WorldWideScience

Sample records for activity transport

  1. Signal focusing through active transport

    Science.gov (United States)

    Godec, Aljaž; Metzler, Ralf

    2015-07-01

    The accuracy of molecular signaling in biological cells and novel diagnostic devices is ultimately limited by the counting noise floor imposed by the thermal diffusion. Motivated by the fact that messenger RNA and vesicle-engulfed signaling molecules transiently bind to molecular motors and are actively transported in biological cells, we show here that the random active delivery of signaling particles to within a typical diffusion distance to the receptor generically reduces the correlation time of the counting noise. Considering a variety of signaling particle sizes from mRNA to vesicles and cell sizes from prokaryotic to eukaryotic cells, we show that the conditions for active focusing—faster and more precise signaling—are indeed compatible with observations in living cells. Our results improve the understanding of molecular cellular signaling and novel diagnostic devices.

  2. Common folds and transport mechanisms of secondary active transporters.

    Science.gov (United States)

    Shi, Yigong

    2013-01-01

    Secondary active transporters exploit the electrochemical potential of solutes to shuttle specific substrate molecules across biological membranes, usually against their concentration gradient. Transporters of different functional families with little sequence similarity have repeatedly been found to exhibit similar folds, exemplified by the MFS, LeuT, and NhaA folds. Observations of multiple conformational states of the same transporter, represented by the LeuT superfamily members Mhp1, AdiC, vSGLT, and LeuT, led to proposals that structural changes are associated with substrate binding and transport. Despite recent biochemical and structural advances, our understanding of substrate recognition and energy coupling is rather preliminary. This review focuses on the common folds and shared transport mechanisms of secondary active transporters. Available structural information generally supports the alternating access model for substrate transport, with variations and extensions made by emerging structural, biochemical, and computational evidence.

  3. Political activity for physical activity: health advocacy for active transport

    Directory of Open Access Journals (Sweden)

    Amun Qa-t-a

    2011-05-01

    Full Text Available Abstract Effective health advocacy is a priority for efforts to increase population participation in physical activity. Local councils are an important audience for this advocacy. The aim of the current study was to describe features of advocacy for active transport via submissions to city council annual plans in New Zealand, and the impact of an information sheet to encourage the health sector to be involved in this process. Written submissions to city council's annual consultation process were requested for 16 city councils over the period of three years (2007/08, 2008/09, and 2009/10. Submissions were reviewed and categories of responses were created. An advocacy information sheet encouraging health sector participation and summarising some of the evidence-base related to physical activity, active transport and health was released just prior to the 2009/10 submission time. Over the period of the study, city councils received 47,392 submissions, 17% of which were related to active transport. Most submissions came from city residents, with a small proportion (2% from the health sector. The largest category of submissions was in support of pedestrian and cycling infrastructure, design and maintenance of facilities and additional features to support use of these transport modes. Health arguments featured prominently in justifications for active transport initiatives, including concerns about injury risk, obesity, physical inactivity, personal safety and facilities for people with disabilities. There was evidence that the information sheet was utilised by some health sector submitters (12.5%, providing tentative support for initiatives of this nature. In conclusion, the study provides novel information about the current nature of health advocacy for active transport and informs future advocacy efforts about areas for emphasis, such as health benefits of active transport, and potential alliances with other sectors such as environmental

  4. Political activity for physical activity: health advocacy for active transport.

    Science.gov (United States)

    Richards, Rosalina; Murdoch, Linda; Reeder, Anthony I; Amun, Qa-t-a

    2011-05-29

    Effective health advocacy is a priority for efforts to increase population participation in physical activity. Local councils are an important audience for this advocacy. The aim of the current study was to describe features of advocacy for active transport via submissions to city council annual plans in New Zealand, and the impact of an information sheet to encourage the health sector to be involved in this process. Written submissions to city council's annual consultation process were requested for 16 city councils over the period of three years (2007/08, 2008/09, and 2009/10). Submissions were reviewed and categories of responses were created. An advocacy information sheet encouraging health sector participation and summarising some of the evidence-base related to physical activity, active transport and health was released just prior to the 2009/10 submission time. Over the period of the study, city councils received 47,392 submissions, 17% of which were related to active transport. Most submissions came from city residents, with a small proportion (2%) from the health sector. The largest category of submissions was in support of pedestrian and cycling infrastructure, design and maintenance of facilities and additional features to support use of these transport modes. Health arguments featured prominently in justifications for active transport initiatives, including concerns about injury risk, obesity, physical inactivity, personal safety and facilities for people with disabilities. There was evidence that the information sheet was utilised by some health sector submitters (12.5%), providing tentative support for initiatives of this nature. In conclusion, the study provides novel information about the current nature of health advocacy for active transport and informs future advocacy efforts about areas for emphasis, such as health benefits of active transport, and potential alliances with other sectors such as environmental sustainability, transport and urban

  5. Activity assay of membrane transport proteins

    Institute of Scientific and Technical Information of China (English)

    Hao Xie

    2008-01-01

    Membrane transport proteins are integral membrane proteins and considered as potential drug targets. Activity assay of transport proteins is essential for developing drugs to target these proteins. Major issues related to activity assessment of transport proteins include availability of transporters,transport activity of transporters, and interactions between ligands and transporters. Researchers need to consider the physiological status of proteins (bound in lipid membranes or purified), availability and specificity of substrates, and the purpose of the activity assay (screening, identifying, or comparing substrates and inhibitors) before choosing appropriate assay strategies and techniques. Transport proteins bound in vesicular membranes can be assayed for transporting substrate across membranes by means of uptake assay or entrance counterflow assay. Alternatively, transport proteins can be assayed for interactions with ligands by using techniques such as isothermal titration calorimetry, nuclear magnetic resonance spectroscopy, or surface plasmon resonance. Other methods and techniques such as fluorometry, scintillation proximity assay, electrophysiological assay, or stopped-flow assay could also be used for activity assay of transport proteins. In this paper the major strategies and techniques for activity assessment of membrane transport proteins are reviewed.

  6. The Transport Properties of Activated Carbon Fibers

    Science.gov (United States)

    di Vittorio, S. L.; Dresselhaus, M. S.; Endo, M.; Issi, J-P.; Piraux, L.

    1990-07-01

    The transport properties of activated isotropic pitch-based carbon fibers with surface area 1000 m{sup 2}/g have been investigated. We report preliminary results on the electrical conductivity, the magnetoresistance, the thermal conductivity and the thermopower of these fibers as a function of temperature. Comparisons are made to transport properties of other disordered carbons.

  7. Nonisothermal activation: nonlinear transport theory

    NARCIS (Netherlands)

    Dekker, H.; Maassen van den Brink, A.

    1998-01-01

    We present the statistical mechanical foundation of nonisothermal stochastic processes, thereby generalizing Kramers' Fokker-Planck model for thermal activation and providing a microscopic context for Rolf Landauer's original ideas on state-dependent diffusion. By applying projection operator method

  8. First Cost Calculation Methods for Road Freight Transport Activity

    Directory of Open Access Journals (Sweden)

    Kovács György

    2017-06-01

    Full Text Available The transport activity is one of the most expensive processes in the supply chain. Forwarding and transport companies focuses on the optimization of transportation and the reduction of transport costs.

  9. Development of novel active transport membrande devices

    Energy Technology Data Exchange (ETDEWEB)

    Laciak, D.V.

    1994-11-01

    Air Products has undertaken a research program to fabricate and evaluate gas separation membranes based upon promising ``active-transport`` (AT) materials recently developed in our laboratories. Active Transport materials are ionic polymers and molten salts which undergo reversible interaction or reaction with ammonia and carbon dioxide. The materials are useful for separating these gases from mixtures with hydrogen. Moreover, AT membranes have the unique property of possessing high permeability towards ammnonia and carbon dioxide but low permeability towards hydrogen and can thus be used to permeate these components from a gas stream while retaining hydrogen at high pressure.

  10. Health Impacts of Active Transportation in Europe.

    Directory of Open Access Journals (Sweden)

    David Rojas-Rueda

    Full Text Available Policies that stimulate active transportation (walking and bicycling have been related to heath benefits. This study aims to assess the potential health risks and benefits of promoting active transportation for commuting populations (age groups 16-64 in six European cities. We conducted a health impact assessment using two scenarios: increased cycling and increased walking. The primary outcome measure was all-cause mortality related to changes in physical activity level, exposure to fine particulate matter air pollution with a diameter <2.5 μm, as well as traffic fatalities in the cities of Barcelona, Basel, Copenhagen, Paris, Prague, and Warsaw. All scenarios produced health benefits in the six cities. An increase in bicycle trips to 35% of all trips (as in Copenhagen produced the highest benefits among the different scenarios analysed in Warsaw 113 (76-163 annual deaths avoided, Prague 61 (29-104, Barcelona 37 (24-56, Paris 37 (18-64 and Basel 5 (3-9. An increase in walking trips to 50% of all trips (as in Paris resulted in 19 (3-42 deaths avoided annually in Warsaw, 11(3-21 in Prague, 6 (4-9 in Basel, 3 (2-6 in Copenhagen and 3 (2-4 in Barcelona. The scenarios would also reduce carbon dioxide emissions in the six cities by 1,139 to 26,423 (metric tonnes per year. Policies to promote active transportation may produce health benefits, but these depend of the existing characteristics of the cities. Increased collaboration between health practitioners, transport specialists and urban planners will help to introduce the health perspective in transport policies and promote active transportation.

  11. Regulators of Slc4 bicarbonate transporter activity

    Directory of Open Access Journals (Sweden)

    Ian M. Thornell

    2015-06-01

    Full Text Available The Slc4 family of transporters is comprised of anion exchangers (AE1-4, Na-coupled bicarbonate transporters (NCBTs including electrogenic Na/bicarbonate cotransporters (NBCe1 and NBCe2, electroneutral Na/bicarbonate cotransporters (NBCn1 and NBCn2, and the electroneutral Na-driven Cl-bicarbonate exchanger (NDCBE, as well as a borate transporter (BTR1. These transporters regulate intracellular pH (pHi and contribute to steady-state pHi, but are also involved in other physiological processes including CO2 carriage by red blood cells and solute secretion/reabsorption across epithelia. Acid-base transporters function as either acid extruders or acid loaders, with the Slc4 proteins moving HCO3– either into or out of cells. According to results from both molecular and functional studies, multiple Slc4 proteins and/or associated splice variants with similar expected effects on pHi are often found in the same tissue or cell. Such apparent redundancy is likely to be physiologically important. In addition to regulating pHi, a HCO3– transporter contributes to a cell’s ability to fine tune the intracellular regulation of the cotransported/exchanged ion(s (e.g., Na+ or Cl–. In addition, functionally similar transporters or splice variants with different regulatory profiles will optimize pH physiology and solute transport under various conditions or within subcellular domains. Such optimization will depend on activated signaling pathways and transporter expression profiles. In this review, we will summarize and discuss both classical and more recently identified regulators of the Slc4 proteins. Some of these regulators include traditional second messengers, lipids, binding proteins, autoregulatory domains, and less conventional regulators. The material presented will provide insight into the diversity and physiological significance of multiple members within the Slc4 gene family.

  12. Berberine acutely activates the glucose transport activity of GLUT1.

    Science.gov (United States)

    Cok, Alexandra; Plaisier, Christina; Salie, Matthew J; Oram, Daniel S; Chenge, Jude; Louters, Larry L

    2011-07-01

    Berberine, which has a long history of use in Chinese medicine, has recently been shown to have efficacy in the treatment of diabetes. While the hypoglycemic effect of berberine has been clearly documented in animal and cell line models, such as 3T3-L1 adipocytes and L6 myotube cells, the mechanism of action appears complex with data implicating activation of the insulin signaling pathway as well as activation of the exercise or AMP kinase-mediated pathway. There have been no reports of the acute affects of berberine on the transport activity of the insulin-insensitive glucose transporter, GLUT1. Therefore, we examined the acute effects of berberine on glucose uptake in L929 fibroblast cells, a cell line that express only GLUT1. Berberine- activated glucose uptake reaching maximum stimulation of five-fold at >40 μM. Significant activation (P berberine effect was not additive to the maximal stimulation by other known stimulants, azide, methylene blue or glucose deprivation, suggesting shared steps between berberine and these stimulants. Berberine significantly reduced the K(m) of glucose uptake from 6.7 ± 1.9 mM to 0.55 ± 0.08 mM, but had no effect on the V(max) of uptake. Compound C, an inhibitor of AMP kinase, did not affect berberine-stimulated glucose uptake, but inhibitors of downstream kinases partially blocked berberine stimulation. SB203580 (inhibitor of p38 MAP kinase) did not affect submaximal berberine activation, but did lower maximal berberine stimulation by 26%, while PD98059 (inhibitor of ERK kinase) completely blocked submaximal berberine activation and decreased the maximal stimulation by 55%. It appears from this study that a portion of the hypoglycemic effects of berberine can be attributed to its acute activation of the transport activity of GLUT1.

  13. Transport in active systems crowded by obstacles

    Science.gov (United States)

    Huang, Mu-Jie; Schofield, Jeremy; Kapral, Raymond

    2017-02-01

    The reactive and diffusive dynamics of a single chemically powered Janus motor in a crowded medium of moving but passive obstacles is investigated using molecular simulation. It is found that the reaction rate of the catalytic motor reaction decreases in a crowded medium as the volume fraction of obstacles increases as a result of a reduction in the Smoluchowski diffusion-controlled reaction rate coefficient that contributes to the overall reaction rate. A continuum model is constructed and analyzed to interpret the dependence of the steady-state reaction rate observed in simulations on the volume fraction of obstacles in the system. The steady-state concentration fields of reactant and product are shown to be sensitive to the local structure of obstacles around the Janus motor. It is demonstrated that the active motor exhibits enhanced diffusive motion at long times with a diffusion constant that decreases as the volume fraction of crowding species increases. In addition, the dynamical properties of a passive tracer particle in a system containing many active Janus motors is studied to investigate how an active environment influences the transport of non-active species. The diffusivity of a passive tracer particle in an active medium is found to be enhanced in systems with forward-moving Janus motors due to the cooperative dynamics of these motors.

