Developing a medication communication framework across continuums of care using the Circle of Care Modeling approach.

PubMed

Kitson, Nicole A; Price, Morgan; Lau, Francis Y; Showler, Grey

2013-10-17

Medication errors are a common type of preventable errors in health care causing unnecessary patient harm, hospitalization, and even fatality. Improving communication between providers and between providers and patients is a key aspect of decreasing medication errors and improving patient safety. Medication management requires extensive collaboration and communication across roles and care settings, which can reduce (or contribute to) medication-related errors. Medication management involves key recurrent activities (determine need, prescribe, dispense, administer, and monitor/evaluate) with information communicated within and between each. Despite its importance, there is a lack of conceptual models that explore medication communication specifically across roles and settings. This research seeks to address that gap. The Circle of Care Modeling (CCM) approach was used to build a model of medication communication activities across the circle of care. CCM positions the patient in the centre of his or her own healthcare system; providers and other roles are then modeled around the patient as a web of relationships. Recurrent medication communication activities were mapped to the medication management framework. The research occurred in three iterations, to test and revise the model: Iteration 1 consisted of a literature review and internal team discussion, Iteration 2 consisted of interviews, observation, and a discussion group at a Community Health Centre, and Iteration 3 consisted of interviews and a discussion group in the larger community. Each iteration provided further detail to the Circle of Care medication communication model. Specific medication communication activities were mapped along each communication pathway between roles and to the medication management framework. We could not map all medication communication activities to the medication management framework; we added Coordinate as a separate and distinct recurrent activity. We saw many examples of coordination activities, for instance, Medical Office Assistants acting as a liaison between pharmacists and family physicians to clarify prescription details. Through the use of CCM we were able to unearth tacitly held knowledge to expand our understanding of medication communication. Drawing out the coordination activities could be a missing piece for us to better understand how to streamline and improve multi-step communication processes with a goal of improving patient safety.

Developing a medication communication framework across continuums of care using the Circle of Care Modeling approach

PubMed Central

2013-01-01

Background Medication errors are a common type of preventable errors in health care causing unnecessary patient harm, hospitalization, and even fatality. Improving communication between providers and between providers and patients is a key aspect of decreasing medication errors and improving patient safety. Medication management requires extensive collaboration and communication across roles and care settings, which can reduce (or contribute to) medication-related errors. Medication management involves key recurrent activities (determine need, prescribe, dispense, administer, and monitor/evaluate) with information communicated within and between each. Despite its importance, there is a lack of conceptual models that explore medication communication specifically across roles and settings. This research seeks to address that gap. Methods The Circle of Care Modeling (CCM) approach was used to build a model of medication communication activities across the circle of care. CCM positions the patient in the centre of his or her own healthcare system; providers and other roles are then modeled around the patient as a web of relationships. Recurrent medication communication activities were mapped to the medication management framework. The research occurred in three iterations, to test and revise the model: Iteration 1 consisted of a literature review and internal team discussion, Iteration 2 consisted of interviews, observation, and a discussion group at a Community Health Centre, and Iteration 3 consisted of interviews and a discussion group in the larger community. Results Each iteration provided further detail to the Circle of Care medication communication model. Specific medication communication activities were mapped along each communication pathway between roles and to the medication management framework. We could not map all medication communication activities to the medication management framework; we added Coordinate as a separate and distinct recurrent activity. We saw many examples of coordination activities, for instance, Medical Office Assistants acting as a liaison between pharmacists and family physicians to clarify prescription details. Conclusions Through the use of CCM we were able to unearth tacitly held knowledge to expand our understanding of medication communication. Drawing out the coordination activities could be a missing piece for us to better understand how to streamline and improve multi-step communication processes with a goal of improving patient safety. PMID:24134454

Testing the Role of p21 Activated Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease

DTIC Science & Technology

2017-06-01

Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease The views, opinions and...Role of p21 Activated Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease Form...NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. The major goal of this research project was to genetically and pharmacologically test the requirement of PAK

The Role of Cholesterol Utilization in a Computational Adrenal Steroidogenesis Model to Improve Predictability of Biochemical Responses to Endocrine Active Chemicals

EPA Science Inventory

Steroids, which have an important role in a wide range of physiological processes, are synthesized primarily in the gonads and adrenal glands through a series of enzyme-mediated reactions. The activity of steroidogenic enzymes can be altered by a variety of endocrine active chem...

Development of a Conceptual Model for Smoking Cessation: Physical Activity, Neurocognition, and Executive Functioning.

PubMed

Loprinzi, Paul D; Herod, Skyla M; Walker, Jerome F; Cardinal, Bradley J; Mahoney, Sara E; Kane, Christy

2015-01-01

Considerable research has shown adverse neurobiological effects of chronic alcohol use, including long-term and potentially permanent changes in the structure and function of the brain; however, much less is known about the neurobiological consequences of chronic smoking, as it has largely been ignored until recently. In this article, we present a conceptual model proposing the effects of smoking on neurocognition and the role that physical activity may play in this relationship as well as its role in smoking cessation. Pertinent published peer-reviewed articles deposited in PubMed delineating the pathways in the proposed model were reviewed. The proposed model, which is supported by emerging research, demonstrates a bidirectional relationship between smoking and executive functioning. In support of our conceptual model, physical activity may moderate this relationship and indirectly influence smoking behavior through physical activity-induced changes in executive functioning. Our model may have implications for aiding smoking cessation efforts through the promotion of physical activity as a mechanism for preventing smoking-induced deficits in neurocognition and executive function.

A Role-Play to Illustrate the Energy Changes Occurring in an Exothermic Reaction.

ERIC Educational Resources Information Center

Tyas, Toby; Cabot, John

1999-01-01

Describes a role-play activity designed to help students understand the energy changes involved in an exothermic reaction by modeling the concepts of bond-breaking takes in energy, activation energy, temperature rise, and bond breaking gives out energy. (WRM)

Maximization of Learning Speed in the Motor Cortex Due to Neuronal Redundancy

PubMed Central

Takiyama, Ken; Okada, Masato

2012-01-01

Many redundancies play functional roles in motor control and motor learning. For example, kinematic and muscle redundancies contribute to stabilizing posture and impedance control, respectively. Another redundancy is the number of neurons themselves; there are overwhelmingly more neurons than muscles, and many combinations of neural activation can generate identical muscle activity. The functional roles of this neuronal redundancy remains unknown. Analysis of a redundant neural network model makes it possible to investigate these functional roles while varying the number of model neurons and holding constant the number of output units. Our analysis reveals that learning speed reaches its maximum value if and only if the model includes sufficient neuronal redundancy. This analytical result does not depend on whether the distribution of the preferred direction is uniform or a skewed bimodal, both of which have been reported in neurophysiological studies. Neuronal redundancy maximizes learning speed, even if the neural network model includes recurrent connections, a nonlinear activation function, or nonlinear muscle units. Furthermore, our results do not rely on the shape of the generalization function. The results of this study suggest that one of the functional roles of neuronal redundancy is to maximize learning speed. PMID:22253586

Partially soluble organics as cloud condensation nuclei: Role of trace soluble and surface active species

NASA Astrophysics Data System (ADS)

Broekhuizen, K.; Kumar, P. Pradeep; Abbatt, J. P. D.

2004-01-01

The ability of partially soluble organic species to act as cloud condensation nuclei (CCN) has been studied. A Köhler model incorporating solute solubility and droplet surface tension describes the behavior of solid adipic and succinic acid particles, whereas solid azelaic acid activates much more efficiently that predicted. In addition, it was shown that trace levels of either sulfate or surface active species have a dramatic effect on the activation of adipic acid, a moderately soluble organic, as predicted by the full Köhler model. For internally mixed particles in the atmosphere, these effects will greatly enhance the role of organic aerosols as CCN.

Roles of Raft-Anchored Adaptor Cbp/PAG1 in Spatial Regulation of c-Src Kinase

PubMed Central

Oneyama, Chitose; Suzuki, Takashi; Okada, Masato

2014-01-01

The tyrosine kinase c-Src is upregulated in numerous human cancers, implying a role for c-Src in cancer progression. Previously, we have shown that sequestration of activated c-Src into lipid rafts via a transmembrane adaptor, Cbp/PAG1, efficiently suppresses c-Src-induced cell transformation in Csk-deficient cells, suggesting that the transforming activity of c-Src is spatially regulated via Cbp in lipid rafts. To dissect the molecular mechanisms of the Cbp-mediated regulation of c-Src, a combined analysis was performed that included mathematical modeling and in vitro experiments in a c-Src- or Cbp-inducible system. c-Src activity was first determined as a function of c-Src or Cbp levels, using focal adhesion kinase (FAK) as a crucial c-Src substrate. Based on these experimental data, two mathematical models were constructed, the sequestration model and the ternary model. The computational analysis showed that both models supported our proposal that raft localization of Cbp is crucial for the suppression of c-Src function, but the ternary model, which includes a ternary complex consisting of Cbp, c-Src, and FAK, also predicted that c-Src function is dependent on the lipid-raft volume. Experimental analysis revealed that c-Src activity is elevated when lipid rafts are disrupted and the ternary complex forms in non-raft membranes, indicating that the ternary model accurately represents the system. Moreover, the ternary model predicted that, if Cbp enhances the interaction between c-Src and FAK, Cbp could promote c-Src function when lipid rafts are disrupted. These findings underscore the crucial role of lipid rafts in the Cbp-mediated negative regulation of c-Src-transforming activity, and explain the positive role of Cbp in c-Src regulation under particular conditions where lipid rafts are perturbed. PMID:24675741

Fractional models of seismoacoustic and electromagnetic activity

NASA Astrophysics Data System (ADS)

Shevtsov, Boris; Sheremetyeva, Olga

2017-10-01

Statistical models of the seismoacoustic and electromagnetic activity caused by deformation disturbances are considered on the basis of compound Poisson process and its fractional generalizations. Wave representations of these processes are used too. It is discussed five regimes of deformation activity and their role in understanding of the earthquakes precursors nature.

Grief and the Role of the Inner Representation of the Deceased.

ERIC Educational Resources Information Center

Marwit, Samuel J.; Klass, Dennis

1995-01-01

Studied whether memories of deceased play active roles in ongoing lives of survivors. Seventy-one people described a significant death. Four roles were reliably identified and labeled role model, situation specific guidance, values clarification, and remembrance formation. Role adoption was predicted by closeness of relationship and suddenness of…

Hispanic/Latino College Student Involvement in Student Organization Leadership Roles

ERIC Educational Resources Information Center

McKinney, Barry Slade

2009-01-01

The study examined attributes associated with Hispanic/Latino college student involvement in student organization leadership roles. The study helped identify attributes that active and involved Hispanic/Latino students felt were most important to them and their leadership roles. The roles that peer influence, role model influence, extraversion,…

Evidence for Model-based Computations in the Human Amygdala during Pavlovian Conditioning

PubMed Central

Prévost, Charlotte; McNamee, Daniel; Jessup, Ryan K.; Bossaerts, Peter; O'Doherty, John P.

2013-01-01

Contemporary computational accounts of instrumental conditioning have emphasized a role for a model-based system in which values are computed with reference to a rich model of the structure of the world, and a model-free system in which values are updated without encoding such structure. Much less studied is the possibility of a similar distinction operating at the level of Pavlovian conditioning. In the present study, we scanned human participants while they participated in a Pavlovian conditioning task with a simple structure while measuring activity in the human amygdala using a high-resolution fMRI protocol. After fitting a model-based algorithm and a variety of model-free algorithms to the fMRI data, we found evidence for the superiority of a model-based algorithm in accounting for activity in the amygdala compared to the model-free counterparts. These findings support an important role for model-based algorithms in describing the processes underpinning Pavlovian conditioning, as well as providing evidence of a role for the human amygdala in model-based inference. PMID:23436990

Development of feedforward receptive field structure of a simple cell and its contribution to the orientation selectivity: a modeling study.

PubMed

Garg, Akhil R; Obermayer, Klaus; Bhaumik, Basabi

2005-01-01

Recent experimental studies of hetero-synaptic interactions in various systems have shown the role of signaling in the plasticity, challenging the conventional understanding of Hebb's rule. It has also been found that activity plays a major role in plasticity, with neurotrophins acting as molecular signals translating activity into structural changes. Furthermore, role of synaptic efficacy in biasing the outcome of competition has also been revealed recently. Motivated by these experimental findings we present a model for the development of simple cell receptive field structure based on the competitive hetero-synaptic interactions for neurotrophins combined with cooperative hetero-synaptic interactions in the spatial domain. We find that with proper balance in competition and cooperation, the inputs from two populations (ON/OFF) of LGN cells segregate starting from the homogeneous state. We obtain segregated ON and OFF regions in simple cell receptive field. Our modeling study supports the experimental findings, suggesting the role of synaptic efficacy and the role of spatial signaling. We find that using this model we obtain simple cell RF, even for positively correlated activity of ON/OFF cells. We also compare different mechanism of finding the response of cortical cell and study their possible role in the sharpening of orientation selectivity. We find that degree of selectivity improvement in individual cells varies from case to case depending upon the structure of RF field and type of sharpening mechanism.

Adapting the Sport Education Model for Children with Disabilities

ERIC Educational Resources Information Center

Presse, Cindy; Block, Martin E.; Horton, Mel; Harvey, William J.

2011-01-01

The sport education model (SEM) has been widely used as a curriculum and instructional model to provide children with authentic and active sport experiences in physical education. In this model, students are assigned various roles to gain a deeper understanding of the sport or activity. This article provides a brief overview of the SEM and…

Conditional Random Fields for Activity Recognition

DTIC Science & Technology

2008-04-01

final match. The final is never used as a training or hold out set. Table 4.1 lists the roles of the CMDragons’07 robot soccer team. The role of Goalie ...is not included because the goalie never changes roles. The classification task, which we formalize below, is to recognize robot roles from the avail...process and pull out the key information from the sensor data. Furthermore, as conditional models, CRFs do not waste modeling effort on the observations

Do I dare? Using role-play as a teaching strategy.

PubMed

Kuipers, J C; Clemens, D L

1998-07-01

Role-play is a teaching strategy that models patient behaviors and nursing interventions that students need to learn in psychiatric nursing. Applications of this strategy can be used in both classroom and clinical settings. Benefits of using role-play range from cost effectiveness and active learning to modeling expected performance/skill levels and increasing self-confidence and assertiveness. Perceived drawbacks can be minimized by using the planning steps prior to the use of role-play.

The relative role of climate change and human activities in the desertification process in Yulin region of northwest China.

PubMed

Wang, Tao; Sun, Jian-Guo; Han, Hui; Yan, Chang-Zhen

2012-12-01

To overcome the shortcoming of existing studies, this paper put forward a statistical vegetation-climate relationship model with integrated temporal and spatial characteristics. Based on this model, we quantitatively discriminated on the grid scale the relative role of climate change and human activities in the desertification dynamics from 1986 to 2000 in Yulin region. Yulin region's desertification development occurred mainly in the southern hilly and gully area and its reverse in the northwest sand and marsh area. This spatial pattern was especially evident and has never changed thoroughly. From the first time section (1986-1990) to the second (1991-1995), the desertification was developing as a whole, and either in the desertification development district or in the reverse district human activities' role was always occupying an overwhelmingly dominant position (they were 98.7% and 101.4%, respectively), the role of climate change was extremely slight. From the second time section (1991-1995) to the third (1996-2000), the desertification process was reaching a state of stability, in the desertification development district the role of climate change was nearly equivalent to that of human activities (they were 46.2% and 53.8% separately), and yet in the desertification reverse district, the role of human activities came up to 119.0%, the role of climate change amounted to -19.0%. In addition, the relative role of climate change and human activities possessed great spatial heterogeneity. The above conclusion rather coincides with the qualitative analysis in many literatures, which indicates that this method has certain rationality and can be utilized as a reference for the monitoring and studying of desertification in other areas.

Business Simulation as an Active Learning Activity for Developing Soft Skills

ERIC Educational Resources Information Center

Levant, Yves; Coulmont, Michel; Sandu, Raluca

2016-01-01

Business simulations are innovative instruction models for active or cooperative learning. In this paper, we look at the social constructionist roots of these education models in light of the current efforts to enhance employability skills in undergraduate and graduate studies. More specifically, we analyse the role of business simulations in…

Computational Steroidogenesis Model To Predict Biochemical Responses to Endocrine Active Chemicals: Model Development and Cross Validation

EPA Science Inventory

Steroids, which have an important role in a wide range of physiological processes, are synthesized primarily in the gonads and adrenal glands through a series of enzyme-mediated reactions. The activity of steroidogenic enzymes can be altered by a variety of endocrine active chem...

Experimental Model to Study the Role of Retinoblastoma Gene Product (pRb) for Determination of Adipocyte Differentiation.

PubMed

Popov, B V; Shilo, P S; Zhidkova, O V; Zaichik, A M; Petrov, N S

2015-06-01

Using stable constitutive expression of retinoblastoma gene product (pRb) in polypotent mesenchymal 10T1/2 cells we obtained stable cell lines hyperexpressing functionally active or inactive mutant pRb. The cells producing active exogenous pRb demonstrated high sensitivity to adipocyte differentiation inductors, whereas production of inactive form of the exogenous protein suppressed adipocyte differentiation. The obtained lines can serve as the experimental model for studying the role of pRb in determination of adipocyte differentiation.

Role Models for the Student Majority.

ERIC Educational Resources Information Center

Kirkland, Janice J.

1997-01-01

While women earn more bachelor's and master's degrees than men annually, college faculty continue to be predominately male, with males more economically secure. This significantly limits the role models for women students. Faculty recruitment should focus more actively on women candidates and provide support mechanisms to retain women faculty.…

An Application of the Trans-Contextual Model of Motivation in Elementary School Physical Education

ERIC Educational Resources Information Center

Ntovolis, Yannis; Barkoukis, Vassilis; Michelinakis, Evaggelos; Tsorbatzoudis, Haralambos

2015-01-01

Elementary school physical education can play a prominent role in promoting children's leisure-time physical activity. The trans-contextual model of motivation has been proven effective in describing the process through which school physical education can affect students' leisure-time physical activity. This model has been tested in secondary…

Naringin in Ganshuang Granule suppresses activation of hepatic stellate cells for anti-fibrosis effect by inhibition of mammalian target of rapamycin.

PubMed

Shi, Hongbo; Shi, Honglin; Ren, Feng; Chen, Dexi; Chen, Yu; Duan, Zhongping

2017-03-01

A previous study has demonstrated that Ganshuang granule (GSG) plays an anti-fibrotic role partially by deactivation of hepatic stellate cells (HSCs). In HSCs activation, mammalian target of rapamycin (mTOR)-autophagy plays an important role. We attempted to investigate the role of mTOR-autophagy in anti-fibrotic effect of GSG. The cirrhotic mouse model was prepared to demonstrate the anti-fibrosis effect of GSG. High performance liquid chromatography (HPLC) analyses were used to identify the active component of GSG. The primary mouse HSCs were isolated and naringin was added into activated HSCs to observe its anti-fibrotic effect. 3-methyladenine (3-MA) and Insulin-like growth factor-1 (IGF-1) was added, respectively, into fully activated HSCs to explore the role of autophagy and mTOR. GSG played an anti-fibrotic role through deactivation of HSCs in cirrhotic mouse model. The concentration of naringin was highest in GSG by HPLC analyses and naringin markedly suppressed HSCs activation in vitro, which suggested that naringin was the main active component of GSG. The deactivation of HSCs caused by naringin was not because of the autophagic activation but mTOR inhibition, which was supported by the following evidence: first, naringin induced autophagic activation, but when autophagy was blocked by 3-MA, deactivation of HSCs was not attenuated or reversed. Second, naringin inhibited mTOR pathway, meanwhile when mTOR was activated by IGF-1, deactivation of HSCs was reversed. In conclusion, we have demonstrated naringin in GSG suppressed activation of HSCs for anti-fibrosis effect by inhibition of mTOR, indicating a potential therapeutic application for liver cirrhosis. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Decisional role preferences, risk knowledge and information interests in patients with multiple sclerosis.

PubMed

Heesen, Christoph; Kasper, Jürgen; Segal, Julia; Köpke, Sascha; Mühlhauser, Ingrid

2004-12-01

Shared decision making is increasingly recognized as the ideal model of patient-physician communication especially in chronic diseases with partially effective treatments as multiple sclerosis (MS). To evaluate prerequisite factors for this kind of decision making we studied patients' decisional role preferences in medical decision making, knowledge on risks, information interests and the relations between these factors in MS. After conducting focus groups to generate hypotheses, 219 randomly selected patients from the MS Outpatient Clinic register (n = 1374) of the University Hospital Hamburg received mailed questionnaires on their knowledge of risks in MS, their perception of their own level of knowledge, information interests and role preferences. Most patients (79%) indicated that they preferred an active role in treatment decisions giving the shared decision and the informed choice model the highest priority. MS risk knowledge was low but questionnaire results depended on disease course, disease duration and ongoing immune therapy. Measured knowledge as well as perceived knowledge was only weakly correlated with preferences of active roles. Major information interests were related to symptom alleviation, diagnostic procedures and prognosis. Patients with MS claimed autonomous roles in their health care decisions. The weak correlation between knowledge and preferences for active roles implicates that other factors largely influence role preferences.

Role of Water in Proton-Hydroxide Conductance Across Model and Biological Membranes

DTIC Science & Technology

1990-09-01

esearch - CONTRACT TITLE: Role of water in proton-hydroxide conductan, e across model Maim and biological membranes. RESEARCH OBJECTIVES: Our goals over...establish a model system for measuring proton flux along hydrogen bonded chains of water in hydrophobic phases. TRAINING ACTIVITIES: Three doctoral and two...to general anesthetics. Biochim. Biophys. Acta 944:40- 48. 6. Deamer, D.W. and Nichols, J.W. (1989) Proton flux in model and biological membranes. J

Executive Control Modulates Cross-Language Lexical Activation during L2 Reading: Evidence from Eye Movements

ERIC Educational Resources Information Center

Pivneva, Irina; Mercier, Julie; Titone, Debra

2014-01-01

Models of bilingual reading such as Bilingual Interactive Activation Plus (Dijkstra & van Heuven, 2002) do not predict a central role for domain-general executive control during bilingual reading, in contrast with bilingual models from other domains, such as production (e.g., the Inhibitory Control Model; Green, 1998). We thus investigated…

The role of Patient Health Engagement Model (PHE-model) in affecting patient activation and medication adherence: A structural equation model

PubMed Central

Graffigna, Guendalina; Bonanomi, Andrea

2017-01-01

Background Increasing bodies of scientific research today examines the factors and interventions affecting patients’ ability to self-manage and adhere to treatment. Patient activation is considered the most reliable indicator of patients’ ability to manage health autonomously. Only a few studies have tried to assess the role of psychosocial factors in promoting patient activation. A more systematic modeling of the psychosocial factors explaining the variance of patient activation is needed. Objective To test the hypothesized effect of patient activation on medication adherence; to test the the hypothesized effects of positive emotions and of the quality of the patient/doctor relationship on patient activation; and to test the hypothesized mediating effect of Patient Health Engagement (PHE-model) in this pathway. Material and methods This cross-sectional study involved 352 Italian-speaking adult chronic patients. The survey included measures of i) patient activation (Patient Activation Measure 13 –short form); ii) Patient Health Engagement model (Patient Health Engagement Scale); iii) patient adherence (4 item-Morinsky Medication Adherence Scale); iv) the quality of the patients’ emotional feelings (Manikin Self Assessment Scale); v) the quality of the patient/doctor relationship (Health Care Climate Questionnaire). Structural equation modeling was used to test the hypotheses proposed. Results According to the theoretical model we hypothesized, research results confirmed that patients’ activation significantly affects their reported medication adherence. Moreover, psychosocial factors, such as the patients’ quality of the emotional feelings and the quality of the patient/doctor relationship were demonstrated to be factors affecting the level of patient activation. Finally, the mediation effect of the Patient Health Engagement model was confirmed by the analysis. Conclusions Consistently with the results of previous studies, these findings demonstrate that the Patient Health Engagement Model is a critical factor in enhancing the quality of care. The Patient Health Engagement Model might acts as a mechanism to increase patient activation and adherence. PMID:28654686

The role of Patient Health Engagement Model (PHE-model) in affecting patient activation and medication adherence: A structural equation model.

PubMed

Graffigna, Guendalina; Barello, Serena; Bonanomi, Andrea

2017-01-01

Increasing bodies of scientific research today examines the factors and interventions affecting patients' ability to self-manage and adhere to treatment. Patient activation is considered the most reliable indicator of patients' ability to manage health autonomously. Only a few studies have tried to assess the role of psychosocial factors in promoting patient activation. A more systematic modeling of the psychosocial factors explaining the variance of patient activation is needed. To test the hypothesized effect of patient activation on medication adherence; to test the the hypothesized effects of positive emotions and of the quality of the patient/doctor relationship on patient activation; and to test the hypothesized mediating effect of Patient Health Engagement (PHE-model) in this pathway. This cross-sectional study involved 352 Italian-speaking adult chronic patients. The survey included measures of i) patient activation (Patient Activation Measure 13 -short form); ii) Patient Health Engagement model (Patient Health Engagement Scale); iii) patient adherence (4 item-Morinsky Medication Adherence Scale); iv) the quality of the patients' emotional feelings (Manikin Self Assessment Scale); v) the quality of the patient/doctor relationship (Health Care Climate Questionnaire). Structural equation modeling was used to test the hypotheses proposed. According to the theoretical model we hypothesized, research results confirmed that patients' activation significantly affects their reported medication adherence. Moreover, psychosocial factors, such as the patients' quality of the emotional feelings and the quality of the patient/doctor relationship were demonstrated to be factors affecting the level of patient activation. Finally, the mediation effect of the Patient Health Engagement model was confirmed by the analysis. Consistently with the results of previous studies, these findings demonstrate that the Patient Health Engagement Model is a critical factor in enhancing the quality of care. The Patient Health Engagement Model might acts as a mechanism to increase patient activation and adherence.

The Role of Small-Scale Processes in Solar Active Region Decay

NASA Astrophysics Data System (ADS)

Meyer, Karen; Mackay, Duncan

2017-08-01

Active regions are locations of intense magnetic activity on the Sun, whose evolution can result in highly energetic eruptive phenomena such as solar flares and coronal mass ejections (CMEs). Therefore, fast and accurate simulation of their evolution and decay is essential in the prediction of Space Weather events. In this talk we present initial results from our new model for the photospheric evolution of active region magnetic fields. Observations show that small-scale processes appear to play a role in the dispersal and decay of solar active regions, for example through cancellation at the boundary of sunspot outflows and erosion of flux by surrounding convective cells. Our active region model is coupled to our existing model for the evolution of small-scale photospheric magnetic features. Focusing first on the active region decay phase, we consider the evolution of its magnetic field due to both large-scale (e.g. differential rotation) and small-scale processes, such as its interaction with surrounding small-scale magnetic features and convective flows.This project is funded by The Carnegie Trust for the Universities of Scotland, through their Research Incentives Grant scheme.

The role of ryanodine receptor type 3 in a mouse model of Alzheimer disease

PubMed Central

Liu, Jie; Supnet, Charlene; Sun, Suya; Zhang, Hua; Good, Levi; Popugaeva, Elena; Bezprozvanny, Ilya

2014-01-01

Dysregulated endoplasmic reticulum (ER) calcium (Ca2+) signaling is reported to play an important role in Alzheimer disease (AD) pathogenesis. The role of ER Ca2+ release channels, the ryanodine receptors (RyanRs), has been extensively studied in AD models and RyanR expression and activity are upregulated in the brains of various familial AD (FAD) models. The objective of this study was to utilize a genetic approach to evaluate the importance of RyanR type 3 (RyanR3) in the context of AD pathology. PMID:24476841

A heuristic mathematical model for the dynamics of sensory conflict and motion sickness

NASA Technical Reports Server (NTRS)

Oman, C. M.

1982-01-01

By consideration of the information processing task faced by the central nervous system in estimating body spatial orientation and in controlling active body movement using an internal model referenced control strategy, a mathematical model for sensory conflict generation is developed. The model postulates a major dynamic functional role for sensory conflict signals in movement control, as well as in sensory-motor adaptation. It accounts for the role of active movement in creating motion sickness symptoms in some experimental circumstance, and in alleviating them in others. The relationship between motion sickness produced by sensory rearrangement and that resulting from external motion disturbances is explicitly defined. A nonlinear conflict averaging model is proposed which describes dynamic aspects of experimentally observed subjective discomfort sensation, and suggests resulting behaviours. The model admits several possibilities for adaptive mechanisms which do not involve internal model updating. Further systematic efforts to experimentally refine and validate the model are indicated.

Fathers' Role in Play: Enhancing Early Language and Literacy of Children with Developmental Delays

ERIC Educational Resources Information Center

Stockall, Nancy; Dennis, Lindsay

2013-01-01

Fathers and paternal role models make a unique contribution to children's development. There is some research to suggest that the types of play males engage in with children is typically more active and thus offers unique possibilities for embedding activities for language and literacy development. In this article, we offer suggestions for how…

The Identification and Comparison of the Tasks for the Occupational Role of Industrial Production Technologist.

ERIC Educational Resources Information Center

Nee, John G.

This paper describes a project designed to: (1) develop a model for determining occupational activity components to be used in any vocational-technical program, (2) produce a list of occupational activity components (tasks) for the occupational roles identified, (3) determine scores, ranks and percentages for each component from each occupational…

Managing School-Based Professional Development Activities

ERIC Educational Resources Information Center

Cheng, Eric C. K.

2017-01-01

Purpose: The purpose of this paper is to present a model to assist school leaders in managing the professional development activities of teachers. The model illustrates the important role of principals in promoting continuing professional development (CPD), chiefly by cultivating a collaborative learning culture and formulating policy.…

Redefining Earthquakes and the Earthquake Machine

ERIC Educational Resources Information Center

Hubenthal, Michael; Braile, Larry; Taber, John

2008-01-01

The Earthquake Machine (EML), a mechanical model of stick-slip fault systems, can increase student engagement and facilitate opportunities to participate in the scientific process. This article introduces the EML model and an activity that challenges ninth-grade students' misconceptions about earthquakes. The activity emphasizes the role of models…

Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

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

Wu, Weibin; Institutes of Biomedical Science, Fudan University, Shanghai 200032; Zhu, Bo

2014-01-03

Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid andmore » glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.« less

Role modeling as an early childhood obesity prevention strategy: effect of parents and teachers on preschool children's healthy lifestyle habits.

PubMed

Natale, Ruby A; Messiah, Sarah E; Asfour, Lila; Uhlhorn, Susan B; Delamater, Alan; Arheart, Kris L

2014-01-01

To assess the effectiveness of a child care center-based parent and teacher healthy lifestyle role-modeling program on child nutrition and physical activity outcomes. Child care centers (N = 28) serving low-income families were randomized to intervention or control arms. Intervention centers (N = 12) implemented (1) menu modifications, (2) a child's healthy lifestyle curriculum, and (3) an adult (teacher- and parent-focused) healthy lifestyle role-modeling curriculum. Control centers (N = 16) received an attention control safety curriculum. Nutrition and physical activity data were collected at the beginning (T1) and at the end (T2) of the school year. Exploratory factor analysis identified positive and negative nutrition and physical activity practices by children, parents, and teachers. Intervention parents' baseline (β = .52, p < .0001) and school year consumption (β = .47, p < .0001) of fruits/vegetables significantly increased their children's consumption of fruits/vegetables from T1 to T2. Intervention parents significantly influenced a decrease in children's junk food consumption (β = -.04, p < .05), whereas control parents significantly influenced an increase in their children's junk food consumption (β = .60, p < .001) from T1 to T2. Control children showed a significant increase in junk food consumption (β = .11, p = .01) and sedentary behavior (β = .09, p < .005) from T1 to T2. Teachers did not significantly influence preschool-age children's nutrition or physical activity patterns from T1 to T2. Parent nutrition and physical activity patterns significantly influence their preschool-age children's consumption of fruits/vegetables, junk food, and level of sedentary behavior. Future obesity prevention intervention efforts targeting this age group should include parents as healthy lifestyle role models for their children.

Medical Writing Competency Model - Section 1: Functions, Tasks, and Activities.

PubMed

Clemow, David B; Wagner, Bertil; Marshallsay, Christopher; Benau, Dan; L'Heureux, Darryl; Brown, David H; Dasgupta, Devjani Ghosh; Girten, Eileen; Hubbard, Frank; Gawrylewski, Helle-Mai; Ebina, Hiroko; Stoltenborg, Janet; York, J P; Green, Kim; Wood, Linda Fossati; Toth, Lisa; Mihm, Michael; Katz, Nancy R; Vasconcelos, Nina-Maria; Sakiyama, Norihisa; Whitsell, Robin; Gopalakrishnan, Shobha; Bairnsfather, Susan; Wanderer, Tatyana; Schindler, Thomas M; Mikyas, Yeshi; Aoyama, Yumiko

2018-01-01

This article provides Section 1 of the 2017 Edition 2 Medical Writing Competency Model that describes the core work functions and associated tasks and activities related to professional medical writing within the life sciences industry. The functions in the Model are scientific communication strategy; document preparation, development, and finalization; document project management; document template, standard, format, and style development and maintenance; outsourcing, alliance partner, and client management; knowledge, skill, ability, and behavior development and sharing; and process improvement. The full Model also includes Section 2, which covers the knowledge, skills, abilities, and behaviors needed for medical writers to be effective in their roles; Section 2 is presented in a companion article. Regulatory, publication, and other scientific writing as well as management of writing activities are covered. The Model was developed to aid medical writers and managers within the life sciences industry regarding medical writing hiring, training, expectation and goal setting, performance evaluation, career development, retention, and role value sharing to cross-functional partners.

INTEGRATED PROBABILISTIC AND DETERMINISTIC MODELING TECHNIQUES IN ESTIMATING EXPOSURE TO WATER-BORNE CONTAMINANTS: PART 1 EXPOSURE MODELING

EPA Science Inventory

Exposure to contaminants originating in the domestic water supply is influenced by a number of factors, including human activities, water use behavior, and physical and chemical processes. The key role of human activities is very apparent in exposure related to volatile water-...

PM ACTIVITY PATTERN RESEARCH

EPA Science Inventory

Human activity/uptake rate data are necessary to estimate potential human exposure and intake dose to environmental pollutants and to refine human exposure models. Personal exposure monitoring studies have demonstrated the critical role that activities play in explaining and pre...

HUMAN EXPOSURE ACTIVITY PATTERNS

EPA Science Inventory

Human activity/uptake rate data are necessary to estimate potential human exposure and intake dose to environmental pollutants and to refine human exposure models. Personal exposure monitoring studies have demonstrated the critical role that activities play in explaining and pre...

Peer Attachment, Coping, and Self-Esteem in Institutionalized Adolescents: The Mediating Role of Social Skills

ERIC Educational Resources Information Center

Mota, Catarina Pinheiro; Matos, Paula Mena

2013-01-01

This study analyzes the contribution of peer attachment in predicting active coping and self-esteem in a sample of 109 institutionalized adolescents. It also explores the mediating role of social skills in the association between peer attachment, coping, and self-esteem. Structural equation modeling identified a model able to predict a positive…

Career Choices: Reducing Sex-Role Stereotyping in Careers. A Model Career Decision-Making Program to Reduce the Effects of Sex-Role Stereotyping in the Career Choices of Senior High Students. Final Project Performance Report.

ERIC Educational Resources Information Center

Murphy, Jody

A model career decision-making program to reduce the effects of sex-role stereotyping in career choices of senior high school students was conducted at Columbine High School (Lakewood, Colorado). Project goals included the following: (1) to provide students with self-awareness and career-decision-making activities designed to broaden options these…

Reducing Disease Activity in Animal Models of MS by Activation of the Protective Arm of the Renin-Angiotensin System

DTIC Science & Technology

2015-10-01

patients, there is little evidence for a role of ACE2/A( 1 -7)/Mas axis, only a solitary assessment showing decreased ACE2 levels in the CSF of MS...project? Major Goals (Year 1 ): 1 : Measure levels of RAS components in the spinal cord of mice with EAE (animal model of MS) prior to, and at multiple...AWARD NUMBER: W81XWH-14- 1 -0523 TITLE: Reducing Disease Activity in Animal Models of MS by Activation of the Protective Arm of the Renin

The Active Role of Instruments in Articulating Knowing and Knowledge: The Case of Animal Qualification Practices in Breeding Organisations

ERIC Educational Resources Information Center

Labatut, Julie; Aggeri, Franck; Astruc, Jean-Michel; Bibe, Bernard; Girard, Nathalie

2009-01-01

Purpose: The purpose of this paper is to investigate the role of instruments defined as artefacts, rules, models or norms, in the articulation between knowing-in-practice and knowledge, in learning processes. Design/methodology/approach: The paper focuses on a distributed, knowledge-intensive and instrumented activity at the core of any collective…

Hsp70 in cancer: back to the future

PubMed Central

Sherman, Michael Y.; Gabai, Vladimir L.

2014-01-01

Mechanistic studies from cell culture and animal models have revealed critical roles for the heat shock protein Hsp70 in cancer initiation and progression. Surprisingly, many effects of Hsp70 on cancer have not been related to its chaperone activity, but rather to its role(s) in regulating cell signaling. A major factor that directs Hsp70 signaling activity appears to be the co-chaperone Bag3. Here, we review these recent breakthroughs, and how these discoveries drive drug development efforts. PMID:25347739

Role of Prefrontal Persistent Activity in Working Memory

PubMed Central

Riley, Mitchell R.; Constantinidis, Christos

2016-01-01

The prefrontal cortex is activated during working memory, as evidenced by fMRI results in human studies and neurophysiological recordings in animal models. Persistent activity during the delay period of working memory tasks, after the offset of stimuli that subjects are required to remember, has traditionally been thought of as the neural correlate of working memory. In the last few years several findings have cast doubt on the role of this activity. By some accounts, activity in other brain areas, such as the primary visual and posterior parietal cortex, is a better predictor of information maintained in visual working memory and working memory performance; dynamic patterns of activity may convey information without requiring persistent activity at all; and prefrontal neurons may be ill-suited to represent non-spatial information about the features and identity of remembered stimuli. Alternative interpretations about the role of the prefrontal cortex have thus been suggested, such as that it provides a top-down control of information represented in other brain areas, rather than maintaining a working memory trace itself. Here we review evidence for and against the role of prefrontal persistent activity, with a focus on visual neurophysiology. We show that persistent activity predicts behavioral parameters precisely in working memory tasks. We illustrate that prefrontal cortex represents features of stimuli other than their spatial location, and that this information is largely absent from early cortical areas during working memory. We examine memory models not dependent on persistent activity, and conclude that each of those models could mediate only a limited range of memory-dependent behaviors. We review activity decoded from brain areas other than the prefrontal cortex during working memory and demonstrate that these areas alone cannot mediate working memory maintenance, particularly in the presence of distractors. We finally discuss the discrepancy between BOLD activation and spiking activity findings, and point out that fMRI methods do not currently have the spatial resolution necessary to decode information within the prefrontal cortex, which is likely organized at the micrometer scale. Therefore, we make the case that prefrontal persistent activity is both necessary and sufficient for the maintenance of information in working memory. PMID:26778980

[Positive Activities Campaign.

ERIC Educational Resources Information Center

Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Center for Substance Abuse Prevention.

This packet contains four pamphlets that are part of a campaign to encourage adults to provide and promote positive activities for youth and to serve as role models for young people. "Positive Activities: A Campaign for Youth" includes information on what positive activities are, how to get involved in helping to provide positive activities for…

Bloom syndrome helicase in meiosis: Pro-crossover functions of an anti-crossover protein.

PubMed

Hatkevich, Talia; Sekelsky, Jeff

2017-09-01

The functions of the Bloom syndrome helicase (BLM) and its orthologs are well characterized in mitotic DNA damage repair, but their roles within the context of meiotic recombination are less clear. In meiotic recombination, multiple repair pathways are used to repair meiotic DSBs, and current studies suggest that BLM may regulate the use of these pathways. Based on literature from Saccharomyces cerevisiae, Arabidopsis thaliana, Mus musculus, Drosophila melanogaster, and Caenorhabditis elegans, we present a unified model for a critical meiotic role of BLM and its orthologs. In this model, BLM and its orthologs utilize helicase activity to regulate the use of various pathways in meiotic recombination by continuously disassembling recombination intermediates. This unwinding activity provides the meiotic program with a steady pool of early recombination substrates, increasing the probability for a DSB to be processed by the appropriate pathway. As a result of BLM activity, crossovers are properly placed throughout the genome, promoting proper chromosomal disjunction at the end of meiosis. This unified model can be used to further refine the complex role of BLM and its orthologs in meiotic recombination. © 2017 WILEY Periodicals, Inc.

Test, revision, and cross-validation of the Physical Activity Self-Definition Model.

PubMed

Kendzierski, Deborah; Morganstein, Mara S

2009-08-01

Structural equation modeling was used to test an extended version of the Kendzierski, Furr, and Schiavoni (1998) Physical Activity Self-Definition Model. A revised model using data from 622 runners fit the data well. Cross-validation indices supported the revised model, and this model also provided a good fit to data from 397 cyclists. Partial invariance was found across activities. In both samples, perceived commitment and perceived ability had direct effects on self-definition, and perceived wanting, perceived trying, and enjoyment had indirect effects. The contribution of perceived ability to self-definition did not differ across activities. Implications concerning the original model, indirect effects, skill salience, and the role of context in self-definition are discussed.

An intrinsic agonist mechanism for activation of glucagon-like peptide-1 receptor by its extracellular domain

PubMed Central

Yin, Yanting; Zhou, X Edward; Hou, Li; Zhao, Li-Hua; Liu, Bo; Wang, Gaihong; Jiang, Yi; Melcher, Karsten; Xu, H Eric

2016-01-01

The glucagon-like peptide-1 receptor is a class B G protein coupled receptor (GPCR) that plays key roles in glucose metabolism and is a major therapeutic target for diabetes. The classic two-domain model for class B GPCR activation proposes that the apo-state receptor is auto-inhibited by its extracellular domain, which physically interacts with the transmembrane domain. The binding of the C-terminus of the peptide hormone to the extracellular domain allows the N-terminus of the hormone to insert into the transmembrane domain to induce receptor activation. In contrast to this model, here we demonstrate that glucagon-like peptide-1 receptor can be activated by N-terminally truncated glucagon-like peptide-1 or exendin-4 when fused to the receptor, raising the question regarding the role of N-terminal residues of peptide hormone in glucagon-like peptide-1 receptor activation. Mutations of cysteine 347 to lysine or arginine in intracellular loop 3 transform the receptor into a G protein-biased receptor and allow it to be activated by a nonspecific five-residue linker that is completely devoid of exendin-4 or glucagon-like peptide-1 sequence but still requires the presence of an intact extracellular domain. Moreover, the extracellular domain can activate the receptor in trans in the presence of an intact peptide hormone, and specific mutations in three extracellular loops abolished this extracellular domain trans-activation. Together, our data reveal a dominant role of the extracellular domain in glucagon-like peptide-1 receptor activation and support an intrinsic agonist model of the extracellular domain, in which peptide binding switches the receptor from the auto-inhibited state to the auto-activated state by releasing the intrinsic agonist activity of the extracellular domain. PMID:27917297

A Multiscale Survival Process for Modeling Human Activity Patterns.

PubMed

Zhang, Tianyang; Cui, Peng; Song, Chaoming; Zhu, Wenwu; Yang, Shiqiang

2016-01-01

Human activity plays a central role in understanding large-scale social dynamics. It is well documented that individual activity pattern follows bursty dynamics characterized by heavy-tailed interevent time distributions. Here we study a large-scale online chatting dataset consisting of 5,549,570 users, finding that individual activity pattern varies with timescales whereas existing models only approximate empirical observations within a limited timescale. We propose a novel approach that models the intensity rate of an individual triggering an activity. We demonstrate that the model precisely captures corresponding human dynamics across multiple timescales over five orders of magnitudes. Our model also allows extracting the population heterogeneity of activity patterns, characterized by a set of individual-specific ingredients. Integrating our approach with social interactions leads to a wide range of implications.

Simulation of action potentials from metabolically impaired cardiac myocytes. Role of ATP-sensitive K+ current.

PubMed

Ferrero, J M; Sáiz, J; Ferrero, J M; Thakor, N V

1996-08-01

The role of the ATP-sensitive K+ current (IK-ATP) and its contribution to electrophysiological changes that occur during metabolic impairment in cardiac ventricular myocytes is still being discussed. The aim of this work was to quantitatively study this issue by using computer modeling. A model of IK-ATP is formulated and incorporated into the Luo-Rudy ionic model of the ventricular action potential. Action potentials under different degrees of activation of IK-ATP are simulated. Our results show that in normal ionic concentrations, only approximately 0.6% of the KATP channels, when open, should account for a 50% reduction in action potential duration. However, increased levels of intracellular Mg2+ counteract this shortening. Under conditions of high [K+]0, such as those found in early ischemia, the activation of only approximately 0.4% of the KATP channels could account for a 50% reduction in action potential duration. Thus, our results suggest that opening of IK-ATP channels should play a significant role in action potential shortening during hypoxic/ischemic episodes, with the fraction of open channels involved being very low ( < 1%). However, the results of the model suggest that activation of IK-ATP alone does not quantitatively account for the observed K+ efflux in metabolically impaired cardiac myocytes. Mechanisms other than KATP channel activation should be responsible for a significant part of the K+ efflux measured in hypoxic/ischemic situations.

Cookie-Ases: Interactive Models for Teaching Genotype-Phenotype Relationships

ERIC Educational Resources Information Center

Seipelt, Rebecca L.

2006-01-01

Several hands-on and wet laboratory activities have been proposed to model the genetic concepts of genotypes and phenotypes and their relationship. The exercise presented in this article is a novel, time effective, student-centered, role-playing activity in which students learn about the intricate connection between genotype and phenotype by…

The Role of Vocational Educators in Planning Vocational Assessment Activities for Handicapped Students: An Indepth Review of a Six Step Model.

ERIC Educational Resources Information Center

Stodden, Robert A.; Boone, Rosalie

1986-01-01

Discusses the role of teachers in providing vocational assessment to disabled students. Steps in this process include (1) establish planning team and conduct information search, (2) define purpose, (3) establish basic considerations, (4) formulate assessment model, (5) establish implementation focus, and (6) pilot test and evaluate assessment…

Role modelling in medical education: the importance of teaching skills.

PubMed

Burgess, Annette; Oates, Kim; Goulston, Kerry

2016-04-01

By observation of role models, and participation in activities, students develop their attitudes, values and professional competencies. Literature suggests that clinical skills and knowledge, personality, and teaching skills are three main areas that students consider central to the identification of positive role models. The aim of this study was to explore junior medical students' opinions of the ideal attributes of a good role model in clinical tutors. The study was conducted with one cohort (n = 301) of students who had completed year 1 of the medical programme in 2013. All students were asked to complete a questionnaire regarding the ideal attributes of a good role model in a clinical tutor. The questionnaire consisted of seven closed items and one open-ended question. The response rate to the questionnaire was 265/301 (88%). Although students found all three key areas important in a good role model, students emphasised the importance of excellence in teaching skills. Specifically, students see good role models as being able to provide a constructive learning environment, a good understanding of the curriculum and an ability to cater to the learning needs of all students. Students see good role models as being able to provide a constructive learning environment While acknowledging the importance of a patient-centred approach, as well as clinical knowledge and skills, our findings reinforce the importance of the actual teaching abilities of role models within medical education. © 2015 John Wiley & Sons Ltd.

Three lines of defence model and the role of internal audit activities as the response to the global economic crisis

NASA Astrophysics Data System (ADS)

Dragičević Radičević, T.; Stojanović Trivanović, M.; Stanojević, Lj

2017-05-01

The existing framework of corporate governance has shown a number of weaknesses, and the result was a new economic crisis at the global level. The main problems were identified as: increased risk of investors, non-transparency of information, conflict of interest between corporation subjects. European Institute of Internal Auditors in response to the strengthening the trust in information, shareholders activism, better communication, which all will lead to the reduction of risks and restore investors confidence, proposed the Model Three Lines of Defence, where the key role has internal audit.

Novel Genetic Models to Study the Role of Inflammation in Brain Injury-Induced Alzheimer’s Pathology

DTIC Science & Technology

2013-10-01

REPORT TYPE Annual 3. DATES COVERED 30 Sep 2012 – 29 Sep 2013 4 . TITLE AND SUBTITLE 5a. CONTRACT NUMBER Novel Genetic Models to Study the Role...infiltration and activation of monocytes due to disruption of the blood-brain barrier [ 4 -6]. Assessing the exact roles of these cells in AD pathogenesis...paradigm of TBI Statement of Work: Task 1. Generate animals required for studies (timeframe, months 2- 4 ) Task 2. Perform FPI (timeframe, months 4 -8

Reasons why undergraduate women comply with unwanted, non-coercive sexual advances: A serial indirect effect model integrating sexual script theory and sexual self-control perspectives.

PubMed

Quinn-Nilas, Christopher; Kennett, Deborah J

2018-01-16

This study explored the predictors of young women's compliance with unwanted sexual activities, integrating the social with the cognitive and behavioral correlates of sexual compliance. In total, 222 young heterosexual women completed measures examining the Sexual Self-Control model, including reasons for consenting, sexual resourcefulness, and compliance with unwanted sex, as well as gender role measures pertaining to sexual script theory, including the sexual double standard, gender role stress, and virginity scripts. An exploratory analysis of serial indirect effects demonstrated that women scoring lower in sexual resourcefulness endorsed higher female gender role stress, which in turn was associated with higher endorsement of reasons for consent, translating into more frequent compliance with unwanted sexual activities. The relationship between one's ability to refuse and their decision to refuse appears quite complex. Understanding one's decision requires consideration of the social aspects of gender role endorsement.

Family Fitness Fun

Cancer.gov

Being active with your family can be a fun way to get everybody moving. All of you will get the health benefits that come from being active. Plus, you’ll be a positive role model, helping your children develop good habits for an active lifetime.

Active Dendrites Enhance Neuronal Dynamic Range

PubMed Central

Gollo, Leonardo L.; Kinouchi, Osame; Copelli, Mauro

2009-01-01

Since the first experimental evidences of active conductances in dendrites, most neurons have been shown to exhibit dendritic excitability through the expression of a variety of voltage-gated ion channels. However, despite experimental and theoretical efforts undertaken in the past decades, the role of this excitability for some kind of dendritic computation has remained elusive. Here we show that, owing to very general properties of excitable media, the average output of a model of an active dendritic tree is a highly non-linear function of its afferent rate, attaining extremely large dynamic ranges (above 50 dB). Moreover, the model yields double-sigmoid response functions as experimentally observed in retinal ganglion cells. We claim that enhancement of dynamic range is the primary functional role of active dendritic conductances. We predict that neurons with larger dendritic trees should have larger dynamic range and that blocking of active conductances should lead to a decrease in dynamic range. PMID:19521531

The Role of Self-Efficacy and Referent Specific Social Support in Promoting Rural Adolescent Girls' Physical Activity

ERIC Educational Resources Information Center

Beets, Michael W.; Pitetti, Kenneth H.; Forlaw, Loretta

2007-01-01

Objective: To examine the role of social support (SS) and self-efficacy (SE) for physical activity (PA) in rural high school girls (N = 259, 15.5+1.2yrs). Methods: Using structural equation modeling, the relationships among PA, SS for PA from mother, father, and peers, and SE for overcoming barriers, seeking support, and resisting competing…

Social support plays a role in the attitude that people have towards taking an active role in medical decision-making.

PubMed

Brabers, Anne E M; de Jong, Judith D; Groenewegen, Peter P; van Dijk, Liset

2016-09-21

There is a growing emphasis towards including patients in medical decision-making. However, not all patients are actively involved in such decisions. Research has so far focused mainly on the influence of patient characteristics on preferences for active involvement. However, it can be argued that a patient's social context has to be taken into account as well, because social norms and resources affect behaviour. This study aims to examine the role of social resources, in the form of the availability of informational and emotional support, on the attitude towards taking an active role in medical decision-making. A questionnaire was sent to members of the Dutch Health Care Consumer Panel (response 70 %; n = 1300) in June 2013. A regression model was then used to estimate the relation between medical and lay informational support and emotional support and the attitude towards taking an active role in medical decision-making. Availability of emotional support is positively related to the attitude towards taking an active role in medical decision-making only in people with a low level of education, not in persons with a middle and high level of education. The latter have a more positive attitude towards taking an active role in medical decision-making, irrespective of the level of emotional support available. People with better access to medical informational support have a more positive attitude towards taking an active role in medical decision-making; but no significant association was found for lay informational support. This study shows that social resources are associated with the attitude towards taking an active role in medical decision-making. Strategies aimed at increasing patient involvement have to address this.

Leptin protects vital organ functions after sepsis through recovering tissue myeloperoxidase activity: an anti-inflammatory role resonating with indomethacin.

PubMed

Lin, Ji; Yan, Guang-Tao; Xue, Hui; Hao, Xiu-Hua; Zhang, Kai; Wang, Lu-Huan

2007-08-01

In this research, the role of leptin on sepsis-induced organ dysfunction was evaluated. Making use of a mice sepsis model, changes of alanine transaminase and uric acid in serum, myeloperoxidase activity, leptin levels and histological alterations in heart, lung, liver and kidney were determined. Results showed that sepsis induced significantly higher levels of serum alanine transaminase and uric acid, decreased tissue myeloperoxidase activity and leptin levels, and triggered distinct histological alterations. However, leptin and indomethacin injections reversed those impairments at 6h and/or 12h after injury. These data reveal a protective role of both leptin and indomethacin on vital organ functions after sepsis by recovering tissue myeloperoxidase activity.

Piezo Is Essential for Amiloride-Sensitive Stretch-Activated Mechanotransduction in Larval Drosophila Dorsal Bipolar Dendritic Sensory Neurons

PubMed Central

Suslak, Thomas J.; Watson, Sonia; Thompson, Karen J.; Shenton, Fiona C.; Bewick, Guy S.; Armstrong, J. Douglas; Jarman, Andrew P.

2015-01-01

Stretch-activated afferent neurons, such as those of mammalian muscle spindles, are essential for proprioception and motor co-ordination, but the underlying mechanisms of mechanotransduction are poorly understood. The dorsal bipolar dendritic (dbd) sensory neurons are putative stretch receptors in the Drosophila larval body wall. We have developed an in vivo protocol to obtain receptor potential recordings from intact dbd neurons in response to stretch. Receptor potential changes in dbd neurons in response to stretch showed a complex, dynamic profile with similar characteristics to those previously observed for mammalian muscle spindles. These profiles were reproduced by a general in silico model of stretch-activated neurons. This in silico model predicts an essential role for a mechanosensory cation channel (MSC) in all aspects of receptor potential generation. Using pharmacological and genetic techniques, we identified the mechanosensory channel, DmPiezo, in this functional role in dbd neurons, with TRPA1 playing a subsidiary role. We also show that rat muscle spindles exhibit a ruthenium red-sensitive current, but found no expression evidence to suggest that this corresponds to Piezo activity. In summary, we show that the dbd neuron is a stretch receptor and demonstrate that this neuron is a tractable model for investigating mechanisms of mechanotransduction. PMID:26186008

Piezo Is Essential for Amiloride-Sensitive Stretch-Activated Mechanotransduction in Larval Drosophila Dorsal Bipolar Dendritic Sensory Neurons.

PubMed

Suslak, Thomas J; Watson, Sonia; Thompson, Karen J; Shenton, Fiona C; Bewick, Guy S; Armstrong, J Douglas; Jarman, Andrew P

2015-01-01

Stretch-activated afferent neurons, such as those of mammalian muscle spindles, are essential for proprioception and motor co-ordination, but the underlying mechanisms of mechanotransduction are poorly understood. The dorsal bipolar dendritic (dbd) sensory neurons are putative stretch receptors in the Drosophila larval body wall. We have developed an in vivo protocol to obtain receptor potential recordings from intact dbd neurons in response to stretch. Receptor potential changes in dbd neurons in response to stretch showed a complex, dynamic profile with similar characteristics to those previously observed for mammalian muscle spindles. These profiles were reproduced by a general in silico model of stretch-activated neurons. This in silico model predicts an essential role for a mechanosensory cation channel (MSC) in all aspects of receptor potential generation. Using pharmacological and genetic techniques, we identified the mechanosensory channel, DmPiezo, in this functional role in dbd neurons, with TRPA1 playing a subsidiary role. We also show that rat muscle spindles exhibit a ruthenium red-sensitive current, but found no expression evidence to suggest that this corresponds to Piezo activity. In summary, we show that the dbd neuron is a stretch receptor and demonstrate that this neuron is a tractable model for investigating mechanisms of mechanotransduction.

A Possible Role for End-Stopped V1 Neurons in the Perception of Motion: A Computational Model

PubMed Central

Zarei Eskikand, Parvin; Kameneva, Tatiana; Ibbotson, Michael R.; Burkitt, Anthony N.; Grayden, David B.

2016-01-01

We present a model of the early stages of processing in the visual cortex, in particular V1 and MT, to investigate the potential role of end-stopped V1 neurons in solving the aperture problem. A hierarchical network is used in which the incoming motion signals provided by complex V1 neurons and end-stopped V1 neurons proceed to MT neurons at the next stage. MT neurons are categorized into two types based on their function: integration and segmentation. The role of integration neurons is to propagate unambiguous motion signals arriving from those V1 neurons that emphasize object terminators (e.g. corners). Segmentation neurons detect the discontinuities in the input stimulus to control the activity of integration neurons. Although the activity of the complex V1 neurons at the terminators of the object accurately represents the direction of the motion, their level of activity is less than the activity of the neurons along the edges. Therefore, a model incorporating end-stopped neurons is essential to suppress ambiguous motion signals along the edges of the stimulus. It is shown that the unambiguous motion signals at terminators propagate over the rest of the object to achieve an accurate representation of motion. PMID:27741307

Physical activity and fatigue in breast cancer survivors: a panel model examining the role of self-efficacy and depression.

PubMed

Phillips, Siobhan M; McAuley, Edward

2013-05-01

Physical activity is associated with reductions in fatigue in breast cancer survivors. However, mechanisms underlying this relationship are not well-understood. The purpose of this study was to longitudinally test a model examining the role of self-efficacy and depression as potential mediators of the relationship between physical activity and fatigue in a sample of breast cancer survivors using both self-report and objective measures of physical activity. All participants (N = 1,527) completed self-report measures of physical activity, self-efficacy, depression, and fatigue at baseline and 6 months. A subsample was randomly selected to wear an accelerometer at both time points. It was hypothesized that physical activity indirectly influences fatigue via self-efficacy and depression. Relationships among model constructs were examined over the 6-month period using panel analysis within a covariance modeling framework. The hypothesized model provided a good model-data fit (χ(2) = 599.66, df = 105, P ≤ 0.001; CFI = 0.96; SRMR = 0.02) in the full sample when controlling for covariates. At baseline, physical activity indirectly influenced fatigue via self-efficacy and depression. These relationships were also supported across time. In addition, the majority of the hypothesized relationships were supported in the subsample with accelerometer data (χ(2) = 387.48, df = 147, P ≤ 0.001, CFI = 0.94, SRMR = 0.04). This study provides evidence to suggest the relationship between physical activity and fatigue in breast cancer survivors may be mediated by more proximal, modifiable outcomes of physical activity participation. Recommendations are made relative to future applications and research concerning these relationships.

A review of the outcome expectancy construct in physical activity research.

PubMed

Williams, David M; Anderson, Eileen S; Winett, Richard A

2005-02-01

Outcome expectancy is a central construct in social cognitive models of health behavior widely used as frameworks for physical activity research. This article provides a review of the outcome expectancy construct and its application to research on physical activity. Theoretical articles describing definitions and placement of outcome expectancy within social cognitive models, as well as empirical research on outcome expectancy and physical activity, were reviewed. Self-efficacy theory, the transtheoretical model, the theory of planned behavior, and protection motivation theory differ in their labeling and conceptualization of outcome expectancy but unanimously include expected outcomes of behavior. Preliminary empirical investigation of the role of outcome expectancy in understanding physical activity has yielded mixed results. Positive outcome expectancy appears to be more predictive of physical activity in older adults than in young to middle-aged adults, and personal barriers appear to be the most predictive subtype of negative outcome expectancy. In addition, a small number of studies indicate relations between outcome expectancy and other theoretical variables, including behavioral intention, stage of change, and self-efficacy. Further research on the role of outcome expectancy is necessary to design effective physical activity interventions. New directions in outcome expectancy research could involve (a) expanding the conceptualization of outcome expectancy to include expected outcomes of sedentary behavior and affective responses to physical activity, (b) further examination of potential moderators of the relation between outcome expectancy and physical activity (such as outcome value and outcome proximity), (c) distinguishing between the role of outcome expectancy in behavior onset versus behavior maintenance, (d) examining outcome expectancy as a mechanism of change in environmental intervention approaches, and (e) further analysis of interrelations between outcome expectancy and other social cognitive variables.

Physical Therapists' Role in Health Promotion as Perceived by the Patient: Descriptive Survey.

PubMed

Black, Beth; Ingman, MarySue; Janes, Jamie

2016-10-01

The importance of health professionals discussing health behaviors with patients is emphasized in Healthy People 2020, the national health objectives established by the US Department of Health and Human Services. Many physical therapists do not routinely discuss health behaviors with their patients. One reason may be uncertainty about how these discussions might be perceived by patients. The primary purpose of this study was to determine patients' opinions regarding physical therapists discussing the topics of physical activity, smoking, fruit and vegetable consumption, and maintaining a healthy weight during clinical visits. A secondary purpose was to determine whether patients believe that physical therapists should be role models for these behaviors. This was a descriptive cross-sectional survey. Patients were surveyed at 8 outpatient clinics in Michigan and Minnesota. A written questionnaire collected information about the participants' health behaviors, their opinions about physical therapists discussing their health behaviors during clinical visits, and their opinions about physical therapists role-modeling healthy behaviors. The survey response rate was 45.6%. A total of 230 patients participated. Most participants agreed that physical therapists should speak to them about physical activity (91.3%), maintaining a healthy weight (73%), and abstaining from smoking (51.3%). Fewer participants agreed that physical therapists should advise them about fruit and vegetable consumption (32.1%). The majority of participants agreed that physical therapists should be role models for engaging in regular physical activity (83.4%), maintaining a healthy weight (71.7%), and abstaining from smoking (63.9%). Limitations of this study include the potential for response bias and limited generalizability. Most participants believed it is appropriate for physical therapists to speak with them about and be role models for the behaviors of physical activity, maintaining a healthy weight, and abstaining from smoking. Physical therapists have the opportunity to support the goals of Healthy People 2020 by discussing health behaviors with their patients. © 2016 American Physical Therapy Association.

The role of multidrug resistance protein (MRP-1) as an active efflux transporter on blood-brain barrier (BBB) permeability.

PubMed

Lingineni, Karthik; Belekar, Vilas; Tangadpalliwar, Sujit R; Garg, Prabha

2017-05-01

Drugs acting on central nervous system (CNS) may take longer duration to reach the market as these compounds have a higher attrition rate in clinical trials due to the complexity of the brain, side effects, and poor blood-brain barrier (BBB) permeability compared to non-CNS-acting compounds. The roles of active efflux transporters with BBB are still unclear. The aim of the present work was to develop a predictive model for BBB permeability that includes the MRP-1 transporter, which is considered as an active efflux transporter. A support vector machine model was developed for the classification of MRP-1 substrates and non-substrates, which was validated with an external data set and Y-randomization method. An artificial neural network model has been developed to evaluate the role of MRP-1 on BBB permeation. A total of nine descriptors were selected, which included molecular weight, topological polar surface area, ClogP, number of hydrogen bond donors, number of hydrogen bond acceptors, number of rotatable bonds, P-gp, BCRP, and MRP-1 substrate probabilities for model development. We identified 5 molecules that fulfilled all criteria required for passive permeation of BBB, but they all have a low logBB value, which suggested that the molecules were effluxed by the MRP-1 transporter.

A heuristic mathematical model for the dynamics of sensory conflict and motion sickness

NASA Technical Reports Server (NTRS)

Oman, C. M.

1982-01-01

The etiology of motion sickness is now usually explained in terms of a qualitatively formulated sensory conflict hypothesis. By consideration of the information processing task faced by the central nervous system in estimating body spatial orientation and in controlling active body movement using an internal model referenced control strategy, a mathematical model for sensory conflict generation is developed. The model postulates a major dynamic functional role for sensory conflict signals in movement control, as well as in sensory motor adaptation. It accounts for the role of active movement in creating motion sickness symptoms in some experimental circumstances, and in alleviating them in others. The relationship between motion sickness produced by sensory rearrangement and that resulting from external motion disturbances is explicitly defined. A nonlinear conflict averaging model describes dynamic aspects of experimentally observed subjective discomfort sensation, and suggests resulting behavior.

A heuristic mathematical model for the dynamics of sensory conflict and motion sickness

NASA Technical Reports Server (NTRS)

Oman, C. M.

1980-01-01

The etiology of motion sickness is explained in terms of a qualitatively formulated sensory conflict hypothesis. By consideration of the information processing task faced by the central nervous system in estimating body spatial orientation and in controlling active body movement using an internal model referenced control strategy, a mathematical model for sensory conflict generation is developed. The model postulates a major dynamic functional role for sensory conflict signals in movement control, as well as in sensory-motor adaptation. It accounts for the role of active movement in creating motion sickness symptoms in some experimental circumstances, and in alleviating them in others. The relationship between motion sickness produced by sensory rearrangement and that resulting from external motion disturbances is explicitly defined. A nonlinear conflict averaging model is proposed which describes dynamic aspects of experimentally observed subjective discomfort sensation, and suggests resulting behaviors.

Teacher Fidelity to a Physical Education Curricular Model and Physical Activity Outcomes

ERIC Educational Resources Information Center

Stylianou, Michalis; Kloeppel, Tiffany; Kulinna, Pamela; van der Mars, Han

2016-01-01

Background: This study was informed by the bodies of literature emphasizing the role of physical education in promoting physical activity (PA) and addressing teacher fidelity to curricular models. Purpose: The purpose of this study was to compare student PA levels, lesson context, and teacher PA promotion behavior among classes where teachers were…

A Qualitative Study of Parental Modeling and Social Support for Physical Activity in Underserved Adolescents

ERIC Educational Resources Information Center

Wright, Marcie S.; Wilson, Dawn K.; Griffin, Sarah; Evans, Alexandra

2010-01-01

This study obtained qualitative data to assess how parental role modeling and parental social support influence physical activity in underserved (minority, low-income) adolescents. Fifty-two adolescents (22 males, 30 females; ages 10-14 years, 85% African-American) participated in a focus group (6-10 per group, same gender). Focus groups were…

Investigation of JAKs/STAT‐3 in lipopolysaccharide‐induced intestinal epithelial cells

PubMed Central

Fu, L.; Wei, L.‐W.; Zhao, M.‐D.; Zhu, J.‐L.; Chen, S.‐Y.; Jia, X.‐B.

