, Ján; Šimůnek, Petr; Královec, Karel; Brůčková, Lenka; Mandíková, Jana; Trejtnar, František

2013-04-01

A series of novel cholinesterase inhibitors based on 2-substituted 6-fluorobenzo[d]thiazole were synthesised and characterised by IR, (1)H, (13)C and (19)F NMR spectroscopy and HRMS. Purity was checked by elemental analyses. The novel carbamates were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The toxicity of the most active compounds was investigated using a standard in vitro test with HepG2 cells, and the ratio between biological activity and toxicity was determined. In addition, the toxicity of the most active compounds was evaluated against MCF7 cells using the xCELLigence system. Structure-activity relationships reflecting the dependence of cholinesterase inhibitors on the lipophilicity of the compounds as well as on the Taft polar and steric substituent constants are discussed. The specific orientation of the inhibitors in the binding site of acetylcholinesterase was determined using molecular docking of the most active compound. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synthesis, antimicrobial activity and advances in structure-activity relationships (SARs) of novel tri-substituted thiazole derivatives.

PubMed

Reddy, Guda Mallikarjuna; Garcia, Jarem Raul; Reddy, Vemulapati Hanuman; de Andrade, Ageo Meier; Camilo, Alexandre; Pontes Ribeiro, Renan Augusto; de Lazaro, Sergio Ricardo

2016-11-10

Trisubstituted thiazoles were synthesized and studied for their antimicrobial activity and supported by theoretical calculations. In addition, MIC, MBC and MFC were also tested. Moreover, the present study was analyzed to scrutinize comprehensive structure-activity relationships. In fact, LUMO orbital energy and orbital orientation was reliable to explain their antibacterial and antifungal assay. Amongst the tested compounds, tri-methyl-substituted thiazole compound showed higher antimicrobial activity and low MIC value due to highest LUMO energy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Analysis of a municipal wastewater treatment plant using a neural network-based pattern analysis

USGS Publications Warehouse

Hong, Y.-S.T.; Rosen, Michael R.; Bhamidimarri, R.

2003-01-01

This paper addresses the problem of how to capture the complex relationships that exist between process variables and to diagnose the dynamic behaviour of a municipal wastewater treatment plant (WTP). Due to the complex biological reaction mechanisms, the highly time-varying, and multivariable aspects of the real WTP, the diagnosis of the WTP are still difficult in practice. The application of intelligent techniques, which can analyse the multi-dimensional process data using a sophisticated visualisation technique, can be useful for analysing and diagnosing the activated-sludge WTP. In this paper, the Kohonen Self-Organising Feature Maps (KSOFM) neural network is applied to analyse the multi-dimensional process data, and to diagnose the inter-relationship of the process variables in a real activated-sludge WTP. By using component planes, some detailed local relationships between the process variables, e.g., responses of the process variables under different operating conditions, as well as the global information is discovered. The operating condition and the inter-relationship among the process variables in the WTP have been diagnosed and extracted by the information obtained from the clustering analysis of the maps. It is concluded that the KSOFM technique provides an effective analysing and diagnosing tool to understand the system behaviour and to extract knowledge contained in multi-dimensional data of a large-scale WTP. ?? 2003 Elsevier Science Ltd. All rights reserved.

Learning global health: a pilot study of an online collaborative intercultural peer group activity involving medical students in Australia and Indonesia.

PubMed

Ambrose, Mark; Murray, Linda; Handoyo, Nicholas E; Tunggal, Deif; Cooling, Nick

2017-01-13

There is limited research to inform effective pedagogies for teaching global health to undergraduate medical students. Theoretically, using a combination of teaching pedagogies typically used in 'international classrooms' may prove to be an effective way of learning global health. This pilot study aimed to explore the experiences of medical students in Australia and Indonesia who participated in a reciprocal intercultural participatory peer e-learning activity (RIPPLE) in global health. Seventy-one third year medical students (49 from Australia and 22 from Indonesia) from the University of Tasmania (Australia) and the University of Nusa Cendana (Indonesia) participated in the RIPPLE activity. Participants were randomly distributed into 11 intercultural 'virtual' groups. The groups collaborated online over two weeks to study a global health topic of their choice, and each group produced a structured research abstract. Pre- and post-RIPPLE questionnaires were used to capture students' experiences of the activity. Descriptive quantitative data were analysed with Microsoft Excel and qualitative data were thematically analysed. Students' motivation to volunteer for this activity included: curiosity about the innovative approach to learning; wanting to expand knowledge of global health; hoping to build personal and professional relationships; and a desire to be part of an intercultural experience. Afer completing the RIPPLE program, participants reported on global health knowledge acquisition, the development of peer relationships, and insight into another culture. Barriers to achieving the learning outcomes associated with RIPPLE included problems with establishing consistent online communication, and effectively managing time to simultaneously complete RIPPLE and other curricula activities. Medical students from both countries found benefits in working together in small virtual groups to complement existing teaching in global health. However, our pilot study demonstrated that while intercultural collaborative peer learning activities like RIPPLE are feasible, they require robust logistical support and an awareness of the need to manage curriculum alignment in ways that facilitate more effective student engagement.

Advances on Semisynthesis, Total Synthesis, and Structure-Activity Relationships of Honokiol and Magnolol Derivatives.

PubMed

Yang, Chun; Zhi, Xiaoyan; Xu, Hui

2016-01-01

Honokiol and magnolol (an isomer of honokiol) are small-molecule polyphenols isolated from the barks of Magnolia officinalis, which have been widely used in traditional Chinese and Japanese medicines. In the last decade, a variety of biological properties of honokiol and magnolol (e.g., anti-oxidativity, antitumor activity, anti-depressant activity, anti-inflammatory activity, neuroprotective activity, anti-diabetic activity, antiviral activity, and antimicrobial activity) have been reported. Meanwhile, certain mechanisms of action of some biological activities were also investigated. Moreover, many analogs of honokiol and magnolol were prepared by structural modification or total synthesis, and some exhibited very potent pharmacological activities with improved water solubility. Therefore, the present review will provide a systematic coverage on recent developments of honokiol and magnolol derivatives in regard to semisynthesis, total synthesis, and structure-activity relationships from 2000 up to now.

An overview of structure-activity relationship studies of curcumin analogs as antioxidant and anti-inflammatory agents.

PubMed

Arshad, Laiba; Haque, Md Areeful; Abbas Bukhari, Syed Nasir; Jantan, Ibrahim

2017-04-01

Curcumin, extracted mainly from Curcuma longa rhizomes, has been reported to possess potent anti-inflammatory and anti-oxidant activities. Although safe at higher doses and exhibiting multiple biological activities, curcumin still has the problem of poor bioavailability which has been an attractive area of research over the last few years. A number of efforts have been made by modifying structural features of curcumin. This review highlights the structurally modified and more stable newly synthesized curcumin analogs that have been screened against antioxidant and anti-inflammatory activities. Also the structure-activity relationship to gain insight into future guidelines for scheming new compounds has been discussed, and further these analogs being more stable may serve as promising agents for use in different pathological conditions.

Physical activity and quality of life in long-term hospitalized patients with severe mental illness: a cross-sectional study.

PubMed

Deenik, Jeroen; Kruisdijk, Frank; Tenback, Diederik; Braakman-Jansen, Annemarie; Taal, Erik; Hopman-Rock, Marijke; Beekman, Aartjan; Tak, Erwin; Hendriksen, Ingrid; van Harten, Peter

2017-08-18

Increasing physical activity in patients with severe mental illness is believed to have positive effects on physical health, psychiatric symptoms and as well quality of life. Till now, little is known about the relationship between physical activity and quality of life in long-term hospitalized patients with severe mental illness and knowledge of the determinants of behavioural change is lacking. The purpose of this study was to elucidate the relationship between objectively measured physical activity and quality of life, and explore modifiable psychological determinants of change in physical activity in long-term hospitalized patients with severe mental illness. In 184 inpatients, physical activity was measured using an accelerometer (ActiGraph GTX+). Quality of life was assessed by EuroQol-5D and WHOQol-Bref. Attitude and perceived self-efficacy towards physical activity were collected using the Physical Activity Enjoyment Scale and the Multidimensional Self Efficacy Questionnaire, respectively. Patient and disease characteristics were derived retrospectively from electronic patient records. Associations and potential predictors were analysed using hierarchical regression. Physical activity was positively related with and a predictor of all quality of life outcomes except on the environmental domain, independent of patient and disease characteristics. However, non-linear relationships showed that most improvement in quality of life lies in the change from sedentary to light activity. Attitude and self-efficacy were not related to physical activity. Physical activity is positively associated with quality of life, especially for patients in the lower spectrum of physical activity. An association between attitude and self-efficacy and physical activity was absent. Therefore, results suggest the need of alternative, more integrated and (peer-)supported interventions to structurally improve physical activity in this inpatient population. Slight changes from sedentary behaviour to physical activity may be enough to improve quality of life.

3D-QSAR and molecular docking studies on designing inhibitors of the hepatitis C virus NS5B polymerase

NASA Astrophysics Data System (ADS)

Li, Wenlian; Si, Hongzong; Li, Yang; Ge, Cuizhu; Song, Fucheng; Ma, Xiuting; Duan, Yunbo; Zhai, Honglin

2016-08-01

Viral hepatitis C infection is one of the main causes of the hepatitis after blood transfusion and hepatitis C virus (HCV) infection is a global health threat. The HCV NS5B polymerase, an RNA dependent RNA polymerase (RdRp) and an essential role in the replication of the virus, has no functional equivalent in mammalian cells. So the research and development of efficient NS5B polymerase inhibitors provides a great strategy for antiviral therapy against HCV. A combined three-dimensional quantitative structure-activity relationship (QSAR) modeling was accomplished to profoundly understand the structure-activity correlation of a train of indole-based inhibitors of the HCV NS5B polymerase to against HCV. A comparative molecular similarity indices analysis (COMSIA) model as the foundation of the maximum common substructure alignment was developed. The optimum model exhibited statistically significant results: the cross-validated correlation coefficient q2 was 0.627 and non-cross-validated r2 value was 0.943. In addition, the results of internal validations of bootstrapping and Y-randomization confirmed the rationality and good predictive ability of the model, as well as external validation (the external predictive correlation coefficient rext2 = 0.629). The information obtained from the COMSIA contour maps enables the interpretation of their structure-activity relationship. Furthermore, the molecular docking study of the compounds for 3TYV as the protein target revealed important interactions between active compounds and amino acids, and several new potential inhibitors with higher activity predicted were designed basis on our analyses and supported by the simulation of molecular docking. Meanwhile, the OSIRIS Property Explorer was introduced to help select more satisfactory compounds. The satisfactory results from this study may lay a reliable theoretical base for drug development of hepatitis C virus NS5B polymerase inhibitors.

The Relationship between Parental Literacy Involvement, Socio-Economic Status and Reading Literacy

ERIC Educational Resources Information Center

Hemmerechts, Kenneth; Agirdag, Orhan; Kavadias, Dimokritos

2017-01-01

In this article, we explore the relationship between parental literacy activities with the child, socio-economic status (SES) and reading literacy. We draw upon the Bourdieusian theory of habitus development to explore this relationship. Multilevel analyses of a survey of 43,870 pupils (with an average age of 10 years) in 10 Western European…

Openness as a predictor of political orientation and conventional and unconventional political activism in Western and Eastern Europe.

PubMed

Roets, Arne; Cornelis, Ilse; Van Hiel, Alain

2014-01-01

This study provides a comprehensive investigation of the relationship between Openness and political orientation and activism in Europe. Analyses were conducted on the 4 waves of the European Social Survey, including large representative samples in up to 26 European countries (total N > 175,000). In line with previous studies, a robust, positive relationship between Openness and left-wing political orientation was obtained in Western Europe. However, in Eastern Europe, the relationship between Openness and political orientation was weaker, and reversed in 3 out of 4 waves. Moreover, Openness yielded significant positive relationships with unconventional activism and to a lesser degree with conventional activism. The magnitude of the relationship between Openness and activism was dependent on political orientation and region. Stronger associations between Openness and activism were found for those having a left-wing orientation in Western Europe, whereas in Eastern Europe, Openness was somewhat stronger related to activism for those having a right-wing orientation. In the discussion we elaborate on the role of the geopolitical context in the relationship between Openness and political variables.

Clustered multistate models with observation level random effects, mover-stayer effects and dynamic covariates: modelling transition intensities and sojourn times in a study of psoriatic arthritis.

PubMed

Yiu, Sean; Farewell, Vernon T; Tom, Brian D M

2018-02-01

In psoriatic arthritis, it is important to understand the joint activity (represented by swelling and pain) and damage processes because both are related to severe physical disability. The paper aims to provide a comprehensive investigation into both processes occurring over time, in particular their relationship, by specifying a joint multistate model at the individual hand joint level, which also accounts for many of their important features. As there are multiple hand joints, such an analysis will be based on the use of clustered multistate models. Here we consider an observation level random-effects structure with dynamic covariates and allow for the possibility that a subpopulation of patients is at minimal risk of damage. Such an analysis is found to provide further understanding of the activity-damage relationship beyond that provided by previous analyses. Consideration is also given to the modelling of mean sojourn times and jump probabilities. In particular, a novel model parameterization which allows easily interpretable covariate effects to act on these quantities is proposed.

40 CFR 132.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Species Act. Existing Great Lakes discharger is any building, structure, facility, or installation from... discharger is any building, structure, facility, or installation from which there is or may be a “discharge... monitoring of the contaminant. Quantitative structure activity relationship (QSAR) or structure activity...

Statistical properties of short-selling and margin-trading activities and their impacts on returns in the Chinese stock markets

NASA Astrophysics Data System (ADS)

Gao, Yan; Gao, Yao

2015-11-01

We investigate the collective behaviors of short-selling and margin-trading between Chinese stocks and their impacts on the co-movements of stock returns by cross-correlation and partial correlation analyses. We find that the collective behaviors of margin-trading are largely attributed to the index cohesive force, while those of short-selling are mainly due to some direct interactions between stocks. Interestingly, the dominant role the finance industry plays in the collective behaviors of short-selling could make it more important in affecting the co-movement structure of stock returns by strengthening its relationship with the market index. By detecting the volume-return and volume-volatility relationships, we find that the investors of the two leverage activities are positively triggered by individual stock volatility first, and next, at the return level, margin-buyers show trend-following properties, while short-sellers are probably informative traders who trade on the information impulse of specific firms. However, the return predictability of the two leverage trading activities and their impacts on stock volatility are not significant. Moreover, both tails of the cumulative distributions of the two leverage trading activities are found following the stretched exponential law better than the power-law.

The Moderating Effect of Health-Improving Workplace Environment on Promoting Physical Activity in White-Collar Employees: A Multi-Site Longitudinal Study Using Multi-Level Structural Equation Modeling.

PubMed

Watanabe, Kazuhiro; Otsuka, Yasumasa; Shimazu, Akihito; Kawakami, Norito

2016-02-01

This longitudinal study aimed to investigate the moderating effect of health-improving workplace environment on relationships between physical activity, self-efficacy, and psychological distress. Data were collected from 16 worksites and 129 employees at two time-points. Health-improving workplace environment was measured using the Japanese version of the Environmental Assessment Tool. Physical activity, self-efficacy, and psychological distress were also measured. Multi-level structural equation modeling was used to investigate the moderating effect of health-improving workplace environment on relationships between psychological distress, self-efficacy, and physical activity. Psychological distress was negatively associated with physical activity via low self-efficacy. Physical activity was negatively related to psychological distress. Physical activity/fitness facilities in the work environment exaggerated the positive relationship between self-efficacy and physical activity. Physical activity/fitness facilities in the workplace may promote employees' physical activity.

Quantitative structure-activity relationship models that stand the test of time.

PubMed

Davis, Andrew M; Wood, David J

2013-04-01

The pharmaceutical industry is in a period of intense change. While this has many drivers, attrition through the development process continues to be an important pressure. The emerging definitions of "compound quality" that are based on retrospective analyses of developmental attrition have highlighted a new direction for medicinal chemistry and the paradigm of "quality at the point of design". The time has come for retrospective analyses to catalyze prospective action. Quality at the point of design places pressure on the quality of our predictive models. Empirical QSAR models when built with care provide true predictive control, but their accuracy and precision can be improved. Here we describe AstraZeneca's experience of automation in QSAR model building and validation, and how an informatics system can provide a step-change in predictive power to project design teams, if they choose to use it.

Relationship between Type of Trauma Exposure and Posttraumatic Stress Disorder among Urban Children and Adolescents

ERIC Educational Resources Information Center

Luthra, Rohini; Abramovitz, Robert; Greenberg, Rick; Schoor, Alan; Newcorn, Jeffrey; Schmeidler, James; Levine, Paul; Nomura, Yoko; Chemtob, Claude M.

2009-01-01

This study examines the association between trauma exposure and posttraumatic stress disorder (PTSD) among 157 help-seeking children (aged 8-17). Structured clinical interviews are carried out, and linear and logistic regression analyses are conducted to examine the relationship between PTSD and type of trauma exposure controlling for age, gender,…

The relationship between hope and patient activation in consumers with schizophrenia: Results from longitudinal analyses.

PubMed

Oles, Sylwia K; Fukui, Sadaaki; Rand, Kevin L; Salyers, Michelle P

2015-08-30

Hope (goal-directed thinking) and patient activation (knowledge and skills to manage one's illness) are both important in managing chronic conditions like schizophrenia. The relationship between hope and patient activation has not been clearly defined. However, hope may be viewed as a foundational, motivating factor that can lead to greater involvement in care and feelings of efficacy. The purpose of the present study was to understand the prospective relationship between hope and patient activation in a sample of adults with schizophrenia (N=118). This study was a secondary data analysis from a study on Illness Management and Recovery (IMR) - a curriculum-based approach to schizophrenia self-management. Data were collected at baseline (prior to any intervention), and at 9 and 18-month follow-up. As predicted, hope and patient activation were significantly related with each other, showing large positive concurrent correlations. Demographics and background characteristics were not significantly related to patient activation or hope. Longitudinal analyses found no specific directional effect, yet suggested that hope and patient activation mutually influence each other over time. Our findings add flexibility in designing recovery-based interventions - fostering hope may not be a pre-requisite for activating consumers to be more involved in their own care. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Individual structural differences in left inferior parietal area are associated with schoolchildrens' arithmetic scores

PubMed Central

Li, Yongxin; Hu, Yuzheng; Wang, Yunqi; Weng, Jian; Chen, Feiyan

2013-01-01

Arithmetic skill is of critical importance for academic achievement, professional success and everyday life, and childhood is the key period to acquire this skill. Neuroimaging studies have identified that left parietal regions are a key neural substrate for representing arithmetic skill. Although the relationship between functional brain activity in left parietal regions and arithmetic skill has been studied in detail, it remains unclear about the relationship between arithmetic achievement and structural properties in left inferior parietal area in schoolchildren. The current study employed a combination of voxel-based morphometry (VBM) for high-resolution T1-weighted images and fiber tracking on diffusion tensor imaging (DTI) to examine the relationship between structural properties in the inferior parietal area and arithmetic achievement in 10-year-old schoolchildren. VBM of the T1-weighted images revealed that individual differences in arithmetic scores were significantly and positively correlated with the gray matter (GM) volume in the left intraparietal sulcus (IPS). Fiber tracking analysis revealed that the forceps major, left superior longitudinal fasciculus (SLF), bilateral inferior longitudinal fasciculus (ILF) and inferior fronto-occipital fasciculus (IFOF) were the primary pathways connecting the left IPS with other brain areas. Furthermore, the regression analysis of the probabilistic pathways revealed a significant and positive correlation between the fractional anisotropy (FA) values in the left SLF, ILF and bilateral IFOF and arithmetic scores. The brain structure-behavior correlation analyses indicated that the GM volumes in the left IPS and the FA values in the tract pathways connecting left IPS were both related to children's arithmetic achievement. The present findings provide evidence that individual structural differences in the left IPS are associated with arithmetic scores in schoolchildren. PMID:24367320

Materials Informatics: Statistical Modeling in Material Science.

PubMed

Yosipof, Abraham; Shimanovich, Klimentiy; Senderowitz, Hanoch

2016-12-01

Material informatics is engaged with the application of informatic principles to materials science in order to assist in the discovery and development of new materials. Central to the field is the application of data mining techniques and in particular machine learning approaches, often referred to as Quantitative Structure Activity Relationship (QSAR) modeling, to derive predictive models for a variety of materials-related "activities". Such models can accelerate the development of new materials with favorable properties and provide insight into the factors governing these properties. Here we provide a comparison between medicinal chemistry/drug design and materials-related QSAR modeling and highlight the importance of developing new, materials-specific descriptors. We survey some of the most recent QSAR models developed in materials science with focus on energetic materials and on solar cells. Finally we present new examples of material-informatic analyses of solar cells libraries produced from metal oxides using combinatorial material synthesis. Different analyses lead to interesting physical insights as well as to the design of new cells with potentially improved photovoltaic parameters. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Patients' experiences of using a smartphone application to increase physical activity: the SMART MOVE qualitative study in primary care.

PubMed

Casey, Monica; Hayes, Patrick S; Glynn, Fergus; OLaighin, Gearóid; Heaney, David; Murphy, Andrew W; Glynn, Liam G

2014-08-01

Regular physical activity is known to help prevent and treat numerous non-communicable diseases. Smartphone applications (apps) have been shown to increase physical activity in primary care but little is known regarding the views of patients using such technology or how such technology may change behaviour. To explore patients' views and experiences of using smartphones to promote physical activity in primary care. This qualitative study was embedded within the SMART MOVE randomised controlled trial, which used an app (Accupedo-Pro Pedometer) to promote physical activity in three primary care centres in the west of Ireland. Taped and transcribed semi-structured interviews with a purposeful sample of 12 participants formed the basis of the investigation. Framework analysis was used to analyse the data. Four themes emerged from the analysis: transforming relationships with exercise; persuasive technology tools; usability; and the cascade effect. The app appeared to facilitate a sequential and synergistic process of positive change, which occurred in the relationship between the participants and their exercise behaviour; the study has termed this the 'Know-Check-Move' effect. Usability challenges included increased battery consumption and adjusting to carrying the smartphone on their person. There was also evidence of a cascade effect involving the families and communities of participants. Notwithstanding technological challenges, an app has the potential to positively transform, in a unique way, participants' relationships with exercise. Such interventions can also have an associated cascade effect within their wider families and communities. © British Journal of General Practice 2014.

Patients’ experiences of using a smartphone application to increase physical activity: the SMART MOVE qualitative study in primary care

PubMed Central

Casey, Monica; Hayes, Patrick S; Glynn, Fergus; ÓLaighin, Gearóid; Heaney, David; Murphy, Andrew W; Glynn, Liam G

2014-01-01

Background Regular physical activity is known to help prevent and treat numerous non-communicable diseases. Smartphone applications (apps) have been shown to increase physical activity in primary care but little is known regarding the views of patients using such technology or how such technology may change behaviour. Aim To explore patients’ views and experiences of using smartphones to promote physical activity in primary care. Design and setting This qualitative study was embedded within the SMART MOVE randomised controlled trial, which used an app (Accupedo-Pro Pedometer) to promote physical activity in three primary care centres in the west of Ireland. Method Taped and transcribed semi-structured interviews with a purposeful sample of 12 participants formed the basis of the investigation. Framework analysis was used to analyse the data. Results Four themes emerged from the analysis: transforming relationships with exercise; persuasive technology tools; usability; and the cascade effect. The app appeared to facilitate a sequential and synergistic process of positive change, which occurred in the relationship between the participants and their exercise behaviour; the study has termed this the ‘Know-Check-Move’ effect. Usability challenges included increased battery consumption and adjusting to carrying the smartphone on their person. There was also evidence of a cascade effect involving the families and communities of participants. Conclusion Notwithstanding technological challenges, an app has the potential to positively transform, in a unique way, participants’ relationships with exercise. Such interventions can also have an associated cascade effect within their wider families and communities. PMID:25071063

Analysing the Relationship between the Problem-Solving-Related Beliefs, Competence and Teaching of Three Cypriot Primary Teachers

ERIC Educational Resources Information Center

Andrews, Paul; Xenofontos, Constantinos

2015-01-01

In this article, we analyse the problem-solving-related beliefs, competence and classroom practice of three Cypriot upper-primary teachers. Data derived from semi-structured interviews focused on teachers' beliefs about the nature of mathematical problems, problem-solving, and their competence as both problem-solvers and teachers of…

How Can the Relationship between Argumentation and Proof Be Analysed?

ERIC Educational Resources Information Center

Pedemonte, Bettina

2007-01-01

The paper presents a characterisation about argumentation and proof in mathematics. On the basis of contemporary linguistic theories, the hypothesis that proof is a special case of argumentation is put forward and Toulmin's model is proposed as a methodological tool to compare them. This model can be used to detect and analyse the structure of an…

The relationship between self-efficacy for behaviors that promote healthy weight and clinical indicators of adiposity in a sample of early adolescents.

PubMed

Steele, Michael M; Daratha, Kenn B; Bindler, Ruth C; Power, Thomas G

2011-12-01

Examine the relationship between self-efficacy and various measures of adiposity in a sample of teens. A total of 132 teens were selected from schools participating in an existing research study titled Teen Eating and Activity Mentoring in Schools (TEAMS). Teens completed demographic questionnaires and healthy eating-specific and physical activity-specific measures of self-efficacy. Waist circumference (WC), triceps skinfold thickness (TSF), and body mass index (BMI) percentile scores were also obtained. Regression analyses indicated that healthy eating-specific and physical activity-specific measures of self-efficacy predicted WC and TSF. ANOVA revealed significant differences in healthy eating-specific self-efficacy levels between students of recommended weight and overweight/obese status. Supplemental analyses showed significant negative relationships between a student's ideal BMI ratio and self-efficacy. Because self-efficacy may be amenable to change, these findings could inform future efforts aimed at increasing behaviors that promote healthy weight status among early adolescents.

Structure-anti-MRSA activity relationship of macrocyclic bis(bibenzyl) derivatives.

PubMed

Sawada, Hiromi; Onoda, Kenji; Morita, Daichi; Ishitsubo, Erika; Matsuno, Kenji; Tokiwa, Hiroaki; Kuroda, Teruo; Miyachi, Hiroyuki

2013-12-15

We synthesized a series of macrocyclic bis(bibenzyl) derivatives, including riccardin-, isoplagiochin- and marchantin-class structures, and evaluated their antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). The structure-activity relationships and the results of molecular dynamics simulations indicated that bis(bibenzyl)s with potent anti-MRSA activity commonly have a 4-hydroxyl group at the D-benzene ring and a 2-hydroxyl group at the C-benzene ring in the hydrophilic part of the molecule, and an unsubstituted phenoxyphenyl group in the hydrophobic part of the molecule containing the A-B-benzene rings. Pharmacological characterization of the bis(bibenzyl) derivatives and 2-phenoxyphenol fragment 25, previously proposed as the minimum structure of riccardin C 1 for anti-MRSA activity, indicated that they have different action mechanisms: the bis(bibenzyl)s are bactericidal, while 25 is bacteriostatic, showing only weak bactericidal activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

TOWARDS REFINED USE OF TOXICITY DATA IN ...

EPA Pesticide Factsheets

In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants. In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants.

Structure-activity relationships of rationally designed AMACR 1A inhibitors.

PubMed

Yevglevskis, Maksims; Lee, Guat L; Nathubhai, Amit; Petrova, Yoana D; James, Tony D; Threadgill, Michael D; Woodman, Timothy J; Lloyd, Matthew D

2018-04-30

α-Methylacyl-CoA racemase (AMACR; P504S) is a promising novel drug target for prostate and other cancers. Assaying enzyme activity is difficult due to the reversibility of the 'racemisation' reaction and the difficulties in the separation of epimeric products; consequently few inhibitors have been described and no structure-activity relationship study has been performed. This paper describes the first structure-activity relationship study, in which a series of 23 known and potential rational AMACR inhibitors were evaluated. AMACR was potently inhibited (IC 50  = 400-750 nM) by ibuprofenoyl-CoA and derivatives. Potency was positively correlated with inhibitor lipophilicity. AMACR was also inhibited by straight-chain and branched-chain acyl-CoA esters, with potency positively correlating with inhibitor lipophilicity. 2-Methyldecanoyl-CoAs were ca. 3-fold more potent inhibitors than decanoyl-CoA, demonstrating the importance of the 2-methyl group for effective inhibition. Elimination substrates and compounds with modified acyl-CoA cores were also investigated, and shown to be potent inhibitors. These results are the first to demonstrate structure-activity relationships of rational AMACR inhibitors and that potency can be predicted by acyl-CoA lipophilicity. The study also demonstrates the utility of the colorimetric assay for thorough inhibitor characterisation. Copyright © 2018 Elsevier Inc. All rights reserved.

The influence of relationships on personhood in dementia care: a qualitative, hermeneutic study

PubMed Central

2013-01-01

Background In dementia personhood can be understood as increasingly concealed rather than lost. The sense of being a person evolves in relationships with others. The aim of this study was to increase the understanding of the nature and quality of relationships between persons with dementia, family carers and professional caregivers and how these relationships influenced personhood in people with dementia. Methods This Norwegian study had a qualitative hermeneutical design based on ten cases. Each case consisted of a triad: the person with dementia, the family carer and the professional caregiver. Inclusion criteria for persons with dementia were (1) 67 years or older (2) diagnosed with dementia (3) Clinical Dementia Rating score 2 ie. moderate dementia (4) able to communicate verbally. A semi-structured interview guide was used in interviews with family carers and professional caregivers. Field notes were written after participant observation of interactions between persons with dementia and professional caregivers during morning care or activities at a day care centre. Data were analysed in two steps: (1) inductive analysis with an interpretive approach and (2) deductive analysis, applying a theoretical framework for person-centred care. Results Relationships that sustained personhood were close emotional bonds between family carers and persons with dementia and professional relationships between caregivers and persons with dementia. Relationships that diminished personhood were task-centred relationships and reluctant helping relationships between family carers and persons with dementia and unprofessional relationships between caregivers and persons with dementia. Conclusions A broad range of relationships was identified. Understanding the complex nature and quality of these relationships added insight as to how they influenced the provision of care and the personhood of persons with dementia. Personhood was not only bestowed upon them by family carers and professional caregivers; they themselves were active agents who gained a sense of self by what they said and did. PMID:24359589

Organic Analysis in Miller Range 090657 and Buckley Island 10933 CR2 Chondrites: Part 1 In-Situ Observation of Carbonaceous Material

NASA Technical Reports Server (NTRS)

Cao, T.; Nakamura-Messenger, K.; Berger, E. L.; Burton, A. S.; Messenger, S.; Clemett, S. J.

2016-01-01

Primitive carbonaceous chondrites contain a wide variety of organic material, ranging from soluble discrete molecules to insoluble unstructured kerogen-like component as well as structured nano-globules of macromolecular carbon. The relationship between the soluble organic molecules, macromolecular organic material, and host minerals are poorly understood. Due to the differences in extractability of soluble and insoluble organic materials, the analysis methods for each differ and are often performed independently. The combination of soluble and insoluble analyses, when performed concurrently, can provide a wider understanding on spatial distribution, and elemental, structural and isotopic composition of organic material in primitive meteorites. Furthermore, they can provide broader perspective on how extraterrestrial organic ma-terials potentially contributed to the synthesis of life's essential compounds such as amino acids, sugar acids, activated phosphates and nucleobases.

Structure-Activity Relationships for in vitro Diuretic Activity of CAP2b in the Housefly

DTIC Science & Technology

2007-01-01

p e p t i d e s 2 8 ( 2 0 0 7 ) 5 7 – 6 1Structure-activity relationships for in vitro diuretic activity of CAP2b in the housefly Ronald J. Nachman a...the peptide Manse-CAP2b (pELYAFPRV-NH2) were assayed for diuretic activity on Malpighian tubules of the housefly Musca domestica (M. domestica). The C...required the C-terminal heptapeptide, which was equipotent with the most active of the native housefly CAP2b peptides. Replacement of Arg7 and Val8 with

Barriers to Screening and Possibilities for Active Detection of Family Medicine Attendees Exposed to Intimate Partner Violence.

PubMed

Kopčavar Guček, Nena; Petek, Davorina; Švab, Igor; Selič, Polona

2016-03-01

In 1996 the World Health Organization declared intimate partner violence (IPV) the most important public health problem. Meta-analyses in 2013 showed every third female globally had been a victim of violence. Experts find screening controversial; family medicine is the preferred environment for identifying victims of violence, but barriers on both sides prevent patients from discussing it with doctors. In July 2014, a qualitative study was performed through semi-structured interviews with ten family doctors of different ages and gender, working in rural or urban environments. Sound recordings of the interviews were transcribed, and the record verified. The data were interpreted using content analysis. A coding scheme was developed and later verified and analysed by two independent researchers. The text of the interviews was analysed according to the coding scheme. Two coding schemes were developed: one for screening, and the other for the active detection of IPV. The main themes emerging as barriers to screening were lack of time, staff turnover, inadequate finance, ignorance of a clear definition, poor commitment to screening, obligatory follow-up, risk of deterioration of the doctor-patient relationship, and insincerity on the part of the patient. Additionally, cultural aspects of violence, uncertainty/ helplessness, fear, lack of competence and qualifications, autonomy/negative experience, and passive role/stigma/ fear on the part of the patients were barriers to active detection. All the participating doctors had had previous experience with active detection of IPV and were aware of its importance. Due to several barriers to screening for violence they preferred active detection.

Barriers to Screening and Possibilities for Active Detection of Family Medicine Attendees Exposed to Intimate Partner Violence

PubMed Central

KOPČAVAR GUČEK, Nena; PETEK, Davorina; ŠVAB, Igor; SELIČ, Polona

2016-01-01

Introduction In 1996 the World Health Organization declared intimate partner violence (IPV) the most important public health problem. Meta-analyses in 2013 showed every third female globally had been a victim of violence. Experts find screening controversial; family medicine is the preferred environment for identifying victims of violence, but barriers on both sides prevent patients from discussing it with doctors. Methods In July 2014, a qualitative study was performed through semi-structured interviews with ten family doctors of different ages and gender, working in rural or urban environments. Sound recordings of the interviews were transcribed, and the record verified. The data were interpreted using content analysis. A coding scheme was developed and later verified and analysed by two independent researchers. The text of the interviews was analysed according to the coding scheme. Results Two coding schemes were developed: one for screening, and the other for the active detection of IPV. The main themes emerging as barriers to screening were lack of time, staff turnover, inadequate finance, ignorance of a clear definition, poor commitment to screening, obligatory follow-up, risk of deterioration of the doctor-patient relationship, and insincerity on the part of the patient. Additionally, cultural aspects of violence, uncertainty/ helplessness, fear, lack of competence and qualifications, autonomy/negative experience, and passive role/stigma/ fear on the part of the patients were barriers to active detection. Conclusion All the participating doctors had had previous experience with active detection of IPV and were aware of its importance. Due to several barriers to screening for violence they preferred active detection. PMID:27647084

Identification of a flavonoid C-glycoside as potent antioxidant.

PubMed

Wen, Lingrong; Zhao, Yupeng; Jiang, Yueming; Yu, Limei; Zeng, Xiaofang; Yang, Jiali; Tian, Miaomiao; Liu, Huiling; Yang, Bao

2017-09-01

Flavonoids have been documented to have good antioxidant activities in vitro. However, reports on the cellular antioxidant activities of flavonoid C-glycosides are very limited. In this work, an apigenin C-glycoside was purified from Artocarpus heterophyllus by column chromatography and was identified to be 2″-O-β-D-xylosylvitexin by nuclear magnetic resonance spectroscopy. The cellular antioxidant activity and anticancer activity of 2″-O-β-D-xylosylvitexin were evaluated for the first time. The quantitative structure-activity relationship was analysed by molecular modeling. Apigenin presented an unexpected cellular antioxidation behaviour. It had an antioxidant activity at low concentration and a prooxidant activity at high concentration, whereas 2″-O-β-D-xylosylvitexin showed a dose-dependent cellular antioxidant activity. It indicated that C-glycosidation improved the cellular antioxidation performance of apigenin and eliminated the prooxidant effect. The ortho-dihydroxyl at C-3'/C-4' and C-3 hydroxyl in the flavonoid skeleton play important roles in the antioxidation behaviour. The cell proliferation assay revealed a low cytotoxicity of 2″-O-β-D-xylosylvitexin. Copyright © 2017 Elsevier Inc. All rights reserved.