  14. A general method for determining secondary active transporter substrate stoichiometry.

    Science.gov (United States)

    Fitzgerald, Gabriel A; Mulligan, Christopher; Mindell, Joseph A

    2017-01-25

    The number of ions required to drive substrate transport through a secondary active transporter determines the protein's ability to create a substrate gradient, a feature essential to its physiological function, and places fundamental constraints on the transporter's mechanism. Stoichiometry is known for a wide array of mammalian transporters, but, due to a lack of readily available tools, not for most of the prokaryotic transporters for which high-resolution structures are available. Here, we describe a general method for using radiolabeled substrate flux assays to determine coupling stoichiometries of electrogenic secondary active transporters reconstituted in proteoliposomes by measuring transporter equilibrium potentials. We demonstrate the utility of this method by determining the coupling stoichiometry of VcINDY, a bacterial Na(+)-coupled succinate transporter, and further validate it by confirming the coupling stoichiometry of vSGLT, a bacterial sugar transporter. This robust thermodynamic method should be especially useful in probing the mechanisms of transporters with available structures.

  15. Integration of a 'proton antenna' facilitates transport activity of the monocarboxylate transporter MCT4.

    Science.gov (United States)

    Noor, Sina Ibne; Pouyssegur, Jacques; Deitmer, Joachim W; Becker, Holger M

    2017-01-01

    Monocarboxylate transporters (MCTs) mediate the proton-coupled transport of high-energy metabolites like lactate and pyruvate and are expressed in nearly every mammalian tissue. We have shown previously that transport activity of MCT4 is enhanced by carbonic anhydrase II (CAII), which has been suggested to function as a 'proton antenna' for the transporter. In the present study, we tested whether creation of an endogenous proton antenna by introduction of a cluster of histidine residues into the C-terminal tail of MCT4 (MCT4-6xHis) could facilitate MCT4 transport activity when heterologously expressed in Xenopus oocytes. Our results show that integration of six histidines into the C-terminal tail does indeed increase transport activity of MCT4 to the same extent as did coexpression of MCT4-WT with CAII. Transport activity of MCT4-6xHis could be further enhanced by coexpression with extracellular CAIV, but not with intracellular CAII. Injection of an antibody against the histidine cluster into MCT4-expressing oocytes decreased transport activity of MCT4-6xHis, while leaving activity of MCT4-WT unaltered. Taken together, these findings suggest that transport activity of the proton-coupled monocarboxylate transporter MCT4 can be facilitated by integration of an endogenous proton antenna into the transporter's C-terminal tail.

  16. Associations between street connectivity and active transportation

    Directory of Open Access Journals (Sweden)

    Pickle Linda W

    2010-04-01

    Full Text Available Abstract Background Past studies of associations between measures of the built environment, particularly street connectivity, and active transportation (AT or leisure walking/bicycling have largely failed to account for spatial autocorrelation of connectivity variables and have seldom examined both the propensity for AT and its duration in a coherent fashion. Such efforts could improve our understanding of the spatial and behavioral aspects of AT. We analyzed spatially identified data from Los Angeles and San Diego Counties collected as part of the 2001 California Health Interview Survey. Results Principal components analysis indicated that ~85% of the variance in nine measures of street connectivity are accounted for by two components representing buffers with short blocks and dense nodes (PRIN1 or buffers with longer blocks that still maintain a grid like structure (PRIN2. PRIN1 and PRIN2 were positively associated with active transportation (AT after adjustment for diverse demographic and health related variables. Propensity and duration of AT were correlated in both Los Angeles (r = 0.14 and San Diego (r = 0.49 at the zip code level. Multivariate analysis could account for the correlation between the two outcomes. After controlling for demography, measures of the built environment and other factors, no spatial autocorrelation remained for propensity to report AT (i.e., report of AT appeared to be independent among neighborhood residents. However, very localized correlation was evident in duration of AT, particularly in San Diego, where the variance of duration, after accounting for spatial autocorrelation, was 5% smaller within small neighborhoods (~0.01 square latitude/longitude degrees = 0.6 mile diameter compared to within larger zip code areas. Thus a finer spatial scale of analysis seems to be more appropriate for explaining variation in connectivity and AT. Conclusions Joint analysis of the propensity and duration of AT behavior and an

  17. Active transport among Czech school-aged children

    Directory of Open Access Journals (Sweden)

    Jan Pavelka

    2012-09-01

    Full Text Available BACKGROUND: Active transport is a very important factor for increasing the level of physical activity in children, which is significant for both their health and positive physical behaviour in adult age. OBJECTIVE: The aim of the study was to establish the proportion of Czech children aged 11 to 15 who select active transport to and from school and, at the same time, describe socio-economic and socio-demographic factors influencing active transport to and from school among children. METHODS: To establish the socio-demographic factors affecting active transport, data of a national representative sample of 11 to 15 year-old elementary school children in the Czech Republic (n = 4,425. Research data collection was performed within an international research study called Health Behaviour in School Aged Children in June 2010. Statistical processing of the results was made using a logistic regression analysis in the statistical programme IBM SPSS v 20. RESULTS: Active transport to and from school is opted for in the Czech Republic by approximately 2/3 of children aged 11 to 15. Differences between genders are not statistically significant; most children opting for active transport are aged 11 (69%. An important factor increasing the probability of active transport as much as 16 times is whether a child's place of residence is in the same municipality as the school. Other factors influencing this choice include BMI, time spent using a computer or a privateroom in a family. A significant factor determining active transport by children is safety; safe road crossing, opportunity to leave a bicycle safely at school, no fear of being assaulted on the way or provision of school lockers where children can leave their items. CONCLUSIONS: Active transport plays an important role in increasing the overall level of physical activity in children. Promotion of active transport should focus on children who spend more time using a computer; attention should also be

  18. Passenger transport and household activity patterns

    DEFF Research Database (Denmark)

    Jørgensen, Kaj

    1997-01-01

    Review of Danish passenger transport patterns and analysis of energy consumption, emissions and safety impacts for selected typical households' travelling......Review of Danish passenger transport patterns and analysis of energy consumption, emissions and safety impacts for selected typical households' travelling...

  19. Air pollution exposure: An activity pattern approach for active transportation

    Science.gov (United States)

    Adams, Matthew D.; Yiannakoulias, Nikolaos; Kanaroglou, Pavlos S.

    2016-09-01

    In this paper, we demonstrate the calculation of personal air pollution exposure during trips made by active transportation using activity patterns without personal monitors. We calculate exposure as the inhaled dose of particulate matter 2.5 μg or smaller. Two modes of active transportation are compared, and they include cycling and walking. Ambient conditions are calculated by combining mobile and stationary monitoring data in an artificial neural network space-time model. The model uses a land use regression framework and has a prediction accuracy of R2 = 0.78. Exposure is calculated at 10 m or shorter intervals during the trips using inhalation rates associated with both modes. The trips are children's routes between home and school. The average dose during morning cycling trips was 2.17 μg, during morning walking trips was 3.19 μg, during afternoon cycling trips was 2.19 μg and during afternoon walking trips was 3.23 μg. The cycling trip dose was significantly lower than the walking trip dose. The air pollution exposure during walking or cycling trips could not be strongly predicted by either the school or household ambient conditions, either individually or in combination. Multiple linear regression models regressing both the household and school ambient conditions against the dose were only able to account for, at most, six percent of the variance in the exposure. This paper demonstrates that incorporating activity patterns when calculating exposure can improve the estimate of exposure compared to its calculation from ambient conditions.

  20. Pedelecs as a physically active transportation mode.

    Science.gov (United States)

    Peterman, James E; Morris, Kalee L; Kram, Rodger; Byrnes, William C

    2016-08-01

    Pedelecs are bicycles that provide electric assistance only when a rider is pedaling and have become increasingly popular. Our purpose was to quantify usage patterns over 4 weeks of real-world commuting with a pedelec and to determine if pedelec use would improve cardiometabolic risk factors. Twenty sedentary commuters visited the laboratory for baseline physiological measurements [body composition, maximum oxygen consumption ([Formula: see text]), mean arterial blood pressure (MAP), blood lipid profile, and 2-h oral glucose tolerance test (OGTT)]. The following 4 weeks, participants were instructed to commute using a pedelec at least 3 days week(-1) for 40 min day(-1) while wearing a heart rate monitor and a GPS device. Metabolic equivalents (METS) were estimated from heart rate data. Following the intervention, we repeated the physiological measurements. Average total distance and time were 317.9 ± 113.8 km and 15.9 ± 3.4 h, respectively. Participants averaged 4.9 ± 1.2 METS when riding. Four weeks of pedelec commuting significantly improved 2-h post-OGTT glucose (5.53 ± 1.18-5.03 ± 0.91 mmol L(-1), p < 0.05), [Formula: see text] (2.21 ± 0.48-2.39 ± 0.52 L min(-1), p < 0.05), and end of [Formula: see text] test power output (165.1 ± 37.1-189.3 ± 38.2 W, p < 0.05). There were trends for improvements in MAP (84.6 ± 10.5-83.2 ± 9.4 mmHg, p = 0.15) and fat mass (28.6 ± 11.3-28.2 ± 11.4 kg, p = 0.07). Participants rode a pedelec in the real world at a self-selected moderate intensity, which helped them meet physical activity recommendations. Pedelec commuting also resulted in significant improvements in 2-h post-OGTT glucose, [Formula: see text], and power output. Pedelecs are an effective form of active transportation that can improve some cardiometabolic risk factors within only 4 weeks.

  1. Transporting Radioactive Waste: An Engineering Activity. Grades 5-12.

    Science.gov (United States)

    HAZWRAP, The Hazardous Waste Remedial Actions Program.

    This brochure contains an engineering activity for upper elementary, middle school, and high school students that examines the transportation of radioactive waste. The activity is designed to inform students about the existence of radioactive waste and its transportation to disposal sites. Students experiment with methods to contain the waste and…

  2. Pedometer-determined physical activity and active transport in girls

    Directory of Open Access Journals (Sweden)

    Schofield Grant

    2008-01-01

    Full Text Available Abstract Background It is well established that the risk of insufficient physical activity is greater in girls than in boys, especially during the adolescent years. The promotion of active transport (AT to and from school has been posited as a practical and convenient solution for increasing girls' total daily activity. However, there is limited information describing the associations between AT choices and girls' physical activity across a range of age, ethnic, and socioeconomic groups. The objectives of this study were to (1 investigate physical activity patterns in a large multiethnic sample of female children and adolescents, and to (2 estimate the physical activity associated with AT to and from school. Methods A total of 1,513 girls aged 5–16 years wore sealed multiday memory (MDM pedometers for three weekdays and two weekend days. The ethnic composition of this sample was 637 European (42.1%, 272 Pacific Island (18.0%, 207 East Asian (13.7%, 179 Maori (11.8%, 142 South Asian (9.4%, and 76 from other ethnic groups (5%. Pedometer compliance and school-related AT were assessed by questionnaire. Results Mean weekday step counts (12,597 ± 3,630 were higher and less variable than mean weekend steps (9,528 ± 4,407. A consistent decline in daily step counts was observed with age: after adjustment for ethnicity and SES, girls in school years 9–10 achieved 2,469 (weekday and 4,011 (weekend fewer steps than girls in years 1–2. Daily step counts also varied by ethnicity, with Maori girls the most active and South Asian girls the least active. Overall, 44.9% of participants used AT for school-related travel. Girls who used AT to and from school averaged 1,052 more weekday steps than those who did not use AT. However, the increases in steps associated with AT were significant only in older girls (school years 5–10 and in those of Maori or European descent. Conclusion Our data suggest that adolescent-aged girls and girls of Asian descent are

  3. Interplay of vacuolar transporters for coupling primary and secondary active transport

    Directory of Open Access Journals (Sweden)

    Michèle Siek

    2016-10-01

    Full Text Available Secondary active transporters are driven by the proton motif force which is generated by primary active transporters such as the vacuolar proton pumps V-ATPase and V-PPase. The vacuole occupies up to 90 % of the mature cell and acidification of the vacuolar lumen is a challenging and energy-consuming task for the plant cell. Therefore, a direct coupling of primary and secondary active transporters is expected to enhance transport efficiency and to reduce energy consumption by transport processes across the tonoplast. This has been addressed by analyzing physical and functional interactions between the V-ATPase and a selection of vacuolar transporters including the primary active proton pump AVP1, the calcium ion/proton exchanger CAX1, the potassium ion/proton symporter KUP5, the sodium ion/proton exchanger NHX1, and the anion/proton exchanger CLC-c. Physical interaction was demonstrated in vivo for the V-ATPase and the secondary active transporters CAX1 and CLC-c, which are responsible for calcium- and anion-accumulation in the vacuole, respectively. Measurements of V-ATPase activity and vacuolar pH revealed a functional interaction of V-ATPase and CAX1, CLC-c that is likely caused by the observed physical interaction. The complex of the V-ATPase further interacts with the nitrate reductase 2, and as a result, nitrate assimilation is directly linked to the energization of vacuolar nitrate accumulation by secondary active anion/proton exchangers.