2016-01-01

Summary Janus‐activated kinase (JAKs)‐signal transducer and activator of transcription 3 (STAT‐3) signalling play critical roles in immunoregulation and immunopathology, which involve inflammatory responses and enteritis. JAK phosphorylates STAT‐3 in response to stimulation by cytokines or growth factors, and then activates or represses the gene expression. STAT‐3 is activated persistently in cancer cells and contributes to the malignant progression of various types of cancer and inflammation. To elucidate the different roles of JAKs in the activation of STAT‐3, the lipopolysaccharide‐induced primary intestinal epithelial cell (IEC) acute inflammatory model was established. Small interference RNAs (siRNAs) were then employed to attenuate the expression levels of JAKs. Real‐time quantitative reverse transcription–polymerase chain reaction (PCR) (qRT–PCR) revealed that JAK mRNA levels were reduced efficiently by JAK‐specific siRNAs. Under the IEC inflammatory model transfected with si‐JAK, which equates to effective silencing, qRT–PCR and Western blot assays, suggested that knockdowns of JAK attenuated the JAK‐induced down‐regulation of STAT‐3 at the mRNA or protein levels. In particular, JAK1 played a key role, which was consistent with the RNA‐Seq results. Subsequently, the expression levels of proinflammatory cytokines interleukin (IL)‐1β and tumour necrosis factor (TNF)‐α were down‐regulated in the IEC inflammatory model transfected with si‐JAK1. JAK1 appears as a direct activator for STAT‐3, whereas treatments targeting JAK1 repressed STAT‐3 sufficiently pathways in the IEC inflammatory model. Therefore, the control of JAK1 using siRNAs has the potential to be an effective strategy against enteritis. PMID:27357529

Electrographic waveform structure predicts laminar focus location in a model of temporal lobe seizures in vitro.

PubMed

Adams, Christopher; Adams, Natalie E; Traub, Roger D; Whittington, Miles A

2015-01-01

Temporal lobe epilepsy is the most common form of partial-onset epilepsy and accounts for the majority of adult epilepsy cases in most countries. A critical role for the hippocampus (and to some extent amygdala) in the pathology of these epilepsies is clear, with selective removal of these regions almost as effective as temporal lobectomy in reducing subsequent seizure risk. However, there is debate about whether hippocampus is 'victim' or 'perpetrator': The structure is ideally placed to 'broadcast' epileptiform activity to a great many other brain regions, but removal often leaves epileptiform events still occurring in cortex, particularly in adjacent areas, and recruitment of the hippocampus into seizure-like activity has been shown to be difficult in clinically-relevant models. Using a very simple model of acute epileptiform activity with known, single primary pathology (GABAA Receptor partial blockade), we track the onset and propagation of epileptiform events in hippocampus, parahippocampal areas and neocortex. In this model the hippocampus acts as a potential seizure focus for the majority of observed events. Events with hippocampal focus were far more readily propagated throughout parahippocampal areas and into neocortex than vice versa. The electrographic signature of events of hippocampal origin was significantly different to those of primary neocortical origin - a consequence of differential laminar activation. These data confirm the critical role of the hippocampus in epileptiform activity generation in the temporal lobe and suggest the morphology of non-invasive electrical recording of neocortical interictal events may be useful in confirming this role.

Electrographic Waveform Structure Predicts Laminar Focus Location in a Model of Temporal Lobe Seizures In Vitro

PubMed Central

Adams, Christopher; Adams, Natalie E.; Traub, Roger D.; Whittington, Miles A.

2015-01-01

Temporal lobe epilepsy is the most common form of partial-onset epilepsy and accounts for the majority of adult epilepsy cases in most countries. A critical role for the hippocampus (and to some extent amygdala) in the pathology of these epilepsies is clear, with selective removal of these regions almost as effective as temporal lobectomy in reducing subsequent seizure risk. However, there is debate about whether hippocampus is ‘victim’ or ‘perpetrator’: The structure is ideally placed to ‘broadcast’ epileptiform activity to a great many other brain regions, but removal often leaves epileptiform events still occurring in cortex, particularly in adjacent areas, and recruitment of the hippocampus into seizure-like activity has been shown to be difficult in clinically-relevant models. Using a very simple model of acute epileptiform activity with known, single primary pathology (GABAA Receptor partial blockade), we track the onset and propagation of epileptiform events in hippocampus, parahippocampal areas and neocortex. In this model the hippocampus acts as a potential seizure focus for the majority of observed events. Events with hippocampal focus were far more readily propagated throughout parahippocampal areas and into neocortex than vice versa. The electrographic signature of events of hippocampal origin was significantly different to those of primary neocortical origin – a consequence of differential laminar activation. These data confirm the critical role of the hippocampus in epileptiform activity generation in the temporal lobe and suggest the morphology of non-invasive electrical recording of neocortical interictal events may be useful in confirming this role. PMID:25799020

Inhibition of EGFR attenuates fibrosis and stellate cell activation in diet-induced model of nonalcoholic fatty liver disease.

PubMed

Liang, Dandan; Chen, Hongjin; Zhao, Leping; Zhang, Wenxin; Hu, Jie; Liu, Zhiguo; Zhong, Peng; Wang, Wei; Wang, Jingying; Liang, Guang

2018-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD begins with steatosis and advances to nonalcoholic steatohepatitis (NASH) and cirrhosis. The molecular mechanisms involved in NAFLD progression are not understood. Based on recent studies showing dysregulation of epidermal growth factor receptor (EGFR) in animal models of liver injury, we sought to determine if inhibition of EGFR mitigates liver fibrosis and HSC activation in NAFLD. We utilized the high fat diet (HFD)-induced murine model of liver injury to study the role of EGFR in NAFLD. The lipid accumulation, oxidative stress, hepatic stellate cell (HSC) activation and matrix deposition were examined in the liver tissues. We also evaluated the EGFR signaling pathway, ROS activation and pro-fibrogenic phenotype in oxidized low density lipoproteins (ox-LDL) challenged cultured HSCs. We demonstrate that EGFR was phosphorylated in liver tissues of HFD murine model of NAFLD. Inhibition of EGFR prevented diet-induced lipid accumulation, oxidative stress, and HSC activation and matrix deposition. In cultured HSCs, we show that ox-LDL caused rapid activation of the EGFR signaling pathway and induce the production of reactive oxygen species. EGFR also mediated HSC activation and promoted a pro-fibrogenic phenotype. In conclusion, our data demonstrate that EGFR plays an important role in NAFLD and is an attractive target for NAFLD therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Individual, social environmental, and physical environmental influences on physical activity among black and white adults: a structural equation analysis.

PubMed

McNeill, Lorna Haughton; Wyrwich, Kathleen W; Brownson, Ross C; Clark, Eddie M; Kreuter, Matthew W

2006-02-01

Social ecological models suggest that conditions in the social and physical environment, in addition to individual factors, play important roles in health behavior change. Using structural equation modeling, this study tested a theoretically and empirically based explanatory model of physical activity to examine theorized direct and indirect effects of individual (e.g., motivation and self-efficacy), social environmental (e.g., social support), and physical environmental factors (e.g., neighborhood quality and availability of facilities). A community-based sample of adults (N = 910) was recruited from 2 public health centers (67% female, 43% African American, 43% < $20,000/year, M age = 33 years) and completed a self-administered survey assessing their current physical activity level, intrinsic and extrinsic motivation for physical activity, perceived social support, self-efficacy, and perceptions of the physical environment. Results indicated that (a) perceptions of the physical environment had direct effects on physical activity, (b) both the social and physical environments had indirect effects on physical activity through motivation and self-efficacy, and (c) social support influenced physical activity indirectly through intrinsic and extrinsic motivation. For all forms of activity, self-efficacy was the strongest direct correlate of physical activity, and evidence of a positive dose-response relation emerged between self-efficacy and intensity of physical activity. Findings from this research highlight the interactive role of individual and environmental influences on physical activity.

Multiscale computational modeling reveals a critical role for TNF-α receptor 1 dynamics in tuberculosis granuloma formation.

PubMed

Fallahi-Sichani, Mohammad; El-Kebir, Mohammed; Marino, Simeone; Kirschner, Denise E; Linderman, Jennifer J

2011-03-15

Multiple immune factors control host responses to Mycobacterium tuberculosis infection, including the formation of granulomas, which are aggregates of immune cells whose function may reflect success or failure of the host to contain infection. One such factor is TNF-α. TNF-α has been experimentally characterized to have the following activities in M. tuberculosis infection: macrophage activation, apoptosis, and chemokine and cytokine production. Availability of TNF-α within a granuloma has been proposed to play a critical role in immunity to M. tuberculosis. However, in vivo measurement of a TNF-α concentration gradient and activities within a granuloma are not experimentally feasible. Further, processes that control TNF-α concentration and activities in a granuloma remain unknown. We developed a multiscale computational model that includes molecular, cellular, and tissue scale events that occur during granuloma formation and maintenance in lung. We use our model to identify processes that regulate TNF-α concentration and cellular behaviors and thus influence the outcome of infection within a granuloma. Our model predicts that TNF-αR1 internalization kinetics play a critical role in infection control within a granuloma, controlling whether there is clearance of bacteria, excessive inflammation, containment of bacteria within a stable granuloma, or uncontrolled growth of bacteria. Our results suggest that there is an interplay between TNF-α and bacterial levels in a granuloma that is controlled by the combined effects of both molecular and cellular scale processes. Finally, our model elucidates processes involved in immunity to M. tuberculosis that may be new targets for therapy.

Defective natural killer cell activity in a mouse model of eczema herpeticum.

PubMed

Kawakami, Yuko; Ando, Tomoaki; Lee, Jong-Rok; Kim, Gisen; Kawakami, Yu; Nakasaki, Tae; Nakasaki, Manando; Matsumoto, Kenji; Choi, Youn Soo; Kawakami, Toshiaki

2017-03-01

Patients with atopic dermatitis (AD) are susceptible to several viruses, including herpes simplex virus (HSV). Some patients experience 1 or more episodes of a severe skin infection caused by HSV termed eczema herpeticum (EH). There are numerous mouse models of AD, but no established model exists for EH. We sought to establish and characterize a mouse model of EH. We infected AD-like skin lesions with HSV1 to induce severe skin lesions in a dermatitis-prone mouse strain of NC/Nga. Gene expression was investigated by using a microarray and quantitative PCR; antibody titers were measured by means of ELISA; and natural killer (NK) cell, cytotoxic T-cell, regulatory T-cell, and follicular helper T-cell populations were evaluated by using flow cytometry. The role of NK cells in HSV1-induced development of severe skin lesions was examined by means of depletion and adoptive transfer. Inoculation of HSV1 induced severe erosive skin lesions in eczematous mice, which had an impaired skin barrier, but milder lesions in small numbers of normal mice. Eczematous mice exhibited lower NK cell activity but similar cytotoxic T-cell activity and humoral immune responses compared with normal mice. The role of NK cells in controlling HSV1-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. A murine model of EH with an impaired skin barrier was established in this study. We demonstrated a critical role of defective NK activities in the development of HSV1-induced severe skin lesions in eczematous mice. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. All rights reserved.

A Catalytic Role for Proangiogenic Marrow-Derived Cells in Tumor Neovascularization

PubMed Central

Seandel, Marco; Butler, Jason; Lyden, David; Rafii, Shahin

2010-01-01

Small numbers of proangiogenic bone marrow-derived cells (BMDCs) can play pivotal roles in tumor progression. In this issue of Cancer Cell, two papers, utilizing different tumor angiogenesis models, both find that activated MMP-9 delivered by BMDCs modulates neovessel remodeling, thereby promoting tumor growth. The changes in microvascular anatomy induced by MMP-9-expressing BMDCs are strikingly different between the preirradiated tumor vascular bed model employed by Ahn and Brown and the invasive glioblastoma model utilized by Du et al., likely mirroring the complexity of the real tumor microenvironment and the intricacy of roles of different BMDC populations in mediating tumor neoangiogenesis. PMID:18328420

Physical Activity, Gender Difference, and Depressive Symptoms.

PubMed

Zhang, Jun; Yen, Steven T

2015-10-01

To investigate the roles of physical activity (exercise) and sociodemographic factors in depressive symptoms among men and women in the United States. 2011 U.S. Behavioral Risk Factor Surveillance System (BRFSS). Patient Health Questionnaire Depression Scale (PHQ-8) scores are aggregated and divided into five categories. An ordered switching probability model with binary endogenous physical activity is developed to accommodate ordinality of depression categories and ameliorate statistical biases due to endogeneity of physical activity. Average treatment effects suggest physical activity ameliorates depressive symptoms among mildly and moderately depressed individuals, most notably among mildly depressed women. Gender differences exist in the roles of sociodemographic factors, with age, income, race, education, employment status, and recent mental health condition playing differentiated roles in affecting depressive symptoms. Regular physical activity reduces depressive symptoms among both men and women with mild to moderate depression, notably among women. © Health Research and Educational Trust.

The role of mobile technologies in health care processes: the case of cancer supportive care.

PubMed

Nasi, Greta; Cucciniello, Maria; Guerrazzi, Claudia

2015-02-12

Health care systems are gradually moving toward new models of care based on integrated care processes shared by different care givers and on an empowered role of the patient. Mobile technologies are assuming an emerging role in this scenario. This is particularly true in care processes where the patient has a particularly enhanced role, as is the case of cancer supportive care. This paper aims to review existing studies on the actual role and use of mobile technology during the different stages of care processes, with particular reference to cancer supportive care. We carried out a review of literature with the aim of identifying studies related to the use of mHealth in cancer care and cancer supportive care. The final sample size consists of 106 records. There is scant literature concerning the use of mHealth in cancer supportive care. Looking more generally at cancer care, we found that mHealth is mainly used for self-management activities carried out by patients. The main tools used are mobile devices like mobile phones and tablets, but remote monitoring devices also play an important role. Text messaging technologies (short message service, SMS) have a minor role, with the exception of middle income countries where text messaging plays a major role. Telehealth technologies are still rarely used in cancer care processes. If we look at the different stages of health care processes, we can see that mHealth is mainly used during the treatment of patients, especially for self-management activities. It is also used for prevention and diagnosis, although to a lesser extent, whereas it appears rarely used for decision-making and follow-up activities. Since mHealth seems to be employed only for limited uses and during limited phases of the care process, it is unlikely that it can really contribute to the creation of new care models. This under-utilization may depend on many issues, including the need for it to be embedded into broader information systems. If the purpose of introducing mHealth is to promote the adoption of integrated care models, using mHealth should not be limited to some activities or to some phases of the health care process. Instead, there should be a higher degree of pervasiveness at all stages and in all health care delivery activities.

The Role of Mobile Technologies in Health Care Processes: The Case of Cancer Supportive Care

PubMed Central

Cucciniello, Maria; Guerrazzi, Claudia

2015-01-01

Background Health care systems are gradually moving toward new models of care based on integrated care processes shared by different care givers and on an empowered role of the patient. Mobile technologies are assuming an emerging role in this scenario. This is particularly true in care processes where the patient has a particularly enhanced role, as is the case of cancer supportive care. Objective This paper aims to review existing studies on the actual role and use of mobile technology during the different stages of care processes, with particular reference to cancer supportive care. Methods We carried out a review of literature with the aim of identifying studies related to the use of mHealth in cancer care and cancer supportive care. The final sample size consists of 106 records. Results There is scant literature concerning the use of mHealth in cancer supportive care. Looking more generally at cancer care, we found that mHealth is mainly used for self-management activities carried out by patients. The main tools used are mobile devices like mobile phones and tablets, but remote monitoring devices also play an important role. Text messaging technologies (short message service, SMS) have a minor role, with the exception of middle income countries where text messaging plays a major role. Telehealth technologies are still rarely used in cancer care processes. If we look at the different stages of health care processes, we can see that mHealth is mainly used during the treatment of patients, especially for self-management activities. It is also used for prevention and diagnosis, although to a lesser extent, whereas it appears rarely used for decision-making and follow-up activities. Conclusions Since mHealth seems to be employed only for limited uses and during limited phases of the care process, it is unlikely that it can really contribute to the creation of new care models. This under-utilization may depend on many issues, including the need for it to be embedded into broader information systems. If the purpose of introducing mHealth is to promote the adoption of integrated care models, using mHealth should not be limited to some activities or to some phases of the health care process. Instead, there should be a higher degree of pervasiveness at all stages and in all health care delivery activities. PMID:25679446

The role of predicted solar activity in TOPEX/Poseidon orbit maintenance maneuver design

NASA Technical Reports Server (NTRS)

Frauenholz, Raymond B.; Shapiro, Bruce E.

1992-01-01

Following launch in June 1992, the TOPEX/Poseidon satellite will be placed in a near-circular frozen orbit at an altitude of about 1336 km. Orbit maintenance maneuvers are planned to assure all nodes of the 127-orbit 10-day repeat ground track remain within a 2 km equatorial longitude bandwidth. Orbit determination, maneuver execution, and atmospheric drag prediction errors limit overall targeting performance. This paper focuses on the effects of drag modeling errors, with primary emphasis on the role of SESC solar activity predictions, especially the 27-day outlook of the 10.7 cm solar flux and geomagnetic index used by a simplified version of the Jacchia-Roberts density model developed for this TOPEX/Poseidon application. For data evaluated from 1983-90, the SESC outlook performed better than a simpler persistence strategy, especially during the first 7-10 days. A targeting example illustrates the use of ground track biasing to compensate for expected orbit predictions errors, emphasizing the role of solar activity prediction errors.

Top-Down Beta Rhythms Support Selective Attention via Interlaminar Interaction: A Model

PubMed Central

Lee, Jung H.; Whittington, Miles A.; Kopell, Nancy J.

2013-01-01

Cortical rhythms have been thought to play crucial roles in our cognitive abilities. Rhythmic activity in the beta frequency band, around 20 Hz, has been reported in recent studies that focused on neural correlates of attention, indicating that top-down beta rhythms, generated in higher cognitive areas and delivered to earlier sensory areas, can support attentional gain modulation. To elucidate functional roles of beta rhythms and underlying mechanisms, we built a computational model of sensory cortical areas. Our simulation results show that top-down beta rhythms can activate ascending synaptic projections from L5 to L4 and L2/3, responsible for biased competition in superficial layers. In the simulation, slow-inhibitory interneurons are shown to resonate to the 20 Hz input and modulate the activity in superficial layers in an attention-related manner. The predicted critical roles of these cells in attentional gain provide a potential mechanism by which cholinergic drive can support selective attention. PMID:23950699

Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis.

PubMed

Silva, Corinne M

2004-10-18

The signal transducers and activators of transcription (STATs) were originally identified in the signaling pathway activated by the nontyrosine kinase containing cytokine receptors. The role of these STATs in hematopoietic cell signaling has been well described. In the case of cytokine receptors, activation of STAT tyrosine phosphorylation occurs through ligand-induced recruitment, and activation of the intracellular JAK kinases. However, STATs can also be activated by growth factor receptors, particularly the EGFR; as well as by members of the Src Family of Kinases (SFKs), particularly c-Src. In many cases, there is a differential activation of the STATs by these tyrosine kinases as compared to activation by the cytokine receptors. This difference provides for the potential of unique actions of STATs in response to growth factor receptor and SFK activation. Since there are many cancers in which SFKs and c-Src in particular, are co-overexpressed with growth factor receptors, it is not surprising that STATs play an important role in the tumorigenesis process induced by c-Src. The activation paradigm and role of STATs in these cancers, with particular emphasis on breast cancer models, is discussed.

Sulforaphane activates the cerebral vascular Nrf2-ARE pathway and suppresses inflammation to attenuate cerebral vasospasm in rat with subarachnoid hemorrhage.

PubMed

Zhao, Xudong; Wen, Liting; Dong, Min; Lu, Xiaojie

2016-12-15

Nrf2-ARE pathway reportedly plays a protective role in several central nervous system diseases. No study has explored the role of the Nrf2-ARE pathway in cerebral vasospasm(CVS) after subarachnoid hemorrhage(SAH). The purpose of the present study was to investigate the activation of the cerebral vascular Nrf2-ARE pathway and to determine the potential role of this pathway in the development of CVS following SAH. We investigated whether the administration of sulforaphane (SFN, a specific Nrf2 activator) modulated vascular caliber, Nrf2-ARE pathway activity, proinflammatory cytokine expression, and clinical behavior in a rat model of SAH. A two-hemorrhage protocol was used to generate an animal model of SAH in male Sprague-Dawley rats. Administration of SFN to these rats following SAH enhanced the activity of the Nrf2-ARE pathway and suppressed the release of proinflammatory cytokines. Vasospasm was markedly attenuated in the basilar arteries after SFN therapy. Additionally, SFN administration significantly ameliorated two behavioral functions disrupted by SAH. These results suggest that SFN has a therapeutic benefit in post-SAH, and this may be due to elevated Nrf2-ARE pathway activity and inhibition of cerebral vascular proinflammatory cytokine expression. Copyright © 2016. Published by Elsevier B.V.

Residues within the Transmembrane Domain of the Glucagon-Like Peptide-1 Receptor Involved in Ligand Binding and Receptor Activation: Modelling the Ligand-Bound Receptor

PubMed Central

Coopman, K.; Wallis, R.; Robb, G.; Brown, A. J. H.; Wilkinson, G. F.; Timms, D.

2011-01-01

The C-terminal regions of glucagon-like peptide-1 (GLP-1) bind to the N terminus of the GLP-1 receptor (GLP-1R), facilitating interaction of the ligand N terminus with the receptor transmembrane domain. In contrast, the agonist exendin-4 relies less on the transmembrane domain, and truncated antagonist analogs (e.g. exendin 9–39) may interact solely with the receptor N terminus. Here we used mutagenesis to explore the role of residues highly conserved in the predicted transmembrane helices of mammalian GLP-1Rs and conserved in family B G protein coupled receptors in ligand binding and GLP-1R activation. By iteration using information from the mutagenesis, along with the available crystal structure of the receptor N terminus and a model of the active opsin transmembrane domain, we developed a structural receptor model with GLP-1 bound and used this to better understand consequences of mutations. Mutation at Y152 [transmembrane helix (TM) 1], R190 (TM2), Y235 (TM3), H363 (TM6), and E364 (TM6) produced similar reductions in affinity for GLP-1 and exendin 9–39. In contrast, other mutations either preferentially [K197 (TM2), Q234 (TM3), and W284 (extracellular loop 2)] or solely [D198 (TM2) and R310 (TM5)] reduced GLP-1 affinity. Reduced agonist affinity was always associated with reduced potency. However, reductions in potency exceeded reductions in agonist affinity for K197A, W284A, and R310A, while H363A was uncoupled from cAMP generation, highlighting critical roles of these residues in translating binding to activation. Data show important roles in ligand binding and receptor activation of conserved residues within the transmembrane domain of the GLP-1R. The receptor structural model provides insight into the roles of these residues. PMID:21868452

Intracellular Fluid Mechanics: Coupling Cytoplasmic Flow with Active Cytoskeletal Gel

NASA Astrophysics Data System (ADS)

Mogilner, Alex; Manhart, Angelika

2018-01-01

The cell is a mechanical machine, and continuum mechanics of the fluid cytoplasm and the viscoelastic deforming cytoskeleton play key roles in cell physiology. We review mathematical models of intracellular fluid mechanics, from cytoplasmic fluid flows, to the flow of a viscous active cytoskeletal gel, to models of two-phase poroviscous flows, to poroelastic models. We discuss application of these models to cell biological phenomena, such as organelle positioning, blebbing, and cell motility. We also discuss challenges of understanding fluid mechanics on the cellular scale.

Modelling the role of Tax expression in HTLV-I persistence in vivo.

PubMed

Li, Michael Y; Lim, Aaron G

2011-12-01

Human T-lymphotropic virus type I (HTLV-I) is a persistent human retrovirus characterized by life-long infection and risk of developing HAM/TSP, a progressive neurological and inflammatory disease, and adult T-cell leukemia (ATL). Chronically infected individuals often harbor high proviral loads despite maintaining a persistently activated immune response. Based on a new hypothesis for the persistence of HTLV-I infection, a three-dimensional compartmental model is constructed that describes the dynamic interactions among latently infected target cells, target-cell activation, and immune responses to HTLV-I, with an emphasis on understanding the role of Tax expression in the persistence of HTLV-I.

Private space exploration: A new way for starting a spacefaring society?

NASA Astrophysics Data System (ADS)

Genta, Giancarlo

2014-11-01

Since the beginning space was an exclusive domain of public organizations, the role of privates is becoming more and more important, and not only in commercial activities. However, the main international treaties dealing with this subject are still based on the assumption that space activities are mostly reserved to states. In the last decade the idea that the role of privates could include the management of space infrastructures and launch vehicles gained support and now private launch services are a reality. An even wider role of privates is now advocated and private exploration and exploitation missions are discussed. This requires that space activity in general can generate an attractive return and those business models are identified.

Predictive Place-Cell Sequences for Goal-Finding Emerge from Goal Memory and the Cognitive Map: A Computational Model

PubMed Central

Gönner, Lorenz; Vitay, Julien; Hamker, Fred H.

2017-01-01

Hippocampal place-cell sequences observed during awake immobility often represent previous experience, suggesting a role in memory processes. However, recent reports of goals being overrepresented in sequential activity suggest a role in short-term planning, although a detailed understanding of the origins of hippocampal sequential activity and of its functional role is still lacking. In particular, it is unknown which mechanism could support efficient planning by generating place-cell sequences biased toward known goal locations, in an adaptive and constructive fashion. To address these questions, we propose a model of spatial learning and sequence generation as interdependent processes, integrating cortical contextual coding, synaptic plasticity and neuromodulatory mechanisms into a map-based approach. Following goal learning, sequential activity emerges from continuous attractor network dynamics biased by goal memory inputs. We apply Bayesian decoding on the resulting spike trains, allowing a direct comparison with experimental data. Simulations show that this model (1) explains the generation of never-experienced sequence trajectories in familiar environments, without requiring virtual self-motion signals, (2) accounts for the bias in place-cell sequences toward goal locations, (3) highlights their utility in flexible route planning, and (4) provides specific testable predictions. PMID:29075187

Multi-scale and multi-physics model of the uterine smooth muscle with mechanotransduction.

PubMed

Yochum, Maxime; Laforêt, Jérémy; Marque, Catherine

2018-02-01

Preterm labor is an important public health problem. However, the efficiency of the uterine muscle during labor is complex and still poorly understood. This work is a first step towards a model of the uterine muscle, including its electrical and mechanical components, to reach a better understanding of the uterus synchronization. This model is proposed to investigate, by simulation, the possible role of mechanotransduction for the global synchronization of the uterus. The electrical diffusion indeed explains the local propagation of contractile activity, while the tissue stretching may play a role in the synchronization of distant parts of the uterine muscle. This work proposes a multi-physics (electrical, mechanical) and multi-scales (cell, tissue, whole uterus) model, which is applied to a realistic uterus 3D mesh. This model includes electrical components at different scales: generation of action potentials at the cell level, electrical diffusion at the tissue level. It then links these electrical events to the mechanical behavior, at the cellular level (via the intracellular calcium concentration), by simulating the force generated by each active cell. It thus computes an estimation of the intra uterine pressure (IUP) by integrating the forces generated by each active cell at the whole uterine level, as well as the stretching of the tissue (by using a viscoelastic law for the behavior of the tissue). It finally includes at the cellular level stretch activated channels (SACs) that permit to create a loop between the mechanical and the electrical behavior (mechanotransduction). The simulation of different activated regions of the uterus, which in this first "proof of concept" case are electrically isolated, permits the activation of inactive regions through the stretching (induced by the electrically active regions) computed at the whole organ scale. This permits us to evidence the role of the mechanotransduction in the global synchronization of the uterus. The results also permit us to evidence the effect on IUP of this enhanced synchronization induced by the presence of SACs. This proposed simplified model will be further improved in order to permit a better understanding of the global uterine synchronization occurring during efficient labor contractions. Copyright © 2017 Elsevier Ltd. All rights reserved.

A critical role for plasma kallikrein in the pathogenesis of autoantibody-induced arthritis.

PubMed

Yang, Aizhen; Zhou, Junsong; Wang, Bo; Dai, Jihong; Colman, Robert W; Song, Wenchao; Wu, Yi

2017-12-01

The plasma kallikrein-kinin system (KKS) consists of serine proteases, prekallikrein (pKal) and factor XII (FXII), and a cofactor, high-MW kininogen (HK). Upon activation, activated pKal and FXII cleave HK to release bradykinin. Activation of this system has been noted in patients with rheumatoid arthritis, and its pathogenic role has been characterized in animal arthritic models. In this study, we generated 2 knockout mouse strains that lacked pKal and HK and determined the role of KKS in autoantibody-induced arthritis. In a K/BxN serum transfer-induced arthritis (STIA) model, mice that lacked HK, pKal, or bradykinin receptors displayed protective phenotypes in joint swelling, histologic changes in inflammation, and cytokine production; however, FXII-deficient mice developed normal arthritis. Inhibition of Kal ameliorated arthritis severity and incidence at early stage STIA and reduced the levels of major cytokines in joints. In addition to releasing bradykinin from HK, Kal directly activated monocytes to produce proinflammatory cytokines, up-regulated their C5aR and FcRIII expression, and released C5a. Immune complex increased pKal activity, which led to HK cleavage. The absence of HK is associated with a decrease in joint vasopermeability. Thus, we identify a critical role for Kal in autoantibody-induced arthritis with pleiotropic effects, which suggests that it is a new target for the inhibition of arthritis.-Yang, A., Zhou, J., Wang, B., Dai, J., Colman, R. W., Song, W., Wu, Y. A critical role for plasma kallikrein in the pathogenesis of autoantibody-induced arthritis. © FASEB.

JPL future missions and energy storage technology implications

NASA Technical Reports Server (NTRS)

Pawlik, Eugene V.

1987-01-01

The mission model for JPL future programs is presented. This model identifies mission areas where JPL is expected to have a major role and/or participate in a significant manner. These missions are focused on space science and applications missions, but they also include some participation in space station activities. The mission model is described in detail followed by a discussion on the needs for energy storage technology required to support these future activities.

The impact of the board's strategy-setting role on board-management relations and hospital performance.

PubMed

Büchner, Vera Antonia; Schreyögg, Jonas; Schultz, Carsten

2014-01-01

The appropriate governance of hospitals largely depends on effective cooperation between governing boards and hospital management. Governing boards play an important role in strategy-setting as part of their support for hospital management. However, in certain situations, this active strategic role may also generate discord within this relationship. The objective of this study is to investigate the impact of the roles, attributes, and processes of governing boards on hospital performance. We examine the impact of the governing board's strategy-setting role on board-management collaboration quality and on financial performance while also analyzing the interaction effects of board diversity and board activity level. The data are derived from a survey that was sent simultaneously to German hospitals and their associated governing board, combined with objective performance information from annual financial statements and quality reports. We use a structural equation modeling approach to test the model. The results indicate that different board characteristics have a significant impact on hospital performance (R = .37). The strategy-setting role and board-management collaboration quality have a positive effect on hospital performance, whereas the impact of strategy-setting on collaboration quality is negative. We find that the positive effect of strategy-setting on performance increases with decreasing board diversity. When board members have more homogeneous backgrounds and exhibit higher board activity levels, the negative effect of the strategy-setting on collaboration quality also increases. Active strategy-setting by a governing board may generally improve hospital performance. Diverse members of governing boards should be involved in strategy-setting for hospitals. However, high board-management collaboration quality may be compromised if managerial autonomy is too highly restricted. Consequently, hospitals should support board-management collaboration about empowered contrasting board roles.

Genetic and Imaging Approaches Reveal Pro-Inflammatory and Immunoregulatory Roles of Mast Cells in Contact Hypersensitivity.

PubMed

Gaudenzio, Nicolas; Marichal, Thomas; Galli, Stephen J; Reber, Laurent L

2018-01-01

Contact hypersensitivity (CHS) is a common T cell-mediated skin disease induced by epicutaneous sensitization to haptens. Mast cells (MCs) are widely deployed in the skin and can be activated during CHS responses to secrete diverse products, including some with pro-inflammatory and anti-inflammatory functions. Conflicting results have been obtained regarding pathogenic versus protective roles of MCs in CHS, and this has been attributed in part to the limitations of certain models for studying MC functions in vivo . This review discusses recent advances in the development and analysis of mouse models to investigate the roles of MCs and MC-associated products in vivo . Notably, fluorescent avidin-based two-photon imaging approaches enable in vivo selective labeling and simultaneous tracking of MC secretory granules (e.g., during MC degranulation) and MC gene activation by real-time longitudinal intravital microscopy in living mice. The combination of such genetic and imaging tools has shed new light on the controversial role played by MCs in mouse models of CHS. On the one hand, they can amplify CHS responses of mild severity while, on the other hand, can limit the inflammation and tissue injury associated with more severe or chronic models, in part by representing an initial source of the anti-inflammatory cytokine IL-10.

In vivo activation of Wnt signaling pathway enhances cognitive function of adult mice and reverses cognitive deficits in an Alzheimer's disease model.

PubMed

Vargas, Jessica Y; Fuenzalida, Marco; Inestrosa, Nibaldo C

2014-02-05

The role of the Wnt signaling pathway during synaptic development has been well established. In the adult brain, different components of Wnt signaling are expressed, but little is known about its role in mature synapses. Emerging in vitro studies have implicated Wnt signaling in synaptic plasticity. Furthermore, activation of Wnt signaling has shown to protect against amyloid-β-induced synaptic impairment. The present study provides the first evidence that in vivo activation of Wnt signaling improves episodic memory, increases excitatory synaptic transmission, and enhances long-term potentiation in adult wild-type mice. Moreover, the activation of Wnt signaling also rescues memory loss and improves synaptic dysfunction in APP/PS1-transgenic mice that model the amyloid pathology of Alzheimer's diseases. These findings indicate that Wnt signaling modulates cognitive function in the adult brain and could be a novel promising target for Alzheimer's disease therapy.

The role of the time-kill kinetics assay as part of a preclinical modeling framework for assessing the activity of anti-tuberculosis drugs.

PubMed

Bax, Hannelore I; Bakker-Woudenberg, Irma A J M; de Vogel, Corné P; van der Meijden, Aart; Verbon, Annelies; de Steenwinkel, Jurriaan E M

2017-07-01

Novel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. The concentration- and time-dependent mycobacterial killing capacities of six anti-tuberculosis drugs were determined during exposure as single drugs or in dual, triple and quadruple combinations towards a Mycobacterium tuberculosis Beijing genotype strain and drug resistance was assessed. Streptomycin, rifampicin and isoniazid were most active against fast-growing M. tuberculosis. Isoniazid with rifampicin or high dose ethambutol were the only synergistic drug combinations. The addition of rifampicin or streptomycin to isoniazid prevented isoniazid resistance. In vitro ranking showed agreement with early bactericidal activity in tuberculosis patients for some but not all anti-tuberculosis drugs. The time-kill kinetics assay provides important information on the mycobacterial killing dynamics of anti-tuberculosis drugs during the early phase of drug exposure. As such, this assay is a valuable component of the preclinical modeling framework. Copyright © 2017 Elsevier Ltd. All rights reserved.

Resveratrol Protects Purkinje Neurons and Restores Muscle Activity in Rat Model of Cerebellar Ataxia.

PubMed

Ghorbani, Zeynab; Farahani, Reza Mastery; Aliaghaei, Abbas; Khodagholi, Fariba; Meftahi, Gholam Houssein; Danyali, Samira; Abdollahifar, Mohammad Amin; Daftari, Mahtab; Boroujeni, Mahdi Eskandarian; Sadeghi, Yousef

2018-05-01

Cerebellar ataxia (CA) is regarded as a miscellaneous cluster of brain disorders related to the cerebellum. Resveratrol is a naturally occurring polyphenolic compound. Previous reports suggest that resveratrol confers neuroprotection in various animal models of brain damage. Indeed, we considered it invaluable to investigate whether a treatment with resveratrol has a therapeutic role against CA induced by 3-acetylpyridine (3-AP) in rats. In addition, no investigation has examined neuroprotective effect of resveratrol in rat model of CA. Initially, 3-AP administration generated CA rat models followed by intraperitoneal injection with resveratrol. Then, motor performance and muscle electromyography (EMG) activity were assessed. Moreover, the anti-apoptotic role of resveratrol in CA and its relationship to protection of Purkinje cells were explored. According to what we have found, resveratrol administration improved the muscle activity and movement coordination in 3-AP-lesioned rats. Also under resveratrol treatment, the total number of the Purkinje neurons increased whereas a reduction in apoptotic bodies was observed. In conclusion, post-treatment with resveratrol evidently ameliorated motor performance as well as muscle activity accompanied by a protection of Purkinje cells in ataxic rats.

On the role of conflict and control in social cognition: event-related brain potential investigations.

PubMed

Bartholow, Bruce D

2010-03-01

Numerous social-cognitive models posit that social behavior largely is driven by links between constructs in long-term memory that automatically become activated when relevant stimuli are encountered. Various response biases have been understood in terms of the influence of such "implicit" processes on behavior. This article reviews event-related potential (ERP) studies investigating the role played by cognitive control and conflict resolution processes in social-cognitive phenomena typically deemed automatic. Neurocognitive responses associated with response activation and conflict often are sensitive to the same stimulus manipulations that produce differential behavioral responses on social-cognitive tasks and that often are attributed to the role of automatic associations. Findings are discussed in the context of an overarching social cognitive neuroscience model in which physiological data are used to constrain social-cognitive theories.

Structural investigation of protein kinase C inhibitors

NASA Technical Reports Server (NTRS)

Barak, D.; Shibata, M.; Rein, R.

1991-01-01

The phospholipid and Ca2+ dependent protein kinase (PKC) plays an essential role in a variety of cellular events. Inhibition of PKC was shown to arrest growth in tumor cell cultures making it a target for possible antitumor therapy. Calphostins are potent inhibitors of PKC with high affinity for the enzyme regulatory site. Structural characteristics of calphostins, which confer the inhibitory activity, are investigated by comparing their optimized structures with the existing models for PKC activation. The resulting model of inhibitory activity assumes interaction with two out of the three electrostatic interaction sites postulated for activators. The model shows two sites of hydrophobic interaction and enables the inhibitory activity of gossypol to be accounted for.

Computational modeling identifies key gene regulatory interactions underlying phenobarbital-mediated tumor promotion

PubMed Central

Luisier, Raphaëlle; Unterberger, Elif B.; Goodman, Jay I.; Schwarz, Michael; Moggs, Jonathan; Terranova, Rémi; van Nimwegen, Erik

2014-01-01

Gene regulatory interactions underlying the early stages of non-genotoxic carcinogenesis are poorly understood. Here, we have identified key candidate regulators of phenobarbital (PB)-mediated mouse liver tumorigenesis, a well-characterized model of non-genotoxic carcinogenesis, by applying a new computational modeling approach to a comprehensive collection of in vivo gene expression studies. We have combined our previously developed motif activity response analysis (MARA), which models gene expression patterns in terms of computationally predicted transcription factor binding sites with singular value decomposition (SVD) of the inferred motif activities, to disentangle the roles that different transcriptional regulators play in specific biological pathways of tumor promotion. Furthermore, transgenic mouse models enabled us to identify which of these regulatory activities was downstream of constitutive androstane receptor and β-catenin signaling, both crucial components of PB-mediated liver tumorigenesis. We propose novel roles for E2F and ZFP161 in PB-mediated hepatocyte proliferation and suggest that PB-mediated suppression of ESR1 activity contributes to the development of a tumor-prone environment. Our study shows that combining MARA with SVD allows for automated identification of independent transcription regulatory programs within a complex in vivo tissue environment and provides novel mechanistic insights into PB-mediated hepatocarcinogenesis. PMID:24464994

Nutraceuticals in rodent models as potential treatments for human Inflammatory Bowel Disease.

PubMed

Ghattamaneni, Naga K R; Panchal, Sunil K; Brown, Lindsay

2018-04-20

Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation of all or part of the digestive tract. Nutraceuticals include bioactive compounds such as polyphenols with anti-inflammatory activities, thus these products have the potential to treat chronic inflammatory diseases. We have emphasized the role of nutraceuticals in ameliorating the symptoms of IBD in rodent models of human IBD through modulation of key pathogenic mechanisms including dysbiosis, oxidative stress, increased inflammatory cytokines, immune system dysregulation, and inflammatory cell signaling pathways. Nutraceuticals have an important role in IBD patients as a preventive approach to extend remission phases and as a therapeutic intervention to suppress active IBD. Further clinical trials on nutraceuticals with positive results in rodent models are warranted. Copyright © 2018. Published by Elsevier Ltd.

A model of metastable dynamics during ongoing and evoked cortical activity

NASA Astrophysics Data System (ADS)

La Camera, Giancarlo

The dynamics of simultaneously recorded spike trains in alert animals often evolve through temporal sequences of metastable states. Little is known about the network mechanisms responsible for the genesis of such sequences, or their potential role in neural coding. In the gustatory cortex of alert rates, state sequences can be observed also in the absence of overt sensory stimulation, and thus form the basis of the so-called `ongoing activity'. This activity is characterized by a partial degree of coordination among neurons, sharp transitions among states, and multi-stability of single neurons' firing rates. A recurrent spiking network model with clustered topology can account for both the spontaneous generation of state sequences and the (network-generated) multi-stability. In the model, each network state results from the activation of specific neural clusters with potentiated intra-cluster connections. A mean field solution of the model shows a large number of stable states, each characterized by a subset of simultaneously active clusters. The firing rate in each cluster during ongoing activity depends on the number of active clusters, so that the same neuron can have different firing rates depending on the state of the network. Because of dense intra-cluster connectivity and recurrent inhibition, in finite networks the stable states lose stability due to finite size effects. Simulations of the dynamics show that the model ensemble activity continuously hops among the different states, reproducing the ongoing dynamics observed in the data. Moreover, when probed with external stimuli, the model correctly predicts the quenching of single neuron multi-stability into bi-stability, the reduction of dimensionality of the population activity, the reduction of trial-to-trial variability, and a potential role for metastable states in the anticipation of expected events. Altogether, these results provide a unified mechanistic model of ongoing and evoked cortical dynamics. NSF IIS-1161852, NIDCD K25-DC013557, NIDCD R01-DC010389.

Identification of novel peroxisome proliferator-activated receptor-gamma (PPARγ) agonists using molecular modeling method

NASA Astrophysics Data System (ADS)

Gee, Veronica M. W.; Wong, Fiona S. L.; Ramachandran, Lalitha; Sethi, Gautam; Kumar, Alan Prem; Yap, Chun Wei

2014-11-01

Peroxisome proliferator-activated receptor-gamma (PPARγ) plays a critical role in lipid and glucose homeostasis. It is the target of many drug discovery studies, because of its role in various disease states including diabetes and cancer. Thiazolidinediones, a synthetic class of agents that work by activation of PPARγ, have been used extensively as insulin-sensitizers for the management of type 2 diabetes. In this study, a combination of QSAR and docking methods were utilised to perform virtual screening of more than 25 million compounds in the ZINC library. The QSAR model was developed using 1,517 compounds and it identified 42,378 potential PPARγ agonists from the ZINC library, and 10,000 of these were selected for docking with PPARγ based on their diversity. Several steps were used to refine the docking results, and finally 30 potentially highly active ligands were identified. Four compounds were subsequently tested for their in vitro activity, and one compound was found to have a K i values of <5 μM.

Active ingredients of ginger as potential candidates in the prevention and treatment of diseases via modulation of biological activities

PubMed Central

Rahmani, Arshad H; shabrmi, Fahad M Al; Aly, Salah M

2014-01-01

The current mode of treatment based on synthetic drugs is expensive and also causes genetic and metabolic alterations. However, safe and sound mode of treatment is needed to control the diseases development and progression. In this regards, medicinal plant and its constituents play an important role in diseases management via modulation of biological activities. Ginger, the rhizome of the Zingiber officinale, has shown therapeutic role in the health management since ancient time and considered as potential chemopreventive agent. Numerous studies based on clinical trials and animal model has shown that ginger and its constituents shows significant role in the prevention of diseases via modulation of genetic and metabolic activities. In this review, we focused on the therapeutics effects of ginger and its constituents in the diseases management, and its impact on genetic and metabolic activities. PMID:25057339

The Effect of the Home Environment on Physical Activity and Dietary Intake in Preschool Children

PubMed Central

Østbye, Truls; Malhotra, Rahul; Stroo, Marissa; Lovelady, Cheryl; Brouwer, Rebecca; Zucker, Nancy; Fuemmeler, Bernard

2013-01-01

Background The effects of the home environment on child health behaviors related to obesity are unclear. Purpose To examine the role of the home physical activity (PA) and food environment on corresponding outcomes in young children, and assess maternal education/work status as a moderator. Methods Overweight or obese mothers reported on the home PA and food environment (accessibility, role modeling and parental policies). Outcomes included child moderate-vigorous PA (MVPA) and sedentary time derived from accelerometer data and two dietary factors (“junk” and healthy food intake scores) based on factor analysis of mother-reported food intake. Linear regression models assessed the net effect (controlling for child demographics, study arm, supplemental timepoint, maternal education/work status, child body mass index and accelerometer wear-time (for PA outcomes)) of the home environment on the outcomes and moderation by maternal education/work status. Data was collected in North Carolina from 2007–2011. Results Parental policies supporting PA increased MVPA time, and limiting access to unhealthy foods increased the healthy food intake score. Role modeling of healthy eating behaviors increased the healthy food intake score among children of mothers with no college education. Among children of mothers with no college education and not working, limiting access to unhealthy foods and role modeling reduced “junk” food intake scores while parental policies supporting family meals increased “junk” food intake scores. Conclusions To promote MVPA, parental policies supporting child PA are warranted. Limited access to unhealthy foods and role modeling of healthy eating may improve the quality of the child’s food intake. PMID:23736357

The effect of the home environment on physical activity and dietary intake in preschool children.

PubMed

Østbye, T; Malhotra, R; Stroo, M; Lovelady, C; Brouwer, R; Zucker, N; Fuemmeler, B

2013-10-01

The effects of the home environment on child health behaviors related to obesity are unclear. To examine the role of the home physical activity (PA) and food environment on corresponding outcomes in young children, and assess maternal education/work status as a moderator. Overweight or obese mothers reported on the home PA and food environment (accessibility, role modeling and parental policies). Outcomes included child moderate-vigorous PA (MVPA) and sedentary time derived from accelerometer data and two dietary factors ('junk' and healthy food intake scores) based on factor analysis of mother-reported food intake. Linear regression models assessed the net effect (controlling for child demographics, study arm, supplemental time point, maternal education/work status, child body mass index and accelerometer wear time (for PA outcomes)) of the home environment on the outcomes and moderation by maternal education/work status. Data were collected in North Carolina from 2007 to 2011. Parental policies supporting PA increased MVPA time, and limiting access to unhealthy foods increased the healthy food intake score. Role modeling of healthy eating behaviors increased the healthy food intake score among children of mothers with no college education. Among children of mothers with no college education and not working, limiting access to unhealthy foods and role modeling reduced 'junk' food intake scores whereas parental policies supporting family meals increased 'junk' food intake scores. To promote MVPA, parental policies supporting child PA are warranted. Limited access to unhealthy foods and role modeling of healthy eating may improve the quality of the child's food intake.

Developing Teachers' Models for Assessing Students' Competence in Mathematical Modelling through Lesson Study

ERIC Educational Resources Information Center

Aydogan Yenmez, Arzu; Erbas, Ayhan Kursat; Cakiroglu, Erdinc; Alacaci, Cengiz; Cetinkaya, Bulent

2017-01-01

Applications and modelling have gained a prominent role in mathematics education reform documents and curricula. Thus, there is a growing need for studies focusing on the effective use of mathematical modelling in classrooms. Assessment is an integral part of using modelling activities in classrooms, since it allows teachers to identify and manage…

Models of Time Use in Paid and Unpaid Work

ERIC Educational Resources Information Center

Beaujot, Roderic; Liu, Jianye

2005-01-01

Models of time use need to consider especially the reproductive and productive activities of women and men. For husband-wife families, the breadwinner, one-earner, or complementary-roles model has advantages in terms of efficiency or specialization and stability; however, it is a high-risk model for women and children. The alternate model has been…

Seeing & Feeling How Enzymes Work Using Tangible Models

ERIC Educational Resources Information Center

Lau, Kwok-chi

2013-01-01

This article presents a tangible model used to help students tackle some misconceptions about enzyme actions, particularly the induced-fit model, enzyme-substrate complementarity, and enzyme inhibition. The model can simulate how substrates induce a change in the shape of the active site and the role of attraction force during enzyme-substrate…

A MECHANISTIC MODEL FOR MERCURY CAPTURE WITH IN-SITU GENERATED TITANIA PARTICLES: ROLE OF WATER VAPOR

EPA Science Inventory

A mechanistic model to predict the capture of gas phase mercury species using in-situ generated titania nanosize particles activated by UV irradiation is developed. The model is an extension of a recently reported model1 for photochemical reactions that accounts for the rates of...

Relationship between self-reported and objectively measured physical activity and subjective memory impairment in breast cancer survivors: role of self-efficacy, fatigue and distress.

PubMed

Phillips, Siobhan M; Lloyd, Gillian R; Awick, Elizabeth A; McAuley, Edward

2017-09-01

Many breast cancer survivors report cancer and cancer treatment-associated cognitive change. However, very little is known about the relationship between physical activity and subjective memory impairment (SMI) in this population. The purpose of this study is to examine the relationship between physical activity and SMI and longitudinally test a model examining the role of self-efficacy, fatigue and distress as potential mediators. Post-treatment breast cancer survivors (N = 1477) completed measures of physical activity, self-efficacy, distress (depression, concerns about recurrence, perceived stress, anxiety), fatigue and SMI at baseline and 6-month follow-up. A subsample (n = 362) was randomly selected to wear an accelerometer. It was hypothesized that physical activity indirectly influences SMI via exercise self-efficacy, distress and fatigue. Relationships were examined using panel analysis within a covariance modeling framework. The hypothesized model provided a good fit in the full sample (χ 2  = 1462.5, df = 469, p = <0.001; CFI = 0.96; SRMR = 0.04) and the accelerometer subsample (χ2 = 961.8, df = 535, p = <0.001, CFI = 0.94, SRMR = 0.05) indicating increased physical activity is indirectly associated with reduction in SMI across time, via increased exercise self-efficacy and reduced distress and fatigue. Higher levels of physical activity, lower levels of fatigue and distress and higher exercise self-efficacy may play an important role in understanding SMI in breast cancer survivors across time. Future research is warranted to replicate and explore these relationships further. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Activation and overexpression of Sirt1 attenuates lung fibrosis via P300.

PubMed

Zeng, Zhilin; Cheng, Sheng; Chen, Huilong; Li, Qinghai; Hu, Yinan; Wang, Qi; Zhu, Xianying; Wang, Jun

2017-05-13

Persistent fibroblast activation is a predominant feature of idiopathic pulmonary fibrosis (IPF), but the transcriptional and epigenetic mechanisms controlling this process are not well understood. Silent information regulator type-1 (Sirt1) is a member of class Ⅲ histone deacetylase with important regulatory roles in a variety of pathophysiologic processes, but its role in fibrotic lung diseases is not clearly elucidated. Sirt1 expression in lung tissues of IPF patients and in a mouse model of bleomycin (BLM)-induced lung fibrosis were evaluated by immunofluorescence. The function of Sirt1 in BLM-induced lung fibrosis in the mouse model or transforming growth factor β1 (TGF-β1)-mediated lung fibroblast cellular model was investigated by Sirt1 activation, overexpression and knockdown of Sirt1. Finally, the involvement of p300 signaling pathways was assessed. In this study, we found up-regulation of Sirt1 in BLM-induced lung fibrosis, as well as in the lungs of IPF patients, including in the aggregated pulmonary fibroblasts of fibrotic foci. Activation or overexpression of Sirt1 attenuated TGF-β1-mediated lung fibroblast differentiation and activation and diminished the severity of experimental lung fibrosis in mice. Whereas knockdown of Sirt1 promoted the pro-fibrogenic activity of TGF-β1 in lung fibroblasts. A potential mechanism for the role of Sirt1 in lung fibrosis was through regulating the expression of p300. Thus, we characterized Sirt1 as an important regulator of lung fibrosis and provides a proof of principle for activation or overexpression of Sirt1 as a potential novel therapeutic strategy for IPF. Copyright © 2017 Elsevier Inc. All rights reserved.

S-nitrosoglutathione reduces tau hyper-phosphorylation and provides neuroprotection in rat model of chronic cerebral hypoperfusion.

PubMed

Won, Je-Seong; Annamalai, Balasubramaniam; Choi, Seungho; Singh, Inderjit; Singh, Avtar K

2015-10-22

We have previously reported that treatment of rats subjected to permanent bilateral common carotid artery occlusion (pBCCAO), a model of chronic cerebral hypoperfusion (CCH), with S-nitrosoglutathione (GSNO), an endogenous nitric oxide carrier, improved cognitive functions and decreased amyloid-β accumulation in the brains. Since CCH has been implicated in tau hyperphosphorylation induced neurodegeneration, we investigated the role of GSNO in regulation of tau hyperphosphorylation in rat pBCCAO model. The rats subjected to pBCCAO had a significant increase in tau hyperphosphorylation with increased neuronal loss in hippocampal/cortical areas. GSNO treatment attenuated not only the tau hyperphosphorylation, but also the neurodegeneration in pBCCAO rat brains. The pBCCAO rat brains also showed increased activities of GSK-3β and Cdk5 (major tau kinases) and GSNO treatment significantly attenuated their activities. GSNO attenuated the increased calpain activities and calpain-mediated cleavage of p35 leading to production of p25 and aberrant Cdk5 activation. In in vitro studies using purified calpain protein, GSNO treatment inhibited calpain activities while 3-morpholinosydnonimine (a donor of peroxynitrite) treatment increased its activities, suggesting the opposing role of GSNO vs. peroxynitrite in regulation of calpain activities. In pBCCAO rat brains, GSNO treatment attenuated the expression of inducible nitric oxide synthase (iNOS) expression and also reduced the brain levels of nitro-tyrosine formation, thereby indicating the protective role of GSNO in iNOS/nitrosative-stress mediated calpain/tau pathologies under CCH conditions. Taken together with our previous report, these data support the therapeutic potential of GSNO, a biological NO carrier, as a neuro- and cognitive-protective agent under conditions of CCH. Published by Elsevier B.V.

The development of an acute care case manager orientation.

PubMed

Strzelecki, S; Brobst, R

1997-01-01

The authors describe the development of an inpatient acute care case manager orientation in a community hospital. Benner's application of the Dreyfus model of skill acquisition provides the basis for the orientation program. The candidates for the case manager position were expert clinicians. Because of the role change it was projected that they would function as advanced beginners. It was also predicted that, as the case managers progressed within the role, the educational process would need to be adapted to facilitate progression of skills to the proficient level. Feedback from participants reinforced that the model supported the case manager in the role transition. In addition, the model provided a predictive framework for ongoing educational activities.

Modeling DNA structure and processes through animation and kinesthetic visualizations

NASA Astrophysics Data System (ADS)

Hager, Christine

There have been many studies regarding the effectiveness of visual aids that go beyond that of static illustrations. Many of these have been concentrated on the effectiveness of visual aids such as animations and models or even non-traditional visual aid activities like role-playing activities. This study focuses on the effectiveness of three different types of visual aids: models, animation, and a role-playing activity. Students used a modeling kit made of Styrofoam balls and toothpicks to construct nucleotides and then bond nucleotides together to form DNA. Next, students created their own animation to depict the processes of DNA replication, transcription, and translation. Finally, students worked in teams to build proteins while acting out the process of translation. Students were given a pre- and post-test that measured their knowledge and comprehension of the four topics mentioned above. Results show that there was a significant gain in the post-test scores when compared to the pre-test scores. This indicates that the incorporated visual aids were effective methods for teaching DNA structure and processes.

Functional role of R462 in the degradation of hyaluronan catalyzed by hyaluronate lyase from Streptococcus pneumoniae.

PubMed

Li, Fengxue; Xu, Dingguo

2015-08-01

Hyaluronan lyase from Streptococcus pneumoniae can degrade hyaluronic acid, which is one of the major components in the extracellular matrix. Hyaluronan can regulate water balance, osmotic pressure, and act as an ion exchange resin. Followed by our recent work on the catalytic reaction mechanism and substrate binding mode, we in this work further investigate the functional role of active site arginine residue, R462, in the degradation of hyaluronan. The site directed mutagenesis simulation of R462A and R462Q were modeled using a combined quantum mechanical and molecular mechanical method. The overall substrate binding features upon mutations do not have significant changes. The energetic profiles for the reaction processes are essentially the same as that in wild type enzyme, but significant activation barrier height changes can be observed. Both mutants were shown to accelerate the overall enzymatic activity, e.g., R462A can reduce the barrier height by about 2.8 kcal mol(-1), while R462Q reduces the activation energy by about 2.9 kcal mol(-1). Consistent with the active site model calculated using density functional theory, our results can support that the positive charge on R462 guanidino side chain group plays a negative role in the catalysis. Finally, the functional role of R462 was proposed to facilitate the formation of initial enzyme-substrate complex, but not in the subsequent catalytic degradation reaction. Graphical Abstract Degradation of hyaluronan catalyzed by hyaluronate lyase from Streptococcus pneumoniae.

Self-regulation resources and physical activity participation among adults with type 2 diabetes.

PubMed

Castonguay, Alexandre; Miquelon, Paule; Boudreau, François

2018-01-01

Physical activity plays a crucial role in the prevention and treatment of type 2 diabetes. Therefore, it is important to understand why so few adults with type 2 diabetes regularly engage in physical activity. The role of self-regulation in the context of health-related behavior adherence, especially in terms of physical activity engagement and adherence, has largely been reviewed based on the strength energy model. Building on this line of research, the aim of this theoretical work was to highlight how self-regulation and ego depletion can influence the lower rate of physical activity participation among adults with type 2 diabetes, compared to adults from the general population.

Self-regulation resources and physical activity participation among adults with type 2 diabetes

PubMed Central

Castonguay, Alexandre; Miquelon, Paule; Boudreau, François

2018-01-01

Physical activity plays a crucial role in the prevention and treatment of type 2 diabetes. Therefore, it is important to understand why so few adults with type 2 diabetes regularly engage in physical activity. The role of self-regulation in the context of health-related behavior adherence, especially in terms of physical activity engagement and adherence, has largely been reviewed based on the strength energy model. Building on this line of research, the aim of this theoretical work was to highlight how self-regulation and ego depletion can influence the lower rate of physical activity participation among adults with type 2 diabetes, compared to adults from the general population. PMID:29372066

Roles and regulations of Hippo signaling during preimplantation mouse development.

PubMed

Sasaki, Hiroshi

2017-01-01

During preimplantation development, mouse embryos form two types of cells, the trophoectoderm (TE) and inner cell mass (ICM), by the early blastocyst stage. This process does not require maternal factors localized in the zygotes, and embryos self-organize at the blastocyst stage through intercellular communications. In terms of the mechanisms of cell fate specification, three historical models have been proposed: the positional model, and the original and newer versions of the polarity model. Recent studies have revealed that the intercellular Hippo signaling pathway plays a central role in the specification of the first cell fates. Hippo signaling is active in the inner cells but inactive in the outer cells. The Hippo-active inner and Hippo-inactive outer cells take the fates of the ICM and the TE, respectively. At the 32-cell stage, E-cadherin-mediated cell-cell adhesion and cell polarization by the Par-aPKC system activates and inactivates the Hippo pathway, respectively. Both mechanisms involve regulation of angiomotin, and cooperation of these mechanisms establishes cell position-dependent activation of Hippo signaling. At the 16-cell stage, however, asymmetric cell division produces the initial differences in Hippo signaling. At this stage, cell polarity is controlled by both Par-aPKC-dependent and -independent mechanisms. All three historical models are explained by the different regulations and roles of Hippo signaling. Based on these findings, I would like to propose the model by which the differences in Hippo signaling among blastomeres is first produced by asymmetric cell division and then enhanced and stabilized by cell position-dependent mechanisms until their fates are fixed. © 2016 Japanese Society of Developmental Biologists.

Role of IL-9 and STATs in hematological malignancies (Review).

PubMed

Chen, Na; Wang, Xin

2014-03-01

Although interleukin-9 (IL-9) exhibits pleiotropic functions in the immune system, it remains a well-known cytokine in hematological malignancies. Previous cell culture and animal model studies have revealed that the Janus kinase-signal transducer and activator of transcription signaling pathway, which may be activated by a number of cytokines including IL-9, is critical in hematological malignancies. The current review summarizes the characterization of the biological activities of IL-9, highlights the clearly defined roles of the cytokine, and outlines questions with regard to the functions of IL-9 that require further exploration and their downstream signaling proteins, signal transducers and activators of transcription.

Do Productive Activities Reduce Inflammation in Later Life? Multiple Roles, Frequency of Activities, and C-Reactive Protein

PubMed Central

Kim, Seoyoun; Ferraro, Kenneth F.

2014-01-01

Purpose of the Study: The study investigates whether productive activities by older adults reduce bodily inflammation, as indicated by C-reactive protein (CRP), a biomeasure associated with the risk of cardiovascular diseases. Design and Methods: The study uses a representative survey of adults aged 57–85 from the National Social Life, Health, and Aging Project (N = 1,790). Linear regression models were used to analyze the effects of multiple roles (employment, volunteering, attending meetings, and caregiving) and the frequency of activity within each role on log values of CRP concentration (mg/L) drawn from assayed blood samples. Results: Number of roles for productive activities was associated with lower levels of CRP net of chronic conditions, lifestyle factors, and socioeconomic resources. When specific types of activity were examined, volunteering manifested the strongest association with lower levels of inflammation, particularly in the 70+ group. There was no evidence that frequent engagement in volunteer activity was associated with heightened inflammation. Implications: Productive activities—and frequent volunteering in particular—may protect individuals from inflammation that is associated with increased risk of hypertension and cardiovascular disease. PMID:23969258

Teaching Mathematics with Intelligent Support in Natural Language. Tertiary Education Students Working with Parametrized Modelling Activities

ERIC Educational Resources Information Center

Rojano, Teresa; García-Campos, Montserrat

2017-01-01

This article reports the outcomes of a study that seeks to investigate the role of feedback, by way of an intelligent support system in natural language, in parametrized modelling activities carried out by a group of tertiary education students. With such a system, it is possible to simultaneously display on a computer screen a dialogue window and…

A role for NF-κB activity in skin hyperplasia and the development of keratoacanthomata in mice.

PubMed

Poligone, Brian; Hayden, Matthew S; Chen, Luojing; Pentland, Alice P; Jimi, Eijiro; Ghosh, Sankar

2013-01-01

Previous studies have implicated NF-κB signaling in both cutaneous development and oncogenesis. However, these studies have been limited in part by the lethality that results from extreme over- or under-expression of NF-κB in available mouse models. Even cre-driven tissue specific expression of transgenes, or targeted deletion of NF-κB can cause cell death. Therefore, the present study was undertaken to evaluate a novel mouse model of enhanced NF-κB activity in the skin. A knock-in homologous recombination technique was utilized to develop a mouse model (referred to as PD mice) with increased NF-κB activity. The data show that increased NF-κB activity leads to hyperproliferation and dysplasia of the mouse epidermis. Chemical carcinogenesis in the context of enhanced NF-κB activity promotes the development of keratoacanthomata. Our findings support an important role for NF-κB in keratinocyte dysplasia. We have found that enhanced NF-κB activity renders keratinocytes susceptible to hyperproliferation and keratoacanthoma (KA) development but is not sufficient for transformation and SCC development. We therefore propose that NF-κB activation in the absence of additional oncogenic events can promote TNF-dependent, actinic keratosis-like dysplasia and TNF-independent, KAs upon chemical carcinogensis. These studies suggest that resolution of KA cannot occur when NF-κB activation is constitutively enforced.

Finding the top influential bloggers based on productivity and popularity features

NASA Astrophysics Data System (ADS)

Khan, Hikmat Ullah; Daud, Ali

2017-07-01

A blog acts as a platform of virtual communication to share comments or views about products, events and social issues. Like other social web activities, blogging actions spread to a large number of people. Users influence others in many ways, such as buying a product, having a particular political or social opinion or initiating new activity. Finding the top influential bloggers is an active research domain as it helps us in various fields, such as online marketing, e-commerce, product search and e-advertisements. There exist various models to find the influential bloggers, but they consider limited features using non-modular approach. This paper proposes a new model, Popularity and Productivity Model (PPM), based on a modular approach to find the top influential bloggers. It consists of popularity and productivity modules which exploit various features. We discuss the role of each proposed and existing features and evaluate the proposed model against the standard baseline models using datasets from the real-world blogs. The analysis using standard performance evaluation measures verifies that both productivity and popularity modules play a vital role to find influential bloggers in blogging community in an effective manner.

Suppression of aberrant choroidal neovascularization through activation of the aryl hydrocarbon receptor.

PubMed

Choudhary, Mayur; Safe, Stephen; Malek, Goldis

2018-05-01

The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor, initially discovered for its role in regulating xenobiotic metabolism. There is extensive evidence supporting a multi-faceted role for AhR, modulating physiological pathways important in cell health and disease. Recently we demonstrated that the AhR plays a role in the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. We found that loss of AhR exacerbates choroidal neovascular (CNV) lesion formation in a murine model. Herein we tested the therapeutic impact of AhR activation on CNV lesion formation and factors associated with aberrant neovascularization. We screened a panel of synthetic drugs and endogenous AhR ligands, assessed their ability to activate AhR in choroidal endothelial cells, and inhibit angiogenesis in vitro. Drugs with an anti-angiogenic profile were then administered to a murine model of CNV. Two compounds, leflunomide and flutamide, significantly inhibited CNV formation concurrent with positive modifying effects on angiogenesis, inflammation, extracellular matrix remodeling, and fibrosis. These results validate the role of the AhR pathway in regulating CNV pathogenesis, identify mechanisms of AhR-based therapies in the eye, and argue in favor of developing AhR as a drug target for the treatment of neovascular AMD. Copyright © 2018 Elsevier B.V. All rights reserved.

