Nuclear cGMP-dependent kinase regulates gene expression via activity-dependent recruitment of a conserved histone deacetylase complex.

Directory of Open Access Journals (Sweden)

Yan Hao

2011-05-01

Full Text Available Elevation of the second messenger cGMP by nitric oxide (NO activates the cGMP-dependent protein kinase PKG, which is key in regulating cardiovascular, intestinal, and neuronal functions in mammals. The NO-cGMP-PKG signaling pathway is also a major therapeutic target for cardiovascular and male reproductive diseases. Despite widespread effects of PKG activation, few molecular targets of PKG are known. We study how EGL-4, the Caenorhabditis elegans PKG ortholog, modulates foraging behavior and egg-laying and seeks the downstream effectors of EGL-4 activity. Using a combination of unbiased forward genetic screen and proteomic analysis, we have identified a conserved SAEG-1/SAEG-2/HDA-2 histone deacetylase complex that is specifically recruited by activated nuclear EGL-4. Gene expression profiling by microarrays revealed >40 genes that are sensitive to EGL-4 activity in a SAEG-1-dependent manner. We present evidence that EGL-4 controls egg laying via one of these genes, Y45F10C.2, which encodes a novel protein that is expressed exclusively in the uterine epithelium. Our results indicate that, in addition to cytoplasmic functions, active EGL-4/PKG acts in the nucleus via a conserved Class I histone deacetylase complex to regulate gene expression pertinent to behavioral and physiological responses to cGMP. We also identify transcriptional targets of EGL-4 that carry out discrete components of the physiological response.

Linear Energy Transfer-Dependent Change in Rice Gene Expression Profile after Heavy-Ion Beam Irradiation.

Science.gov (United States)

Ishii, Kotaro; Kazama, Yusuke; Morita, Ryouhei; Hirano, Tomonari; Ikeda, Tokihiro; Usuda, Sachiko; Hayashi, Yoriko; Ohbu, Sumie; Motoyama, Ritsuko; Nagamura, Yoshiaki; Abe, Tomoko

2016-01-01

A heavy-ion beam has been recognized as an effective mutagen for plant breeding and applied to the many kinds of crops including rice. In contrast with X-ray or γ-ray, the heavy-ion beam is characterized by a high linear energy transfer (LET). LET is an important factor affecting several aspects of the irradiation effect, e.g. cell survival and mutation frequency, making the heavy-ion beam an effective mutagen. To study the mechanisms behind LET-dependent effects, expression profiling was performed after heavy-ion beam irradiation of imbibed rice seeds. Array-based experiments at three time points (0.5, 1, 2 h after the irradiation) revealed that the number of up- or down-regulated genes was highest 2 h after irradiation. Array-based experiments with four different LETs at 2 h after irradiation identified LET-independent regulated genes that were up/down-regulated regardless of the value of LET; LET-dependent regulated genes, whose expression level increased with the rise of LET value, were also identified. Gene ontology (GO) analysis of LET-independent up-regulated genes showed that some GO terms were commonly enriched, both 2 hours and 3 weeks after irradiation. GO terms enriched in LET-dependent regulated genes implied that some factor regulates genes that have kinase activity or DNA-binding activity in cooperation with the ATM gene. Of the LET-dependent up-regulated genes, OsPARP3 and OsPCNA were identified, which are involved in DNA repair pathways. This indicates that the Ku-independent alternative non-homologous end-joining pathway may contribute to repairing complex DNA legions induced by high-LET irradiation. These findings may clarify various LET-dependent responses in rice.

Discriminant Profile of Young Internet Dependents: The Role of Family Relationships

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Michele Terres-Trindade

2015-12-01

Full Text Available AbstractInternational studies have shown effects of family relations on Internet addiction in young people. This research aimed to outline a discriminant profile of young people classified as dependent and not dependent on the Internet regarding to socio-biodemographic variables to parenting practices, parent-child conflict and interparental conflict. The sample consisted of 200 students (152 girls and 48 boys, between 15 and 24 years of age, 85.5% reside in Rio Grande do Sul and 14.5% in other Brazilian states. Participants responded individually to the protocol available online. The results showed that interparental conflict, parent-child conflict and the educational practice of supervision of paternal behavior discriminate dependents on Internet. The educational practice of maternal emotional support was the only discriminating variable for non-dependents. These national findings corroborate the international context studies and reinforce the importance of including the family in promotion and prevention of mental health of young people.

Controlling the Glycosylation Profile in mAbs Using Time-Dependent Media Supplementation

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Devesh Radhakrishnan

2017-12-01

Full Text Available In order to meet desired drug product quality targets, the glycosylation profile of biotherapeutics such as monoclonal antibodies (mAbs must be maintained consistently during manufacturing. Achieving consistent glycan distribution profiles requires identifying factors that influence glycosylation, and manipulating them appropriately via well-designed control strategies. Now, the cell culture media supplement, MnCl2, is known to alter the glycosylation profile in mAbs generally, but its effect, particularly when introduced at different stages during cell growth, has yet to be investigated and quantified. In this study, we evaluate the effect of time-dependent addition of MnCl2 on the glycan profile quantitatively, using factorial design experiments. Our results show that MnCl2 addition during the lag and exponential phases affects the glycan profile significantly more than stationary phase supplementation does. Also, using a novel computational technique, we identify various combinations of glycan species that are affected by this dynamic media supplementation scheme, and quantify the effects mathematically. Our experiments demonstrate the importance of taking into consideration the time of addition of these trace supplements, not just their concentrations, and our computational analysis provides insight into what supplements to add, when, and how much, in order to induce desired changes.

Parent Prevention Communication Profiles and Adolescent Substance Use: A Latent Profile Analysis and Growth Curve Model

Science.gov (United States)

Choi, Hye Jeong; Miller-Day, Michelle; Shin, YoungJu; Hecht, Michael L.; Pettigrew, Jonathan; Krieger, Janice L.; Lee, JeongKyu; Graham, John W.

2017-01-01

This current study identifies distinct parent prevention communication profiles and examines whether youth with different parental communication profiles have varying substance use trajectories over time. Eleven schools in two rural school districts in the Midwestern United States were selected, and 784 students were surveyed at three time points from the beginning of 7th grade to the end of 8th grade. A series of latent profile analyses were performed to identify discrete profiles/subgroups of substance-specific prevention communication (SSPC). The results revealed a 4-profile model of SSPC: Active-Open, Passive-Open, Active-Silent, and Passive-Silent. A growth curve model revealed different rates of lifetime substance use depending on the youth’s SSPC profile. These findings have implications for parenting interventions and tailoring messages for parents to fit specific SSPC profiles. PMID:29056872

Substrate-Competitive Activity-Based Profiling of Ester Prodrug Activating Enzymes.

Science.gov (United States)

Xu, Hao; Majmudar, Jaimeen D; Davda, Dahvid; Ghanakota, Phani; Kim, Ki H; Carlson, Heather A; Showalter, Hollis D; Martin, Brent R; Amidon, Gordon L

2015-09-08

Understanding the mechanistic basis of prodrug delivery and activation is critical for establishing species-specific prodrug sensitivities necessary for evaluating preclinical animal models and potential drug-drug interactions. Despite significant adoption of prodrug methodologies for enhanced pharmacokinetics, functional annotation of prodrug activating enzymes is laborious and often unaddressed. Activity-based protein profiling (ABPP) describes an emerging chemoproteomic approach to assay active site occupancy within a mechanistically similar enzyme class in native proteomes. The serine hydrolase enzyme family is broadly reactive with reporter-linked fluorophosphonates, which have shown to provide a mechanism-based covalent labeling strategy to assay the activation state and active site occupancy of cellular serine amidases, esterases, and thioesterases. Here we describe a modified ABPP approach using direct substrate competition to identify activating enzymes for an ethyl ester prodrug, the influenza neuraminidase inhibitor oseltamivir. Substrate-competitive ABPP analysis identified carboxylesterase 1 (CES1) as an oseltamivir-activating enzyme in intestinal cell homogenates. Saturating concentrations of oseltamivir lead to a four-fold reduction in the observed rate constant for CES1 inactivation by fluorophosphonates. WWL50, a reported carbamate inhibitor of mouse CES1, blocked oseltamivir hydrolysis activity in human cell homogenates, confirming CES1 is the primary prodrug activating enzyme for oseltamivir in human liver and intestinal cell lines. The related carbamate inhibitor WWL79 inhibited mouse but not human CES1, providing a series of probes for analyzing prodrug activation mechanisms in different preclinical models. Overall, we present a substrate-competitive activity-based profiling approach for broadly surveying candidate prodrug hydrolyzing enzymes and outline the kinetic parameters for activating enzyme discovery, ester prodrug design, and

Linear Energy Transfer-Dependent Change in Rice Gene Expression Profile after Heavy-Ion Beam Irradiation.

Directory of Open Access Journals (Sweden)

Kotaro Ishii

Full Text Available A heavy-ion beam has been recognized as an effective mutagen for plant breeding and applied to the many kinds of crops including rice. In contrast with X-ray or γ-ray, the heavy-ion beam is characterized by a high linear energy transfer (LET. LET is an important factor affecting several aspects of the irradiation effect, e.g. cell survival and mutation frequency, making the heavy-ion beam an effective mutagen. To study the mechanisms behind LET-dependent effects, expression profiling was performed after heavy-ion beam irradiation of imbibed rice seeds. Array-based experiments at three time points (0.5, 1, 2 h after the irradiation revealed that the number of up- or down-regulated genes was highest 2 h after irradiation. Array-based experiments with four different LETs at 2 h after irradiation identified LET-independent regulated genes that were up/down-regulated regardless of the value of LET; LET-dependent regulated genes, whose expression level increased with the rise of LET value, were also identified. Gene ontology (GO analysis of LET-independent up-regulated genes showed that some GO terms were commonly enriched, both 2 hours and 3 weeks after irradiation. GO terms enriched in LET-dependent regulated genes implied that some factor regulates genes that have kinase activity or DNA-binding activity in cooperation with the ATM gene. Of the LET-dependent up-regulated genes, OsPARP3 and OsPCNA were identified, which are involved in DNA repair pathways. This indicates that the Ku-independent alternative non-homologous end-joining pathway may contribute to repairing complex DNA legions induced by high-LET irradiation. These findings may clarify various LET-dependent responses in rice.

Profile of organic food consumers

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Kranjac Mirjana

2017-01-01

Full Text Available The aim of this study is to prove that profile of organic food consumers is dependent on their socio-demographic characteristics as well as to shape universal organic food consumer profile. The survey included 398 consumers in Serbia. Results indicate existence of typical consumer's profile. The findings could be generalized proving that socio-demographic profiles in a larger population are strictly related to the decision to utilize organic food. The study finally contributes to the stakeholders in general, since the knowledge of the attributes can help all of them to play more active role in this supply chain. It should stimulate the personalized approach to the particular groups of consumers based on socio-demographic characteristics in order to intensify consumption of organic food and to create different marketing plans dependent on the particular countries or areas.

Surface activity, lipid profiles and their implications in cervical cancer.

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Preetha A

2005-01-01

Full Text Available Background: The profiles of lipids in normal and cancerous tissues may differ revealing information about cancer development and progression. Lipids being surface active, changes in lipid profiles can manifest as altered surface activity profiles. Langmuir monolayers offer a convenient model for evaluating surface activity of biological membranes. Aims: The aims of this study were to quantify phospholipids and their effects on surface activity of normal and cancerous human cervical tissues as well as to evaluate the role of phosphatidylcholine (PC and sphingomyelin (SM in cervical cancer using Langmuir monolayers. Methods and Materials: Lipid quantification was done using thin layer chromatography and phosphorus assay. Surface activity was evaluated using Langmuir monolayers. Monolayers were formed on the surface of deionized water by spreading tissue organic phase corresponding to 1 mg of tissue and studying their surface pressure-area isotherms at body temperature. The PC and SM contents of cancerous human cervical tissues were higher than those of the normal human cervical tissues. Role of PC and SM were evaluated by adding varying amounts of these lipids to normal cervical pooled organic phase. Statistical analysis: Student′s t-test (p < 0.05 and one-way analysis of variance (ANOVA was used. Results: Our results reveals that the phosphatidylglycerol level in cancerous cervical tissue was nearly five folds higher than that in normal cervical tissue. Also PC and sphingomyelin SM were found to be the major phospholipid components in cancerous and normal cervical tissues respectively. The addition of either 1.5 µg DPPC or 0.5 µg SM /mg of tissue to the normal organic phase changed its surface activity profile to that of the cancerous tissues. Statistically significant surface activity parameters showed that PC and SM have remarkable roles in shifting the normal cervical lipophilic surface activity towards that of cancerous lipophilic

Assessing Sources of Stress to Aquatic Ecosystems: Using Biomarkers and Bioindicators to Characterize Exodure-Response Profiles of Anthropogenic Activities

Energy Technology Data Exchange (ETDEWEB)

Adams, S.M.

1999-03-29

Establishing causal relationships between sources of environmental stressors and aquatic ecosystem health if difficult because of the many biotic and abiotic factors which can influence or modify responses of biological systems to stress, the orders of magnitude involved in extrapolation over both spatial and temporal scales, and compensatory mechanisms such as density-dependent responses that operate in populations. To address the problem of establishing causality between stressors and effects on aquatic systems, a diagnostic approach, based on exposure-response profiles for various anthropogenic activities, was developed to help identify sources of stress responsible for effects on aquatic systems at ecological significant levels of biological organization (individual, population, community). To generate these exposure-effects profiles, biomarkers of exposure were plotted against bioindicators of corresponding effects for several major anthropogenic activities including petrochemical , pulp and paper, domestic sewage, mining operations, land-development activities, and agricultural activities. Biomarkers of exposure to environmental stressors varied depending on the type of anthropogenic activity involved. Bioindicator effects, however, including histopathological lesions, bioenergetic status, individual growth, reproductive impairment, and community-level responses were similar among many of the major anthropogenic activities. This approach is valuable to help identify and diagnose sources of stressors in environments impacted by multiple stressors. By identifying the types and sources of environmental stressors, aquatic ecosystems can be more effectively protected and managed to maintain acceptable levels of environmental quality and ecosystem fitness.

Prediction of Process-Induced Distortions in L-Shaped Composite Profiles Using Path-Dependent Constitutive Law

Science.gov (United States)

Ding, Anxin; Li, Shuxin; Wang, Jihui; Ni, Aiqing; Sun, Liangliang; Chang, Lei

2016-10-01

In this paper, the corner spring-in angles of AS4/8552 L-shaped composite profiles with different thicknesses are predicted using path-dependent constitutive law with the consideration of material properties variation due to phase change during curing. The prediction accuracy mainly depends on the properties in the rubbery and glassy states obtained by homogenization method rather than experimental measurements. Both analytical and finite element (FE) homogenization methods are applied to predict the overall properties of AS4/8552 composite. The effect of fiber volume fraction on the properties is investigated for both rubbery and glassy states using both methods. And the predicted results are compared with experimental measurements for the glassy state. Good agreement is achieved between the predicted results and available experimental data, showing the reliability of the homogenization method. Furthermore, the corner spring-in angles of L-shaped composite profiles are measured experimentally and the reliability of path-dependent constitutive law is validated as well as the properties prediction by FE homogenization method.

Quantitative genetic activity graphical profiles for use in chemical evaluation

Energy Technology Data Exchange (ETDEWEB)

Waters, M.D. [Environmental Protection Agency, Washington, DC (United States); Stack, H.F.; Garrett, N.E.; Jackson, M.A. [Environmental Health Research and Testing, Inc., Research Triangle Park, NC (United States)

1990-12-31

A graphic approach, terms a Genetic Activity Profile (GAP), was developed to display a matrix of data on the genetic and related effects of selected chemical agents. The profiles provide a visual overview of the quantitative (doses) and qualitative (test results) data for each chemical. Either the lowest effective dose or highest ineffective dose is recorded for each agent and bioassay. Up to 200 different test systems are represented across the GAP. Bioassay systems are organized according to the phylogeny of the test organisms and the end points of genetic activity. The methodology for producing and evaluating genetic activity profile was developed in collaboration with the International Agency for Research on Cancer (IARC). Data on individual chemicals were compiles by IARC and by the US Environmental Protection Agency (EPA). Data are available on 343 compounds selected from volumes 1-53 of the IARC Monographs and on 115 compounds identified as Superfund Priority Substances. Software to display the GAPs on an IBM-compatible personal computer is available from the authors. Structurally similar compounds frequently display qualitatively and quantitatively similar profiles of genetic activity. Through examination of the patterns of GAPs of pairs and groups of chemicals, it is possible to make more informed decisions regarding the selection of test batteries to be used in evaluation of chemical analogs. GAPs provided useful data for development of weight-of-evidence hazard ranking schemes. Also, some knowledge of the potential genetic activity of complex environmental mixtures may be gained from an assessment of the genetic activity profiles of component chemicals. The fundamental techniques and computer programs devised for the GAP database may be used to develop similar databases in other disciplines. 36 refs., 2 figs.

Strong orientation dependence of surface mass density profiles of dark haloes at large scales

Science.gov (United States)

Osato, Ken; Nishimichi, Takahiro; Oguri, Masamune; Takada, Masahiro; Okumura, Teppei

2018-06-01

We study the dependence of surface mass density profiles, which can be directly measured by weak gravitational lensing, on the orientation of haloes with respect to the line-of-sight direction, using a suite of N-body simulations. We find that, when major axes of haloes are aligned with the line-of-sight direction, surface mass density profiles have higher amplitudes than those averaged over all halo orientations, over all scales from 0.1 to 100 Mpc h-1 we studied. While the orientation dependence at small scales is ascribed to the halo triaxiality, our results indicate even stronger orientation dependence in the so-called two-halo regime, up to 100 Mpc h-1. The orientation dependence for the two-halo term is well approximated by a multiplicative shift of the amplitude and therefore a shift in the halo bias parameter value. The halo bias from the two-halo term can be overestimated or underestimated by up to {˜ } 30 per cent depending on the viewing angle, which translates into the bias in estimated halo masses by up to a factor of 2 from halo bias measurements. The orientation dependence at large scales originates from the anisotropic halo-matter correlation function, which has an elliptical shape with the axis ratio of ˜0.55 up to 100 Mpc h-1. We discuss potential impacts of halo orientation bias on other observables such as optically selected cluster samples and a clustering analysis of large-scale structure tracers such as quasars.

Lipidic profile and the level of physical activity of adolescent scholars

Directory of Open Access Journals (Sweden)

Renato Canevari Dutra da Silva

2011-12-01

Full Text Available Objective: To assess the relationship between lipid profile and physical activity level of adolescent students in Rio Verde-GO, Brazil. Methods: A descriptive and cross-sectionalstudy, conducted in 2006, with a population comprised by 1,229 adolescent students of both genders, aged 15 to 17 years (X = 15.9 years, SD + 0.81, from public and private schools. The level of physical activity was assessed through the International PhysicalActivity Questionnaire (IPAQ. Later, 48 teenagers underwent a lipidogram (lipid profile. Lipid concentrations of total cholesterol (TC, HDL-c (high density lipoprotein and LDL (low density lipoprotein and triglycerides (TGL were determined and assessed according to cutoff points proposed by the III Brazilian Guidelines on dyslipidemias and Guideline of Atherosclerosis, Department of Atherosclerosis of Brazilian Society of Cardiology. Statisticalanalysis was performed by binomial test for proportions and Pearson’s correlation test, adopting p <0.05. Results: Applying IPAQ we found a percentage of 77.7% active adolescents and 22.3% of insufficiently active adolescents, with the highest percentage of active teens inmales (p = 0.0000. Adolescents of both sexes from public network were considered more active than teens from private schools. The lipid profile of the studied adolescents was within normal range. Conclusion: There was no relationship between physical activity level and lipid profile of the adolescents assessed.

Investigation of fitting capability of active mirror for controlling ICF's focal profile

International Nuclear Information System (INIS)

Zeng Zhige; Ling Ning; Jiang Wenhan

1998-01-01

Laser beam's profile at focal plane can be controlled using active mirror in ICF system because the beam's profile has strong relationship with the surface of active mirror, the surface of active mirror can be changed at any time and maintained for a long time. The capabilities of fitting given wave-front (computed by Geometric Transformation Method) at conditions of different actuator numbers and different arrangement have been investigated by computer simulation. The computing results present that the needed laser profile can obtained by adaptive optical technology

Using Activity Metrics for DEVS Simulation Profiling

Directory of Open Access Journals (Sweden)

Muzy A.

2014-01-01

Full Text Available Activity metrics can be used to profile DEVS models before and during the simulation. It is critical to get good activity metrics of models before and during their simulation. Having a means to compute a-priori activity of components (analytic activity may be worth when simulating a model (or parts of it for the first time. After, during the simulation, analytic activity can be corrected using dynamic one. In this paper, we introduce McCabe cyclomatic complexity metric (MCA to compute analytic activity. Both static and simulation activity metrics have been implemented through a plug-in of the DEVSimPy (DEVS Simulator in Python language environment and applied to DEVS models.

Parametric dependencies of JET electron temperature profiles

Energy Technology Data Exchange (ETDEWEB)

Schunke, B [Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking; Imre, K; Riedel, K [New York Univ., NY (United States)

1994-07-01

The JET Ohmic, L-Mode and H-Mode electron temperature profiles obtained from the LIDAR Thomson Scattering Diagnostic are parameterized in terms of the normalized flux parameter and a set of the engineering parameters like plasma current, toroidal field, line averages electron density... It is shown that the electron temperature profiles fit a log-additive model well. It is intended to use the same model to predict the profile shape for D-T discharges in JET and in ITER. 2 refs., 5 figs.

State-dependent alterations of lipid profiles in patients with bipolar disorder.

Science.gov (United States)

Huang, Yu-Jui; Tsai, Shang-Ying; Chung, Kuo-Hsuan; Chen, Pao-Huan; Huang, Shou-Hung; Kuo, Chian-Jue

2018-07-01

Objective Serum lipid levels may be associated with the affective severity of bipolar disorder, but data on lipid profiles in Asian patients with bipolar disorder and the lipid alterations in different states of opposite polarities are scant. We investigated the lipid profiles of patients in the acute affective, partial, and full remission state in bipolar mania and depression. Methods The physically healthy patients aged between 18 and 45 years with bipolar I disorder, as well as age-matched healthy normal controls were enrolled. We compared the fasting blood levels of glucose, cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein of manic or depressed patients in the acute phase and subsequent partial and full remission with those of their normal controls. Results A total of 32 bipolar manic patients (12 women and 20 men), 32 bipolar depressed participants (18 women and 14 men), and 64 healthy control participants took part in this study. The mean cholesterol level in acute mania was significantly lower than that in acute depression (p bipolar mania. Conclusion Circulating lipid profiles may be easily affected by affective states. The acute manic state may be accompanied by state-dependent lower cholesterol and triglyceride levels relative to that in other mood states.

The Genetic Activity Profile database.

Science.gov (United States)

Waters, M D; Stack, H F; Garrett, N E; Jackson, M A

1991-12-01

A graphic approach termed a Genetic Activity Profile (GAP) has been developed to display a matrix of data on the genetic and related effects of selected chemical agents. The profiles provide a visual overview of the quantitative (doses) and qualitative (test results) data for each chemical. Either the lowest effective dose (LED) or highest ineffective dose (HID) is recorded for each agent and bioassay. Up to 200 different test systems are represented across the GAP. Bioassay systems are organized according to the phylogeny of the test organisms and the end points of genetic activity. The methodology for the production and evaluation of GAPs has been developed in collaboration with the International Agency for Research on Cancer. Data on individual chemicals have been compiled by IARC and by the U.S. Environmental Protection Agency. Data are available on 299 compounds selected from volumes 1-50 of the IARC Monographs and on 115 compounds identified as Superfund Priority Substances. Software to display the GAPs on an IBM-compatible personal computer is available from the authors. Structurally similar compounds frequently display qualitatively and quantitatively similar GAPs. By examining the patterns of GAPs of pairs and groups of chemicals, it is possible to make more informed decisions regarding the selection of test batteries to be used in evaluating chemical analogs. GAPs have provided useful data for the development of weight-of-evidence hazard ranking schemes. Also, some knowledge of the potential genetic activity of complex environmental mixtures may be gained from assessing the GAPs of component chemicals. The fundamental techniques and computer programs devised for the GAP database may be used to develop similar databases in other disciplines.

Whole-body profile scanner for in vivo quantitative activity measurement

International Nuclear Information System (INIS)

Bergmann, H.

1978-01-01

A whole-body profile scanner has been developed by fitting parallel slit collimators to a shadow shield whole-body counter. Sensitivity, uniformity and resolution measurements were performed using a number of different counting conditions. It is shown that improved accuracy of activity measurements is obtained by using a wide window counting technique for low and medium energy gamma emitters (99m Tc, 131 I), whereas a photopeak window should be used for high energy gamma emitters (47 Ca). Due to the finite spatial resolution of the system a systematic error in evaluating regional activities from the counting rate profile occurs which is characterized by a spatial spillover factor. The spatial spillover factor is measured and is subsequently used to calculate the error on basis of a simple model. It is shown that only small errors are caused by spatial spillover when the length of a region is at least three times the full width half maximum of the point spread function. Applying the above mentioned simple rules it is concluded that profile scanning is a sensitive and accurate technique for activity measurements in vivo. Two examples of clinical applications (measurement of bone accretion rates of calcium and Tc-pyrophosphate, regional radioiodine retention in patients with thyroid carcinoma) and a review of the papers on profile scanning demonstrate the types of investigations in which profile scanning is superior to alternative techniques. (author)

Characteristic Changes in the Aroma Profile of Patchouli Depending on Manufacturing Process.

Science.gov (United States)

Hasegawa, Toshio; Yoshitome, Kazuma; Fujihara, Takashi; Santoso, Mardi; Aziz, Muhammad Abdul

2017-08-01

Patchouli is used as an incense material and essential oil. The characteristic odor of patchouli leaves results from the drying process used in their production; however, there have to date been no reports on the changes in the odor of patchouli leaves during the drying process. We investigated the aroma profile of dried patchouli leaves using the hexane extracts of fresh and dried patchouli leaves. We focused on the presence or absence of the constituents of the fresh and dried extracts, and the differences in the content of the common constituents. Fourteen constituents were identified as characteristic of dried patchouli extract odor by gas chromatography-olfactometry analysis. The structures of seven of the 14 constituents were determined by gas chromatography-mass spectrometry (α-patchoulene, seychellene, humulene, α-bulnesene, isoaromadendrene epoxide, caryophyllene oxide, and patchouli alcohol). The aroma profile of the essential oil obtained from the dried patchouli leaves was clearly different from that of dried patchouli. The aroma profile of the essential oil was investigated by a similar method. We identified 12 compounds as important odor constituents. The structures of nine of the 12 constituents were determined by gas chromatography-mass spectrometry (cis-thujopsene, caryophyllene, α-guaiene, α-patchoulene, seychellene, α-bulnesene, isoaromadendrene epoxide, patchouli alcohol, and corymbolone). Comparing the odors and constituents demonstrated that the aroma profile of patchouli depends on the manufacturing process.

Deciphering of ADP-induced, phosphotyrosine-dependent signaling networks in human platelets by Src-homology 2 region (SH2)-profiling.

Science.gov (United States)

Schweigel, Hardy; Geiger, Jörg; Beck, Florian; Buhs, Sophia; Gerull, Helwe; Walter, Ulrich; Sickmann, Albert; Nollau, Peter

2013-03-01

Tyrosine phosphorylation plays a central role in signal transduction controlling many important biological processes. In platelets, the activity of several signaling proteins is controlled by tyrosine phosphorylation ensuring proper platelet activation and aggregation essential for regulation of the delicate balance between bleeding and hemostasis. Here, we applied Src-homology 2 region (SH2)-profiling for deciphering of the phosphotyrosine state of human platelets activated by adenosine diphosphate (ADP). Applying a panel of 31 SH2-domains, rapid and complex regulation of the phosphotyrosine state of platelets was observed after ADP stimulation. Specific inhibition of platelet P2Y receptors by synthetic drugs revealed a major role for the P2Y1 receptor in tyrosine phosphorylation. Concomitant activation of protein kinase A (PKA) abolished ADP-induced tyrosine phosphorylation in a time and concentration-dependent manner. Given the fact that PKA activity is negatively regulated by the P2Y12 receptor, our data provide evidence for a novel link of synergistic control of the state of tyrosine phosphorylation by both P2Y receptors. By SH2 domain pull down and MS/MS analysis, we identified distinct tyrosine phosphorylation sites in cell adhesion molecules, intracellular adapter proteins and phosphatases suggesting a major, functional role of tyrosine phosphorylation of theses candidate proteins in ADP-dependent signaling in human platelets. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Linezolid-Dependent Function and Structure Adaptation of Ribosomes in a Staphylococcus epidermidis Strain Exhibiting Linezolid Dependence

Science.gov (United States)

Kokkori, Sofia; Apostolidi, Maria; Tsakris, Athanassios; Pournaras, Spyros

2014-01-01

Linezolid-dependent growth was recently reported in Staphylococcus epidermidis clinical strains carrying mutations associated with linezolid resistance. To investigate this unexpected behavior at the molecular level, we isolated active ribosomes from one of the linezolid-dependent strains and we compared them with ribosomes isolated from a wild-type strain. Both strains were grown in the absence and presence of linezolid. Detailed biochemical and structural analyses revealed essential differences in the function and structure of isolated ribosomes which were assembled in the presence of linezolid. The catalytic activity of peptidyltransferase was found to be significantly higher in the ribosomes derived from the linezolid-dependent strain. Interestingly, the same ribosomes exhibited an abnormal ribosomal subunit dissociation profile on a sucrose gradient in the absence of linezolid, but the profile was restored after treatment of the ribosomes with an excess of the antibiotic. Our study suggests that linezolid most likely modified the ribosomal assembly procedure, leading to a new functional ribosomal population active only in the presence of linezolid. Therefore, the higher growth rate of the partially linezolid-dependent strains could be attributed to the functional and structural adaptations of ribosomes to linezolid. PMID:24890589

The activity profile of elite male amateur boxing.

Science.gov (United States)

Davis, Philip; Benson, Peter R; Pitty, James D; Connorton, Andrew J; Waldock, Robert

2015-01-01

An activity profile of competitive 3 × 3-min elite-level amateur boxing was created from video footage of 29 Olympic final and semifinal bouts in 39 male boxers (mean ± SD) age 25.1 ± 3.6 y, height 178.3 ± 10.4 cm, and body mass 69.7 ± 16.5 kg. Boxing at this level requires the ability to maintain an activity rate of ~1.4 actions/s, consisting of ~20 punches, ~2.5 defensive movements, and ~47 vertical hip movements, all per minute, over 3 subsequent rounds lasting ~200 s each. Winners had higher total punches landed (P = .041) and a lower ratio of punches thrown to landed (P = .027) than losers in round 3. The hook rear-hand landed was also higher for winners than losers in round 2 (P = .038) and round 3 (P = .016), and defensive movements were used less by winners (P = .036). However, the results suggest that technical discrimination between winners and losers is difficult; bout outcome may be more dependent on which punch is "lucky" enough to be scored by the judges or who appears to be dominant on the day. This study gives both boxers and coaches a good idea of where subelite boxers need to aim if they want to become among the best amateur boxers in the world.

Elite futsal refereeing: Activity profile and physiological demands

DEFF Research Database (Denmark)

Rebelo, António N.; Ascensão, António A.; Magalhães, José F.

2011-01-01

Rebelo, AN, Ascensão, AA, Magalhães, JF, Bischoff, R, Bendiksen, M, and Krustrup, P. Elite futsal refereeing: activity profile and physiological demands. J Strength Cond Res 24(X): 000-000, 2010-The purpose of this study was to determine the physiological demands and to establish the relationship...... between activity profile and endurance capacity of futsal referees. Eighteen elite futsal referees (33.0 ± 5.1 years, 173 ± 5 cm, and 73.2 ± 8.4 kg) were studied. Video filming (n = 18) and heart rate (HR) recordings were performed throughout games. Blood lactate (n = 14) was determined at rest and after....... Considering the data obtained in the present study, the use of match-specific intermittent fitness tests to evaluate futsal referees seems to be required....

DS86 neutron dose. Monte Carlo analysis for depth profile of {sup 152}Eu activity in a large stone sample

Energy Technology Data Exchange (ETDEWEB)

Endo, Satoru; Hoshi, Masaharu; Takada, Jun [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine; Iwatani, Kazuo; Oka, Takamitsu; Shizuma, Kiyoshi; Imanaka, Tetsuji; Fujita, Shoichiro; Hasai, Hiromi

1999-06-01

The depth profile of {sup 152}Eu activity induced in a large granite stone pillar by Hiroshima atomic bomb neutrons was calculated by a Monte Carlo N-Particle Transport Code (MCNP). The pillar was on the Motoyasu Bridge, located at a distance of 132 m (WSW) from the hypocenter. It was a square column with a horizontal sectional size of 82.5 cm x 82.5 cm and height of 179 cm. Twenty-one cells from the north to south surface at the central height of the column were specified for the calculation and {sup 152}Eu activities for each cell were calculated. The incident neutron spectrum was assumed to be the angular fluence data of the Dosimetry System 1986 (DS86). The angular dependence of the spectrum was taken into account by dividing the whole solid angle into twenty-six directions. The calculated depth profile of specific activity did not agree with the measured profile. A discrepancy was found in the absolute values at each depth with a mean multiplication factor of 0.58 and also in the shape of the relative profile. The results indicated that a reassessment of the neutron energy spectrum in DS86 is required for correct dose estimation. (author)

The human red cell voltage-dependent cation channel. Part III: Distribution homogeneity and pH dependence

DEFF Research Database (Denmark)

Bennekou, P.; Barksmann, T. L.; Christophersen, P.

2006-01-01

The homogeneity of the distribution of the non-selective voltage-dependent cation channel (the NSVDC channel) in the human erythrocyte, and the pH dependence was investigated. Activation of this channel caused a uniform cellular dehydration, which was characterized by the changes in the erythrocyte...... osmotic resistance profiles: After 1/2 h of activation, the osmolarity at 50% hemolysis changed from 73 mM (control) to 34 mM NaCl, corresponding to 0.48% and 0.21% NaCl respectively. Unchanging standard deviations show participation of the entire erythrocyte population, which implies an even distribution...... of the NSVDC channel among the cells. Inactivation of the NSVDC channel with N-ethyl-maleimide (NEM) or blocking of the Cl- conductance with NS1652 retarded the migration of the resistance profiles towards lower osmolarities. The NSVDC channel activation was blocked by a decrease of the intracellular...

Dependence of ideal MHD kink and ballooning modes on plasma shape and profiles in tokamaks

International Nuclear Information System (INIS)

Todd, A.M.M.; Manickam, J.; Okabayashi, M.; Chance, M.S.; Grimm, R.C.; Greene, J.M.; Johnson, J.L.

1978-08-01

Extensive numerical studies of ideal MHD instabilities have been carried out to gain insight into the parametric dependence of critical β's in tokamaks. The large number of interrelated equilibrium quantities involved in establishing a critical β has demanded a careful, systematic survey in order to isolate this dependence. The results of this survey establish the scaling with geometrical quantities including aspect ratio, elongation, and triangularity in the parameter regimes appropriate for both current and reactor-sized plasmas. A moderate dependence on the pressure profile and a strong variation with the current profile is found. The principal result is that for aspect ratio R/a approximately equal to 3, critical β's are of the order of 2% for circular cross sections and 5% for plasmas with elongation K approximately equal to 2; somewhat higher values could be achieved with more optimal shaping. Finally, sequences of equilibria have been analyzed to compare critical β as a function of toroidal mode number n. We conclude that the infinite-n analytic ballooning theory provides a sufficient condition for ideal MHD internal mode stability. Low-n free boundary modes appear to set a lower limit

Activity-Based Profiling of Retaining β-Glucosidases: A Comparative Study

NARCIS (Netherlands)

Witte, Martin D.; Walvoort, Marthe T. C.; Li, Kah-Yee; Kallemeijn, Wouter W.; Donker-Koopman, Wilma E.; Boot, Rolf G.; Aerts, Johannes M. F. G.; Codée, Jeroen D. C.; van der Marel, Gijsbert A.; Overkleeft, Herman S.

2011-01-01

Activity-based protein profiling (ABPP) is a versatile strategy to report on enzyme activity in vitro, in situ, and in vivo. The development and use of ABPP tools and techniques has met with considerable success in monitoring physiological processes involving esterases and proteases. Activity-based

Activity-Based Profiling of Retaining beta-Glucosidases : A Comparative Study

NARCIS (Netherlands)

Witte, Martin D.; Walvoort, Marthe T. C.; Li, Kah-Yee; Kallemeijn, Wouter W.; Donker-Koopman, Wilma E.; Boot, Rolf G.; Aerts, Johannes M. F. G.; Codee, Jeroen D. C.; van der Marel, Gijsbert A.; Overkleeft, Herman S.

2011-01-01

Activity-based protein profiling (ABPP) is a versatile strategy to report on enzyme activity in vitro, in situ, and in vivo. The development and use of ABPP tools and techniques has met with considerable success in monitoring physiological processes involving esterases and proteases. Activity-based

Activity-Based Profiling of Retaining β-Glucosidases : A Comparative Study

NARCIS (Netherlands)

Witte, Martin D.; Walvoort, Marthe T.C.; Li, Kah-Yee; Kallemeijn, Wouter W.; Donker-Koopman, Wilma E.; Boot, Rolf G.; Aerts, Johannes M.F.G.; Codée, Jeroen D.C.; Marel, Gijsbert A. van der; Overkleeft, Herman S.

2011-01-01

Activity-based protein profiling (ABPP) is a versatile strategy to report on enzyme activity in vitro, in situ, and in vivo. The development and use of ABPP tools and techniques has met with considerable success in monitoring physiological processes involving esterases and proteases. Activity-based

Temporal profiles of age-dependent changes in cytokine mRNA expression and glial cell activation after status epilepticus in postnatal rat hippocampus.

Science.gov (United States)

Järvelä, Juha T; Lopez-Picon, Francisco R; Plysjuk, Anna; Ruohonen, Saku; Holopainen, Irma E

2011-04-08

Status epilepticus (SE) is proposed to lead to an age-dependent acute activation of a repertoire of inflammatory processes, which may contribute to neuronal damage in the hippocampus. The extent and temporal profiles of activation of these processes are well known in the adult brain, but less so in the developing brain. We have now further elucidated to what extent inflammation is activated by SE by investigating the acute expression of several cytokines and subacute glial reactivity in the postnatal rat hippocampus. SE was induced by an intraperitoneal (i.p.) injection of kainic acid (KA) in 9- and 21-day-old (P9 and P21) rats. The mRNA expression of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), matrix metalloproteinase-9 (MMP-9), glial-derived neurotrophic factor (GDNF), interferon gamma (IFN-γ), and transforming growth factor-beta 1 (TGF-β1) were measured from 4 h up to 3 days after KA injection with real-time quantitative PCR (qPCR). IL-1β protein expression was studied with ELISA, GFAP expression with western blotting, and microglial and astrocyte morphology with immunohistochemistry 3 days after SE. SE increased mRNA expression of IL-1β, TNF-α and IL-10 mRNA in hippocampus of both P9 and P21 rats, their induction being more rapid and pronounced in P21 than in P9 rats. MMP-9 expression was augmented similarly in both age groups and GDNF expression augmented only in P21 rats, whereas neither IFN-γ nor TGF-β1 expression was induced in either age group. Microglia and astrocytes exhibited activated morphology in the hippocampus of P21 rats, but not in P9 rats 3 d after SE. Microglial activation was most pronounced in the CA1 region and also detected in the basomedial amygdala. Our results suggest that SE provokes an age-specific cytokine expression in the acute phase, and age-specific glial cell activation in the subacute phase as verified now in the postnatal rat hippocampus. In the juvenile hippocampus

Comparing The Profile Of Chemical Dependents Hospitalized At A Chemical Dependency Unit In Porto Alegre/RS In 2002 And 2006

Directory of Open Access Journals (Sweden)

Leonel Tesch Formiga

2009-09-01

Full Text Available Background: Studies on the use of psychoactive substances have been focused on identifying risk and protective factors related to this behavior based on the definition of the epidemiologic profile of such populations. The objective of the present study is to compare the profiles of samples of chemical dependent patients hospitalized at a Detoxification Unit (DU in Porto Alegre, state of Rio Grande do Sul, Brazil, in 2002 with the patients hospitalized in 2006. Method: This is a cross-sectional, descriptive and retrospective study. The research was carried out using medical records. We used a convenience sample divided into two groups: 1 all patients hospitalized at the DU from September to December 2006 (n=118; 2 all patients hospitalized at the same Unit from April to May 2002 (n=202. Results: There was a significant increase in the use of marijuana, inhaled cocaine and crack and a decrease in the use of solvents; there was no change concerning the use of alcohol and injected cocaine. It is important to mention the increase in the prevalence of crack users, which increased from 21.8% to 61.9%. There was a decrease of almost 30% in the number of alcoholics who did not use other psychoactive substances except for tobacco in the 2006 sample. Psychiatric comorbidities were quite prevalent, and we can highlight a significant increase in the number of patients with personality disorders. Conclusion: We conclude that the profile of chemical dependents hospitalized for detoxification is changing; therefore, it is important that new therapeutic strategies are planned in order to better assist this population.

Probability of primordial black hole formation and its dependence on the radial profile of initial configurations

International Nuclear Information System (INIS)

Hidalgo, J. C.; Polnarev, A. G.

2009-01-01

In this paper we derive the probability of the radial profiles of spherically symmetric inhomogeneities in order to provide an improved estimation of the number density of primordial black holes (PBHs). We demonstrate that the probability of PBH formation depends sensitively on the radial profile of the initial configuration. We do this by characterizing this profile with two parameters chosen heuristically: the amplitude of the inhomogeneity and the second radial derivative, both evaluated at the center of the configuration. We calculate the joint probability of initial cosmological inhomogeneities as a function of these two parameters and then find a correspondence between these parameters and those used in numerical computations of PBH formation. Finally, we extend our heuristic study to evaluate the probability of PBH formation taking into account for the first time the radial profile of curvature inhomogeneities.

Profiles and Pauses: Two Practical Activities for the Writing Class

Directory of Open Access Journals (Sweden)

Ernest Hall

1998-01-01

Full Text Available Abstract : This article describes two classroom activities, "Profiling" and "Pause Analysis", that can be successfully used in ESL writing classes. "Profiling" addresses such problems as poor development of ideas, simplistic ideas, and lack of coherence in written texts. "Pause Analysis" focusses on the thinking processes that students engage in while drafting text, processes such as searching for ideas, evaluat­ing ideas, and postponing ideas. Both activities enable the instructor to assume the role of intervener in the students' writing processes, rather than evaluator of the text produced. In drawing The attention of the student write to both product and process, "Profiling" and "Pause Analysis" help them develop an awareness of the relation-ship between ideas in English expository text and the thinking pro­cesses that writers engage in while drafting such text.

Profiling Occupant Behaviour in Danish Dwellings using Time Use Survey Data - Part I: Data Description and Activity Profiling

DEFF Research Database (Denmark)

Barthelmes, V.M.; Li, R.; Andersen, R.K.

2018-01-01

Occupant behaviour has been shown to be one of the key driving factors of uncertainty in prediction of energy consumption in buildings. Building occupants affect building energy use directly and indirectly by interacting with building energy systems such as adjusting temperature set...... occupant profiles for prediction of energy use to reduce the gap between predicted and real building energy consumptions. To generate accurate occupant profiles for the residential sector in Denmark, the Danish time use surveys are considered an essential data source. The latest Danish diarybased time use......-points, switching lights on/off, using electrical devices and opening/closing windows. Furthermore, building inhabitants’ daily activity profiles clearly shape the timing of energy demand in households. Modelling energy-related human activities throughout the day, therefore, is crucial to defining more realistic...

Aripiprazole and Haloperidol Activate GSK3β-Dependent Signalling Pathway Differentially in Various Brain Regions of Rats.

Science.gov (United States)

Pan, Bo; Huang, Xu-Feng; Deng, Chao

2016-03-28

Aripiprazole, a dopamine D₂ receptor (D₂R) partial agonist, possesses a unique clinical profile. Glycogen synthase kinase 3β (GSK3β)-dependent signalling pathways have been implicated in the pathophysiology of schizophrenia and antipsychotic drug actions. The present study examined whether aripiprazole differentially affects the GSK3β-dependent signalling pathways in the prefrontal cortex (PFC), nucleus accumbens (NAc), and caudate putamen (CPu), in comparison with haloperidol (a D₂R antagonist) and bifeprunox (a D₂R partial agonist). Rats were orally administrated aripiprazole (0.75 mg/kg), bifeprunox (0.8 mg/kg), haloperidol (0.1 mg/kg) or vehicle three times per day for one week. The levels of protein kinase B (Akt), p-Akt, GSK3β, p-GSK3β, dishevelled (Dvl)-3, and β-catenin were measured by Western Blots. Aripiprazole increased GSK3β phosphorylation in the PFC and NAc, respectively, while haloperidol elevated it in the NAc only. However, Akt activity was not changed by any of these drugs. Additionally, both aripiprazole and haloperidol, but not bifeprunox, increased the expression of Dvl-3 and β-catenin in the NAc. The present study suggests that activation of GSK3β phosphorylation in the PFC and NAc may be involved in the clinical profile of aripiprazole; additionally, aripiprazole can increase GSK3β phosphorylation via the Dvl-GSK3β-β-catenin signalling pathway in the NAc, probably due to its relatively low intrinsic activity at D₂Rs.

Teachers’ goal orientation profiles and participation in professional development activities

NARCIS (Netherlands)

Kunst, E.M.; van Woerkom, M.; Poell, R.F.

2018-01-01

Participation in professional development activities is important for teachers to continuously improve their knowledge and skills. However, teachers differ in their attitude towards learning activities. This paper examined how different goal orientation profiles are related to participation in

A ranking method for the concurrent learning of compounds with various activity profiles.

Science.gov (United States)

Dörr, Alexander; Rosenbaum, Lars; Zell, Andreas

2015-01-01

In this study, we present a SVM-based ranking algorithm for the concurrent learning of compounds with different activity profiles and their varying prioritization. To this end, a specific labeling of each compound was elaborated in order to infer virtual screening models against multiple targets. We compared the method with several state-of-the-art SVM classification techniques that are capable of inferring multi-target screening models on three chemical data sets (cytochrome P450s, dehydrogenases, and a trypsin-like protease data set) containing three different biological targets each. The experiments show that ranking-based algorithms show an increased performance for single- and multi-target virtual screening. Moreover, compounds that do not completely fulfill the desired activity profile are still ranked higher than decoys or compounds with an entirely undesired profile, compared to other multi-target SVM methods. SVM-based ranking methods constitute a valuable approach for virtual screening in multi-target drug design. The utilization of such methods is most helpful when dealing with compounds with various activity profiles and the finding of many ligands with an already perfectly matching activity profile is not to be expected.

Direct transverse load profile determination using the polarization-dependent loss spectral response of a chirped fiber Bragg grating.

Science.gov (United States)

Descamps, Frédéric; Bette, Sébastien; Kinet, Damien; Caucheteur, Christophe

2016-06-01

The determination of stress profiles created by transverse loads was proved to be important in different domains, such as structural health monitoring and biomechanics, and, more specifically, in the prostheses domain. In this paper, we report an original method to estimate the transverse load profile from the polarization-dependent loss (PDL) spectrum of a chirped fiber Bragg grating (CFBG). This method makes use of the relationship between the integration of the PDL of a CFBG, and the force profile has the advantage of not requiring any iterative method to estimate the transverse load profile. The relationship linking the integration of the PDL and the force profile is demonstrated using an analytical approximation of the transmission spectrum of CFBGs. The validity of this method for the determination of non-uniform load profiles is then shown using a numerical analysis. An experimental demonstration is finally reported using a 48 mm-long CFBG subject to different step transverse load profiles.

Muscle activity pattern dependent pain development and alleviation.

Science.gov (United States)

Sjøgaard, Gisela; Søgaard, Karen

2014-12-01

Muscle activity is for decades considered to provide health benefits irrespectively of the muscle activity pattern performed and whether it is during e.g. sports, transportation, or occupational work tasks. Accordingly, the international recommendations for public health-promoting physical activity do not distinguish between occupational and leisure time physical activity. However, in this body of literature, attention has not been paid to the extensive documentation on occupational physical activity imposing a risk of impairment of health - in particular musculoskeletal health in terms of muscle pain. Focusing on muscle activity patterns and musculoskeletal health it is pertinent to elucidate the more specific aspects regarding exposure profiles and body regional pain. Static sustained muscle contraction for prolonged periods often occurs in the neck/shoulder area during occupational tasks and may underlie muscle pain development in spite of rather low relative muscle load. Causal mechanisms include a stereotype recruitment of low threshold motor units (activating type 1 muscle fibers) characterized by a lack of temporal as well as spatial variation in recruitment. In contrast during physical activities at leisure and sport the motor recruitment patterns are more dynamic including regularly relatively high muscle forces - also activating type 2 muscles fibers - as well as periods of full relaxation even of the type 1 muscle fibers. Such activity is unrelated to muscle pain development if adequate recovery is granted. However, delayed muscle soreness may develop following intensive eccentric muscle activity (e.g. down-hill skiing) with peak pain levels in thigh muscles 1-2 days after the exercise bout and a total recovery within 1 week. This acute pain profile is in contrast to the chronic muscle pain profile related to repetitive monotonous work tasks. The painful muscles show adverse functional, morphological, hormonal, as well as metabolic characteristics. Of

Application of metabolite profiling and antioxidant activity in ...

African Journals Online (AJOL)

This paper investigates the effect of processing and extraction method on chemical profiles and antioxidant activity of Malaysian stingless bee propolis. High Performance Thin Layer Chromatography (HPTLC) analysis in combination with chemometric shows that some of the compounds were degraded or not detected in ...

Activity-Based Protein Profiling of Ammonia Monooxygenase in Nitrosomonas europaea

Energy Technology Data Exchange (ETDEWEB)

Bennett, Kristen; Sadler, Natalie C.; Wright, Aaron T.; Yeager, Chris; Hyman, Michael R.; Löffler, F. E.

2016-01-29

Nitrosomonas europaeais an aerobic nitrifying bacterium that oxidizes ammonia (NH₃) to nitrite (NO₂^₋) through the sequential activities of ammonia monooxygenase (AMO) and hydroxylamine dehydrogenase (HAO). Many alkynes are mechanism-based inactivators of AMO, and here we describe an activity-based protein profiling method for this enzyme using 1,7-octadiyne (17OD) as a probe. Inactivation of NH₄⁺-dependent O₂uptake byN. europaeaby 17OD was time- and concentration-dependent. The effects of 17OD were specific for ammonia-oxidizing activity, andde novoprotein synthesis was required to reestablish this activity after cells were exposed to 17OD. Cells were reacted with Alexa Fluor 647 azide using a copper-catalyzed azide-alkyne cycloaddition (CuAAC) (click) reaction, solubilized, and analyzed by SDS-PAGE and infrared (IR) scanning. A fluorescent 28-kDa polypeptide was observed for cells previously exposed to 17OD but not for cells treated with either allylthiourea or acetylene prior to exposure to 17OD or for cells not previously exposed to 17OD. The fluorescent polypeptide was membrane associated and aggregated when heated with β-mercaptoethanol and SDS. The fluorescent polypeptide was also detected in cells pretreated with other diynes, but not in cells pretreated with structural homologs containing a single ethynyl functional group. The membrane fraction from 17OD-treated cells was conjugated with biotin-azide and solubilized in SDS. Streptavidin affinity-purified polypeptides were on-bead trypsin-digested, and amino acid sequences of the peptide fragments were determined by liquid chromatography-mass spectrometry (LC-MS) analysis. Peptide fragments from AmoA were the predominant peptides detected in 17OD-treated samples. In-gel digestion and

Chemical profiling and antioxidant activity of Bolivian propolis.

Science.gov (United States)

Nina, Nélida; Quispe, Cristina; Jiménez-Aspee, Felipe; Theoduloz, Cristina; Giménez, Alberto; Schmeda-Hirschmann, Guillermo

2016-04-01

Propolis is a relevant research subject worldwide. However, there is no information so far on Bolivian propolis. Ten propolis samples were collected from regions with high biodiversity in the main honey production places in Bolivia and were analyzed for their total phenolics (TP), flavonoids (TF) and antioxidant activity. The chemical profiles of the samples were assessed by TLC, HPLC-DAD, HPLC-DAD-MS/MS(n) and NMR analysis. TP, TF, TLC and NMR analysis showed significant chemical differences between the samples. Isolation of the main constituents by chromatography and identification by HPLC-DAD-MS/MS(n) achieved more than 35 constituents. According to their profiles, the Bolivian propolis can be classified into phenolic-rich and triterpene-rich samples. Propolis from the valleys (Cochabamba, Chuquisaca and Tarija) contained mainly prenylated phenylpropanoids, while samples from La Paz and Santa Cruz contained cycloartane and pentacyclic triterpenes. Phenolic-rich samples presented moderate to strong antioxidant activity while the triterpene-rich propolis were weakly active. High chemical diversity and differential antioxidant effects were found in Bolivian propolis. Our results provide additional evidence on the chemical composition and bioactivity of South American propolis. © 2015 Society of Chemical Industry.

Adolescent Physical Activity and Motivational Profiles While Keeping a Physical Activity Record

Science.gov (United States)

Fullmer, Matthew O.; Wilkinson, Carol; Prusak, Keven A.; Eggett, Dennis; Pennington, Todd

2018-01-01

Purpose: This study examined the relationship between adolescents (N = 124) from physical education classes keeping a daily online leisure-time physical activity (LTPA) record and feelings of competence toward LTPA, motivational profiles toward LTPA, and LTPA behaviors. Method: A repeated measures ANCOVA was used to examine the relationships…

Voltage Dependence of a Neuromodulator-Activated Ionic Current123

Science.gov (United States)

2016-01-01

Abstract The neuromodulatory inward current (IMI) generated by crab Cancer borealis stomatogastric ganglion neurons is an inward current whose voltage dependence has been shown to be crucial in the activation of oscillatory activity of the pyloric network of this system. It has been previously shown that IMI loses its voltage dependence in conditions of low extracellular calcium, but that this effect appears to be regulated by intracellular calmodulin. Voltage dependence is only rarely regulated by intracellular signaling mechanisms. Here we address the hypothesis that the voltage dependence of IMI is mediated by intracellular signaling pathways activated by extracellular calcium. We demonstrate that calmodulin inhibitors and a ryanodine antagonist can reduce IMI voltage dependence in normal Ca2+, but that, in conditions of low Ca2+, calmodulin activators do not restore IMI voltage dependence. Further, we show evidence that CaMKII alters IMI voltage dependence. These results suggest that calmodulin is necessary but not sufficient for IMI voltage dependence. We therefore hypothesize that the Ca2+/calmodulin requirement for IMI voltage dependence is due to an active sensing of extracellular calcium by a GPCR family calcium-sensing receptor (CaSR) and that the reduction in IMI voltage dependence by a calmodulin inhibitor is due to CaSR endocytosis. Supporting this, preincubation with an endocytosis inhibitor prevented W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride)-induced loss of IMI voltage dependence, and a CaSR antagonist reduced IMI voltage dependence. Additionally, myosin light chain kinase, which is known to act downstream of the CaSR, seems to play a role in regulating IMI voltage dependence. Finally, a Gβγ-subunit inhibitor also affects IMI voltage dependence, in support of the hypothesis that this process is regulated by a G-protein-coupled CaSR. PMID:27257619

Nicotine Dependence, Physical Activity, and Sedentary Behavior among Adult Smokers.

Science.gov (United States)

Loprinzi, Paul D; Walker, Jerome F

2015-03-01

Research has previously demonstrated an inverse association between smoking status and physical activity; however, few studies have examined the association between nicotine dependence and physical activity or sedentary behavior. This study examined the association between nicotine dependence and accelerometer-determined physical activity and sedentary behavior. Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used. A total of 851 adult (≥20 years) smokers wore an accelerometer for ≥4 days and completed the Fagerstrom Test for Nicotine Dependence scale. Regression models were used to examine the association between nicotine dependence and physical activity/sedentary behavior. After adjusting for age, gender, race-ethnicity, poverty level, hypertension, emphysema, bronchitis, body mass index (BMI), cotinine, and accelerometer wear time, smokers 50 + years of age with greater nicotine dependence engaged in more sedentary behavior (β = 11.4, P = 0.02) and less light-intensity physical activity (β = -9.6, P = 0.03) and moderate-to-vigorous physical activity (MVPA; β = -0.14, P = 0.003) than their less nicotine dependent counterparts. Older adults who are more nicotine dependent engage in less physical activity (both MVPA and light-intensity) and more sedentary behavior than their less nicotine dependent counterparts.

Complexity in pH-Dependent Ribozyme Kinetics: Dark pKa Shifts and Wavy Rate-pH Profiles.

Science.gov (United States)

Frankel, Erica A; Bevilacqua, Philip C

2018-02-06

Charged bases occur in RNA enzymes, or ribozymes, where they play key roles in catalysis. Cationic bases donate protons and perform electrostatic catalysis, while anionic bases accept protons. We previously published simulations of rate-pH profiles for ribozymes in terms of species plots for the general acid and general base that have been useful for understanding how ribozymes respond to pH. In that study, we did not consider interaction between the general acid and general base or interaction with other species on the RNA. Since that report, diverse small ribozyme classes have been discovered, many of which have charged nucleobases or metal ions in the active site that can either directly interact and participate in catalysis or indirectly interact as "influencers". Herein, we simulate experimental rate-pH profiles in terms of species plots in which reverse protonated charged nucleobases interact. These analyses uncover two surprising features of pH-dependent enzyme kinetics. (1) Cooperativity between the general acid and general base enhances population of the functional forms of a ribozyme and manifests itself as hidden or "dark" pK a shifts, real pK a shifts that accelerate the reaction but are not readily observed by standard experimental approaches, and (2) influencers favorably shift the pK a s of proton-transferring nucleobases and manifest themselves as "wavy" rate-pH profiles. We identify parallels with the protein enzyme literature, including reverse protonation and wavelike behavior, while pointing out that RNA is more prone to reverse protonation. The complexities uncovered, which arise from simple pairwise interactions, should aid deconvolution of complex rate-pH profiles for RNA and protein enzymes and suggest veiled catalytic devices for promoting catalysis that can be tested by experiment and calculation.

Secondary metabolites profiles and antioxidant activities of germinated brown and red rice

Science.gov (United States)

Nurnaistia, Y.; Aisyah, S.; Munawaroh, H. S. H.; Zackiyah

2018-05-01

The research aims to investigate the effect of germination on the secondary metabolite profiles and antioxidant activity of brown and red rice. The germination was performed by using a simple laboratory-scale machine that was designed and optimized to provide conditions that support the germination process. The germination was carried out for 2 days in dark conditions at 26°C and 99% humidity. Analysis of the secondary metabolite profile of ungerminated and germinated rice was performed using LC-MS. The antioxidant activities of ungerminated and germinated rice were done by using DPPH method. The results showed that the profiles of secondary metabolites of brown and red rice changed after germination. Some peaks were found to be induced in the germinated rice. However, some peaks were also loss during germination. The antioxidant activity of brown rice was slightly increased due to the germination, from 11.2% to 22.5%. Meanwhile the antioxidant activity of red rice was decreased after germination, from 73.8% to 60.0%.