Structure-Activity Relationships of 33 Piperidines as Toxicants Against Female Adults of Aedes aegypti (Diptera: Culicidae)

DTIC Science & Technology

2007-03-01

alkaloid piperine and 12 syn- thetic derivatives have been evaluated against epimas- tigote and amastigote forms of the protozoan parasite Trypanosoma...O. Kris- tiansen, P. Maienfisch, A. Pascual, and A. Rindlisbacher. 2001. Synthesis and structure-activity relationships of benzophenone hydrazone...Am. J. Trop. Med. Hyg. 22: 124Ð 129. Creemer, L. C., H. A. Kirst, J.W. Paschal, and T. V.Worden. 2000. Synthesis and insecticidal activity of spinosyn

Adolescents' physical activities and peer norms: the mediating role of self-efficacy.

PubMed

Lu, Frank J H; Lin, Ju-Han; Hsu, Ya-Wen; Chou, Chien-Chih; Wang, Erica T W; Yeh, Li-Chin

2014-04-01

The purpose of the present study was to examine the relations among adolescents' self-efficacy and social norms, and physical activity and whether self-efficacy mediated the relationship between social norms and physical activity. 400 junior high school students (202 boys, 198 girls, 2 not identified; M age = 15.3yr., SD = 0.6) completed a demographic questionnaire, the International Physical Activity Questionnaire (IPAQ), the Perceived Self-Efficacy in Physical Activity Scale, and the Physical Activity Social Norms Scale. Regression analyses indicated that both self-efficacy and social norms predicted physical activity. Self-efficacy fully mediated the relationship between peer norms and physical activity for boys but partially mediated the relationship for girls. An application of the results may be to foster self-efficacy and peer norms as a motivational strategy for supporting increased physical activity.

GirlPOWER! Strengthening Mentoring Relationships through a Structured, Gender-Specific Program

ERIC Educational Resources Information Center

Pryce, Julia M.; Silverthorn, Naida; Sanchez, Bernadette; DuBois, David L.

2010-01-01

The authors examine GirlPOWER! an innovative program that uses structure and group-based activities to enhance one-to-one mentoring relationships for young adolescent girls from the perspective of the focus, purpose, and authorship dimensions of mentoring relationships that Karcher and Nakkula described. The discussion draws on several sources of…

Barriers and facilitators to integrating care: experiences from the English Integrated Care Pilots

PubMed Central

Ling, Tom; Brereton, Laura; Conklin, Annalijn; Newbould, Jennifer; Roland, Martin

2012-01-01

Background: In 2008, the English Department of Health appointed 16 ‘Integrated Care Pilots’ which used a range of approaches to provide better integrated care. We report qualitative analyses from a three-year multi-method evaluation to identify barriers and facilitators to successful integration of care. Theory and methods: Data were analysed from transcripts of 213 in-depth staff interviews, and from semi-structured questionnaires (the ‘Living Document’) completed by staff in pilot sites at six points over a two-year period. Emerging findings were therefore built from ‘bottom up’ and grounded in the data. However, we were then interested in how these findings compared and contrasted with more generic analyses. Therefore after our analyses were complete we then systematically compared and contrasted the findings with the analysis of barriers and facilitators to quality improvement identified in a systematic review by Kaplan et al. (2010) and the analysis of more micro-level shapers of behaviour found in Normalisation Process Theory (May et al. 2007). Neither of these approaches claims to be full blown theories but both claim to provide mid-range theoretical arguments which may be used to structure existing data and which can be undercut or reinforced by new data. Results and discussion: Many barriers and facilitators to integrating care are those of any large-scale organisational change. These include issues relating to leadership, organisational culture, information technology, physician involvement, and availability of resources. However, activities which appear particularly important for delivering integrated care include personal relationships between leaders in different organisations, the scale of planned activities, governance and finance arrangements, support for staff in new roles, and organisational and staff stability. We illustrate our analyses with a ‘routemap’ which identifies questions that providers may wish to consider when planning interventions to improve the integration of care. PMID:23593044

Connectivity and functional profiling of abnormal brain structures in pedophilia

PubMed Central

Poeppl, Timm B.; Eickhoff, Simon B.; Fox, Peter T.; Laird, Angela R.; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

2015-01-01

Despite its 0.5–1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multi-modal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

Connectivity and functional profiling of abnormal brain structures in pedophilia.

PubMed

Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

2015-06-01

Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. © 2015 Wiley Periodicals, Inc.

Inactivation and unfolding of protein tyrosine phosphatase from Thermus thermophilus HB27 during urea and guanidine hydrochloride denaturation.

PubMed

Wang, Yejing; He, Huawei; Liu, Lina; Gao, Chunyan; Xu, Shui; Zhao, Ping; Xia, Qingyou

2014-01-01

The effects of urea and guanidine hydrochloride (GdnHCl) on the activity, conformation and unfolding process of protein tyrosine phosphatase (PTPase), a thermostable low molecular weight protein from Thermus thermophilus HB27, have been studied. Enzymatic activity assays showed both urea and GdnHCl resulted in the inactivation of PTPase in a concentration and time-dependent manner. Inactivation kinetics analysis suggested that the inactivation of PTPase induced by urea and GdnHCl were both monophasic and reversible processes, and the effects of urea and GdnHCl on PTPase were similar to that of mixed-type reversible inhibitors. Far-ultraviolet (UV) circular dichroism (CD), Tryptophan and 1-anilinonaphthalene -8-sulfonic acid (ANS) fluorescence spectral analyses indicated the existence of a partially active and an inactive molten globule-like intermediate during the unfolding processes induced by urea and GdnHCl, respectively. Based on the sequence alignment and the homolog Tt1001 protein structure, we discussed the possible conformational transitions of PTPase induced by urea and GdnHCl and compared the conformations of these unfolding intermediates with the transient states in bovine PTPase and its complex structures in detail. Our results may be able to provide some valuable clues to reveal the relationship between the structure and enzymatic activity, and the unfolding pathway and mechanism of PTPase.

Inactivation and Unfolding of Protein Tyrosine Phosphatase from Thermus thermophilus HB27 during Urea and Guanidine Hydrochloride Denaturation

PubMed Central

Liu, Lina; Gao, Chunyan; Xu, Shui; Zhao, Ping; Xia, Qingyou

2014-01-01

The effects of urea and guanidine hydrochloride (GdnHCl) on the activity, conformation and unfolding process of protein tyrosine phosphatase (PTPase), a thermostable low molecular weight protein from Thermus thermophilus HB27, have been studied. Enzymatic activity assays showed both urea and GdnHCl resulted in the inactivation of PTPase in a concentration and time-dependent manner. Inactivation kinetics analysis suggested that the inactivation of PTPase induced by urea and GdnHCl were both monophasic and reversible processes, and the effects of urea and GdnHCl on PTPase were similar to that of mixed-type reversible inhibitors. Far-ultraviolet (UV) circular dichroism (CD), Tryptophan and 1-anilinonaphthalene -8-sulfonic acid (ANS) fluorescence spectral analyses indicated the existence of a partially active and an inactive molten globule-like intermediate during the unfolding processes induced by urea and GdnHCl, respectively. Based on the sequence alignment and the homolog Tt1001 protein structure, we discussed the possible conformational transitions of PTPase induced by urea and GdnHCl and compared the conformations of these unfolding intermediates with the transient states in bovine PTPase and its complex structures in detail. Our results may be able to provide some valuable clues to reveal the relationship between the structure and enzymatic activity, and the unfolding pathway and mechanism of PTPase. PMID:25255086

Integrating the philosophy and psychology of aesthetic experience: development of the aesthetic experience scale.

PubMed

Stamatopoulou, Despina

2004-10-01

This study assessed the dynamic relationship between person and object in aesthetic experience. Patterns of the structure of aesthetic experience were derived from a conceptual model based on philosophical and psychological ideas. These patterns were further informed by interviewing individuals with extensive involvement in aesthetic activities and 25 secondary students. Accordingly, patterns were tested by developing a large pool of items attempting to identify measurable structural components of aesthetic experience. Refined first in a pilot study, the 36-item questionnaire was administered to 652 Greek students, aged from 13 to 15 years. Correlation matrices and exploratory factor analyses on principal components were used to examine internal structural relationships. The obliquely rotated five-factor solution of the refined instrument accounted for the 44.1% of the total variance and was combatible with the conceptual model of aesthetic experience, indicating the plausibility of both. The internal consistency of the items was adequate and external correlational analysis offered preliminary support for subsequent development of a self-report measure that serves to operationalize the major constructs of aesthetic experience in the general adolescent population. The results also raise theoretical issues for those interested in empirical aesthetics, suggesting that in experiential functioning, expressive perception and affect may play a more constructive role in cognitive processes than is generally acknowledged.

Hybrid FSWeld-bonded joint fatigue behaviour

NASA Astrophysics Data System (ADS)

Lertora, Enrico; Mandolfino, Chiara; Gambaro, Carla; Pizzorni, Marco

2018-05-01

Aluminium alloys, widely used in aeronautics, are increasingly involved in the automotive industry due to the good relationship between mechanical strength and specific weight. The lightening of the structures is the first objective, which allows the decreasing in the weight in motion. The use of aluminium alloys has also seen the introduction of the Friction Stir Welding (FSW) technique for the production of structural overlapping joints. FSW allows us to weld overlap joints free from defects, but with the presence of a structural notch further aggravated by the presence of a "hook" defect near the edge of the weld. Furthermore, FSW presents a weld penetration area connected to the tool geometry and penetration. The experimental activity will be focused on the combination of two different joining techniques, which can synergistically improve the final joint resistance. In particular, the welding and bonding process most commonly known as weld-bonding is defined as a hybrid process, as it combines two different junction processes. In this paper we analyse FSWelded AA6082 aluminium alloy overlapped joint with the aim of quantitatively evaluating the improvement provided by the presence of an epoxy adhesive between the plates. After optimising the weld-bonding process, the mechanical behaviour of welded joints will be analysed by static and dynamic tests. The presence of the adhesive should limit the negative effect of the structural notch inevitable in a FSW overlapped joint.

Redox properties of structural Fe in clay minerals: 3. Relationships between smectite redox and structural properties.

PubMed

Gorski, Christopher A; Klüpfel, Laura E; Voegelin, Andreas; Sander, Michael; Hofstetter, Thomas B

2013-01-01

Structural Fe in clay minerals is an important redox-active species in many pristine and contaminated environments as well as in engineered systems. Understanding the extent and kinetics of redox reactions involving Fe-bearing clay minerals has been challenging due to the inability to relate structural Fe(2+)/Fe(total) fractions to fundamental redox properties, such as reduction potentials (EH). Here, we overcame this challenge by using mediated electrochemical reduction (MER) and oxidation (MEO) to characterize the fraction of redox-active structural Fe (Fe(2+)/Fe(total)) in smectites over a wide range of applied EH-values (-0.6 V to +0.6 V). We examined Fe(2+)/Fe(total )- EH relationships of four natural Fe-bearing smectites (SWy-2, SWa-1, NAu-1, NAu-2) in their native, reduced, and reoxidized states and compared our measurements with spectroscopic observations and a suite of mineralogical properties. All smectites exhibited unique Fe(2+)/Fe(total) - EH relationships, were redox active over wide EH ranges, and underwent irreversible electron transfer induced structural changes that were observable with X-ray absorption spectroscopy. Variations among the smectite Fe(2+)/Fe(total) - EH relationships correlated well with both bulk and molecular-scale properties, including Fe(total) content, layer charge, and quadrupole splitting values, suggesting that multiple structural parameters determined the redox properties of smectites. The Fe(2+)/Fe(total) - EH relationships developed for these four commonly studied clay minerals may be applied to future studies interested in relating the extent of structural Fe reduction or oxidation to EH-values.

Towards a physics-based multiscale modelling of the electro-mechanical coupling in electro-active polymers.

PubMed

Cohen, Noy; Menzel, Andreas; deBotton, Gal

2016-02-01

Owing to the increasing number of industrial applications of electro-active polymers (EAPs), there is a growing need for electromechanical models which accurately capture their behaviour. To this end, we compare the predicted behaviour of EAPs undergoing homogeneous deformations according to three electromechanical models. The first model is a phenomenological continuum-based model composed of the mechanical Gent model and a linear relationship between the electric field and the polarization. The electrical and the mechanical responses according to the second model are based on the physical structure of the polymer chain network. The third model incorporates a neo-Hookean mechanical response and a physically motivated microstructurally based long-chains model for the electrical behaviour. In the microstructural-motivated models, the integration from the microscopic to the macroscopic levels is accomplished by the micro-sphere technique. Four types of homogeneous boundary conditions are considered and the behaviours determined according to the three models are compared. For the microstructurally motivated models, these analyses are performed and compared with the widely used phenomenological model for the first time. Some of the aspects revealed in this investigation, such as the dependence of the intensity of the polarization field on the deformation, highlight the need for an in-depth investigation of the relationships between the structure and the behaviours of the EAPs at the microscopic level and their overall macroscopic response.

Validation of the French Autism Spectrum Quotient scale and its relationships with schizotypy and Eysenckian personality traits.

PubMed

Sierro, Guillaume; Rossier, Jérôme; Mohr, Christine

2016-07-01

Autism and schizophrenia spectra were long considered distinct entities. Yet, recent studies emphasized overlapping clinical and personality features suggesting common mechanisms and liabilities. Independent notions, however, highlight that the two spectra oppose each other socially (positive schizotypal hyper-mentalism versus autistic hypo-mentalism). To clarify these relationships, we used data from 921 French-speaking Swiss undergraduates to firstly validate the French Autism Spectrum Questionnaire (AQ) identifying an optimal factor structure. Secondly, we assessed relationships between this AQ structure and schizotypic personality traits. Results from correlational and principal component analyses replicated both overlapping and opposing relationships. We conjecture that autistic traits opposing positive schizotypy represent autistic mentalizing deficits. We discuss implications of our findings relative to theories of autism and schizophrenia spectrum relationships. Copyright © 2016 Elsevier Inc. All rights reserved.

Social Influences, School Motivation and Gender Differences: An Application of the Expectancy-Value Theory

ERIC Educational Resources Information Center

Fan, Weihua

2011-01-01

The present study examined the structural relations of social influences, task values, ability beliefs, educational expectation and academic engagement for both boys and girls. The structural equation modelling analyses provided nationally representative evidence of gender differences in: (1) the links from teacher-student relationship and peer…

Spatial scaling and multi-model inference in landscape genetics: Martes americana in northern Idaho

Treesearch

Tzeidle N. Wasserman; Samuel A. Cushman; Michael K. Schwartz; David O. Wallin

2010-01-01

Individual-based analyses relating landscape structure to genetic distances across complex landscapes enable rigorous evaluation of multiple alternative hypotheses linking landscape structure to gene flow. We utilize two extensions to increase the rigor of the individual-based causal modeling approach to inferring relationships between landscape patterns and gene flow...

Examining gray matter structure associated with academic performance in a large sample of Chinese high school students.

PubMed

Wang, Song; Zhou, Ming; Chen, Taolin; Yang, Xun; Chen, Guangxiang; Wang, Meiyun; Gong, Qiyong

2017-04-18

Achievement in school is crucial for students to be able to pursue successful careers and lead happy lives in the future. Although many psychological attributes have been found to be associated with academic performance, the neural substrates of academic performance remain largely unknown. Here, we investigated the relationship between brain structure and academic performance in a large sample of high school students via structural magnetic resonance imaging (S-MRI) using voxel-based morphometry (VBM) approach. The whole-brain regression analyses showed that higher academic performance was related to greater regional gray matter density (rGMD) of the left dorsolateral prefrontal cortex (DLPFC), which is considered a neural center at the intersection of cognitive and non-cognitive functions. Furthermore, mediation analyses suggested that general intelligence partially mediated the impact of the left DLPFC density on academic performance. These results persisted even after adjusting for the effect of family socioeconomic status (SES). In short, our findings reveal a potential neuroanatomical marker for academic performance and highlight the role of general intelligence in explaining the relationship between brain structure and academic performance.

PLS-based quantitative structure-activity relationship for substituted benzamides of clebopride type. Application of experimental design in drug design.

PubMed

Norinder, U; Högberg, T

1992-04-01

The advantageous approach of using an experimentally designed training set as the basis for establishing a quantitative structure-activity relationship with good predictive capability is described. The training set was selected from a fractional factorial design scheme based on a principal component description of physico-chemical parameters of aromatic substituents. The derived model successfully predicts the activities of additional substituted benzamides of 6-methoxy-N-(4-piperidyl)salicylamide type. The major influence on activity of the 3-substituent is demonstrated.

Structure-activity relationships of tetramethylpiperidine-substituted phenazines against Mycobacterium leprae in vitro.

PubMed Central

Franzblau, S G; White, K E; O'Sullivan, J F

1989-01-01

In a previous study of structure-activity relationships of selected phenazines against Mycobacterium leprae in vitro, compounds containing a 2,2,6,6-tetramethylpiperidine substitution at the imino nitrogen were most active. Therefore, the effect of substitution at the para positions of the phenyl and anilino groups in tetramethylpiperidine-substituted phenazines was assessed. As determined by radiorespirometry, activity in ascending order was observed in compounds substituted with hydrogens or fluorines, ethoxy groups, methyl groups, chlorines, and bromines and correlated with partition coefficients in octanol-water. PMID:2692516

Discovery of imidazo[1,2-b]pyridazine derivatives as IKKbeta inhibitors. Part 1: Hit-to-lead study and structure-activity relationship.

PubMed

Shimizu, Hiroki; Tanaka, Shinji; Toki, Tadashi; Yasumatsu, Isao; Akimoto, Toshihiko; Morishita, Kaoru; Yamasaki, Tomonori; Yasukochi, Takanori; Iimura, Shin

2010-09-01

Imidazo[1,2-b]pyridazine derivatives from high-throughput screening were developed as IKKbeta inhibitors. By the optimization of the 3- and 6-position of imidazo[1,2-b]pyridazine scaffold, cell-free IKKbeta inhibitory activity and TNFalpha inhibitory activity in THP-1 cell increased. Also, these compounds showed high kinase selectivity. The structure-activity relationship was revealed and the interaction model of imidazo[1,2-b]pyridazine compounds with IKKbeta was constructed. Copyright 2010. Published by Elsevier Ltd.

Inflammation Modulates Murine Venous Thrombosis Resolution In Vivo: Assessment by Multimodal Fluorescence Molecular Imaging

PubMed Central

Ripplinger, Crystal M.; Kessinger, Chase W.; Li, Chunqiang; Kim, Jin Won; McCarthy, Jason R.; Weissleder, Ralph; Henke, Peter K.; Lin, Charles P.; Jaffer, Farouc A.

2012-01-01

Objective Assessment of thrombus inflammation in vivo could provide new insights into deep vein thrombosis (DVT) resolution. Here we develop and evaluate two integrated fluorescence molecular-structural imaging strategies to quantify DVT-related inflammation and architecture, and to assess the effect of thrombus inflammation on subsequent DVT resolution in vivo. Methods and Results Murine DVT were created with topical 5% FeCl3 application to thigh or jugular veins (n=35). On day 3, mice received macrophage and matrix metalloproteinase (MMP) activity fluorescence imaging agents. On day 4, integrated assessment of DVT inflammation and architecture was performed using confocal fluorescence intravital microscopy (IVM). Day 4 analyses showed robust relationships among in vivo thrombus macrophages, MMP activity, and FITC-dextran deposition (r>0.70, p<0.01). In a serial two-timepoint study, mice with DVT underwent IVM at day 4 and at day 6. Analyses revealed that the intensity of thrombus inflammation at day 4 predicted the magnitude of DVT resolution at day 6 (p<0.05). In a second approach, noninvasive fluorescence molecular tomography-computed tomography (FMT-CT) was employed, and detected macrophages within jugular DVT (p<0.05 vs. sham-controls). Conclusions Integrated fluorescence molecular-structural imaging demonstrates that the DVT-induced inflammatory response can be readily assessed in vivo, and can inform the magnitude of thrombus resolution. PMID:22995524

Identification of mutagenic transformation products generated during oxidation of 3-methyl-4-nitrophenol solutions by orbitrap tandem mass spectrometry and quantitative structure-activity relationship analyses.

PubMed

Matsushita, Taku; Honda, Shiho; Kuriyama, Taisuke; Fujita, Yuki; Kondo, Takashi; Matsui, Yoshihiko; Shirasaki, Nobutaka; Takanashi, Hirokazu; Kameya, Takashi

2018-02-01

We used Ames assays to investigate the effects of ozonation (designated O 3 ), ozonation followed by chlorination (O 3 /Cl), an advanced oxidation process (AOP, UV/H 2 O 2 ), and AOP followed by chlorination (AOP/Cl) on the mutagenicity of solutions of 3-methyl-4-nitrophenol (3M4NP), a major environmental degradation product of the organophosphorus insecticide fenitrothion. Whereas O 3 did not induce mutagenicity, O 3 /Cl, AOP, and AOP/Cl converted 3M4NP into mutagenic transformation products (TPs). Using liquid chromatography-mass spectrometry, we detected a total of 138 peaks in the solutions subjected to O 3 /Cl, AOP, and AOP/Cl. To elucidate the TPs responsible for the observed mutagenicity, we performed simple regression analyses of the relationship between the area of each peak and the observed mutagenicity of samples withdrawn periodically during each oxidation process. The area of each of 10 peaks was found to be positively correlated (r 2  ≥ 0.8) with the observed mutagenicity, suggesting that the TPs corresponding to these peaks contributed to the mutagenicity. After taking into account the consistency of mutagenicity induction by the oxidation processes and analyzing the peaks by tandem mass spectrometry, we identified 3 TPs, corresponding to 6 peaks, as candidate mutagens. These TPs were assessed by means of 4 quantitative structure-activity relationship (QSAR) models, and all 3 were predicted to be mutagenic by at least one model. This result was consistent with our assumption that these TPs were mutagens. Ames assays of an authentic sample of one of the 3 TPs revealed that it did not contribute to the mutagenicity. This left 3-methoxy-4-nitrophenol and 2-[(E)-[(2,5-dihydroxyphenyl) methylidene]amino]-5-dihydroxybenzaldehyde on the list of mutagens suspected of contributing to the mutagenicity induced by AOP. No TPs were identified as candidate mutagens responsible for the mutagenicity induced by O 3 /Cl and AOP/Cl. Copyright © 2017 Elsevier Ltd. All rights reserved.

3-cyanoindole-based inhibitors of inosine monophosphate dehydrogenase: synthesis and initial structure-activity relationships.

PubMed

Dhar, T G Murali; Shen, Zhongqi; Gu, Henry H; Chen, Ping; Norris, Derek; Watterson, Scott H; Ballentine, Shelley K; Fleener, Catherine A; Rouleau, Katherine A; Barrish, Joel C; Townsend, Robert; Hollenbaugh, Diane L; Iwanowicz, Edwin J

2003-10-20

A series of novel small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH), based upon a 3-cyanoindole core, were explored. IMPDH catalyzes the rate determining step in guanine nucleotide biosynthesis and is a target for anticancer, immunosuppressive and antiviral therapy. The synthesis and the structure-activity relationships (SAR), derived from in vitro studies, for this new series of inhibitors is given.

Studies of structure-activity relationship on plant polyphenol-induced suppression of human liver cancer cells.

PubMed

Loa, Jacky; Chow, Pierce; Zhang, Kai

2009-05-01

To study anticancer activities of 68 plant polyphenols with different backbone structures and various substitutions and to analyze the structure-activity relationships. Antiproliferative activity of 68 plant polyphenols on human liver cancer cells were screened by the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide method. Structure-activity relationships were analyzed by comparison of their activities with selected structures. Cell cycle progression was assayed by flow cytometry analysis and apoptosis was analyzed by DNA fragment assay. Based on their backbone structures, 68 polyphenols were sub-classed to flavonoids (chalcones, flavanones, flavones and isoflavones), chromones and coumarins. The order of their potency to suppress the human liver cancer cells is chalcones > flavones > chromones > isoflavones > flavanones > coumarins. Chalcones comprise the most potent group with IC(50) values ranging from 21.69 to 197 microM. Top nine most potent chalcones in the group have hydroxylation at 2'-carbon position in B-ring. Flavones ranked second in their potencies. Quercetin, 4-hydroxyflavone and luteolin are three hydroxyflavones with highest potencies in this group. Their IC(50) values are 30.81, 39.29 and 71.17 microM, respectively. Chromones, isoflavones, flavanones and coumarins showed much lower potencies when compared to the first two groups with IC(50) ranges of 61 to >400, 131 to >400, 138 to >400 and 360.85 to >400 microM, respectively. In mechanistic studies, the most potent chalcone, 2,2'-dihydroxychalcone could induce G2/M arrest and then apoptosis of the cancer cells. An analysis of structure-activity relationship showed that following structures are required for their inhibitory potencies on human liver cancer cells: (1) of the six sub-classes of the polyphenols tested, the unique backbone structure of chalcones with a open C-ring; (2) within the chalcone group, hydroxyl substitution at 2'-carbon of B-ring; (3) hydroxyl substitution at 3'-carbon in B-ring of flavones. However, some other structures were found to decrease their potencies: e.g. substitutions by sugar moieties in flavones. These data are valuable for design and modification of new polyphenols, which could be potential antiproliferative agents of cancer cells.

Structure-activity relationship and docking studies of thiazolidinedione-type compounds with monoamine oxidase B.

PubMed

Carroll, Richard T; Dluzen, Dean E; Stinnett, Hilary; Awale, Prabha S; Funk, Max O; Geldenhuys, Werner J

2011-08-15

The neuroprotective activity of pioglitazone and rosiglitazone in the MPTP parkinsonian mouse prompted us to evaluate a set of thiazolidinedione (TZD) type compounds for monoamine oxidase A and B inhibition activity. These compounds were able to inhibit MAO-B over several log units of magnitude (82 nM to 600 μM). Initial structure-activity relationship studies identified key areas to modify the aromatic substituted TZD compounds. Primarily, substitutions on the aromatic group and the TZD nitrogen were key areas where activity was enhanced within this group of compounds. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structure-activity relationship of prenyl-substituted polyphenols from Artocarpus heterophyllus as inhibitors of melanin biosynthesis in cultured melanoma cells.

PubMed

Arung, Enos Tangke; Shimizu, Kuniyoshi; Kondo, Ryuichiro

2007-09-01

A series of prenylated, flavone-based polyphenols, compounds 1-8, were isolated from the wood of Artocarpus heterophyllus. These compounds, which have previously been shown not to inhibit tyrosinase activity, were found to be active inhibitors of the in vivo melanin biosynthesis in B16 melanoma cells, with little or no cytotoxicity. To clarify the structural requirement for inhibition, some structure-activity relationships were studied, in comparison with related compounds lacking prenyl side chains. Our experiments indicate that both prenyl and OH groups, as well as the type of substitution pattern, are crucial for the inhibition of melanin production in B16 melanoma cells.

Synthesis of novel 1-[5-(4-methoxy-phenyl)-[1,3,4]oxadiazol-2-yl]-piperazine derivatives and evaluation of their in vivo anticonvulsant activity.

PubMed

Harish, Kikkeri P; Mohana, Kikkeri N; Mallesha, Lingappa; Prasanna Kumar, Basavapatna N

2013-07-01

A series of novel 1-[5-(4-methoxy-phenyl)-[1,3,4]oxadiazol-2-yl]-piperazine derivatives 8(a-o) were synthesized and characterized by elemental analyses, (1)H NMR, (13)C NMR and mass spectral studies. The newly synthesized compounds were screened for their anticonvulsant activity against maximal electroshock seizure (MES) model in male wistar rats and compared with the standard drug phenytoin. The neurotoxic effects were determined by rotorod test by using mice. Compounds 8d, 8e, 8f and 8h were found to be most potent of this series. The same compounds showed no neurotoxicity at the maximum dose administered (100 mg/kg). The efforts were also made to establish the structure activity relationships among synthesized compounds. The pharmacophore model was used to validate the anticonvulsant activity of the synthesized molecules. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Design, synthesis and exploring the quantitative structure-activity relationship of some antioxidant flavonoid analogues.

PubMed

Das, Sreeparna; Mitra, Indrani; Batuta, Shaikh; Niharul Alam, Md; Roy, Kunal; Begum, Naznin Ara

2014-11-01

A series of flavonoid analogues were synthesized and screened for the in vitro antioxidant activity through their ability to quench 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical. The activity of these compounds, measured in comparison to the well-known standard antioxidants (29-32), their precursors (38-42) and other bioactive moieties (38-42) resembling partially the flavone skeleton was analyzed further to develop Quantitative Structure-Activity Relationship (QSAR) models using the Genetic Function Approximation (GFA) technique. Based on the essential structural requirements predicted by the QSAR models, some analogues were designed, synthesized and tested for activity. The predicted and experimental activities of these compounds were well correlated. Flavone analogue 20 was found to be the most potent antioxidant. Copyright © 2014 Elsevier Ltd. All rights reserved.

Quantitative Structure-Antifungal Activity Relationships for cinnamate derivatives.

PubMed

Saavedra, Laura M; Ruiz, Diego; Romanelli, Gustavo P; Duchowicz, Pablo R

2015-12-01

Quantitative Structure-Activity Relationships (QSAR) are established with the aim of analyzing the fungicidal activities of a set of 27 active cinnamate derivatives. The exploration of more than a thousand of constitutional, topological, geometrical and electronic molecular descriptors, which are calculated with Dragon software, leads to predictions of the growth inhibition on Pythium sp and Corticium rolfsii fungi species, in close agreement to the experimental values extracted from the literature. A set containing 21 new structurally related cinnamate compounds is prepared. The developed QSAR models are applied to predict the unknown fungicidal activity of this set, showing that cinnamates like 38, 28 and 42 are expected to be highly active for Pythium sp, while this is also predicted for 28 and 34 in C. rolfsii. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular architectures of benzoic acid-specific type III polyketide synthases

PubMed Central

Stewart, Charles; Woods, Kate; Macias, Greg; Allan, Andrew C.; Noel, Joseph P.

2017-01-01

Biphenyl synthase and benzophenone synthase constitute an evolutionarily distinct clade of type III polyketide synthases (PKSs) that use benzoic acid-derived substrates to produce defense metabolites in plants. The use of benzoyl-CoA as an endogenous substrate is unusual for type III PKSs. Moreover, sequence analyses indicate that the residues responsible for the functional diversification of type III PKSs are mutated in benzoic acid-specific type III PKSs. In order to gain a better understanding of structure–function relationships within the type III PKS family, the crystal structures of biphenyl synthase from Malus × domestica and benzophenone synthase from Hypericum androsaemum were compared with the structure of an archetypal type III PKS: chalcone synthase from Malus × domestica. Both biphenyl synthase and benzophenone synthase contain mutations that reshape their active-site cavities to prevent the binding of 4-coumaroyl-CoA and to favor the binding of small hydrophobic substrates. The active-site cavities of biphenyl synthase and benzophenone synthase also contain a novel pocket associated with their chain-elongation and cyclization reactions. Collectively, these results illuminate structural determinants of benzoic acid-specific type III PKSs and expand the understanding of the evolution of specialized metabolic pathways in plants. PMID:29199980

Using Theoretical Descriptors in Structural Activity Relationships: 4. Molecular Orbital Basicity and Electrostatic Basicity

DTIC Science & Technology

1988-11-01

rates.6 The Hammet equation , also called the Linear Free Energy Relationship (LFER) because of the relationship of the Gibb’s Free Energy to the... equations for numerous biological and physicochemical properties. Linear Solvation Enery Relationship (LSER), a sub-set of QSAR have been used by...originates from thermodynamics, where Hammet recognized the relationship of structure to the Gibb’s Free Energy, and ultimately to equilibria and reaction

Developing sensor activity relationships for the JPL electronic nose sensors using molecular modeling and QSAR techniques

NASA Technical Reports Server (NTRS)

Shevade, A. V.; Ryan, M. A.; Homer, M. L.; Jewell, A. D.; Zhou, H.; Manatt, K.; Kisor, A. K.

2005-01-01

We report a Quantitative Structure-Activity Relationships (QSAR) study using Genetic Function Approximations (GFA) to describe the polymer-carbon composite sensor activities in the JPL Electronic Nose, when exposed to chemical vapors at parts-per-million concentration levels.

Factor structure of the happiness-increasing strategies scales (H-ISS): activities and coping strategies in relation to positive and negative affect.

PubMed

Al Nima, Ali; Garcia, Danilo

2015-01-01

Background. Previous research (Tkach & Lyubomirsky, 2006) shows that there are eight general happiness-increasing strategies: social affiliation, partying, mental control, goal pursuit, passive leisure, active leisure, religion, and direct attempts. The present study investigates the factor structure of the happiness-increasing strategies scales (H-ISS) and their relationship to positive and negative affect. Method. The present study used participants' (N = 1,050 and age mean = 34.21 sd = 12.73) responses to the H-ISS in structural equation modeling analyses. Affect was measured using the Positive Affect Negative Affect Schedule. Results. After small modifications we obtained a good model that contains the original eight factors/scales. Moreover, we found that women tend to use social affiliation, mental control, passive leisure, religion, and direct attempts more than men, while men preferred to engage in partying and clubbing more than women. The H-ISS explained significantly the variance of positive affect (R (2) = .41) and the variance of negative affect (R (2) = .27). Conclusions. Our study is an addition to previous research showing that the factor structure of the happiness-increasing strategies is valid and reliable. However, due to the model fitting issues that arise in the present study, we give some suggestions for improving the instrument.

If you come from a well-known organisation, I will trust you: Exploring and understanding the community's attitudes towards healthcare research in Cambodia.

PubMed

Pol, Sreymom; Fox-Lewis, Shivani; Neou, Leakhena; Parker, Michael; Kingori, Patricia; Turner, Claudia

2018-01-01

To explore Cambodian community members' understanding of and attitudes towards healthcare research. This qualitative study generated data from semi-structured interviews and focus group discussions. This study was conducted at a non-governmental paediatric hospital and in nearby villages in Siem Reap province, Cambodia. A total of ten semi-structured interviews and four focus group discussions were conducted, involving 27 participants. Iterative data collection and analysis were performed concurrently. Data were analysed by thematic content analysis and the coding structure was developed using relevant literature. Participants did not have a clear understanding of what activities related to research compared with those for routine healthcare. Key attitudes towards research were responsibility and trust: personal (trust of the researcher directly) and institutional (trust of the institution as a whole). Villagers believe the village headman holds responsibility for community activities, while the village headman believes that this responsibility should be shared across all levels of the government system. It is essential for researchers to understand the structure and relationship within the community they wish to work with in order to develop trust among community participants. This aids effective communication and understanding among all parties, enabling high quality ethical research to be conducted.

Synthesis, structure-activity relationships, and in vivo evaluation of N3-phenylpyrazinones as novel corticotropin-releasing factor-1 (CRF1) receptor antagonists.

PubMed

Hartz, Richard A; Ahuja, Vijay T; Arvanitis, Argyrios G; Rafalski, Maria; Yue, Eddy W; Denhart, Derek J; Schmitz, William D; Ditta, Jonathan L; Deskus, Jeffrey A; Brenner, Allison B; Hobbs, Frank W; Payne, Joseph; Lelas, Snjezana; Li, Yu-Wen; Molski, Thaddeus F; Mattson, Gail K; Peng, Yong; Wong, Harvey; Grace, James E; Lentz, Kimberley A; Qian-Cutrone, Jingfang; Zhuo, Xiaoliang; Shu, Yue-Zhong; Lodge, Nicholas J; Zaczek, Robert; Combs, Andrew P; Olson, Richard E; Bronson, Joanne J; Mattson, Ronald J; Macor, John E

2009-07-23

Evidence suggests that corticotropin-releasing factor-1 (CRF(1)) receptor antagonists may offer therapeutic potential for the treatment of diseases associated with elevated levels of CRF such as anxiety and depression. A pyrazinone-based chemotype of CRF(1) receptor antagonists was discovered. Structure-activity relationship studies led to the identification of numerous potent analogues including 12p, a highly potent and selective CRF(1) receptor antagonist with an IC(50) value of 0.26 nM. The pharmacokinetic properties of 12p were assessed in rats and Cynomolgus monkeys. Compound 12p was efficacious in the defensive withdrawal test (an animal model of anxiety) in rats. The synthesis, structure-activity relationships and in vivo properties of compounds within the pyrazinone chemotype are described.