  4. Transport and biological activities of bile acids.

    Science.gov (United States)

    Zwicker, Brittnee L; Agellon, Luis B

    2013-07-01

    Bile acids have emerged as important biological molecules that support the solubilization of various lipids and lipid-soluble compounds in the gut, and the regulation of gene expression and cellular function. Bile acids are synthesized from cholesterol in the liver and eventually released into the small intestine. The majority of bile acids are recovered in the distal end of the small intestine and then returned to the liver for reuse. The components of the mechanism responsible for the recycling of bile acids within the enterohepatic circulation have been identified whereas the mechanism for intracellular transport is less understood. Recently, the ileal lipid binding protein (ILBP; human gene symbol FABP6) was shown to be needed for the efficient transport of bile acids from the apical side to the basolateral side of enterocytes in the distal intestine. This review presents an overview of the transport of bile acids between the liver and the gut as well as within hepatocytes and enterocytes. A variety of pathologies is associated with the malfunction of the bile acid transport system.

  5. Study of active cooling for supersonic transports

    Science.gov (United States)

    Brewer, G. D.; Morris, R. E.

    1975-01-01

    The potential benefits of using the fuel heat sink of hydrogen fueled supersonic transports for cooling large portions of the aircraft wing and fuselage are examined. The heat transfer would be accomplished by using an intermediate fluid such as an ethylene glycol-water solution. Some of the advantages of the system are: (1) reduced costs by using aluminum in place of titanium, (2) reduced cabin heat loads, and (3) more favorable environmental conditions for the aircraft systems. A liquid hydrogen fueled, Mach 2.7 supersonic transport aircraft design was used for the reference uncooled vehicle. The cooled aircraft designs were analyzed to determine their heat sink capability, the extent and location of feasible cooled surfaces, and the coolant passage size and spacing.

  6. TRISNET; a Network of Transportation Information Services and Activities.

    Science.gov (United States)

    Department of Transportation, Washington, DC. Office of the Assistant Secretary for Systems Development and Technology.

    A national Transportation Research Information Services Network (TRISNET) is being developed by the Department of Transportation (DOT) linking libraries, data bases, and retrieval services with DOT information activities. Core services provide switch and referral, indexing and abstracting, online retrieval, and document delivery. (JY)

  7. Schisandrin A and B induce organic anion transporting polypeptide 1B1 transporter activity.

    Science.gov (United States)

    Guo, Cheng-Xian; Deng, Sheng; Yin, Ji-Ye; Liu, Zhao-Qian; Zhang, Wei; Zhou, Hong-Hao

    2015-01-01

    Organic anion transporting polypeptide 1B1 (OATP1B1) is the most important transporter in the organic anion transporting polypeptide family. OATP1B1 plays an important role in the hepatic uptake of many endogenous compounds and xenobiotics, including many clinical drugs. At present, the combinational usage of Chinese traditional herbal medicines and conventional chemical pharmaceuticals may affect the activity of enzymes and transporters activity and cause absorption of their substrates and metabolic changes. In this study, we aimed to investigate the effect of schisandrin A, schisandrin B and tanshinone IIA, which were extracted from medicinal plants, on OATP1B1 activity. HepG2 cells are used as in vitro models for OATP1B1 activity studies. A combination of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tertazolium bromide (MTT) assays, real-time RT-PCR, and transporter activity analysis were employed. We found that schisandrin A and B increased OATP1B1 mRNA levels by 1.81-fold (p Schisandrin A of 1 μM and 10 μM and schisandrin B of 10 μM significantly increased the uptake of [3H] estrone-3-sulfate (p schisandrin A and B induced OATP1B1 expression and increased its transporter activity in HepG2 cells.

  8. A general method for determining secondary active transporter substrate stoichiometry

    Science.gov (United States)

    Fitzgerald, Gabriel A; Mulligan, Christopher; Mindell, Joseph A

    2017-01-01

    The number of ions required to drive substrate transport through a secondary active transporter determines the protein’s ability to create a substrate gradient, a feature essential to its physiological function, and places fundamental constraints on the transporter’s mechanism. Stoichiometry is known for a wide array of mammalian transporters, but, due to a lack of readily available tools, not for most of the prokaryotic transporters for which high-resolution structures are available. Here, we describe a general method for using radiolabeled substrate flux assays to determine coupling stoichiometries of electrogenic secondary active transporters reconstituted in proteoliposomes by measuring transporter equilibrium potentials. We demonstrate the utility of this method by determining the coupling stoichiometry of VcINDY, a bacterial Na+-coupled succinate transporter, and further validate it by confirming the coupling stoichiometry of vSGLT, a bacterial sugar transporter. This robust thermodynamic method should be especially useful in probing the mechanisms of transporters with available structures. DOI: http://dx.doi.org/10.7554/eLife.21016.001 PMID:28121290

  9. THE TIME FACTOR IN MARITIME TRANSPORT AND PORT LOGISTICS ACTIVITIES

    Directory of Open Access Journals (Sweden)

    Florin NICOLAE

    2016-06-01

    Full Text Available Execution of the carriage contract requires compliance to all the conditions in it, by all those involved in the transport. Main obligations incumbent upon the vessel, and obviously, to other transporters, who must provide transportation according to deadlines and safety. Contract compliance is certifying transport participants about their seriousness and an appropriate market quotation. Therefore, present work pragmatically sets schematics reference time associated implementation of the carriage contract. Also, are demonstrated relationships established between maritime transport “players” and sequence of activities related to the operation of the vessel in port. The authors propose a set of concepts and terms whose utility is established to solve practical problems in this area of activity.

  10. Effects of a Danish multicomponent physical activity intervention on active school transport

    DEFF Research Database (Denmark)

    Breum, Lars; Toftager, Mette; Ersbøll, Annette K.;

    2014-01-01

    AbstractIntroduction Walking and bicycling to school yields great potential in increasing the physical activity levels of adolescents, but to date very few intervention studies have been evaluated. The aim of this study was to evaluate the effect of a multicomponent school-based physical activity...... activity, active transport and after-school fitness program. Transport mode to school was assessed through a 5-day transportation diary. Results The proportion of active transport was high at baseline (86.0%) and was maintained at the two-year follow-up (87.0%). There was no difference in active travel...

  11. Active Transportation Safety Features around Schools in Canada

    Directory of Open Access Journals (Sweden)

    Bryn Pinkerton

    2013-10-01

    Full Text Available The purpose of this study was to describe the presence and quality of active transportation safety features in Canadian school environments that relate to pedestrian and bicycle safety. Variations in these features and associated traffic concerns as perceived by school administrators were examined by geographic status and school type. The study was based on schools that participated in 2009/2010 Health Behaviour in School-aged Children (HBSC survey. ArcGIS software version 10 and Google Earth were used to assess the presence and quality of ten different active transportation safety features. Findings suggest that there are crosswalks and good sidewalk coverage in the environments surrounding most Canadian schools, but a dearth of bicycle lanes and other traffic calming measures (e.g., speed bumps, traffic chokers. Significant urban/rural inequities exist with a greater prevalence of sidewalk coverage, crosswalks, traffic medians, and speed bumps in urban areas. With the exception of bicycle lanes, the active transportation safety features that were present were generally rated as high quality. Traffic was more of a concern to administrators in urban areas. This study provides novel information about active transportation safety features in Canadian school environments. This information could help guide public health efforts aimed at increasing active transportation levels while simultaneously decreasing active transportation injuries.

  12. Active transportation safety features around schools in Canada.

    Science.gov (United States)

    Pinkerton, Bryn; Rosu, Andrei; Janssen, Ian; Pickett, William

    2013-10-31

    The purpose of this study was to describe the presence and quality of active transportation safety features in Canadian school environments that relate to pedestrian and bicycle safety. Variations in these features and associated traffic concerns as perceived by school administrators were examined by geographic status and school type. The study was based on schools that participated in 2009/2010 Health Behaviour in School-aged Children (HBSC) survey. ArcGIS software version 10 and Google Earth were used to assess the presence and quality of ten different active transportation safety features. Findings suggest that there are crosswalks and good sidewalk coverage in the environments surrounding most Canadian schools, but a dearth of bicycle lanes and other traffic calming measures (e.g., speed bumps, traffic chokers). Significant urban/rural inequities exist with a greater prevalence of sidewalk coverage, crosswalks, traffic medians, and speed bumps in urban areas. With the exception of bicycle lanes, the active transportation safety features that were present were generally rated as high quality. Traffic was more of a concern to administrators in urban areas. This study provides novel information about active transportation safety features in Canadian school environments. This information could help guide public health efforts aimed at increasing active transportation levels while simultaneously decreasing active transportation injuries.

  13. Entropic Ratchet transport of interacting active Brownian particles

    Energy Technology Data Exchange (ETDEWEB)

    Ai, Bao-Quan, E-mail: aibq@hotmail.com [Laboratory of Quantum Engineering and Quantum Materials, School of Physics and Telecommunication Engineering, South China Normal University, 510006 Guangzhou (China); He, Ya-Feng [College of Physics Science and Technology, Hebei University, 071002 Baoding (China); Zhong, Wei-Rong, E-mail: wrzhong@jnu.edu.cn [Department of Physics and Siyuan Laboratory, College of Science and Engineering, Jinan University, 510632 Guangzhou (China)

    2014-11-21

    Directed transport of interacting active (self-propelled) Brownian particles is numerically investigated in confined geometries (entropic barriers). The self-propelled velocity can break thermodynamical equilibrium and induce the directed transport. It is found that the interaction between active particles can greatly affect the ratchet transport. For attractive particles, on increasing the interaction strength, the average velocity first decreases to its minima, then increases, and finally decreases to zero. For repulsive particles, when the interaction is very weak, there exists a critical interaction at which the average velocity is minimal, nearly tends to zero, however, for the strong interaction, the average velocity is independent of the interaction.

  14. Active urea transport in lower vertebrates and mammals.

    Science.gov (United States)

    Bankir, Lise

    2014-01-01

    Some unicellular organisms can take up urea from the surrounding fluids by an uphill pumping mechanism. Several active (energy-dependent) urea transporters (AUTs) have been cloned in these organisms. Functional studies show that active urea transport also occurs in elasmobranchs, amphibians, and mammals. In the two former groups, active urea transport may serve to conserve urea in body fluids in order to balance external high ambient osmolarity or prevent desiccation. In mammals, active urea transport may be associated with the need to either store and/or reuse nitrogen in the case of low nitrogen supply, or to excrete nitrogen efficiently in the case of excess nitrogen intake. There are probably two different families of AUTs, one with a high capacity able to establish only a relatively modest transepithelial concentration difference (renal tubule of some frogs, pars recta of the mammalian kidney, early inner medullary collecting duct in some mammals eating protein-poor diets) and others with a low capacity but able to maintain a high transepithelial concentration difference that has been created by another mechanism or in another organ (elasmobranch gills, ventral skin of some toads, and maybe mammalian urinary bladder). Functional characterization of these transporters shows that some are coupled to sodium (symports or antiports) while others are sodium-independent. In humans, only one genetic anomaly, with a mild phenotype (familial azotemia), is suspected to concern one of these transporters. In spite of abundant functional evidence for such transporters in higher organisms, none have been molecularly identified yet.

  15. Health Impacts of Active Transportation in Europe

    DEFF Research Database (Denmark)

    Rojas-Rueda, David; de Nazelle, Audrey; Andersen, Zorana J

    2016-01-01

    impact assessment using two scenarios: increased cycling and increased walking. The primary outcome measure was all-cause mortality related to changes in physical activity level, exposure to fine particulate matter air pollution with a diameter

  16. Regional differences in rat conjunctival ion transport activities

    OpenAIRE

    2012-01-01

    Active ion transport and coupled osmotic water flow are essential to maintain ocular surface health. We investigated regional differences in the ion transport activities of the rat conjunctivas and compared these activities with those of cornea and lacrimal gland. The epithelial sodium channel (ENaC), sodium/glucose cotransporter 1 (Slc5a1), transmembrane protein 16 (Tmem16a, b, f, and g), cystic fibrosis transmembrane conductance regulator (Cftr), and mucin (Muc4, 5ac, and 5b) mRNA expressio...

  17. Coupling of Active Motion and Advection Shapes Intracellular Cargo Transport

    CERN Document Server

    Trong, P Khuc; Goldstein, R E; 10.1103/PhysRevLett.109.028104

    2012-01-01

    Intracellular cargo transport can arise from passive diffusion, active motor-driven transport along cytoskeletal filament networks, and passive advection by fluid flows entrained by such motor/cargo motion. Active and advective transport are thus intrinsically coupled as related, yet different representations of the same underlying network structure. A reaction-advection-diffusion system is used here to show that this coupling affects the transport and localization of a passive tracer in a confined geometry. For sufficiently low diffusion, cargo localization to a target zone is optimized either by low reaction kinetics and decoupling of bound and unbound states, or by a mostly disordered cytoskeletal network with only weak directional bias. These generic results may help to rationalize subtle features of cytoskeletal networks, for example as observed for microtubules in fly oocytes.

  18. Sintering as a process of transport of activated volume

    Directory of Open Access Journals (Sweden)

    Nikolić Nataša S.

    2002-01-01

    Full Text Available Starting with the fact that sintering is the consequence of the process of transport of activated volume, it has been shown how the kinetics of the sintering process can be defined. The activated volume was in principle defined as a parameter which describes a system’s deffectivity on an atomic level.