Teachers' Goal Orientation Profiles and Participation in Professional Development Activities

Science.gov (United States)

Kunst, Eva M.; van Woerkom, Marianne; Poell, Rob F.

2018-01-01

Participation in professional development activities is important for teachers to continuously improve their knowledge and skills. However, teachers differ in their attitude towards learning activities. This paper examined how different goal orientation profiles are related to participation in professional development activities (acquiring…

Distribution of Metabolically Active Prokaryotes (Archaea and Bacteria) throughout the Profiles of Chernozem and Brown Semidesert Soil

Science.gov (United States)

Semenov, M. V.; Manucharova, N. A.; Stepanov, A. L.

2016-02-01

The distribution of metabolically active cells of archaea and bacteria in the profiles of typical chernozems (Voronezh oblast) and brown semidesert soils (Astrakhan oblast) of natural and agricultural ecosystems was studied using the method of fluorescent in situ hybridization (FISH). The studied soils differed sharply in the microbial biomass and in the numbers of metabolically active cells of archaea and bacteria. The number of active bacterial cells was 3.5-7.0 times greater than that of archaea. In the arable chernozem, the numbers of active cells of archaea and bacteria were 2.6 and 1.5 times, respectively, lower than those in the chernozem under the shelterbelt. The agricultural use of the brown semidesert soil had little effect on the abundances of bacteria and archaea. The soil organic carbon content was the major factor controlling the numbers of metabolically active cells of both domains. However, the dependence of the abundance of bacteria on the organic matter content was more pronounced. The decrease in the organic carbon and total nitrogen contents down the soil profiles was accompanied by the decrease in the bacteria: archaea ratio attesting to a better adaptation of archaea to the permanent deficiency of carbon and nitrogen. The bacteria: archaea ratio can serve as an ecotrophic indicator of the state of soil microbial communities.

Zinc-ion-dependent acid phosphatase exhibits magnesium-ion-dependent myo-inositol-1-phosphatase activity.

Science.gov (United States)

Fujimoto, S; Okano, I; Tanaka, Y; Sumida, Y; Tsuda, J; Kawakami, N; Shimohama, S

1996-06-01

We have purified bovine brain Zn(2+)-dependent acid phosphatase (Zn(2+)-APase), which requires Zn2+ ions to hydrolyze the substrate p-nitrophenyl phosphate (pNPP) in an acidic environment. The substrate specificity and metal requirement of Zn(2+)-APase at a physiological pH was also studied. The enzyme exhibited hydrolytic activity on myo-inositol-1- and -2-monophosphates, 2'-adenosine monophosphate, 2'-guanosine monophosphate, and the alpha- and beta-glycerophosphates, glucose-1-phosphate, and fructose-6-phosphate in 50 mM Tris-HCl buffer (pH 7.4) in the presence of Mg2+ ions, but not on pNPP and phosphotyrosine. Zn2+, Mn2+ and Co2+ ions were less effective for activation. Among the above substrates, myo-inositol-1-phosphate was the most susceptible to hydrolysis by the enzyme in the presence of 3 mM Mg2+ ions. The enzyme exhibited an optimum pH at around 8 for myo-inositol-1-phosphate in the presence of 3 mM Mg2+ ions. The Mg(2+)-dependent myo-inositol-1-phosphatase activity of the enzyme was significantly inhibited by Li+ ions. The Zn(2+)-dependent p-nitrophenyl phosphatase activity and Mg(2+)-dependent myo-inositol-1-phosphatase activity of the purified enzyme fraction exhibited similar behavior on Sephadex G-100 and Mono Q colomns. These findings suggest that Zn(2+)-APase also exhibits Mg(2+)-dependent myo-inositol-1-phosphatase activity under physiological conditions.

Relationships between physical education students' motivational profiles, enjoyment, state anxiety, and self-reported physical activity.

Science.gov (United States)

Yli-Piipari, Sami; Watt, Anthony; Jaakkola, Timo; Liukkonen, Jarmo; Nurmi, Jari-Erik

2009-01-01

The purpose of this study was to analyze motivational profiles based on the self-determination theory (Deci and Ryan, 2000) and how these profiles are related to physical education students' enjoyment, state anxiety, and physical activity. The participants, 429 sixth grade students (girls = 216; boys = 213) completed SMS, Sport Enjoyment Scale, PESAS, and Physical Activity Scale. Cluster analyses identified two motivational profiles: 1) the "High motivation profile", in which the students had high intrinsic and extrinsic motivation, and low levels of amotivation, and 2) the "Low motivation profile", in which the students had low intrinsic and extrinsic motivation, and low levels of amotivation. The students in the first cluster enjoyed physical education more and were physically more active. The results revealed that students may be motivated towards physical education lessons both intrinsically and extrinsically, and still experience enjoyment in physical education. Key pointsTWO MOTIVATIONAL PROFILES WERE REVEALED: 1) the "High motivation profile", in which the students had high intrinsic and extrinsic motivation, and low levels of amotivation, and 2) the "Low motivation profile", in which the students had low intrinsic and extrinsic motivation, and low levels of amotivation.The students in the first profile enjoyed physical education more and were physically more active than the students in the second profile.Moreover, the representatives of the "High motivation profile "experienced greater anxiety toward physical education than the representatives of the "Low motivation profile"These findings raised an interesting question whether students engaging in physical education benefit more from the presence of both self-determined and non-self-determined forms of motivation, or are the benefits higher if students are primarily self-determined?

Activity-dependent modulation of neural circuit synaptic connectivity

Directory of Open Access Journals (Sweden)

Charles R Tessier

2009-07-01

Full Text Available In many nervous systems, the establishment of neural circuits is known to proceed via a two-stage process; 1 early, activity-independent wiring to produce a rough map characterized by excessive synaptic connections, and 2 subsequent, use-dependent pruning to eliminate inappropriate connections and reinforce maintained synapses. In invertebrates, however, evidence of the activity-dependent phase of synaptic refinement has been elusive, and the dogma has long been that invertebrate circuits are “hard-wired” in a purely activity-independent manner. This conclusion has been challenged recently through the use of new transgenic tools employed in the powerful Drosophila system, which have allowed unprecedented temporal control and single neuron imaging resolution. These recent studies reveal that activity-dependent mechanisms are indeed required to refine circuit maps in Drosophila during precise, restricted windows of late-phase development. Such mechanisms of circuit refinement may be key to understanding a number of human neurological diseases, including developmental disorders such as Fragile X syndrome (FXS and autism, which are hypothesized to result from defects in synaptic connectivity and activity-dependent circuit function. This review focuses on our current understanding of activity-dependent synaptic connectivity in Drosophila, primarily through analyzing the role of the fragile X mental retardation protein (FMRP in the Drosophila FXS disease model. The particular emphasis of this review is on the expanding array of new genetically-encoded tools that are allowing cellular events and molecular players to be dissected with ever greater precision and detail.

Partial dust obscuration in active galactic nuclei as a cause of broad-line profile and lag variability, and apparent accretion disc inhomogeneities

Science.gov (United States)

Gaskell, C. Martin; Harrington, Peter Z.

2018-04-01

The profiles of the broad emission lines of active galactic nuclei (AGNs) and the time delays in their response to changes in the ionizing continuum ("lags") give information about the structure and kinematics of the inner regions of AGNs. Line profiles are also our main way of estimating the masses of the supermassive black holes (SMBHs). However, the profiles often show ill-understood, asymmetric structure and velocity-dependent lags vary with time. Here we show that partial obscuration of the broad-line region (BLR) by outflowing, compact, dusty clumps produces asymmetries and velocity-dependent lags similar to those observed. Our model explains previously inexplicable changes in the ratios of the hydrogen lines with time and velocity, the lack of correlation of changes in line profiles with variability of the central engine, the velocity dependence of lags, and the change of lags with time. We propose that changes on timescales longer than the light-crossing time do not come from dynamical changes in the BLR, but are a natural result of the effect of outflowing dusty clumps driven by radiation pressure acting on the dust. The motion of these clumps offers an explanation of long-term changes in polarization. The effects of the dust complicate the study of the structure and kinematics of the BLR and the search for sub-parsec SMBH binaries. Partial obscuration of the accretion disc can also provide the local fluctuations in luminosity that can explain sizes deduced from microlensing.

Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans.

Science.gov (United States)

Higaki, Kazutaka; Choe, Sally Y; Löbenberg, Raimar; Welage, Lynda S; Amidon, Gordon L

2008-09-01

The relationship of gastric motor activity and gastric emptying of 0.7 mm caffeine pellets with their absorption was investigated in the fed state in healthy human subjects by simultaneous monitoring of antral motility and plasma concentrations. A kinetic model for gastric emptying-dependent absorption yielded multiple phases of gastric emptying and rate constants (k(g)) with large inter-individual differences and large variability in onset of gastric emptying (50-175 min). The model suggests that 50% of the dose is emptied in 1-2h and over 90% emptied by 3.5h following dosing, in all subjects. The maximum values of k(g) (k(g)(max)) were much greater than those reported for emptying of liquids in the fasted state and were comparable to k(g) values in the late Phase II/III of the migrating motor complex (MMC). The model described the observed irregular absorption rate-time and plasma concentration-time profiles adequately but not in detail. The model was more successful at simulating double-peak phenomena in absorption rate profiles and onset of caffeine absorption. The results suggest that gastric emptying regulates drug absorption of small particles in the fed state. Further, estimates of k(a) derived using the time-dependent absorption model were closer to the intrinsic absorption rate constant for caffeine.

Profiling of REST-dependent microRNAs reveals dynamic modes of expression

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Zhengliang eGao

2012-05-01

Full Text Available Multipotent neural stem cells (NSCs possess the ability to self-renew and differentiate into both neurons and glia. However, the detailed mechanisms underlying NSC fate decisions are not well understood. Recent work suggest that the interaction between cell-type specific transcription factors and microRNAs (miRNAs is important as resident neural stem/progenitor cells give rise to functionally mature neurons. Recently, we demonstrated that the transcriptional repressor REST (RE1-silencing transcription factor is essential to prevent precocious neuronal differentiation and maintain NSC self-renewal in the adult hippocampus. Here we show that REST is required for orchestrating the expression of distinct subsets of miRNAs in primary mouse NSC cultures, a physiologically relevant cell type. Using miRNA array profiling, we identified known REST-regulated miRNA genes, as well as previously uncharacterized REST-dependent miRNAs. Interestingly, REST-regulated miRNAs undergo dynamic expression changes under differentiation conditions over time, but not under proliferation conditions. These results suggest that REST functions in a context-dependent manner through its target miRNAs for mediating neuronal production.

Impact of Physical Activity on Obesity and Lipid Profile of Adults with Intellectual Disability

Science.gov (United States)

Gawlik, Krystyna; Zwierzchowska, Anna; Celebanska, Diana

2018-01-01

Introduction: This study assessed overweight, obesity and lipid profiles in adults with intellectual disability and compared these metrics with their physical activity. Materials and Method: Basic somatic parameters, lipid profile and weekly physical activity were examined in 27 adults with moderate intellectual disability. Chi-square independence…

Neurotrophin release by neurotrophins: Implications for activity-dependent neuronal plasticity

OpenAIRE

Canossa, Marco; Griesbeck, Oliver; Berninger, Benedikt; Campana, Gabriele; Kolbeck, Roland; Thoenen, Hans

1997-01-01

Neurotrophins, secreted in an activity-dependent manner, are thought to be involved in the activity-dependent refinement of synaptic connections. Here we demonstrate that in hippocampal neurons and the rat pheochromocytoma cell line PC12 application of exogenous neurotrophins induces secretion of neurotrophins, an effect that is mediated by the activation of tyrosine kinase neurotrophin receptors (Trks). Like activity-dependent secretion of neurotrophins, neurotrophin-induced neurotrophin sec...

Puerarin activates endothelial nitric oxide synthase through estrogen receptor-dependent PI3-kinase and calcium-dependent AMP-activated protein kinase

International Nuclear Information System (INIS)

Hwang, Yong Pil; Kim, Hyung Gyun; Hien, Tran Thi; Jeong, Myung Ho; Jeong, Tae Cheon; Jeong, Hye Gwang

2011-01-01

The cardioprotective properties of puerarin, a natural product, have been attributed to the endothelial nitric oxide synthase (eNOS)-mediated production of nitric oxide (NO) in EA.hy926 endothelial cells. However, the mechanism by which puerarin activates eNOS remains unclear. In this study, we sought to identify the intracellular pathways underlying eNOS activation by puerarin. Puerarin induced the activating phosphorylation of eNOS on Ser1177 and the production of NO in EA.hy926 cells. Puerarin-induced eNOS phosphorylation required estrogen receptor (ER)-mediated phosphatidylinositol 3-kinase (PI3K)/Akt signaling and was reversed by AMP-activated protein kinase (AMPK) and calcium/calmodulin-dependent kinase II (CaMKII) inhibition. Importantly, puerarin inhibited the adhesion of tumor necrosis factor (TNF)-α-stimulated monocytes to endothelial cells and suppressed the TNF-α induced expression of intercellular cell adhesion molecule-1. Puerarin also inhibited the TNF-α-induced nuclear factor-κB activation, which was attenuated by pretreatment with N G -nitro-L-arginine methyl ester, a NOS inhibitor. These results indicate that puerarin stimulates eNOS phosphorylation and NO production via activation of an estrogen receptor-mediated PI3K/Akt- and CaMKII/AMPK-dependent pathway. Puerarin may be useful for the treatment or prevention of endothelial dysfunction associated with diabetes and cardiovascular disease. -- Highlights: ► Puerarin induced the phosphorylation of eNOS and the production of NO. ► Puerarin activated eNOS through ER-dependent PI3-kinase and Ca 2+ -dependent AMPK. ► Puerarin-induced NO was involved in the inhibition of NF-kB activation. ► Puerarin may help for prevention of vascular dysfunction and diabetes.

HCl and ClO in activated Arctic air; first retrieved vertical profiles from TELIS submillimetre limb spectra

Directory of Open Access Journals (Sweden)

A. de Lange

2012-02-01

Full Text Available The first profile retrieval results of the Terahertz and submillimeter Limb Sounder (TELIS balloon instrument are presented. The spectra are recorded during a 13-h balloon flight on 24 January 2010 from Kiruna, Sweden. The TELIS instrument was mounted on the MIPAS-B2 gondola and shared this platform with the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS and the mini-Differential Optical Absorption Spectroscopy (mini-DOAS instruments. The flight took place within the Arctic vortex at an altitude of ≈34 km in chlorine activated air, and both active (ClO and inactive chlorine (HCl were measured over an altitude range of respectively ≈16–32 km and ≈10–32 km. In this altitude range, the increase of ClO concentration levels during sunrise has been recorded with a temporal resolution of one minute. During the daytime equilibrium, a maximum ClO level of 2.1 ± 0.3 ppbv has been observed at an altitude of 23.5 km. This equilibrium profile is validated against the ClO profile by the satellite instrument Microwave Limb Sounder (MLS aboard EOS Aura. HCl profiles have been determined from two different isotopes – H³⁵Cl and H³⁷Cl – and are also validated against MLS. The precision of all profiles is well below 0.01 ppbv and the overall accuracy is therefore governed by systematic effects. The total uncertainty of these effects is estimated to be maximal 0.3 ppbv for ClO around its peak value at 23.5 km during the daytime equilibrium, and for HCl it ranges from 0.05 to 0.4 ppbv, depending on altitude. In both cases the main uncertainty stems from a largely unknown non-linear response in the detector.

Profiles of Nature Exposure and Outdoor Activities Associated With Occupational Well-Being Among Employees

Science.gov (United States)

Hyvönen, Katriina; Törnroos, Kaisa; Salonen, Kirsi; Korpela, Kalevi; Feldt, Taru; Kinnunen, Ulla

2018-01-01

This research addresses the profiles of nature exposure and outdoor activities in nature among Finnish employees (N = 783). The profiles were formed on the bases of nature exposure at work and the frequency and type of outdoor activities in nature engaged in during leisure time. The profiles were investigated in relation to work engagement and burnout. The latent profile analysis identified a five-class solution as the best model: High exposure (8%), Versatile exposure (22%), Unilateral exposure (38%), Average exposure (13%), and Low exposure (19%). An Analysis of Covariance (ANCOVA) was conducted for each well-being outcome in order to evaluate how the identified profiles related to occupational well-being. Participants with a High, Versatile, or Unilateral exposure profile reported significantly higher work engagement in the dimensions of vigor and dedication than did the participants with a Low exposure profile. The participants with the High exposure profile also reported lower burnout in the dimensions of cynicism and professional inadequacy than the participants with the Low exposure profile. Nature exposure during the workday and leisure time is an under researched but important aspect in promoting occupational well-being. PMID:29867699

Use of focused ultrasonication in activity-based profiling of deubiquitinating enzymes in tissue

OpenAIRE

Nanduri, Bindu; Shack, Leslie A.; Rai, Aswathy N.; Epperson, William B.; Baumgartner, Wes; Schmidt, Ty B.; Edelmann, Mariola J.

2016-01-01

To develop a reproducible tissue-lysis method that retains enzyme function for activity-based protein profiling, we compared four different tissue lysis methods of bovine lung tissue: focused ultrasonication, standard sonication, mortar & pestle method, and homogenization combined with standard sonication. Focused ultrasonication and mortar & pestle methods were sufficiently effective for activity-based profiling of deubiquitinases in tissue and focused ultrasonication had also the fastest pr...

Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions.

Science.gov (United States)

Ismail, Hanafy M; O'Neill, Paul M; Hong, David W; Finn, Robert D; Henderson, Colin J; Wright, Aaron T; Cravatt, Benjamin F; Hemingway, Janet; Paine, Mark J I

2013-12-03

Pyrethroid insecticides are used to control diseases spread by arthropods. We have developed a suite of pyrethroid mimetic activity-based probes (PyABPs) to selectively label and identify P450s associated with pyrethroid metabolism. The probes were screened against pyrethroid-metabolizing and nonmetabolizing mosquito P450s, as well as rodent microsomes, to measure labeling specificity, plus cytochrome P450 oxidoreductase and b5 knockout mouse livers to validate P450 activation and establish the role for b5 in probe activation. Using PyABPs, we were able to profile active enzymes in rat liver microsomes and identify pyrethroid-metabolizing enzymes in the target tissue. These included P450s as well as related detoxification enzymes, notably UDP-glucuronosyltransferases, suggesting a network of associated pyrethroid-metabolizing enzymes, or "pyrethrome." Considering the central role P450s play in metabolizing insecticides, we anticipate that PyABPs will aid in the identification and profiling of P450s associated with insecticide pharmacology in a wide range of species, improving understanding of P450-insecticide interactions and aiding the development of unique tools for disease control.

Use of focused ultrasonication in activity-based profiling of deubiquitinating enzymes in tissue.

Science.gov (United States)

Nanduri, Bindu; Shack, Leslie A; Rai, Aswathy N; Epperson, William B; Baumgartner, Wes; Schmidt, Ty B; Edelmann, Mariola J

2016-12-15

To develop a reproducible tissue lysis method that retains enzyme function for activity-based protein profiling, we compared four different methods to obtain protein extracts from bovine lung tissue: focused ultrasonication, standard sonication, mortar & pestle method, and homogenization combined with standard sonication. Focused ultrasonication and mortar & pestle methods were sufficiently effective for activity-based profiling of deubiquitinases in tissue, and focused ultrasonication also had the fastest processing time. We used focused-ultrasonicator for subsequent activity-based proteomic analysis of deubiquitinases to test the compatibility of this method in sample preparation for activity-based chemical proteomics. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of parameters of bone profile and homocysteine in physically active and non-active postmenopausal females.

Science.gov (United States)

Tariq, Sundus; Lone, Khalid Parvez; Tariq, Saba

2016-01-01

Optimal physical activity is important in attaining a peak bone mass. Physically active women have better bone mineral density and reduce fracture risk as compared to females living a sedentary life. The objective of this study was to compare parameters of bone profile and serum homocysteine levels in physically active and non-active postmenopausal females. In this cross sectional study postmenopausal females between 50-70 years of age were recruited and divided into two groups: Physically inactive (n=133) performing light physical activity and Physically active (n=34) performing moderate physical activity. Physical activity (in metabolic equivalents), bone mineral density and serum homocysteine levels were assessed. Spearman's rho correlation was applied to observe correlations. Two independent sample t test and Mann Whitney U test were applied to compare groups. P-value ≤ 0.05 was taken statistically significant. Parameters of bone profile were significantly higher and serum homocysteine levels were significantly lower in postmenopausal females performing moderate physical activity as compared to females performing light physical activity. Homocysteine was not significantly related to T-score and Z-score in both groups. Improving physical activity could be beneficial for improving the quality of bone, decreasing fracture risk and decreasing serum homocysteine levels.

Puerarin activates endothelial nitric oxide synthase through estrogen receptor-dependent PI3-kinase and calcium-dependent AMP-activated protein kinase

Energy Technology Data Exchange (ETDEWEB)

Hwang, Yong Pil; Kim, Hyung Gyun [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Hien, Tran Thi [College of Pharmacy, Chosun University, Gwangju (Korea, Republic of); Jeong, Myung Ho [Heart Research Center, Chonnam National University Hospital, Gwangju (Korea, Republic of); Jeong, Tae Cheon, E-mail: taecheon@ynu.ac.kr [College of Pharmacy, Yeungnam University, Gyungsan (Korea, Republic of); Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of)

2011-11-15

The cardioprotective properties of puerarin, a natural product, have been attributed to the endothelial nitric oxide synthase (eNOS)-mediated production of nitric oxide (NO) in EA.hy926 endothelial cells. However, the mechanism by which puerarin activates eNOS remains unclear. In this study, we sought to identify the intracellular pathways underlying eNOS activation by puerarin. Puerarin induced the activating phosphorylation of eNOS on Ser1177 and the production of NO in EA.hy926 cells. Puerarin-induced eNOS phosphorylation required estrogen receptor (ER)-mediated phosphatidylinositol 3-kinase (PI3K)/Akt signaling and was reversed by AMP-activated protein kinase (AMPK) and calcium/calmodulin-dependent kinase II (CaMKII) inhibition. Importantly, puerarin inhibited the adhesion of tumor necrosis factor (TNF)-{alpha}-stimulated monocytes to endothelial cells and suppressed the TNF-{alpha} induced expression of intercellular cell adhesion molecule-1. Puerarin also inhibited the TNF-{alpha}-induced nuclear factor-{kappa}B activation, which was attenuated by pretreatment with N{sup G}-nitro-L-arginine methyl ester, a NOS inhibitor. These results indicate that puerarin stimulates eNOS phosphorylation and NO production via activation of an estrogen receptor-mediated PI3K/Akt- and CaMKII/AMPK-dependent pathway. Puerarin may be useful for the treatment or prevention of endothelial dysfunction associated with diabetes and cardiovascular disease. -- Highlights: Black-Right-Pointing-Pointer Puerarin induced the phosphorylation of eNOS and the production of NO. Black-Right-Pointing-Pointer Puerarin activated eNOS through ER-dependent PI3-kinase and Ca{sup 2+}-dependent AMPK. Black-Right-Pointing-Pointer Puerarin-induced NO was involved in the inhibition of NF-kB activation. Black-Right-Pointing-Pointer Puerarin may help for prevention of vascular dysfunction and diabetes.

Examining the profile of high-potency cannabis and its association with severity of cannabis dependence.

Science.gov (United States)

Freeman, T P; Winstock, A R

2015-11-01

Cannabis use is decreasing in England and Wales, while demand for cannabis treatment in addiction services continues to rise. This could be partly due to an increased availability of high-potency cannabis. Adults residing in the UK were questioned about their drug use, including three types of cannabis (high potency: skunk; low potency: other grass, resin). Cannabis types were profiled and examined for possible associations between frequency of use and (i) cannabis dependence, (ii) cannabis-related concerns. Frequent use of high-potency cannabis predicted a greater severity of dependence [days of skunk use per month: b = 0.254, 95% confidence interval (CI) 0.161-0.357, p effect became stronger as age decreased (b = -0.006, 95% CI -0.010 to -0.002, p = 0.004). By contrast, use of low-potency cannabis was not associated with dependence (days of other grass use per month: b = 0.020, 95% CI -0.029 to 0.070, p = 0.436; days of resin use per month: b = 0.025, 95% CI -0.019 to 0.067, p = 0.245). Frequency of cannabis use (all types) did not predict severity of cannabis-related concerns. High-potency cannabis was clearly distinct from low-potency varieties by its marked effects on memory and paranoia. It also produced the best high, was preferred, and most available. High-potency cannabis use is associated with an increased severity of dependence, especially in young people. Its profile is strongly defined by negative effects (memory, paranoia), but also positive characteristics (best high, preferred type), which may be important when considering clinical or public health interventions focusing on cannabis potency.

Solutions of the Bogoliubov–de Gennes equation with position dependent Fermi-velocity and gap profiles

Energy Technology Data Exchange (ETDEWEB)

Presilla, M. [Dipartimento di Fisica e Geologia, Università degli Studi di Perugia, Via A. Pascoli, I-06123 Perugia (Italy); Panella, O., E-mail: orlando.panella@pg.infn.it [Istituto Nazionale di Fisica Nucleare, Sezione di Perugia, Via A. Pascoli, I-06123 Perugia (Italy); Roy, P. [Physics and Applied Mathematics Unit, Indian Statistical Institute, Kolkata-700108 (India)

2017-02-19

It is shown that bound state solutions of the one dimensional Bogoliubov–de Gennes (BdG) equation may exist when the Fermi velocity becomes dependent on the space coordinate. The existence of bound states in continuum (BIC) like solutions has also been confirmed both in the normal phase as well as in the super-conducting phase. We also show that a combination of Fermi velocity and gap parameter step-like profiles provides scattering solutions with normal reflection and transmission. - Highlights: • Bound states of BdG equation via Fermi velocity modulation. • Existence of bound states in continuum in both the normal and the superconducting phase. • Scattering solutions and bound states within a combination of step-like Fermi velocity and gap profiles.

RELATIONSHIPS BETWEEN PHYSICAL EDUCATION STUDENTS' MOTIVATIONAL PROFILES, ENJOYMENT, STATE ANXIETY, AND SELF-REPORTED PHYSICAL ACTIVITY

Directory of Open Access Journals (Sweden)

Sami Yli-Piipari

2009-09-01

Full Text Available The purpose of this study was to analyze motivational profiles based on the self-determination theory (Deci and Ryan, 2000 and how these profiles are related to physical education students' enjoyment, state anxiety, and physical activity. The participants, 429 sixth grade students (girls = 216; boys = 213 completed SMS, Sport Enjoyment Scale, PESAS, and Physical Activity Scale. Cluster analyses identified two motivational profiles: 1 the "High motivation profile", in which the students had high intrinsic and extrinsic motivation, and low levels of amotivation, and 2 the "Low motivation profile", in which the students had low intrinsic and extrinsic motivation, and low levels of amotivation. The students in the first cluster enjoyed physical education more and were physically more active. The results revealed that students may be motivated towards physical education lessons both intrinsically and extrinsically, and still experience enjoyment in physical education.

Passion and dependency in online shopping activities.

Science.gov (United States)

Wang, Chih-Chien; Yang, Hui-Wen

2007-04-01

This study examines the influence of harmonious passion (HP) and obsessive passion (OP) to online shopping dependency. The results show that both HP and OP might lead to online shopping dependency and online shoppers with OP are more dependent on online shopping activities. In addition, this study also found out that HP and OP could be denoted as a sequence of different intensities of passion, where HP might be a necessity of OP.

Variability of activity profile during medium-sided games in professional soccer

DEFF Research Database (Denmark)

Rago, Vincenzo; Silva, João R; Mohr, Magni

2018-01-01

BACKGROUND: In Southern European countries it is very frequent to perform medium-sized games (MSG) as last training drill. We analyzed the individual variability and changes in activity patterns during MSG throughout the preseason. METHODS: Activity profile during MSGs (10v10+goalkeepers, duratio...

Light-dependent electrogenic activity of cyanobacteria.

Directory of Open Access Journals (Sweden)

John M Pisciotta

2010-05-01

Full Text Available Cyanobacteria account for 20-30% of Earth's primary photosynthetic productivity and convert solar energy into biomass-stored chemical energy at the rate of approximately 450 TW [1]. These single-cell microorganisms are resilient predecessors of all higher oxygenic phototrophs and can be found in self-sustaining, nitrogen-fixing communities the world over, from Antarctic glaciers to the Sahara desert [2].Here we show that diverse genera of cyanobacteria including biofilm-forming and pelagic strains have a conserved light-dependent electrogenic activity, i.e. the ability to transfer electrons to their surroundings in response to illumination. Naturally-growing biofilm-forming photosynthetic consortia also displayed light-dependent electrogenic activity, demonstrating that this phenomenon is not limited to individual cultures. Treatment with site-specific inhibitors revealed the electrons originate at the photosynthetic electron transfer chain (P-ETC. Moreover, electrogenic activity was observed upon illumination only with blue or red but not green light confirming that P-ETC is the source of electrons. The yield of electrons harvested by extracellular electron acceptor to photons available for photosynthesis ranged from 0.05% to 0.3%, although the efficiency of electron harvesting likely varies depending on terminal electron acceptor.The current study illustrates that cyanobacterial electrogenic activity is an important microbiological conduit of solar energy into the biosphere. The mechanism responsible for electrogenic activity in cyanobacteria appears to be fundamentally different from the one exploited in previously discovered electrogenic bacteria, such as Geobacter, where electrons are derived from oxidation of organic compounds and transported via a respiratory electron transfer chain (R-ETC [3], [4]. The electrogenic pathway of cyanobacteria might be exploited to develop light-sensitive devices or future technologies that convert solar

Prenatal and adult androgen activities in alcohol dependence.

Science.gov (United States)

Lenz, B; Mühle, C; Braun, B; Weinland, C; Bouna-Pyrrou, P; Behrens, J; Kubis, S; Mikolaiczik, K; Muschler, M-R; Saigali, S; Sibach, M; Tanovska, P; Huber, S E; Hoppe, U; Eichler, A; Heinrich, H; Moll, G H; Engel, A; Goecke, T W; Beckmann, M W; Fasching, P A; Müller, C P; Kornhuber, J

2017-07-01

Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013-2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005-2007) and measured the 2D : 4D of their children (2013-2016). The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients' liver transaminase activities (P alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12-month hospital readmission in alcohol-dependent patients (P alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D). Androgen activities in alcohol-dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Match score affects activity profile and skill performance in professional Australian Football players.

Science.gov (United States)

Sullivan, Courtney; Bilsborough, Johann C; Cianciosi, Michael; Hocking, Joel; Cordy, Justin; Coutts, Aaron J

2014-05-01

To examine the influence of quarter outcome and the margin of the score differential on both the physical activity profile and skill performance of players during professional Australian Football matches. Prospective, longitudinal. Physical activity profiles were assessed via microtechnology (Global Positioning System and accelerometer) from 40 professional AF players from the same team during 15 Australian Football League games. Skill performance measures (involvement and effectiveness) and player rank scores (Champion Data(©) Rank) were provided by a commercial statistical provider. The physical performance variables, skill involvements and individual player performance scores were expressed relative to playing time for each quarter. The influence of the quarter result (i.e. win vs. loss) and score margin (i.e. small: 19 points) on activity profile and skill involvements and skill efficiency performance of players were examined. Skill involvements (total disposals/min, long kicks/min, marks/min, running bounces/min and player rank/min) were greater in quarters won (all p14.5 km h(-1), HSR/min), sprints/min and peak speed were higher in losing quarters (all pProfessional AF players are likely to have an increased physical activity profile and decreased skill involvement and proficiency when their team is less successful. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Dependence of L-mode confinement on the electron cyclotron power deposition profile in the TCV tokamak

Science.gov (United States)

Kirneva, N. A.; Razumova, K. A.; Pochelon, A.; Behn, R.; Coda, S.; Curchod, L.; Duval, B. P.; Goodman, T. P.; Labit, B.; Karpushov, A. N.; Rancic, M.; Sauter, O.; Silva, M.; TCV Team

2012-01-01

Scenarios with different electron cyclotron heating power profile distributions and widths were compared for the first time in experiments on the Tokamak à Configuration Variable (TCV). The heating profile was changed from shot to shot over a wide range from localized on-axis, with normalized minor radius half-width at half maximum σ1/2 ~ 0.1, up to a widely distributed heating power profile with σ1/2 ~ 0.4 and finally to a profile peaked far off-axis. The global confinement, MHD activity, density, temperature and electron pressure profile evolution were compared. In particular, the energy confinement properties of discharges with localized on-axis heating and distributed on-axis heating were very similar, with degradation close to that predicted by the ITER L-mode scaling; in the case of off-axis heating, on the other hand, the confinement degradation was even stronger.

Strain-dependent profile of misfolded prion protein aggregates.

Science.gov (United States)

Morales, Rodrigo; Hu, Ping Ping; Duran-Aniotz, Claudia; Moda, Fabio; Diaz-Espinoza, Rodrigo; Chen, Baian; Bravo-Alegria, Javiera; Makarava, Natallia; Baskakov, Ilia V; Soto, Claudio

2016-02-15

Prions are composed of the misfolded prion protein (PrP(Sc)) organized in a variety of aggregates. An important question in the prion field has been to determine the identity of functional PrP(Sc) aggregates. In this study, we used equilibrium sedimentation in sucrose density gradients to separate PrP(Sc) aggregates from three hamster prion strains (Hyper, Drowsy, SSLOW) subjected to minimal manipulations. We show that PrP(Sc) aggregates distribute in a wide range of arrangements and the relative proportion of each species depends on the prion strain. We observed a direct correlation between the density of the predominant PrP(Sc) aggregates and the incubation periods for the strains studied. The relative presence of PrP(Sc) in fractions of different sucrose densities was indicative of the protein deposits present in the brain as analyzed by histology. Interestingly, no association was found between sensitivity to proteolytic degradation and aggregation profiles. Therefore, the organization of PrP molecules in terms of the density of aggregates generated may determine some of the particular strain properties, whereas others are independent from it. Our findings may contribute to understand the mechanisms of strain variation and the role of PrP(Sc) aggregates in prion-induced neurodegeneration.

Size-dependent mortality rate profiles.

Science.gov (United States)

Roa-Ureta, Ruben H

2016-08-07

Knowledge of mortality rates is crucial to the understanding of population dynamics in populations of free-living fish and invertebrates in marine and freshwater environments, and consequently to sustainable resource management. There is a well developed theory of population dynamics based on age distributions that allow direct estimation of mortality rates. However, for most cases the aging of individuals is difficult or age distributions are not available for other reasons. The body size distribution is a widely available alternative although the theory underlying the formation of its shape is more complicated than in the case of age distributions. A solid theory of the time evolution of a population structured by any physiological variable has been developed in 1960s and 1970s by adapting the Hamilton-Jacobi formulation of classical mechanics, and equations to estimate the body size-distributed mortality profile have been derived for simple cases. Here I extend those results with regards to the size-distributed mortality profile to complex cases of non-stationary populations, individuals growing according to a generalised growth model and seasonally patterned recruitment pulses. I apply resulting methods to two cases in the marine environment, a benthic crustacean population that was growing during the period of observation and whose individuals grow with negative acceleration, and a sea urchin coastal population that is undergoing a stable cycle of two equilibrium points in population size whose individuals grow with varying acceleration that switches sign along the size range. The extension is very general and substantially widens the applicability of the theory. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dependence of the DIII-D beta limit on the current profile

Energy Technology Data Exchange (ETDEWEB)

Strait, E.J.; Chu, M.S.; Ferron, J.R.; Lao, L.L.; Osborne, T.H.; Taylor, T.S.; Turnbull, A.D. (General Atomics, San Diego, CA (United States)); Lazarus, E.A. (Oak Ridge National Lab., TN (United States))

1991-01-01

The maximum beta values achieved in DIII-D are not fully described by the simple scaling law [beta][sub max][proportional to]I/aB. There is, in addition, a dependence on the form of the current profile as parameterized by the safety factor q and internal inductance l[sub i]. The maximum experimentally achieved value of normalized beta [beta][sub N] = [beta]/(I/aB) varies from 3.5 at low safety factor q (q[sub 95]<3) to 5 at higher values of q. At low q, discharges are terminated by disruptions at high [beta][sub N] and at both the low and high l[sub i] boundaries of the stable range. These disruptions are attributed to external and global kink modes. At higher q, such disruptions are much less frequent, and beta is limited by slowly growing resistive modes, fishbones, and possibly by ballooning modes. At each value of q, the maximum beta tends to increase with internal inductance l[sub i]. A numerical study of kink mode stability has shown a similar trend for optimized pressure profiles. These observations have suggested a new scaling law for the operational beta limit: [beta][sub max]=4l[sub i](I/aB), which fits the DIII-D data well. (author) 13 refs., 4 figs.

Seasonal Dependence of Geomagnetic Active-Time Northern High-Latitude Upper Thermospheric Winds

Science.gov (United States)

Dhadly, Manbharat S.; Emmert, John T.; Drob, Douglas P.; Conde, Mark G.; Doornbos, Eelco; Shepherd, Gordon G.; Makela, Jonathan J.; Wu, Qian; Nieciejewski, Richard J.; Ridley, Aaron J.

2018-01-01

This study is focused on improving the poorly understood seasonal dependence of northern high-latitude F region thermospheric winds under active geomagnetic conditions. The gaps in our understanding of the dynamic high-latitude thermosphere are largely due to the sparseness of thermospheric wind measurements. With current observational facilities, it is infeasible to construct a synoptic picture of thermospheric winds, but enough data with wide spatial and temporal coverage have accumulated to construct a meaningful statistical analysis. We use long-term data from eight ground-based and two space-based instruments to derive climatological wind patterns as a function of magnetic local time, magnetic latitude, and season. These diverse data sets possess different geometries and different spatial and solar activity coverage. The major challenge is to combine these disparate data sets into a coherent picture while overcoming the sampling limitations and biases among them. In our previous study (focused on quiet time winds), we found bias in the Gravity Field and Steady State Ocean Circulation Explorer (GOCE) cross-track winds. Here we empirically quantify the GOCE bias and use it as a correction profile for removing apparent bias before empirical wind formulation. The assimilated wind patterns exhibit all major characteristics of high-latitude neutral circulation. The latitudinal extent of duskside circulation expands almost 10∘ from winter to summer. The dawnside circulation subsides from winter to summer. Disturbance winds derived from geomagnetic active and quiet winds show strong seasonal and latitudinal variability. Comparisons between wind patterns derived here and Disturbance Wind Model (DWM07) (which have no seasonal dependence) suggest that DWM07 is skewed toward summertime conditions.

Analysis of whey protein hydrolysates: peptide profile and ACE inhibitory activity

Directory of Open Access Journals (Sweden)

Marialice Pinto Coelho Silvestre

2012-12-01

Full Text Available The aim of this study was to prepare enzymatic hydrolysates from whey protein concentrate with a nutritionally adequate peptide profile and the ability to inhibit angiotensin-converting enzyme (ACE activity. The effects of the type of enzyme used (pancreatin or papain, the enzyme:substrate ratio (E:S ratio=0.5:100, 1:100, 2:100 and 3:100 and the use of ultrafiltration (UF were investigated. The fractionation of peptides was performed by size-exclusion-HPLC, and the quantification of the components of the chromatographic fractions was carried out by a rapid Corrected Fraction Area method. The ACE inhibitory activity (ACE-IA was determined by Reverse Phase-HPLC. All parameters tested affected both the peptide profile and the ACE-IA. The best peptide profile was achieved for the hydrolysates obtained with papain, whereas pancreatin was more advantageous in terms of ACE-IA. The beneficial effect of using a lower E:S ratio on the peptide profile and ACE-IA was observed for both enzymes depending on the conditions used to prepare the hydrolysates. The beneficial effect of not using UF on the peptide profile was observed in some cases for pancreatin and papain. However, the absence of UF yielded greater ACE-IA only when using papain.O objetivo deste estudo foi preparar hidrolisados enzimáticos do concentrado proteico do soro de leite com perfil peptídico nutricionalmente adequado e com capacidade para inibir a atividade da enzima conversora da angiotensina (ECA. Os efeitos do tipo de enzima usado (pancreatina ou papaína, da relação enzima:substrato (E:S=0,5:100, 1:100, 2:100 e 3:100 e do uso da ultrafiltração (UF foram investigados. O fracionamento dos peptídeos foi feito por CLAE de exclusão molecular e a quantificação dos componentes das frações cromatográficas foi realizada pelo método da Área Corrigida da Fração. A atividade inibitória da ECA (AI-ECA foi determinada por CLAE de fase reversa. Todos os parâmetros testados afetaram

Spectral backward radiation profile

International Nuclear Information System (INIS)

Kwon, Sung Duck; Lee, Keun Hyun; Kim, Bo Ra; Yoon, Suk Soo

2004-01-01

Ultrasonic backward radiation profile is frequency-dependent when incident region has deptional gradient of acoustical properties or multi-layers. Until now, we have measured the profiles of principal frequencies of used transducers so that it was not easy to understand the change of the frequency component and spectrum of backward radiation from the profile. We tried to measure the spectral backward radiation profiles using DFP(digital filer package) Lecroy DSO. The very big changes in the shape and pattern of spectral backward radiation profiles leads to the conclusion that this new try could be very effective tool to evaluate frequency dependent surface area.

Activity-Based Protein Profiling of Rhomboid Proteases in Liposomes

Czech Academy of Sciences Publication Activity Database

Wolf, E. V.; Seybold, M.; Hadravová, Romana; Stříšovský, Kvido; Verhelst, S. H. L.

2015-01-01

Roč. 16, č. 11 (2015), s. 1616-1621 ISSN 1439-4227 R&D Projects: GA MŠk(CZ) LK11206; GA MŠk LO1302 Institutional support: RVO:61388963 Keywords : activity-based protein profiling * chemical probes * inhibitors * intramembrane proteases * liposomes Subject RIV: CE - Biochemistry Impact factor: 2.850, year: 2015

Active Learning Strategies for Phenotypic Profiling of High-Content Screens.

Science.gov (United States)

Smith, Kevin; Horvath, Peter

2014-06-01

High-content screening is a powerful method to discover new drugs and carry out basic biological research. Increasingly, high-content screens have come to rely on supervised machine learning (SML) to perform automatic phenotypic classification as an essential step of the analysis. However, this comes at a cost, namely, the labeled examples required to train the predictive model. Classification performance increases with the number of labeled examples, and because labeling examples demands time from an expert, the training process represents a significant time investment. Active learning strategies attempt to overcome this bottleneck by presenting the most relevant examples to the annotator, thereby achieving high accuracy while minimizing the cost of obtaining labeled data. In this article, we investigate the impact of active learning on single-cell-based phenotype recognition, using data from three large-scale RNA interference high-content screens representing diverse phenotypic profiling problems. We consider several combinations of active learning strategies and popular SML methods. Our results show that active learning significantly reduces the time cost and can be used to reveal the same phenotypic targets identified using SML. We also identify combinations of active learning strategies and SML methods which perform better than others on the phenotypic profiling problems we studied. © 2014 Society for Laboratory Automation and Screening.

Gamma-ray scanning of neutron activated geological sediments for studying elemental profile distributions

International Nuclear Information System (INIS)

Ellinger, M.; Janghorbani, M.; Starke, K.

1976-01-01

Gamma-ray scanning for application to elemental profile studies of geological samples was studied with a neutron activated Baltic Shield sediment. Profile distribution of seven elements were measured. The capabilities and limitations of gamma-ray scanning are discussed by comparing the results with profiles obtained after the mechanical subdivision of the sample and the activation of the appropriately sized separates. With respect to the merits and limitations of scanning gamma-ray spectrometry applied to activated complex matrices the following conclusions were drawn. Qualitatively, the scanning method yields the same information as the much more laborious method of mechanical sudbisubdivision. Quantitatively, it is significantly less accurate. The scanning method has the significant advantage of allowing preservation of the sample. This could be important for such speciments as lunar and archeological materials. The method reduces sample preparation time and the possibility of sample contamination. (T.G.)

Field dependence-independence and participation in physical activity by college students.

Science.gov (United States)

Liu, Wenhao

2006-06-01

Field-independent individuals, compared with field-dependent individuals, have higher sports potential and advantages in sport-related settings. Little research, however, has been conducted on the association of field dependence-independence and participation in physical activity. The study examined this association for college students who participated in physical activities in and beyond physical education classes. The Group Embedded Figures Test distinguished 40 field-dependent from 40 field-independent participants. Activity logs during one semester showed that field-independent participants were significantly more physically active and their physical activity behaviors were more sport-related than those of field-dependent participants.

Physiological response and activity profile in recreational small-sided football

DEFF Research Database (Denmark)

Randers, Morten Bredsgaard; Nielsen, Jens Jung; Bangsbo, Jens

2014-01-01

We examined the effect of the number of players on the activity profile and physiological response to small-sided recreational football games with fixed relative pitch size. Twelve untrained men (age: 33.0 ± 6.4 (± standard deviation) years, fat%: 22.4 ± 6.1%, VO2 max: 43.3 ± 5.2 mL/min/kg) compl......We examined the effect of the number of players on the activity profile and physiological response to small-sided recreational football games with fixed relative pitch size. Twelve untrained men (age: 33.0 ± 6.4 (± standard deviation) years, fat%: 22.4 ± 6.1%, VO2 max: 43.3 ± 5.2 m......L/min/kg) completed three football sessions of 4 times 12 min with 3v3, 5v5, or 7v7 in a randomized order. Pitch sizes were 80 m(2) per player. Activity profile (10 Hz global positioning system), heart rate (HR), and rating of perceived exertion (RPE) were measured, and blood samples were collected before and during...... accelerations (500 ± 139 vs 459 ± 143 and 396 ± 144) were higher (P football games, with similar physiological responses for 6-14 players when pitch size is adapted, providing further evidence...

Profiling physical activity motivation based on self-determination theory: a cluster analysis approach.

Science.gov (United States)

Friederichs, Stijn Ah; Bolman, Catherine; Oenema, Anke; Lechner, Lilian

2015-01-01

In order to promote physical activity uptake and maintenance in individuals who do not comply with physical activity guidelines, it is important to increase our understanding of physical activity motivation among this group. The present study aimed to examine motivational profiles in a large sample of adults who do not comply with physical activity guidelines. The sample for this study consisted of 2473 individuals (31.4% male; age 44.6 ± 12.9). In order to generate motivational profiles based on motivational regulation, a cluster analysis was conducted. One-way analyses of variance were then used to compare the clusters in terms of demographics, physical activity level, motivation to be active and subjective experience while being active. Three motivational clusters were derived based on motivational regulation scores: a low motivation cluster, a controlled motivation cluster and an autonomous motivation cluster. These clusters differed significantly from each other with respect to physical activity behavior, motivation to be active and subjective experience while being active. Overall, the autonomous motivation cluster displayed more favorable characteristics compared to the other two clusters. The results of this study provide additional support for the importance of autonomous motivation in the context of physical activity behavior. The three derived clusters may be relevant in the context of physical activity interventions as individuals within the different clusters might benefit most from different intervention approaches. In addition, this study shows that cluster analysis is a useful method for differentiating between motivational profiles in large groups of individuals who do not comply with physical activity guidelines.

THE PROFILE OF OPIOID–DEPENDENT PATIENTS REFERRED TO SEMBADA HOSPITAL, MEDAN, INDONESIA

Directory of Open Access Journals (Sweden)

DATTEN BANGUN

2006-01-01

Full Text Available Drug dependence has become a real concern among parents in Indonesia and is now a national, as well as global health problem. The objectives of this study were to find out the profile of opioid-dependent patients referred to Sembada Hospital, Medan, North Sumatera Indonesia for treatment. Patients were interviewed when they were sober, using questionnaires. There were 45 participants, mostly below 30 years old, male, and not well educated and single or divorced. Almost all of them (95.6% had a smoking habit, which started at an early age. Most of the participants were either the eldest child (24.4% or the youngest child (35.6% in the family. Their first illicit drug was mostly marijuana (66.7%, which they started using before the age of 20 years. Polysubstance use was common. It was usually a combination of opioids, tobacco, cannabis and amphetamine. They used opioid by injection (heroin injecting drug user and out of 22 participants who agreed to a blood test, 20 were positive for hepatitis C. Many had been previously involved in various crimes.

Transcriptional profiling provides insights into metronomic cyclophosphamide-activated, innate immune-dependent regression of brain tumor xenografts

International Nuclear Information System (INIS)

Doloff, Joshua C; Waxman, David J

2015-01-01

Cyclophosphamide treatment on a six-day repeating metronomic schedule induces a dramatic, innate immune cell-dependent regression of implanted gliomas. However, little is known about the underlying mechanisms whereby metronomic cyclophosphamide induces innate immune cell mobilization and recruitment, or about the role of DNA damage and cell stress response pathways in eliciting the immune responses linked to tumor regression. Untreated and metronomic cyclophosphamide-treated human U251 glioblastoma xenografts were analyzed on human microarrays at two treatment time points to identify responsive tumor cell-specific factors and their upstream regulators. Mouse microarray analysis across two glioma models (human U251, rat 9L) was used to identify host factors and gene networks that contribute to the observed immune and tumor regression responses. Metronomic cyclophosphamide increased expression of tumor cell-derived DNA damage, cell stress, and cell death genes, which may facilitate innate immune activation. Increased expression of many host (mouse) immune networks was also seen in both tumor models, including complement components, toll-like receptors, interferons, and cytolysis pathways. Key upstream regulators activated by metronomic cyclophosphamide include members of the interferon, toll-like receptor, inflammatory response, and PPAR signaling pathways, whose activation may contribute to anti-tumor immunity. Many upstream regulators inhibited by metronomic cyclophosphamide, including hypoxia-inducible factors and MAP kinases, have glioma-promoting activity; their inhibition may contribute to the therapeutic effectiveness of the six-day repeating metronomic cyclophosphamide schedule. Large numbers of responsive cytokines, chemokines and immune regulatory genes linked to innate immune cell recruitment and tumor regression were identified, as were several immunosuppressive factors that may contribute to the observed escape of some tumors from metronomic CPA

ALIENATION, SENSATION SEEKING AND MULTIPHASIC PERSONALITY QUESTIONNAIRE PROFILE IN MEN BEING TREATED FOR ALCOHOL AND/OR OPIOID DEPENDENCE

Science.gov (United States)

Mattoo, Surendra K.; Varma, Vijoy K.; Singh, Ram Avatar; Khurana, Hitesh; Kaur, Rajinder; Sharma, Suresh K.

2001-01-01

Two hundred and thirty men, being treated for ICD-10 diagnosed dependence on alcohol, opioids or both, were studied 2-4 weeks after the last use of alcohol or opioids. Alienation Scale, Sensation Seeking Scale and Muliphasic Personality Questionnaire (MPQ), and selected sociodemographic and family history data were studied. All three groups showed high alienation (more in opioid cases), high sensation seeking (more in alcohol cases, more for boredom susceptibility), and a disturbed MPQ profile. The dual dependence group was similar to opioid group for age, but closer to alcohol group in terms of personality profile. Only alcohol cases showed a significantly positive correlation between alienation and sensation seeking- in terms of total scale, and boredom susceptibility and disinhibition subscales only. Thus, substance specificity was not reflected prominently in the inter-relationships between alienation, sensation seeking and MPQ scores, and sociodemographic variables. PMID:21407879

Comparison of parameters of bone profile and homocysteine in physically active and non-active postmenopausal females

OpenAIRE

Tariq, Sundus; Lone, Khalid Parvez; Tariq, Saba

2016-01-01

Background and objectives: Optimal physical activity is important in attaining a peak bone mass. Physically active women have better bone mineral density and reduce fracture risk as compared to females living a sedentary life. The objective of this study was to compare parameters of bone profile and serum homocysteine levels in physically active and non-active postmenopausal females. Methods: In this cross sectional study postmenopausal females between 50-70 years of age were recruited and di...

Determination of the neutron activation profile of core drill samples by gamma-ray spectrometry.

Science.gov (United States)

Gurau, D; Boden, S; Sima, O; Stanga, D

2018-04-01

This paper provides guidance for determining the neutron activation profile of core drill samples taken from the biological shield of nuclear reactors using gamma spectrometry measurements. Thus, it provides guidance for selecting a model of the right form to fit data and using least squares methods for model fitting. The activity profiles of two core samples taken from the biological shield of a nuclear reactor were determined. The effective activation depth and the total activity of core samples along with their uncertainties were computed by Monte Carlo simulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

The impact of cyclin-dependent kinase 5 depletion on poly(ADP-ribose) polymerase activity and responses to radiation

International Nuclear Information System (INIS)

Bolin, Celeste; Boudra, Mohammed-Tayyib; Fernet, Marie; Vaslin, Laurence; Pennaneach, Vincent; Zaremba, Tomasz; Favaudon, Vincent; Megnin-Chanet, Frederique; Hall, Janet; Biard, Denis; Cordelieres, Fabrice P.

2012-01-01

Cyclin-dependent kinase 5 (Cdk5) has been identified as a determinant of sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Here, the consequences of its depletion on cell survival, PARP activity, the recruitment of base excision repair (BER) proteins to DNA damage sites, and overall DNA single-strand break (SSB) repair were investigated using isogenic HeLa stably depleted (KD) and Control cell lines. Synthetic lethality achieved by disrupting PARP activity in Cdk5-deficient cells was confirmed, and the Cdk5KD cells were also found to be sensitive to the killing effects of ionizing radiation (IR) but not methyl methanesulfonate or neocarzinostatin. The recruitment profiles of GFP-PARP-1 and XRCC1-YFP to sites of micro irradiated Cdk5KD cells were slower and reached lower maximum values, while the profile of GFP-PCNA recruitment was faster and attained higher maximum values compared to Control cells. Higher basal, IR, and hydrogen peroxide-induced polymer levels were observed in Cdk5KD compared to Control cells. Recruitment of GFP-PARP-1 in which serines 782, 785, and 786, potential Cdk5 phosphorylation targets, were mutated to alanines in micro-irradiated Control cells was also reduced. We hypothesize that Cdk5- dependent PARP-1 phosphorylation on one or more of these serines results in an attenuation of its ribosylating activity facilitating persistence at DNA damage sites. Despite these deficiencies, Cdk5KD cells are able to effectively repair SSBs probably via the long patch BER pathway, suggesting that the enhanced radiation sensitivity of Cdk5KD cells is due to a role of Cdk5 in other pathways or the altered polymer levels. (authors)

Enzyme activity measurement via spectral evolution profiling and PARAFAC

DEFF Research Database (Denmark)

Baum, Andreas; Meyer, Anne S.; Garcia, Javier Lopez

2013-01-01

The recent advances in multi-way analysis provide new solutions to traditional enzyme activity assessment. In the present study enzyme activity has been determined by monitoring spectral changes of substrates and products in real time. The method relies on measurement of distinct spectral...... fingerprints of the reaction mixture at specific time points during the course of the whole enzyme catalyzed reaction and employs multi-way analysis to detect the spectral changes. The methodology is demonstrated by spectral evolution profiling of Fourier Transform Infrared (FTIR) spectral fingerprints using...

Adolescents' physical activity in physical education, school recess, and extra-curricular sport by motivational profiles.

Science.gov (United States)

Mayorga-Vega, Daniel; Viciana, Jesús

2014-06-01

The main purpose of this study was to evaluate the differences in adolescents´ objective physical activity levels and perceived effort in physical education, school recess, and extra-curricular organized sport by motivational profiles in physical education. A sample of 102 students 11-16 yr. old completed a self-report questionnaire assessing self-determined motivation toward physical education. Subsequently, students' objective physical activity levels (steps/min., METs, and moderate-to-vigorous physical activity) and perceived effort were evaluated for each situation. Cluster analysis identified a two-cluster structure: "Moderate motivation toward physical education profile" and "High motivation toward physical education profile." Adolescents in the second cluster had higher physical activity and perceived effort values than adolescents in the first cluster, except for METs and moderate-to-vigorous physical activity in extra-curricular sport. These results support the importance of physical education teachers who should promote self-determined motivation toward physical education so that students can reach the recommended physical activity levels.

Responsiveness of the rehabilitation activities profile and the Barthel index

NARCIS (Netherlands)

van Bennekom, C. A.; Jelles, F.; Lankhorst, G. J.; Bouter, L. M.

1996-01-01

The goal of this study was to compare the responsiveness for clinically meaningful change over time of a newly designed functional status scale, the Rehabilitation Activities Profile (RAP), with more frequently used Barthel Index (BI). Four techniques for the quantification of responsiveness were

Pyrethroid Activity-Based Probes for Profiling Cytochrome P450 Activities Associated with Insecticide Interactions

Energy Technology Data Exchange (ETDEWEB)

Ismail, Hanafy M.; O' Neill, Paul M.; Hong, David; Finn, Robert; Henderson, Colin; Wright, Aaron T.; Cravatt, Benjamin; Hemingway, Janet; Paine, Mark J.

2014-01-18

Pyrethroid insecticides are used to control a diverse spectrum of diseases spread by arthropods. We have developed a suite of pyrethroid mimetic activity based probes (PyABPs) to selectively label and identify P450s associated with pyrethroid metabolism. The probes were screened against pyrethroid metabolizing and non-metabolizing mosquito P450s, as well as rodent microsomes to measure labeling specificity, plus CPR and b5 knockout mouse livers to validate P450 activation and establish the role for b5 in probe activation. Using a deltamethrin mimetic PyABP we were able to profile active enzymes in rat liver microsomes and identify pyrethroid metabolizing enzymes in the target tissue. The most reactive enzyme was a P450, CYP2C11, which is known to metabolize deltamethrin. Furthermore, several other pyrethroid metabolizers were identified (CYPs 2C6, 3A4, 2C13 and 2D1) along with related detoxification enzymes, notably UDP-g’s 2B1 - 5, suggesting a network of associated pyrethroid metabolizing enzymes, or ‘pyrethrome’. Considering the central role that P450s play in metabolizing insecticides, we anticipate that PyABPs will aid the identification and profiling of P450s associated with insecticide pharmacology in a wide range of species, improving understanding of P450-insecticide interactions and aiding the development of new tools for disease control.