Strain of optic-fiber/giant magnetostrictive film structure in magnetic field by finite element analysis

NASA Astrophysics Data System (ADS)

Hu, Jiafei; Pan, Mengchun; Xin, Jianguang; Chen, Dixiang

2008-12-01

The magnetostrictive transducer is the most important part of the optic-fiber magnetic field sensor, and the optic-fiber/giant magnetostrictive(GMS) film coupled structure is a novel coupling form of the magnetostrictive transducer. Always we analyze the coupled structure based on the entire coupled structure being sputtered GMS material without tail-fibers. In practical application, the coupled structure has tail-fibers without films at two ends. When the entire coupled structure is immersed in the detected magnetic field, the detected magnetic field causes the GMS film strain then causing optic-fiber strain. This strain transmission process is different from it in the coupled structure entirely with GMS films without tail-fibers. The strain transmission relationship can be calculated theoretically in the coupled structure without tail-fibers, but it's complicated to theoretically calculate the strain transmission relationship in the coupled structure with tail-fibers. After large numbers of calculations and analyses by ANSYS software, we figure out some relationships of the two strain transmission processes in the respective structures and the stress distribution in the tail-fibers. These results are helpful to the practical application of the optic-fiber/ GMS film coupled structure.

A novel approach for modelling vegetation distributions and analysing vegetation sensitivity through trait-climate relationships in China

PubMed Central

Yang, Yanzheng; Zhu, Qiuan; Peng, Changhui; Wang, Han; Xue, Wei; Lin, Guanghui; Wen, Zhongming; Chang, Jie; Wang, Meng; Liu, Guobin; Li, Shiqing

2016-01-01

Increasing evidence indicates that current dynamic global vegetation models (DGVMs) have suffered from insufficient realism and are difficult to improve, particularly because they are built on plant functional type (PFT) schemes. Therefore, new approaches, such as plant trait-based methods, are urgently needed to replace PFT schemes when predicting the distribution of vegetation and investigating vegetation sensitivity. As an important direction towards constructing next-generation DGVMs based on plant functional traits, we propose a novel approach for modelling vegetation distributions and analysing vegetation sensitivity through trait-climate relationships in China. The results demonstrated that a Gaussian mixture model (GMM) trained with a LMA-Nmass-LAI data combination yielded an accuracy of 72.82% in simulating vegetation distribution, providing more detailed parameter information regarding community structures and ecosystem functions. The new approach also performed well in analyses of vegetation sensitivity to different climatic scenarios. Although the trait-climate relationship is not the only candidate useful for predicting vegetation distributions and analysing climatic sensitivity, it sheds new light on the development of next-generation trait-based DGVMs. PMID:27052108

Glomerular structural-functional relationship models of diabetic nephropathy are robust in type 1 diabetic patients.

PubMed

Mauer, Michael; Caramori, Maria Luiza; Fioretto, Paola; Najafian, Behzad

2015-06-01

Studies of structural-functional relationships have improved understanding of the natural history of diabetic nephropathy (DN). However, in order to consider structural end points for clinical trials, the robustness of the resultant models needs to be verified. This study examined whether structural-functional relationship models derived from a large cohort of type 1 diabetic (T1D) patients with a wide range of renal function are robust. The predictability of models derived from multiple regression analysis and piecewise linear regression analysis was also compared. T1D patients (n = 161) with research renal biopsies were divided into two equal groups matched for albumin excretion rate (AER). Models to explain AER and glomerular filtration rate (GFR) by classical DN lesions in one group (T1D-model, or T1D-M) were applied to the other group (T1D-test, or T1D-T) and regression analyses were performed. T1D-M-derived models explained 70 and 63% of AER variance and 32 and 21% of GFR variance in T1D-M and T1D-T, respectively, supporting the substantial robustness of the models. Piecewise linear regression analyses substantially improved predictability of the models with 83% of AER variance and 66% of GFR variance explained by classical DN glomerular lesions alone. These studies demonstrate that DN structural-functional relationship models are robust, and if appropriate models are used, glomerular lesions alone explain a major proportion of AER and GFR variance in T1D patients. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

HomoSAR: bridging comparative protein modeling with quantitative structural activity relationship to design new peptides.

PubMed

Borkar, Mahesh R; Pissurlenkar, Raghuvir R S; Coutinho, Evans C

2013-11-15

Peptides play significant roles in the biological world. To optimize activity for a specific therapeutic target, peptide library synthesis is inevitable; which is a time consuming and expensive. Computational approaches provide a promising way to simply elucidate the structural basis in the design of new peptides. Earlier, we proposed a novel methodology termed HomoSAR to gain insight into the structure activity relationships underlying peptides. Based on an integrated approach, HomoSAR uses the principles of homology modeling in conjunction with the quantitative structural activity relationship formalism to predict and design new peptide sequences with the optimum activity. In the present study, we establish that the HomoSAR methodology can be universally applied to all classes of peptides irrespective of sequence length by studying HomoSAR on three peptide datasets viz., angiotensin-converting enzyme inhibitory peptides, CAMEL-s antibiotic peptides, and hAmphiphysin-1 SH3 domain binding peptides, using a set of descriptors related to the hydrophobic, steric, and electronic properties of the 20 natural amino acids. Models generated for all three datasets have statistically significant correlation coefficients (r(2)) and predictive r2 (r(pred)2) and cross validated coefficient ( q(LOO)2). The daintiness of this technique lies in its simplicity and ability to extract all the information contained in the peptides to elucidate the underlying structure activity relationships. The difficulties of correlating both sequence diversity and variation in length of the peptides with their biological activity can be addressed. The study has been able to identify the preferred or detrimental nature of amino acids at specific positions in the peptide sequences. Copyright © 2013 Wiley Periodicals, Inc.

Structure-activity relationship of crustacean peptide hormones.

PubMed

Katayama, Hidekazu

2016-01-01

In crustaceans, various physiological events, such as molting, vitellogenesis, and sex differentiation, are regulated by peptide hormones. To understanding the functional sites of these hormones, many structure-activity relationship (SAR) studies have been published. In this review, the author focuses the SAR of crustacean hyperglycemic hormone-family peptides and androgenic gland hormone and describes the detailed results of our and other research groups. The future perspectives will be also discussed.

Associations among social capital, parenting for active lifestyles, and youth physical activity in rural families living in upstate New York.

PubMed

Davison, Kirsten K; Nishi, Akihiro; Kranz, Sibylle; Wyckoff, Lynae; May, John J; Earle-Richardson, Giulia B; Strogatz, David S; Jenkins, Paul L

2012-10-01

While emerging research supports a positive relationship between social capital and youth physical activity (PA), few studies have examined possible mechanisms explaining this relationship and no studies have focused on rural youth. In this study, we examined parents' support of children's PA as an intermediary factor linking social capital and youth PA in a largely rural cross sectional sample of American children aged 6- to 19-years and their parents/guardians (N=767 families) living in upstate New York. Parents completed a self-administered survey assessing demographic factors, perceived social capital, support for children's PA, and children's PA including time spent outdoors and days per week of sufficient PA. Structural equation modeling was used to test the hypothesis that higher social capital is linked with higher parental support for PA and, in turn, higher PA in children. Analyses were conducted separately for younger (6-12 years) and older (13-19 years) children and controlled for demographic factors (child age, household education, participation in a food assistance program) and perceived neighborhood safety. Anticipated relationships among social capital, parents' activity-related support, and children's PA were identified for older, but not younger children. Findings suggest that parent support for children's PA is one possible mechanism linking social capital and youth PA and the parents of adolescents may rely more heavily on cues from their social environment to shape their approaches to supporting their children's PA than parents of younger children. Copyright © 2012 Elsevier Ltd. All rights reserved.

Quantitative structure-activation barrier relationship modeling for Diels-Alder ligations utilizing quantum chemical structural descriptors.

PubMed

Nandi, Sisir; Monesi, Alessandro; Drgan, Viktor; Merzel, Franci; Novič, Marjana

2013-10-30

In the present study, we show the correlation of quantum chemical structural descriptors with the activation barriers of the Diels-Alder ligations. A set of 72 non-catalysed Diels-Alder reactions were subjected to quantitative structure-activation barrier relationship (QSABR) under the framework of theoretical quantum chemical descriptors calculated solely from the structures of diene and dienophile reactants. Experimental activation barrier data were obtained from literature. Descriptors were computed using Hartree-Fock theory using 6-31G(d) basis set as implemented in Gaussian 09 software. Variable selection and model development were carried out by stepwise multiple linear regression methodology. Predictive performance of the quantitative structure-activation barrier relationship (QSABR) model was assessed by training and test set concept and by calculating leave-one-out cross-validated Q2 and predictive R2 values. The QSABR model can explain and predict 86.5% and 80% of the variances, respectively, in the activation energy barrier training data. Alternatively, a neural network model based on back propagation of errors was developed to assess the nonlinearity of the sought correlations between theoretical descriptors and experimental reaction barriers. A reasonable predictability for the activation barrier of the test set reactions was obtained, which enabled an exploration and interpretation of the significant variables responsible for Diels-Alder interaction between dienes and dienophiles. Thus, studies in the direction of QSABR modelling that provide efficient and fast prediction of activation barriers of the Diels-Alder reactions turn out to be a meaningful alternative to transition state theory based computation.

Relationship between Chemical Structure and Antimicrobial Activities of Isothiocyanates from Cruciferous Vegetables against Oral Pathogens.

PubMed

Ko, Mi-Ok; Kim, Mi-Bo; Lim, Sang-Bin

2016-12-28

We evaluated the potentials of 10 isothiocyanates (ITCs) from cruciferous vegetables and radish root hydrolysate for inhibiting the growth of oral pathogens, with an emphasis on assessing any structure-function relationship. Structural differences in ITCs impacted their antimicrobial activities against oral pathogens differently. The indolyl ITC (indol-3-carbinol) was the most potent inhibitor of the growth of oral pathogens, followed by aromatic ITCs (benzyl ITC (BITC) and phenylethyl ITC (PEITC)) and aliphatic ITCs (erucin, iberin, and sulforaphene). Sulforaphene, which is similar in structure, but has one double bond, showed higher antimicrobial activity than sulforaphane. Erucin, which has a thiol group, showed higher antimicrobial activity than sulforaphane, which has a sulfinyl group. BITC and iberin with a short chain exhibited higher antimicrobial potential than PEITC and sulforaphane with a longer chain, respectively. ITCs have strong antimicrobial activities and may be useful in the prevention and management of dental caries.

The mediating effect of social relationships on the association between socioeconomic status and subjective health - results from the Heinz Nixdorf Recall cohort study.

PubMed

Vonneilich, Nico; Jöckel, Karl-Heinz; Erbel, Raimund; Klein, Jens; Dragano, Nico; Siegrist, Johannes; von dem Knesebeck, Olaf

2012-04-17

Socioeconomic status (SES) is an important determinant of population health. Explanatory approaches on how SES determines health have so far included numerous factors, amongst them psychosocial factors such as social relationships. However, it is unclear whether social relationships can help explain socioeconomic differences in general subjective health. Do different aspects of social relationships contribute differently to the explanation? Based on a cohort study of middle and older aged residents (45 to 75 years) from the Ruhr Area in Germany our study tries to clarify the matter. For the analyses data from the population-based prospective Heinz Nixdorf Recall (HNR) Study is used. As indicators of SES education, equivalent household income and occupational status were employed. Social relations were assessed by including structural as well as functional aspects. Structural aspects were estimated by the Social Integration Index (SII) and functional aspects were measured by availability of emotional and instrumental support. Data on general subjective health status was available for both baseline examination (2000-2003) and a 5-year follow-up (2006-2008). The sample consists of 4,146 men and women. Four logistic regression models were calculated: in the first model we controlled for age and subjective health at baseline, while in models 2 and 3, either functional or structural aspects of social relationships were introduced separately. Model 4 then included all variables. As former studies indicated different health effects of SES and social relations in men and women, analyses were conducted with the overall sample as well as for each gender alone. Prospective associations of SES and subjective health were reduced after introducing social relationships into the regression models. Percentage reductions between 2% and 30% were observed in the overall sample when all aspects of social relations were included. The percentage reductions were strongest in the lowest SES group. Gender specific analyses revealed mediating effects of social relationships in women and men. The magnitude of mediating effects varied depending on the indicators of SES and social relations. Social relationships substantially contribute to the explanation of SES differences in subjective health. Interventions for improving social relations which especially focus on socially deprived groups are likely to help reducing socioeconomic disparities in health.

Design and prediction of new anticoagulants as a selective Factor IXa inhibitor via three-dimensional quantitative structure-property relationships of amidinobenzothiophene derivatives.

PubMed

Gao, Jia-Suo; Tong, Xu-Peng; Chang, Yi-Qun; He, Yu-Xuan; Mei, Yu-Dan; Tan, Pei-Hong; Guo, Jia-Liang; Liao, Guo-Chao; Xiao, Gao-Keng; Chen, Wei-Min; Zhou, Shu-Feng; Sun, Ping-Hua

2015-01-01

Factor IXa (FIXa), a blood coagulation factor, is specifically inhibited at the initiation stage of the coagulation cascade, promising an excellent approach for developing selective and safe anticoagulants. Eighty-four amidinobenzothiophene antithrombotic derivatives targeting FIXa were selected to establish three-dimensional quantitative structure-activity relationship (3D-QSAR) and three-dimensional quantitative structure-selectivity relationship (3D-QSSR) models using comparative molecular field analysis and comparative similarity indices analysis methods. Internal and external cross-validation techniques were investigated as well as region focusing and bootstrapping. The satisfactory q (2) values of 0.753 and 0.770, and r (2) values of 0.940 and 0.965 for 3D-QSAR and 3D-QSSR, respectively, indicated that the models are available to predict both the inhibitory activity and selectivity on FIXa against Factor Xa, the activated status of Factor X. This work revealed that the steric, hydrophobic, and H-bond factors should appropriately be taken into account in future rational design, especially the modifications at the 2'-position of the benzene and the 6-position of the benzothiophene in the R group, providing helpful clues to design more active and selective FIXa inhibitors for the treatment of thrombosis. On the basis of the three-dimensional quantitative structure-property relationships, 16 new potent molecules have been designed and are predicted to be more active and selective than Compound 33, which has the best activity as reported in the literature.

Family Structure, Parental Investment, and Educational Outcomes among Black South Africans. Population Studies Center Research Report.

ERIC Educational Resources Information Center

Anderson, Kermyt G.

This study examined the relationship between family structure, expenditures on education, and children's educational outcomes for black South Africans, using the nationally representative 1995 October Household Survey. The analyses focused on 28,215 individuals, ages 10 to 24 years, who had not completed secondary schools. The findings indicated…

Structural Modeling of Variables Related to Parental Support in Mexican Children's Perfomance on Reading and Writing

ERIC Educational Resources Information Center

Bazan-Ramirez, Aldo; Castellanos-Simons, Doris; Lopez-Valenzuela, Mercedes

2010-01-01

This paper aims at analysing the structural relationships among some latent and observed variables related to the assessment of written language performance in 139 fourth grade students of Elementary School selected from nine public schools of the northwest of Mexico. Questionnaires were also applied to the children's parents and teachers. The…

An Alternative Approach for the Analyses and Interpretation of Attachment Sort Items

ERIC Educational Resources Information Center

Kirkland, John; Bimler, David; Drawneek, Andrew; McKim, Margaret; Scholmerich, Axel

2004-01-01

Attachment Q-Sort (AQS) is a tool for quantifying observations about toddler/caregiver relationships. Previous studies have applied factor analysis to the full 90 AQS item set to explore the structure underlying them. Here we explore that structure by applying multidimensional scaling (MDS) to judgements of inter-item similarity. AQS items are…

The Decline of Industrial Unionism in the Meatpacking Industry: Event-Structure Analyses of Labor Unrest, 1946-1987.

ERIC Educational Resources Information Center

Brueggemann, John; Brown, Cliff

2003-01-01

A study of the United Packinghouse Workers of America compared the postwar years and the Reagan era. Using event-structure analysis, the development of new corporate strategies (new technologies, production reorganization, cheap nonunion labor) fundamentally transformed the capital-labor relationship and led to the collapse of industrial unionism…

Synthesis, fungicidal activity, structure-activity relationships (SARs) and density functional theory (DFT) studies of novel strobilurin analogues containing arylpyrazole rings.

PubMed

Liu, Yuanyuan; Lv, Kunzhi; Li, Yi; Nan, Qiuli; Xu, Jinyuan

2018-05-18

A series of novel strobilurin analogues (1a-1f, 2a-2e, 3a-3e) containing arylpyrazole rings were synthesized and characterized by NMR spectroscopy. The structures of 1f, 2b and 3b were also determined by single crystal X-ray diffraction analysis. These analogues were collected together with other twenty-eight similar compounds 4a-4f, 5a-5h, 6a-6h and 7a-7f from our previous studies, for in vitro bioassays and thorough structure-activity relationships (SARs) studies. Most compounds exhibited excellent-to-good fungicidal activity against Rhizoctonia solani, especially 5c, 7a, 6c, and 3b with 98.94%, 83.40%, 71.40% and 65.87% inhibition rates at 0.1 μg mL -1 , respectively, better than commercial pyraclostrobin. Comparative molecular field analysis (CoMFA) was employed to study three-dimensional quantitative structure-activity relationships (3D-QSARs). Density functional theory (DFT) calculation was also carried out to provide more information regarding SARs. The present work provided some hints for developing novel strobilurin fungicides.

Repeated head trauma is associated with smaller thalamic volumes and slower processing speed: the Professional Fighters’ Brain Health Study

PubMed Central

Bernick, Charles; Banks, Sarah J; Shin, Wanyong; Obuchowski, Nancy; Butler, Sam; Noback, Michael; Phillips, Michael; Lowe, Mark; Jones, Stephen; Modic, Michael

2015-01-01

Objectives Cumulative head trauma may alter brain structure and function. We explored the relationship between exposure variables, cognition and MRI brain structural measures in a cohort of professional combatants. Methods 224 fighters (131 mixed martial arts fighters and 93 boxers) participating in the Professional Fighters Brain Health Study, a longitudinal cohort study of licensed professional combatants, were recruited, as were 22 controls. Each participant underwent computerised cognitive testing and volumetric brain MRI. Fighting history including years of fighting and fights per year was obtained from self-report and published records. Statistical analyses of the baseline evaluations were applied cross-sectionally to determine the relationship between fight exposure variables and volumes of the hippocampus, amygdala, thalamus, caudate, putamen. Moreover, the relationship between exposure and brain volumes with cognitive function was assessed. Results Increasing exposure to repetitive head trauma measured by number of professional fights, years of fighting, or a Fight Exposure Score (FES) was associated with lower brain volumes, particularly the thalamus and caudate. In addition, speed of processing decreased with decreased thalamic volumes and with increasing fight exposure. Higher scores on a FES used to reflect exposure to repetitive head trauma were associated with greater likelihood of having cognitive impairment. Conclusions Greater exposure to repetitive head trauma is associated with lower brain volumes and lower processing speed in active professional fighters. PMID:25633832

Cytotoxic prenylated flavones from the stem and root bark of Daphne giraldii.

PubMed

Sun, Qian; Wang, Di; Li, Fei-Fei; Yao, Guo-Dong; Li, Xue; Li, Ling-Zhi; Huang, Xiao-Xiao; Song, Shao-Jiang

2016-08-15

Three new prenylated flavones (1-3), along with three known analogues (4-6), were isolated from the stem and root bark of Daphne giraldii. Their structures were determined by comprehensive NMR and HRESIMS spectroscopic data analyses. The absolute configurations of compounds 2 and 3 were assigned by optical rotation comparison, CD and [Rh2(OCOCF3)4]-induced CD spectral methods. The in vitro cytotoxicity experiments carried out involving five cancer cell lines (U251, A549, HepG2, MCF-7 and Bcap37) showed that 2 markedly inhibited the proliferation of all tested cells with IC50 values ranging from 4.26 to 20.82μM. The preliminary structure-activity relationships of these flavones are discussed. In addition, compound 2 was found to effectively induce apoptosis in HepG2 cells according to a flow cytometry analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Structural equation modeling: building and evaluating causal models: Chapter 8

USGS Publications Warehouse

Grace, James B.; Scheiner, Samuel M.; Schoolmaster, Donald R.

2015-01-01

Scientists frequently wish to study hypotheses about causal relationships, rather than just statistical associations. This chapter addresses the question of how scientists might approach this ambitious task. Here we describe structural equation modeling (SEM), a general modeling framework for the study of causal hypotheses. Our goals are to (a) concisely describe the methodology, (b) illustrate its utility for investigating ecological systems, and (c) provide guidance for its application. Throughout our presentation, we rely on a study of the effects of human activities on wetland ecosystems to make our description of methodology more tangible. We begin by presenting the fundamental principles of SEM, including both its distinguishing characteristics and the requirements for modeling hypotheses about causal networks. We then illustrate SEM procedures and offer guidelines for conducting SEM analyses. Our focus in this presentation is on basic modeling objectives and core techniques. Pointers to additional modeling options are also given.

Structure-activity relationships between sterols and their thermal stability in oil matrix.

PubMed

Hu, Yinzhou; Xu, Junli; Huang, Weisu; Zhao, Yajing; Li, Maiquan; Wang, Mengmeng; Zheng, Lufei; Lu, Baiyi

2018-08-30

Structure-activity relationships between 20 sterols and their thermal stabilities were studied in a model oil system. All sterol degradations were found to be consistent with a first-order kinetic model with determination of coefficient (R 2 ) higher than 0.9444. The number of double bonds in the sterol structure was negatively correlated with the thermal stability of sterol, whereas the length of the branch chain was positively correlated with the thermal stability of sterol. A quantitative structure-activity relationship (QSAR) model to predict thermal stability of sterol was developed by using partial least squares regression (PLSR) combined with genetic algorithm (GA). A regression model was built with R 2 of 0.806. Almost all sterol degradation constants can be predicted accurately with R 2 of cross-validation equals to 0.680. Four important variables were selected in optimal QSAR model and the selected variables were observed to be related with information indices, RDF descriptors, and 3D-MoRSE descriptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

Augmented multivariate image analysis applied to quantitative structure-activity relationship modeling of the phytotoxicities of benzoxazinone herbicides and related compounds on problematic weeds.

PubMed

Freitas, Mirlaine R; Matias, Stella V B G; Macedo, Renato L G; Freitas, Matheus P; Venturin, Nelson

2013-09-11

Two of major weeds affecting cereal crops worldwide are Avena fatua L. (wild oat) and Lolium rigidum Gaud. (rigid ryegrass). Thus, development of new herbicides against these weeds is required; in line with this, benzoxazinones, their degradation products, and analogues have been shown to be important allelochemicals and natural herbicides. Despite earlier structure-activity studies demonstrating that hydrophobicity (log P) of aminophenoxazines correlates to phytotoxicity, our findings for a series of benzoxazinone derivatives do not show any relationship between phytotoxicity and log P nor with other two usual molecular descriptors. On the other hand, a quantitative structure-activity relationship (QSAR) analysis based on molecular graphs representing structural shape, atomic sizes, and colors to encode other atomic properties performed very accurately for the prediction of phytotoxicities of these compounds against wild oat and rigid ryegrass. Therefore, these QSAR models can be used to estimate the phytotoxicity of new congeners of benzoxazinone herbicides toward A. fatua L. and L. rigidum Gaud.

Anthracene-based Inhibitors of Dengue Virus NS2B-NS3 Protease†

PubMed Central

Tomlinson, Suzanne M.; Watowich, Stanley J.

2010-01-01

Summary Dengue virus (DENV) is a mosquito-borne flavivirus that has strained global healthcare systems throughout tropical and subtropical regions of the world. In addition to plaguing developing nations, it has re-emerged in several developed countries with recent outbreaks in the USA (CDC, 2010), Australia (Hanna et al., 2009), Taiwan (Kuan et al., 2010) and France (La Ruche et al., 2010). DENV infection can cause significant disease, including dengue fever, dengue hemorrhagic fever, dengue shock syndrome, and death. There are no approved vaccines or antiviral therapies to prevent or treat dengue-related illnesses. However, the viral NS2B-NS3 protease complex provides a strategic target for antiviral drug development since NS3 protease activity is required for virus replication. Recently, we reported two compounds with inhibitory activity against the DENV protease in vitro and antiviral activity against dengue 2 (DEN2V) in cell culture (Tomlinson et al., 2009a). Analogs of one of the lead compounds were purchased, tested in protease inhibition assays, and the data evaluated with detailed kinetic analyses. A structure activity relationship (SAR) identified key atomic determinants (i.e. functional groups) important for inhibitory activity. Four “second series” analogs were selected and tested to validate our SAR and structural models. Here, we report improvements to inhibitory activity ranging between ~2- and 60-fold, resulting in selective low micromolar dengue protease inhibitors. PMID:21185332

Structure investigation of codeine drug using mass spectrometry, thermal analyses and semi-emperical molecular orbital (MO) calculations

NASA Astrophysics Data System (ADS)

Zayed, M. A.; Hawash, M. F.; Fahmey, M. A.

2006-05-01

Codeine is an analgesic with uses similar to morphine, but it has a mild sedative effect. It is preferable used as phosphate form and it is often administrated by mouth with aspirin or paracetamol. Therefore, it is important to investigate its structure to know the active groups and weak bonds responsible for its medical activity. Consequently in the present work, codeine was investigated by mass spectrometry and thermal analyses (TG, DTG and DTA) and confirming by semi-empirical MO-calculation (PM3 method) in the neutral and positively charged forms of the drug. Some results of studying the d-block element complexes of codeine were used to declare the relationship between drug structure and its chemical reactivity in vitro system. The mass spectra and thermal analyses fragmentation pathways were proposed and compared to each other to select the most suitable scheme representing the correct fragmentation of this drug. From EI mass spectra, the main primary cleavage site of the charged drug molecule is that due to β-cleavage to nitrogen atom in its skeleton. It occurs in two parallel mechanisms with the same possibility, i.e. no difference in appearance activation energy between them. In the neutral drug form the primary site cleavage is that occurs in the ether ring. Thermal analyses of the neutral form of the drug revealed the high response of the drug to the temperature variation with very fast rate. It decomposed in several sequential steps in the temperature range 200-600 °C. The initial thermal fragments are very similar to that obtained by mass spectrometric fragmentation. Therefore, comparison between mass and thermal helps in selection of the proper pathway representing the fragmentation of this drug. This comparison successfully confirmed by MOC. These calculations give the bond order, charge distribution, heat of formation and possible hybridization of some atoms in different position of the drug skeleton. This helps the successful choice of the weakest bond at which both mass and thermal fragmentation occurs. Therefore, the best fragmentation pathway of this drug is correctly selected. The effect of such fragmentation on the drug behavior in the human body can be expected as a result of comparing these data with that obtained on studying codeine metal complexes using mass and thermal fragmentation techniques.

Emotion dysregulation mediates the relationship between child maltreatment and psychopathology: A structural equation model.

PubMed

Jennissen, Simone; Holl, Julia; Mai, Hannah; Wolff, Sebastian; Barnow, Sven

2016-12-01

The present study investigated the mediating effects of emotion dysregulation on the relationship between child maltreatment and psychopathology. An adult sample (N=701) from diverse backgrounds of psychopathology completed the Childhood Trauma Questionnaire (CTQ), the Difficulties in Emotion Regulation Scale (DERS), the Brief Symptom Inventory (BSI), and the negative affect subscale of the Positive and Negative Affect Schedule (PANAS) in a cross-sectional online survey. Correlational analyses showed that all types of child maltreatment were uniformly associated with emotion dysregulation, and dimensions of emotion dysregulation were strongly related to psychopathology. Limited access to strategies for emotion regulation emerged as the most powerful predictor. Structural equation modeling analyses revealed that emotion dysregulation partially mediated the relationship between child maltreatment and psychopathology, even after controlling for shared variance with negative affect. These findings emphasize the importance of emotion dysregulation as a possible mediating mechanism in the association between child maltreatment and later psychopathology. Additionally, interventions targeting specific emotion regulation strategies may be effective to reduce psychopathology in victims of child maltreatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Importance of Leisure Activities in the Relationship between Physical Health and Well-Being in a Life Span Sample.

PubMed

Paggi, Michelle E; Jopp, Daniela; Hertzog, Christopher

2016-01-01

Previous studies have examined the relationships between physical health and leisure activities and between leisure activities and well-being, but, to our knowledge, none has examined these relationships simultaneously. This study investigated the relationships between leisure activities, health and well-being considering the role of age, and whether leisure activities mediate the relationship between physical health and well-being. Utilizing a cross-sectional database of 259 adults (ages 18-81 years) who completed several questionnaires, linear regression models and mediation models were tested. Regression analyses indicated that physical health was related to leisure activities and leisure activities were related to well-being. When physical health was measured by subjective ratings, age had a stronger relationship with leisure activities. However, when physical health was indicated by health restrictions, physical health had a stronger relationship with leisure activities than did age. Leisure activities were a partial mediator of the relationship between physical health and well-being. The results demonstrated that the reduction in leisure activities with age has more to do with physical health limitations than with older age itself. In addition, regardless of age, the benefits of physical health for well-being are due in part to the level of leisure activity participation. These results highlight the importance of leisure activities for successful aging throughout the adult life span. Interventions designed to improve well-being through increasing leisure activity participation should take physical health into consideration, particularly for older adults. © 2016 S. Karger AG, Basel.

Maintenance: organizational modes, activities and health and safety. Use of a French national survey and in-situ analyses.

PubMed

Grusenmeyer, Corinne

2014-12-01

Maintenance activities are identified as critical both to operator safety and to systems safety and reliability. However, it is still difficult to identify maintenance workers in French occupational accident and disease statistics. Moreover, few analyses of these activities and of organizational changes in this field have been conducted. This paper presents two different approaches to this same issue. Analyses were aimed firstly at identifying the occupational exposures of these operators and at comparing them with occupational exposures of production staff and, secondly at developing understanding of normal real maintenance activities, i.e. maintenance activities that are normally actually carried out, while taking into account the socio-technical system and maintenance organization within which they lie. The use of the French SUMER 2003 survey shows that occupational exposures of maintenance staff to various constraints are more frequent than occupational exposures of their production colleagues. However, maintenance staff appear to have greater independence. Analyses were also conducted in a subcontracting urban public transport company, who outsources some maintenance work. Those analyses highlight a complex network of companies involved in maintenance activities, a substantial number of work interruptions and a significant fragmentation of the internal technicians' activities that can be cognitively costly, reduce anticipation possibilities and lead to incidents or accidents. Above all they underline internal technicians' contributions to the completion of outsourced interventions and interdependent relationships between the activities of the internal and the external technicians. Outsourcing maintenance interventions thus raises the question of risks associated with the interdependence of actual work activities undertaken by the different types of staff, since they contribute to the same maintenance intervention. This study therefore pinpoints the need to integrate inter-organizational interactions in order to understand the variability of maintenance activities and its relationships with reliability and safety. In this respect, some suggestions are provided with a prevention aim. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure-activity relationships of rosiglitazone for peroxisome proliferator-activated receptor gamma transrepression.

PubMed

Toyota, Yosuke; Nomura, Sayaka; Makishima, Makoto; Hashimoto, Yuichi; Ishikawa, Minoru

2017-06-15

Anti-inflammatory effects of peroxisome proliferator-activated receptor gamma (PPRAγ) ligands are thought to be largely due to PPARγ-mediated transrepression. Thus, transrepression-selective PPARγ ligands without agonistic activity or with only partial agonistic activity should exhibit anti-inflammatory properties with reduced side effects. Here, we investigated the structure-activity relationships (SARs) of PPARγ agonist rosiglitazone, focusing on transrepression activity. Alkenic analogs showed slightly more potent transrepression with reduced efficacy of transactivating agonistic activity. Removal of the alkyl group on the nitrogen atom improved selectivity for transrepression over transactivation. Among the synthesized compounds, 3l exhibited stronger transrepressional activity (IC 50 : 14μM) and weaker agonistic efficacy (11%) than rosiglitazone or pioglitazone. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relationship between structure and antiproliferative activity of polymethoxyflavones towards HL60 cells.

PubMed

Kawaii, Satoru; Ikuina, Tomoyasu; Hikima, Takeshi; Tokiwano, Tetsuo; Yoshizawa, Yuko

2012-12-01

As part of our continuing investigation of polymethoxyflavone (PMF) derivatives as potential anticancer substances, a series of PMF derivatives was synthesized. The synthesized compounds were evaluated for cytotoxicity against the promyelocytic leukemic HL60 cell line, and structure-activity relationship correlations were investigated along with previously isolated PMFs from the peel of king orange (Citrus nobilis). 7,3'-Dimethoxyflavone demonstrated the most potent activity among the synthetic PMFs. Consideration of correlation between the methoxylation pattern and antiproliferative activity revealed the importance of the 3'-methoxyl group and the higher degree of methoxylation on the A-ring moiety of PMFs.

Ring-substituted 4-hydroxy-1H-quinolin-2-ones: preparation and biological activity.

PubMed

Jampilek, Josef; Musiol, Robert; Pesko, Matus; Kralova, Katarina; Vejsova, Marcela; Carroll, James; Coffey, Aidan; Finster, Jacek; Tabak, Dominik; Niedbala, Halina; Kozik, Violetta; Polanski, Jaroslaw; Csollei, Jozef; Dohnal, Jiri

2009-03-13

In the study, a series of twelve ring-substituted 4-hydroxy-1H-quinolin-2-one derivatives were prepared. The procedures for synthesis of the compounds are presented. The compounds were analyzed using RP-HPLC to determine lipophilicity and tested for their photosynthesis-inhibiting activity using spinach (Spinacia oleracea L.) chloroplasts. All the synthesized compounds were also evaluated for antifungal activity using in vitro screening with eight fungal strains. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed, as well as their structure-activity relationships (SAR).

Solid-phase synthesis and structure-activity relationships of novel biarylethers as melanin-concentrating hormone receptor-1 antagonists.

PubMed

Ma, Vu; Bannon, Anthony W; Baumgartner, Jamie; Hale, Clarence; Hsieh, Faye; Hulme, Christopher; Rorrer, Kirk; Salon, John; van Staden, Carlo; Tempest, Paul

2006-10-01

Melanin-concentrating hormone (MCH) is a cyclic 19 amino acid orexigenic neuropeptide. The action of MCH on feeding is thought to involve the activation of its respective G protein-coupled receptor MCH-R1. Consequently, antagonists that block MCH regulated MCH-R1 activity may provide a viable approach to the treatment of diet-induced obesity. This communication reports the discovery of a novel MCH-R1 receptor antagonist, the biarylether 7, identified through high throughput screening. The solid-phase synthesis and structure-activity relationship of related analogs is described.

Family Instability and Early Initiation of Sexual Activity in Western Kenya

PubMed Central

2014-01-01

Epidemiological, economic, and social forces have produced high levels of volatility in family and household structure for young people growing up in sub-Saharan Africa in recent decades. However, scholarship on the family to date has not examined the influence of this family instability on young people’s well-being. The current study employs unique life history calendar data from Western Kenya to investigate the relationship between instability in caregiving and early initiation of sexual activity. It draws on a body of work on parental union instability in the United States, and examines new dimensions of family change. Analyses reveal a positive association between transitions in primary caregiver and the likelihood of early sexual debut that is rapidly manifested following caregiver change and persists for a short period. The association is strongest at early ages, and there is a cumulative effect of multiple caregiver changes. The results highlight the importance of studying family stability in sub-Saharan Africa, as distinct from family structure, and for attention to dimensions such as age and recency. PMID:23055236

Investigation on Quantitative Structure Activity Relationships of a Series of Inducible Nitric Oxide.