  19. Substrate regulation of ascorbate transport activity in astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, J.X.; Jaworski, E.M.; Kulaga, A.; Dixon, S.J. (Univ. of Western Ontario, London (Canada))

    1990-10-01

    Astrocytes possess a concentrative L-ascorbate (vitamin C) uptake mechanism involving a Na(+)-dependent L-ascorbate transporter located in the plasma membrane. The present experiments examined the effects of deprivation and supplementation of extracellular L-ascorbate on the activity of this transport system. Initial rates of L-ascorbate uptake were measured by incubating primary cultures of rat astrocytes with L-(14C)ascorbate for 1 min at 37 degrees C. We observed that the apparent maximal rate of uptake (Vmax) increased rapidly (less than 1 h) when cultured cells were deprived of L-ascorbate. In contrast, there was no change in the apparent affinity of the transport system for L-(14C)ascorbate. The increase in Vmax was reversed by addition of L-ascorbate, but not D-isoascorbate, to the medium. The effects of external ascorbate on ascorbate transport activity were specific in that preincubation of cultures with L-ascorbate did not affect uptake of 2-deoxy-D-(3H(G))glucose. We conclude that the astroglial ascorbate transport system is modulated by changes in substrate availability. Regulation of transport activity may play a role in intracellular ascorbate homeostasis by compensating for regional differences and temporal fluctuations in external ascorbate levels.

  20. Presentation and exhibition activities for promoting theexportof transport services

    Directory of Open Access Journals (Sweden)

    Darya Vladimirovna Nesterova

    2012-03-01

    Full Text Available Development of presentation and exhibition activities is considered as an important factor in providing new competitive advantages at the strategic markets for exporting of transportation services. A specific role for exhibition activities as a factor to overcome market failures arose from imperfect information and incomplete markets is displayed. Exhibitions are considered as a true reflection of most market parameters, as a means to get correct information concerning market capacity and its borders, as an instrument to access to new markets. At the firm level presentation and branding activities should be considered as a modern technology (especially it concerns Russian companies which provide to hold up already existed markets and to conquer new ones. Presentation and branding activities are an effective technology to promote company trade-mark, competitive advantages for market demand increasing. Comparative analysis of the main exhibitions on transport and logistics issues is fulfilled on the data basecollected by authors. Data observes geographical distribution of transport exhibition and exhibition facilities development at several regions for the last years. The analyses allow to revealing a geographical structure of the exhibitions and its distribution by type of transport. The most promising and economically favorable exhibition areas for the promotion of Russian transport services are shown.

  1. Advocacy for active transport: advocate and city council perspectives

    Directory of Open Access Journals (Sweden)

    Rosenby Marieah

    2010-01-01

    Full Text Available Abstract Background Effective advocacy is an important part of efforts to increase population participation in physical activity. Research about effective health advocacy is scarce, however, the health sector can learn from the experiences and knowledge of community advocates and those who are on the receiving end of this advocacy. The aim of this study is to explore advocacy for active transport from the perspectives of community advocates and representatives from City councils. Methods Cycling and walking advocates were identified from the local contact list of Cycling Advocates Network and Living Streets Aotearoa. Semi-structured telephone interviews were conducted with cycle and walking advocates from throughout New Zealand. Advocates also nominated a suitable council officer at their local City council to be interviewed. Interviews were recorded and transcribed and categories of responses for each of the questions created. Results Several processes were used by advocates to engage with council staff, including formal council submissions, meetings, stakeholder forums and partnership in running community events promoting active transport. Several other agencies were identified as being influential for active transport, some as potential coalition partners and others as potential adversaries. Barriers to improving conditions for active transport included a lack of funding, a lack of will-power among either council staff or councillors, limited council staff capacity (time or training and a culture of providing infrastructure for motor vehicles instead of people. Several suggestions were made about how the health sector could contribute to advocacy efforts, including encouraging political commitment, engaging the media, communicating the potential health benefits of active transport to the general public and being role models in terms of personal travel mode choice and having workplaces that support participation in active transport

  2. Carbonless footprints: promoting health and climate stabilization through active transportation.

    Science.gov (United States)

    Frank, Lawrence D; Greenwald, Michael J; Winkelman, Steve; Chapman, James; Kavage, Sarah

    2010-01-01

    Our objective was to describe how active transportation can help meet health and greenhouse gas emissions goals, and the ability of urban form strategies to impact both issues. In addition, we wanted to assess if there is an inverse relationship between active and motorized forms of travel. A cross-sectional analysis of travel diary data was used to measure relationships among energy (kcal) burned from walking, energy (kcal) burned from motorized transportation, and the ratio of the two (the transport energy index) with regional accessibility and local walkability when adjusting for demographic factors. Multiple linear regression and descriptive statistics were employed to estimate these relationships. Transit accessibility, residential density, and intersection density were positive predictors of walk energy and the energy index and inverse predictors of motorized energy. The land use mix variable was negatively and significantly associated with energy burned from walking and from motorized transportation, with no significant impact on the transport energy index. Because a mixed land use pattern places destinations closer together, it reduces distances and thus energy demands for both walking and driving. The results support the concept, previously untested empirically, that similar urban form strategies can have cobenefits for both physical activity and climate change.

  3. Transport of active ellipsoidal particles in ratchet potentials

    Energy Technology Data Exchange (ETDEWEB)

    Ai, Bao-Quan, E-mail: aibq@scnu.edu.cn; Wu, Jian-Chun [Laboratory of Quantum Engineering and Quantum Materials, School of Physics and Telecommunication Engineering, South China Normal University, 510006 Guangzhou (China)

    2014-03-07

    Rectified transport of active ellipsoidal particles is numerically investigated in a two-dimensional asymmetric potential. The out-of-equilibrium condition for the active particle is an intrinsic property, which can break thermodynamical equilibrium and induce the directed transport. It is found that the perfect sphere particle can facilitate the rectification, while the needlelike particle destroys the directed transport. There exist optimized values of the parameters (the self-propelled velocity, the torque acting on the body) at which the average velocity takes its maximal value. For the ellipsoidal particle with not large asymmetric parameter, the average velocity decreases with increasing the rotational diffusion rate, while for the needlelike particle (very large asymmetric parameter), the average velocity is a peaked function of the rotational diffusion rate. By introducing a finite load, particles with different shapes (or different self-propelled velocities) will move to the opposite directions, which is able to separate particles of different shapes (or different self-propelled velocities)

  4. Engineering intracellular active transport systems as in vivo biomolecular tools.

    Energy Technology Data Exchange (ETDEWEB)

    Bachand, George David; Carroll-Portillo, Amanda

    2006-11-01

    Active transport systems provide essential functions in terms of cell physiology and metastasis. These systems, however, are also co-opted by invading viruses, enabling directed transport of the virus to and from the cell's nucleus (i.e., the site of virus replication). Based on this concept, fundamentally new approaches for interrogating and manipulating the inner workings of living cells may be achievable by co-opting Nature's active transport systems as an in vivo biomolecular tool. The overall goal of this project was to investigate the ability to engineer kinesin-based transport systems for in vivo applications, specifically the collection of effector proteins (e.g., transcriptional regulators) within single cells. In the first part of this project, a chimeric fusion protein consisting of kinesin and a single chain variable fragment (scFv) of an antibody was successfully produced through a recombinant expression system. The kinesin-scFv retained both catalytic and antigenic functionality, enabling selective capture and transport of target antigens. The incorporation of a rabbit IgG-specific scFv into the kinesin established a generalized system for functionalizing kinesin with a wide range of target-selective antibodies raised in rabbits. The second objective was to develop methods of isolating the intact microtubule network from live cells as a platform for evaluating kinesin-based transport within the cytoskeletal architecture of a cell. Successful isolation of intact microtubule networks from two distinct cell types was demonstrated using glutaraldehyde and methanol fixation methods. This work provides a platform for inferring the ability of kinesin-scFv to function in vivo, and may also serve as a three-dimensional scaffold for evaluating and exploiting kinesin-based transport for nanotechnological applications. Overall, the technology developed in this project represents a first-step in engineering active transport system for in vivo

  5. Berberine acutely activates the glucose transport activity of GLUT1

    OpenAIRE

    Cok, Alexandra; Plaisier, Christina; Salie, Matthew J.; Oram, Daniel S.; Chenge, Jude; Louters, Larry L.

    2011-01-01

    Berberine, which has a long history of use in Chinese medicine, has recently been shown to have efficacy in the treatment of diabetes. While the hypoglycemic effect of berberine has been clearly documented in animal and cell line models, such as 3T3-L1 adipocytes and L6 myotube cells, the mechanism of action appears complex with data implicating activation of the insulin signaling pathway as well as activation of the exercise or AMP kinase-mediated pathway. There have been no reports of the a...

  6. Pore mutations in ammonium transporter AMT1 with increased electrogenic ammonium transport activity.

    Science.gov (United States)

    Loqué, Dominique; Mora, Silvia I; Andrade, Susana L A; Pantoja, Omar; Frommer, Wolf B

    2009-09-11

    AMT/Mep ammonium transporters mediate high affinity ammonium/ammonia uptake in bacteria, fungi, and plants. The Arabidopsis AMT1 proteins mediate uptake of the ionic form of ammonium. AMT transport activity is controlled allosterically via a highly conserved cytosolic C terminus that interacts with neighboring subunits in a trimer. The C terminus is thus capable of modulating the conductivity of the pore. To gain insight into the underlying mechanism, pore mutants suppressing the inhibitory effect of mutations in the C-terminal trans-activation domain were characterized. AMT1;1 carrying the mutation Q57H in transmembrane helix I (TMH I) showed increased ammonium uptake but reduced capacity to take up methylammonium. To explore whether the transport mechanism was altered, the AMT1;1-Q57H mutant was expressed in Xenopus oocytes and analyzed electrophysiologically. AMT1;1-Q57H was characterized by increased ammonium-induced and reduced methylammonium-induced currents. AMT1;1-Q57H possesses a 100x lower affinity for ammonium (K(m)) and a 10-fold higher V(max) as compared with the wild type form. To test whether the trans-regulatory mechanism is conserved in archaeal homologs, AfAmt-2 from Archaeoglobus fulgidus was expressed in yeast. The transport function of AfAmt-2 also depends on trans-activation by the C terminus, and mutations in pore-residues corresponding to Q57H of AMT1;1 suppress nonfunctional AfAmt-2 mutants lacking the activating C terminus. Altogether, our data suggest that bacterial and plant AMTs use a conserved allosteric mechanism to control ammonium flux, potentially using a gating mechanism that limits flux to protect against ammonium toxicity.

  7. Modulation Effects of Curcumin on Erythrocyte Ion-Transporter Activity

    Directory of Open Access Journals (Sweden)

    Prabhakar Singh

    2015-01-01

    Full Text Available Curcumin ((1E,6E-1,7-Bis(4-hydroxy-3-methoxyphenyl-1,6-heptadiene-3,5-dione, the yellow biphenolic pigment isolated from turmeric (Curcuma longa, has various medicinal benefits through antioxidation, anti-inflammation, cardiovascular protection, immunomodulation, enhancing of the apoptotic process, and antiangiogenic property. We explored the effects of curcumin in vitro (10−5 M to 10−8 M and in vivo (340 and 170 mg/kg b.w., oral on Na+/K+ ATPase (NKA, Na+/H+ exchanger (NHE activity, and membrane lipid hydroperoxides (ROOH in control and experimental oxidative stress erythrocytes of Wistar rats. As a result, we found that curcumin potently modulated the membrane transporters activity with protecting membrane lipids against hydro-peroxidation in control as well as oxidatively challenged erythrocytes evidenced by stimulation of NKA, downregulation of NHE, and reduction of ROOH in the membrane. The observed results corroborate membrane transporters activity with susceptibility of erythrocyte membrane towards oxidative damage. Results explain the protective mechanism of curcumin against oxidative stress mediated impairment in ions-transporters activity and health beneficial effects.

  8. The Asymmetric Active Coupler: Stable Nonlinear Supermodes and Directed Transport

    CERN Document Server

    Kominis, Yannis; Flach, Sergej

    2016-01-01

    We consider the asymmetric active coupler (AAC) consisting of two coupled dissimilar waveguides with gain and loss. We show that under generic conditions, not restricted by parity-time symmetry, there exist finite-power, constant-intensity nonlinear supermodes (NS), resulting from the balance between gain, loss, nonlinearity, coupling and dissimilarity. The system is shown to possess nonreciprocal dynamics enabling directed power transport and optical isolation functionality.

  9. Activation of CFTR-mediated Cl- Transport by Magnolin

    Institute of Scientific and Technical Information of China (English)

    JIN Ling-ling; LIU Xin; SUN Yan; LIN Sen; ZHOU Na; XU Li-na; YU BO; HOU Shu-guang; YANG Hong

    2008-01-01

    Magnolin is a herbal compound from Magnolia biondii Pamp.It possesses numerous biological activities.Cystic fibrosis transmembrane conductance regulator(CFTR)is all epithelial chloride channel that plays a key role in the fluid secretion of various exocrine organs.In the present study,the activation of CFTR-mediated chloride transport by magnolin is indentified and characterized.In CFTR stably trailsfected FRT cells.magnolin increases CFTR Cl- currents in a concentration-dependent manner.The activation of magnolin on CFTR is rapid,reversible,and cAMP-dependent.Magnolin does not elevate cellular cAMP level.indicating that it activates CFTR by direct binding and interaction with CFTR protein.Magnolin selectively activates wildtype CFTR rather than mutant CFTIL Magnolin may present a novel class of therapeutic lead compound for the treatment of diseases associated with reduced CFTR function such as keratoconjunctivitis sicca,idiopathic chronic pancreatiti,and chromc constipation.

  10. Associations between built environment and active transport in Danish adolescents

    DEFF Research Database (Denmark)

    Breum, Lars

    Introduction: Active commuting to school in Denmark is common but differentiates between schools. What is the association between the surrounding school environment assessed with a three component index and active commuting in adolescents? Methods: Materials: The study material consists of 1348...... adolescents (11-13 years) attending 5th or 6th grade in 14 different schools in Region Southern Denmark. Measures: - 5-day commuting diary. Mode of transport was reported from home to school and return (walk, bike, car, bus, train and other). - Web based questionnaire to asses perceived safety of bike route...