HYPOTHALAMIC DIGOXIN AND SCHIZOPHRENIA - A MODEL FOR CONSCIOUS AND SUBLIMINAL PERCEPTION AND ITS DYSFUNCTION IN SCHIZOPHRENIA

PubMed Central

Kurup, Ravikumar A.; Augustine, Jyothi; Kurup, P.A.

1999-01-01

In view of reports of an upregulated cation pump in genetically related Bipolar Affective Disorders the role of hypothalamic digoxin, an endogenous regulator of the cation pump was studied with special reference to its role as a modulator of glycoprotein synthesis. The study demonstrated elevated serum digoxin levels, elevated HMG CoA reductase activity suggesting increased digoxin synthesis, reduced sodium-potassium ATPase activity and altered sugar residues of serum glycoprotein in schizophrenia. A hypothalamic digoxin mediated model for conscious and subliminal perception is proposed and the significance of its dysfunction due to abnormal glycoprotein induced synaptic connectivity defects in schizophrenia is discussed. PMID:21455390

NF-κB Activation Protects Oligodendrocytes against Inflammation

PubMed Central

Stone, Sarrabeth; Jamison, Stephanie; Yue, Yuan; Durose, Wilaiwan

2017-01-01

NF-κB is a key player in inflammatory diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the effects of NF-κB activation on oligodendrocytes in MS and EAE remain unknown. We generated a mouse model that expresses IκBαΔN, a super-suppressor of NF-κB, specifically in oligodendrocytes and demonstrated that IκBαΔN expression had no effect on oligodendrocytes under normal conditions (both sexes). Interestingly, we showed that oligodendrocyte-specific expression of IκBαΔN blocked NF-κB activation in oligodendrocytes and resulted in exacerbated oligodendrocyte death and hypomyelination in young, developing mice that express IFN-γ ectopically in the CNS (both sexes). We also showed that NF-κB inactivation in oligodendrocytes aggravated IFN-γ-induced remyelinating oligodendrocyte death and remyelination failure in the cuprizone model (male mice). Moreover, we found that NF-κB inactivation in oligodendrocytes increased the susceptibility of mice to EAE (female mice). These findings imply the cytoprotective effects of NF-κB activation on oligodendrocytes in MS and EAE. SIGNIFICANCE STATEMENT Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. NF-κB is a major player in inflammatory diseases that acts by regulating inflammation and cell viability. Data indicate that NF-κB activation in inflammatory cells facilitates the development of MS. However, to date, attempts to understand the role of NF-κB activation in oligodendrocytes in MS have been unsuccessful. Herein, we generated a mouse model that allows for inactivation of NF-κB specifically in oligodendrocytes and then used this model to determine the precise role of NF-κB activation in oligodendrocytes in models of MS. The results presented in this study represent the first demonstration that NF-κB activation acts cell autonomously to protect oligodendrocytes against inflammation in animal models of MS. PMID:28842413

Active learning in capstone design courses.

PubMed

Goldberg, Jay R

2012-01-01

There is a growing trend to encourage students to take a more active role in their own education. Many schools are moving away from the sage on the stage to the guide on the side model where the instructor is a facilitator of learning. In this model, the emphasis is more on learning and less on teaching, and it requires instructors to incorporate more active and student-centered learning methods into their courses. These methods include collaborative, cooperative, problem-based, and project-based learning.

Emerging role of the KCNT1 Slack channel in intellectual disability.

PubMed

Kim, Grace E; Kaczmarek, Leonard K

2014-01-01

The sodium-activated potassium KNa channels Slack and Slick are encoded by KCNT1 and KCNT2, respectively. These channels are found in neurons throughout the brain, and are responsible for a delayed outward current termed I KNa. These currents integrate into shaping neuronal excitability, as well as adaptation in response to maintained stimulation. Abnormal Slack channel activity may play a role in Fragile X syndrome, the most common cause for intellectual disability and inherited autism. Slack channels interact directly with the fragile X mental retardation protein (FMRP) and I KNa is reduced in animal models of Fragile X syndrome that lack FMRP. Human Slack mutations that alter channel activity can also lead to intellectual disability, as has been found for several childhood epileptic disorders. Ongoing research is elucidating the relationship between mutant Slack channel activity, development of early onset epilepsies and intellectual impairment. This review describes the emerging role of Slack channels in intellectual disability, coupled with an overview of the physiological role of neuronal I KNa currents.

Why Do Bystanders of Bullying Help or Not? A Multidimensional Model

ERIC Educational Resources Information Center

Pozzoli, Tiziana; Gini, Gianluca

2013-01-01

The authors employed Latane and Darley's model about bystanders' behavior to explain children's active defending and passive bystanding behavior in school bullying. The three central steps of the model were operationalized by measuring provictim attitudes, personal responsibility for intervention, and coping strategies. Moreover, the role of…

Interleukin-32 promotes detachment and activation of human Langerhans cells in a human skin explant model.

PubMed

Gonnet, J; Perrin, H; Hutton, A J; Boccara, D; Bonduelle, O; Mimoun, M; Atlan, M; Soria, A; Combadière, B

2018-05-28

Cross-talk between skin keratinocytes (KCs) and Langerhans cells (LCs) plays a fundamental role in the body's first line of immunological defences. However, the mechanism behind the interaction between these two major epidermal cells is unknown. Interleukin (IL)-32 is produced in inflammatory skin disorders. We questioned the role of IL-32 in the epidermis. We aimed to determine the role of IL-32 produced by KCs on surrounding LCs. We used an ex vivo human explant model from healthy donors and investigated the role of IL-32 on LC activation using imaging, flow cytometry, reverse transcriptase quantitative polymerase chain reaction and small interfering (si)RNA treatment. Modified vaccinia virus ankara (MVA) infection induced KC death alongside the early production of the proinflammatory cytokine IL-32. We demonstrated that IL-32 produced by MVA-infected KCs induced modest but significant morphological changes in LCs and downregulation of adhesion molecules, such as epithelial cell adhesion molecule and very late antigen-4, and CXCL10 production. The treatment of KCs with IL-32-specific siRNA, and anti-IL-32 blocking antibody significantly inhibited LC activation, demonstrating the role of IL-32 in LC activation. We also found that some Toll-like receptor ligands induced a very high level of IL-32 production by KCs, which initiated LC activation. We propose, for the first time, that IL-32 is a molecular link between KCs and LCs in healthy skin, provoking LC migration from the epidermis to the dermis prior to their migration to the draining lymph nodes. © 2018 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

The gender role motivation model of women's sexually submissive behavior and satisfaction in heterosexual couples.

PubMed

Sanchez, Diana T; Phelan, Julie E; Moss-Racusin, Corinne A; Good, Jessica J

2012-04-01

Previous findings suggest that women are more likely than men to take on the submissive role during sexual activities (e.g., waiting for their partner to initiate and orchestrate sexual activities), often to the detriment of their sexual satisfaction. Extending previous research on gender role motivation, the authors recruited 181 heterosexual couples to examine scripted sexual behavior, motivation for such behavior, and relationship outcomes (sexual satisfaction, perceptions of closeness, and relationship satisfaction) for both women and their partners. Using the actor-partner interdependence model, path analyses revealed that women's submissive behavior had negative links to personal sexual satisfaction and their partner's sexual satisfaction but only when their submission was inconsistent with their sexual preferences. Moreover, the authors show there are negative downstream consequences of diminished sexual satisfaction on perceptions of closeness and overall relationship satisfaction for both partners in the relationship.

An AKT activity threshold regulates androgen-dependent and androgen-independent PSA expression in prostate cancer cell lines.

PubMed

Paliouras, Miltiadis; Diamandis, Eleftherios P

2008-06-01

The androgen receptor (AR) plays an important role in early prostate cancer by activating transcription of a number of genes participating in cell proliferation and growth and cancer progression. However, as the cancer progresses, prostate cancer cells transform from an androgen-dependent to an androgen-independent state. Androgen-independent prostate cancer can manifest itself in several forms, including a percentage of cancers that show reduced levels of prostate-specific antigen (PSA) and can progress without the need for the ligand or active receptor. Therefore, our goal was to examine the role of intracellular signaling pathways in an androgen-independent prostate cancer in vitro model. Using the cell line PC3(AR)(2), we stimulated cells with 5-alpha-dihydrotestosterone (DHT) and epidermal growth factor (EGF) and then analyzed PSA expression. We observed lower PSA expression when cells were jointly stimulated with DHT and EGF, and this was associated with an increase in AKT activity. We examined the role of AKT in AR activity and PSA expression by creating stable PC3(AR)(2) cell lines transfected with a PI3K-Ras-effector loop mutant. These cell lines showed lower DHT-stimulated PSA expression that correlated to changes in the phosphorylated state of AR. Therefore, we propose an in vitro androgen-independent model in which a PI3K/AKT activity threshold and subsequent AR transactivation regulate PSA expression.

RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism.

PubMed

Aslanukov, Azamat; Bhowmick, Reshma; Guruju, Mallikarjuna; Oswald, John; Raz, Dorit; Bush, Ronald A; Sieving, Paul A; Lu, Xinrong; Bock, Cheryl B; Ferreira, Paulo A

2006-10-01

The Ran-binding protein 2 (RanBP2) is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of RanBP2 have been identified. Yet, the significance of these interactions with RanBP2 and the genetic and physiological role(s) of RanBP2 in a whole-animal model remain elusive. Here, we report the identification of two novel partners of RanBP2 and a novel physiological role of RanBP2 in a mouse model. RanBP2 associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis, hexokinase type I (HKI) via its leucine-rich domain. The leucine-rich domain of RanBP2 also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of RanBP2 in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and RanBP2 suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of RanBP2 and its role in HKI function, a mouse model harboring a genetically disrupted RanBP2 locus was generated. RanBP2(-/-) are embryonically lethal, and haploinsufficiency of RanBP2 in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred RanBP2(+/-) mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence, RanBP2 and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies.

The Role of Informal and Formal Leisure Activities in the Disablement Process

ERIC Educational Resources Information Center

Janke, Megan C.; Payne, Laura L.; Van Puymbroeck, Marieke

2008-01-01

The disablement process model has been used as a framework to investigate factors that accelerate or decelerate disablement among older adults. Although very little is known about the direct and moderating effects of involvement in leisure activities on the disablement process, research has suggested that participation in leisure activities may…

Effects of change in physical activity on physical function limitations in older women: mediating roles of physical function performance and self-efficacy.

PubMed

McAuley, Edward; Morris, Katherine S; Doerksen, Shawna E; Motl, Robert W; Liang, Hu; White, Siobhan M; Wójcicki, Thomas R; Rosengren, Karl

2007-12-01

To examine the hypothesis that changes in self-efficacy and functional performance mediate, in part, the beneficial effect of physical activity on functional limitations over time. Prospective, observational study. Community-based. Two hundred forty-nine community-dwelling older women. Participants completed measures of self-reported physical activity, functional limitations, and self-efficacy. Four measures of physical function performance were also assessed. Measures were completed at baseline and 24 months. Data were analyzed using a panel model within a covariance modeling framework. Results indicated that increases in physical activity over time were associated with greater improvements in self-efficacy, which was associated in turn with improved physical function performance, both of which mediated the association between physical activity and functional limitations. Fewer functional limitations at baseline were also associated with higher levels of self-efficacy at 24 months. Age, race, and health status covariates did not significantly change these relationships. The findings support the mediating roles of self-efficacy and physical function performance in the relationship between longitudinal changes in physical activity and functional limitations in older women.

Epistatic role of base excision repair and mismatch repair pathways in mediating cisplatin cytotoxicity

PubMed Central

Kothandapani, Anbarasi; Sawant, Akshada; Dangeti, Venkata Srinivas Mohan Nimai; Sobol, Robert W.; Patrick, Steve M.

2013-01-01

Base excision repair (BER) and mismatch repair (MMR) pathways play an important role in modulating cis-Diamminedichloroplatinum (II) (cisplatin) cytotoxicity. In this article, we identified a novel mechanistic role of both BER and MMR pathways in mediating cellular responses to cisplatin treatment. Cells defective in BER or MMR display a cisplatin-resistant phenotype. Targeting both BER and MMR pathways resulted in no additional resistance to cisplatin, suggesting that BER and MMR play epistatic roles in mediating cisplatin cytotoxicity. Using a DNA Polymerase β (Polβ) variant deficient in polymerase activity (D256A), we demonstrate that MMR acts downstream of BER and is dependent on the polymerase activity of Polβ in mediating cisplatin cytotoxicity. MSH2 preferentially binds a cisplatin interstrand cross-link (ICL) DNA substrate containing a mismatch compared with a cisplatin ICL substrate without a mismatch, suggesting a novel mutagenic role of Polβ in activating MMR in response to cisplatin. Collectively, these results provide the first mechanistic model for BER and MMR functioning within the same pathway to mediate cisplatin sensitivity via non-productive ICL processing. In this model, MMR participation in non-productive cisplatin ICL processing is downstream of BER processing and dependent on Polβ misincorporation at cisplatin ICL sites, which results in persistent cisplatin ICLs and sensitivity to cisplatin. PMID:23761438

Role of transforming growth factor-beta (TGF) beta in the physiopathology of rheumatoid arthritis.

PubMed

Gonzalo-Gil, Elena; Galindo-Izquierdo, María

2014-01-01

Transforming growth factor-beta (TGF-β) is a cytokine with pleiotropic functions in hematopoiesis, angiogenesis, cell proliferation, differentiation, migration and apoptosis. Although its role in rheumatoid arthritis is not well defined, TGF-β activation leads to functional immunomodulatory effects according to environmental conditions. The function of TGF-β in the development of arthritis in murine models has been extensively studied with controversial results. Recent findings point to a non-relevant role for TGF-β in a mice model of collagen-induced arthritis. The study of TGF-β on T-cell responses has shown controversial results as an inhibitor or promoter of the inflammatory response. This paper presents a review of the role of TGF-β in animal models of arthritis. Copyright © 2013 Elsevier España, S.L. All rights reserved.

The Role of Probability-Based Inference in an Intelligent Tutoring System.

ERIC Educational Resources Information Center

Mislevy, Robert J.; Gitomer, Drew H.

Probability-based inference in complex networks of interdependent variables is an active topic in statistical research, spurred by such diverse applications as forecasting, pedigree analysis, troubleshooting, and medical diagnosis. This paper concerns the role of Bayesian inference networks for updating student models in intelligent tutoring…

Role of Socializing Agents in Female Sport Involvement

ERIC Educational Resources Information Center

Greendorfer, Susan L.

1977-01-01

Research into the socializing of women into sports activities revealed that peers were most influential at all life-cycle stages, family was the most influential during childhood, and coaches and teachers during adolescence; in addition, males were the predominant role models during childhood, and females during adolescence and adult life. (MB)

Coding of visual object features and feature conjunctions in the human brain.

PubMed

Martinovic, Jasna; Gruber, Thomas; Müller, Matthias M

2008-01-01

Object recognition is achieved through neural mechanisms reliant on the activity of distributed coordinated neural assemblies. In the initial steps of this process, an object's features are thought to be coded very rapidly in distinct neural assemblies. These features play different functional roles in the recognition process--while colour facilitates recognition, additional contours and edges delay it. Here, we selectively varied the amount and role of object features in an entry-level categorization paradigm and related them to the electrical activity of the human brain. We found that early synchronizations (approx. 100 ms) increased quantitatively when more image features had to be coded, without reflecting their qualitative contribution to the recognition process. Later activity (approx. 200-400 ms) was modulated by the representational role of object features. These findings demonstrate that although early synchronizations may be sufficient for relatively crude discrimination of objects in visual scenes, they cannot support entry-level categorization. This was subserved by later processes of object model selection, which utilized the representational value of object features such as colour or edges to select the appropriate model and achieve identification.

Role of X-linked Inhibitor of Apoptosis in Breast Cancer

DTIC Science & Technology

2009-04-01

stimuli, and XIAP was a necessary anti -apoptotic molecule in these cells and required caspase-inhibitory residues D148 and W310 for this activity...cells to chemotherapeutic agents in breast cancer and a number of other cancers. In order to establish models in which to evaluate the role of XIAP in...xenograft models using cultured cell lines, in particular for the effects of in vitro cell culture on expression of pro- and anti -apoptotic proteins

The role of adrenal hormones in the activation of tryptophan 2,3-dioxygenase by nicotinic acid in rat liver.

PubMed

Sainio, E L

1997-09-01

In this study, our previous finding that nicotinic acid activates tryptophan 2,3-dioxygenase as strongly as tryptophan was investigated in further detail. This study focused on the role of the adrenals in the activation process. Adrenalectomy abolished the activation due to nicotinic acid, but not the activation caused by tryptophan. The role of corticoids and/or adrenomedullary hormones in the enzyme activation was studied, by supplementing these hormones in adrenalectomized rats using minipumps implanted under the skin. The results showed that the enhanced activity of tryptophan 2,3-dioxygenase caused by nicotinic acid was partly restored by adrenaline following adrenalectomy but not by corticosterone supplementation. The results were supported by further experiments in which the rats were treated with adrenaline or corticosterone intraperitoneally before nicotinic acid administration. The conclusion that adrenaline participates in the regulation of tryptophan 2,3-dioxygenase should promote further study to determine whether adrenaline is a general modulator of this enzyme. This experimental model generated new information on the activation mechanism of tryptophan 2,3-dioxygenase by nicotinic acid.

Position- and polarity-dependent Hippo signaling regulates cell fates in preimplantation mouse embryos.

PubMed

Sasaki, Hiroshi

2015-12-01

During the preimplantation stage, mouse embryos establish two cell lineages by the time of early blastocyst formation: the trophectoderm (TE) and the inner cell mass (ICM). Historical models have proposed that the establishment of these two lineages depends on the cell position within the embryo (e.g., the positional model) or cell polarization along the apicobasal axis (e.g., the polarity model). Recent findings have revealed that the Hippo signaling pathway plays a central role in the cell fate-specification process: active and inactive Hippo signaling in the inner and outer cells promote ICM and TE fates, respectively. Intercellular adhesion activates, while apicobasal polarization suppresses Hippo signaling, and a combination of these processes determines the spatially regulated activation of the Hippo pathway in 32-cell-stage embryos. Therefore, there is experimental evidence in favor of both positional and polarity models. At the molecular level, phosphorylation of the Hippo-pathway component angiomotin at adherens junctions (AJs) in the inner (apolar) cells activates the Lats protein kinase and triggers Hippo signaling. In the outer cells, however, cell polarization sequesters Amot from basolateral AJs and suppresses activation of the Hippo pathway. Other mechanisms, including asymmetric cell division and Notch signaling, also play important roles in the regulation of embryonic development. In this review, I discuss how these mechanisms cooperate with the Hippo signaling pathway during cell fate-specification processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

The role of titin in eccentric muscle contraction.

PubMed

Herzog, Walter

2014-08-15

Muscle contraction and force regulation in skeletal muscle have been thought to occur exclusively through the relative sliding of and the interaction between the contractile filaments actin and myosin. While this two-filament sarcomere model has worked well in explaining the properties of isometrically and concentrically contracting muscle, it has failed miserably in explaining experimental observations in eccentric contractions. Here, I suggest, and provide evidence, that a third filament, titin, is involved in force regulation of sarcomeres by adjusting its stiffness in an activation-dependent (calcium) and active force-dependent manner. Upon muscle activation, titin binds calcium at specific sites, thereby increasing its stiffness, and cross-bridge attachment to actin is thought to free up binding sites for titin on actin, thereby reducing titin's free-spring length, thus increasing its stiffness and force upon stretch of active muscle. This role of titin as a third force regulating myofilament in sarcomeres, although not fully proven, would account for many of the unexplained properties of eccentric muscle contraction, while simultaneously not affecting the properties predicted by the two-filament cross-bridge model in isometric and concentric muscle function. Here, I identify the problems of the two-filament sarcomere model and demonstrate the advantages of the three-filament model by providing evidence of titin's contribution to active force in eccentric muscle function. © 2014. Published by The Company of Biologists Ltd.

[Autism: educational models for a quality life].

PubMed

Tamarit, J

2005-01-15

Our aim is to describe the change that is taking place in the field of education in developmental disabilities from models centred on the clinical symptoms and on the limitations in the adaptive skills to models that focus on valuable personal results in terms of quality of life. In order to understand these changes, we outline some of the key points that have given rise to a particular cultural construction of disability and we also discuss how the situation is changing towards models aimed at achieving important personal results. In autism, as in the other developmental disorders, special emphasis has traditionally been placed on an education focusing on symptoms and on skills, and, although things are now beginning to head in that direction, little attention has been given to education based on the person and his or her quality of life. These changes imply new roles for the professionals attending these people. These roles involve combining technique with empathy and ethics, and they are more firmly based on the active role of individuals with autism, together with their rights, interests and opinions. Models of intervention must pay special attention to the pursuit of valuable personal results, which are oriented towards living a quality life and must involve the active participation of the individuals themselves as well as their relatives.

Do productive activities reduce inflammation in later life? Multiple roles, frequency of activities, and C-reactive protein.

PubMed

Kim, Seoyoun; Ferraro, Kenneth F

2014-10-01

The study investigates whether productive activities by older adults reduce bodily inflammation, as indicated by C-reactive protein (CRP), a biomeasure associated with the risk of cardiovascular diseases. The study uses a representative survey of adults aged 57-85 from the National Social Life, Health, and Aging Project (N = 1,790). Linear regression models were used to analyze the effects of multiple roles (employment, volunteering, attending meetings, and caregiving) and the frequency of activity within each role on log values of CRP concentration (mg/L) drawn from assayed blood samples. Number of roles for productive activities was associated with lower levels of CRP net of chronic conditions, lifestyle factors, and socioeconomic resources. When specific types of activity were examined, volunteering manifested the strongest association with lower levels of inflammation, particularly in the 70+ group. There was no evidence that frequent engagement in volunteer activity was associated with heightened inflammation. Productive activities-and frequent volunteering in particular-may protect individuals from inflammation that is associated with increased risk of hypertension and cardiovascular disease. © The Author 2013. 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.

Frequency of leisure activities and depressive symptomatology in elderly people: the moderating role of rumination.

PubMed

Fernández-Fernández, Virginia; Márquez-González, María; Losada-Baltar, Andrés; Romero-Moreno, Rosa

2014-02-01

The positive effects of leisure activities on depressive symptomatology are well known. However, the extent to which emotional regulation variables moderate that relationship has scarcely been studied, especially in older people. The aim of this study is to analyze the moderating role of rumination in the relation between leisure activities and depressive symptoms. Participants in this study were 311 people, aged 60 to 90 years (mean age: 71.27 years; SD: 6.99; 71.7% women). We evaluated depressive symptomatology, frequency of leisure activities, and rumination. We carried out a hierarchical regression analysis to confirm the moderating role of rumination. We obtained a model that explains 39.4% of the variance of depressive symptomatology. Main effects were found for the frequency of leisure activities (β = -0.397; p < 0.01) and for rumination (β = 0.497; p < 0.01). Moreover, we found a significant effect of the interaction between frequency of leisure activities and rumination (β = 0.110; p < 0.05), suggesting that rumination plays a moderating role in the relation between leisure activities and depressive symptomatology. A risk profile of elderly people may consist of those who engage in low levels of leisure activities but also use more frequently the dysfunctional emotional regulation strategy of rumination.

Social influences on eating and physical activity behaviours of urban, minority youths.

PubMed

Anderson Steeves, Elizabeth T; Johnson, Katherine A; Pollard, Suzanne L; Jones-Smith, Jessica; Pollack, Keshia; Lindstrom Johnson, Sarah; Hopkins, Laura; Gittelsohn, Joel

2016-12-01

Social relationships can impact youths' eating and physical activity behaviours; however, the best strategies for intervening in the social environment are unknown. The objectives of the present study were to provide in-depth information on the social roles that youths' parents and friends play related to eating and physical activity behaviours and to explore the impact of other social relationships on youths' eating and physical activity behaviours. Convergent parallel mixed-methods design. Low-income, African American, food desert neighbourhoods in Baltimore City, MD, USA. Data were collected from 297 youths (53 % female, 91 % African American, mean age 12·3 (sd 1·5) years) using structured questionnaires and combined with in-depth interviews from thirty-eight youths (42 % female, 97 % African American, mean age 11·4 (sd 1·5) years) and ten parents (80 % female, 50 % single heads of house, 100 % African American). Combined interpretation of the results found that parents and caregivers have multiple, dynamic roles influencing youths' eating and physical activity behaviours, such as creating health-promoting rules, managing the home food environment and serving as a role model for physical activity. Other social relationships have specific, but limited roles. For example, friends served as partners for physical activity, aunts provided exposure to novel food experiences, and teachers and doctors provided information related to eating and physical activity. Obesity prevention programmes should consider minority youths' perceptions of social roles when designing interventions. Specifically, future research is needed to test the effectiveness of intervention strategies that enhance or expand the supportive roles played by social relationships.

Dynamic change of SGK expression and its role in neuron apoptosis after traumatic brain injury.

PubMed

Wu, Xinmin; Mao, Hui; Liu, Jiao; Xu, Jian; Cao, Jianhua; Gu, Xingxing; Cui, Gang

2013-01-01

Activation of specific signaling pathways in response to mechanical trauma causes delayed neuronal apoptosis; GSK-3β/β-catenin signaling plays a critical role in the apoptosis of neurons in CNS diseases, SGK was discovered as a regulator of GSK-3β/β-catenin pathway, The goal of this study was to determine if the mechanism of cell death or survival mediated by the SGK/GSK-3β/β-catenin pathway is involved in a rat model of TBI. Here, an acute traumatic brain injury model was applied to investigate the expression change and possible roles of SGK, Expression of SGK, and total-GSK-3β, phospho-GSK3β on ser-9, beta-catenin, and caspase-3 were examined by immunohistochemistry and Western blot analysis. Double immunofluorescent staining was used to observe the SGK localizations. Si-RNA was performed to identify whether SGK regulates neuron apoptosis via GSK-3β/β-catenin pathway, ultimately inhibit caspase-3 activation. Temporally, SGK expression showed an increase pattern after TBI and reached a peak at day 3. Spatially, SGK was widely expressed in the neuron, rarely in astrocytes and oligodendrocytes; in addition, the expression patterns of active caspase-3 and phospho-GSK3β were parallel with that of SGK, at the same time, the expression of β-catenin shows similarity with SGK. In vitro, to further investigate the function of SGK, a neuronal cell line PC12 was employed to establish an apoptosis model. We analyzed the association of SGK with apoptosis on PC12 cells by western blot, immunofluorescent labeling and siRNA. the results implied that SGK plays an important role in neuron apoptosis via the regulation of GSK3β/β-catenin signaling pathway; ultimately inhibit caspase-3 activation. Taken together, we inferred traumatic brain injury induced an upregulation of SGK in the central nervous system, which show a protective role in neuron apoptosis.

Role of co-regulators in metabolic and transcriptional actions of thyroid hormone.

PubMed

Astapova, Inna

2016-04-01

Thyroid hormone (TH) controls a wide range of physiological processes through TH receptor (TR) isoforms. Classically, TRs are proposed to function as tri-iodothyronine (T3)-dependent transcription factors: on positively regulated target genes, unliganded TRs mediate transcriptional repression through recruitment of co-repressor complexes, while T3 binding leads to dismissal of co-repressors and recruitment of co-activators to activate transcription. Co-repressors and co-activators were proposed to play opposite roles in the regulation of negative T3 target genes and hypothalamic-pituitary-thyroid axis, but exact mechanisms of the negative regulation by TH have remained elusive. Important insights into the roles of co-repressors and co-activators in different physiological processes have been obtained using animal models with disrupted co-regulator function. At the same time, recent studies interrogating genome-wide TR binding have generated compelling new data regarding effects of T3, local chromatin structure, and specific response element configuration on TR recruitment and function leading to the proposal of new models of transcriptional regulation by TRs. This review discusses data obtained in various mouse models with manipulated function of nuclear receptor co-repressor (NCoR or NCOR1) and silencing mediator of retinoic acid receptor and thyroid hormone receptor (SMRT or NCOR2), and family of steroid receptor co-activators (SRCs also known as NCOAs) in the context of TH action, as well as insights into the function of co-regulators that may emerge from the genome-wide TR recruitment analysis. © 2016 Society for Endocrinology.

Growing up and role modeling: a theory in Iranian nursing students' education.

PubMed

Mokhtari Nouri, Jamileh; Ebadi, Abbas; Alhani, Fatemeh; Rejeh, Nahid

2014-11-16

One of the key strategies in students' learning is being affected by models. Understanding the role-modeling process in education will help to make greater use of this training strategy. The aim of this grounded theory study was to explore Iranian nursing students and instructors' experiences about role modeling process. Data was analyzed by Glaserian's Grounded Theory methodology through semi-structured interviews with 7 faculty members, 2 nursing students; the three focus group discussions with 20 nursing students based on purposive and theoretical sampling was done for explaining role modeling process from four nursing faculties in Tehran. Through basic coding, an effort to comprehensive growth and excellence was made with the basic social process consisting the core category and through selective coding three phases were identified as: realizing and exposure to inadequate human and professional growth, facilitating human and professional growth and evolution. The role modeling process is taking place unconscious, involuntary, dynamic and with positive progressive process in order to facilitate overall growth in nursing student. Accordingly, the design and implementation of the designed model can be used to make this unconscious to conscious, active and voluntarily processes a process to help education administrators of nursing colleges and supra organization to prevent threats to human and professional in nursing students' education and promote nursing students' growth.

SPARC's Stratospheric Sulfur and its Role in Climate Activity (SSiRC)

NASA Technical Reports Server (NTRS)

Thomason, Larry

2015-01-01

The stratospheric aerosol layer is a key component in the climate system. It affects the radiative balance of the atmosphere directly through interactions with solar and terrestrial radiation, and indirectly through its effect on stratospheric ozone. Because the stratospheric aerosol layer is prescribed in many climate models and Chemistry-Climate Models (CCMs), model simulations of future atmospheric conditions and climate generally do not account for the interaction between the aerosol-sulfur cycle and changes in the climate system. The present understanding of how the stratospheric aerosol layer may be affected by future climate change and how the stratospheric aerosol layer may drive climate change is, therefore, very limited. The purposes of SSiRC (Stratospheric Sulfur and its Role in Climate) include: (i) providing a coordinating structure for the various individual activities already underway in different research centers; (ii) encouraging and supporting new instrumentation and measurements of sulfur containing compounds, such as COS, DMS, and non-volcanic SO2 in the UT/LS globally; and (iii) initiating new model/data inter-comparisons. SSiRC is developing collaborations with a number of other SPARC activities including CCMI and ACAM. This presentation will highlight the scientific goals of this project and on-going activities and propose potential interactions between SSiRC and ACAM.

A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease

PubMed Central

Bagnara, Davide; Kaufman, Matthew S.; Calissano, Carlo; Marsilio, Sonia; Patten, Piers E. M.; Simone, Rita; Chum, Philip; Yan, Xiao-Jie; Allen, Steven L.; Kolitz, Jonathan E.; Baskar, Sivasubramanian; Rader, Christoph; Mellstedt, Hakan; Rabbani, Hodjattallah; Lee, Annette; Gregersen, Peter K.; Rai, Kanti R.

2011-01-01

Chronic lymphocytic leukemia (CLL) is an incurable adult disease of unknown etiology. Understanding the biology of CLL cells, particularly cell maturation and growth in vivo, has been impeded by lack of a reproducible adoptive transfer model. We report a simple, reproducible system in which primary CLL cells proliferate in nonobese diabetes/severe combined immunodeficiency/γcnull mice under the influence of activated CLL-derived T lymphocytes. By cotransferring autologous T lymphocytes, activated in vivo by alloantigens, the survival and growth of primary CFSE-labeled CLL cells in vivo is achieved and quantified. Using this approach, we have identified key roles for CD4+ T cells in CLL expansion, a direct link between CD38 expression by leukemic B cells and their activation, and support for CLL cells preferentially proliferating in secondary lymphoid tissues. The model should simplify analyzing kinetics of CLL cells in vivo, deciphering involvement of nonleukemic elements and nongenetic factors promoting CLL cell growth, identifying and characterizing potential leukemic stem cells, and permitting preclinical studies of novel therapeutics. Because autologous activated T lymphocytes are 2-edged swords, generating unwanted graph-versus-host and possibly autologous antitumor reactions, the model may also facilitate analyses of T-cell populations involved in immune surveillance relevant to hematopoietic transplantation and tumor cytoxicity. PMID:21385850

Results of an Oncology Clinical Trial Nurse Role Delineation Study.

PubMed

Purdom, Michelle A; Petersen, Sandra; Haas, Barbara K

2017-09-01

To evaluate the relevance of a five-dimensional model of clinical trial nursing practice in an oncology clinical trial nurse population. 
. Web-based cross-sectional survey.
. Online via Qualtrics.
. 167 oncology nurses throughout the United States, including 41 study coordinators, 35 direct care providers, and 91 dual-role nurses who provide direct patient care and trial coordination.
. Principal components analysis was used to determine the dimensions of oncology clinical trial nursing practice.
. Self-reported frequency of 59 activities.
. The results did not support the original five-dimensional model of nursing care but revealed a more multidimensional model.
. An analysis of frequency data revealed an eight-dimensional model of oncology research nursing, including care, manage study, expert, lead, prepare, data, advance science, and ethics.
. This evidence-based model expands understanding of the multidimensional roles of oncology nurses caring for patients with cancer enrolled in clinical trials.

Successfully performing a university student's role despite disabilities: challenges of an inclusive environment and appropriate task modification.

PubMed

Rochette, Annie; Loiselle, Frederic

2012-01-01

To reflect on what it means to successfully perform a university student's role despite the presence of impairments. The Disability Creation Process (DCP) model is used as a tool to zoom in the different activities and tasks required for a successful education as well as to describe how the social and physical environment can be as inclusive as possible to compensate for different impairments. One activity in the student's role (reading) is used to illustrate and reflect on potential challenges in compensating for impairments by way of environmental or task modifications. The student's role is a complex one, characterized by different actions such as getting admitted, moving around, attending courses, studying and participating in student life. Environmental factors or time can facilitate or impede the level of participation in the education domain. One challenge may be to differentiate between compensation for learning (processes) as compared to outcomes (competency level for future employment) as well as to determine how much assistance is acceptable. Intuitive single-case analysis should be replaced by a systematic analysis relying on a conceptual model such as the DCP. To avoid discrimination and to ensure transparency, acceptable amount of compensation for an activity should be defined.

Daily Physical Activity and Hot Flashes in the Study of Women's Health Across the Nation FLASHES Study

PubMed Central

Gibson, Carolyn; Matthews, Karen; Thurston, Rebecca

2014-01-01

Objective To examine the role of physical activity in menopausal hot flashes. Competing models conceptualize physical activity as a risk or protective factor for hot flashes. Few studies have examined this relationship prospectively using physiologic measures of hot flashes and physical activity. Design Over two 48 hour-periods, 51 participants wore a physiologic hot flash monitor and activity monitor, and reported their hot flashes in an electronic diary. Physiologic hot flashes, reported hot flashes and reported hot flashes without physiological corroboration were related to activity changes using hierarchical generalized linear modeling, adjusting for potential confounders. Setting Community. Patients Midlife women. Interventions None. Main Outcome Measures Physiologically-detected hot flashes and reported hot flashes with and without physiologic corroboration. Results Hot flash reports without physiologic corroboration were more likely after activity increases (OR 1.04, 95% CI: 1.00-1.10, p=.01), particularly among women with higher levels of depressive symptoms (interaction p=.02). No other types of hot flashes were related to physical activity. Conclusion Acute increases in physical activity were associated with increased reporting of hot flashes lacking physiologic corroboration, particularly among women with depressive symptoms. Clinicians should consider the role of symptom perception and reporting in relations between physical activity and hot flashes. PMID:24491454

[Adsorption of a dye by sludges and the roles of extracellular polymeric substances].

PubMed

Kong, Wang-sheng; Liu, Yan

2007-12-01

This paper investigated the adsorption of a dye, acid turquoise blue A, by four kinds of sludges including activated sludge, anaerobic sludge, dried activated sludge, and dried anaerobic sludge, respectively. The roles of extracellular polymeric substances (EPS) including the soluble EPS (SEPS) and bound EPS (BEPS) for the biosorption of activated sludge and anaerobic sludge were further studied. Results show that the relation between four kinds of sludge adsorption amount and remained concentration of the dye fitted well both Freundlich model (R2: 0.921-0.995) and Langmuir model (R2: 0.958-0.993), but not quite fitted BET model (R2: 0.07-0.863). The adsorption capability of dried anaerobic sludge ranked the highest, and dried activated sludge was the lowest. According to Langmuir isotherm, the maximum adsorption amount of dried anaerobic, anaerobic, activated, and dried activated sludge was 104 mg/g, 86 mg/g, 65 mg/g, 20 mg/g, respectively. The amount of the dye found in EPS for both activated sludge and anaerobic sludge were over 50%, illustrating that EPS adsorption was predominant in adsorption of the dye by sludge. The amount of adsorbed dye by BEPS was greater than that by SEPS for anaerobic sludge, but for activated sludge the result was quite opposite. The amount of adsorbed dye by unit mass SEPS was much higher than the corresponding values of BEPS for both sludges. The average amount of adsorbed dye by unit mass SEPS was 52 times of the corresponding value of BEPS for activated sludge, and 10 times for anaerobic sludge. The relation between adsorption amount of dye by BEPS from anaerobic sludge and remained concentration of the dye in mixed liquor was best fitted to Langmuir model (R2: 0.9986).

Activities, self-referent memory beliefs, and cognitive performance: evidence for direct and mediated relations.

PubMed

Jopp, Daniela; Hertzog, Christopher

2007-12-01

In this study, the authors investigated the role of activities and self-referent memory beliefs for cognitive performance in a life-span sample. A factor analysis identified 8 activity factors, including Developmental Activities, Experiential Activities, Social Activities, Physical Activities, Technology Use, Watching Television, Games, and Crafts. A second-order general activity factor was significantly related to a general factor of cognitive function as defined by ability tests. Structural regression models suggested that prediction of cognition by activity level was partially mediated by memory beliefs, controlling for age, education, health, and depressive affect. Models adding paths from general and specific activities to aspects of crystallized intelligence suggested additional unique predictive effects for some activities. In alternative models, nonsignificant effects of beliefs on activities were detected when cognition predicted both variables, consistent with the hypothesis that beliefs derive from monitoring cognition and have no influence on activity patterns. PsycINFO Database Record (c) 2008 APA, all rights reserved.

From homeostasis to behavior: Balanced activity in an exploration of embodied dynamic environmental-neural interaction.

PubMed

Hellyer, Peter John; Clopath, Claudia; Kehagia, Angie A; Turkheimer, Federico E; Leech, Robert

2017-08-01

In recent years, there have been many computational simulations of spontaneous neural dynamics. Here, we describe a simple model of spontaneous neural dynamics that controls an agent moving in a simple virtual environment. These dynamics generate interesting brain-environment feedback interactions that rapidly destabilize neural and behavioral dynamics demonstrating the need for homeostatic mechanisms. We investigate roles for homeostatic plasticity both locally (local inhibition adjusting to balance excitatory input) as well as more globally (regional "task negative" activity that compensates for "task positive", sensory input in another region) balancing neural activity and leading to more stable behavior (trajectories through the environment). Our results suggest complementary functional roles for both local and macroscale mechanisms in maintaining neural and behavioral dynamics and a novel functional role for macroscopic "task-negative" patterns of activity (e.g., the default mode network).

King Chulalongkorn: biography and his activities in medicine and public health.

PubMed

Charulukananan, Somrat; Sueblinvong, Tada

2003-06-01

King Rama V, or Chulalongkorn, was the fifth monarch of the Chakri Dynasty. He was one of the most beloved of the Thai kings due to his many activities including abolishing slavery without bloodshed and especially his skillful diplomacy which succeeded in steering Siam out of the grips of the colonial powers. His activities also included reform of the administration of the kingdom according to the European model and in bringing Siam into the modern era with such exquisite skills that he is still vividly remembered today. His reign also saw many developments in medicine and public health. The King's role in these areas, however, were clouded by his more visible activities in politics and diplomacy. The result is that the Thai public learned rather little about his role in these areas. This article aims at collecting this and to show the King's very important role in modernizing medicine and public health in Siam.

Determining the optimal model for role-substitution in NHS dental services in the United Kingdom.

PubMed

Brocklehurst, Paul; Birch, Stephen; McDonald, Ruth; Tickle, Martin

2013-09-24

Role-substitution describes a model of dental care where Dental Care Professionals (DCPs) provide some of the clinical activity previously undertaken by General Dental Practitioners. This has the potential to increase technical efficiency, the capacity to care and reduce costs. Technical efficiency is defined as the production of the maximum amount of output from a given amount of input so that the service operates at the production frontier i.e. optimal level of productivity. Academic research into technical efficiency is becoming increasingly utilised in health care, although no studies have investigated the efficiency of NHS dentistry or role-substitution in high-street dental practices. The aim of this study is to examine the barriers and enablers that exist for role-substitution in general dental practices in the NHS and to determine the most technically efficient model for role-substitution. A screening questionnaire will be sent to DCPs to determine the type and location of role-substitutive models employed in NHS dental practices in the United Kingdom (UK). Semi-structured interviews will then be conducted with practice owners, DCPs and patients at selected sites identified by the questionnaire. Detail will be recorded about the organisational structure of the dental team, the number of NHS hours worked and the clinical activity undertaken. The interviews will continue until saturation and will record the views and attitudes of the members of the dental team. Final numbers of interviews will be determined by saturation.The second work-stream will examine the technical efficiency of the selected practices using Data Envelopment Analysis and Stochastic Frontier Modeling. The former is a non-parametric technique and is considered to be a highly flexible approach for applied health applications. The latter is parametric and is based on frontier regression models that estimate a conventional cost function. Maximising health for a given level and mix of resources is an ethical imperative for health service planners. This study will determine the technical efficiency of role-substitution and so address one of the key recommendations of the Independent Review of NHS dentistry in England.

Determining the optimal model for role-substitution in NHS dental services in the United Kingdom

PubMed Central

2013-01-01

Background Role-substitution describes a model of dental care where Dental Care Professionals (DCPs) provide some of the clinical activity previously undertaken by General Dental Practitioners. This has the potential to increase technical efficiency, the capacity to care and reduce costs. Technical efficiency is defined as the production of the maximum amount of output from a given amount of input so that the service operates at the production frontier i.e. optimal level of productivity. Academic research into technical efficiency is becoming increasingly utilised in health care, although no studies have investigated the efficiency of NHS dentistry or role-substitution in high-street dental practices. The aim of this study is to examine the barriers and enablers that exist for role-substitution in general dental practices in the NHS and to determine the most technically efficient model for role-substitution. Methods/design A screening questionnaire will be sent to DCPs to determine the type and location of role-substitutive models employed in NHS dental practices in the United Kingdom (UK). Semi-structured interviews will then be conducted with practice owners, DCPs and patients at selected sites identified by the questionnaire. Detail will be recorded about the organisational structure of the dental team, the number of NHS hours worked and the clinical activity undertaken. The interviews will continue until saturation and will record the views and attitudes of the members of the dental team. Final numbers of interviews will be determined by saturation. The second work-stream will examine the technical efficiency of the selected practices using Data Envelopment Analysis and Stochastic Frontier Modeling. The former is a non-parametric technique and is considered to be a highly flexible approach for applied health applications. The latter is parametric and is based on frontier regression models that estimate a conventional cost function. Discussion Maximising health for a given level and mix of resources is an ethical imperative for health service planners. This study will determine the technical efficiency of role-substitution and so address one of the key recommendations of the Independent Review of NHS dentistry in England. PMID:24063247

BehavePlus fire modeling system: Past, present, and future

Treesearch

Patricia L. Andrews

2007-01-01

Use of mathematical fire models to predict fire behavior and fire effects plays an important supporting role in wildland fire management. When used in conjunction with personal fire experience and a basic understanding of the fire models, predictions can be successfully applied to a range of fire management activities including wildfire behavior prediction, prescribed...

Notable Mexican American Women.

ERIC Educational Resources Information Center

Ford, Judith

This paper describes the careers of four notable Mexican American women, including their educational and family backgrounds, achievements, and importance as role models for young Hispanic women. Marie Acosta-Colon's political activism began as a college student volunteering for presidential candidate Eugene McCarthy in 1968. Active in political…

Topical Review: Translating Translational Research in Behavioral Science.

PubMed

Hommel, Kevin A; Modi, Avani C; Piazza-Waggoner, Carrie; Myers, James D

2015-01-01

To present a model of translational research for behavioral science that communicates the role of behavioral research at each phase of translation. A task force identified gaps in knowledge regarding behavioral translational research processes and made recommendations regarding advancement of knowledge. A comprehensive model of translational behavioral research was developed. This model represents T1, T2, and T3 research activities, as well as Phase 1, 2, 3, and 4 clinical trials. Clinical illustrations of translational processes are also offered as support for the model. Behavioral science has struggled with defining a translational research model that effectively articulates each stage of translation and complements biomedical research. Our model defines key activities at each phase of translation from basic discovery to dissemination/implementation. This should be a starting point for communicating the role of behavioral science in translational research and a catalyst for better integration of biomedical and behavioral research. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Active Role of the Ocean in the Temporal Evolution of Climate Sensitivity

DOE PAGES

Garuba, Oluwayemi A.; Lu, Jian; Liu, Fukai; ...

2017-11-30

Here, the temporal evolution of the effective climate sensitivity is shown to be influenced by the changing pattern of sea surface temperature (SST) and ocean heat uptake (OHU), which in turn have been attributed to ocean circulation changes. A set of novel experiments are performed to isolate the active role of the ocean by comparing a fully coupled CO 2 quadrupling community Earth System Model (CESM) simulation against a partially coupled one, where the effect of the ocean circulation change and its impact on surface fluxes are disabled. The active OHU is responsible for the reduced effective climate sensitivity andmore » weaker surface warming response in the fully coupled simulation. The passive OHU excites qualitatively similar feedbacks to CO 2 quadrupling in a slab ocean model configuration due to the similar SST spatial pattern response in both experiments. Additionally, the nonunitary forcing efficacy of the active OHU (1.7) explains the very different net feedback parameters in the fully and partially coupled responses.« less

The Active Role of the Ocean in the Temporal Evolution of Climate Sensitivity

NASA Astrophysics Data System (ADS)

Garuba, Oluwayemi A.; Lu, Jian; Liu, Fukai; Singh, Hansi A.

2018-01-01

The temporal evolution of the effective climate sensitivity is shown to be influenced by the changing pattern of sea surface temperature (SST) and ocean heat uptake (OHU), which in turn have been attributed to ocean circulation changes. A set of novel experiments are performed to isolate the active role of the ocean by comparing a fully coupled CO2 quadrupling community Earth System Model (CESM) simulation against a partially coupled one, where the effect of the ocean circulation change and its impact on surface fluxes are disabled. The active OHU is responsible for the reduced effective climate sensitivity and weaker surface warming response in the fully coupled simulation. The passive OHU excites qualitatively similar feedbacks to CO2 quadrupling in a slab ocean model configuration due to the similar SST spatial pattern response in both experiments. Additionally, the nonunitary forcing efficacy of the active OHU (1.7) explains the very different net feedback parameters in the fully and partially coupled responses.

The Active Role of the Ocean in the Temporal Evolution of Climate Sensitivity

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

Garuba, Oluwayemi A.; Lu, Jian; Liu, Fukai

Here, the temporal evolution of the effective climate sensitivity is shown to be influenced by the changing pattern of sea surface temperature (SST) and ocean heat uptake (OHU), which in turn have been attributed to ocean circulation changes. A set of novel experiments are performed to isolate the active role of the ocean by comparing a fully coupled CO 2 quadrupling community Earth System Model (CESM) simulation against a partially coupled one, where the effect of the ocean circulation change and its impact on surface fluxes are disabled. The active OHU is responsible for the reduced effective climate sensitivity andmore » weaker surface warming response in the fully coupled simulation. The passive OHU excites qualitatively similar feedbacks to CO 2 quadrupling in a slab ocean model configuration due to the similar SST spatial pattern response in both experiments. Additionally, the nonunitary forcing efficacy of the active OHU (1.7) explains the very different net feedback parameters in the fully and partially coupled responses.« less

Complement in the Initiation and Evolution of Rheumatoid Arthritis

PubMed Central

Holers, V. Michael; Banda, Nirmal K.

2018-01-01

The complement system is a major component of the immune system and plays a central role in many protective immune processes, including circulating immune complex processing and clearance, recognition of foreign antigens, modulation of humoral and cellular immunity, removal of apoptotic and dead cells, and engagement of injury resolving and tissue regeneration processes. In stark contrast to these beneficial roles, however, inadequately controlled complement activation underlies the pathogenesis of human inflammatory and autoimmune diseases, including rheumatoid arthritis (RA) where the cartilage, bone, and synovium are targeted. Recent studies of this disease have demonstrated that the autoimmune response evolves over time in an asymptomatic preclinical phase that is associated with mucosal inflammation. Notably, experimental models of this disease have demonstrated that each of the three major complement activation pathways plays an important role in recognition of injured joint tissue, although the lectin and amplification pathways exhibit particularly impactful roles in the initiation and amplification of damage. Herein, we review the complement system and focus on its multi-factorial role in human patients with RA and experimental murine models. This understanding will be important to the successful integration of the emerging complement therapeutics pipeline into clinical care for patients with RA. PMID:29892280

A Redundant Role of Human Thyroid Peroxidase Propeptide for Cellular, Enzymatic, and Immunological Activity

PubMed Central

Góra, Monika; Buckle, Ashley M.; Porebski, Benjamin T.; Kemp, E. Helen; Sutton, Brian J.; Czarnocka, Barbara; Banga, J. Paul

2014-01-01

Background: Thyroid peroxidase (TPO) is a dimeric membrane-bound enzyme of thyroid follicular cells, responsible for thyroid hormone biosynthesis. TPO is also a common target antigen in autoimmune thyroid disease (AITD). With two active sites, TPO is an unusual enzyme, and thus there is much interest in understanding its structure and role in AITD. Homology modeling has shown TPO to be composed of different structural modules, as well as a propeptide sequence. During the course of studies to obtain homogeneous preparations of recombinant TPO for structural studies, we investigated the role of the large propeptide sequence in TPO. Methods: An engineered recombinant human TPO preparation expressed in Chinese hamster ovary (CHO) cells lacking the propeptide (TPOΔpro; amino acid residues 21–108) was characterized and its properties compared to wild-type TPO. Plasma membrane localization was determined by cell surface protein biotinylation, and biochemical studies were performed to evaluate enzymatic activity and the effect of deglycosylation. Immunological investigations using autoantibodies from AITD patients and other epitope-specific antibodies that recognize conformational determinants on TPO were evaluated for binding to TPOΔpro by flow cytometry, immunocytochemistry, and capture enzyme-linked immunosorbent assay. Molecular modeling and dynamics simulation of TPOΔpro comprising a dimer of myeloperoxidase-like domains was performed in order to investigate the impact of propeptide removal and the role of glycosylation. Results: The TPOΔpro was expressed on the cell surface at comparable levels to wild-type TPO. The TPOΔpro was enzymatically active and recognized by patients' autoantibodies and a panel of epitope-specific antibodies, confirming structural integrity of the two major conformational determinants recognized by autoantibodies. Faithful intracellular trafficking and N-glycosylation of TPOΔpro was also maintained. Molecular modeling and dynamics simulations were consistent with these observations. Conclusions: Our results point to a redundant role for the propeptide sequence in TPO. The successful expression of TPOΔpro in a membrane-anchored, enzymatically active form that is insensitive to intramolecular proteolysis, and importantly is recognized by patients' autoantibodies, is a key advance for purification of substantial quantities of homogeneous preparation of TPO for crystallization, structural, and immunological studies. PMID:23668778

A redundant role of human thyroid peroxidase propeptide for cellular, enzymatic, and immunological activity.

PubMed

Godlewska, Marlena; Góra, Monika; Buckle, Ashley M; Porebski, Benjamin T; Kemp, E Helen; Sutton, Brian J; Czarnocka, Barbara; Banga, J Paul

2014-02-01

Thyroid peroxidase (TPO) is a dimeric membrane-bound enzyme of thyroid follicular cells, responsible for thyroid hormone biosynthesis. TPO is also a common target antigen in autoimmune thyroid disease (AITD). With two active sites, TPO is an unusual enzyme, and thus there is much interest in understanding its structure and role in AITD. Homology modeling has shown TPO to be composed of different structural modules, as well as a propeptide sequence. During the course of studies to obtain homogeneous preparations of recombinant TPO for structural studies, we investigated the role of the large propeptide sequence in TPO. An engineered recombinant human TPO preparation expressed in Chinese hamster ovary (CHO) cells lacking the propeptide (TPOΔpro; amino acid residues 21-108) was characterized and its properties compared to wild-type TPO. Plasma membrane localization was determined by cell surface protein biotinylation, and biochemical studies were performed to evaluate enzymatic activity and the effect of deglycosylation. Immunological investigations using autoantibodies from AITD patients and other epitope-specific antibodies that recognize conformational determinants on TPO were evaluated for binding to TPOΔpro by flow cytometry, immunocytochemistry, and capture enzyme-linked immunosorbent assay. Molecular modeling and dynamics simulation of TPOΔpro comprising a dimer of myeloperoxidase-like domains was performed in order to investigate the impact of propeptide removal and the role of glycosylation. The TPOΔpro was expressed on the cell surface at comparable levels to wild-type TPO. The TPOΔpro was enzymatically active and recognized by patients' autoantibodies and a panel of epitope-specific antibodies, confirming structural integrity of the two major conformational determinants recognized by autoantibodies. Faithful intracellular trafficking and N-glycosylation of TPOΔpro was also maintained. Molecular modeling and dynamics simulations were consistent with these observations. Our results point to a redundant role for the propeptide sequence in TPO. The successful expression of TPOΔpro in a membrane-anchored, enzymatically active form that is insensitive to intramolecular proteolysis, and importantly is recognized by patients' autoantibodies, is a key advance for purification of substantial quantities of homogeneous preparation of TPO for crystallization, structural, and immunological studies.

Systems analysis of effector caspase activation and its control by X-linked inhibitor of apoptosis protein

PubMed Central

Rehm, Markus; Huber, Heinrich J; Dussmann, Heiko; Prehn, Jochen H M

2006-01-01

Activation of effector caspases is a final step during apoptosis. Single-cell imaging studies have demonstrated that this process may occur as a rapid, all-or-none response, triggering a complete substrate cleavage within 15 min. Based on biochemical data from HeLa cells, we have developed a computational model of apoptosome-dependent caspase activation that was sufficient to remodel the rapid kinetics of effector caspase activation observed in vivo. Sensitivity analyses predicted a critical role for caspase-3-dependent feedback signalling and the X-linked-inhibitor-of-apoptosis-protein (XIAP), but a less prominent role for the XIAP antagonist Smac. Single-cell experiments employing a caspase fluorescence resonance energy transfer substrate verified these model predictions qualitatively and quantitatively. XIAP was predicted to control this all-or-none response, with concentrations as high as 0.15 μM enabling, but concentrations >0.30 μM significantly blocking substrate cleavage. Overexpression of XIAP within these threshold concentrations produced cells showing slow effector caspase activation and submaximal substrate cleavage. Our study supports the hypothesis that high levels of XIAP control caspase activation and substrate cleavage, and may promote apoptosis resistance and sublethal caspase activation in vivo. PMID:16932741

Physiological roles of STIM1 and Orai1 homologs and CRAC channels in the genetic model organism Caenorhabditis elegans

PubMed Central

Strange, Kevin; Yan, Xiaohui; Lorin-Nebel, Catherine; Xing, Juan

2007-01-01

Summary The nematode Caenorhabditis elegans provides numerous experimental advantages for developing an integrative molecular understanding of physiological processes and has proven to be a valuable model for characterizing Ca2+ signaling mechanisms. This review will focus on the role of Ca2+ release activated Ca2+ (CRAC) channel activity in function of the worm gonad and intestine. Inositol 1,4,5-trisphosphate (IP3)-dependent oscillatory Ca2+ signaling regulates contractile activity of the gonad and rhythmic posterior body wall muscle contraction (pBoc) required for ovulation and defecation, respectively. The C. elegans genome contains a single homolog of both STIM1 and Orai1, proteins required for CRAC channel function in mammalian and Drosophila cells. C. elegans STIM-1 and ORAI-1 are coexpressed in the worm gonad and intestine and give rise to robust CRAC channel activity when coexpressed in HEK293 cells. STIM-1 or ORAI-1 knockdown causes complete sterility demonstrating that the genes are essential components of gonad Ca2+ signaling. Knockdown of either protein dramatically inhibits intestinal cell CRAC channel activity, but surprisingly has no effect on pBoc, intestinal Ca2+ oscillations or intestinal ER Ca2+ store homeostasis. CRAC channels thus do not play obligate roles in all IP3-dependent signaling processes in C. elegans. Instead, we suggest that CRAC channels carry out highly specialized and cell specific signaling roles and that they may function as a failsafe mechanism to prevent Ca2+ store depletion under pathophysiological and stress conditions. PMID:17376526

Trivalent methylated arsenical-induced phosphatidylserine exposure and apoptosis in platelets may lead to increased thrombus formation

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

Bae, Ok-Nam; Lim, Kyung-Min; AMOREPACIFIC CO/R and D Center, Gyeonggi-do 446-729

2009-09-01

Trivalent methylated metabolites of arsenic, monomethylarsonous acid (MMA{sup III}) and dimethylarsinous acid (DMA{sup III}), have been found highly reactive and toxic in various cells and in vivo animal models, suggesting their roles in the arsenic-associated toxicity. However, their effects on cardiovascular system including blood cells, one of the most important targets for arsenic toxicity, remain poorly understood. Here we found that MMA{sup III} and DMA{sup III} could induce procoagulant activity and apoptosis in platelets, which play key roles in the development of various cardiovascular diseases (CVDs) through excessive thrombus formation. In freshly isolated human platelets, treatment of MMA{sup III} resultedmore » in phosphatidylserine (PS) exposure, a hallmark of procoagulant activation, accompanied by distinctive apoptotic features including mitochondrial membrane potential disruption, cytochrome c release, and caspase-3 activation. These procoagulant activation and apoptotic features were found to be mediated by the depletion of protein thiol and intracellular ATP, and flippase inhibition by MMA{sup III}, while the intracellular calcium increase or reactive oxygen species generation was not involved. Importantly, increased platelet procoagulant activity by MMA{sup III} resulted in enhanced blood coagulation and excessive thrombus formation in a rat in vivo venous thrombosis model. DMA{sup III} also induced PS-exposure with apoptotic features mediated by protein thiol depletion, which resulted in enhanced thrombin generation. In summary, we believe that this study provides an important evidence for the role of trivalent methylated arsenic metabolites in arsenic-associated CVDs, giving a novel insight into the role of platelet apoptosis in toxicant-induced cardiovascular toxicity.« less

Models Role within Active Learning in Biology. A Case Study

ERIC Educational Resources Information Center

Pop-Pacurar, Irina; Tirla, Felicia-Doina

2009-01-01

In order to integrate ideas and information creatively, to motivate students and activate their thinking, we have used in Biology classes a series of active methods, among which the methods of critical thinking, which had very good results. Still, in the case of some intuitive, abstract, more difficult topics, such as the cell structure,…

Guilty as charged: all available evidence implicates complement's role in fetal demise.

PubMed

Girardi, Guillermina

2008-03-01

Appropriate complement inhibition is an absolute requirement for normal pregancy. Uncontrolled complement activation in the maternal-fetal interface leads to fetal death. Here we show that complement activation is a crucial and early mediator of pregnancy loss in two different mouse models of pregnancy loss. Using a mouse model of fetal loss and growth restriction (IUGR) induced by antiphospholipid antibodies (aPL), we examined the role of complement activation in fetal loss and IUGR. We found that C5a-C5aR interaction and neutrophils are key mediators of fetal injury. Treatment with heparin, the standard therapy for pregnant patients with aPL, prevents complement activation and protects mice from pregnancy complications induced by aPL, and anticoagulants that do not inhibit complement do not protect pregnancies. In an antibody-independent mouse model of spontaneous miscarriage and IUGR (CBA/JxDBA/2) we also identified C5a as an essential mediator. Complement activation caused dysregulation of the angiogenic factors required for normal placental development. In CBA/JxDBA/2 mice, we observed inflammatory infiltrates in placentas, functional deficiency of free vascular endothelial growth factor (VEGF), elevated levels of soluble VEGF receptor-1 (sVEGFR-1, also known as sFlt-1; a potent anti-angiogenic molecule), and defective placental development. Inhibition of complement activation blocked the increase in sVEGFR-1 and rescued pregnancies. Our studies in antibody-dependent and antibody-independent models of pregnancy complications identified complement activation as the key mediator of damage and will allow development of new interventions to prevent pregnancy loss and IUGR.

Spiritual activities as a resistance resource for women with human immunodeficiency virus.

PubMed

Sowell, R; Moneyham, L; Hennessy, M; Guillory, J; Demi, A; Seals, B

2000-01-01

Few studies have investigated the role that spiritual activities play in the adaptational outcomes of women with human immunodeficiency virus (HIV) disease. To examine the role of spiritual activities as a resource that may reduce the negative effects of disease-related stressors on the adaptational outcomes in HIV-infected women. A theoretically based causal model was tested to examine the role of spiritual activities as a moderator of the impact of HIV-related stressors (functional impairment, work impairment, and HIV-related symptoms) on two stress-related adaptational outcomes (emotional distress and quality of life), using a clinic-based sample of 184 HIV-positive women. Findings indicated that as spiritual activities increased, emotional distress decreased even when adjustments were made for HIV-related stressors. A positive relationship between spiritual activities and quality of life was found, which approached significance. Findings showed that HIV-related stressors have a significant negative effect on both emotional distress and quality of life. The findings support the hypothesis that spiritual activities are an important psychological resource accounting for individual variability in adjustment to the stressors associated with HIV disease.

Controlling Distributed Planning

NASA Technical Reports Server (NTRS)

Clement, Bradley; Barrett, Anthony

2004-01-01

A system of software implements an extended version of an approach, denoted shared activity coordination (SHAC), to the interleaving of planning and the exchange of plan information among organizations devoted to different missions that normally communicate infrequently except that they need to collaborate on joint activities and/or the use of shared resources. SHAC enables the planning and scheduling systems of the organizations to coordinate by resolving conflicts while optimizing local planning solutions. The present software provides a framework for modeling and executing communication protocols for SHAC. Shared activities are represented in each interacting planning system to establish consensus on joint activities or to inform the other systems of consumption of a common resource or a change in a shared state. The representations of shared activities are extended to include information on (1) the role(s) of each participant, (2) permissions (defined as specifications of which participant controls what aspects of shared activities and scheduling thereof), and (3) constraints on the parameters of shared activities. Also defined in the software are protocols for changing roles, permissions, and constraints during the course of coordination and execution.

Peroxisome proliferator activator receptor gamma coactivator-1alpha (PGC-1α) improves motor performance and survival in a mouse model of amyotrophic lateral sclerosis

PubMed Central

2011-01-01

Background Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects spinal cord and cortical motor neurons. An increasing amount of evidence suggests that mitochondrial dysfunction contributes to motor neuron death in ALS. Peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) is a principal regulator of mitochondrial biogenesis and oxidative metabolism. Results In this study, we examined whether PGC-1α plays a protective role in ALS by using a double transgenic mouse model where PGC-1α is over-expressed in an SOD1 transgenic mouse (TgSOD1-G93A/PGC-1α). Our results indicate that PGC-1α significantly improves motor function and survival of SOD1-G93A mice. The behavioral improvements were accompanied by reduced blood glucose level and by protection of motor neuron loss, restoration of mitochondrial electron transport chain activities and inhibition of stress signaling in the spinal cord. Conclusion Our results demonstrate that PGC-1α plays a beneficial role in a mouse model of ALS, suggesting that PGC-1α may be a potential therapeutic target for ALS therapy. PMID:21771318

Distinct Behaviour of Sorafenib in Experimental Cachexia-Inducing Tumours: The Role of STAT3

PubMed Central

Busquets, Sílvia; López-Soriano, Francisco J.; Argilés, Josep M.

2014-01-01

The presence of a tumour is very often associated with wasting in the host, affecting both skeletal muscle and adipose tissue. In the present study we used sorafenib, a multi-kinase inhibitor with anti-tumour activity, in order to investigate the effects of chemotherapy on wasting. Three different experimental mouse tumour models were included: C26 colon carcinoma, B16 melanoma and Lewis lung carcinoma (LLC). The results obtained clearly show that sorafenib was effective in reducing tumour growth in LLC and B16 models, while it had no effect on C26. Interestingly, sorafenib treatment reduced the signs of muscle wasting and improved the physical activity in the LLC model and also in the C26, despite the absence of antineoplastic action in the latter. Our results discard a role for IL-6 in the action of sorafenib since the drug did not affect the levels of this cytokine. Conversely, sorafenib seems to act by influencing both STAT3 and ERK activity at muscle level, leading to reduced accumulation of Pax7 and atrogin-1. Sorafenib may interfere with muscle wasting by decreasing the activation of these signal transduction pathways. PMID:25436606

Finasteride Inhibits the Disease-Modifying Activity of Progesterone in the Hippocampus Kindling Model of Epileptogenesis

PubMed Central

Reddy, Doodipala Samba; Ramanathan, G.