PubMed

Sharma, Mukesh C; Sharma, S

2016-12-01

A series of 2-dihydro-4-quinazolin with potent highly selective inhibitors of inducible nitric oxide synthase activities was subjected to quantitative structure activity relationships (QSAR) analysis. Statistically significant equations with high correlation coefficient (r 2  = 0.8219) were developed. The k-nearest neighbor model has showed good cross-validated correlation coefficient and external validation values of 0.7866 and 0.7133, respectively. The selected electrostatic field descriptors the presence of blue ball around R1 and R4 in the quinazolinamine moiety showed electronegative groups favorable for nitric oxide synthase activity. The QSAR models may lead to the structural requirements of inducible nitric oxide compounds and help in the design of new compounds.

Orbital operation study. Volume 2: Interfacing activities analysis. Part 1: Introduction and summary

NASA Technical Reports Server (NTRS)

Anderson, N. R.

1972-01-01

The summary of the interfacing activity analyses for the orbital operations study is presented. The significant analyses are grouped into categories as follows: (1) structural and mechanical activity, (2) data management, and (3) support operations. Specific subjects concerning payload deployment, communications, rendezvous, and stationkeeping are discussed.

Molecularly stabilised ultrasmall gold nanoparticles: synthesis, characterization and bioactivity

NASA Astrophysics Data System (ADS)

Leifert, Annika; Pan-Bartnek, Yu; Simon, Ulrich; Jahnen-Dechent, Willi

2013-06-01

Gold nanoparticles (AuNPs) are widely used as contrast agents in electron microscopy as well as for diagnostic tests. Due to their unique optical and electrical properties and their small size, there is also a growing field of potential applications in medical fields of imaging and therapy, for example as drug carriers or as active compounds in thermotherapy. Besides their intrinsic optical properties, facile surface decoration with (bio)functional ligands renders AuNPs ideally suited for many industrial and medical applications. However, novel AuNPs may have toxicological profiles differing from bulk and therefore a thorough analysis of the quantitative structure-activity relationship (QSAR) is required. Several mechanisms are proposed that cause adverse effects of nanoparticles in biological systems. Catalytic generation of reactive species due to the large and chemically active surface area of nanomaterials is well established. Because nanoparticles approach the size of biological molecules and subcellular structures, they may overcome natural barriers by active or passive uptake. Ultrasmall AuNPs with sizes of 2 nm or less may even behave as molecular ligands. These types of potential interactions would imply a size and ligand-dependent behaviour of any nanomaterial towards biological systems. Thus, to fully understand their QSAR, AuNPs bioactivity should be analysed in biological systems of increasing complexity ranging from cell culture to whole animal studies.

Characterization of substituted aryl meroterpenoids from red seaweed Hypnea musciformis as potential antioxidants.

PubMed

Chakraborty, Kajal; Joseph, Deepu; Joy, Minju; Raola, Vamshi Krishna

2016-12-01

The ethyl acetate fraction of red seaweed Hypnea musciformis was purified to yield three substituted aryl meroterpenoids, namely, 2-(tetrahydro-5-(4-hydroxyphenyl)-4-pentylfuran-3-yl)-ethyl-4-hydroxybenzoate (1), 2-2-[(4-hydroxybenzoyl)-oxy]-ethyl-4-methoxy-4-2-[(4-methylpentyl)oxy]-3,4-dihydro-2H-6-pyranylbutanoic acid (2) and 3-((5-butyl-3-methyl-5,6-dihydro-2H-pyran-2-yl)-methyl)-4-methoxy-4-oxobutyl benzoate (3). The structures of these compounds, as well as their relative stereochemistries, were confirmed by exhaustive NMR spectroscopic data analyses. Compound 1 exhibited similar 2,2'-diphenylpicrylhydrazyl radical inhibiting and Fe(2+) ion chelating activities (IC50 25.05 and 350.7μM, respectively) as that of commercial antioxidant gallic acid (IC50 32.3 and 646.6μM, respectively), followed by 3 (IC50 231.2 and 667.9μM, respectively), and 2 (IC50 322.4 and 5115.3μM, respectively), in descending order of activities. Structure-activity relationship analysis revealed that the antioxidant activities of these compounds were directly proportional to the steric and hydrophobic parameters. The seaweed derived aryl meroterpenoids might serve as potential lead antioxidative molecules for use in pharmaceutical and food industries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Structure-antioxidant activity relationships of flavonoids isolated from the resinous exudate of Heliotropium sinuatum.

PubMed

Modak, Brenda; Contreras, M Leonor; González-Nilo, Fernando; Torres, René

2005-01-17

Relationships between the structural characteristics of flavonoids isolated from the resinous exudate of Heliotropium sinuatum and their antioxidant activity were studied. Radical formation energies, DeltaH of dehydrogenation and spin densities were calculated using DFT methods (B3LYP/6-31G*). Results show that studied flavonoids can be divided into two sets according to their activity. It has been found that antioxidant activity depends both on substitution pattern of hydroxyl groups of the flavonoid skeleton and the presence of an unsaturation at the C2-C3 bond. A good tendency between DeltaH of dehydrogenation and antioxidant activity was established.

Statistical modeling implicates neuroanatomical circuit mediating stress relief by ‘comfort’ food

PubMed Central

Ulrich-Lai, Yvonne M.; Christiansen, Anne M.; Wang, Xia; Song, Seongho; Herman, James P.

2015-01-01

A history of eating highly-palatable foods reduces physiological and emotional responses to stress. For instance, we have previously shown that limited sucrose intake (4 ml of 30% sucrose twice daily for 14 days) reduces hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress. However, the neural mechanisms underlying stress relief by such ‘comfort’ foods are unclear, and could reveal an endogenous brain pathway for stress mitigation. As such, the present work assessed the expression of several proteins related to neuronal activation and/or plasticity in multiple stress- and reward-regulatory brain regions of rats after limited sucrose (vs. water control) intake. These data were then subjected to a series of statistical analyses, including Bayesian modeling, to identify the most likely neurocircuit mediating stress relief by sucrose. The analyses suggest that sucrose reduces HPA activation by dampening an excitatory basolateral amygdala - medial amygdala circuit, while also potentiating an inhibitory bed nucleus of the stria terminalis principle subdivision-mediated circuit, resulting in reduced HPA activation after stress. Collectively, the results support the hypothesis that sucrose limits stress responses via plastic changes to the structure and function of stress-regulatory neural circuits. The work also illustrates that advanced statistical methods are useful approaches to identify potentially novel and important underlying relationships in biological data sets. PMID:26246177

Statistical modeling implicates neuroanatomical circuit mediating stress relief by 'comfort' food.

PubMed

Ulrich-Lai, Yvonne M; Christiansen, Anne M; Wang, Xia; Song, Seongho; Herman, James P

2016-07-01

A history of eating highly palatable foods reduces physiological and emotional responses to stress. For instance, we have previously shown that limited sucrose intake (4 ml of 30 % sucrose twice daily for 14 days) reduces hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress. However, the neural mechanisms underlying stress relief by such 'comfort' foods are unclear, and could reveal an endogenous brain pathway for stress mitigation. As such, the present work assessed the expression of several proteins related to neuronal activation and/or plasticity in multiple stress- and reward-regulatory brain regions of rats after limited sucrose (vs. water control) intake. These data were then subjected to a series of statistical analyses, including Bayesian modeling, to identify the most likely neurocircuit mediating stress relief by sucrose. The analyses suggest that sucrose reduces HPA activation by dampening an excitatory basolateral amygdala-medial amygdala circuit, while also potentiating an inhibitory bed nucleus of the stria terminalis principle subdivision-mediated circuit, resulting in reduced HPA activation after stress. Collectively, the results support the hypothesis that sucrose limits stress responses via plastic changes to the structure and function of stress-regulatory neural circuits. The work also illustrates that advanced statistical methods are useful approaches to identify potentially novel and important underlying relationships in biological datasets.

Synthesis and quantitative structure-antifungal activity relationships of clovane derivatives against Botrytis cinerea.

PubMed

Saiz-Urra, Liane; Racero, Juan C; Macías-Sáchez, Antonio J; Hernández-Galán, Rosario; Hanson, James R; Perez-Gonzalez, Maykel; Collado, Isidro G

2009-03-25

Twenty-three clovane derivatives, nine described here for the first time, bearing substituents on carbon C-2, have been synthesized and evaluated for their in vitro antifungal activity against the phytopathogenic fungus Botrytis cinerea. The results showed that compounds 9, 14, 16, and 18 bearing nitrogen atoms in the chain attached at C-2 displayed potent antifungal activity, whereas mercapto derivatives 13, 19, and 22 displayed low activity. The antifungal activity showed a clear structure-activity relationship (SAR) trend, which confirmed the importance of the nature of the C-2 chain on the antifungal activity. On the basis of these observations, the metabolism of compounds 8 and 14 by the fungus B. cinerea, and the metabolism of other clovanes by this fungus, described previously, a pro-drug action mechanism for 2-alkoxyclovane compounds is proposed. Quantitative structure-activity relationship (QSAR) studies were performed to rationalize the results and to suggest further optimization, using a topological sub-structural molecular design (TOPS-MODE) approach. The model displayed good fit and predictive capability, describing 85.5% of the experimental variance, with a standard deviation of 9.502 and yielding high values of cross-validation determination coefficients (q2CV-LOO = 0.784 and q2boot = 0.673). The most significant variables were the spectral moments weighted by bond dipole moment (Dip), hydrophobicity (Hyd), and the combined dipolarity/polarizability Abraham molecular descriptor (Ab-pi2H).

The structural analysis of the mitochondrial SSUrRNA implies a close phylogenetic relationship between mitochondria from plants and from the heterotrophic alga Prototheca wickerhamii.

PubMed

Wolff, G; Kück, U

1990-04-01

The gene for the mitochondrial small subunit rRNA (SSUrRNA) from the heterotrophic alga Prototheca wickerhamii has been isolated from a gene library of extranuclear DNA. Sequence and structural analyses allow the determination of a secondary structure model for this rRNA. In addition, several sequence motifs are present which are typically found in SSUrRNAs of various mitochondrial origins. Unexpectedly, the Prototheca RNA sequence has more features in common with mitochondrial SSUrRNAs from plants than with that from the green alga Chlamydomonas reinhardtii. The phylogenetic relationship between mitochondria from plants and algae is discussed.

Electron-density descriptors as predictors in quantitative structure--activity/property relationships and drug design.

PubMed

Matta, Chérif F; Arabi, Alya A

2011-06-01

The use of electron density-based molecular descriptors in drug research, particularly in quantitative structure--activity relationships/quantitative structure--property relationships studies, is reviewed. The exposition starts by a discussion of molecular similarity and transferability in terms of the underlying electron density, which leads to a qualitative introduction to the quantum theory of atoms in molecules (QTAIM). The starting point of QTAIM is the topological analysis of the molecular electron-density distributions to extract atomic and bond properties that characterize every atom and bond in the molecule. These atomic and bond properties have considerable potential as bases for the construction of robust quantitative structure--activity/property relationships models as shown by selected examples in this review. QTAIM is applicable to the electron density calculated from quantum-chemical calculations and/or that obtained from ultra-high resolution x-ray diffraction experiments followed by nonspherical refinement. Atomic and bond properties are introduced followed by examples of application of each of these two families of descriptors. The review ends with a study whereby the molecular electrostatic potential, uniquely determined by the density, is used in conjunction with atomic properties to elucidate the reasons for the biological similarity of bioisosteres.

Factor structure of the Korean version of illness intrusiveness rating scale: cross-cultural implications.

PubMed

Kim, Daeho; Kim, Kwang-iel; Lee, Haewon; Choi, Joonho; Park, Yong-Chon

2005-04-01

The Illness Intrusiveness Rating Scale (IIRS) measures illness-induced disruptions to 13 domains of lifestyles, activities, and interests. A stable three-factor structure has been well documented; however, the cross-cultural validity of this scale needs to be tested. This study investigated the factor structure of the Korean version of IIRS in 712 outpatients at a university medical center. A predominant diagnosis of the patients was rheumatoid arthritis (47%). The Center for Epidemiological Studies-Depression Scale (CES-D), and Health Assessment Questionnaire (HAQ) were also administered. Exploratory Principal Component Analysis identified a two-factor structure, "Relationships and Personal Development (RPD)" and "Instrumental", accounting for 57% of the variance. Confirmatory analyses extracted an identical factor structure. However, a goodness-of-the fit test failed to support two-factor solution (chi(2)=138.2, df=43, p<.001). Two factors had high internal consistency (RPD, alpha=.89; Instrumental, alpha=.75) and significantly correlated with scores of HAQ (RPD, r=.53, p<.001; Instrumental, .r=44, p<.001) and CES-D (RPD, .r=55, p<.001; Instrumental, .r=43, p<.001). These findings supported construct validity of the Korean version of IIRS, but did not support cross-cultural equivalence of the factor structure.

Structural insights into a key carotenogenesis related enzyme phytoene synthase of P. falciparum: a novel drug target for malaria.

PubMed

Agarwal, Shalini; Sharma, Vijeta; Phulera, Swastik; Abdin, M Z; Ayana, R; Singh, Shailja

2015-12-01

Carotenoids represent a diverse group of pigments derived from the common isoprenoid precursors and fulfill a variety of critical functions in plants and animals. Phytoene synthase (PSY), a transferase enzyme that catalyzes the first specific step in carotenoid biosynthesis plays a central role in the regulation of a number of essential functions mediated via carotenoids. PSYs have been deeply investigated in plants, bacteria and algae however in apicomplexans it is poorly studied. In an effort to characterize PSY in apicomplexans especially the malaria parasite Plasmodium falciparum (P. falciparum), a detailed bioinformatics analysis is undertaken. We have analysed the Phylogenetic relationship of PSY also referred to as octaprenyl pyrophosphate synthase (OPPS) in P. falciparum with other taxonomic groups. Further, we in silico characterized the secondary and tertiary structures of P. falciparum PSY/OPPS and compared the tertiary structures with crystal structure of Thermotoga maritima (T. maritima) OPPS. Our results evidenced the resemblance of P. falciparum PSY with the active site of T. maritima OPPS. Interestingly, the comparative structural analysis revealed an unconserved unique loop in P. falciparum OPPS/PSY. Such structural insights might contribute novel accessory functions to the protein thus, offering potential drug targets.

Factors influencing nurse participation in continuing professional development activities: Survey results from the Netherlands.

PubMed

Brekelmans, Gerard; Maassen, Susanne; Poell, Rob F; Weststrate, Jan; Geurdes, Ed

2016-05-01

Professionals are individually responsible for planning and carrying out continuing professional development (CPD) activities, ensuring their relevance to current practice and career development. The key factors that encourage nurses to undertake CPD activities are not yet clear. Several studies have investigated motives of nurses to participate in CPD programmes ("Motives"), the importance they attach to CPD ("Importance"), the conditions they consider necessary for participation ("Conditions"), and their actual participation in CPD activities ("Pursued"). The relationships among these variables, however, have neither been investigated nor reported to date. The aim of this study is to investigate the nature of the relationships among those factors that influence nurse participation in CPD in the Netherlands. An exploratory cross-sectional study was carried out using quantitative data collected with the previously validated Questionnaire Professional Development of Nurses (Q-PDN). A convenience sample of 5500 registered nurses working at one Dutch university hospital and several general hospitals was addressed. A descriptive study using a survey was undertaken. The questionnaire was completed and returned by 1226 nurses. Correlation analyses were conducted to determine which factors were related to nurses undertaking CPD activities. Structural equation modelling was deployed to determine the relationships among the variables. "Conditions" was found to be moderately related to "Motives", which itself was strongly related to "Importance", which itself was very strongly related to "CPD activities pursued". If nurses considered a CPD activity important they were highly likely to pursue it; however, the importance attached to specific CPD activities was influenced by the presence of particular motives, which depended in part on the way CPD conditions were perceived. The key factor influencing CPD participation of nurses is how important they deem particular CPD activities; the latter is a function of their CPD motives and of their perceptions that the right conditions for participation are in place. Implications are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Design, Synthesis, and Biological and Structural Evaluations of Novel HIV-1 Protease Inhibitors To Combat Drug Resistance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parai, Maloy Kumar; Huggins, David J.; Cao, Hong

2012-09-11

A series of new HIV-1 protease inhibitors (PIs) were designed using a general strategy that combines computational structure-based design with substrate-envelope constraints. The PIs incorporate various alcohol-derived P2 carbamates with acyclic and cyclic heteroatomic functionalities into the (R)-hydroxyethylamine isostere. Most of the new PIs show potent binding affinities against wild-type HIV-1 protease and three multidrug resistant (MDR) variants. In particular, inhibitors containing the 2,2-dichloroacetamide, pyrrolidinone, imidazolidinone, and oxazolidinone moieties at P2 are the most potent with Ki values in the picomolar range. Several new PIs exhibit nanomolar antiviral potencies against patient-derived wild-type viruses from HIV-1 clades A, B, and Cmore » and two MDR variants. Crystal structure analyses of four potent inhibitors revealed that carbonyl groups of the new P2 moieties promote extensive hydrogen bond interactions with the invariant Asp29 residue of the protease. These structure-activity relationship findings can be utilized to design new PIs with enhanced enzyme inhibitory and antiviral potencies.« less

Colour-induced relationship between affect and reaching kinematics during a goal-directed aiming task.

PubMed

Williams, Camille K; Grierson, Lawrence E M; Carnahan, Heather

2011-08-01

A link between affect and action has been supported by the discovery that threat information is prioritized through an action-centred pathway--the dorsal visual stream. Magnocellular afferents, which originate from the retina and project to dorsal stream structures, are suppressed by exposure to diffuse red light, which diminishes humans' perception of threat-based images. In order to explore the role of colour in the relationship between affect and action, participants donned different pairs of coloured glasses (red, yellow, green, blue and clear) and completed Positive and Negative Affect Scale questionnaires as well as a series of target-directed aiming movements. Analyses of affect scores revealed a significant main effect for affect valence and a significant interaction between colour and valence: perceived positive affect was significantly smaller for the red condition. Kinematic analyses of variable error in the primary movement direction and Pearson correlation analyses between the displacements travelled prior to and following peak velocity indicated reduced accuracy and application of online control processes while wearing red glasses. Variable error of aiming was also positively and significantly correlated with negative affect scores under the red condition. These results suggest that only red light modulates the affect-action link by suppressing magnocellular activity, which disrupts visual processing for movement control. Furthermore, previous research examining the effect of the colour red on psychomotor tasks and perceptual acceleration of threat-based imagery suggest that stimulus-driven motor performance tasks requiring online control may be particularly susceptible to this effect.

Structure-activity relationship studies of chalcone leading to 3-hydroxy-4,3',4',5'-tetramethoxychalcone and its analogues as potent nuclear factor kappaB inhibitors and their anticancer activities.

PubMed

Srinivasan, Balasubramanian; Johnson, Thomas E; Lad, Rahul; Xing, Chengguo

2009-11-26

Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappaB) activation. The structures of chalcone-based NF-kappaB inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappaB inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappaB inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappaB inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappaB inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappaB inhibitory activities, suggesting that suppressing NF-kappaB activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.

Sedentary Activity and Body Composition of Middle School Girls: The Trial of Activity for Adolescent Girls

ERIC Educational Resources Information Center

Pratt, Charlotte; Webber, Larry S.; Baggett, Chris D.; Ward, Dianne; Pate, Russell R.; Murray, David; Lohman, Timothy; Lytle, Leslie; Elder, John P.

2008-01-01

This study describes the relationships between sedentary activity and body composition in 1,458 sixth-grade girls from 36 middle schools across the United States. Multivariate associations between sedentary activity and body composition were examined with regression analyses using general linear mixed models. Mean age, body mass index, and…

Biological activity of antitumoural MGBG: the structural variable.

PubMed

Marques, M P M; Gil, F P S C; Calheiros, R; Battaglia, V; Brunati, A M; Agostinelli, E; Toninello, A

2008-05-01

The present study aims at determining the structure-activity relationships (SAR's) ruling the biological function of MGBG (methylglyoxal bis(guanylhydrazone)), a competitive inhibitor of S-adenosyl-L-methionine decarboxylase displaying anticancer activity, involved in the biosynthesis of the naturally occurring polyamines spermidine and spermine. In order to properly understand its biochemical activity, MGBG's structural preferences at physiological conditions were ascertained, by quantum mechanical (DFT) calculations.

Hope-inspiring therapeutic relationships, professional expectations and social inclusion for young people with psychosis.

PubMed

Berry, Clio; Greenwood, Kathryn

2015-10-01

Personal recovery accounts suggest that a positive therapeutic relationship with an optimistic mental health professional may facilitate social inclusion. However, little empirical research has investigated the role of the therapeutic relationship in social outcomes or explored potential mechanisms of change within community psychosis care. This study investigated the direct predictive associations of the therapeutic relationship and professional expectancies for social inclusion and vocational activity for young people with psychosis, and indirect associations through hopefulness. Young people with psychosis and their main mental health professional (n=51 dyads) participated across two time points. Measures of therapeutic relationships, professional expectancies, and vocational activity were obtained at baseline. Measures of hopefulness, social inclusion and vocational activity were obtained at follow-up. Direct and indirect associations between variables were analysed using path modelling. Directed path models were consistent with a positive therapeutic relationship and positive professional expectancies predicting social inclusion and vocational activity through mediation by increased patient domain-specific hopefulness. The professional-rated therapeutic relationship more directly predicts change in vocational activity status. Change in vocational activity status predicts increased patient hopefulness. The therapeutic relationship between professionals and young people with psychosis appears hope-inspiring and important to patients' social inclusion and vocational outcomes. Vocational activity may produce reciprocal gains in hopefulness. Copyright © 2015 Elsevier B.V. All rights reserved.

Relationships between physical properties and sequence in silkworm silks

PubMed Central

Malay, Ali D.; Sato, Ryota; Yazawa, Kenjiro; Watanabe, Hiroe; Ifuku, Nao; Masunaga, Hiroyasu; Hikima, Takaaki; Guan, Juan; Mandal, Biman B.; Damrongsakkul, Siriporn; Numata, Keiji

2016-01-01

Silk has attracted widespread attention due to its superlative material properties and promising applications. However, the determinants behind the variations in material properties among different types of silk are not well understood. We analysed the physical properties of silk samples from a variety of silkmoth cocoons, including domesticated Bombyx mori varieties and several species from Saturniidae. Tensile deformation tests, thermal analyses, and investigations on crystalline structure and orientation of the fibres were performed. The results showed that saturniid silks produce more highly-defined structural transitions compared to B. mori, as seen in the yielding and strain hardening events during tensile deformation and in the changes observed during thermal analyses. These observations were analysed in terms of the constituent fibroin sequences, which in B. mori are predicted to produce heterogeneous structures, whereas the strictly modular repeats of the saturniid sequences are hypothesized to produce structures that respond in a concerted manner. Within saturniid fibroins, thermal stability was found to correlate with the abundance of poly-alanine residues, whereas differences in fibre extensibility can be related to varying ratios of GGX motifs versus bulky hydrophobic residues in the amorphous phase. PMID:27279149

Relationships between physical properties and sequence in silkworm silks

NASA Astrophysics Data System (ADS)

Malay, Ali D.; Sato, Ryota; Yazawa, Kenjiro; Watanabe, Hiroe; Ifuku, Nao; Masunaga, Hiroyasu; Hikima, Takaaki; Guan, Juan; Mandal, Biman B.; Damrongsakkul, Siriporn; Numata, Keiji

2016-06-01

Silk has attracted widespread attention due to its superlative material properties and promising applications. However, the determinants behind the variations in material properties among different types of silk are not well understood. We analysed the physical properties of silk samples from a variety of silkmoth cocoons, including domesticated Bombyx mori varieties and several species from Saturniidae. Tensile deformation tests, thermal analyses, and investigations on crystalline structure and orientation of the fibres were performed. The results showed that saturniid silks produce more highly-defined structural transitions compared to B. mori, as seen in the yielding and strain hardening events during tensile deformation and in the changes observed during thermal analyses. These observations were analysed in terms of the constituent fibroin sequences, which in B. mori are predicted to produce heterogeneous structures, whereas the strictly modular repeats of the saturniid sequences are hypothesized to produce structures that respond in a concerted manner. Within saturniid fibroins, thermal stability was found to correlate with the abundance of poly-alanine residues, whereas differences in fibre extensibility can be related to varying ratios of GGX motifs versus bulky hydrophobic residues in the amorphous phase.

Structure activity relationship study of curcumin analogues toward the amyloid-beta aggregation inhibitor.

PubMed

Endo, Hitoshi; Nikaido, Yuri; Nakadate, Mamiko; Ise, Satomi; Konno, Hiroyuki

2014-12-15

Inhibition of the amyloid β aggregation process could possibly prevent the onset of Alzheimer's disease. In this article, we report a structure-activity relationship study of curcumin analogues for anti amyloid β aggregation activity. Compound 7, the ideal amyloid β aggregation inhibitor in vitro among synthesized curcumin analogues, has not only potent anti amyloid β aggregation effects, but also water solubility more than 160 times that of curcumin. In addition, new approaches to improve water solubility of curcumin-type compounds are proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer's Disease.

PubMed

Liu-Seifert, Hong; Siemers, Eric; Price, Karen; Han, Baoguang; Selzler, Katherine J; Henley, David; Sundell, Karen; Aisen, Paul; Cummings, Jeffrey; Raskin, Joel; Mohs, Richard

2015-01-01

The temporal relationship of cognitive deficit and functional impairment in Alzheimer's disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression. To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials. Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time. In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa. Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process.

The Relationship between Phonological and Auditory Processing and Brain Organization in Beginning Readers

ERIC Educational Resources Information Center

Pugh, Kenneth R.; Landi, Nicole; Preston, Jonathan L.; Mencl, W. Einar; Austin, Alison C.; Sibley, Daragh; Fulbright, Robert K.; Seidenberg, Mark S.; Grigorenko, Elena L.; Constable, R. Todd; Molfese, Peter; Frost, Stephen J.

2013-01-01

We employed brain-behavior analyses to explore the relationship between performance on tasks measuring phonological awareness, pseudoword decoding, and rapid auditory processing (all predictors of reading (dis)ability) and brain organization for print and speech in beginning readers. For print-related activation, we observed a shared set of…

Understanding and Measuring Coach–Teacher Alliance: A Glimpse Inside the ‘Black Box’

PubMed Central

Pas, Elise T.; Bradshaw, Catherine P.

2016-01-01

Coaching models are increasingly used in schools to enhance fidelity and effectiveness of evidence-based interventions; yet, little is known about the relationship between the coach and teacher (i.e., coach–teacher alliance), which may indirectly enhance teacher and student outcomes through improved implementation quality. There is also limited research on measures of coach–teacher alliance, further hindering the field from understanding the active components for successful coaching. The current study examined the factor structure and psychometric characteristics of a measure of coach–teacher alliance as reported by both teachers and coaches and explored the extent to which teachers and coaches reliably rate their alliance. Data come from a sample of 147 teachers who received implementation support from one of four coaches; both the teacher and the coach completed an alliance questionnaire. Separate confirmatory factor analyses for each informant revealed four factors (relationship, process, investment, and perceived benefits) as well as an additional coach-rated factor (perceived teacher barriers). A series of analyses, including cross-rater correlations, intraclass correlation coefficients, and Kuder-Richardson reliability estimates suggested that teachers and coaches provide reliable, though not redundant, information about the alliance. Implications for future research and the utilization of the parallel coach–teacher alliance measures to increase the effectiveness of coaching are discussed. PMID:26872479

Response of rocky invertebrate diversity, structure and function to the vertical layering of vegetation

NASA Astrophysics Data System (ADS)

Bustamante, María; Tajadura, Javier; Gorostiaga, José María; Saiz-Salinas, José Ignacio

2014-06-01

Macroalgae comprise a prominent part of the rocky benthos where many invertebrates develop, and are believed to be undergoing severe declines worldwide. In order to investigate how the vegetation structure (crustose, basal and canopy layers) contributes to the diversity, structure and function of benthic invertebrates, a total of 31 subtidal transects were sampled along the northeast Atlantic coast of Spain. Significant positive relationships were found between the canopy layer and faunal abundance, taxonomic diversity and functional group diversity. Canopy forming algae were also related to epiphytic invertebrates, medium size forms, colonial strategy and suspensivores. By contrast, basal algae showed negative relationships with all variables tested except for detritivores. Multivariate multiple regression analyses (DISTLM) point to crustose as well as canopy layers as the best link between seaweeds and invertebrate assemblage structure. A close relationship was found between taxonomic and functional diversities. In general, low levels of taxonomic redundancy were detected for functional groups correlated with vegetation structure. A conceptual model based on the results is proposed, describing distinct stages of invertebrate assemblages in relation to the vertical structure of vegetation.

The relationship between motivational structure, sense of control, intrinsic motivation and university students' alcohol consumption.

PubMed

Shamloo, Zohreh Sepehri; Cox, W Miles

2010-02-01

The aim of this study was to determine how sense of control and intrinsic motivation are related to university students' motivational structure and alcohol consumption. Participants were 94 university students who completed the Personal Concerns Inventory, Shapiro Control Inventory, Helplessness Questionnaire, Intrinsic-Extrinsic Aspirations Scale, and Alcohol Use Questionnaire. Results showed that sense of control and intrinsic motivation were positively correlated with adaptive motivation and negatively correlated with alcohol consumption. Mediational analyses indicated that adaptive motivation fully mediated the relationship between sense of control/intrinsic motivation and alcohol consumption.

Origin, Migration Routes and Worldwide Population Genetic Structure of the Wheat Yellow Rust Pathogen Puccinia striiformis f.sp. tritici

PubMed Central

Ali, Sajid; Gladieux, Pierre; Leconte, Marc; Gautier, Angélique; Justesen, Annemarie F.; Hovmøller, Mogens S.; Enjalbert, Jérôme; de Vallavieille-Pope, Claude

2014-01-01

Analyses of large-scale population structure of pathogens enable the identification of migration patterns, diversity reservoirs or longevity of populations, the understanding of current evolutionary trajectories and the anticipation of future ones. This is particularly important for long-distance migrating fungal pathogens such as Puccinia striiformis f.sp. tritici (PST), capable of rapid spread to new regions and crop varieties. Although a range of recent PST invasions at continental scales are well documented, the worldwide population structure and the center of origin of the pathogen were still unknown. In this study, we used multilocus microsatellite genotyping to infer worldwide population structure of PST and the origin of new invasions based on 409 isolates representative of distribution of the fungus on six continents. Bayesian and multivariate clustering methods partitioned the set of multilocus genotypes into six distinct genetic groups associated with their geographical origin. Analyses of linkage disequilibrium and genotypic diversity indicated a strong regional heterogeneity in levels of recombination, with clear signatures of recombination in the Himalayan (Nepal and Pakistan) and near-Himalayan regions (China) and a predominant clonal population structure in other regions. The higher genotypic diversity, recombinant population structure and high sexual reproduction ability in the Himalayan and neighboring regions suggests this area as the putative center of origin of PST. We used clustering methods and approximate Bayesian computation (ABC) to compare different competing scenarios describing ancestral relationship among ancestral populations and more recently founded populations. Our analyses confirmed the Middle East-East Africa as the most likely source of newly spreading, high-temperature-adapted strains; Europe as the source of South American, North American and Australian populations; and Mediterranean-Central Asian populations as the origin of South African populations. Although most geographic populations are not markedly affected by recent dispersal events, this study emphasizes the influence of human activities on recent long-distance spread of the pathogen. PMID:24465211

Sunspot activity and influenza pandemics: a statistical assessment of the purported association.

PubMed

Towers, S

2017-10-01

Since 1978, a series of papers in the literature have claimed to find a significant association between sunspot activity and the timing of influenza pandemics. This paper examines these analyses, and attempts to recreate the three most recent statistical analyses by Ertel (1994), Tapping et al. (2001), and Yeung (2006), which all have purported to find a significant relationship between sunspot numbers and pandemic influenza. As will be discussed, each analysis had errors in the data. In addition, in each analysis arbitrary selections or assumptions were also made, and the authors did not assess the robustness of their analyses to changes in those arbitrary assumptions. Varying the arbitrary assumptions to other, equally valid, assumptions negates the claims of significance. Indeed, an arbitrary selection made in one of the analyses appears to have resulted in almost maximal apparent significance; changing it only slightly yields a null result. This analysis applies statistically rigorous methodology to examine the purported sunspot/pandemic link, using more statistically powerful un-binned analysis methods, rather than relying on arbitrarily binned data. The analyses are repeated using both the Wolf and Group sunspot numbers. In all cases, no statistically significant evidence of any association was found. However, while the focus in this particular analysis was on the purported relationship of influenza pandemics to sunspot activity, the faults found in the past analyses are common pitfalls; inattention to analysis reproducibility and robustness assessment are common problems in the sciences, that are unfortunately not noted often enough in review.

SOD activity of carboxyfullerenes predicts their neuroprotective efficacy: A structure-activity study

PubMed Central

Ali, Sameh Saad; Hardt, Joshua I.; Dugan, Laura L.

2008-01-01

Superoxide radical anion is a biologically important oxidant that has been linked to tissue injury and inflammation in several diseases. Here we carried out a structure-activity study on 6 different carboxyfullerene superoxide dismutase (SOD) mimetics with distinct electronic and biophysical characteristics. Neurotoxicity via NMDA receptors, which involves intracellular superoxide, was used as a model to evaluate structure-activity relationships between reactivity towards superoxide and neuronal rescue by these drugs. A significant correlation between neuroprotection by carboxyfullerenes and their ki towards superoxide radical was observed. Computer-assistant molecular modeling demonstrated that the reactivity towards superoxide is sensitive to changes in dipole moment which are dictated not only by the number of carboxyl groups, but also by their distribution on the fullerene ball. These results indicate that the SOD activity of these cell-permeable compounds predicts neuroprotection, and establishes a structure-activity relationship to aid in future studies on the biology of superoxide across disciplines. PMID:18656425

Quasi-causal associations of physical activity and neighborhood walkability with body mass index: a twin study.

PubMed

Duncan, Glen E; Cash, Stephanie Whisnant; Horn, Erin E; Turkheimer, Eric

2015-01-01

Physical activity, neighborhood walkability, and body mass index (BMI, kg/m(2)) associations were tested using quasi-experimental twin methods. We hypothesized that physical activity and walkability were independently associated with BMI within twin pairs, controlling for genetic and environmental background shared between them. Data were from 6376 (64% female; 58% identical) same-sex pairs, University of Washington Twin Registry, 2008-2013. Neighborhood walking, moderate-to-vigorous physical activity (MVPA), and BMI were self-reported. Residential address was used to calculate walkability. Phenotypic (non-genetically informed) and biometric (genetically informed) regression was employed, controlling for age, sex, and race. Walking and MVPA were associated with BMI in phenotypic analyses; associations were attenuated but significant in biometric analyses (Ps<0.05). Walkability was not associated with BMI, however, was associated with walking (but not MVPA) in both phenotypic and biometric analyses (Ps<0.05), with no attenuation accounting for shared genetic and environmental background. The association between activity and BMI is largely due to shared genetic and environmental factors, but a significant causal relationship remains accounting for shared background. Although walkability is not associated with BMI, it is associated with neighborhood walking (but not MVPA) accounting for shared background, suggesting a causal relationship between them. Copyright © 2014 Elsevier Inc. All rights reserved.

Constraints on the diversity and distribution of coral-reef assemblages in the volcanic Northern Mariana Islands

NASA Astrophysics Data System (ADS)

Houk, P.; Starmer, J.