  11. Examining Changes in Radioxenon Isotope Activity Ratios during Subsurface Transport

    Science.gov (United States)

    Annewandter, Robert

    2014-05-01

    The Non-Proliferation Experiment (NPE) has demonstrated and modelled the usefulness of barometric pumping induced gas transport and subsequent soil gas sampling during On-Site inspections. Generally, gas transport has been widely studied with different numerical codes. However, gas transport of radioxenons and radioiodines in the post-detonation regime and their possible fractionation is still neglected in the open peer-reviewed literature. Atmospheric concentrations of the radioxenons Xe-135, Xe-133m, Xe-133 and Xe-131m can be used to discriminate between civilian releases (nuclear power plants or medical isotope facilities), and nuclear explosion sources. It is based on the multiple isotopic activity ratio method. Yet it is not clear whether subsurface migration of the radionuclides, with eventual release into the atmosphere, can affect the activity ratios due to fractionation. Fractionation can be caused by different mass diffusivities due to mass differences between the radionuclides. Cyclical changes in atmospheric pressure can drive subsurface gas transport. This barometric pumping phenomenon causes an oscillatoric flow in upward trending fractures or highly conductive faults which, combined with diffusion into the porous matrix, leads to a net transport of gaseous components - a so-called ratcheting effect. We use a general purpose reservoir simulator (Complex System Modelling Platform, CSMP++) which is recognized by the oil industry as leading in Discrete Fracture-Matrix (DFM) simulations. It has been applied in a range of fields such as deep geothermal systems, three-phase black oil simulations, fracture propagation in fractured, porous media, and Navier-Stokes pore-scale modelling among others. It is specifically designed to account for structurally complex geologic situation of fractured, porous media. Parabolic differential equations are solved by a continuous Galerkin finite-element method, hyperbolic differential equations by a complementary finite

  12. Differences in associations between active transportation and built environmental exposures when expressed using different components of individual activity spaces.

    Science.gov (United States)

    van Heeswijck, Torbjorn; Paquet, Catherine; Kestens, Yan; Thierry, Benoit; Morency, Catherine; Daniel, Mark

    2015-05-01

    This study assessed relationships between built environmental exposures measured within components of individual activity spaces (i.e., travel origins, destinations and paths in-between), and use of active transportation in a metropolitan setting. Individuals (n=37,165) were categorised as using active or sedentary transportation based on travel survey data. Generalised Estimating Equations analysis was used to test relationships with active transportation. Strength and significance of relationships between exposures and active transportation varied for different components of the activity space. Associations were strongest when including travel paths in expression of the built environment. Land use mix and greenness were negatively related to active transportation.

  13. Modelling of electron transport and of sawtooth activity in tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Angioni, C

    2001-10-01

    Transport phenomena in tokamak plasmas strongly limit the particle and energy confinement and represent a crucial obstacle to controlled thermonuclear fusion. Within the vast framework of transport studies, three topics have been tackled in the present thesis: first, the computation of neoclassical transport coefficients for general axisymmetric equilibria and arbitrary collisionality regime; second, the analysis of the electron temperature behaviour and transport modelling of plasma discharges in the Tokamak a configuration Variable (TCV); third, the modelling and simulation of the sawtooth activity with different plasma heating conditions. The work dedicated to neoclassical theory has been undertaken in order to first analytically identify a set of equations suited for implementation in existing Fokker-Planck codes. Modifications of these codes enabled us to compute the neoclassical transport coefficients considering different realistic magnetic equilibrium configurations and covering a large range of variation of three key parameters: aspect ratio, collisionality, and effective charge number. A comparison of the numerical results with an analytical limit has permitted the identification of two expressions for the trapped particle fraction, capable of encapsulating the geometrical effects and thus enabling each transport coefficient to be fitted with a single analytical function. This has allowed us to provide simple analytical formulae for all the neoclassical transport coefficients valid for arbitrary aspect ratio and collisionality in general realistic geometry. This work is particularly useful for a correct evaluation of the neoclassical contribution in tokamak scenarios with large bootstrap cur- rent fraction, or improved confinement regimes with low anomalous transport and for the determination of the plasma current density profile, since the plasma conductivity is usually assumed neoclassical. These results have been included in the plasma transport code

  14. Curcumin directly inhibits the transport activity of GLUT1.

    Science.gov (United States)

    Gunnink, Leesha K; Alabi, Ola D; Kuiper, Benjamin D; Gunnink, Stephen M; Schuiteman, Sam J; Strohbehn, Lauren E; Hamilton, Kathryn E; Wrobel, Kathryn E; Louters, Larry L

    2016-06-01

    Curcumin, a major ingredient in turmeric, has a long history of medicinal applications in a wide array of maladies including treatment for diabetes and cancer. Seemingly counterintuitive to the documented hypoglycemic effects of curcumin, however, a recent report indicates that curcumin directly inhibits glucose uptake in adipocytes. The major glucose transporter in adipocytes is GLUT4. Therefore, this study investigates the effects of curcumin in cell lines where the major transporter is GLUT1. We report that curcumin has an immediate inhibitory effect on basal glucose uptake in L929 fibroblast cells with a maximum inhibition of 80% achieved at 75 μM curcumin. Curcumin also blocks activation of glucose uptake by azide, glucose deprivation, hydroxylamine, or phenylarsine oxide. Inhibition does not increase with exposure time and the inhibitory effects reverse within an hour. Inhibition does not appear to involve a reaction between curcumin and the thiol side chain of a cysteine residue since neither prior treatment of cells with iodoacetamide nor curcumin with cysteine alters curcumin's inhibitory effects. Curcumin is a mixed inhibitor reducing the Vmax of 2DG transport by about half with little effect on the Km. The inhibitory effects of curcumin are not additive to the effects of cytochalasin B and 75 μM curcumin actually reduces specific cytochalasin B binding by 80%. Taken together, the data suggest that curcumin binds directly to GLUT1 at a site that overlaps with the cytochalasin B binding site and thereby inhibits glucose transport. A direct inhibition of GLUT proteins in intestinal epithelial cells would likely reduce absorption of dietary glucose and contribute to a hypoglycemic effect of curcumin. Also, inhibition of GLUT1 activity might compromise cancer cells that overexpress GLUT1 and be another possible mechanism for the documented anticancer effects of curcumin. Copyright © 2016. Published by Elsevier B.V.

  15. Evaluation of the physical activity biography: sport and transport.

    Science.gov (United States)

    Rogen, Sandra; Hofmann, Peter; Bauernhofer, Thomas; Müller, Wolfram

    2014-05-01

    Beside the genetic disposition, physical activity (PA) is one of the major health factors and can play a large role in the prevention and therapy of many diseases (cardiovascular diseases, cancer, obesity-related diseases etc.). In contrast to the genetic disposition, PA can be deliberately influenced by lifestyle. Therefore, it is of high importance to assess PA patterns. In order to assess PA reliably and validly, a new questionnaire (Physical Activity Biography, PAB) was created. The PAB assesses recreational PA (sport and transport) and enables to distinguish between endurance intensity levels and considers strength and high speed activity patterns throughout life. This study aims to evaluate the PAB by means of item analysis, retest-reliability and validity (criteria were physical fitness assessed by the questionnaire FFB-mot and by exercise tests). 141 participants answered the PAB. For deriving retest-reliability, 81 participants completed the PAB after a retest-interval of one month again. 55 participated in exercise tests and answered the FFB-mot to determine construct validity. Retest-reliability (ICC) above 0.7 was found for most items. For the items assessing recent PA, the criteria of convergent and discriminant validity were given. Despite the complexity of the question under study, the results fulfilled the expectations concerning reliability and validity. The PAB enables to assess the amount of sport and locomotion a person has accomplished during different life time frames and, because of the protective effects of PA on various diseases, may become an important tool for risk assessment. Key pointsThe risk of chronic diseases depends largely on physical activity biography.A new questionnaire (PAB) assessing recent and lifetime physical activity was created.The PAB assesses physical activity during sports and transport.The results of the evaluation of the PAB fulfilled the expectations.The PAB enables to determine a person's amount of recreational

  16. Dopamine Transporter Activity Is Modulated by α-Synuclein.

    Science.gov (United States)

    Butler, Brittany; Saha, Kaustuv; Rana, Tanu; Becker, Jonas P; Sambo, Danielle; Davari, Paran; Goodwin, J Shawn; Khoshbouei, Habibeh

    2015-12-04

    The duration and strength of the dopaminergic signal are regulated by the dopamine transporter (DAT). Drug addiction and neurodegenerative and neuropsychiatric diseases have all been associated with altered DAT activity. The membrane localization and the activity of DAT are regulated by a number of intracellular proteins. α-Synuclein, a protein partner of DAT, is implicated in neurodegenerative disease and drug addiction. Little is known about the regulatory mechanisms of the interaction between DAT and α-synuclein, the cellular location of this interaction, and the functional consequences of this interaction on the basal, amphetamine-induced DAT-mediated dopamine efflux, and membrane microdomain distribution of the transporter. Here, we found that the majority of DAT·α-synuclein protein complexes are found at the plasma membrane of dopaminergic neurons or mammalian cells and that the amphetamine-mediated increase in DAT activity enhances the association of these proteins at the plasma membrane. Further examination of the interaction of DAT and α-synuclein revealed a transient interaction between these two proteins at the plasma membrane. Additionally, we found DAT-induced membrane depolarization enhances plasma membrane localization of α-synuclein, which in turn increases dopamine efflux and enhances DAT localization in cholesterol-rich membrane microdomains.

  17. Artemisinin inhibits chloroplast electron transport activity: mode of action.

    Directory of Open Access Journals (Sweden)

    Adyasha Bharati

    Full Text Available Artemisinin, a secondary metabolite produced in Artemisia plant species, besides having antimalarial properties is also phytotoxic. Although, the phytotoxic activity of the compound has been long recognized, no information is available on the mechanism of action of the compound on photosynthetic activity of the plant. In this report, we have evaluated the effect of artemisinin on photoelectron transport activity of chloroplast thylakoid membrane. The inhibitory effect of the compound, under in vitro condition, was pronounced in loosely and fully coupled thylakoids; being strong in the former. The extent of inhibition was drastically reduced in the presence of uncouplers like ammonium chloride or gramicidin; a characteristic feature described for energy transfer inhibitors. The compound, on the other hand, when applied to plants (in vivo, behaved as a potent inhibitor of photosynthetic electron transport. The major site of its action was identified to be the Q(B; the secondary quinone moiety of photosystemII complex. Analysis of photoreduction kinetics of para-benzoquinone and duroquinone suggest that the inhibition leads to formation of low pool of plastoquinol, which becomes limiting for electron flow through photosystemI. Further it was ascertained that the in vivo inhibitory effect appeared as a consequence of the formation of an unidentified artemisinin-metabolite rather than by the interaction of the compound per se. The putative metabolite of artemisinin is highly reactive in instituting the inhibition of photosynthetic electron flow eventually reducing the plant growth.

  18. Promoting physical activity and reducing climate change : Opportunities to replace short car trips with active transportation

    NARCIS (Netherlands)

    Maibach, E.; Steg, L.; Anable, J.

    2009-01-01

    Automobile use is a significant contributor to climate change, local air pollution, pedestrian injuries and deaths, declines in physical activity and obesity. A significant proportion of car use is for short trips that can relatively easily be taken with active transportation options - walking or

  19. CFD Model of Water Droplet Transport for ISS Hygiene Activity

    Science.gov (United States)

    Son, Chang H.

    2011-01-01

    The goal of the study is to assess the impacts of free water propagation in the Waste and Hygiene Compartment (WHC). Free water can be generated inside the WHC in small quantities due to crew hygiene activity. To mitigate potential impact of free water in Node 3 cabin the WHC doorway is enclosed by a waterproof bump-out, Kabin, with openings at the top and bottom. At the overhead side of the rack, there is a screen that prevents large drops of water from exiting. However, as the avionics fan in the WHC causes airflow toward the deck side of the rack, small quantities of free water may exit at the bottom of the Kabin. A Computational Fluid Dynamics (CFD) analysis of Node 3 cabin airflow made possible to identify the paths of water transport. The Node 3 airflow was computed for several ventilation scenarios. To simulate the droplet transport the Lagrangian discrete phase approach was used. Various initial droplet distributions were considered in the study. The droplet diameter was varied in the range of 2-20 mm. The results of the computations showed that most of the drops fall to the rack surface not far from the WHC curtain. The probability of the droplet transport to the adjacent rack surface with electronic equipment was predicted.

  20. Oscillations and multiple steady states in active membrane transport models.

    Science.gov (United States)

    Vieira, F M; Bisch, P M

    1994-01-01

    The dynamic behavior of some non-linear extensions of the six-state alternating access model for active membrane transport is investigated. We use stoichio-metric network analysis to study the stability of steady states. The bifurcation analysis has been done through standard numerical methods. For the usual six-state model we have proved that there is only one steady state, which is globally asymptotically stable. When we added an autocatalytic step we found self-oscillations. For the competition between a monomer cycle and a dimer cycle, with steps of dimer formation, we have also found self-oscillations. We have also studied models involving the formation of a complex with other molecules. The addition of two steps for formation of a complex of the monomer with another molecule does not alter either the number or the stability of steady states of the basic six-state model. The model which combines the formation of a complex with an autocatalytic step shows both self-oscillations and multiple steady states. The results lead us to conclude that oscillations could be produced by active membrane transport systems if the transport cycle contains a sufficiently large number of steps (six in the present case) and is coupled to at least one autocatalytic reaction,. Oscillations are also predicted when the monomer cycle is coupled to a dimer cycle. In fact, the autocatalytic reaction can be seen as a simplification of the model involving competition between monomer and dimer cycles, which seems to be a more realistic description of biological systems. A self-regulation mechanism of the pumps, related to the multiple stationary states, is expected only for a combined effect of autocatalysis and formation of complexes with other molecules. Within the six-state model this model also leads to oscillation.