2012-01-01

Progesterone (P) plays an important role in seizure susceptibility in women with epilepsy. Preclinical and experimental studies suggest that P appears to interrupt epileptogenesis, which is a process whereby a normal brain becomes progressively epileptic due to precipitating risk factors. P has not been investigated widely for its potential disease-modifying activity in epileptogenic models. Recently, P has been shown to exert disease-modifying effects in the kindling model of epileptogenesis. However, the mechanisms underlying the protective effects of P against epileptogenesis remain unclear. In this study, we investigated the role of P-derived neurosteroids in the disease-modifying activity of P. It is hypothesized that 5α-reductase converts P to allopregnanolone and related neurosteroids that retard epileptogenesis in the brain. To test this hypothesis, we utilized the mouse hippocampus kindling model of epileptogenesis and investigated the effect of finasteride, a 5α-reductase and neurosteroid synthesis inhibitor. P markedly retarded the development of epileptogenesis and inhibited the rate of kindling acquisition to elicit stage 5 seizures. Pretreatment with finasteride led to complete inhibition of the P-induced retardation of limbic epileptogenesis in mice. Finasteride did not significantly influence the acute seizure expression in fully-kindled mice expressing stage 5 seizures. Thus, neurosteroids that potentiate phasic and tonic inhibition in the hippocampus, such as allopregnanolone, may mediate the disease-modifying effect of P, indicating a new role of neurosteroids in acquired limbic epileptogenesis and temporal lobe epilepsy. PMID:22835430

Engaging Pre-Service Science Teachers to Act as Active Designers of Technology Integration: A MAGDAIRE Framework

ERIC Educational Resources Information Center

Chien, Yu-Ta; Chang, Chun-Yen; Yeh, Ting-Kuang; Chang, Kuo-En

2012-01-01

This paper describes our efforts in developing the MAGDAIRE framework (abbreviated from Modeled Analysis, Guided Development, Articulated Implementation, and Reflected Evaluation) to transform pre-service science teachers' roles in a teacher education course: moving pre-service teachers from the roles of passive users of technology, as they…

Third-Grade Students' Mental Models of Energy Expenditure during Exercise

ERIC Educational Resources Information Center

Pasco, Denis; Ennis, Catherine D.

2015-01-01

Background: Students' prior knowledge plays an important role in learning new knowledge. In physical education (PE) and physical activity settings, studies have confirmed the role of students' prior knowledge. According to Placek and Griffin, these studies demonstrate that: "our students are not empty balls waiting to be filled with knowledge…

SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model.

PubMed

Xu, Siqi; Gao, Youguang; Zhang, Qin; Wei, Siwei; Chen, Zhongqing; Dai, Xingui; Zeng, Zhenhua; Zhao, Ke-Seng

2016-01-01

Sepsis often results in damage to multiple organ systems, possibly due to severe mitochondrial dysfunction. Two members of the sirtuin family, SIRT1 and SIRT3, have been implicated in the reversal of mitochondrial damage. The aim of this study was to determine the role of SIRT1/3 in acute kidney injury (AKI) following sepsis in a septic rat model. After drug pretreatment and cecal ligation and puncture (CLP) model reproduction in the rats, we performed survival time evaluation and kidney tissue extraction and renal tubular epithelial cell (RTEC) isolation. We observed reduced SIRT1/3 activity, elevated acetylated SOD2 (ac-SOD2) levels and oxidative stress, and damaged mitochondria in RTECs following sepsis. Treatment with resveratrol (RSV), a chemical SIRT1 activator, effectively restored SIRT1/3 activity, reduced acetylated SOD2 levels, ameliorated oxidative stress and mitochondrial function of RTECs, and prolonged survival time. However, the beneficial effects of RSV were greatly abrogated by Ex527, a selective inhibitor of SIRT1. These results suggest a therapeutic role for SIRT1 in the reversal of AKI in septic rat, which may rely on SIRT3-mediated deacetylation of SOD2. SIRT1/3 activation could therefore be a promising therapeutic strategy to treat sepsis-associated AKI.

Investigating the role of model-based reasoning while troubleshooting an electric circuit

NASA Astrophysics Data System (ADS)

Dounas-Frazer, Dimitri R.; Van De Bogart, Kevin L.; Stetzer, MacKenzie R.; Lewandowski, H. J.

2016-06-01

We explore the overlap of two nationally recognized learning outcomes for physics lab courses, namely, the ability to model experimental systems and the ability to troubleshoot a malfunctioning apparatus. Modeling and troubleshooting are both nonlinear, recursive processes that involve using models to inform revisions to an apparatus. To probe the overlap of modeling and troubleshooting, we collected audiovisual data from think-aloud activities in which eight pairs of students from two institutions attempted to diagnose and repair a malfunctioning electrical circuit. We characterize the cognitive tasks and model-based reasoning that students employed during this activity. In doing so, we demonstrate that troubleshooting engages students in the core scientific practice of modeling.

Ecological Model of Australian Indigenous Men's Health.

PubMed

McCabe, Marita P; Mellor, David; Ricciardelli, Lina A; Mussap, Alexander J; Hallford, David J

2016-11-01

This study was designed to examine the health behaviors as well as the enablers and barriers to health behaviors among Indigenous Australian men. One hundred and fifty Indigenous Australian men in rural, regional, and urban locations were interviewed about their health behaviors. The results revealed several themes of importance: (a) role of community activities, (b) the Indigenous man as a leader and role model, (c) negative impact of discrimination/racism, (d) importance of partner and family, (e) positive and negative role of peer relationships, (f) central role of culturally appropriate health care facilities, and (g) association between employment and health care problems. These findings highlight the importance of broad community-based (rather than individualistic) approaches to promoting health behavior in Indigenous men. © The Author(s) 2015.

Research on a dynamic workflow access control model

NASA Astrophysics Data System (ADS)

Liu, Yiliang; Deng, Jinxia

2007-12-01

In recent years, the access control technology has been researched widely in workflow system, two typical technologies of that are RBAC (Role-Based Access Control) and TBAC (Task-Based Access Control) model, which has been successfully used in the role authorizing and assigning in a certain extent. However, during the process of complicating a system's structure, these two types of technology can not be used in minimizing privileges and separating duties, and they are inapplicable when users have a request of frequently changing on the workflow's process. In order to avoid having these weakness during the applying, a variable flow dynamic role_task_view (briefly as DRTVBAC) of fine-grained access control model is constructed on the basis existed model. During the process of this model applying, an algorithm is constructed to solve users' requirements of application and security needs on fine-grained principle of privileges minimum and principle of dynamic separation of duties. The DRTVBAC model is implemented in the actual system, the figure shows that the task associated with the dynamic management of role and the role assignment is more flexible on authority and recovery, it can be met the principle of least privilege on the role implement of a specific task permission activated; separated the authority from the process of the duties completing in the workflow; prevented sensitive information discovering from concise and dynamic view interface; satisfied with the requirement of the variable task-flow frequently.

Role of the epidermal growth factor receptor in signaling strain-dependent activation of the brain natriuretic peptide gene.

PubMed

Anderson, Hope D I; Wang, Feng; Gardner, David G

2004-03-05

The epidermal growth factor receptor (EGFR) and ectoshedding of heparin-binding epidermal growth factor (HBEGF), an EGFR ligand, have been linked to the development of cardiac myocyte hypertrophy. However, the precise role that the liganded EGFR plays in the transcriptional activation of the gene program that accompanies hypertrophy remains undefined. Utilizing the human (h) BNP gene as a model of hypertrophy-dependent gene activation, we show that activation of the EGFR plays an important role in mediating mechanical strain-dependent stimulation of the hBNP promoter. Strain promotes endothelin (ET) generation through NAD(P)H oxidase-dependent production of reactive oxygen species. ET in turn induces metalloproteinase-mediated cleavage of pro-HBEGF and ectoshedding of HBEGF, which activates the EGFR and stimulates hBNP promoter activity. HBEGF also stimulates other phenotypic markers of hypertrophy including protein synthesis and sarcomeric assembly. The antioxidant N-acetylcysteine or the NAD(P)H oxidase inhibitor, apocynin, inhibited strain-dependent activation of the ET-1 promoter, HBEGF shedding, and hBNP promoter activation. The metalloproteinase inhibitor, GM-6001, prevented the induction of HBEGF ectoshedding and the hBNP promoter response to strain, suggesting a critical role for the metalloproteinase-dependent cleavage event in signaling the strain response. These findings suggest that metalloproteinase activity as an essential step in this pathway may prove to be a relevant therapeutic target in the management of cardiac hypertrophy.

Calcium and Egg Activation in Drosophila

PubMed Central

Sartain, Caroline V.; Wolfner, Mariana F.

2012-01-01

Summary In many animals, a rise in intracellular calcium levels is the trigger for egg activation, the process by which an arrested mature oocyte transitions to prepare for embryogenesis. In nearly all animals studied to date, this calcium rise, and thus egg activation, is triggered by the fertilizing sperm. However in the insects that have been examined, fertilization is not necessary to activate their oocytes. Rather, these insects’ eggs activate as they transit through the female’s reproductive tract, regardless of male contribution. Recent studies in Drosophila have shown that egg activation nevertheless requires calcium and that the downstream events and molecules of egg activation are also conserved, despite the difference in initial trigger. Genetic studies have uncovered essential roles for the calcium-dependent enzyme calcineurin and its regulator calcipressin, and have hinted at roles for calmodulin, in Drosophila egg activation. Physiological and in vitro studies have led to a model in which mechanical forces that impact the Drosophila oocyte as it moves through the reproductive tract triggers the influx of calcium from the external environment, thereby initiating egg activation. Future research will aim to test this model, as well as to determine the spatiotemporal dynamics of cytoplasmic calcium flux and mode of signal propagation in this unique system. PMID:23218670

Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia

PubMed Central

Deb, Ishani; Manhas, Namratta; Poddar, Ranjana; Rajagopal, Sathyanarayanan; Allan, Andrea M.; Lombroso, Paul J.; Rosenberg, Gary A.; Candelario-Jalil, Eduardo

2013-01-01

The striatal-enriched phosphatase (STEP) is a component of the NMDA-receptor-mediated excitotoxic signaling pathway, which plays a key role in ischemic brain injury. Using neuronal cultures and a rat model of ischemic stroke, we show that STEP plays an initial role in neuroprotection, during the insult, by disrupting the p38 MAPK pathway. Degradation of active STEP during reperfusion precedes ischemic brain damage and is associated with secondary activation of p38 MAPK. Application of a cell-permeable STEP-derived peptide that is resistant to degradation and binds to p38 MAPK protects cultured neurons from hypoxia-reoxygenation injury and reduces ischemic brain damage when injected up to 6 h after the insult. Conversely, genetic deletion of STEP in mice leads to sustained p38 MAPK activation and exacerbates brain injury and neurological deficits after ischemia. Administration of the STEP-derived peptide at the onset of reperfusion not only prevents the sustained p38 MAPK activation but also reduces ischemic brain damage in STEP KO mice. The findings indicate a neuroprotective role of STEP and suggest a potential role of the STEP-derived peptide in stroke therapy. PMID:24198371

Models to support students’ understanding of measuring area of circles

NASA Astrophysics Data System (ADS)

Rejeki, S.; Putri, R. I. I.

2018-01-01

Many studies showed that enormous students got confused about the concepts of measuring area of circles. The main reason is because mathematics classroom practices emphasized on memorizing formulas rather than understanding concepts. Therefore, in this study, a set of learning activities were designed as an innovation in learning area measurement of circles. The activities involved two models namely grid paper and reshaping which are respectively as a means and a strategy to support students’ learning of area measurement of circles. Design research was used as the research approach to achieve the aim. Thirty-eight of 8th graders in Indonesia were involved in this study. In this study, together with the contextual problems, the grid paper and reshaping sectors, which used as the models in this learning, helped the students to gradually develop their understanding of the area measurement of circles. The grid papers plays important role in comparing and estimating areas. Whereas, the reshaping sectors might support students’ understanding of the circumference and the area measurement of circles. Those two models could be the tool for promoting the informal theory of area measurement. Besides, the whole activities gave important role on distinguishing the area and perimeter of circles.

Role of mast cells in bronchial contraction in nonallergic obstructive lung pathology.

PubMed

Kuzubova, Nataliya A; Lebedeva, Elena S; Titova, Olga N; Fedin, Anatoliy N; Dvorakovskaya, Ivetta V

2017-01-01

The role of mast cells in contractile bronchial smooth muscle activity has been evaluated in a model of chronic obstructive pulmonary disease induced in rats that were intermittently exposed to nitrogen dioxide (NO 2 ) for 60 days. Starting from the 31st day, one group of rats inhaled sodium cromoglycate before exposure to NO 2 to stabilize mast cell membranes. The second group (control) was not treated. Isometric smooth muscle contraction was analysed in isolated bronchial samples in response to nerve and smooth muscle stimulation. Histological analysis revealed large numbers of mast cells in lung tissue of COPD model rats. The inhibition of mast cell degranulation by sodium cromoglycate prevented the development of nerve-stimulated bronchial smooth muscle hyperactivity in COPD model rats. Histamine or adenosine-induced hyperactivity on nerve stimulation was also inhibited by sodium cromoglycate in bronchial smooth muscle in both control and COPD model rats. This suggests that the mechanism of contractile activity enhancement of bronchial wall smooth muscle cells may be mediated through the activation of resident mast cells transmembrane adenosine receptors resulting in their partial degranulation, with the released histamine acting upon histamine H1-receptors which trigger reflex pathways via intramural ganglion neurons.

Role of mast cells in bronchial contraction in nonallergic obstructive lung pathology

PubMed Central

Kuzubova, Nataliya A.; Lebedeva, Elena S.; Titova, Olga N.; Fedin, Anatoliy N.; Dvorakovskaya, Ivetta V.

2017-01-01

Abstract The role of mast cells in contractile bronchial smooth muscle activity has been evaluated in a model of chronic obstructive pulmonary disease induced in rats that were intermittently exposed to nitrogen dioxide (NO2) for 60 days. Starting from the 31st day, one group of rats inhaled sodium cromoglycate before exposure to NO2 to stabilize mast cell membranes. The second group (control) was not treated. Isometric smooth muscle contraction was analysed in isolated bronchial samples in response to nerve and smooth muscle stimulation. Histological analysis revealed large numbers of mast cells in lung tissue of COPD model rats. The inhibition of mast cell degranulation by sodium cromoglycate prevented the development of nerve-stimulated bronchial smooth muscle hyperactivity in COPD model rats. Histamine or adenosine-induced hyperactivity on nerve stimulation was also inhibited by sodium cromoglycate in bronchial smooth muscle in both control and COPD model rats. This suggests that the mechanism of contractile activity enhancement of bronchial wall smooth muscle cells may be mediated through the activation of resident mast cells transmembrane adenosine receptors resulting in their partial degranulation, with the released histamine acting upon histamine H1-receptors which trigger reflex pathways via intramural ganglion neurons. PMID:28867718

Contrasting faith-based and traditional substance abuse treatment programs.

PubMed

Neff, James Alan; Shorkey, Clayton T; Windsor, Liliane Cambraia

2006-01-01

This article (a) discusses the definition of faith-based substance abuse treatment programs, (b) juxtaposes Durkheim's theory regarding religion with treatment process model to highlight key dimensions of faith-based and traditional programs, and (c) presents results from a study of seven programs to identify key program dimensions and to identify differences/similarities between program types. Focus group/Concept Mapping techniques yielded a clear "spiritual activities, beliefs, and rituals" dimension, rated as significantly more important to faith-based programs. Faith-based program staff also rated "structure and discipline" as more important and "work readiness" as less important. No differences were found for "group activities/cohesion" and "role modeling/mentoring," "safe, supportive environment," and "traditional treatment modalities." Programs showed substantial similarities with regard to core social processes of treatment such as mentoring, role modeling, and social cohesion. Implications are considered for further research on treatment engagement, retention, and other outcomes.

Inhibition of plasmin-mediated TAFI activation may affect development but not progression of abdominal aortic aneurysms

PubMed Central

Bridge, Katherine; Revill, Charlotte; Macrae, Fraser; Bailey, Marc; Yuldasheva, Nadira; Wheatcroft, Stephen; Butlin, Roger; Foster, Richard; Scott, D. Julian; Gils, Ann; Ariёns, Robert

2017-01-01

Objective Thrombin-activatable fibrinolysis inhibitor (TAFI) reduces the breakdown of fibrin clots through its action as an indirect inhibitor of plasmin. Studies in TAFI-deficient mice have implicated a potential role for TAFI in Abdominal Aortic Aneurysm (AAA) disease. The role of TAFI inhibition on AAA formation in adult ApoE-/- mice is unknown. The aim of this paper was to investigate the effects of TAFI inhibition on AAA development and progression. Methods Using the Angiotensin II model of AAA, male ApoE-/- mice were infused with Angiotensin II 750ng/kg/min with or without a monoclonal antibody inhibitor of plasmin-mediated activation of TAFI, MA-TCK26D6, or a competitive small molecule inhibitor of TAFI, UK-396082. Results Inhibition of TAFI in the Angiotensin II model resulted in a decrease in the mortality associated with AAA rupture (from 40.0% to 16.6% with MA-TCK26D6 (log-rank Mantel Cox test p = 0.16), and 8.3% with UK-396082 (log-rank Mantel Cox test p = 0.05)). Inhibition of plasmin-mediated TAFI activation reduced the incidence of AAA from 52.4% to 30.0%. However, late treatment with MA-TCK26D6 once AAA were already established had no effect on the progression of AAA in this model. Conclusions The formation of intra-mural thrombus is responsible for the dissection and early rupture in the angiotensin II model of AAA, and this process can be prevented through inhibition of TAFI. Late treatment with a TAFI inhibitor does not prevent AAA progression. These data may indicate a role for inhibition of plasmin-mediated TAFI activation in the early stages of AAA development, but not in its progression. PMID:28472123

Autonomy Support and Its Links to Physical Activity and Competitive Performance: Mediations through Motivation, Competence, Action Orientation and Harmonious Passion, and the Moderator Role of Autonomy Support by Perceived Competence

ERIC Educational Resources Information Center

Halvari, Hallgeir; Ulstad, Svein Olav; Bagoien, Tor Egil; Skjesol, Knut

2009-01-01

The purpose of the present study was to test a Self-Determination Theory (SDT) process model in relation to involvement in physical activity and competitive performance among students (N = 190). In this model, perceived autonomy support from teachers and coaches was expected to be positively related to autonomous motivation, perceived competence,…

Regulation of aromatase activity in bone-derived cells: possible role of mitogen-activated protein kinase.

PubMed

Shozu, M; Sumitani, H; Murakami, K; Segawa, T; Yang, H J; Inoue, M

2001-12-01

Fetal human osteoblast-like cells and the THP-1 cell line that differentiates into macrophage/osteoblast-like cells in the presence of Vitamin D3 and which possesses high aromatase activity, constitute a useful model with which to study the regulation of aromatase in bone. We showed that dexamethasone (DEX)-induced aromatase activity in the THP-1 cell line is completely suppressed by forskolin and by dibutyryl cAMP. We therefore investigated the contribution of mitogen-activated protein kinase (MAPK) to the regulation of aromatase, because cAMP inhibits MAPK in many cells. We examined the role of MAPK on aromatase activity using PD98059, a selective inhibitor of MEK-1. PD98059 (100 microM) reduced DEX+interleukin (IL)-1beta-induced aromatase activity in human osteoblast-like cells by more than 90%, whereas 50% of the aromatase mRNA concentration was retained compared with the control incubated with DEX+IL-1beta. PD98059 (50 microM) reduced the activity of aromatase in THP-1 cells by 80% without significantly affecting the mRNA level. These results indicated that MAPK plays an important role in aromatase activation at the post-transcriptional level.

STAT3 activation in pressure-overloaded feline myocardium: role for integrins and the tyrosine kinase BMX.

PubMed

Willey, Christopher D; Palanisamy, Arun P; Johnston, Rebecca K; Mani, Santhosh K; Shiraishi, Hirokazu; Tuxworth, William J; Zile, Michael R; Balasubramanian, Sundaravadivel; Kuppuswamy, Dhandapani

2008-06-27

Growth, survival and cytoskeletal rearrangement of cardiomyocytes are critical for cardiac hypertrophy. Signal transducer and activator of transcription-3 (STAT3) activation is an important cardioprotective factor associated with cardiac hypertrophy. Although STAT3 activation has been reported via signaling through Janus Kinase 2 (JAK2) in several cardiac models of hypertrophy, the importance of other nonreceptor tyrosine kinases (NTKs) has not been explored. Utilizing an in vivo feline right ventricular pressure-overload (RVPO) model of hypertrophy, we demonstrate that in 48 h pressure-overload (PO) myocardium, STAT3 becomes phosphorylated and redistributed to detergent-insoluble fractions with no accompanying JAK2 activation. PO also caused increased levels of phosphorylated STAT3 in both cytoplasmic and nuclear fractions. To investigate the role of other NTKs, we used our established in vitro cell culture model of hypertrophy where adult feline cardiomyocytes are embedded three-dimensionally (3D) in type-I collagen and stimulated with an integrin binding peptide containing an Arg-Gly-Asp (RGD) motif that we have previously shown to recapitulate the focal adhesion complex (FAC) formation of 48 h RVPO. RGD stimulation of adult cardiomyocytes in vitro caused both STAT3 redistribution and activation that were accompanied by the activation and redistribution of c-Src and the TEC family kinase, BMX, but not JAK2. However, infection with dominant negative c-Src adenovirus was unable to block RGD-stimulated changes on either STAT3 or BMX. Further analysis in vivo in 48 h PO myocardium showed the presence of both STAT3 and BMX in the detergent-insoluble fraction with their complex formation and phosphorylation. Therefore, these studies indicate a novel mechanism of BMX-mediated STAT3 activation within a PO model of cardiac hypertrophy that might contribute to cardiomyocyte growth and survival.

Petri Net computational modelling of Langerhans cell Interferon Regulatory Factor Network predicts their role in T cell activation.

PubMed

Polak, Marta E; Ung, Chuin Ying; Masapust, Joanna; Freeman, Tom C; Ardern-Jones, Michael R

2017-04-06

Langerhans cells (LCs) are able to orchestrate adaptive immune responses in the skin by interpreting the microenvironmental context in which they encounter foreign substances, but the regulatory basis for this has not been established. Utilising systems immunology approaches combining in silico modelling of a reconstructed gene regulatory network (GRN) with in vitro validation of the predictions, we sought to determine the mechanisms of regulation of immune responses in human primary LCs. The key role of Interferon regulatory factors (IRFs) as controllers of the human Langerhans cell response to epidermal cytokines was revealed by whole transcriptome analysis. Applying Boolean logic we assembled a Petri net-based model of the IRF-GRN which provides molecular pathway predictions for the induction of different transcriptional programmes in LCs. In silico simulations performed after model parameterisation with transcription factor expression values predicted that human LC activation of antigen-specific CD8 T cells would be differentially regulated by epidermal cytokine induction of specific IRF-controlled pathways. This was confirmed by in vitro measurement of IFN-γ production by activated T cells. As a proof of concept, this approach shows that stochastic modelling of a specific immune networks renders transcriptome data valuable for the prediction of functional outcomes of immune responses.

Activated sludge pilot plant: comparison between experimental and predicted concentration profiles using three different modelling approaches.

PubMed

Le Moullec, Y; Potier, O; Gentric, C; Leclerc, J P

2011-05-01

This paper presents an experimental and numerical study of an activated sludge channel pilot plant. Concentration profiles of oxygen, COD, NO(3) and NH(4) have been measured for several operating conditions. These profiles have been compared to the simulated ones with three different modelling approaches, namely a systemic approach, CFD and compartmental modelling. For these three approaches, the kinetics model was the ASM-1 model (Henze et al., 2001). The three approaches allowed a reasonable simulation of all the concentration profiles except for ammonium for which the simulations results were far from the experimental ones. The analysis of the results showed that the role of the kinetics model is of primary importance for the prediction of activated sludge reactors performance. The fact that existing kinetics parameters in the literature have been determined by parametric optimisation using a systemic model limits the reliability of the prediction of local concentrations and of the local design of activated sludge reactors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Biological/Genetic Regulation of Physical Activity Level: Consensus from GenBioPAC.

PubMed

Lightfoot, J Timothy; DE Geus, Eco J C; Booth, Frank W; Bray, Molly S; DEN Hoed, Marcel; Kaprio, Jaakko; Kelly, Scott A; Pomp, Daniel; Saul, Michael C; Thomis, Martine A; Garland, Theodore; Bouchard, Claude

2018-04-01

Physical activity unquestionably maintains and improves health; however, physical activity levels globally are low and not rising despite all the resources devoted to this goal. Attention in both the research literature and the public policy domain has focused on social-behavioral factors; however, a growing body of literature suggests that biological determinants play a significant role in regulating physical activity levels. For instance, physical activity level, measured in various manners, has a genetic component in both humans and nonhuman animal models. This consensus article, developed as a result of an American College of Sports Medicine-sponsored round table, provides a brief review of the theoretical concepts and existing literature that supports a significant role of genetic and other biological factors in the regulation of physical activity. Future research on physical activity regulation should incorporate genetics and other biological determinants of physical activity instead of a sole reliance on social and other environmental determinants.

Dynamical analysis of Parkinsonian state emulated by hybrid Izhikevich neuron models

NASA Astrophysics Data System (ADS)

Liu, Chen; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xile; Li, Huiyan; Loparo, Kenneth A.; Fietkiewicz, Chris

2015-11-01

Computational models play a significant role in exploring novel theories to complement the findings of physiological experiments. Various computational models have been developed to reveal the mechanisms underlying brain functions. Particularly, in the development of therapies to modulate behavioral and pathological abnormalities, computational models provide the basic foundations to exhibit transitions between physiological and pathological conditions. Considering the significant roles of the intrinsic properties of the globus pallidus and the coupling connections between neurons in determining the firing patterns and the dynamical activities of the basal ganglia neuronal network, we propose a hypothesis that pathological behaviors under the Parkinsonian state may originate from combined effects of intrinsic properties of globus pallidus neurons and synaptic conductances in the whole neuronal network. In order to establish a computational efficient network model, hybrid Izhikevich neuron model is used due to its capacity of capturing the dynamical characteristics of the biological neuronal activities. Detailed analysis of the individual Izhikevich neuron model can assist in understanding the roles of model parameters, which then facilitates the establishment of the basal ganglia-thalamic network model, and contributes to a further exploration of the underlying mechanisms of the Parkinsonian state. Simulation results show that the hybrid Izhikevich neuron model is capable of capturing many of the dynamical properties of the basal ganglia-thalamic neuronal network, such as variations of the firing rates and emergence of synchronous oscillations under the Parkinsonian condition, despite the simplicity of the two-dimensional neuronal model. It may suggest that the computational efficient hybrid Izhikevich neuron model can be used to explore basal ganglia normal and abnormal functions. Especially it provides an efficient way of emulating the large-scale neuron network and potentially contributes to development of improved therapy for neurological disorders such as Parkinson's disease.

PLC-mediated PI(4,5)P2 hydrolysis regulates activation and inactivation of TRPC6/7 channels

PubMed Central

Itsuki, Kyohei; Imai, Yuko; Hase, Hideharu; Okamura, Yasushi; Inoue, Ryuji

2014-01-01

Transient receptor potential classical (or canonical) (TRPC)3, TRPC6, and TRPC7 are a subfamily of TRPC channels activated by diacylglycerol (DAG) produced through the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) by phospholipase C (PLC). PI(4,5)P2 depletion by a heterologously expressed phosphatase inhibits TRPC3, TRPC6, and TRPC7 activity independently of DAG; however, the physiological role of PI(4,5)P2 reduction on channel activity remains unclear. We used Förster resonance energy transfer (FRET) to measure PI(4,5)P2 or DAG dynamics concurrently with TRPC6 or TRPC7 currents after agonist stimulation of receptors that couple to Gq and thereby activate PLC. Measurements made at different levels of receptor activation revealed a correlation between the kinetics of PI(4,5)P2 reduction and those of receptor-operated TRPC6 and TRPC7 current activation and inactivation. In contrast, DAG production correlated with channel activation but not inactivation; moreover, the time course of channel inactivation was unchanged in protein kinase C–insensitive mutants. These results suggest that inactivation of receptor-operated TRPC currents is primarily mediated by the dissociation of PI(4,5)P2. We determined the functional dissociation constant of PI(4,5)P2 to TRPC channels using FRET of the PLCδ Pleckstrin homology domain (PHd), which binds PI(4,5)P2, and used this constant to fit our experimental data to a model in which channel gating is controlled by PI(4,5)P2 and DAG. This model predicted similar FRET dynamics of the PHd to measured FRET in either human embryonic kidney cells or smooth muscle cells, whereas a model lacking PI(4,5)P2 regulation failed to reproduce the experimental data, confirming the inhibitory role of PI(4,5)P2 depletion on TRPC currents. Our model also explains various PLC-dependent characteristics of channel activity, including limitation of maximum open probability, shortening of the peak time, and the bell-shaped response of total current. In conclusion, our studies demonstrate a fundamental role for PI(4,5)P2 in regulating TRPC6 and TRPC7 activity triggered by PLC-coupled receptor stimulation. PMID:24470487

Social influences on eating and physical activity behaviours of urban, minority youths

PubMed Central

Steeves, Elizabeth T Anderson; Johnson, Katherine A; Pollard, Suzanne L; Jones-Smith, Jessica; Pollack, Keshia; Johnson, Sarah Lindstrom; Hopkins, Laura; Gittelsohn, Joel

2017-01-01

Objective Social relationships can impact youths’ eating and physical activity behaviours; however, the best strategies for intervening in the social environment are unknown. The objectives of the present study were to provide in-depth information on the social roles that youths’ parents and friends play related to eating and physical activity behaviours and to explore the impact of other social relationships on youths’ eating and physical activity behaviours. Design Convergent parallel mixed-methods design. Setting Low-income, African American, food desert neighbourhoods in Baltimore City, MD, USA. Subjects Data were collected from 297 youths (53 % female, 91 % African American, mean age 12·3 (SD 1·5) years) using structured questionnaires and combined with in-depth interviews from thirty-eight youths (42 % female, 97 % African American, mean age 11·4 (SD 1·5) years) and ten parents (80 % female, 50 % single heads of house, 100 % African American). Results Combined interpretation of the results found that parents and caregivers have multiple, dynamic roles influencing youths’ eating and physical activity behaviours, such as creating health-promoting rules, managing the home food environment and serving as a role model for physical activity. Other social relationships have specific, but limited roles. For example, friends served as partners for physical activity, aunts provided exposure to novel food experiences, and teachers and doctors provided information related to eating and physical activity. Conclusions Obesity prevention programmes should consider minority youths’ perceptions of social roles when designing interventions. Specifically, future research is needed to test the effectiveness of intervention strategies that enhance or expand the supportive roles played by social relationships. PMID:27491967

Using animal models to determine the significance of complement activation in Alzheimer's disease

PubMed Central

Loeffler, David A

2004-01-01

Complement inflammation is a major inflammatory mechanism whose function is to promote the removal of microorganisms and the processing of immune complexes. Numerous studies have provided evidence for an increase in this process in areas of pathology in the Alzheimer's disease (AD) brain. Because complement activation proteins have been demonstrated in vitro to exert both neuroprotective and neurotoxic effects, the significance of this process in the development and progression of AD is unclear. Studies in animal models of AD, in which brain complement activation can be experimentally altered, should be of value for clarifying this issue. However, surprisingly little is known about complement activation in the transgenic animal models that are popular for studying this disorder. An optimal animal model for studying the significance of complement activation on Alzheimer's – related neuropathology should have complete complement activation associated with senile plaques, neurofibrillary tangles (if present), and dystrophic neurites. Other desirable features include both classical and alternative pathway activation, increased neuronal synthesis of native complement proteins, and evidence for an increase in complement activation prior to the development of extensive pathology. In order to determine the suitability of different animal models for studying the role of complement activation in AD, the extent of complement activation and its association with neuropathology in these models must be understood. PMID:15479474

The examination of nursing work through a role accountability framework.

PubMed

White, Deborah E; Jackson, Karen; Besner, Jeanne; Norris, Jill M

2015-07-01

To use work analysis data to describe the amount of time registered nurses (RNs) and health care aides (HCA) spent on key clinical role accountabilities and other work activities. Health care providers are not effectively utilized. To improve their efficiency and effectiveness, it is necessary to understand how nursing providers enact their role accountabilities. Using palm pilot Function Analysis technology, observers recorded the activities of 35 registered nurse and 17 health care aides shifts on a second-by-second basis over 5 days. Work activities were classified using the Nursing Role Effectiveness Model, which conceptualizes nursing practice in terms of clinical role accountabilities. The registered nurses spent a considerable amount of time on bio-medical assessment/surveillance, relatively little time was spent on patient and family psycho-social-cultural-spiritual assessment/surveillance and support. Unlike other work sampling studies, this research project examined nursing work within a role accountability framework; an important first step in the call for the measurement of the impact of nursing care. Changes to how registered nurses and health care aides enact their role will require a clear vision by unit managers and their staff of their role accountabilities, and the gap between ideal and actual practice. © 2013 John Wiley & Sons Ltd.

The Role of Model Building in Problem Solving and Conceptual Change

ERIC Educational Resources Information Center

Lee, Chwee Beng; Jonassen, David; Teo, Timothy

2011-01-01

This study examines the effects of the activity of building systems models for school-based problems on problem solving and on conceptual change in elementary science classes. During a unit on the water cycle in an Asian elementary school, students constructed systems models of the water cycle. We found that representing ill-structured problems as…

Mathematical Modelling with Technology: The Role of Dynamic Representations

ERIC Educational Resources Information Center

Arzarello, Ferdinando; Ferrara, Francesca; Robutti, Ornella

2012-01-01

In this research we present the use of some technologies in problem solving activities (at different secondary school grades), aimed at finding a model for a geometric configuration, and representing this model in various ways: through a construction, through a Cartesian graph, etc. The task is part of a teaching experiment, in which students used…

Understanding Female Sport Attrition in a Stereotypical Male Sport within the Framework of Eccles's Expectancy-Value Model

ERIC Educational Resources Information Center

Guillet, Emma; Sarrazin, Philippe; Fontayne, Paul; Brustad, Robert J.

2006-01-01

An empirical research study based upon the expectancy-value model of Eccles and colleagues (1983) investigated the effect of gender-role orientations on psychological dimensions of female athletes' sport participation and the likelihood of their continued participation in a stereotypical masculine activity. The model (Eccles et al., 1983) posits…

Mitochondria play an important role in the cell proliferation suppressing activity of berberine

PubMed Central

Yan, Xiao-Jin; Yu, Xuan; Wang, Xin-Pei; Jiang, Jing-Fei; Yuan, Zhi-Yi; Lu, Xi; Lei, Fan; Xing, Dong-Ming

2017-01-01

After being studied for approximately a century, berberine (BBR) has been found to act on various targets and pathways. A great challenge in the pharmacological analysis of BBR at present is to identify which target(s) plays a decisive role. In the study described herein, a rescue experiment was designed to show the important role of mitochondria in BBR activity. A toxic dose of BBR was applied to inhibit cell proliferation and mitochondrial activity, then α-ketobutyrate (AKB), an analogue of pyruvate that serves only as an electron receptor of NADH, was proven to partially restore cell proliferation. However, mitochondrial morphology damage and TCA cycle suppression were not recovered by AKB. As the AKB just help to regenerate NAD+, which is make up for part function of mitochondrial, the recovered cell proliferation stands for the contribution of mitochondria to the activity of BBR. Our results also indicate that BBR suppresses tumour growth and reduces energy charge and mitochondrial DNA (mtDNA) copy number in a HepG2 xenograft model. In summary, our study suggests that mitochondria play an important role in BBR activity regarding tumour cell proliferation and metabolism. PMID:28181523

Distinct roles of N- and O-glycans in cellulase activity and stability

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

Amore, Antonella; Knott, Brandon C.; Supekar, Nitin T.

In nature, many microbes secrete mixtures of glycoside hydrolases, oxidoreductases, and accessory enzymes to deconstruct polysaccharides and lignin in plants. These enzymes are often decorated with N- and O-glycosylation, the roles of which have been broadly attributed to protection from proteolysis, as the extracellular milieu is an aggressive environment. Glycosylation has been shown to sometimes affect activity, but these effects are not fully understood. In this paper, we examine N- and O-glycosylation on a model, multimodular glycoside hydrolase family 7 cellobiohydrolase (Cel7A), which exhibits an O-glycosylated carbohydrate-binding module (CBM) and an O-glycosylated linker connected to an N- and O-glycosylated catalyticmore » domain (CD) - a domain architecture common to many biomass-degrading enzymes. We report consensus maps for Cel7A glycosylation that include glycan sites and motifs. Additionally, we examine the roles of glycans on activity, substrate binding, and thermal and proteolytic stability. N-glycan knockouts on the CD demonstrate that N-glycosylation has little impact on cellulose conversion or binding, but does have major stability impacts. O-glycans on the CBM have little impact on binding, proteolysis, or activity in the whole-enzyme context. However, linker O-glycans greatly impact cellulose conversion via their contribution to proteolysis resistance. Molecular simulations predict an additional role for linker O-glycans, namely that they are responsible for maintaining separation between ordered domains when Cel7A is engaged on cellulose, as models predict a-helix formation and decreased cellulose interaction for the nonglycosylated linker. In conclusion, this study reveals key roles for N- and O-glycosylation that are likely broadly applicable to other plant cell-wall-degrading enzymes.« less

Distinct roles of N- and O-glycans in cellulase activity and stability

DOE PAGES

Amore, Antonella; Knott, Brandon C.; Supekar, Nitin T.; ...

2017-12-11

In nature, many microbes secrete mixtures of glycoside hydrolases, oxidoreductases, and accessory enzymes to deconstruct polysaccharides and lignin in plants. These enzymes are often decorated with N- and O-glycosylation, the roles of which have been broadly attributed to protection from proteolysis, as the extracellular milieu is an aggressive environment. Glycosylation has been shown to sometimes affect activity, but these effects are not fully understood. In this paper, we examine N- and O-glycosylation on a model, multimodular glycoside hydrolase family 7 cellobiohydrolase (Cel7A), which exhibits an O-glycosylated carbohydrate-binding module (CBM) and an O-glycosylated linker connected to an N- and O-glycosylated catalyticmore » domain (CD) - a domain architecture common to many biomass-degrading enzymes. We report consensus maps for Cel7A glycosylation that include glycan sites and motifs. Additionally, we examine the roles of glycans on activity, substrate binding, and thermal and proteolytic stability. N-glycan knockouts on the CD demonstrate that N-glycosylation has little impact on cellulose conversion or binding, but does have major stability impacts. O-glycans on the CBM have little impact on binding, proteolysis, or activity in the whole-enzyme context. However, linker O-glycans greatly impact cellulose conversion via their contribution to proteolysis resistance. Molecular simulations predict an additional role for linker O-glycans, namely that they are responsible for maintaining separation between ordered domains when Cel7A is engaged on cellulose, as models predict a-helix formation and decreased cellulose interaction for the nonglycosylated linker. In conclusion, this study reveals key roles for N- and O-glycosylation that are likely broadly applicable to other plant cell-wall-degrading enzymes.« less

On the role of passion for work in burnout: a process model.

PubMed

Vallerand, Robert J; Paquet, Yvan; Philippe, Frederick L; Charest, Julie

2010-02-01

The purpose of the present research was to test a model on the role of passion for work in professional burnout. This model posits that obsessive passion produces conflict between work and other life activities because the person cannot let go of the work activity. Conversely, harmonious passion is expected to prevent conflict while positively contributing to work satisfaction. Finally, conflict is expected to contribute to burnout, whereas work satisfaction should prevent its occurrence. This model was tested in 2 studies with nurses in 2 cultures. Using a cross-sectional design, Study 1 (n=97) provided support for the model with nurses from France. In Study 2 (n=258), a prospective design was used to further test the model with nurses from the Province of Quebec over a 6-month period. Results provided support for the model. Specifically, harmonious passion predicted an increase in work satisfaction and a decrease in conflict. Conversely, obsessive passion predicted an increase of conflict. In turn, work satisfaction and conflict predicted decreases and increases in burnout changes that took place over time. The results have important implications for theory and research on passion as well as burnout.

The relationship between vigorous physical activity and juvenile delinquency: a mediating role for self-esteem?

PubMed

Faulkner, Guy E J; Adlaf, Edward M; Irving, Hyacinth M; Allison, Kenneth R; Dwyer, John J M; Goodman, Jack

2007-04-01

Many policy-related reviews of the potential social value of sport and physical activity list the prevention of juvenile delinquency. We examined the relationships among vigorous physical activity, self-esteem, and delinquent behavior among adolescents in a large cross-sectional survey of Ontario adolescents. Data are based on questionnaires from 3,796 students (range 11-20 years) derived from the 2005 Ontario Student Drug Use Survey. Negative binominal regression methods were used to estimate both additive and interactive models predicting delinquent behavior. Vigorous physical activity was positively associated with delinquent behavior; however, this pattern of association was observed only among male adolescents. There was no evidence of a mediating role for self-esteem. Our findings suggest that physical activity is not the solution for reducing juvenile delinquency.

Warming Up to STS. Activities to Encourage Environmental Awareness.

ERIC Educational Resources Information Center

Rosenthal, Dorothy B.

1990-01-01

Developed is an interdisciplinary unit that deals with global warming and the greenhouse effect. Included are 10 lessons that can be used to supplement existing plans or used as a basis for developing a new unit. Included are modeling, laboratory, graphing, role-playing, and discussion activities. (KR)

Group Investigation: Structuring an Inquiry-Based Curriculum.

ERIC Educational Resources Information Center

Huhtala, Jack

Group investigation is an organizational approach that allows a class to work actively and collaboratively in small groups and enables students to take an active role in determining their own learning goals and processes. As part of reform and restructuring efforts, Beaverton High School (Oregon) implemented the Group Investigation model with…

Improved starch digestion of sucrase deficient shrews treated with oral glucoamylase enzyme supplements

USDA-ARS?s Scientific Manuscript database

Although named because of its sucrose hydrolytic activity, this mucosal enzyme plays a leading role in starch digestion because of its maltase and glucoamylase activities. Sucrase deficient mutant shrews, Suncus murinus, were used as a model to investigate starch digestion in patients with Congenita...

Against All Odds: Latinas Activate Agency to Secure Access to College

ERIC Educational Resources Information Center

Sapp, Vicki T.; Kiyama, Judy Marquez; Dache-Gerbino, Amalia

2016-01-01

This qualitative study seeks to understand Latinas' college-going behaviors by examining their agency and role in securing opportunity for college. The authors examine the activation of agency among 16 urban Latinas when navigating the structures influencing college opportunity through a cultural ecological model. Examples of agency are…

Measuring research progress in photovoltaics

NASA Technical Reports Server (NTRS)

Jackson, B.; Mcguire, P.

1986-01-01

The role and some results of the project analysis and integration function in the Flat-plate Solar Array (FSA) Project are presented. Activities included supporting the decision-making process, preparation of plans for project direction, setting goals for project activities, measuring progress within the project, and the development and maintenance of analytical models.

Models of Traumatic Experiences and Children's Psychological Adjustment: The Roles of Perceived Parenting and the Children's Own Resources and Activity.

ERIC Educational Resources Information Center

Punamaki, Raija-Leena; Qouta, Samir; El Sarraj, Eyad

1997-01-01

Used path analysis to examine relations between trauma, perceived parenting, resources, political activity, and adjustment in Palestinian 11- and 12-year olds. Found that the more trauma experienced, the more negative parenting the children experienced, the more political activity they showed, and the more they suffered from adjustment problems.…

Participating in Sport and Music Activities in Adolescence: The Role of Activity Participation and Motivational Beliefs during Elementary School

ERIC Educational Resources Information Center

Simpkins, Sandra D.; Vest, Andrea E.; Becnel, Jennifer N.

2010-01-01

This investigation examined the precursors of adolescents' participation in sport and music activities in the United States by testing a developmental model across 7 years. Data were drawn from youth questionnaires in the Childhood and Beyond Study (92% European American; N = 594). Findings suggest that patterns of participation across a 3-year…

Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia.

PubMed

Pawlinski, Rafal; Pedersen, Brian; Schabbauer, Gernot; Tencati, Michael; Holscher, Todd; Boisvert, William; Andrade-Gordon, Patricia; Frank, Rolf Dario; Mackman, Nigel

2004-02-15

Sepsis is associated with a systemic activation of coagulation and an excessive inflammatory response. Anticoagulants have been shown to inhibit both coagulation and inflammation in sepsis. In this study, we used both genetic and pharmacologic approaches to analyze the role of tissue factor and protease-activated receptors in coagulation and inflammation in a mouse endotoxemia model. We used mice expressing low levels of the procoagulant molecule, tissue factor (TF), to analyze the effects of TF deficiency either in all tissues or selectively in hematopoietic cells. Low TF mice had reduced coagulation, inflammation, and mortality compared with control mice. Similarly, a deficiency of TF expression by hematopoietic cells reduced lipopolysaccharide (LPS)-induced coagulation, inflammation, and mortality. Inhibition of the down-stream coagulation protease, thrombin, reduced fibrin deposition and prolonged survival without affecting inflammation. Deficiency of either protease activated receptor-1 (PAR-1) or protease activated receptor-2 (PAR-2) alone did not affect inflammation or survival. However, a combination of thrombin inhibition and PAR-2 deficiency reduced inflammation and mortality. These data demonstrate that hematopoietic cells are the major pathologic site of TF expression during endotoxemia and suggest that multiple protease-activated receptors mediate crosstalk between coagulation and inflammation.

The Activation of Incompetence Schemas in Response to Negative Sexual Events in Heterosexual and Lesbian Women: The Moderator Role of Personality Traits and Dysfunctional Sexual Beliefs.

PubMed

Peixoto, Maria Manuela; Nobre, Pedro

2017-01-01

Personality traits and dysfunctional sexual beliefs have been described as vulnerability factors for sexual dysfunction in women, and have also been proposed as dispositional variables for the activation of incompetence schemas in response to negative sexual events. However, no study has tested the role of personality traits and dysfunctional sexual beliefs in the activation of incompetence schemas. The current study aimed to assess the moderator role of neuroticism, extraversion, and dysfunctional sexual beliefs in the association between frequency of unsuccessful sexual episodes and activation of incompetence schemas in heterosexual and lesbian women. An online survey was completed by 1,121 women (831 heterosexual; 290 lesbian). Participants completed the NEO Five-Factor Inventory (NEO-FFI), the Sexual Dysfunctional Beliefs Questionnaire-Female Version (SDBQ), and the Questionnaire of Cognitive Schemas Activated in Sexual Context (QCSASC). Findings indicate that neuroticism moderates the association between frequency of negative sexual events and activation of incompetence schemas in heterosexual women. Moreover, several sexual beliefs also act as moderators of the relationship between negative sexual episodes and the activation of cognitive schemas in both heterosexual and lesbian women. Overall, findings support the cognitive-emotional model of sexual dysfunctions, emphasizing the role of personality traits and dysfunctional sexual beliefs as facilitators of the activation of incompetence schemas in response to negative events in women.

Sirt1 Protects against Oxidative Stress-Induced Apoptosis in Fibroblasts from Psoriatic Patients: A New Insight into the Pathogenetic Mechanisms of Psoriasis.

PubMed

Becatti, Matteo; Barygina, Victoria; Mannucci, Amanda; Emmi, Giacomo; Prisco, Domenico; Lotti, Torello; Fiorillo, Claudia; Taddei, Niccolò

2018-05-25

Psoriasis, a multisystem chronic disease characterized by abnormal keratinocyte proliferation, has an unclear pathogenesis where systemic inflammation and oxidative stress play mutual roles. Dermal fibroblasts, which are known to provide a crucial microenvironment for epidermal keratinocyte function, represented the selected experimental model in our study which aimed to clarify the potential role of SIRT1 in the pathogenetic mechanisms of the disease. We firstly detected the presence of oxidative stress (lipid peroxidation and total antioxidant capacity), significantly reduced SIRT1 expression level and activity, mitochondrial damage and apoptosis (caspase-3, -8 and -9 activities) in psoriatic fibroblasts. Upon SIRT1 activation, redox balance was re-established, mitochondrial function was restored and apoptosis was no longer evident. Furthermore, we examined p38, ERK and JNK activation, which was strongly altered in psoriatic fibroblasts, in response to SIRT1 activation and we measured caspase-3 activity in the presence of specific MAPK inhibitors demonstrating the key role of the SIRT1 pathway against apoptotic cell death via MAPK modulation. Our results clearly demonstrate the involvement of SIRT1 in the protective mechanisms related to fibroblast injury in psoriasis. SIRT1 activation exerts an active role in restoring both mitochondrial function and redox balance via modulation of MAPK signaling. Hence, SIRT1 can be proposed as a specific tool for the treatment of psoriasis.

Thermal activation of dislocations in large scale obstacle bypass

NASA Astrophysics Data System (ADS)

Sobie, Cameron; Capolungo, Laurent; McDowell, David L.; Martinez, Enrique

2017-08-01

Dislocation dynamics simulations have been used extensively to predict hardening caused by dislocation-obstacle interactions, including irradiation defect hardening in the athermal case. Incorporating the role of thermal energy on these interactions is possible with a framework provided by harmonic transition state theory (HTST) enabling direct access to thermally activated reaction rates using the Arrhenius equation, including rates of dislocation-obstacle bypass processes. Moving beyond unit dislocation-defect reactions to a representative environment containing a large number of defects requires coarse-graining the activation energy barriers of a population of obstacles into an effective energy barrier that accurately represents the large scale collective process. The work presented here investigates the relationship between unit dislocation-defect bypass processes and the distribution of activation energy barriers calculated for ensemble bypass processes. A significant difference between these cases is observed, which is attributed to the inherent cooperative nature of dislocation bypass processes. In addition to the dislocation-defect interaction, the morphology of the dislocation segments pinned to the defects play an important role on the activation energies for bypass. A phenomenological model for activation energy stress dependence is shown to describe well the effect of a distribution of activation energies, and a probabilistic activation energy model incorporating the stress distribution in a material is presented.

Strategic Planning as a Basis for Restructuring Schools.

ERIC Educational Resources Information Center

Adams, Charles F.; Mecca, Thomas V.

An educational planning model and instructional approach to prepare school administrators for the role of strategic planners are described. The model, ED QUEST, integrates future research techniques and divergent thinking modes into a participatory group process that provides visions of alternative futures. Primary activities in the process…

New technologies for examining the role of neuronal ensembles in drug addiction and fear.

PubMed

Cruz, Fabio C; Koya, Eisuke; Guez-Barber, Danielle H; Bossert, Jennifer M; Lupica, Carl R; Shaham, Yavin; Hope, Bruce T

2013-11-01

Correlational data suggest that learned associations are encoded within neuronal ensembles. However, it has been difficult to prove that neuronal ensembles mediate learned behaviours because traditional pharmacological and lesion methods, and even newer cell type-specific methods, affect both activated and non-activated neurons. In addition, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviourally activated and non-activated neurons. Here, we describe three new approaches--Daun02 inactivation, FACS sorting of activated neurons and Fos-GFP transgenic rats--that have been used to selectively target and study activated neuronal ensembles in models of conditioned drug effects and relapse. We also describe two new tools--Fos-tTA transgenic mice and inactivation of CREB-overexpressing neurons--that have been used to study the role of neuronal ensembles in conditioned fear.

A mechanistic model for mercury capture with in situ-generated titania particles: role of water vapor.

PubMed

Rodríguez, Sylian; Almquist, Catherine; Lee, Tai Gyu; Furuuchi, Masami; Hedrick, Elizabeth; Biswas, Pratim

2004-02-01

A mechanistic model to predict the capture of gas-phase mercury (Hg) species using in situ-generated titania nanosize particles activated by UV irradiation is developed. The model is an extension of a recently reported model for photochemical reactions by Almquist and Biswas that accounts for the rates of electron-hole pair generation, the adsorption of the compound to be oxidized, and the adsorption of water vapor. The role of water vapor in the removal efficiency of Hg was investigated to evaluate the rates of Hg oxidation at different water vapor concentrations. As the water vapor concentration is increased, more hydroxy radical species are generated on the surface of the titania particle, increasing the number of active sites for the photooxidation and capture of Hg. At very high water vapor concentrations, competitive adsorption is expected to be important and reduce the number of sites available for photooxidation of Hg. The predictions of the developed phenomenological model agreed well with the measured Hg oxidation rates in this study and with the data on oxidation of organic compounds reported in the literature.

Resveratrol-Activated AMPK/SIRT1/Autophagy in Cellular Models of Parkinson's Disease

PubMed Central

Wu, Yuncheng; Li, Xinqun; Zhu, Julie Xiaohong; Xie, Wenjie; Le, Weidong; Fan, Zhen; Jankovic, Joseph; Pan, Tianhong

2011-01-01

Excessive misfolded proteins and/or dysfunctional mitochondria, which may cause energy deficiency, have been implicated in the etiopathogenesis of Parkinson's disease (PD). Enhanced clearance of misfolded proteins or injured mitochondria via autophagy has been reported to have neuroprotective roles in PD models. The fact that resveratrol is a known compound with multiple beneficial effects similar to those associated with energy metabolism led us to explore whether neuroprotective effects of resveratrol are related to its role in autophagy regulation. We tested whether modulation of mammalian silent information regulator 2 (SIRT1) and/or metabolic energy sensor AMP-activated protein kinase (AMPK) are involved in autophagy induction by resveratrol, leading to neuronal survival. Our results showed that resveratrol protected against rotenone-induced apoptosis in SH-SY5Y cells and enhanced degradation of α-synucleins in α-synuclein-expressing PC12 cell lines via autophagy induction. We found that suppression of AMPK and/or SIRT1 caused decrease of protein level of LC3-II, indicating that AMPK and/or SIRT1 are required in resveratrol-mediated autophagy induction. Moreover, suppression of AMPK caused inhibition of SIRT1 activity and attenuated protective effects of resveratrol on rotenone-induced apoptosis, further suggesting that AMPK-SIRT1-autophagy pathway plays an important role in the neuroprotection by resveratrol on PD cellular models. PMID:21778691

Injury-stimulated Sonic hedgehog expression in microglia contributes to neuroinflammatory response in the MPTP model of Parkinson's disease

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

Lee, Jeong Hwi; Department of Biochemistry & Molecular Biology, School of Medicine Kyung Hee University, Seoul 130-701; Chung, Young Cheul

Parkinson's disease (PD) is a progressive neurodegenerative disorder in which dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) region are selectively destroyed. Sonic hedgehog (Shh) has been well known to play a key role in a variety of processes such as embryogenesis, cell proliferation and protection, and tissue repair during inflammation. However, the evidences for the innate role of Shh in adult brain injury are presently lacking and studies have been needed to unveil the importance of Shh in the process of neurodegeneration. Here, we investigated the role of Shh in the pathologic progress of Parkinson's disease inmore » MPTP-induced animal model system. Interestingly, we observed that Shh expression was gradually increased in MPTP affected SNpc region. Activated microglia exclusively expressed SHH in vivo and we could recapitulate Shh induction in activated cultured primary microglia cells. Using the SHH responsive Cre-loxP binary genetic reporter transgenic mouse system, we also found that most of the cell types except for oligodendrocyte in the SNpc region reacted to the SHH by MPTP injection. Taken together, activated microglia induced Shh expression and most neural cells except oligodendrocyte responded to microglia-derived SHH in MPTP-treated SN. These results suggest that SHH in activated microglia by MPTP-injection might be involved in the innate processes of recovery from neurotoxin induced injury in the PD animal model system. - Highlights: • Sonic hedgehog (Shh) was induced by MPTP neurotoxin at the Substantia Nigra (SN) in vivo. • Activated microglia are major cell type for SHH expression in vivo and in vitro. • Different types of cells in the brain, except oligodendrocyte, respond to microglia-derived SHH in SN region.« less

Cofilin Inhibition Restores Neuronal Cell Death in Oxygen-Glucose Deprivation Model of Ischemia.

PubMed

Madineni, Anusha; Alhadidi, Qasim; Shah, Zahoor A

2016-03-01

Ischemia is a condition associated with decreased blood supply to the brain, eventually leading to death of neurons. It is associated with a diverse cascade of responses involving both degenerative and regenerative mechanisms. At the cellular level, the changes are initiated prominently in the neuronal cytoskeleton. Cofilin, a cytoskeletal actin severing protein, is known to be involved in the early stages of apoptotic cell death. Evidence supports its intervention in the progression of disease states like Alzheimer's and ischemic kidney disease. In the present study, we have hypothesized the possible involvement of cofilin in ischemia. Using PC12 cells and mouse primary cultures of cortical neurons, we investigated the potential role of cofilin in ischemia in two different in vitro ischemic models: chemical induced oxidative stress and oxygen-glucose deprivation/reperfusion (OGD/R). The expression profile studies demonstrated a decrease in phosphocofilin levels in all models of ischemia, implying stress-induced cofilin activation. Furthermore, calcineurin and slingshot 1L (SSH) phosphatases were found to be the signaling mediators of the cofilin activation. In primary cultures of cortical neurons, cofilin was found to be significantly activated after 1 h of OGD. To delineate the role of activated cofilin in ischemia, we knocked down cofilin by small interfering RNA (siRNA) technique and tested the impact of cofilin silencing on neuronal viability. Cofilin siRNA-treated neurons showed a significant reduction of cofilin levels in all treatment groups (control, OGD, and OGD/R). Additionally, cofilin siRNA-reduced cofilin mitochondrial translocation and caspase 3 cleavage, with a concomitant increase in neuronal viability. These results strongly support the active role of cofilin in ischemia-induced neuronal degeneration and apoptosis. We believe that targeting this protein mediator has a potential for therapeutic intervention in ischemic brain injury and stroke.

Understanding the determinants of selectivity in drug metabolism through modeling of dextromethorphan oxidation by cytochrome P450

PubMed Central

Oláh, Julianna; Mulholland, Adrian J.; Harvey, Jeremy N.

2011-01-01

Cytochrome P450 enzymes play key roles in the metabolism of the majority of drugs. Improved models for prediction of likely metabolites will contribute to drug development. In this work, two possible metabolic routes (aromatic carbon oxidation and O-demethylation) of dextromethorphan are compared using molecular dynamics (MD) simulations and density functional theory (DFT). The DFT results on a small active site model suggest that both reactions might occur competitively. Docking and MD studies of dextromethorphan in the active site of P450 2D6 show that the dextromethorphan is located close to heme oxygen in a geometry apparently consistent with competitive metabolism. In contrast, calculations of the reaction path in a large protein model [using a hybrid quantum mechanical–molecular mechanics (QM/MM) method] show a very strong preference for O-demethylation, in accordance with experimental results. The aromatic carbon oxidation reaction is predicted to have a high activation energy, due to the active site preventing formation of a favorable transition-state structure. Hence, the QM/MM calculations demonstrate a crucial role of many active site residues in determining reactivity of dextromethorphan in P450 2D6. Beyond substrate binding orientation and reactivity of Compound I, successful metabolite predictions must take into account the detailed mechanism of oxidation in the protein. These results demonstrate the potential of QM/MM methods to investigate specificity in drug metabolism. PMID:21444768

Neuronal pattern separation of motion-relevant input in LIP activity

PubMed Central

Berberian, Nareg; MacPherson, Amanda; Giraud, Eloïse; Richardson, Lydia

2016-01-01

In various regions of the brain, neurons discriminate sensory stimuli by decreasing the similarity between ambiguous input patterns. Here, we examine whether this process of pattern separation may drive the rapid discrimination of visual motion stimuli in the lateral intraparietal area (LIP). Starting with a simple mean-rate population model that captures neuronal activity in LIP, we show that overlapping input patterns can be reformatted dynamically to give rise to separated patterns of neuronal activity. The population model predicts that a key ingredient of pattern separation is the presence of heterogeneity in the response of individual units. Furthermore, the model proposes that pattern separation relies on heterogeneity in the temporal dynamics of neural activity and not merely in the mean firing rates of individual neurons over time. We confirm these predictions in recordings of macaque LIP neurons and show that the accuracy of pattern separation is a strong predictor of behavioral performance. Overall, results propose that LIP relies on neuronal pattern separation to facilitate decision-relevant discrimination of sensory stimuli. NEW & NOTEWORTHY A new hypothesis is proposed on the role of the lateral intraparietal (LIP) region of cortex during rapid decision making. This hypothesis suggests that LIP alters the representation of ambiguous inputs to reduce their overlap, thus improving sensory discrimination. A combination of computational modeling, theoretical analysis, and electrophysiological data shows that the pattern separation hypothesis links neural activity to behavior and offers novel predictions on the role of LIP during sensory discrimination. PMID:27881719

An aPPARent Functional Consequence in Skeletal Muscle Physiology via Peroxisome Proliferator-Activated Receptors.

PubMed

Phua, Wendy Wen Ting; Wong, Melissa Xin Yu; Liao, Zehuan; Tan, Nguan Soon

2018-05-10

Skeletal muscle comprises 30⁻40% of the total body mass and plays a central role in energy homeostasis in the body. The deregulation of energy homeostasis is a common underlying characteristic of metabolic syndrome. Over the past decades, peroxisome proliferator-activated receptors (PPARs) have been shown to play critical regulatory roles in skeletal muscle. The three family members of PPAR have overlapping roles that contribute to the myriad of processes in skeletal muscle. This review aims to provide an overview of the functions of different PPAR members in energy homeostasis as well as during skeletal muscle metabolic disorders, with a particular focus on human and relevant mouse model studies.

An aPPARent Functional Consequence in Skeletal Muscle Physiology via Peroxisome Proliferator-Activated Receptors

PubMed Central

Phua, Wendy Wen Ting; Wong, Melissa Xin Yu; Liao, Zehuan

2018-01-01

Skeletal muscle comprises 30–40% of the total body mass and plays a central role in energy homeostasis in the body. The deregulation of energy homeostasis is a common underlying characteristic of metabolic syndrome. Over the past decades, peroxisome proliferator-activated receptors (PPARs) have been shown to play critical regulatory roles in skeletal muscle. The three family members of PPAR have overlapping roles that contribute to the myriad of processes in skeletal muscle. This review aims to provide an overview of the functions of different PPAR members in energy homeostasis as well as during skeletal muscle metabolic disorders, with a particular focus on human and relevant mouse model studies. PMID:29747466

Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors.

PubMed

Teissier, Anne; Chemiakine, Alexei; Inbar, Benjamin; Bagchi, Sneha; Ray, Russell S; Palmiter, Richard D; Dymecki, Susan M; Moore, Holly; Ansorge, Mark S

2015-12-01

Despite the well-established role of serotonin signaling in mood regulation, causal relationships between serotonergic neuronal activity and behavior remain poorly understood. Using a pharmacogenetic approach, we find that selectively increasing serotonergic neuronal activity in wild-type mice is anxiogenic and reduces floating in the forced-swim test, whereas inhibition has no effect on the same measures. In a developmental mouse model of altered emotional behavior, increased anxiety and depression-like behaviors correlate with reduced dorsal raphé and increased median raphé serotonergic activity. These mice display blunted responses to serotonergic stimulation and behavioral rescues through serotonergic inhibition. Furthermore, we identify opposing consequences of dorsal versus median raphé serotonergic neuron inhibition on floating behavior, together suggesting that median raphé hyperactivity increases anxiety, whereas a low dorsal/median raphé serotonergic activity ratio increases depression-like behavior. Thus, we find a critical role of serotonergic neuronal activity in emotional regulation and uncover opposing roles of median and dorsal raphé function. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Disease-Causing Mutations in the G Protein Gαs Subvert the Roles of GDP and GTP.

PubMed

Hu, Qi; Shokat, Kevan M

2018-05-17

The single most frequent cancer-causing mutation across all heterotrimeric G proteins is R201C in Gαs. The current model explaining the gain-of-function activity of the R201 mutations is through the loss of GTPase activity and resulting inability to switch off to the GDP state. Here, we find that the R201C mutation can bypass the need for GTP binding by directly activating GDP-bound Gαs through stabilization of an intramolecular hydrogen bond network. Having found that a gain-of-function mutation can convert GDP into an activator, we postulated that a reciprocal mutation might disrupt the normal role of GTP. Indeed, we found R228C, a loss-of-function mutation in Gαs that causes pseudohypoparathyroidism type 1a (PHP-Ia), compromised the adenylyl cyclase-activating activity of Gαs bound to a non-hydrolyzable GTP analog. These findings show that disease-causing mutations in Gαs can subvert the canonical roles of GDP and GTP, providing new insights into the regulation mechanism of G proteins. Copyright © 2018 Elsevier Inc. All rights reserved.

An attachment model of depression: integrating findings from the mood disorder laboratory.

PubMed

Holmes, Jeremy

2013-01-01

This paper is written from a psychodynamic clinician's perspective, juxtaposing a psychoanalytic-attachment model of depression with recent developments in neuroscience. Three main components of the attachment approach are described: the role of loss, of childhood trauma predisposing to depression in later life, and failure of co-regulation of role of primitive emotions, such as fear, despair, and helplessness. Blatt's distinction between anaclitic and introjective depression is delineated and related to hyper- and de-activation of the attachment dynamic. Recent advances in evolutionary, sociological, epigenetic, biochemical, and neuro-imaging studies of depression are reviewed. A dynamic model of depression is proposed, linking interpersonal and intra-psychic perspectives with neuro-anatomical models. The final section of the paper considers the specific role of psychodynamic approaches to the treatment of refractory depression. These include length of treatment, capacity to rework implicit memories, and focus on transference and counter-transference.