2010-03-01

A central problem for jurisdictional scientists and managers is to reconcile how multiple environmental regimes, encompassing continuous, intermittent and human disturbances, influence pertinent ecological management targets. The presence of heterogeneous environments throughout the volcanic Northern Mariana Islands (NMI), coupled with the availability of descriptive physical data, form the basis examining environmental-ecological relationships. Since 2003, coral abundances and macrobiota (all visibly recognizable taxa greater than 2 cm) occurrences have been estimated at 42 reef slopes along the volcanic archipelago. Analyses showed that reef types acted as surrogates of coral growth capacity and the modern assemblages residing upon them, being highest and most favorable, respectively, where relatively high salinity levels, low-to-moderate wave exposure, and an absence of volcanic activity for ~90 years existed. However, island size was the greatest constraint on species richness overall, but relations with corals were dampened by volcanic activity and increased for sponges and algae where greater connection with the island aquifer existed (i.e., relatively low salinity levels). The number of years since volcanic activity has occurred was positively related to the residuals of species-area relationships and coral cover, with a ~90-year time frame predicted for recovery. Notably, no relationships with watershed characteristics or distance from CNMI’s main fishing port and coral-reef assemblages or species richness were found. Further examination of specific management concerns, such as fisheries and feral animal populations, should be designed to account for the inherent differences in driving environmental regimes. Management strategies focused upon conserving biodiversity and ecosystem function should be centered at the island level, matching the operational scale of dominant environmental-ecological relationships. Marine reserves represent a strategy pertinent for the remote NMI; a spatial structure is discussed.

Promoting Teachers' Implementation of Classroom-Based Prevention Programming Through Coaching: The Mediating Role of the Coach-Teacher Relationship.

PubMed

Johnson, Stacy R; Pas, Elise T; Bradshaw, Catherine P; Ialongo, Nicholas S

2018-05-01

There is growing awareness of the importance of implementation fidelity and the supports, such as coaching, to optimize it. This study examined how coaching activities (i.e., check-ins, needs assessment, modeling, and technical assistance) related directly and indirectly to implementation dosage and quality of the PAX Good Behavior Game, via a mediating pathway through working relationship. Mediation analyses of 138 teachers revealed direct effects of modeling and working relationship on implementation dosage, whereas needs assessment was associated with greater dosage indirectly, by higher ratings of the working relationship. Understanding how coaching activities promote implementation fidelity elements has implications for improving program effectiveness.

Relationship between haemolytic and adjuvant activity and structure of protopanaxadiol-type saponins from the roots of Panax notoginseng.

PubMed

Sun, Hong-Xiang; Qin, Feng; Ye, Yi-Ping

2005-12-01

Four protopanaxadiol-type saponins (PDS), ginsenosides-Rb(1), -Rd, notoginsenosides-K, -R(4) isolated from the roots of Panax notoginseng were evaluated for their haemolytic activities and adjuvant potentials on the cellular and humoral immune responses of ICR mice against ovalbumin (OVA). The effect of the substitution pattern of these PDS on their biological activities was investigated and structure-activity relationships were established. Among four PDS, the ranking of the haemolytic activity was K>R(4)>Rb(1)>Rd (P<0.01 or <0.001). Rd, Rb(1), and K could significantly enhance mitogen- and OVA-induced splenocyte proliferation in the OVA-immunized mice (P<0.001), with the order in terms of stimulation index being Rd>Rb(1)>K>R(4). OVA-specific IgG, IgG1, IgG2a and IgG2b antibody levels in the OVA-immunized mice were significantly enhanced by four PDS. Adjuvant potentials of Rd on antibody responses were higher than those of other three PDS. Meanwhile, Rd also significantly enhanced the production of the Th1 and Th2 cytokines in OVA-immunized mice (P<0.05 or <0.01). The structure-activity relationship studies suggested that the length of sugar side chains at position C-20 and the linkage of glucose moiety at position C-3 of protopanaxadiol could affect the haemolytic and adjuvant activities of PDS. The information about this structure/function relationship might be useful for developing semisynthetic tetracyclic triterpenoid saponin derivatives with immunological adjuvant activity, as well as a reference to the distribution of the functional groups composing the saponin molecule.

Work Dissatisfaction and Sleep Problems among Canadians in the Latter Half of Life.

PubMed

Brown, Kyla; Bierman, Alex

2017-09-01

This study examined the relationship between work dissatisfaction and sleep problems among Canadian adults in the latter half of life, as well as how gender and social contact moderate this relationship. Data were obtained from the Canadian General Social Survey, Cycle 21 (2007), which sampled adults aged 45 and older in 2007. Analyses focused on individuals with employment as their main activity. Analyses show that work dissatisfaction positively predicts trouble sleeping. There are no significant gender differences in this relationship. Social contact with friends buffers this relationship, but social contact with family does not, and buffering does not vary significantly between men and women. This research contributes to knowledge on sleep problems by showing that work dissatisfaction is adversely associated with sleep problems among Canadians in the latter half of life, but social contact with friends can weaken this deleterious relationship.

Is cultural activity at work related to mental health in employees?

PubMed

Theorell, Töres; Osika, Walter; Leineweber, Constanze; Magnusson Hanson, Linda L; Bojner Horwitz, Eva; Westerlund, Hugo

2013-04-01

To examine relationships between work-based cultural activities and mental employee health in working Swedes. A positive relationship between frequent cultural activity at work and good employee health was expected. Random sample of working Swedish men and women in three waves, 2006, 2008 and 2010, on average 60 % participation rate. A postal questionnaire with questions about cultural activities organised for employees and about emotional exhaustion (Maslach) and depressive symptoms (short form of SCL). Employee assessments of "non-listening manager" and work environment ("psychological demands" and "decision latitude") as well as socioeconomic variables were covariates. Cross-sectional analyses for each study year as well as prospective analyses for 2006-2008 and 2008-2010 were performed. Lower frequency of cultural activities at work during the period of high unemployment. The effects of relationships with emotional exhaustion were more significant than those with depressive symptoms. The associations were attenuated when adjustments were made for manager function (does your manager listen?) and demand/control. Associations were more pronounced during the period with low unemployment and high cultural activity at work (2008). In a prospective analysis, cultural activity at work in 2008 had an independent statistically significant "protective" effect on emotional exhaustion in 2010. No corresponding such association was found between 2006 and 2008. Cultural activities at work vary according to business cycle and have a statistical association with mental employee health, particularly with emotional exhaustion. There are particularly pronounced statistical protective effects of frequent cultural activity at work on likelihood of emotional exhaustion among employees.

Could occupational physical activity mitigate the link between moderate kidney dysfunction and coronary heart disease?

PubMed

Esquirol, Yolande; Tully, Mark; Ruidavets, Jean-Bernard; Fogarty, Damian; Ferrieres, Jean; Quinn, Michael; Hughes, Maria; Kee, Frank

2014-12-20

Chronic kidney disease is now regarded as a risk factor for cardiovascular disease. The impact of occupational or non-occupational physical activity (PA) on moderate decreases of renal function is uncertain. We aimed to identify the potential association of PA (occupational and leisure-time) on early decline of estimated glomerular filtration rate (eGFR) and to determine the potential mediating effect of PA on the relationship between eGFR and heart disease. From the PRIME study analyses were conducted in 1058 employed men. Energy expended during leisure, work and commuting was calculated. Linear regression analyses were used to determine the link between types of PA and moderate decrements of eGFR determined with the KDIGO guideline at the baseline assessment. Cox proportional hazards analyses were used to explore the potential effect of PA on the relationship between eGFR and heart disease, ascertained during follow-up over 10 years. For these employed men, and after adjustment for known confounders of GFR change, more time spent sitting at work was associated with increased risk of moderate decline in kidney function, while carrying objects or being active at work was associated with decreased risk. In contrast, no significant link with leisure PA was apparent. No potential mediating effect of occupational PA was found for the relationship between eGFR and coronary heart disease. Occupational PA (potential modifiable factors) could provide a dual role on early impairment of renal function, without influence on the relationship between early decrease of e-GFR and CHD risk. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Physical activity reduces the influence of genetic effects on BMI and waist circumference: a study in young adult twins.

PubMed

Mustelin, L; Silventoinen, K; Pietiläinen, K; Rissanen, A; Kaprio, J

2009-01-01

Both obesity and exercise behavior are influenced by genetic and environmental factors. However, whether obesity and physical inactivity share the same genetic vs environmental etiology has rarely been studied. We therefore analyzed these complex relationships, and also examined whether physical activity modifies the degree of genetic influence on body mass index (BMI) and waist circumference (WC). The FinnTwin16 Study is a population-based, longitudinal study of five consecutive birth cohorts (1975-1979) of Finnish twins. Data on height, weight, WC and physical activity of 4343 subjects at the average age of 25 (range, 22-27 years) years were obtained by a questionnaire and self-measurement of WC. Quantitative genetic analyses based on linear structural equations were carried out by the Mx statistical package. The modifying effect of physical activity on genetic and environmental influences was analyzed using gene-environment interaction models. The overall heritability estimates were 79% in males and 78% in females for BMI, 56 and 71% for WC and 55 and 54% for physical activity, respectively. There was an inverse relationship between physical activity and WC in males (r = -0.12) and females (r=-0.18), and between physical activity and BMI in females (r = -0.12). Physical activity significantly modified the heritability of BMI and WC, with a high level of physical activity decreasing the additive genetic component in BMI and WC. Physically active subjects were leaner than sedentary ones, and physical activity reduced the influence of genetic factors to develop high BMI and WC. This suggests that the individuals at greatest genetic risk for obesity would benefit the most from physical activity.

Relationships between bat occupancy and habitat and landscape structure along a savanna, woodland, forest gradient in the Missouri Ozarks

Treesearch

Clarissa A. Starbuck; Sybill K. Amelon; Frank R. III Thompson

2015-01-01

Many land-management agencies are restoring savannas and woodlands using prescribed fire and forest thinning, and information is needed on how wildlife species respond to these management activities. Our objectives were to evaluate support for relationships of bat site occupancy with vegetation structure and management and landscape composition and structure across a...

Quantitative structure-property relationship (correlation analysis) of phosphonic acid-based chelates in design of MRI contrast agent.

PubMed

Tiwari, Anjani K; Ojha, Himanshu; Kaul, Ankur; Dutta, Anupama; Srivastava, Pooja; Shukla, Gauri; Srivastava, Rakesh; Mishra, Anil K

2009-07-01

Nuclear magnetic resonance imaging is a very useful tool in modern medical diagnostics, especially when gadolinium (III)-based contrast agents are administered to the patient with the aim of increasing the image contrast between normal and diseased tissues. With the use of soft modelling techniques such as quantitative structure-activity relationship/quantitative structure-property relationship after a suitable description of their molecular structure, we have studied a series of phosphonic acid for designing new MRI contrast agent. Quantitative structure-property relationship studies with multiple linear regression analysis were applied to find correlation between different calculated molecular descriptors of the phosphonic acid-based chelating agent and their stability constants. The final quantitative structure-property relationship mathematical models were found as--quantitative structure-property relationship Model for phosphonic acid series (Model 1)--log K(ML) = {5.00243(+/-0.7102)}- MR {0.0263(+/-0.540)}n = 12 l r l = 0.942 s = 0.183 F = 99.165 quantitative structure-property relationship Model for phosphonic acid series (Model 2)--log K(ML) = {5.06280(+/-0.3418)}- MR {0.0252(+/- .198)}n = 12 l r l = 0.956 s = 0.186 F = 99.256.

Structure-Activity Relationships for the Antifungal Activity of Selective Estrogen Receptor Antagonists Related to Tamoxifen

PubMed Central

Butts, Arielle; Martin, Jennifer A.; DiDone, Louis; Bradley, Erin K.; Mutz, Mitchell; Krysan, Damian J.

2015-01-01

Cryptococcosis is one of the most important invasive fungal infections and is a significant contributor to the mortality associated with HIV/AIDS. As part of our program to repurpose molecules related to the selective estrogen receptor modulator (SERM) tamoxifen as anti-cryptococcal agents, we have explored the structure-activity relationships of a set of structurally diverse SERMs and tamoxifen derivatives. Our data provide the first insights into the structural requirements for the antifungal activity of this scaffold. Three key molecular characteristics affecting anti-cryptococcal activity emerged from our studies: 1) the presence of an alkylamino group tethered to one of the aromatic rings of the triphenylethylene core; 2) an appropriately sized aliphatic substituent at the 2 position of the ethylene moiety; and 3) electronegative substituents on the aromatic rings modestly improved activity. Using a cell-based assay of calmodulin antagonism, we found that the anti-cryptococcal activity of the scaffold correlates with calmodulin inhibition. Finally, we developed a homology model of C. neoformans calmodulin and used it to rationalize the structural basis for the activity of these molecules. Taken together, these data and models provide a basis for the further optimization of this promising anti-cryptococcal scaffold. PMID:26016941

Study of Factors Preventing Children from Enrolment in Primary School in the Republic of Honduras: Analysis Using Structural Equation Modelling

ERIC Educational Resources Information Center

Ashida, Akemi

2015-01-01

Studies have investigated factors that impede enrolment in Honduras. However, they have not analysed individual factors as a whole or identified the relationships among them. This study used longitudinal data for 1971 children who entered primary schools from 1986 to 2000, and employed structural equation modelling to examine the factors…

Synthesis of mixed MOR/KOR efficacy cyclic opioid peptide analogs with antinociceptive activity after systemic administration.

PubMed

Perlikowska, Renata; Piekielna, Justyna; Gentilucci, Luca; De Marco, Rossella; Cerlesi, Maria Camilla; Calo, Girolamo; Artali, Roberto; Tömböly, Csaba; Kluczyk, Alicja; Janecka, Anna

2016-02-15

Cyclic pentapeptide Tyr-c[D-Lys-Phe-Phe-Asp]NH2, based on the structure of endomorphin-2 (EM-2), which shows high affinity to the μ-opioid receptor (MOR) and a very strong antinociceptive activity in mice was used as a parent compound for the structure-activity relationship studies. In this report we synthesized analogs of a general sequence Dmt-c[D-Lys-Xaa-Yaa-Asp]NH2, with D-1- or D-2-naphthyl-3-alanine (D-1-Nal or D-2-Nal) in positions 3 or 4. In our earlier papers we have indicated that replacing a phenylalanine residue by the more extended aromatic system of naphthylalanines may result in increased bioactivities of linear analogs. The data obtained here showed that only cyclopeptides modified in position 4 retained the sub-nanomolar MOR and nanomolar κ-opioid receptor (KOR) affinity, similar but not better than that of a parent cyclopeptide. In the in vivo mouse hot-plate test, the most potent analog, Dmt-c[D-Lys-Phe-D-1-Nal-Asp]NH2, exhibited higher than EM-2 but slightly lower than the cyclic parent peptide antinociceptive activity after peripheral (ip) and also central administration (icv). Conformational analyses in a biomimetic environment and molecular docking studies disclosed the structural determinants responsible for the different pharmacological profiles of position 3- versus position 4-modified analogs. Copyright © 2015. Published by Elsevier Masson SAS.

Syntheses and anti-MRSA activities of the C3 analogs of mansonone F, a potent anti-bacterial sesquiterpenoid: insights into its structural requirements for anti-MRSA activity.

PubMed

Shin, Dong-Yun; Kim, Sun Nam; Chae, Jung-Hyun; Hyun, Soon-Sil; Seo, Seung-Yong; Lee, Yong-Sil; Lee, Kwang-Ok; Kim, Seok-Ho; Lee, Yun-Sang; Jeong, Jae Min; Choi, Nam-Song; Suh, Young-Ger

2004-09-06

Syntheses and excellent anti-MRSA activities of the mansonone F analogs are reported. In addition, the minimal structural requirements for its anti-MRSA activities as well as its structure-activity relationship including the C3 substituents effects on anti-MRSA activity are also described. In particular, this study revealed that both ortho-quinone and tricyclic systems of mansonone F are essential for anti-MRSA activities.

Physical activity and calorie intake mediate the relationship from depression to body fat mass among female Mexican health workers.

PubMed

Quezada, Amado D; Macías-Waldman, Nayeli; Salmerón, Jorge; Swigart, Tessa; Gallegos-Carrillo, Katia

2017-11-17

Depression is a foremost cause of morbidity throughout the world and the prevalence of depression in women is about twice as high as men. Additionally, overweight and obesity are major global health concerns. We explored the relationship between depression and body fat, and the role of physical activity and diet as mediators of this relationship in a sample of 456 adult female Mexican health workers. Longitudinal and cross-sectional analyses using data from adult women of the Health Workers Cohort Study (HWCS) Measures of body fat mass (kg from DEXA), dietary intake (kcal from FFQ), leisure time activity (METs/wk) and depression (CES-D) were determined in two waves (2004-2006 and 2010-2011). We explored the interrelation between body fat, diet, leisure time, physical activity, and depression using a cross-lagged effects model fitted to longitudinal data. We also fitted a structural equations model to cross-sectional data with body fat as the main outcome, and dietary intake and physical activity from leisure time as mediators between depression and body fat. Baseline depression was significantly related to higher depression, higher calorie intake, and lower leisure time physical activity at follow-up. From our cross-sectional model, each standard deviation increase in the depression score was associated with an average increase of 751 ± 259 g (± standard error) in body fat through the mediating effects of calorie intake and physical activity. The results of this study show how depression may influence energy imbalance between calories consumed and calories expended, resulting in higher body fat among those with a greater depression score. Evaluating the role of mental conditions like depression in dietary and physical activity behaviors should be positioned as a key research goal for better designed and targeted public health interventions. The HealthWorkers Cohort Study (HWCS) has been approved by the Institutional IRB. Number: 2005-785-012.

The relationship between school multiculturalism and interpersonal violence: an exploratory study.

PubMed

Le, Thao N; Johansen, Samantha

2011-11-01

Multiculturalism has been purported to be supportive of positive youth development and outcomes. This study examined the relationship between perceived school multiculturalism-whether youth felt and thought that their school and teachers supported and provided activities for diverse intergroup interactions-and serious interpersonal violence, and explored whether this relation was mediated by civic engagement, ethnic identity, ethnocultural empathy, and positive peers. An ethnically diverse sample of 324 middle-school youth (mean age: 12.5 years; range: 11-15 years; sex: 50% female) from a city in northern California participated in the study. Analyses consisted of structural equation modeling with bootstrapping. The results revealed a negative association between school multiculturalism and interpersonal violence that was fully mediated by positive peers and civic engagement. Although school multiculturalism was positively associated with ethnic identity, ethnic identity, in turn, was not significantly associated with interpersonal violence. School multiculturalism is an important protective factor against youth violence by facilitating positive peer relationships and community engagement among youth. Teachers, administrators, and health officials need to consider the ways in which they can facilitate and encourage greater understanding, openness, and respect for diversity, and promote harmonious interactions among different groups at schools. Greater institutional support for school multiculturalism through implementation of tolerance curriculum and activities, for example, could in turn facilitate favorable youth outcomes. © 2011, American School Health Association.

Computational Studies of Free Radical-Scavenging Properties of Phenolic Compounds

PubMed Central

Alov, Petko; Tsakovska, Ivanka; Pajeva, Ilza

2015-01-01

For more than half a century free radical-induced alterations at cellular and organ levels have been investigated as a probable underlying mechanism of a number of adverse health conditions. Consequently, significant research efforts have been spent for discovering more effective and potent antioxidants / free radical scavengers for treatment of these adverse conditions. Being by far the most used antioxidants among natural and synthetic compounds, mono- and polyphenols have been the focus of both experimental and computational research on mechanisms of free radical scavenging. Quantum chemical studies have provided a significant amount of data on mechanisms of reactions between phenolic compounds and free radicals outlining a number of properties with a key role for the radical scavenging activity and capacity of phenolics. The obtained quantum chemical parameters together with other molecular descriptors have been used in quantitative structure-activity relationship (QSAR) analyses for the design of new more effective phenolic antioxidants and for identification of the most useful natural antioxidant phenolics. This review aims at presenting the state of the art in quantum chemical and QSAR studies of phenolic antioxidants and at analysing the trends observed in the field in the last decade. PMID:25547098

Computational studies of free radical-scavenging properties of phenolic compounds.

PubMed

Alov, Petko; Tsakovska, Ivanka; Pajeva, Ilza

2015-01-01

For more than half a century free radical-induced alterations at cellular and organ levels have been investigated as a probable underlying mechanism of a number of adverse health conditions. Consequently, significant research efforts have been spent for discovering more effective and potent antioxidants / free radical scavengers for treatment of these adverse conditions. Being by far the most used antioxidants among natural and synthetic compounds, mono- and polyphenols have been the focus of both experimental and computational research on mechanisms of free radical scavenging. Quantum chemical studies have provided a significant amount of data on mechanisms of reactions between phenolic compounds and free radicals outlining a number of properties with a key role for the radical scavenging activity and capacity of phenolics. The obtained quantum chemical parameters together with other molecular descriptors have been used in quantitative structure-activity relationship (QSAR) analyses for the design of new more effective phenolic antioxidants and for identification of the most useful natural antioxidant phenolics. This review aims at presenting the state of the art in quantum chemical and QSAR studies of phenolic antioxidants and at analysing the trends observed in the field in the last decade.

Development and implementation of (Q)SAR modeling within the CHARMMing web-user interface.

PubMed

Weidlich, Iwona E; Pevzner, Yuri; Miller, Benjamin T; Filippov, Igor V; Woodcock, H Lee; Brooks, Bernard R

2015-01-05

Recent availability of large publicly accessible databases of chemical compounds and their biological activities (PubChem, ChEMBL) has inspired us to develop a web-based tool for structure activity relationship and quantitative structure activity relationship modeling to add to the services provided by CHARMMing (www.charmming.org). This new module implements some of the most recent advances in modern machine learning algorithms-Random Forest, Support Vector Machine, Stochastic Gradient Descent, Gradient Tree Boosting, so forth. A user can import training data from Pubchem Bioassay data collections directly from our interface or upload his or her own SD files which contain structures and activity information to create new models (either categorical or numerical). A user can then track the model generation process and run models on new data to predict activity. © 2014 Wiley Periodicals, Inc.

Function in the Human Connectome: Task-fMRI and Individual Differences in Behavior

PubMed Central

Barch, Deanna M.; Burgess, Gregory C.; Harms, Michael P.; Petersen, Steven E.; Schlaggar, Bradley L.; Corbetta, Maurizio; Glasser, Matthew F.; Curtiss, Sandra; Dixit, Sachin; Feldt, Cindy; Nolan, Dan; Bryant, Edward; Hartley, Tucker; Footer, Owen; Bjork, James M.; Poldrack, Russ; Smith, Steve; Johansen-Berg, Heidi; Snyder, Abraham Z.; Van Essen, David C.

2014-01-01

The primary goal of the Human Connectome Project (HCP) is to delineate the typical patterns of structural and functional connectivity in the healthy adult human brain. However, we know that there are important individual differences in such patterns of connectivity, with evidence that this variability is associated with alterations in important cognitive and behavioral variables that affect real world function. The HCP data will be a critical stepping-off point for future studies that will examine how variation in human structural and functional connectivity play a role in adult and pediatric neurological and psychiatric disorders that account for a huge amount of public health resources. Thus, the HCP is collecting behavioral measures of a range of motor, sensory, cognitive and emotional processes that will delineate a core set of functions relevant to understanding the relationship between brain connectivity and human behavior. In addition, the HCP is using task-fMRI (tfMRI) to help delineate the relationships between individual differences in the neurobiological substrates of mental processing and both functional and structural connectivity, as well as to help characterize and validate the connectivity analyses to be conducted on the structural and functional connectivity data. This paper describes the logic and rationale behind the development of the behavioral, individual difference, and tfMRI batteries and provides preliminary data on the patterns of activation associated with each of the fMRI tasks, at both a group and individual level. PMID:23684877

NSF Workshop Report: Discovering General Principles of Nervous System Organization by Comparing Brain Maps across Species

PubMed Central

Striedter, Georg F.; Belgard, T. Grant; Chen, Chun-Chun; Davis, Fred P.; Finlay, Barbara L.; Güntürkün, Onur; Hale, Melina E.; Harris, Julie A.; Hecht, Erin E.; Hof, Patrick R.; Hofmann, Hans A.; Holland, Linda Z.; Iwaniuk, Andrew N.; Jarvis, Erich D.; Karten, Harvey J.; Katz, Paul S.; Kristan, William B.; Macagno, Eduardo R.; Mitra, Partha P.; Moroz, Leonid L.; Preuss, Todd M.; Ragsdale, Clifton W.; Sherwood, Chet C.; Stevens, Charles F.; Stüttgen, Maik C.; Tsumoto, Tadaharu; Wilczynski, Walter

2014-01-01

Efforts to understand nervous system structure and function have received new impetus from the federal Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Comparative analyses can contribute to this effort by leading to the discovery of general principles of neural circuit design, information processing, and gene-structure-function relationships that are not apparent from studies on single species. We here propose to extend the comparative approach to nervous system ‘maps’ comprising molecular, anatomical, and physiological data. This research will identify which neural features are likely to generalize across species, and which are unlikely to be broadly conserved. It will also suggest causal relationships between genes, development, adult anatomy, physiology, and, ultimately, behavior. These causal hypotheses can then be tested experimentally. Finally, insights from comparative research can inspire and guide technological development. To promote this research agenda, we recommend that teams of investigators coalesce around specific research questions and select a set of ‘reference species’ to anchor their comparative analyses. These reference species should be chosen not just for practical advantages, but also with regard for their phylogenetic position, behavioral repertoire, well-annotated genome, or other strategic reasons. We envision that the nervous systems of these reference species will be mapped in more detail than those of other species. The collected data may range from the molecular to the behavioral, depending on the research question. To integrate across levels of analysis and across species, standards for data collection, annotation, archiving, and distribution must be developed and respected. To that end, it will help to form networks or consortia of researchers and centers for science, technology, and education that focus on organized data collection, distribution, and training. These activities could be supported, at least in part, through existing mechanisms at NSF, NIH, and other agencies. It will also be important to develop new integrated software and database systems for cross-species data analyses. Multidisciplinary efforts to develop such analytical tools should be supported financially. Finally, training opportunities should be created to stimulate multidisciplinary, integrative research into brain structure, function, and evolution. PMID:24603302

Anterior insular cortex mediates bodily sensibility and social anxiety

PubMed Central

Shibata, Midori; Moriguchi, Yoshiya; Umeda, Satoshi

2013-01-01

Studies in psychiatry and cognitive neuroscience have reported an important relationship between individual interoceptive accuracy and anxiety level. This indicates that greater attention to one’s bodily state may contribute to the development of intense negative emotions and anxiety disorders. We hypothesized that reactivity in the anterior insular cortex underlies the intensity of interoceptive awareness and anxiety. To elucidate this triadic mechanism, we conducted functional magnetic resonance imaging (fMRI) and mediation analyses to examine the relationship between emotional disposition and activation in the anterior insular cortex while participants evaluated their own emotional and bodily states. Our results indicated that right anterior insular activation was positively correlated with individual levels of social anxiety and neuroticism and negatively correlated with agreeableness and extraversion. The results of the mediation analyses revealed that activity in the right anterior insula mediated the activity of neural correlates of interoceptive sensibility and social fear. Our findings suggest that attention to interoceptive sensation affects personality traits through how we feel emotion subjectively in various situations. PMID:22977199

Inbreeding Avoidance Drives Consistent Variation of Fine-Scale Genetic Structure Caused by Dispersal in the Seasonal Mating System of Brandt’s Voles

PubMed Central

Liu, Xiao Hui; Yue, Ling Fen; Wang, Da Wei; Li, Ning; Cong, Lin

2013-01-01

Inbreeding depression is a major evolutionary and ecological force influencing population dynamics and the evolution of inbreeding-avoidance traits such as mating systems and dispersal. Mating systems and dispersal are fundamental determinants of population genetic structure. Resolving the relationships among genetic structure, seasonal breeding-related mating systems and dispersal will facilitate our understanding of the evolution of inbreeding avoidance. The goals of this study were as follows: (i) to determine whether females actively avoided mating with relatives in a group-living rodent species, Brandt’s voles (Lasiopodomys brandtii), by combined analysis of their mating system, dispersal and genetic structure; and (ii) to analyze the relationships among the variation in fine-genetic structure, inbreeding avoidance, season-dependent mating strategies and individual dispersal. Using both individual- and population-level analyses, we found that the majority of Brandt’s vole groups consisted of close relatives. However, both group-specific FISs, an inbreeding coefficient that expresses the expected percentage rate of homozygosity arising from a given breeding system, and relatedness of mates showed no sign of inbreeding. Using group pedigrees and paternity analysis, we show that the mating system of Brandt’s voles consists of a type of polygyny for males and extra-group polyandry for females, which may decrease inbreeding by increasing the frequency of mating among distantly-related individuals. The consistent variation in within-group relatedness, among-group relatedness and fine-scale genetic structures was mostly due to dispersal, which primarily occurred during the breeding season. Biologically relevant variation in the fine-scale genetic structure suggests that dispersal during the mating season may be a strategy to avoid inbreeding and drive the polygynous and extra-group polyandrous mating system of this species. PMID:23516435

Potential mediating pathways through which sports participation relates to reduced risk of suicidal ideation.

PubMed

Taliaferro, Lindsay A; Rienzo, Barbara A; Miller, M David; Pigg, R Morgan; Dodd, Virginia J

2010-09-01

Suicide ranks as the third leading cause of death for American youth. Researchers examining sport participation and suicidal behavior have regularly found inverse relationships. This study represents the first effort to test a model depicting potential mechanisms through which sport participation relates to reduced risk of suicidal ideation. The participants were 450 undergraduate students. Measures assessed participants' involvement in university-run sports and other activities; frequency of physical activity; and perceived social support, self-esteem, depression, hopelessness, loneliness, and suicidal ideation. Regression analyses confirmed a path model and tested for mediation effects. Vigorous activity mediated relationships between sport participation and self-esteem and depression; and self-esteem and depression mediated the relationship between vigorous activity and suicidal ideation. Social support mediated relationships between sport participation and depression, hopelessness, and loneliness; and each of these risk factors partially mediated the relationship between social support and suicidal ideation. However no variable fully mediated the relationship between sport participation and suicidal ideation. This study provides a foundation for research designed to examine pathways through which sport participation relates to reduced risk of suicidal behavior.

3D-quantitative structure-activity relationship studies on benzothiadiazepine hydroxamates as inhibitors of tumor necrosis factor-alpha converting enzyme.

PubMed

Murumkar, Prashant R; Giridhar, Rajani; Yadav, Mange Ram

2008-04-01

A set of 29 benzothiadiazepine hydroxamates having selective tumor necrosis factor-alpha converting enzyme inhibitory activity were used to compare the quality and predictive power of 3D-quantitative structure-activity relationship, comparative molecular field analysis, and comparative molecular similarity indices models for the atom-based, centroid/atom-based, data-based, and docked conformer-based alignment. Removal of two outliers from the initial training set of molecules improved the predictivity of models. Among the 3D-quantitative structure-activity relationship models developed using the above four alignments, the database alignment provided the optimal predictive comparative molecular field analysis model for the training set with cross-validated r(2) (q(2)) = 0.510, non-cross-validated r(2) = 0.972, standard error of estimates (s) = 0.098, and F = 215.44 and the optimal comparative molecular similarity indices model with cross-validated r(2) (q(2)) = 0.556, non-cross-validated r(2) = 0.946, standard error of estimates (s) = 0.163, and F = 99.785. These models also showed the best test set prediction for six compounds with predictive r(2) values of 0.460 and 0.535, respectively. The contour maps obtained from 3D-quantitative structure-activity relationship studies were appraised for activity trends for the molecules analyzed. The comparative molecular similarity indices models exhibited good external predictivity as compared with that of comparative molecular field analysis models. The data generated from the present study helped us to further design and report some novel and potent tumor necrosis factor-alpha converting enzyme inhibitors.

Modeling process-structure-property relationships for additive manufacturing

NASA Astrophysics Data System (ADS)

Yan, Wentao; Lin, Stephen; Kafka, Orion L.; Yu, Cheng; Liu, Zeliang; Lian, Yanping; Wolff, Sarah; Cao, Jian; Wagner, Gregory J.; Liu, Wing Kam

2018-02-01

This paper presents our latest work on comprehensive modeling of process-structure-property relationships for additive manufacturing (AM) materials, including using data-mining techniques to close the cycle of design-predict-optimize. To illustrate the processstructure relationship, the multi-scale multi-physics process modeling starts from the micro-scale to establish a mechanistic heat source model, to the meso-scale models of individual powder particle evolution, and finally to the macro-scale model to simulate the fabrication process of a complex product. To link structure and properties, a highefficiency mechanistic model, self-consistent clustering analyses, is developed to capture a variety of material response. The model incorporates factors such as voids, phase composition, inclusions, and grain structures, which are the differentiating features of AM metals. Furthermore, we propose data-mining as an effective solution for novel rapid design and optimization, which is motivated by the numerous influencing factors in the AM process. We believe this paper will provide a roadmap to advance AM fundamental understanding and guide the monitoring and advanced diagnostics of AM processing.

Moderating effect of gender on the prospective relation of physical activity with psychosocial outcomes and asthma control in adolescents: a longitudinal study.

PubMed

Tiggelman, Dana; van de Ven, Monique O M; van Schayck, Onno C P; Engels, Rutger C M E

2014-12-01

Adolescents with asthma experience more psychosocial and physiological problems compared to their healthy peers. Physical activity (PA) might decrease these problems. This study was the first observational longitudinal study to examine whether habitual PA could predict changes in psychosocial outcomes (i.e., symptoms of anxiety and depression, quality of life [QOL] and stress) and asthma control over time in adolescents with asthma and whether gender moderated these relationships. Adolescents with asthma (N = 253; aged 10-14 years at baseline) were visited at home in the spring/summer of 2012 and 2013. They completed questionnaires assessing their habitual PA, symptoms of anxiety and depression, QOL, perceived stress and asthma control. Path analyses using Mplus were conducted to examine longitudinal relationships among habitual PA, psychosocial outcomes and asthma control (controlled for body mass index, age and gender). Using multi-group analyses, we examined whether gender moderated these relationships. Path analyses in the total group showed that habitual PA did not predict changes in psychosocial outcomes or asthma control over time. Multi-group analyses showed that gender moderated the relation of habitual PA with anxiety and depression. Habitual PA only significantly predicted a decrease in anxiety and depression over time for girls but not for boys. Increasing habitual PA in girls with asthma might decrease their symptoms of anxiety and depression.

Relationship between brain plasticity, learning and foraging performance in honey bees.

PubMed

Cabirol, Amélie; Cope, Alex J; Barron, Andrew B; Devaud, Jean-Marc

2018-01-01

Brain structure and learning capacities both vary with experience, but the mechanistic link between them is unclear. Here, we investigated whether experience-dependent variability in learning performance can be explained by neuroplasticity in foraging honey bees. The mushroom bodies (MBs) are a brain center necessary for ambiguous olfactory learning tasks such as reversal learning. Using radio frequency identification technology, we assessed the effects of natural variation in foraging activity, and the age when first foraging, on both performance in reversal learning and on synaptic connectivity in the MBs. We found that reversal learning performance improved at foraging onset and could decline with greater foraging experience. If bees started foraging before the normal age, as a result of a stress applied to the colony, the decline in learning performance with foraging experience was more severe. Analyses of brain structure in the same bees showed that the total number of synaptic boutons at the MB input decreased when bees started foraging, and then increased with greater foraging intensity. At foraging onset MB structure is therefore optimized for bees to update learned information, but optimization of MB connectivity deteriorates with foraging effort. In a computational model of the MBs sparser coding of information at the MB input improved reversal learning performance. We propose, therefore, a plausible mechanistic relationship between experience, neuroplasticity, and cognitive performance in a natural and ecological context.

Analysis of moment structures for assessing relationships among perceived chewing ability, dentition status, muscle strength, and balance in community-dwelling older adults.

PubMed

Moriya, Shingo; Notani, Kenji; Murata, Ayumi; Inoue, Nobuo; Miura, Hiroko

2014-12-01

The aim of this study was to assess relationships among perceived chewing ability, dentition status, muscle strength and balance in community-dwelling older adults using analysis of moment structures (Amos). Physical performance parameters such as muscle strength and balance can predict the future onset of disabilities in activities of daily living among older adults. In this context, elucidation of the relationships among oral conditions and physical performance parameters is necessary. Data on occlusal contact patterns of natural teeth (OPNT), self-assessed masticatory ability (mastication), body mass index (BMI), handgrip strength (HG) and one-leg standing time with eyes open (OLST) were collected from 501 independently living adults aged 65-74 years. The relationships among these parameters were analysed using Spearman's rank correlation coefficients and Amos. Subjects of both genders showed significant correlations among OPNT, mastication, HG and OLST, evaluated using Spearman's rank correlation coefficients. For each Amos model, the goodness-of-fit statistic indicated a good level of fit. In both men and women, OPNT was significantly related to mastication, and mastication was related to HG but not to OLST. OPNT was related to neither HG nor OLST in women and was related to OLST but not HG in men. The findings observed in this study present a possible importance of dental status and perceived chewing ability for the onset of disability by influencing physical performance in community-dwelling older adults. © 2012 The Gerodontology Society and John Wiley & Sons A/S.