  1. Assessing Barriers and Motivators for Use of a Trail for Active Transportation in a College Town

    OpenAIRE

    FitzPatrick, Timothy Michael

    2017-01-01

    A high amount of the US population is not physically active, contributing to rates of heart disease and obesity. One strategy to increase physical activity is to use more active transportation, defined as walking or biking for transit. Besides increasing physical activity levels, active transportation can provide other benefits such as decreased air pollution from cars. College campuses provide opportunities for active transportation as most residences are close to campus. Therefore, we exami...

  2. Socioeconomic and regional differences in active transportation in Brazil

    Directory of Open Access Journals (Sweden)

    Thiago Hérick de Sá

    2016-01-01

    Full Text Available ABSTRACT OBJECTIVE To present national estimates regarding walking or cycling for commuting in Brazil and in 10 metropolitan regions. METHODS By using data from the Health section of 2008’s Pesquisa Nacional por Amostra de Domicílio (Brazil’s National Household Sample Survey, we estimated how often employed people walk or cycle to work, disaggregating our results by sex, age range, education level, household monthly income per capita, urban or rural address, metropolitan regions, and macro-regions in Brazil. Furthermore, we estimated the distribution of this same frequency according to quintiles of household monthly income per capita in each metropolitan region of the country. RESULTS A third of the employed men and women walk or cycle from home to work in Brazil. For both sexes, this share decreases as income and education levels rise, and it is higher among younger individuals, especially among those living in rural areas and in the Northeast region of the country. Depending on the metropolitan region, the practice of active transportation is two to five times more frequent among low-income individuals than among high-income individuals. CONCLUSIONS Walking or cycling to work in Brazil is most frequent among low-income individuals and the ones living in less economically developed areas. Active transportation evaluation in Brazil provides important information for public health and urban mobility policy-making

  3. Coupled ATPase-adenylate kinase activity in ABC transporters

    Science.gov (United States)

    Kaur, Hundeep; Lakatos-Karoly, Andrea; Vogel, Ramona; Nöll, Anne; Tampé, Robert; Glaubitz, Clemens

    2016-01-01

    ATP-binding cassette (ABC) transporters, a superfamily of integral membrane proteins, catalyse the translocation of substrates across the cellular membrane by ATP hydrolysis. Here we demonstrate by nucleotide turnover and binding studies based on 31P solid-state NMR spectroscopy that the ABC exporter and lipid A flippase MsbA can couple ATP hydrolysis to an adenylate kinase activity, where ADP is converted into AMP and ATP. Single-point mutations reveal that both ATPase and adenylate kinase mechanisms are associated with the same conserved motifs of the nucleotide-binding domain. Based on these results, we propose a model for the coupled ATPase-adenylate kinase mechanism, involving the canonical and an additional nucleotide-binding site. We extend these findings to other prokaryotic ABC exporters, namely LmrA and TmrAB, suggesting that the coupled activities are a general feature of ABC exporters. PMID:28004795

  4. Adult active transport in the Netherlands: an analysis of its contribution to physical activity requirements.

    Directory of Open Access Journals (Sweden)

    Elliot Fishman

    Full Text Available Modern, urban lifestyles have engineered physical activity out of everyday life and this presents a major threat to human health. The Netherlands is a world leader in active travel, particularly cycling, but little research has sought to quantify the cumulative amount of physical activity through everyday walking and cycling.Using data collected as part of the Dutch National Travel Survey (2010 - 2012, this paper determines the degree to which Dutch walking and cycling contributes to meeting minimum level of physical activity of 150 minutes of moderate intensity aerobic activity throughout the week. The sample includes 74,465 individuals who recorded at least some travel on the day surveyed. As physical activity benefits are cumulative, all walking and cycling trips are analysed, including those to and from public transport. These trips are then converted into an established measure of physical activity intensity, known as metabolic equivalents of tasks. Multivariate Tobit regression models were performed on a range of socio-demographic, transport resources, urban form and meteorological characteristics.The results reveal that Dutch men and women participate in 24 and 28 minutes of daily physical activity through walking and cycling, which is 41% and 55% more than the minimum recommended level. It should be noted however that some 57% of the entire sample failed to record any walking or cycling, and an investigation of this particular group serves as an important topic of future research. Active transport was positively related with age, income, bicycle ownership, urban density and air temperature. Car ownership had a strong negative relationship with physically active travel.The results of this analysis demonstrate the significance of active transport to counter the emerging issue of sedentary lifestyle disease. The Dutch experience provides other countries with a highly relevant case study in the creation of environments and cultures that

  5. Body Composition, Physical Activity and Active Transportation in Adolescents of Metropolitan Region of Curitiba, Brazil

    Directory of Open Access Journals (Sweden)

    Leandra Ulbrict

    2014-06-01

    Full Text Available Background: Physical activity is a part of a healthy lifestyle, however sed entary habits are currently prevalent among adolescents which impacts rates of overweight and obesity in this group. This study aims to describe the relationship of physical activity with the use of active transportation to school (ATS and its relationshi p with body composition in adolescents. Materials and Methods: Information about physical activity, sedentary behavior and active transportation were collected through two survey instruments, one completed by a responsible parent/guardian and other by the adolescent. Body composition was assessed by dual - energy x - ray absorptiometry (DXA. Excess body fat was defined as ≥ 25% in male and ≥ 30% among female adolescents. Less than 60 minutes of moderate to vigorous daily physical activity defined one as sede ntary and greater than 2 hours of screen time per day was defined as excessive. Results: The prevalence of excess body fat was 46.5%. Only 24.7% of the sample performed recommended amounts of physical activity and 92.3% engaged in excess screen time. Appro ximately one - fifth of our sample (19.2% used ATS. The main barriers to active transport were traffic, distance and safety. Those that used ATS had lower body fat and fewer hours of sedentary behavior.

  6. Variability and seasonality of active transportation in USA: evidence from the 2001 NHTS

    Directory of Open Access Journals (Sweden)

    Bingham C Raymond

    2011-09-01

    Full Text Available Abstract Background Active transportation including walking and bicycling is an important source of physical activity. Promoting active transportation is a challenge for the fields of public health and transportation. Descriptive data on the predictors of active transportation, including seasonal patterns in active transportation in the US as a whole, is needed to inform interventions and policies. Methods This study analyzed monthly variation in active transportation for the US using National Household Travel Survey 2001 data. For each age group of children, adolescents, adults and elderly, logistic regression models were used to identify predictors of the odds of active transportation including gender, race/ethnicity, household income level, geographical region, urbanization level, and month. Results The probability of engaging in active transportation was generally higher for children and adolescents than for adults and the elderly. Active transportation was greater in the lower income groups (except in the elderly, was lower in the South than in other regions of the US, and was greater in areas with higher urbanization. The percentage of people using active transportation exhibited clear seasonal patterns: high during summer months and low during winter months. Children and adolescents were more sensitive to seasonality than other age groups. Women, non-Caucasians, persons with lower household income, who resided in the Midwest or Northeast, and who lived in more urbanized areas had greater seasonal variation. Conclusions These descriptive results suggest that interventions and policies that target the promotion of active transportation need to consider socio-demographic factors and seasonality.

  7. Active transport and obesity prevention - A transportation sector obesity impact scoping review and assessment for Melbourne, Australia.

    Science.gov (United States)

    Brown, V; Moodie, M; Mantilla Herrera, A M; Veerman, J L; Carter, R

    2017-03-01

    Given the alarming prevalence of obesity worldwide and the need for interventions to halt the growing epidemic, more evidence on the role and impact of transport interventions for obesity prevention is required. This study conducts a scoping review of the current evidence of association between modes of transport (motor vehicle, walking, cycling and public transport) and obesity-related outcomes. Eleven reviews and thirty-three primary studies exploring associations between transport behaviours and obesity were identified. Cohort simulation Markov modelling was used to estimate the effects of body mass index (BMI) change on health outcomes and health care costs of diseases causally related to obesity in the Melbourne, Australia population. Results suggest that evidence for an obesity effect of transport behaviours is inconclusive (29% of published studies reported expected associations, 33% mixed associations), and any potential BMI effect is likely to be relatively small. Hypothetical scenario analyses suggest that active transport interventions may contribute small but significant obesity-related health benefits across populations (approximately 65 health adjusted life years gained per year). Therefore active transport interventions that are low cost and targeted to those most amenable to modal switch are the most likely to be effective and cost-effective from an obesity prevention perspective. The uncertain but potentially significant opportunity for health benefits warrants the collection of more and better quality evidence to fully understand the potential relationships between transport behaviours and obesity. Such evidence would contribute to the obesity prevention dialogue and inform policy across the transportation, health and environmental sectors.

  8. Thermally activated charge transport in microbial protein nanowires.

    Science.gov (United States)

    Lampa-Pastirk, Sanela; Veazey, Joshua P; Walsh, Kathleen A; Feliciano, Gustavo T; Steidl, Rebecca J; Tessmer, Stuart H; Reguera, Gemma

    2016-03-24

    The bacterium Geobacter sulfurreducens requires the expression of conductive protein filaments or pili to respire extracellular electron acceptors such as iron oxides and uranium and to wire electroactive biofilms, but the contribution of the protein fiber to charge transport has remained elusive. Here we demonstrate efficient long-range charge transport along individual pili purified free of metal and redox organic cofactors at rates high enough to satisfy the respiratory rates of the cell. Carrier characteristics were within the orders reported for organic semiconductors (mobility) and inorganic nanowires (concentration), and resistivity was within the lower ranges reported for moderately doped silicon nanowires. However, the pilus conductance and the carrier mobility decreased when one of the tyrosines of the predicted axial multistep hopping path was replaced with an alanine. Furthermore, low temperature scanning tunneling microscopy demonstrated the thermal dependence of the differential conductance at the low voltages that operate in biological systems. The results thus provide evidence for thermally activated multistep hopping as the mechanism that allows Geobacter pili to function as protein nanowires between the cell and extracellular electron acceptors.

  9. Hypoxia inhibits colonic ion transport via activation of AMP kinase.

    LENUS (Irish Health Repository)

    Collins, Danielle

    2012-02-01

    BACKGROUND AND AIMS: Mucosal hypoxia is a common endpoint for many pathological processes including ischemic colitis, colonic obstruction and anastomotic failure. Previous studies suggest that hypoxia modulates colonic mucosal function through inhibition of chloride secretion. However, the molecular mechanisms underlying this observation are poorly understood. AMP-activated protein kinase (AMPK) is a metabolic energy regulator found in a wide variety of cells and has been linked to cystic fibrosis transmembrane conductance regulator (CFTR) mediated chloride secretion in several different tissues. We hypothesized that AMPK mediates many of the acute effects of hypoxia on human and rat colonic electrolyte transport. METHODS: The fluorescent chloride indicator dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide was used to measure changes in intracellular chloride concentrations in isolated single rat colonic crypts. Ussing chamber experiments in human colonic mucosa were conducted to evaluate net epithelial ion transport. RESULTS: This study demonstrates that acute hypoxia inhibits electrogenic chloride secretion via AMPK mediated inhibition of CFTR. Pre-treatment of tissues with the AMPK inhibitor 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo [1,5-a] pyrimidine (compound C) in part reversed the effects of acute hypoxia on chloride secretion. CONCLUSION: We therefore suggest that AMPK is a key component of the adaptive cellular response to mucosal hypoxia in the colon. Furthermore, AMPK may represent a potential therapeutic target in diseased states or in prevention of ischemic intestinal injury.

  10. Measuring the performance of multi-agency programmatic permits for Washington State Department of Transportation activities

    OpenAIRE

    2005-01-01

    In 2001, the Washington State Legislature established the Transportation Permit Efficiency and Accountability Committee (TPEAC) to identify measures to streamline permit procedures for transportation activities and improve environmental outcomes. A programmatic subcommittee was created to develop a multi-agency approach for developing programmatic permits that would cover 60 to 70 percent of Washington State Department of Transportation (WSDOT) activities (mostly maintenance and preservation ...

  11. Reliability and validity of the transport and physical activity questionnaire (TPAQ for assessing physical activity behaviour.

    Directory of Open Access Journals (Sweden)

    Emma J Adams

    Full Text Available BACKGROUND: No current validated survey instrument allows a comprehensive assessment of both physical activity and travel behaviours for use in interdisciplinary research on walking and cycling. This study reports on the test-retest reliability and validity of physical activity measures in the transport and physical activity questionnaire (TPAQ. METHODS: The TPAQ assesses time spent in different domains of physical activity and using different modes of transport for five journey purposes. Test-retest reliability of eight physical activity summary variables was assessed using intra-class correlation coefficients (ICC and Kappa scores for continuous and categorical variables respectively. In a separate study, the validity of three survey-reported physical activity summary variables was assessed by computing Spearman correlation coefficients using accelerometer-derived reference measures. The Bland-Altman technique was used to determine the absolute validity of survey-reported time spent in moderate-to-vigorous physical activity (MVPA. RESULTS: In the reliability study, ICC for time spent in different domains of physical activity ranged from fair to substantial for walking for transport (ICC = 0.59, cycling for transport (ICC = 0.61, walking for recreation (ICC = 0.48, cycling for recreation (ICC = 0.35, moderate leisure-time physical activity (ICC = 0.47, vigorous leisure-time physical activity (ICC = 0.63, and total physical activity (ICC = 0.56. The proportion of participants estimated to meet physical activity guidelines showed acceptable reliability (k = 0.60. In the validity study, comparison of survey-reported and accelerometer-derived time spent in physical activity showed strong agreement for vigorous physical activity (r = 0.72, p<0.001, fair but non-significant agreement for moderate physical activity (r = 0.24, p = 0.09 and fair agreement for MVPA (r = 0.27, p = 0.05. Bland

  12. Safety and Health Perceptions in Work-related Transport Activities in Ghanaian Industries

    Directory of Open Access Journals (Sweden)

    Charles Atombo

    2017-06-01

    Conclusion: OSH culture is not fully complied in industries transport activities. This study, therefore, supports the use of safety seminars and training sessions for industry workers responsible for transport operations for better integration of safety standards.