Activity-Dependent Bidirectional Regulation of GAD Expression in a Homeostatic Fashion Is Mediated by BDNF-Dependent and Independent Pathways

Science.gov (United States)

Hanno-Iijima, Yoko; Tanaka, Masami; Iijima, Takatoshi

2015-01-01

Homeostatic synaptic plasticity, or synaptic scaling, is a mechanism that tunes neuronal transmission to compensate for prolonged, excessive changes in neuronal activity. Both excitatory and inhibitory neurons undergo homeostatic changes based on synaptic transmission strength, which could effectively contribute to a fine-tuning of circuit activity. However, gene regulation that underlies homeostatic synaptic plasticity in GABAergic (GABA, gamma aminobutyric) neurons is still poorly understood. The present study demonstrated activity-dependent dynamic scaling in which NMDA-R (N-methyl-D-aspartic acid receptor) activity regulated the expression of GABA synthetic enzymes: glutamic acid decarboxylase 65 and 67 (GAD65 and GAD67). Results revealed that activity-regulated BDNF (brain-derived neurotrophic factor) release is necessary, but not sufficient, for activity-dependent up-scaling of these GAD isoforms. Bidirectional forms of activity-dependent GAD expression require both BDNF-dependent and BDNF-independent pathways, both triggered by NMDA-R activity. Additional results indicated that these two GAD genes differ in their responsiveness to chronic changes in neuronal activity, which could be partially caused by differential dependence on BDNF. In parallel to activity-dependent bidirectional scaling in GAD expression, the present study further observed that a chronic change in neuronal activity leads to an alteration in neurotransmitter release from GABAergic neurons in a homeostatic, bidirectional fashion. Therefore, the differential expression of GAD65 and 67 during prolonged changes in neuronal activity may be implicated in some aspects of bidirectional homeostatic plasticity within mature GABAergic presynapses. PMID:26241953

NESmapper: accurate prediction of leucine-rich nuclear export signals using activity-based profiles.

Directory of Open Access Journals (Sweden)

Shunichi Kosugi

2014-09-01

Full Text Available The nuclear export of proteins is regulated largely through the exportin/CRM1 pathway, which involves the specific recognition of leucine-rich nuclear export signals (NESs in the cargo proteins, and modulates nuclear-cytoplasmic protein shuttling by antagonizing the nuclear import activity mediated by importins and the nuclear import signal (NLS. Although the prediction of NESs can help to define proteins that undergo regulated nuclear export, current methods of predicting NESs, including computational tools and consensus-sequence-based searches, have limited accuracy, especially in terms of their specificity. We found that each residue within an NES largely contributes independently and additively to the entire nuclear export activity. We created activity-based profiles of all classes of NESs with a comprehensive mutational analysis in mammalian cells. The profiles highlight a number of specific activity-affecting residues not only at the conserved hydrophobic positions but also in the linker and flanking regions. We then developed a computational tool, NESmapper, to predict NESs by using profiles that had been further optimized by training and combining the amino acid properties of the NES-flanking regions. This tool successfully reduced the considerable number of false positives, and the overall prediction accuracy was higher than that of other methods, including NESsential and Wregex. This profile-based prediction strategy is a reliable way to identify functional protein motifs. NESmapper is available at http://sourceforge.net/projects/nesmapper.

On Active Current Selection for Lagrangian Profilers

Directory of Open Access Journals (Sweden)

J. Jouffroy

2013-01-01

Full Text Available Autonomous Lagrangian profilers are now widely used as measurement and monitoring platforms, notably in observation programs as Argo. In a typical mode of operation, the profilers drift passively at their parking depthbefore making a vertical profile to go back to the surface. This paperpresents simple and computationally-efficient control strategies to activelyselect and use ocean currents so that a profiler can autonomously reach adesired destination. After briefly presenting a typical profiler andpossible mechanical modifications for a coastal environment, we introducesimple mathematical models for the profiler and the currents it will use. Wethen present simple feedback controllers that, using the direction of thecurrents and taking into account the configuration of the environment(coastal or deep-sea, is able to steer the profiler to any desiredhorizontal location. To illustrate the approach, a few results are presentedusing both simulated currents and real current velocity profiles from theNorth Sea.

Lipid, lipoprotein, and apolipoprotein profiles in active and sedentary men with tetraplegia

NARCIS (Netherlands)

Dallmeijer, A J; Hopman, M T; van der Woude, L H

1997-01-01

OBJECTIVE: To investigate whether the risk profile of coronary heart disease (CHD) is more favorable in physically active men with tetraplegia compared with sedentary men with tetraplegia. DESIGN: Using a cross-sectional design, the lipid and (apo)lipoprotein concentrations of 11 active and 13

Iterative approach to self-adapting and altitude-dependent regularization for atmospheric profile retrievals.

Science.gov (United States)

Ridolfi, Marco; Sgheri, Luca

2011-12-19

In this paper we present the IVS (Iterative Variable Strength) method, an altitude-dependent, self-adapting Tikhonov regularization scheme for atmospheric profile retrievals. The method is based on a similar scheme we proposed in 2009. The new method does not need any specifically tuned minimization routine, hence it is more robust and faster. We test the self-consistency of the method using simulated observations of the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS). We then compare the new method with both our previous scheme and the scalar method currently implemented in the MIPAS on-line processor, using both synthetic and real atmospheric limb measurements. The IVS method shows very good performances.

Nicotine dependence, physical activity, and sedentary behavior among adult smokers

OpenAIRE

Paul D Loprinzi; Jerome F Walker

2015-01-01

Background: Research has previously demonstrated an inverse association between smoking status and physical activity; however, few studies have examined the association between nicotine dependence and physical activity or sedentary behavior. Aim: This study examined the association between nicotine dependence and accelerometer-determined physical activity and sedentary behavior. Materials and Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used....

Profiles of recreational activities of daily living (RADL) in patients with mental disorders.

Science.gov (United States)

Linden, Michael; Gehrke, G; Geiselmann, B

2009-12-01

Activities of daily living, play a key role in the measurement of functional health as defined by the International Classification of Functioning, Disability and Health (ICF) and in prevention and treatment of mental or somatic illnesses. From a clinical context it is important to discriminate between basic "activities of daily living, ADL", "intentional activities of daily living, IADL", and "recreational activities of daily living, RADL". While ADL and IADL have gained much attention in dementia, the elderly, or severe somatic illnesses, there is a lack of research on RADL, which are important in depression, anxiety, or other neurotic disorders. 154 unselected inpatients of a department of behavioral and psychosomatic medicine filled in the "Check List of Recreational Activities" to assess the rates and profiles of RADL. Patients reported on average 19.3 (s.d. 7.0) activities (range 4 - 40), i.e. males 21.3 (s.d. 6.5, 9 - 34) and females 18.9 (s.d. 7.1, 4 - 40). Most frequent RADL were passive and unspecific activities like "watching tv" (93.4%). Least frequent were activities which need special skills or preparation like "horse back riding" (0.7%). Low rates were also found for activities which are in the centre of inpatient occupational therapy like "ceramics" (4.7%) or "silk-painting" (2.6%). There are differences between sexes but not in respect to age (18 to 60), sick leave and unemployment, or diagnostic status. When patients were asked what they would like to do in the future, the same activity profile emerged as when looking at what they had done in the last month The data give a reference profile for recreational activities, help to define what can be considered a normal frequency and spectrum of RADL, and, by this, can guide therapeutic interventions.

Real-time cell toxicity profiling of Tox21 10K compounds reveals cytotoxicity dependent toxicity pathway linkage.

Directory of Open Access Journals (Sweden)

Jui-Hua Hsieh

Full Text Available Cytotoxicity is a commonly used in vitro endpoint for evaluating chemical toxicity. In support of the U.S. Tox21 screening program, the cytotoxicity of ~10K chemicals was interrogated at 0, 8, 16, 24, 32, & 40 hours of exposure in a concentration dependent fashion in two cell lines (HEK293, HepG2 using two multiplexed, real-time assay technologies. One technology measures the metabolic activity of cells (i.e., cell viability, glo while the other evaluates cell membrane integrity (i.e., cell death, flor. Using glo technology, more actives and greater temporal variations were seen in HEK293 cells, while results for the flor technology were more similar across the two cell types. Chemicals were grouped into classes based on their cytotoxicity kinetics profiles and these classes were evaluated for their associations with activity in the Tox21 nuclear receptor and stress response pathway assays. Some pathways, such as the activation of H2AX, were associated with the fast-responding cytotoxicity classes, while others, such as activation of TP53, were associated with the slow-responding cytotoxicity classes. By clustering pathways based on their degree of association to the different cytotoxicity kinetics labels, we identified clusters of pathways where active chemicals presented similar kinetics of cytotoxicity. Such linkages could be due to shared underlying biological processes between pathways, for example, activation of H2AX and heat shock factor. Others involving nuclear receptor activity are likely due to shared chemical structures rather than pathway level interactions. Based on the linkage between androgen receptor antagonism and Nrf2 activity, we surmise that a subclass of androgen receptor antagonists cause cytotoxicity via oxidative stress that is associated with Nrf2 activation. In summary, the real-time cytotoxicity screen provides informative chemical cytotoxicity kinetics data related to their cytotoxicity mechanisms, and with our

Organosulphide profile and hydrogen sulphide-releasing activity of garlic fermented by Lactobacillus plantarum

NARCIS (Netherlands)

Tocmo, Restituto; Lai, Abigail Nianci; Wu, Yuchen; Liang, Dong; Fogliano, Vincenzo; Huang, Dejian

2017-01-01

Blanched and unblanched garlic were fermented using L. plantarum for investigation of organosulphide profiles, hydrogen sulphide-releasing activity, pH, titratable activity and microbial growth. Both raw and blanched garlic preparations allowed growth of L. plantarum with corresponding lowering of

Transcriptional profiling of the dose response: a more powerful approach for characterizing drug activities.

Directory of Open Access Journals (Sweden)

Rui-Ru Ji

2009-09-01

Full Text Available The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmacological parameters such as the EC50, and enable an in-depth analysis of coordinated dose-dependent treatment effects. The approach was applied to a transcriptional profiling study that evaluated four kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901 across a six-logarithm dose range, using 12 arrays per compound. The transcript responses proved a powerful means to characterize and compare the compounds: the distribution of EC50 values for the transcriptome was linked to specific targets, dose-dependent effects on cellular processes were identified using automated pathway analysis, and a connection was seen between EC50s in standard cellular assays and transcriptional EC50s. Our approach greatly enriches the information that can be obtained from standard transcriptional profiling technology. Moreover, these methods are automated, robust to non-optimized assays, and could be applied to other sources of quantitative data.

Biological activity and chemical profile of Lavatera thuringiaca L. extracts obtained by different extraction approaches.

Science.gov (United States)

Mašković, Pavle Z; Veličković, Vesna; Đurović, Saša; Zeković, Zoran; Radojković, Marija; Cvetanović, Aleksandra; Švarc-Gajić, Jaroslava; Mitić, Milan; Vujić, Jelena

2018-01-01

Lavatera thuringiaca L. is herbaceous perennial plant from Malvaceae family, which is known for its biological activity and richness in polyphenolic compounds. Despite this, the information regarding the biological activity and chemical profile is still insufficient. Aim of this study was to investigate biological potential and chemical profile of Lavatera thuringiaca L., as well as influence of applied extraction technique on them. Two conventional and four non-conventional extraction techniques were applied in order to obtain extracts rich in bioactive compound. Extracts were further tested for total phenolics, flavonoids, condensed tannins, gallotannins and anthocyanins contents using spectrophotometric assays. Polyphenolic profile was established using HPLC-DAD analysis. Biological activity was investigated regarding antioxidant, cytotoxic and antibacterial activities. Four antioxidant assays were applied as well as three different cell lines for cytotoxic and fifteen bacterial strain for antibacterial activity. Results showed that subcritical water extraction (SCW) dominated over the other extraction techniques, where SCW extract exhibited the highest biological activity. Study indicates that plant Lavatera thuringiaca L. may be used as a potential source of biologically compounds. Copyright © 2017 Elsevier GmbH. All rights reserved.

Nerve growth factor enhances the CRE-dependent transcriptional activity activated by nobiletin in PC12 cells.

Science.gov (United States)

Takito, Jiro; Kimura, Junko; Kajima, Koji; Uozumi, Nobuyuki; Watanabe, Makoto; Yokosuka, Akihito; Mimaki, Yoshihiro; Nakamura, Masanori; Ohizumi, Yasushi

2016-07-01

Prevention and treatment of Alzheimer disease are urgent problems for elderly people in developed countries. We previously reported that nobiletin, a poly-methoxylated flavone from the citrus peel, improved the symptoms in various types of animal models of memory loss and activated the cAMP responsive element (CRE)-dependent transcription in PC12 cells. Nobiletin activated the cAMP/PKA/MEK/Erk/MAPK signaling pathway without using the TrkA signaling activated by nerve growth factor (NGF). Here, we examined the effect of combination of nobiletin and NGF on the CRE-dependent transcription in PC12 cells. Although NGF alone had little effect on the CRE-dependent transcription, NGF markedly enhanced the CRE-dependent transcription induced by nobiletin. The NGF-induced enhancement was neutralized by a TrkA antagonist, K252a. This effect of NGF was effective on the early signaling event elicited by nobiletin. These results suggested that there was crosstalk between NGF and nobiletin signaling in activating the CRE-dependent transcription in PC12 cells.

Concentration- and time-dependent genotoxicity profiles of isoprene monoepoxides and diepoxide, and the cross-linking potential of isoprene diepoxide in cells

Directory of Open Access Journals (Sweden)

Yan Li

2014-01-01

Full Text Available Isoprene, a possible carcinogen, is a petrochemical and a natural product being primarily produced by plants. It is biotransformed to 2-ethenyl-2-methyloxirane (IP-1,2-O and 2-(1-methylethenyloxirane (IP-3,4-O, both of which can be further metabolized to 2-methyl-2,2′-bioxirane (MBO. MBO is mutagenic, but IP-1,2-O and IP-3,4-O are not. While IP-1,2-O has been reported being genotoxic, the genotoxicity of IP-3,4-O and MBO, and the cross-linking potential of MBO have not been examined. In the present study, we used the comet assay to investigate the concentration- and time-dependent genotoxicity profiles of the three metabolites and the cross-linking potential of MBO in human hepatocyte L02 cells. For the incubation time of 1 h, all metabolites showed positive concentration-dependent profiles with a potency rank order of IP-3,4-O > MBO > IP-1,2-O. In human hepatocellular carcinoma (HepG2 and human leukemia (HL60 cells, IP-3,4-O was still more potent in inducing DNA breaks than MBO at high concentrations (>200 μM, although at low concentrations (≤200 μM IP-3,4-O exhibited slightly lower or similar potency to MBO. Interestingly, their time-dependent genotoxicity profiles (0.5–4 h in L02 cells were different from each other: IP-1,2-O and MBO (200 μM exhibited negative and positive profiles, respectively, with IP-3,4-O lying in between, namely, IP-3,4-O-caused DNA breaks did not change over the exposure time. Further experiments demonstrated that hydrolysis of IP-1,2-O contributed to the negative profile and MBO induced cross-links at high concentrations and long incubation times. Collectively, the results suggested that IP-3,4-O might play a significant role in the toxicity of isoprene.

Variations in Tectonic Activities of the Central and Southwestern Foothills, Taiwan, Inferred from River Hack Profiles

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Yen-Chieh Chen

2006-01-01

Full Text Available A longitudinal profile of a river under static equilibrium shows no degradation or aggradation and can be ideally described as a straight line on a semi-logarithmic graph. This type of profile is called a “Hack profile”. If a river runs across uprising active structure systems, its Hack profile becomes convex. Accumulated tectonic strain varies positively with the intensity of the upwarping in Hack-profile convexity. In this paper, we compare curvature changes in Hack profiles of a series of rivers running through faults in the central and southwestern Foothills of Taiwan. Longitudinal profiles of these rivers were derived from two versions of topographic maps (1904 and 1985 and recent DTM data (2000. Prior to comparisons, we calibrated the 1904 topographic map, named “Taiwan Bautu”, by “offsetting” horizontal coordinates north and westward approximately 440 m and then “linear transforming” the elevation values. The Tungtzchiau fault of the central Foothills has remained inactive since 1935. Here relatively high uplift activity near the Wu River is indicated by significantly convex Hack profiles. This strain accumulation can be attributed to a lack of small magnitude earthquakes along the fault over the past 70 years. In the southwestern Foothills, relatively high uplift activity of similar intensity to the central Foothills is indicted near the Neocho River. Significant profiles with concave segments below the ideal graded profiles, at the lower reaches of rivers where continuous small magnitude strain release events have occurred, can only be found along the Sandieh, Neocho and Bazhang rivers in the southwestern Foothills. All these findings indicate that fault systems in the central Foothills tend to be locked and these faults could yield large earthquakes similar to the Chi-Chi event.

Activity Pattern Profiles: Relationship With Affect, Daily Functioning, Impairment, and Variables Related to Life Goals.

Science.gov (United States)

Esteve, Rosa; López-Martínez, Alicia E; Peters, Madelon L; Serrano-Ibáñez, Elena R; Ruíz-Párraga, Gema T; González-Gómez, Henar; Ramírez-Maestre, Carmen

2017-05-01

The aim of this cross-sectional study was to identify subgroups of patients on the basis of their activity patterns and to investigate their relationship with life goals, optimism, affect, and functioning. The sample was comprised of 276 patients with chronic musculoskeletal pain. Hierarchical cluster analysis was performed on the activity pattern variables and the resulting clusters were compared using 1-way analysis of variance. The 4-cluster was the optimal solution. The 4 clusters comprised: 1) avoiders: patients with high levels of avoidance and low levels of persistence, who use pacing to reduce pain, 2) doers: patients with high levels of persistence and low levels of pacing and avoidance, 3) extreme cyclers: patients with high levels of avoidance and persistence and low levels of pacing, and 4) medium cyclers: patients with moderately high levels of avoidance and persistence and high levels of pacing. Comparison of the clusters showed that doers had the most adaptive profile, whereas avoiders, followed by extreme cyclers, had unhealthy profiles. Doers showed a high level of optimism and a good balance between goal value, expectancy, and conflict. It is useful to distinguish profiles on the basis of various activity patterns. In contrast to profiles characterized by avoidance, profiles characterized by high persistence and low avoidance were associated with adaptive results. Patients with this profile also showed a high level of optimism and a good balance between goal value, expectancy, and conflict. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The cell biology of T-dependent B cell activation

DEFF Research Database (Denmark)

Owens, T; Zeine, R

1989-01-01

The requirement that CD4+ helper T cells recognize antigen in association with class II Major Histocompatibility Complex (MHC) encoded molecules constrains T cells to activation through intercellular interaction. The cell biology of the interactions between CD4+ T cells and antigen-presenting cells...... includes multipoint intermolecular interactions that probably involve aggregation of both polymorphic and monomorphic T cell surface molecules. Such aggregations have been shown in vitro to markedly enhance and, in some cases, induce T cell activation. The production of T-derived lymphokines that have been...... implicated in B cell activation is dependent on the T cell receptor for antigen and its associated CD3 signalling complex. T-dependent help for B cell activation is therefore similarly MHC-restricted and involves T-B intercellular interaction. Recent reports that describe antigen-independent B cell...

Symptoms of exercise dependence and physical activity in students.

Science.gov (United States)

MacLaren, Vance V; Best, Lisa A

2007-12-01

Health professionals recognize the benefits of moderate physical activity and encourage clients to engage in some form of activity on a regular basis. In spite of these recognized benefits, there are growing concerns that some may exercise at levels detrimental to health. The term exercise dependence refers to those individuals whose extreme exercise schedules interfere with their social, occupational, and family lives. The purpose of this study was to examine the relationship between weekly exercise habits and scores on the Exercise Dependence Questionnaire in a sample of undergraduate students (213 women and 79 men). Overall, participants who reported high activity scored higher than those reporting low activity on subscales measuring interference with family and social life, positive reward, withdrawal, exercise for social reasons, exercise for health reasons, and stereotyped behavior.

Physical activity and sleep profiles in Finnish men and women.

Science.gov (United States)

Wennman, Heini; Kronholm, Erkki; Partonen, Timo; Tolvanen, Asko; Peltonen, Markku; Vasankari, Tommi; Borodulin, Katja

2014-01-27

Physical activity (PA) and sleep are related to cardiovascular diseases (CVD) and their risk factors. The interrelationship between these behaviors has been studied, but there remain questions regarding the association of different types of PA, such as occupational, commuting, and leisure time to sleep, including quality, duration and sufficiency. It is also unclear to what extent sleep affects peoples' PA levels and patterns. Our aim is to investigate the interrelationship between PA and sleep behaviors in the Finnish population, including employment status and gender. The study comprised population based data from the FINRISK 2012 Study. A stratified, random sample of 10,000 Finns, 25 to 74 years-old, were sent a questionnaire and an invitation to a health examination. The participation rate was 64% (n = 6,414). Latent class analysis was used to search for different underlying profiles of PA and sleep behavior in men and women, respectively. Models with one through five latent profiles were fitted to the data. Based on fit indicators, a four-class model for men and women, respectively, was decided to be the best fitted model. Four different profiles of PA and sleep were found in both men and women. The most common profile of men comprised 45% of the total participants, and in women, 47%. These profiles were distinguished by probabilities for high leisure time PA and sleep, subjectively rated as sufficient, as well as sleep duration of 7-7.9 hours. The least common profiles represented 5% (men) and 11% (women) of the population, and were characterized by probabilities for physical inactivity, short sleep, and evening type for women and morning type for men. There was also one profile in both genders characterized by likelihood for both high occupational PA and subjectively experienced insufficient sleep. The use of latent class analysis in investigating the interrelationship between PA and sleep is a novel perspective. The method provides information on the

Year in school and physical activity stage of change as discriminators of variation in the physical activity correlate profile of adolescent females.

Science.gov (United States)

Burns, Con; Murphy, John J; MacDonncha, Ciaran

2014-05-01

Knowledge of the physical activity correlate profile of adolescent females will provide insight into decreasing physical activity patterns among adolescent females. Correlates of physical activity and physical activity stage of change were assessed during 2007-2008 among 871 Irish adolescent females in years 1-6 in secondary schools (15.28 ± 1.8 years). Multivariate Analysis of Variance was used to identify whether differences in correlates of physical activity could be detected across year in school and physical activity stages of change. Significant differences (P physically active (partial eta range (ηp2) .21-.25) to be the most important predictors of physical activity stage of change. Females in more senior years in school and in earlier physical activity stages of change reported a significantly less positive physical activity correlate profile than females in junior years and in later physical activity stages of change. This finding supports the construct validity of the physical activity stages of change.

Strand specific RNA-sequencing and membrane lipid profiling reveals growth phase-dependent cold stress response mechanisms in Listeria monocytogenes

Science.gov (United States)

Hingston, Patricia; Chen, Jessica; Allen, Kevin; Truelstrup Hansen, Lisbeth

2017-01-01

The human pathogen Listeria monocytogenes continues to pose a challenge in the food industry, where it is known to contaminate ready-to-eat foods and grow during refrigerated storage. Increased knowledge of the cold-stress response of this pathogen will enhance the ability to control it in the food-supply-chain. This study utilized strand-specific RNA sequencing and whole cell fatty acid (FA) profiling to characterize the bacterium’s cold stress response. RNA and FAs were extracted from a cold-tolerant strain at five time points between early lag phase and late stationary-phase, both at 4°C and 20°C. Overall, more genes (1.3×) were suppressed than induced at 4°C. Late stationary-phase cells exhibited the greatest number (n = 1,431) and magnitude (>1,000-fold) of differentially expressed genes (>2-fold, pmonocytogenes, the growth-phase dependency of its cold-stress regulon, and the active roles of antisense transcripts in regulating its cold stress response. PMID:28662112

Cation dependency of the hydrolytic activity of activated bovine Protein C

International Nuclear Information System (INIS)

Hill, K.A.W.

1986-01-01

The hydrolytic activity of activated bovine plasma Protein C (APC) is dependent upon monovalent or divalent cations. The kinetics of APC activity were examined with a variety of monovalent and divalent cations, and significant differences were observed. Similar studies were performed with des(1-41, light chain)APC (GDAPC), from which all γ-carboxyglutamic acid residues have been removed. These studies provided useful information concerning the cation dependency. Divalent cations apparently stimulate APC and GDAPC kinetic activity through association at a single γ-carboxyglutamic acid-independent high affinity binding site. A Mn(II) binding site of this nature of GDAPC was determined by EPR spectroscopy, to possess a dissociation constant of 53 +/- 8 uM. Monovalent cations stimulate GDAPC activity through association at an apparently single binding site that is distinct from the divalent cation site. The monovalent cation , Tl(I), was determined, by 205 Tl(I) NMR spectroscopy, to bind to APC and GDAPC with dissociation constants of 16 +/- 8 mM and 32+/- 11 mM, respectively. Both NMR and EPR spectroscopy have been utilized to estimate topographical relationships between divalent cation sites, monovalent cation sites, and the active site of GDAPC. By observing the paramagnetic effects of either Mn(II) or an active site directed spin-label on the longitudinal relaxation rates of Tl(I) nuclei bound to this enzyme, the average interatomic distance between Mn(II) and Tl(I) was calculated to be 8.3 +/- 0.3 A, and the average distance between Tl(I) and the spin-label free electron was estimated to be 3.8 +/- 0.2 A

Nicotine dependence matters: examining longitudinal association between smoking and physical activity among Canadian adults.

Science.gov (United States)

Azagba, Sunday; Asbridge, Mark

2013-11-01

A number of studies point to the inverse relationship between physical activity and smoking; however, none has examined the role of nicotine dependence in physical activity participation among smokers. This study examined whether levels of nicotine dependence modify the association between leisure time physical activity and smoking status. The study used longitudinal data on 6795 adults from the Canadian National Population Health Survey (2004-2010). Generalized estimating equations were used to examine the association between physical activity, smoking, and nicotine dependence. We found that nicotine dependent smokers were significantly less likely to be physically active compared to non-smokers. Specifically, using the Fagerstrom Test for Nicotine Dependence, nicotine dependent smokers (OR 0.65, 95% CI 0.55-0.76) were less likely to be physically active while no significant difference was found for non-dependent smokers (OR 0.90, 95% CI 0.80-1.02) compared to non-smokers. Nicotine dependence matters in shaping engagement in physical activity among daily smokers. Efforts directed at promoting smoking cessation through nicotine dependence treatment intervention may provide additional benefits to health and well-being through an increased participation in physical activity. © 2013.

A COMPARATIVE STUDY OF LIPID PROFILE IN SEDENTARY AND ACTIVE ADULT FEMALES

Directory of Open Access Journals (Sweden)

Suhasini Sanda

2018-11-01

Full Text Available BACKGROUND Lipids and lipoproteins are essential constituents of the body and their activities assist in maintenance of body homeostasis. Sedentary lifestyle has been shown to lead to inactivity, which could lead to lipid disorders. Hyperlipidaemias is one of the major independent risk factor, which affects the cardiovascular system adversely resulting eventually damage to various organs most notably heart, kidneys and brain. The present study is therefore designed to ascertain the effect of sedentary lifestyle on lipid status of sedentary adult females when compared to that of the lipid status of active adult females. MATERIALS AND METHODS The present study comprised of Group I - 50 sedentary adult females and Group II - 50 active adult females aged between 30 to 60 years. The subjects selected in both groups were matched for age and dietary habits. The subjects with hypertension, diabetes, smokers, pregnancy and subjects with Body Mass Index (BMI greater than 30 are excluded. After overnight fasting of 12 to 14 hours, 5 mL of blood is collected from the subjects and fasting Total Serum Cholesterol (TC, Total Serum Triglycerides (TG, HDL cholesterol (HDL-C, LDL cholesterol (LDL-C and total serum cholesterol/HDL-C ratio are measured and data is statistically analysed. RESULTS The evaluation of lipid profile patterns in above subjects showed hypercholesterolaemia, hypertriglyceridaemia, increased LDLC and total serum cholesterol/HDL-C ratio in sedentary adult females and also decreased HDL-C levels in them when compared to the normal healthy lipid profile patterns in active adult females. A statistically significant increased lipid profiles (P-value <0.001 was observed in the sedentary adult females than in active adult females. CONCLUSION This study shows that sedentary lifestyle predisposes to hyperlipidaemias, one of the major risk factor of cardiovascular disease and lack of exercise worsens the situation.

Approximate Stokes Drift Profiles in Deep Water

Science.gov (United States)

Breivik, Øyvind; Janssen, Peter A. E. M.; Bidlot, Jean-Raymond

2014-09-01

A deep-water approximation to the Stokes drift velocity profile is explored as an alternative to the monochromatic profile. The alternative profile investigated relies on the same two quantities required for the monochromatic profile, viz the Stokes transport and the surface Stokes drift velocity. Comparisons with parametric spectra and profiles under wave spectra from the ERA-Interim reanalysis and buoy observations reveal much better agreement than the monochromatic profile even for complex sea states. That the profile gives a closer match and a more correct shear has implications for ocean circulation models since the Coriolis-Stokes force depends on the magnitude and direction of the Stokes drift profile and Langmuir turbulence parameterizations depend sensitively on the shear of the profile. The alternative profile comes at no added numerical cost compared to the monochromatic profile.

Reconstructing Dynamic Promoter Activity Profiles from Reporter Gene Data.

Science.gov (United States)

Kannan, Soumya; Sams, Thomas; Maury, Jérôme; Workman, Christopher T

2018-03-16

Accurate characterization of promoter activity is important when designing expression systems for systems biology and metabolic engineering applications. Promoters that respond to changes in the environment enable the dynamic control of gene expression without the necessity of inducer compounds, for example. However, the dynamic nature of these processes poses challenges for estimating promoter activity. Most experimental approaches utilize reporter gene expression to estimate promoter activity. Typically the reporter gene encodes a fluorescent protein that is used to infer a constant promoter activity despite the fact that the observed output may be dynamic and is a number of steps away from the transcription process. In fact, some promoters that are often thought of as constitutive can show changes in activity when growth conditions change. For these reasons, we have developed a system of ordinary differential equations for estimating dynamic promoter activity for promoters that change their activity in response to the environment that is robust to noise and changes in growth rate. Our approach, inference of dynamic promoter activity (PromAct), improves on existing methods by more accurately inferring known promoter activity profiles. This method is also capable of estimating the correct scale of promoter activity and can be applied to quantitative data sets to estimate quantitative rates.

Spontaneous appetence for wheel-running: a model of dependency on physical activity in rat.

Science.gov (United States)

Ferreira, Anthony; Lamarque, Stéphanie; Boyer, Patrice; Perez-Diaz, Fernando; Jouvent, Roland; Cohen-Salmon, Charles

2006-12-01

According to human observations of a syndrome of physical activity dependence and its consequences, we tried to examine if running activity in a free activity paradigm, where rats had a free access to activity wheel, may present a valuable animal model for physical activity dependence and most generally to behavioral dependence. The pertinence of reactivity to novelty, a well-known pharmacological dependence predictor was also tested. Given the close linkage observed in human between physical activity and drugs use and abuse, the influence of free activity in activity wheels on reactivity to amphetamine injection and reactivity to novelty were also assessed. It appeared that (1) free access to wheel may be used as a valuable model for physical activity addiction, (2) two populations differing in activity amount also differed in dependence to wheel-running. (3) Reactivity to novelty did not appeared as a predictive factor for physical activity dependence (4) activity modified novelty reactivity and (5) subjects who exhibited a high appetence to wheel-running, presented a strong reactivity to amphetamine. These results propose a model of dependency on physical activity without any pharmacological intervention, and demonstrate the existence of individual differences in the development of this addiction. In addition, these data highlight the development of a likely vulnerability to pharmacological addiction after intense and sustained physical activity, as also described in man. This model could therefore prove pertinent for studying behavioral dependencies and the underlying neurobiological mechanisms. These results may influence the way psychiatrists view behavioral dependencies and phenomena such as doping in sport or addiction to sport itself.

Physical activity levels and health profiles of adult women living in ...

African Journals Online (AJOL)

This study investigated the physical activity levels and health profiles of adult women living in the Mmasechaba informal settlement in Gauteng. Apart from the questionnaire, anthropometric measurements were recorded and body mass index and waist-to-hip ratios were calculated. The results indicated that the incidence of ...

Impact of the Road Profile on Vehicle Deceleration

Directory of Open Access Journals (Sweden)

Vidas Žuraulis

2012-11-01

Full Text Available The article analyzes the impact of the longitudinal road profile on the efficiency of car braking estimated applying deceleration value. Different formulas are used for theoretical calculations, and therefore experimental brakes in different road slopes were performed to obtain the most accurate results. Deceleration, as one of the most important safety parameters, depends on the technical condition of the braking system, road conditions and structural and dynamic properties of the other car. Road alignments can significantly affect car manageability, because of weight transfer and extra track resistance, which may change the overall balance of the car and affect the nature of dynamic characteristics that may vary from certain critical values. The results of corrections to deceleration dependence on the road profile can be used for investigating traffic accidents, optimizing traffic control arrangements and implementing advanced systems for automotive active safety.

Great red spot dependence on solar activity

International Nuclear Information System (INIS)

Schatten, K.H.

1979-01-01

A new inquiry has been made into the question of whether Jupiter's Great Red Spot shows a solar activity dependence. From 1892 to 1947 a clear correlation was present. A dearth of sightings in the seventeenth century, along with the Maunder Minimum, further supports the relation. An anticorrelation, however, from l948 to l967 removed support for such an effect. The old observations have reexamined and recent observations have also been studied. The author reexamines this difficult question and suggests a possible physical mechanism for a Sun-Jovian weather relation. Prinn and Lewis' conversion reaction of Phosphine gas to triclinic red phosphorous crystals is a reaction dependent upon solar radiation. It may explain the dependence found, as well as the striking appearance of the Great Red Spot in the UV

Time-dependent effects of ultraviolet and nonthermal atmospheric pressure plasma on the biological activity of titanium

Science.gov (United States)

Choi, Sung-Hwan; Jeong, Won-Seok; Cha, Jung-Yul; Lee, Jae-Hoon; Yu, Hyung-Seog; Choi, Eun-Ha; Kim, Kwang-Mahn; Hwang, Chung-Ju

2016-09-01

Here, we evaluated time-dependent changes in the effects of ultraviolet (UV) and nonthermal atmospheric pressure plasma (NTAPPJ) on the biological activity of titanium compared with that of untreated titanium. Grade IV machined surface titanium discs (12-mm diameter) were used immediately and stored up to 28 days after 15-min UV or 10-min NTAPPJ treatment. Changes of surface characteristics over time were evaluated using scanning electron microscopy, surface profiling, contact angle analysis, X-ray photoelectron spectroscopy, and surface zeta-potential. Changes in biological activity over time were as determined by analysing bovine serum albumin adsorption, MC3T3-E1 early adhesion and morphometry, and alkaline phosphatase (ALP) activity between groups. We found no differences in the effects of treatment on titanium between UV or NTAPPJ over time; both treatments resulted in changes from negatively charged hydrophobic (bioinert) to positively charged hydrophilic (bioactive) surfaces, allowing enhancement of albumin adsorption, osteoblastic cell attachment, and cytoskeleton development. Although this effect may not be prolonged for promotion of cell adhesion until 4 weeks, the effects were sufficient to maintain ALP activity after 7 days of incubation. This positive effect of UV and NTAPPJ treatment can enhance the biological activity of titanium over time.

The spatio-temporal dynamics of PKA activity profile during mitosis and its correlation to chromosome segregation

Science.gov (United States)

Vandame, Pauline; Spriet, Corentin; Trinel, Dave; Gelaude, Armance; Caillau, Katia; Bompard, Coralie; Biondi, Emanuele; Bodart, Jean-François

2014-01-01

The cyclic adenosine monophosphate dependent kinase protein (PKA) controls a variety of cellular processes including cell cycle regulation. Here, we took advantages of genetically encoded FRET-based biosensors, using an AKAR-derived biosensor to characterize PKA activity during mitosis in living HeLa cells using a single-cell approach. We measured PKA activity changes during mitosis. HeLa cells exhibit a substantial increase during mitosis, which ends with telophase. An AKAREV T>A inactive form of the biosensor and H89 inhibitor were used to ascertain for the specificity of the PKA activity measured. On a spatial point of view, high levels of activity near to chromosomal plate during metaphase and anaphase were detected. By using the PKA inhibitor H89, we assessed the role of PKA in the maintenance of a proper division phenotype. While this treatment in our hands did not impaired cell cycle progression in a drastic manner, inhibition of PKA leads to a dramatic increase in chromososme misalignement on the spindle during metaphase that could result in aneuploidies. Our study emphasizes the insights that can be gained with genetically encoded FRET-based biosensors, which enable to overcome the shortcomings of classical methologies and unveil in vivo PKA spatiotemporal profiles in HeLa cells. PMID:25485503

The spatio-temporal dynamics of PKA activity profile during mitosis and its correlation to chromosome segregation.

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Vandame, Pauline; Spriet, Corentin; Trinel, Dave; Gelaude, Armance; Caillau, Katia; Bompard, Coralie; Biondi, Emanuele; Bodart, Jean-François

2014-01-01

The cyclic adenosine monophosphate dependent kinase protein (PKA) controls a variety of cellular processes including cell cycle regulation. Here, we took advantages of genetically encoded FRET-based biosensors, using an AKAR-derived biosensor to characterize PKA activity during mitosis in living HeLa cells using a single-cell approach. We measured PKA activity changes during mitosis. HeLa cells exhibit a substantial increase during mitosis, which ends with telophase. An AKAREV T>A inactive form of the biosensor and H89 inhibitor were used to ascertain for the specificity of the PKA activity measured. On a spatial point of view, high levels of activity near to chromosomal plate during metaphase and anaphase were detected. By using the PKA inhibitor H89, we assessed the role of PKA in the maintenance of a proper division phenotype. While this treatment in our hands did not impaired cell cycle progression in a drastic manner, inhibition of PKA leads to a dramatic increase in chromososme misalignement on the spindle during metaphase that could result in aneuploidies. Our study emphasizes the insights that can be gained with genetically encoded FRET-based biosensors, which enable to overcome the shortcomings of classical methologies and unveil in vivo PKA spatiotemporal profiles in HeLa cells.

pH-dependent solubility and permeability profiles: A useful tool for prediction of oral bioavailability.

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Sieger, P; Cui, Y; Scheuerer, S

2017-07-15

pH-dependent solubility - permeability profiles offer a simple way to predict bioavailability after oral application, if bioavailability is only solubility and permeability driven. Combining both pH-dependent solubility and pH-dependent permeability in one diagram provides a pH-window (=ΔpH sol-perm ) from which the conditions for optimal oral bioavailability can be taken. The size of this window is directly proportional to the observed oral bioavailability. A set of 21 compounds, with known absolute human oral bioavailability, was used to establish this correlation. Compounds with ΔpH sol-perm bioavailability (bioavailability typically by approximately 25%. For compounds where ΔpH sol-perm ≥3 but still showing poor bioavailability, most probably other pharmacokinetic aspects (e.g. high clearance), are limiting exposure. Interestingly, the location of this pH-window seems to have a negligible influence on the observed oral bioavailability. In scenarios, where the bioavailability is impaired by certain factors, like for example proton pump inhibitor co-medication or food intake, the exact position of this pH-window might be beneficial for understanding the root cause. Copyright © 2017 Elsevier B.V. All rights reserved.

Continuous Water Vapor Profiles from Operational Ground-Based Active and Passive Remote Sensors

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Turner, D. D.; Feltz, W. F.; Ferrare, R. A.

2000-01-01

The Atmospheric Radiation Measurement program's Southern Great Plains Cloud and Radiation Testbed site central facility near Lamont, Oklahoma, offers unique operational water vapor profiling capabilities, including active and passive remote sensors as well as traditional in situ radiosonde measurements. Remote sensing technologies include an automated Raman lidar and an automated Atmospheric Emitted Radiance Interferometer (AERI), which are able to retrieve water vapor profiles operationally through the lower troposphere throughout the diurnal cycle. Comparisons of these two water vapor remote sensing methods to each other and to radiosondes over an 8-month period are presented and discussed, highlighting the accuracy and limitations of each method. Additionally, the AERI is able to retrieve profiles of temperature while the Raman lidar is able to retrieve aerosol extinction profiles operationally. These data, coupled with hourly wind profiles from a 915-MHz wind profiler, provide complete specification of the state of the atmosphere in noncloudy skies. Several case studies illustrate the utility of these high temporal resolution measurements in the characterization of mesoscale features within a 3-day time period in which passage of a dryline, warm air advection, and cold front occurred.

Opioid-Induced Glial Activation: Mechanisms of Activation and Implications for Opioid Analgesia, Dependence, and Reward

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Mark R. Hutchinson

2007-01-01

Full Text Available This review will introduce the concept of toll-like receptor (TLR–mediated glial activation as central to all of the following: neuropathic pain, compromised acute opioid analgesia, and unwanted opioid side effects (tolerance, dependence, and reward. Attenuation of glial activation has previously been demonstrated both to alleviate exaggerated pain states induced by experimental pain models and to reduce the development of opioid tolerance. Here we demonstrate that selective acute antagonism of TLR4 results in reversal of neuropathic pain as well as potentiation of opioid analgesia. Attenuating central nervous system glial activation was also found to reduce the development of opioid dependence, and opioid reward at a behavioral (conditioned place preference and neurochemical (nucleus accumbens microdialysis of morphine-induced elevations in dopamine level of analysis. Moreover, a novel antagonism of TLR4 by (+- and (˗-isomer opioid antagonists has now been characterized, and both antiallodynic and morphine analgesia potentiating activity shown. Opioid agonists were found to also possess TLR4 agonistic activity, predictive of glial activation. Targeting glial activation is a novel and as yet clinically unexploited method for treatment of neuropathic pain. Moreover, these data indicate that attenuation of glial activation, by general or selective TLR antagonistic mechanisms, may also be a clinical method for separating the beneficial (analgesia and unwanted (tolerance, dependence, and reward actions of opioids, thereby improving the safety and efficacy of their use.

Abscisic acid-dependent multisite phosphorylation regulates the activity of a transcription activator AREB1.

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Furihata, Takashi; Maruyama, Kyonoshin; Fujita, Yasunari; Umezawa, Taishi; Yoshida, Riichiro; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2006-02-07

bZIP-type transcription factors AREBs/ABFs bind an abscisic acid (ABA)-responsive cis-acting element named ABRE and transactivate downstream gene expression in Arabidopsis. Because AREB1 overexpression could not induce downstream gene expression, activation of AREB1 requires ABA-dependent posttranscriptional modification. We confirmed that ABA activated 42-kDa kinase activity, which, in turn, phosphorylated Ser/Thr residues of R-X-X-S/T sites in the conserved regions of AREB1. Amino acid substitutions of R-X-X-S/T sites to Ala suppressed transactivation activity, and multiple substitution of these sites resulted in almost complete suppression of transactivation activity in transient assays. In contrast, substitution of the Ser/Thr residues to Asp resulted in high transactivation activity without exogenous ABA application. A phosphorylated, transcriptionally active form was achieved by substitution of Ser/Thr in all conserved R-X-X-S/T sites to Asp. Transgenic plants overexpressing the phosphorylated active form of AREB1 expressed many ABA-inducible genes, such as RD29B, without ABA treatment. These results indicate that the ABA-dependent multisite phosphorylation of AREB1 regulates its own activation in plants.

Lipid reducing activity and toxicity profiles of a library of polyphenol derivatives.

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Urbatzka, Ralph; Freitas, Sara; Palmeira, Andreia; Almeida, Tiago; Moreira, João; Azevedo, Carlos; Afonso, Carlos; Correia-da-Silva, Marta; Sousa, Emilia; Pinto, Madalena; Vasconcelos, Vitor

2018-05-10

Obesity is an increasing epidemic worldwide and novel treatments are urgently needed. Polyphenols are natural compounds derived from plants, which are known in particular for their antioxidant properties. However, some polyphenols were described to possess anti-obesity activities in vitro and in vivo. In this study, we aimed to screen a library of 85 polyphenol derivatives for their lipid reducing activity and toxicity. Compounds were analyzed at 5 μM with the zebrafish Nile red fluorescence fat metabolism assay and for general toxicity in vivo. To improve the safety profile, compounds were screened at 50 μM in murine preadipocytes in vitro for cytotoxicity. Obtained activity data were used to create a 2D-QSAR (quantitative structure activity relationship) model. 38 polyphenols showed strong lipid reducing activity. Toxicity analysis revealed that 18 of them did not show any toxicity in vitro or in vivo. QSAR analysis revealed the importance of the number of rings, fractional partial positively charged surface area, relative positive charge, relative number of oxygen atoms, and partial negative surface area for lipid-reducing activity. The five most potent compounds with EC 50 values in the nanomolar range for lipid reducing activity and without any toxic effects are strong candidates for future research and development into anti-obesity drugs. Molecular profiling for fasn, sirt1, mtp and ppary revealed one compound that reduced significantly fasn mRNA expression. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Protein kinase activity of phosphoinositide 3-kinase regulates cytokine-dependent cell survival.

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Daniel Thomas

Full Text Available The dual specificity protein/lipid kinase, phosphoinositide 3-kinase (PI3K, promotes growth factor-mediated cell survival and is frequently deregulated in cancer. However, in contrast to canonical lipid-kinase functions, the role of PI3K protein kinase activity in regulating cell survival is unknown. We have employed a novel approach to purify and pharmacologically profile protein kinases from primary human acute myeloid leukemia (AML cells that phosphorylate serine residues in the cytoplasmic portion of cytokine receptors to promote hemopoietic cell survival. We have isolated a kinase activity that is able to directly phosphorylate Ser585 in the cytoplasmic domain of the interleukin 3 (IL-3 and granulocyte macrophage colony stimulating factor (GM-CSF receptors and shown it to be PI3K. Physiological concentrations of cytokine in the picomolar range were sufficient for activating the protein kinase activity of PI3K leading to Ser585 phosphorylation and hemopoietic cell survival but did not activate PI3K lipid kinase signaling or promote proliferation. Blockade of PI3K lipid signaling by expression of the pleckstrin homology of Akt1 had no significant impact on the ability of picomolar concentrations of cytokine to promote hemopoietic cell survival. Furthermore, inducible expression of a mutant form of PI3K that is defective in lipid kinase activity but retains protein kinase activity was able to promote Ser585 phosphorylation and hemopoietic cell survival in the absence of cytokine. Blockade of p110α by RNA interference or multiple independent PI3K inhibitors not only blocked Ser585 phosphorylation in cytokine-dependent cells and primary human AML blasts, but also resulted in a block in survival signaling and cell death. Our findings demonstrate a new role for the protein kinase activity of PI3K in phosphorylating the cytoplasmic tail of the GM-CSF and IL-3 receptors to selectively regulate cell survival highlighting the importance of targeting

Motor demand-dependent activation of ipsilateral motor cortex.

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Buetefisch, Cathrin M; Revill, Kate Pirog; Shuster, Linda; Hines, Benjamin; Parsons, Michael

2014-08-15

The role of ipsilateral primary motor cortex (M1) in hand motor control during complex task performance remains controversial. Bilateral M1 activation is inconsistently observed in functional (f)MRI studies of unilateral hand performance. Two factors limit the interpretation of these data. As the motor tasks differ qualitatively in these studies, it is conceivable that M1 contributions differ with the demand on skillfulness. Second, most studies lack the verification of a strictly unilateral execution of the motor task during the acquisition of imaging data. Here, we use fMRI to determine whether ipsilateral M1 activity depends on the demand for precision in a pointing task where precision varied quantitatively while movement trajectories remained equal. Thirteen healthy participants used an MRI-compatible joystick to point to targets of four different sizes in a block design. A clustered acquisition technique allowed simultaneous fMRI/EMG data collection and confirmed that movements were strictly unilateral. Accuracy of performance increased with target size. Overall, the pointing task revealed activation in contralateral and ipsilateral M1, extending into contralateral somatosensory and parietal areas. Target size-dependent activation differences were found in ipsilateral M1 extending into the temporal/parietal junction, where activation increased with increasing demand on accuracy. The results suggest that ipsilateral M1 is active during the execution of a unilateral motor task and that its activity is modulated by the demand on precision. Copyright © 2014 the American Physiological Society.

Deciphering Phosphotyrosine-Dependent Signaling Networks in Cancer by SH2 Profiling

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Machida, Kazuya; Khenkhar, Malik

2012-01-01

It has been a decade since the introduction of SH2 profiling, a modular domain-based molecular diagnostics tool. This review covers the original concept of SH2 profiling, different analytical platforms, and their applications, from the detailed analysis of single proteins to broad screening in translational research. Illustrated by practical examples, we discuss the uniqueness and advantages of the approach as well as its limitations and challenges. We provide guidance for basic researchers and oncologists who may consider SH2 profiling in their respective cancer research, especially for those focusing on tyrosine phosphoproteomics. SH2 profiling can serve as an alternative phosphoproteomics tool to dissect aberrant tyrosine kinase pathways responsible for individual malignancies, with the goal of facilitating personalized diagnostics for the treatment of cancer. PMID:23226573

Space-Time Dependent Transport, Activation, and Dose Rates for Radioactivated Fluids.

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Gavazza, Sergio

Two methods are developed to calculate the space - and time-dependent mass transport of radionuclides, their production and decay, and the associated dose rates generated from the radioactivated fluids flowing through pipes. The work couples space- and time-dependent phenomena, treated as only space- or time-dependent in the open literature. The transport and activation methodology (TAM) is used to numerically calculate space- and time-dependent transport and activation of radionuclides in fluids flowing through pipes exposed to radiation fields, and volumetric radioactive sources created by radionuclide motions. The computer program Radionuclide Activation and Transport in Pipe (RNATPA1) performs the numerical calculations required in TAM. The gamma ray dose methodology (GAM) is used to numerically calculate space- and time-dependent gamma ray dose equivalent rates from the volumetric radioactive sources determined by TAM. The computer program Gamma Ray Dose Equivalent Rate (GRDOSER) performs the numerical calculations required in GAM. The scope of conditions considered by TAM and GAM herein include (a) laminar flow in straight pipe, (b)recirculating flow schemes, (c) time-independent fluid velocity distributions, (d) space-dependent monoenergetic neutron flux distribution, (e) space- and time-dependent activation process of a single parent nuclide and transport and decay of a single daughter radionuclide, and (f) assessment of space- and time-dependent gamma ray dose rates, outside the pipe, generated by the space- and time-dependent source term distributions inside of it. The methodologies, however, can be easily extended to include all the situations of interest for solving the phenomena addressed in this dissertation. A comparison is made from results obtained by the described calculational procedures with analytical expressions. The physics of the problems addressed by the new technique and the increased accuracy versus non -space and time-dependent methods

Inflammatory sensitization of nociceptors depends on activation of NMDA receptors in DRG satellite cells.

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Ferrari, Luiz Fernando; Lotufo, Celina Monteiro; Araldi, Dionéia; Rodrigues, Marcos A; Macedo, Larissa P; Ferreira, Sérgio H; Parada, Carlos Amilcar

2014-12-23

The present study evaluated the role of N-methyl-D-aspartate receptors (NMDARs) expressed in the dorsal root ganglia (DRG) in the inflammatory sensitization of peripheral nociceptor terminals to mechanical stimulation. Injection of NMDA into the fifth lumbar (L5)-DRG induced hyperalgesia in the rat hind paw with a profile similar to that of intraplantar injection of prostaglandin E2 (PGE2), which was significantly attenuated by injection of the NMDAR antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP-5) in the L5-DRG. Moreover, blockade of DRG AMPA receptors by the antagonist 6,7-dinitroquinoxaline-2,3-dione had no effect in the PGE2-induced hyperalgesia in the paw, showing specific involvement of NMDARs in this modulatory effect and suggesting that activation of NMDAR in the DRG plays an important role in the peripheral inflammatory hyperalgesia. In following experiments we observed attenuation of PGE2-induced hyperalgesia in the paw by the knockdown of NMDAR subunits NR1, NR2B, NR2D, and NR3A with antisense-oligodeoxynucleotide treatment in the DRG. Also, in vitro experiments showed that the NMDA-induced sensitization of cultured DRG neurons depends on satellite cell activation and on those same NMDAR subunits, suggesting their importance for the PGE2-induced hyperalgesia. In addition, fluorescent calcium imaging experiments in cultures of DRG cells showed induction of calcium transients by glutamate or NMDA only in satellite cells, but not in neurons. Together, the present results suggest that the mechanical inflammatory nociceptor sensitization is dependent on glutamate release at the DRG and subsequent NMDAR activation in satellite glial cells, supporting the idea that the peripheral hyperalgesia is an event modulated by a glutamatergic system in the DRG.

Editor's Highlight: Transcriptome Profiling Reveals Bisphenol A Alternatives Activate Estrogen Receptor Alpha in Human Breast Cancer Cells.

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Mesnage, Robin; Phedonos, Alexia; Arno, Matthew; Balu, Sucharitha; Corton, J Christopher; Antoniou, Michael N

2017-08-01

Plasticizers with estrogenic activity, such as bisphenol A (BPA), have potential adverse health effects in humans. Due to mounting evidence of these health effects, BPA is being phased out and replaced by other bisphenol variants in "BPA-free" products. We have compared estrogenic activity of BPA with 6 bisphenol analogues [bisphenol S (BPS); bisphenol F (BPF); bisphenol AP (BPAP); bisphenol AF (BPAF); bisphenol Z (BPZ); bisphenol B (BPB)] in 3 human breast cancer cell lines. Estrogenicity was assessed (10-11-10-4 M) by cell growth in an estrogen receptor (ER)-mediated cell proliferation assay, and by the induction of estrogen response element-mediated transcription in a luciferase assay. BPAF was the most potent bisphenol, followed by BPB > BPZ ∼ BPA > BPF ∼ BPAP > BPS. The addition of ICI 182,780 antagonized the activation of ERs. Data mining of ToxCast high-throughput screening assays confirm our results but also show divergence in the sensitivities of the assays. Gene expression profiles were determined in MCF-7 cells by microarray analysis. The comparison of transcriptome profile alterations resulting from BPA alternatives with an ERα gene expression biomarker further indicates that all BPA alternatives act as ERα agonists in MCF-7 cells. These results were confirmed by Illumina-based RNA sequencing. In conclusion, BPA alternatives are not necessarily less estrogenic than BPA in human breast cancer cells. BPAF, BPB, and BPZ were more estrogenic than BPA. These findings point to the importance of better understanding the risk of adverse effects from exposure to BPA alternatives, including hormone-dependent breast cancer. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology.

Cardiac autonomic profile in different sports disciplines during all-day activity.

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Sztajzel, J; Jung, M; Sievert, K; Bayes De Luna, A

2008-12-01

Physical training and sport activity have a beneficial effect on cardiac autonomic activity. However, the exact impact of different types of sports disciplines on cardiac autonomic function is still unclear. The aim of this study was to evaluate the cardiac autonomic profile in different sports discplines and to determine their impact on cardiac autonomic function by using heart rate variability (HRV), a noninvasive electrocardiographic (ECG) analysis of the sympatho-vagal balance. Temporal and spectral HRV parameters determined from 24-hour continuous ECG monitoring were studied in 40 subjects, including 12 endurance athletes, 14 hockey players and 14 untrained male volunteers (control group). Each participant had to wear a Holter recorder during 24 hours and to continue his everyday activities. All HRV parameters were compared between the 3 study groups. All heart rate values were lower and all parasympathetic-related time domain indices, including root mean square of successive differences (RMSSD) and pNN50 (NN50 count divided by the total number of all NN intervals), were higher in both athletes groups as compared with controls (PHRV, were significantly higher only in endurance athletes (PHRV (higher SDNN), indicating thereby that this type sports discipline may have a more substantially favorable effect on the cardiac autonomic profile.

Lipidic profile and the level of physical activity of adolescent scholars - doi:10.5020/18061230.2011.p384

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Renato Canevari Dutra da Silva

2012-01-01

Full Text Available Objective: To assess the relationship between lipid profile and physical activity level of adolescent students in Rio Verde-GO, Brazil. Methods: A descriptive and cross-sectional study, conducted in 2006, with a population comprised by 1,229 adolescent students of both genders, aged 15 to 17 years (X = 15.9 years, SD + 0.81, from public and private schools. The level of physical activity was assessed through the International Physical Activity Questionnaire (IPAQ. Later, 48 teenagers underwent a lipidogram (lipid profile. Lipid concentrations of total cholesterol (TC, HDL-c (high density lipoprotein and LDL (low density lipoprotein and triglycerides (TGL were determined and assessed according to cutoff points proposed by the III Brazilian Guidelines on dyslipidemias and Guideline of Atherosclerosis, Department of Atherosclerosis of Brazilian Society of Cardiology. Statistical analysis was performed by binomial test for proportions and Pearson’s correlation test, adopting p <0.05. Results: Applying IPAQ we found apercentage of 77.7% active adolescents and 22.3% of insufficiently active adolescents, with the highest percentage of active teens in males (p = 0.0000. Adolescents of both sexes from public network were considered more active than teens from private schools. The lipid profile of the studied adolescents was within normal range. Conclusion: There was no relationship between physical activity level and lipid profile of the adolescents assessed.

Recovery of rhythmic activity in a central pattern generator: analysis of the role of neuromodulator and activity-dependent mechanisms.

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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.

Physical qualities and activity profiles of sub-elite and recreational Australian football players.

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Stein, Josh G; Gabbett, Tim J; Townshend, Andrew D; Dawson, Brian T

2015-11-01

To investigate the relationship between physical qualities and match activity profiles of recreational Australian football players. Prospective cohort study. Forty players from three recreational Australian football teams (Division One, Two and Three) underwent a battery of fitness tests (vertical jump, 10 and 40 m sprint, 6 m × 30 m repeated sprint test, Yo-Yo intermittent recovery level Two and 2-km time trial). The activity profiles of competitive match-play were quantified using 10-Hz Global Positioning System units. Division One players possessed greater maximum velocity, Yo-Yo level Two and 2-km time trial performances than Division Two and Three players. In addition, Division One players covered greater relative distance, and relative distances at moderate- and high-intensities during match-play than Division Two and Three players. Division Two players had better 2-km time trial performances than Division Three players. Positive associations (P football players competing at a higher level exhibit greater physical qualities and match-play activity profiles than lesser-skilled recreational players. Acceleration and maximum velocity, 2-km time trial and Yo-Yo level Two performances discriminate between players of different playing levels, and are related to physical match performance in recreational Australian football. The development of these qualities is likely to contribute to improved match performance in recreational Australian football players. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

NPM1 directs PIDDosome-dependent caspase-2 activation in the nucleolus.

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Ando, Kiyohiro; Parsons, Melissa J; Shah, Richa B; Charendoff, Chloé I; Paris, Sheré L; Liu, Peter H; Fassio, Sara R; Rohrman, Brittany A; Thompson, Ruth; Oberst, Andrew; Sidi, Samuel; Bouchier-Hayes, Lisa

2017-06-05

The PIDDosome (PIDD-RAIDD-caspase-2 complex) is considered to be the primary signaling platform for caspase-2 activation in response to genotoxic stress. Yet studies of PIDD-deficient mice show that caspase-2 activation can proceed in the absence of PIDD. Here we show that DNA damage induces the assembly of at least two distinct activation platforms for caspase-2: a cytoplasmic platform that is RAIDD dependent but PIDD independent, and a nucleolar platform that requires both PIDD and RAIDD. Furthermore, the nucleolar phosphoprotein nucleophosmin (NPM1) acts as a scaffold for PIDD and is essential for PIDDosome assembly in the nucleolus after DNA damage. Inhibition of NPM1 impairs caspase-2 processing, apoptosis, and caspase-2-dependent inhibition of cell growth, demonstrating that the NPM1-dependent nucleolar PIDDosome is a key initiator of the caspase-2 activation cascade. Thus we have identified the nucleolus as a novel site for caspase-2 activation and function. © 2017 Ando et al.