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment.

PubMed

Papma, Janne M; Smits, Marion; de Groot, Marius; Mattace Raso, Francesco U; van der Lugt, Aad; Vrooman, Henri A; Niessen, Wiro J; Koudstaal, Peter J; van Swieten, John C; van der Veen, Frederik M; Prins, Niels D

2017-09-01

Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. • PCC functioning during episodic memory relates to hippocampal functioning in MCI. • PCC functioning during episodic memory does not relate to hippocampal structure in MCI. • Functional network changes are an important predictor of PCC functioning in MCI.

Simulated Screens of DNA Encoded Libraries: The Potential Influence of Chemical Synthesis Fidelity on Interpretation of Structure-Activity Relationships.

PubMed

Satz, Alexander L

2016-07-11

Simulated screening of DNA encoded libraries indicates that the presence of truncated byproducts complicates the relationship between library member enrichment and equilibrium association constant (these truncates result from incomplete chemical reactions during library synthesis). Further, simulations indicate that some patterns observed in reported experimental data may result from the presence of truncated byproducts in the library mixture and not structure-activity relationships. Potential experimental methods of minimizing the presence of truncates are assessed via simulation; the relationship between enrichment and equilibrium association constant for libraries of differing purities is investigated. Data aggregation techniques are demonstrated that allow for more accurate analysis of screening results, in particular when the screened library contains significant quantities of truncates.

The Significance of G Protein-Coupled Receptor Crystallography for Drug Discovery

PubMed Central

Salon, John A.; Lodowski, David T.

2011-01-01

Crucial as molecular sensors for many vital physiological processes, seven-transmembrane domain G protein-coupled receptors (GPCRs) comprise the largest family of proteins targeted by drug discovery. Together with structures of the prototypical GPCR rhodopsin, solved structures of other liganded GPCRs promise to provide insights into the structural basis of the superfamily's biochemical functions and assist in the development of new therapeutic modalities and drugs. One of the greatest technical and theoretical challenges to elucidating and exploiting structure-function relationships in these systems is the emerging concept of GPCR conformational flexibility and its cause-effect relationship for receptor-receptor and receptor-effector interactions. Such conformational changes can be subtle and triggered by relatively small binding energy effects, leading to full or partial efficacy in the activation or inactivation of the receptor system at large. Pharmacological dogma generally dictates that these changes manifest themselves through kinetic modulation of the receptor's G protein partners. Atomic resolution information derived from increasingly available receptor structures provides an entrée to the understanding of these events and practically applying it to drug design. Supported by structure-activity relationship information arising from empirical screening, a unified structural model of GPCR activation/inactivation promises to both accelerate drug discovery in this field and improve our fundamental understanding of structure-based drug design in general. This review discusses fundamental problems that persist in drug design and GPCR structural determination. PMID:21969326

Characterisation of genetic structure of the Mayan population in Guatemala by autosomal STR analysis.

PubMed

Martinez-Gonzalez, L J; Alvarez-Cubero, M J; Saiz, M; Alvarez, J C; Martinez-Labarga, C; Lorente, J A

2016-09-01

Currently, the Guatemalan population comprises genetically isolated groups due to geographic, linguistic and cultural factors. For example, Mayan groups within the Guatemala population have preserved their own language, culture and religion. These practices have limited genetic admixture and have maintained the genetic identity of Mayan populations. This study is designed to define the genetic structure of the Mayan-Guatemalan groups Kaqchiquel, K'iche', Mam and Q'eqchi' through autosomal short tandem repeat (STR) polymorphisms and to analyse the genetic relationships between them and with other Mayan groups. Fifteen STR polymorphisms were analysed in 200 unrelated donors belonging to the Kaqchiquel (n = 50), K'iche' (n = 50), Mam (n = 50) and Q'eqchi' (n = 50) groups living in Guatemala. Genetic distance, non-metric MDS and AMOVA were used to analyse the genetic relationships between population groups. Within the Mayan population, the STRs D18S51 and FGA were the most informative markers and TH01 was the least informative. AMOVA and genetic distance analyses showed that the Guatemalan-Native American populations are highly similar to Mayan populations living in Mexico. The Mayan populations from Guatemala and other Native American groups display high genetic homogeneity. Genetic relationships between these groups are more affected by cultural and linguistic factors than geographical and local flow. This study represents one of the first steps in understanding Mayan-Guatemalan populations, the associations between their sub-populations and differences in gene diversity with other populations. This article also demonstrates that the Mestizo population shares most of its ancestral genetic components with the Guatemala Mayan populations.

The right drug, but from whose perspective? A framework for analysing the structure and activities of drug and therapeutics committees.

PubMed

Hoffmann, Mikael

2013-05-01

During the last five decades drug and therapeutics committees (DTCs), have evolved from mainly hospital-based groups of experts in pharmacotherapy and drug logistics into an arena for healthcare professionals employing evidence-based methods of promoting rational drug use. The purpose of this study was to suggest a framework for analysing the structure and activities of DTCs. A literature search was carried out in the Medline, Cinahl and Web of Sciences databases for the period 1993-2012. A total of 207 articles were included. Based on these articles a framework for the analysis of the DTCs based on the role of the DTC, target groups, budget perspective and type of economic decisions could be suggested. In order to respond to future demands the DTCs will have to develop their skill in pharmacoeconomics. Their processes will have to be standardised and made more transparent in order to be better adapted to evidence-based decision-making. They will also have to embrace the possibilities created by electronic health records in both influencing the decisions of physicians, and in improving quality assurance programmes and longitudinal follow-up of drug therapy and outcomes. They will have to find new ways of interacting with the public and policy makers in order to get the resources needed for their work. Finally, they will have to handle the conflict among national, regional and local decision-making processes and the relationship between formularies and therapeutic guidelines.

Is There Consistency between the Binding Affinity and Inhibitory Potential of Natural Polyphenols as α-amylase Inhibitors?

PubMed

Xu, Wei; Shao, Rong; Xiao, Jianbo

2016-07-26

The inhibitory potential of natural polyphenols for α-amylases has attracted great interests among researchers. The structure-affinity properties of natural polyphenols binding to α-amylase and the structure-activity relationship of dietary polyphenols inhibiting α-amylase were deeply investigated. There is a lack of consistency between the structure-affinity relationship and the structure-activity relationship of natural polyphenols as α-amylase inhibitors. Is it consistent between the binding affinity and inhibitory potential of natural polyphenols as with α-amylase inhibitors? It was found that the consistency between the binding affinity and inhibitory potential of natural polyphenols as with α-amylase inhibitors is not equivocal. For example, there is no consistency between the binding affinity and the inhibitory potential of quercetin and its glycosides as α-amylase inhibitors. However, catechins with higher α-amylase inhibitory potential exhibited higher affinity with α-amylase.

First discovery of insecticidal activity of 9,9'-epoxylignane and dihydroguaiaretic acid against houseflies and the structure-activity relationship.

PubMed

Wukirsari, Tuti; Nishiwaki, Hisashi; Hasebe, Ayaka; Shuto, Yoshihiro; Yamauchi, Satoshi

2013-05-08

The insecticidal activity of (-)-(8R,8'R)-3,3'-dimethoxy-9,9'-epoxylignane-4,4'-diol (1) against houseflies was clarified for the first time. The activities of other stereoisomers were weaker than that of the (8R,8'R)-stereoisomer. In the course of research into structure-activity relationships involving 30 newly synthesized (8R,8'R)-derivatives, 5-fold higher activity (ED50 = 0.91 nmol/fly) was observed for (-)-(8R,8'R)-3,3',4-trimethoxy-9,9'-epoxylignan-4'-ol (21) than for the naturally occurring compound (1). The activity of 1 was weaker than that of (-)-(8R,8'R)-dihydroguaiaretic acid ((-)-DGA) (4); however, compound 21 showed almost the same level of activity as 4.

Division of Labor in Vocabulary Structure: Insights From Corpus Analyses.

PubMed

Christiansen, Morten H; Monaghan, Padraic

2016-07-01

Psychologists have used experimental methods to study language for more than a century. However, only with the recent availability of large-scale linguistic databases has a more complete picture begun to emerge of how language is actually used, and what information is available as input to language acquisition. Analyses of such "big data" have resulted in reappraisals of key assumptions about the nature of language. As an example, we focus on corpus-based research that has shed new light on the arbitrariness of the sign: the longstanding assumption that the relationship between the sound of a word and its meaning is arbitrary. The results reveal a systematic relationship between the sound of a word and its meaning, which is stronger for early acquired words. Moreover, the analyses further uncover a systematic relationship between words and their lexical categories-nouns and verbs sound differently from each other-affecting how we learn new words and use them in sentences. Together, these results point to a division of labor between arbitrariness and systematicity in sound-meaning mappings. We conclude by arguing in favor of including "big data" analyses into the language scientist's methodological toolbox. Copyright © 2015 Cognitive Science Society, Inc.

Structure-activity relationships of lanostane-type triterpenoids from Ganoderma lingzhi as α-glucosidase inhibitors.

PubMed

Fatmawati, Sri; Kondo, Ryuichiro; Shimizu, Kuniyoshi

2013-11-01

A series of lanostane-type triterpenoids, identified as ganoderma alcohols and ganoderma acids, were isolated from the fruiting body of Ganoderma lingzhi. Some of these compounds were confirmed as active inhibitors of the in vitro human recombinant aldose reductase. This paper aims to explain the structural requirement for α-glucosidase inhibition. Our structure-activity studies of ganoderma alcohols showed that the OH substituent at C-3 and the double-bond moiety at C-24 and C-25 are necessary to increase α-glucosidase inhibitory activity. The structure-activity relationships of ganoderma acids revealed that the OH substituent at C-11 is an important feature and that the carboxylic group in the side chain is essential for the recognition of α-glucosidase inhibitory activity. Moreover, the double-bond moiety at C-20 and C-22 in the side chain and the OH substituent at C-3 of ganoderma acids improve α-glucosidase inhibitory activity. These results provide an approach with which to consider the structural requirements of lanostane-type triterpenoids from G. lingzhi. An understanding of these requirements is considered necessary in order to improve a new type of α-glucosidase inhibitor. Copyright © 2013 Elsevier Ltd. All rights reserved.

Assessment of Motivational Cognitions in Diabetes Self-Care: the Motivation Thought Frequency Scales for Glucose Testing, Physical Activity and Healthy Eating.

PubMed

Parham, Sophie C; Kavanagh, David J; Gericke, Christian A; King, Neil; May, Jon; Andrade, Jackie

2017-06-01

There is a need for improved measurement of motivation for diabetes self-care. The Elaborated Intrusion Theory of Desire offers a coherent framework for understanding and identifying the cognitive-affective events that constitute the subjective experience of motivation and may therefore inform the development of such an instrument. Recent research has shown the resultant Motivation Thought Frequency scale (MTF) to have a stable factor structure (Intensity, Incentives Imagery, Self-Efficacy Imagery, Availability) when applied to physical activity, excessive snacking or alcohol use in the general population. The current study aimed to confirm the four-factor structure of the MTF for glucose testing, physical activity and healthy eating in people with type 2 diabetes. Associations with self-reports of concurrent diabetic self-care behaviours were also examined. Confirmatory factor analyses tested the internal structure, and multiple regressions assessed the scale's relationship with concurrent self-care behaviours. The MTF was completed by 340 adults with type 2 diabetes, and 237 from that sample also reported self-care behaviours. Separate MTFs assessed motivation for glucose testing, physical activity and healthy eating. Self-care was assessed using questions from the Summary of Diabetes Self-Care Activities. The MTF for each goal achieved an acceptable fit on all indices after selected errors within factors were allowed to intercorrelate. Intensity and Self-Efficacy Imagery provided the strongest and most consistent correlations with relevant self-care behaviours. Results provide preliminary support for the MTF in a diabetes sample. Testing of its sensitivity to change and its predictive utility over time is needed.

Cytotoxic and antifungal activities of melleolide antibiotics follow dissimilar structure-activity relationships.

PubMed

Bohnert, Markus; Nützmann, Hans-Wilhelm; Schroeckh, Volker; Horn, Fabian; Dahse, Hans-Martin; Brakhage, Axel A; Hoffmeister, Dirk

2014-09-01

The fungal genus Armillaria is unique in that it is the only natural source of melleolide antibiotics, i.e., protoilludene alcohols esterified with orsellinic acid or its derivatives. This class of natural products is known to exert antimicrobial and cytotoxic effects. Here, we present a refined relationship between the structure and the antimicrobial activity of the melleolides. Using both agar diffusion and broth dilution assays, we identified the Δ(2,4)-double bond of the protoilludene moiety as a key structural feature for antifungal activity against Aspergillus nidulans, Aspergillus flavus, and Penicillium notatum. These findings contrast former reports on cytotoxic activities and may indicate a different mode of action towards susceptible fungi. We also report the isolation and structure elucidation of five melleolides (6'-dechloroarnamial, 6'-chloromelleolide F, 10-hydroxy-5'-methoxy-6'-chloroarmillane, and 13-deoxyarmellides A and B), along with the finding that treatment with an antifungal melleolide impacts transcription of A. nidulans natural product genes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analytical investigations of seismic responses for reinforced concrete bridge columns subjected to strong near-fault ground motion

NASA Astrophysics Data System (ADS)

Su, Chin-Kuo; Sung, Yu-Chi; Chang, Shuenn-Yih; Huang, Chao-Hsun

2007-09-01

Strong near-fault ground motion, usually caused by the fault-rupture and characterized by a pulse-like velocity-wave form, often causes dramatic instantaneous seismic energy (Jadhav and Jangid 2006). Some reinforced concrete (RC) bridge columns, even those built according to ductile design principles, were damaged in the 1999 Chi-Chi earthquake. Thus, it is very important to evaluate the seismic response of a RC bridge column to improve its seismic design and prevent future damage. Nonlinear time history analysis using step-by-step integration is capable of tracing the dynamic response of a structure during the entire vibration period and is able to accommodate the pulsing wave form. However, the accuracy of the numerical results is very sensitive to the modeling of the nonlinear load-deformation relationship of the structural member. FEMA 273 and ATC-40 provide the modeling parameters for structural nonlinear analyses of RC beams and RC columns. They use three parameters to define the plastic rotation angles and a residual strength ratio to describe the nonlinear load-deformation relationship of an RC member. Structural nonlinear analyses are performed based on these parameters. This method provides a convenient way to obtain the nonlinear seismic responses of RC structures. However, the accuracy of the numerical solutions might be further improved. For this purpose, results from a previous study on modeling of the static pushover analyses for RC bridge columns (Sung et al. 2005) is adopted for the nonlinear time history analysis presented herein to evaluate the structural responses excited by a near-fault ground motion. To ensure the reliability of this approach, the numerical results were compared to experimental results. The results confirm that the proposed approach is valid.

Relationships between bullying, school climate, and student risk behaviors.

PubMed

Klein, Jennifer; Cornell, Dewey; Konold, Timothy

2012-09-01

This study examined whether characteristics of a positive school climate were associated with lower student risk behavior in a sample of 3,687 high school students who completed the School Climate Bullying Survey and questions about risk behavior from the Youth Risk Behavior Surveillance Survey (YRBS). Confirmatory factor analyses established fit for 20 items with three hypothesized school climate scales measuring (1) prevalence of bullying and teasing; (2) aggressive attitudes; and (3) student willingness to seek help. Structural equation modeling established the relationship of these measures with student reports of risk behavior. Multigroup analyses identified differential effects across gender and race. A positive school climate could be an important protective factor in preventing student risk behavior.

Morphological relationships in the chromospheric H-alpha fine structure

NASA Technical Reports Server (NTRS)

Foukal, P.

1971-01-01

A continuous relationship is proposed between the basic elements of the dark fine structure of the quiet and active chromosphere. A progression from chromospheric bushes to fibrils, then to chromospheric threads and active region filaments, and finally to diffuse quiescent filaments, is described. It is shown that the horizontal component of the field on opposite sides of an active region quiescent filament can be in the same direction and closely parallel to the filament axis. Consequently, it is unnecessary to postulate twisted or otherwise complex field configurations to reconcile the support mechanism of filaments with the observed motion along their axis.

Rational design, synthesis, biologic evaluation, and structure-activity relationship studies of novel 1-indanone alpha(1)-adrenoceptor antagonists.

PubMed

Li, Minyong; Xia, Lin

2007-11-01

In the present report, a novel series of 1-indanone alpha(1)-adrenoceptor antagonists were designed and synthesized based on 3D-pharmacophore model. Their in vitro alpha(1)-adrenoceptor antagonistic assay showed that three compounds (2a, 2m, and 2o) had similar or improved alpha(1)-adrenoceptor antagonistic activities relative to the positive control prazosin. Based on these results, a three-dimensional quantitative structure-activity relationship study was performed using a Self-Organizing Molecular Field Analysis method to provide insight for the future development of alpha(1)-adrenoceptor antagonists.

Pedagogical Beliefs, Activity Choice and Structure, and Adult-Child Interaction in Nursery Classrooms

ERIC Educational Resources Information Center

Blay, Josepha A.; Ireson, Judith

2009-01-01

A qualitative analysis of four cooking activities undertaken in two nursery classes reveals relationships between the adults' pedagogical beliefs, the choice and structuring of activities, and the nature of adult-child participation. Four adults each planned and carried out separately, one cooking activity of their choice with a small group of…

Computational & experimental evaluation of the structure/activity relationship of β-carbolines as DYRK1A inhibitors.

PubMed

Drung, Binia; Scholz, Christoph; Barbosa, Valéria A; Nazari, Azadeh; Sarragiotto, Maria H; Schmidt, Boris

2014-10-15

DYRK1A has been associated with Down's syndrome and neurodegenerative diseases, therefore it is an important target for novel pharmacological interventions. We combined a ligand-based pharmacophore design with a structure-based protein/ligand docking using the software MOE in order to evaluate the underlying structure/activity relationship. Based on this knowledge we synthesized several novel β-carboline derivatives to validate the theoretical model. Furthermore we identified a modified lead structure as a potent DYRK1A inhibitor (IC50=130 nM) with significant selectivity against MAO-A, DYRK2, DYRK3, DYRK4 & CLK2. Copyright © 2014 Elsevier Ltd. All rights reserved.

Depressive symptoms, lifestyle structure, and ART adherence among HIV-infected individuals: a longitudinal mediation analysis.

PubMed

Magidson, Jessica F; Blashill, Aaron J; Safren, Steven A; Wagner, Glenn J

2015-01-01

Despite the well-documented relationship between depression and antiretroviral therapy (ART) nonadherence, few studies have identified explanatory pathways through which depression affects adherence. The current study tested lifestyle structure-the degree of organization and routinization of daily activities-as a mediator of this relationship, given previous evidence of lifestyle structure being associated with both depression and ART nonadherence. HIV-infected individuals starting or re-starting ART in the California Collaborative Treatment Group 578 study (n = 199) were assessed over 48 weeks. Adherence was measured using electronic monitoring caps to determine dose timing and doses taken, and viral load was assessed. The mediating role of lifestyle structure was tested using generalized linear mixed-effects modeling and bootstrapping. Lifestyle significantly mediated the relationship between depression and both measures of ART adherence behavior. Interventions that minimize disruptions to lifestyle structure and link adherence to daily activities may be useful for individuals with depression and ART nonadherence.

A School-Level Analysis of Adolescent Extracurricular Activity, Delinquency, and Depression: The Importance of Situational Context

ERIC Educational Resources Information Center

Guest, Andrew M.; McRee, Nick

2009-01-01

In this article we investigate the extent to which the relationship between extracurricular activities and youth development depends on situational contexts. Using a national sample including 13,466 youths in grades 7-12 across 120 schools, we conduct school-level analyses of the association between extracurricular activities, delinquency, and…

Working memory, reasoning, and expertise in medicine-insights into their relationship using functional neuroimaging.

PubMed

Hruska, Pam; Krigolson, Olav; Coderre, Sylvain; McLaughlin, Kevin; Cortese, Filomeno; Doig, Christopher; Beran, Tanya; Wright, Bruce; Hecker, Kent G

2016-12-01

Clinical reasoning is dependent upon working memory (WM). More precisely, during the clinical reasoning process stored information within long-term memory is brought into WM to facilitate the internal deliberation that affords a clinician the ability to reason through a case. In the present study, we examined the relationship between clinical reasoning and WM while participants read clinical cases with functional magnetic resonance imaging (fMRI). More specifically, we examined the impact of clinical case difficulty (easy, hard) and clinician level of expertise (2nd year medical students, senior gastroenterologists) on neural activity within regions of cortex associated with WM (i.e., the prefrontal cortex) during the reasoning process. fMRI was used to scan ten second-year medical students and ten practicing gastroenterologists while they reasoned through sixteen clinical cases [eight straight forward (easy) and eight complex (hard)] during a single 1-h scanning session. Within-group analyses contrasted the easy and hard cases which were then subsequently utilized for a between-group analysis to examine effects of expertise (novice > expert, expert > novice). Reading clinical cases evoked multiple neural activations in occipital, prefrontal, parietal, and temporal cortical regions in both groups. Importantly, increased activation in the prefrontal cortex in novices for both easy and hard clinical cases suggests novices utilize WM more so than experts during clinical reasoning. We found that clinician level of expertise elicited differential activation of regions of the human prefrontal cortex associated with WM during clinical reasoning. This suggests there is an important relationship between clinical reasoning and human WM. As such, we suggest future models of clinical reasoning take into account that the use of WM is not consistent throughout all clinical reasoning tasks, and that memory structure may be utilized differently based on level of expertise.

Abnormalities of thalamic activation and cognition in schizophrenia.

PubMed

Andrews, Jessica; Wang, Lei; Csernansky, John G; Gado, Mokhtar H; Barch, Deanna M

2006-03-01

Functional and structural magnetic resonance imaging (MRI) was used to investigate relationships among structure, functional activation, and cognitive deficits related to the thalamus in individuals with schizophrenia and healthy comparison subjects. Thirty-six schizophrenia subjects and 28 healthy comparison subjects matched by age, gender, race, and parental socioeconomic status underwent structural and functional MRI while performing a series of memory tasks, including an N-back task (working memory), intentional memorization of a series of pictures or words (episodic encoding), and a yes/no recognition task. Functional activation magnitudes in seven regions of interest within the thalamic complex, as defined by anatomical and functional criteria, were computed for each group. Participants with schizophrenia exhibited decreased activation within the whole thalamus, the anterior nuclei, and the medial dorsal nucleus. These nuclei overlap with subregions of the thalamic surface that the authors previously reported to exhibit morphological abnormalities in schizophrenia. However, there were no significant correlations between specific dimensions of thalamic shape variation (i.e., eigenvectors) and the activation patterns within thalamic regions of interest. Better performance on the working memory task among individuals with schizophrenia was significantly associated with increased activation in the anterior nuclei, the centromedian nucleus, the pulvinar, and the ventrolateral nuclei. These results suggest that there are limited relationships between morphological and functional abnormalities of the thalamus in schizophrenia subjects and highlight the importance of investigating relationships between brain structure and function.

Leisure Activity Engagement and Positive Affect Partially Mediate the Relationship Between Positive Views on Aging and Physical Health.

PubMed

Hicks, Stephanie A; Siedlecki, Karen L

2017-03-01

To examine leisure activity engagement and positive affect as potential mediators for the relationships between positive views on aging (PVA) and two health outcomes: subjective health and physical limitations. Data from 5,194 participants from the German Ageing Survey (aged 40-91 years) were used to examine relationships between PVA to subjective health (assessed by self-rated health and perceived health change from past) and physical limitations (assessed via self-reported limitations on 10 activities). Leisure activity engagement and positive affect were examined as potential mediators in latent variable path analyses. Age moderation among these relationships was also examined. Leisure activity engagement and positive affect separately and jointly served to partially mediate the relationships between PVA and the health outcomes. When entered as joint mediators, positive affect no longer significantly predicted physical limitations, indicating a shared variance with leisure activity engagement. Age moderated the relationship between PVA and physical limitations; the relationship was stronger among older adults than among middle-aged adults. Leisure activity engagement and positive affect were shown to help explain the relationship between PVA and health, but differently for different health constructs and also among middle-aged and older adults. Findings provide further insight into ways in which PVA influence health. © 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.

Classification of the treble clef zinc finger: noteworthy lessons for structure and function evolution.

PubMed

Kaur, Gurmeet; Subramanian, Srikrishna

2016-08-26

Treble clef (TC) zinc fingers constitute a large fold-group of structural zinc-binding protein domains that mediate numerous cellular functions. We have analysed the sequence, structure, and function relationships among all TCs in the Protein Data Bank. This led to the identification of novel TCs, such as lsr2, YggX and TFIIIC τ 60 kDa subunit, and prediction of a nuclease-like function for the DUF1364 family. The structural malleability of TCs is evident from the many examples with variations to the core structural elements of the fold. We observe domains wherein the structural core of the TC fold is circularly permuted, and also some examples where the overall fold resembles both the TC motif and another unrelated fold. All extant TC families do not share a monophyletic origin, as several TC proteins are known to have been present in the last universal common ancestor and the last eukaryotic common ancestor. We identify several TCs where the zinc-chelating site and residues are not merely responsible for structure stabilization but also perform other functions, such as being redox active in C1B domain of protein kinase C, a nucleophilic acceptor in Ada and catalytic in organomercurial lyase, MerB.

Classification of the treble clef zinc finger: noteworthy lessons for structure and function evolution

NASA Astrophysics Data System (ADS)

Kaur, Gurmeet; Subramanian, Srikrishna

2016-08-01

Treble clef (TC) zinc fingers constitute a large fold-group of structural zinc-binding protein domains that mediate numerous cellular functions. We have analysed the sequence, structure, and function relationships among all TCs in the Protein Data Bank. This led to the identification of novel TCs, such as lsr2, YggX and TFIIIC τ 60 kDa subunit, and prediction of a nuclease-like function for the DUF1364 family. The structural malleability of TCs is evident from the many examples with variations to the core structural elements of the fold. We observe domains wherein the structural core of the TC fold is circularly permuted, and also some examples where the overall fold resembles both the TC motif and another unrelated fold. All extant TC families do not share a monophyletic origin, as several TC proteins are known to have been present in the last universal common ancestor and the last eukaryotic common ancestor. We identify several TCs where the zinc-chelating site and residues are not merely responsible for structure stabilization but also perform other functions, such as being redox active in C1B domain of protein kinase C, a nucleophilic acceptor in Ada and catalytic in organomercurial lyase, MerB.

Recent Advances in Marine Algae Polysaccharides: Isolation, Structure, and Activities.

PubMed

Xu, Shu-Ying; Huang, Xuesong; Cheong, Kit-Leong

2017-12-13

Marine algae have attracted a great deal of interest as excellent sources of nutrients. Polysaccharides are the main components in marine algae, hence a great deal of attention has been directed at isolation and characterization of marine algae polysaccharides because of their numerous health benefits. In this review, extraction and purification approaches and chemico-physical properties of marine algae polysaccharides (MAPs) are summarized. The biological activities, which include immunomodulatory, antitumor, antiviral, antioxidant, and hypolipidemic, are also discussed. Additionally, structure-function relationships are analyzed and summarized. MAPs' biological activities are closely correlated with their monosaccharide composition, molecular weights, linkage types, and chain conformation. In order to promote further exploitation and utilization of polysaccharides from marine algae for functional food and pharmaceutical areas, high efficiency, and low-cost polysaccharide extraction and purification methods, quality control, structure-function activity relationships, and specific mechanisms of MAPs activation need to be extensively investigated.

Relationship between chemical structure of soil organic matter and intra-aggregate pore structure: evidence from X-ray computed micro-tomography

NASA Astrophysics Data System (ADS)

Kravchenko, Alexandra; Grandy, Stuart A.

2014-05-01

Understanding chemical structure of soil organic matter (SOM) and factors that affect it are vital for gaining understanding of mechanisms of C sequestration by soil. Physical protection of C by adsorption to mineral particles and physical disconnection between C sources and microbial decomposers is now regarded as the key component of soil C sequestration. Both of the processes are greatly influenced by micro-scale structure and distribution of soil pores. However, because SOM chemical structure is typically studied in disturbed (ground and sieved) soil samples the experimental evidence of the relationships between soil pore structure and chemical structure of SOM are still scarce. Our study takes advantage of the X-ray computed micro-tomography (µ-CT) tools that enable non-destructive analysis of pore structure in intact soil samples. The objective of this study is to examine the relationship between SOM chemical structure and pore-characteristics in intact soil macro-aggregates from two contrasting long-term land uses. The two studied land use treatments are a conventionally tilled corn-soybean-wheat rotation treatment and a native succession vegetation treatment removed from agricultural use >20 years ago. The study is located in southwest Michigan, USA, on sandy-loam Typic Hapludalfs. For this study we used soil macro-aggregates 4-6 mm in size collected at 0-15 cm depth. The aggregate size was selected so as both to enable high resolution of µ-CT and to provide sufficient amount of soil for C measurements. X-ray µ-CT scanning was conducted at APS Argonne at a scanning resolution of 14 µm. Two scanned aggregates (1 per treatment) were used in this preliminary study. Each aggregate was cut into 7 "geo-referenced" sections. Analyses of pore characteristics in each section were conducted using 3DMA and ImageJ image analysis tools. SOM chemistry was analyzed using pyrolysis/gas chromatography-mass spectroscopy. Results demonstrated that the relationships between SOM chemical structure and pore characteristics differed in the aggregates of the two treatments. For example, in the agricultural treatment, the aggregate sections with prevalence of small pores had lower relative lignin abundance, while higher lignin abundances occurred in aggregate sections with more large pores. This relationship could be reflecting the low accessibility of the sections dominated by small pores to plant roots. It is interesting to note that no relationship between pores and lignin were observed in the aggregate from the native succession treatment. In the native succession aggregate we found that a larger presence of protein and N-bearing compounds was associated with sections with greater presence of 35-90 µm pores. This could be a result of fungal activities, as pores of this size constitute a primary fungal habitat and fungi are known for secreting proteins. Fewer fungi in the soil under agricultural management are likely the reason that no such relationship was observed in the aggregate from the agricultural treatment. Our preliminary results indicate that substantial spatial variability patterns in SOM chemical structure can exist even within a single macro-aggregate and that pores are likely a main driver of intra-aggregate SOM chemistry.

The relationship between outdoor activity and health in older adults using GPS.

PubMed

Kerr, Jacqueline; Marshall, Simon; Godbole, Suneeta; Neukam, Suvi; Crist, Katie; Wasilenko, Kari; Golshan, Shahrokh; Buchner, David

2012-12-01

Physical activity (PA) provides health benefits in older adults. Research suggests that exposure to nature and time spent outdoors may also have effects on health. Older adults are the least active segment of our population, and are likely to spend less time outdoors than other age groups. The relationship between time spent in PA, outdoor time, and various health outcomes was assessed for 117 older adults living in retirement communities. Participants wore an accelerometer and GPS device for 7 days. They also completed assessments of physical, cognitive, and emotional functioning. Analyses of variance were employed with a main and interaction effect tested for ±30 min PA and outdoor time. Significant differences were found for those who spent >30 min in PA or outdoors for depressive symptoms, fear of falling, and self-reported functioning. Time to complete a 400 m walk was significantly different by PA time only. QoL and cognitive functioning scores were not significantly different. The interactions were also not significant. This study is one of the first to demonstrate the feasibility of using accelerometer and GPS data concurrently to assess PA location in older adults. Future analyses will shed light on potential causal relationships and could inform guidelines for outdoor activity.

The Relationship Between Outdoor Activity and Health in Older Adults Using GPS

PubMed Central

Kerr, Jacqueline; Marshall, Simon; Godbole, Suneeta; Neukam, Suvi; Crist, Katie; Wasilenko, Kari; Golshan, Shahrokh; Buchner, David

2012-01-01

Physical activity (PA) provides health benefits in older adults. Research suggests that exposure to nature and time spent outdoors may also have effects on health. Older adults are the least active segment of our population, and are likely to spend less time outdoors than other age groups. The relationship between time spent in PA, outdoor time, and various health outcomes was assessed for 117 older adults living in retirement communities. Participants wore an accelerometer and GPS device for 7 days. They also completed assessments of physical, cognitive, and emotional functioning. Analyses of variance were employed with a main and interaction effect tested for ±30 min PA and outdoor time. Significant differences were found for those who spent >30 min in PA or outdoors for depressive symptoms, fear of falling, and self-reported functioning. Time to complete a 400 m walk was significantly different by PA time only. QoL and cognitive functioning scores were not significantly different. The interactions were also not significant. This study is one of the first to demonstrate the feasibility of using accelerometer and GPS data concurrently to assess PA location in older adults. Future analyses will shed light on potential causal relationships and could inform guidelines for outdoor activity. PMID:23330225

NMR Studies of Structure-Reactivity Relationships in Carbonyl Reduction: A Collaborative Advanced Laboratory Experiment

ERIC Educational Resources Information Center

Marincean, Simona; Smith, Sheila R.; Fritz, Michael; Lee, Byung Joo; Rizk, Zeinab

2012-01-01

An upper-division laboratory project has been developed as a collaborative investigation of a reaction routinely taught in organic chemistry courses: the reduction of carbonyl compounds by borohydride reagents. Determination of several trends regarding structure-activity relationship was possible because each student contributed his or her results…

Parent-Child Relations and Peer Associations as Mediators of the Family Structure--Substance Use Relationship

ERIC Educational Resources Information Center

Crawford, Lizabeth A.; Novak, Katherine B.

2008-01-01

Using data from the National Education Longitudinal Survey of 1988, the authors assess the extent to which adolescents' levels of parental attachment and opportunities for participating in delinquent activities mediate the family structure--substance use relationship. A series of hierarchical regressions supported the hypotheses that high levels…

Quantitative structure-activity relationship modeling on in vitro endocrine effects and metabolic stability involving 26 selected brominated flame retardants.

PubMed

Harju, Mikael; Hamers, Timo; Kamstra, Jorke H; Sonneveld, Edwin; Boon, Jan P; Tysklind, Mats; Andersson, Patrik L

2007-04-01

In this work, quantitative structure-activity relationships (QSARs) were developed to aid human and environmental risk assessment processes for brominated flame retardants (BFRs). Brominated flame retardants, such as the high-production-volume chemicals polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A, and hexabromocyclododecane, have been identified as potential endocrine disruptors. Quantitative structure-activity relationship models were built based on the in vitro potencies of 26 selected BFRs. The in vitro assays included interactions with, for example, androgen, progesterone, estrogen, and dioxin (aryl hydrocarbon) receptor, plus competition with thyroxine for its plasma carrier protein (transthyretin), inhibition of estradiol sulfation via sulfotransferase, and finally, rate of metabolization. The QSAR modeling, a number of physicochemical parameters were calculated describing the electronic, lipophilic, and structural characteristics of the molecules. These include frontier molecular orbitals, molecular charges, polarities, log octanol/water partitioning coefficient, and two- and three-dimensional molecularproperties. Experimental properties were included and measured for PBDEs, such as their individual ultraviolet spectra (200-320 nm) and retention times on three different high-performance liquid chromatography columns and one nonpolar gas chromatography column. Quantitative structure-activity relationship models based on androgen antagonism and metabolic degradation rates generally gave similar results, suggesting that lower-brominated PBDEs with bromine substitutions in ortho positions and bromine-free meta- and para positions had the highest potencies and metabolic degradation rates. Predictions made for the constituents of the technical flame retardant Bromkal 70-5DE found BDE 17 to be a potent androgen antagonist and BDE 66, which is a relevant PBDE in environmental samples, to be only a weak antagonist.