  13. The Influence of Urban Land-Use and Public Transport Facilities on Active Commuting in Wellington, New Zealand: Active Transport Forecasting Using the WILUTE Model

    Directory of Open Access Journals (Sweden)

    Joreintje Dingena Mackenbach

    2016-03-01

    Full Text Available Physical activity has numerous physical and mental health benefits, and active commuting (walking or cycling to work can help meet physical activity recommendations. This study investigated socioeconomic differences in active commuting, and assessed the impact of urban land-use and public transport policies on active commuting in the Wellington region in New Zealand. We combined data from the New Zealand Household Travel Survey and GIS data on land-use and public transport facilities with the Wellington Integrated Land-Use, Transportation and Environment (WILUTE model, and forecasted changes in active commuter trips associated with changes in the built environment. Results indicated high income individuals were more likely to commute actively than individuals on low income. Several land-use and transportation factors were associated with active commuting and results from the modelling showed a potential increase in active commuting following an increase in bus frequency and parking fees. In conclusion, regional level policies stimulating environmental factors that directly or indirectly affect active commuting may be a promising strategy to increase population level physical activity. Access to, and frequency of, public transport in the neighbourhood can act as a facilitator for a more active lifestyle among its residents without negatively affecting disadvantaged groups.

  14. Uterine activity, sperm transport, and the role of boar stimuli around insemination in sows

    NARCIS (Netherlands)

    Langendijk, P.; Soede, N.M.; Kemp, B.

    2005-01-01

    This paper describes changes in spontaneous myometrial activity around estrus, factors that affect myometrial activity, and the possible role of uterine contractions in the process of (artificial) insemination, sperm transport and fertilization. Myometrial activity in the sow increases during estrus

  15. Evaluation of the Physical Activity Biography: Sport and Transport

    Directory of Open Access Journals (Sweden)

    Sandra Rogen

    2014-06-01

    Full Text Available Beside the genetic disposition, physical activity (PA is one of the major health factors and can play a large role in the prevention and therapy of many diseases (cardiovascular diseases, cancer, obesity-related diseases etc.. In contrast to the genetic disposition, PA can be deliberately influenced by lifestyle. Therefore, it is of high importance to assess PA patterns. In order to assess PA reliably and validly, a new questionnaire (Physical Activity Biography, PAB was created. The PAB assesses recreational PA (sport and transport and enables to distinguish between endurance intensity levels and considers strength and high speed activity patterns throughout life. This study aims to evaluate the PAB by means of item analysis, retest-reliability and validity (criteria were physical fitness assessed by the questionnaire FFB-mot and by exercise tests. 141 participants answered the PAB. For deriving retest-reliability, 81 participants completed the PAB after a retest-interval of one month again. 55 participated in exercise tests and answered the FFB-mot to determine construct validity. Retest-reliability (ICC above 0.7 was found for most items. For the items assessing recent PA, the criteria of convergent and discriminant validity were given. Despite the complexity of the question under study, the results fulfilled the expectations concerning reliability and validity. The PAB enables to assess the amount of sport and locomotion a person has accomplished during different life time frames and, because of the protective effects of PA on various diseases, may become an important tool for risk assessment.

  16. Adolescents who engage in active school transport are also more active in other contexts

    DEFF Research Database (Denmark)

    Stewart, Tom; Duncan, Scott; Schipperijn, Jasper

    2017-01-01

    and travel behaviours across time- and space-classified domains. METHODS: A total of 196 adolescents wore a Global Positioning System receiver and an accelerometer for 7 days. All data were classified into one of four domains: home, school, transport, or leisure. Generalized linear mixed models were used......BACKGROUND: Although active school travel (AST) is important for increasing moderate-to-vigorous physical activity (MVPA), it is unclear how AST is related to context-specific physical activity and non-school travel. This study investigated how school travel is related to physical activity...... to compare domain-specific PA and non-school trips between active and passive school travellers. RESULTS: Active travellers accumulated 13 and 14 more min of MVPA on weekdays and weekend days, respectively. They also spent 15min less time in vehicular travel during non-school trips, and accrued an additional...

  17. The Association between Access to Public Transportation and Self-Reported Active Commuting

    Directory of Open Access Journals (Sweden)

    Sune Djurhuus

    2014-12-01

    Full Text Available Active commuting provides routine-based regular physical activity which can reduce the risk of chronic diseases. Using public transportation involves some walking or cycling to a transit stop, transfers and a walk to the end location and users of public transportation have been found to accumulate more moderate physical activity than non-users. Understanding how public transportation characteristics are associated with active transportation is thus important from a public health perspective. This study examines the associations between objective measures of access to public transportation and self-reported active commuting. Self-reported time spent either walking or cycling commuting each day and the distance to workplace were obtained for adults aged 16 to 65 in the Danish National Health Survey 2010 (n = 28,928. Access to public transportation measures were computed by combining GIS-based road network distances from home address to public transit stops an integrating their service level. Multilevel logistic regression was used to examine the association between access to public transportation measures and active commuting. Distance to bus stop, density of bus stops, and number of transport modes were all positively associated with being an active commuter and with meeting recommendations of physical activity. No significant association was found between bus services at the nearest stop and active commuting. The results highlight the importance of including detailed measurements of access to public transit in order to identify the characteristics that facilitate the use of public transportation and active commuting.

  18. BicaudalD actively regulates microtubule motor activity in lipid droplet transport.

    Directory of Open Access Journals (Sweden)

    Kristoffer S Larsen

    Full Text Available BACKGROUND: A great deal of sub-cellular organelle positioning, and essentially all minus-ended organelle transport, depends on cytoplasmic dynein, but how dynein's function is regulated is not well understood. BicD is established to play a critical role in mediating dynein function-loss of BicD results in improperly localized nuclei, mRNA particles, and a dispersed Golgi apparatus-however exactly what BicD's role is remains unknown. Nonetheless, it is widely believed that BicD may act to tether dynein to cargos. Here we use a combination of biophysical and biochemical studies to investigate BicD's role in lipid droplet transport during Drosophila embryogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Functional loss of BicD impairs the embryo's ability to control the net direction of droplet transport; the developmentally controlled reversal in transport is eliminated. We find that minimal BicD expression (near-BicD(null decreases the average run length of both plus and minus end directed microtubule (MT based transport. A point mutation affecting the BicD N-terminus has very similar effects on transport during cellularization (phase II, but in phase III (gastrulation motion actually appears better than in the wild-type. CONCLUSIONS/SIGNIFICANCE: In contrast to a simple static tethering model of BicD function, or a role only in initial dynein recruitment to the cargo, our data uncovers a new dynamic role for BicD in actively regulating transport. Lipid droplets move bi-directionally, and our investigations demonstrate that BicD plays a critical-and temporally changing-role in balancing the relative contributions of plus-end and minus-end motors to control the net direction of transport. Our results suggest that while BicD might contribute to recruitment of dynein to the cargo it is not absolutely required for such dynein localization, and it clearly contributes to regulation, helping activation/inactivation of the motors.

  19. Regulation of dopamine transporter activity by carboxypeptidase E

    Directory of Open Access Journals (Sweden)

    Zhang Heping

    2009-05-01

    Full Text Available Abstract Background The dopamine transporter (DAT plays a critical role in terminating the action of dopamine by rapid reuptake into the presynaptic neuron. Previous studies have revealed that the DAT carboxyl terminus (DAT-CT can directly interact with other cellular proteins and regulate DAT function and trafficking. Results Here, we have identified that carboxypeptidase E (CPE, a prohormone processing exopeptidase and sorting receptor for the regulated secretory pathway, interacts with the DAT-CT and affects DAT function. Mammalian cell lines coexpressing CPE and DAT exhibited increased DAT-mediated dopamine uptake activity compared to cells expressing DAT alone. Moreover, coexpression of an interfering DAT-CT minigene inhibited the effects of CPE on DAT. Functional changes caused by CPE could be attributed to enhanced DAT expression and subsequent increase in DAT cell surface localization, due to decreased DAT degradation. In addition, CPE association could reduce the phosphorylation state of DAT on serine residues, potentially leading to reduced internalization, thus stabilizing plasmalemmal DAT localization. Conclusion Taken together, our results reveal a novel role for CPE in the regulation of DAT trafficking and DAT-mediated DA uptake, which may provide a novel target in the treatment of dopamine-governed diseases such as drug addiction and obesity.

  20. Phosphorylation regulates NCC stability and transporter activity in vivo.

    Science.gov (United States)

    Yang, Sung-Sen; Fang, Yu-Wei; Tseng, Min-Hua; Chu, Pei-Yi; Yu, I-Shing; Wu, Han-Chung; Lin, Shu-Wha; Chau, Tom; Uchida, Shinichi; Sasaki, Sei; Lin, Yuh-Feng; Sytwu, Huey-Kang; Lin, Shih-Hua

    2013-10-01

    A T60M mutation in the thiazide-sensitive sodium chloride cotransporter (NCC) is common in patients with Gitelman's syndrome (GS). This mutation prevents Ste20-related proline and alanine-rich kinase (SPAK)/oxidative stress responsive kinase-1 (OSR1)-mediated phosphorylation of NCC and alters NCC transporter activity in vitro. Here, we examined the physiologic effects of NCC phosphorylation in vivo using a novel Ncc T58M (human T60M) knock-in mouse model. Ncc(T58M/T58M) mice exhibited typical features of GS with a blunted response to thiazide diuretics. Despite expressing normal levels of Ncc mRNA, these mice had lower levels of total Ncc and p-Ncc protein that did not change with a low-salt diet that increased p-Spak. In contrast to wild-type Ncc, which localized to the apical membrane of distal convoluted tubule cells, T58M Ncc localized primarily to the cytosolic region and caused an increase in late distal convoluted tubule volume. In MDCK cells, exogenous expression of phosphorylation-defective NCC mutants reduced total protein expression levels and membrane stability. Furthermore, our analysis found diminished total urine NCC excretion in a cohort of GS patients with homozygous NCC T60M mutations. When Wnk4(D561A/+) mice, a model of pseudohypoaldosteronism type II expressing an activated Spak/Osr1-Ncc, were crossed with Ncc(T58M/T58M) mice, total Ncc and p-Ncc protein levels decreased and the GS phenotype persisted over the hypertensive phenotype. Overall, these data suggest that SPAK-mediated phosphorylation of NCC at T60 regulates NCC stability and function, and defective phosphorylation at this residue corrects the phenotype of pseudohypoaldosteronism type II.

  1. Individual, Social, and Environmental Correlates of Active Transportation Patterns in French Women

    Directory of Open Access Journals (Sweden)

    Camille Perchoux

    2017-01-01

    Full Text Available The objectives were (1 to define physical activity (PA and sedentary behaviors (SB patterns in daily life contexts (work, leisure, and transportation in French working women from NutriNet-Santé web-cohort and (2 to identify pattern(s of active transportation and their individual, social, and environmental correlates. 23,432 participants completed two questionnaires to evaluate PA and SB in daily life contexts and individual representations of residential neighborhood and transportation modes. Hierarchical cluster analysis was performed which identified 6 distinct movement behavior patterns: (i active occupation, high sedentary leisure, (ii sedentary occupation, low leisure, (iii sedentary transportation, (iv sedentary occupation and leisure, (v active transportation, and (vi active leisure. Multinomial logistic regressions were performed to identify correlates of the “active transportation” cluster. The perceived environmental characteristics positively associated with “active transportation” included “high availability of destinations around home,” “presence of bicycle paths,” and “low traffic.” A “positive image of walking/cycling,” the “individual feeling of being physically active,” and a “high use of active transport modes by relatives/friends” were positively related to “active transportation,” identified as a unique pattern regarding individual and environmental correlates. Identification of PA and SB context-specific patterns will help to understand movement behaviors’ complexity and to design interventions to promote active transportation in specific subgroups.

  2. Effects of surfactants and thermodynamic activity of model active ingredient on transport over plant leaf cuticle.

    Science.gov (United States)

    Fagerström, Anton; Kocherbitov, Vitaly; Ruzgas, Tautgirdas; Westbye, Peter; Bergström, Karin; Engblom, Johan

    2013-03-01

    The main objective of this study was to investigate the mechanism of molecular transport across the cuticle of Clivia leaves. In vitro diffusion methodology was used to investigate the transport of a systemic fungicide, tebuconazole, over a model silicone membrane, enzymatically isolated cuticle membranes, and dermatomed leaves. It was shown that dermatomed leaves may replace enzymatically isolated cuticles. Furthermore, the effects of two surfactants, C(10)EO(7) and C(8)G(1.6), on the fungicide transport were investigated. Tebuconazole cuticle permeation was described using Fick's first law of diffusion, expressed by the thermodynamic activity of the solute in the membrane. A new method for calculation of diffusion coefficients in the membrane is proposed. To access the thermodynamic activity of the fungicide in the membranes, sorption isotherms of tebuconazole in the membrane materials studied were recorded. The thermodynamic activity of the fungicide in aqueous solutions was calculated from solubility data. For that purpose, the effect of surfactants on tebuconazole solubility was studied. The results show that addition of surfactants allows for higher concentrations of tebuconazole available for penetration. Nonetheless, at a fixed fungicide thermodynamic activity, all formulations produced the same flux over the silicone membrane independently on the fungicide concentration. This shows that the driving force across non-responding membranes is the gradient of thermodynamic activity, rather than the gradient of the fungicide concentration. In case of leaves, surfactants induced the same quantitative increase in both flux and diffusion coefficient of solute in the cuticle, while the cuticle-water partition coefficient was unaffected.