Growing up and Role Modeling: A Theory in Iranian Nursing Students’ Education

PubMed Central

Nouri, Jamileh Mokhtari; Ebadi, Abbas; Alhani, Fatemeh; Rejeh, Nahid

2015-01-01

One of the key strategies in students’ learning is being affected by models. Understanding the role-modeling process in education will help to make greater use of this training strategy. The aim of this grounded theory study was to explore Iranian nursing students and instructors’ experiences about role modeling process. Data was analyzed by Glaserian’s Grounded Theory methodology through semi-structured interviews with 7 faculty members, 2 nursing students; the three focus group discussions with 20 nursing students based on purposive and theoretical sampling was done for explaining role modeling process from four nursing faculties in Tehran. Through basic coding, an effort to comprehensive growth and excellence was made with the basic social process consisting the core category and through selective coding three phases were identified as: realizing and exposure to inadequate human and professional growth, facilitating human and professional growth and evolution. The role modeling process is taking place unconscious, involuntary, dynamic and with positive progressive process in order to facilitate overall growth in nursing student. Accordingly, the design and implementation of the designed model can be used to make this unconscious to conscious, active and voluntarily processes a process to help education administrators of nursing colleges and supra organization to prevent threats to human and professional in nursing students’ education and promote nursing students’ growth. PMID:25716391

G-protein signaling modulator 1 deficiency accelerates cystic disease in an orthologous mouse model of autosomal dominant polycystic kidney disease

PubMed Central

Kwon, Michelle; Pavlov, Tengis S.; Nozu, Kandai; Rasmussen, Shauna A.; Ilatovskaya, Daria V.; Lerch-Gaggl, Alexandra; North, Lauren M.; Kim, Hyunho; Qian, Feng; Sweeney, William E.; Avner, Ellis D.; Blumer, Joe B.; Staruschenko, Alexander; Park, Frank

2012-01-01

Polycystic kidney diseases are the most common genetic diseases that affect the kidney. There remains a paucity of information regarding mechanisms by which G proteins are regulated in the context of polycystic kidney disease to promote abnormal epithelial cell expansion and cystogenesis. In this study, we describe a functional role for the accessory protein, G-protein signaling modulator 1 (GPSM1), also known as activator of G-protein signaling 3, to act as a modulator of cyst progression in an orthologous mouse model of autosomal dominant polycystic kidney disease (ADPKD). A complete loss of Gpsm1 in the Pkd1V/V mouse model of ADPKD, which displays a hypomorphic phenotype of polycystin-1, demonstrated increased cyst progression and reduced renal function compared with age-matched cystic Gpsm1+/+ and Gpsm1+/− mice. Electrophysiological studies identified a role by which GPSM1 increased heteromeric polycystin-1/polycystin-2 ion channel activity via Gβγ subunits. In summary, the present study demonstrates an important role for GPSM1 in controlling the dynamics of cyst progression in an orthologous mouse model of ADPKD and presents a therapeutic target for drug development in the treatment of this costly disease. PMID:23236168

Dual Roles of Endogenous Platelet-activating Factor Acetylhydrolase in a Murine Model of Necrotizing Enterocolitis

PubMed Central

Lu, Jing; Pierce, Marissa; Franklin, Andrew; Jilling, Tamas; Stafforini, Diana M.; Caplan, Michael

2010-01-01

Human preterm infants with necrotizing enterocolitis (NEC) have increased circulating and luminal levels of platelet-activating factor (PAF) and decreased serum PAF-acetylhydrolase (PAF-AH), the enzyme that inactivates PAF. Formula supplemented with recombinant PAF-AH decreases NEC in a neonatal rat model. We hypothesized that endogenous PAF-AH contributes to neonatal intestinal homeostasis, and therefore developed PAF-AH−/− mice using standard approaches to study the role of this enzyme in the neonatal NEC model. Following exposure to a well-established NEC model, intestinal tissues were evaluated for histology, pro-inflammatory cytokine mRNA synthesis, and death using standard techniques. We found that mortality rates were significantly lower in PAF-AH−/− pups compared to wild-type controls before 24 hours of life but surviving PAF-AH−/− animals were more susceptible to NEC development compared to wild-type controls. Increased NEC incidence was associated with prominent inflammation characterized by elevated intestinal mRNA expression of sPLA2, iNOS and CXCL1. In conclusion, the data support a protective role for endogenous PAF-AH in the development of NEC, and since preterm neonates have endogenous PAF-AH deficiency, this may place them at increased risk for disease. PMID:20531249

Using peer-assisted learning and role-playing to teach generic skills to dental students: the health care simulation model.

PubMed

El Tantawi, Maha M A; Abdelaziz, Hytham; AbdelRaheem, Amira S; Mahrous, Ahmed A

2014-01-01

Increasing importance is attached to teaching generic skills to undergraduate students in various disciplines. This article describes an extracurricular, student-led activity for teaching generic skills using the Model United Nations over three months. The activity used the Health Care Simulation Model (HCSM) with peer learning and role-playing to accomplish its objectives. An interview was used to select from undergraduate and postgraduate dental students at Alexandria University, Alexandria, Egypt, to develop a group of staff to act as peer teachers after receiving training (n=77). These peer teachers provided training for 123 undergraduate dental students to serve as delegates who acted as trainees or peer learners. At the end of the training sessions, a conference was held in which the students played the roles of delegates representing officials responsible for health care systems in ten countries. The students reported improvement in generic skills, enjoyed several aspects of the experience, and disliked other aspects of the model to a lesser extent. In multivariate analysis, perceived usefulness of the HCSM was significantly greater for staff than delegates and increased as self-reported improvement in knowledge of health care systems increased. This study suggests that innovative, student-centered educational methods can be effective for teaching generic skills and factual information.

The Role of Oxysterols in a Computational Steroidogenesis Model of Human H295R Cells to Improve Predictability of Biochemical Responses to Endocrine Disruptors

EPA Science Inventory

Steroids, which have an important role in a wide range of physiological processes, are synthesized primarily in the gonads and adrenal glands through a series of enzyme mediated reactions. The activity of steroidogenic enzymes can be altered by a variety of endocrine disruptors (...

The quiescent chromospheres and transition regions of active dwarf stars - What are we learning from recent observations and models?

NASA Technical Reports Server (NTRS)

Linsky, J. L.

1983-01-01

Progress in understanding active dwarf stars based on recent IUE, Einstein, and ground-based observations is reviewed. The extent of magnetic field control over nonflare phenomena in active dwarf stars is considered, and the spatial homogeneity and time variability of active dwarf atmospheres is discussed. The possibility that solar like flux tubes can explain enhanced heating in active dwarf stars in examined, and the roles of systematic flows in active dwarf star atmospheres are considered. The relation between heating rates in different layers of active dwarf stars is summarized, and the mechanism of chromosphere and transition region heating in these stars are discussed. The results of one-component and two-component models of active dwarf stars are addressed.

Effect of PAR-2 Deficiency in Mice on KC Expression after Intratracheal LPS Administration

PubMed Central

Williams, Julie C.; Lee, Rebecca D.; Doerschuk, Claire M.; Mackman, Nigel

2011-01-01

Protease activated receptors (PAR) have been shown to play a role in inflammation. PAR-2 is expressed by numerous cells in the lung and has either proinflammatory, anti-inflammatory, or no effect depending on the model. Here, we examined the role of PAR-2 in a model of LPS-induced lung inflammation. We found that PAR-2-deficient mice had significantly less KC expression in bronchial lavage fluid compared with wild-type mice but there was no difference in MIP-2 or TNF-α expression. We also found that isolated alveolar and resident peritoneal macrophages lacking PAR-2 showed a similar deficit in KC after LPS stimulation without differences in MIP-2 or TNF-α. Infiltration of neutrophils and macrophages into the lung following LPS administration was not affected by an absence of PAR-2. Our results support the notion that PAR-2 plays a role in LPS activation of TLR4 signaling in macrophages. PMID:22175012

Effect of PAR-2 Deficiency in Mice on KC Expression after Intratracheal LPS Administration.

PubMed

Williams, Julie C; Lee, Rebecca D; Doerschuk, Claire M; Mackman, Nigel

2011-01-01

Protease activated receptors (PAR) have been shown to play a role in inflammation. PAR-2 is expressed by numerous cells in the lung and has either proinflammatory, anti-inflammatory, or no effect depending on the model. Here, we examined the role of PAR-2 in a model of LPS-induced lung inflammation. We found that PAR-2-deficient mice had significantly less KC expression in bronchial lavage fluid compared with wild-type mice but there was no difference in MIP-2 or TNF-α expression. We also found that isolated alveolar and resident peritoneal macrophages lacking PAR-2 showed a similar deficit in KC after LPS stimulation without differences in MIP-2 or TNF-α. Infiltration of neutrophils and macrophages into the lung following LPS administration was not affected by an absence of PAR-2. Our results support the notion that PAR-2 plays a role in LPS activation of TLR4 signaling in macrophages.

Basal ganglia circuit loops, dopamine and motivation: A review and enquiry

PubMed Central

Ikemoto, Satoshi; Yang, Chen; Tan, Aaron

2015-01-01

Dopamine neurons located in the midbrain play a role in motivation that regulates approach behavior (approach motivation). In addition, activation and inactivation of dopamine neurons regulate mood and induce reward and aversion, respectively. Accumulating evidence suggests that such motivational role of dopamine neurons is not limited to those located in the ventral tegmental area, but also in the substantia nigra. The present paper reviews previous rodent work concerning dopamine’s role in approach motivation and the connectivity of dopamine neurons, and proposes two working models: One concerns the relationship between extracellular dopamine concentration and approach motivation. High, moderate and low concentrations of extracellular dopamine induce euphoric, seeking and aversive states, respectively. The other concerns circuit loops involving the cerebral cortex, basal ganglia, thalamus, epithalamus, and midbrain through which dopaminergic activity alters approach motivation. These models should help to generate hypothesis-driven research and provide insights for understanding altered states associated with drugs of abuse and affective disorders. PMID:25907747

Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned

PubMed Central

Gudi, Viktoria; Gingele, Stefan; Skripuletz, Thomas; Stangel, Martin

2014-01-01

Although astrogliosis and microglia activation are characteristic features of multiple sclerosis (MS) and other central nervous system (CNS) lesions the exact functions of these events are not fully understood. Animal models help to understand the complex interplay between the different cell types of the CNS and uncover general mechanisms of damage and repair of myelin sheaths. The so called cuprizone model is a toxic model of demyelination in the CNS white and gray matter, which lacks an autoimmune component. Cuprizone induces apoptosis of mature oligodendrocytes that leads to a robust demyelination and profound activation of both astrocytes and microglia with regional heterogeneity between different white and gray matter regions. Although not suitable to study autoimmune mediated demyelination, this model is extremely helpful to elucidate basic cellular and molecular mechanisms during de- and particularly remyelination independently of interactions with peripheral immune cells. Phagocytosis and removal of damaged myelin seems to be one of the major roles of microglia in this model and it is well known that removal of myelin debris is a prerequisite of successful remyelination. Furthermore, microglia provide several signals that support remyelination. The role of astrocytes during de- and remyelination is not well defined. Both supportive and destructive functions have been suggested. Using the cuprizone model we could demonstrate that there is an important crosstalk between astrocytes and microglia. In this review we focus on the role of glial reactions and interaction in the cuprizone model. Advantages and limitations of as well as its potential therapeutic relevance for the human disease MS are critically discussed in comparison to other animal models. PMID:24659953

The Road to Creative Achievement: A Latent Variable Model of Ability and Personality Predictors

PubMed Central

Jauk, Emanuel; Benedek, Mathias; Neubauer, Aljoscha C

2014-01-01

This study investigated the significance of different well-established psychometric indicators of creativity for real-life creative outcomes. Specifically, we tested the effects of creative potential, intelligence, and openness to experiences on everyday creative activities and actual creative achievement. Using a heterogeneous sample of 297 adults, we performed latent multiple regression analyses by means of structural equation modelling. We found openness to experiences and two independent indicators of creative potential, ideational originality and ideational fluency, to predict everyday creative activities. Creative activities, in turn, predicted actual creative achievement. Intelligence was found to predict creative achievement, but not creative activities. Moreover, intelligence moderated the effect of creative activities on creative achievement, suggesting that intelligence may play an important role in transforming creative activities into publically acknowledged creative achievements. This study supports the view of creativity as a multifaceted construct and provides an integrative model illustrating the potential interplay between its different facets. PMID:24532953

Alternative complement pathway activation increases mortality in a model of burn injury in mice.

PubMed Central

Gelfand, J A; Donelan, M; Hawiger, A; Burke, J F

1982-01-01

We have studied the role of the complement system in burn injury in an experimental model in mice. A 25% body surface area, full-thickness scald wound was produced in anesthetized animals. Massive activation of the alternative complement pathway, but not the classical pathway, was seen. This activation was associated with the generation of neutrophil aggregating activity in the plasma, neutrophil aggregates in the lungs, increased pulmonary vascular permeability, and increased lung edema formation. Decomplementation with cobra venom factor (CVF) or genetic C5 deficiency diminished these pathologic changes, and CVF pretreatment substantially reduced burn mortality in the first 24 h. Preliminary data show that human burn patients have a similar pattern of complement activation involving predominantly the alternative pathway, indicating the possible relevance of the murine model to human disease. Images PMID:7174787

PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR) AGONISTS AS PROMISING NEW MEDICATIONS FOR DRUG ADDICTION: PRECLINICAL EVIDENCE

PubMed Central

Foll, Bernard Le; Ciano, Patricia Di; Panlilio, Leigh V.; Goldberg, Steven R.; Ciccocioppo, Roberto

2013-01-01

This review examines the growing literature on the role of peroxisome proliferator-activated receptors (PPARs) in addiction. There are two subtypes of PPAR receptors that have been studied in addiction: PPAR-α and PPAR-γ. The role of each PPAR subtype in common models of addictive behavior, mainly pre-clinical models, is summarized. In particular, studies are reviewed that investigated the effects of PPAR-α agonists on relapse, sensitization, conditioned place preference, withdrawal and drug intake, and effects of PPAR-γ agonists on relapse, withdrawal and drug intake. Finally, studies that investigated the effects of PPAR agonists on neural pathways of addiction are reviewed. Taken together this preclinical data indicates that PPAR agonists are promising new medications for drug addiction treatment. PMID:23614675

Spring-Loaded Model Revisited: Paramyxovirus Fusion Requires Engagement of a Receptor Binding Protein beyond Initial Triggering of the Fusion Protein▿

PubMed Central

Porotto, Matteo; DeVito, Ilaria; Palmer, Samantha G.; Jurgens, Eric M.; Yee, Jia L.; Yokoyama, Christine C.; Pessi, Antonello; Moscona, Anne

2011-01-01

During paramyxovirus entry into a host cell, receptor engagement by a specialized binding protein triggers conformational changes in the adjacent fusion protein (F), leading to fusion between the viral and cell membranes. According to the existing paradigm of paramyxovirus membrane fusion, the initial activation of F by the receptor binding protein sets off a spring-loaded mechanism whereby the F protein progresses independently through the subsequent steps in the fusion process, ending in membrane merger. For human parainfluenza virus type 3 (HPIV3), the receptor binding protein (hemagglutinin-neuraminidase [HN]) has three functions: receptor binding, receptor cleaving, and activating F. We report that continuous receptor engagement by HN activates F to advance through the series of structural rearrangements required for fusion. In contrast to the prevailing model, the role of HN-receptor engagement in the fusion process is required beyond an initiating step, i.e., it is still required even after the insertion of the fusion peptide into the target cell membrane, enabling F to mediate membrane merger. We also report that for Nipah virus, whose receptor binding protein has no receptor-cleaving activity, the continuous stimulation of the F protein by a receptor-engaged binding protein is key for fusion. We suggest a general model for paramyxovirus fusion activation in which receptor engagement plays an active role in F activation, and the continued engagement of the receptor binding protein is essential to F protein function until the onset of membrane merger. This model has broad implications for the mechanism of paramyxovirus fusion and for strategies to prevent viral entry. PMID:21976650

Spring-loaded model revisited: paramyxovirus fusion requires engagement of a receptor binding protein beyond initial triggering of the fusion protein.

PubMed

Porotto, Matteo; Devito, Ilaria; Palmer, Samantha G; Jurgens, Eric M; Yee, Jia L; Yokoyama, Christine C; Pessi, Antonello; Moscona, Anne

2011-12-01

During paramyxovirus entry into a host cell, receptor engagement by a specialized binding protein triggers conformational changes in the adjacent fusion protein (F), leading to fusion between the viral and cell membranes. According to the existing paradigm of paramyxovirus membrane fusion, the initial activation of F by the receptor binding protein sets off a spring-loaded mechanism whereby the F protein progresses independently through the subsequent steps in the fusion process, ending in membrane merger. For human parainfluenza virus type 3 (HPIV3), the receptor binding protein (hemagglutinin-neuraminidase [HN]) has three functions: receptor binding, receptor cleaving, and activating F. We report that continuous receptor engagement by HN activates F to advance through the series of structural rearrangements required for fusion. In contrast to the prevailing model, the role of HN-receptor engagement in the fusion process is required beyond an initiating step, i.e., it is still required even after the insertion of the fusion peptide into the target cell membrane, enabling F to mediate membrane merger. We also report that for Nipah virus, whose receptor binding protein has no receptor-cleaving activity, the continuous stimulation of the F protein by a receptor-engaged binding protein is key for fusion. We suggest a general model for paramyxovirus fusion activation in which receptor engagement plays an active role in F activation, and the continued engagement of the receptor binding protein is essential to F protein function until the onset of membrane merger. This model has broad implications for the mechanism of paramyxovirus fusion and for strategies to prevent viral entry.

Modeling: An Important Ingredient in Higher Education for American Indian Women Students.

ERIC Educational Resources Information Center

Edwards, E. Daniel; And Others

1984-01-01

Discusses characteristics and behaviors of effective role models for American Indian women, based on surveys of graduates of the American Indian Social Work Career Training Program at the University of Utah. Recruitment and retention of American Indian women students will require an active support system. (JAC)

Problem Solving Techniques for the Design of Algorithms.

ERIC Educational Resources Information Center

Kant, Elaine; Newell, Allen

1984-01-01

Presents model of algorithm design (activity in software development) based on analysis of protocols of two subjects designing three convex hull algorithms. Automation methods, methods for studying algorithm design, role of discovery in problem solving, and comparison of different designs of case study according to model are highlighted.…

Socializing Giftedness: Toward an ACCEL-S Approach

ERIC Educational Resources Information Center

Glaveanu, Vlad P.; Kaufman, James C.

2017-01-01

In this response, we commend Sternberg's Active Concerned Citizenship and Ethical Leadership (ACCEL) model yet urge him to consider an ACCEL-S model that more fully incorporates society's integrative role in giftedness. ACCEL-S builds on the highly complex and contextual view of giftedness proposed by Sternberg and transforms it into a…

Augmenting Literacy: The Role of Expertise in Digital Writing

ERIC Educational Resources Information Center

Van Ittersum, Derek

2011-01-01

This essay presents a model of reflective use of writing technologies, one that provides a means of more fully exploiting the possibilities of these tools for transforming writing activity. Derived from the work of computer designer Douglas Engelbart, the "bootstrapping" model of reflective use extends current arguments in the field…

Role of Peroxisome Proliferator-Activated Receptors in Inflammation Control

PubMed Central

Badr, Mostafa

2004-01-01

Peroxisome proliferator-activated receptors (PPARs) were discovered over a decade ago, and were classified as orphan members of the nuclear receptor superfamily. To date, three PPAR subtypes have been discovered and characterized (PPARα, β/δ, γ). Different PPAR subtypes have been shown to play crucial roles in important diseases and conditions such as obesity, diabetes, atherosclerosis, cancer, and fertility. Among the most studied roles of PPARs is their involvement in inflammatory processes. Numerous studies have revealed that agonists of PPARα and PPARγ exert anti-inflammatory effects both in vitro and in vivo. Using the carrageenan-induced paw edema model of inflammation, a recent study in our laboratories showed that these agonists hinder the initiation phase, but not the late phase of the inflammatory process. Furthermore, in the same experimental model, we recently also observed that activation of PPARδ exerted an anti-inflammatory effect. Despite the fact that exclusive dependence of these effects on PPARs has been questioned, the bulk of evidence suggests that all three PPAR subtypes, PPARα, δ, γ, play a significant role in controlling inflammatory responses. Whether these subtypes act via a common mechanism or are independent of each other remains to be elucidated. However, due to the intensity of research efforts in this area, it is anticipated that these efforts will result in the development of PPAR ligands as therapeutic agents for the treatment of inflammatory diseases. PMID:15292582

Predicting the Functional Roles of Knee Joint Muscles from Internal Joint Moments.

PubMed

Flaxman, Teresa E; Alkjær, Tine; Simonsen, Erik B; Krogsgaard, Michael R; Benoit, Daniel L

2017-03-01

Knee muscles are commonly labeled as flexors or extensors and aptly stabilize the knee against sagittal plane loads. However, how these muscles stabilize the knee against adduction-abduction and rotational loads remains unclear. Our study sought 1) to classify muscle roles as they relate to joint stability by quantifying the relationship between individual muscle activation patterns and internal net joint moments in all three loading planes and 2) to determine whether these roles change with increasing force levels. A standing isometric force matching protocol required subjects to modulate ground reaction forces to elicit various combinations and magnitudes of sagittal, frontal, and transverse internal joint moments. Surface EMG measured activities of 10 lower limb muscles. Partial least squares regressions determined which internal moment(s) were significantly related to the activation of individual muscles. Rectus femoris and tensor fasciae latae were classified as moment actuators for knee extension and hip flexion. Hamstrings were classified as moment actuators for hip extension and knee flexion. Gastrocnemius and hamstring muscles were classified as specific joint stabilizers for knee rotation. Vastii were classified as general joint stabilizers because activation was independent of moment generation. Muscle roles did not change with increasing effort levels. Our findings indicate muscle activation is not dependent on anatomical orientation but perhaps on its role in maintaining knee joint stability in the frontal and transverse loading planes. This is useful for delineating the roles of biarticular knee joint muscles and could have implications in robotics, musculoskeletal modeling, sports sciences, and rehabilitation.

Hsp31, a member of the DJ-1 superfamily, is a multitasking stress responder with chaperone activity

PubMed Central

Aslam, Kiran; Hazbun, Tony R.

2016-01-01

ABSTRACT Among different types of protein aggregation, amyloids are a biochemically well characterized state of protein aggregation that are associated with a large number of neurodegenerative diseases including Parkinson's disease, Alzheimer and Creutzfeldt-Jakob disease. Yeast, Saccharomyces cerevisiae is an insightful model to understand the underlying mechanism of protein aggregation. Many yeast molecular chaperones can modulate aggregation and misfolding of proteins including α-Syn and the Sup35 prion. Hsp31 is a homodimeric protein structurally similar to human DJ-1, a Parkinson's disease-linked protein, and both are members of the DJ-1/ThiJ/PfpI superfamily. An emerging view is that Hsp31 and its associated superfamily members each have divergent multitasking functions that have the common theme of responding and managing various types of cellular stress. Hsp31 has several biochemical activities including chaperone and detoxifying enzyme activities that modulate at various points of a stress pathway such as toxicity associated with protein misfolding. However, we have shown the protective role of Hsp31's chaperone activity can operate independent of detoxifying enzyme activities in preventing the early stages of protein aggregate formation and associated cellular toxicities. We provide additional data that collectively supports the multiple functional roles that can be accomplished independent of each other. We present data indicating Hsp31 purified from yeast is more active compared to expression and purification from E. coli suggesting that posttranslational modifications could be important for Hsp31 to be fully active. We also compare the similarities and differences in activities among paralogs of Hsp31 supporting a model in which this protein family has overlapping but diverging roles in responding to various sources of cellular stresses. PMID:27097320

Modeling Cytoskeletal Active Matter Systems

NASA Astrophysics Data System (ADS)

Blackwell, Robert

Active networks of filamentous proteins and crosslinking motor proteins play a critical role in many important cellular processes. One of the most important microtubule-motor protein assemblies is the mitotic spindle, a self-organized active liquid-crystalline structure that forms during cell division and that ultimately separates chromosomes into two daughter cells. Although the spindle has been intensively studied for decades, the physical principles that govern its self-organization and function remain mysterious. To evolve a better understanding of spindle formation, structure, and dynamics, I investigate course-grained models of active liquid-crystalline networks composed of microtubules, modeled as hard spherocylinders, in diffusive equilibrium with a reservoir of active crosslinks, modeled as hookean springs that can adsorb to microtubules and and translocate at finite velocity along the microtubule axis. This model is investigated using a combination of brownian dynamics and kinetic monte carlo simulation. I have further refined this model to simulate spindle formation and kinetochore capture in the fission yeast S. pombe. I then make predictions for experimentally realizable perturbations in motor protein presence and function in S. pombe.

Active subthreshold dendritic conductances shape the local field potential

PubMed Central

Ness, Torbjørn V.; Remme, Michiel W. H.

2016-01-01

Key points The local field potential (LFP), the low‐frequency part of extracellular potentials recorded in neural tissue, is often used for probing neural circuit activity. Interpreting the LFP signal is difficult, however.While the cortical LFP is thought mainly to reflect synaptic inputs onto pyramidal neurons, little is known about the role of the various subthreshold active conductances in shaping the LFP.By means of biophysical modelling we obtain a comprehensive qualitative understanding of how the LFP generated by a single pyramidal neuron depends on the type and spatial distribution of active subthreshold currents.For pyramidal neurons, the h‐type channels probably play a key role and can cause a distinct resonance in the LFP power spectrum.Our results show that the LFP signal can give information about the active properties of neurons and imply that preferred frequencies in the LFP can result from those cellular properties instead of, for example, network dynamics. Abstract The main contribution to the local field potential (LFP) is thought to stem from synaptic input to neurons and the ensuing subthreshold dendritic processing. The role of active dendritic conductances in shaping the LFP has received little attention, even though such ion channels are known to affect the subthreshold neuron dynamics. Here we used a modelling approach to investigate the effects of subthreshold dendritic conductances on the LFP. Using a biophysically detailed, experimentally constrained model of a cortical pyramidal neuron, we identified conditions under which subthreshold active conductances are a major factor in shaping the LFP. We found that, in particular, the hyperpolarization‐activated inward current, I h, can have a sizable effect and cause a resonance in the LFP power spectral density. To get a general, qualitative understanding of how any subthreshold active dendritic conductance and its cellular distribution can affect the LFP, we next performed a systematic study with a simplified model. We found that the effect on the LFP is most pronounced when (1) the synaptic drive to the cell is asymmetrically distributed (i.e. either basal or apical), (2) the active conductances are distributed non‐uniformly with the highest channel densities near the synaptic input and (3) when the LFP is measured at the opposite pole of the cell relative to the synaptic input. In summary, we show that subthreshold active conductances can be strongly reflected in LFP signals, opening up the possibility that the LFP can be used to characterize the properties and cellular distributions of active conductances. PMID:27079755

Program Planners’ Perspectives of Promotora Roles, Recruitment, and Selection

PubMed Central

Koskan, Alexis; Hilfinger Messias, DeAnne K.; Friedman, Daniela B.; Brandt, Heather M.; Walsemann, Katrina M.

2013-01-01

Objective Program planners work with promotoras (the Spanish term for female community health workers) to reduce health disparities among underserved populations. Based on the Role-Outcomes Linkage Evaluation Model for Community Health Workers (ROLES) conceptual model, we explored how program planners conceptualized the promotora role and the approaches and strategies they used to recruit, select, and sustain promotoras. Design We conducted semi-structured, in-depth interviews with a purposive convenience sample of 24 program planners, program coordinators, promotora recruiters, research principal investigators, and other individuals who worked closely with promotoras on United States-based health programs for Hispanic women (ages 18 and older). Results Planners conceptualized the promotora role based on their personal experiences and their understanding of the underlying philosophical tenets of the promotora approach. Recruitment and selection methods reflected planners’ conceptualizations and experiences of promotoras as paid staff or volunteers. Participants described a variety of program planning and implementation methods. They focused on sustainability of the programs, the intended health behavior changes or activities, and the individual promotoras. Conclusion To strengthen health programs employing the promotora delivery model, job descriptions should delineate role expectations and boundaries and better guide promotora evaluations. We suggest including additional components such as information on funding sources, program type and delivery, and sustainability outcomes to enhance the ROLES conceptual model. The expanded model can be used to guide program planners in the planning, implementing, and evaluating of promotora health programs. PMID:23039847

Generalization of value in reinforcement learning by humans.

PubMed

Wimmer, G Elliott; Daw, Nathaniel D; Shohamy, Daphna

2012-04-01

Research in decision-making has focused on the role of dopamine and its striatal targets in guiding choices via learned stimulus-reward or stimulus-response associations, behavior that is well described by reinforcement learning theories. However, basic reinforcement learning is relatively limited in scope and does not explain how learning about stimulus regularities or relations may guide decision-making. A candidate mechanism for this type of learning comes from the domain of memory, which has highlighted a role for the hippocampus in learning of stimulus-stimulus relations, typically dissociated from the role of the striatum in stimulus-response learning. Here, we used functional magnetic resonance imaging and computational model-based analyses to examine the joint contributions of these mechanisms to reinforcement learning. Humans performed a reinforcement learning task with added relational structure, modeled after tasks used to isolate hippocampal contributions to memory. On each trial participants chose one of four options, but the reward probabilities for pairs of options were correlated across trials. This (uninstructed) relationship between pairs of options potentially enabled an observer to learn about option values based on experience with the other options and to generalize across them. We observed blood oxygen level-dependent (BOLD) activity related to learning in the striatum and also in the hippocampus. By comparing a basic reinforcement learning model to one augmented to allow feedback to generalize between correlated options, we tested whether choice behavior and BOLD activity were influenced by the opportunity to generalize across correlated options. Although such generalization goes beyond standard computational accounts of reinforcement learning and striatal BOLD, both choices and striatal BOLD activity were better explained by the augmented model. Consistent with the hypothesized role for the hippocampus in this generalization, functional connectivity between the ventral striatum and hippocampus was modulated, across participants, by the ability of the augmented model to capture participants' choice. Our results thus point toward an interactive model in which striatal reinforcement learning systems may employ relational representations typically associated with the hippocampus. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

An update on the potential role of intestinal first-pass metabolism for the prediction of drug-drug interactions: the role of PBPK modeling.

PubMed

Alqahtani, Saeed; Bukhari, Ishfaq; Albassam, Ahmed; Alenazi, Maha

2018-05-28

The intestinal absorption process is a combination of several events that are governed by various factors. Several transport mechanisms are involved in drug absorption through enterocytes via active and/or passive processes. The transported molecules then undergo intestinal metabolism, which together with intestinal transport may affect the systemic availability of drugs. Many studies have provided clear evidence on the significant role of intestinal first-pass metabolism on drug bioavailability and degree of drug-drug interactions (DDIs). Areas covered: This review provides an update on the role of intestinal first-pass metabolism in the oral bioavailability of drugs and prediction of drug-drug interactions. It also provides a comprehensive overview and summary of the latest update in the role of PBPK modeling in prediction of intestinal metabolism and DDIs in humans. Expert opinion: The contribution of intestinal first-pass metabolism in the oral bioavailability of drugs and prediction of DDIs has become more evident over the last few years. Several in vitro, in situ, and in vivo models have been developed to evaluate the role of first-pass metabolism and to predict DDIs. Currently, physiologically based pharmacokinetic modeling is considered the most valuable tool for the prediction of intestinal first-pass metabolism and DDIs.

When the model fits the frame: the impact of regulatory fit on efficacy appraisal and persuasion in health communication.

PubMed

Bosone, Lucia; Martinez, Frédéric; Kalampalikis, Nikos

2015-04-01

In health-promotional campaigns, positive and negative role models can be deployed to illustrate the benefits or costs of certain behaviors. The main purpose of this article is to investigate why, how, and when exposure to role models strengthens the persuasiveness of a message, according to regulatory fit theory. We argue that exposure to a positive versus a negative model activates individuals' goals toward promotion rather than prevention. By means of two experiments, we demonstrate that high levels of persuasion occur when a message advertising healthy dietary habits offers a regulatory fit between its framing and the described role model. Our data also establish that the effects of such internal regulatory fit by vicarious experience depend on individuals' perceptions of response-efficacy and self-efficacy. Our findings constitute a significant theoretical complement to previous research on regulatory fit and contain valuable practical implications for health-promotional campaigns. © 2015 by the Society for Personality and Social Psychology, Inc.

A neuron-astrocyte transistor-like model for neuromorphic dressed neurons.

PubMed

Valenza, G; Pioggia, G; Armato, A; Ferro, M; Scilingo, E P; De Rossi, D

2011-09-01

Experimental evidences on the role of the synaptic glia as an active partner together with the bold synapse in neuronal signaling and dynamics of neural tissue strongly suggest to investigate on a more realistic neuron-glia model for better understanding human brain processing. Among the glial cells, the astrocytes play a crucial role in the tripartite synapsis, i.e. the dressed neuron. A well-known two-way astrocyte-neuron interaction can be found in the literature, completely revising the purely supportive role for the glia. The aim of this study is to provide a computationally efficient model for neuron-glia interaction. The neuron-glia interactions were simulated by implementing the Li-Rinzel model for an astrocyte and the Izhikevich model for a neuron. Assuming the dressed neuron dynamics similar to the nonlinear input-output characteristics of a bipolar junction transistor, we derived our computationally efficient model. This model may represent the fundamental computational unit for the development of real-time artificial neuron-glia networks opening new perspectives in pattern recognition systems and in brain neurophysiology. Copyright © 2011 Elsevier Ltd. All rights reserved.

Anti-quorum sensing activity of AgCl-TiO2 nanoparticles with potential use as active food packaging material.

PubMed

Naik, K; Kowshik, M

2014-10-01

To study the anti-quorum sensing (anti-QS) activity of AgCl-TiO2 nanoparticles (ATNPs) and its mechanism. Anti-QS activity of ATNPs was evaluated using the bacterial model Chromobacterium violaceum. Silver present in ATNPs significantly reduced violacein production in a concentration-dependent manner, indicating inhibition of QS. Anti-QS activity was confirmed by the absence of signalling molecule, oxo-octanoyl homoserine lactone during growth in the presence of ATNPs. TiO2 acted as a good supporting matrix facilitating controlled release of silver with prolonged residual activity. ATNPs are proposed as QS inhibitors with potential for use as an antipathogenic but nontoxic bioactive material. Although silver is well known for its bioactive potential of antibacterial, antifungal and antiviral properties, this study adds further note on its anti-QS activity and its potential use in food packaging industry. Food spoilage is a major socio-economic problem, and the potential role of QS in food spoilage and food safety has been indicated. Anti-QS materials such as ATNPs are proposed as efficient models for controlling food spoilage. ATNPs incorporated in food packaging materials could play an important role in food preservation and ensure safety of food by prolonging their shelf life. © 2014 The Society for Applied Microbiology.

Computational biology analysis of platelet signaling reveals roles of feedbacks through phospholipase C and inositol 1,4,5-trisphosphate 3-kinase in controlling amplitude and duration of calcium oscillations.

PubMed

Balabin, Fedor A; Sveshnikova, Anastasia N

2016-06-01

Blood platelet activation is required to allow their participation in hemostasis and thrombosis. It is regulated by a complicated signaling network, whose functioning has been recently attracting attention for basic research and pharmacological purposes. Phospholipase С (PLC) is an enzyme playing an important role in platelet calcium signaling and responsible for release of inositol triphosphate (IP3) into platelet cytoplasm thus controlling intracellular calcium concentration. Using a comprehensive computational model of platelet calcium signaling, we studied the influence of the positive feedback executed by cytosolic calcium on the PLC isoform β2 during platelet activation. With the positive feedback, the model predicted hyperintensive response to platelet activation by thrombin, where non-physiologically high calcium concentrations arose. However, if one took into account a negative feedback determined by IP3 3-kinase (IP3K), combination of the feedback resulted in the formation of a stepped response (with a stable oscillation amplitude and activation-dependent duration). Stochastic simulations confirmed that PLC and IP3K should act in pair to ensure platelet's "all-or-none" response to activation, when the activation level sets the probability of platelet activation, but not its intensity. Copyright © 2016 Elsevier Inc. All rights reserved.

The NBS Energy Model Assessment project: Summary and overview

NASA Astrophysics Data System (ADS)

Gass, S. I.; Hoffman, K. L.; Jackson, R. H. F.; Joel, L. S.; Saunders, P. B.

1980-09-01

The activities and technical reports for the project are summarized. The reports cover: assessment of the documentation of Midterm Oil and Gas Supply Modeling System; analysis of the model methodology characteristics of the input and other supporting data; statistical procedures undergirding construction of the model and sensitivity of the outputs to variations in input, as well as guidelines and recommendations for the role of these in model building and developing procedures for their evaluation.

Extending the Trans-Contextual Model in Physical Education and Leisure-Time Contexts: Examining the Role of Basic Psychological Need Satisfaction

ERIC Educational Resources Information Center

Barkoukis, Vassilis; Hagger, Martin S.; Lambropoulos, George; Tsorbatzoudis, Haralambos

2010-01-01

Background: The trans-contextual model (TCM) is an integrated model of motivation that aims to explain the processes by which agentic support for autonomous motivation in physical education promotes autonomous motivation and physical activity in a leisure-time context. It is proposed that perceived support for autonomous motivation in physical…

The Role of Familiarity, Priming and Perception in Similarity Judgments

DTIC Science & Technology

2013-08-01

Goldstone, & Markman, 1995), and memory (Roediger, 1990). As with many aspects of human cognition, however, the mechanisms that determine similarity are...activation, which disperses activation be- tween different, associated concepts in declarative memory (Anderson, 1983; Harrison & Trafton, 2010). In...over time the model builds up declarative memories that may contribute to spreading activation in later trials. This explains the two main effects

Reading Aloud: Discrete Stage(s) Redux

PubMed Central

Robidoux, Serje; Besner, Derek

2017-01-01

Interactive activation accounts of processing have had a broad and deep influence on cognitive psychology, particularly so in the context of computational accounts of reading aloud at the single word level. Here we address the issue of whether such a framework can simulate the joint effects of stimulus quality and word frequency (which have been shown to produce both additive and interactive effects depending on the context). We extend previous work on this question by considering an alternative implementation of a stimulus quality manipulation, and the role of interactive activation. Simulations with a version of the Dual Route Cascaded model (a model with interactive activation dynamics along the lexical route) demonstrate that the model is unable to simulate the entire pattern seen in human performance. We discuss how a hybrid interactive activation model that includes some context dependent staged processing could accommodate these data. PMID:28289395

Modelling proteins' hidden conformations to predict antibiotic resistance

NASA Astrophysics Data System (ADS)

Hart, Kathryn M.; Ho, Chris M. W.; Dutta, Supratik; Gross, Michael L.; Bowman, Gregory R.

2016-10-01

TEM β-lactamase confers bacteria with resistance to many antibiotics and rapidly evolves activity against new drugs. However, functional changes are not easily explained by differences in crystal structures. We employ Markov state models to identify hidden conformations and explore their role in determining TEM's specificity. We integrate these models with existing drug-design tools to create a new technique, called Boltzmann docking, which better predicts TEM specificity by accounting for conformational heterogeneity. Using our MSMs, we identify hidden states whose populations correlate with activity against cefotaxime. To experimentally detect our predicted hidden states, we use rapid mass spectrometric footprinting and confirm our models' prediction that increased cefotaxime activity correlates with reduced Ω-loop flexibility. Finally, we design novel variants to stabilize the hidden cefotaximase states, and find their populations predict activity against cefotaxime in vitro and in vivo. Therefore, we expect this framework to have numerous applications in drug and protein design.

Role played by Disabled-2 in albumin induced MAP Kinase signalling

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

Diwakar, Ramaswamy; Pearson, Alexander L.; Colville-Nash, Paul

2008-02-15

Albumin has been shown to activate the mitogen activated protein kinase (MAPK) pathway in proximal tubular cells (PTECs) of the kidney. Megalin, the putative receptor for albumin has potential signalling properties. However, the mechanisms by which megalin signals are unclear. The adaptor phosphoprotein Disabled-2 (Dab2) is known to interact with the cytoplasmic tail of megalin and may be involved in albumin-mediated MAPK signalling. In this study, we investigated the role of Dab2 in albumin-mediated MAPK signalling and further studied the role of Dab2 in albumin-induced TGF{beta}-1 secretion, a MAPK dependent event. We used RNA interference to knockdown Dab2 protein abundancemore » in HKC-8 cells a model of human PTECs. Albumin activated ERK1,2 and Elk-1 in a MEK-1 dependent manner and resulted in secretion of TGF{beta}-1. In the absence of albumin, knockdown of Dab2 resulted in a trend towards increase in pERK1,2 consistent with its putative role as an inhibitor of cell proliferation. However albumin-induced ERK1,2 activation was completely abolished by Dab2 knockdown. Dab2 knockdown did not however result in inhibition of albumin-induced TGF{beta}-1 secretion. These results suggest that Dab2 is a ligand dependent bi-directional regulator of ERK1,2 activity by demonstrating that in addition to its more traditional role as an inhibitor of ERK1,2 it may also activate ERK1,2.« less

Dissection of the components for PIP2 activation and thermosensation in TRP channels

PubMed Central

Brauchi, Sebastian; Orta, Gerardo; Mascayano, Carolina; Salazar, Marcelo; Raddatz, Natalia; Urbina, Hector; Rosenmann, Eduardo; Gonzalez-Nilo, Fernando; Latorre, Ramon

2007-01-01

Phosphatidylinositol 4,5-bisphosphate (PIP2) plays a central role in the activation of several transient receptor potential (TRP) channels. The role of PIP2 on temperature gating of thermoTRP channels has not been explored in detail, and the process of temperature activation is largely unexplained. In this work, we have exchanged different segments of the C-terminal region between cold-sensitive (TRPM8) and heat-sensitive (TRPV1) channels, trying to understand the role of the segment in PIP2 and temperature activation. A chimera in which the proximal part of the C-terminal of TRPV1 replaces an equivalent section of TRPM8 C-terminal is activated by PIP2 and confers the phenotype of heat activation. PIP2, but not temperature sensitivity, disappears when positively charged residues contained in the exchanged region are neutralized. Shortening the exchanged segment to a length of 11 aa produces voltage-dependent and temperature-insensitive channels. Our findings suggest the existence of different activation domains for temperature, PIP2, and voltage. We provide an interpretation for channel–PIP2 interaction using a full-atom molecular model of TRPV1 and PIP2 docking analysis. PMID:17548815

Does active ageing contribute to life satisfaction for older people? Testing a new model of active ageing.

PubMed

Marsillas, Sara; De Donder, Liesbeth; Kardol, Tinie; van Regenmortel, Sofie; Dury, Sarah; Brosens, Dorien; Smetcoren, An-Sofie; Braña, Teresa; Varela, Jesús

2017-09-01

Several debates have emerged across the literature about the conceptualisation of active ageing. The aim of this study is to develop a model of the construct that is focused on the individual, including different elements of people's lives that have the potential to be modified by intervention programs. Moreover, the paper examines the contributions of active ageing to life satisfaction, as well as the possible predictive role of coping styles on active ageing. For this purpose, a representative sample of 404 Galician (Spain) community-dwelling older adults (aged ≥60 years) were interviewed using a structured survey. The results demonstrate that the proposed model composed of two broad categories is valid. The model comprises status variables (related to physical, psychological, and social health) as well as different types of activities, called processual variables. This model is tested using partial least squares (PLS) regression. The findings show that active ageing is a fourth-order, formative construct. In addition, PLS analyses indicate that active ageing has a moderate and positive path on life satisfaction and that coping styles may predict active ageing. The discussion highlights the potential of active ageing as a relevant concept for people's lives, drawing out policy implications and suggestions for further research.

The Role of Prominence in Pronoun Resolution: Active versus Passive Representations

ERIC Educational Resources Information Center

Foraker, Stephani; McElree, Brian

2007-01-01

A prominent antecedent facilitates anaphor resolution. Speed-accuracy tradeoff modeling in Experiments 1 and 3 indicated that clefting did not affect the speed of accessing an antecedent representation, which is inconsistent with claims that discourse-focused information is actively maintained in focal attention [e.g., Gundel, J. K. (1999). "On…

Affective Decision-Making and Externalizing Behaviors: The Role of Autonomic Activity

ERIC Educational Resources Information Center

Bubier, Jennifer L.; Drabick, Deborah A. G.

2008-01-01

We tested a conceptual model involving the inter-relations among affective decision-making (indexed by a gambling task), autonomic nervous system (ANS) activity, and attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in a largely impoverished, inner city sample of first through third grade children (N…

The Role of Entrepreneurship Program Models and Experiential Activities on Engineering Student Outcomes

ERIC Educational Resources Information Center

Duval-Couetil, Nathalie; Shartrand, Angela; Reed, Teri

2016-01-01

Entrepreneurship education is being delivered to greater numbers of engineering students through a variety of courses, programs, and experiential learning activities. Some of these opportunities are designed primarily to serve engineering students in their departments and colleges, while others are cross-campus, university-wide efforts to serve…

H[subscript 2]O and You

ERIC Educational Resources Information Center

Jackson, Julie

2009-01-01

Learning about states of matter is fun and exciting when students, acting as water molecules, role-play moving from a solid to a liquid to a gas. The 5-E lesson plan model provides the framework for this activity, ensuring that students actively engage in inquiry science while creatively constructing knowledge. (Contains 2 figures.)

Constitutively active mutants of the alpha 1B-adrenergic receptor: role of highly conserved polar amino acids in receptor activation.

PubMed Central

Scheer, A; Fanelli, F; Costa, T; De Benedetti, P G; Cotecchia, S

1996-01-01

Site-directed mutagenesis and molecular dynamics simulations of the alpha 1B-adrenergic receptor (AR) were combined to explore the potential molecular changes correlated with the transition from R (inactive state) to R (active state). Using molecular dynamics analysis we compared the structural/dynamic features of constitutively active mutants with those of the wild type and of an inactive alpha 1B-AR to build a theoretical model which defines the essential features of R and R. The results of site-directed mutagenesis were in striking agreement with the predictions of the model supporting the following hypothesis. (i) The equilibrium between R and R depends on the equilibrium between the deprotonated and protonated forms, respectively, of D142 of the DRY motif. In fact, replacement of D142 with alanine confers high constitutive activity to the alpha 1B-AR. (ii) The shift of R143 of the DRY sequence out of a conserved 'polar pocket' formed by N63, D91, N344 and Y348 is a feature common to all the active structures, suggesting that the role of R143 is fundamental for mediating receptor activation. Disruption of these intramolecular interactions by replacing N63 with alanine constitutively activates the alpha 1B-AR. Our findings might provide interesting generalities about the activation process of G protein-coupled receptors. Images PMID:8670860

How the Group Investigation Model and the Six-Mirror Model Changed Teachers' Roles and Teachers' and Students' Attitudes towards Diversity

ERIC Educational Resources Information Center

Damini, Marialuisa

2014-01-01

This paper is based on research that demonstrates the positive effects of the cooperative learning model Group Investigation (GI) and the Six-Mirror model on teacher effectiveness in organizing and scaffolding CL activities, and changing students' and teachers' views of diversity. We explain how the connection between the two models…

Controlling Nuclear Jaks and Stats for Specific Gene Activation by Ifn γ and Other Cytokines: A Possible Steroid-like Connection

PubMed Central

Johnson, Howard M.; Noon-Song, Ezra; Ahmed, Chulbul M.

2011-01-01

The mechanism of specific gene activation by cytokines that use JAK/STAT signalling pathway is unknown. There are four different types of JAKs and seven different types of STATs. In the classical model of signaling, ligand interacts solely with the receptor extracellular domain, which triggers JAK activation at the receptor cytoplasmic domain. Activated STATs are then said to carry out nuclear events of specific gene activation, including associated epigenetic changes that cause heterochromatin destabilization. Ligand, receptor, and JAKs play no further role in the classical model. Given the limited number of STATs and the activation of the same STATs by cytokines with different functions, the mechanism of the specificity of their signalling is not obvious. Focusing on gamma interferon (IFNγ), we have shown that ligand, receptor, and activated JAKs are involved in nuclear events that are associated with specific gene activation. In this model, receptor subunit IFNGR1 functions as a transcription/cotranscription factor and the JAKs are involved in key epigenetic events that are required for specific gene activation. The model has implications for gene activation in cancer as well as stem cell differentiation. PMID:22924155

Controlling Nuclear Jaks and Stats for Specific Gene Activation by Ifn γ and Other Cytokines: A Possible Steroid-like Connection.

PubMed

Johnson, Howard M; Noon-Song, Ezra; Ahmed, Chulbul M

2011-09-03

The mechanism of specific gene activation by cytokines that use JAK/STAT signalling pathway is unknown. There are four different types of JAKs and seven different types of STATs. In the classical model of signaling, ligand interacts solely with the receptor extracellular domain, which triggers JAK activation at the receptor cytoplasmic domain. Activated STATs are then said to carry out nuclear events of specific gene activation, including associated epigenetic changes that cause heterochromatin destabilization. Ligand, receptor, and JAKs play no further role in the classical model. Given the limited number of STATs and the activation of the same STATs by cytokines with different functions, the mechanism of the specificity of their signalling is not obvious. Focusing on gamma interferon (IFNγ), we have shown that ligand, receptor, and activated JAKs are involved in nuclear events that are associated with specific gene activation. In this model, receptor subunit IFNGR1 functions as a transcription/cotranscription factor and the JAKs are involved in key epigenetic events that are required for specific gene activation. The model has implications for gene activation in cancer as well as stem cell differentiation.

Constitutively active transforming growth factor β receptor 1 in the mouse ovary promotes tumorigenesis

PubMed Central

Gao, Yang; Vincent, David F.; Davis, Anna Jane; Sansom, Owen J.; Bartholin, Laurent; Li, Qinglei

2016-01-01

Despite the well-established tumor suppressive role of TGFβ proteins, depletion of key TGFβ signaling components in the mouse ovary does not induce a growth advantage. To define the role of TGFβ signaling in ovarian tumorigenesis, we created a mouse model expressing a constitutively active TGFβ receptor 1 (TGFBR1) in ovarian somatic cells using conditional gain-of-function approach. Remarkably, these mice developed ovarian sex cord-stromal tumors with complete penetrance, leading to reproductive failure and mortality. The tumors expressed multiple granulosa cell markers and caused elevated serum inhibin and estradiol levels, reminiscent of granulosa cell tumors. Consistent with the tumorigenic effect, overactivation of TGFBR1 altered tumor microenvironment by promoting angiogenesis and enhanced ovarian cell proliferation, accompanied by impaired cell differentiation and dysregulated expression of critical genes in ovarian function. By further exploiting complementary genetic models, we substantiated our finding that constitutively active TGFBR1 is a potent oncogenic switch in mouse granulosa cells. In summary, overactivation of TGFBR1 drives gonadal tumor development. The TGFBR1 constitutively active mouse model phenocopies a number of morphological, hormonal, and molecular features of human granulosa cell tumors and are potentially valuable for preclinical testing of targeted therapies to treat granulosa cell tumors, a class of poorly defined ovarian malignancies. PMID:27344183

Investigation of interaction between Pax-5 isoforms and thioredoxin using de novo modelling methods.

PubMed

Cuperlovic-Culf, Miroslava; Robichaud, Gilles A; Nardini, Michel; Ouellette, Rodney J

2003-01-01

Pax-5 transcription factor plays a crucial role in B-cell development, activation and differentiation. In murine B-cells four different isoforms of Pax-5 have been identified, and their role in the regulation of the activity of the wild-type protein was revealed although still not fully understood. Using theoretical methods, we investigated the properties of one region of the Pax-5e and Pax-5d isoforms (named UDE domain) and we present a possible theoretical model for the interaction of this domain with thioredoxin that have been previously postulated based on the experimental results. Domain UDE (MW 4.8 kDa) is characterised by an extremely high ratio of positively charged residues (8) in comparisons to negatively charged amino acids (3), as well as unusually large concentrations of prolines (11.6%) and cysteines (4.7%). This is indicative of its role in protein-protein interaction. The experimental 3D structure for either UDE domain or for any analogous sequence is not yet available, and therefore we resorted to various bioinformatics methods in order to predict the secondary and 3D structure from the primary sequence of UDE. Physicochemical properties of the predicted UDE structure gave more indication about possibilities for UDE-thioredoxin binding. In addition, UDE domain was shown to have both sequence and structure analogous to a segment of NAD-reducing hydrogenase HOXS a subunit which is believed to interact with thioredoxin. These studies showed that the UDE domain in Pax-5d and Pax-5e represents an ideal binding site for thioredoxin and we developed a model of UDE-TRX complex with two disulphide bridges. The active site of thioredoxin remained exposed after binding to UDE in this model and therefore binding of thioredoxin to Pax-5d could explain the unexpectedly high resistance of this isoform to oxidation. The complex between thioredoxin and Pax-5e can be a method for transportation of thioredoxin into the nucleus and also into the the vicinity of Pax-5a, explaining the observed activator role of Pax-5e.

Regulation of transcriptional activators by DNA-binding domain ubiquitination

PubMed Central

Landré, Vivien; Revi, Bhindu; Mir, Maria Gil; Verma, Chandra; Hupp, Ted R; Gilbert, Nick; Ball, Kathryn L

2017-01-01

Ubiquitin is a key component of the regulatory network that maintains gene expression in eukaryotes, yet the molecular mechanism(s) by which non-degradative ubiquitination modulates transcriptional activator (TA) function is unknown. Here endogenous p53, a stress-activated transcription factor required to maintain health, is stably monoubiquitinated, following pathway activation by IR or Nutlin-3 and localized to the nucleus where it becomes tightly associated with chromatin. Comparative structure–function analysis and in silico modelling demonstrate a direct role for DNA-binding domain (DBD) monoubiquitination in TA activation. When attached to the DBD of either p53, or a second TA IRF-1, ubiquitin is orientated towards, and makes contact with, the DNA. The contact is made between a predominantly cationic surface on ubiquitin and the anionic DNA. Our data demonstrate an unexpected role for ubiquitin in the mechanism of TA-activity enhancement and provides insight into a new level of transcriptional regulation. PMID:28362432

Hippocampal Erk Mechanisms Linking Prediction Error to Fear Extinction: Roles of Shock Expectancy and Contextual Aversive Valence

ERIC Educational Resources Information Center

Huh, Kyu Hwan; Guzman, Yomayra F.; Tronson, Natalie C.; Guedea, Anita L.; Gao, Can; Radulovic, Jelena

2009-01-01

Extinction of fear requires learning that anticipated aversive events no longer occur. Animal models reveal that sustained phosphorylation of the extracellular signal-regulated kinase (Erk) in hippocampal CA1 neurons plays an important role in this process. However, the key signals triggering and regulating the activity of Erk are not known. By…

Left Inferior Frontal Cortex and Syntax: Function, Structure and Behaviour in Patients with Left Hemisphere Damage

ERIC Educational Resources Information Center

Tyler, Lorraine K.; Marslen-Wilson, William D.; Randall, Billi; Wright, Paul; Devereux, Barry J.; Zhuang, Jie; Papoutsi, Marina; Stamatakis, Emmanuel A.

2011-01-01

For the past 150 years, neurobiological models of language have debated the role of key brain regions in language function. One consistently debated set of issues concern the role of the left inferior frontal gyrus in syntactic processing. Here we combine measures of functional activity, grey matter integrity and performance in patients with left…

THE ROLE OF ANDROGENS AND ESTROGENS IN THE DEVELOPMENT OF BRAIN AND PERIPHERAL NERVOUS SYSTEM: APPROACHES TO DEVELOPING ANIMAL MODELS FOR SEXUALLY DIMORPHIC BEHAVIORS

EPA Science Inventory

This presentation provides an overview of research on the effects of hormonally active chemicals on sexual differentiation of the brain including (a) research on the role of androgens and estrogens in the development of the brain and peripheral nervous system, (b) approaches to d...

Context-dependent role of IL-18 in cancer biology and counter-regulation by IL-18BP.

PubMed

Fabbi, Marina; Carbotti, Grazia; Ferrini, Silvano

2015-04-01

IL-18 is a proinflammatory and immune regulatory cytokine, member of the IL-1 family. IL-18 was initially identified as an IFN-γ-inducing factor in T and NK cells, involved in Th1 responses. IL-18 is produced as an inactive precursor (pro-IL-18) that is enzymatically processed into a mature form by Casp1. Different cells, such as macrophages, DCs, microglial cells, synovial fibroblasts, and epithelial cells, express pro-IL-18, and the production of bioactive IL-18 is mainly regulated at the processing level. PAMP or DAMP molecules activate inflammasomes, which trigger Casp1 activation and IL-18 conversion. The natural inhibitor IL-18BP , whose production is enhanced by IFN-γ and IL-27, further regulates IL-18 activity in the extracellular environment. Inflammasomes and IL-18 represent double-edged swords in cancer, as their activation may promote tumor development and progression or oppositely, enhance anti-tumor immunity and limit tumor growth. IL-18 has shown anti-tumor activity in different preclinical models of cancer immunotherapy through the activation of NK and/or T cell responses and has been tested in clinical studies in cancer patients. However, the dual role of IL-18 in different experimental tumor models and human cancers raises critical issues on its therapeutic use in cancer. This review will summarize the biology of the IL-18/IL-18R/IL-18BP system and will address the role of IL-18 and its inhibitor, IL-18BP, in cancer biology and immunotherapy. © Society for Leukocyte Biology.

Australian athletes' health behaviours and perceptions of role modelling and marketing of unhealthy products.

PubMed

Grunseit, Anne C; MacNiven, Rona; Orr, Rhonda; Grassmayr, Matt; Kelly, Bridget; Davies, Daniel; Colagiuri, Stephen; Bauman, Adrian E

2012-04-01

This study examined Australian athletes' support for athletes' role in promoting physical activity and obesity prevention, the acceptability of unhealthy products promotion in sport, and their own health behaviours. Surveys were conducted with (n = 1990) elite and sub-elite athletes recruited from 22 sports across Australia. Athletes' perceptions and behaviours were analysed across demographic and sport-related factors (e.g. individual vs team sport) and correlations calculated between perceptions and health behaviours. Most respondents supported a role for athletes in promoting physical activity and obesity prevention, and disagreed that athletes should promote unhealthy foods and alcohol (73.9%). Athletes reported low smoking rates, but high rates of binge drinking. Female, younger, individual and amateur athletes had more health-positive perceptions and healthier behaviours than older, male, team and professional athletes. More sympathy towards junk food and alcohol advertising in sport and less support for athletes as role models were associated with more unhealthy behaviours. Elite athletes are receptive to supporting health promotion through sport and many are not in agreement with the promotion of unhealthy products in sport or by sports people. Improving elite athletes' health behaviours would benefit not only the individual but also health promotion within elite sport.

Building and Breaking the Cell Wall in Four Acts: A Kinesthetic and Tactile Role-Playing Exercise for Teaching Beta-Lactam Antibiotic Mechanism of Action and Resistance †

PubMed Central

Popovich, John; Stephens, Michelle; Celaya, Holly; Suwarno, Serena; Barclay, Shizuka; Yee, Emily; Dean, David A.; Farris, Megan; Haydel, Shelley E.

2018-01-01

“Building and breaking the cell wall” is designed to review the bacterial cell envelope, previously learned in lower-division biology classes, while introducing new topics such as antibiotics and bacterial antibiotic resistance mechanisms. We developed a kinesthetic and tactile modeling activity where students act as cellular components and construct the cell wall. In the first two acts, students model a portion of the gram-positive bacterial cell envelope and then demonstrate in detail how the peptidoglycan is formed. Act III involves student demonstration of the addition of β-lactam antibiotics to the environment and how they inhibit the formation of peptidoglycan, thereby preventing bacterial replication. Using Staphylococcus aureus as a model for gram-positive bacteria, students finish the activity (Act IV) by acting out how S. aureus often becomes resistant to β-lactam antibiotics. A high level of student engagement was observed, and the activity received positive feedback. In an assessment administered prior to and two months after the activity, significant improvements in scores were observed (p < 0.0001), demonstrating increased understanding and retention. This activity allows students to (i) visualize, role play, and kinesthetically “build” the cell envelope and form the peptidoglycan layer, (ii) understand the mechanism of action for β-lactam antibiotics, as well as how gene acquisition and protein changes result in resistance, and (iii) work cooperatively and actively to promote long-term retention of the subject material. PMID:29904519

CRAFFT: An Activity Prediction Model based on Bayesian Networks

PubMed Central

Nazerfard, Ehsan; Cook, Diane J.

2014-01-01

Recent advances in the areas of pervasive computing, data mining, and machine learning offer unique opportunities to provide health monitoring and assistance for individuals facing difficulties to live independently in their homes. Several components have to work together to provide health monitoring for smart home residents including, but not limited to, activity recognition, activity discovery, activity prediction, and prompting system. Compared to the significant research done to discover and recognize activities, less attention has been given to predict the future activities that the resident is likely to perform. Activity prediction components can play a major role in design of a smart home. For instance, by taking advantage of an activity prediction module, a smart home can learn context-aware rules to prompt individuals to initiate important activities. In this paper, we propose an activity prediction model using Bayesian networks together with a novel two-step inference process to predict both the next activity features and the next activity label. We also propose an approach to predict the start time of the next activity which is based on modeling the relative start time of the predicted activity using the continuous normal distribution and outlier detection. To validate our proposed models, we used real data collected from physical smart environments. PMID:25937847

CRAFFT: An Activity Prediction Model based on Bayesian Networks.

PubMed

Nazerfard, Ehsan; Cook, Diane J

2015-04-01

Recent advances in the areas of pervasive computing, data mining, and machine learning offer unique opportunities to provide health monitoring and assistance for individuals facing difficulties to live independently in their homes. Several components have to work together to provide health monitoring for smart home residents including, but not limited to, activity recognition, activity discovery, activity prediction, and prompting system. Compared to the significant research done to discover and recognize activities, less attention has been given to predict the future activities that the resident is likely to perform. Activity prediction components can play a major role in design of a smart home. For instance, by taking advantage of an activity prediction module, a smart home can learn context-aware rules to prompt individuals to initiate important activities. In this paper, we propose an activity prediction model using Bayesian networks together with a novel two-step inference process to predict both the next activity features and the next activity label. We also propose an approach to predict the start time of the next activity which is based on modeling the relative start time of the predicted activity using the continuous normal distribution and outlier detection. To validate our proposed models, we used real data collected from physical smart environments.

Enteric glia.

PubMed

Rühl, A; Nasser, Y; Sharkey, K A

2004-04-01

The enteric nervous system is composed of both enteric neurones and enteric glia. Enteric glial cells were first described by Dogiel and are now known to outnumber neurones approximately 4 : 1. In the past, these cells were assumed to subserve a largely supportive role; however, recent evidence indicates that enteric glial cells may play a more active role in the control of gut function. In transgenic mouse models, where enteric glial cells are selectively ablated, the loss of glia results in intestinal inflammation and disruption of the epithelial barrier. Enteric glia are activated specifically by inflammatory insults and may contribute actively to inflammatory pathology via antigen presentation and cytokine synthesis. Enteric glia also express receptors for neurotransmitters and so may serve as intermediaries in enteric neurotransmission. Thus, enteric glia may serve as a link between the nervous and immune systems of the gut and may also have an important role in maintaining the integrity of the mucosal barrier and in other aspects of intestinal homeostasis.

Autophagy and genomic integrity

PubMed Central

Vessoni, A T; Filippi-Chiela, E C; Menck, C FM; Lenz, G

2013-01-01

DNA lesions, constantly produced by endogenous and exogenous sources, activate the DNA damage response (DDR), which involves detection, signaling and repair of the damage. Autophagy, a lysosome-dependent degradation pathway that is activated by stressful situations such as starvation and oxidative stress, regulates cell fate after DNA damage and also has a pivotal role in the maintenance of nuclear and mitochondrial genomic integrity. Here, we review important evidence regarding the role played by autophagy in preventing genomic instability and tumorigenesis, as well as in micronuclei degradation. Several pathways governing autophagy activation after DNA injury and the influence of autophagy upon the processing of genomic lesions are also discussed herein. In this line, the mechanisms by which several proteins participate in both DDR and autophagy, and the importance of this crosstalk in cancer and neurodegeneration will be presented in an integrated fashion. At last, we present a hypothetical model of the role played by autophagy in dictating cell fate after genotoxic stress. PMID:23933813

Glucose metabolism determines resistance of cancer cells to bioenergetic crisis after cytochrome-c release

PubMed Central

Huber, Heinrich J; Dussmann, Heiko; Kilbride, Seán M; Rehm, Markus; Prehn, Jochen H M

2011-01-01

Many anticancer drugs activate caspases via the mitochondrial apoptosis pathway. Activation of this pathway triggers a concomitant bioenergetic crisis caused by the release of cytochrome-c (cyt-c). Cancer cells are able to evade these processes by altering metabolic and caspase activation pathways. In this study, we provide the first integrated system study of mitochondrial bioenergetics and apoptosis signalling and examine the role of mitochondrial cyt-c release in these events. In accordance with single-cell experiments, our model showed that loss of cyt-c decreased mitochondrial respiration by 95% and depolarised mitochondrial membrane potential ΔΨm from −142 to −88 mV, with active caspase-3 potentiating this decrease. ATP synthase was reversed under such conditions, consuming ATP and stabilising ΔΨm. However, the direction and level of ATP synthase activity showed significant heterogeneity in individual cancer cells, which the model explained by variations in (i) accessible cyt-c after release and (ii) the cell's glycolytic capacity. Our results provide a quantitative and mechanistic explanation for the protective role of enhanced glucose utilisation for cancer cells to avert the otherwise lethal bioenergetic crisis associated with apoptosis initiation. PMID:21364572

Modeling meiotic chromosome pairing: nuclear envelope attachment, telomere-led active random motion, and anomalous diffusion

PubMed Central

Marshall, Wallace F.; Fung, Jennifer C.

2016-01-01

The recognition and pairing of homologous chromosomes during meiosis is a complex physical and molecular process involving a combination of polymer dynamics and molecular recognition events. Two highly conserved features of meiotic chromosome behavior are the attachment of telomeres to the nuclear envelope and the active random motion of telomeres driven by their interaction with cytoskeletal motor proteins. Both of these features have been proposed to facilitate the process of homolog pairing, but exactly what role these features play in meiosis remains poorly understood. Here we investigate the roles of active motion and nuclear envelope tethering using a Brownian dynamics simulation in which meiotic chromosomes are represented by a Rouse polymer model subjected to tethering and active forces at the telomeres. We find that tethering telomeres to the nuclear envelope slows down pairing relative to the rates achieved by un-attached chromosomes, but that randomly-directed active forces applied to the telomeres speeds up pairing dramatically in a manner that depends on the statistical properties of the telomere force fluctuations. The increased rate of initial pairing cannot be explained by stretching out of the chromosome conformation but instead seems to correlate with anomalous diffusion of sub-telomeric regions. PMID:27046097

Gamma band oscillations: a key to understanding schizophrenia symptoms and neural circuit abnormalities.

PubMed

McNally, James M; McCarley, Robert W

2016-05-01

We review our current understanding of abnormal γ band oscillations in schizophrenia, their association with symptoms and the underlying cortical circuit abnormality, with a particular focus on the role of fast-spiking parvalbumin gamma-aminobutyric acid (GABA) neurons in the disease state. Clinical electrophysiological studies of schizophrenia patients and pharmacological models of the disorder show an increase in spontaneous γ band activity (not stimulus-evoked) measures. These findings provide a crucial link between preclinical and clinical work examining the role of γ band activity in schizophrenia. MRI-based experiments measuring cortical GABA provides evidence supporting impaired GABAergic neurotransmission in schizophrenia patients, which is correlated with γ band activity level. Several studies suggest that stimulation of the cortical circuitry, directly or via subcortical structures, has the potential to modulate cortical γ activity, and improve cognitive function. Abnormal γ band activity is observed in patients with schizophrenia and disease models in animals, and is suggested to underlie the psychosis and cognitive/perceptual deficits. Convergent evidence from both clinical and preclinical studies suggest the central factor in γ band abnormalities is impaired GABAergic neurotransmission, particularly in a subclass of neurons which express parvalbumin. Rescue of γ band abnormalities presents an intriguing option for therapeutic intervention.