Ambivalent Sexism in Close Relationships: (Hostile) Power and (Benevolent) Romance Shape Relationship Ideals

PubMed Central

Lee, Tiane L.; Fiske, Susan T.; Glick, Peter; Chen, Zhixia

2013-01-01

Gender-based structural power and heterosexual dependency produce ambivalent gender ideologies, with hostility and benevolence separately shaping close-relationship ideals. The relative importance of romanticized benevolent versus more overtly power-based hostile sexism, however, may be culturally dependent. Testing this, northeast US (N=311) and central Chinese (N=290) undergraduates rated prescriptions and proscriptions (ideals) for partners and completed Ambivalent Sexism and Ambivalence toward Men Inventories (ideologies). Multiple regressions analyses conducted on group-specific relationship ideals revealed that benevolent ideologies predicted partner ideals, in both countries, especially for US culture’s romance-oriented relationships. Hostile attitudes predicted men’s ideals, both American and Chinese, suggesting both societies’ dominant-partner advantage. PMID:23914004

Structure-affinity relationship of the interaction between phenolic acids and their derivatives and β-lactoglobulin and effect on antioxidant activity.

PubMed

Wu, Simin; Zhang, Yunyue; Ren, Fazheng; Qin, Yinghui; Liu, Jiaxin; Liu, Jingwen; Wang, Qingyu; Zhang, Hao

2018-04-15

In this study, 71 phenolic acids and their derivatives were used to investigate the structure-affinity relationship of β-lactoglobulin binding, and the effect of this interaction on antioxidant activity. Based on a fluorescence quenching method, an improved mathematical model was adopted to calculate the binding constants, with a correction for the inner-filter effect. Hydroxylation at the 3-position increased the affinity of the phenolic acids for β-lactoglobulin, while hydroxylation at the 2- or 4-positions had a negative effect. Complete methylation of all hydroxy groups, except at the 3-position, enhanced the binding affinity. Replacing the hydroxy groups with methyl groups at the 2-position also had a positive effect. Hydrogen bonding was one of the binding forces for the interaction. The antioxidant activity of phenolic acid-β-lactoglobulin complexes was higher than that of phenolic acids alone. These findings provide an understanding of the structure-activity relationship of the interaction between β-lactoglobulin and phenolic acids. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of Novel p16INK4a Mimetics as Anticancer Therapy

DTIC Science & Technology

2015-10-01

peptide (or substituted peptide) or the crystal structure of the relevant sequence from p16INK4 ( PDB 1BI7) was used as the starting structure . Model...small peptides that interact with CDK4/6. The specific aims are as follows. (1) Determine structure -function relationships of overlapping peptides...Determine structure -function relationships of overlapping peptides derived from p16 INK4a that inhibit the activity of CDK4/6 and identify stabilized

4,6-Diaryl/heteroarylpyrimidin-2(1H)-ones as a new class of xanthine oxidase inhibitors.

PubMed

Shukla, Shiwani; Kumar, Dinesh; Ojha, Ritu; Gupta, Manish K; Nepali, Kunal; Bedi, Preet M S

2014-07-01

A series of 4,6-diaryl/heteroarylpyrimidones was synthesized employing silica-supported fluoroboric acid under solvent-free conditions in a microwave reactor. The catalytic influence of HBF4-SiO2 was investigated in detail to optimize the reaction conditions. The synthesized compounds were evaluated for in vitro xanthine oxidase (XO) inhibitory activity for the first time. Structure-activity relationship analyses are also presented. Among the synthesized compounds, VA-5, -9, -10, -12, -22, -23, and -25 were the active inhibitors with IC50 values ranging from 6.45 to 13.46 µM. Compound VA-25 with a pyridinyl ring as ring A and a thiophenyl ring as ring B emerged as the most potent XO inhibitor (IC50 = 6.45 µM) in comparison to allopurinol (IC50 = 12.24 µM). Some of the important interactions of VA-25 with the amino acid residues of the active site of XO were figured out by molecular modeling studies. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel Linear Lipopeptide Paenipeptins with Potential for Eradicating Biofilms and Sensitizing Gram-Negative Bacteria to Rifampicin and Clarithromycin.

PubMed

Moon, Sun Hee; Zhang, Xuan; Zheng, Guangrong; Meeker, Daniel G; Smeltzer, Mark S; Huang, En

2017-12-14

We report the structure-activity relationship analyses of 17 linear lipopeptide paenipeptin analogues. Analogues 7, 12, and 17 were more potent than the lead compound. Analogue 17 was active against carbapenem-resistant and polymyxin-resistant pathogens. This compound at 40 μg/mL resulted in 3 log and 2.6 log reductions of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, respectively, in catheter-associated biofilms in vitro. Analogue 17 showed little hemolysis at 32 μg/mL and lysed 11% of red blood cells at 64 μg/mL. Analogues 9 and 16 were nonhemolytic and retained potent P. aeruginosa-specific antimicrobial activity. These two analogues when used alone lacked activity against Acinetobacter baumannii and Klebsiella pneumoniae; however, analogue 9 and 16 at 4 μg/mL decreased the MIC of rifampicin and clarithromycin against the same pathogens from 16 to 32 μg/mL to nanomolar levels (sensitization factor: 2048-8192). Therefore, paenipeptins, alone or in combination with rifampicin or clarithromycin, are promising candidates for treating bacterial infections.

Antibacterial Activity of Polyphenols: Structure-Activity Relationship and Influence of Hyperglycemic Condition.

PubMed

Xie, Yixi; Chen, Jing; Xiao, Aiping; Liu, Liangliang

2017-11-06

Polyphenols are plant-derived natural products with well-documented health benefits to human beings, such as antibacterial activities. However, the antibacterial activities of polyphenols under hyperglycemic conditions have been rarely studied, which could be relevant to their antibacterial efficacy in disease conditions, such as in diabetic patients. Herein, the antibacterial activities of 38 polyphenols under mimicked hyperglycemic conditions were evaluated. The structure-antibacterial activity relationships of polyphenols were also tested and analyzed. The presence of glucose apparently promoted the growth of the bacterial strains tested in this study. The OD600 values of tested bacteria strains increased from 1.09-fold to 1.49-fold by adding 800 mg/dL glucose. The polyphenols showed structurally dependent antibacterial activities, which were significantly impaired under the hyperglycemic conditions. The results from this study indicated that high blood glucose might promote bacterial infection, and the hyperglycemic conditions resulting from diabetes were likely to suppress the antibacterial benefits of polyphenols.

Structure-activity relationship studies of (+/-)-terbutaline and (+/-)-fenoterol on beta3-adrenoceptors in the guinea pig gastric fundus.

PubMed

Horinouchi, T; Nakagawa, Y; Wakabayashi, M; Koike, K

2001-08-01

(+/-)-Terbutaline and (+/-)-fenoterol are both arylethanolamine analogs that have tertbutyl and aryliso-propyl substituents respectively at the a position on the nitrogen of the ethanolamine side chain. In the present study, we have investigated the structure-activity relationships of (+/-)-terbutaline and (+/-)-fenoterol as beta3-adrenoceptor agonists in the guinea pig gastric fundus. (+/-)-Terbutaline and (+/-)-fenoterol induced concentration-dependent relaxation of the precontracted gastric fundus with pD2 values of 4.45+/-0.10 and 5.90+/-0.09, and intrinsic activities of 1.00+/-0.03 and 0.99+/-0.01 respectively. The combination of the selective beta1-adrenoceptor antagonist (+/-)-atenolol (100 microM), and the selective beta2-adrenoceptor antagonist (+/-)-butoxamine (100 microM), produced a 2 and 6 fold rightward shift of the concentration-response curves for (+/-)-terbutaline and (+/-)-fenoterol respectively, without depressing the maximal responses. The order of potency of these agonists was (pD2 value): (+/-)-fenoterol (5.09+/-0.10) > (+/-)-terbutaline (4.13+/-0.08). In the presence of (+/-)-atenolol and (+/-)-butoxamine, however, the non-selective beta1, beta2- and beta3-adrenoceptor antagonist (+/-)-bupranolol caused a concentration-dependent rightward shift of the concentration-response curves for (+/-)-terbutaline and (+/-)-fenoterol. Schild plot analyses of the effects of (+/-)-bupranolol against these agonists gave pA2 values of 6.21+/-0.07 ((+/-)-terbutaline) and 6.37+/-0.06 ((+/-)-fenoterol) respectively, and the slopes of the Schild plot were not significantly different from unity (p>0.05). These results suggest that the relaxant responses to (+/-)-terbutaline and (+/-)-fenoterol are mainly mediated through beta3-adrenoceptors in the guinea pig gastric fundus. The beta3-adrenoceptor agonist potencies of arylethanolamine analogs depend on the size of the end of the alkylamine side chain.

Structure-Antiplatelet Activity Relationships of Novel Ruthenium (II) Complexes: Investigation of Its Molecular Targets.

PubMed

Hsia, Chih-Hsuan; Jayakumar, Thanasekaran; Sheu, Joen-Rong; Tsao, Shin-Yi; Velusamy, Marappan; Hsia, Chih-Wei; Chou, Duen-Suey; Chang, Chao-Chien; Chung, Chi-Li; Khamrang, Themmila; Lin, Kao-Chang

2018-02-22

The regulation of platelet function by pharmacological agents that modulate platelet signaling has proven to be a positive approach to the prevention of thrombosis. Ruthenium complexes are fascinating for the development of new drugs, as they possess numerous chemical and biological properties. The present study aims to evaluate the structure-activity relationship (SAR) of newly synthesized ruthenium (II) complexes, TQ-1, TQ-2 and TQ-3 in agonists-induced washed human platelets. Silica gel column chromatography, aggregometry, immunoblotting, NMR, and X-ray analyses were performed in this study. Of the three tested compounds, TQ-3 showed a concentration (1-5 μM) dependent inhibitory effect on platelet aggregation induced by collagen (1 μg/mL) and thrombin (0.01 U/mL) in washed human platelets; however, TQ-1 and TQ-2 had no response even at 250 μM of collagen and thrombin-induced aggregation. TQ-3 was effective with inhibiting collagen-induced ATP release, calcium mobilization ([Ca 2+ ]i) and P-selectin expression without cytotoxicity. Moreover, TQ-3 significantly abolished collagen-induced Lyn-Fyn-Syk, Akt-JNK and p38 mitogen-activated protein kinases (p38 MAPKs) phosphorylation. The compound TQ-3 containing an electron donating amino group with two phenyl groups of the quinoline core could be accounted for by its hydrophobicity and this nature might be the reason for the noted antiplatelet effects of TQ-3. The present results provide a molecular basis for the inhibition by TQ-3 in collagen-induced platelet aggregation, through the suppression of multiple machineries of the signaling pathway. These results may suggest that TQ-3 can be considered a potential agent for the treatment of vascular diseases.

Solution NMR structure and inhibitory effect against amyloid-β fibrillation of Humanin containing a D-isomerized serine residue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alsanousi, Nesreen; Sugiki, Toshihiko, E-mail: sugiki@protein.osaka-u.ac.jp; Furuita, Kyoko

Humanin comprising 24 amino acid residues is a bioactive peptide that has been isolated from the brain tissue of patients with Alzheimer's disease. Humanin reportedly suppressed aging-related death of various cells due to amyloid fibrils and oxidative stress. There are reports that the cytoprotective activity of Humanin was remarkably enhanced by optical isomerization of the Ser14 residue from L to D form, but details of the molecular mechanism remained unclear. Here we demonstrated that Humanin D-Ser14 exhibited potent inhibitory activity against fibrillation of amyloid-β and remarkably higher binding affinity for amyloid-β than that of the Humanin wild-type and S14G mutant.more » In addition, we determined the solution structure of Humanin D-Ser14 by nuclear magnetic resonance (NMR) and showed that D-isomerization of the Ser14 residue enables drastic conformational rearrangement of Humanin. Furthermore, we identified an amyloid-β-binding site on Humanin D-Ser14 at atomic resolution by NMR. These biophysical and high-resolution structural analyses clearly revealed structure–function relationships of Humanin and explained the driving force of the drastic conformational change and molecular basis of the potent anti-amyloid-β fibrillation activity of Humanin caused by D-isomerization of the Ser14 residue. This is the first study to show correlations between the functional activity, tertiary structure, and partner recognition mode of Humanin and may lead to elucidation of the molecular mechanisms of the cytoprotective activity of Humanin. - Highlights: • Humanin D-Ser14 showed the strongest inhibitory activity against Aβ40 fibrillation. • NMR structure of Humanin D-Ser14 was determined in alcohol/water mixture solution. • Humanin D-Ser14 directly bound Aβ40 stronger than Humanin wild-type and Humanin S14G. • Aβ40 and zinc ion binding sites of Humanin D-Ser14 were identified. • Structure around Ser14 of Humanin is critical for Aβ40 binding and inhibitory activity.« less

Design, synthesis and structure-activity relationship evaluation of novel LpxC inhibitors as Gram-negative antibacterial agents.

PubMed

Ding, Shi; Dai, Rui-Yang; Wang, Wen-Ke; Cao, Qiao; Lan, Le-Fu; Zhou, Xian-Li; Yang, Yu-She

2018-01-15

LpxC inhibitors are new-type antibacterial agents developed in the last twenty years, mainly against Gram-negative bacteria infections. To develop novel LpxC inhibitors with good antibacterial activities and biological metabolism, we summarized the basic skeleton of reported LpxC inhibitors, designed and synthesized several series of compounds and tested their antibacterial activities against Escherichial coli and Pseudomonas aeruginosa in vitro. Structure-activity relationships have been discussed in this article. The metabolism stability of YDL-2, YDL-5, YDL-8, YDL-14, YDL-20-YDL-23 have been evaluated in liver microsomes, which indicated that the 2-amino isopropyl group may be a preferred structure than the 2-hydroxy ethyl group in the design of LpxC inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sesterterpenes as tubulin tyrosine ligase inhibitors. First insight of structure-activity relationships and discovery of new lead.

PubMed

Dal Piaz, Fabrizio; Vassallo, Antonio; Lepore, Laura; Tosco, Alessandra; Bader, Ammar; De Tommasi, Nunziatina

2009-06-25

Twenty-four new sesterterpenes, compounds 1-24, were isolated from the aerial parts of Salvia dominica. Their structures were elucidated by 1D and 2D NMR experiments as well as ESIMS analysis and chemical methods. The evaluation of the biological activity of Salvia dominica sesterterpenes by means of a panel of chemical and biological approaches, including chemical proteomics, surface plasmon resonance (SPR) measurements, and biochemical assays were realized. Obtained results showed that 18 out of the 24 sesterterpene lactones isolated from Salvia dominica interact with tubulin-tyrosine ligase (TTL) an enzyme involved in the tyrosination cycle of the C-terminal of tubulin, and inhibit TTL activity in cancer cells. Besides, results of our studies provided an activity/structure relationship that can be used to design effective TTL inhibitors.

Anger as a predictor of psychological distress and self-harm ideation in inmates: a structured self-assessment diary study.

PubMed

Humber, Naomi; Emsley, Richard; Pratt, Daniel; Tarrier, Nicholas

2013-11-30

Suicidal ideation and behaviour are common among inmates. Anger is found at exaggerated levels and has been associated with suicidal ideation and behaviour in inmate samples suggesting its possible salience in the prediction of suicide. The study investigated relationships between anger, psychological distress, and self-harm/suicidal ideation among inmates. The principles of Ecological Momentary Assessment were considered and a structured self-assessment diary was utilised to examine relationships between the variables of interest. Participants completed a structured self-assessment diary for six consecutive days which included momentary ratings of items describing psychological states of concurrent affects, thoughts, and appraisals related to anger, psychological distress, and self-harm/suicidal ideation. Psychometric assessment measures were also conducted. Temporal associations between predictors and outcomes were investigated. Multilevel modelling analyses were performed. Increased anger was significantly associated with concurrent high levels of self-harm ideation in inmates, when controlling for depression and hopelessness. Temporal analyses also revealed that anger at one time point did not predict suicidal ideation at the next time point. Elucidating the temporal nature of the relationship between anger, psychological distress, and self-harm/suicidal ideation has advanced understanding of the mechanisms of suicidal behaviour, by demonstrating an increased risk of suicide when a male inmate is angry. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Relationships between adaptive and neutral genetic diversity and ecological structure and functioning: a meta-analysis

PubMed Central

Whitlock, Raj

2014-01-01

Understanding the effects of intraspecific genetic diversity on the structure and functioning of ecological communities is a fundamentally important part of evolutionary ecology and may also have conservation relevance in identifying the situations in which genetic diversity coincides with species-level diversity.Early studies within this field documented positive relationships between genetic diversity and ecological structure, but recent studies have challenged these findings. Conceptual synthesis has been hampered because studies have used different measures of intraspecific variation (phenotypically adaptive vs. neutral) and have considered different measures of ecological structure in different ecological and spatial contexts. The aim of this study is to strengthen conceptual understanding by providing an empirical synthesis quantifying the relationship between genetic diversity and ecological structure.Here, I present a meta-analysis of the relationship between genetic diversity within plant populations and the structure and functioning of associated ecological communities (including 423 effect sizes from 70 studies). I used Bayesian meta-analyses to examine (i) the strength and direction of this relationship, (ii) the extent to which phenotypically adaptive and neutral (molecular) measures of diversity differ in their association with ecological structure and (iii) variation in outcomes among different measures of ecological structure and in different ecological contexts.Effect sizes measuring the relationship between adaptive diversity (genotypic richness) and both community- and ecosystem-level ecological responses were small, but significantly positive. These associations were supported by genetic effects on species richness and productivity, respectively.There was no overall association between neutral genetic diversity and measures of ecological structure, but a positive correlation was observed under a limited set of demographic conditions. These results suggest that adaptive and neutral genetic diversity should not be treated as ecologically equivalent measures of intraspecific variation.Synthesis. This study advances the debate over whether relationships between genetic diversity and ecological structure are either simply positive or negative, by showing how the strength and direction of these relationships changes with different measures of diversity and in different ecological contexts. The results provide a solid foundation for assessing when and where an expanded synthesis between ecology and genetics will be most fruitful. PMID:25210204

Habitat structure and body size distributions: Cross-ecosystem comparison for taxa with determinate and indeterminate growth

USGS Publications Warehouse

Nash, Kirsty L.; Allen, Craig R.; Barichievy, Chris; Nystrom, Magnus; Sundstrom, Shana M.; Graham, Nicholas A.J.

2014-01-01

Habitat structure across multiple spatial and temporal scales has been proposed as a key driver of body size distributions for associated communities. Thus, understanding the relationship between habitat and body size is fundamental to developing predictions regarding the influence of habitat change on animal communities. Much of the work assessing the relationship between habitat structure and body size distributions has focused on terrestrial taxa with determinate growth, and has primarily analysed discontinuities (gaps) in the distribution of species mean sizes (species size relationships or SSRs). The suitability of this approach for taxa with indeterminate growth has yet to be determined. We provide a cross-ecosystem comparison of bird (determinate growth) and fish (indeterminate growth) body mass distributions using four independent data sets. We evaluate three size distribution indices: SSRs, species size–density relationships (SSDRs) and individual size–density relationships (ISDRs), and two types of analysis: looking for either discontinuities or abundance patterns and multi-modality in the distributions. To assess the respective suitability of these three indices and two analytical approaches for understanding habitat–size relationships in different ecosystems, we compare their ability to differentiate bird or fish communities found within contrasting habitat conditions. All three indices of body size distribution are useful for examining the relationship between cross-scale patterns of habitat structure and size for species with determinate growth, such as birds. In contrast, for species with indeterminate growth such as fish, the relationship between habitat structure and body size may be masked when using mean summary metrics, and thus individual-level data (ISDRs) are more useful. Furthermore, ISDRs, which have traditionally been used to study aquatic systems, present a potentially useful common currency for comparing body size distributions across terrestrial and aquatic ecosystems.

Molecular and pharmacological characterization of the Chelicerata pyrokinin receptor from the southern cattle tick, Rhipicephalus (Boophilus) microplus.

PubMed

Yang, Yunlong; Nachman, Ronald J; Pietrantonio, Patricia V

2015-05-01

We identified the first pyrokinin receptor (Rhimi-PKR) in Chelicerata and analyzed structure-activity relationships of cognate ligand neuropeptides and their analogs. Based on comparative and phylogenetic analyses, this receptor, which we cloned from larvae of the cattle tick Rhipicephalus microplus (Acari: Ixodidae), is the ortholog of the insect pyrokinin (PK)/pheromone biosynthesis activating neuropeptide (PBAN)/diapause hormone (DH) neuropeptide family receptor. Rhimi-PKR functional analyses using calcium bioluminescence were performed with a developed stable recombinant CHO-K1 cell line. Rhimi-PKR was activated by four endogenous PKs from the Lyme disease vector, the tick Ixodes scapularis (EC50s range: 85.4 nM-546 nM), and weakly by another tick PRX-amide peptide, periviscerokinin (PVK) (EC50 = 24.5 μM). PK analogs with substitutions of leucine, isoleucine or valine at the C-terminus for three tick PK peptides, Ixosc-PK1, Ixosc-PK2, and Ixosc-PK3, retained their potency on Rhimi-PKR. Therefore, Rhimi-PKR is less selective and substantially more tolerant than insect PK receptors of C-terminal substitutions of leucine to isoleucine or valine, a key structural feature that serves to distinguish insect PK from PVK/CAP2b receptors. In females, ovary and synganglion had the highest Rhimi-PKR relative transcript abundance followed by the rectal sac, salivary glands, Malpighian tubules, and midgut. This is the first pharmacological analysis of a PK/PBAN/DH-like receptor from the Chelicerata, which will now permit the discovery of the endocrinological roles of this neuropeptide family in vectors of vertebrate pathogens. Copyright © 2015 Elsevier Ltd. All rights reserved.

Successful emotion regulation is predicted by amygdala activity and aspects of personality: A latent variable approach.

PubMed

Morawetz, Carmen; Alexandrowicz, Rainer W; Heekeren, Hauke R

2017-04-01

The experience of emotions and their cognitive control are based upon neural responses in prefrontal and subcortical regions and could be affected by personality and temperamental traits. Previous studies established an association between activity in reappraisal-related brain regions (e.g., inferior frontal gyrus and amygdala) and emotion regulation success. Given these relationships, we aimed to further elucidate how individual differences in emotion regulation skills relate to brain activity within the emotion regulation network on the one hand, and personality/temperamental traits on the other. We directly examined the relationship between personality and temperamental traits, emotion regulation success and its underlying neuronal network in a large sample (N = 82) using an explicit emotion regulation task and functional MRI (fMRI). We applied a multimethodological analysis approach, combing standard activation-based analyses with structural equation modeling. First, we found that successful downregulation is predicted by activity in key regions related to emotion processing. Second, the individual ability to successfully upregulate emotions is strongly associated with the ability to identify feelings, conscientiousness, and neuroticism. Third, the successful downregulation of emotion is modulated by openness to experience and habitual use of reappraisal. Fourth, the ability to regulate emotions is best predicted by a combination of brain activity and personality as well temperamental traits. Using a multimethodological analysis approach, we provide a first step toward a causal model of individual differences in emotion regulation ability by linking biological systems underlying emotion regulation with descriptive constructs. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Associations between children's social functioning and physical activity participation are not mediated by social acceptance: a cross-sectional study.

PubMed

Sebire, Simon J; Jago, Russell; Fox, Kenneth R; Page, Angie S; Brockman, Rowan; Thompson, Janice L

2011-09-30

Physical activity (PA) during childhood often occurs in social contexts. As such, children's ability to develop and maintain friendship groups may be important in understanding their PA. This paper investigates the associations among children's social functioning, and physical activity and whether perceptions of social acceptance mediate any social functioning-PA association. A cross sectional survey in which 652 10-11 year olds self-reported their peer (e.g. difficulties with friends) and conduct (e.g. anger/aggression) problems, prosocial behaviours (e.g. being kind to others) and perceptions of social acceptance. Physical activity was objectively assessed by Actigraph GT1M accelerometers to estimate counts per minute, (CPM) and minutes of moderate-to-vigorous physical activity (MVPA). Linear regression analyses were conducted to investigate associations between social functioning and PA. Indirect effects were analysed to explore mediation by social acceptance. Among boys, peer problems were negatively associated with CPM and MVPA and conduct problems were positively associated with CPM and MVPA. Prosocial behaviour was unrelated to PA in boys. Social functioning was not associated with PA among girls. Social acceptance did not mediate the social functioning-PA relationship. Boys' conduct and peer problems were associated positively and negatively respectively with their PA but this relationship was not mediated by perceptions of social acceptance. Future research should study alternative mediators to understand the processes underpinning this relationship.

Finite element predictions of active buckling control of stiffened panels

NASA Astrophysics Data System (ADS)

Thompson, Danniella M.; Griffin, O. H., Jr.

1993-04-01

Materials systems and structures that can respond 'intelligently' to their environment are currently being proposed and investigated. A series of finite element analyses was performed to investigate the potential for active buckling control of two different stiffened panels by embedded shape memory alloy (SMA) rods. Changes in the predicted buckling load increased with the magnitude of the actuation level for a given structural concept. Increasing the number of actuators for a given concept yielded greater predicted increases in buckling load. Considerable control authority was generated with a small number of actuators, with greater authority demonstrated for those structural concepts where the activated SMA rods could develop greater forces and moments on the structure. Relatively simple and inexpensive analyses were performed with standard finite elements to determine such information, indicating the viability of these types of models for design purposes.

The power of social networks and social support in promotion of physical activity and body mass index among African American adults.

PubMed

Flórez, Karen R; Richardson, Andrea S; Ghosh-Dastidar, Madhumita Bonnie; Troxel, Wendy; DeSantis, Amy; Colabianchi, Natalie; Dubowitz, Tamara

2018-04-01

Social support and social networks can elucidate important structural and functional aspects of social relationships that are associated with health-promoting behaviors, including Physical Activity (PA) and weight. A growing number of studies have investigated the relationship between social support, social networks, PA and obesity specifically among African Americans; however, the evidence is mixed and many studies focus exclusively on African American women. Most studies have also focused on either functional or structural aspects of social relationships (but not both) and few have objectively measured moderate-to-vigorous physical activity (MVPA) and body mass index (BMI). Cross-sectional surveys of adult African American men and women living in two low-income predominantly African American neighborhoods in Pittsburgh, PA (N = 799) measured numerous structural features as well as functional aspects of social relationships. Specifically, structural features included social isolation, and social network size and diversity. Functional aspects included perceptions of social support for physical activity from the social network in general as well as from family and friends specifically. Height, weight, and PA were objectively measured. From these, we derived Body Mass Index (BMI) and moderate-to-vigorous physical activity (MVPA). All regression models were stratified by gender, and included age, income, education, employment, marital status, physical limitations, and a neighborhood indicator. Greater social isolation was a significant predictor of lower BMI among men only. Among women only, social isolation was significantly associated with increased MVPA whereas, network diversity was significantly associated with reduced MVPA. Future research would benefit from in-depth qualitative investigations to understand how social networks may act to influence different types of physical activity among African Americans, as well as understand how they can be possible levers for health promotion and prevention.

An Extended Structure-Activity Relationship of Nondioxin-Like PCBs Evaluates and Supports Modeling Predictions and Identifies Picomolar Potency of PCB 202 Towards Ryanodine Receptors.

PubMed

Holland, Erika B; Feng, Wei; Zheng, Jing; Dong, Yao; Li, Xueshu; Lehmler, Hans-Joachim; Pessah, Isaac N

2017-01-01

Nondioxin-like polychlorinated biphenyls (NDL PCBs) activate ryanodine-sensitive Ca 2+  channels (RyRs) and this activation has been associated with neurotoxicity in exposed animals. RyR-active congeners follow a distinct structure-activity relationship and a quantitative structure-activity relationship (QSAR) predicts that a large number of PCBs likely activate the receptor, which requires validation. Additionally, previous structural based conclusions have been established using receptor ligand binding assays but the impact of varying PCB structures on ion channel gating behavior is not understood. We used [ 3 H]Ryanodine ([ 3 H]Ry) binding to assess the RyR-activity of 14 previously untested PCB congeners evaluating the predictability of the QSAR. Congeners determined to display widely varying potency were then assayed with single channel voltage clamp analysis to assess direct influences on channel gating kinetics. The RyR-activity of individual PCBs assessed in in vitro assays followed the general pattern predicted by the QSAR but binding and lipid bilayer experiments demonstrated higher potency than predicted. Of the 49 congeners tested to date, tetra-ortho PCB 202 was found to be the most potent RyR-active congener increasing channel open probability at 200 pM. Shifting meta-substitutions to the para-position resulted in a > 100-fold reduction in potency as seen with PCB 197. Non-ortho PCB 11 was found to lack activity at the receptor supporting a minimum mono-ortho substitution for PCB RyR activity. These findings expand and support previous SAR assessments; where out of the 49 congeners tested to date 42 activate the receptor demonstrating that the RyR is a sensitive and common target of PCBs. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Relationships between youth sport participation and selected health risk behaviors from 1999 to 2007.

PubMed

Taliaferro, Lindsay A; Rienzo, Barbara A; Donovan, Kristine A

2010-08-01

How adolescents spend their out-of-school time represents one of the most important factors for predicting positive youth development. Sport participation relates to many beneficial outcomes. However, current economic conditions threaten high school sport programs around the United States. This investigation examined relationships by year between sport participation and numerous health risk behaviors among high school students. Data were derived from the Centers for Disease Control and Prevention's Youth Risk Behavior Surveys administered every 2 years from 1999 through 2007. Items assessed were sport participation, vigorous physical activity, dietary habits, weight loss, sexual activity, interpersonal violence and suicidality, and substance use. Multiple logistic regression analyses were used to examine relationships between sport participation and each health behavior. Interaction effects tested whether relationships varied by year, sex, age, and/or race/ethnicity. Analyses revealed some consistencies across years in relationships between sport participation and health risk behaviors for both sexes. However, most relationships varied by race/ethnicity. Among White students, sport participation related to multiple positive health behaviors. Conversely, African American, Hispanic, and Other athletes showed fewer positive health behaviors and some negative behaviors. Findings suggest that participation in organized sports affords many health benefits to most adolescents, but relates to some negative health behaviors in certain subgroups. Information regarding sport participation and health risk behaviors among subgroups across years can inform school policy, practice, and future research.

Fourier transform infrared (FTIR) spectroscopy to monitor the cellular impact of newly synthesized platinum derivatives.

PubMed

Berger, Gilles; Gasper, Régis; Lamoral-Theys, Delphine; Wellner, Anja; Gelbcke, Michel; Gust, Ronald; Nève, Jean; Kiss, Robert; Goormaghtigh, Erik; Dufrasne, François

2010-09-01

Platinum complexes remain widely used to combat various types of cancers. Three platinum complexes, cisplatin, carboplatin and oxaliplatin, are marketed for various oncological purposes. Additionally, nedaplatin, lobaplatin and heptaplatin have gained regionally limited approval for oncology purposes. Furthermore, various platinum derivatives are currently under clinical trials. More than 40 years after their discovery, however, the precise mechanism of action of platinum antitumor complexes remains elusive, partly because these compounds display numerous intracellular targets. Structure-activity-relationship analyses are therefore difficult to conduct to optimize the synthesis of novel platinum derivatives. The aim of the present study is to illustrate the potential of using Fourier Transform Infrared (FTIR) analyses to monitor the cellular modifications induced by the new platinum derivatives that we have synthesized. We show in the present study the advantages of combining an in vitro assay to determine the IC50 growth inhibition concentrations of a series of compounds belonging to a given chemical series and FTIR analyses carried out at the IC50 concentrations for each compound to identify potential hits within this series of compounds. The original pharmacological approach proposed here could, therefore, avoid large-scale pharmacological experiments to find hits within a given chemical series.

Synthesis, cytotoxicity and haemolytic activity of Pulsatilla saponin A, D derivatives.

PubMed

Chen, Zhong; Duan, Huaqing; Wang, Minglei; Han, Li; Liu, Yanli; Zhu, Yongming; Yang, Shilin

2015-06-15

The strong haemolytic activity of Pulsatilla saponin A (PSA), D (PSD) hampered their clinical development of antitumor agents. In order to solve this problem, C-28 position modification derivatives of PSA/PSD were synthesized. The cytotoxicity and haemolytic activity of these compounds were evaluated. Structure-activity relationship and structure-toxicity relationship had been observed. The mice acute toxicity of compound 11 was reduced greatly than that of PSA. This study indicates that compound 11 may represent an interesting class of potent antitumor agents from triterpenoid saponins avoiding the haemolysis problem. The present study has important significance for the development of antitumor saponins. Copyright © 2015 Elsevier Ltd. All rights reserved.

The differential effect of the teacher-student interpersonal relationship on student outcomes for students with different ethnic backgrounds.

PubMed

den Brok, Perry; van Tartwijk, Jan; Wubbels, Theo; Veldman, Ietje

2010-06-01

The differential effectiveness of schools and teachers receives a growing interest, but few studies focused on the relevance of student ethnicity for this effectiveness and only a small number of these studies investigated teaching in terms of the teacher-student interpersonal relationship. Furthermore, the methodology employed often restricted researchers to investigating direct effects between variables across large samples of students. This study uses causal modelling to investigate associations between student background characteristics, students' perceptions of the teacher-student interpersonal relationship, and student outcomes, across and within several population subgroups in Dutch secondary multi-ethnic classes. Multi-group structural equation modelling was used to investigate causal paths between variables in four ethnic groups: Dutch (N=387), Turkish first- and second-generation immigrant students (N=267), Moroccan first and second generation (N=364), and Surinamese second-generation students (N=101). Different structural paths were necessary to explain associations between variables in the different (sub) groups. Different amounts of variance in student attitudes could be explained by these variables. The teacher-student interpersonal relationship is more important for students with a non-Dutch background than for students with a Dutch background. Results suggest that the teacher-student relationship is more important for second generation than for first-generation immigrant students. Multi-group causal model analyses can provide a better, more differentiated picture of the associations between student background variables, teacher behaviour, and student outcomes than do more traditional types of analyses.

Discovery of novel glitazones incorporated with phenylalanine and tyrosine: synthesis, antidiabetic activity and structure-activity relationships.

PubMed

Prashantha Kumar, B R; Baig, Nasir R; Sudhir, Sai; Kar, Koyal; Kiranmai, M; Pankaj, M; Joghee, Nanjan M

2012-12-01

We report a series of new glitazones incorporated with phenylalanine and tyrosine. All the compounds were tested for their in vitro glucose uptake activity using rat-hemidiaphragm, both in presence and absence of insulin. Six of the most active compounds from the in vitro screening were taken forward for their in vivo triglyceride and glucose lowering activity against dexamethazone induced hyperlipidemia and insulin resistance in Wistar rats. The liver samples of rats that received the most active compounds, 23 and 24, in the in vivo studies, were subjected to histopathological examination to assess their short term hepatotoxicity. The investigations on the in vitro glucose uptake, in vivo triglyceride and glucose lowering activity are described here along with the quantitative structure-activity relationships. Copyright © 2012 Elsevier Inc. All rights reserved.

An in-silico insight into the characteristics of β-propeller phytase.

PubMed

Mathew, Akash; Verma, Anukriti; Gaur, Smriti

2014-06-01

Phytase is an enzyme that is found extensively in the plant kingdom and in some species of bacteria and fungi. This paper identifies and analyses the available full length sequences of β-propeller phytases (BPP). BPP was chosen due to its potential applicability in the field of aquaculture. The sequences were obtained from the Uniprot database and subject to various online bioinformatics tools to elucidate the physio-chemical characteristics, secondary structures and active site compositions of BPP. Protparam and SOPMA were used to analyse the physiochemical and secondary structure characteristics, while the Expasy online modelling tool and CASTp were used to model the 3-D structure and identify the active sites of the BPP sequences. The amino acid compositions of the four sequences were compared and composed in a graphical format to identify similarities and highlight the potentially important amino acids that form the active site of BPP. This study aims to analyse BPP and contribute to the clarification of the molecular mechanism involved in the enzyme activity of BPP and contribute in part to the possibility of constructing a synthetic version of BPP.

High Add Valued Application of Turpentine in Crop Production through Structural Modification and QSAR Analysis.