The Stress-Dependent Activation Parameters for Dislocation Nucleation in Molybdenum Nanoparticles.

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Chachamovitz, Doron; Mordehai, Dan

2018-03-02

Many specimens at the nanoscale are pristine of dislocations, line defects which are the main carriers of plasticity. As a result, they exhibit extremely high strengths which are dislocation-nucleation controlled. Since nucleation is a thermally activated process, it is essential to quantify the stress-dependent activation parameters for dislocation nucleation in order to study the strength of specimens at the nanoscale and its distribution. In this work, we calculate the strength of Mo nanoparticles in molecular dynamics simulations and we propose a method to extract the activation free-energy barrier for dislocation nucleation from the distribution of the results. We show that by deforming the nanoparticles at a constant strain rate, their strength distribution can be approximated by a normal distribution, from which the activation volumes at different stresses and temperatures are calculated directly. We found that the activation energy dependency on the stress near spontaneous nucleation conditions obeys a power-law with a critical exponent of approximately 3/2, which is in accordance with critical exponents found in other thermally activated processes but never for dislocation nucleation. Additionally, significant activation entropies were calculated. Finally, we generalize the approach to calculate the activation parameters for other driving-force dependent thermally activated processes.

Effect of moderate walnut consumption on lipid profile, arterial stiffness and platelet activation in humans.

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Din, J N; Aftab, S M; Jubb, A W; Carnegy, F H; Lyall, K; Sarma, J; Newby, D E; Flapan, A D

2011-02-01

A large intake of walnuts may improve lipid profile and endothelial function. The effect of moderate walnut consumption is not known. We investigated whether a moderate intake of walnuts would affect lipid profile, arterial stiffness and platelet activation in healthy volunteers. A total of 30 healthy males were recruited into a single-blind randomized controlled crossover trial of 4 weeks of dietary walnut supplementation (15 g/day) and 4 weeks of control (no walnuts). Arterial stiffness was assessed using pulse waveform analysis to determine the augmentation index and augmented pressure. Platelet activation was determined using flow cytometry to measure circulating platelet-monocyte aggregates. There were no differences in lipid profile after 4 weeks of walnut supplementation compared with control. Dietary intake of α-linolenic acid was increased during the walnut diet (2.1±0.4 g/day versus 0.7±0.4 g/day, Pprofile, arterial stiffness or platelet activation in man. Our results suggest that the potentially beneficial cardiac effects of walnuts may not be apparent at lower and more practical levels of consumption.

Cognitive profile of emotional dependence in University Students from Medellín, Colombia [Perfil cognitivo de la dependencia emocional en estudiantes universitarios en Medellín, Colombia

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Mariantonia Lemos Hoyos

2012-06-01

Full Text Available The objective of this study was to identify the cognitive profile of university students with emotional dependency. This is considered as a pattern oriented to another person as a source of satisfaction and personal safety, where the cognitive profile will make them to interpret the facts in a different way in order to cover their unsatisfied emotional needs. We use a random sample of 569 university students. The results showed a characteristic profile which explains 89.3% of the variability and a high predictive model capacity (sensitivity 91.4% and specificity 97.7%, formed by the schema of mistrust/abuse, the cores beliefs of paranoid and dependent personality disorders, fallacy of change as cognitive distortion and underdeveloped autonomy as a coping skill.

Lateral dimension-dependent antibacterial activity of graphene oxide sheets.

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Liu, Shaobin; Hu, Ming; Zeng, Tingying Helen; Wu, Ran; Jiang, Rongrong; Wei, Jun; Wang, Liang; Kong, Jing; Chen, Yuan

2012-08-21

Graphene oxide (GO) is a promising precursor to produce graphene-family nanomaterials for various applications. Their potential health and environmental impacts need a good understanding of their cellular interactions. Many factors may influence their biological interactions with cells, and the lateral dimension of GO sheets is one of the most relevant material properties. In this study, a model bacterium, Escherichia coli ( E. coli ), was used to evaluate the antibacterial activity of well-dispersed GO sheets, whose lateral size differs by more than 100 times. Our results show that the antibacterial activity of GO sheets toward E. coli cells is lateral size dependent. Larger GO sheets show stronger antibacterial activity than do smaller ones, and they have different time- and concentration-dependent antibacterial activities. Large GO sheets lead to most cell loss after 1 h incubation, and their concentration strongly influences antibacterial activity at relative low concentration (oxidation capacity toward glutathione is similar, consistent with X-ray photoelectron spectroscopy and ultraviolet-visible absorption spectroscopy results. This suggests the lateral size-dependent antibacterial activity of GO sheets is caused by neither their aggregation states, nor oxidation capacity. Atomic force microscope analysis of GO sheets and cells shows that GO sheets interact strongly with cells. Large GO sheets more easily cover cells, and cells cannot proliferate once fully covered, resulting in the cell viability loss observed in the followed colony counting test. In contrast, small GO sheets adhere to the bacterial surfaces, which cannot effectively isolate cells from environment. This study highlights the importance of tailoring the lateral dimension of GO sheets to optimize the application potential with minimal risks for environmental health and safety.

Activity-dependent neurorehabilitation beyond physical trainings: "mental exercise" through mirror neuron activation

OpenAIRE

Yuan, Ti-Fei; Chen, Wei; Shan, Chunlei; Rocha, Nuno; Arias-Carrión, Oscar; Paes, Flávia; de Sa, Alberto Souza; Machado, Sergio

2015-01-01

The activity dependent brain repair mechanism has been widely adopted in many types of neurorehabilitation. The activity leads to target specific and non-specific beneficial effects in different brain regions, such as the releasing of neurotrophic factors, modulation of the cytokines and generation of new neurons in adult hood. However physical exercise program clinically are limited to some of the patients with preserved motor functions; while many patients suffered from paralysis cannot mak...

H-mode profile parametrization for extrapolation and control

International Nuclear Information System (INIS)

Imre, K.; Riedel, K.S.; Schissel, D.P.; Schunke, B.

1996-01-01

A steady-state ELMy H-mode profile data set of 68 DIII-D discharges and 74 JET discharges is fitted with an error of 7-8%. The advantages of a parametrization of the plasma profiles in terms of a semi-parametric representation, T(ρ, I p , n-bar, B t , P L , R), are described. The shape of the temperature profile depends almost exclusively upon the size, R and q 95 , with a secondary dependence on the heating power. The density profile depends primarily upon q95 with a secondary dependence on n-bar. The line-average temperature T-bar e scales as n-bar -0.31 instead of T-bar∼''n-bar'' -1.0 . The predicted ITER temperature is T-bar = 17.1 keV. (Author)

Topside electron density: comparison of experimental and IRI model profiles during low solar activity period

International Nuclear Information System (INIS)

Alazo, K.; Coisson, P.; Radicella, S.M.

2003-01-01

The pattern of the topside electron density profiles is not yet very well represented by the IRI model. In this work the topside profiles obtained by the ISIS-2 satellite during low solar activity conditions are compared to those modeled by IRI. We take the quantitative parameter ε to measure the deviation of the model from the observed profiles. The results showed that the IRI overestimation of the topside profile is higher for low dip latitudes. The dispersion of the epsilon values is from 40 to 140%, more in equinoctial months and some lower for Winter. The best modeling is about 20% to 40% in middle and high latitudes of the North Hemisphere. (author)

DREAM Controls the On/Off Switch of Specific Activity-Dependent Transcription Pathways

Science.gov (United States)

Mellström, Britt; Sahún, Ignasi; Ruiz-Nuño, Ana; Murtra, Patricia; Gomez-Villafuertes, Rosa; Savignac, Magali; Oliveros, Juan C.; Gonzalez, Paz; Kastanauskaite, Asta; Knafo, Shira; Zhuo, Min; Higuera-Matas, Alejandro; Errington, Michael L.; Maldonado, Rafael; DeFelipe, Javier; Jefferys, John G. R.; Bliss, Tim V. P.; Dierssen, Mara

2014-01-01

Changes in nuclear Ca2+ homeostasis activate specific gene expression programs and are central to the acquisition and storage of information in the brain. DREAM (downstream regulatory element antagonist modulator), also known as calsenilin/KChIP-3 (K+ channel interacting protein 3), is a Ca2+-binding protein that binds DNA and represses transcription in a Ca2+-dependent manner. To study the function of DREAM in the brain, we used transgenic mice expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). Using genome-wide analysis, we show that DREAM regulates the expression of specific activity-dependent transcription factors in the hippocampus, including Npas4, Nr4a1, Mef2c, JunB, and c-Fos. Furthermore, DREAM regulates its own expression, establishing an autoinhibitory feedback loop to terminate activity-dependent transcription. Ablation of DREAM does not modify activity-dependent transcription because of gene compensation by the other KChIP family members. The expression of daDREAM in the forebrain resulted in a complex phenotype characterized by loss of recurrent inhibition and enhanced long-term potentiation (LTP) in the dentate gyrus and impaired learning and memory. Our results indicate that DREAM is a major master switch transcription factor that regulates the on/off status of specific activity-dependent gene expression programs that control synaptic plasticity, learning, and memory. PMID:24366545

Effects of gamma irradiation on chickpea seeds vis-a-vis total seed storage proteins, antioxidant activity and protein profiling.

Science.gov (United States)

Bhagyawant, S S; Gupta, N; Shrivastava, N

2015-10-23

The present work describes radiation—induced effects on seed composition vis—à—vis total seed proteins, antioxidant levels and protein profiling employing two dimensional gel electrophoresis (2D—GE) in kabuli and desi chickpea varities. Seeds were exposed to the radiation doses of 1,2,3,4 and 5 kGy. The total protein concentrations decreased and antioxidant levels were increased with increasing dose compared to control seed samples. Radiation induced effects were dose dependent to these seed parameters while it showed tolerance to 1 kGy dose. Increase in the dose was complimented with increase in antioxidant levels, like 5 kGy enhanced % scavenging activities in all the seed extracts. Precisely, the investigations reflected that the dose range from 2 to 5 kGy was effective for total seed storage proteins, as depicted quantitatively and qualitative 2D—GE means enhance antioxidant activities in vitro.

Integration of miRNA and protein profiling reveals coordinated neuroadaptations in the alcohol-dependent mouse brain.

Directory of Open Access Journals (Sweden)

Giorgio Gorini

Full Text Available The molecular mechanisms underlying alcohol dependence involve different neurochemical systems and are brain region-dependent. Chronic Intermittent Ethanol (CIE procedure, combined with a Two-Bottle Choice voluntary drinking paradigm, represents one of the best available animal models for alcohol dependence and relapse drinking. MicroRNAs, master regulators of the cellular transcriptome and proteome, can regulate their targets in a cooperative, combinatorial fashion, ensuring fine tuning and control over a large number of cellular functions. We analyzed cortex and midbrain microRNA expression levels using an integrative approach to combine and relate data to previous protein profiling from the same CIE-subjected samples, and examined the significance of the data in terms of relative contribution to alcohol consumption and dependence. MicroRNA levels were significantly altered in CIE-exposed dependent mice compared with their non-dependent controls. More importantly, our integrative analysis identified modules of coexpressed microRNAs that were highly correlated with CIE effects and predicted target genes encoding differentially expressed proteins. Coexpressed CIE-relevant proteins, in turn, were often negatively correlated with specific microRNA modules. Our results provide evidence that microRNA-orchestrated translational imbalances are driving the behavioral transition from alcohol consumption to dependence. This study represents the first attempt to combine ex vivo microRNA and protein expression on a global scale from the same mammalian brain samples. The integrative systems approach used here will improve our understanding of brain adaptive changes in response to drug abuse and suggests the potential therapeutic use of microRNAs as tools to prevent or compensate multiple neuroadaptations underlying addictive behavior.

Analysis of the activation profile of dendritic cells derived from the bone marrow of interleukin-12/interleukin-23-deficient mice

Science.gov (United States)

Bastos, Karina R B; de Deus Vieira de Moraes, Luciana; Zago, Cláudia A; Marinho, Cláudio R F; Russo, Momtchilo; Alvarez, José M M; D'Império Lima, Maria R

2005-01-01

We have previously shown that macrophages from interleukin (IL)-12p40 gene knockout (IL-12/IL-23−/−) mice have a bias towards the M2 activation profile, spontaneously secreting large quantities of transforming growth factor-β1 (TGF-β1) and producing low levels of nitric oxide (NO) in response to lipopolysaccharide (LPS) and interferon-γ (IFN-γ). To verify whether the activation profile of dendritic cells (DCs) is also influenced by the absence of IL-12/IL-23, bone marrow-derived DCs from IL-12/IL-23−/− and C57BL/6 mice were evaluated. At first we noticed that ≈ 50% of the C57BL/6 DCs were dead after LPS-induced maturation, whereas the mortality of IL-12/IL-23−/− DCs was < 10%, a protective effect that diminished when recombinant IL-12 (rIL-12) was added during maturation. Similarly to macrophages, mature IL-12/IL-23−/− DCs (mDCs) produced higher levels of TGF-β1 and lower levels of NO than C57BL/6 mDCs. NO release was IFN-γ-dependent, as evidenced by the poor response of IFN-γ−/− and IL-12/IL-23−/−IFN-γ−/− mDCs. Nevertheless, IFN-γ deficiency was not the sole reason for the weak NO response observed in the absence of IL-12/IL-23. The high level of TGF-β1 secretion by IL-12/IL-23−/− mDCs could explain why exogenous IFN-γ partially restored the NO production of IFN-γ−/− mDCs, while IL-12/IL-23−/− IFN-γ−/− mDCs remained unresponsive. We also showed that CD4+ T-cell proliferation was inhibited by C57BL/6 mDCs, but not by IL-12/IL-23−/− mDCs. IFN-γ and NO appear to mediate this antiproliferative effect because this effect was not observed in the presence of mDCs from IFN-γ−/− or IL-12/IL-23−/− IFN-γ−/− mice and it was attenuated by aminoguanidine. We conclude that the presence of IL-12/IL-23 during LPS-induced maturation influences the activation profile of DCs by a mechanism that is, only in part, IFN-γ dependent. PMID:15804287

[Flexibility of cognitive activity depends on its context].

Science.gov (United States)

Kostandov, É A

2010-01-01

The main purpose of this survey is to explain the importance of set-shifting for a flexible cognitive activity. Working memory overload may result in set-shifting slowdown, i.e., in a more rigid set and in a less flexible cognitive activity. This effect displays itself in an increase of erroneous perceptions of external stimuli. Set rigidity level also depends on the cognitive activity context (i.e., on the type of external stimuli the person has to deal with). We analyzed EEG-coherence function and induced synchronization/desynchronization responses in theta (4-7 Hz) and low alpha (8-10 Hz) bands. Basing on these data, we discuss the role of tonic and phasic forms of cortico-hippocampal and fronto-thalamic systems' activation in cognitive activity flexibility.

Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells

International Nuclear Information System (INIS)

Lambert, Carine B.; Spire, Catherine; Claude, Nancy; Guillouzo, Andre

2009-01-01

Phenobarbital (PB) induces or represses a wide spectrum of genes in rodent liver. Much less is known about its effects in human liver. We used pangenomic cDNA microarrays to analyze concentration- and time-dependent gene expression profile changes induced by PB in the well-differentiated human HepaRG cell line. Changes in gene expression profiles clustered at specific concentration ranges and treatment times. The number of correctly annotated genes significantly modulated by at least three different PB concentration ranges (spanning 0.5 to 3.2 mM) at 20 h exposure amounted to 77 and 128 genes (p ≤ 0.01) at 2- and 1.8-fold filter changes, respectively. At low concentrations (0.5 and 1 mM), PB-responsive genes included the well-recognized CAR- and PXR-dependent responsive cytochromes P450 (CYP2B6, CYP3A4), sulfotransferase 2A1 and plasma transporters (ABCB1, ABCC2), as well as a number of genes critically involved in various metabolic pathways, including lipid (CYP4A11, CYP4F3), vitamin D (CYP24A1) and bile (CYP7A1 and CYP8B1) metabolism. At concentrations of 3.2 mM or higher after 20 h, and especially 48 h, increased cytotoxic effects were associated with disregulation of numerous genes related to oxidative stress, DNA repair and apoptosis. Primary human hepatocyte cultures were also exposed to 1 and 3.2 mM PB for 20 h and the changes were comparable to those found in HepaRG cells treated under the same conditions. Taken altogether, our data provide further evidence that HepaRG cells closely resemble primary human hepatocytes and provide new information on the effects of PB in human liver. These data also emphasize the importance of investigating dose- and time-dependent effects of chemicals when using toxicogenomic approaches

The fatty acid profile in different wheat cultivars depending on the level of contamination with microscopic fungi.

Science.gov (United States)

Stuper-Szablewska, Kinga; Buśko, Maciej; Góral, Tomasz; Perkowski, Juliusz

2014-06-15

Analyses were conducted on 30 winter wheat samples growing under controlled conditions and following inoculation with fungi Fusarium culmorum. In inoculated samples the mean concentration of 30 analysed fatty acids was significantly higher in relation to the control and amounted to 1,396 mg/kg vs. 1,046 mg/kg in the control kernels. Recorded concentrations for individual cultivars were significantly correlated with the concentration of fungal biomass. Higher concentration in the control was recorded only for the acid trans C18:2n-6. It was also found that the acid profiles are characteristic of individual cultivars. Statistical analysis showed that trans C18:2n-6, C18:1, C18:3n-3 and C18:3n-6 were the acids with the greatest discriminatory power in distinguishing inoculated samples from the control. Discriminatory analysis separated individual cultivars into quality classes of winter wheat cultivars depending on the presence of a specific fatty acid profile. Copyright © 2014 Elsevier Ltd. All rights reserved.

Universal Temporal Profile of Replication Origin Activation in Eukaryotes

Science.gov (United States)

Goldar, Arach

2011-03-01

The complete and faithful transmission of eukaryotic genome to daughter cells involves the timely duplication of mother cell's DNA. DNA replication starts at multiple chromosomal positions called replication origin. From each activated replication origin two replication forks progress in opposite direction and duplicate the mother cell's DNA. While it is widely accepted that in eukaryotic organisms replication origins are activated in a stochastic manner, little is known on the sources of the observed stochasticity. It is often associated to the population variability to enter S phase. We extract from a growing Saccharomyces cerevisiae population the average rate of origin activation in a single cell by combining single molecule measurements and a numerical deconvolution technique. We show that the temporal profile of the rate of origin activation in a single cell is similar to the one extracted from a replicating cell population. Taking into account this observation we exclude the population variability as the origin of observed stochasticity in origin activation. We confirm that the rate of origin activation increases in the early stage of S phase and decreases at the latter stage. The population average activation rate extracted from single molecule analysis is in prefect accordance with the activation rate extracted from published micro-array data, confirming therefore the homogeneity and genome scale invariance of dynamic of replication process. All these observations point toward a possible role of replication fork to control the rate of origin activation.

Arrhenius temperature dependence of in vitro tissue plasminogen activator thrombolysis

International Nuclear Information System (INIS)

Shaw, George J; Dhamija, Ashima; Bavani, Nazli; Wagner, Kenneth R; Holland, Christy K

2007-01-01

Stroke is a devastating disease and a leading cause of death and disability. Currently, the only FDA approved therapy for acute ischemic stroke is the intravenous administration of the thrombolytic medication, recombinant tissue plasminogen activator (tPA). However, this treatment has many contraindications and can have dangerous side effects such as intra-cerebral hemorrhage. These treatment limitations have led to much interest in potential adjunctive therapies, such as therapeutic hypothermia (T ≤ 35 deg. C) and ultrasound enhanced thrombolysis. Such interest may lead to combining these therapies with tPA to treat stroke, however little is known about the effects of temperature on the thrombolytic efficacy of tPA. In this work, we measure the temperature dependence of the fractional clot mass loss Δm(T) resulting from tPA exposure in an in vitro human clot model. We find that the temperature dependence is well described by an Arrhenius temperature dependence with an effective activation energy E eff of 42.0 ± 0.9 kJ mole -1 . E eff approximates the activation energy of the plasminogen-to-plasmin reaction of 48.9 kJ mole -1 . A model to explain this temperature dependence is proposed. These results will be useful in predicting the effects of temperature in future lytic therapies

Arrhenius temperature dependence of in vitro tissue plasminogen activator thrombolysis

Energy Technology Data Exchange (ETDEWEB)

Shaw, George J [Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0769 (United States); Dhamija, Ashima [Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0769 (United States); Bavani, Nazli [Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0769 (United States); Wagner, Kenneth R [Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0769 (United States); Holland, Christy K [Department of Biomedical Engineering, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0769 (United States)

2007-06-07

Stroke is a devastating disease and a leading cause of death and disability. Currently, the only FDA approved therapy for acute ischemic stroke is the intravenous administration of the thrombolytic medication, recombinant tissue plasminogen activator (tPA). However, this treatment has many contraindications and can have dangerous side effects such as intra-cerebral hemorrhage. These treatment limitations have led to much interest in potential adjunctive therapies, such as therapeutic hypothermia (T {<=} 35 deg. C) and ultrasound enhanced thrombolysis. Such interest may lead to combining these therapies with tPA to treat stroke, however little is known about the effects of temperature on the thrombolytic efficacy of tPA. In this work, we measure the temperature dependence of the fractional clot mass loss {delta}m(T) resulting from tPA exposure in an in vitro human clot model. We find that the temperature dependence is well described by an Arrhenius temperature dependence with an effective activation energy E{sub eff} of 42.0 {+-} 0.9 kJ mole{sup -1}. E{sub eff} approximates the activation energy of the plasminogen-to-plasmin reaction of 48.9 kJ mole{sup -1}. A model to explain this temperature dependence is proposed. These results will be useful in predicting the effects of temperature in future lytic therapies.

pH-Dependent Binding of Chloride to a Marine Alkaline Phosphatase Affects the Catalysis, Active Site Stability, and Dimer Equilibrium.

Science.gov (United States)

Hjörleifsson, Jens G; Ásgeirsson, Bjarni

2017-09-26

The effect of ionic strength on enzyme activity and stability varies considerably between enzymes. Ionic strength is known to affect the catalytic activity of some alkaline phosphatases (APs), such as Escherichia coli AP, but how ions affect APs is debated. Here, we studied the effect of various ions on a cold-adapted AP from Vibrio splendidus (VAP). Previously, we have found that the active form of VAP is extremely unstable at low ionic strengths. Here we show that NaCl increased the activity and stability of VAP and that the effect was pH-dependent in the range of pH 7-10. The activity profile as a function of pH formed two maxima, indicating a possible conformational change. Bringing the pH from the neutral to the alkaline range was accompanied by a large increase in both the K i for inorganic phosphate (product inhibition) and the K M for p-nitrophenyl phosphate. The activity transitions observed as the pH was varied correlated with structural changes as monitored by tryptophan fluorescence. Thermal and urea-induced inactivation was shown to be accompanied by neither dissociation of the active site metal ions nor dimer dissociation. This would suggest that the inactivation involved subtle changes in active site conformation. Furthermore, the VAP dimer equilibrium was studied for the first time and shown to highly favor dimerization, which was dependent on pH and NaCl concentration. Taken together, the data support a model in which anions bind to some specific acceptor in the active site of VAP, resulting in great stabilization and catalytic rate enhancement, presumably through a different mechanism.

IRI profile parameters at equatorial latitudes

International Nuclear Information System (INIS)

Reinisch, B.W.; Huang Xueqin; Conway, J.

2002-01-01

The IRI bottom-side electron density profile is specified as a function of three parameters B0, B1, and D1 describing the F2 layer thickness and shape, and the shape of the F1 layer, respectively. Together with the URSI or CCIR coefficients for the F2 layer peak density and height, they completely specify the profiles as function of time, season and solar activity. In support of the international effort of determining the best set of parameters we have analyzed the diurnal variations of B0, B1, and D1 for Jicamarca for high solar activity during 1999 and 2000 for different seasons and magnetic activity. The B0 values vary from a minimum of ∼95 km at 0300 LT to ∼250 km at local noon (1700 UT). The diurnal variation is similar to the IRI2000 prediction. B1 varies from ∼1.9 at daytime to ∼2.2 at night. The value of D1 is ∼0.5. The parameters show little Kp dependence. Standard deviations are shown. We calculated the ionospheric total electron contents for March and April 1998 from the ionogram profiles at Jicamarca and compared them with IRI predictions using the IRI 2000 parameters. While there is fair agreement, a significant time shift of 1 to 2 hours occurs in the transition from night to daytime values. (author)

Behaviorally activated mRNA expression profiles produce signatures of learning and enhanced inhibition in aged rats with preserved memory.

Science.gov (United States)

Haberman, Rebecca P; Colantuoni, Carlo; Koh, Ming Teng; Gallagher, Michela

2013-01-01

Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally-induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to

Comprehensive analysis of PPARa-dependent regulation of hepatic lipid metabolism by expression profiling

NARCIS (Netherlands)

Rakhshandehroo, Maryam; Sanderson-Kjellberg, L.M.; Matilainen, Merja; Stienstra, Rinke; Carlberg, Carsten; Groot, de Philip; Muller, Michael; Kersten, Sander

2007-01-01

PPARalpha is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARalpha in hepatic lipid metabolism, many PPARalpha-dependent pathways and genes have yet to be discovered. In order to

Heart rate and activity profile for young female soccer players

OpenAIRE

Barbero Álvarez, José Carlos; Gómez López, Maite; Barbero Álvarez, Verónica; Granda Vera, Juan; Castagna, Carlo

2008-01-01

The physical and physiological demands of high-level male soccer have been studied extensively, while few studies have investigated the demands placed on females during match-play, however, there is no information available about the heart rate and activity profile of young female soccer players during match play. Therefore, the aim of this study was to examine cardiovascular (heart-rates HR) and physical demands of young female soccer players during a match. Players were observed during a fr...

Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats

International Nuclear Information System (INIS)

Kuperman, D.A.; Sninsky, C.A.; Lynch, D.F.

1987-01-01

The authors investigated (1) the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, (2) whether bacterial overgrowth developed in morphine-dependent rats, and (3) the effect of naloxone and methylbromide naltrexone, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. They also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-[ 14 C]xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in 14 CO 2 excretion was noted in the morphine-dependent rats. They conclude from their studies that (1) myoelectric activity of the small intestine develops incomplete tolerance to morphine; (2) bacterial overgrowth is not a feature of morphine dependence in the rat; (3) alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an α 2 -adrenergic agonist

Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats

Energy Technology Data Exchange (ETDEWEB)

Kuperman, D.A.; Sninsky, C.A.; Lynch, D.F.

1987-04-01

The authors investigated (1) the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, (2) whether bacterial overgrowth developed in morphine-dependent rats, and (3) the effect of naloxone and methylbromide naltrexone, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. They also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-(/sup 14/C)xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in /sup 14/CO/sub 2/ excretion was noted in the morphine-dependent rats. They conclude from their studies that (1) myoelectric activity of the small intestine develops incomplete tolerance to morphine; (2) bacterial overgrowth is not a feature of morphine dependence in the rat; (3) alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an ..cap alpha../sub 2/-adrenergic agonist.

Lexical learning in mild aphasia: gesture benefit depends on patholinguistic profile and lesion pattern.

Science.gov (United States)

Kroenke, Klaus-Martin; Kraft, Indra; Regenbrecht, Frank; Obrig, Hellmuth

2013-01-01

Gestures accompany speech and enrich human communication. When aphasia interferes with verbal abilities, gestures become even more relevant, compensating for and/or facilitating verbal communication. However, small-scale clinical studies yielded diverging results with regard to a therapeutic gesture benefit for lexical retrieval. Based on recent functional neuroimaging results, delineating a speech-gesture integration network for lexical learning in healthy adults, we hypothesized that the commonly observed variability may stem from differential patholinguistic profiles in turn depending on lesion pattern. Therefore we used a controlled novel word learning paradigm to probe the impact of gestures on lexical learning, in the lesioned language network. Fourteen patients with chronic left hemispheric lesions and mild residual aphasia learned 30 novel words for manipulable objects over four days. Half of the words were trained with gestures while the other half were trained purely verbally. For the gesture condition, rootwords were visually presented (e.g., Klavier, [piano]), followed by videos of the corresponding gestures and the auditory presentation of the novel words (e.g., /krulo/). Participants had to repeat pseudowords and simultaneously reproduce gestures. In the verbal condition no gesture-video was shown and participants only repeated pseudowords orally. Correlational analyses confirmed that gesture benefit depends on the patholinguistic profile: lesser lexico-semantic impairment correlated with better gesture-enhanced learning. Conversely largely preserved segmental-phonological capabilities correlated with better purely verbal learning. Moreover, structural MRI-analysis disclosed differential lesion patterns, most interestingly suggesting that integrity of the left anterior temporal pole predicted gesture benefit. Thus largely preserved semantic capabilities and relative integrity of a semantic integration network are prerequisites for successful use of

Physicochemical properties, fatty acid profile and antioxidant activity of peanut oil

International Nuclear Information System (INIS)

Shad, M.A.; Pervez, H.; Zafar, Z.I.

2011-01-01

The oil from seeds of 4 pea nut (Arachis hypogaea L.) varieties: Golden, Bari 2000, Mongphalla, and Mongphalli 334 cultivated in arid zones, was subjected to the comparative evaluation of its physicochemical properties, fatty acid profile and antioxidant activity. Pea nut seeds were found to be a rich source of crude fat (45.09-51.63 g/100 g dry weight). The physicochemical properties of the oil were investigated as specific gravity (0.915 +-0.008-0.918+-0.008), acid value (3.96+-0.22-4.95+-0.71 mg KOH/g oil), saponification value ( 226.40+-3.59-246.56+-2.04 mg KOH/g oil) and unsaponifiable matter (3.20 +- 0.23-4.20+-0.04 g/100 g oil). The higher amounts of unsaturated fatty acids (82.06-85.93%) were found to be present in each variety. A significant variation (p<0.05) was observed among the varieties regarding crude oil content, saponification value, oleic/linoleic (O/L) ratios, phenolic acid content and total antioxidant content. Golden was found to be high in oil content, O/L ratio, antioxidant profile and DPPH scavenging activity but low in iodine value. (author)

Selective functional activity measurement of a PEGylated protein with a modification-dependent activity assay.

Science.gov (United States)

Weber, Alfred; Engelmaier, Andrea; Mohr, Gabriele; Haindl, Sonja; Schwarz, Hans Peter; Turecek, Peter L

2017-01-05

BAX 855 (ADYNOVATE) is a PEGylated recombinant factor VIII (rFVIII) that showed prolonged circulatory half-life compared to unmodified rFVIII in hemophilic patients. Here, the development and validation of a novel assay is described that selectively measures the activity of BAX 855 as cofactor for the serine protease factor IX, which actives factor X. This method type, termed modification-dependent activity assay, is based on PEG-specific capture of BAX 855 by an anti-PEG IgG preparation, followed by a chromogenic FVIII activity assay. The assay principle enabled sensitive measurement of the FVIII cofactor activity of BAX 855 down to the pM-range without interference by non-PEGylated FVIII. The selectivity of the capture step, shown by competition studies to primarily target the terminal methoxy group of PEG, also allowed assessment of the intactness of the attached PEG chains. Altogether, the modification-dependent activity not only enriches, but complements the group of methods to selectively, accurately, and precisely measure a PEGylated drug in complex biological matrices. In contrast to all other methods described so far, it allows measurement of the biological activity of the PEGylated protein. Data obtained demonstrate that this new method principle can be extended to protein modifications other than PEGylation and to a variety of functional activity assays. Copyright © 2016 Elsevier B.V. All rights reserved.

Phenolic profile and free radical-scavenging activity of Cabernet Sauvignon wines of different geographical origins from the Balkan region.

Science.gov (United States)

Radovanović, Blaga C; Radovanović, Aleksandra N; Souquet, Jean-Marc

2010-11-01

The phenolic profile, determined by the relative proportions of different phenolic compounds, is characteristic for each grape variety and its corresponding wine. The aim of this study was to determine the phenolic and hydroxycinnamate acid, flavan-3-ol and flavonol contents and free radical-scavenging activity of single-cultivar (Cabernet Sauvignon) wines from selected Balkan vineyard regions by spectrophotometric methods and high-performance liquid chromatography with photodiode array and fluorescence detection. The contents of phenolic compounds varied depending on the agroclimatic factors and oenological practices of the vineyard region. The antioxidant activity of wine samples was estimated by their ability to scavenge the stable 2,2'-diphenyl-1-picrylhydrazyl free radical (DPPH). All wines showed high DPPH-scavenging activity (70.03-83.53%, mean 73.76%). Significant correlations between catechin (R(2) = 0.8504) and quercetin (R(2) = 0.8488) concentrations and DPPH-scavenging ability of the wines were found. The concentrations of the main components catechin and quercetin can be used as biochemical markers for the authentication of red grape cultivars and their corresponding single-cultivar wines. 2010 Society of Chemical Industry

Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca2+/Calmodulin-Dependent Protein Kinase II α Activity

Science.gov (United States)

Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena

2015-01-01

Chronic use of opioid analgesics has been hindered by the development of opioid addiction and tolerance. We have reported that curcumin, a natural flavonoid from the rhizome of Curcuma longa, attenuated opioid tolerance, although the underlying mechanism remains unclear. In this study, we tested the hypothesis that curcumin may inhibit Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα), a protein kinase that has been previously proposed to be critical for opioid tolerance and dependence. In this study, we used state-of-the-art polymeric formulation technology to produce poly(lactic-co-glycolic acid) (PLGA)-curcumin nanoparticles (nanocurcumin) to overcome the drug’s poor solubility and bioavailability, which has made it extremely difficult for studying in vivo pharmacological actions of curcumin. We found that PLGA-curcumin nanoparticles reduced the dose requirement by 11- to 33-fold. Pretreatment with PLGA-curcumin (by mouth) prevented the development of opioid tolerance and dependence in a dose-dependent manner, with ED50 values of 3.9 and 3.2 mg/kg, respectively. PLGA-curcumin dose-dependently attenuated already-established opioid tolerance (ED50 = 12.6 mg/kg p.o.) and dependence (ED50 = 3.1 mg/kg p.o.). Curcumin or PLGA-curcumin did not produce antinociception by itself or affect morphine (1–10 mg/kg) antinociception. Moreover, we found that the behavioral effects of curcumin on opioid tolerance and dependence correlated with its inhibition of morphine-induced CaMKIIα activation in the brain. These results suggest that curcumin may attenuate opioid tolerance and dependence by suppressing CaMKIIα activity. PMID:25515789

The euryhaline yeast Debaryomyces hansenii has two catalase genes encoding enzymes with differential activity profile.

Science.gov (United States)

Segal-Kischinevzky, Claudia; Rodarte-Murguía, Beatriz; Valdés-López, Victor; Mendoza-Hernández, Guillermo; González, Alicia; Alba-Lois, Luisa

2011-03-01

Debaryomyces hansenii is a spoilage yeast able to grow in a variety of ecological niches, from seawater to dairy products. Results presented in this article show that (i) D. hansenii has an inherent resistance to H2O2 which could be attributed to the fact that this yeast has a basal catalase activity which is several-fold higher than that observed in Saccharomyces cerevisiae under the same culture conditions, (ii) D. hansenii has two genes (DhCTA1 and DhCTT1) encoding two catalase isozymes with a differential enzymatic activity profile which is not strictly correlated with a differential expression profile of the encoding genes.

Gene expression profiling in Ishikawa cells: A fingerprint for estrogen active compounds

International Nuclear Information System (INIS)

Boehme, Kathleen; Simon, Stephanie; Mueller, Stefan O.

2009-01-01

Several anthropogenous and naturally occurring substances, referred to as estrogen active compounds (EACs), are able to interfere with hormone and in particular estrogen receptor signaling. EACs can either cause adverse health effects in humans and wildlife populations or have beneficial effects on estrogen-dependent diseases. The aim of this study was to examine global gene expression profiles in estrogen receptor (ER)-proficient Ishikawa plus and ER-deficient Ishikawa minus endometrial cancer cells treated with selected well-known EACs (Diethylstilbestrol, Genistein, Zearalenone, Resveratrol, Bisphenol A and o,p'-DDT). We also investigated the effect of the pure antiestrogen ICI 182,780 (ICI) on the expression patterns caused by these compounds. Transcript levels were quantified 24 h after compound treatment using Illumina BeadChip Arrays. We identified 87 genes with similar expression changes in response to all EAC treatments in Ishikawa plus. ICI lowered the magnitude or reversed the expression of these genes, indicating ER dependent regulation. Apart from estrogenic gene regulation, Bisphenol A, o,p'-DDT, Zearalenone, Genistein and Resveratrol displayed similarities to ICI in their expression patterns, suggesting mixed estrogenic/antiestrogenic properties. In particular, the predominant antiestrogenic expression response of Resveratrol could be clearly distinguished from the other test compounds, indicating a distinct mechanism of action. Divergent gene expression patterns of the phytoestrogens, as well as weaker estrogenic gene expression regulation determined for the anthropogenous chemicals Bisphenol A and o,p'-DDT, warrants a careful assessment of potential detrimental and/or beneficial effects of EACs. The characteristic expression fingerprints and the identified subset of putative marker genes can be used for screening chemicals with an unknown mode of action and for predicting their potential to exert endocrine disrupting effects

Going the distance: Memory and control processes in active dependency construction.

Science.gov (United States)

Wagers, Matthew W; Phillips, Colin

2014-01-01

Filler-gap dependencies make strong demands on working memory in language comprehension because they cannot always be immediately resolved. In a series of three reading-time studies, we test the idea that these demands can be decomposed into active maintenance processes and retrieval events. Results indicate that the fact that a displaced phrase exists and the identity of its basic syntactic category both immediately impact comprehension at potential gap sites. In contrast, specific lexical details of the displaced phrase show an immediate effect only for short dependencies and a much later effect for longer dependencies. We argue that coarse-grained information about the filler is actively maintained and is used to make phrase structure parsing decisions, whereas finer grained information is more quickly released from active maintenance and consequently has to be retrieved at the gap site.

Frequency-dependent spatiotemporal profiles of visual responses recorded with subdural ECoG electrodes in awake monkeys: Differences between high- and low-frequency activity.

Science.gov (United States)

Takaura, Kana; Tsuchiya, Naotsugu; Fujii, Naotaka

2016-01-01

Electrocorticography (ECoG) constitutes a powerful and promising neural recording modality in humans and animals. ECoG signals are often decomposed into several frequency bands, among which the so-called high-gamma band (80-250Hz) has been proposed to reflect local cortical functions near the cortical surface below the ECoG electrodes. It is typically assumed that the lower the frequency bands, the lower the spatial resolution of the signals; thus, there is not much to gain by analyzing the event-related changes of the ECoG signals in the lower-frequency bands. However, differences across frequency bands have not been systematically investigated. To address this issue, we recorded ECoG activity from two awake monkeys performing a retinotopic mapping task. We characterized the spatiotemporal profiles of the visual responses in the time-frequency domain. We defined the preferred spatial position, receptive field (RF), and response latencies of band-limited power (BLP) (i.e., alpha [3.9-11.7Hz], beta [15.6-23.4Hz], low [30-80Hz] and high [80-250Hz] gamma) for each electrode and compared them across bands and time-domain visual evoked potentials (VEPs). At the population level, we found that the spatial preferences were comparable across bands and VEPs. The high-gamma power showed a smaller RF than the other bands and VEPs. The response latencies for the alpha band were always longer than the latencies for the other bands and fastest in VEPs. Comparing the response profiles in both space and time for each cortical region (V1, V4+, and TEO/TE) revealed regional idiosyncrasies. Although the latencies of visual responses in the beta, low-, and high-gamma bands were almost identical in V1 and V4+, beta and low-gamma BLP occurred about 17ms earlier than high-gamma power in TEO/TE. Furthermore, TEO/TE exhibited a unique pattern in the spatial response profile: the alpha and high-gamma responses tended to prefer the foveal regions, whereas the beta and low-gamma responses

Aroma profile and volatiles odor activity along gold cultivar pineapple flesh.

Science.gov (United States)

Montero-Calderón, Marta; Rojas-Graü, María Alejandra; Martín-Belloso, Olga

2010-01-01

Physicochemical attributes, aroma profile, and odor contribution of pineapple flesh were studied for the top, middle, and bottom cross-sections cut along the central axis of Gold cultivar pineapple. Relationships between volatile and nonvolatile compounds were also studied. Aroma profile constituents were determined by headspace solid-phase microextraction at 30 °C, followed by gas chromatography/mass spectrometry analysis. A total of 20 volatile compounds were identified and quantified. Among them, esters were the major components which accounted for 90% of total extracted aroma. Methyl butanoate, methyl 2-methyl butanoate, and methyl hexanoate were the 3 most abundant components representing 74% of total volatiles in pineapple samples. Most odor active contributors were methyl and ethyl 2-methyl butanoate and 2,5-dimethyl 4-methoxy 3(2H)-furanone (mesifuran). Aroma profile components did not vary along the fruit, but volatile compounds content significantly varied (P fresh-cut pineapple trays, compromising consumer perception and acceptance of the product. Such finding highlighted the need to include volatiles content and SSC/TA ratio and their variability along the fruit as selection criteria for pineapples to be processed and quality assessment of the fresh-cut fruit. © 2010 Institute of Food Technologists®

Plasma renin activity profile in normal and hypertensive Filipinos

International Nuclear Information System (INIS)

Guevara, R.; Torres, J. Jr.; Abundo, H.P.; Perez, A.P.

To establish a base line profile of plasma renin activity in normotensive and hypertensive Filipinos, 1.019 cases, 479 males and 540 females with an age range 14 - 89 years (mean - 46 + -20) were studied at the Santo Tomas University Hospital of various life styles from the Metro-Manila area, 248 comprised the normotensive group (male - 122 or 49.2 %, female 126 or 50.8 %) and 771 were hypertensive. Of these, 711 (92.6 %) has essential hypertension and are presented in this report. Plasma Renin Activity was determined by radioimmunoassay using Dainabot Renin-Ricket. Concurrent 24 hr. urine sodium and potassium were determined. Nomograms of plasma renin activity as related to urine sodium excretion were drawn after computerized statistical analysis of data. The normal mean value of plasma renin activity was found to be 1.64 + - 0.81 ng./ml./hr. in the upright position and 1.15 + - .68 ng./ml./hr. in the supine position. Based on the nomogram derived, the values obtained in the 711 cases of essential hypertension were classified into High Renin - 14.3 % Normal Renin - 56.1 % and Low Renin - 29.6 %. This study establishes normal levels of plasma renin activity as well as define and classify same renin activity among hypertensive Filipinos, a useful and practicable guide for treatment and can be of prognostic significance. (author)

Response of temperature and density profiles to heat deposition profile and its impact on global scaling in LHD

International Nuclear Information System (INIS)

Yamada, H.

2002-01-01

Significant density dependence of the energy confinement time as described in the ISS95 scaling has been demonstrated in the extended parameter regimes in LHD. However, recent experiments have indicated that this density dependence is lost at a certain density under specific conditions. This paper discusses the cause of this saturation and related characteristics of anomalous transport. The saturation of the energy confinement time is observed in the density ramp-up phase of NBI heated plasmas. In contrast to the global energy confinement time, the local heat conduction coefficient still indicates the temperature dependence which is a companion to the density dependence of the energy confinement time. The apparent contradiction between the global confinement and the local transport can be attributed to the change of the heat deposition profile. Through this study, the response of temperature and density profiles to the heat deposition profile is highlighted, which is contrasted to the concept of stiffness or profile consistency observed in tokamaks. The major anomalous transport models based on ITG/TEM and interchange/ballooning modes are assessed. (author)

Bioorthogonal chemistry: applications in activity-based protein profiling.

Science.gov (United States)

Willems, Lianne I; van der Linden, Wouter A; Li, Nan; Li, Kah-Yee; Liu, Nora; Hoogendoorn, Sascha; van der Marel, Gijs A; Florea, Bogdan I; Overkleeft, Herman S

2011-09-20

of chemical biology research include contributions from many areas of the multifaceted discipline of chemistry, and particularly from organic chemistry. Researchers apply knowledge inherent to organic chemistry, such as reactivity and selectivity, to the manipulation of specific biomolecules in biological samples (cell extracts, living cells, and sometimes even animal models) to gain insight into the biological phenomena in which these molecules participate. In this Account, we highlight some of the recent developments in chemical biology research driven by organic chemistry, with a focus on bioorthogonal chemistry in relation to activity-based protein profiling. The rigorous demands of bioorthogonality have not yet been realized in a truly bioorthogonal reagent pair, but remarkable progress has afforded a range of tangible contributions to chemical biology research. Activity-based protein profiling, which aims to obtain information on the workings of a protein (or protein family) within the larger context of the full biological system, has in particular benefited from these advances. Both activity-based protein profiling and bioorthogonal chemistry have been around for approximately 15 years, and about 8 years ago the two fields very profitably intersected. We expect that each discipline, both separately and in concert, will continue to make important contributions to chemical biology research. © 2011 American Chemical Society

Activity Profiles and Physiological Responses of Representative Tag Football Players in Relation to Playing Position and Physical Fitness

Science.gov (United States)

2015-01-01

This study determined the physical fitness, match-activity profiles and physiological responses of representative tag football players and examined the relationship between physical fitness and the match-activity profile. Microtechnology devices and heart rate (HR) chest straps were used to determine the match-activity profiles of sixteen tag football players for five matches during the 2014 Australian National Championships. The relationships between lower body muscular power, straight line running speed and Yo-Yo intermittent recovery test level 2 (Yo-Yo IR2) and the match-activity profile were examined using Pearson’s correlation coefficients. Outside players had greater lower body muscular power (ES = 0.98) and straight line running speed (ES = 1.03–1.18) than inside players, and also covered greater very high-speed running (VHSR) distance/min (ES = 0.67) and reached higher peak running speeds (ES = 0.95) during matches. Inside and outside players performed a similar number of repeated high-intensity effort (RHIE) bouts and reported similar mean and maximum efforts per RHIE bout. However, there were differences between playing positions for mean and maximal RHIE effort durations (ES = 0.69–1.15) and mean RHIE bout recovery (ES = 0.56). Inside and outside players also reported small to moderate differences (ES = 0.43–0.80) for times spent in each HR zone. There were a number of moderate to very large correlations between physical fitness measures and match-activity profile variables. This study found lower body muscular power, straight line running speed and Yo-Yo IR2 to be related to the match-activities of representative tag football players, although differences between inside and outside players suggest that athlete testing and training practices should be modified for different playing positions. PMID:26642320

HEART RATE VARIABILITY PARAMETERS IN PATIENTS WITH ARTERIAL HYPERTENSION IN DEPENDENCE ON THE TYPE OF DAILY BLOOD PRESSURE PROFILE

Directory of Open Access Journals (Sweden)

S. G. B. K. Gorantla

2017-06-01

Full Text Available Violation of functioning of the autonomic nervous system is an important factor in the formation and progression of arterial hypertension (AH. Abnormal nocturnal blood pressure (BP reduction is regarded as an independent prognostic factor for cardiovascular complications in patients with AH. One of the possible factors that determine the violation of BP circadian rhythm can be imbalance of different parts of autonomic nervous system. The aim of our study was to study heart rate variability (HRV in patients with AH, dependently of BP profile. 72 patients with AH were examined. Average age was 57 ± 11 years. All patients underwent ambulatory BP (ABPM and ECG monitoring. To define the daily profile the nocturnal BP dip was quantified and for HRV evaluation the frequency analysis method was used. HRV changes in patients with AH present with reduced total power and with a violation in the ratio of the powers of very low, low and high frequencies, enhanced sympathycotension and influence of humoral factors. Violations of systolic BP (SBP daily profile was mainly characterized by an increase in the power of low frequency waves, which indicates an intensification of sympathetic and decreased parasympathetic influences. Violations of diastolic BP (DBP daily profile were mainly characterized by a relative increase in the power of very low frequency waves. The obtained results showed that in the management of patients with AH it is important not only to control the circadian SBP and DBP profiles, but the evaluation of HRV also.

Frictional coefficient depending on active friction radius with BPV ...

African Journals Online (AJOL)

Frictional coefficient depending on active friction radius with BPV and BTV in automobile disc braking system. ... International Journal of Engineering, Science and Technology. Journal Home · ABOUT ... AJOL African Journals Online. HOW TO ...

pH-dependent biotransformation of ionizable organic micropollutants in activated sludge.

Science.gov (United States)

Gulde, Rebekka; Helbling, Damian E; Scheidegger, Andreas; Fenner, Kathrin

2014-12-02

Removal of micropollutants (MPs) during activated sludge treatment can mainly be attributed to biotransformation and sorption to sludge flocs, whereby the latter process is known to be of minor importance for polar organic micropollutants. In this work, we investigated the influence of pH on the biotransformation of MPs with cationic-neutral speciation in an activated sludge microbial community. We performed batch biotransformation, sorption control, and abiotic control experiments for 15 MPs with cationic-neutral speciation, one control MP with neutral-anionic speciation, and two neutral MPs at pHs 6, 7, and 8. Biotransformation rate constants corrected for sorption and abiotic processes were estimated from measured concentration time series with Bayesian inference. We found that biotransformation is pH-dependent and correlates qualitatively with the neutral fraction of the ionizable MPs. However, a simple speciation model based on the assumption that only the neutral species is efficiently taken up and biotransformed by the cells tends to overpredict the effect of speciation. Therefore, additional mechanisms such as uptake of the ionic species and other more complex attenutation mechanisms are discussed. Finally, we observed that the sorption coefficients derived from our control experiments were small and showed no notable pH-dependence. From this we conclude that pH-dependent removal of polar, ionizable organic MPs in activated sludge systems is less likely an effect of pH-dependent sorption but rather of pH-dependent biotransformation. The latter has the potential to cause marked differences in the removal of polar, ionizable MPs at different operational pHs during activated sludge treatment.

Response of temperature and density profiles to heat deposition profile and its impact on global scaling in LHD

International Nuclear Information System (INIS)

Yamada, H.; Murakami, S.; Yamazaki, K.

2002-01-01

Energy confinement and heat transport of net current-free NBI-heated plasmas in the Large Helical Device (LHD) are discussed with an emphasis on density dependence. Although the apparent density dependence of the energy confinement time has been demonstrated in a wide parameter range in LHD, the loss of this dependence has been observed in the high density regime under the specific condition. Broad heat deposition due to off-axis alignment and shallow penetration of neutral beams degrades the global energy confinement while the local heat transport maintains a clear temperature dependence lying between Bohm and gyro-Bohm characteristics. The central heat deposition inclines towards an intrinsic density dependence like τ E ∝(n-bar e /P) 0.6 from the saturated state. The broadening of the temperature profile due to the broad heat deposition profile contrasts with the invariant property which has observed widely as profile consistency and stiffness in tokamak experiments. (author)

Response of temperature and density profiles to heat deposition profile and its impact on global scaling in LHD

International Nuclear Information System (INIS)

Yamada, H.; Murakami, S.; Yamazaki, K.

2003-01-01

Energy confinement and heat transport of net current-free NBI-heated plasmas in the Large Helical Device (LHD) are discussed with an emphasis on density dependence. Although the apparent density dependence of the energy confinement time has been demonstrated in a wide parameter range in LHD, the loss of this dependence has been observed in the high density regime under the specific condition. Broad heat deposition due to off-axis alignment and shallow penetration of neutral beams degrades the global energy confinement while the local heat transport maintains a clear temperature dependence lying between Bohm and gyro-Bohm characteristics. The central heat deposition inclines towards an intrinsic density dependence like τ E ∝(n-bars e /P) 0.6 from the saturated state. The broadening of the temperature profile due to the broad heat deposition profile contrasts with the invariant property which has observed widely as profile consistency and stiffness in tokamak experiments. (author)

"Exercise Dependence"--A Problem or Natural Result of High Activity?

Science.gov (United States)

Phelan, Suzanne; Bond, Dale S.; Lang, Wei; Jordan, Dustin; Wing, Rena R.

2011-01-01

Objectives: To compare physical activity (PA) and exercise dependence (ED) in 267 weight-loss maintainers (WLM) and 213 normal-weight (NW) controls. Methods: PA and ED assessed via accelerometery and the Exercise Dependence Questionnaire. Results: WLM had higher PA levels and ED scores than those of NW (P less than 0.0001). WLM status (P = 0.006)…

Power-dependent photocatalytic activity of ZnO

Energy Technology Data Exchange (ETDEWEB)

Chun, So Yeon; Han, Noh Soo; Jeong, Seong Hyun; Park, Seung Min; Song, Jae Kyu [Dept. of Chemistry, Kyung Hee University, Seoul (Korea, Republic of); Moon, Cheol Joo; Choi, Myong Yong [Dept. of Chemistry (BK21) and Research Institute of Natural Science, Gyeongsang NationalUniversity, Jinju (Korea, Republic of)

2017-03-15

the power-dependent photocatalytic activity of ZnO was examined for the photoreduction processes of Rh101 and AN in the presence of hole scavengers, where the fluorescence spectra were measured as a function of irradiation time and excitation intensity. The concentration of the reactants decreased, while the concentration of the products increased accordingly, which indicated the single-electron reduction process by electrons supplied from the conduction band of ZnO. Despite the single-electron process, the efficiency of the photoreaction depended nonlinearly on the excitation intensity, which was explained by the saturation of defect states in ZnO. The enhanced ratio of available electrons in ZnO led to a superlinear increase in the photoreduction efficiency, while the single-electron process linearly reflected the electrons available in ZnO.

Urban Adolescents' Out-of-School Activity Profiles: Associations with Youth, Family, and School Transition Characteristics

Science.gov (United States)

Pedersen, Sara

2005-01-01

This study applied individual growth trajectory analyses and person-oriented analysis to identify common profiles of out-of-school activity engagement trajectories among racially and ethnically diverse inner city teens (N = 1,430). On average, teens exhibited declining trajectories of participation in school-based and team sports activities and…

Abscisic acid-dependent multisite phosphorylation regulates the activity of a transcription activator AREB1

OpenAIRE

Furihata, Takashi; Maruyama, Kyonoshin; Fujita, Yasunari; Umezawa, Taishi; Yoshida, Riichiro; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2006-01-01

bZIP-type transcription factors AREBs/ABFs bind an abscisic acid (ABA)-responsive cis-acting element named ABRE and transactivate downstream gene expression in Arabidopsis. Because AREB1 overexpression could not induce downstream gene expression, activation of AREB1 requires ABA-dependent posttranscriptional modification. We confirmed that ABA activated 42-kDa kinase activity, which, in turn, phosphorylated Ser/Thr residues of R-X-X-S/T sites in the conserved regions of AREB1. Amino acid subs...

Anti-inflammatory activity and phenolic profile of propolis from two locations in Región Metropolitana de Santiago, Chile.

Science.gov (United States)

Valenzuela-Barra, Gabriela; Castro, Consuelo; Figueroa, Catalina; Barriga, Andrés; Silva, Ximena; de Las Heras, Beatriz; Hortelano, Sonsoles; Delporte, Carla

2015-06-20

Propolis has long been used as a popular folk medicine due to its wide spectrum of alleged biological and pharmaceutical properties. In Chile, propolis is widely used by folklore medicine as an anti-inflammatory agent; however, this property has not been demonstrated by scientific methods. The objective of this study was to determine the anti-inflammatory activity in vivo and in vitro and to establish the phenolic profile of propolis collected in two localities in Región Metropolitana de Santiago (RM), Chile. Propolis was collected in the areas of Caleu and Buin, RM Chile. Following that, the samples were unwaxed to obtain the global ethanolic extracts of propolis (EEPs) and, from these, the serial extracts of dichloromethane (EEP-DCMs) and ethanol (EEP-EtOHs). The topic anti-inflammatory effect was evaluated through mice ear edema induced by arachidonic acid (AA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) at a dose of 3 mg/ear. Nitric oxide (NO) measurements were determined spectrophotometrically (Greiss reagent) by the accumulation of nitrite in the medium of macrophages RAW 264.7 stimulated with the lipopolysaccharide (LPS, 1 μg/mL) for 20 h at different concentrations of the EEPs, EEP-DCMs and EEP-EtOHs (6.25-50.00 μg/mL). The content of total phenols and flavonoids were determined through the methods of Folin-Ciocalteau and AlCl3, respectively. The profile of phenolic compounds was determined by HPLC-UV-ESI-MS/MS. The EEP-EtOH (64%) and EEP (59%) of Buin were the most active in the inflammation induced by TPA and AA respectively, being the anti-inflammatory effect stronger than the same Caleu extracts. Regarding the release of NO, all the extracts from the Buin propolis inhibited significantly its release in a concentration-dependent manner, this inhibition was stronger than the extracts from Caleu propolis. Our research shows for the first time a comparative study of the topical in vivo activity of two Chilean propolis. Both propolis showed in vivo

Vertical grid of retrieved atmospheric profiles

International Nuclear Information System (INIS)

Ceccherini, Simone; Carli, Bruno; Raspollini, Piera

2016-01-01

The choice of the vertical grid of atmospheric profiles retrieved from remote sensing observations is discussed considering the two cases of profiles used to represent the results of individual measurements and of profiles used for subsequent data fusion applications. An ozone measurement of the MIPAS instrument is used to assess, for different vertical grids, the quality of the retrieved profiles in terms of profile values, retrieval errors, vertical resolutions and number of degrees of freedom. In the case of individual retrievals no evident advantage is obtained with the use of a grid finer than the one with a reduced number of grid points, which are optimized according to the information content of the observations. Nevertheless, this instrument dependent vertical grid, which seems to extract all the available information, provides very poor results when used for data fusion applications. A loss of about a quarter of the degrees of freedom is observed when the data fusion is made using the instrument dependent vertical grid relative to the data fusion made using a vertical grid optimized for the data fusion product. This result is explained by the analysis of the eigenvalues of the Fisher information matrix and leads to the conclusion that different vertical grids must be adopted when data fusion is the expected application. - Highlights: • Data fusion application is taken into account for the choice of the vertical grid. • The study is performed using ozone profiles retrieved from MIPAS measurements. • A very fine vertical grid is not needed for the analysis of a single instrument. • The instrument dependent vertical grid is not the best choice for data fusion. • A data fusion dependent vertical grid must be used for profiles that will be fused.