Magnetite-Amyloid-β deteriorates activity and functional organization in an in vitro model for Alzheimer’s disease

NASA Astrophysics Data System (ADS)

Teller, Sara; Tahirbegi, Islam Bogachan; Mir, Mònica; Samitier, Josep; Soriano, Jordi

2015-11-01

The understanding of the key mechanisms behind human brain deterioration in Alzheimer’ disease (AD) is a highly active field of research. The most widespread hypothesis considers a cascade of events initiated by amyloid-β peptide fibrils that ultimately lead to the formation of the lethal amyloid plaques. Recent studies have shown that other agents, in particular magnetite, can also play a pivotal role. To shed light on the action of magnetite and amyloid-β in the deterioration of neuronal circuits, we investigated their capacity to alter spontaneous activity patterns in cultured neuronal networks. Using a versatile experimental platform that allows the parallel monitoring of several cultures, the activity in controls was compared with the one in cultures dosed with magnetite, amyloid-β and magnetite-amyloid-β complex. A prominent degradation in spontaneous activity was observed solely when amyloid-β and magnetite acted together. Our work suggests that magnetite nanoparticles have a more prominent role in AD than previously thought, and may bring new insights in the understanding of the damaging action of magnetite-amyloid-β complex. Our experimental system also offers new interesting perspectives to explore key biochemical players in neurological disorders through a controlled, model system manner.

Modeling meiotic chromosome pairing: nuclear envelope attachment, telomere-led active random motion, and anomalous diffusion

NASA Astrophysics Data System (ADS)

Marshall, Wallace F.; Fung, Jennifer C.

2016-04-01

The recognition and pairing of homologous chromosomes during meiosis is a complex physical and molecular process involving a combination of polymer dynamics and molecular recognition events. Two highly conserved features of meiotic chromosome behavior are the attachment of telomeres to the nuclear envelope and the active random motion of telomeres driven by their interaction with cytoskeletal motor proteins. Both of these features have been proposed to facilitate the process of homolog pairing, but exactly what role these features play in meiosis remains poorly understood. Here we investigate the roles of active motion and nuclear envelope tethering using a Brownian dynamics simulation in which meiotic chromosomes are represented by a Rouse polymer model subjected to tethering and active forces at the telomeres. We find that tethering telomeres to the nuclear envelope slows down pairing relative to the rates achieved by unattached chromosomes, but that randomly directed active forces applied to the telomeres speed up pairing dramatically in a manner that depends on the statistical properties of the telomere force fluctuations. The increased rate of initial pairing cannot be explained by stretching out of the chromosome conformation but instead seems to correlate with anomalous diffusion of sub-telomeric regions.

JAK/STAT3 and Smad3 activities are required for the wound healing properties of Periplaneta americana extracts.

PubMed

Song, Qin; Xie, Yuxin; Gou, Qiheng; Guo, Xiaoqiang; Yao, Qian; Gou, Xiaojun

2017-08-01

Periplaneta americana extracts (PAEs) play a crucial role in skin wound healing. However, their molecular effects and signaling pathways in regenerating tissues and cells are not clear. In this study, we refined the PAE from Periplaneta americana to investigate the mechanisms underlying skin wound healing. The human keratinocyte line HaCaT was selected and a mouse model of deep second-degree thermal burn was established for in vitro and in vivo studies, respectively. PAE treatment induced the proliferation and migration of HaCaT cells and wound healing in the burn model. Furthermore, the effects of PAE on wound healing were found to depend on the Janus-activated kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway and Smad3 activities, according to western blot analysis and immunohistochemical (IHC) assays in vitro and in vivo. Pretreatment with a STAT3 inhibitor blocked the cell proliferation and migration induced by PAE. The results indicate the wound-healing function of PAE via enhanced JAK/STAT3 signaling and Smad3 activities. Our studies provide a theoretical basis underlying the role of PAE in cutaneous wound healing.

Role of mechanics in the appearance of oscillatory instability and standing waves of the mechanochemical activity in the Physarum polycephalum plasmodium

NASA Astrophysics Data System (ADS)

Teplov, Vladimir A.

2017-06-01

The modes of continuously distributed mechanochemical self-sustained oscillations (autowaves) exhibited by the Physarum plasmodium under different experimental conditions are reviewed. The role of the stretch-induced activation of contractile oscillations in the spatiotemporal self-organization of the plasmodium is elucidated. Different mathematical models describing contractile autowaves in ectoplasm and the streaming of the endoplasm are considered. Our mathematical models, which are based on the hypothesis of local positive feedback between the deformation and contraction of the contractile apparatus, are also presented. The feedback is mediated through a chemical regulatory system, whose kinetics involves the coupling to the mechanical strain. The mathematical analysis and computer simulations have demonstrated that the solutions of the models agree quantitatively with the experimental data. In particular, the only hydrodynamic interactions between the different parts of the plasmodium via the streaming endoplasm can lead to globally coordinated ectoplasmic contractions and vigorous shuttle endoplasmic streaming. These models, with empirically determined values of the viscoelastic parameters, well simulate the form and duration of the transient contractile processes observed after the isolation of the strands as well as the subsequent excitation of auto-oscillations and their stretch-induced activation under isotonic and isometric conditions.

Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration

PubMed Central

Dong, Yun; Fischer, Roman; Naudé, Petrus J. W.; Maier, Olaf; Nyakas, Csaba; Duffey, Maëlle; Van der Zee, Eddy A.; Dekens, Doortje; Douwenga, Wanda; Herrmann, Andreas; Guenzi, Eric; Kontermann, Roland E.; Pfizenmaier, Klaus; Eisel, Ulrich L. M.

2016-01-01

Despite the recognized role of tumor necrosis factor (TNF) in inflammation and neuronal degeneration, anti-TNF therapeutics failed to treat neurodegenerative diseases. Animal disease models had revealed the antithetic effects of the two TNF receptors (TNFR) in the central nervous system, whereby TNFR1 has been associated with inflammatory degeneration and TNFR2 with neuroprotection. We here show the therapeutic potential of selective inhibition of TNFR1 and activation of TNFR2 by ATROSAB, a TNFR1-selective antagonistic antibody, and EHD2-scTNFR2, an agonistic TNFR2-selective TNF, respectively, in a mouse model of NMDA-induced acute neurodegeneration. Coadministration of either ATROSAB or EHD2-scTNFR2 into the magnocellular nucleus basalis significantly protected cholinergic neurons and their cortical projections against cell death, and reverted the neurodegeneration-associated memory impairment in a passive avoidance paradigm. Simultaneous blocking of TNFR1 and TNFR2 signaling, however, abrogated the therapeutic effect. Our results uncover an essential role of TNFR2 in neuroprotection. Accordingly, the therapeutic activity of ATROSAB is mediated by shifting the balance of the antithetic activity of endogenous TNF toward TNFR2, which appears essential for neuroprotection. Our data also explain earlier results showing that complete blocking of TNF activity by anti-TNF drugs was detrimental rather than protective and argue for the use of next-generation TNFR-selective TNF therapeutics as an effective approach in treating neurodegenerative diseases. PMID:27791020

Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration.

PubMed

Dong, Yun; Fischer, Roman; Naudé, Petrus J W; Maier, Olaf; Nyakas, Csaba; Duffey, Maëlle; Van der Zee, Eddy A; Dekens, Doortje; Douwenga, Wanda; Herrmann, Andreas; Guenzi, Eric; Kontermann, Roland E; Pfizenmaier, Klaus; Eisel, Ulrich L M

2016-10-25

Despite the recognized role of tumor necrosis factor (TNF) in inflammation and neuronal degeneration, anti-TNF therapeutics failed to treat neurodegenerative diseases. Animal disease models had revealed the antithetic effects of the two TNF receptors (TNFR) in the central nervous system, whereby TNFR1 has been associated with inflammatory degeneration and TNFR2 with neuroprotection. We here show the therapeutic potential of selective inhibition of TNFR1 and activation of TNFR2 by ATROSAB, a TNFR1-selective antagonistic antibody, and EHD2-scTNF R2 , an agonistic TNFR2-selective TNF, respectively, in a mouse model of NMDA-induced acute neurodegeneration. Coadministration of either ATROSAB or EHD2-scTNF R2 into the magnocellular nucleus basalis significantly protected cholinergic neurons and their cortical projections against cell death, and reverted the neurodegeneration-associated memory impairment in a passive avoidance paradigm. Simultaneous blocking of TNFR1 and TNFR2 signaling, however, abrogated the therapeutic effect. Our results uncover an essential role of TNFR2 in neuroprotection. Accordingly, the therapeutic activity of ATROSAB is mediated by shifting the balance of the antithetic activity of endogenous TNF toward TNFR2, which appears essential for neuroprotection. Our data also explain earlier results showing that complete blocking of TNF activity by anti-TNF drugs was detrimental rather than protective and argue for the use of next-generation TNFR-selective TNF therapeutics as an effective approach in treating neurodegenerative diseases.

Tumor necrosis factor-alpha potentiates the cytotoxicity of amiodarone in Hepa1c1c7 cells: roles of caspase activation and oxidative stress.

PubMed

Lu, Jingtao; Miyakawa, Kazuhisa; Roth, Robert A; Ganey, Patricia E

2013-01-01

Amiodarone (AMD), a class III antiarrhythmic drug, causes idiosyncratic hepatotoxicity in human patients. We demonstrated previously that tumor necrosis factor-alpha (TNF-α) plays an important role in a rat model of AMD-induced hepatotoxicity under inflammatory stress. In this study, we developed a model in vitro to study the roles of caspase activation and oxidative stress in TNF potentiation of AMD cytotoxicity. AMD caused cell death in Hepa1c1c7 cells, and TNF cotreatment potentiated its toxicity. Activation of caspases 9 and 3/7 was observed in AMD/TNF-cotreated cells, and caspase inhibitors provided minor protection from cytotoxicity. Intracellular reactive oxygen species (ROS) generation and lipid peroxidation were observed after treatment with AMD and were further elevated by TNF cotreatment. Adding water-soluble antioxidants (trolox, N-acetylcysteine, glutathione, or ascorbate) produced only minor attenuation of AMD/TNF-induced cytotoxicity and did not influence the effect of AMD alone. On the other hand, α-tocopherol (TOCO), which reduced lipid peroxidation and ROS generation, prevented AMD toxicity and caused pronounced reduction in cytotoxicity from AMD/TNF cotreatment. α-TOCO plus a pancaspase inhibitor completely abolished AMD/TNF-induced cytotoxicity. In summary, activation of caspases and oxidative stress were observed after AMD/TNF cotreatment, and caspase inhibitors and a lipid-soluble free-radical scavenger attenuated AMD/TNF-induced cytotoxicity.

Tumor Necrosis Factor-alpha Potentiates the Cytotoxicity of Amiodarone in Hepa1c1c7 Cells: Roles of Caspase Activation and Oxidative Stress

PubMed Central

Ganey, Patricia E.

2013-01-01

Amiodarone (AMD), a class III antiarrhythmic drug, causes idiosyncratic hepatotoxicity in human patients. We demonstrated previously that tumor necrosis factor-alpha (TNF-α) plays an important role in a rat model of AMD-induced hepatotoxicity under inflammatory stress. In this study, we developed a model in vitro to study the roles of caspase activation and oxidative stress in TNF potentiation of AMD cytotoxicity. AMD caused cell death in Hepa1c1c7 cells, and TNF cotreatment potentiated its toxicity. Activation of caspases 9 and 3/7 was observed in AMD/TNF-cotreated cells, and caspase inhibitors provided minor protection from cytotoxicity. Intracellular reactive oxygen species (ROS) generation and lipid peroxidation were observed after treatment with AMD and were further elevated by TNF cotreatment. Adding water-soluble antioxidants (trolox, N-acetylcysteine, glutathione, or ascorbate) produced only minor attenuation of AMD/TNF-induced cytotoxicity and did not influence the effect of AMD alone. On the other hand, α-tocopherol (TOCO), which reduced lipid peroxidation and ROS generation, prevented AMD toxicity and caused pronounced reduction in cytotoxicity from AMD/TNF cotreatment. α-TOCO plus a pancaspase inhibitor completely abolished AMD/TNF-induced cytotoxicity. In summary, activation of caspases and oxidative stress were observed after AMD/TNF cotreatment, and caspase inhibitors and a lipid-soluble free-radical scavenger attenuated AMD/TNF-induced cytotoxicity. PMID:23042730

The effect of CXCR2 inhibition on seizure activity in the pilocarpine epilepsy mouse model.

PubMed

Xu, Tao; Yu, Xinyuan; Wang, Teng; Liu, Ying; Liu, Xi; Ou, Shu; Chen, Yangmei

2017-09-01

C-X-C motif chemokine receptor 2 (CXCR2) is one of the most well characterized chemokine receptors and is a potential target for treating brain pathologies involving inflammatory processes, including epilepsy. However, the role of CXCR2 in epilepsy has not been investigated, and whether CXCR2 modulates seizure activity in temporal lobe epilepsy (TLE) remains unknown. In this study, we aimed to determine the potential role of CXCR2 in intractable TLE patients and in pilocarpine-induced epileptic mice. Here, through Western blotting and semi-quantitative immunohistochemistry, we detected that CXCR2 protein expression was up-regulated (by nearly 50%) in the temporal neocortex of TLE patients and in the hippocampus and adjacent temporal cortex of pilocarpine mice model. Double-label immunofluorescence and immunohistochemical analysis indicated that CXCR2 was expressed in neurons. To investigate the effect of the CXCR2 selective antagonist SB225002 on seizure activity, SB225002 was i.p. administered during the latency window of spontaneous recurrent seizures (SRSs). This treatment increased (by nearly 40%) the latency of SRSs and reduced (by nearly 50%) the frequency of SRSs during the chronic period of epilepsy. This study suggests that CXCR2 plays a critical role in modifying epileptic seizure activity and that CXCR2 blockade could be a potential molecular therapeutic target for epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

The mediational role of physical activity, social contact and stroke on the association between age, education, employment and dementia in an Asian older adult population.

PubMed

Abdin, Edimansyah; Chong, Siow Ann; Peh, Chao Xu; Vaingankar, Janhavi Ajit; Chua, Boon Yiang; Verma, Swapna; Jeyagurunathan, Anitha; Shafie, Saleha; Subramaniam, Mythily

2017-03-20

Our study aimed to investigate the pathways by which socio-demographic factors, modifiable health and lifestyle risk factors influence each other, and subsequently, lead to dementia. We used data from the Well-being of the Singapore Elderly study, a nationally representative survey of the older adult population aged 60 years and above in Singapore. Dementia diagnosis was established using 10/66 dementia criteria. Structural equation modelling (SEM) without latent variable was applied to confirm the hypothesized model. The results of SEM supported the hypothesized model (χ 2 = 14.999, df = 10, p = 0.132). The final model showed that those aged 75-84 years and 85 years and over (vs. 60-74 years), having no formal education, who had completed primary or secondary education (vs. completed tertiary), who were homemakers and retired (vs. paid work), and with a history of stroke were directly associated with higher odds of having dementia, while those who had more frequent contact with friends and neighbors as well as being physically active were directly associated with lower odds of having dementia diagnosis. The study also found that physical activity, more frequent contact with friends and stroke played a significant role as mediators in these relationships. The overall pathways model explained 57.7% of the variance in dementia. Our results suggest that physical activity, social contact and stroke were potential mediators in the relationship between age, education, employment and dementia. Intervention programmes focusing on physical activity such as exercise and social contact may be useful in reducing the risk of dementia among older adults.

Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells

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

Singaravelu, Ragunath; National Research Council of Canada, Ottawa, Ontario K1A 0R6; Lyn, Rodney K.

Highlights: •Human serum induced differentiation of hepatoma cells increases cellular lipid droplet (LD) size. •The observed increase in LD size correlates with increased PGC-1α and CIDEB expression. •Induction of CIDEB expression correlates with rescue of VLDL secretion and loss of ADRP. •siRNA knockdown of CIDEB impairs the human serum mediated increase in LD size. •This system represents a cost-efficient model to study CIDEB’s role in lipid biology. -- Abstract: Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limitedmore » cell culture models readily available to study CIDEB’s role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1α, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEB’s role in LD fusion, and presents a new model system to study the PGC-1α/CIDEB pathway’s role in LD dynamics and the VLDL pathway.« less

Patterns of hippocampal-neocortical interactions in the retrieval of episodic autobiographical memories across the entire life-span of aged adults

PubMed Central

Viard, Armelle; Lebreton, Karine; Chételat, Gaël; Desgranges, Béatrice; Landeau, Brigitte; Young, Alan; De La Sayette, Vincent; Eustache, Francis; Piolino, Pascale

2010-01-01

We previously demonstrated that Episodic Autobiographical Memories (EAMs) rely on a network of brain regions comprising the medial temporal lobe (MTL) and distributed neocortical regions regardless of their remoteness. The findings supported the model of memory consolidation which proposes a permanent role of MTL during EAM retrieval (Multiple-Trace Theory or MTT) rather than a temporary role (standard model). Our present aim was to expand the results by examining the interactions between the MTL and neocortical regions (or MTL-neocortical links) during EAM retrieval with varying retention intervals. We used an experimental paradigm specially designed to engage aged participants in the recollection of EAMs, extracted from five different time-periods, covering their whole life-span, in order to examine correlations between activation in the MTL and neocortical regions. The nature of the memories was checked at debriefing by means of behavioral measures to control the degree of episodicity and properties of memories. Targeted correlational analyses carried out on the MTL, frontal, lateral temporal and posterior regions revealed strong links between the MTL and neocortex during the retrieval of both recent and remote EAMs, challenging the standard model of memory consolidation and supporting MTT instead. Further confirmation was given by results showing that activation in the left and right hippocampi significantly correlated during the retrieval of both recent and remote memories. Correlations among extra-MTL neocortical regions also emerged for all time-periods, confirming the critical role of the prefrontal, temporal (lateral temporal cortex and temporal pole), precuneus and posterior cingulate regions in EAM retrieval. Overall, this paper emphasizes the role of a bilateral network of MTL and neocortical areas whose activation correlate during the recollection of rich phenomenological recent and remote EAMs. PMID:19338022

The Role of External Inputs and Internal Cycling in Shaping the Global Ocean Cobalt Distribution: Insights From the First Cobalt Biogeochemical Model

NASA Astrophysics Data System (ADS)

Tagliabue, Alessandro; Hawco, Nicholas J.; Bundy, Randelle M.; Landing, William M.; Milne, Angela; Morton, Peter L.; Saito, Mak A.

2018-04-01

Cobalt is an important micronutrient for ocean microbes as it is present in vitamin B12 and is a co-factor in various metalloenzymes that catalyze cellular processes. Moreover, when seawater availability of cobalt is compared to biological demands, cobalt emerges as being depleted in seawater, pointing to a potentially important limiting role. To properly account for the potential biological role for cobalt, there is therefore a need to understand the processes driving the biogeochemical cycling of cobalt and, in particular, the balance between external inputs and internal cycling. To do so, we developed the first cobalt model within a state-of-the-art three-dimensional global ocean biogeochemical model. Overall, our model does a good job in reproducing measurements with a correlation coefficient of >0.7 in the surface and >0.5 at depth. We find that continental margins are the dominant source of cobalt, with a crucial role played by supply under low bottom-water oxygen conditions. The basin-scale distribution of cobalt supplied from margins is facilitated by the activity of manganese-oxidizing bacteria being suppressed under low oxygen and low temperatures, which extends the residence time of cobalt. Overall, we find a residence time of 7 and 250 years in the upper 250 m and global ocean, respectively. Importantly, we find that the dominant internal resupply process switches from regeneration and recycling of particulate cobalt to dissolution of scavenged cobalt between the upper ocean and the ocean interior. Our model highlights key regions of the ocean where biological activity may be most sensitive to cobalt availability.

Essential role of TRPC6 channels in G2/M phase transition and development of human glioma.

PubMed

Ding, Xia; He, Zhuohao; Zhou, Kechun; Cheng, Ju; Yao, Hailan; Lu, Dongliang; Cai, Rong; Jin, Yening; Dong, Bin; Xu, Yinghui; Wang, Yizheng

2010-07-21

Patients with glioblastoma multiforme, the most aggressive form of glioma, have a median survival of approximately 12 months. Calcium (Ca(2+)) signaling plays an important role in cell proliferation, and some members of the Ca(2+)-permeable transient receptor potential canonical (TRPC) family of channel proteins have demonstrated a role in the proliferation of many types of cancer cells. In this study, we investigated the role of TRPC6 in cell cycle progression and in the development of human glioma. TRPC6 protein and mRNA expression were assessed in glioma (n = 33) and normal (n = 17) brain tissues from patients and in human glioma cell lines U251, U87, and T98G. Activation of TRPC6 channels was tested by platelet-derived growth factor-induced Ca(2+) imaging. The effect of inhibiting TRPC6 activity or expression using the dominant-negative mutant TRPC6 (DNC6) or RNA interference, respectively, was tested on cell growth, cell cycle progression, radiosensitization of glioma cells, and development of xenografted human gliomas in a mouse model. The green fluorescent protein (GFP) and wild-type TRPC6 (WTC6) were used as controls. Survival of mice bearing xenografted tumors in the GFP, DNC6, and WTC6 groups (n = 13, 15, and 13, respectively) was compared using Kaplan-Meier analysis. All statistical tests were two-sided. Functional TRPC6 was overexpressed in human glioma cells. Inhibition of TRPC6 activity or expression attenuated the increase in intracellular Ca(2+) by platelet-derived growth factor, suppressed cell growth and clonogenic ability, induced cell cycle arrest at the G2/M phase, and enhanced the antiproliferative effect of ionizing radiation. Cyclin-dependent kinase 1 activation and cell division cycle 25 homolog C expression regulated the cell cycle arrest. Inhibition of TRPC6 activity also reduced tumor volume in a subcutaneous mouse model of xenografted human tumors (P = .014 vs GFP; P < .001 vs WTC6) and increased mean survival in mice in an intracranial model (P < .001 vs GFP or WTC6). In this preclinical model, TRPC6 channels were essential for glioma development via regulation of G2/M phase transition. This study suggests that TRPC6 might be a new target for therapeutic intervention of human glioma.

Testing a Theoretical Model of Immigration Transition and Physical Activity.

PubMed

Chang, Sun Ju; Im, Eun-Ok

2015-01-01

The purposes of the study were to develop a theoretical model to explain the relationships between immigration transition and midlife women's physical activity and test the relationships among the major variables of the model. A theoretical model, which was developed based on transitions theory and the midlife women's attitudes toward physical activity theory, consists of 4 major variables, including length of stay in the United States, country of birth, level of acculturation, and midlife women's physical activity. To test the theoretical model, a secondary analysis with data from 127 Hispanic women and 123 non-Hispanic (NH) Asian women in a national Internet study was used. Among the major variables of the model, length of stay in the United States was negatively associated with physical activity in Hispanic women. Level of acculturation in NH Asian women was positively correlated with women's physical activity. Country of birth and level of acculturation were significant factors that influenced physical activity in both Hispanic and NH Asian women. The findings support the theoretical model that was developed to examine relationships between immigration transition and physical activity; it shows that immigration transition can play an essential role in influencing health behaviors of immigrant populations in the United States. The NH theoretical model can be widely used in nursing practice and research that focus on immigrant women and their health behaviors. Health care providers need to consider the influences of immigration transition to promote immigrant women's physical activity.

Activation of Corticostriatal Circuitry Relieves Chronic Neuropathic Pain

PubMed Central

Lee, Michelle; Manders, Toby R.; Eberle, Sarah E.; Su, Chen; D'amour, James; Yang, Runtao; Lin, Hau Yueh; Deisseroth, Karl; Froemke, Robert C.

2015-01-01

Neural circuits that determine the perception and modulation of pain remain poorly understood. The prefrontal cortex (PFC) provides top-down control of sensory and affective processes. While animal and human imaging studies have shown that the PFC is involved in pain regulation, its exact role in pain states remains incompletely understood. A key output target for the PFC is the nucleus accumbens (NAc), an important component of the reward circuitry. Interestingly, recent human imaging studies suggest that the projection from the PFC to the NAc is altered in chronic pain. The function of this corticostriatal projection in pain states, however, is not known. Here we show that optogenetic activation of the PFC produces strong antinociceptive effects in a rat model (spared nerve injury model) of persistent neuropathic pain. PFC activation also reduces the affective symptoms of pain. Furthermore, we show that this pain-relieving function of the PFC is likely mediated by projections to the NAc. Thus, our results support a novel role for corticostriatal circuitry in pain regulation. PMID:25834050

Turnip vein clearing virus movement protein nuclear activity: Do Tobamovirus movement proteins play a role in immune response suppression?

PubMed

Levy, Amit

2015-01-01

Plant viruses' cell-to-cell movement requires the function of virally encoded movement proteins (MPs). The Tobamovirus, Tobacco mosaic virus (TMV) has served as the model virus to study the activities of single MPs. However, since TMV does not infect the model plant Arabidopsis thaliana I have used a related Tobamovirus, Turnip vein-clearing virus (TVCV). I recently showed that, despite belonging to the same genus, the behavior of the 2 viruses MPs differ significantly during infection. Most notably, MP(TVCV), but not MP(TMV), targets the nucleus and induces the formation of F actin-containing filaments that associate with chromatin. Mutational analyses showed that nuclear localization of MP(TVCV) was necessary for TVCV local and systemic infection in both Nicotiana benthamiana and Arabidopsis. In this addendum, I propose possible targets for the MP(TVCV) nuclear activity, and suggest viewing MPs as viral effector-like proteins, playing a role in the inhibition of plant defense.

Silibinin and STAT3: A natural way of targeting transcription factors for cancer therapy.

PubMed

Bosch-Barrera, Joaquim; Menendez, Javier A

2015-06-01

Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in many different types of cancer and plays a pivotal role in tumor growth and metastasis. Retrospective studies have established that STAT3 expression or phospho-STAT3 (pSTAT3 or activated STAT3) are poor prognostic markers for breast, colon, prostate and non-small cell lung cancer. Silibinin or silybin is a natural polyphenolic flavonoid which is present in seed extracts of milk thistle (Silybum marianum). Silibinin has been shown to inhibit multiple cancer cell signaling pathways in preclinical models, demonstrating promising anticancer effects in vitro and in vivo. This review summarizes evidence suggesting that silibinin can inhibit pSTAT3 in preclinical cancer models. We also discuss current strategies to overcome the limitations of oral administration of silibinin to cancer patients to translate the bench results to the bed side. Finally, we review the ongoing clinical trials exploring the role of silibinin in cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fathers’ perspectives on the diets and physical activity behaviours of their young children

PubMed Central

Hesketh, Kylie D.; van der Pligt, Paige; Cameron, Adrian J.; Crawford, David; Campbell, Karen J.

2017-01-01

Background Children’s learning about food and physical activity is considerable during their formative years, with parental influence pivotal. Research has focused predominantly on maternal influences with little known about the relationships between fathers’ and young children’s dietary and physical activity behaviours. A greater understanding of paternal beliefs regarding young children’s dietary and physical activity behaviours is important to inform the design and delivery of child-focussed health promotion interventions. This study aimed to describe fathers’ perceived roles in their children’s eating and physical activity behaviours. It also sought to document fathers’ views regarding how they could be best supported to promote healthy eating and physical activity behaviours in their young children. Methods In depth, semi-structured interviews were conducted with twenty fathers living in socio-economically diverse areas of metropolitan Melbourne, Australia who had at least one child aged five years or less. All interviews were audio recorded, transcribed verbatim and thematically analysed. Results Thematic analysis of the transcripts revealed eight broad themes about fathers’ beliefs, perceptions and attitudes towards the dietary and physical activity behaviours of their young children: (i) shared responsibility and consultation; (ii) family meal environment; (iii) parental role modelling; (iv) parental concerns around food; (v) food rewards; (vi) health education; (vii) limiting screen time; and (viii) parental knowledge. Analysis of themes according to paternal education/employment revealed no substantial differences in the views of fathers. Conclusions This exploratory study presents the views of a socio-economically diverse group of fathers regarding the dietary and physical activity behaviours of their young children and the insights into the underlying perceptions informing these views. The findings suggest that fathers believe healthy eating behaviours and being physically active are important for their young children. Fathers believe these behaviours can be promoted and supported in different ways including through the provision of appropriate meal and physical activity environments and parental role modelling of desired dietary and physical activity behaviours. PMID:28604810

Newly-recognized roles of factor XIII in thrombosis

PubMed Central

Byrnes, James R.; Wolberg, Alisa S.

2017-01-01

Arterial and venous thrombosis are major contributors to coagulation-associated morbidity and mortality. Greater understanding of mechanisms leading to thrombus formation and stability is expected to lead to improved treatment strategies. Factor XIII (FXIII) is a transglutaminase found in plasma and platelets. During thrombosis, activated FXIII crosslinks fibrin and promotes thrombus stability. Recent studies have provided new information about FXIII activity during coagulation and its effects on clot composition and function. These findings reveal newly-recognized roles for FXIII in thrombosis. Herein, we review published literature on FXIII biology and effects on fibrin structure and stability, epidemiologic data associating FXIII with thrombosis, and evidence from animal models indicating FXIII has an essential role in determining thrombus stability, composition, and size. PMID:27056150

Predictors of activity level and retention among African American lay health advisors (LHAs) from The National Witness Project: Implications for the implementation and sustainability of community-based LHA programs from a longitudinal study.

PubMed

Shelton, Rachel C; Dunston, Sheba King; Leoce, Nicole; Jandorf, Lina; Thompson, Hayley S; Crookes, Danielle M; Erwin, Deborah O

2016-03-22

Lay health advisor (LHA) programs are increasingly being implemented in the USA and globally in the context of health promotion and disease prevention. LHAs are effective in addressing health disparities when used to reach medically underserved populations, with strong evidence among African American and Hispanic women. Despite their success and the evidence supporting implementation of LHA programs in community settings, there are tremendous barriers to sustaining LHA programs and little is understood about their implementation and sustainability in "real-world" settings. The purpose of this study was to (1) propose a conceptual framework to investigate factors at individual, social, and organizational levels that impact LHA activity and retention; and (2) use prospective data to investigate the individual, social, and organizational factors that predict activity level and retention among a community-based sample of African American LHAs participating in an effective, evidence-based LHA program (National Witness Project; NWP). Seventy-six LHAs were recruited from eight NWP sites across the USA. Baseline predictor data was collected from LHAs during a telephone questionnaire administered between 2010 and 2011. Outcome data on LHA participation and program activity levels were collected in the fall of 2012 from NWP program directors. Chi-square and ANOVA tests were used to identify differences between retained and completely inactive LHAs, and LHAs with high/moderate vs. low/no activity levels. Multivariable logistic regression models were conducted to identify variables that predicted LHA retention and activity levels. In multivariable models, LHAs based at sites with academic partnerships had increased odds of retention and high/moderate activity levels, even after adjusting for baseline LHA activity level. Higher religiosity among LHAs was associated with decreased odds of being highly/moderately active. LHA role clarity and self-efficacy were associated with retention and high/moderate activity in multivariable models unadjusted for baseline LHA activity level. Organizational and role-related factors are critical in influencing the retention and activity levels of LHAs. Developing and fostering partnerships with academic institutions will be important strategies to promote successful implementation and sustainability of LHA programs. Clarifying role expectations and building self-efficacy during LHA recruitment and training should be further explored to promote LHA retention and participation.

Relating the bipolar spectrum to dysregulation of behavioural activation: a perspective from dynamical modelling.

PubMed

Steinacher, Arno; Wright, Kim A

2013-01-01

Bipolar Disorders affect a substantial minority of the population and result in significant personal, social and economic costs. Understanding of the causes of, and consequently the most effective interventions for, this condition is an area requiring development. Drawing upon theories of Bipolar Disorder that propose the condition to be underpinned by dysregulation of systems governing behavioural activation or approach motivation, we present a mathematical model of the regulation of behavioural activation. The model is informed by non-linear, dynamical principles and as such proposes that the transition from "non-bipolar" to "bipolar" diagnostic status corresponds to a switch from mono- to multistability of behavioural activation level, rather than an increase in oscillation of mood. Consistent with descriptions of the behavioural activation or approach system in the literature, auto-activation and auto-inhibitory feedback is inherent within our model. Comparison between our model and empirical, observational data reveals that by increasing the non-linearity dimension in our model, important features of Bipolar Spectrum disorders are reproduced. Analysis from stochastic simulation of the system reveals the role of noise in behavioural activation regulation and indicates that an increase of nonlinearity promotes noise to jump scales from small fluctuations of activation levels to longer lasting, but less variable episodes. We conclude that further research is required to relate parameters of our model to key behavioural and biological variables observed in Bipolar Disorder.

Can Condensing Organic Aerosols Lead to Less Cloud Particles?

NASA Astrophysics Data System (ADS)

Gao, C. Y.; Tsigaridis, K.; Bauer, S.

2017-12-01

We examined the impact of condensing organic aerosols on activated cloud number concentration in a new aerosol microphysics box model, MATRIX-VBS. The model includes the volatility-basis set (VBS) framework in an aerosol microphysical scheme MATRIX (Multiconfiguration Aerosol TRacker of mIXing state) that resolves aerosol mass and number concentrations and aerosol mixing state. Preliminary results show that by including the condensation of organic aerosols, the new model (MATRIX-VBS) has less activated particles compared to the original model (MATRIX), which treats organic aerosols as non-volatile. Parameters such as aerosol chemical composition, mass and number concentrations, and particle sizes which affect activated cloud number concentration are thoroughly evaluated via a suite of Monte-Carlo simulations. The Monte-Carlo simulations also provide information on which climate-relevant parameters play a critical role in the aerosol evolution in the atmosphere. This study also helps simplifying the newly developed box model which will soon be implemented in the global model GISS ModelE as a module.

The Trans-Contextual Model of Autonomous Motivation in Education

PubMed Central

Hagger, Martin S.; Chatzisarantis, Nikos L. D.

2015-01-01

The trans-contextual model outlines the processes by which autonomous motivation toward activities in a physical education context predicts autonomous motivation toward physical activity outside of school, and beliefs about, intentions toward, and actual engagement in, out-of-school physical activity. In the present article, we clarify the fundamental propositions of the model and resolve some outstanding conceptual issues, including its generalizability across multiple educational domains, criteria for its rejection or failed replication, the role of belief-based antecedents of intentions, and the causal ordering of its constructs. We also evaluate the consistency of model relationships in previous tests of the model using path-analytic meta-analysis. The analysis supported model hypotheses but identified substantial heterogeneity in the hypothesized relationships across studies unattributed to sampling and measurement error. Based on our meta-analysis, future research needs to provide further replications of the model in diverse educational settings beyond physical education and test model hypotheses using experimental methods. PMID:27274585

The Trans-Contextual Model of Autonomous Motivation in Education: Conceptual and Empirical Issues and Meta-Analysis.

PubMed

Hagger, Martin S; Chatzisarantis, Nikos L D

2016-06-01

The trans-contextual model outlines the processes by which autonomous motivation toward activities in a physical education context predicts autonomous motivation toward physical activity outside of school, and beliefs about, intentions toward, and actual engagement in, out-of-school physical activity. In the present article, we clarify the fundamental propositions of the model and resolve some outstanding conceptual issues, including its generalizability across multiple educational domains, criteria for its rejection or failed replication, the role of belief-based antecedents of intentions, and the causal ordering of its constructs. We also evaluate the consistency of model relationships in previous tests of the model using path-analytic meta-analysis. The analysis supported model hypotheses but identified substantial heterogeneity in the hypothesized relationships across studies unattributed to sampling and measurement error. Based on our meta-analysis, future research needs to provide further replications of the model in diverse educational settings beyond physical education and test model hypotheses using experimental methods.

The roles of lesson study in the development of mathematics learning instrument based on learning trajectory

NASA Astrophysics Data System (ADS)

Misnasanti; Dien, C. A.; Azizah, F.

2018-03-01

This study is aimed to describe Lesson Study (LS) activity and its roles in the development of mathematics learning instruments based on Learning Trajectory (LT). This study is a narrative study of teacher’s experiences in joining LS activity. Data collecting in this study will use three methods such as observation, documentations, and deep interview. The collected data will be analyzed with Milles and Huberman’s model that consists of reduction, display, and verification. The study result shows that through LS activity, teachers know more about how students think. Teachers also can revise their mathematics learning instrument in the form of lesson plan. It means that LS activity is important to make a better learning instruments and focus on how student learn not on how teacher teach.

A simulation study on the constancy of cardiac energy metabolites during workload transition.

PubMed

Saito, Ryuta; Takeuchi, Ayako; Himeno, Yukiko; Inagaki, Nobuya; Matsuoka, Satoshi

2016-12-01

The cardiac energy metabolites such as ATP, phosphocreatine, ADP and NADH are kept relatively constant during physiological cardiac workload transition. How this is accomplished is not yet clarified, though Ca 2+ has been suggested to be one of the possible mechanisms. We constructed a detailed mathematical model of cardiac mitochondria based on experimental data and studied whether known Ca 2+ -dependent regulation mechanisms play roles in the metabolite constancy. Model simulations revealed that the Ca 2+ -dependent regulation mechanisms have important roles under the in vitro condition of isolated mitochondria where malate and glutamate were mitochondrial substrates, while they have only a minor role and the composition of substrates has marked influence on the metabolite constancy during workload transition under the simulated in vivo condition where many substrates exist. These results help us understand the regulation mechanisms of cardiac energy metabolism during physiological cardiac workload transition. The cardiac energy metabolites such as ATP, phosphocreatine, ADP and NADH are kept relatively constant over a wide range of cardiac workload, though the mechanisms are not yet clarified. One possible regulator of mitochondrial metabolism is Ca 2+ , because it activates several mitochondrial enzymes and transporters. Here we constructed a mathematical model of cardiac mitochondria, including oxidative phosphorylation, substrate metabolism and ion/substrate transporters, based on experimental data, and studied whether the Ca 2+ -dependent activation mechanisms play roles in metabolite constancy. Under the in vitro condition of isolated mitochondria, where malate and glutamate were used as mitochondrial substrates, the model well reproduced the Ca 2+ and inorganic phosphate (P i ) dependences of oxygen consumption, NADH level and mitochondrial membrane potential. The Ca 2+ -dependent activations of the aspartate/glutamate carrier and the F 1 F o -ATPase, and the P i -dependent activation of Complex III were key factors in reproducing the experimental data. When the mitochondrial model was implemented in a simple cardiac cell model, simulation of workload transition revealed that cytoplasmic Ca 2+ concentration ([Ca 2+ ] cyt ) within the physiological range markedly increased NADH level. However, the addition of pyruvate or citrate attenuated the Ca 2+ dependence of NADH during the workload transition. Under the simulated in vivo condition where malate, glutamate, pyruvate, citrate and 2-oxoglutarate were used as mitochondrial substrates, the energy metabolites were more stable during the workload transition and NADH level was almost insensitive to [Ca 2+ ] cyt . It was revealed that mitochondrial substrates have a significant influence on metabolite constancy during cardiac workload transition, and Ca 2+ has only a minor role under physiological conditions. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Affective decision-making and externalizing behaviors: the role of autonomic activity.

PubMed

Bubier, Jennifer L; Drabick, Deborah A G

2008-08-01

We tested a conceptual model involving the inter-relations among affective decision-making (indexed by a gambling task), autonomic nervous system (ANS) activity, and attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in a largely impoverished, inner city sample of first through third grade children (N=63, 54% male). The present study hypothesized that impaired affective decision-making and decreased sympathetic and parasympathetic activation would be associated with higher levels of ADHD and ODD symptoms, and that low sympathetic and parasympathetic activation during an emotion-inducing task would mediate the relation between affective decision-making and child externalizing symptoms. In support of our model, disadvantageous decision-making on a gambling task was associated with ADHD hyperactivity/impulsivity symptoms among boys, and attenuated sympathetic activation during an emotion-inducing task mediated this relation. Support for the model was not found among girls.

Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

DOE PAGES

Leal, Stephanie L.; Landau, Susan M.; Bell, Rachel K.; ...

2017-02-08

The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baselinemore » was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.« less

Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

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

Leal, Stephanie L.; Landau, Susan M.; Bell, Rachel K.

The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baselinemore » was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.« less

A Developmental Model for Educational Planning: Democratic Rationalities and Dispositions

ERIC Educational Resources Information Center

Hess, Michael; Johnson, Jerry; Reynolds, Sharon

2014-01-01

The Developmental Democratic Planning (DDP) model frames educational planning as a process that extends beyond the immediate focus of a particular planning effort to acknowledge and cultivate the potential of all members of the organization to fulfill their roles as active participants in the democratic life of the organization. The DDP model…

Evolving Approaches and Technologies to Enhance the Role of Ecological Modeling in Decision Making

Treesearch

Eric Gustafson; John Nestler; Louis Gross; Keith M. Reynolds; Daniel Yaussy; Thomas P. Maxwell; Virginia H. Dale

2002-01-01

Understanding the effects of management activities is difficult for natural resource managers and decision makers because ecological systems are highly complex and their behavior is difficult to predict. Furthermore, the empirical studies necessary to illuminate all management questions quickly become logistically complicated and cost prohibitive. Ecological models...

The Practicum Course Model: Embracing the Museum-University Culture Clash

ERIC Educational Resources Information Center

Kingsley, Jennifer P.

2016-01-01

Museums and universities have natural connections. Yet with few exceptions, collaborations between them segregate each partner to its traditional sphere of activity. This article presents a practicum course model that blurs and overlaps the distinctive roles of the museum and university in productive and mutually beneficial ways. In particular,…

Curricular Learning Communities and Unprepared Students: How Faculty Can Provide a Foundation for Success

ERIC Educational Resources Information Center

Engstrom, Cathy McHugh

2008-01-01

The pedagogical assumptions and teaching practices of learning community models reflect exemplary conditions for learning, so using these models with unprepared students seems desirable and worthy of investigation. This chapter describes the key role of faculty in creating active, integrative learning experiences for students in basic skills…

Cytotoxic effect of a family of peroxisome proliferator-activated receptor antagonists in colorectal and pancreatic cancer cell lines.

PubMed

Ammazzalorso, Alessandra; De Lellis, Laura; Florio, Rosalba; Bruno, Isabella; De Filippis, Barbara; Fantacuzzi, Marialuigia; Giampietro, Letizia; Maccallini, Cristina; Perconti, Silvia; Verginelli, Fabio; Cama, Alessandro; Amoroso, Rosa

2017-11-01

Recent studies report an interesting role of peroxisome proliferator-activated receptor (PPAR) antagonists in different tumor models, being these compounds able to perturb metabolism and viability in cancer cells. In this work, the identification of a novel PPAR antagonist, showing inhibitory activity on PPARα and a weaker antagonism on PPARγ, is described. The activity of this compound and of a series of chemical analogues was investigated in selected tumor cell lines, expressing both PPARα and PPARγ. Data obtained show a dose-dependent cytotoxic effect of the novel PPAR antagonist in colorectal and pancreatic cancer models. © 2017 John Wiley & Sons A/S.

Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation.

PubMed

Reddy, Jay P; Peddibhotla, Sirisha; Bu, Wen; Zhao, Jing; Haricharan, Svasti; Du, Yi-Chieh Nancy; Podsypanina, Katrina; Rosen, Jeffrey M; Donehower, Larry A; Li, Yi

2010-02-23

p53, apoptosis, and senescence are frequently activated in preneoplastic lesions and are barriers to progression to malignancy. These barriers have been suggested to result from an ATM-mediated DNA damage response (DDR), which may follow oncogene-induced hyperproliferation and ensuing DNA replication stress. To elucidate the currently untested role of DDR in breast cancer initiation, we examined the effect of oncogene expression in several murine models of breast cancer. We did not observe a detectable DDR in early hyperplastic lesions arising in transgenic mice expressing several different oncogenes. However, DDR signaling was strongly induced in preneoplastic lesions arising from individual mammary cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus, activation of an oncogene after normal tissue development causes a DDR. Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required for p53 stabilization, apoptosis, and senescence. In palpable tumors in this model, p53 stabilization and apoptosis are lost, but unexpectedly senescence remains in many tumor cells. Thus, this murine model fully recapitulates early DDR signaling; the eventual suppression of its endpoints in tumorigenesis provides compelling evidence that ErbB2-induced aberrant mammary cell proliferation leads to an ATM-mediated DDR that activates apoptosis and senescence, and at least the former must be overcome to progress to malignancy. This in vivo study also uncovers an unexpected effect of ErbB2 activation previously known for its prosurvival roles, and suggests that protection of the ATM-mediated DDR-p53 signaling pathway may be important in breast cancer prevention.

The reversal of pulmonary vascular remodeling through inhibition of p38 MAPK-alpha: a potential novel anti-inflammatory strategy in pulmonary hypertension

PubMed Central

Martin, Damien H.; Wadsworth, Roger; Bryson, Gareth; Fisher, Andrew J.; Welsh, David J.; Peacock, Andrew J.

2015-01-01

The p38 mitogen-activated protein kinase (MAPK) system is increasingly recognized as an important inflammatory pathway in systemic vascular disease but its role in pulmonary vascular disease is unclear. Previous in vitro studies suggest p38 MAPKα is critical in the proliferation of pulmonary artery fibroblasts, an important step in the pathogenesis of pulmonary vascular remodeling (PVremod). In this study the role of the p38 MAPK pathway was investigated in both in vitro and in vivo models of pulmonary hypertension and human disease. Pharmacological inhibition of p38 MAPKα in both chronic hypoxic and monocrotaline rodent models of pulmonary hypertension prevented and reversed the pulmonary hypertensive phenotype. Furthermore, with the use of a novel and clinically available p38 MAPKα antagonist, reversal of pulmonary hypertension was obtained in both experimental models. Increased expression of phosphorylated p38 MAPK and p38 MAPKα was observed in the pulmonary vasculature from patients with idiopathic pulmonary arterial hypertension, suggesting a role for activation of this pathway in the PVremod A reduction of IL-6 levels in serum and lung tissue was found in the drug-treated animals, suggesting a potential mechanism for this reversal in PVremod. This study suggests that the p38 MAPK and the α-isoform plays a pathogenic role in both human disease and rodent models of pulmonary hypertension potentially mediated through IL-6. Selective inhibition of this pathway may provide a novel therapeutic approach that targets both remodeling and inflammatory pathways in pulmonary vascular disease. PMID:26024891

Modeling of Depth Cue Integration in Manual Control Tasks

NASA Technical Reports Server (NTRS)

Sweet, Barbara T.; Kaiser, Mary K.; Davis, Wendy

2003-01-01

Psychophysical research has demonstrated that human observers utilize a variety of visual cues to form a perception of three-dimensional depth. However, most of these studies have utilized a passive judgement paradigm, and failed to consider depth-cue integration as a dynamic and task-specific process. In the current study, we developed and experimentally validated a model of manual control of depth that examines how two potential cues (stereo disparity and relative size) are utilized in both first- and second-order active depth control tasks. We found that stereo disparity plays the dominate role for determining depth position, while relative size dominates perception of depth velocity. Stereo disparity also plays a reduced role when made less salient (i.e., when viewing distance is increased). Manual control models predict that position information is sufficient for first-order control tasks, while velocity information is required to perform a second-order control task. Thus, the rules for depth-cue integration in active control tasks are dependent on both task demands and cue quality.

"RePlay Health": An Experiential Role-Playing Sport for Modeling Healthcare Decisions, Policies, and Outcomes.

PubMed

Kaufman, Geoff; Flanagan, Mary; Seidman, Max; Wien, Simone

2015-08-01

This article presents the design and empirical investigation of the "RePlay Health" game ( www.replayhealth.com/ ), a novel "role-playing sport" derived from a complex, data-driven, computational simulation of healthcare dynamics. By immersing players in a fictional world in which they take on the role of characters facing specific behavioral and environmental risk factors, the "RePlay Health" game models the impact of health and healthcare policy on individual-level livelihood and community-level productivity. A randomized experiment tested the efficacy of the game for inspiring shifts in thinking about public health and healthcare policy. This study compared the impact of actively playing the game versus passively spectating: 31 young adults were assigned to one of these two roles. Participants completed pretest and posttest measures of their subjective ranking of healthcare policies and attributions for health outcomes. Active players (compared with spectators) reported significantly higher prioritizations (from pretest to posttest) in their subjective ranking of several health policies modeled by the game, such as "improving postdischarge care" and "increasing access to healthy foods." Furthermore, players, but not spectators, were significantly more likely following gameplay to identify environmental or systemic factors as potential causes of health problems. The fact that significant results emerged with a 1-week gap between gameplay and measurement demonstrates that the game could exert a lasting impact on attitudes and perceptions. More broadly, this work illustrates the value of incorporating experiential components, such as narrative, embodiment, and role-playing, in designing efficacious games for health.

Enhanced effects of amphetamine but reduced effects of the hallucinogen, 5-MeO-DMT, on locomotor activity in 5-HT(1A) receptor knockout mice: implications for schizophrenia.

PubMed

van den Buuse, Maarten; Ruimschotel, Emma; Martin, Sally; Risbrough, Victoria B; Halberstadt, Adam L

2011-01-01

Serotonin-1A (5-HT(1A)) receptors may play a role in schizophrenia and the effects of certain antipsychotic drugs. However, the mechanism of interaction of 5-HT(1A) receptors with brain systems involved in schizophrenia, remains unclear. Here we show that 5-HT(1A) receptor knockout mice display enhanced locomotor hyperactivity to acute treatment with amphetamine, a widely used animal model of hyperdopaminergic mechanisms in psychosis. In contrast, the effect of MK-801 on locomotor activity, modeling NMDA receptor hypoactivity, was unchanged in the knockouts. The effect of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) was markedly reduced in 5-HT(1A) receptor knockout mice. There were no changes in apomorphine-induced disruption of PPI, a model of sensory gating deficits seen in schizophrenia. Similarly, there were no major changes in density of dopamine transporters (DAT) or dopamine D(1) or D(2) receptors which could explain the behavioural changes observed in 5-HT(1A) receptor knockout mice. These results extend our insight into the possible role of these receptors in aspects of schizophrenia. As also suggested by previous studies using agonist and antagonist drugs, 5-HT(1A) receptors may play an important role in hallucinations and to modulate dopaminergic activity in the brain. Copyright © 2011 Elsevier Ltd. All rights reserved.

Modeling study on the cleavage step of the self-splicing reaction in group I introns

NASA Technical Reports Server (NTRS)

Setlik, R. F.; Garduno-Juarez, R.; Manchester, J. I.; Shibata, M.; Ornstein, R. L.; Rein, R.

1993-01-01

A three-dimensional model of the Tetrahymena thermophila group I intron is used to further explore the catalytic mechanism of the transphosphorylation reaction of the cleavage step. Based on the coordinates of the catalytic core model proposed by Michel and Westhof (Michel, F., Westhof, E. J. Mol. Biol. 216, 585-610 (1990)), we first converted their ligation step model into a model of the cleavage step by the substitution of several bases and the removal of helix P9. Next, an attempt to place a trigonal bipyramidal transition state model in the active site revealed that this modified model for the cleavage step could not accommodate the transition state due to insufficient space. A lowering of P1 helix relative to surrounding helices provided the additional space required. Simultaneously, it provided a better starting geometry to model the molecular contacts proposed by Pyle et al. (Pyle, A. M., Murphy, F. L., Cech, T. R. Nature 358, 123-128. (1992)), based on mutational studies involving the J8/7 segment. Two hydrated Mg2+ complexes were placed in the active site of the ribozyme model, using the crystal structure of the functionally similar Klenow fragment (Beese, L.S., Steitz, T.A. EMBO J. 10, 25-33 (1991)) as a guide. The presence of two metal ions in the active site of the intron differs from previous models, which incorporate one metal ion in the catalytic site to fulfill the postulated roles of Mg2+ in catalysis. The reaction profile is simulated based on a trigonal bipyramidal transition state, and the role of the hydrated Mg2+ complexes in catalysis is further explored using molecular orbital calculations.

A battery model that enables consideration of realistic anisotropic environment surrounding an active material particle and its application

NASA Astrophysics Data System (ADS)

Lin, Xianke; Lu, Wei

2017-07-01

This paper proposes a model that enables consideration of the realistic anisotropic environment surrounding an active material particle by incorporating both diffusion and migration of lithium ions and electrons in the particle. This model makes it possible to quantitatively evaluate effects such as fracture on capacity degradation. In contrast, the conventional model assumes isotropic environment and only considers diffusion in the active particle, which cannot capture the effect of fracture since it would predict results contradictory to experimental observations. With the developed model we have investigated the effects of active material electronic conductivity, particle size, and State of Charge (SOC) swing window when fracture exists. The study shows that the low electronic conductivity of active material has a significant impact on the lithium ion pattern. Fracture increases the resistance for electron transport and therefore reduces lithium intercalation/deintercalation. Particle size plays an important role in lithium ion transport. Smaller particle size is preferable for mitigating capacity loss when fracture happens. The study also shows that operating at high SOC reduces the impact of fracture.

Models as Artefacts of a Dual Nature: A Philosophical Contribution to Teaching about Models Designed and Used in Engineering Practice

ERIC Educational Resources Information Center

Nia, Mahdi G.; de Vries, Marc J.

2017-01-01

Although '"models" play a significant role in engineering activities, not much has yet been developed to enhance the technological literacy of students in this regard. This contribution intends to help fill this gap and deliver a comprehensive account as to the nature and various properties of these engineering tools. It begins by…

The Role of Sex of Peers and Gender-Typed Activities in Young Children's Peer Affiliative Networks: A Longitudinal Analysis of Selection and Influence

ERIC Educational Resources Information Center

Martin, Carol Lynn; Kornienko, Olga; Schaefer, David R.; Hanish, Laura D.; Fabes, Richard A.; Goble, Priscilla

2013-01-01

A stochastic actor-based model was used to investigate the origins of sex segregation by examining how similarity in sex of peers and time spent in gender-typed activities affected affiliation network selection and how peers influenced children's ("N" = 292; "M"[subscript age] = 4.3 years) activity involvement. Gender had…

Systems Modeling of Molecular Mechanisms Controlling Cytokine-driven CD4+ T Cell Differentiation and Phenotype Plasticity

PubMed Central

Carbo, Adria; Hontecillas, Raquel; Kronsteiner, Barbara; Viladomiu, Monica; Pedragosa, Mireia; Lu, Pinyi; Philipson, Casandra W.; Hoops, Stefan; Marathe, Madhav; Eubank, Stephen; Bisset, Keith; Wendelsdorf, Katherine; Jarrah, Abdul; Mei, Yongguo; Bassaganya-Riera, Josep

2013-01-01

Differentiation of CD4+ T cells into effector or regulatory phenotypes is tightly controlled by the cytokine milieu, complex intracellular signaling networks and numerous transcriptional regulators. We combined experimental approaches and computational modeling to investigate the mechanisms controlling differentiation and plasticity of CD4+ T cells in the gut of mice. Our computational model encompasses the major intracellular pathways involved in CD4+ T cell differentiation into T helper 1 (Th1), Th2, Th17 and induced regulatory T cells (iTreg). Our modeling efforts predicted a critical role for peroxisome proliferator-activated receptor gamma (PPARγ) in modulating plasticity between Th17 and iTreg cells. PPARγ regulates differentiation, activation and cytokine production, thereby controlling the induction of effector and regulatory responses, and is a promising therapeutic target for dysregulated immune responses and inflammation. Our modeling efforts predict that following PPARγ activation, Th17 cells undergo phenotype switch and become iTreg cells. This prediction was validated by results of adoptive transfer studies showing an increase of colonic iTreg and a decrease of Th17 cells in the gut mucosa of mice with colitis following pharmacological activation of PPARγ. Deletion of PPARγ in CD4+ T cells impaired mucosal iTreg and enhanced colitogenic Th17 responses in mice with CD4+ T cell-induced colitis. Thus, for the first time we provide novel molecular evidence in vivo demonstrating that PPARγ in addition to regulating CD4+ T cell differentiation also plays a major role controlling Th17 and iTreg plasticity in the gut mucosa. PMID:23592971

Motivational factors associated with physical activity and quality of life in people with severe mental illness.

PubMed

Farholm, Anders; Sørensen, Marit; Halvari, Hallgeir

2017-12-01

There has been increasing interest for investigating the role of motivation in physical activity among people with severe mental illness (SMI). Autonomous motivation has been suggested to have a potentially important role in adoption and maintenance of physical activity. However, the knowledge about factors that facilitate autonomous motivation among people with SMI is scarce. The aim of this study was to examine factors associated with motivation for physical activity as well as the relationships between motivation, physical activity and health-related quality of life in individuals with SMI that were currently physically active. A cross-sectional design was used, and 88 participants were recruited from a public health network promoting physical activity for people with SMI. They answered a questionnaire package consisting of scales measuring psychological need support - psychological need satisfaction - and motivation for physical activity, physical activity and health-related quality of life. The majority of participants reported to be in regular physical activity. Associations between variables were tested according to the self-determination theory process model. Structural equation modelling yielded good fit of the process model to the data. Specifically, a need-supportive environment was positively associated with psychological need satisfaction, while psychological need satisfaction was positively associated with autonomous motivation and mental health-related quality of life, and negatively associated with controlled motivation and amotivation. Physical activity was positively associated with autonomous motivation and physical health-related quality of life, and negatively associated with amotivation. This study indicates that individuals with SMI can be regularly physically active when provided with suitable opportunities. Furthermore, the present results suggest that it is vital for health-care practitioners to emphasise creating a need-supportive environment when organising physical activity because such an environment is associated with both increased autonomous motivation for physical activity and mental health-related quality of life. © 2016 Nordic College of Caring Science.

The role of peer physical activity champions in the workplace: a qualitative study.

PubMed

Edmunds, Sarah; Clow, Angela

2016-05-01

Peer health champions have been suggested as an important component of multilevel workplace interventions to promote healthy behaviours such as physical activity (PA). There is accumulating quantitative evidence of their effectiveness but as yet little exploration of why and how champions influence peer behaviour. The current study explores the role of peer physical activity champions (PPACs) in influencing colleagues' PA behaviour from the perspectives of both champions and colleagues. Seven months after the introduction of a workplace PA programme in 17 small- and medium-sized enterprises (SMEs), two focus groups were held with PPACs and four with programme participants. Data were analysed using inductive thematic analysis. Three overarching themes were developed: how PPACs encourage PA, valuable PPAC characteristics and sustaining motivation for the PPAC role. Both direct encouragement from PPACs and facilitation of wider PA supportive social networks within the workplace encouraged behaviour change. PA behaviour change is a delicate subject and it was important that PPACs provided enthusiastic and persistent encouragement without seeming judgemental. Being a PA role model was also a valuable characteristic. The PPACs found it satisfying to see positive changes in their colleagues who had become more active. However, colleagues often did not engage in suggested activities and PPACs required resilience to maintain personal motivation for the role despite this. Incorporating PPACs into SME-based PA interventions is acceptable to employees. It is recommended that PPAC training includes suggestions for facilitating social connections between colleagues. Sensitivity is required when initiating and engaging in conversations with colleagues about increasing their PA. Programmes should ensure PPACs themselves are provided with social support, especially from others in the same role, to help sustain motivation for their role. These findings will be useful to health-promotion professionals developing workplace health programmes. © Royal Society for Public Health 2015.

The Influence of Curriculum, Instruction, Technology, and Social Interactions on Two Fifth-Grade Students' Epistemologies in Modeling Throughout a Model-Based Curriculum Unit

NASA Astrophysics Data System (ADS)

Baek, Hamin; Schwarz, Christina V.

2015-04-01

In the past decade, reform efforts in science education have increasingly attended to engaging students in scientific practices such as scientific modeling. Engaging students in scientific modeling can help them develop their epistemologies by allowing them to attend to the roles of mechanism and empirical evidence when constructing and revising models. In this article, we present our in-depth case study of how two fifth graders—Brian and Joon—who were students in a public school classroom located in a Midwestern state shifted their epistemologies in modeling as they participated in the enactment of a technologically enhanced, model-based curriculum unit on evaporation and condensation. First, analyses of Brian's and Joon's models indicate that their epistemologies in modeling related to explanation and empirical evidence shifted productively throughout the unit. Additionally, while their initial and final epistemologies in modeling were similar, the pathways in which their epistemologies in modeling shifted differed. Next, analyses of the classroom activities illustrate how various components of the learning ecology including technological tools, the teacher's scaffolding remarks, and students' collective activities and conversations, were marshaled in the service of the two students' shifting epistemologies in modeling. These findings suggest a nuanced view of individual learners' engagement in scientific modeling, their epistemological shifts in the practice, and the roles of technology and other components of a modeling-oriented learning environment for such shifts.

Unsolved Mysteries in NLR Biology

PubMed Central

Lupfer, Christopher; Kanneganti, Thirumala-Devi

2013-01-01

NOD-like receptors (NLRs) are a class of cytoplasmic pattern-recognition receptors. Although most NLRs play some role in immunity, their functions range from regulating antigen presentation (NLRC5, CIITA) to pathogen/damage sensing (NLRP1, NLRP3, NLRC1/2, NLRC4) to suppression or modulation of inflammation (NLRC3, NLRP6, NLRP12, NLRX1). However, NLRP2, NLRP5, and NLRP7 are also involved in non-immune pathways such as embryonic development. In this review, we highlight some of the least well-understood aspects of NLRs, including the mechanisms by which they sense pathogens or damage. NLRP3 recognizes a diverse range of stimuli and numerous publications have presented potential unifying models for NLRP3 activation, but no single mechanism proposed thus far appears to account for all possible NLRP3 activators. Additionally, NLRC3, NLRP6, and NLRP12 inhibit NF-κB activation, but whether direct ligand sensing is a requirement for this function is not known. Herein, we review the various mechanisms of sensing and activation proposed for NLRP3 and other inflammasome activators. We also discuss the role of NLRC3, NLRP6, NLRP12, and NLRX1 as inhibitors and how they are activated and function in their roles to limit inflammation. Finally, we present an overview of the emerging roles that NLRP2, NLRP5, and NLRP7 play during embryonic development and postulate on the potential pathways involved. PMID:24062750

A participatory evaluation model for Healthier Communities: developing indicators for New Mexico.

PubMed Central

Wallerstein, N

2000-01-01

Participatory evaluation models that invite community coalitions to take an active role in developing evaluations of their programs are a natural fit with Healthy Communities initiatives. The author describes the development of a participatory evaluation model for New Mexico's Healthier Communities program. She describes evaluation principles, research questions, and baseline findings. The evaluation model shows the links between process, community-level system impacts, and population health changes. PMID:10968754

Mathematical Modeling of Cancer Invasion: The Role of Membrane-Bound Matrix Metalloproteinases

PubMed Central

Deakin, Niall E.; Chaplain, Mark A. J.

2013-01-01

One of the hallmarks of cancer growth and metastatic spread is the process of local invasion of the surrounding tissue. Cancer cells achieve protease-dependent invasion by the secretion of enzymes involved in proteolysis. These overly expressed proteolytic enzymes then proceed to degrade the host tissue allowing the cancer cells to disseminate throughout the microenvironment by active migration and interaction with components of the extracellular matrix (ECM) such as collagen. In this paper we develop a mathematical model of cancer invasion which consider the role of matrix metalloproteinases (MMPs). Specifically our model will focus on two distinct types of MMP, i.e., soluble, diffusible MMPs (e.g., MMP-2) and membrane-bound MMPs (e.g., MT1-MMP), and the roles each of these plays in cancer invasion. The implications of MMP-2 activation by MMP-14 and the tissue inhibitor of metalloproteinases-2 are considered alongside the effect the architecture of the matrix may have when applied to a model of cancer invasion. Elements of the ECM architecture investigated include pore size of the matrix, since in some highly dense collagen structures such as breast tissue, the cancer cells are unable to physically fit through a porous region, and the crosslinking of collagen fibers. In this scenario, cancer cells rely on membrane-bound MMPs to forge a path through which degradation by other MMPs and movement of cancer cells becomes possible. PMID:23565505

Persistence of low levels of plasma viremia and of the latent reservoir in patients under ART: A fractional-order approach

NASA Astrophysics Data System (ADS)

Pinto, Carla M. A.

2017-02-01

Low levels of viral load are found in HIV-infected patients, after many years under successful suppressive anti-retroviral therapy (ART). The factors leading to this persistence are still under debate, but it is now more or less accepted that the latent reservoir may be crucial to the maintenance of this residual viremia. In this paper, we study the role of the latent reservoir in the persistence of the latent reservoir and of the plasma viremia in a fractional-order (FO) model for HIV infection. Our model assumes that (i) the latently infected cells may undergo bystander proliferation, without active viral production, (ii) the latent cell activation rate decreases with time on ART, (iii) the productively infected cells' death rate is a function of the infected cell density. The proposed model provides new insights on the role of the latent reservoir in the persistence of the latent reservoir and of the plasma virus. Moreover, the fractional-order derivative distinguishes distinct velocities in the dynamics of the latent reservoir and of plasma virus. The later may be used to better approximations of HIV-infected patients data. To our best knowledge, this is the first FO model that deals with the role of the latent reservoir in the persistence of low levels of viremia and of the latent reservoir.

Modeling the data systems role of the scientist (for the NEEDS Command and Control Task)

NASA Technical Reports Server (NTRS)

Hei, D. J., Jr.; Winter, W. J., Jr.; Brookes, R.; Locke, M.

1981-01-01

Research was conducted into the command and control activities of the scientists for five space missions: International Ultraviolet Explorer, Solar Maximum Mission, International Sun-Earth Explorer, High-Energy Astronomy Observatory 1, and Atmospheric Explorer 5. A basis for developing a generalized description of the scientists' activities was obtained. Because of this characteristic, it was decided that a series of flowcharts would be used. This set of flowcharts constitutes a model of the scientists' activities within the total data system. The model was developed through three levels of detail. The first is general and provides a conceptual framework for discussing the system. The second identifies major functions and should provide a fundamental understanding of the scientists' command and control activities. The third level expands the major functions into a more detailed description.