PubMed

Gao, Yanqing; Li, Jingjing; Li, Jian; Song, Zhanqian; Shang, Shibin; Rao, Xiaoping

2018-02-08

Turpentine is a volatile component of resin, which is an abundant forest resource in Southern China. As one of the most important components, the integrated application of β-pinene has been studied. The broad-spectrum evaluation of β-pinene and its analogues has, therefore, been necessary. In an attempt to expand the scope of agro-activity trials, the preparation and the evaluation of the herbicidal activity of a series of β-pinene analogues against three agricultural herbs were carried out. In accordance with the overall herbicidal activity, it is noteworthy that compounds 6k , 6l , and 6m demonstrated extreme activity with IC 50 values of 0.065, 0.065, and 0.052 mol active ingredients/hectare against E. crus-galli . The preliminary structure-activity relationship (SAR) was analyzed and the compounds with the appropriate volatility and substituent type that had beneficial herbicidal activity were analyzed. Simultaneously, the quantitative structure-activity relationship (QSAR) model was built and the most important structural features were indicated, which was, to a certain extent, in line with the SAR study. The study aimed to study the application of the forest resource turpentine in agriculture as a potential and alternative approach for comprehensive utilization.

Discovery and Structure-Activity Relationships of the Neoseptins: A New Class of Toll-like Receptor-4 (TLR4) Agonists.

PubMed

Morin, Matthew D; Wang, Ying; Jones, Brian T; Su, Lijing; Surakattula, Murali M R P; Berger, Michael; Huang, Hua; Beutler, Elliot K; Zhang, Hong; Beutler, Bruce; Boger, Dale L

2016-05-26

Herein, we report studies leading to the discovery of the neoseptins and a comprehensive examination of the structure-activity relationships (SARs) of this new class of small-molecule mouse Toll-like receptor 4 (mTLR4) agonists. The compounds in this class, which emerged from screening an α-helix mimetic library, stimulate the immune response, act by a well-defined mechanism (mouse TLR4 agonist), are easy to produce and structurally manipulate, exhibit exquisite SARs, are nontoxic, and elicit improved and qualitatively different responses compared to lipopolysaccharide, even though they share the same receptor.

Molecular systematics of the freshwater stingrays (myliobatiformes: potamotrygonidae) of the Amazon, Orinoco, Magdalena, Esequibo, Caribbean, and Maracaibo basins (Colombia - Venezuela): evidence from three mitochondrial genes.

PubMed

Garcia, David Alejandro; Lasso, Carlos Andres; Morales, Monica; Caballero, Susana Josefina

2016-11-01

Lack of adequate information about the taxonomic and evolutionary relationships, ecology, biology, and distribution of several species belonging to the family Potamotrygonidae makes these species vulnerable to anthropic activities, including commercial overexploitation for the ornamental fish market. The aim of this study was to investigate the systematic relationships among genera and species belonging to this family by analyses of three mitochondrial gene regions. Samples were collected from the main river basins in Colombia and Venezuela for four genera and seven species of the family, as well as for what appear to be unidentified species. Three mitochondrial molecular markers COI, Cytb, and ATP6 were amplified and sequenced. Maximum likelihood and Bayesian inference analysis were performed to obtain topologies for each marker and for a concatenated dataset including the three genes. Small dataset may compromise some methods estimations of sequence divergence in the ATP6 marker. Monophyly of the four genera in Potamotrygonidae was confirmed and phylogenetic relationships among members of the Potamotrygon genus were not clearly resolved. However, results obtained with the molecular marker Cytb appear to offer a good starting point to differentiate among genera and species as a tool that could be used for barcoding. The application of this gene as a barcode could be applied for management and regulation of extraction practices for these genera. Sequencing complete mitochondrial genomes would be the next step for testing evolutionary hypothesis among these genera. Population structure analyses should be undertaken for Paratrygon, Potamotrygon magdalenae and motoro.

Racial and Cultural Factors Affecting the Mental Health of Asian Americans

PubMed Central

Miller, Matthew J.; Yang, Minji; Farrell, Jerome A.; Lin, Li-Ling

2011-01-01

In this study, we employed structural equation modeling to test the degree to which racism-related stress, acculturative stress, and bicultural self-efficacy were predictive of mental health in a predominantly community-based sample of 367 Asian American adults. We also tested whether bicultural self-efficacy moderated the relationship between acculturative stress and mental health. Finally, we examined whether generational status moderated the impact of racial and cultural predictors of mental health by testing our model across immigrant and U.S.-born samples. Results indicated that our hypothesized structural model represented a good fit to the total sample data. While racism-related stress, acculturative stress, and bicultural self-efficacy were significant predictors of mental health in the total sample analyses, our generational analyses revealed a differential predictive pattern across generational status. Finally, we found that the buffering effect of bicultural self-efficacy on the relationship between acculturative stress and mental health was significant for U.S.-born individuals only. Implications for research and service delivery are explored. PMID:21977934

Heterometric sediment and benthic micro-habitat: In situ and experimental approaches.

NASA Astrophysics Data System (ADS)

Navon, Maxime; Dauvin, Jean-Claude; Lesourd, Sandric

2016-04-01

The eastern Bay of Seine and its estuary are characterized by complex sediment structures with high temporal, spatial and vertical heterogeneities. As the result of different hydrodynamics forcing, estuary is a particular area with fine sediment accumulation since the last decades. This complex system involves particular relationships between benthic species and the environment. Dominant species show particular traits of life: bentho-pelagic reproductive cycle, burrowing, tubicoulous, surface and subsurface species. Moreover, species behaviours are different according to the sediment properties: grain size, stratification, texture, silt and clay contents… Although benthic macrofauna and sediment relationship is often describe as the major factor structuring benthic communities, no spatial and temporal relationships has been highlighted in this area. So, our study is focused on the relationship between species and sediment at the individual scale and on micro-habitats. The aim of the study is to define the macrofauna vertical distribution to understand how the sediment structure acts on organisms and the organism behaviour in a heterometric sediment context, i.e. how organisms act in return on the sediment structure. An in situ approach is used to answer these questions with four campaigns on board on the Oceanographic Vessel 'Le Côtes de la Manche'. A total of 43 cores (16 cm diameter, 35 cm high) in three typical sediment facies are sampled. Cores are analysed with Computer-Aided Tomography scan (Cyceron Laboratory, Caen) to 3D visualize organisms and to determine volumetric space occupation by biogenic structures. The same cores are transversally cut to check the species out and to analyse sediment parameters (grain size, organic matter and other chemical components on XRF device). Results show that most of the organism are closed to the surface sediment but also that some species, even small size individuals, are found deeper in the sediment-column until 9 cm depth. This approach gives nondestructive 3D picture on the organism position in sediment and provides information on the manner how sediment structure acts on organisms and in return how organisms disturb sediment structure.

Synthesis, Antifungal Activity and Structure-Activity Relationships of Novel 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic Acid Amides.

PubMed

Du, Shijie; Tian, Zaimin; Yang, Dongyan; Li, Xiuyun; Li, Hong; Jia, Changqing; Che, Chuanliang; Wang, Mian; Qin, Zhaohai

2015-05-08

A series of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-yl)phenyl)-3-(difluoro-methyl)-1-methyl-1H-pyrazole-4-carboxamide (9m) exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH.

The sexual erotic market as an analytical framework for understanding erotic-affective exchanges in interracial sexually intimate and affective relationships.

PubMed

Vigoya, Mara Viveros

2015-01-01

This paper examines the way in which erotic-affective exchanges in interracial relationships have been analysed in Latin America. It considers how race, gender and class operate within a market of values such that erotic, affective and economic status are shaped by racial, gender and class hierarchies. In this paper I analyse historical and social arrangements that embody the region's political economy of race and sex. Such a perspective allows me to address the simultaneous co-existence of socio-racial exclusion and inclusion and the repressive and productive effects of power, attraction and anxiety as aspects of lived experiences in relation to sexuality. From there, I outline an analytical framework that references an erotic or pleasure-based market in which capital and other resources are exchanged from a structural perspective stressing relationship alliances. I conclude by identifying the scope and limits of such an approach.

A multivariate model of parent-adolescent relationship variables in early adolescence.

PubMed

McKinney, Cliff; Renk, Kimberly

2011-08-01

Given the importance of predicting outcomes for early adolescents, this study examines a multivariate model of parent-adolescent relationship variables, including parenting, family environment, and conflict. Participants, who completed measures assessing these variables, included 710 culturally diverse 11-14-year-olds who were attending a middle school in a Southeastern state. The parents of a subset of these adolescents (i.e., 487 mother-father pairs) participated in this study as well. Correlational analyses indicate that authoritative and authoritarian parenting, family cohesion and adaptability, and conflict are significant predictors of early adolescents' internalizing and externalizing problems. Structural equation modeling analyses indicate that fathers' parenting may not predict directly externalizing problems in male and female adolescents but instead may act through conflict. More direct relationships exist when examining mothers' parenting. The impact of parenting, family environment, and conflict on early adolescents' internalizing and externalizing problems and the importance of both gender and cross-informant ratings are emphasized.

Generational Solidarity in Europe and Israel.

PubMed

Katz, Ruth; Lowenstein, Ariela; Halperin, Dafna; Tur-Sinai, Aviad

2015-09-01

This study explored various dimensions of generational relationships between older parents and their adult children using the second wave of SHARE (Survey of Health, Ageing and Retirement in Europe), comparing it to Dykstra's and Fokkema's (2011) analyses of the first wave. Results were further compared to the OASIS study (Old Age and Autonomy: The Role of Service Systems and Intergenerational Solidarity). The intergenerational solidarity model served as the main conceptual framework. Analyses yielded four family relationship types present in all countries, albeit with different frequencies. Around half of the respondents in the 11 countries were identified with close ties and flow of support. Four conclusions were drawn: (1) importance of personal resources; (2) cultural differences and meanings for families; (3) highlighting within-country difference; and (4) strength of intergenerational solidarity. The importance of understanding generational relationships in the current era with higher longevity and changing family structures is emphasized and explicated.

Physiological and Proteomics Analyses Reveal Low-Phosphorus Stress Affected the Regulation of Photosynthesis in Soybean.

PubMed

Chu, Shanshan; Li, Hongyan; Zhang, Xiangqian; Yu, Kaiye; Chao, Maoni; Han, Suoyi; Zhang, Dan

2018-06-06

Previous studies have revealed a significant genetic relationship between phosphorus (P)-efficiency and photosynthesis-related traits in soybean. In this study, we used proteome profiling in combination with expression analysis, biochemical investigations, and leaf ultrastructural analysis to identify the underlying physiological and molecular responses. The expression analysis and ultrastructural analysis showed that the photosynthesis key genes were decreased at transcript levels and the leaf mesophyll and chloroplast were severely damaged after low-P stress. Approximately 55 protein spots showed changes under low-P condition by mass spectrometry, of which 17 were involved in various photosynthetic processes. Further analysis revealed the depression of photosynthesis caused by low-P stress mainly involves the regulation of leaf structure, adenosine triphosphate (ATP) synthesis, absorption and transportation of CO₂, photosynthetic electron transport, production of assimilatory power, and levels of enzymes related to the Calvin cycle. In summary, our findings indicated that the existence of a stringent relationship between P supply and the genomic control of photosynthesis in soybean. As an important strategy to protect soybean photosynthesis, P could maintain the stability of cell structure, up-regulate the enzymes’ activities, recover the process of photosystem II (PSII), and induce the expression of low-P responsive genes and proteins.

Associations of religious behavior and experiences with extent of regional atrophy in the orbitofrontal cortex during older adulthood

PubMed Central

Hayward, R. David; Owen, Amy D.; Koenig, Harold G.; Steffens, David C.; Payne, Martha E.

2011-01-01

The orbitofrontal cortex (OFC) is a region of the brain that has been empirically linked with religious or spiritual activity, and atrophy in this region has been shown to contribute to serious mental illness in late life. This study used structural magnetic resonance imaging to examine the association between religious or spiritual factors and volume of the orbitalfrontal cortex (OFC). Change in the volume of participants’ left and right OFC was measured longitudinally over a period of two to eight years. Multiple linear regression analyses showed that religious or spiritual factors were related to extent of atrophy in the left OFC. Significantly less atrophy of the left OFC was observed in participants who reported a life-changing religious or spiritual experience during the course of the study, and in members of Protestant religious groups who reported being born-again when entering the study. Significantly greater atrophy of the left OFC was also associated with more frequent participation in public religious worship. No significant relationship was observed between religious or spiritual factors and extent of atrophy in the right OFC. These results support the presence of a long-term relationship between religious or spiritual experience and brain structure, which may have clinical implications. PMID:22611519

The drosomycin multigene family: three-disulfide variants from Drosophila takahashii possess antibacterial activity

PubMed Central

Gao, Bin; Zhu, Shunyi

2016-01-01

Drosomycin (DRS) is a strictly antifungal peptide in Drosophila melanogaster, which contains four disulfide bridges (DBs) with three buried in molecular interior and one exposed on molecular surface to tie the amino- and carboxyl-termini of the molecule together (called wrapper disulfide bridge, WDB). Based on computational analysis of genomes of Drosophila species belonging to the Oriental lineage, we identified a new multigene family of DRS in Drosphila takahashii that includes a total of 11 DRS-encoding genes (termed DtDRS-1 to DtDRS-11) and a pseudogene. Phylogenetic tree and synteny analyses reveal orthologous relationship between DtDRSs and DRSs, indicating that orthologous genes of DRS-1, DRS-2, DRS-3 and DRS-6 have undergone duplication in D. takahashii and three amplifications (DtDRS-9 to DtDRS-11) of DRS-3 have lost WDB. Among the 11 genes, five are transcriptionally active in adult fruitflies. The ortholog of DRS (DtDRS-1) shows high structural and functional similarity to DRS while two WDB-deficient members display antibacterial activity accompanying complete loss or remarkable reduction of antifungal activity. To the best of our knowledge, this is the first report on the presence of three-disulfide antibacterial DRSs in a specific Drosophila species, suggesting a potential role of DB loss in neofunctionalization of a protein via structural adjustment. PMID:27562645

Structural and kinetic studies of a novel nerol dehydrogenase from Persicaria minor, a nerol-specific enzyme for citral biosynthesis.

PubMed

Tan, Cheng Seng; Hassan, Maizom; Mohamed Hussein, Zeti Azura; Ismail, Ismanizan; Ho, Kok Lian; Ng, Chyan Leong; Zainal, Zamri

2018-02-01

Geraniol degradation pathway has long been elucidated in microorganisms through bioconversion studies, yet weakly characterised in plants; enzyme with specific nerol-oxidising activity has not been reported. A novel cDNA encodes nerol dehydrogenase (PmNeDH) was isolated from Persicaria minor. The recombinant PmNeDH (rPmNeDH) is a homodimeric enzyme that belongs to MDR (medium-chain dehydrogenases/reductases) superfamily that catalyses the first oxidative step of geraniol degradation pathway in citral biosynthesis. Kinetic analysis revealed that rPmNeDH has a high specificity for allylic primary alcohols with backbone ≤10 carbons. rPmNeDH has ∼3 fold higher affinity towards nerol (cis-3,7-dimethyl-2,6-octadien-1-ol) than its trans-isomer, geraniol. To our knowledge, this is the first alcohol dehydrogenase with higher preference towards nerol, suggesting that nerol can be effective substrate for citral biosynthesis in P. minor. The rPmNeDH crystal structure (1.54 Å) showed high similarity with enzyme structures from MDR superfamily. Structure guided mutation was conducted to describe the relationships between substrate specificity and residue substitutions in the active site. Kinetics analyses of wild-type rPmNeDH and several active site mutants demonstrated that the substrate specificity of rPmNeDH can be altered by changing any selected active site residues (Asp 280 , Leu 294 and Ala 303 ). Interestingly, the L294F, A303F and A303G mutants were able to revamp the substrate preference towards geraniol. Furthermore, mutant that exhibited a broader substrate range was also obtained. This study demonstrates that P. minor may have evolved to contain enzyme that optimally recognise cis-configured nerol as substrate. rPmNeDH structure provides new insights into the substrate specificity and active site plasticity in MDR superfamily. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar G.; Swaminathan S.; Kumaran, D.

Clostridium botulinum neurotoxins are classified as Category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). The seven serotypes (A-G) of the botulinum neurotoxin, the causative agent of the disease botulism, block neurotransmitter release by specifically cleaving one of the three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and induce flaccid paralysis. Using a structure-based drug-design approach, a number of peptide inhibitors were designed and their inhibitory activity against botulinum serotype A (BoNT/A) protease was determined. The most potent peptide, RRGF, inhibited BoNT/A protease with an IC{sub 50} of 0.9 {micro}M and a K{sub i} ofmore » 358 nM. High-resolution crystal structures of various peptide inhibitors in complex with the BoNT/A protease domain were also determined. Based on the inhibitory activities and the atomic interactions deduced from the cocrystal structures, the structure-activity relationship was analyzed and a pharmacophore model was developed. Unlike the currently available models, this pharmacophore model is based on a number of enzyme-inhibitor peptide cocrystal structures and improved the existing models significantly, incorporating new features.« less

Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling.

PubMed

Kumar, Gyanendra; Kumaran, Desigan; Ahmed, S Ashraf; Swaminathan, Subramanyam

2012-05-01

Clostridium botulinum neurotoxins are classified as Category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). The seven serotypes (A-G) of the botulinum neurotoxin, the causative agent of the disease botulism, block neurotransmitter release by specifically cleaving one of the three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and induce flaccid paralysis. Using a structure-based drug-design approach, a number of peptide inhibitors were designed and their inhibitory activity against botulinum serotype A (BoNT/A) protease was determined. The most potent peptide, RRGF, inhibited BoNT/A protease with an IC(50) of 0.9 µM and a K(i) of 358 nM. High-resolution crystal structures of various peptide inhibitors in complex with the BoNT/A protease domain were also determined. Based on the inhibitory activities and the atomic interactions deduced from the cocrystal structures, the structure-activity relationship was analyzed and a pharmacophore model was developed. Unlike the currently available models, this pharmacophore model is based on a number of enzyme-inhibitor peptide cocrystal structures and improved the existing models significantly, incorporating new features. © 2012 International Union of Crystallography

Structure-activity relationships on the study of β-galactosidase folding/unfolding due to interactions with immobilization additives: Triton X-100 and ethanol.

PubMed

Soto, Dayana; Escobar, Sindy; Guzmán, Fanny; Cárdenas, Constanza; Bernal, Claudia; Mesa, Monica

2017-03-01

Improving the enzyme stability is a challenge for allowing their practical application. The surfactants are stabilizing agents, however, there are still questions about their influence on enzyme properties. The structure-activity/stability relationship for β-galactosidase from Bacillus circulans is studied here by Circular Dichroism and activity measurements, as a function of temperature and pH. The tendency of preserving the β-sheet and α-helix structures at temperatures below 65°C and different pH is the result of the balance between the large- and short-range effects, respecting to the active site. This information is fundamental for explaining the structural changes of this enzyme in the presence of Triton X-100 surfactant and ethanol. The enzyme thermal stabilization in the presence of this surfactant responds to the rearrangement of the secondary structure for having optimal activity/stability. The effect of ethanol is more related with changes in the dielectric properties of the aqueous solution than with protein structural transformations. These results contribute to understand the effects of surfactant-enzyme interactions on the enzyme behavior, from the structural point of view and to rationalize the surfactant-based stabilizing strategies for β-galactosidades. Copyright © 2016 Elsevier B.V. All rights reserved.

Imidazole derivatives as angiotensin II AT1 receptor blockers: Benchmarks, drug-like calculations and quantitative structure-activity relationships modeling

NASA Astrophysics Data System (ADS)

Alloui, Mebarka; Belaidi, Salah; Othmani, Hasna; Jaidane, Nejm-Eddine; Hochlaf, Majdi

2018-03-01

We performed benchmark studies on the molecular geometry, electron properties and vibrational analysis of imidazole using semi-empirical, density functional theory and post Hartree-Fock methods. These studies validated the use of AM1 for the treatment of larger systems. Then, we treated the structural, physical and chemical relationships for a series of imidazole derivatives acting as angiotensin II AT1 receptor blockers using AM1. QSAR studies were done for these imidazole derivatives using a combination of various physicochemical descriptors. A multiple linear regression procedure was used to design the relationships between molecular descriptor and the activity of imidazole derivatives. Results validate the derived QSAR model.

Impact of organisational characteristics on turnover intention among care workers in nursing homes in Korea: a structural equation model.

PubMed

Ha, Jong Goon; Man Kim, Ji; Hwang, Won Ju; Lee, Sang Gyu

2014-09-01

The aim of the present study was to analyse the impact of organisational characteristics on the turnover intention of care workers working at nursing homes in Korea. Study participants included 504 care workers working at 14 nursing homes in Korea. The variables measured were: high-performance work practices, consisting of five subfactors (official training, employment stability, autonomy, employee participation and group-based payment); organisational commitment, consisting of three subfactors (affective, normative and continuance commitment); organisational support; and turnover intention. The inter-relationship between high-performance work practices, organisational support, organisational commitment and turnover intention and the fit of the hypothetical model were analysed using structural equation modelling. According to our analysis, high-performance work practices not only had a direct effect on turnover intention, but also an indirect effect by mediating organisational support and commitment. The factor having the largest direct influence on turnover intention was organisational commitment. The results of the present study suggest that to improve health conditions for frail elderly patients at nursing homes, as well as the efficiency of nursing homes through the continuance of nursing service and enhancement of quality of service, long-term care facilities should reduce the turnover intention of care workers by increasing their organisational commitment by actively implementing high-performance work practices.

Longitudinal change mechanisms for substance use and illegal activity for adolescents in treatment.

PubMed

Hunter, Brooke D; Godley, Susan H; Hesson-McInnis, Matthew S; Roozen, Hendrik G

2014-06-01

The current study investigated: (a) the relationships of exposure to the Adolescent Community Reinforcement Approach (A-CRA) with reductions in substance use, illegal activity, and juvenile justice system involvement in adolescents diagnosed with a substance use disorder, and (b) the pathways by which reductions in the target behaviors were achieved. This study is a secondary data analysis of longitudinal data from a large-scale implementation effort for A-CRA. The sample consisted of 1,467 adolescents who presented to substance use treatment and reported past-year engagement in illegal activity. Participants had an average age of 15.8 years (SD = 1.3) and were 25% female, 14% African American, 29% Hispanic, 35% Caucasian, 16% mixed ethnicity, and 6% other ethnicity. Path analyses provided support that participation in A-CRA had a significant, direct association with reduced substance use; a significant, indirect association with reduced illegal activity through reductions in substance use; and a significant indirect association with reduced juvenile justice system involvement through reductions in both substance use and illegal activity. In addition, post hoc analyses using a bootstrapping strategy provided evidence that reductions in substance use partially mediated the relationship between A-CRA and illegal activity.

Physical Activity and Bone Health in Schoolchildren: The Mediating Role of Fitness and Body Fat

PubMed Central

Torres-Costoso, Ana; Gracia-Marco, Luis; Sánchez-López, Mairena; Notario-Pacheco, Blanca; Arias-Palencia, Natalia; Martínez-Vizcaíno, Vicente

2015-01-01

Background The relationship between physical activity (PA) and bone health is well known, although the role of percent body fat (%BF) and fitness as confounders or mediators in this relationship remains uncertain. Objective To examine whether the association between PA and bone mineral content (BMC) is mediated by %BF and cardiorespiratory fitness (CRF). Methods In this cross sectional study, BMC, total %BF (by DXA), vigorous PA (VPA), CRF, age and height were measured in 132 schoolchildren (62 boys, aged 8–11 years). ANCOVA was used to test differences in BMC by %BF, CRF and VPA, controlling for different sets of confounders. Simple mediation analyses and serial multiple mediation analyses were fitted to examine whether the relationship between PA and BMC is mediated by %BF and fitness. Results Children with high %BF had higher total body BMC than their peers after controlling for all sets of confounders. Children with good CRF or VPA had significantly less total body BMC after controlling for age and sex but in children with good CRF this inverse relation disappeared after adjusting by %BF. %BF and CRF both act as a full mediator in the association between VPA and BMC, after inclusion of the potential confounders in the models. Conclusion Fitness and %BF seem to have a mediator role on the relationship between physical activity and bone mass. PMID:25915941

Structural Probing of Off-Target G Protein-Coupled Receptor Activities within a Series of Adenosine/Adenine Congeners

PubMed Central

Paoletta, Silvia; Tosh, Dilip K.; Salvemini, Daniela; Jacobson, Kenneth A.

2014-01-01

We studied patterns of off-target receptor interactions, mostly at G protein-coupled receptors (GPCRs) in the µM range, of nucleoside derivatives that are highly engineered for nM interaction with adenosine receptors (ARs). Because of the considerable interest of using AR ligands for treating diseases of the CNS, we used the Psychoactive Drug Screening Program (PDSP) for probing promiscuity of these adenosine/adenine congeners at 41 diverse receptors, channels and a transporter. The step-wise truncation of rigidified, trisubstituted (at N6, C2, and 5′ positions) nucleosides revealed unanticipated interactions mainly with biogenic amine receptors, such as adrenergic receptors and serotonergic receptors, with affinities as high as 61 nM. The unmasking of consistent sets of structure activity relationship (SAR) at novel sites suggested similarities between receptor families in molecular recognition. Extensive molecular modeling of the GPCRs affected suggested binding modes of the ligands that supported the patterns of SAR at individual receptors. In some cases, the ligand docking mode closely resembled AR binding and in other cases the ligand assumed different orientations. The recognition patterns for different GPCRs were clustered according to which substituent groups were tolerated and explained in light of the complementarity with the receptor binding site. Thus, some likely off-target interactions, a concern for secondary drug effects, can be predicted for analogues of this set of substructures, aiding the design of additional structural analogues that either eliminate or accentuate certain off-target activities. Moreover, similar analyses could be performed for unrelated structural families for other GPCRs. PMID:24859150

Structural probing of off-target G protein-coupled receptor activities within a series of adenosine/adenine congeners.

PubMed

Paoletta, Silvia; Tosh, Dilip K; Salvemini, Daniela; Jacobson, Kenneth A

2014-01-01

We studied patterns of off-target receptor interactions, mostly at G protein-coupled receptors (GPCRs) in the µM range, of nucleoside derivatives that are highly engineered for nM interaction with adenosine receptors (ARs). Because of the considerable interest of using AR ligands for treating diseases of the CNS, we used the Psychoactive Drug Screening Program (PDSP) for probing promiscuity of these adenosine/adenine congeners at 41 diverse receptors, channels and a transporter. The step-wise truncation of rigidified, trisubstituted (at N6, C2, and 5' positions) nucleosides revealed unanticipated interactions mainly with biogenic amine receptors, such as adrenergic receptors and serotonergic receptors, with affinities as high as 61 nM. The unmasking of consistent sets of structure activity relationship (SAR) at novel sites suggested similarities between receptor families in molecular recognition. Extensive molecular modeling of the GPCRs affected suggested binding modes of the ligands that supported the patterns of SAR at individual receptors. In some cases, the ligand docking mode closely resembled AR binding and in other cases the ligand assumed different orientations. The recognition patterns for different GPCRs were clustered according to which substituent groups were tolerated and explained in light of the complementarity with the receptor binding site. Thus, some likely off-target interactions, a concern for secondary drug effects, can be predicted for analogues of this set of substructures, aiding the design of additional structural analogues that either eliminate or accentuate certain off-target activities. Moreover, similar analyses could be performed for unrelated structural families for other GPCRs.

Inhibitor-based validation of a homology model of the active-site of tripeptidyl peptidase II.

PubMed

De Winter, Hans; Breslin, Henry; Miskowski, Tamara; Kavash, Robert; Somers, Marijke

2005-04-01

A homology model of the active site region of tripeptidyl peptidase II (TPP II) was constructed based on the crystal structures of four subtilisin-like templates. The resulting model was subsequently validated by judging expectations of the model versus observed activities for a broad set of prepared TPP II inhibitors. The structure-activity relationships observed for the prepared TPP II inhibitors correlated nicely with the structural details of the TPP II active site model, supporting the validity of this model and its usefulness for structure-based drug design and pharmacophore searching experiments.

Synthesis-Structure-Activity Relationships in Co3O4 Catalyzed CO Oxidation

NASA Astrophysics Data System (ADS)

Mingle, Kathleen; Lauterbach, Jochen

2018-05-01

In this work, a statistical design and analysis platform was used to develop cobalt oxide based oxidation catalysts prepared via one pot metal salt reduction. An emphasis was placed upon understanding the effects of synthesis conditions, such as heating regimen and Co2+ concentration on the metal salt reduction mechanism, the resultant nanomaterial properties (i.e. size, crystal structure, and crystal faceting), and the catalytic activity in CO oxidation. This was accomplished by carrying out XRD, TEM, and FTIR studies on synthesis intermediates and products. Additionally, high-throughput experimentation was employed to study the performance of Co3O4 oxidation catalysts over a wide range of reaction conditions using a 16-channel fixed bed reactor equipped with a parallel infrared imaging system. Specifically, Co3O4 nanomaterials of varying properties were evaluated for their performance as CO oxidation catalysts. Figure-of-merits including light-off temperatures and activation energies were measured and mapped back to the catalyst properties and synthesis conditions. Statistical analysis methods were used to elucidate significant property-activity relationships as well as the design rules relevant in the synthesis of active catalysts. It was found that CO oxidation light off temperatures could be decreased to <90°C by utilizing the discovered synthesis-structure-activity relationships.

Sources of Phoneme Errors in Repetition: Perseverative, Neologistic, and Lesion Patterns in Jargon Aphasia

PubMed Central

Pilkington, Emma; Keidel, James; Kendrick, Luke T.; Saddy, James D.; Sage, Karen; Robson, Holly

2017-01-01

This study examined patterns of neologistic and perseverative errors during word repetition in fluent Jargon aphasia. The principal hypotheses accounting for Jargon production indicate that poor activation of a target stimulus leads to weakly activated target phoneme segments, which are outcompeted at the phonological encoding level. Voxel-lesion symptom mapping studies of word repetition errors suggest a breakdown in the translation from auditory-phonological analysis to motor activation. Behavioral analyses of repetition data were used to analyse the target relatedness (Phonological Overlap Index: POI) of neologistic errors and patterns of perseveration in 25 individuals with Jargon aphasia. Lesion-symptom analyses explored the relationship between neurological damage and jargon repetition in a group of 38 aphasia participants. Behavioral results showed that neologisms produced by 23 jargon individuals contained greater degrees of target lexico-phonological information than predicted by chance and that neologistic and perseverative production were closely associated. A significant relationship between jargon production and lesions to temporoparietal regions was identified. Region of interest regression analyses suggested that damage to the posterior superior temporal gyrus and superior temporal sulcus in combination was best predictive of a Jargon aphasia profile. Taken together, these results suggest that poor phonological encoding, secondary to impairment in sensory-motor integration, alongside impairments in self-monitoring result in jargon repetition. Insights for clinical management and future directions are discussed. PMID:28522967

Factor Structure of the Korean Version of Illness Intrusiveness Rating Scale: Cross-cultural Implications

PubMed Central

Kim, Kwang-iel; Lee, Haewon; Choi, Joonho; Park, Yong-Chon

2005-01-01

The Illness Intrusiveness Rating Scale (IIRS) measures illness-induced disruptions to 13 domains of lifestyles, activities, and interests. A stable three-factor structure has been well documented; however, the cross-cultural validity of this scale needs to be tested. This study investigated the factor structure of the Korean version of IIRS in 712 outpatients at a university medical center. A predominant diagnosis of the patients was rheumatoid arthritis (47%). The Center for Epidemiological Studies-Depression Scale (CES-D), and Health Assessment Questionnaire (HAQ) were also administered. Exploratory Principal Component Analysis identified a two-factor structure, "Relationships and Personal Development (RPD)" and "Instrumental", accounting for 57% of the variance. Confirmatory analyses extracted an identical factor structure. However, a goodness-of-the fit test failed to support two-factor solution (χ2=138.2, df=43, p<.001). Two factors had high internal consistency (RPD, α=.89; Instrumental, α=.75) and significantly correlated with scores of HAQ (RPD, r=.53, p<.001; Instrumental, .r=44, p<.001) and CES-D (RPD, .r=55, p<.001; Instrumental, .r=43, p<.001). These findings supported construct validity of the Korean version of IIRS, but did not support cross-cultural equivalence of the factor structure. PMID:15832005

Neural responses to maternal praise and criticism: Relationship to depression and anxiety symptoms in high-risk adolescent girls

PubMed Central

Aupperle, Robin L.; Morris, Amanda S.; Silk, Jennifer S.; Criss, Michael M.; Judah, Matt R.; Eagleton, Sally G.; Kirlic, Namik; Byrd-Craven, Jennifer; Phillips, Raquel; Alvarez, Ruben P.

2016-01-01

Background The parent-child relationship may be an important factor in the development of adolescent depressive and anxious symptoms. In adults, depressive symptoms relate to increased amygdala and attenuated prefrontal activation to maternal criticism. The current pilot study examined how depressive and anxiety symptoms in a high-risk adolescent population relate to neural responses to maternal feedback. Given previous research relating oxytocin to maternal behavior, we conducted exploratory analyses using oxytocin receptor (OXTR) genotype. Methods Eighteen females (ages 12–16) listened to maternal praise, neutral, and critical statements during functional magnetic resonance imaging. Participants completed the Mood and Feelings Questionnaire and the Screen for Child Anxiety Related Emotional Disorders. The OXTR single nucleotide polymorphism, rs53576, was genotyped. Linear mixed models were used to identify symptom or allele (GG, AA/AG) by condition (critical, neutral, praise) interaction effects on brain activation. Results Greater symptoms related to greater right amygdala activation for criticism and reduced activation to praise. For left amygdala, greater symptoms related to reduced activation to both conditions. Anxiety symptoms related to differences in superior medial PFC activation patterns. Parental OXTR AA/AG allele related to reduced activation to criticism and greater activation to praise within the right amygdala. Conclusions Results support a relationship between anxiety and depressive symptoms and prefrontal-amygdala responses to maternal feedback. The lateralization of amygdala findings suggests separate neural targets for interventions reducing reactivity to negative feedback or increasing salience of positive feedback. Exploratory analyses suggest that parents' OXTR genetic profile influences parent-child interactions and related adolescent brain responses. PMID:27158587

Neural responses to maternal praise and criticism: Relationship to depression and anxiety symptoms in high-risk adolescent girls.

PubMed

Aupperle, Robin L; Morris, Amanda S; Silk, Jennifer S; Criss, Michael M; Judah, Matt R; Eagleton, Sally G; Kirlic, Namik; Byrd-Craven, Jennifer; Phillips, Raquel; Alvarez, Ruben P

2016-01-01

The parent-child relationship may be an important factor in the development of adolescent depressive and anxious symptoms. In adults, depressive symptoms relate to increased amygdala and attenuated prefrontal activation to maternal criticism. The current pilot study examined how depressive and anxiety symptoms in a high-risk adolescent population relate to neural responses to maternal feedback. Given previous research relating oxytocin to maternal behavior, we conducted exploratory analyses using oxytocin receptor (OXTR) genotype. Eighteen females (ages 12-16) listened to maternal praise, neutral, and critical statements during functional magnetic resonance imaging. Participants completed the Mood and Feelings Questionnaire and the Screen for Child Anxiety Related Emotional Disorders. The OXTR single nucleotide polymorphism, rs53576, was genotyped. Linear mixed models were used to identify symptom or allele (GG, AA/AG) by condition (critical, neutral, praise) interaction effects on brain activation. Greater symptoms related to greater right amygdala activation for criticism and reduced activation to praise. For left amygdala, greater symptoms related to reduced activation to both conditions. Anxiety symptoms related to differences in superior medial PFC activation patterns. Parental OXTR AA/AG allele related to reduced activation to criticism and greater activation to praise within the right amygdala. Results support a relationship between anxiety and depressive symptoms and prefrontal-amygdala responses to maternal feedback. The lateralization of amygdala findings suggests separate neural targets for interventions reducing reactivity to negative feedback or increasing salience of positive feedback. Exploratory analyses suggest that parents' OXTR genetic profile influences parent-child interactions and related adolescent brain responses.