Profiling of Concanavalin A-Binding Glycoproteins in Human Hepatic Stellate Cells Activated with Transforming Growth Factor-β1

Directory of Open Access Journals (Sweden)

Yannan Qin

2014-11-01

Full Text Available Glycoproteins play important roles in maintaining normal cell functions depending on their glycosylations. Our previous study indicated that the abundance of glycoproteins recognized by concanavalin A (ConA was increased in human hepatic stellate cells (HSCs following activation by transforming growth factor-β1 (TGF-β1; however, little is known about the ConA-binding glycoproteins (CBGs of HSCs. In this study, we employed a targeted glycoproteomics approach using lectin-magnetic particle conjugate-based liquid chromatography-tandem mass spectrometry to compare CBG profiles between LX-2 HSCs with and without activation by TGF-β1, with the aim of discovering novel CBGs and determining their possible roles in activated HSCs. A total of 54 and 77 proteins were identified in the quiescent and activated LX-2 cells, respectively. Of the proteins identified, 14.3% were glycoproteins and 73.3% were novel potential glycoproteins. Molecules involved in protein processing in the endoplasmic reticulum (e.g., calreticulin and calcium signaling (e.g., 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase β-2 [PLCB2] were specifically identified in activated LX-2 cells. Additionally, PLCB2 expression was upregulated in the cytoplasm of the activated LX-2 cells, as well as in the hepatocytes and sinusoidal cells of liver cirrhosis tissues. In conclusion, the results of this study may aid future investigations to find new molecular mechanisms involved in HSC activation and antifibrotic therapeutic targets.

NF-kB activity-dependent P-selectin involved in ox-LDL-induced foam cell formation in U937 cell

International Nuclear Information System (INIS)

Wang, Yi; Wang, Xiang; Sun, Minghui; Zhang, Zhenyu; Cao, Heng; Chen, Xiaoqing

2011-01-01

Highlights: → Ox-LDL induced foam cell formation in the human U937 promonocytic cell line in a dose- and time-dependent manner. → Ox-LDL induced expression of P-selectin through degradation of IkBa and augment of NF-kB activity and protein level during macrophage-derived foam cell formation. → P-selectin and NF-kB may be identified as pivotal regulators of ox-LDL-induced foam cell formation. → Therapy based on the inhibition of P-selectin and NF-kB may complement conventional treatments to prevent atherosclerosis. -- Abstract: Oxidized low-density lipoprotein (ox-LDL) plays a critical role in regulation of atherosclerosis. However, little is known about the role of Nuclear factor kB (NF-kB) activity-dependent P-selectin in ox-LDL-induced foam cell formation during atherosclerosis. In this study, we first investigated ox-LDL induced foam cell formation in the human U937 promonocytic cell line in a dose- and time-dependent manner. Treatment of U937 cells with ox-LDL increased lipid accumulation as well as intracellular cholesterol content. Next, a comparative analysis of gene expression profiling using cDNA microarray and Real-time-PCR indicated that ox-LDL exposure induced, in three treated groups, an extremely marked increase in the mRNA level of P-selectin. Protein levels of P-selectin and its upstream regulators IkBa and NF-kB showed that NF-kB pathway is involved in the ox-LDL-induced foam cell formation. Finally, overexpression of NF-kB significantly accelerated, whereas, inhibition of NF-kB with siRNA remarkably attenuated ox-LDL-induced macrophage-derived foam cell formation. It was concluded that the activity of NF-kB is augmented during macrophage-derived foam cell formation. Activation of NF-kB increased, whereas, inhibition of NF-kB decreased ox-LDL-induced P-selectin expression and lipid accumulation in macrophages, suggesting ox-LDL induced expression of P-selectin through degradation of IkBa and activation of NF-kB in the regulation of foam

NF-kB activity-dependent P-selectin involved in ox-LDL-induced foam cell formation in U937 cell

Energy Technology Data Exchange (ETDEWEB)

Wang, Yi, E-mail: wangyi2004a@126.com [Department of Cardiology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080 (China); Wang, Xiang; Sun, Minghui; Zhang, Zhenyu; Cao, Heng; Chen, Xiaoqing [Department of Cardiology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080 (China)

2011-08-05

Highlights: {yields} Ox-LDL induced foam cell formation in the human U937 promonocytic cell line in a dose- and time-dependent manner. {yields} Ox-LDL induced expression of P-selectin through degradation of IkBa and augment of NF-kB activity and protein level during macrophage-derived foam cell formation. {yields} P-selectin and NF-kB may be identified as pivotal regulators of ox-LDL-induced foam cell formation. {yields} Therapy based on the inhibition of P-selectin and NF-kB may complement conventional treatments to prevent atherosclerosis. -- Abstract: Oxidized low-density lipoprotein (ox-LDL) plays a critical role in regulation of atherosclerosis. However, little is known about the role of Nuclear factor kB (NF-kB) activity-dependent P-selectin in ox-LDL-induced foam cell formation during atherosclerosis. In this study, we first investigated ox-LDL induced foam cell formation in the human U937 promonocytic cell line in a dose- and time-dependent manner. Treatment of U937 cells with ox-LDL increased lipid accumulation as well as intracellular cholesterol content. Next, a comparative analysis of gene expression profiling using cDNA microarray and Real-time-PCR indicated that ox-LDL exposure induced, in three treated groups, an extremely marked increase in the mRNA level of P-selectin. Protein levels of P-selectin and its upstream regulators IkBa and NF-kB showed that NF-kB pathway is involved in the ox-LDL-induced foam cell formation. Finally, overexpression of NF-kB significantly accelerated, whereas, inhibition of NF-kB with siRNA remarkably attenuated ox-LDL-induced macrophage-derived foam cell formation. It was concluded that the activity of NF-kB is augmented during macrophage-derived foam cell formation. Activation of NF-kB increased, whereas, inhibition of NF-kB decreased ox-LDL-induced P-selectin expression and lipid accumulation in macrophages, suggesting ox-LDL induced expression of P-selectin through degradation of IkBa and activation of NF-kB in the

UML Profile for Mining Process: Supporting Modeling and Simulation Based on Metamodels of Activity Diagram

Directory of Open Access Journals (Sweden)

Andrea Giubergia

2014-01-01

Full Text Available An UML profile describes lightweight extension mechanism to the UML by defining custom stereotypes, tagged values, and constraints. They are used to adapt UML metamodel to different platforms and domains. In this paper we present an UML profile for models supporting event driving simulation. In particular, we use the Arena simulation tool and we focus on the mining process domain. Profiles provide an easy way to obtain well-defined specifications, regulated by the Object Management Group (OMG. They can be used as a presimulation technique to obtain solid models for the mining industry. In this work we present a new profile to extend the UML metamodel; in particular we focus on the activity diagram. This extended model is applied to an industry problem involving loading and transportation of minerals in the field of mining process.

Radial dependence of surface streamer-channel luminosity: experimental evidence of Gaussian radiative profiles in Ar and N2

International Nuclear Information System (INIS)

Šimek, M; Ambrico, P F

2012-01-01

Radial distributions of electronically excited species produced during surface streamer propagation were obtained by applying the Abel inverse transform to projected luminosities of single streamers. The streamers were generated in an argon and nitrogen surface coplanar dielectric barrier discharge at atmospheric pressure and their magnified microscopic images were registered with high time resolution. Selected regions of the projected luminosities were processed by the Abel inverse transform procedure based on the Hankel–Fourier method assuming cylindrical symmetry of the streamer channel. Projected as well as Abel-inverted profiles were fitted by Gaussian functions. It is shown that the projected profiles, in addition to the Abel-inverted ones, can be well approximated by the sum of two coaxial Gaussians with two different half-widths and weights. The sharper Gaussian component with higher weight characterizes the radial dependence of the primary cathode-directed streamer-channel luminosity. The second (broader) Gaussian component probably originates either from the pre-breakdown Townsend phase or from the second wave propagating towards the anode. (paper)

Distinct BOLD activation profiles following central and peripheral oxytocin administration in awake rats

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Craig F Ferris

2015-09-01

Full Text Available A growing body of literature has suggested that intranasal oxytocin (OT or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain-barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level dependent (BOLD signal intensity in response to peripheral OT injections (0.1, 0.5 or 2.5 mg/kg during functional magnetic resonance (fMRI in awake rats imaged at 7.0 tesla. These data were compared to OT (1ug/5 µl given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

Distinct BOLD Activation Profiles Following Central and Peripheral Oxytocin Administration in Awake Rats.

Science.gov (United States)

Ferris, Craig F; Yee, Jason R; Kenkel, William M; Dumais, Kelly Marie; Moore, Kelsey; Veenema, Alexa H; Kulkarni, Praveen; Perkybile, Allison M; Carter, C Sue

2015-01-01

A growing body of literature has suggested that intranasal oxytocin (OT) or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level-dependent (BOLD) signal intensity in response to peripheral OT injections (0.1, 0.5, or 2.5 mg/kg) during functional magnetic resonance imaging (fMRI) in awake rats imaged at 7.0 T. These data were compared to OT (1 μg/5 μl) given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis, we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors, e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

Tea and herbal infusions: Their antioxidant activity and phenolic profile

International Nuclear Information System (INIS)

Atoui, A.; Mansouri, A.; Panagiotis Kefalas; Boskou, G.

2005-01-01

Tea and herbal infusions have been studied for their polyphenolic content, antioxidant activity and phenolic profile. The total phenolics recovered by ethyl acetate from the water extract, were determined by the Folin-Ciocalteu procedure and ranged from 88.1 ± 0.42 (Greek mountain tea) to 1216 ± 32.0 mg (Chinese green tea) GAE (Gallic acid equivalents)/cup. The antioxidant activity was evaluated by two methods, DPPH and chemiluminescence assays, using Trolox and quercetin as standards. The EC50 of herbal extracts ranged from 0.151 ± 0.002 mg extract/mg DPPH (0.38 quercetin equivalents and 0.57 Trolox equivalents), for Chinese green tea, to 0.77 ± 0.012 mg extract/mg DPPH (0.08 quercetin equivalents and 0.13 Trolox equivalents), for Greek mountain tea. Chemiluminescence assay results showed that the IC50 ranged from 0.17 ± 3.4 x 103 lg extract/ml of the final solution in the measuring cell (1.89 quercetin and 5.89 Trolox equivalents) for Chinese green tea, to 1.10 ± 1.86 x 102 g extract/ml of the final solution in the measuring cell (0.29 quercetin and 0.90 Trolox equivalents) for Greek mountain tea. The phenolic profile in the herbal infusions was investigated by LC-DAD-MS in the positive electrospray ionization (ESI) mode. About 60 different flavo- noids, phenolic acids and their derivatives have been identified. (author)

Problems of determination of principle of psychological profile of unknown criminal person in investigational activity

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Galina Getman

2017-03-01

By the author of the article of analysis different determinations of «psychological profile of unknown criminal person» were subjected. They are set positive lines and separate positions that in opinion of author are not expedient and important are subjected to criticism. That is why, the author points in conclusions the argued positions in relation to the necessity of the use of psychological profile of  unknown criminal person during investigation of criminal realizations in activity of investigator.

Network-dependent modulation of brain activity during sleep.

Science.gov (United States)

Watanabe, Takamitsu; Kan, Shigeyuki; Koike, Takahiko; Misaki, Masaya; Konishi, Seiki; Miyauchi, Satoru; Miyahsita, Yasushi; Masuda, Naoki

2014-09-01

Brain activity dynamically changes even during sleep. A line of neuroimaging studies has reported changes in functional connectivity and regional activity across different sleep stages such as slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. However, it remains unclear whether and how the large-scale network activity of human brains changes within a given sleep stage. Here, we investigated modulation of network activity within sleep stages by applying the pairwise maximum entropy model to brain activity obtained by functional magnetic resonance imaging from sleeping healthy subjects. We found that the brain activity of individual brain regions and functional interactions between pairs of regions significantly increased in the default-mode network during SWS and decreased during REM sleep. In contrast, the network activity of the fronto-parietal and sensory-motor networks showed the opposite pattern. Furthermore, in the three networks, the amount of the activity changes throughout REM sleep was negatively correlated with that throughout SWS. The present findings suggest that the brain activity is dynamically modulated even in a sleep stage and that the pattern of modulation depends on the type of the large-scale brain networks. Copyright © 2014 Elsevier Inc. All rights reserved.

Cognitive profile and activities of daily living

DEFF Research Database (Denmark)

Borgwardt, Line Gutte; Thuesen, A M; Olsen, K J

2015-01-01

on the cognitive function and activities of daily living in patients with AM. METHODS: Thirty five AM patients, age 6-35 years, were included in the study. As a cognitive function test, we used the Leiter international performance scale-revised (Leiter-R), which consists of two batteries: the visual function...... and reasoning battery and the memory and attention battery, the latter including a memory screening. Additional two questionnaires, The Childhood Health Assessment Questionnaire (CHAQ) and EQ-5D-5 L, were filled out. RESULTS: We found IQ in the range of 30-81 in our cohort. The total equivalent age (mental age......) was significantly reduced, between 3-9 years old for the visual function and reasoning battery, between 2.3-10.2 years for the memory screening. Data suggested a specific developmental profile for AM with a positive intellectual development until the chronological age 10-12 years, followed by a static or slightly...

Physical activity moderates the association between nicotine dependence and depression among U.S. smokers.

Science.gov (United States)

Loprinzi, Paul D; Walker, Jerome F; Kane, Christy; Cardinal, Bradley J

2014-01-01

Research demonstrates that nicotine dependence and depression are associated and that physical activity is effective in reducing depression symptoms. However, our understanding of the potential beneficial effects of physical activity on depression in current smokers is more limited. The purpose of this study was to examine whether physical activity moderates the association between nicotine dependence and depression in U.S. smokers. Cross-sectional. National Health and Nutrition Examination Survey 2005-2006. Four hundred forty-one current adult smokers. Participants wore an accelerometer for at least 4 days and completed questionnaires to assess nicotine dependence and depression. Effect modification and statistical interaction models were used. Both models were significant. With regard to the statistical interaction model, and after controlling for age, gender, race/ethnicity, education, comorbidity index, homocysteine, cotinine, total cholesterol, sedentary behavior, and vitamins C, D, and E, objectively measured physical activity moderated the association between nicotine dependence and depression (interaction variable: odds ratio = 3.43; 95% confidence interval: 1.02-11.51; p = .04). In this national sample of current smokers, physical activity moderated the association between nicotine dependence and depression. These results suggest that those individuals with nicotine dependence and who are less physically active are more likely to be depressed than what would be expected on the basis of the individual effects of nicotine and physical inactivity separately.

Comparison between the International Physical Activity Questionnaire and the American College of Sports Medicine/American Heart Association criteria to classify the physical activity profile in adults.

Science.gov (United States)

de Moraes, Suzana Alves; Suzuki, Cláudio Shigueki; de Freitas, Isabel Cristina Martins

2013-01-01

the study aims to evaluate the reproducibility between the International Physical Activity Questionnaire and the American College of Sports Medicine/American Heart Association criteria to classify the physical activity profile in an adult population living in Ribeirão Preto, SP, Brazil. population-based cross-sectional study, including 930 adults of both genders. The reliability was evaluated by Kappa statistics, estimated according to socio-demographic strata. the kappa estimates showed good agreement between the two criteria in all strata. However, higher prevalence of "actives" was found by using the American College of Sports Medicine/American Heart Association. although the estimates have indicated good agreement, the findings suggest caution in choosing the criteria to classify physical activity profile mainly when "walking" is the main modality of physical activity.

Circadian profile of cardiac autonomic nervous modulation in healthy subjects

DEFF Research Database (Denmark)

Bonnemeier, Hendrik; Richardt, Gert; Potratz, Jürgen

2003-01-01

UNLABELLED: Circadian Profile of Heart Rate Variability. INTRODUCTION: Although heart rate variability (HRV) has been established as a tool to study cardiac autonomic activity, almost no data are available on the circadian patterns of HRV in healthy subjects aged 20 to 70 years. METHODS AND RESULTS...... higher in men. Younger men also exhibited significantly higher values...... parasympathetic activity. The significant gender-related difference of HRV decreases with aging. These findings emphasize the need to determine age-, gender-, and nycthemeral-dependent normal ranges for HRV assessment....

Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children : The ABCD Study

NARCIS (Netherlands)

Vrijkotte, Tanja G M; van den Born, Bert-Jan H; Hoekstra, Christine M C A; Gademan, Maaike G J; van Eijsden, Manon; de Rooij, Susanne R; Twickler, Marcel T B

2015-01-01

BACKGROUND: In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system

Online Activity Levels Are Related to Caffeine Dependency.

Science.gov (United States)

Phillips, James G; Landhuis, C Erik; Shepherd, Daniel; Ogeil, Rowan P

2016-05-01

Online activity could serve in the future as behavioral markers of emotional states for computer systems (i.e., affective computing). Hence, this study considered relationships between self-reported stimulant use and online study patterns. Sixty-two undergraduate psychology students estimated their daily caffeine use, and this was related to study patterns as tracked by their use of a Learning Management System (Blackboard). Caffeine dependency was associated with less time spent online, lower rates of file access, and fewer online activities completed. Reduced breadth or depth of processing during work/study could be used as a behavioral marker of stimulant use.

Physical activity and depression symptom profiles in young men and women with major depression.

Science.gov (United States)

McKercher, Charlotte; Patton, George C; Schmidt, Michael D; Venn, Alison J; Dwyer, Terence; Sanderson, Kristy

2013-05-01

This study explored whether young adults with major depression who are physically active differ in their depression symptom profile from those physically inactive. Analyses included data from 950 (47.6%) men and 1045 women (mean [standard deviation] age = 31.5 [2.6] years) participating in a national study. Participants reported leisure physical activity (International Physical Activity Questionnaire) and ambulatory activity (pedometer steps per day). Diagnosis and symptoms of major depression were assessed using the Composite International Diagnostic Interview. Prevalence of major depression was 5.5% (n = 52) for men and 11.6% (n = 121) for women. Interactions between physical activity and sex were observed for depressed mood, appetite changes, vacillating thoughts, and suicidality (all, p physically active men were significantly less likely to endorse the presence of insomnia (prevalence ratio [PR] = 0.78, 95% confidence interval [CI] = 0.63-0.96), fatigue (PR = 0.82, 95% CI = 0.69-0.99), and suicidality (PR = 0.69, 95% CI = 0.49-0.96) compared with inactive men. Physically active women were significantly less likely to endorse hypersomnia (PR = 0.50, 95% CI = 0.27-0.95), excessive/irrational guilt (PR = 0.76, 95% CI = 0.59-0.97), vacillating thoughts (PR = 0.74, 95% CI = 0.58-0.95), and suicidality (PR = 0.43, 95% CI = 0.20-0.89) compared with inactive women. Associations were adjusted for age, physical health, educational attainment, depression severity, and other depressive symptoms. Among adults with major depression, those physically active seem to differ in their depression symptom profile from those physically inactive.

Time-Dependent Expression Profiles of microRNAs and mRNAs in Rat Milk Whey

Science.gov (United States)

Izumi, Hirohisa; Kosaka, Nobuyoshi; Shimizu, Takashi; Sekine, Kazunori; Ochiya, Takahiro; Takase, Mitsunori

2014-01-01

Functional RNAs, such as microRNA (miRNA) and mRNA, are present in milk, but their roles are unknown. To clarify the roles of milk RNAs, further studies using experimental animals such as rats are needed. However, it is unclear whether rat milk also contains functional RNAs and what their time dependent expression profiles are. Thus, we prepared total RNA from whey isolated from rat milk collected on days 2, 9, and 16 postpartum and analyzed using microarrays and quantitative PCR. The concentration of RNA in colostrum whey (day 2) was markedly higher than that in mature milk whey (days 9 and 16). Microarray analysis detected 161 miRNAs and 10,948 mRNA transcripts. Most of the miRNAs and mRNA transcripts were common to all tested milks. Finally, we selected some immune- and development-related miRNAs and mRNAs, and analysed them by quantitative PCR (in equal sample volumes) to determine their time-dependent changes in expression in detail. Some were significantly more highly expressed in colostrum whey than in mature milk whey, but some were expressed equally. And mRNA expression levels of some cytokines and hormones did not reflect the protein levels. It is still unknown whether RNAs in milk play biological roles in neonates. However, our data will help guide future in vivo studies using experimental animals such as rats. PMID:24533154

Comprehensive analysis of PPARα-dependent regulation of hepatic lipid metabolism by expression profiling - 5

NARCIS (Netherlands)

Rakhshandehroo, Maryam; Sanderson-Kjellberg, L.M.; Matilainen, Merja; Stienstra, Rinke; Carlberg, Carsten; Groot, de Philip; Muller, Michael; Kersten, Sander

2007-01-01

PPARα is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARα in hepatic lipid metabolism, many PPARα-dependent pathways and genes have yet to be discovered. In order to obtain an

Comparison of the free and bound phenolic profiles and cellular antioxidant activities of litchi pulp extracts from different solvents

Science.gov (United States)

2014-01-01

alkaline hydrolysis method. Conclusions The free and bound phenolic contents and profiles and antioxidant activities of the extracts were found to be dependent on the extraction solvent used. Litchi exhibited good cellular antioxidant activity and could be a potentially useful natural source of antioxidants. PMID:24405977

Do Training Programs Work? An Assessment of Pharmacists Activities in the Field of Chemical Dependency.

Science.gov (United States)

Brooks, Valerie G.; Brock, Tina Penick; Ahn, Jungeun

2001-01-01

Seeks to determine if pharmacists who attended a chemical dependency training program were performing more chemical dependency related activities. Results reveal that participants were more likely to perform the following activities: lecture to community groups about chemical dependency; participate in a pharmacists' recovery program; provide…

Active Tectonics Revealed by River Profiles along the Puqu Fault

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Ping Lu

2015-04-01

Full Text Available The Puqu Fault is situated in Southern Tibet. It is influenced by the eastward extrusion of Northern Tibet and carries the clockwise rotation followed by the southward extrusion. Thus, the Puqu Fault is bounded by the principal dynamic zones and the tectonic evolution remains active alongside. This study intends to understand the tectonic activity in the Puqu Fault Region from the river profiles obtained from the remotely sensed satellite imagery. A medium resolution Digital Elevation Model (DEM, 20 m was generated from an Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER stereo pair of images and the stream network in this region was extracted from this DEM. The indices of slope and drainage area were subsequently calculated from this ASTER DEM. Based on the stream power law, the area-slope plots of the streams were delineated to derive the indices of channel concavity and steepness, which are closely related to tectonic activity. The results show the active tectonics varying significantly along the Puqu Fault, although the potential influence of glaciations may exist. These results are expected to be useful for a better understanding of tectonic evolution in Southeastern Tibet.

Activity-Dependent Plasticity of Spike Pauses in Cerebellar Purkinje Cells

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Giorgio Grasselli

2016-03-01

Full Text Available The plasticity of intrinsic excitability has been described in several types of neurons, but the significance of non-synaptic mechanisms in brain plasticity and learning remains elusive. Cerebellar Purkinje cells are inhibitory neurons that spontaneously fire action potentials at high frequencies and regulate activity in their target cells in the cerebellar nuclei by generating a characteristic spike burst-pause sequence upon synaptic activation. Using patch-clamp recordings from mouse Purkinje cells, we find that depolarization-triggered intrinsic plasticity enhances spike firing and shortens the duration of spike pauses. Pause plasticity is absent from mice lacking SK2-type potassium channels (SK2−/− mice and in occlusion experiments using the SK channel blocker apamin, while apamin wash-in mimics pause reduction. Our findings demonstrate that spike pauses can be regulated through an activity-dependent, exclusively non-synaptic, SK2 channel-dependent mechanism and suggest that pause plasticity—by altering the Purkinje cell output—may be crucial to cerebellar information storage and learning.

Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children: The ABCD Study.

Directory of Open Access Journals (Sweden)

Tanja G M Vrijkotte

Full Text Available In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system activation and metabolic profile and its components in children at age of 5-6 years.Cross-sectional data from an apparently healthy population (within the ABCD study were collected at age 5-6 years in 1540 children. Heart rate (HR, respiratory sinus arrhythmia (RSA; parasympathetic activity and pre-ejection period (PEP; sympathetic activity were assessed during rest. Metabolic components were waist-height ratio (WHtR, systolic blood pressure (SBP, fasting triglycerides, glucose and HDL-cholesterol. Individual components, as well as a cumulative metabolic score, were analyzed.In analysis adjusted for child's physical activity, sleep, anxiety score and other potential confounders, increased HR and decreased RSA were associated with higher WHtR (P< 0.01, higher SBP (p<0.001 and a higher cumulative metabolic score (HR: p < 0.001; RSA: p < 0.01. Lower PEP was only associated with higher SBP (p <0.05. Of all children, 5.6% had 3 or more (out of 5 adverse metabolic components; only higher HR was associated with this risk (per 10 bpm increase: OR = 1.56; p < 0.001.This study shows that decreased parasympathetic activity is associated with central adiposity and higher SBP, indicative of increased metabolic risk, already at age 5-6 years.

Constructing bioactive peptides with pH-dependent activities.

Science.gov (United States)

Tu, Zhigang; Volk, Melanie; Shah, Khushali; Clerkin, Kevin; Liang, Jun F

2009-08-01

Many bioactive peptides are featured by their arginine and lysine rich contents. In this study, lysine and arginine residues in lytic peptides were selectively replaced by histidines. Although resulting histidine-containing lytic peptides had decreased activity, they did show pH-dependent cytotoxicity. The activity of the constructed histidine-containing lytic peptides increased 2-8 times as the solution pH changed from 7.4 to 5.5. More importantly, these histidine-containing peptides maintain the same cell killing mechanism as their parent peptides by causing cell lysis. Both the activity and pH-sensitivity of histidine-containing peptides are tunable by adjusting histidine substitution numbers and positions. This study has presented a general strategy to create bioactive peptides with desired pH-sensitivity to meet the needs of various applications such as cancer treatments.

Active Boundary Layer Control on a Highly Loaded Turbine Exit Case Profile

Directory of Open Access Journals (Sweden)

Julia Kurz

2018-03-01

Full Text Available A highly loaded turbine exit guide vane with active boundary layer control was investigated experimentally in the High Speed Cascade Wind Tunnel at the University of the German Federal Armed Forces, Munich. The experiments include profile Mach number distributions, wake traverse measurements as well as boundary layer investigations with a flattened Pitot probe. Active boundary layer control by fluidic oscillators was applied to achieve improved performance in the low Reynolds number regime. Low solidity, which can be applied to reduce the number of blades, increases the risk of flow separation resulting in increased total pressure losses. Active boundary layer control is supposed to overcome these negative effects. The experiments show that active boundary layer control by fluidic oscillators is an appropriate way to suppress massive open separation bubbles in the low Reynolds number regime.

The Rehabilitation Activities Profile: a validation study of its use as a disability index with stroke patients

NARCIS (Netherlands)

van Bennekom, C. A.; Jelles, F.; Lankhorst, G. J.; Bouter, L. M.

1995-01-01

This study evaluates the criterion, content, and construct validity of the Rehabilitation Activities Profile (RAP) in patients with stroke. This instrument is constructed for screening, monitoring, and prognosis purposes to assist clinical rehabilitation. It consists of 21 activities, covering the

Assessment of leisure-time physical activity for the prediction of inflammatory status and cardiometabolic profile.

Science.gov (United States)

Pires, Milena Monfort; Salvador, Emanuel P; Siqueira-Catania, Antonela; Folchetti, Luciana D; Cezaretto, Adriana; Ferreira, Sandra Roberta G

2012-11-01

Associations of leisure-time physical activity (LTPA), commuting and total physical activity with inflammatory markers, insulin resistance and metabolic profile in individuals at high cardiometabolic risk were investigated. This was a cross-sectional study. A total of 193 prediabetic adults were compared according to physical activity levels measured by the international physical activity questionnaire; p for trend and logistic regression was employed. The most active subset showed lower BMI and abdominal circumference, reaching significance only for LTPA (p for trend=0.02). Lipid profile improved with increased physical activity levels. Interleukin-6 decreased with increased total physical activity and LTPA (p for trend=0.02 and 0.03, respectively), while adiponectin increased in more active subsets for LTPA (p for trend=0.03). Elevation in adjusted OR for hypercholesterolemia was significant for lower LTPA durations (p for trend=0.04). High apolipoprotein B/apolipoprotein A ratio was inversely associated with LTPA, commuting and total physical activity. Increase in adjusted OR for insulin resistance was found from the highest to the lowest category of LTPA (p for trend=0.04) but significance disappeared after adjustments for BMI and energy intake. No association of increased C-reactive protein with physical activity domains was observed. In general, the associations of LTPA, but not commuting or total physical activity, with markers of cardiometabolic risk reinforces the importance of initiatives to increase this domain in programs for the prevention of lifestyle-related diseases. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Comparative Analysis of Click Chemistry Mediated Activity-Based Protein Profiling in Cell Lysates

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Yinliang Yang

2013-10-01

Full Text Available Activity-based protein profiling uses chemical probes that covalently attach to active enzyme targets. Probes with conventional tags have disadvantages, such as limited cell permeability or steric hindrance around the reactive group. A tandem labeling strategy with click chemistry is now widely used to study enzyme targets in situ and in vivo. Herein, the probes are reacted in live cells, whereas the ensuing detection by click chemistry takes place in cell lysates. We here make a comparison of the efficiency of the activity-based tandem labeling strategy by using Cu(I-catalyzed and strain-promoted click chemistry, different ligands and different lysis conditions.

Fenofibrate activates Nrf2 through p62-dependent Keap1 degradation

International Nuclear Information System (INIS)

Park, Jeong Su; Kang, Dong Hoon; Lee, Da Hyun; Bae, Soo Han

2015-01-01

Peroxisome proliferator-activated receptor α (PPARα) activates the β-oxidation of fatty acids in the liver. Fenofibrate is a potent agonist of PPARα and is used in the treatment of hyperlipidemia. Fenofibrate treatment often induces the production of intracellular reactive oxygen species (ROS), leading to cell death. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is an essential component of the defense mechanism against oxidative stress. However, the molecular mechanism underlying the regulation of the Nrf2-Keap1 pathway in fenofibrate-induced cell death is not known. In this study, we demonstrated that fenofibrate induces Keap1 degradation and Nrf2 activation. This fenofibrate-mediated Keap1 degradation is partly dependent on autophagy. Furthermore, fenofibrate-induced Keap1 degradation followed by Nrf2 activation is mainly mediated by p62, which functions as an adaptor protein in the autophagic pathway. Consistent with these findings, ablation of p62 increased fenofibrate-mediated apoptotic cell death associated with ROS accumulation. These results strongly suggest that p62 plays a crucial role in preventing fenofibrate-induced cell death. - Highlights: • Fenofibrate induces cell death by increasing ROS production. • The underlying defense mechanism against this effect is unknown. • Fenofibrate induces autophagy-dependent Keap1 degradation and Nrf2 activation. • This process is p62-dependent; lack of p62 enhanced fenofibrate-mediated apoptosis. • p62 plays a crucial role in preventing fenofibrate-induced cell death

Fenofibrate activates Nrf2 through p62-dependent Keap1 degradation

Energy Technology Data Exchange (ETDEWEB)

Park, Jeong Su [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

2015-09-25

Peroxisome proliferator-activated receptor α (PPARα) activates the β-oxidation of fatty acids in the liver. Fenofibrate is a potent agonist of PPARα and is used in the treatment of hyperlipidemia. Fenofibrate treatment often induces the production of intracellular reactive oxygen species (ROS), leading to cell death. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is an essential component of the defense mechanism against oxidative stress. However, the molecular mechanism underlying the regulation of the Nrf2-Keap1 pathway in fenofibrate-induced cell death is not known. In this study, we demonstrated that fenofibrate induces Keap1 degradation and Nrf2 activation. This fenofibrate-mediated Keap1 degradation is partly dependent on autophagy. Furthermore, fenofibrate-induced Keap1 degradation followed by Nrf2 activation is mainly mediated by p62, which functions as an adaptor protein in the autophagic pathway. Consistent with these findings, ablation of p62 increased fenofibrate-mediated apoptotic cell death associated with ROS accumulation. These results strongly suggest that p62 plays a crucial role in preventing fenofibrate-induced cell death. - Highlights: • Fenofibrate induces cell death by increasing ROS production. • The underlying defense mechanism against this effect is unknown. • Fenofibrate induces autophagy-dependent Keap1 degradation and Nrf2 activation. • This process is p62-dependent; lack of p62 enhanced fenofibrate-mediated apoptosis. • p62 plays a crucial role in preventing fenofibrate-induced cell death.

Psychopathological profile and prevalence of dual pathology on patients with alcoholic dependence undergoing outpatient treatment.

Science.gov (United States)

García-Carretero, Miguel A; Novalbos-Ruiz, José P; Robles-Martínez, María; Jordán-Quintero, María A; O'Ferrall-González, Cristina

2017-01-01

Assess the prevalence of dual pathology in patients with alcohol dependence and describe the psychopathological profile of mental disorders, impulsiveness, ADHD presence and craving. It is a cross-sectional study about dual pathology, carried out on 102 patients undergoing outpatient treatment. The presence of dual pathology is established by means of the MINI-5 interview and the MCMI-III test; DSM-IV being used as the alcohol abuse criteria. Impulsiveness, ADHD presence, craving and quality of life were measured through SIS, ASRSv1, MACS and SF-36. The prevalence of dual pathology ranges from 45.1% to 80.4% according to MCMI-III and MINI-5, respectively. The most frequent pathologies are current major depressive episodes, followed by current generalized anxiety disorders, suicide risk and current dysthymia disorders; 73.2% of dual patients present a moderate and intense global score according to MACS, 56.1% got a meaningful score in impulsiveness according to SIS and 41.5% has highly consistent symptoms with ADHD. As regards quality of life, 53.7% of the sample had bad mental health. In the case of dual patients consuming other substances, 30% had a history of bipolar disorders and 10% had a high suicide risk. The prevalence of psychiatric comorbidity in patients with alcohol dependence undergoing outpatient treatment varies depending on the detection method, MINI being the one identifying a greater number of cases. More than half of dual patients present impulsive behavior, a bad mental health state and high craving levels. Special attention should be paid to dual patients consuming other substances.

Phytochemical profiles and antioxidant activity of 27 cultivars of tea.

Science.gov (United States)

Zeng, Liang; Luo, Liyong; Li, Hongjun; Liu, Ruihai

2017-08-01

Tea, rich in phytochemicals, has been suggested to have human health benefits. The phenolic profiles, antioxidant and antiproliferative activities of 27 tea cultivars were determined. Wide ranges of variation were found in analyzed cultivars for the contents of water-soluble phenolics (121.6-223.7 mg/g dry weight (DW)), total catechins (TC) (90.5-177.2 mg/g DW), antioxidant activities (PSC values 627.3-2332.3 μmol of vitamin C equiv/g DW, ORAC values (1865.1-3489.3 μmol of vitamin C equiv/g DW), CAA values (37.7-134.3 μmol of QE/g DW without PBS wash and 25.3-75.4 μmol of QE/g DW with PBS wash) and antiproliferative activity (53.0-90.8% at the concentration of 400 μg/mL extracts). The PSC, ORAC and CAA values were significantly correlated with phenolics, epicatechin gallate (ECG), CC and TC. Knowledge of specific differences among tea cultivars is important for breeding tea cultivars and gives sights to its potential application to promote health.

Temperature profiles of time dependent tokamak plasmas from the parallel Ohm's law

International Nuclear Information System (INIS)

Micozzi, P.; Roccella, M.

1993-01-01

Profile consistency based on the parallel component of Ohm's law has been used to obtain electron temperature profiles. A resistive neoclassical term and a term that accounts for the bootstrap current contributions have been considered in Ohm's law. A numerical code has been developed to find solutions according to the MHD equilibrium equations. For stationary plasmas, the temperature profiles, obtained by a procedure in which a pseudo-parabolic shape of (J φ /R) is assumed and the peak temperature known from experiments is used, are close to the experimental data for several very different machines (JET, TFTR, ASDEX, ALCATOR-C and FT). The main feature of the model is its capability to provide an easy parametrization of Ohm's law also in non-stationary cases, without going through the complication of a detailed solution of the magnetic field diffusion equation. A rule for estimating a maximum value of the current diffusion time inside the plasma volume in such situations is given. This rule accounts for both the temperature profiles and the stabilization times in some non-stationary pulses observed in JET. (author). 28 refs, 12 figs

Cytotoxic activity of abietane diterpenoids from roots of Salvia sahendica by HPLC-based activity profiling

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Fahimeh Moradi-Afrapoli

Full Text Available ABSTRACT Screening of medicinal plants from Iranian flora against human cancer cell-lines have shown that an hexane extract from roots of Salvia sahendica Boiss. & Buhse, Lamiaceae, is active against human cervical cancer (HeLa and colorectal adenocarcinoma (Caco-2 cell-lines at the test concentration of 100 µg/ml (100% inhibition. Cytotoxicity of the extract was localized with the aid of HPLC-time-based activity profiling adapted to the tetrazolium colorimetric bioassay. Four abietane-type diterpenoids in active time-windows were identified as cytotoxic compounds namely: sahandone (1, sahandol (2, 12-deoxy-salvipisone (3 and sahandinone (4. Compound 1 showed the highest toxicity against HeLa cells (IC50 = 5.6 ± 0.1 µg/ml, which was comparable with betulinic acid (IC50 = 4.3 ± 1.2 µg/ml, the positive control. Compound 2 was active against the HeLa cells (IC50 = 8.9 ± 0.7 µg/ml but not the Caco-2 cell-line. Compounds 1, 3 and 4 exhibited moderate activity (IC50 = 22.9–41.4 µg/ml against the Caco-2 cells. This study reveals that the HeLa cells are more sensitive to all tested compounds than the Caco-2 cells. In silico molecular docking study showed a rigid binding of the compounds to tyrosine kinase pp60src, and proved their cytotoxic activity.

Chirality, Metallicity, and Transition Dependent Asymmetries in Resonance Raman Excitation Profiles of Chirality-Enriched Carbon Nanotubes

Science.gov (United States)

Doorn, Stephen; Duque, Juan; Telg, Hagen; Haroz, Erik; Tu, Xiaomin; Zheng, Ming

2014-03-01

Access to carbon nanotube samples enriched in single chiralities allows the observation of new photophysical behaviors obscured or difficult to demonstrate in mixed-chirality ensembles. Recent examples include the observation of strongly asymmetric G-band excitation profiles resulting from non-Condon effects1 and the unambiguous demonstration of Raman interference effects.2 We present here our most recent results demonstrating the generality of the non-Condon behavior to include metallic species (specifically several armchair chiralities). Additionally, the Eii dependence in non-Condon behavior with excitations from E11 thru E44 for both RBM and G modes will be discussed. 1. J.G. Duque, et. al., ACS Nano, 5, 5233 (2011). 2. J.G. Duque, et. al., Phys. Rev. Lett. 108, 117404 (2012).

Striatal activation and frontostriatal connectivity during non-drug reward anticipation in alcohol dependence.

Science.gov (United States)

Becker, Alena; Kirsch, Martina; Gerchen, Martin Fungisai; Kiefer, Falk; Kirsch, Peter

2017-05-01

According to prevailing neurobiological theories of addiction, altered function in neural reward circuitry is a central mechanism of alcohol dependence. Growing evidence postulates that the ventral striatum (VS), as well as areas of the prefrontal cortex, contribute to the increased incentive salience of alcohol-associated cues, diminished motivation to pursue non-drug rewards and weakened strength of inhibitory cognitive control, which are central to addiction. The present study aims to investigate the neural response and functional connectivity underlying monetary, non-drug reward processing in alcohol dependence. We utilized a reward paradigm to investigate the anticipation of monetary reward in 32 alcohol-dependent inpatients and 35 healthy controls. Functional magnetic resonance imaging was used to measure task-related brain activation and connectivity. Alcohol-dependent patients showed increased activation of the VS during anticipation of monetary gain compared with healthy controls. Generalized psychophysiological interaction analyses revealed decreased functional connectivity between the VS and the dorsolateral prefrontal cortex in alcohol dependent patients relative to controls. Increased activation of the VS and reduced frontostriatal connectivity were associated with increased craving. These findings provide evidence that alcohol dependence is rather associated with disrupted integration of striatal and prefrontal processes than with a global reward anticipation deficit. © 2016 Society for the Study of Addiction.

Blood lactate clearance after maximal exercise depends on active recovery intensity.

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Devlin, J; Paton, B; Poole, L; Sun, W; Ferguson, C; Wilson, J; Kemi, O J

2014-06-01

High-intensity exercise is time-limited by onset of fatigue, marked by accumulation of blood lactate. This is accentuated at maximal, all-out exercise that rapidly accumulates high blood lactate. The optimal active recovery intensity for clearing lactate after such maximal, all-out exercise remains unknown. Thus, we studied the intensity-dependence of lactate clearance during active recovery after maximal exercise. We constructed a standardized maximal, all-out treadmill exercise protocol that predictably lead to voluntary exhaustion and blood lactate concentration>10 mM. Next, subjects ran series of all-out bouts that increased blood lactate concentration to 11.5±0.2 mM, followed by recovery exercises ranging 0% (passive)-100% of the lactate threshold. Repeated measurements showed faster lactate clearance during active versus passive recovery (P40%>passive recovery, Pexercise clears accumulated blood lactate faster than passive recovery in an intensity-dependent manner, with maximum clearance occurring at active recovery of 80% of lactate threshold.

Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease.

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Vanesa Sanchez-Guajardo

Full Text Available Post-mortem analysis of brains from Parkinson's disease (PD patients strongly supports microglia activation and adaptive immunity as factors contributing to disease progression. Such responses may be triggered by alpha-synuclein (alpha-syn, which is known to be the main constituent of the aggregated proteins found in Lewy bodies in the brains of PD patients. To investigate this we used a recombinant viral vector to express human alpha-syn in rat midbrain at levels that induced neuronal pathology either in the absence or the presence of dopaminergic cell death, thereby mimicking early or late stages of the disease. Microglia activation was assessed by stereological quantification of Mac1+ cells, as well as the expression patterns of CD68 and MCH II. In our study, when alpha-syn induced neuronal pathology but not cell death, a fast transient increase in microglia cell numbers resulted in the long-term induction of MHC II+ microglia, denoting antigen-presenting ability. On the other hand, when alpha-syn induced both neuronal pathology and cell death, there was a delayed increase in microglia cell numbers, which correlated with long-lasting CD68 expression and a morphology reminiscent of peripheral macrophages. In addition T-lymphocyte infiltration, as judged by the presence of CD4+ and CD8+ cells, showed distinct kinetics depending on the degree of neurodegeneration, and was significantly higher when cell death occurred. We have thus for the first time shown that the microglial response differs depending on whether alpha-syn expression results on cell death or not, suggesting that microglia may play different roles during disease progression. Furthermore, our data suggest that the microglial response is modulated by early events related to alpha-syn expression in substantia nigra and persists at the long term.

Heating and active control of profiles and transport by IBW in the HT-7 tokamak

International Nuclear Information System (INIS)

Zhao Yanping; Wan Baonian; Li Jiangang

2003-01-01

Significant progress on Ion Bernstein Wave (IBW) heating and control of profiles has been obtained in HT-7. Both on-axis and off-axis electron heating with global peaked and local steep electron pressure profiles were realized if the position of the resonant layer was selected to be plasma far from the plasma edge region. Reduction of electron heat transport has been observed from sawtooth heat pulse propagation. Improvement of both particle and energy confinement was slight in the on-axis and considerable in the off-axis heating cases. The improved confinement in off-axis heating mode may be due to the extension of the high performance plasma volume caused by IBW. These studies demonstrate that IBWs are potentially a tool for active control of plasma profiles and transport. (author)

Model-driven dependability assessment of software systems

CERN Document Server

Bernardi, Simona; Petriu, Dorina C

2013-01-01

In this book, the authors present cutting-edge model-driven techniques for modeling and analysis of software dependability. Most of them are based on the use of UML as software specification language. From the software system specification point of view, such techniques exploit the standard extension mechanisms of UML (i.e., UML profiling). UML profiles enable software engineers to add non-functional properties to the software model, in addition to the functional ones. The authors detail the state of the art on UML profile proposals for dependability specification and rigorously describe the t

Physical fitness and activity, metabolic profile, adipokines and endothelial function in children.

Science.gov (United States)

Penha, Jociene Terra da; Gazolla, Fernanda Mussi; Carvalho, Cecília Noronha de Miranda; Madeira, Isabel Rey; Rodrigues-Junior, Flávio; Machado, Elisabeth de Amorim; Sicuro, Fernando Lencastre; Farinatti, Paulo; Bouskela, Eliete; Collett-Solberg, Paulo Ferrez

2018-05-29

The prevalence of obesity is increasing. The aim of this study was to investigate if there is endothelial dysfunction in children with normal or excess weight, and whether the metabolic profile, adipokines, and endothelial dysfunction would be more strongly associated with physical fitness or with physical activity levels. Cross-sectional study involving children aged 5-12 years. The evaluation included venous occlusion plethysmography, serum levels of adiponectin, leptin and insulin, lipid profile, physical activity score (PAQ-C questionnaire), and physical fitness evaluation (Yo-Yo test). A total of 62 children participated in this study. Based on the body mass index, 27 were eutrophic, 10 overweight and 25 obese. Triglycerides, LDL cholesterol, HOMA-IR, and leptin were higher in the obese and excess-weight groups compared to the eutrophic group (pPAQ-C. The Yo-Yo test was significantly associated with HDL cholesterol (rho=-0.41; p=0.01), and this association remained after adjusting for body mass index z-score (rho=0.28; p=0.03). This study showed that endothelial dysfunction is already present in obese children, suggesting a predisposition to atherosclerotic disease. Moreover, HDL cholesterol levels were correlated with physical fitness, regardless of body mass index. Copyright © 2018. Published by Elsevier Editora Ltda.

Profile-IQ: Web-based data query system for local health department infrastructure and activities.

Science.gov (United States)

Shah, Gulzar H; Leep, Carolyn J; Alexander, Dayna

2014-01-01

To demonstrate the use of National Association of County & City Health Officials' Profile-IQ, a Web-based data query system, and how policy makers, researchers, the general public, and public health professionals can use the system to generate descriptive statistics on local health departments. This article is a descriptive account of an important health informatics tool based on information from the project charter for Profile-IQ and the authors' experience and knowledge in design and use of this query system. Profile-IQ is a Web-based data query system that is based on open-source software: MySQL 5.5, Google Web Toolkit 2.2.0, Apache Commons Math library, Google Chart API, and Tomcat 6.0 Web server deployed on an Amazon EC2 server. It supports dynamic queries of National Profile of Local Health Departments data on local health department finances, workforce, and activities. Profile-IQ's customizable queries provide a variety of statistics not available in published reports and support the growing information needs of users who do not wish to work directly with data files for lack of staff skills or time, or to avoid a data use agreement. Profile-IQ also meets the growing demand of public health practitioners and policy makers for data to support quality improvement, community health assessment, and other processes associated with voluntary public health accreditation. It represents a step forward in the recent health informatics movement of data liberation and use of open source information technology solutions to promote public health.

Patterns of screen-based sedentary behavior and physical activity and associations with overweight among Norwegian adolescents: a latent profile approach

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Ole Melkevik

2011-03-01

Full Text Available Background: Physical activity and screen based sedentary behaviors are both related to energy balance and to risk for becoming overweight. The aim of this study is to find out if these behaviors cluster together in order to find out whether groups of adolescents have particularly unfortunate levels of both physical activity and screen-based sedentary behaviors. Methods: Data are from the Norwegian 2005/2006 sample of the international "Health Behaviour in School-aged Children (HBSC study; A WHO cross-National Survey". Data were collected through questionnaires from 13-, 15- and 16-year-olds. The final sample included 4848 adolescents. Gender-stratified latent profile analysis was used to identify the different profiles. Results: Six profiles were identified for both boys and girls. Less than 30% of adolescents were found to have behavioral patterns which were associated with higher risk for overweight relative to the most healthy behavioral profile. Physical activity and screen-based sedentary behaviors cluster together in different ways suggesting independence between the behaviors. Low levels of physical activity was the most important predictor for overweight among boys. Screen-based sedentary behaviors were more important predictors of overweight among girls. Conclusions: Physical activity and screen-based sedentary behaviors are independent behaviors and may cluster together in manners which lead to low energy expenditure and subsequent increased risk for overweight among adolescents.

Activated rat hepatic stellate cells influence Th1/Th2 profile in vitro.

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Xing, Zhi-Zhi; Huang, Liu-Ye; Wu, Cheng-Rong; You, Hong; Ma, Hong; Jia, Ji-Dong

2015-06-21

To investigate the effects of activated rat hepatic stellate cells (HSCs) on rat Th1/Th2 profile in vitro. Growth and survival of activated HSCs and CD4(+) T lymphocytes cultured alone or together was assessed after 24 or 48 h. CD4(+) T lymphocytes were then cultured with or without activated HSCs for 24 or 48 h and the proportion of Th1 [interferon (IFN)-γ(+)] and Th2 [interleukin (IL)-4(+)] cells was assessed by flow cytometry. Th1 and Th2 cell apoptosis was assessed after 24 h of co-culture using a caspase-3 staining procedure. Differentiation rates of Th1 and Th2 cells from CD4(+) T lymphocytes that were positive for CD25 but did not express IFN-γ or IL-4 were also assessed after 48 h of co-culture with activated HSCs. Galectin-9 expression in HSCs was determined by immunofluorescence and Western blotting. ELISA was performed to assess galectin-9 secretion from activated HSCs. Co-culture of CD4(+) T lymphocytes with activated rat HSCs for 48 h significantly reduced the proportion of Th1 cells compared to culture-alone conditions (-1.73% ± 0.71%; P Th1/Th2 ratio was significantly decreased (-0.44 ± 0.13; P Th1 cells was decreased (-65.71 ± 9.67; P Th1 (12.27% ± 0.99%; P Th1 cell apoptosis rate was significantly higher than in Th2 cells (P Th1 and Th2 cells; however, the increase in the proportion of Th2 cells was significantly higher than that of Th1 cells (1.85% ± 0.48%; P Th1/Th2 profile, inhibiting the Th1 response and enhancing the Th2 response, and this may be a novel pathway for liver fibrogenesis.

Phospho-dependent Accumulation of GABABRs at Presynaptic Terminals after NMDAR Activation.

Science.gov (United States)

Hannan, Saad; Gerrow, Kim; Triller, Antoine; Smart, Trevor G

2016-08-16

Here, we uncover a mechanism for regulating the number of active presynaptic GABAB receptors (GABABRs) at nerve terminals, an important determinant of neurotransmitter release. We find that GABABRs gain access to axon terminals by lateral diffusion in the membrane. Their relative accumulation is dependent upon agonist activation and the presence of the two distinct sushi domains that are found only in alternatively spliced GABABR1a subunits. Following brief activation of NMDA receptors (NMDARs) using glutamate, GABABR diffusion is reduced, causing accumulation at presynaptic terminals in a Ca(2+)-dependent manner that involves phosphorylation of GABABR2 subunits at Ser783. This signaling cascade indicates how synaptically released glutamate can initiate, via a feedback mechanism, increased levels of presynaptic GABABRs that limit further glutamate release and excitotoxicity. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Compound Structure-Independent Activity Prediction in High-Dimensional Target Space.

Science.gov (United States)

Balfer, Jenny; Hu, Ye; Bajorath, Jürgen

2014-08-01

Profiling of compound libraries against arrays of targets has become an important approach in pharmaceutical research. The prediction of multi-target compound activities also represents an attractive task for machine learning with potential for drug discovery applications. Herein, we have explored activity prediction in high-dimensional target space. Different types of models were derived to predict multi-target activities. The models included naïve Bayesian (NB) and support vector machine (SVM) classifiers based upon compound structure information and NB models derived on the basis of activity profiles, without considering compound structure. Because the latter approach can be applied to incomplete training data and principally depends on the feature independence assumption, SVM modeling was not applicable in this case. Furthermore, iterative hybrid NB models making use of both activity profiles and compound structure information were built. In high-dimensional target space, NB models utilizing activity profile data were found to yield more accurate activity predictions than structure-based NB and SVM models or hybrid models. An in-depth analysis of activity profile-based models revealed the presence of correlation effects across different targets and rationalized prediction accuracy. Taken together, the results indicate that activity profile information can be effectively used to predict the activity of test compounds against novel targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Proteomic and activity profiles of ascorbate-glutathione cycle enzymes in germinating barley embryo

DEFF Research Database (Denmark)

Bønsager, Birgit Christine; Shahpiri, Azar; Finnie, Christine

2010-01-01

Enzymes involved in redox control are important during seed germination and seedling growth. Ascorbate-glutathione cycle enzymes in barley embryo extracts were monitored both by 2D-gel electrophoresis and activity measurements from 4 to 144 h post imbibition (PI). Strikingly different activity...... profiles were observed. No ascorbate peroxidase (APX) activity was present in mature seeds but activity was detected after 24 h PI and increased 14-fold up to 144 h PI. In contrast, dehydroascorbate reductase (DHAR) activity was present at 4 h PI and first decreased by 9-fold until 72 h PI followed by a 5......-fold increase at 144 h PI. Glutathione reductase and monodehydroascorbate reductase activities were also detected at 4 h PI, and showed modest increases of 1.8- and 2.7-fold, respectively, by 144 h PI. The combination of functional analysis with the proteomics approach enabled correlation...

Activity-Dependent Neurorehabilitation Beyond Physical Trainings: "Mental Exercise" Through Mirror Neuron Activation.

Science.gov (United States)

Yuan, Ti-Fei; Chen, Wei; Shan, Chunlei; Rocha, Nuno; Arias-Carrión, Oscar; Paes, Flávia; de Sá, Alberto Souza; Machado, Sergio

2015-01-01

The activity dependent brain repair mechanism has been widely adopted in many types of neurorehabilitation. The activity leads to target specific and non-specific beneficial effects in different brain regions, such as the releasing of neurotrophic factors, modulation of the cytokines and generation of new neurons in adult hood. However physical exercise program clinically are limited to some of the patients with preserved motor functions; while many patients suffered from paralysis cannot make such efforts. Here the authors proposed the employment of mirror neurons system in promoting brain rehabilitation by "observation based stimulation". Mirror neuron system has been considered as an important basis for action understanding and learning by mimicking others. During the action observation, mirror neuron system mediated the direct activation of the same group of motor neurons that are responsible for the observed action. The effect is clear, direct, specific and evolutionarily conserved. Moreover, recent evidences hinted for the beneficial effects on stroke patients after mirror neuron system activation therapy. Finally some music-relevant therapies were proposed to be related with mirror neuron system.

Xanthene derivatives increase glucose utilization through activation of LKB1-dependent AMP-activated protein kinase.

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Yonghoon Kwon

Full Text Available 5' AMP-activated protein kinase (AMPK is a highly conserved serine-threonine kinase that regulates energy expenditure by activating catabolic metabolism and suppressing anabolic pathways to increase cellular energy levels. Therefore AMPK activators are considered to be drug targets for treatment of metabolic diseases such as diabetes mellitus. To identify novel AMPK activators, we screened xanthene derivatives. We determined that the AMPK activators 9H-xanthene-9-carboxylic acid {2,2,2-trichloro-1-[3-(3-nitro-phenyl-thioureido]-ethyl}-amide (Xn and 9H-xanthene-9-carboxylic acid {2,2,2-trichloro-1-[3-(3-cyano-phenyl-thioureido]-ethyl}-amide (Xc elevated glucose uptake in L6 myotubes by stimulating translocation of glucose transporter type 4 (GLUT4. Treatment with the chemical AMPK inhibitor compound C and infection with dominant-negative AMPKa2-virus inhibited AMPK phosphorylation and glucose uptake in myotubes induced by either Xn or Xc. Of the two major upstream kinases of AMPK, we found that Xn and Xc showed LKB1 dependency by knockdown of STK11, an ortholog of human LKB1. Single intravenous administration of Xn and Xc to high-fat diet-induced diabetic mice stimulated AMPK phosphorylation of skeletal muscle and improved glucose tolerance. Taken together, these results suggest that Xn and Xc regulate glucose homeostasis through LKB1-dependent AMPK activation and that the compounds are potential candidate drugs for the treatment of type 2 diabetes mellitus.

Wind profiler observations of a monsoon low-level jet over a tropical Indian station

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M. C. R. Kalapureddy

2007-11-01

Full Text Available Three-year high-resolution wind observations of the wind profiler have been utilized to characterize the diurnal and seasonal features of the monsoon Low-Level Jet (LLJ over a tropical station, Gadanki (13.5° N, 79.2° E, with a focus on the diurnal variability of low-level winds. The Boreal summer monsoon winds show a conspicuously strong westerly LLJ with average wind speed exceeding 20 m s⁻¹. The L-band wind profiler measurements have shown an advantage of better height and time resolutions over the conventional radiosonde method for diurnal wind measurements. An interesting diurnal oscillation of LLJ core has been observed. It is varying in the height range of 1.8±0.6 km with the maximum and minimum intensity noticed during the early morning and afternoon hours, respectively. The jet core (wind maxima height is observed to coincide with the inversion height. Strong wind shears are normally located beneath the LLJ core. The sole wind profiler observations are capable of identifying the monsoon phases, such as onset, break and active spells, etc. The mutual influence between the LLJ and the boundary layer has been discussed. One notices that the observed LLJ diurnal structures depend on the local convective activity, wind shears and turbulence activity associated with boundary layer winds. The day-to-day change in the LLJ structure depends on the latitudinal position of the LLJ core.

Genotype modulates testosterone-dependent activity and reactivity in male mice.

Science.gov (United States)

Broida, J; Svare, B

1983-03-01

Adult castration significantly reduced the homecage locomotor activity of both inbred C57BL/6J and DBA/2J and outbred Rockland-Swiss (R-S) male mice. Castrated C57BL animals exhibited greater reductions in this behavior than did the other genotypes. Locomotor activity in a novel environment (reactivity) was also reduced by castration but only for inbred males. In both test situations, postcastration reductions in ambulation were prevented by implants of testosterone (T)-containing Silastic capsules. Thus, testicular hormones promote activity and reactivity in the male mouse in a genotype-dependent fashion.

Potential antimalarial activity of Methyl Jasmonate and its effect on lipid profiles in Plasmodium Berghei infected mice.

Science.gov (United States)

Oyinloye, Oladapo E; Kosoko, Ayokulehin M; Emikpe, Benjamin; Falade, Catherine O; Ademowo, Olusegun G

2015-09-01

The antimalarial activity and lipid profiles of Methyl Jasmonate (MJ) were investigated against established malaria infection in vivo using BALB/c mice. Arteether (AE) and chloroquine (CQ) were used as reference drugs while ethanol was used as the vehicle for drug delivery for MJ. Mice treated with 10 and 25 mg/kg MJ showed a remarkable reduction in percentage parasitemia by 68.3% and 78.2% on day 10(post treatment) respectively while 45.4% and 87.2% reduction in percentage parasitemia were observed in the group treated with 50 mg/kg on day 3 and 10 (post treatment) respectively. The highest mean survival time was observed in CQ followed by AE and MJ in dose-dependent manner. A progressive decrease in packed cell volume (PCV) was observed in infected untreated mice which led to the death of all the mice by day 9 (post treatment). Infected mice treated with MJ showed reduced level of HDL and LDL compared with infected untreated group. As the dose of MJ increased in infected mice cholesterol levels increased while there was reduction in triglyceride. Overall there was marked decrease in parasitemia in Plasmodium berghei infected mice treated with graded doses of MJ but appears to have reduced antimalarial activity compared with CQ and AE.

BWR AXIAL PROFILE

International Nuclear Information System (INIS)

Huffer, J.