Analysis of the binding sites of vitamin D 1α-hydroxylase (CYP27B1) and vitamin D 24-hydroxylase (CYP24A1) for the design of selective CYP24A1 inhibitors: Homology modelling, molecular dynamics simulations and identification of key binding requirements.

PubMed

Taban, Ismail M; Zhu, Jinge; DeLuca, Hector F; Simons, Claire

2017-10-15

A homology model of human CYP27B1 was built using MOE and was further optimised by molecular dynamics simulations of the hCYP27B1 homology model and a hCYP27B1-SDZ-88357 complex. Docking results from the hCYP27B1-SDZ-88357 complex showed amino acids Arg107, Asn387 and Asp320 have an important role in binding interaction, with Asp320 part of the important acid-alcohol pair situated in the I-helix with the conserved sequence (A/G) GX (E/D) (T/S), which assumes an essential role in the binding of an oxygen molecule for catalysis. Additional docking experiments with selective hCYP27B1 or hCYP24A1 inhibitors using both the hCYP27B1 model and a triple mutant hCYP24A1 model provided further support for the importance of H-bonding interactions with the three identified active site amino acids. To confirm the role of Arg107, Asn387 and Asp320 in the active site of hCYP27B1 compounds were designed that would form H-bonding interactions, as determined from docking experiments with the hCYP27B1 model. Subsequent synthesis and CYP24A1 and CYP27B1 enzyme assays of the designed compounds 1a and 1b showed a∼5-fold selectivity for CYP27B1 confirming the importance of Asp320 in particular and also Asn387 and Arg107 as important amino acids for CYP27B1 inhibitory activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Easier said than done: a qualitative study conducted in the USA exploring Latino family child care home providers as role models for healthy eating and physical activity behaviours.

PubMed

Lindsay, Ana Cristina; Greaney, Mary L; Wallington, Sherrie F; Wright, Julie A

2017-11-12

Latinos are the largest and most rapidly growing minority population group in the USA and are disproportionally affected by obesity and related chronic diseases. Child care providers likely influence the eating and physical activity behaviours of children in their care, and therefore are important targets for interventions designed to prevent childhood obesity. Nonetheless, there is a paucity of research examining the behaviours of family child care home (FCCH) providers and whether they model healthy eating and physical activity behaviours. Therefore, this study explored Latino FCCH providers' beliefs and practices related to healthy eating, physical activity and sedentary behaviours, and how they view their ability to serve as role models for these behaviours for young children in their care. This is a qualitative study consisting of six focus groups conducted in Spanish with a sample of 44 state-licensed Latino FCCH providers in the state of Massachusetts. Translated transcripts were analysed using thematic analyses to identify meaningful patterns. Analyses revealed that Latino FCCH providers have positive beliefs and attitudes about the importance of healthy eating and physical activity for children in their care, but personally struggle with these same behaviours and with maintaining a healthy weight status. The ability of Latino FCCH providers to model healthy eating and physical activity may be limited by their low self-efficacy in their ability to be physically active, eat a healthy diet and maintain a healthy weight. Interventions designed to improve healthy eating and physical activity behaviours of children enrolled in FCCHs should address providers' own health behaviours as well as their modelling of these health behaviours. Future research can build on the findings of this qualitative study by quantifying Latino FCCH providers' eating and physical activity behaviours, and determining how these behaviours influence behaviours and health outcomes of children in their care. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Seven Activities for Enhancing the Replicability of Evidence-Based Practices. Research-to-Results Brief. Publication #2007-30

ERIC Educational Resources Information Center

Metz, Allison J. R.; Bowie, Lillian; Blase, Karen

2007-01-01

This brief will define program replication, describe the critical role of "core components" in program replication, and outline seven activities that program developers and researchers can conduct to enhance the replicability of effective program models and facilitate their adoption by other organizations and programs. Outlined is seven specific…

Predicting Adolescents' Organized Activity Involvement: The Role of Maternal Depression History, Family Relationship Quality, and Adolescent Cognitions

ERIC Educational Resources Information Center

Bohnert, Amy M.; Martin, Nina C.; Garber, Judy

2007-01-01

Although the potential benefits of organized activity involvement during high school have been documented, little is known about what familial and individual characteristics are associated with higher levels of participation. Using structural equation modeling, this longitudinal study examined the extent to which maternal depression history (i.e.,…

Outreach to Inspire Girls in Geology: A Recipe for Success (Invited)

NASA Astrophysics Data System (ADS)

Kekelis, L.

2010-12-01

Geology and engineering careers can seem very abstract to a young girl, especially to a girl who has no role model in technical fields. Many girls want to make the world a better place but don’t see how their interests connect with geology or engineering. Role models and field trips to worksites are instrumental in encouraging girls to consider careers in geoscience and engineering. The opportunities to see real-world applications of technology and meet with role models who work in technical fields are extremely impactful and can have a strong influence on a girl’s career path. Together we need to do a better job of communicating what geoscience and engineering have to offer girls and what girls have to offer these fields. This presentation will provide practical tips to help combat stereotypes, 2) share resources for outreach at one-day special events, summer camps, visits to the classroom and field trips to corporate sites and college campuses, and 3) highlight strategies for groups to work collaboratively in outreach. This presentation will help those currently involved in outreach who want to improve on existing efforts, along with those who have never done outreach and are interested in getting started. Techbridge will share a “recipe for success” for planning and hosting role model visits to the classroom and field trips. A case study of outreach by Chevron with Techbridge girls will be shared including the pre-event planning that made this event a success. Activities that make geology fun and friendly to girls and tips for dispelling stereotypes about careers in geology and engineering will also be shared. Participants will be invited to ask questions and share on topics of interest, such as “Challenges with outreach,” “How to get involved without burning out,” and “How to show your manager or organization that outreach is worth the effort.” We will also promote a candid discussion of the challenges that can arise along with way and how to overcome them. Participants will receive a copy of our role model outreach guide and CD toolkit, Get Involved. Make a Difference, developed by the Techbridge team. This guide includes practical tips and suggestions as well as successful case studies in outreach to K-12. These materials include sample icebreakers and hands-on activities, biographies of students and role models, questions to facilitate conversations between role models and students, scavenger hunts for tours, suggested schedule and timeline, evaluations, tips for success, and more.

Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota

PubMed Central

van den Hoogen, Ward J.; Laman, Jon D.; ’t Hart, Bert A.

2017-01-01

Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gut microbiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gut microbiota and dietary components in MS. Here, we review these recent studies on gut microbiota and dietary interventions in MS and its animal model experimental autoimmune encephalomyelitis. We also propose directions for future research. PMID:28928747

Neural Energy Supply-Consumption Properties Based on Hodgkin-Huxley Model

PubMed Central

2017-01-01

Electrical activity is the foundation of the neural system. Coding theories that describe neural electrical activity by the roles of action potential timing or frequency have been thoroughly studied. However, an alternative method to study coding questions is the energy method, which is more global and economical. In this study, we clearly defined and calculated neural energy supply and consumption based on the Hodgkin-Huxley model, during firing action potentials and subthreshold activities using ion-counting and power-integral model. Furthermore, we analyzed energy properties of each ion channel and found that, under the two circumstances, power synchronization of ion channels and energy utilization ratio have significant differences. This is particularly true of the energy utilization ratio, which can rise to above 100% during subthreshold activity, revealing an overdraft property of energy use. These findings demonstrate the distinct status of the energy properties during neuronal firings and subthreshold activities. Meanwhile, after introducing a synapse energy model, this research can be generalized to energy calculation of a neural network. This is potentially important for understanding the relationship between dynamical network activities and cognitive behaviors. PMID:28316842

Neuroprotective Role of Novel Triazine Derivatives by Activating Wnt/β Catenin Signaling Pathway in Rodent Models of Alzheimer's Disease.

PubMed

Sinha, Anshuman; Tamboli, Riyaj S; Seth, Brashket; Kanhed, Ashish M; Tiwari, Shashi Kant; Agarwal, Swati; Nair, Saumya; Giridhar, Rajani; Chaturvedi, Rajnish Kumar; Yadav, Mange Ram

2015-08-01

It has been reported in the literature that cholinesterase inhibitors provide protection in Alzheimer's disease (AD). Recent reports have implicated triazine derivatives as cholinesterase inhibitors. These findings led us to investigate anti-cholinestrase property of some novel triazine derivatives synthesized in this laboratory. In vitro cholinesterase inhibition assay was performed using Ellman method. The potent compounds screened out from in vitro assay were further evaluated using scopolamine-induced amnesic mice model. Further, in vitro reactive oxygen species (ROS) scavenging and anti-apoptotic property of the potent compounds were demonstrated against Aβ1-42-induced neurotoxicity in rat hippocampal cells. Their neuroprotective role was assessed using Aβ1-42-induced Alzheimer's-like phenotype in rats. Further, the role of compounds on the activation of the Wnt/β-catenin pathway was studied. The results showed that the chosen compounds are having protective effect in Alzheimer's-like condition; the ex vivo results advocated their anti-cholinestrase and anti-oxidant activities. Treatment with TRZ-15 and TRZ-20 showed neuroprotective ability of the compounds as evidenced from the improved cognitive ability in the animals, and decrease in Aβ1-42 burden and cytochrome c and cleaved caspase-3 levels in the brain. This study also demonstrates positive involvement of the novel triazine derivatives in the Wnt/β-catenin pathway. Immunoblot and immunofluorescence data suggested that ratio of pGSK3/GSK3 and β-catenin got dramatically improved after treatment with TRZ-15 and TRZ-20. TRZ-15 and TRZ-20 showed neuroprotection in scopolamine-induced amnesic mice and Aβ1-42-induced Alzheimer's rat model and also activate the Wnt/β-catenin signaling pathway. These findings conclude that TRZ-15 and TRZ-20 could be a therapeutic approach to treat AD.

Non-invasive detection of matrix-metalloproteinase activity in a mouse model of cerebral ischemia using multispectral optoacoustic tomography

NASA Astrophysics Data System (ADS)

Ni, Ruiqing; Vaas, Markus; Ren, Wuwei; Klohs, Jan

2018-02-01

Matrix metalloproteinases (MMPs) play important roles in the pathophysiology of cerebral ischemia. Here we visualized in vivo MMP activity in the transient middle cerebral artery occlusion (tMCAO) mouse model using multispectral optoacoustic imaging (MSOT) with a MMP-activatable probe. MSOT data was co-registered with structural magnetic resonance imaging (MRI) obtained at 7 T for localization of signal distribution. We demonstrated upregulated MMP signal within the focal ischemic lesion in the tMCAO mouse model using MSOT/MRI multimodal imaging. This convenient non-invasive method will allow repetitive measurement following the time course of MMP-lesion development in ischemic stroke animal model.

Stakeholders in the German and Swiss Vocational Educational and Training System: Their Role in Innovating Apprenticeships against the Background of Academisation

ERIC Educational Resources Information Center

Deissinger, Thomas; Gonon, Philipp

2016-01-01

Purpose: The purpose of this paper is to compare stakeholders' roles in Germany and Switzerland when it comes to promoting innovation in the dual apprenticeship model. In both countries, the relevant stakeholders who represent the various occupations and, in a more narrow sense, the social partners, actively shape vocational education and training…

Further Evidence of Gender Stereotype Priming in Language: Semantic Facilitation and Inhibition in Italian Role Nouns

ERIC Educational Resources Information Center

Cacciari, Cristina; Padovani, Roberto

2007-01-01

Two experiments tested the activation of gender stereotypes for Italian role nouns (e.g., "teacher"). The experimental paradigm was modeled on the one proposed by a study by Banaji and Hardin: participants were shown a prime word followed by a target pronoun ("he" or "she") on which they performed a gender decision task. The prime words were…

Role of plasma kallikrein in diabetes and metabolism.

PubMed

Feener, E P; Zhou, Q; Fickweiler, W

2013-09-01

Plasma kallikrein (PK) is a serine protease generated from plasma prekallikrein, an abundant circulating zymogen expressed by the Klkb1 gene. The physiological actions of PK have been primarily attributed to its production of bradykinin and activation of coagulation factor XII, which promotes inflammation and the intrinsic coagulation pathway. Recent genetic, molecular, and pharmacological studies of PK have provided further insight into its role in physiology and disease. Genetic analyses have revealed common Klkb1 variants that are association with blood metabolite levels, hypertension, and coagulation. Characterisation of animal models with Klkb1 deficiency and PK inhibition have demonstrated effects on inflammation, vascular function, blood pressure regulation, thrombosis, haemostasis, and metabolism. These reports have also identified a host of PK substrates and interactions, which suggest an expanded physiological role for this protease beyond the bradykinin system and coagulation. The review summarises the mechanisms that contribute to PK activation and its emerging role in diabetes and metabolism.

Innate and adaptive immunity in experimental glomerulonephritis: a pathfinder tale.

PubMed

Artinger, Katharina; Kirsch, Alexander H; Aringer, Ida; Moschovaki-Filippidou, Foteini; Eller, Philipp; Rosenkranz, Alexander R; Eller, Kathrin

2017-06-01

The role of innate and adaptive immune cells in the experimental model of nephrotoxic serum nephritis (NTS) has been rigorously studied in recent years. The model is dependent on kidney-infiltrating T helper (TH) 17 and TH1 cells, which recruit neutrophils and macrophages, respectively, and cause sustained kidney inflammation. In a later phase of disease, regulatory T cells (Tregs) infiltrate the kidney in an attempt to limit disease activity. In the early stage of NTS, lymph node drainage plays an important role in disease initiation since dendritic cells present the antigen to T cells in the T cell zones of the draining lymph nodes. This results in the differentiation and proliferation of TH17 and TH1 cells. In this setting, immune regulatory cells (Tregs), namely, CCR7-expressing Tregs and mast cells (MCs), which are recruited by Tregs via the production of interleukin-9, exert their immunosuppressive capacity. Together, these two cell populations inhibit T cell differentiation and proliferation, thereby limiting disease activity by as yet unknown mechanisms. In contrast, the spleen plays no role in immune activation in NTS, but constitutes a place of extramedullary haematopoiesis. The complex interactions of immune cells in NTS are still under investigation and might ultimately lead to targeted therapies in glomerulonephritis.

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Activates Type I Interferon Signals in Lupus Nephritis.

PubMed

Xue, Leixi; Liu, Lei; Huang, Jun; Wen, Jian; Yang, Ru; Bo, Lin; Tang, Mei; Zhang, Yi; Liu, Zhichun

2017-01-01

Type I interferon (IFN) plays a central role in pathogenesis of systemic lupus erythematosus (SLE); tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has been associated with a pathogenic role in lupus nephritis (LN). Thus we investigated whether TWEAK could induce the activation of type I IFN pathway in LN. We examined this in patient-derived peripheral blood mononuclear cells (PBMCs) as well as MRL/lpr mice, a murine LN model. Relative to the control cohorts, MRL/lpr mice showed severe histological changes, high index levels of renal damage, and elevated expression of type I IFN-inducible genes. After shRNA suppression of TWEAK, we observed that renal damage was significantly attenuated and expression of type I IFN-inducible genes was reduced in MRL/lpr mice. In parallel, siRNA of TWEAK also significantly reduced the expression of type I IFN-inducible genes in PBMCs relative to control transfections. In PBMCs, TWEAK stimulation also led to expression of type I IFN-inducible genes. Our results illustrate a novel regulatory role of TWEAK, in which its activity positively regulates type I IFN pathway in LN based on preclinical models. Our findings suggest TWEAK could act as a critical target in preventing renal damage in patients with LN.

Critical Roles of the Direct GABAergic Pallido-cortical Pathway in Controlling Absence Seizures

PubMed Central

Li, Min; Ma, Tao; Wu, Shengdun; Ma, Jingling; Cui, Yan; Xia, Yang; Xu, Peng; Yao, Dezhong

2015-01-01

The basal ganglia (BG), serving as an intermediate bridge between the cerebral cortex and thalamus, are believed to play crucial roles in controlling absence seizure activities generated by the pathological corticothalamic system. Inspired by recent experiments, here we systematically investigate the contribution of a novel identified GABAergic pallido-cortical pathway, projecting from the globus pallidus externa (GPe) in the BG to the cerebral cortex, to the control of absence seizures. By computational modelling, we find that both increasing the activation of GPe neurons and enhancing the coupling strength of the inhibitory pallido-cortical pathway can suppress the bilaterally synchronous 2–4 Hz spike and wave discharges (SWDs) during absence seizures. Appropriate tuning of several GPe-related pathways may also trigger the SWD suppression, through modulating the activation level of GPe neurons. Furthermore, we show that the previously discovered bidirectional control of absence seizures due to the competition between other two BG output pathways also exists in our established model. Importantly, such bidirectional control is shaped by the coupling strength of this direct GABAergic pallido-cortical pathway. Our work suggests that the novel identified pallido-cortical pathway has a functional role in controlling absence seizures and the presented results might provide testable hypotheses for future experimental studies. PMID:26496656

The relationship between physical activity levels and pain in children with juvenile idiopathic arthritis.

PubMed

Limenis, Elizaveta; Grosbein, Haddas A; Feldman, Brian M

2014-02-01

Pain and reduced physical activity levels are common in children with juvenile idiopathic arthritis (JIA). Currently, there is no consensus about the role of physical activity in managing pain in JIA. The purpose of our study was to assess the relationship between physical activity level and pain in children ages 11 to 18 years with JIA. A random sample of 50 patients with JIA were approached by mailed questionnaires. Physical activity was determined using the Physical Activity Questionnaire (PAQ). Pain measures included the Numerical Rating Scale (pain severity), SUPER-KIDZ body diagram (number of painful areas), and the Child Activities Limitations Inventory-21 (pain interference). Generalized linear models were used to assess the relationship between physical activity and pain, as well as the roles of sex and age. The response rate was 84%. Thirty-four respondents completed the questionnaire package. The median age was 15 years. The mean PAQ score was 2.16/5. Physical activity declines with increasing age in youth with JIA (r = 0.53, p = 0.0014). Lower physical activity is associated with greater pain interference (r = 0.39, p = 0.0217) and more severe pain (r = 0.35, p = 0.0422). Children with JIA report significantly less activity than healthy children based on PAQ scores, with physical activity declining throughout adolescence. Physical activity is inversely related to pain interference and severity in children with JIA. Our findings suggest that physical activity interventions may play an important role in the management of pain in JIA.

Initial Assessment of β3-Adrenoceptor-Activated Brown Adipose Tissue in Streptozotocin-Induced Type 1 Diabetes Rodent Model Using [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

PubMed

Baranwal, Aparna; Mirbolooki, M Reza; Mukherjee, Jogeshwar

2015-01-01

Metabolic activity of brown adipose tissue (BAT) is activated by β3-adrenoceptor agonists and norepinephrine transporter (NET) blockers and is measurable using [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography/computed tomography (PET/CT) in rats. Using the streptozotocin (STZ)-treated rat model of type 1 diabetes mellitus (T1DM), we investigated BAT activity in this rat model under fasting and nonfasting conditions using [(18)F]FDG PET/CT. Drugs that enhance BAT activity may have a potential for therapeutic development in lowering blood sugar in insulin-resistant diabetes. Rats were rendered diabetic by administration of STZ and confirmed by glucose measures. [(18)F]FDG was injected in the rats (fasted or nonfasted) pretreated with either saline or β3-adrenoceptor agonist CL316,243 or the NET blocker atomoxetine for PET/CT scans. [(18)F]FDG metabolic activity was computed as standard uptake values (SUVs) in interscapular brown adipose tissue (IBAT) and compared across the different drug treatment conditions. Blood glucose levels > 500 mg/dL were established for the STZ-treated diabetic rats. Under fasting conditions, average uptake of [(18)F]FDG in the IBAT of STZ-treated diabetic rats was approximately 70% lower compared to that of normal rats. Both CL316,243 and atomoxetine activated IBAT in normal rats had an SUV > 5, whereas activation in STZ-treated rats was significantly lower. The agonist CL316,243 activated IBAT up to threefold compared to saline in the fasted STZ-treated rat. In the nonfasted rat, the IBAT activation was up by twofold by CL316243. Atomoxetine had a greater effect on lowering blood sugar levels compared to CL316,243 in the nonfasted rats. A significant reduction in metabolic activity was observed in the STZ-treated diabetic rodent model. Increased IBAT activity in the STZ-treated diabetic rat under nonfasted conditions using the β3-adrenoceptor agonist CL316,243 suggests a potential role of BAT in modulating blood sugar levels. Further studies are needed to evaluate the therapeutic role of β3-adrenoceptor agonists in insulin-resistant T1DM.

Recovery of rhythmic activity in a central pattern generator: analysis of the role of neuromodulator and activity-dependent mechanisms.

PubMed

Zhang, Yili; Golowasch, Jorge

2011-11-01

The pyloric network of decapods crustaceans can undergo dramatic rhythmic activity changes. Under normal conditions the network generates low frequency rhythmic activity that depends obligatorily on the presence of neuromodulatory input from the central nervous system. When this input is removed (decentralization) the rhythmic activity ceases. In the continued absence of this input, periodic activity resumes after a few hours in the form of episodic bursting across the entire network that later turns into stable rhythmic activity that is nearly indistinguishable from control (recovery). It has been proposed that an activity-dependent modification of ionic conductance levels in the pyloric pacemaker neuron drives the process of recovery of activity. Previous modeling attempts have captured some aspects of the temporal changes observed experimentally, but key features could not be reproduced. Here we examined a model in which slow activity-dependent regulation of ionic conductances and slower neuromodulator-dependent regulation of intracellular Ca(2+) concentration reproduce all the temporal features of this recovery. Key aspects of these two regulatory mechanisms are their independence and their different kinetics. We also examined the role of variability (noise) in the activity-dependent regulation pathway and observe that it can help to reduce unrealistic constraints that were otherwise required on the neuromodulator-dependent pathway. We conclude that small variations in intracellular Ca(2+) concentration, a Ca(2+) uptake regulation mechanism that is directly targeted by neuromodulator-activated signaling pathways, and variability in the Ca(2+) concentration sensing signaling pathway can account for the observed changes in neuronal activity. Our conclusions are all amenable to experimental analysis.

STAT3 Activation in Pressure-Overloaded Feline Myocardium: Role for Integrins and the Tyrosine Kinase BMX

PubMed Central

Willey, Christopher D.; Palanisamy, Arun P.; Johnston, Rebecca K.; Mani, Santhosh K.; Shiraishi, Hirokazu; Tuxworth, William J.; Zile, Michael R.; Balasubramanian, Sundaravadivel; Kuppuswamy, Dhandapani

2008-01-01

Growth, survival and cytoskeletal rearrangement of cardiomyocytes are critical for cardiac hypertrophy. Signal transducer and activator of transcription-3 (STAT3) activation is an important cardioprotective factor associated with cardiac hypertrophy. Although STAT3 activation has been reported via signaling through Janus Kinase 2 (JAK2) in several cardiac models of hypertrophy, the importance of other nonreceptor tyrosine kinases (NTKs) has not been explored. Utilizing an in vivo feline right ventricular pressure-overload (RVPO) model of hypertrophy, we demonstrate that in 48 h pressure-overload (PO) myocardium, STAT3 becomes phosphorylated and redistributed to detergent-insoluble fractions with no accompanying JAK2 activation. PO also caused increased levels of phosphorylated STAT3 in both cytoplasmic and nuclear fractions. To investigate the role of other NTKs, we used our established in vitro cell culture model of hypertrophy where adult feline cardiomyocytes are embedded three-dimensionally (3D) in type-I collagen and stimulated with an integrin binding peptide containing an Arg-Gly-Asp (RGD) motif that we have previously shown to recapitulate the focal adhesion complex (FAC) formation of 48 h RVPO. RGD stimulation of adult cardiomyocytes in vitro caused both STAT3 redistribution and activation that were accompanied by the activation and redistribution of c-Src and the TEC family kinase, BMX, but not JAK2. However, infection with dominant negative c-Src adenovirus was unable to block RGD-stimulated changes on either STAT3 or BMX. Further analysis in vivo in 48 h PO myocardium showed the presence of both STAT3 and BMX in the detergent-insoluble fraction with their complex formation and phosphorylation. Therefore, these studies indicate a novel mechanism of BMX-mediated STAT3 activation within a PO model of cardiac hypertrophy that might contribute to cardiomyocyte growth and survival. PMID:18612371

Parkin New Cargos: a New ROS Independent Role for Parkin in Regulating Cell Division.

PubMed

Stieg, David C; Cooper, Katrina F

2016-01-01

Cell cycle progression requires the destruction of key cell cycle regulators by the multi-subunit E3 ligase called the anaphase promoting complex (APC/C). As the cell progresses through the cell cycle, the APC/C is sequentially activated by two highly conserved co-activators called Cdc20 and Cdh1. Importantly, APC/C Cdc20 is required to degrade substrates in G2/M whereas APC Cdh1 drives the cells into G1. Recently, Parkin, a monomeric E3 ligase that is required for ubiquitin-mediated mitophagy following mitochondrial stress, was shown to both bind and be activated by Cdc20 or Cdh1 during the cell cycle. This mitotic role for Parkin does not require an activating phosphorylation by its usual kinase partner PINK. Rather, mitotic Parkin activity requires phosphorylation on a different serine by the polo-like kinase Plk1. Interestingly, although Parkin Cdc20 and Parkin Cdh1 activity is independent of the APC/C, it mediates degradation of an overlapping subset of substrates. However, unlike the APC/C, Parkin is not necessary for cell cycle progression. Despite this, loss of Parkin activity accelerates genome instability and tumor growth in xenograft models. These findings provide a mechanism behind the previously described, but poorly understood, tumor suppressor role for Parkin. Taken together, studies suggest that the APC/C and Parkin have similar and unique roles to play in cell division, possibly being dependent upon the different subcellular address of these two ligases.

Exploring the role of MKK7 in excitotoxicity and cerebral ischemia: a novel pharmacological strategy against brain injury

PubMed Central

Vercelli, A; Biggi, S; Sclip, A; Repetto, I E; Cimini, S; Falleroni, F; Tomasi, S; Monti, R; Tonna, N; Morelli, F; Grande, V; Stravalaci, M; Biasini, E; Marin, O; Bianco, F; di Marino, D; Borsello, T

2015-01-01

Excitotoxicity following cerebral ischemia elicits a molecular cascade, which leads to neuronal death. c-Jun-N-terminal kinase (JNK) has a key role in excitotoxic cell death. We have previously shown that JNK inhibition by a specific cell-permeable peptide significantly reduces infarct size and neuronal death in an in vivo model of cerebral ischemia. However, systemic inhibition of JNK may have detrimental side effects, owing to blockade of its physiological function. Here we designed a new inhibitor peptide (growth arrest and DNA damage-inducible 45β (GADD45β-I)) targeting mitogen-activated protein kinase kinase 7 (MKK7), an upstream activator of JNK, which exclusively mediates JNK's pathological activation. GADD45β-I was engineered by optimizing the domain of the GADD45β, able to bind to MKK7, and by linking it to the TAT peptide sequence, to allow penetration of biological membranes. Our data clearly indicate that GADD45β-I significantly reduces neuronal death in excitotoxicity induced by either N-methyl-D-aspartate exposure or by oxygen–glucose deprivation in vitro. Moreover, GADD45β-I exerted neuroprotection in vivo in two models of ischemia, obtained by electrocoagulation and by thromboembolic occlusion of the middle cerebral artery (MCAo). Indeed, GADD45β-I reduced the infarct size when injected 30 min before the lesion in both models. The peptide was also effective when administrated 6 h after lesion, as demonstrated in the electrocoagulation model. The neuroprotective effect of GADD45β-I is long lasting; in fact, 1 week after MCAo the infarct volume was still reduced by 49%. Targeting MKK7 could represent a new therapeutic strategy for the treatment of ischemia and other pathologies involving MKK7/JNK activation. Moreover, this new inhibitor can be useful to further dissect the physiological and pathological role of the JNK pathway in the brain. PMID:26270349

A computational model of pattern separation efficiency in the dentate gyrus with implications in schizophrenia

PubMed Central

Faghihi, Faramarz; Moustafa, Ahmed A.

2015-01-01

Information processing in the hippocampus begins by transferring spiking activity of the entorhinal cortex (EC) into the dentate gyrus (DG). Activity pattern in the EC is separated by the DG such that it plays an important role in hippocampal functions including memory. The structural and physiological parameters of these neural networks enable the hippocampus to be efficient in encoding a large number of inputs that animals receive and process in their life time. The neural encoding capacity of the DG depends on its single neurons encoding and pattern separation efficiency. In this study, encoding by the DG is modeled such that single neurons and pattern separation efficiency are measured using simulations of different parameter values. For this purpose, a probabilistic model of single neurons efficiency is presented to study the role of structural and physiological parameters. Known neurons number of the EC and the DG is used to construct a neural network by electrophysiological features of granule cells of the DG. Separated inputs as activated neurons in the EC with different firing probabilities are presented into the DG. For different connectivity rates between the EC and DG, pattern separation efficiency of the DG is measured. The results show that in the absence of feedback inhibition on the DG neurons, the DG demonstrates low separation efficiency and high firing frequency. Feedback inhibition can increase separation efficiency while resulting in very low single neuron’s encoding efficiency in the DG and very low firing frequency of neurons in the DG (sparse spiking). This work presents a mechanistic explanation for experimental observations in the hippocampus, in combination with theoretical measures. Moreover, the model predicts a critical role for impaired inhibitory neurons in schizophrenia where deficiency in pattern separation of the DG has been observed. PMID:25859189

Transporter-Mediated Disposition, Clinical Pharmacokinetics and Cholestatic Potential of Glyburide and Its Primary Active Metabolites.

PubMed

Li, Rui; Bi, Yi-An; Vildhede, Anna; Scialis, Renato J; Mathialagan, Sumathy; Yang, Xin; Marroquin, Lisa D; Lin, Jian; Varma, Manthena V S

2017-07-01

Glyburide is widely used for the treatment of type 2 diabetes. We studied the mechanisms involved in the disposition of glyburide and its pharmacologically active hydroxy metabolites M1 and M2b and evaluated their clinical pharmacokinetics and the potential role in glyburide-induced cholestasis employing physiologically based pharmacokinetic (PBPK) modeling. Transport studies of parent and metabolites in human hepatocytes and transfected cell systems imply hepatic uptake mediated by organic anion-transporting polypeptides. Metabolites are also subjected to basolateral and biliary efflux by P-glycoprotein, breast cancer resistance protein, and multidrug resistance-associated proteins, and are substrates to renal organic anion transporter 3. A PBPK model in combination with a Bayesian approach was developed considering the identified disposition mechanisms. The model reasonably described plasma concentration time profiles and urinary recoveries of glyburide and the metabolites, implying the role of multiple transport processes in their pharmacokinetics. Predicted free liver concentrations of the parent (∼30-fold) and metabolites (∼4-fold) were higher than their free plasma concentrations. Finally, all three compounds showed bile salt export pump inhibition in vitro; however, significant in vivo inhibition was not apparent for any compound on the basis of a predicted unbound liver exposure-response effect model using measured in vitro IC 50 values. In conclusion, this study demonstrates the important role of multiple drug transporters in the disposition of glyburide and its active metabolites, suggesting that variability in the function of these processes may lead to pharmacokinetic variability in the parent and the metabolites, potentially translating to pharmacodynamic variability. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Sumoylation Dynamics During Keratinocyte Differentiation

PubMed Central

Deyrieux, Adeline F.; Rosas-Acosta, Germán; Ozbun, Michelle A.; Wilson, Van G.

2012-01-01

Summary SUMO modification regulates the activity of numerous transcription factors that have a direct role in cell cycle progression, apoptosis, cellular proliferation, and development, but its role in differentiation processes is less clear. Keratinocyte differentiation requires the coordinated activation of a series of transcription factors, and as several critical keratinocyte transcription factors are known to be SUMO substrates, we investigated the role of sumoylation in keratinocyte differentiation. In a human keratinocyte cell line model (HaCaT cells), calcium-induced differentiation led to the transient and coordinated transcriptional activation of the genes encoding critical sumoylation system components, including SAE1, SAE2, Ubc9, SENP1, Miz-1 (PIASxβ), SUMO2, and SUMO3. The increased gene expression resulted in higher levels of the respective proteins and changes in the pattern of sumoylated substrate proteins during the differentiation process. Similar to the HaCaT results, stratified human foreskin keratinocytes showed an upregulation of Ubc9 in the suprabasal layers. Lastly, abrogation of sumoylation by Gam1 expression severely disrupted normal HaCaT differentiation, consistent with an important role for sumoylation in the proper progression of this biological process. PMID:17164289

Help Your Child Stay at a Healthy Weight

MedlinePlus

... be more likely to make those choices, too. Plus, being active and preparing healthy meals together are ... role model for your child by eating healthy . Plus, a healthy diet can help protect you from ...

Ratchet Effects in Active Matter Systems

NASA Astrophysics Data System (ADS)

Reichhardt, C. J. Olson; Reichhardt, C.

2017-03-01

Ratchet effects can arise for single or collectively interacting Brownian particles on an asymmetric substrate when a net dc transport is produced by an externally applied ac driving force or by periodically flashing the substrate. Recently, a new class of active ratchet systems that do not require the application of external driving has been realized through the use of active matter; they are self-propelled units that can be biological or nonbiological in nature. When active materials such as swimming bacteria interact with an asymmetric substrate, a net dc directed motion can arise even without external driving, opening a wealth of possibilities such as sorting, cargo transport, or micromachine construction. We review the current status of active matter ratchets for swimming bacteria, cells, active colloids, and swarming models, focusing on the role of particle-substrate interactions. We describe ratchet reversals produced by collective effects and the use of active ratchets to transport passive particles. We discuss future directions including deformable substrates or particles, the role of different swimming modes, varied particle-particle interactions, and nondissipative effects.

MCP-1-mediated activation of microglia promotes white matter lesions and cognitive deficits by chronic cerebral hypoperfusion in mice.

PubMed

Yuan, Bangqing; Shi, Hui; Zheng, Kuang; Su, Zulu; Su, Hai; Zhong, Ming; He, Xuenong; Zhou, Changlong; Chen, Hao; Xiong, Qijiang; Zhang, Yi; Yang, Zhao

2017-01-01

Microglia activation played a vital role in the pathogenesis of white matter lesions (WMLs) by chronic cerebral hypoperfusion. In addition, hypoxia induced up-regulated expression of MCP-1, promotes the activation of microglia. However, the role of MCP-1-mediated microglia activation in chronic cerebral ischemia is still unknown. To explore that, chronic cerebral hypoperfusion model was established by permanent stenosis of bilateral common carotid artery in mice. The activation of microglia and the related signal pathway p38MAPK/PKC in white matter, and working memory of mice were observed. We found that stenosis of common carotid arteries could induce MCP-1-mediated activation of microglia through p38MAPK/PKC pathway and white matter lesions. Taken together, our findings represent a novel mechanism of MCP-1 involved in activation of microglia and provide a novel therapeutical strategy for chronic cerebral hypoperfusion. Copyright © 2016 Elsevier Inc. All rights reserved.

Driven to be inactive? The genetics of physical activity.

PubMed

Moore-Harrison, Trudy; Lightfoot, J Timothy

2010-01-01

The health implications of physical inactivity, including its integral role in promoting obesity, are well known and have been well documented. Physical activity is a multifactorial behavior with various factors playing a role in determining individual physical activity levels. Research using both human and animal models in the past several years has clearly indicated that genetics is associated with physical activity. Furthermore, researchers have identified several significant and suggestive genomic quantitative trait loci associated with physical activity. To date, the identities of the causal genes underlying physical activity regulation are unclear, with few strong candidate genes. The current research provides a foundation from which future confirmatory research can be launched as well as determination of the mechanisms through which the genetic factors act. The application of this knowledge could significantly augment the information available for physical activity behavior change interventions resulting in more efficient programs for those predisposed to be inactive. Copyright © 2010 Elsevier Inc. All rights reserved.

The actin cytoskeleton in store-mediated calcium entry

PubMed Central

Rosado, Juan A; Sage, Stewart O

2000-01-01

Store-mediated Ca2+ entry is the main pathway for Ca2+ influx in platelets and many other cells. Several hypotheses have considered both direct and indirect coupling mechanisms between the endoplasmic reticulum and the plasma membrane. Here we pay particular attention to new insights into the regulation of store-mediated Ca2+ entry: the role of the cytoskeleton in a secretion-like coupling model. In this model, Ca2+ entry may be mediated by a reversible trafficking and coupling of the endoplasmic reticulum with the plasma membrane, that shows close parallels to the events mediating secretion. As with secretion, the actin cytoskeleton plays an inhibitory role in the activation of Ca2+ entry by preventing the approach and coupling of the endoplasmic reticulum with the plasma membrane, making cytoskeletal remodelling a key event in the activation of Ca2+ entry. We also review recent advances investigating the regulation of store-mediated Ca2+ entry by small GTPases and phosphoinositides, which might be involved in the store-mediated Ca2+ entry pathway through roles in the remodelling of the cytoskeleton. PMID:10896713

The complete practitioner: still a work in progress.

PubMed

Barnett, Jeffrey E

2009-11-01

When one is reflecting on a career as a practitioner, a number of important influences, themes, and elements that contribute to being a successful practitioner are evident. The achievement of this success is not a solitary activity. Many role models and mentors serve as important influences and guides for developing as a professional over the course of one's career. Ultimately, the goal is to aspire to become a complete practitioner. This includes being a passionate professional, clinically competent, a psychotherapist and clinician, an active consumer of research findings, ethical, a role model, a mentor, psychologically healthy, an advocate, a leader, a volunteer, an educator, a scholar, a colleague, a business person and entrepreneur, and an innovator and visionary; focusing on diversity and multicultural competence; and having a comprehensive vision of health. Because the goal of being a complete practitioner is aspirational, one never fully masters each of these roles and attributes but remains a work in progress. Yet, the process of endeavoring to become a complete practitioner is rewarding, gratifying, and meaningful. It is a journey well worth taking. Copyright 2009 by the American Psychological Association

[Patient's role and chronic disease in Mali: between policies and expert and lay practices].

PubMed

Gobatto, Isabelle; Tijou Traoré, Annick; Martini, Jessica

2016-01-01

The growing burden of non-communicable diseases challenges health systems of low-and middle-income countries and requires health care reform by the introduction of models focused on patient participation. This article puts into perspective the management of two chronic diseases, diabetes and HIV/AIDS, in Mali. It explores the way in which the patient’s role is conceived and implemented at three levels: policy-makers, healthcare professionals and patients, in order to more clearly understand the dynamics and rationales underlying promotion of the patient’s role in the context of a low-income country. Results were derived from qualitative interviews conducted between 2010 and 2012 with key stakeholders involved in policy, healthcare professionals and patients, and from observations of healthcare relationships in two specialized healthcare structures in Bamako. The chronic nature of the disease is not sufficient to define the patient’s role in healthcare. Other factors also influence the emergence and practice of an active patient care model: the political, clinical and social history of the disease; the institutional work contexts of healthcare professionals; patients’ representations and practices. Patients are well aware of the role they need to play in the management of a chronic disease and they develop resources to remain active. These various dynamics should be better taken into account to make effective changes in the health care system and to strengthen patients’ autonomy.

Role of adipose tissue in methionine-choline-deficient model of non-alcoholic steatohepatitis (NASH).

PubMed

Jha, Pooja; Knopf, Astrid; Koefeler, Harald; Mueller, Michaela; Lackner, Carolin; Hoefler, Gerald; Claudel, Thierry; Trauner, Michael

2014-07-01

Methionine-choline-deficient (MCD) diet is a widely used dietary model of non-alcoholic steatohepatitis (NASH) in rodents. However, the contribution of adipose tissue to MCD-induced steatosis, and inflammation as features of NASH are not fully understood. The goal of this study was to elucidate the role of adipose tissue fatty acid (FA) metabolism, adipogenesis, lipolysis, inflammation and subsequent changes in FA profiles in serum and liver in the pathogenesis of steatohepatitis. We therefore fed ob/ob mice with control or MCD diet for 5 weeks. MCD-feeding increased adipose triglyceride lipase and hormone sensitive lipase activities in all adipose depots which may be attributed to increased systemic FGF21 levels. The highest lipase enzyme activity was exhibited by visceral WAT. Non-esterified fatty acid (NEFA)-18:2n6 was the predominantly elevated FA species in serum and liver of MCD-fed ob/ob mice, while overall serum total fatty acid (TFA) composition was reduced. In contrast, an overall increase of all FA species from TFA pool was found in liver, reflecting the combined effects of increased FA flux to liver, decreased FA oxidation and decrease in lipase activity in liver. NAFLD activity score was increased in liver, while WAT showed no changes and BAT showed even reduced inflammation. This study demonstrates a key role for adipose tissue lipases in the pathogenesis of NASH and provides a comprehensive lipidomic profiling of NEFA and TFA homeostasis in serum and liver. Our findings provide novel mechanistic insights for the role of WAT in progression of MCD-induced liver injury. Copyright © 2014. Published by Elsevier B.V.

The role of renal proximal tubule P450 enzymes in chloroform-induced nephrotoxicity: Utility of renal specific P450 reductase knockout mouse models

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

Liu, Senyan; Wadsworth Center, New York State Department of Health, and School of Public Health, State University of New York, Albany, NY 12201; Yao, Yunyi

The kidney is a primary target for numerous toxic compounds. Cytochrome P450 enzymes (P450) are responsible for the metabolic activation of various chemical compounds, and in the kidney are predominantly expressed in proximal tubules. The aim of this study was to test the hypothesis that renal proximal tubular P450s are critical for nephrotoxicity caused by chemicals such as chloroform. We developed two new mouse models, one having proximal tubule-specific deletion of the cytochrome P450 reductase (Cpr) gene (the enzyme required for all microsomal P450 activities), designated proximal tubule-Cpr-null (PTCN), and the other having proximal tubule-specific rescue of CPR activity withmore » the global suppression of CPR activity in all extra-proximal tubular tissues, designated extra-proximal tubule-Cpr-low (XPT-CL). The PTCN, XPT-CL, Cpr-low (CL), and wild-type (WT) mice were treated with a single oral dose of chloroform at 200 mg/kg. Blood, liver and kidney samples were obtained at 24 h after the treatment. Renal toxicity was assessed by measuring BUN and creatinine levels, and by pathological examination. The blood and tissue levels of chloroform were determined. The severity of toxicity was less in PTCN and CL mice, compared with that of WT and XPT-CL mice. There were no significant differences in chloroform levels in the blood, liver, or kidney, between PTCN and WT mice, or between XPT-CL and CL mice. These findings indicate that local P450-dependent activities play an important role in the nephrotoxicity induced by chloroform. Our results also demonstrate the usefulness of these novel mouse models for studies of chemical-induced kidney toxicity. - Highlights: • New mouse models were developed with varying P450 activities in the proximal tubule. • These mouse models were treated with chloroform, a nephrotoxicant. • Studies showed the importance of local P450s in chloroform-induced nephrotoxicity.« less

The role of the posterior cingulate cortex in cognition and disease

PubMed Central

Sharp, David J.

2014-01-01

The posterior cingulate cortex is a highly connected and metabolically active brain region. Recent studies suggest it has an important cognitive role, although there is no consensus about what this is. The region is typically discussed as having a unitary function because of a common pattern of relative deactivation observed during attentionally demanding tasks. One influential hypothesis is that the posterior cingulate cortex has a central role in supporting internally-directed cognition. It is a key node in the default mode network and shows increased activity when individuals retrieve autobiographical memories or plan for the future, as well as during unconstrained ‘rest’ when activity in the brain is ‘free-wheeling’. However, other evidence suggests that the region is highly heterogeneous and may play a direct role in regulating the focus of attention. In addition, its activity varies with arousal state and its interactions with other brain networks may be important for conscious awareness. Understanding posterior cingulate cortex function is likely to be of clinical importance. It is well protected against ischaemic stroke, and so there is relatively little neuropsychological data about the consequences of focal lesions. However, in other conditions abnormalities in the region are clearly linked to disease. For example, amyloid deposition and reduced metabolism is seen early in Alzheimer’s disease. Functional neuroimaging studies show abnormalities in a range of neurological and psychiatric disorders including Alzheimer’s disease, schizophrenia, autism, depression and attention deficit hyperactivity disorder, as well as ageing. Our own work has consistently shown abnormal posterior cingulate cortex function following traumatic brain injury, which predicts attentional impairments. Here we review the anatomy and physiology of the region and how it is affected in a range of clinical conditions, before discussing its proposed functions. We synthesize key findings into a novel model of the region’s function (the ‘Arousal, Balance and Breadth of Attention’ model). Dorsal and ventral subcomponents are functionally separated and differences in regional activity are explained by considering: (i) arousal state; (ii) whether attention is focused internally or externally; and (iii) the breadth of attentional focus. The predictions of the model can be tested within the framework of complex dynamic systems theory, and we propose that the dorsal posterior cingulate cortex influences attentional focus by ‘tuning’ whole-brain metastability and so adjusts how stable brain network activity is over time. PMID:23869106

Redefinition of rubisco carboxylase reaction reveals origin of water for hydration and new roles for active-site residues.

PubMed

Kannappan, Babu; Gready, Jill E

2008-11-12

Crystallographic, mutagenesis, kinetic, and computational studies on Rubisco over three decades have revealed much about its catalytic mechanism and the role played by several active-site residues. However, key questions remain unanswered. Specific details of the carboxylase and oxygenase mechanisms, required to underpin the rational re-engineering of Rubisco, are still speculative. Here we address critical gaps in knowledge with a definitive comprehensive computational investigation of the mechanism of carboxylase activity at the Rubisco active site. Density functional theory calculations (B3LYP/6-31G(d,p)) were performed on active-site fragment models of a size up to 77 atoms, not previously possible computationally. All amino acid residues suspected to play roles in the acid-base chemistry in the multistep reaction, and interacting directly with the central Mg (2+) atom and the reactive moiety of substrate and intermediates, were included. The results provide a firm basis for us to propose a novel mechanism for the entire sequence of reactions in the carboxylase catalysis and to define precise roles for the active-site residues, singly and in concert. In this mechanism, the carbamylated LYS201 plays a more limited role than previously proposed but is crucial for initiating the reaction by acting as a base in the enolization. We suggest a wider role for HIS294, with involvement in the carboxylation, hydration, and C2-C3 bond-scission steps, consistent with the suggestion of Harpel et al. (1998) but contrary to the consensus view of Cleland et al. (1998). In contrast to the common assumption that the water molecule for the hydration step comes from within the active site, we propose that the Mg-coordinated water is not dissociated at the start of the gas-addition reaction but rather remains coordinated and is used for the hydration of the C3 carbon atom. New roles are also proposed for LYS175, GLU204, and HIS294. The mechanism suggests roles in the gas-addition step for residues in three spatially distinct regions of the active site, HIS294 and LYS334 in the C-terminal domain of the large subunit (LSU), but also hitherto unsuspected roles for a cluster of three residues (ASN123, GLU60, and TYR20) in the N-terminal domain of the partner LSU of the dimer containing the active site. Our new mechanism is supported by existing experimental data, provides new convincing interpretations of previously puzzling data, and allows new insights into mutational strategies for improving Rubisco activity.

Role of hormones and neurosteroids in epileptogenesis

PubMed Central

Reddy, Doodipala Samba

2013-01-01

This article describes the emerging evidence of hormonal influence on epileptogenesis, which is a process whereby a brain becomes progressively epileptic due to an initial precipitating event of diverse origin such as brain injury, stroke, infection, or prolonged seizures. The molecular mechanisms underlying the development of epilepsy are poorly understood. Neuroinflammation and neurodegeneration appear to trigger epileptogenesis. There is an intense search for drugs that truly prevent the development of epilepsy in people at risk. Hormones play an important role in children and adults with epilepsy. Corticosteroids, progesterone, estrogens, and neurosteroids have been shown to affect seizure activity in animal models and in clinical studies. However, the impact of hormones on epileptogenesis has not been investigated widely. There is emerging new evidence that progesterone, neurosteroids, and endogenous hormones may play a role in regulating the epileptogenesis. Corticosterone has excitatory effects and triggers epileptogenesis in animal models. Progesterone has disease-modifying activity in epileptogenic models. The antiepileptogenic effect of progesterone has been attributed to its conversion to neurosteroids, which binds to GABA-A receptors and enhances phasic and tonic inhibition in the brain. Neurosteroids are robust anticonvulsants. There is pilot evidence that neurosteroids may have antiepileptogenic properties. Future studies may generate new insight on the disease-modifying potential of hormonal agents and neurosteroids in epileptogenesis. PMID:23914154

The Autoimmune Skin Disease Bullous Pemphigoid: The Role of Mast Cells in Autoantibody-Induced Tissue Injury

PubMed Central

Fang, Hui; Zhang, Yang; Li, Ning; Wang, Gang; Liu, Zhi

2018-01-01

Bullous pemphigoid (BP) is an autoimmune and inflammatory skin disease associated with subepidermal blistering and autoantibodies directed against the hemidesmosomal components BP180 and BP230. Animal models of BP were developed by passively transferring anti-BP180 IgG into mice, which recapitulates the key features of human BP. By using these in vivo model systems, key cellular and molecular events leading to the BP disease phenotype are identified, including binding of pathogenic IgG to its target, complement activation of the classical pathway, mast cell degranulation, and infiltration and activation of neutrophils. Proteinases released by infiltrating neutrophils cleave BP180 and other hemidesmosome-associated proteins, causing DEJ separation. Mast cells and mast cell-derived mediators including inflammatory cytokines and proteases are increased in lesional skin and blister fluids of BP. BP animal model evidence also implicates mast cells in the pathogenesis of BP. However, recent studies questioned the pathogenic role of mast cells in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and epidermolysis bullosa acquisita. This review highlights the current knowledge on BP pathophysiology with a focus on a potential role for mast cells in BP and mast cell-related critical issues needing to be addressed in the future. PMID:29545809

The human role in space (THURIS) applications study. Final briefing

NASA Technical Reports Server (NTRS)

Maybee, George W.

1987-01-01

The THURIS (The Human Role in Space) application is an iterative process involving successive assessments of man/machine mixes in terms of performance, cost and technology to arrive at an optimum man/machine mode for the mission application. The process begins with user inputs which define the mission in terms of an event sequence and performance time requirements. The desired initial operational capability date is also an input requirement. THURIS terms and definitions (e.g., generic activities) are applied to the input data converting it into a form which can be analyzed using the THURIS cost model outputs. The cost model produces tabular and graphical outputs for determining the relative cost-effectiveness of a given man/machine mode and generic activity. A technology database is provided to enable assessment of support equipment availability for selected man/machine modes. If technology gaps exist for an application, the database contains information supportive of further investigation into the relevant technologies. The present study concentrated on testing and enhancing the THURIS cost model and subordinate data files and developing a technology database which interfaces directly with the user via technology readiness displays. This effort has resulted in a more powerful, easy-to-use applications system for optimization of man/machine roles. Volume 1 is an executive summary.

Testing the Role of p21-Activated Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease

DTIC Science & Technology

2015-06-01

preclinical models of NF1? Can whole kinome analysis predict pathways for drug resistance in treated mice? Procuring Contracting/Grants Officer: Emily...cells. b) Evaluate transduction of hydroxyethyl starch (HES)-processed hematopoietic cells. c) Monitor gene transfer in primary FANCC-/- progenitors

Overlapping Parietal Activity in Memory and Perception: Evidence for the Attention to Memory Model

ERIC Educational Resources Information Center

Cabeza, Roberto; Mazuz, Yonatan S.; Stokes, Jared; Kragel, James E.; Woldorff, Marty G.; Ciaramelli, Elisa; Olson, Ingrid R.; Moscovitch, Morris

2011-01-01

The specific role of different parietal regions to episodic retrieval is a topic of intense debate. According to the Attention to Memory (AtoM) model, dorsal parietal cortex (DPC) mediates top-down attention processes guided by retrieval goals, whereas ventral parietal cortex (VPC) mediates bottom-up attention processes captured by the retrieval…

The human element in technology transfer

NASA Technical Reports Server (NTRS)

Peake, H. J.

1978-01-01

A transfer model composed of three roles and their linkages was considered. This model and a growing body of experience was analyzed to provide guidance in the human elements of technology transfer. For example, criteria for selection of technology transfer agents was described, and some needed working climate factors were known. These concepts were successfully applied to transfer activities.

Detangling Spaghetti: Tracking Deep Ocean Currents in the Gulf of Mexico

ERIC Educational Resources Information Center

Curran, Mary Carla; Bower, Amy S.; Furey, Heather H.

2017-01-01

Creation of physical models can help students learn science by enabling them to be more involved in the scientific process of discovery and to use multiple senses during investigations. This activity achieves these goals by having students model ocean currents in the Gulf of Mexico. In general, oceans play a key role in influencing weather…

The Role of Feature Selection and Statistical Weighting in Predicting In Vivo Toxicity Using In Vitro Assay and QSAR Data (SOT)

EPA Science Inventory

Our study assesses the value of both in vitro assay and quantitative structure activity relationship (QSAR) data in predicting in vivo toxicity using numerous statistical models and approaches to process the data. Our models are built on datasets of (i) 586 chemicals for which bo...

Does ACCEL Excel as a Model of Giftedness? A Reply to Commentators

ERIC Educational Resources Information Center

Sternberg, Robert J.

2017-01-01

In this essay, I respond to commentators on my article on the Active Concerned Citizenship and Ethical Leadership (ACCEL) model for understanding giftedness. I cover a number of topics that arose in or out of the commentaries, in particular, systems inertia; toxic leadership; teaching for creativity; flight from reality; the role of science,…

Developing Students' Scientific Writing and Presentation Skills through Argument Driven Inquiry: An Exploratory Study

ERIC Educational Resources Information Center

C¸etin, Pinar Seda; Eymur, Gülüzar

2017-01-01

In this study, we employed a new instructional model that helps students develop scientific writing and presentation skills. Argument-driven inquiry (ADI) is one of the most novel instructional models that emphasizes the role of argumentation and inquiry in science education equally. This is an exploratory study where five ADI lab activities take…

Involvement of Infralimbic Prefrontal Cortex but not Lateral Habenula in Dopamine Attenuation After Chronic Mild Stress.

PubMed

Moreines, Jared L; Owrutsky, Zoe L; Grace, Anthony A

2017-03-01

Emerging evidence supports a role for dopamine in major depressive disorder (MDD). We recently reported fewer spontaneously active ventral tegmental area (VTA) dopamine neurons (ie, reduced dopamine neuron population activity) in the chronic mild stress (CMS) rodent model of MDD. In this study, we examined the role of two brain regions that have been implicated in MDD in humans, the infralimbic prefrontal cortex (ILPFC)-that is, rodent homolog of Brodmann area 25 (BA25), and the lateral habenula (LHb) in the CMS-induced attenuation of dopamine neuron activity. The impact of activating the ILPFC or LHb was evaluated using single-unit extracellular recordings of identified VTA dopamine neurons. The involvement of each region in dopamine neuron attenuation following 5-7 weeks of CMS was then evaluated by selective inactivation. Activation of either ILPFC or LHb in normal rats potently suppressed dopamine neuron population activity, but in unique patterns. ILPFC activation selectively inhibited dopamine neurons in medial VTA, which were most impacted by CMS. Conversely, LHb activation selectively inhibited dopamine neurons in lateral VTA, which were unaffected by CMS. Moreover, only ILPFC inactivation restored dopamine neuron population activity to normal levels following CMS; LHb inactivation had no restorative effect. These data suggest that, in the CMS model of MDD, the ILPFC is the primary driver of diminished dopamine neuron responses. These findings support a neural substrate for ILPFC/BA25 linking affective and motivational circuitry dysfunction in MDD.

Localized Fluctuant Oscillatory Activity by Working Memory Load: A Simultaneous EEG-fMRI Study.

PubMed

Zhao, Xiaojie; Li, Xiaoyun; Yao, Li

2017-01-01

Working memory (WM) is a resource-limited memory system for temporary storage and processing of brain information during the execution of cognitive tasks. Increased WM load will increase the amount and difficulty of memory information. Several studies have used electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) to explore load-dependent cognition processing according to the time courses of electrophysiological activity or the spatial pattern of blood oxygen metabolic activity. However, the relationships between these two activities and the underlying neural mechanism are still unclear. In this study, using simultaneously collected EEG and fMRI data under an n-back verbal WM task, we modeled the spectral perturbation of EEG oscillation and fMRI activation through joint independent component analysis (JICA). Multi-channel oscillation features were also introduced into the JICA model for further analysis. The results showed that time-locked activity of theta and beta were modulated by memory load in the early stimuli evaluation stage, corresponding to the enhanced activation in the frontal and parietal lobe, which were involved in stimulus discrimination, information encoding and delay-period activity. In the late response selection stage, alpha and gamma activity changes dependent on the load correspond to enhanced activation in the areas of frontal, temporal and parietal lobes, which played important roles in attention, information extraction and memory retention. These findings suggest that the increases in memory load not only affect the intensity and time course of the EEG activities, but also lead to the enhanced activation of brain regions which plays different roles during different time periods of cognitive process of WM.

The Significance of Ras Activity in Pancreatic Cancer Initiation

PubMed Central

Logsdon, Craig D.; Lu, Weiqin

2016-01-01

The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of K-RAS. However, oncogenic K-Rasmt alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others, have physiological effects at low concentrations that are mediated in part through modest increases in K-Ras activity. However, at high concentrations, they induce inflammation that, in the presence of oncogenic K-Ras expression, substantially accelerates PDAC formation. The mechanism involves increased activity of oncogenic K-Rasmt. Unlike what has been proposed in the standard paradigm for the role of Ras in oncogenesis, oncogenic K-Rasmt is now known to not be constitutively active. Rather, it can be activated by standard mechanisms similar to wild-type K-Ras, but its activity is sustained for a prolonged period. Furthermore, if the level of K-Ras activity exceeds a threshold at which it begins to generate its own activators, then a feed-forward loop is formed between K-Ras activity and inflammation and pathological processes including oncogenesis are initiated. Oncogenic K-Rasmt activation, a key event in PDAC initiation and development, is subject to complex regulatory mechanisms. Reagents which inhibit inflammation, such as the Cox2 inhibitor celecoxib, block the feed-forward loop and prevent induction of PDAC in models with endogenous oncogenic K-Rasmt. Increased understanding of the role of activating and inhibitory mechanisms on oncogenic K-Rasmt activity is of paramount importance for the development of preventive and therapeutic strategies to fight against this lethal disease. PMID:26929740

HESFIRE: a global fire model to explore the role of anthropogenic and weather drivers

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

Le Page, Yannick LB; Morton, Douglas; Bond-Lamberty, Benjamin

Vegetation fires are a major driver of ecosystem dynamics and greenhouse gas emissions. Anticipating potential changes in fire activity and their impacts relies first on a realistic model of fire activity (e.g., fire incidence and interannual variability) and second on a model accounting for fire impacts (e.g., mortality and emissions). In this paper, we focus on our understanding of fire activity and describe a new fire model, HESFIRE (Human–Earth System FIRE), which integrates the influence of weather, vegetation characteristics, and human activities on fires in a stand-alone framework. It was developed with a particular emphasis on allowing fires to spreadmore » over consecutive days given their major contribution to burned areas in many ecosystems. A subset of the model parameters was calibrated through an optimization procedure using observation data to enhance our knowledge of regional drivers of fire activity and improve the performance of the model on a global scale. Modeled fire activity showed reasonable agreement with observations of burned area, fire seasonality, and interannual variability in many regions, including for spatial and temporal domains not included in the optimization procedure. Significant discrepancies are investigated, most notably regarding fires in boreal regions and in xeric ecosystems and also fire size distribution. The sensitivity of fire activity to model parameters is analyzed to explore the dominance of specific drivers across regions and ecosystems. The characteristics of HESFIRE and the outcome of its evaluation provide insights into the influence of anthropogenic activities and weather, and their interactions, on fire activity.« less

HESFIRE: a global fire model to explore the role of anthropogenic and weather drivers

DOE PAGES

Le Page, Yannick LB; Morton, Douglas; Bond-Lamberty, Benjamin; ...

2015-02-13

Vegetation fires are a major driver of ecosystem dynamics and greenhouse gas emissions. Anticipating potential changes in fire activity and their impacts relies first on a realistic model of fire activity (e.g., fire incidence and interannual variability) and second on a model accounting for fire impacts (e.g., mortality and emissions). In this paper, we focus on our understanding of fire activity and describe a new fire model, HESFIRE (Human–Earth System FIRE), which integrates the influence of weather, vegetation characteristics, and human activities on fires in a stand-alone framework. It was developed with a particular emphasis on allowing fires to spreadmore » over consecutive days given their major contribution to burned areas in many ecosystems. A subset of the model parameters was calibrated through an optimization procedure using observation data to enhance our knowledge of regional drivers of fire activity and improve the performance of the model on a global scale. Modeled fire activity showed reasonable agreement with observations of burned area, fire seasonality, and interannual variability in many regions, including for spatial and temporal domains not included in the optimization procedure. Significant discrepancies are investigated, most notably regarding fires in boreal regions and in xeric ecosystems and also fire size distribution. The sensitivity of fire activity to model parameters is analyzed to explore the dominance of specific drivers across regions and ecosystems. The characteristics of HESFIRE and the outcome of its evaluation provide insights into the influence of anthropogenic activities and weather, and their interactions, on fire activity.« less

Characterizing the structural ensemble of γ-secretase using a multiscale molecular dynamics approach† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc00980a Click here for additional data file.

PubMed Central

Aguayo-Ortiz, Rodrigo; Chávez-García, Cecilia; Straub, John E.

2017-01-01

γ-Secretase is an intramembrane-cleaving aspartyl protease that plays an essential role in the processing of a variety of integral membrane proteins. Its role in the ultimate cleavage step in the processing of amyloid precursor protein to form amyloid-β (Aβ) peptide makes it an important therapeutic target in Alzheimer's disease research. Significant recent advances have been made in structural studies of this critical membrane protein complex. However, details of the mechanism of activation of the enzyme complex remain unclear. Using a multiscale computational modeling approach, combining multiple coarse-grained microsecond dynamic trajectories with all-atom models, the structure and two conformational states of the γ-secretase complex were evaluated. The transition between enzymatic state 1 and state 2 is shown to critically depend on the protonation states of the key catalytic residues Asp257 and Asp385 in the active site domain. The active site formation, related to our γ-secretase state 2, is observed to involve a concerted movement of four transmembrane helices from the catalytic subunit, resulting in the required localization of the catalytic residues. Global analysis of the structural ensemble of the enzyme complex was used to identify collective fluctuations important to the mechanism of substrate recognition and demonstrate that the corresponding fluctuations observed were uncorrelated with structural changes associated with enzyme activation. Overall, this computational study provides essential insight into the role of structure and dynamics in the activation and function of γ-secretase. PMID:28970936

Relative Expression Levels Rather Than Specific Activity Plays the Major Role in Determining In Vivo AKT Isoform Substrate Specificity

PubMed Central

Lee, Rachel S.; House, Colin M.; Cristiano, Briony E.; Hannan, Ross D.; Pearson, Richard B.; Hannan, Katherine M.

2011-01-01

The AKT protooncogene mediates many cellular processes involved in normal development and disease states such as cancer. The three structurally similar isoforms: AKT1, AKT2, and AKT3 exhibit both functional redundancy and isoform-specific functions; however the basis for their differential signalling remains unclear. Here we show that in vitro, purified AKT3 is ∼47-fold more active than AKT1 at phosphorylating peptide and protein substrates. Despite these marked variations in specific activity between the individual isoforms, a comprehensive analysis of phosphorylation of validated AKT substrates indicated only subtle differences in signalling via individual isoforms in vivo. Therefore, we hypothesise, at least in this model system, that relative tissue/cellular abundance, rather than specific activity, plays the dominant role in determining AKT substrate specificity in situ. PMID:21869924

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

Saravanan, Ramalingam

During the course of this project, we have accomplished the following: 1) Explored the parameter space of component models to minimize regional model bias 2) Assessed the impact of air-sea interaction on hurricanes, focusing in particular on the role of the oceanic barrier layer 3) Contributed to the activities of the U.S. CLIVAR Hurricane Working Group 4) Assessed the impact of lateral and lower boundary conditions on extreme flooding events in the U.S. Midwest in regional model simulations 5) Analyzed the concurrent impact of El Niño-Southern Oscillation and Atlantic Meridional Mode on Atlantic Hurricane activity using observations and regional modelmore » simulations« less

Chemometric modeling of 5-Phenylthiophenecarboxylic acid derivatives as anti-rheumatic agents.

PubMed

Adhikari, Nilanjan; Jana, Dhritiman; Halder, Amit K; Mondal, Chanchal; Maiti, Milan K; Jha, Tarun

2012-09-01

Arthritis involves joint inflammation, synovial proliferation and damage of cartilage. Interleukin-1 undergoes acute and chronic inflammatory mechanisms of arthritis. Non-steroidal anti-inflammatory drugs can produce symptomatic relief but cannot act through mechanisms of arthritis. Diseases modifying anti-rheumatoid drugs reduce the symptoms of arthritis like decrease in pain and disability score, reduction of swollen joints, articular index and serum concentration of acute phage proteins. Recently, some literature references are obtained on molecular modeling of antirheumatic agents. We have tried chemometric modeling through 2D-QSAR studies on a dataset of fifty-one compounds out of which forty-four 5-Phenylthiophenecarboxylic acid derivatives have IL-1 inhibitory activity and forty-six 5-Phenylthiophenecarboxylic acid derivatives have %AIA suppressive activity. The work was done to find out the structural requirements of these anti-rheumatic agents. 2D QSAR models were generated by 2D and 3D descriptors by using multiple linear regression and partial least square method where IL-1 antagonism was considered as the biological activity parameter. Statistically significant models were developed on the training set developed by k-means cluster analysis. Sterimol parameters, electronic interaction at atom number 9, 2D autocorrelation descriptors, information content descriptor, average connectivity index chi-3, radial distribution function, Balaban 3D index and 3D-MoRSE descriptors were found to play crucial roles to modulate IL-1 inhibitory activity. 2D autocorrelation descriptors like Broto-Moreau autocorrelation of topological structure-lag 3 weighted by atomic van der Waals volumes, Geary autocorrelation-lag 7 associated with weighted atomic Sanderson electronegativities and 3D-MoRSE descriptors like 3D-MoRSE-signal 22 related to atomic van der Waals volumes, 3D-MoRSE-signal 28 related to atomic van der Waals volumes and 3D-MoRSE-signal 9 which was unweighted, were found to play important roles to model %AIA suppressive activity.