2004-01-01

The purpose of this calculation is to develop axial profiles for estimating the axial variation in burnup of a boiling water reactor (BWR) assembly spent nuclear fuel (SNF) given the average burnup of an assembly. A discharged fuel assembly typically exhibits higher burnup in the center and lower burnup at the ends of the assembly. Criticality safety analyses taking credit for SNF burnup must account for axially varying burnup relative to calculations based on uniformly distributed assembly average burnup due to the under-burned tips. Thus, accounting for axially varying burnup in criticality analyses is also referred to as accounting for the ''end effect'' reactivity. The magnitude of the reactivity change due to ''end effect'' is dependent on the initial assembly enrichment, the assembly average burnup, and the particular axial profile characterizing the burnup distribution. The set of bounding axial profiles should incorporate multiple BWR core designs and provide statistical confidence (95 percent confidence that 95 percent of the population is bound by the profile) that end nodes are conservatively represented. The profiles should also conserve the overall burnup of the fuel assembly. More background on BWR axial profiles is provided in Attachment I

Motivational Profiles for Physical Activity Practice in Adults with Type 2 Diabetes: A Self-Determination Theory Perspective.

Science.gov (United States)

Gourlan, Mathieu; Trouilloud, David; Boiché, Julie

2016-01-01

Drawing on Self-Determination Theory, this study explored the motivational profiles toward Physical Activity (PA) among adults with type 2 diabetes and the relationships between motivational profile, perceived competence and PA. Participants were 350 men and women (Mean age 62.77 years) who were interviewed on their motivations toward PA, perceived level of competence to practice, and PA practice. Cluster analyses reveal the existence of three distinct profiles: "High Combined" (ie, high scores on motivations ranging from intrinsic to external regulation, moderate level on amotivation), "Self-Determined" (ie, high scores on intrinsic, integrated, and identified regulations; low scores on other regulations), and "Moderate" (ie, moderate scores on all regulations). Participants with "High Combined" and "Self-Determined" profiles reported higher perceived competence and longer leisure-time PA practice in comparison to those with a "Moderate" profile. This study highlights the necessity of adopting a person-centered approach to better understand motivation toward PA among type 2 diabetics.

Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting

Science.gov (United States)

Wing, S. S.; Goldberg, A. L.; Goldberger, A. L. (Principal Investigator)

1993-01-01

Glucocorticoids are essential for the increase in protein breakdown in skeletal muscle normally seen during fasting. To determine which proteolytic pathway(s) are activated upon fasting, leg muscles from fed and fasted normal rats were incubated under conditions that block or activate different proteolytic systems. After food deprivation (1 day), the nonlysosomal ATP-dependent process increased by 250%, as shown in experiments involving depletion of muscle ATP. Also, the maximal capacity of the lysosomal process increased 60-100%, but no changes occurred in the Ca(2+)-dependent or the residual energy-independent proteolytic processes. In muscles from fasted normal and adrenalectomized (ADX) rats, the protein breakdown sensitive to inhibitors of the lysosomal or Ca(2+)-dependent pathways did not differ. However, the ATP-dependent process was 30% slower in muscles from fasted ADX rats. Administering dexamethasone to these animals or incubating their muscles with dexamethasone reversed this defect. During fasting, when the ATP-dependent process rises, muscles show a two- to threefold increase in levels of ubiquitin (Ub) mRNA. However, muscles of ADX animals failed to show this response. Injecting dexamethasone into the fasted ADX animals increased muscle Ub mRNA within 6 h. Thus glucocorticoids activate the ATP-Ub-dependent proteolytic pathway in fasting apparently by enhancing the expression of components of this system such as Ub.

Effect of Tomato Industrial Processing on Phenolic Profile and Antiplatelet Activity

Directory of Open Access Journals (Sweden)

Iván Palomo

2013-09-01

Full Text Available Background: Regular consumption of fruits and vegetables (e.g., tomatoes has been shown to be beneficial in terms of reducing the incidence of cardiovascular diseases. The industrial processing of tomatoes into tomato-based products includes several thermal treatments. Very little is known on the effect of tomato industrial processing on antiaggregatory activity and phenolic profile. Methods: It was assessed the effect of tomato and by-products extracts on platelet aggregation induced by ADP, collagen, TRAP-6 and arachidonic acid. These in vitro antithrombotic properties were further supported in an in vivo model of thrombosis. A set of antiplatelet compounds has been selected for HPLC analysis in the different extracts. Results: Some natural compounds such as chlorogenic, caffeic, ferulic and p-coumaric acids were identified by HPLC in tomatoes and its products may inhibit platelet activation. Red tomatoes, tomato products (sauce, ketchup and juice and by-products extracts inhibited platelet aggregation induced adenosine 5'-diphosphate, collagen, thrombin receptor activator peptide-6 and arachidonic acid, but to a different extent. Also, pomace extract presents antithrombotic activity. Conclusions: Processed tomatoes may have a higher content of health-benefiting compounds than fresh ones. Pomace even presents the best antiplatelet activity. Finally, tomato products may be used as a functional ingredient adding antiplatelet activities to processed foods.

Stage-specific and age-dependent profiles of zinc, copper, manganese, and selenium in rat seminiferous tubules

International Nuclear Information System (INIS)

Homma-Takeda, S.; Nishimura, Y.; Watanabe, Y.; Imaseki, H.; Yukawa, M.

2004-01-01

Stage-specific and age-dependent profiles of zinc, copper, manganese, and selenium in testis were examined in Wistar rats by both inductively coupled argon plasma-mass spectrometry (ICP-MS) with a microdissection technique and in situ elemental imaging of micro-PIXE analysis. The young adult animals (10 weeks old) contained higher levels of zinc and manganese in the seminiferous tubules at stages VII-VIII than stages XI through VI and IX-X and the levels were higher than those of the immature and old animals. Copper and selenium levels at stages VII-VIII of the young adult animals were also higher than those of the immature and old animals. In stages VII and VIII, zinc was higher in the central area of the seminiferous epithelium, where spermatozoa were localized, demonstrating a cell-specific property. (author)

JET steady state ITB operation with active control of the pressure profile

Energy Technology Data Exchange (ETDEWEB)

Crisanti, F.; Litaudon, X.; Mailloux, J. [and others

2002-07-01

Stationary operations have been achieved at JET in ITBs scenarios, with the discharge time limited only by plant constraints. Full current drive was obtained, all over the high performance phase, with the current density profile frozen by using Lower Hybrid current drive. For the first time a feed-back control on the total pressure and on the electron temperature profile was implemented by using respectively the Neutral Beams and the Ion Cyclotron waves. Although impurity accumulation could be a problem in steady state ITBs, these experiments bring some elements to answer to it. Tokamak operation in enhanced confinement regimes, characterized by edge and/or Internal Transport Barriers (respectively known as H-mode and ITB), is attractive as it represents an important step towards the approach of ignition conditions. Moreover, the necessity of steady state operation in a Tokamak reactor, has led to the concept of the Advanced Tokamak, in which the current density profile is no longer tied to the plasma conductivity and is non inductively driven. Since the bootstrap current is a consequence of the pressure gradient, one of the primary goal of the Advanced Tokamak studies is to maximize the bootstrap fraction, with a proper alignment, both in H mode and in ITB regimes. However, for several reasons, it is difficult to envisage an operational situation in which the bootstrap fraction is close to 100%: for instance, there are few chances of pressure or/and current profile control to optimize the MHD stability. So far, various experiments have been performed with improved confinement regimes lasting up to tens of the confinement time and up to some current relaxation times. In some experiments a large non inductive plasma current (< 75%) was obtained with about 50% from bootstrap and 25% from Neutral Beam Injection (NBI); however, no full current drive operation was achieved and, moreover, with the available heating systems, no active feedback control of the current

Variations in Decision-Making Profiles by Age and Gender: A Cluster-Analytic Approach

Science.gov (United States)

Delaney, Rebecca; Strough, JoNell; Parker, Andrew M.; de Bruin, Wandi Bruine

2015-01-01

Using cluster-analysis, we investigated whether rational, intuitive, spontaneous, dependent, and avoidant styles of decision making (Scott & Bruce, 1995) combined to form distinct decision-making profiles that differed by age and gender. Self-report survey data were collected from 1,075 members of RAND’s American Life Panel (56.2% female, 18–93 years, Mage = 53.49). Three decision-making profiles were identified: affective/experiential, independent/self-controlled, and an interpersonally-oriented dependent profile. Older people were less likely to be in the affective/experiential profile and more likely to be in the independent/self-controlled profile. Women were less likely to be in the affective/experiential profile and more likely to be in the interpersonally-oriented dependent profile. Interpersonally-oriented profiles are discussed as an overlooked but important dimension of how people make important decisions. PMID:26005238

Variations in Decision-Making Profiles by Age and Gender: A Cluster-Analytic Approach.

Science.gov (United States)

Delaney, Rebecca; Strough, JoNell; Parker, Andrew M; de Bruin, Wandi Bruine

2015-10-01

Using cluster-analysis, we investigated whether rational, intuitive, spontaneous, dependent, and avoidant styles of decision making (Scott & Bruce, 1995) combined to form distinct decision-making profiles that differed by age and gender. Self-report survey data were collected from 1,075 members of RAND's American Life Panel (56.2% female, 18-93 years, M age = 53.49). Three decision-making profiles were identified: affective/experiential, independent/self-controlled, and an interpersonally-oriented dependent profile. Older people were less likely to be in the affective/experiential profile and more likely to be in the independent/self-controlled profile. Women were less likely to be in the affective/experiential profile and more likely to be in the interpersonally-oriented dependent profile. Interpersonally-oriented profiles are discussed as an overlooked but important dimension of how people make important decisions.

Chemical profile of a polysaccharide from Psidium guajava leaves and it's in vivo antitussive activity.

Science.gov (United States)

Khawas, Sadhana; Sivová, Veronika; Anand, Namrata; Bera, Kaushik; Ray, Bimalendu; Nosáľová, Gabriela; Ray, Sayani

2018-04-01

Decoction of Psidium guajava leaves has been used as medication for chronic coughs and breathlessness for ages. Despite demonstration of antitussive activity, the specific molecule responsible for this remains unidentified. Herein, we report chemical profile and antitussive activity of its water extract (WE) and a polysaccharide (F1) present therein. This polysaccharide (F1), purified from WE by precipitation with ethanol and then through Cu(II)acetate, contains Ara, Gal, Rha, Glc and GalA residues, and has a molecular mass of 156 kDa. It comprises of terminal-, (1,5)- and (1,3,5)-linked Araf; (1,3)-, (1,6)- and (1,3,6)-linked Galp alongside (1,2)- and (1,2,4)-linked Rhap residues. Oligosaccharides indicating polysaccharide structure have been generated by Smith degradation and characterized. The WE fraction suppressed citric acid induced cough efforts in guinea pigs in the dose of 50 mg kg -1 . Assessment of antitussive activity of fractions prepared from WE namely F1 (polysaccharide) and F2 (ethanol soluble fraction) revealed that polysaccharide is the active component. Remarkably, tested samples do not alter the specific airway smooth muscle reactivity in animals significantly. The simple extraction method, prominent activity and favorable reactions profile suggest that this macromolecule could be an antitussive drug candidate. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of Polyphenol Profile and Antimutagenic and Antioxidant Activities in Two Species Used as Source of Solidaginis herba - Goldenrod.

Science.gov (United States)

Woźniak, Dorota; Ślusarczyk, Sylwester; Domaradzki, Krzysztof; Dryś, Andrzej; Matkowski, Adam

2018-04-01

European Pharmacopoeia accepts two equivalent species Solidago canadensis L. and S. gigantea Aiton as goldenrod (Solidaginis herba). We compared phytochemical profile of both species from invasive populations in Poland. Further, we compared in vitro antimutagenic and antioxidant activities of solvent extracts from aerial (AP) and underground parts (UP). In S. gigantea, flavonoid profile was dominated by quercetin glycosides, with quercitrin as the major compound. In S. canadensis, quercetin and kaempferol rutinosides were two major constituents. Caffeoylquinic acids (CQAs) were less diverse with 5-CQA as a main compound. In UP, over 20 putative diterpenoids were detected, mostly unidentified. Several CQAs were present in higher amounts than in AP. Antioxidant and antimutagenic activities were different between species and organs, with the strongest inhibition of lipid peroxidation by Et 2 O and AcOEt fractions from AP of both species (IC 50 13.33 - 16.89 μg/mL) and BuOH fraction from S. gigantea UP (IC 50  = 13.32 μg/mL). Chemical mutagenesis was completely inhibited by non-polar fractions, but oxidative mutagenesis was inhibited up to 35% only by S. canadensis. No clear relationship was found between chemical profiles and antimutagenic activity. In conclusion, both species have diverse activity and their phytochemical profiles should be considered in quality evaluation. UP of these weeds can also provide potential chemopreventive substances for further studies. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

Antioxidant activity and profile fatty acids of jabuticaba seeds (Myrciaria cauliflora berg)

International Nuclear Information System (INIS)

Jorge, Neuza; Bruna Jorge Bertanha; Moreno Luzia, Debora Maria

2011-01-01

Numerous natural compounds found in fruits, grains and vegetables have antioxidant activity. This work aimed to characterize jabuticaba seeds (Myrciaria cauliflora berg) by proximate composition, antioxidant activity and fatty acids profile of their extracted oil. To obtain the extract, the dehydrated and triturated seeds were extracted with ethyl alcohol for 30 min, at a proportion of 1:3 of seeds: ethyl alcohol, under continuous agitation, at room temperature. Afterwards, the mixture was filtered and the supernatant dehydrated at 40 Celsius degrade aiming to determine, by direct weighing, the extracts dry matter yield. According to the results, the jabuticaba seeds are an important source of total carbohydrates, and also presented relevant antioxidant activity. In the jabuticaba seeds oil, a significant percentage of polyunsaturated fatty acids stood out, with linoleic and α-linolenic being the main component, essentials fatty acids.

Evolutionary Profiling of Group II Pyridoxal-Phosphate-Dependent Decarboxylases Suggests Expansion and Functional Diversification of Histidine Decarboxylases in Tomato

Directory of Open Access Journals (Sweden)

Rahul Kumar

2016-03-01

Full Text Available Pyridoxal phosphate (PLP-dependent enzymes are one of the most important enzymes involved in plant N metabolism. Here, we explored the evolution of group II PLP-dependent decarboxylases (PLP_deC, including aromatic L-amino acid decarboxylase, glutamate decarboxylase, and histidine decarboxylase in the plant lineage. Gene identification analysis revealed a higher number of genes encoding PLP_deC in higher plants than in lower plants. Expression profiling of PLP_deC orthologs and syntelogs in (L. Heynh., pepper ( L., and tomato ( L. pointed toward conserved as well as distinct roles in developmental processes such as fruit maturation and ripening and abiotic stress responses. We further characterized a putative promoter of tomato ripening-associated gene ( operating in a complex regulatory circuit. Our analysis provides a firm basis for further in-depth exploration of the PLP_deC gene family, particularly in the economically important Solanaceae family.

Validation of the human activity profile questionnaire as a measure of physical activity levels in older community-dwelling women.

Science.gov (United States)

Bastone, Alessandra de Carvalho; Moreira, Bruno de Souza; Vieira, Renata Alvarenga; Kirkwood, Renata Noce; Dias, João Marcos Domingues; Dias, Rosângela Corrêa

2014-07-01

The purpose of this study was to assess the validity of the Human Activity Profile (HAP) by comparing scores with accelerometer data and by objectively testing its cutoff points. This study included 120 older women (age 60-90 years). Average daily time spent in sedentary, moderate, and hard activity; counts; number of steps; and energy expenditure were measured using an accelerometer. Spearman rank order correlations were used to evaluate the correlation between the HAP scores and accelerometer variables. Significant relationships were detected (rho = .47-.75, p < .001), indicating that the HAP estimates physical activity at a group level well; however, scatterplots showed individual errors. Receiver operating characteristic curves were constructed to determine HAP cutoff points on the basis of physical activity level recommendations, and the cutoff points found were similar to the original HAP cutoff points. The HAP is a useful indicator of physical activity levels in older women.

Dependence of CIT [Compact Ignition Tokamak] PF [poloidal field] coil currents on profile and shape parameters using the Control Matrix

International Nuclear Information System (INIS)

Strickler, D.J.; Peng, Y-K.M.; Jardin, S.C.; Pomphrey, N.

1990-01-01

The plasma shaping flexibility of the Compact Ignition Tokamak (CIT) poloidal field (PF) coil set is demonstrated through MHD equilibrium calculations of optimal PF coil current distributions and their variation with poloidal beta, internal inductance, plasma 95% elongation, and 95% triangularity. Calculations of the magnetic stored energy are used to compare solutions associated with various plasma parameters. The Control Matrix (CM) equilibrium code, together with the nonlinear equation and numerical optimization software packages HYBRD, and VMCON, respectively, are used to find equilibrium coil current distributions for fixed divertor geometry, volt-seconds, and plasma profiles in order to isolate the dependence on individual parameters. A reference equilibrium and coil current distribution are chosen, and correction currents dI are determined using the CM equilibrium method to obtain other specified plasma shapes. The reference equilibrium is the κ = 2 divertor at beginning of flattop (BOFT) with a minimum stored energy solution for the coil current distribution. The pressure profile function is fixed

Effect of seafood mediated PCB exposure on desaturase activity and PUFA profile in Faroese septuagenarians

DEFF Research Database (Denmark)

Tøttenborg, Sandra Søgaard; Choi, Anna L; Bjerve, Kristian S

2015-01-01

and desaturase activity. In multiple regression models, PCB exposure was inversely related to the estimated Δ6 desaturase activity resulting in accumulation of precursor fatty acids and decrease in the corresponding product PUFAs. A positive association between PCB and Δ5 desaturation was also found. A relative...... increase in EA was also observed, though only in the third tertile of PCB exposure. Non-linear relationships between the exposure and the desaturase activity were not found. Consuming fish and seafood may not be translated into beneficial fatty acid profiles if the diet simultaneously causes exposure...

Mitigating the negative impacts of tall wind turbines on bats: Vertical activity profiles and relationships to wind speed.

Science.gov (United States)

Wellig, Sascha D; Nusslé, Sébastien; Miltner, Daniela; Kohle, Oliver; Glaizot, Olivier; Braunisch, Veronika; Obrist, Martin K; Arlettaz, Raphaël

2018-01-01

Wind turbines represent a source of hazard for bats, especially through collision with rotor blades. With increasing technical development, tall turbines (rotor-swept zone 50-150 m above ground level) are becoming widespread, yet we lack quantitative information about species active at these heights, which impedes proposing targeted mitigation recommendations for bat-friendly turbine operation. We investigated vertical activity profiles of a bat assemblage, and their relationships to wind speed, within a major valley of the European Alps where tall wind turbines are being deployed. To monitor bat activity we installed automatic recorders at sequentially increasing heights from ground level up to 65 m, with the goal to determine species-specific vertical activity profiles and to link them to wind speed. Bat call sequences were analysed with an automatic algorithm, paying particular attention to mouse-eared bats (Myotis myotis and Myotis blythii) and the European free-tailed bat (Tadarida teniotis), three locally rare species. The most often recorded bats were the Common pipistrelle (Pipistrellus pipistrellus) and Savi's pipistrelle (Hypsugo savii). Mouse-eared bats were rarely recorded, and mostly just above ground, appearing out of risk of collision. T. teniotis had a more evenly distributed vertical activity profile, often being active at rotor level, but its activity at that height ceased above 5 ms-1 wind speed. Overall bat activity in the rotor-swept zone declined with increasing wind speed, dropping below 5% above 5.4 ms-1. Collision risk could be drastically reduced if nocturnal operation of tall wind turbines would be restricted to wind speeds above 5 ms-1. Such measure should be implemented year-round because T. teniotis remains active in winter. This operational restriction is likely to cause only small energy production losses at these tall wind turbines, although further analyses are needed to assess these losses precisely.

Amateur boxing: activity profile of winners and losers.

Science.gov (United States)

Davis, Philip; Wittekind, Anna; Beneke, Ralph

2013-01-01

An activity profile of competitive 3 × 2-min novice-level amateur boxing was created based on video footage and postbout blood [La] in 32 male boxers (mean ± SD) age 19.3 ± 1.4 y, body mass 62.6 ± 4.1 kg. Winners landed 18 ± 11 more punches than losers by applying more lead-hand punches in round 1 (34.2 ± 10.9 vs 26.5 ± 9.4), total punches to the head (121.3 ± 10.2 vs 96.0 ± 9.8), and block and counterpunch combinations (2.8 ± 1.1 vs. 0.1 ± 0.2) over all 3 rounds and punching combinations (44.3 ± 6.4 vs 28.8 ± 6.7) in rounds 1 and 3 (all P < .05). In 16 boxers, peak postbout blood [La] was 11.8 ± 1.6 mmol/L irrespective of winning or losing. The results suggest that landing punches requires the ability to maintain a high frequency of attacking movements, in particular the lead-hand straight punch to the head together with punching combinations. Defensive movements must initiate a counterattack. Postbout blood [La] suggests that boxers must be able to tolerate a lactate production rate of 1.8 mmol · L-1 · min-1 and maintain skillful techniques at a sufficient activity rate.

Use of isotopes in root activities and distribution studies

International Nuclear Information System (INIS)

Nario M, Adriana; Pino N, Ines; Albornoz G, Maria Paz; Baherle V, Pedro

2003-01-01

Several studies shown the relevance of the plant's root activity pattern knowledge, across the profile, to determine the suitable zone to apply the nutrients and irrigation to the plant. In Chile, the studies with the isotopes 15 N and 32 P had been used to carry out applications in solution across the soil profile and in lateral distances from the plant in fruit trees and prairies to determine root activity pattern. In peaches, under furrow irrigation, the major root concentration was found at 20 cm depth and 1 m lateral distance from the trunk. Table grapes, under drip irrigation, presented more root activity at 40 cm depth and under the dripper line in lateral distance. In prairies, the root activity was found between 10 to 40 cm depth, depending on the root capacity to explore the profile (author)

A conceptual framework for a sports knee injury performance profile (SKIPP) and return to activity criteria (RTAC).

Science.gov (United States)

Logerstedt, David; Arundale, Amelia; Lynch, Andrew; Snyder-Mackler, Lynn

2015-01-01

Injuries to the knee, including intra-articular fractures, ligamentous ruptures, and meniscal and articular cartilage lesions, are commonplace within sports. Despite advancements in surgical techniques and enhanced rehabilitation, athletes returning to cutting, pivoting, and jumping sports after a knee injury are at greater risk of sustaining a second injury. The clinical utility of objective criteria presents a decision-making challenge to ensure athletes are fully rehabilitated and safe to return to sport. A system centered on specific indicators that can be used to develop a comprehensive profile to monitor rehabilitation progression and to establish return to activity criteria is recommended to clear athletes to begin a progressive and systematic approach to activities and sports. Integration of a sports knee injury performance profile with return to activity criteria can guide clinicians in facilitating an athlete's safe return to sport, prevention of subsequent injury, and life-long knee joint health.

A conceptual framework for a sports knee injury performance profile (SKIPP and return to activity criteria (RTAC

Directory of Open Access Journals (Sweden)

David Logerstedt

2015-10-01

Full Text Available ABSTRACTInjuries to the knee, including intra-articular fractures, ligamentous ruptures, and meniscal and articular cartilage lesions, are commonplace within sports. Despite advancements in surgical techniques and enhanced rehabilitation, athletes returning to cutting, pivoting, and jumping sports after a knee injury are at greater risk of sustaining a second injury. The clinical utility of objective criteria presents a decision-making challenge to ensure athletes are fully rehabilitated and safe to return to sport. A system centered on specific indicators that can be used to develop a comprehensive profile to monitor rehabilitation progression and to establish return to activity criteria is recommended to clear athletes to begin a progressive and systematic approach to activities and sports. Integration of a sports knee injury performance profile with return to activity criteria can guide clinicians in facilitating an athlete's safe return to sport, prevention of subsequent injury, and life-long knee joint health.

The profile of physical activity and coronary risk factors in Monica Jakarta survey

Directory of Open Access Journals (Sweden)

Dede Kusmana

2001-03-01

Full Text Available A population study was done to know the profile of daily physical activity including sports, and its influence on major coronary risk factors in three districts of Jakarta using questionnaire, physicaL and laboratory examination, and 12 leads ECC. The questionnaire gave the data about physical activity (work load and sport, and smoking habit. Work load was divided into light, moderate and heavy. Sport activity was divided into regular (≥ twice a week, 20 minutes or more, irregular (≤ once or occasional, and no sport activity. In addition, blood pressure  (hypertension was grouped according to WHO criteria, total cholesterol (regarded as hypercholesterolemia when > 200 mg%, and ECG were measured. ECG interpretation was done using Minnesota Code. Statistical analysis was done using SPSS. Out of 2400 people there were  2073(86.4%  respondents that consist of 1086 females and 987 males. The profile of physical activity as a whole showed 33.4% light, 50.7% moderate and 15.8% heavy activity. OnLy 22.5% of respondents had sport regularly, while 30.3% had sport irregularly, and 47.2% had no sport activity. The type of sport was walking (45.0%, callisthenic (22.0% jogging/running (15.6%, badminton (6.5%, volley ball/soccer (4.1%, tennis (3.8%, and golf (0.1%. There was a significant difference in the prevalence of hypertension between people with heavy (12.0%, moderate (44.8% and light work load (43.2% (P<0.003, in the prevalence of hypercholesterolemia (13.2%: 50.8%: 36% (P<0.0003, and smoking (19.7%; 44.1%: 36.2% (P<0.00001, respectively. The difference also occurred in the prevalence of abnormal ECG (Q/QS, ST and T  abnormalities between people having regular sport (19.0%, irregular (22.7%, and no sport activity (58.3% (P<0.05. The number of respondents having enough physical activity (including regular sport was relatively low. Therefore, promotion should be done as a preventive method to overcome cardiovascular risk factors. (Med J Indones

Ocular Toxicity Profile of ST-162 and ST-168 as Novel Bifunctional MEK/PI3K Inhibitors.

Science.gov (United States)

Smith, Andrew; Pawar, Mercy; Van Dort, Marcian E; Galbán, Stefanie; Welton, Amanda R; Thurber, Greg M; Ross, Brian D; Besirli, Cagri G

2018-04-30

ST-162 and ST-168 are small-molecule bifunctional inhibitors of MEK and PI3K signaling pathways that are being developed as novel antitumor agents. Previous small-molecule and biologic MEK inhibitors demonstrated ocular toxicity events that were dose limiting in clinical studies. We evaluated in vitro and in vivo ocular toxicity profiles of ST-162 and ST-168. Photoreceptor cell line 661W and adult retinal pigment epithelium cell line ARPE-19 were treated with increasing concentrations of bifunctional inhibitors. Western blots, cell viability, and caspase activity assays were performed to evaluate MEK and PI3K inhibition and dose-dependent in vitro toxicity, and compared with monotherapy. In vivo toxicity profile was assessed by intravitreal injection of ST-162 and ST-168 in Dutch-Belted rabbits, followed by ocular examination and histological analysis of enucleated eyes. Retinal cell lines treated with ST-162 or ST-168 exhibited dose-dependent inhibition of MEK and PI3K signaling. Compared with inhibition by monotherapies and their combinations, bifunctional inhibitors demonstrated reduced cell death and caspase activity. In vivo, both bifunctional inhibitors exhibited a more favorable toxicity profile when compared with MEK inhibitor PD0325901. Novel MEK and PI3K bifunctional inhibitors ST-162 and ST-168 demonstrate favorable in vitro and in vivo ocular toxicity profiles, supporting their further development as potential therapeutic agents targeting multiple aggressive tumors.

Latitude dependence of long-term geomagnetic activity and its solar wind drivers

Energy Technology Data Exchange (ETDEWEB)

Myllys, M. [Helsinki Univ. (Finland). Dept. of Physics; Partamies, N. [Finnish Meteorological Institute, Helsinki (Finland); University Centre in Svalbard, Longyearbyen (Norway). Dept. of Arctic Geophysics; Juusola, L. [Finnish Meteorological Institute, Helsinki (Finland)

2015-09-01

To validate the usage of global indices in studies of geomagnetic activity, we have examined the latitude dependence of geomagnetic variations in Fennoscandia and Svalbard from 1994 to 2010. Daily standard deviation (SD) values of the horizontal magnetic field have been used as a measure of the ground magnetic disturbance level.We found that the timing of the geomagnetic minimum depends on the latitude region: corresponding to the minimum of sunspot cycle 22 (in 1996), the geomagnetic minimum occurred between the geomagnetic latitudes 57-61 in 1996 and at the latitudes 64-67 in 1997, which are the average auroral oval latitudes. During sunspot cycle 23, all latitude regions experienced the minimum in 2009, a year after the sunspot minimum. These timing differences are due to the latitude dependence of the 10 s daily SD on the different solar wind drivers. In the latitude region of 64-67 , the impact of the high-speed solar wind streams (HSSs) on the geomagnetic activity is the most pronounced compared to the other latitude groups, while in the latitude region of 57-61 , the importance of the coronal mass ejections (CMEs) dominates. The geomagnetic activity maxima during ascending solar cycle phases are typically caused by CME activity and occur especially in the oval and sub-auroral regions. The strongest geomagnetic activity occurs during the descending solar cycle phases due to a mixture of CME and HSS activity. Closer to the solar minimum, less severe geomagnetic activity is driven by HSSs and mainly visible in the poleward part of the auroral region. According to our study, however, the timing of the geomagnetic activity minima (and maxima) in different latitude bands is different, due to the relative importance of different solar wind drivers at different latitudes.

Latitude dependence of long-term geomagnetic activity and its solar wind drivers

International Nuclear Information System (INIS)

Myllys, M.

2015-01-01

To validate the usage of global indices in studies of geomagnetic activity, we have examined the latitude dependence of geomagnetic variations in Fennoscandia and Svalbard from 1994 to 2010. Daily standard deviation (SD) values of the horizontal magnetic field have been used as a measure of the ground magnetic disturbance level.We found that the timing of the geomagnetic minimum depends on the latitude region: corresponding to the minimum of sunspot cycle 22 (in 1996), the geomagnetic minimum occurred between the geomagnetic latitudes 57-61 in 1996 and at the latitudes 64-67 in 1997, which are the average auroral oval latitudes. During sunspot cycle 23, all latitude regions experienced the minimum in 2009, a year after the sunspot minimum. These timing differences are due to the latitude dependence of the 10 s daily SD on the different solar wind drivers. In the latitude region of 64-67 , the impact of the high-speed solar wind streams (HSSs) on the geomagnetic activity is the most pronounced compared to the other latitude groups, while in the latitude region of 57-61 , the importance of the coronal mass ejections (CMEs) dominates. The geomagnetic activity maxima during ascending solar cycle phases are typically caused by CME activity and occur especially in the oval and sub-auroral regions. The strongest geomagnetic activity occurs during the descending solar cycle phases due to a mixture of CME and HSS activity. Closer to the solar minimum, less severe geomagnetic activity is driven by HSSs and mainly visible in the poleward part of the auroral region. According to our study, however, the timing of the geomagnetic activity minima (and maxima) in different latitude bands is different, due to the relative importance of different solar wind drivers at different latitudes.

Indirect macrophage responses to ionizing radiation: implications for genotype-dependent bystander signaling.

Science.gov (United States)

Coates, Philip J; Rundle, Jana K; Lorimore, Sally A; Wright, Eric G

2008-01-15

In addition to the directly mutagenic effects of energy deposition in DNA, ionizing radiation is associated with a variety of untargeted and delayed effects that result in ongoing bone marrow damage. Delayed effects are genotype dependent with CBA/Ca mice, but not C57BL/6 mice, susceptible to the induction of damage and also radiation-induced acute myeloid leukemia. Because macrophages are a potential source of ongoing damaging signals, we have determined their gene expression profiles and we show that bone marrow-derived macrophages show widely different intrinsic expression patterns. The profiles classify macrophages derived from CBA/Ca mice as M1-like (pro-inflammatory) and those from C57BL/6 mice as M2-like (anti-inflammatory); measurements of NOS2 and arginase activity in normal bone marrow macrophages confirm these findings. After irradiation in vivo, but not in vitro, C57BL/6 macrophages show a reduction in NOS2 and an increase in arginase activities, indicating a further M2 response, whereas CBA/Ca macrophages retain an M1 phenotype. Activation of specific signal transducer and activator of transcription signaling pathways in irradiated hemopoietic tissues supports these observations. The data indicate that macrophage activation is not a direct effect of radiation but a tissue response, secondary to the initial radiation exposure, and have important implications for understanding genotype-dependent responses and the mechanisms of the hemotoxic and leukemogenic consequences of radiation exposure.

Nε-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure-Activity Relationships, and Pharmacokinetic Profiling.

Science.gov (United States)

Wodtke, Robert; Hauser, Christoph; Ruiz-Gómez, Gloria; Jäckel, Elisabeth; Bauer, David; Lohse, Martin; Wong, Alan; Pufe, Johanna; Ludwig, Friedrich-Alexander; Fischer, Steffen; Hauser, Sandra; Greif, Dieter; Pisabarro, M Teresa; Pietzsch, Jens; Pietsch, Markus; Löser, Reik

2018-05-24

Transglutaminase 2 (TGase 2)-catalyzed transamidation represents an important post-translational mechanism for protein modification with implications in physiological and pathophysiological conditions, including fibrotic and neoplastic processes. Consequently, this enzyme is considered a promising target for the diagnosis of and therapy for these diseases. In this study, we report on the synthesis and kinetic characterization of N ε -acryloyllysine piperazides as irreversible inhibitors of TGase 2. Systematic structural modifications on 54 new compounds were performed with a major focus on fluorine-bearing substituents due to the potential of such compounds to serve as radiotracer candidates for positron emission tomography. The determined inhibitory activities ranged from 100 to 10 000 M -1 s -1 , which resulted in comprehensive structure-activity relationships. Structure-activity correlations using various substituent parameters accompanied by covalent docking studies provide an advanced understanding of the molecular recognition for this inhibitor class within the active site of TGase 2. Selectivity profiling of selected compounds for other transglutaminases demonstrated an excellent selectivity toward transglutaminase 2. Furthermore, an initial pharmacokinetic profiling of selected inhibitors was performed, including the assessment of potential membrane permeability and liver microsomal stability.

Activity profile of 10-12-year-old Danish school girls participating in “FIFA 11 for Health” for Europe

DEFF Research Database (Denmark)

Ørntoft, Christina Øyangen; Madsen, Mads; Lind, Rune Rasmussen

sessions were delivered during school time by trained teachers over 11-week-period, 2x45 min per week. Methods: A total of 34 girls were monitored. The activity profile was monitored using the ZXY tracking system (ChyronHego, Norway), during 4 of the 22 “FIFA 11 for Health” in Europe sessions for a total......Introduction: To evaluate activity profile of the girls in the health education programme, “FIFA 11 for Health” for Europe and to examine potential differences between girls involved in leisure-time sports club activities, i.e. football and other sports, and non-sport-club active girls. The 22...... of 34 girls of which 8 were football club active, 15 were involved in other leisure-time sports and 11 were non-sport-club active. Distance covered in various speed zones (Walking (0-4 km/h), jogging (4.1-8.0 km/h), running (8.1-12.0 km/h), high intensity running (12.1-16.0 km/h) and sprinting (>16 km...

Charge-collection efficiency of GaAs field effect transistors fabricated with a low temperature grown buffer layer: dependence on charge deposition profile

International Nuclear Information System (INIS)

McMorrow, D.; Knudson, A.R.; Melinger, J.S.; Buchner, S.

1999-01-01

The results presented here reveal a surprising dependence of the charge-collection efficiency of LT GaAs FETs (field effect transistors) on the depth profile of the deposited charge. Investigation of the temporal dependence of the signal amplitude, carrier density contours, and potential contours reveals different mechanisms for charge collection arising from carriers deposited above and below the LT GaAs buffer layer, respectively. In particular, carriers deposited below the LT GaAs buffer layer dissipate slowly and give rise to a persistent charge collection that is associated with a bipolar-like gain process. These results may be of significance in understanding the occurrence of single-event upsets from protons, neutrons, and large-angle, glancing heavy-ion strikes. (authors)

3-Phosphoinositide-dependent Protein Kinase-1 (PDK1) promotes invasion and activation of matrix metalloproteinases

International Nuclear Information System (INIS)

Xie, Zhihui; Yuan, Hongyan; Yin, Yuzhi; Zeng, Xiao; Bai, Renkui; Glazer, Robert I

2006-01-01

Metastasis is a major cause of morbidity and mortality in breast cancer with tumor cell invasion playing a crucial role in the metastatic process. PDK1 is a key molecule that couples PI3K to cell proliferation and survival signals in response to growth factor receptor activation, and is oncogenic when expressed in mouse mammary epithelial cells. We now present evidence showing that PDK1-expressing cells exhibit enhanced anchorage-dependent and -independent cell growth and are highly invasive when grown on Matrigel. These properties correlate with induction of MMP-2 activity, increased MT1-MMP expression and a unique gene expression profile. Invasion assays in Matrigel, MMP-2 zymogram analysis, gene microarray analysis and mammary isografts were used to characterize the invasive and proliferative function of cells expressing PDK1. Tissue microarray analysis of human breast cancers was used to measure PDK1 expression in invasive tumors by IHC. Enhanced invasion on Matrigel in PDK1-expressing cells was accompanied by increased MMP-2 activity resulting from stabilization against proteasomal degradation. Increased MMP-2 activity was accompanied by elevated levels of MT1-MMP, which is involved in generating active MMP-2. Gene microarray analysis identified increased expression of the ECM-associated genes decorin and type I procollagen, whose gene products are substrates of MT1-MMP. Mammary fat pad isografts of PDK1-expressing cells produced invasive adenocarcinomas. Tissue microarray analysis of human invasive breast cancer indicated that PDK1pSer241 was strongly expressed in 90% of samples. These results indicate that PDK1 serves as an important effector of mammary epithelial cell growth and invasion in the transformed phenotype. PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collagen. The presence of increased PDK1 expression in the majority of invasive breast cancers suggests its

State-dependent, bidirectional modulation of neural network activity by endocannabinoids.

Science.gov (United States)

Piet, Richard; Garenne, André; Farrugia, Fanny; Le Masson, Gwendal; Marsicano, Giovanni; Chavis, Pascale; Manzoni, Olivier J

2011-11-16

The endocannabinoid (eCB) system and the cannabinoid CB1 receptor (CB1R) play key roles in the modulation of brain functions. Although actions of eCBs and CB1Rs are well described at the synaptic level, little is known of their modulation of neural activity at the network level. Using microelectrode arrays, we have examined the role of CB1R activation in the modulation of the electrical activity of rat and mice cortical neural networks in vitro. We find that exogenous activation of CB1Rs expressed on glutamatergic neurons decreases the spontaneous activity of cortical neural networks. Moreover, we observe that the net effect of the CB1R antagonist AM251 inversely correlates with the initial level of activity in the network: blocking CB1Rs increases network activity when basal network activity is low, whereas it depresses spontaneous activity when its initial level is high. Our results reveal a complex role of CB1Rs in shaping spontaneous network activity, and suggest that the outcome of endogenous neuromodulation on network function might be state dependent.

Supported rhodium catalysts for ammonia-borane hydrolysis. Dependence of the catalytic activity on the highest occupied state of the single rhodium atoms

Energy Technology Data Exchange (ETDEWEB)

Wang, Liangbing; Li, Hongliang; Zhang, Wenbo; Zhao, Xiao; Qiu, Jianxiang; Li, Aowen; Zheng, Xusheng; Zeng, Jie [Hefei National Lab. for Physical Sciences at the Microscale, Key Lab. of Strongly-Coupled Quantum Matter Physics, Chinese Academy of Sciences, Hefei, Anhui(China); Department of Chemical Physics, University of Science and Technology of China, Hefei, Anhui (China); Hu, Zhenpeng [School of Physics, Nankai University, Tianjin (China); Si, Rui [Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences (China)

2017-04-18

Supported metal nanocrystals have exhibited remarkable catalytic performance in hydrogen generation reactions, which is influenced and even determined by their supports. Accordingly, it is of fundamental importance to determine the direct relationship between catalytic performance and metal-support interactions. Herein, we provide a quantitative profile for exploring metal-support interactions by considering the highest occupied state in single-atom catalysts. The catalyst studied consisted of isolated Rh atoms dispersed on the surface of VO{sub 2} nanorods. It was observed that the activation energy of ammonia-borane hydrolysis changed when the substrate underwent a phase transition. Mechanistic studies indicate that the catalytic performance depended directly on the highest occupied state of the single Rh atoms, which was determined by the band structure of the substrates. Other metal catalysts, even with non-noble metals, that exhibited significant catalytic activity towards NH{sub 3}BH{sub 3} hydrolysis were rationally designed by adjusting their highest occupied states. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

Anthropometric profile and habits of physical activity of a scho ol students Mapuches rural Temuco, Chile

Directory of Open Access Journals (Sweden)

Pablo Antonio Valdés-Badilla

2015-04-01

Full Text Available Introduction: The nutritional status of children can be a predictor of health in adulthood element, the Mapuche population has a non-Mapuche population that increased prevalence of obesity in Chile. The aim of this study was to determine the anthropometric profile and physical activity habits of Mapuche students of a particular charter school in the rural of Temuco city.Material and Methods: The design is not experimental, descriptive, transversal, with a quantitative approach. The sample included all students of the educational establishment Mapuches (n=23, in both sexes. He underwent anthropometric assessment ISAK and total time physical activity was estimated by the International Physical Activity Questionnaire, short version in Spanish (IPAQ-A. To correlate the variables a partial correlation was used.Results: The students average about 35.4% of fat mass, muscle mass 34.1%, 11.4% of residual mass, 12% of bone mass, 7% of residual mass and somatotype 4.9–5.1–1.8 that meso-endomorph classified as balanced. Regarding the total time physical activity, students reach 2225.9 minutes/week, your energy expenditure is 9592.1 (METs/min/week and stay seated equals 228.6 minutes per week, finally negative correlation was found between BMI and total time of physical activity.Conclusions: The students have a mostly standard anthropometric profile, but with a troubling obesity rate. His activity level is high, placing them as active subjects according to normative tables.

Structure-dependent binding and activation of perfluorinated compounds on human peroxisome proliferator-activated receptor γ

Energy Technology Data Exchange (ETDEWEB)

Zhang, Lianying [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, 18 Shuangqing Road, Beijing 100085 (China); College of Life Science, Dezhou University, Dezhou 253023 (China); Ren, Xiao-Min; Wan, Bin [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, 18 Shuangqing Road, Beijing 100085 (China); Guo, Liang-Hong, E-mail: LHGuo@rcees.ac.cn [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871, 18 Shuangqing Road, Beijing 100085 (China)

2014-09-15

Perfluorinated compounds (PFCs) have been shown to disrupt lipid metabolism and even induce cancer in rodents through activation of peroxisome proliferator-activated receptors (PPARs). Lines of evidence showed that PPARα was activated by PFCs. However, the information on the binding interactions between PPARγ and PFCs and subsequent alteration of PPARγ activity is still limited and sometimes inconsistent. In the present study, in vitro binding of 16 PFCs to human PPARγ ligand binding domain (hPPARγ-LBD) and their activity on the receptor in cells were investigated. The results showed that the binding affinity was strongly dependent on their carbon number and functional group. For the eleven perfluorinated carboxylic acids (PFCAs), the binding affinity increased with their carbon number from 4 to 11, and then decreased slightly. The binding affinity of the three perfluorinated sulfonic acids (PFSAs) was stronger than their PFCA counterparts. No binding was detected for the two fluorotelomer alcohols (FTOHs). Circular dichroim spectroscopy showed that PFC binding induced distinctive structural change of the receptor. In dual luciferase reporter assays using transiently transfected Hep G2 cells, PFCs acted as hPPARγ agonists, and their potency correlated with their binding affinity with hPPARγ-LBD. Molecular docking showed that PFCs with different chain length bind with the receptor in different geometry, which may contribute to their differences in binding affinity and transcriptional activity. - Highlights: • Binding affinity between PFCs and PPARγ was evaluated for the first time. • The binding strength was dependent on fluorinated carbon chain and functional group. • PFC binding induced distinctive structural change of the receptor. • PFCs could act as hPPARγ agonists in Hep G2 cells.

Temperature dependence of radiation chemistry of polymers

International Nuclear Information System (INIS)

Garrett, R.W.; Hill, D.J.T.; Le, T.T.; Milne, K.A.; O'Donnell, J.H.; Perera, S.M.C.; Pomery, P.J.

1990-01-01

Chemical reactions which occur during radiolysis of polymers usually show an increase in rate with increasing temperature that can be described by an Arrhenius relationship. The magnitude of the activation energy can vary widely and is affected by physical, as well as chemical, factors. Different reaction rates may be expected in crystalline and amorphous morphologies, and in glassy and rubbery regions. The temperature dependence of radiolysis reactions can be expected to show discontinuities at the glass and melting transitions, T g and T m . The ceiling temperature, T c , for polymerization/depolymerization will also affect the rate of degradation, especially for depropagation to monomer. The temperature for this effect depends on the molecular structure of the polymer. The temperature dependence of free radical reactions can be studied by cryogenic trapping and ESR spectroscopy during thermal profiling. Increased degradation rates at high dose rates can be due to increased temperatures resulting from energy absorption

Control of neuropeptide expression by parallel activity-dependent pathways in caenorhabditis elegans

DEFF Research Database (Denmark)

Rojo Romanos, Teresa; Petersen, Jakob Gramstrup; Pocock, Roger

2017-01-01

Monitoring of neuronal activity within circuits facilitates integrated responses and rapid changes in behavior. We have identified a system in Caenorhabditis elegans where neuropeptide expression is dependent on the ability of the BAG neurons to sense carbon dioxide. In C. Elegans, CO 2 sensing...... is predominantly coordinated by the BAG-expressed receptor-type guanylate cyclase GCY-9. GCY-9 binding to CO 2 causes accumulation of cyclic GMP and opening of the cGMP-gated TAX-2/TAX-4 cation channels; provoking an integrated downstream cascade that enables C. Elegans to avoid high CO 2. Here we show that c...... that expression of flp-19::GFP is controlled in parallel to GCY-9 by the activity-dependent transcription factor CREB (CRH-1) and the cAMP-dependent protein kinase (KIN-2) signaling pathway. We therefore show that two parallel pathways regulate neuropeptide gene expression in the BAG sensory neurons: the ability...

Age-dependent regulation of ERF-VII transcription factor activity in Arabidopsis thaliana.

Science.gov (United States)

Giuntoli, Beatrice; Shukla, Vinay; Maggiorelli, Federica; Giorgi, Federico M; Lombardi, Lara; Perata, Pierdomenico; Licausi, Francesco

2017-10-01

The Group VII Ethylene Responsive Factors (ERFs-VII) RAP2.2 and RAP2.12 have been mainly characterized with regard to their contribution as activators of fermentation in plants. However, transcriptional changes measured in conditions that stabilize these transcription factors exceed the mere activation of this biochemical pathway, implying additional roles performed by the ERF-VIIs in other processes. We evaluated gene expression in transgenic Arabidopsis lines expressing a stabilized form of RAP2.12, or hampered in ERF-VII activity, and identified genes affected by this transcriptional regulator and its homologs, including some involved in oxidative stress response, which are not universally induced under anaerobic conditions. The contribution of the ERF-VIIs in regulating this set of genes in response to chemically induced or submergence-stimulated mitochondria malfunctioning was found to depend on the plant developmental stage. A similar age-dependent mechanism also restrained ERF-VII activity upon the core-hypoxic genes, independently of the N-end rule pathway, which is accounted for the control of the anaerobic response. To conclude, this study shed new light on a dual role of ERF-VII proteins under submergence: as positive regulators of the hypoxic response and as repressors of oxidative-stress related genes, depending on the developmental stage at which plants are challenged by stress conditions. © 2017 John Wiley & Sons Ltd.

Electromyographic Patterns during Golf Swing: Activation Sequence Profiling and Prediction of Shot Effectiveness.

Science.gov (United States)

Verikas, Antanas; Vaiciukynas, Evaldas; Gelzinis, Adas; Parker, James; Olsson, M Charlotte

2016-04-23

This study analyzes muscle activity, recorded in an eight-channel electromyographic (EMG) signal stream, during the golf swing using a 7-iron club and exploits information extracted from EMG dynamics to predict the success of the resulting shot. Muscles of the arm and shoulder on both the left and right sides, namely flexor carpi radialis, extensor digitorum communis, rhomboideus and trapezius, are considered for 15 golf players (∼5 shots each). The method using Gaussian filtering is outlined for EMG onset time estimation in each channel and activation sequence profiling. Shots of each player revealed a persistent pattern of muscle activation. Profiles were plotted and insights with respect to player effectiveness were provided. Inspection of EMG dynamics revealed a pair of highest peaks in each channel as the hallmark of golf swing, and a custom application of peak detection for automatic extraction of swing segment was introduced. Various EMG features, encompassing 22 feature sets, were constructed. Feature sets were used individually and also in decision-level fusion for the prediction of shot effectiveness. The prediction of the target attribute, such as club head speed or ball carry distance, was investigated using random forest as the learner in detection and regression tasks. Detection evaluates the personal effectiveness of a shot with respect to the player-specific average, whereas regression estimates the value of target attribute, using EMG features as predictors. Fusion after decision optimization provided the best results: the equal error rate in detection was 24.3% for the speed and 31.7% for the distance; the mean absolute percentage error in regression was 3.2% for the speed and 6.4% for the distance. Proposed EMG feature sets were found to be useful, especially when used in combination. Rankings of feature sets indicated statistics for muscle activity in both the left and right body sides, correlation-based analysis of EMG dynamics and features

Electromyographic Patterns during Golf Swing: Activation Sequence Profiling and Prediction of Shot Effectiveness

Directory of Open Access Journals (Sweden)

Antanas Verikas

2016-04-01

Full Text Available This study analyzes muscle activity, recorded in an eight-channel electromyographic (EMG signal stream, during the golf swing using a 7-iron club and exploits information extracted from EMG dynamics to predict the success of the resulting shot. Muscles of the arm and shoulder on both the left and right sides, namely flexor carpi radialis, extensor digitorum communis, rhomboideus and trapezius, are considered for 15 golf players (∼5 shots each. The method using Gaussian filtering is outlined for EMG onset time estimation in each channel and activation sequence profiling. Shots of each player revealed a persistent pattern of muscle activation. Profiles were plotted and insights with respect to player effectiveness were provided. Inspection of EMG dynamics revealed a pair of highest peaks in each channel as the hallmark of golf swing, and a custom application of peak detection for automatic extraction of swing segment was introduced. Various EMG features, encompassing 22 feature sets, were constructed. Feature sets were used individually and also in decision-level fusion for the prediction of shot effectiveness. The prediction of the target attribute, such as club head speed or ball carry distance, was investigated using random forest as the learner in detection and regression tasks. Detection evaluates the personal effectiveness of a shot with respect to the player-specific average, whereas regression estimates the value of target attribute, using EMG features as predictors. Fusion after decision optimization provided the best results: the equal error rate in detection was 24.3% for the speed and 31.7% for the distance; the mean absolute percentage error in regression was 3.2% for the speed and 6.4% for the distance. Proposed EMG feature sets were found to be useful, especially when used in combination. Rankings of feature sets indicated statistics for muscle activity in both the left and right body sides, correlation-based analysis of EMG

A Test of the Active-Day Fraction Method of Sunspot Group Number Calibration: Dependence on the Level of Solar Activity

Science.gov (United States)

Willamo, T.; Usoskin, I. G.; Kovaltsov, G. A.

2018-04-01

The method of active-day fraction (ADF) was proposed recently to calibrate different solar observers to standard observational conditions. The result of the calibration may depend on the overall level of solar activity during the observational period. This dependency is studied quantitatively using data of the Royal Greenwich Observatory by formally calibrating synthetic pseudo-observers to the full reference dataset. It is shown that the sunspot group number is precisely estimated by the ADF method for periods of moderate activity, may be slightly underestimated by 0.5 - 1.5 groups ({≤} 10%) for strong and very strong activity, and is strongly overestimated by up to 2.5 groups ({≤} 30%) for weak-to-moderate activity. The ADF method becomes inapplicable for the periods of grand minima of activity. In general, the ADF method tends to overestimate the overall level of activity and to reduce the long-term trends.

Chromatogram Profiles and Cytotoxic Activity of Irradiated Mahkota Dewa (Phaleria Macrocarpa (Scheff.) Boerl) Leaves

International Nuclear Information System (INIS)

Katrin, E.; Winarno, H.; Selvie

2011-01-01

Gamma irradiation has been used by the industries for preservation of herbal medicine, but it has not been studied the effect of gamma irradiation on their efficacy, especially their bioactivity as anticancer substances. The purpose of this research was to study the effect of gamma irradiation on the mahkota dewa leaves which has been claimed to contain potent anticancer substances. Maceration of dried mahkota dewa leaves successively with n-hexane, ethyl acetate, and ethanol gave crude extracts which the ethyl acetate was the most cytotoxic extract against leukemia L1210 cells with an inhibition concentration fifty (IC 50 ) value of 10.3 μg/ml. Further separation of ethyl acetate extract by column chromatograph gave 7 fractions, and fraction 2 showed the most cytotoxic fraction exhibited the most cytotoxic extract against leukemia L1210 cells with an IC 50 value of 1.9 μg/ml. Since, the fraction 2 of ethyl acetate extract was the most potent fraction, the irradiated samples were treated with the same procedure as treatment of fraction 2 from control sample. Cytotoxic activity test of fractions 2 from irradiated samples showed that the cytotoxic activity decreased depending on increasing of irradiation dose. Gamma irradiation dose up to 7.5 kGy on mahkota dewa leaves could decreased the cytotoxic activity of fraction 2 as the most cytotoxic-potential fraction against leukemia L1210 cells, but decreasing the cytotoxic activity has not exceeded the limit of the fraction declared inactive. So that the irradiation dose up to 7.5 kGy can be used for decontamination of bacteria and fungus/yeast without eliminating the cytotoxic activity. Gamma irradiation also caused changes in the thin layer chromatograph (TLC) spots and HPLC chromatograms profiles of fraction 2 which was the most cytotoxic fraction in ethyl acetate extract of mahkota dewa leaves against leukemia L1210 cells. One of the main peaks (peak 1) on HPLC chromatograms decreased with increasing the

Chromatogram Profiles and Cytotoxic Activity of Irradiated Mahkota Dewa (Phaleria Macrocarpa Scheff. Boerl Leaves

Directory of Open Access Journals (Sweden)

E. Katrin1

2011-04-01

Full Text Available Gamma irradiation has been used by the industries for preservation of herbal medicine, but it has not been studied the effect of gamma irradiation on their efficacy, especially their bioactivity as anticancer substances. The purpose of this research was to study the effect of gamma irradiation on the mahkota dewa leaves which has been claimed to contain potent anticancer substances. Maceration of dried mahkota dewa leaves successively with n-hexane, ethyl acetate, and ethanol gave crude extracts which the ethyl acetate was the most cytotoxic extract against leukemia L1210 cells with an inhibition concentration fifty (IC50 value of 10.3 µg/ml. Further separation of ethyl acetate extract by column chromatograph gave 7 fractions, and fraction 2 showed the most cytotoxic fraction exhibited the most cytotoxic extract against leukemia L1210 cells with an IC50 value of 1.9 µg/ml. Since, the fraction 2 of ethyl acetate extract was the most potent fraction, the irradiated samples were treated with the same procedure as treatment of fraction 2 from control sample. Cytotoxic activity test of fractions 2 from irradiated samples showed that the cytotoxic activity decreased depending on increasing of irradiation dose. Gamma irradiation dose up to 7.5 kGy on mahkota dewa leaves could decreased the cytotoxic activity of fraction 2 as the most cytotoxic-potential fraction against leukemia L1210 cells, but decreasing the cytotoxic activity has not exceeded the limit of the fraction declared inactive. So that the irradiation dose up to 7.5 kGy can be used for decontamination of bacteria and fungus/yeast without eliminating the cytotoxic activity. Gamma irradiation also caused changes in the thin layer chromatograph (TLC spots and HPLC chromatograms profiles of fraction 2 which was the most cytotoxic fraction in ethyl acetate extract of mahkota dewa leaves against leukemia L1210 cells. One of the main peaks (peak 1 on HPLC chromatograms decreased with increasing

Constitutive NADPH-dependent electron transferase activity of the Nox4 dehydrogenase domain.

Science.gov (United States)

Nisimoto, Yukio; Jackson, Heather M; Ogawa, Hisamitsu; Kawahara, Tsukasa; Lambeth, J David

2010-03-23

NADPH oxidase 4 (Nox4) is constitutively active, while Nox2 requires the cytosolic regulatory subunits p47(phox) and p67(phox) and activated Rac with activation by phorbol 12-myristate 13-acetate (PMA). This study was undertaken to identify the domain on Nox4 that confers constitutive activity. Lysates from Nox4-expressing cells exhibited constitutive NADPH- but not NADH-dependent hydrogen peroxide production with a K(m) for NADPH of 55 +/- 10 microM. The concentration of Nox4 in cell lysates was estimated using Western blotting and allowed calculation of a turnover of approximately 200 mol of H(2)O(2) min(-1) (mol of Nox4)(-1). A chimeric protein (Nox2/4) consisting of the Nox2 transmembrane (TM) domain and the Nox4 dehydrogenase (DH) domain showed H(2)O(2) production in the absence of cytosolic regulatory subunits. In contrast, chimera Nox4/2, consisting of the Nox4 TM and Nox2 DH domains, exhibited PMA-dependent activation that required coexpression of regulatory subunits. Nox DH domains from several Nox isoforms were purified and evaluated for their electron transferase activities. Nox1 DH, Nox2 DH, and Nox5 DH domains exhibited barely detectable activities toward artificial electron acceptors, while the Nox4 DH domain exhibited significant rates of reduction of cytochrome c (160 min(-1), largely superoxide dismutase-independent), ferricyanide (470 min(-1)), and other electron acceptors (artificial dyes and cytochrome b(5)). Rates were similar to those observed for H(2)O(2) production by the Nox4 holoenzyme in cell lysates. The activity required added FAD and was seen with NADPH but not NADH. These results indicate that the Nox4 DH domain exists in an intrinsically activated state and that electron transfer from NADPH to FAD is likely to be rate-limiting in the NADPH-dependent reduction of oxygen by holo-Nox4.

Design and application of natural product derived probes for activity based protein profiling

OpenAIRE

Battenberg, Oliver Alexander

2015-01-01

The identification of new antibacterial protein targets by activity based protein profiling (ABPP) is an important approach to face the increasing emergence of resistant bacteria. The scope of this work focuses on three new strategies for the labeling of antibacterial protein-targets with natural product derived ABPP-probes: A.) Evaluation of the intrinsic photo-reactivity of α-pyrones and pyrimidones for use as photo-crosslinkers. B.) Synthesis of a benzophenone-tag that combines photo-cross...

Similar expression patterns of bestrophin-4 and cGMP dependent Ca2+-activated chloride channel activity in the vasculature

DEFF Research Database (Denmark)

Bouzinova, Elena V.; Larsen, Per; Matchkov, Vladimir

2008-01-01

(abstract by Matchkov et. al) that siRNA mediated downregulation of bestrophin-4 is associated with the disappearance of a recently demonstrated2 cGMP-dependent Ca2+-activated Cl- current in vascular smooth muscle cells (SMCs). Here we study the distribution of bestrophin-4-and cGMP dependent Cl- channel...... expressed epitope) Western blot detected a ~65 kDa band in cell lysates from rat mesenteric small arteries and aorta, which was not seen in pulmonary arteries and when preincubated with the immunizing peptide. The distribution of bestrophin-4 mRNA and protein has a pattern similar to the cGMP-dependent Cl......- current in SMCs of different origins. Immunohistochemistry identified bestrophin-4 both in endothelial and SMCs of the vascular tree in the brain, heart, kidney and mesentery, but not in the lungs. We suggest that bestrophin-4 is important for the cGMP dependent, Ca2+ activated Cl- conductance in many...

Activation of Peripheral κ-Opioid Receptors Normalizes Caffeine Effects Modified in Nicotine-Dependent Rats during Nicotine Withdrawal.

Science.gov (United States)

Sudakov, S K; Bogdanova, N G

2016-10-01

The study examined the effect of peripheral (intragastric) ICI-204,448, an agonist of gastric κ-opioid receptors, on the psychostimulating and anxiolytic effects of caffeine in nicotinedependent rats at the stage of nicotine withdrawal. In these rats, the effects of caffeine (10 mg/kg) were perverted. In nicotine-dependent rats, caffeine produced an anxiolytic effect accompanied by pronounced stimulation of motor activity, in contrast to anxiogenic effect induced by caffeine in intact rats without nicotine dependence. During nicotine withdrawal, nicotine-dependent rats demonstrated enhanced sensitivity to nicotine. Intragastric administration of κ-opioid receptor agonist ICI-204,448 normalized the effect of caffeine in nicotinedependent rats. We have previously demonstrated that activation of peripheral κ-opioid receptors inhibited central κ-opioid activity and eliminated manifestations of nicotine withdrawal syndrome in nicotine-dependent rats, e.g. metabolism activation, stimulation of motor activity, and enhancement of food consumption. In its turn, inhibition of central κ-opioid structures activates the brain adenosine system, which can attenuate the caffeine-induced effects in nicotine-dependent rats.

P17, an Original Host Defense Peptide from Ant Venom, Promotes Antifungal Activities of Macrophages through the Induction of C-Type Lectin Receptors Dependent on LTB4-Mediated PPARγ Activation

Directory of Open Access Journals (Sweden)

Khaddouj Benmoussa

2017-11-01

Full Text Available Despite the growing knowledge with regard to the immunomodulatory properties of host defense peptides, their impact on macrophage differentiation and on its associated microbicidal functions is still poorly understood. Here, we demonstrated that the P17, a new cationic antimicrobial peptide from ant venom, induces an alternative phenotype of human monocyte-derived macrophages (h-MDMs. This phenotype is characterized by a C-type lectin receptors (CLRs signature composed of mannose receptor (MR and Dectin-1 expression. Concomitantly, this activation is associated to an inflammatory profile characterized by reactive oxygen species (ROS, interleukin (IL-1β, and TNF-α release. P17-activated h-MDMs exhibit an improved capacity to recognize and to engulf Candida albicans through the overexpression both of MR and Dectin-1. This upregulation requires arachidonic acid (AA mobilization and the activation of peroxisome proliferator-activated receptor gamma (PPARγ nuclear receptor through the leukotriene B4 (LTB4 production. AA/LTB4/PPARγ/Dectin-1-MR signaling pathway is crucial for P17-mediated anti-fungal activity of h-MDMs, as indicated by the fact that the activation of this axis by P17 triggered ROS production and inflammasome-dependent IL-1β release. Moreover, we showed that the increased anti-fungal immune response of h-MDMs by P17 was dependent on intracellular calcium mobilization triggered by the interaction of P17 with pertussis toxin-sensitive G-protein-coupled receptors on h-MDMs. Finally, we also demonstrated that P17-treated mice infected with C. albicans develop less severe gastrointestinal infection related to a higher efficiency of their macrophages to engulf Candida, to produce ROS and IL-1β and to kill the yeasts. Altogether, these results identify P17 as an original activator of the fungicidal response of macrophages that acts upstream PPARγ/CLRs axis and offer new immunomodulatory therapeutic perspectives in the field of

Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection.

Science.gov (United States)

Farias, L H S; Rodrigues, A P D; Coêlho, E C; Santos, M F; Sampaio, S C; Silva, E O

2017-09-01

American tegumentary leishmaniasis is caused by different species of Leishmania. This protozoan employs several mechanisms to subvert the microbicidal activity of macrophages and, given the limited efficacy of current therapies, the development of alternative treatments is essential. Animal venoms are known to exhibit a variety of pharmacological activities, including antiparasitic effects. Crotoxin (CTX) is the main component of Crotalus durissus terrificus venom, and it has several biological effects. Nevertheless, there is no report of CTX activity during macrophage - Leishmania interactions. Thus, the main objective of this study was to evaluate whether CTX has a role in macrophage M1 polarization during Leishmania infection murine macrophages, Leishmania amazonensis promastigotes and L. amazonensis-infected macrophages were challenged with CTX. MTT [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide] toxicity assays were performed on murine macrophages, and no damage was observed in these cells. Promastigotes, however, were affected by treatment with CTX (IC50 = 22·86 µg mL-1) as were intracellular amastigotes. Macrophages treated with CTX also demonstrated increased reactive oxygen species production. After they were infected with Leishmania, macrophages exhibited an increase in nitric oxide production that converged into an M1 activation profile, as suggested by their elevated production of the cytokines interleukin-6 and tumour necrosis factor-α and changes in their morphology. CTX was able to reverse the L. amazonensis-mediated inhibition of macrophage immune responses and is capable of polarizing macrophages to the M1 profile, which is associated with a better prognosis for cutaneous leishmaniasis treatment.

A statistical approach to plasma profile analysis

International Nuclear Information System (INIS)

Kardaun, O.J.W.F.; McCarthy, P.J.; Lackner, K.; Riedel, K.S.

1990-05-01

A general statistical approach to the parameterisation and analysis of tokamak profiles is presented. The modelling of the profile dependence on both the radius and the plasma parameters is discussed, and pertinent, classical as well as robust, methods of estimation are reviewed. Special attention is given to statistical tests for discriminating between the various models, and to the construction of confidence intervals for the parameterised profiles and the associated global quantities. The statistical approach is shown to provide a rigorous approach to the empirical testing of plasma profile invariance. (orig.)

Activation of cGAS-dependent antiviral responses by DNA intercalating agents.

Science.gov (United States)

Pépin, Geneviève; Nejad, Charlotte; Thomas, Belinda J; Ferrand, Jonathan; McArthur, Kate; Bardin, Philip G; Williams, Bryan R G; Gantier, Michael P

2017-01-09

Acridine dyes, including proflavine and acriflavine, were commonly used as antiseptics before the advent of penicillins in the mid-1940s. While their mode of action on pathogens was originally attributed to their DNA intercalating activity, work in the early 1970s suggested involvement of the host immune responses, characterized by induction of interferon (IFN)-like activities through an unknown mechanism. We demonstrate here that sub-toxic concentrations of a mixture of acriflavine and proflavine instigate a cyclic-GMP-AMP (cGAMP) synthase (cGAS)-dependent type-I IFN antiviral response. This pertains to the capacity of these compounds to induce low level DNA damage and cytoplasmic DNA leakage, resulting in cGAS-dependent cGAMP-like activity. Critically, acriflavine:proflavine pre-treatment of human primary bronchial epithelial cells significantly reduced rhinovirus infection. Collectively, our findings constitute the first evidence that non-toxic DNA binding agents have the capacity to act as indirect agonists of cGAS, to exert potent antiviral effects in mammalian cells. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Memory and pattern storage in neural networks with activity dependent synapses

Science.gov (United States)

Mejias, J. F.; Torres, J. J.

2009-01-01

We present recently obtained results on the influence of the interplay between several activity dependent synaptic mechanisms, such as short-term depression and facilitation, on the maximum memory storage capacity in an attractor neural network [1]. In contrast with the case of synaptic depression, which drastically reduces the capacity of the network to store and retrieve activity patterns [2], synaptic facilitation is able to enhance the memory capacity in different situations. In particular, we find that a convenient balance between depression and facilitation can enhance the memory capacity, reaching maximal values similar to those obtained with static synapses, that is, without activity-dependent processes. We also argue, employing simple arguments, that this level of balance is compatible with experimental data recorded from some cortical areas, where depression and facilitation may play an important role for both memory-oriented tasks and information processing. We conclude that depressing synapses with a certain level of facilitation allow to recover the good retrieval properties of networks with static synapses while maintaining the nonlinear properties of dynamic synapses, convenient for information processing and coding.

Goal- and retrieval-dependent activity in the striatum during memory recognition.

Science.gov (United States)

Clos, Mareike; Schwarze, Ulrike; Gluth, Sebastian; Bunzeck, Nico; Sommer, Tobias

2015-06-01

The striatum has been associated with successful memory retrieval but the precise functional link still remains unclear. One hypothesis is that striatal activity reflects an active evaluation process of the retrieval outcome dependent on the current behavioral goals rather than being a consequence of memory reactivation. We have recently shown that the striatum also correlates with confidence in memory recognition, which could reflect high subjective value ascribed to high certainty decisions. To examine whether striatal activity during memory recognition reflects subjective value indeed, we conducted an fMRI study using a recognition memory paradigm in which the participants rated not only the recognition confidence but also indicated the pleasantness associated with the previous memory retrieval. The results demonstrated a high positive correlation between confidence and pleasantness both on the behavioral and brain activation level particularly in the striatum. As almost all of variance in the striatal confidence signal could be explained by experienced pleasantness, this part of the striatal memory recognition response probably corresponds to greater subjective value of high confidence responses. While perceived oldness was also strongly correlated with striatal activity, this activation pattern was clearly distinct from that associated with confidence and pleasantness and thus could not be explained by higher subjective value to detect "old" items. Together, these results show that at least two independent processes contribute to striatal activation in recognition memory: a more flexible evaluation response dependent on context and goals captured by memory confidence and a potentially retrieval-related response captured by perceived oldness. Copyright © 2015 Elsevier Ltd. All rights reserved.

Triton burnup in JET - profile effects

Energy Technology Data Exchange (ETDEWEB)

Jarvis, O.N.; Conroy, S.W.; Marcus, F.B.; Sadler, G.J.; Belle, P. van (Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking); Adams, J.M.; Watkins, N. (AEA Industrial Technology, Harwell Laboratory (United Kingdom))

1991-01-01

Measurements of the 14 MeV neutron emission from triton burnup show that the 14 MeV emission profile shadows closely the 2,5 MeV profile but after a delay corresponding to the triton slowing down time. The slightly greater width of the 14 MeV neutron profile is a consequence of the finite Larmor radius of the tritons. It has not so far been possible to identify unambiguously any effects on the triton burnup that are attributable to sawtooth crashes. Finally, the time dependence of the triton profile indicates that the triton diffusion coefficient is very small (<<0.1 m[sup 2]/s). (author) 4 refs., 3 figs.

Triton burnup in JET - profile effects

International Nuclear Information System (INIS)

Jarvis, O.N.; Conroy, S.W.; Marcus, F.B.; Sadler, G.J.; Belle, P. van

1991-01-01

Measurements of the 14 MeV neutron emission from triton burnup show that the 14 MeV emission profile shadows closely the 2,5 MeV profile but after a delay corresponding to the triton slowing down time. The slightly greater width of the 14 MeV neutron profile is a consequence of the finite Larmor radius of the tritons. It has not so far been possible to identify unambiguously any effects on the triton burnup that are attributable to sawtooth crashes. Finally, the time dependence of the triton profile indicates that the triton diffusion coefficient is very small ( 2 /s). (author) 4 refs., 3 figs

Interpretation of pH-activity profiles for acid-base catalysis from molecular simulations.

Science.gov (United States)

Dissanayake, Thakshila; Swails, Jason M; Harris, Michael E; Roitberg, Adrian E; York, Darrin M

2015-02-17

The measurement of reaction rate as a function of pH provides essential information about mechanism. These rates are sensitive to the pK(a) values of amino acids directly involved in catalysis that are often shifted by the enzyme active site environment. Experimentally observed pH-rate profiles are usually interpreted using simple kinetic models that allow estimation of "apparent pK(a)" values of presumed general acid and base catalysts. One of the underlying assumptions in these models is that the protonation states are uncorrelated. In this work, we introduce the use of constant pH molecular dynamics simulations in explicit solvent (CpHMD) with replica exchange in the pH-dimension (pH-REMD) as a tool to aid in the interpretation of pH-activity data of enzymes and to test the validity of different kinetic models. We apply the methods to RNase A, a prototype acid-base catalyst, to predict the macroscopic and microscopic pK(a) values, as well as the shape of the pH-rate profile. Results for apo and cCMP-bound RNase A agree well with available experimental data and suggest that deprotonation of the general acid and protonation of the general base are not strongly coupled in transphosphorylation and hydrolysis steps. Stronger coupling, however, is predicted for the Lys41 and His119 protonation states in apo RNase A, leading to the requirement for a microscopic kinetic model. This type of analysis may be important for other catalytic systems where the active forms of the implicated general acid and base are oppositely charged and more highly correlated. These results suggest a new way for CpHMD/pH-REMD simulations to bridge the gap with experiments to provide a molecular-level interpretation of pH-activity data in studies of enzyme mechanisms.

Endothelial activation and cardiometabolic profiles of treated and never-treated HIV infected Africans.

Science.gov (United States)

Fourie, C M T; Schutte, A E; Smith, W; Kruger, A; van Rooyen, J M

2015-05-01

The role the human immunodeficiency virus (HIV) and antiretroviral treatment on endothelial activation, and the subsequent relationship with cardiovascular disease, is not well understood. We investigated endothelial activation, inflammatory and cardiometabolic profiles, and measures of vascular structure and function of 66 antiretroviral treated (ART), 78 never-treated (no-ART) HIV infected and 165 HIV free Africans. Blood samples were obtained for biochemical analysis and blood pressure, pulse wave velocity (PWV) and carotid intima-media thickness (IMT) measurements were performed. The HIV infection duration was at least five years and the treatment 2.86±0.13 years. The intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) levels were elevated in the HIV infected groups compared to the controls. The odds of higher adhesion molecule levels were increased when HIV infected (especially in the no-ART group); OR no-ART vs. no-HIV: ICAM 3.92 (2.2-7.0); VCAM 16.2 (7.5-35). ICAM and VCAM associated with HIV status and interleukin-6 (IL-6) in the total group (all pART: β=-0.28, p=0.01; ART: β=-0.22, p=0.07) and TC (no-ART: β=-0.36, pART: β=-0.27, p=0.03). The ART group had an unfavourable lipid profile compared to the no-ART group. The inflammatory markers (C-reactive protein (CRP) and IL-6), PWV and IMT did not differ between the three groups. HIV infected Africans showed endothelial activation when compared to HIV free controls. The endothelial activation was not accompanied by increased inflammation (as measured with CRP and IL-6), arterial stiffness or sub-clinical atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Time-dependent restricted-active-space self-consistent-field theory for laser-driven many-electron dynamics

DEFF Research Database (Denmark)

Miyagi, Haruhide; Madsen, Lars Bojer

2013-01-01

We present the time-dependent restricted-active-space self-consistent-field (TD-RASSCF) theory as a framework for the time-dependent many-electron problem. The theory generalizes the multiconfigurational time-dependent Hartree-Fock (MCTDHF) theory by incorporating the restricted-active-space scheme...... well known in time-independent quantum chemistry. Optimization of the orbitals as well as the expansion coefficients at each time step makes it possible to construct the wave function accurately while using only a relatively small number of electronic configurations. In numerical calculations of high...

Size and shape-dependent cytotoxicity profile of gold nanoparticles for biomedical applications.

Science.gov (United States)

Woźniak, Anna; Malankowska, Anna; Nowaczyk, Grzegorz; Grześkowiak, Bartosz F; Tuśnio, Karol; Słomski, Ryszard; Zaleska-Medynska, Adriana; Jurga, Stefan

2017-06-01

Metallic nanoparticles, in particular gold nanoparticles (AuNPs), offer a wide spectrum of applications in biomedicine. A crucial issue is their cytotoxicity, which depends greatly on various factors, including morphology of nanoparticles. Because metallic nanoparticles have an effect on cell membrane integrity, their shape and size may affect the viability of cells, due to their different geometries as well as physical and chemical interactions with cell membranes. Variations in the size and shape of gold nanoparticles may indicate particular nanoparticle morphologies that provide strong cytotoxicity effects. Synthesis of different sized and shaped bare AuNPs was performed with spherical (~ 10 nm), nanoflowers (~ 370 nm), nanorods (~ 41 nm), nanoprisms (~ 160 nm) and nanostars (~ 240 nm) morphologies. These nanostructures were characterized and interacting with cancer (HeLa) and normal (HEK293T) cell lines and cell viability tests were performed by WST-1 tests and fluorescent live/dead cell imaging experiments. It was shown that various shapes and sizes of gold nanostructures may affect the viability of the cells. Gold nanospheres and nanorods proved to be more toxic than star, flower and prism gold nanostructures. This may be attributed to their small size and aggregation process. This is the first report concerning a comparison of cytotoxic profile in vitro with a wide spectrum of bare AuNPs morphology. The findings show their possible use in biomedical applications.

Exploring the activity profile of health care assistants and nurses in home nursing.

Science.gov (United States)

De Vliegher, Kristel; Aertgeerts, Bert; Declercq, Anja; Moons, Philip

2015-12-01

Are home nurses (also known as community nurses) ready for their changing role in primary care? A quantitative study was performed in home nursing in Flanders, Belgium, to explore the activity profile of home nurses and health care assistants, using the 24-hour recall instrument for home nursing. Seven dates were determined, covering each day of the week and the weekend, on which data collection would take place. All the home nurses and health care assistants from the participating organisations across Flanders were invited to participate in the study. All data were measured at nominal level. A total of 2478 home nurses and 277 health care assistants registered 336 128 (47 977 patients) and 36 905 (4558 patients) activities, respectively. Home nurses and health care assistants mainly perform 'self-care facilitation' activities in combination with 'psychosocial care' activities. Health care assistants also support home nurses in the 'selfcare facilitation' of patients who do not have a specific nursing indication.

Time-dependent changes in rat lymphocyte activity in response to isolation

International Nuclear Information System (INIS)

Jessop, J.J.; Bayer, B.M.

1986-01-01

The authors have found that isolation of rats, previously adapted to group-housing conditions, resulted in time-dependent changes in mitogenic and cytolytic responses of lymphocytes. A depression (40-60%) of the uptake of 3 H-thymidine by splenic and blood lymphocytes stimulated with either phytohemagglutinin (PHA) or lipopolysaccharide (LPS) was observed during the first 48 hours after transfer of the animals to individual cages. Within 4 days the mitogenic response increased and was comparable to that of animals which had been continuously group-housed. The response continued to increase and by 10 days was enhanced by 2 to 4 fold and remained elevated for at least 8 weeks. Similar changes in activity were observed with both splenic and blood lymphocytes, however, thymic lymphocytes taken from isolated animals demonstrated no change in reactivity to PHA. As with mitogenic responses, the cytolytic activity of splenic lymphocytes was also depressed during the initial days of isolation and as isolation continued, the activity returned to normal and was significantly enhanced (80%) within 5 weeks. These data show that changes in lymphocyte activity are dependent on the duration of exposure to isolated housing conditions and may be a part of the acute, adaptive and chronic phases of the response of rats to the stress of isolation

Dependence of Photocatalytic Activity of TiO2-SiO2 Nanopowders

Directory of Open Access Journals (Sweden)

M. Riazian

2014-10-01

Full Text Available Structural properties and chemical composition change the photocatalytic activity in TiO2-SiO2 nanopowder composite. The SiO2-TiO2 nanostructure is synthesized based on sol–gel method. The nanoparticles are characterized by x-ray fluorescents (XRF, x- ray diffraction (XRD, tunneling electron microscopy (TEM, field emission scanning electron microscopy (FE-SEM, UV-vis. Spectrophotometer and furrier transmission create infrared absorption (FTIR techniques. The rate constant k for the degradation of methylen blue in its aqueous solution under UV irradiation is determined as a measure of photocatalytic activity. Dependence between photocatalytic activity and SiO2 content in the composite is determined. Rate constant k is found dependent on the content of SiO2 in the composite that calcined at 900 oC. The addition of low composition SiO2 to the TiO2 matrix (lower than 45% enhances the photocatalytic activity due to thermal stability and increasing in the surface area. The effects of chemical compositions on the surface topography and the crystallization of phases are studied.

Free radical activity during development of insulin-dependent diabetes mellitus in the rat

Energy Technology Data Exchange (ETDEWEB)

Pitkaenen, O.M.; Akerblom, H.K.; Sariola, H.; Andersson, S.M. (Univ. of Helsinki (Finland)); Martin, J.M. (Hospital for Sick Children, Toronto, Ontario (Canada)); Hallman, M. (Univ. of California, Irvine (United States))

1991-01-01

Free radical-induced lipid peroxidation was quantified by measuring expired pentane from diabetic prone BB Wistar rats of 45-90 d of age. Insulin-dependent diabetes mellitus was manifest at the age of 71 {plus minus} 8 d. Expired pentane increased from 2.1 {plus minus} 0.7 to 5.0 {plus minus}3.0 pmol/100g/min (p <0.01) at manifestation of the disease and remained high throughout the test period. In healthy age-matched control rats it persisted low. In rats made diabetic with streptozotocin, expired pentane remained low. The changes in expired pentane suggest that the development of endogenous insulin-dependent diabetes mellitus in BB rats is associated with increased free radical activity. This is not due to hyperglycemia or ketosis per se, and reflects a fundamental difference in the free radical activity between the spontaneously diabetic BB rats and the disease produced by streptozotocin. Development of spontaneous insulin-dependent diabetes in BB rats is associated with increased free radical activity that persists after the manifestation of the disease.

Characterizing context-dependent differential firing activity in the hippocampus and entorhinal cortex.

Science.gov (United States)

Prerau, Michael J; Lipton, Paul A; Eichenbaum, Howard B; Eden, Uri T

2014-04-01

The rat hippocampus and entorhinal cortex have been shown to possess neurons with place fields that modulate their firing properties under different behavioral contexts. Such context-dependent changes in neural activity are commonly studied through electrophysiological experiments in which a rat performs a continuous spatial alternation task on a T-maze. Previous research has analyzed context-based differential firing during this task by describing differences in the mean firing activity between left-turn and right-turn experimental trials. In this article, we develop qualitative and quantitative methods to characterize and compare changes in trial-to-trial firing rate variability for sets of experimental contexts. We apply these methods to cells in the CA1 region of hippocampus and in the dorsocaudal medial entorhinal cortex (dcMEC), characterizing the context-dependent differences in spiking activity during spatial alternation. We identify a subset of cells with context-dependent changes in firing rate variability. Additionally, we show that dcMEC populations encode turn direction uniformly throughout the T-maze stem, whereas CA1 populations encode context at major waypoints in the spatial trajectory. Our results suggest scenarios in which individual cells that sparsely provide information on turn direction might combine in the aggregate to produce a robust population encoding. Copyright © 2014 Wiley Periodicals, Inc.

Bacteria and viruses modulate FcεRI-dependent mast cell activity 

Directory of Open Access Journals (Sweden)

Aleksandra Słodka

2013-03-01

Full Text Available Undoubtedly, mast cells play a central role in allergic processes. Specific allergen cross-linking of IgE bound to the high affinity receptors (FcεRI on the mast cell surface leads to the release of preformed mediators and newly synthesized mediators, i.e. metabolites of arachidonic acid and cytokines. More and more data indicate that bacteria and viruses can influence FcεRI-dependent mast cell activation. Some bacterial and viral components can reduce the surface expression of FcεRI. There are also findings that ligation of Toll-like receptors (TLRs by bacterial or viral antigens can affect IgE-dependent mast cell degranulation and preformed mediator release as well as eicosanoid production. The synergistic interaction of TLR ligands and allergen can also modify cytokine synthesis by mast cells stimulated via FcεRI. Moreover, data suggest that specific IgE for bacterial or viral antigens can influence mast cell activity. What is more, some bacterial and viral components or some endogenous proteins produced during viral infection can act as superantigens by interacting with the VH3 domain of IgE. All these observations indicate that bacterial and viral infections modify the course of allergic diseases by affecting FcεRI-dependent mast cell activation. 

Approximate Stokes Drift Profiles and their use in Ocean Modelling

Science.gov (United States)

Breivik, Oyvind; Bidlot, Jea-Raymond; Janssen, Peter A. E. M.; Mogensen, Kristian

2016-04-01

Deep-water approximations to the Stokes drift velocity profile are explored as alternatives to the monochromatic profile. The alternative profiles investigated rely on the same two quantities required for the monochromatic profile, viz the Stokes transport and the surface Stokes drift velocity. Comparisons against parametric spectra and profiles under wave spectra from the ERA-Interim reanalysis and buoy observations reveal much better agreement than the monochromatic profile even for complex sea states. That the profiles give a closer match and a more correct shear has implications for ocean circulation models since the Coriolis-Stokes force depends on the magnitude and direction of the Stokes drift profile and Langmuir turbulence parameterizations depend sensitively on the shear of the profile. Of the two Stokes drift profiles explored here, the profile based on the Phillips spectrum is by far the best. In particular, the shear near the surface is almost identical to that influenced by the f-5 tail of spectral wave models. The NEMO general circulation ocean model was recently extended to incorporate the Stokes-Coriolis force along with two other wave-related effects. The ECWMF coupled atmosphere-wave-ocean ensemble forecast system now includes these wave effects in the ocean model component (NEMO).

Constitutive NADPH-Dependent Electron Transferase Activity of the Nox4 Dehydrogenase Domain?

OpenAIRE

Nisimoto, Yukio; Jackson, Heather M.; Ogawa, Hisamitsu; Kawahara, Tsukasa; Lambeth, J. David

2010-01-01

NADPH oxidase 4 (Nox4) is constitutively active, while Nox2 requires the cytosolic regulatory subunits p47 phox and p67 phox and activated Rac with activation by phorbol 12-myristate 13-acetate (PMA). This study was undertaken to identify the domain on Nox4 that confers constitutive activity. Lysates from Nox4-expressing cells exhibited constitutive NADPH- but not NADH-dependent hydrogen peroxide production with a K m for NADPH of 55 ? 10 ?M. The concentration of Nox4 in cell lysates was esti...

Origins and implications of temperature-dependent activation energy barriers for dislocation nucleation in face-centered cubic metals

International Nuclear Information System (INIS)

Warner, D.H.; Curtin, W.A.

2009-01-01

The linking of atomistic simulations of stress-driven processes to experimentally observed mechanical behavior via the computation of activation energy barriers is a topic of intense current research. Using dislocation nucleation from a crack tip as the reaction process, long-time multiscale molecular dynamics simulations show that the activation barrier can exhibit significant temperature dependence. Using an analytic model for the nucleation process and computing the relevant material properties (elastic constants and stacking fault energies), the temperature dependence is shown to arise primarily from the temperature dependence of the material parameters for both Al and Ni. After thermally activated emission of the first partial dislocation, there is then a competition between two other thermally activated processes: twinning and full dislocation emission. Because the activation barriers depend on temperature, this transition is more complex than usually envisioned. Simulations in Al reveal that a transition from twinning to full dislocation emission back to twinning occurs with increasing temperature, which is counter to traditional metallurgical wisdom. Temperature-dependent activation energies are thus essential to accurate understanding and prediction of those phenomena that control fracture and deformation in metals at realistic loading rates.

Active ion transport in the renal proximal tubule. II. Ionic dependence of the Na pump

OpenAIRE

1984-01-01

The dependence of Na pump activity on intracellular and extracellular Na+ and K+ was investigated using a suspension of rabbit cortical tubules that contained mostly (86%) proximal tubules. The ouabain- sensitive rate of respiration (QO2) was used to measure the Na pump activity of intact tubules, and the Na,K-ATPase hydrolytic activity was measured using lysed proximal tubule membranes. The dependence (K0.5) of the Na pump on intracellular Na+ was affected by the relative intracellular conce...

Atmospheric profiles from active space-based radio measurements

Science.gov (United States)

Hardy, Kenneth R.; Hinson, David P.; Tyler, G. L.; Kursinski, E. R.

1992-01-01

The paper describes determinations of atmospheric profiles from space-based radio measurements and the retrieval methodology used, with special attention given to the measurement procedure and the characteristics of the soundings. It is speculated that reliable profiles of the terrestrial atmosphere can be obtained by the occultation technique from the surface to a height of about 60 km. With the full complement of 21 the Global Positioning System (GPS) satellites and one GPS receiver in sun synchronous polar orbit, a maximum of 42 soundings could be obtained for each complete orbit or about 670 per day, providing almost uniform global coverage.

Phospholipase A2 activity-dependent and -independent fusogenic activity of Naja nigricollis CMS-9 on zwitterionic and anionic phospholipid vesicles.

Science.gov (United States)

Chiou, Yi-Ling; Chen, Ying-Jung; Lin, Shinne-Ren; Chang, Long-Sen

2011-11-01

CMS-9, a phospholipase A(2) (PLA(2)) from Naja nigricollis venom, induced the death of human breast cancer MCF-7 cells accompanied with the formation of cell clumps without clear boundaries between cells. Annexin V-FITC staining indicated that abundant phosphatidylserine appeared on the outer membrane of MCF-7 cell clumps, implying the possibility that CMS-9 may promote membrane fusion via anionic phospholipids. To validate this proposition, fusogenic activity of CMS-9 on vesicles composed of zwitterionic phospholipid alone or a combination of zwitterionic and anionic phospholipids was examined. Although CMS-9-induced fusion of zwitterionic phospholipid vesicles depended on PLA(2) activity, CMS-9-induced fusion of vesicles containing anionic phospholipids could occur without the involvement of PLA(2) activity. Membrane-damaging activity of CMS-9 was associated with its fusogenicity. Moreover, CMS-9 induced differently membrane leakage and membrane fusion of vesicles with different compositions. Membrane fluidity and binding capability with phospholipid vesicles were not related to the fusogenicity of CMS-9. However, membrane-bound conformation and mode of CMS-9 depended on phospholipid compositions. Collectively, our data suggest that PLA(2) activity-dependent and -independent fusogenicity of CMS-9 are closely related to its membrane-bound modes and targeted membrane compositions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Shaping inhibition: activity dependent structural plasticity of GABAergic synapses

Directory of Open Access Journals (Sweden)

Carmen E Flores

2014-10-01

Full Text Available Inhibitory transmission through the neurotransmitter Ɣ-aminobutyric acid (GABA shapes network activity in the mammalian cerebral cortex by filtering synaptic incoming information and dictating the activity of principal cells. The incredibly diverse population of cortical neurons that use GABA as neurotransmitter shows an equally diverse range of mechanisms that regulate changes in the strength of GABAergic synaptic transmission and allow them to dynamically follow and command the activity of neuronal ensembles. Similarly to glutamatergic synaptic transmission, activity-dependent functional changes in inhibitory neurotransmission are accompanied by alterations in GABAergic synapse structure that range from morphological reorganization of postsynaptic density to de novo formation and elimination of inhibitory contacts. Here we review several aspects of structural plasticity of inhibitory synapses, including its induction by different forms of neuronal activity, behavioral and sensory experience and the molecular mechanisms and signaling pathways involved. We discuss the functional consequences of GABAergic synapse structural plasticity for information processing and memory formation in view of the heterogenous nature of the structural plasticity phenomena affecting inhibitory synapses impinging on somatic and dendritic compartments of cortical and hippocampal neurons.

Frequency dependence of the active impedance component of silicon thin-film resistors

International Nuclear Information System (INIS)

Belogurov, S.V.; Gostilo, V.V.; Yurov, A.S.

1987-01-01

A high-resistant resistor on the silicon thin-film substrate considerably superior in noise and frequency performance than commercial resistors is described. The frequency dependence of the active impedance component is tested for determining noise and frequency dependences of silicon thin-film resistors. The obtained results permit to calculate the energy equivalent of resistor noise in nuclear radiation detection units at any temperature according to its frequency characteristic at room temperature

Time-dependent restricted-active-space self-consistent-field theory for bosonic many-body systems

International Nuclear Information System (INIS)

Lévêque, Camille; Madsen, Lars Bojer

2017-01-01

We develop an ab initio time-dependent wavefunction based theory for the description of a many-body system of cold interacting bosons. Like the multi-configurational time-dependent Hartree method for bosons (MCTDHB), the theory is based on a configurational interaction Ansatz for the many-body wavefunction with time-dependent self-consistent-field orbitals. The theory generalizes the MCTDHB method by incorporating restrictions on the active space of the orbital excitations. The restrictions are specified based on the physical situation at hand. The equations of motion of this time-dependent restricted-active-space self-consistent-field (TD-RASSCF) theory are derived. The similarity between the formal development of the theory for bosons and fermions is discussed. The restrictions on the active space allow the theory to be evaluated under conditions where other wavefunction based methods due to exponential scaling in the numerical effort cannot, and to clearly identify the excitations that are important for an accurate description, significantly beyond the mean-field approach. For ground state calculations we find it to be important to allow a few particles to have the freedom to move in many orbitals, an insight facilitated by the flexibility of the restricted-active-space Ansatz . Moreover, we find that a high accuracy can be obtained by including only even excitations in the many-body self-consistent-field wavefunction. Time-dependent simulations of harmonically trapped bosons subject to a quenching of their noncontact interaction, show failure of the mean-field Gross-Pitaevskii approach within a fraction of a harmonic oscillation period. The TD-RASSCF theory remains accurate at much reduced computational cost compared to the MCTDHB method. Exploring the effect of changes of the restricted-active-space allows us to identify that even self-consistent-field excitations are mainly responsible for the accuracy of the method. (paper)

Cre-dependent DNA recombination activates a STING-dependent innate immune response

Science.gov (United States)

Pépin, Geneviève; Ferrand, Jonathan; Höning, Klara; Jayasekara, W. Samantha N.; Cain, Jason E.; Behlke, Mark A.; Gough, Daniel J.; G. Williams, Bryan R.; Hornung, Veit

2016-01-01

Abstract Gene-recombinase technologies, such as Cre/loxP-mediated DNA recombination, are important tools in the study of gene function, but have potential side effects due to damaging activity on DNA. Here we show that DNA recombination by Cre instigates a robust antiviral response in mammalian cells, independent of legitimate loxP recombination. This is due to the recruitment of the cytosolic DNA sensor STING, concurrent with Cre-dependent DNA damage and the accumulation of cytoplasmic DNA. Importantly, we establish a direct interplay between this antiviral response and cell–cell interactions, indicating that low cell densities in vitro could be useful to help mitigate these effects of Cre. Taking into account the wide range of interferon stimulated genes that may be induced by the STING pathway, these results have broad implications in fields such as immunology, cancer biology, metabolism and stem cell research. Further, this study sets a precedent in the field of gene-engineering, possibly applicable to other enzymatic-based genome editing technologies. PMID:27166376

Synthesis and Antidepressant Activity Profile of Some Novel Benzothiazole Derivatives

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Ümide Demir Özkay

2017-09-01

Full Text Available Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives 3a–3h. The chemical structures of the synthesized compounds were elucidated by spectroscopic methods. Test compounds were administered orally at a dose of 40 mg/kg to mice 24, 5 and 1 h before performing tail suspension, modified forced swimming, and activity cage tests. The obtained results showed that compounds 3c, 3d, 3f–3h reduced the immobility time of mice as assessed in the tail suspension test. Moreover, in the modified forced swimming tests, the same compounds significantly decreased the immobility, but increased the swimming frequencies of mice, without any alteration in the climbing frequencies. These results, similar to the results induced by the reference drug fluoxetine (20 mg/kg, po, indicated the antidepressant-like activities of the compounds 3c, 3d, 3f–3h. Owing to the fact that test compounds did not induce any significant alteration in the total number of spontaneous locomotor activities, the antidepressant-like effects of these derivatives seemed to be specific. In order to predict ADME parameters of the synthesized compounds 3a–3h, some physicochemical parameters were calculated. The ADME prediction study revealed that all synthesized compounds may possess good pharmacokinetic profiles.

Task-dependent modulation of oscillatory neural activity during movements

DEFF Research Database (Denmark)

Herz, D. M.; Christensen, M. S.; Reck, C.

2011-01-01

connectivity was strongest between central and cerebellar regions. Our results show that neural coupling within motor networks is modulated in distinct frequency bands depending on the motor task. They provide evidence that dynamic causal modeling in combination with EEG source analysis is a valuable tool......Neural oscillations in different frequency bands have been observed in a range of sensorimotor tasks and have been linked to coupling of spatially distinct neurons. The goal of this study was to detect a general motor network that is activated during phasic and tonic movements and to study the task......-dependent modulation of frequency coupling within this network. To this end we recorded 122-multichannel EEG in 13 healthy subjects while they performed three simple motor tasks. EEG data source modeling using individual MR images was carried out with a multiple source beamformer approach. A bilateral motor network...

FUNCTIONAL PROFILE OF ACTIVE OLDER ADULTS WITH LOW BACK PAIN, ACCORDING TO THE ICF

Directory of Open Access Journals (Sweden)

Andersom Ricardo Fréz

Full Text Available ABSTRACT Introduction: The International Classification of Functioning, Disability and Health (ICF considers multiples aspects of functionality. It is believed that this tool can help to classify the functionality of older adults with low back pain (LBP . Objectives: To describe the functionality of active older adults with LBP according to the ICF. Methods: A transversal study was conducted using the brief ICF core set for low back pain, to establish functional profiles of 40 older adults. The ICF categories were considered valid when ≥20% of participants showed some disability. Results: Thirty-two of the 35 categories of the brief ICF core set could be considered representative of the sample. Conclusion: The brief ICF core set for LBP results demonstrated that this classification system is representative for describing the functional profile of the sample.

Prostasin-dependent activation of epithelial Na+ channels by low plasmin concentrations

DEFF Research Database (Denmark)

Svenningsen, Per; Uhrenholt, Torben R; Palarasah, Yaseelan

2009-01-01

by which plasmin stimulates ENaC activity. Cy3-labeled plasmin was found to bind to the surface of the mouse cortical collecting duct cell line, M-1. Binding depended on a glycosylphosphatidylinositol (GPI)-anchored protein. Biotin-label transfer showed that plasmin interacted with the GPI-anchored protein...... plasmin-stimulated ENaC current in monolayers of M-1 cells at low plasmin concentration (1-4 microg/ml). At a high plasmin concentration of 30 microg/ml, there was no difference between cell layers treated with or without PI-PLC. Knockdown of prostasin attenuated binding of plasmin to M1 cells and blocked...... labeling of M-1 cells. Pretreatment with plasmin abolished labeling of M-1 cells in a prostasin-dependent way. We conclude that, at low concentrations, plasmin interacts with GPI-anchored prostasin, which leads to cleavage of the gamma-subunit and activation of ENaC, while at higher concentrations, plasmin...

Molecular mechanism of bacterial Hsp90 pH-dependent ATPase activity.

Science.gov (United States)

Jin, Yi; Hoxie, Reyal S; Street, Timothy O

2017-06-01

Hsp90 is a dimeric molecular chaperone that undergoes an essential and highly regulated open-to-closed-to-open conformational cycle upon ATP binding and hydrolysis. Although it has been established that a large energy barrier to closure is responsible for Hsp90's low ATP hydrolysis rate, the specific molecular contacts that create this energy barrier are not known. Here we discover that bacterial Hsp90 (HtpG) has a pH-dependent ATPase activity that is unique among other Hsp90 homologs. The underlying mechanism is a conformation-specific electrostatic interaction between a single histidine, H255, and bound ATP. H255 stabilizes ATP only while HtpG adopts a catalytically inactive open configuration, resulting in a striking anti-correlation between nucleotide binding affinity and chaperone activity over a wide range of pH. Linkage analysis reveals that the H255-ATP salt bridge contributes 1.5 kcal/mol to the energy barrier of closure. This energetic contribution is structurally asymmetric, whereby only one H255-ATP salt-bridge per dimer of HtpG controls ATPase activation. We find that a similar electrostatic mechanism regulates the ATPase of the endoplasmic reticulum Hsp90, and that pH-dependent activity can be engineered into eukaryotic cytosolic Hsp90. These results reveal site-specific energetic information about an evolutionarily conserved conformational landscape that controls Hsp90 ATPase activity. © 2017 The Protein Society.

Synthesis and Analgesic Activity Evaluation of Some Agmatine Derivatives

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Song Li

2006-06-01

Full Text Available A series of N,N’-disubstituted-2-nitroethene-1,1-diamine and N,N’-disubstituted- N’’-cyanoguanidine derivatives were prepared and evaluated for in vivo analgesic activity. The blood brain barrier (BBB VolSurf model was used to predict the BBB permeation profiles of our synthesized compounds. Some compounds show both remarkable analgesic activity and good BBB permeation profiles, and these compounds might be developed for treatment of opioid tolerance and dependence.

The nuclear immune receptor RPS4 is required for RRS1SLH1-dependent constitutive defense activation in Arabidopsis thaliana.

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Kee Hoon Sohn

2014-10-01

Full Text Available Plant nucleotide-binding leucine-rich repeat (NB-LRR disease resistance (R proteins recognize specific "avirulent" pathogen effectors and activate immune responses. NB-LRR proteins structurally and functionally resemble mammalian Nod-like receptors (NLRs. How NB-LRR and NLR proteins activate defense is poorly understood. The divergently transcribed Arabidopsis R genes, RPS4 (resistance to Pseudomonas syringae 4 and RRS1 (resistance to Ralstonia solanacearum 1, function together to confer recognition of Pseudomonas AvrRps4 and Ralstonia PopP2. RRS1 is the only known recessive NB-LRR R gene and encodes a WRKY DNA binding domain, prompting suggestions that it acts downstream of RPS4 for transcriptional activation of defense genes. We define here the early RRS1-dependent transcriptional changes upon delivery of PopP2 via Pseudomonas type III secretion. The Arabidopsis slh1 (sensitive to low humidity 1 mutant encodes an RRS1 allele (RRS1SLH1 with a single amino acid (leucine insertion in the WRKY DNA-binding domain. Its poor growth due to constitutive defense activation is rescued at higher temperature. Transcription profiling data indicate that RRS1SLH1-mediated defense activation overlaps substantially with AvrRps4- and PopP2-regulated responses. To better understand the genetic basis of RPS4/RRS1-dependent immunity, we performed a genetic screen to identify suppressor of slh1 immunity (sushi mutants. We show that many sushi mutants carry mutations in RPS4, suggesting that RPS4 acts downstream or in a complex with RRS1. Interestingly, several mutations were identified in a domain C-terminal to the RPS4 LRR domain. Using an Agrobacterium-mediated transient assay system, we demonstrate that the P-loop motif of RPS4 but not of RRS1SLH1 is required for RRS1SLH1 function. We also recapitulate the dominant suppression of RRS1SLH1 defense activation by wild type RRS1 and show this suppression requires an intact RRS1 P-loop. These analyses of RRS1SLH1 shed

Convolution based profile fitting

International Nuclear Information System (INIS)

Kern, A.; Coelho, A.A.; Cheary, R.W.

2002-01-01

Full text: In convolution based profile fitting, profiles are generated by convoluting functions together to form the observed profile shape. For a convolution of 'n' functions this process can be written as, Y(2θ)=F 1 (2θ)x F 2 (2θ)x... x F i (2θ)x....xF n (2θ). In powder diffractometry the functions F i (2θ) can be interpreted as the aberration functions of the diffractometer, but in general any combination of appropriate functions for F i (2θ) may be used in this context. Most direct convolution fitting methods are restricted to combinations of F i (2θ) that can be convoluted analytically (e.g. GSAS) such as Lorentzians, Gaussians, the hat (impulse) function and the exponential function. However, software such as TOPAS is now available that can accurately convolute and refine a wide variety of profile shapes numerically, including user defined profiles, without the need to convolute analytically. Some of the most important advantages of modern convolution based profile fitting are: 1) virtually any peak shape and angle dependence can normally be described using minimal profile parameters in laboratory and synchrotron X-ray data as well as in CW and TOF neutron data. This is possible because numerical convolution and numerical differentiation is used within the refinement procedure so that a wide range of functions can easily be incorporated into the convolution equation; 2) it can use physically based diffractometer models by convoluting the instrument aberration functions. This can be done for most laboratory based X-ray powder diffractometer configurations including conventional divergent beam instruments, parallel beam instruments, and diffractometers used for asymmetric diffraction. It can also accommodate various optical elements (e.g. multilayers and monochromators) and detector systems (e.g. point and position sensitive detectors) and has already been applied to neutron powder diffraction systems (e.g. ANSTO) as well as synchrotron based

Hypoxia-ischemia or excitotoxin-induced tissue plasminogen activator- dependent gelatinase activation in mice neonate brain microvessels.

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Priscilla L Omouendze

Full Text Available Hypoxia-ischemia (HI and excitotoxicity are validated causes of neonatal brain injuries and tissue plasminogen activator (t-PA participates in the processes through proteolytic and receptor-mediated pathways. Brain microvascular endothelial cells from neonates in culture, contain and release more t-PA and gelatinases upon glutamate challenge than adult cells. We have studied t-PA to gelatinase (MMP-2 and MMP-9 activity links in HI and excitotoxicity lesion models in 5 day-old pups in wild type and in t-PA or its inhibitor (PAI-1 genes inactivated mice. Gelatinolytic activities were detected in SDS-PAGE zymograms and by in situ fluorescent DQ-gelatin microscopic zymographies. HI was achieved by unilateral carotid ligature followed by a 40 min hypoxia (8%O₂. Excitotoxic lesions were produced by intra parenchymal cortical (i.c. injections of 10 µg ibotenate (Ibo. Gel zymograms in WT cortex revealed progressive extinction of MMP-2 and MMP-9 activities near day 15 or day 8 respectively. MMP-2 expression was the same in all strains while MMP-9 activity was barely detectable in t-PA⁻/⁻ and enhanced in PAI-1⁻/⁻ mice. HI or Ibo produced activation of MMP-2 activities 6 hours post-insult, in cortices of WT mice but not in t-PA⁻/⁻ mice. In PAI-1⁻/⁻ mice, HI or vehicle i.c. injection increased MMP-2 and MMP-9 activities. In situ zymograms using DQ-gelatin revealed vessel associated gelatinolytic activity in lesioned areas in PAI-1⁻/⁻ and in WT mice. In WT brain slices incubated ex vivo, glutamate (200 µM induced DQ-gelatin activation in vessels. The effect was not detected in t-PA⁻/⁻ mice, but was restored by concomitant exposure to recombinant t-PA (20 µg/mL. In summary, neonatal brain lesion paradigms and ex vivo excitotoxic glutamate evoked t-PA-dependent gelatinases activation in vessels. Both MMP-2 and MMP-9 activities appeared t-PA-dependent. The data suggest that vascular directed protease inhibition may have

Numerical studies of active current profile control in the reversed-field pinch

International Nuclear Information System (INIS)

Dahlin, J-E; Scheffel, J; Anderson, J K

2007-01-01

Quenching of the reversed-field pinch (RFP) dynamo is observed in numerical simulations using current profile control. A novel algorithm employing active feedback of the dynamo field has been utilized. The quasi-steady state achieved represents an important improvement as compared with earlier numerical work and may indicate a direction for the design of future experiments. Both earlier and the novel schemes of feedback control result in quasi-single helicity states. The energy confinement time and poloidal beta are observed to be substantially increased, as compared with the conventional RFP, in both the cases. Different techniques for experimental implementation are discussed

Comparative phenolic compound profiles and antioxidative activity of the fruit, leaves, and roots of Korean ginseng (Panax ginseng Meyer) according to cultivation years

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Chung, Ill-Min; Lim, Ju-Jin; Ahn, Mun-Seob; Jeong, Haet-Nim; An, Tae-Jin; Kim, Seung-Hyun

2015-01-01

Background The study of phenolic compounds profiles and antioxidative activity in ginseng fruit, leaves, and roots with respect to cultivation years, and has been little reported to date. Hence, this study examined the phenolic compounds profiles and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free-radical-scavenging activities in the fruit, leaves, and roots of Korean ginseng (Panax ginseng Meyer) as a function of cultivation year. Methods Profiling of 23 phenolic compounds in ginseng fruit, leaves, and roots was investigated using ultra-high performance liquid chromatography with the external calibration method. Antioxidative activity of ginseng fruit, leaves, and roots were evaluated using the method of DPPH free-radical-scavenging activity. Results The total phenol content in ginseng fruit and leaves was higher than in ginseng roots (p phenol content in the ginseng samples was significantly correlated to the DPPH free-radical-scavenging activity (r = 0.928****). In particular, p-coumaric acid (r = 0.847****) and ferulic acid (r = 0.742****) greatly affected the DPPH activity. Among the 23 phenolic compounds studied, phenolic acids were more abundant in ginseng fruit, leaves, and roots than the flavonoids and other compounds (p phenolic compounds in 3–6-yr-old ginseng fruit, leaves, and roots. Conclusion This study provides basic information about the antioxidative activity and phenolic compounds profiles in fruit, leaves, and roots of Korean ginseng with cultivation years. This information is potentially useful to ginseng growers and industries involved in the production of high-quality and nutritional ginseng products. PMID:26843824

Activation of cAMP-dependent signaling induces oxidative modification of the cardiac Na+-K+ pump and inhibits its activity.

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White, Caroline N; Liu, Chia-Chi; Garcia, Alvaro; Hamilton, Elisha J; Chia, Karin K M; Figtree, Gemma A; Rasmussen, Helge H

2010-04-30

Cellular signaling can inhibit the membrane Na(+)-K(+) pump via protein kinase C (PKC)-dependent activation of NADPH oxidase and a downstream oxidative modification, glutathionylation, of the beta(1) subunit of the pump alpha/beta heterodimer. It is firmly established that cAMP-dependent signaling also regulates the pump, and we have now examined the hypothesis that such regulation can be mediated by glutathionylation. Exposure of rabbit cardiac myocytes to the adenylyl cyclase activator forskolin increased the co-immunoprecipitation of NADPH oxidase subunits p47(phox) and p22(phox), required for its activation, and increased superoxide-sensitive fluorescence. Forskolin also increased glutathionylation of the Na(+)-K(+) pump beta(1) subunit and decreased its co-immunoprecipitation with the alpha(1) subunit, findings similar to those already established for PKC-dependent signaling. The decrease in co-immunoprecipitation indicates a decrease in the alpha(1)/beta(1) subunit interaction known to be critical for pump function. In agreement with this, forskolin decreased ouabain-sensitive electrogenic Na(+)-K(+) pump current (arising from the 3:2 Na(+):K(+) exchange ratio) of voltage-clamped, internally perfused myocytes. The decrease was abolished by the inclusion of superoxide dismutase, the inhibitory peptide for the epsilon-isoform of PKC or inhibitory peptide for NADPH oxidase in patch pipette solutions that perfuse the intracellular compartment. Pump inhibition was also abolished by inhibitors of protein kinase A and phospholipase C. We conclude that cAMP- and PKC-dependent inhibition of the cardiac Na(+)-K(+) pump occurs via a shared downstream oxidative signaling pathway involving NADPH oxidase activation and glutathionylation of the pump beta(1) subunit.

Activity-Dependent IGF-1 Exocytosis is Controlled by the Ca2+-Sensor Synaptotagmin-10

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Cao, Peng; Maximov, Anton; Südhof, Thomas C.

2011-01-01

Synaptotagmins Syt1, Syt2, Syt7, and Syt9 act as Ca2+-sensors for synaptic and neuroendocrine exocytosis, but the function of other synaptotagmins remains unknown. Here, we show that olfactory bulb neurons secrete IGF-1 by an activity-dependent pathway of exocytosis, and that Syt10 functions as the Ca2+-sensor that triggers IGF-1 exocytosis in these neurons. Deletion of Syt10 impaired activity-dependent IGF-1 secretion in olfactory bulb neurons, resulting in smaller neurons and an overall decrease in synapse numbers. Exogenous IGF-1 completely reversed the Syt10 knockout phenotype. Syt10 co-localized with IGF-1 in somatodendritic vesicles of olfactory bulb neurons, and Ca2+-binding to Syt10 caused these vesicles to undergo exocytosis, thereby secreting IGF-1. Thus, Syt10 controls a previously unrecognized pathway of Ca2+-dependent exocytosis that is spatially and temporally distinct from Ca2+-dependent synaptic vesicle exocytosis controlled by Syt1 in the same neurons, and two different synaptotagmins regulate distinct Ca2+-dependent membrane fusion reactions during exocytosis in the same neuron. PMID:21496647

Long lasting protein synthesis- and activity-dependent spine shrinkage and elimination after synaptic depression.

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Yazmín Ramiro-Cortés

Full Text Available Neuronal circuits modify their response to synaptic inputs in an experience-dependent fashion. Increases in synaptic weights are accompanied by structural modifications, and activity dependent, long lasting growth of dendritic spines requires new protein synthesis. When multiple spines are potentiated within a dendritic domain, they show dynamic structural plasticity changes, indicating that spines can undergo bidirectional physical modifications. However, it is unclear whether protein synthesis dependent synaptic depression leads to long lasting structural changes. Here, we investigate the structural correlates of protein synthesis dependent long-term depression (LTD mediated by metabotropic glutamate receptors (mGluRs through two-photon imaging of dendritic spines on hippocampal pyramidal neurons. We find that induction of mGluR-LTD leads to robust and long lasting spine shrinkage and elimination that lasts for up to 24 hours. These effects depend on signaling through group I mGluRs, require protein synthesis, and activity. These data reveal a mechanism for long lasting remodeling of synaptic inputs, and offer potential insights into mental retardation.

Glutathionylation regulates cytosolic NADP+-dependent isocitrate dehydrogenase activity.

Science.gov (United States)

Shin, Seoung Woo; Oh, Chang Joo; Kil, In Sup; Park, Jeen-Woo

2009-04-01

Cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) is susceptible to inactivation by numerous thiol-modifying reagents. This study now reports that Cys269 of IDPc is a target for S-glutathionylation and that this modification is reversed by dithiothreitol as well as enzymatically by cytosolic glutaredoxin in the presence of GSH. Glutathionylated IDPc was significantly less susceptible than native protein to peptide fragmentation by reactive oxygen species and proteolytic digestion. Glutathionylation may play a protective role in the degradation of protein through the structural alterations of IDPc. HEK293 cells treated with diamide displayed decreased IDPc activity and accumulated glutathionylated enzyme. Using immunoprecipitation with an anti-IDPc IgG and immunoblotting with an anti-GSH IgG, we purified and positively identified glutathionylated IDPc from the kidneys of mice subjected to ischemia/reperfusion injury and from the livers of ethanol-administered rats. These results suggest that IDPc activity is modulated through enzymatic glutathionylation and deglutathionylation during oxidative stress.

Radiosensitivity profiles from a panel of ovarian cancer cell lines exhibiting genetic alterations in p53 and disparate DNA-dependent protein kinase activities

Energy Technology Data Exchange (ETDEWEB)

Langland, Gregory T.; Yannone, Steven M.; Langland, Rachel A.; Nakao, Aki; Guan, Yinghui; Long, Sydney B.T.; Vonguyen, Lien; Chen, David J.; Gray, Joe W; Chen, Fanqing

2009-09-07

The variability of radiation responses in ovarian tumors and tumor-derived cell lines is poorly understood. Since both DNA repair capacity and p53 status can significantly alter radiation sensitivity, we evaluated these factors along with radiation sensitivity in a panel of sporadic human ovarian carcinoma cell lines. We observed a gradation of radiation sensitivity among these sixteen lines, with a five-fold difference in the LD50 between the most radiosensitive and the most radioresistant cells. The DNA-dependent protein kinase (DNA-PK) is essential for the repair of radiation induced DNA double-strand breaks in human somatic cells. Therefore, we measured gene copy number, expression levels, protein abundance, genomic copy and kinase activity for DNA-PK in all of our cell lines. While there were detectable differences in DNA-PK between the cell lines, there was no clear correlation with any of these differences and radiation sensitivity. In contrast, p53 function as determined by two independent methods, correlated well with radiation sensitivity, indicating p53 mutant ovarian cancer cells are typically radioresistant relative to p53 wild-type lines. These data suggest that the activity of regulatory molecules such as p53 may be better indicators of radiation sensitivity than DNA repair enzymes such as DNAPK in ovarian cancer.

Effect of seafood mediated PCB exposure on desaturase activity and PUFA profile in Faroese septuagenarians.

Science.gov (United States)

Tøttenborg, Sandra Søgaard; Choi, Anna L; Bjerve, Kristian S; Weihe, Pal; Grandjean, Philippe

2015-07-01

Polychlorinated biphenyl (PCB) exposure may affect serum concentrations of polyunsaturated fatty acids (PUFAs) by inhibiting desaturases ∆5 and ∆6 that drive their synthesis from precursor fatty acids. Such changes in the composition of fatty acids may affect cardiovascular disease risk, which is thought to increase at elevated PCB exposures. This population-based cross-sectional study examined 712 Faroese men and women aged 70-74 years. The serum phospholipid fraction of fasting blood samples was used to determine the PUFA profile, including linoleic acid, dihomo-γ-linolenic acid, arachidonic acid, eicosatrienoic acid, and other relevant fatty acids. Ratios between precursor and metabolite fatty acids were used as proxies for ∆5 and ∆6 desaturase activity. Tertiles of serum-PCB concentrations were used in multiple regression analyses to determine the association between the exposure and desaturase activity. In multiple regression models, PCB exposure was inversely related to the estimated Δ6 desaturase activity resulting in accumulation of precursor fatty acids and decrease in the corresponding product PUFAs. A positive association between PCB and Δ5 desaturation was also found. A relative increase in EA was also observed, though only in the third tertile of PCB exposure. Non-linear relationships between the exposure and the desaturase activity were not found. Consuming fish and seafood may not be translated into beneficial fatty acid profiles if the diet simultaneously causes exposure to PCBs. Although the desaturase estimates were likely influenced by dietary intakes of product PUFAs, the association between PCB exposure and ∆6 desaturase activity is plausible and may affect cardiovascular disease risk. Copyright © 2015 Elsevier Inc. All rights reserved.

Entropy-Based Privacy against Profiling of User Mobility

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Alicia Rodriguez-Carrion

2015-06-01

Full Text Available Location-based services (LBSs flood mobile phones nowadays, but their use poses an evident privacy risk. The locations accompanying the LBS queries can be exploited by the LBS provider to build the user profile of visited locations, which might disclose sensitive data, such as work or home locations. The classic concept of entropy is widely used to evaluate privacy in these scenarios, where the information is represented as a sequence of independent samples of categorized data. However, since the LBS queries might be sent very frequently, location profiles can be improved by adding temporal dependencies, thus becoming mobility profiles, where location samples are not independent anymore and might disclose the user’s mobility patterns. Since the time dimension is factored in, the classic entropy concept falls short of evaluating the real privacy level, which depends also on the time component. Therefore, we propose to extend the entropy-based privacy metric to the use of the entropy rate to evaluate mobility profiles. Then, two perturbative mechanisms are considered to preserve locations and mobility profiles under gradual utility constraints. We further use the proposed privacy metric and compare it to classic ones to evaluate both synthetic and real mobility profiles when the perturbative methods proposed are applied. The results prove the usefulness of the proposed metric for mobility profiles and the need for tailoring the perturbative methods to the features of mobility profiles in order to improve privacy without completely loosing utility.