Neutrophil-cytokine interactions in a rat model of sulindac-induced idiosyncratic liver injury.

PubMed

Zou, Wei; Roth, Robert A; Younis, Husam S; Malle, Ernst; Ganey, Patricia E

2011-12-18

Previous studies indicated that lipopolysaccharide (LPS) interacts with the nonsteroidal anti-inflammatory drug sulindac (SLD) to produce liver injury in rats. In the present study, the mechanism of SLD/LPS-induced liver injury was further investigated. Accumulation of polymorphonuclear neutrophils (PMNs) in the liver was greater in SLD/LPS-cotreated rats compared to those treated with SLD or LPS alone. In addition, PMN activation occurred specifically in livers of rats cotreated with SLD/LPS. The hypothesis that PMNs and proteases released from them play critical roles in the hepatotoxicity was tested. SLD/LPS-induced liver injury was attenuated by prior depletion of PMNs or by treatment with the PMN protease inhibitor, eglin C. Previous studies suggested that tumor necrosis factor-α (TNF) and the hemostatic system play critical roles in the pathogenesis of liver injury induced by SLD/LPS. TNF and plasminogen activator inhibitor-1 (PAI-1) can contribute to hepatotoxicity by affecting PMN activation and fibrin deposition. Therefore, the role of TNF and PAI-1 in PMN activation and fibrin deposition in the SLD/LPS-induced liver injury model was tested. Neutralization of TNF or inhibition of PAI-1 attenuated PMN activation. TNF had no effect on PAI-1 production or fibrin deposition. In contrast, PAI-1 contributed to fibrin deposition in livers of rats treated with SLD/LPS. In summary, PMNs, TNF and PAI-1 contribute to the liver injury induced by SLD/LPS cotreatment. TNF and PAI-1 independently contributed to PMN activation, which is critical to the pathogenesis of liver injury. Moreover, PAI-1 contributed to liver injury by promoting fibrin deposition. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

BMI and attitudes and beliefs about physical activity and nutrition of parents of adolescents with intellectual disabilities.

PubMed

George, V A; Shacter, S D; Johnson, P M

2011-11-01

The purpose of this study was: (1) to evaluate the beliefs, attitudes and behaviours associated with nutrition and physical activity of parents with adolescents with intellectual disabilities (ID); (2) to determine if these variables related to the body mass index (BMI) of the adolescents and the parents' BMI; and (3) to investigate if the parents' perception of their child's weight status was accurate. A survey was used to collect information on BMI and attitudes and beliefs about nutrition and physical activity from parents (n = 207) of adolescents with ID attending schools participating in the Best Buddies Program. Approximately 45% of the adolescents were overweight or obese and over two-thirds of the parents were either overweight or obese. There was a significant difference in child's BMI by parents' description, F(3,158) = 72.75, P < 0.001. Factor analysis on questions on physical activity and nutrition revealed three factors (Factor 1 - Family Healthy Habits, Factor 2 - Parental Role and Factor 3 - Parental Activity) extracting 63% of the variance. The BMI of the adolescents significantly correlated with Factors 2 and 3. Children categorised as having a lower BMI had parents who agreed significantly more (r = -0.22, P < 0.005) with questions about being role models. There was a significant correlation between BMI for both the parents and adolescents and frequency of fast foods purchased. Efforts need to be made to provide parents of adolescents with ID tailored information about how they can assist their child in managing their weight. This information should emphasise to parents the important part they play as role models and as providers for healthy choices for physical activity as well as nutrition. © 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.

Generalization of value in reinforcement learning by humans

PubMed Central

Wimmer, G. Elliott; Daw, Nathaniel D.; Shohamy, Daphna

2012-01-01

Research in decision making has focused on the role of dopamine and its striatal targets in guiding choices via learned stimulus-reward or stimulus-response associations, behavior that is well-described by reinforcement learning (RL) theories. However, basic RL is relatively limited in scope and does not explain how learning about stimulus regularities or relations may guide decision making. A candidate mechanism for this type of learning comes from the domain of memory, which has highlighted a role for the hippocampus in learning of stimulus-stimulus relations, typically dissociated from the role of the striatum in stimulus-response learning. Here, we used fMRI and computational model-based analyses to examine the joint contributions of these mechanisms to RL. Humans performed an RL task with added relational structure, modeled after tasks used to isolate hippocampal contributions to memory. On each trial participants chose one of four options, but the reward probabilities for pairs of options were correlated across trials. This (uninstructed) relationship between pairs of options potentially enabled an observer to learn about options’ values based on experience with the other options and to generalize across them. We observed BOLD activity related to learning in the striatum and also in the hippocampus. By comparing a basic RL model to one augmented to allow feedback to generalize between correlated options, we tested whether choice behavior and BOLD activity were influenced by the opportunity to generalize across correlated options. Although such generalization goes beyond standard computational accounts of RL and striatal BOLD, both choices and striatal BOLD were better explained by the augmented model. Consistent with the hypothesized role for the hippocampus in this generalization, functional connectivity between the ventral striatum and hippocampus was modulated, across participants, by the ability of the augmented model to capture participants’ choice. Our results thus point toward an interactive model in which striatal RL systems may employ relational representations typically associated with the hippocampus. PMID:22487039

The role of social media use in improving cancer survivors' emotional well-being: a moderated mediation study.

PubMed

Jiang, Shaohai

2017-06-01

In the USA, levels of emotional well-being among cancer survivors remain low. Social media is recognized as important to improve their emotional well-being. However, little is known about social mechanisms that underlie the impact of health-related social media in cancer care. This study proposed a moderated mediation model to signify a pathway linking social media use to emotional well-being. Four-hundred and fifty-nine cancer survivors identified through the 2013 US-based Health Information National Trends Survey were included for data analysis. First, structural equation modeling was conducted to examine the path from social media use to emotional well-being, mediated by patient activation. Second, hierarchical regression was performed to test the moderation effect of emotion management. Last, a normal theory-based approach was used to explore the final moderated mediation model. The effect of health-related social media use on emotional well-being was completely mediated by patient activation. Also, emotion management positively moderated the effect of patient activation on emotional well-being. Last, emotion management positively moderated the mediation pathway from health-related social media use to patient activation, and finally, to emotional well-being. Health-related social media, by itself, is not sufficient to bring about improvement in cancer survivors' emotional well-being. Patient activation and emotion management play a significant role. In future interventions designed to improve cancer survivors' emotional health, health practitioners should not only encourage cancer survivors to use social media for health purposes, but also activate them in the course of care, and improve their emotion self-management skills.

Linking neuronal brain activity to the glucose metabolism.

PubMed

Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

2013-08-29

Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported.

Linking neuronal brain activity to the glucose metabolism

PubMed Central

2013-01-01

Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. Methods First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Results Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. Conclusions The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported. PMID:23988084

Calixarenes and Their Biomimetic Applications

PubMed Central

Agrawal, Y. K.; Bhatt, Harshit

2004-01-01

The synthetic models for the structures, spectroscopic properties and catalytic activities of metalloprotein active sites have been reviewed. Calixarenes were used as new biomimetic catalysts because of their advantage of providing preorganiiation of the catalytic group, which can bind the substrate dynamically that results in fast turnover and fast release of the products. Functional and structural models based on calixarenes are presented and in addition importance of molecular recognition and non-covalent interactions e.g. hydrogen bonding and their role in biological systems are discussed with the help of synthetic systems. PMID:18365079

Adaptive exponential integrate-and-fire model as an effective description of neuronal activity.

PubMed

Brette, Romain; Gerstner, Wulfram

2005-11-01

We introduce a two-dimensional integrate-and-fire model that combines an exponential spike mechanism with an adaptation equation, based on recent theoretical findings. We describe a systematic method to estimate its parameters with simple electrophysiological protocols (current-clamp injection of pulses and ramps) and apply it to a detailed conductance-based model of a regular spiking neuron. Our simple model predicts correctly the timing of 96% of the spikes (+/-2 ms) of the detailed model in response to injection of noisy synaptic conductances. The model is especially reliable in high-conductance states, typical of cortical activity in vivo, in which intrinsic conductances were found to have a reduced role in shaping spike trains. These results are promising because this simple model has enough expressive power to reproduce qualitatively several electrophysiological classes described in vitro.

Spiking and bursting patterns of fractional-order Izhikevich model

NASA Astrophysics Data System (ADS)

Teka, Wondimu W.; Upadhyay, Ranjit Kumar; Mondal, Argha

2018-03-01

Bursting and spiking oscillations play major roles in processing and transmitting information in the brain through cortical neurons that respond differently to the same signal. These oscillations display complex dynamics that might be produced by using neuronal models and varying many model parameters. Recent studies have shown that models with fractional order can produce several types of history-dependent neuronal activities without the adjustment of several parameters. We studied the fractional-order Izhikevich model and analyzed different kinds of oscillations that emerge from the fractional dynamics. The model produces a wide range of neuronal spike responses, including regular spiking, fast spiking, intrinsic bursting, mixed mode oscillations, regular bursting and chattering, by adjusting only the fractional order. Both the active and silent phase of the burst increase when the fractional-order model further deviates from the classical model. For smaller fractional order, the model produces memory dependent spiking activity after the pulse signal turned off. This special spiking activity and other properties of the fractional-order model are caused by the memory trace that emerges from the fractional-order dynamics and integrates all the past activities of the neuron. On the network level, the response of the neuronal network shifts from random to scale-free spiking. Our results suggest that the complex dynamics of spiking and bursting can be the result of the long-term dependence and interaction of intracellular and extracellular ionic currents.

The idealized self and the situated self as predictors of employee work behaviors.

PubMed

Farmer, Steven M; Van Dyne, Linn

2010-05-01

This article presents a model integrating research on idealized and situated selves. Our key premise is that identity-relevant behaviors are most likely to occur in the workplace when identities are psychologically central and activating forces make those identities salient. Analysis of matched data from 278 employees, supervisors, and organizational records generally supported our model. Helping identity and industrious work identity were positively associated with related role behaviors only when time-based occupancy in the role of organization member was high. Industrious work identity was positively associated with role behaviors only when reflected appraisals from coworkers were consistent with that identity. In contrast, reflected appraisal of helping identity had an independent relationship with identity-relevant role behaviors. Results demonstrate the importance of theory linking the idealized self and the situated self to understanding identity relations with work performances. PsycINFO Database Record (c) 2010 APA, all rights reserved.

Cell death/proliferation roles for nc886, a non-coding RNA, in the Protein Kinase R pathway in cholangiocarcinoma

PubMed Central

Kunkeaw, Nawapol; Jeon, Sung Ho; Lee, Kwanbok; Johnson, Betty H.; Tanasanvimon, Suebpong; Javle, Milind; Pairojkul, Chawalit; Chamgramol, Yaovalux; Wongfieng, Wipaporn; Gong, Bin; Leelayuwat, Chanvit; Lee, Yong Sun

2013-01-01

We have recently identified nc886 (pre-miR-886 or vtRNA2-1) as a novel type of non-coding RNA that inhibits activation of PKR (Protein Kinase RNA-activated). PKR's pro-apoptotic role through eIF2α phosphorylation is well established in the host defense against viral infection. Paradoxically, some cancer patients have elevated PKR activity; however, its cause and consequence are not understood. Initially we evaluated the expression of nc886, PKR and eIF2α in non-malignant cholangiocyte and cholangiocarcinoma (CCA) cells. nc886 is repressed in CCA cells and this repression is the cause of PKR's activation therein. nc886 alone is necessary and sufficient for suppression of PKR via direct physical interaction. Consistently, artificial suppression of nc886 in cholangiocyte cells activates the canonical PKR/eIF2α cell death pathway, suggesting a potential significance of the nc886 suppression and the consequent PKR activation in eliminating pre-malignant cells during tumorigenesis. In comparison, active PKR in CCA cells does not induce phospho-eIF2α nor apoptosis, but promotes the pro-survival NF-κB pathway. Thus, PKR plays a dual life or death role during tumorigenesis. Similarly to the CCA cell lines, nc886 tends to be decreased but PKR tends to be activated in our clinical samples from CCA patients. Collectively from our data, we propose a tumor surveillance model for nc886's role in the PKR pathway during tumorigenesis. PMID:22926522

Modeling arson - An exercise in qualitative model building

NASA Technical Reports Server (NTRS)

Heineke, J. M.

1975-01-01

A detailed example is given of the role of von Neumann and Morgenstern's 1944 'expected utility theorem' (in the theory of games and economic behavior) in qualitative model building. Specifically, an arsonist's decision as to the amount of time to allocate to arson and related activities is modeled, and the responsiveness of this time allocation to changes in various policy parameters is examined. Both the activity modeled and the method of presentation are intended to provide an introduction to the scope and power of the expected utility theorem in modeling situations of 'choice under uncertainty'. The robustness of such a model is shown to vary inversely with the number of preference restrictions used in the analysis. The fewer the restrictions, the wider is the class of agents to which the model is applicable, and accordingly more confidence is put in the derived results. A methodological discussion on modeling human behavior is included.

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

Scientists as role models in space science outreach

NASA Astrophysics Data System (ADS)

Alexander, D.

The direct participation of scientists significantly enhances the impact of any E/PO effort. This is particularly true when the scientists come from minority or traditionally under-represented groups and, consequently, become role models for a large number of students while presenting positive counter-examples to the usual stereotypes. In this paper I will discuss the impact of scientists as role models through the successful implementation of a set of space physics games and activities, called Solar Week. Targetted at middle-school girls, the key feature of Solar Week is the "Ask a Scientist" section enabling direct interaction between participating students and volunteer scientists. All of the contributing scientists are women, serving as experts in their field and providing role models to whom the students can relate. Solar Week has completed four sessions with a total of some 140 edcuators and 12,000+ students in over 28 states and 9 countries. A major success of the Solar Week program has been the ability of the students to learn more about the scientists as people, through online biographies, and to discuss a variety of topics ranging from science, to careers and common hobbies.

Potential Paradigms and Possible Problems for CALL.

ERIC Educational Resources Information Center

Phillips, Martin

1987-01-01

Describes three models of CALL (computer assisted language learning) activity--games, the expert system, and the prosthetic approaches. A case is made for CALL development within a more instrumental view of the role of computers. (Author/CB)

Broad MICA/B expression in the small bowel mucosa: a link between cellular stress and celiac disease.

PubMed

Allegretti, Yessica L; Bondar, Constanza; Guzman, Luciana; Cueto Rua, Eduardo; Chopita, Nestor; Fuertes, Mercedes; Zwirner, Norberto W; Chirdo, Fernando G

2013-01-01

The MICA/B genes (MHC class I chain related genes A and B) encode for non conventional class I HLA molecules which have no role in antigen presentation. MICA/B are up-regulated by different stress conditions such as heat-shock, oxidative stress, neoplasic transformation and viral infection. Particularly, MICA/B are expressed in enterocytes where they can mediate enterocyte apoptosis when recognised by the activating NKG2D receptor present on intraepithelial lymphocytes. This mechanism was suggested to play a major pathogenic role in active celiac disease (CD). Due to the importance of MICA/B in CD pathogenesis we studied their expression in duodenal tissue from CD patients. By immunofluorescence confocal microscopy and flow cytometry we established that MICA/B was mainly intracellularly located in enterocytes. In addition, we identified MICA/B(+) T cells in both the intraepithelial and lamina propria compartments. We also found MICA/B(+) B cells, plasma cells and some macrophages in the lamina propria. The pattern of MICA/B staining in mucosal tissue in severe enteropathy was similar to that found in in vitro models of cellular stress. In such models, MICA/B were located in stress granules that are associated to the oxidative and ER stress response observed in active CD enteropathy. Our results suggest that expression of MICA/B in the intestinal mucosa of CD patients is linked to disregulation of mucosa homeostasis in which the stress response plays an active role.

Broad MICA/B Expression in the Small Bowel Mucosa: A Link between Cellular Stress and Celiac Disease

PubMed Central

Allegretti, Yessica L.; Bondar, Constanza; Guzman, Luciana; Cueto Rua, Eduardo; Chopita, Nestor; Fuertes, Mercedes; Zwirner, Norberto W.; Chirdo, Fernando G.

2013-01-01

The MICA/B genes (MHC class I chain related genes A and B) encode for non conventional class I HLA molecules which have no role in antigen presentation. MICA/B are up-regulated by different stress conditions such as heat-shock, oxidative stress, neoplasic transformation and viral infection. Particularly, MICA/B are expressed in enterocytes where they can mediate enterocyte apoptosis when recognised by the activating NKG2D receptor present on intraepithelial lymphocytes. This mechanism was suggested to play a major pathogenic role in active celiac disease (CD). Due to the importance of MICA/B in CD pathogenesis we studied their expression in duodenal tissue from CD patients. By immunofluorescence confocal microscopy and flow cytometry we established that MICA/B was mainly intracellularly located in enterocytes. In addition, we identified MICA/B+ T cells in both the intraepithelial and lamina propria compartments. We also found MICA/B+ B cells, plasma cells and some macrophages in the lamina propria. The pattern of MICA/B staining in mucosal tissue in severe enteropathy was similar to that found in in vitro models of cellular stress. In such models, MICA/B were located in stress granules that are associated to the oxidative and ER stress response observed in active CD enteropathy. Our results suggest that expression of MICA/B in the intestinal mucosa of CD patients is linked to disregulation of mucosa homeostasis in which the stress response plays an active role. PMID:24058482

Solar Week 2000: Using role models to encourage an interest in science

NASA Astrophysics Data System (ADS)

Alexander, D.

2000-12-01

Solar Week 2000 is a week-long set of games and activities allowing students to interact directly with solar science and solar scientists. The main goal of Solar Week was to provide young women, primarily in grades 6-8, with access to role models in the sciences. The scientists participating in Solar Week are women from a variety of backgrounds and with a variety of scientific expertise. An online bulletin board was used to foster discussion between the students and the scientists about both science and career issues. In this presentation I will discuss the successes and failures of the first run of Solar Week which occurred on 9-13 October 2000. Our aim is to provide some insight into doing activity-based space science on the web and to discuss the lessons-learned from tailoring to a specific group of participants.

Dopamine prediction errors in reward learning and addiction: from theory to neural circuitry

PubMed Central

Keiflin, Ronald; Janak, Patricia H.

2015-01-01

Summary Midbrain dopamine (DA) neurons are proposed to signal reward prediction error (RPE), a fundamental parameter in associative learning models. This RPE hypothesis provides a compelling theoretical framework for understanding DA function in reward learning and addiction. New studies support a causal role for DA-mediated RPE activity in promoting learning about natural reward; however, this question has not been explicitly tested in the context of drug addiction. In this review, we integrate theoretical models with experimental findings on the activity of DA systems, and on the causal role of specific neuronal projections and cell types, to provide a circuit-based framework for probing DA-RPE function in addiction. By examining error-encoding DA neurons in the neural network in which they are embedded, hypotheses regarding circuit-level adaptations that possibly contribute to pathological error-signaling and addiction can be formulated and tested. PMID:26494275

Contribution of correlated noise and selective decoding to choice probability measurements in extrastriate visual cortex.

PubMed

Gu, Yong; Angelaki, Dora E; DeAngelis, Gregory C

2014-07-01

Trial by trial covariations between neural activity and perceptual decisions (quantified by choice Probability, CP) have been used to probe the contribution of sensory neurons to perceptual decisions. CPs are thought to be determined by both selective decoding of neural activity and by the structure of correlated noise among neurons, but the respective roles of these factors in creating CPs have been controversial. We used biologically-constrained simulations to explore this issue, taking advantage of a peculiar pattern of CPs exhibited by multisensory neurons in area MSTd that represent self-motion. Although models that relied on correlated noise or selective decoding could both account for the peculiar pattern of CPs, predictions of the selective decoding model were substantially more consistent with various features of the neural and behavioral data. While correlated noise is essential to observe CPs, our findings suggest that selective decoding of neuronal signals also plays important roles.

Edge instability in incompressible planar active fluids

NASA Astrophysics Data System (ADS)

Nesbitt, David; Pruessner, Gunnar; Lee, Chiu Fan

2017-12-01

Interfacial instability is highly relevant to many important biological processes. A key example arises in wound healing experiments, which observe that an epithelial layer with an initially straight edge does not heal uniformly. We consider the phenomenon in the context of active fluids. Improving upon the approximation used by Zimmermann, Basan, and Levine [Eur. Phys. J.: Spec. Top. 223, 1259 (2014), 10.1140/epjst/e2014-02189-7], we perform a linear stability analysis on a two-dimensional incompressible hydrodynamic model of an active fluid with an open interface. We categorize the stability of the model and find that for experimentally relevant parameters, fingering instability is always absent in this minimal model. Our results point to the crucial role of density variation in the fingering instability in tissue regeneration.

Acute and chronic suppression of the central ghrelin signaling system reveals a role in food anticipatory activity.

PubMed

Verhagen, Linda A W; Egecioglu, Emil; Luijendijk, Mieneke C M; Hillebrand, Jacquelien J G; Adan, Roger A H; Dickson, Suzanne L

2011-05-01

Using the rodent activity-based anorexia (ABA) model that mimics clinical features of anorexia nervosa that include food restriction-induced hyperlocomotion, we found that plasma ghrelin levels are highly associated with food anticipatory behaviour, measured by running wheel activity in rats. Furthermore, we showed that ghrelin receptor (GHS-R1A) knockout mice do not anticipate food when exposed to the ABA model, unlike their wild type littermate controls. Likewise, food anticipatory activity in the ABA model was suppressed by a GHS-R1A antagonist administered either by acute central (ICV) injection to rats or by chronic peripheral treatment to mice. Interestingly, the GHS-R1A antagonist did not alter food intake in any of these models. Therefore, we hypothesize that suppression of the central ghrelin signaling system via GHS-R1A provides an interesting therapeutic target to treat hyperactivity in patients suffering from anorexia nervosa. Copyright © 2010. Published by Elsevier B.V.

Calcium, Synaptic Plasticity and Intrinsic Homeostasis in Purkinje Neuron Models

PubMed Central

Achard, Pablo; De Schutter, Erik

2008-01-01

We recently reproduced the complex electrical activity of a Purkinje cell (PC) with very different combinations of ionic channel maximum conductances, suggesting that a large parameter space is available to homeostatic mechanisms. It has been hypothesized that cytoplasmic calcium concentrations control the homeostatic activity sensors. This raises many questions for PCs since in these neurons calcium plays an important role in the induction of synaptic plasticity. To address this question, we generated 148 new PC models. In these models the somatic membrane voltages are stable, but the somatic calcium dynamics are very variable, in agreement with experimental results. Conversely, the calcium signal in spiny dendrites shows only small variability. We demonstrate that this localized control of calcium conductances preserves the induction of long-term depression for all models. We conclude that calcium is unlikely to be the sole activity-sensor in this cell but that there is a strong relationship between activity homeostasis and synaptic plasticity. PMID:19129937

Passive vs. Active Control of Rhythmic Ball Bouncing: The Role of Visual Information

ERIC Educational Resources Information Center

Siegler, Isabelle A.; Bardy, Benoit G.; Warren, William H.

2010-01-01

The simple task of bouncing a ball on a racket offers a model system for studying how human actors exploit the physics and information of the environment to control their behavior. Previous work shows that people take advantage of a passively stable solution for ball bouncing but can also use perceptual information to actively stabilize bouncing.…

An Investigation of the Role of Grapheme Units in Word Recognition

ERIC Educational Resources Information Center

Lupker, Stephen J.; Acha, Joana; Davis, Colin J.; Perea, Manuel

2012-01-01

In most current models of word recognition, the word recognition process is assumed to be driven by the activation of letter units (i.e., that letters are the perceptual units in reading). An alternative possibility is that the word recognition process is driven by the activation of grapheme units, that is, that graphemes, rather than letters, are…

The Role of Perceived and Actual Motor Competency on Children's Physical Activity and Cardiorespiratory Fitness during Middle Childhood

ERIC Educational Resources Information Center

Gu, Xiangli; Thomas, Katherine Thomas; Chen, Yu-Lin

2017-01-01

Purpose: Guided by Stodden et al.'s (2008) conceptual model, the purpose of this study was to examine the associations among perceived competence, actual motor competence (MC), physical activity (PA), and cardiorespiratory fitness in elementary children. The group differences were also investigated as a function of MC levels. Methods: A…

Ecological Correlates of Spanish Adolescents' Physical Activity during Physical Education Classes

ERIC Educational Resources Information Center

Molina-García, Javier; Queralt, Ana; Estevan, Isaac; Sallis, James F.

2016-01-01

The public health benefit of school physical education (PE) depends in large part on physical activity (PA) provided during class. According to the literature, PE has a valuable role in public health, and PA levels during PE classes depend on a wide range of factors. The main objective of this study, based on ecological models of behaviour, was to…

Do Learning Activities Improve Students' Ability to Construct Explanatory Models with a Prism Foil Problem?

ERIC Educational Resources Information Center

Gojkošek, Mihael; Sliško, Josip; Planinšic, Gorazd

2013-01-01

The transfer of knowledge is considered to be a fundamental goal of education; therefore, knowing and understanding the conditions that influence the efficiency of the transfer from learning activity to problem solving play a decisive role in the improvement of science education. In this article, the results of a study of 196 high school students'…

Mechanistic Computational Model of Steroidgenesis in H295R Cells: Role of (Oxysterols and Cell Proliferation to Improve Predictability of Biochemical Response to Endocrine Active Chemical-Metyrapone

EPA Science Inventory

The human adrenocortical carcinoma cell line H295R is being used as an in vitro steroidogenesis screening assay to assess the impact of endocrine active chemicals (EACs) capable of altering steroid biosynthesis. To enhance the interpretation and quantitative application of measur...

Inflammatory Ly6Chigh Monocytes Protect against Candidiasis through IL-15-Driven NK Cell/Neutrophil Activation.

PubMed

Domínguez-Andrés, Jorge; Feo-Lucas, Lidia; Minguito de la Escalera, María; González, Leticia; López-Bravo, María; Ardavín, Carlos

2017-06-20

Neutrophils play a crucial role in defense against systemic candidiasis, a disease associated with a high mortality rate in patients receiving immunosuppressive therapy, although the early immune mechanisms that boost the candidacidal activity of neutrophils remain to be defined in depth. Here, we used a murine model of systemic candidiasis to explore the role of inflammatory Ly6C high monocytes in NK cell-mediated neutrophil activation during the innate immune response against C. albicans. We found that efficient anti-Candida immunity required a collaborative response between the spleen and kidney, which relied on type I interferon-dependent IL-15 production by spleen inflammatory Ly6C high monocytes to drive efficient activation and GM-CSF release by spleen NK cells; this in turn was necessary to boost the Candida killing potential of kidney neutrophils. Our findings unveil a role for IL-15 as a critical mediator in defense against systemic candidiasis and hold promise for the design of IL-15-based antifungal immunotherapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Passion for an activity and quality of interpersonal relationships: the mediating role of emotions.

PubMed

Philippe, Frederick L; Vallerand, Robert J; Houlfort, Nathalie; Lavigne, Geneviève L; Donahue, Eric G

2010-06-01

Our purpose in this research was to investigate the role of passion (Vallerand et al., 2003) for a given activity in the quality of interpersonal relationships experienced within the context of that activity in 4 studies. Study 1 demonstrated that a harmonious passion was positively associated with the quality of interpersonal relationships within the context of the passionate activity, whereas an obsessive passion was unrelated to it. Furthermore, in line with the broaden-and-build theory (Fredrickson, 2001), results also showed that positive emotions experienced at work fully mediated the relation between harmonious passion and quality of interpersonal relationships. Obsessive passion was not associated with positive emotions. Study 2 replicated the results from Study 1 while controlling for trait extraversion. Also, in Study 2, we examined the negative mediating role of negative emotions between obsessive passion and quality of interpersonal relationships. Finally, Studies 3 and 4 replicated the results of Study 2 with prospective designs and with objective ratings of interpersonal relationships quality. Implications for the dualistic model of passion and the broaden-and-build theory are discussed. (c) 2010 APA, all rights reserved).

Role of Cell-to-Cell Variability in Activating a Positive Feedback Antiviral Response in Human Dendritic Cells

PubMed Central

Hu, Jianzhong; Nudelman, German; Shimoni, Yishai; Kumar, Madhu; Ding, Yaomei; López, Carolina; Hayot, Fernand; Wetmur, James G.; Sealfon, Stuart C.

2011-01-01

In the first few hours following Newcastle disease viral infection of human monocyte-derived dendritic cells, the induction of IFNB1 is extremely low and the secreted type I interferon response is below the limits of ELISA assay. However, many interferon-induced genes are activated at this time, for example DDX58 (RIGI), which in response to viral RNA induces IFNB1. We investigated whether the early induction of IFNBI in only a small percentage of infected cells leads to low level IFN secretion that then induces IFN-responsive genes in all cells. We developed an agent-based mathematical model to explore the IFNBI and DDX58 temporal dynamics. Simulations showed that a small number of early responder cells provide a mechanism for efficient and controlled activation of the DDX58-IFNBI positive feedback loop. The model predicted distributions of single cell responses that were confirmed by single cell mRNA measurements. The results suggest that large cell-to-cell variation plays an important role in the early innate immune response, and that the variability is essential for the efficient activation of the IFNB1 based feedback loop. PMID:21347441

Ferulic acid exerts antitumor activity and inhibits metastasis in breast cancer cells by regulating epithelial to mesenchymal transition.

PubMed

Zhang, Xiang; Lin, Dan; Jiang, Rong; Li, Hongzhong; Wan, Jingyuan; Li, Hongyuan

2016-07-01

Metastasis, which frequently occurs in breast cancer, is the major cause of mortality; therefore, new treatment strategies are urgently needed. Ferulic acid, isolated from Ferula foetida, a perennial herb, has shown antineoplastic activity in various types of cancers, such as colon and lung cancer, and central nervous system tumors. However, its potential role in suppressing breast cancer metastasis has not been fully understood. In the present study, we evaluated the antitumor activity of ferulic acid in breast cancer cell line-based in vitro and in vivo models. We first showed that ferulic acid treatment resulted in decreased viability, increased apoptosis and suppression of metastatic potential in breast cancer cell line MDA-MB-231. Furthermore, it was demonstrated that the antitumor activity of ferulic acid and its role in suppressing metastasis were regulated by the reversal of epithelial-mesenchymal transition (EMT). Consistent with our findings in vitro, the antitumor potential of ferulic acid was also verified in an MDA-MB-231 xenograft mouse model where significantly decreased tumor volume, weight and increased apoptosis were observed. Taken together, these results indicate that ferulic acid may be used as an effective therapeutic agent against breast cancer.

A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle.

PubMed

Linke, Christian; Chasapi, Anastasia; González-Novo, Alberto; Al Sawad, Istabrak; Tognetti, Silvia; Klipp, Edda; Loog, Mart; Krobitsch, Sylvia; Posas, Francesc; Xenarios, Ioannis; Barberis, Matteo

2017-01-01

Precise timing of cell division is achieved by coupling waves of cyclin-dependent kinase (Cdk) activity with a transcriptional oscillator throughout cell cycle progression. Although details of transcription of cyclin genes are known, it is unclear which is the transcriptional cascade that modulates their expression in a timely fashion. Here, we demonstrate that a Clb/Cdk1-mediated regulation of the Fkh2 transcription factor synchronizes the temporal mitotic CLB expression in budding yeast. A simplified kinetic model of the cyclin/Cdk network predicts a linear cascade where a Clb/Cdk1-mediated regulation of an activator molecule drives CLB3 and CLB2 expression. Experimental validation highlights Fkh2 as modulator of CLB3 transcript levels, besides its role in regulating CLB2 expression. A Boolean model based on the minimal number of interactions needed to capture the information flow of the Clb/Cdk1 network supports the role of an activator molecule in the sequential activation, and oscillatory behavior, of mitotic Clb cyclins. This work illustrates how transcription and phosphorylation networks can be coupled by a Clb/Cdk1-mediated regulation that synchronizes them.

Active Brownian rods

NASA Astrophysics Data System (ADS)

Peruani, Fernando

2016-11-01

Bacteria, chemically-driven rods, and motility assays are examples of active (i.e. self-propelled) Brownian rods (ABR). The physics of ABR, despite their ubiquity in experimental systems, remains still poorly understood. Here, we review the large-scale properties of collections of ABR moving in a dissipative medium. We address the problem by presenting three different models, of decreasing complexity, which we refer to as model I, II, and III, respectively. Comparing model I, II, and III, we disentangle the role of activity and interactions. In particular, we learn that in two dimensions by ignoring steric or volume exclusion effects, large-scale nematic order seems to be possible, while steric interactions prevent the formation of orientational order at large scales. The macroscopic behavior of ABR results from the interplay between active stresses and local alignment. ABR exhibit, depending on where we locate ourselves in parameter space, a zoology of macroscopic patterns that ranges from polar and nematic bands to dynamic aggregates.

Modelling proteins’ hidden conformations to predict antibiotic resistance

PubMed Central

Hart, Kathryn M.; Ho, Chris M. W.; Dutta, Supratik; Gross, Michael L.; Bowman, Gregory R.

2016-01-01

TEM β-lactamase confers bacteria with resistance to many antibiotics and rapidly evolves activity against new drugs. However, functional changes are not easily explained by differences in crystal structures. We employ Markov state models to identify hidden conformations and explore their role in determining TEM’s specificity. We integrate these models with existing drug-design tools to create a new technique, called Boltzmann docking, which better predicts TEM specificity by accounting for conformational heterogeneity. Using our MSMs, we identify hidden states whose populations correlate with activity against cefotaxime. To experimentally detect our predicted hidden states, we use rapid mass spectrometric footprinting and confirm our models’ prediction that increased cefotaxime activity correlates with reduced Ω-loop flexibility. Finally, we design novel variants to stabilize the hidden cefotaximase states, and find their populations predict activity against cefotaxime in vitro and in vivo. Therefore, we expect this framework to have numerous applications in drug and protein design. PMID:27708258

Attenuated atherosclerotic lesions in apoe-fc gamma-chain-deficient hyperlipidemic mouse model is associated with inhibition of Th17 cells and promotion of regulatory T cells

USDA-ARS?s Scientific Manuscript database

Though the presence of antioxidized low-density lipoprotein IgG is well documented in clinical and animal studies, the role for Fc gamma Rs to the progression of atherosclerosis has not been studied in detail. In the current study, we investigated the role for activating Fc gamma R in the progressio...

Structural model of the dimeric Parkinson’s protein LRRK2 reveals a compact architecture involving distant interdomain contacts

PubMed Central

Guaitoli, Giambattista; Raimondi, Francesco; Gilsbach, Bernd K.; Gómez-Llorente, Yacob; Deyaert, Egon; Renzi, Fabiana; Li, Xianting; Schaffner, Adam; Jagtap, Pravin Kumar Ankush; Boldt, Karsten; von Zweydorf, Felix; Gotthardt, Katja; Lorimer, Donald D.; Yue, Zhenyu; Burgin, Alex; Janjic, Nebojsa; Sattler, Michael; Versées, Wim; Ueffing, Marius; Ubarretxena-Belandia, Iban; Kortholt, Arjan; Gloeckner, Christian Johannes

2016-01-01

Leucine-rich repeat kinase 2 (LRRK2) is a large, multidomain protein containing two catalytic domains: a Ras of complex proteins (Roc) G-domain and a kinase domain. Mutations associated with familial and sporadic Parkinson’s disease (PD) have been identified in both catalytic domains, as well as in several of its multiple putative regulatory domains. Several of these mutations have been linked to increased kinase activity. Despite the role of LRRK2 in the pathogenesis of PD, little is known about its overall architecture and how PD-linked mutations alter its function and enzymatic activities. Here, we have modeled the 3D structure of dimeric, full-length LRRK2 by combining domain-based homology models with multiple experimental constraints provided by chemical cross-linking combined with mass spectrometry, negative-stain EM, and small-angle X-ray scattering. Our model reveals dimeric LRRK2 has a compact overall architecture with a tight, multidomain organization. Close contacts between the N-terminal ankyrin and C-terminal WD40 domains, and their proximity—together with the LRR domain—to the kinase domain suggest an intramolecular mechanism for LRRK2 kinase activity regulation. Overall, our studies provide, to our knowledge, the first structural framework for understanding the role of the different domains of full-length LRRK2 in the pathogenesis of PD. PMID:27357661

The role of trauma in the hormonal interplay of cortisol, testosterone, and oxytocin in adolescent aggression.

PubMed

Fragkaki, Iro; Cima, Maaike; Granic, Isabela

2018-02-01

Although numerous studies have examined the neuroendocrinology of aggression, the findings are mixed and focused on cortisol and testosterone. We argue that past findings remain inconclusive partly because the key roles of oxytocin and trauma have not been systematically integrated yet. Oxytocin is associated with social behavior and interacts with cortisol and testosterone, whereas trauma is a crucial risk factor of aggression that strongly affects hormonal activity. In this review, we investigate the role of trauma in the hormonal interplay of cortisol, testosterone, and oxytocin in aggression during adolescence. We first discuss how these hormones interact with each other and how trauma influences these interactions and then we propose a model that highlights the role of trauma in the hormonal interplay in aggression. We suggest that the timing of trauma has a distinct effect on hormonal activity and it should be integrated into any comprehensive model. Current trauma is linked to different levels of oxytocin, cortisol, testosterone, and testosterone/cortisol ratio than childhood trauma, but this distinction is also influenced by gender and type of aggression. We conclude that in order to better understand the neuroendocrinology of aggression, it is crucial to incorporate the investigation of oxytocin and trauma in future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of an alginate suspension on pepsin and bile acids - key aggressors in the gastric refluxate. Does this have implications for the treatment of gastro-oesophageal reflux disease?

PubMed

Strugala, Vicki; Avis, Jeanine; Jolliffe, Ian G; Johnstone, Lesley M; Dettmar, Peter W

2009-08-01

During a reflux event the oesophagus is exposed to a heterogeneous mixture of gastric juice components. The role of non-acid components of the refluxate in causing damage to the oesophagus is now well established but no therapeutic option exists to address this. The role of Gaviscon Advance (GA), a raft-forming alginate suspension, in protecting the oesophagus from damage by pepsin and bile acids (aggressors) was investigated using a series of in-vitro models. GA was able to dose-dependently inhibit pepsin activity over and above the neutralisation effect of the formulation. This was evident against both protein and collagen substrates using two distinct colorimetric assays. GA was able to retard the diffusion of pepsin and multiple bile acids using a Franz cell model. Using the raft-forming mode of action GA was able to remove both pepsin and multiple bile acids from a simulated reflux event. There was capacity in the GA raft to accommodate aggressors from multiple reflux events. GA can specifically remove both pepsin and bile acids from the refluxate, limit their diffusion and affect enzymatic activity of pepsin. There is a role for GA to reduce the damaging potential of the refluxate and thus protect the oesophagus.

The Role of Regulatory T Cell in Nontypeable Haemophilus influenzae-Induced Acute Exacerbation of Chronic Obstructive Pulmonary Disease

PubMed Central

Guan, Xuewa; Lu, Yanjiao; Wang, Guoqiang; Fang, Keyong; Wang, Ziyan; Pang, Zhiqiang; Guo, Yingqiao; Lu, Junying; Yuan, Yuze; Ran, Nan

2018-01-01

Chronic obstructive pulmonary disease (COPD) is associated with irreversible persistent airflow limitation and enhanced inflammation. The episodes of acute exacerbation (AECOPD) largely depend on the colonized pathogens such as nontypeable Haemophilus influenzae (NTHi), one of the most commonly isolated bacteria. Regulatory T cells (Tregs) are critical in controlling inflammatory immune responses and maintaining tolerance; however, their role in AECOPD is poorly understood. In this study, we hypothesized a regulatory role of Tregs, as NTHi participated in the progress of COPD. Immunological pathogenesis was investigated in a murine COPD model induced by cigarette smoke (CS). NTHi was administrated through intratracheal instillation for an acute exacerbation. Weight loss and lung function decline were observed in smoke-exposed mice. Mice in experimental groups exhibited serious inflammatory responses via histological and cytokine assessment. Expression levels of Tregs and Th17 cells with specific cytokines TGF-β1 and IL-17 were detected to assess the balance of pro-/anti-inflammatory influence partially. Our findings suggested an anti-inflammatory activity of Tregs in CS-induced model. But this activity was suppressed after NTHi administration. Collectively, these data suggested that NTHi might play a necessary role in downregulating Foxp3 to impair the function of Tregs, helping development into AECOPD. PMID:29725272

Predicting organizational citizenship behavior from the functional analysis and role identity perspectives: further evidence in Spanish employees.

PubMed

Dávila, Ma Celeste; Finkelstein, Marcia A

2010-05-01

Organizational citizenship behavior (OCB) is a prosocial activity with similarities to volunteerism. The purpose of this work is to contribute new evidence about the relevance to OCB of two models of sustained volunteerism, functional analysis and role identity theory. A total of 983 Spanish employees at49 organizations completed surveys measuring amount of OCB, motives for engaging in citizenship behavior, and the degree to which respondents developed an organizational citizen role identity. The results showed that both motives and role identity were significant predictors of OCB, with motive partially mediating the role identity-OCB relationship. The findings suggest that similar mechanisms are involved in sustaining volunteerism and OCB.

Roles of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase in Angiogenesis: Isoform-Specific Effects

PubMed Central

Wang, Haibo; Hartnett, M. Elizabeth

2017-01-01

Angiogenesis is the formation of new blood vessels from preexisting ones and is implicated in physiologic vascular development, pathologic blood vessel growth, and vascular restoration. This is in contrast to vasculogenesis, which is de novo growth of vessels from vascular precursors, or from vascular repair that occurs when circulating endothelial progenitor cells home into an area and develop into blood vessels. The objective of this review is to discuss the isoform-specific role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in physiologic and pathologic angiogenesis and vascular repair, but will not specifically address vasculogenesis. As the major source of reactive oxygen species (ROS) in vascular endothelial cells (ECs), NOX has gained increasing attention in angiogenesis. Activation of NOX leads to events necessary for physiologic and pathologic angiogenesis, including EC migration, proliferation and tube formation. However, activation of different NOX isoforms has different effects in angiogenesis. Activation of NOX2 promotes pathologic angiogenesis and vascular inflammation, but may be beneficial in revascularization in the hindlimb ischemic model. In contrast, activation of NOX4 appears to promote physiologic angiogenesis mainly by protecting the vasculature during ischemia, hypoxia and inflammation and by restoring vascularization, except in models of oxygen-induced retinopathy and diabetes where NOX4 activation leads to pathologic angiogenesis. PMID:28587189

Gamma band oscillations: a key to understanding schizophrenia symptoms and neural circuit abnormalities

PubMed Central

McNally, James M.; McCarley, Robert W.

2016-01-01

Purpose of review We review our current understanding of abnormal γ band oscillations in schizophrenia, their association with symptoms and the underlying cortical circuit abnormality, with a particular focus on the role of fast-spiking parvalbumin gamma-aminobutyric acid (GABA) neurons in the disease state. Recent findings Clinical electrophysiological studies of schizophrenia patients and pharmacological models of the disorder show an increase in spontaneous γ band activity (not stimulus-evoked) measures. These findings provide a crucial link between preclinical and clinical work examining the role of γ band activity in schizophrenia. MRI-based experiments measuring cortical GABA provides evidence supporting impaired GABAergic neurotransmission in schizophrenia patients, which is correlated with γ band activity level. Several studies suggest that stimulation of the cortical circuitry, directly or via subcortical structures, has the potential to modulate cortical γ activity, and improve cognitive function. Summary Abnormal γ band activity is observed in patients with schizophrenia and disease models in animals, and is suggested to underlie the psychosis and cognitive/perceptual deficits. Convergent evidence from both clinical and preclinical studies suggest the central factor in γ band abnormalities is impaired GABAergic neurotransmission, particularly in a subclass of neurons which express parvalbumin. Rescue of γ band abnormalities presents an intriguing option for therapeutic intervention. PMID:26900672

Peroxisome proliferator-activated receptors (PPARs) as therapeutic target in neurodegenerative disorders

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

Agarwal, Swati; Yadav, Anuradha; Academy of Scientific and Innovative Research

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and they serve to be a promising therapeutic target for several neurodegenerative disorders, which includes Parkinson disease, Alzheimer's disease, Huntington disease and Amyotrophic Lateral Sclerosis. PPARs play an important role in the downregulation of mitochondrial dysfunction, proteasomal dysfunction, oxidative stress, and neuroinflammation, which are the major causes of the pathogenesis of neurodegenerative disorders. In this review, we discuss about the role of PPARs as therapeutic targets in neurodegenerative disorders. Several experimental approaches suggest potential application of PPAR agonist as well as antagonist in the treatment of neurodegenerative disorders. Several epidemiological studies found thatmore » the regular usage of PPAR activating non-steroidal anti-inflammatory drugs is effective in decreasing the progression of neurodegenerative diseases including PD and AD. We also reviewed the neuroprotective effects of PPAR agonists and associated mechanism of action in several neurodegenerative disorders both in vitro as well as in vivo animal models. - Highlights: • Peroxisome -activated receptors (PPARs) serve to be a promising therapeutic target for several neurodegenerative disorders. • PPAR agonist as well as provides neuroprotection in vitro as well as in vivo animal models of neurodegenerative disorders. • PPAR activating anti-inflammatory drugs use is effective in decreasing progression of neurodegenerative diseases.« less

Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation

PubMed Central

Reddy, Jay P.; Peddibhotla, Sirisha; Bu, Wen; Zhao, Jing; Haricharan, Svasti; Du, Yi-Chieh Nancy; Podsypanina, Katrina; Rosen, Jeffrey M.; Donehower, Larry A.; Li, Yi

2010-01-01

p53, apoptosis, and senescence are frequently activated in preneoplastic lesions and are barriers to progression to malignancy. These barriers have been suggested to result from an ATM-mediated DNA damage response (DDR), which may follow oncogene-induced hyperproliferation and ensuing DNA replication stress. To elucidate the currently untested role of DDR in breast cancer initiation, we examined the effect of oncogene expression in several murine models of breast cancer. We did not observe a detectable DDR in early hyperplastic lesions arising in transgenic mice expressing several different oncogenes. However, DDR signaling was strongly induced in preneoplastic lesions arising from individual mammary cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus, activation of an oncogene after normal tissue development causes a DDR. Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required for p53 stabilization, apoptosis, and senescence. In palpable tumors in this model, p53 stabilization and apoptosis are lost, but unexpectedly senescence remains in many tumor cells. Thus, this murine model fully recapitulates early DDR signaling; the eventual suppression of its endpoints in tumorigenesis provides compelling evidence that ErbB2-induced aberrant mammary cell proliferation leads to an ATM-mediated DDR that activates apoptosis and senescence, and at least the former must be overcome to progress to malignancy. This in vivo study also uncovers an unexpected effect of ErbB2 activation previously known for its prosurvival roles, and suggests that protection of the ATM-mediated DDR-p53 signaling pathway may be important in breast cancer prevention. PMID:20133707

IGF-1R Regulates the Extracellular Level of Active MMP-2, Pathological Neovascularization, and Functionality in Retinas of OIR Mouse Model.

PubMed

Lorenc, Valeria E; Subirada Caldarone, Paula V; Paz, María C; Ferrer, Darío G; Luna, José D; Chiabrando, Gustavo A; Sánchez, María C

2018-02-01

In ischemic proliferative diseases such as retinopathies, persistent hypoxia leads to the release of numerous neovascular factors that participate in the formation of abnormal vessels and eventually cause blindness. The upregulation and activation of metalloproteinases (MMP-2 and MMP-9) represent a final common pathway in this process. Although many regulators of the neovascular process have been identified, the complete role of the insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) appears to be significantly more complex. In this study, we used an oxygen-induced retinopathy (OIR) mouse model as well as an in vitro model of hypoxia to study the role of MMP-2 derived from Müller glial cells (MGCs) and its relation with the IGF-1/IGF-1R system. We demonstrated that MMP-2 protein expression increased in P17 OIR mice, which coincided with the active phase of the neovascular process. Also, glutamine synthetase (GS)-positive cells were also positive for MMP-2, whereas IGF-1R was expressed by GFAP-positive cells, indicating that both proteins were expressed in MGCs. In addition, in the OIR model a single intravitreal injection of the IGF-1R blocking antibody (αIR3) administered at P12 effectively prevented pathologic neovascularization, accelerated physiological revascularization, and improved retinal functionality at P17. Finally, in MGC supernatants, the blocking antibody abolished the IGF-1 effect on active MMP-2 under normoxic and hypoxic conditions without affecting the extracellular levels of pro-MMP-2. These results demonstrate, for the first time, that the IGF-1/IGF-1R system regulates active MMP-2 levels in MGCs, thus contributing to MEC remodeling during the retinal neovascular process.

Novel model of neuronal bioenergetics: postsynaptic utilization of glucose but not lactate correlates positively with Ca2+ signalling in cultured mouse glutamatergic neurons

PubMed Central

Bak, Lasse K.; Obel, Linea F.; Walls, Anne B.; Schousboe, Arne; Faek, Sevan A.A.; Jajo, Farah S.; Waagepetersen, Helle S.

2012-01-01

We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA (N-methyl-d-aspartate)-induced synaptic activity and that lactate alone is not able to support neurotransmitter glutamate homoeostasis. Subsequently, a model was proposed to explain these results at the cellular level. In brief, the intermittent rises in intracellular Ca2+ during activation cause influx of Ca2+ into the mitochondrial matrix thus activating the tricarboxylic acid cycle dehydrogenases. This will lead to a lower activity of the MASH (malate–aspartate shuttle), which in turn will result in anaerobic glycolysis and lactate production rather than lactate utilization. In the present work, we have investigated the effect of an ionomycin-induced increase in intracellular Ca2+ (i.e. independent of synaptic activity) on neuronal energy metabolism employing 13C-labelled glucose and lactate and subsequent mass spectrometric analysis of labelling in glutamate, alanine and lactate. The results demonstrate that glucose utilization is positively correlated with intracellular Ca2+ whereas lactate utilization is not. This result lends further support for a significant role of glucose in neuronal bioenergetics and that Ca2+ signalling may control the switch between glucose and lactate utilization during synaptic activity. Based on the results, we propose a compartmentalized CiMASH (Ca2+-induced limitation of the MASH) model that includes intracellular compartmentation of glucose and lactate metabolism. We define pre- and post-synaptic compartments metabolizing glucose and glucose plus lactate respectively in which the latter displays a positive correlation between oxidative metabolism of glucose and Ca2+ signalling. PMID:22385215

Novel model of neuronal bioenergetics: postsynaptic utilization of glucose but not lactate correlates positively with Ca2+ signalling in cultured mouse glutamatergic neurons.

PubMed

Bak, Lasse K; Obel, Linea F; Walls, Anne B; Schousboe, Arne; Faek, Sevan A A; Jajo, Farah S; Waagepetersen, Helle S

2012-04-05

We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA (N-methyl-d-aspartate)-induced synaptic activity and that lactate alone is not able to support neurotransmitter glutamate homoeostasis. Subsequently, a model was proposed to explain these results at the cellular level. In brief, the intermittent rises in intracellular Ca2+ during activation cause influx of Ca2+ into the mitochondrial matrix thus activating the tricarboxylic acid cycle dehydrogenases. This will lead to a lower activity of the MASH (malate-aspartate shuttle), which in turn will result in anaerobic glycolysis and lactate production rather than lactate utilization. In the present work, we have investigated the effect of an ionomycin-induced increase in intracellular Ca2+ (i.e. independent of synaptic activity) on neuronal energy metabolism employing 13C-labelled glucose and lactate and subsequent mass spectrometric analysis of labelling in glutamate, alanine and lactate. The results demonstrate that glucose utilization is positively correlated with intracellular Ca2+ whereas lactate utilization is not. This result lends further support for a significant role of glucose in neuronal bioenergetics and that Ca2+ signalling may control the switch between glucose and lactate utilization during synaptic activity. Based on the results, we propose a compartmentalized CiMASH (Ca2+-induced limitation of the MASH) model that includes intracellular compartmentation of glucose and lactate metabolism. We define pre- and post-synaptic compartments metabolizing glucose and glucose plus lactate respectively in which the latter displays a positive correlation between oxidative metabolism of glucose and Ca2+ signalling.

Differences in neighborhood social cohesion and aerobic physical activity by Latino subgroup.

PubMed

Murillo, Rosenda; Echeverria, Sandra; Vasquez, Elizabeth

2016-12-01

Previous research has examined the role of neighborhood social cohesion in physical activity outcomes; however, less is known about this relationship across Latino subgroups. The purpose of our study was to examine the association between neighborhood social cohesion and aerobic leisure-time physical activity (LTPA) among Latino adults and to determine whether these associations differ by Latino subgroup. We used cross-sectional 2013-2014 National Health Interview Survey (NHIS) data on Latinos originating from 5 countries/regions (i.e., Latinos of Puerto Rican, Mexican/Mexican-American, Cuban/Cuban-American, Dominican and Central or South American origin) aged ≥18 years (n=11,126). Multivariable logistic regression models were used to estimate associations between self-reported neighborhood social cohesion and meeting aerobic LTPA guidelines. Models were adjusted for age, sex, education, and acculturation. We also investigated whether associations varied by Latino subgroup. In adjusted models for all Latino adults, compared with those reporting low social cohesion, individuals who reported high social cohesion (Odds Ratio [OR]: 1.33; 95% Confidence Interval [CI]: 1.17-1.52) were significantly more likely to meet the aerobic physical activity guideline. When stratified by Latino subgroups, among Mexican/Mexicans-Americans (OR: 1.39; 95% CI: 1.16, 1.66) and Cuban/Cuban Americans (OR: 1.73; 95% CI: 1.00, 2.97) high social cohesion was associated with meeting the aerobic activity guideline. Among Dominicans, those who reported medium social cohesion (OR: 0.52, 95% CI: 0.29, 0.93) were less likely to meet the aerobic activity guideline. When examining aerobic physical activity outcomes in the Latino population, the role of neighborhood social cohesion and the variability among Latino subgroups should be considered.

Role of Passive Diffusion, Transporters, and Membrane Trafficking-Mediated Processes in Cellular Drug Transport.

PubMed

Cocucci, E; Kim, J Y; Bai, Y; Pabla, N

2017-01-01

Intracellular drug accumulation is thought to be dictated by two major processes, passive diffusion through the lipid membrane or membrane transporters. The relative role played by these distinct processes remains actively debated. Moreover, the role of membrane-trafficking in drug transport remains underappreciated and unexplored. Here we discuss the distinct processes involved in cellular drug distribution and propose that better experimental models are required to elucidate the differential contributions of various processes in intracellular drug accumulation. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Pigment-Dispersing Factor Signaling and Circadian Rhythms in Insect Locomotor Activity

PubMed Central

Shafer, Orie T.; Yao, Zepeng

2014-01-01

Though expressed in relatively few neurons in insect nervous systems, pigment-dispersing factor (PDF) plays many roles in the control of behavior and physiology. PDF’s role in circadian timekeeping is its best-understood function and the focus of this review. Here we recount the isolation and characterization of insect PDFs, review the evidence that PDF acts as a circadian clock output factor, and discuss emerging models of how PDF functions within circadian clock neuron network of Drosophila, the species in which this peptide’s circadian roles are best understood. PMID:25386391

Pallidostriatal Projections Promote β Oscillations in a Dopamine-Depleted Biophysical Network Model

PubMed Central

Corbit, Victoria L.; Whalen, Timothy C.; Zitelli, Kevin T.; Crilly, Stephanie Y.; Rubin, Jonathan E.

2016-01-01

In the basal ganglia, focused rhythmicity is an important feature of network activity at certain stages of motor processing. In disease, however, the basal ganglia develop amplified rhythmicity. Here, we demonstrate how the cellular architecture and network dynamics of an inhibitory loop in the basal ganglia yield exaggerated synchrony and locking to β oscillations, specifically in the dopamine-depleted state. A key component of this loop is the pallidostriatal pathway, a well-characterized anatomical projection whose function has long remained obscure. We present a synaptic characterization of this pathway in mice and incorporate these data into a computational model that we use to investigate its influence over striatal activity under simulated healthy and dopamine-depleted conditions. Our model predicts that the pallidostriatal pathway influences striatal output preferentially during periods of synchronized activity within GPe. We show that, under dopamine-depleted conditions, this effect becomes a key component of a positive feedback loop between the GPe and striatum that promotes synchronization and rhythmicity. Our results generate novel predictions about the role of the pallidostriatal pathway in shaping basal ganglia activity in health and disease. SIGNIFICANCE STATEMENT This work demonstrates that functional connections from the globus pallidus externa (GPe) to striatum are substantially stronger onto fast-spiking interneurons (FSIs) than onto medium spiny neurons. Our circuit model suggests that when GPe spikes are synchronous, this pallidostriatal pathway causes synchronous FSI activity pauses, which allow a transient window of disinhibition for medium spiny neurons. In simulated dopamine-depletion, this GPe-FSI activity is necessary for the emergence of strong synchronization and the amplification and propagation of β oscillations, which are a hallmark of parkinsonian circuit dysfunction. These results suggest that GPe may play a central role in propagating abnormal circuit activity to striatum, which in turn projects to downstream basal ganglia structures. These findings warrant further exploration of GPe as a target for interventions for Parkinson's disease. PMID:27194335

Single Canonical Model of Reflexive Memory and Spatial Attention

PubMed Central

Patel, Saumil S.; Red, Stuart; Lin, Eric; Sereno, Anne B.

2015-01-01

Many neurons in the dorsal and ventral visual stream have the property that after a brief visual stimulus presentation in their receptive field, the spiking activity in these neurons persists above their baseline levels for several seconds. This maintained activity is not always correlated with the monkey’s task and its origin is unknown. We have previously proposed a simple neural network model, based on shape selective neurons in monkey lateral intraparietal cortex, which predicts the valence and time course of reflexive (bottom-up) spatial attention. In the same simple model, we demonstrate here that passive maintained activity or short-term memory of specific visual events can result without need for an external or top-down modulatory signal. Mutual inhibition and neuronal adaptation play distinct roles in reflexive attention and memory. This modest 4-cell model provides the first simple and unified physiologically plausible mechanism of reflexive spatial attention and passive short-term memory processes. PMID:26493949

Compound activity prediction using models of binding pockets or ligand properties in 3D

PubMed Central

Kufareva, Irina; Chen, Yu-Chen; Ilatovskiy, Andrey V.; Abagyan, Ruben

2014-01-01

Transient interactions of endogenous and exogenous small molecules with flexible binding sites in proteins or macromolecular assemblies play a critical role in all biological processes. Current advances in high-resolution protein structure determination, database development, and docking methodology make it possible to design three-dimensional models for prediction of such interactions with increasing accuracy and specificity. Using the data collected in the Pocketome encyclopedia, we here provide an overview of two types of the three-dimensional ligand activity models, pocket-based and ligand property-based, for two important classes of proteins, nuclear and G-protein coupled receptors. For half the targets, the pocket models discriminate actives from property matched decoys with acceptable accuracy (the area under ROC curve, AUC, exceeding 84%) and for about one fifth of the targets with high accuracy (AUC > 95%). The 3D ligand property field models performed better than 95% in half of the cases. The high performance models can already become a basis of activity predictions for new chemicals. Family-wide benchmarking of the models highlights strengths of both approaches and helps identify their inherent bottlenecks and challenges. PMID:23116466

NKT cells in leishmaniasis.

PubMed

Zamora-Chimal, Jaime; Hernández-Ruiz, Joselín; Becker, Ingeborg

2017-04-01

The role of NKT cells in the resistance or susceptibility towards Leishmania infections remains to be defined, since controversial data persist. The response of these cells seems to depend on many variables such as the infection site, the number of infecting parasites, the virulence of the strain and the Leishmania species. We here revise the activation pathways leading to NKT cell activation. NKT cells can be activated by the direct pathway, in which Leishmania glycolipids are presented by CD1d molecules on antigen presenting cells, such as dendritic cells (DC), leading to the secretion of diverse cytokines by NKT. NKT cells can also be activated by the indirect pathway, in which Leishmania glycolipids, such as LPG, stimulate TLR2 in DC, inducing their IL-12 production, which in turn activates NKT cells. The review further analyzes the role of NKT cells in disease development, both in humans as in mouse models. Finally we propose the activation of NKT cells for controlling Leishmania infections. Copyright © 2016 Elsevier GmbH. All rights reserved.

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

Reichhardt, Cynthia Jane; Reichhardt, Charles

Ratchet effects can arise for single or collectively interacting Brownian particles on an asymmetric substrate when a net dc transport is produced by an externally applied ac driving force or by periodically flashing the substrate. Recently, a new class of active ratchet systems that do not require the application of external driving has been realized through the use of active matter; they are self-propelled units that can be biological or nonbiological in nature. When active materials such as swimming bacteria interact with an asymmetric substrate, a net dc directed motion can arise even without external driving, opening a wealth ofmore » possibilities such as sorting, cargo transport, or micromachine construction. We review the current status of active matter ratchets for swimming bacteria, cells, active colloids, and swarming models, focusing on the role of particle-substrate interactions. Here, we describe ratchet reversals produced by collective effects and the use of active ratchets to transport passive particles. We discuss future directions including deformable substrates or particles, the role of different swimming modes, varied particle–particle interactions, and nondissipative effects.« less

The role of asymmetric frontal cortical activity in emotion-related phenomena: a review and update.

PubMed

Harmon-Jones, Eddie; Gable, Philip A; Peterson, Carly K

2010-07-01

Conceptual and empirical approaches to the study of the role of asymmetric frontal cortical activity in emotional processes are reviewed. Although early research suggested that greater left than right frontal cortical activity was associated with positive affect, more recent research, primarily on anger, suggests that greater left than right frontal cortical activity is associated with approach motivation, which can be positive (e.g., enthusiasm) or negative in valence (e.g., anger). In addition to reviewing this research on anger, research on guilt, bipolar disorder, and various types of positive affect is reviewed with relation to their association with asymmetric frontal cortical activity. The reviewed research not only contributes to a more complete understanding of the emotive functions of asymmetric frontal cortical activity, but it also points to the importance of considering motivational direction as separate from affective valence in psychological models of emotional space. Copyright © 2009 Elsevier B.V. All rights reserved.

Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling.

PubMed

Zeng, Wei-Zheng; Liu, Di-Shi; Liu, Lu; She, Liang; Wu, Long-Jun; Xu, Tian-Le

2015-09-15

Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICs in vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system.

CNG and HCN channels: two peas, one pod.

PubMed

Craven, Kimberley B; Zagotta, William N

2006-01-01

Cyclic nucleotide-activated ion channels play a fundamental role in a variety of physiological processes. By opening in response to intracellular cyclic nucleotides, they translate changes in concentrations of signaling molecules to changes in membrane potential. These channels belong to two families: the cyclic nucleotide-gated (CNG) channels and the hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels. The two families exhibit high sequence similarity and belong to the superfamily of voltage-gated potassium channels. Whereas HCN channels are activated by voltage and CNG channels are virtually voltage independent, both channels are activated by cyclic nucleotide binding. Furthermore, the channels are thought to have similar channel structures, leading to similar mechanisms of activation by cyclic nucleotides. However, although these channels are structurally and behaviorally similar, they have evolved to perform distinct physiological functions. This review describes the physiological roles and biophysical behavior of CNG and HCN channels. We focus on how similarities in structure and activation mechanisms result in common biophysical models, allowing CNG and HCN channels to be viewed as a single genre.

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

Gastelum, Zoe N.; Harvey, Julia B.

The International Atomic Energy Agency State Evaluation Process: The Role of Information Analysis in Reaching Safeguards Conclusions (Mathews et al. 2008), several examples of nonproliferation models using analytical software were developed that may assist the IAEA with collecting, visualizing, analyzing, and reporting information in support of the State Evaluation Process. This paper focuses on one of the examples a set of models developed in the Proactive Scenario Production, Evidence Collection, and Testing (ProSPECT) software that evaluates the status and nature of a state’s nuclear activities. The models use three distinct subject areas to perform this assessment: the presence of nuclearmore » activities, the consistency of those nuclear activities with national nuclear energy goals, and the geopolitical context in which those nuclear activities are taking place. As a proof-of-concept for the models, a crude case study was performed. The study, which attempted to evaluate the nuclear activities taking place in Syria prior to September 2007, yielded illustrative, yet inconclusive, results. Due to the inconclusive nature of the case study results, changes that may improve the model’s efficiency and accuracy are proposed.« less

The role of body-related self-conscious emotions in motivating women's physical activity.

PubMed

Sabiston, Catherine M; Brunet, Jennifer; Kowalski, Kent C; Wilson, Philip M; Mack, Diane E; Crocker, Peter R E

2010-08-01

The purpose of this study was to test a model where body-related self-conscious emotions of shame, guilt, and pride were associated with physical activity regulations and behavior. Adult women (N = 389; M age = 29.82, SD = 15.20 years) completed a questionnaire assessing body-related pride, shame, and guilt, motivational regulations, and leisure-time physical activity. The hypothesized measurement and structural models were deemed adequate, as was a revised model examining shame-free guilt and guilt-free shame. In the revised structural model, body-related pride was positively significantly related to identified and intrinsic regulations. Body-related shame-free guilt was significantly associated with external, introjected, and identified regulations. Body-related guilt-free shame was significantly positively related to external and introjected regulation, and negatively associated with intrinsic regulation. Identified and intrinsic regulations were significantly positively related to physical activity (R2 = .62). These findings highlight the importance of targeting and understanding the realm of body-related self-conscious emotions and the associated links to regulations and physical activity behavior.

Models of traumatic experiences and children's psychological adjustment: the roles of perceived parenting and the children's own resources and activity.

PubMed

Punamäki, R L; Qouta, S; el Sarraj, E

1997-08-01

The relations between traumatic events, perceived parenting styles, children's resources, political activity, and psychological adjustment were examined among 108 Palestinian boys and girls of 11-12 years of age. The results showed that exposure to traumatic events increased psychological adjustment problems directly and via 2 mediating paths. First, the more traumatic events children had experienced, the more negative parenting they experienced. And, the poorer they perceived parenting, the more they suffered from high neuroticism and low self-esteem. Second, the more traumatic events children had experienced, the more political activity they showed, and the more active they were, the more they suffered from psychological adjustment problems. Good perceived parenting protected children's psychological adjustment by making them less vulnerable in two ways. First, traumatic events decreased their intellectual, creative, and cognitive resources, and a lack of resources predicted many psychological adjustment problems in a model excluding perceived parenting. Second, political activity increased psychological adjustment problems in the same model, but not in the model including good parenting.