Scaling of divertor heat flux profile widths in DIII-D

International Nuclear Information System (INIS)

Lasnier, C.J.; Makowski, M.A.; Boedo, J.A.; Allen, S.L.; Brooks, N.H.; Hill, D.N.; Leonard, A.W.; Watkins, J.G.; West, W.P.

2011-01-01

New scalings of the dependence of divertor heat flux peak and profile width, important parameters for the design of future large tokamaks, have been obtained from recent DIII-D experiments. We find the peak heat flux depends linearly on input power, decreases linearly with increasing density, and increases linearly with plasma current. The profile width has a weak dependence on input power, is independent of density up to the onset of detachment, and is inversely proportional to the plasma current. We compare these results with previously published scalings, and present mathematical expressions incorporating these results.

Field dependence-independence as related to young women's participation in sports activity.

Science.gov (United States)

Lambrecht, Jeanne L; Cuevas, Jacqueline L

2007-06-01

To estimate association between field dependence-independence measured by scores on the Group Embedded Figures Test and young women's participation in sports activity. Participants were 37 undergraduate college women between the ages of 18 and 25 years (M=21). Participants were categorized into two groups, one high in participation in sports activity and one low. A one-tailed independent samples t test yielded no significant difference. Correlations of .36 and .18 were significant but account for little common variance. An ad hoc analysis performed without participants who reported softball activity but who were highly involved in sport activities was significant.

Seismic constraints on the radial dependence of the internal rotation profiles of six Kepler subgiants and young red giants

Science.gov (United States)

Deheuvels, S.; Doğan, G.; Goupil, M. J.; Appourchaux, T.; Benomar, O.; Bruntt, H.; Campante, T. L.; Casagrande, L.; Ceillier, T.; Davies, G. R.; De Cat, P.; Fu, J. N.; García, R. A.; Lobel, A.; Mosser, B.; Reese, D. R.; Regulo, C.; Schou, J.; Stahn, T.; Thygesen, A. O.; Yang, X. H.; Chaplin, W. J.; Christensen-Dalsgaard, J.; Eggenberger, P.; Gizon, L.; Mathis, S.; Molenda-Żakowicz, J.; Pinsonneault, M.

2014-04-01

Context. We still do not understand which physical mechanisms are responsible for the transport of angular momentum inside stars. The recent detection of mixed modes that contain the clear signature of rotation in the spectra of Kepler subgiants and red giants gives us the opportunity to make progress on this question. Aims: Our aim is to probe the radial dependence of the rotation profiles for a sample of Kepler targets. For this purpose, subgiants and early red giants are particularly interesting targets because their rotational splittings are more sensitive to the rotation outside the deeper core than is the case for their more evolved counterparts. Methods: We first extracted the rotational splittings and frequencies of the modes for six young Kepler red giants. We then performed a seismic modeling of these stars using the evolutionary codes Cesam2k and astec. By using the observed splittings and the rotational kernels of the optimal models, we inverted the internal rotation profiles of the six stars. Results: We obtain estimates of the core rotation rates for these stars, and upper limits to the rotation in their convective envelope. We show that the rotation contrast between the core and the envelope increases during the subgiant branch. Our results also suggest that the core of subgiants spins up with time, while their envelope spins down. For two of the stars, we show that a discontinuous rotation profile with a deep discontinuity reproduces the observed splittings significantly better than a smooth rotation profile. Interestingly, the depths that are found to be most probable for the discontinuities roughly coincide with the location of the H-burning shell, which separates the layers that contract from those that expand. Conclusions: We characterized the differential rotation pattern of six young giants with a range of metallicities, and with both radiative and convective cores on the main sequence. This will bring observational constraints to the

Dysregulation of Macrophage Activation Profiles by Engineered Nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Kodali, Vamsi; Littke, Matthew H.; Tilton, Susan C.; Teeguarden, Justin G.; Shi, Liang; Frevert, Charles W.; Wang, Wei; Pounds, Joel G.; Thrall, Brian D.

2013-08-27

Although the potential human health impacts from exposure to engineered nanoparticles (ENPs) are uncertain, past epidemiological studies have established correlations between exposure to ambient air pollution particulates and the incidence of pneumonia and lung infections. Using amorphous silica and superparamagnetic iron oxide (SPIO) as model high production volume ENPs, we examined how macrophage activation by bacterial lipopolysaccharide (LPS) or the lung pathogen Streptococcus pneumoniae is altered by ENP pretreatment. Neither silica nor SPIO treatment elicited direct cytotoxic or pro-inflammatory effects in bone marrow-derived macrophages. However, pretreatment of macrophages with SPIO caused extensive reprogramming of nearly 500 genes regulated in response to LPS challenge, hallmarked by exaggerated activation of oxidative stress response pathways and suppressed activation of both pro- and anti-inflammatory pathways. Silica pretreatment altered regulation of only 67 genes, but there was strong correlation with gene sets affected by SPIO. Macrophages exposed to SPIO displayed a phenotype suggesting an impaired ability to transition from an M1 to M2-like activation state, characterized by suppressed IL-10 induction, enhanced TNFα production, and diminished phagocytic activity toward S. pneumoniae. Studies in macrophages deficient in scavenger receptor A (SR-A) showed SR-A participates in cell uptake of both the ENPs and S. pneumonia and co-regulates the anti-inflammatory IL-10 pathway. Thus, mechanisms for dysregulation of innate immunity exist by virtue that common receptor recognition pathways are used by some ENPs and pathogenic bacteria, although the extent of transcriptional reprogramming of macrophage function depends on the physicochemical properties of the ENP after internalization. Our results also illustrate that biological effects of ENPs may be indirectly manifested only after challenging normal cell function. Finally, nanotoxicology screening

Transcriptional and Cytokine Profiles Identify CXCL9 as a Biomarker of Disease Activity in Morphea.

Science.gov (United States)

O'Brien, Jack C; Rainwater, Yevgeniya Byekova; Malviya, Neeta; Cyrus, Nika; Auer-Hackenberg, Lorenz; Hynan, Linda S; Hosler, Gregory A; Jacobe, Heidi T

2017-08-01

IFN-related pathways have not been studied in morphea, and biomarkers are needed. We sought to characterize morphea serum cytokine imbalance and IFN-related gene expression in blood and skin to address this gap by performing a case-control study of 87 participants with morphea and 26 healthy control subjects. We used multiplexed immunoassays to determine serum cytokine concentrations, performed transcriptional profiling of whole blood and lesional morphea skin, and used double-staining immunohistochemistry to determine the cutaneous cellular source of CXCL9. We found that CXCL9 was present at increased concentrations in morphea serum (P morphea skin (fold change = 30.6, P = 0.006), and preliminary transcriptional profiling showed little evidence for IFN signature in whole blood. Double-staining immunohistochemistry showed CXCL9 co-localized with CD68 + dermal macrophages. In summary, inflammatory morphea is characterized by T helper type 1 cytokine imbalance in serum, particularly CXCL9, which is associated with disease activity. CXCL9 expression in lesional macrophages implicates the skin as the source of circulating cytokines. CXCL9 is a promising biomarker of disease activity in morphea. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Depth profiling of residual activity of ^{237}U fragments as a range verification technique for ^{238}U primary ion beam

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I. Strašík

2012-07-01

Full Text Available Experimental and simulation data concerning fragmentation of ^{238}U ion beam in aluminum, copper, and stainless-steel targets with the initial energy 500 and 950  MeV/u are collected in the paper. A range-verification technique based on depth profiling of residual activity is presented. The irradiated targets were constructed in the stacked-foil geometry and analyzed using gamma-ray spectroscopy. One of the purposes of these experiments was depth profiling of residual activity of induced nuclides and projectile fragments. Among the projectile fragments, special attention is paid to the ^{237}U isotope that has a range very close to the range of the primary ^{238}U ions. Therefore, the depth profiling of the ^{237}U isotope can be utilized for experimental verification of the ^{238}U primary-beam range, which is demonstrated and discussed in the paper. The experimental data are compared with computer simulations by FLUKA, SRIM, and ATIMA, as well as with complementary experiments.

Activation of peroxisome proliferator-activated receptor-γ (PPARγ) induces cell death through MAPK-dependent mechanism in osteoblastic cells

International Nuclear Information System (INIS)

Kim, Sung Hun; Yoo, Chong Il; Kim, Hui Taek; Park, Ji Yeon; Kwon, Chae Hwa; Keun Kim, Yong

2006-01-01

The present study was undertaken to determine the role of the mitogen-activated protein kinase (MAPK) subfamilies in cell death induced by PPARγ agonists in osteoblastic cells. Ciglitazone and troglitazone, PPARγ agonists, resulted in a concentration- and time-dependent cell death, which was largely attributed to apoptosis. But a PPARα agonist ciprofibrate did not affect the cell death. Ciglitazone caused reactive oxygen species (ROS) generation and ciglitazone-induced cell death was prevented by antioxidants, suggesting an important role of ROS generation in the ciglitazone-induced cell death. ROS generation and cell death induced by ciglitazone were inhibited by the PPARγ antagonist GW9662. Ciglitazone treatment caused activation of extracellular signal-regulated kinase (ERK) and p38. Activation of ERK was dependent on epidermal growth factor receptor (EGFR) and that of p38 was independent. Ciglitazone-induced cell death was significantly prevented by PD98059, an inhibitor of ERK upstream kinase MEK1/2, and SB203580, a p38 inhibitor. Ciglitazone treatment increased Bax expression and caused a loss of mitochondrial membrane potential, and its effect was prevented by N-acetylcysteine, PD98059, and SB203580. Ciglitazone induced caspase activation, which was prevented by PD98059 and SB203580. The general caspase inhibitor z-DEVD-FMK and the specific inhibitor of caspases-3 DEVD-CHO exerted the protective effect against the ciglitazone-induced cell death. The EGFR inhibitors AG1478 and suramin protected against the ciglitazone-induced cell death. Taken together, these findings suggest that the MAPK signaling pathways play an active role in mediating the ciglitazone-induced cell death of osteoblasts and function upstream of a mitochondria-dependent mechanism. These data may provide a novel insight into potential therapeutic strategies for treatment of osteoporosis

Generation of Domestic Hot Water, Space Heating and Driving Pattern Profiles for Integration Analysis of Active Loads in Low Voltage Grids

DEFF Research Database (Denmark)

Diaz de Cerio Mendaza, Iker; Pigazo, Alberto; Bak-Jensen, Birgitte

2013-01-01

at household level. Despite of the well-known flexible service that this kind of loads can provide, their flexibility is highly dependent of the domestic hot water and space heating demand and the driving habits of each user. This paper presents two methodologies employed to randomly generate thermal power......The changes in the Danish energy sector, consequence of political agreements, are expected to have direct impact in the actual power distribution systems. Large number of electric boiler, heat pumps and electric vehicles are planned and will cope large percentage of the future power consumption...... demand and electric vehicle driving profiles, to be used for power grid calculations. The generated thermal profiles relied on a statistical analysis made from real domestic hot water and space heating data from 25 households of a typical Danish residential area. The driving profiles instead were formed...

Aldose Reductase Inhibitor Protects against Hyperglycemic Stress by Activating Nrf2-Dependent Antioxidant Proteins.

Science.gov (United States)

Shukla, Kirtikar; Pal, Pabitra Bikash; Sonowal, Himangshu; Srivastava, Satish K; Ramana, Kota V

2017-01-01

We have shown earlier that pretreatment of cultured cells with aldose reductase (AR) inhibitors prevents hyperglycemia-induced mitogenic and proinflammatory responses. However, the effects of AR inhibitors on Nrf2-mediated anti-inflammatory responses have not been elucidated yet. We have investigated how AR inhibitor fidarestat protects high glucose- (HG-) induced cell viability changes by increasing the expression of Nrf2 and its dependent phase II antioxidant enzymes. Fidarestat pretreatment prevents HG (25 mM)-induced Thp1 monocyte viability. Further, treatment of Thp1 monocytes with fidarestat caused a time-dependent increase in the expression as well as the DNA-binding activity of Nrf2. In addition, fidarestat augmented the HG-induced Nrf2 expression and activity and also upregulated the expression of Nrf2-dependent proteins such as hemeoxygenase-1 (HO1) and NQO1 in Thp1 cells. Similarly, treatment with AR inhibitor also induced the expression of Nrf2 and HO1 in STZ-induced diabetic mice heart and kidney tissues. Further, AR inhibition increased the HG-induced expression of antioxidant enzymes such as SOD and catalase and activation of AMPK- α 1 in Thp1 cells. Our results thus suggest that pretreatment with AR inhibitor prepares the monocytes against hyperglycemic stress by overexpressing the Nrf2-dependent antioxidative proteins.

Phenolic Profile and Antioxidant Activity of Methanolic Extract of Carduus acicularis Bertol. (Asteraceae

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Iliya Zh. Slavov

2016-06-01

Full Text Available Phenolic acid and flavonoid profiles of Carduus acicularis were investigated for the first time. Eleven phenolic acids and eight flavonoids were identified and quantified in the inflorescences, by high performance liquid chromatography. The main phenolic compounds were found to be: sinapic acid (930.41 ± 21.72 µg/g dw, chlorogenic acid (582.66 ± 13.60 µg/g dw, rutin (545.65 ± 12.82 µg/g dw, apigenin (478.75 ± 11.38 µg/g dw, luteolin (288.46 ± 6.86 µg/g dw and myricetin (276.32 ± 5.21 µg/g dw. The antioxidant activity of methanolic extract of inflorescences has been investigated, employing four different established testing systems: scavenging activity on 2,2-diphenil-1-picrylhydrazyl (DPPH, 2,2’-azinobis-(3-ethyl-benzothiazoline-6-sulfonate (ABTS radical cation decolorization assay, ferric reducing antioxidant power (FRAP and copper reduction antioxidant assays (FRAP. The highest antioxidant activity values were measured by the ABTS assay, among all performed methods.

Comparison of the glucooligosaccharide profiles produced from maltose by two different transglucosidases from Aspergillus niger

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Goffin, D.

2010-01-01

Full Text Available Prebiotic isomaltooligosaccharide (IMO preparations contain α-D-glucooligosaccharides and their structure is the key factor for their prebiotic potential. The transglucosylation selectivity is known to depend on the enzyme specificity and moreover, maltose and α-glucooligosaccharides can actually act as both glucosyl donor and acceptor in the reaction. Thus, two commercial enzymes, a glucosyltransferase and an α-glucosidase, were tested alone and in combination on pure maltose to study their specificities and the IMO profile obtained. The reactions were monitored using a step-forward AEC-PAD analytical method which permitted to detect and resolve new unknown IMO. Structural determination of unknown IMO was attempted using their retention times and relative abundance. As a general rule, the α-glucosidase has a more expressed hydrolyzing activity leading to products containing less residual digestible α-(1-4 linkages such as isomaltose, isomaltotriose, isomaltotetraose, kojibiose and nigerose while the glucosyltransferase produces important amount of panose. Finally, the combination of the two enzymes leaded to an intermediate IMO profile. IMO syrups composition was thus proved to be dependant on the specificity of the transglucosylating enzyme so that products profiles can be designed using different enzymes and in different proportion.

Heme Oxygenase-1 Inhibits HLA Class I Antibody-Dependent Endothelial Cell Activation.

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Eva Zilian

Full Text Available Antibody-mediated rejection (AMR is a key limiting factor for long-term graft survival in solid organ transplantation. Human leukocyte antigen (HLA class I (HLA I antibodies (Abs play a major role in the pathogenesis of AMR via their interactions with HLA molecules on vascular endothelial cells (ECs. The antioxidant enzyme heme oxygenase (HO-1 has anti-inflammatory functions in the endothelium. As complement-independent effects of HLA I Abs can activate ECs, it was the goal of the current study to investigate the role of HO-1 on activation of human ECs by HLA I Abs. In cell cultures of various primary human macro- and microvascular ECs treatment with monoclonal pan- and allele-specific HLA I Abs up-regulated the expression of inducible proinflammatory adhesion molecules and chemokines (vascular cell adhesion molecule-1 [VCAM-1], intercellular cell adhesion molecule-1 [ICAM-1], interleukin-8 [IL-8] and monocyte chemotactic protein 1 [MCP-1]. Pharmacological induction of HO-1 with cobalt-protoporphyrin IX reduced, whereas inhibition of HO-1 with either zinc-protoporphyrin IX or siRNA-mediated knockdown increased HLA I Ab-dependent up-regulation of VCAM-1. Treatment with two carbon monoxide (CO-releasing molecules, which liberate the gaseous HO product CO, blocked HLA I Ab-dependent EC activation. Finally, in an in vitro adhesion assay exposure of ECs to HLA I Abs led to increased monocyte binding, which was counteracted by up-regulation of HO-1. In conclusion, HLA I Ab-dependent EC activation is modulated by endothelial HO-1 and targeted induction of this enzyme may be a novel therapeutic approach for the treatment of AMR in solid organ transplantation.

Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

KAUST Repository

Ferreira, Ari J S

2014-06-12

Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world\\'s oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

KAUST Repository

Ferreira, Ari J S; Siam, Rania; Setubal, Joã o C; Moustafa, Ahmed; Sayed, Ahmed; Chambergo, Felipe S; Dawe, Adam S; Ghazy, Mohamed A; Sharaf, Hazem; Ouf, Amged; Alam, Intikhab; Abdel-Haleem, Alyaa M; Lehvä slaiho, Heikki; Ramadan, Eman; Antunes, André ; Stingl, Ulrich; Archer, John A.C.; Jankovic, Boris R; Sogin, Mitchell; Bajic, Vladimir B.; El-Dorry, Hamza

2014-01-01

Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

Directory of Open Access Journals (Sweden)

Ari J S Ferreira

Full Text Available Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

A Profile of Active Transportation in Colorado Public Schools, 2014-2015.

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Behrens, Timothy K; Osman, Randa; Whitney, Paige; Carpenter, Dick; Tucker, Elizabeth; Field, Julaine; Kelly, Cheryl

2017-02-01

Active transportation (AT) may represent an ideal opportunity to accumulate physical activity (PA). Thus, the purpose of this study was to describe the AT profile among students from two Colorado school districts. Students completed a survey on AT resulting in a final dataset (n = 3738) from which descriptive and inferential statics were calculated. Respondents were 11.32 ± 2.82 years of age (Boys = 48.27 %; Girls = 51.73 %). Most students (87.29 %) traveled to or from school via automobile, while 11.17 % walked and 1.53 % biked. Boys rode bicycles to school significantly more (p biking (p biking (p < 0.0001) to school than middle school and elementary school respondents. These findings indicate that travel to school by automobile is still the dominant mode of travel for most public school students. Further, males were generally more likely to obtain extra time in AT. Moreover, older students were more likely to engage in AT, and to spend more time during their AT.

The temperature dependence of the BK channel activity - kinetics, thermodynamics, and long-range correlations.

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Wawrzkiewicz-Jałowiecka, Agata; Dworakowska, Beata; Grzywna, Zbigniew J

2017-10-01

Large-conductance, voltage dependent, Ca 2+ -activated potassium channels (BK) are transmembrane proteins that regulate many biological processes by controlling potassium flow across cell membranes. Here, we investigate to what extent temperature (in the range of 17-37°C with ΔT=5°C step) is a regulating parameter of kinetic properties of the channel gating and memory effect in the series of dwell-time series of subsequent channel's states, at membrane depolarization and hyperpolarization. The obtained results indicate that temperature affects strongly the BK channels' gating, but, counterintuitively, it exerts no effect on the long-range correlations, as measured by the Hurst coefficient. Quantitative differences between dependencies of appropriate channel's characteristics on temperature are evident for different regimes of voltage. Examining the characteristics of BK channel activity as a function of temperature allows to estimate the net activation energy (E act ) and changes of thermodynamic parameters (ΔH, ΔS, ΔG) by channel opening. Larger E act corresponds to the channel activity at membrane hyperpolarization. The analysis of entropy and enthalpy changes of closed to open channel's transition suggest the entropy-driven nature of the increase of open state probability during voltage activation and supports the hypothesis about the voltage-dependent geometry of the channel vestibule. Copyright © 2017 Elsevier B.V. All rights reserved.

Zinc-dependent multi-conductance channel activity in mitochondria isolated from ischemic brain.

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Bonanni, Laura; Chachar, Mushtaque; Jover-Mengual, Teresa; Li, Hongmei; Jones, Adrienne; Yokota, Hidenori; Ofengeim, Dimitry; Flannery, Richard J; Miyawaki, Takahiro; Cho, Chang-Hoon; Polster, Brian M; Pypaert, Marc; Hardwick, J Marie; Sensi, Stefano L; Zukin, R Suzanne; Jonas, Elizabeth A

2006-06-21

Transient global ischemia is a neuronal insult that induces delayed cell death. A hallmark event in the early post-ischemic period is enhanced permeability of mitochondrial membranes. The precise mechanisms by which mitochondrial function is disrupted are, as yet, unclear. Here we show that global ischemia promotes alterations in mitochondrial membrane contact points, a rise in intramitochondrial Zn2+, and activation of large, multi-conductance channels in mitochondrial outer membranes by 1 h after insult. Mitochondrial channel activity was associated with enhanced protease activity and proteolytic cleavage of BCL-xL to generate its pro-death counterpart, deltaN-BCL-xL. The findings implicate deltaN-BCL-xL in large, multi-conductance channel activity. Consistent with this, large channel activity was mimicked by introduction of recombinant deltaN-BCL-xL to control mitochondria and blocked by introduction of a functional BCL-xL antibody to post-ischemic mitochondria via the patch pipette. Channel activity was also inhibited by nicotinamide adenine dinucleotide, indicative of a role for the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane. In vivo administration of the membrane-impermeant Zn2+ chelator CaEDTA before ischemia or in vitro application of the membrane-permeant Zn2+ chelator tetrakis-(2-pyridylmethyl) ethylenediamine attenuated channel activity, suggesting a requirement for Zn2+. These findings reveal a novel mechanism by which ischemic insults disrupt the functional integrity of the outer mitochondrial membrane and implicate deltaN-BCL-xL and VDAC in the large, Zn2+-dependent mitochondrial channels observed in post-ischemic hippocampal mitochondria.

Gene expression profile of endoscopically active and inactive ulcerative colitis: preliminary data.

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Ţieranu, Cristian George; Dobre, Maria; Mănuc, Teodora Ecaterina; Milanesi, Elena; Pleşea, Iancu Emil; Popa, Caterina; Mănuc, Mircea; Ţieranu, Ioana; Preda, Carmen Monica; Diculescu, Mihai Mircea; Ionescu, Elena Mirela; Becheanu, Gabriel

2017-01-01

Multiple cytokines and chemokines related to immune response, apoptosis and inflammation have been identified as molecules implicated in ulcerative colitis (UC) pathogenesis. The aim of this study was to identify the differences at gene expression level of a panel of candidate genes in mucosa from patients with active UC (UCA), patients in remission (UCR), and normal controls. Eleven individuals were enrolled in the study: eight UC patients (four with active lesions, four with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression profile was evaluated by polymerase chain reaction (PCR) array, investigating 84 genes implicated in apoptosis, inflammation, immune response, cellular adhesion, tissue remodeling and mucous secretion. Seventeen and three genes out of 84 were found significantly differentially expressed in UCA and UCR compared to controls, respectively. In particular, REG1A and CHI3L1 genes reported an up-regulation in UCA with a fold difference above 200. In UCR patients, the levels of CASP1, LYZ and ISG15 were different compared to controls. However, since a significant up-regulation of both CASP1 and LYZ was observed also in the UCA group, only ISG15 levels remained associated to the remission state. ISG15, that plays a key role in the innate immune response, seemed to be specifically associated to the UC remission state. These preliminary data represent a starting point for defining the gene profile of UC in different stages in Romanian population. Identification of genes implicated in UC pathogenesis could be useful to select new therapeutic targets.

Activity-dependent changes in excitability of perirhinal cortex networks in vitro.

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Biagini, Giuseppe; D'Antuono, Margherita; Inaba, Yuji; Kano, Toshiyuki; Ragsdale, David; Avoli, Massimo

2015-04-01

Rat brain slices comprising the perirhinal cortex (PC) and a portion of the lateral nucleus of the amygdala (LA), in standard medium, can generate synchronous oscillatory activity that is associated with action potential discharge and reflects the activation of glutamatergic and GABAergic receptors. We report here that similar synchronous oscillatory events are recorded in the PC in response to single-shock, electrical stimuli delivered in LA. In addition, we found that the latency of these responses progressively increased when the stimulus interval was varied from 10 to 1 s; for example, the response latency during stimuli delivered at 1 Hz was more than twofold longer than that seen during stimulation at 0.1 Hz. This prolongation in latency occurred after approximately 5 stimuli, attained a steady value after 24-35 stimuli, and recovered to control values 30 s after stimulation arrest. These frequency-dependent changes in latency continued to occur during NMDA receptor antagonism but weakened following application of GABAA and/or GABAB receptor blockers. Our findings identify a new type of short-term plasticity that is mediated by GABA receptor function and may play a role in decreasing neuronal network synchronization during repeated activation. We propose that this frequency-dependent adaptive mechanism influences the excitability of limbic networks, thus potentially controlling epileptiform synchronization.

Sex-dependent differences in voluntary physical activity.

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Rosenfeld, Cheryl S

2017-01-02

Numbers of overweight and obese individuals are increasing in the United States and globally, and, correspondingly, the associated health care costs are rising dramatically. More than one-third of children are currently considered obese with a predisposition to type 2 diabetes, and it is likely that their metabolic conditions will worsen with age. Physical inactivity has also risen to be the leading cause of many chronic, noncommunicable diseases (NCD). Children are more physically inactive now than they were in past decades, which may be due to intrinsic and extrinsic factors. In rodents, the amount of time engaged in spontaneous activity within the home cage is a strong predictor of later adiposity and weight gain. Thus, it is important to understand primary motivators stimulating physical activity (PA). There are normal sex differences in PA levels in rodents and humans. The perinatal environment can induce sex-dependent differences in PA disturbances. This Review considers the current evidence for sex differences in PA in rodents and humans. The rodent studies showing that early exposure to environmental chemicals can shape later adult PA responses are discussed. Next, whether there are different motivators stimulating exercise in male vs. female humans are examined. Finally, the brain regions, genes, and pathways that modulate PA in rodents, and possibly by translation in humans, are described. A better understanding of why each sex remains physically active through the life span could open new avenues for preventing and treating obesity in children and adults. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Synergistic activity profile of griffithsin in combination with tenofovir, maraviroc and enfuvirtide against HIV-1 clade C

International Nuclear Information System (INIS)

Ferir, Geoffrey; Palmer, Kenneth E.; Schols, Dominique

2011-01-01

Griffithsin (GRFT) is possibly the most potent anti-HIV peptide found in natural sources. Due to its potent and broad-spectrum antiviral activity and unique safety profile it has great potential as topical microbicide component. Here, we evaluated various combinations of GRFT against HIV-1 clade B and clade C isolates in primary peripheral blood mononuclear cells (PBMCs) and in CD4 + MT-4 cells. In all combinations tested, GRFT showed synergistic activity profile with tenofovir, maraviroc and enfuvirtide based on the median effect principle with combination indices (CI) varying between 0.34 and 0.79 at the calculated EC 95 level. Furthermore, the different glycosylation patterns on the viral envelope of clade B and clade C gp120 had no observable effect on the synergistic interactions. Overall, we can conclude that the evaluated two-drug combination increases their antiviral potency and supports further clinical investigations in pre-exposure prophylaxis for GRFT combinations in the context of HIV-1 clade C infection.

Aberrant regional brain activities in alcohol dependence: a functional magnetic resonance imaging study

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Tu XZ

2018-03-01

Full Text Available Xianzhu Tu,1 Juanjuan Wang,2 Xuming Liu,3 Jiyong Zheng4 1Department of Psychiatry, Seventh People’s Hospital of Wenzhou City, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Radiology, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 4Department of Medical Imaging, The Affiliated Huai’an No 1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China Objective: Whether moderate alcohol consumption has health benefits remains controversial, but the harmful effects of excessive alcohol consumption on behavior and brain function are well recognized. The aim of this study was to investigate alcohol-induced regional brain activities and their relationships with behavioral factors. Subjects and methods: A total of 29 alcohol-dependent subjects (9 females and 20 males and 29 status-matched healthy controls (11 females and 18 males were recruited. Severity of alcohol dependence questionnaire (SADQ and alcohol use disorders identification test (AUDIT were used to evaluate the severity of alcohol craving. Regional homogeneity (ReHo analysis was used to explore the alcohol-induced regional brain changes. Receiver operating characteristic (ROC curve was used to investigate the ability of regional brain activities to distinguish alcohol-dependent subjects from healthy controls. Pearson correlations were used to investigate the relationships between alcohol-induced ReHo differences and behavioral factors. Results: Alcohol-dependent subjects related to healthy controls showed higher ReHo areas in the right superior frontal gyrus (SFG, bilateral medial frontal gyrus (MFG, left precentral gyrus (PG, bilateral middle temporal gyrus (MTG, and right inferior temporal gyrus (ITG and lower ReHo areas in

Tetrandrine, an Activator of Autophagy, Induces Autophagic Cell Death via PKC-α Inhibition and mTOR-Dependent Mechanisms

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Vincent Kam Wai Wong

2017-06-01

Full Text Available Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet from herbal plant, Radix stephaniae tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes. In addition, tetrandrine induces cell death in a panel of apoptosis-resistant cell lines that are deficient for caspase 3, caspase 7, caspase 3 and 7, or Bax-Bak respectively. We also showed that tetrandrine-induced cell death is independent of necrotic cell death. Mechanistically, tetrandrine induces autophagy that depends on mTOR inactivation. Furthermore, tetrandrine induces autophagy in a calcium/calmodulin-dependent protein kinase kinase-β (CaMKK-β, 5′ AMP-activated protein kinase (AMPK independent manner. Finally, by kinase profiling against 300 WT kinases and computational molecular docking analysis, we showed that tetrandrine is a novel PKC-α inhibitor, which lead to autophagic induction through PKC-α inactivation. This study provides detailed insights into the novel cytotoxic mechanism of an anti-tumor compound originated from the herbal plant, which may be useful in promoting autophagy mediated- cell death in cancer cell that is resistant to apoptosis.

Antiretroviral treatment is associated with increased attentional load-dependent brain activation in HIV patients.

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Chang, L; Yakupov, R; Nakama, H; Stokes, B; Ernst, T

2008-06-01

The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection. Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n = 18), HIV subjects treated with antiretroviral medications (HIV+ARV, n = 12), or not treated with antiretroviral medications (HIV+NARV, n = 12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging. HIV subjects, both groups combined, showed greater load-dependent increases in brain activation in the right frontal regions compared to SN (p-corrected = 0.006). HIV+ARV additionally showed greater load-dependent increases in activation compared to SN in bilateral superior frontal regions (p-corrected = 0.032) and a lower percent accuracy on the performance of the most difficult task (tracking four balls). Region of interest analyses further demonstrated that SN showed load-dependent decreases (with repeated trials despite increasing difficulty), while HIV subjects showed load-dependent increases in activation with the more difficult tasks, especially those on ARVs. These findings suggest that chronic ARV treatments may lead to greater requirement of the attentional network reserve and hence less efficient usage of the network and less practice effects in these HIV patients. As the brain has a limited reserve capacity, exhausting the reserve capacity in HIV+ARV would lead to declined performance with more difficult tasks that require more attention.

Distinct age and differentiation-state dependent metabolic profiles of oligodendrocytes under optimal and stress conditions.

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Vijayaraghava T S Rao

Full Text Available Within the microenvironment of multiple sclerosis lesions, oligodendrocytes are subject to metabolic stress reflecting effects of focal ischemia and inflammation. Previous studies have shown that under optimal conditions in vitro, the respiratory activity of human adult brain-derived oligodendrocytes is lower and more predominantly glycolytic compared to oligodendrocytes differentiated in vitro from post natal rat brain oligodendrocyte progenitor cells. In response to sub-lethal metabolic stress, adult human oligodendrocytes reduce overall energy production rate impacting the capacity to maintain myelination. Here, we directly compare the metabolic profiles of oligodendrocytes derived from adult rat brain with oligodendrocytes newly differentiated in vitro from oligodendrocyte progenitor cells obtained from the post natal rat brain, under both optimal culture and metabolic stress (low/no glucose conditions. Oxygen consumption and extracellular acidification rates were measured using a Seahorse extracellular flux analyzer. Our findings indicate that under optimal conditions, adult rat oligodendrocytes preferentially use glycolysis whereas newly differentiated post natal rat oligodendrocytes, and the oligodendrocyte progenitor cells from which they are derived, mainly utilize oxidative phosphorylation to produce ATP. Metabolic stress increases the rate of ATP production via oxidative phosphorylation and significantly reduces glycolysis in adult oligodendrocytes. The rate of ATP production was relatively unchanged in newly differentiated post natal oligodendrocytes under these stress conditions, while it was significantly reduced in oligodendrocyte progenitor cells. Our study indicates that both age and maturation influence the metabolic profile under optimal and stressed conditions, emphasizing the need to consider these variables for in vitro studies that aim to model adult human disease.

From retinal waves to activity-dependent retinogeniculate map development.

Science.gov (United States)

Markowitz, Jeffrey; Cao, Yongqiang; Grossberg, Stephen

2012-01-01

A neural model is described of how spontaneous retinal waves are formed in infant mammals, and how these waves organize activity-dependent development of a topographic map in the lateral geniculate nucleus, with connections from each eye segregated into separate anatomical layers. The model simulates the spontaneous behavior of starburst amacrine cells and retinal ganglion cells during the production of retinal waves during the first few weeks of mammalian postnatal development. It proposes how excitatory and inhibitory mechanisms within individual cells, such as Ca(2+)-activated K(+) channels, and cAMP currents and signaling cascades, can modulate the spatiotemporal dynamics of waves, notably by controlling the after-hyperpolarization currents of starburst amacrine cells. Given the critical role of the geniculate map in the development of visual cortex, these results provide a foundation for analyzing the temporal dynamics whereby the visual cortex itself develops.

Impaired Na⁺-dependent regulation of acetylcholine-activated inward-rectifier K⁺ current modulates action potential rate dependence in patients with chronic atrial fibrillation.

Science.gov (United States)

Voigt, Niels; Heijman, Jordi; Trausch, Anne; Mintert-Jancke, Elisa; Pott, Lutz; Ravens, Ursula; Dobrev, Dobromir

2013-08-01

Shortened action-potential duration (APD) and blunted APD rate adaptation are hallmarks of chronic atrial fibrillation (cAF). Basal and muscarinic (M)-receptor-activated inward-rectifier K(+) currents (IK1 and IK,ACh, respectively) contribute to regulation of human atrial APD and are subject to cAF-dependent remodeling. Intracellular Na(+) ([Na(+)]i) enhances IK,ACh in experimental models but the effect of [Na(+)]i-dependent regulation of inward-rectifier K(+) currents on APD in human atrial myocytes is currently unknown. Here, we report a [Na(+)]i-dependent inhibition of outward IK1 in atrial myocytes from sinus rhythm (SR) or cAF patients. In contrast, IK,ACh activated by carbachol, a non-selective M-receptor agonist, increased with elevation of [Na(+)]i in SR. This [Na(+)]i-dependent IK,ACh regulation was absent in cAF. Including [Na(+)]i dependence of IK1 and IK,ACh in a recent computational model of the human atrial myocyte revealed that [Na(+)]i accumulation at fast rates inhibits IK1 and blunts physiological APD rate dependence in both groups. [Na(+)]i-dependent IK,ACh augmentation at fast rates increased APD rate dependence in SR, but not in cAF. These results identify impaired Na(+)-sensitivity of IK,ACh as one potential mechanism contributing to the blunted APD rate dependence in patients with cAF. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes". Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Inter- and Intra-method Variability of VS Profiles and VS30 at ARRA-funded Sites

Science.gov (United States)

Yong, A.; Boatwright, J.; Martin, A. J.

2015-12-01

The 2009 American Recovery and Reinvestment Act (ARRA) funded geophysical site characterizations at 191 seismographic stations in California and in the central and eastern United States. Shallow boreholes were considered cost- and environmentally-prohibitive, thus non-invasive methods (passive and active surface- and body-wave techniques) were used at these stations. The drawback, however, is that these techniques measure seismic properties indirectly and introduce more uncertainty than borehole methods. The principal methods applied were Array Microtremor (AM), Multi-channel Analysis of Surface Waves (MASW; Rayleigh and Love waves), Spectral Analysis of Surface Waves (SASW), Refraction Microtremor (ReMi), and P- and S-wave refraction tomography. Depending on the apparent geologic or seismic complexity of the site, field crews applied one or a combination of these methods to estimate the shear-wave velocity (VS) profile and calculate VS30, the time-averaged VS to a depth of 30 meters. We study the inter- and intra-method variability of VS and VS30 at each seismographic station where combinations of techniques were applied. For each site, we find both types of variability in VS30 remain insignificant (5-10% difference) despite substantial variability observed in the VS profiles. We also find that reliable VS profiles are best developed using a combination of techniques, e.g., surface-wave VS profiles correlated against P-wave tomography to constrain variables (Poisson's ratio and density) that are key depth-dependent parameters used in modeling VS profiles. The most reliable results are based on surface- or body-wave profiles correlated against independent observations such as material properties inferred from outcropping geology nearby. For example, mapped geology describes station CI.LJR as a hard rock site (VS30 > 760 m/s). However, decomposed rock outcrops were found nearby and support the estimated VS30 of 303 m/s derived from the MASW (Love wave) profile.

Aldose Reductase Inhibitor Protects against Hyperglycemic Stress by Activating Nrf2-Dependent Antioxidant Proteins

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Kirtikar Shukla

2017-01-01

Full Text Available We have shown earlier that pretreatment of cultured cells with aldose reductase (AR inhibitors prevents hyperglycemia-induced mitogenic and proinflammatory responses. However, the effects of AR inhibitors on Nrf2-mediated anti-inflammatory responses have not been elucidated yet. We have investigated how AR inhibitor fidarestat protects high glucose- (HG- induced cell viability changes by increasing the expression of Nrf2 and its dependent phase II antioxidant enzymes. Fidarestat pretreatment prevents HG (25 mM-induced Thp1 monocyte viability. Further, treatment of Thp1 monocytes with fidarestat caused a time-dependent increase in the expression as well as the DNA-binding activity of Nrf2. In addition, fidarestat augmented the HG-induced Nrf2 expression and activity and also upregulated the expression of Nrf2-dependent proteins such as hemeoxygenase-1 (HO1 and NQO1 in Thp1 cells. Similarly, treatment with AR inhibitor also induced the expression of Nrf2 and HO1 in STZ-induced diabetic mice heart and kidney tissues. Further, AR inhibition increased the HG-induced expression of antioxidant enzymes such as SOD and catalase and activation of AMPK-α1 in Thp1 cells. Our results thus suggest that pretreatment with AR inhibitor prepares the monocytes against hyperglycemic stress by overexpressing the Nrf2-dependent antioxidative proteins.

Sex- and dose-dependency in the pharmacokinetics and pharmacodynamics of (+)-methamphetamine and its metabolite (+)-amphetamine in rats

International Nuclear Information System (INIS)

Milesi-Halle, Alessandra; Hendrickson, Howard P.; Laurenzana, Elizabeth M.; Gentry, W. Brooks; Owens, S. Michael

2005-01-01

These studies investigated how (+)-methamphetamine (METH) dose and rat sex affect the pharmacological response to METH in Sprague-Dawley rats. The first set of experiments determined the pharmacokinetics of METH and its pharmacologically active metabolite (+)-amphetamine (AMP) in male and female Sprague-Dawley rats after 1.0 and 3.0 mg/kg METH doses. The results showed significant sex-dependent changes in METH pharmacokinetics, and females formed significantly lower amounts of AMP. While the area under the serum concentration-time curve in males increased proportionately with the METH dose, the females showed a disproportional increase. The sex differences in systemic clearance, renal clearance, volume of distribution, and percentage of unchanged METH eliminated in the urine suggested dose-dependent pharmacokinetics in female rats. The second set of studies sought to determine the behavioral implications of these pharmacokinetic differences by quantifying locomotor activity in male and female rats after saline, 1.0, and 3.0 mg/kg METH. The results showed sex- and dose-dependent differences in METH-induced locomotion, including profound differences in the temporal profile of effects at higher dose. These findings show that the pharmacokinetic and metabolic profile of METH (slower METH clearance and lower AMP metabolite formation) plays a significant role in the differential pharmacological response to METH in male and female rats

Computer simulation and interpretation of 45Ca efflux profile patterns

International Nuclear Information System (INIS)

Borle, A.B.; Uchikawa, T.; Anderson, J.H.

1982-01-01

Stimulations or inhibitions by various agents of 45 Ca efflux from prelabeled cells or tissues display distinct and reproducible profile patterns when the results are plotted against time as fractional efflux ratios (FER). FER is the fractional efflux of 45 Ca from stimulated cells divided by the fractional efflux from a control unstimulated group. These profile patterns fall into three categories: peak patterns, exponential patterns, and mixed patterns. Each category can be positive (stimulation) or negative (inhibition). The interpretation of these profiles is difficult because 45 Ca efflux depends on three variables: the rate of calcium transport out of the cell, the specific activity of the cell compartment from which the calcium originates, and the concentration of free calcium in this compartment. A computer model based on data obtained by kinetic analyses of 45 Ca desaturation curves and consisting of two distinct intracellular pools was designed to follow the concentration of the traced substance ( 40 Ca), the tracer ( 45 Ca), and the specific activity of each compartment before, during, and after the stimulation or the inhibition of calcium fluxes at various pool boundaries. The computer model can reproduce all the FER profiles obtained experimentally and bring information which may be helpful to the interpretation of this type of data. Some predictions of the model were tested experimentally, and the results support the views that a peak pattern may reflect a sustained change in calcium transport across the plasma membrane, that an exponential pattern arises from calcium mobilization from an internal subcellular pool, and that a mixed pattern may be caused by a simultaneous change in calcium fluxes at both compartment boundaries

Profiling gene expression induced by protease-activated receptor 2 (PAR2 activation in human kidney cells.

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Jacky Y Suen

Full Text Available Protease-Activated Receptor-2 (PAR2 has been implicated through genetic knockout mice with cytokine regulation and arthritis development. Many studies have associated PAR2 with inflammatory conditions (arthritis, airways inflammation, IBD and key events in tumor progression (angiogenesis, metastasis, but they have relied heavily on the use of single agonists to identify physiological roles for PAR2. However such probes are now known not to be highly selective for PAR2, and thus precisely what PAR2 does and what mechanisms of downstream regulation are truly affected remain obscure. Effects of PAR2 activation on gene expression in Human Embryonic Kidney cells (HEK293, a commonly studied cell line in PAR2 research, were investigated here by comparing 19,000 human genes for intersecting up- or down-regulation by both trypsin (an endogenous protease that activates PAR2 and a PAR2 activating hexapeptide (2f-LIGRLO-NH(2. Among 2,500 human genes regulated similarly by both agonists, there were clear associations between PAR2 activation and cellular metabolism (1,000 genes, the cell cycle, the MAPK pathway, HDAC and sirtuin enzymes, inflammatory cytokines, and anti-complement function. PAR-2 activation up-regulated four genes more than 5 fold (DUSP6, WWOX, AREG, SERPINB2 and down-regulated another six genes more than 3 fold (TXNIP, RARG, ITGB4, CTSD, MSC and TM4SF15. Both PAR2 and PAR1 activation resulted in up-regulated expression of several genes (CD44, FOSL1, TNFRSF12A, RAB3A, COPEB, CORO1C, THBS1, SDC4 known to be important in cancer. This is the first widespread profiling of specific activation of PAR2 and provides a valuable platform for better understanding key mechanistic roles of PAR2 in human physiology. Results clearly support the development of both antagonists and agonists of human PAR2 as potential disease modifying therapeutic agents.

MicroRNA expression profiling identifies activated B cell status in chronic lymphocytic leukemia cells.

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Shuqiang Li

2011-03-01

Full Text Available Chronic lymphocytic leukemia (CLL is thought to be a disease of resting lymphocytes. However, recent data suggest that CLL cells may more closely resemble activated B cells. Using microRNA (miRNA expression profiling of highly-enriched CLL cells from 38 patients and 9 untransformed B cells from normal donors before acute CpG activation and 5 matched B cells after acute CpG activation, we demonstrate an activated B cell status for CLL. Gene set enrichment analysis (GSEA identified statistically-significant similarities in miRNA expression between activated B cells and CLL cells including upregulation of miR-34a, miR-155, and miR-342-3p and downregulation of miR-103, miR-181a and miR-181b. Additionally, decreased levels of two CLL signature miRNAs miR-29c and miR-223 are associated with ZAP70(+ and IgV(H unmutated status and with shorter time to first therapy. These data indicate an activated B cell status for CLL cells and suggest that the direction of change of individual miRNAs may predict clinical course in CLL.

GABAergic activities control spike timing- and frequency-dependent long-term depression at hippocampal excitatory synapses

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Makoto Nishiyama

2010-06-01

Full Text Available GABAergic interneuronal network activities in the hippocampus control a variety of neural functions, including learning and memory, by regulating θ and γ oscillations. How these GABAergic activities at pre- and post-synaptic sites of hippocampal CA1 pyramidal cells differentially contribute to synaptic function and plasticity during their repetitive pre- and post-synaptic spiking at θ and γ oscillations is largely unknown. We show here that activities mediated by postsynaptic GABAARs and presynaptic GABABRs determine, respectively, the spike timing- and frequency-dependence of activity-induced synaptic modifications at Schaffer collateral-CA1 excitatory synapses. We demonstrate that both feedforward and feedback GABAAR-mediated inhibition in the postsynaptic cell controls the spike timing-dependent long-term depression of excitatory inputs (“e-LTD” at the θ frequency. We also show that feedback postsynaptic inhibition specifically causes e-LTD of inputs that induce small postsynaptic currents (<70 pA with LTP timing, thus enforcing the requirement of cooperativity for induction of long-term potentiation at excitatory inputs (“e-LTP”. Furthermore, under spike-timing protocols that induce e-LTP and e-LTD at excitatory synapses, we observed parallel induction of LTP and LTD at inhibitory inputs (“i-LTP” and “i-LTD” to the same postsynaptic cells. Finally, we show that presynaptic GABABR-mediated inhibition plays a major role in the induction of frequency-dependent e-LTD at α and β frequencies. These observations demonstrate the critical influence of GABAergic interneuronal network activities in regulating the spike timing and frequency dependences of long-term synaptic modifications in the hippocampus.

Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium

Energy Technology Data Exchange (ETDEWEB)

Wernimont, Amy K; Artz, Jennifer D.; Jr, Patrick Finerty; Lin, Yu-Hui; Amani, Mehrnaz; Allali-Hassani, Abdellah; Senisterra, Guillermo; Vedadi, Masoud; Tempel, Wolfram; Mackenzie, Farrell; Chau, Irene; Lourido, Sebastian; Sibley, L. David; Hui, Raymond (Toronto); (WU-MED)

2010-09-21

Calcium-dependent protein kinases (CDPKs) have pivotal roles in the calcium-signaling pathway in plants, ciliates and apicomplexan parasites and comprise a calmodulin-dependent kinase (CaMK)-like kinase domain regulated by a calcium-binding domain in the C terminus. To understand this intramolecular mechanism of activation, we solved the structures of the autoinhibited (apo) and activated (calcium-bound) conformations of CDPKs from the apicomplexan parasites Toxoplasma gondii and Cryptosporidium parvum. In the apo form, the C-terminal CDPK activation domain (CAD) resembles a calmodulin protein with an unexpected long helix in the N terminus that inhibits the kinase domain in the same manner as CaMKII. Calcium binding triggers the reorganization of the CAD into a highly intricate fold, leading to its relocation around the base of the kinase domain to a site remote from the substrate binding site. This large conformational change constitutes a distinct mechanism in calcium signal-transduction pathways.

Profiles of Cognitive Deficits in Paranoid Schizophrenia and Schizotypal Disorder

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Lebedeva G.

2017-03-01

Full Text Available The article is devoted to the search for more accurate psycho-diagnostic methods and assessment tools for determining the degree of cognitive deficits in patients with schizophrenic disorders. The concepts of "cognitive deficits" and "cognitive profile", understood as the ratio of intact and damaged components of cognitive processes and their schematic representation are discussed. The authors substantiate the need for a clear gradation of cognitive impairments in schizophrenia, development of universal translation algorithms of traditional qualitative results (meaningful analysis of violations of cognitive activity in quantitative indicators. The article is based on the results of experimental psychological study. The investigation involved 128 patients: 76 people with Paranoid schizophrenia (F20 according to ICD-10 and 52 persons with Schizotypal disorder (F21 according to ICD-10. To assess the cognitive deficit, both traditional domestic methods and foreign tests, rarely used in the practice of a medical psychologist were conducted. The study analyzed the difference in cognitive tests performance between groups of patients with several types of schizophrenia and with different disease duration (up to 5 years and more. On the basis of quantitative data, a "cognitive profile" was lined for each disease. As a result, different variants of cognitive deficits, depending on the shape and course of the disease have been identified. The structure and dynamics of the cognitive deficits associated with schizophrenia and various forms depending on the different duration of the disease is described in detail. Also cognitive profiles compiled on this basis.

A copper-methionine interaction controls the pH-dependent activation of peptidylglycine monooxygenase.

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Bauman, Andrew T; Broers, Brenda A; Kline, Chelsey D; Blackburn, Ninian J

2011-12-20

The pH dependence of native peptidylglycine monooxygenase (PHM) and its M314H variant has been studied in detail. For wild-type (WT) PHM, the intensity of the Cu-S interaction visible in the Cu(I) extended X-ray absorption fine structure (EXAFS) data is inversely proportional to catalytic activity over the pH range of 3-8. A previous model based on more limited data was interpreted in terms of two protein conformations involving an inactive Met-on form and an active flexible Met-off form [Bauman, A. T., et al. (2006) Biochemistry 45, 11140-11150] that derived its catalytic activity from the ability to couple into vibrational modes critical for proton tunneling. The new studies comparing the WT and M314H variant have led to the evolution of this model, in which the Met-on form has been found to be derived from coordination of an additional Met residue, rather than a more rigid conformer of M314 as previously proposed. The catalytic activity of the mutant decreased by 96% because of effects on both k(cat) and K(M), but it displayed the same activity-pH profile with a maximum around pH 6. At pH 8, the reduced Cu(I) form gave spectra that could be simulated by replacement of the Cu(M) Cu-S(Met) interaction with a Cu-N/O interaction, but the data did not unambiguously assign the ligand to the imidazole side chain of H314. At pH 3.5, the EXAFS still showed the presence of a strong Cu-S interaction, establishing that the Met-on form observed at low pH in WT cannot be due to a strengthening of the Cu(M)-methionine interaction but must arise from a different Cu-S interaction. Therefore, lowering the pH causes a conformational change at one of the Cu centers that brings a new S donor residue into a favorable orientation for coordination to copper and generates an inactive form. Cys coordination is unlikely because all Cys residues in PHM are engaged in disulfide cross-links. Sequence comparison with the PHM homologues tyramine β-monooxygenase and dopamine �

Bilateral versus ipsilesional cortico-subcortical activity patterns in stroke show hemispheric dependence.

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Vidal, Ana C; Banca, Paula; Pascoal, Augusto G; Cordeiro, Gustavo; Sargento-Freitas, João; Gouveia, Ana; Castelo-Branco, Miguel

2018-01-01

Background Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods We used a functional magnetic resonance imaging block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction (n = 20, with balanced left/right lesion sites). Results Analysis of 10 right hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right hemispheric stroke. Left hemispheric stroke was, in general, characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion The observed hemispheric-dependent activation/deactivation shifts is novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation.

Physical activity level is impaired and diet dependent in preterm newborn pigs

DEFF Research Database (Denmark)

Cao, Muqing; Andersen, Anders Daniel; Van Ginneken, Chris

2015-01-01

and neonatal physical activity. METHODS: In experiment 1, preterm and term pigs were fed parenteral nutrition (PN) or PN plus bovine colostrum (BC, 16-64 ml/kg/d enterally) for 5 d. In experiment 2, preterm pigs were fed PN+BC or PN+formula for 5 d. In experiment 3, preterm pigs were fed BC, formula, or human...... feeding increased HCA, intestinal weights, and necrotizing enteritis resistance, relative to formula (experiment 3). CONCLUSION: Preterm pigs show decreased physical activity, and the first enteral feeds diet dependently stimulate both gut growth and physical activity. The effects may arise from...

Exercise dependence score in patients with longstanding eating disorders and controls: the importance of affect regulation and physical activity intensity.

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Bratland-Sanda, Solfrid; Martinsen, Egil W; Rosenvinge, Jan H; Rø, Oyvind; Hoffart, Asle; Sundgot-Borgen, Jorunn

2011-01-01

To examine associations among exercise dependence score, amount of physical activity and eating disorder (ED) symptoms in patients with longstanding ED and non-clinical controls. Adult female inpatients (n = 59) and 53 age-matched controls participated in this cross sectional study. Assessments included the eating disorders examination, eating disorders inventory, exercise dependence scale, reasons for exercise inventory, and MTI Actigraph accelerometer. Positive associations were found among vigorous, not moderate, physical activity, exercise dependence score and ED symptoms in patients. In the controls, ED symptoms were negatively associated with vigorous physical activity and not correlated with exercise dependence score. Exercise for negative affect regulation, not weight/appearance, and amount of vigorous physical activity were explanatory variables for exercise dependence score in both groups. The positive associations among exercise dependence score, vigorous physical activity and ED symptoms need proper attention in the treatment of longstanding ED. Copyright © 2011 John Wiley & Sons, Ltd and Eating Disorders Association.

A Novel Time-Dependent CENP-E Inhibitor with Potent Antitumor Activity.

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Akihiro Ohashi

Full Text Available Centromere-associated protein E (CENP-E regulates both chromosome congression and the spindle assembly checkpoint (SAC during mitosis. The loss of CENP-E function causes chromosome misalignment, leading to SAC activation and apoptosis during prolonged mitotic arrest. Here, we describe the biological and antiproliferative activities of a novel small-molecule inhibitor of CENP-E, Compound-A (Cmpd-A. Cmpd-A inhibits the ATPase activity of the CENP-E motor domain, acting as a time-dependent inhibitor with an ATP-competitive-like behavior. Cmpd-A causes chromosome misalignment on the metaphase plate, leading to prolonged mitotic arrest. Treatment with Cmpd-A induces antiproliferation in multiple cancer cell lines. Furthermore, Cmpd-A exhibits antitumor activity in a nude mouse xenograft model, and this antitumor activity is accompanied by the elevation of phosphohistone H3 levels in tumors. These findings demonstrate the potency of the CENP-E inhibitor Cmpd-A and its potential as an anticancer therapeutic agent.

Metabolomic profile and nucleoside composition of Cordyceps nidus sp. nov. (Cordycipitaceae: A new source of active compounds.

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Juan Chiriví

Full Text Available Cordyceps sensu lato is a genus of arthropod-pathogenic fungi, which have been used traditionally as medicinal in Asia. Within the genus, Ophiocordyceps sinensis is the most coveted and expensive species in China. Nevertheless, harvesting wild specimens has become a challenge given that natural populations of the fungus are decreasing and because large-scale culture of it has not yet been achieved. The worldwide demand for products derived from cultivable fungal species with medicinal properties has increased recently. In this study, we propose a new species, Cordyceps nidus, which parasitizes underground nests of trapdoor spiders. This species is phylogenetically related to Cordyceps militaris, Cordyceps pruinosa, and a sibling species of Cordyceps caloceroides. It is found in tropical rainforests from Bolivia, Brazil, Colombia and Ecuador. We also investigated the medicinal potential of this fungus based on its biochemical properties when grown on four different culture media. The metabolic profile particularly that of nucleosides, in polar and non-polar extracts was determined by UPLC, and then correlated to their antimicrobial activity and total phenolic content. The metabolome showed a high and significant dependency on the substrate used for fungal growth. The mass intensities of nucleosides and derivative compounds were higher in natural culture media in comparison to artificial culture media. Among these compounds, cordycepin was the predominant, showing the potential use of this species as an alternative to O. sinensis. Furthermore, methanol fractions showed antimicrobial activity against gram-positive bacteria, and less than 3.00 mg of gallic acid equivalents per g of dried extract were obtained when assessing its total phenolic content by modified Folin-Ciocalteu method. The presence of polyphenols opens the possibility of further exploring the antioxidant capacity and the conditions that may enhance this characteristic. The metabolic

Glucosinolate profiles by HPLC-DAD, phenolic compositions and antioxidant activity of Eruca vesicaria longirostris: Impact of plant part and origin

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Bouacida, Saoussen; Koubaier, Hayet Ben Haj; Snoussi, Ahmed; Fauconnier, Marie-Laure; Bouzouita, Nabiha

2016-01-01

The glucosinolate profiles, phenol and flavonoid contents and the antioxidant activity of Eruca vesicaria longirostris were studied for different organs and origins. Eleven desulpho-glucosinolates (DS-GLSs) were isolated and quantified by lipid chromatography- DAD. Similarity between profiles was obtained. Total DS-GLS content, expressed as sinigrin equivalents (SE) revealed a certain variabilily ranging between (76.07-45.61), (27.01-13.53), (4.52 -18.01), (9.39-3.37) and (1.16-13.99) µmol /g...

Definition of regional dependence of activity antioxidative enzymes means of the dispersive analysis

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Anatoly T. Bykov

2011-05-01

Full Text Available In article application of the dispersive analysis for an estimation of dependence of activity antioxidative enzymes from region of constant residing, age, sex and the disease diagnosis is considered.

From retinal waves to activity-dependent retinogeniculate map development.

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Jeffrey Markowitz

Full Text Available A neural model is described of how spontaneous retinal waves are formed in infant mammals, and how these waves organize activity-dependent development of a topographic map in the lateral geniculate nucleus, with connections from each eye segregated into separate anatomical layers. The model simulates the spontaneous behavior of starburst amacrine cells and retinal ganglion cells during the production of retinal waves during the first few weeks of mammalian postnatal development. It proposes how excitatory and inhibitory mechanisms within individual cells, such as Ca(2+-activated K(+ channels, and cAMP currents and signaling cascades, can modulate the spatiotemporal dynamics of waves, notably by controlling the after-hyperpolarization currents of starburst amacrine cells. Given the critical role of the geniculate map in the development of visual cortex, these results provide a foundation for analyzing the temporal dynamics whereby the visual cortex itself develops.