  3. Socioeconomic and regional differences in active transportation in Brazil.

    Science.gov (United States)

    Sá, Thiago Hérick de; Pereira, Rafael Henrique Moraes; Duran, Ana Clara; Monteiro, Carlos Augusto

    2016-06-27

    To present national estimates regarding walking or cycling for commuting in Brazil and in 10 metropolitan regions. By using data from the Health section of 2008's Pesquisa Nacional por Amostra de Domicílio (Brazil's National Household Sample Survey), we estimated how often employed people walk or cycle to work, disaggregating our results by sex, age range, education level, household monthly income per capita, urban or rural address, metropolitan regions, and macro-regions in Brazil. Furthermore, we estimated the distribution of this same frequency according to quintiles of household monthly income per capita in each metropolitan region of the country. A third of the employed men and women walk or cycle from home to work in Brazil. For both sexes, this share decreases as income and education levels rise, and it is higher among younger individuals, especially among those living in rural areas and in the Northeast region of the country. Depending on the metropolitan region, the practice of active transportation is two to five times more frequent among low-income individuals than among high-income individuals. Walking or cycling to work in Brazil is most frequent among low-income individuals and the ones living in less economically developed areas. Active transportation evaluation in Brazil provides important information for public health and urban mobility policy-making. Apresentar estimativas nacionais sobre o deslocamento a pé ou de bicicleta no trajeto casa-trabalho no Brasil e em 10 de suas regiões metropolitanas. Utilizando dados do Suplemento sobre Saúde da Pesquisa Nacional por Amostra de Domicílios de 2008, estimamos a frequência de pessoas empregadas que se deslocam a pé ou de bicicleta no trajeto casa-trabalho estratificada por sexo, e segundo faixa etária, escolaridade, renda domiciliar per capita, residência em área urbana ou rural, regiões metropolitanas e macrorregiões do país. Adicionalmente, estimamos a distribuição da mesma frequ

  4. Brucella abortus ure2 region contains an acid-activated urea transporter and a nickel transport system

    Directory of Open Access Journals (Sweden)

    García-Lobo Juan M

    2010-04-01

    Full Text Available Abstract Background Urease is a virulence factor that plays a role in the resistance of Brucella to low pH conditions, both in vivo and in vitro. Brucella contains two separate urease gene clusters, ure1 and ure2. Although only ure1 codes for an active urease, ure2 is also transcribed, but its contribution to Brucella biology is unknown. Results Re-examination of the ure2 locus showed that the operon includes five genes downstream of ureABCEFGDT that are orthologs to a nikKMLQO cluster encoding an ECF-type transport system for nickel. ureT and nikO mutants were constructed and analyzed for urease activity and acid resistance. A non-polar ureT mutant was unaffected in urease activity at neutral pH but showed a significantly decreased activity at acidic pH. It also showed a decreased survival rate to pH 2 at low concentration of urea when compared to the wild type. The nikO mutant had decreased urease activity and acid resistance at all urea concentrations tested, and this phenotype could be reverted by the addition of nickel to the growth medium. Conclusions Based on these results, we concluded that the operon ure2 codes for an acid-activated urea transporter and a nickel transporter necessary for the maximal activity of the urease whose structural subunits are encoded exclusively by the genes in the ure1 operon.

  5. What Moves Them? Active Transport among Inhabitants of Dutch Deprived Districts

    Directory of Open Access Journals (Sweden)

    Carla Saris

    2013-01-01

    Full Text Available Background. Active modes of transport like walking and cycling have been shown to be valuable contributions to daily physical activity. The current study investigates associations between personal and neighbourhood environmental characteristics and active transport among inhabitants of Dutch deprived districts. Method. Questionnaires about health, neighbourhoods, and physical activity behaviour were completed by 742 adults. Data was analysed by means of multivariate linear regression analyses. Results. Being younger, female, and migrant and having a normal weight were associated with more walking for active transport. Being younger, male, and native Dutch and having a normal weight were associated with more cycling for active transport. Neighbourhood characteristics were generally not correlated with active transport. Stratified analyses, based on significant person-environment interactions, showed that migrants and women walked more when cars did not exceed maximum speed in nearby streets and that younger people walked more when speed of traffic in nearby streets was perceived as low. Among migrants, more cycling was associated with the perceived attractiveness of the neighbourhood surroundings. Discussion and Conclusion. Results indicated that among inhabitants of Dutch deprived districts, personal characteristics were associated with active transport, whereas neighbourhood environmental characteristics were generally not associated with active transport. Nevertheless, interaction effects showed differences among subgroups that should be considered in intervention development.

  6. Glutamate transporter activity promotes enhanced Na+/K+-ATPase-mediated extracellular K+ management during neuronal activity

    DEFF Research Database (Denmark)

    Larsen, Brian Roland; Holm, Rikke; Vilsen, Bente;

    2016-01-01

    , in addition, Na+/K+-ATPase-mediated K+ clearance could be governed by astrocytic [Na+]i. During most neuronal activity, glutamate is released in the synaptic cleft and is re-absorbed by astrocytic Na+-coupled glutamate transporters, thereby elevating [Na+]i. It thus remains unresolved whether the different Na...... constellations in Xenopus oocytes and determined their apparent Na+ affinity in intact oocytes and isolated membranes. The Na+/K+-ATPase was not fully saturated at basal astrocytic [Na+]i, irrespective of isoform constellation, although the β1 subunit conferred lower apparent Na+ affinity to the α1 and α2...

  7. The Association between Access to Public Transportation and Self-Reported Active Commuting

    DEFF Research Database (Denmark)

    Djurhuus, Sune; Hansen, Henning S; Aadahl, Mette

    2014-01-01

    more moderate physical activity than non-users. Understanding how public transportation characteristics are associated with active transportation is thus important from a public health perspective. This study examines the associations between objective measures of access to public transportation...... and self-reported active commuting. Self-reported time spent either walking or cycling commuting each day and the distance to workplace were obtained for adults aged 16 to 65 in the Danish National Health Survey 2010 (n = 28,928). Access to public transportation measures were computed by combining GIS......-based road network distances from home address to public transit stops an integrating their service level. Multilevel logistic regression was used to examine the association between access to public transportation measures and active commuting. Distance to bus stop, density of bus stops, and number...

  8. Drug Transporter Expression and Activity in Human Hepatoma HuH-7 Cells

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    Elodie Jouan

    2016-12-01

    Full Text Available Human hepatoma cells may represent a valuable alternative to the use of human hepatocytes for studying hepatic drug transporters, which is now a regulatory issue during drug development. In the present work, we have characterized hepatic drug transporter expression, activity and regulation in human hepatoma HuH-7 cells, in order to determine the potential relevance of these cells for drug transport assays. HuH-7 cells displayed notable multidrug resistance-associated protein (MRP activity, presumed to reflect expression of various hepatic MRPs, including MRP2. By contrast, they failed to display functional activities of the uptake transporters sodium taurocholate co-transporting polypeptide (NTCP, organic anion-transporting polypeptides (OATPs and organic cation transporter 1 (OCT1, and of the canalicular transporters P-glycoprotein and breast cancer resistance protein (BCRP. Concomitantly, mRNA expressions of various sinusoidal and canalicular hepatic drug transporters were not detected (NTCP, OATP1B1, organic anion transporter 2 (OAT2, OCT1 and bile salt export pump or were found to be lower (OATP1B3, OATP2B1, multidrug and toxin extrusion protein 1, BCRP and MRP3 in hepatoma HuH-7 cells than those found in human hepatocytes, whereas other transporters such as OAT7, MRP4 and MRP5 were up-regulated. HuH-7 cells additionally exhibited farnesoid X receptor (FXR- and nuclear factor erythroid 2-related factor 2 (Nrf2-related up-regulation of some transporters. Such data indicate that HuH-7 cells, although expressing rather poorly some main hepatic drug transporters, may be useful for investigating interactions of drugs with MRPs, notably MRP2, and for studying FXR- or Nrf2-mediated gene regulation.

  9. A fully resolved active musculo-mechanical model for esophageal transport

    CERN Document Server

    Kou, Wenjun; Griffith, Boyce E; Pandolfino, John E; Kahrilas, Peter J; Patankar, Neelesh A

    2015-01-01

    Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multi-layered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, which is modeled as an actively contracting, fiber-reinforced tube. A simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are then extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation i...

  10. Canine amino acid transport system Xc(-): cDNA sequence, distribution and cystine transport activity in lens epithelial cells.

    Science.gov (United States)

    Maruo, Takuya; Kanemaki, Nobuyuki; Onda, Ken; Sato, Reiichiro; Ichihara, Nobuteru; Ochiai, Hideharu

    2014-04-01

    The cystine transport activity of a lens epithelial cell line originated from a canine mature cataract was investigated. The distinct cystine transport activity was observed, which was inhibited to 28% by extracellular 1 mM glutamate. The cDNA sequences of canine cysteine/glutamate exchanger (xCT) and 4F2hc were determined. The predicted amino acid sequences were 527 and 533 amino acid polypeptides, respectively. The amino acid sequences of canine xCT and 4F2hc showed high similarities (>80%) to those of humans. The expression of xCT in lens epithelial cell line was confirmed by western blot analysis. RT-PCR analysis revealed high level expression only in the brain, and it was below the detectable level in other tissues.

  11. Multimotor transport in a system of active and inactive kinesin-1 motors.

    Science.gov (United States)

    Scharrel, Lara; Ma, Rui; Schneider, René; Jülicher, Frank; Diez, Stefan

    2014-07-15

    Long-range directional transport in cells is facilitated by microtubule-based motor proteins. One example is transport in a nerve cell, where small groups of motor proteins, such as kinesins and cytoplasmic dynein, work together to ensure the supply and clearance of cellular material along the axon. Defects in axonal transport have been linked to Alzheimer's and other neurodegenerative diseases. However, it is not known in detail how multimotor-based cargo transport is impaired if a fraction of the motors are defective. To mimic impaired multimotor transport in vitro, we performed gliding motility assays with varying fractions of active kinesin-1 motors and inactive kinesin-1 motor mutants. We found that impaired transport manifests in multiple motility regimes: 1), a fast-motility regime characterized by gliding at velocities close to the single-molecule velocity of the active motors; 2), a slow-motility regime characterized by gliding at close-to zero velocity or full stopping; and 3), a regime in which fast and slow motilities coexist. Notably, the transition from the fast to the slow regime occurred sharply at a threshold fraction of active motors. Based on single-motor parameters, we developed a stochastic model and a mean-field theoretical description that explain our experimental findings. Our results demonstrate that impaired multimotor transport mostly occurs in an either/or fashion: depending on the ratio of active to inactive motors, transport is either performed at close to full speed or is out of action.

  12. Individual public transportation accessibility is positively associated with self-reported active commuting

    Directory of Open Access Journals (Sweden)

    Sune eDjurhuus

    2014-11-01

    Full Text Available Background: Active commuters have lower risk of chronic disease. Understanding which of the, to some extent, modifiable characteristics of public transportation that facilitate its use is thus important in a public health perspective. The aim of the study was to examine the association between individual public transportation accessibility and self-reported active commuting, and whether the associations varied with commute distance, age and gender. Methods: 28,928 commuters in the Capital Region of Denmark reported self-reported time spent either walking or cycling to work or study each day and the distance to work or study. Data were obtained from the Danish National Health Survey collected in February to April 2010. Individual accessibility by public transportation was calculated using a multimodal network in a GIS. Multilevel logistic regression was used to analyze the association between accessibility, expressed as access area, and being an active commuter.Results: Public transport accessibility area based on all stops within walking and cycling distance was positively associated with being an active commuter. Distance to work, age and gender modified the associations. Residing within 10 km commuting distance and in areas of high accessibility was associated with being an active commuter and meeting the recommendations of physical activity. For the respondents above 29 years, Individual public transportation accessibility was positively associated with being an active commuter. Women having high accessibility had significantly higher odds of being an active commuter compared to having a low accessibility. For men the associations were insignificant.Conclusions: This study extends the knowledge about the driving forces of using public transportation for commuting by examining the individual public transportation accessibility. Findings suggest that transportation accessibility supports active commuting and planning of improved public transit

  13. Inhibition of Human Drug Transporter Activities by the Pyrethroid Pesticides Allethrin and Tetramethrin.

    Science.gov (United States)

    Chedik, Lisa; Bruyere, Arnaud; Le Vee, Marc; Stieger, Bruno; Denizot, Claire; Parmentier, Yannick; Potin, Sophie; Fardel, Olivier

    2017-01-01

    Pyrethroids are widely-used chemical insecticides, to which humans are commonly exposed, and known to alter functional expression of drug metabolizing enzymes. Limited data have additionally suggested that drug transporters, that constitute key-actors of the drug detoxification system, may also be targeted by pyrethroids. The present study was therefore designed to analyze the potential regulatory effects of these pesticides towards activities of main ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, using transporter-overexpressing cells. The pyrethroids allethrin and tetramethrin were found to inhibit various ABC and SLC drug transporters, including multidrug resistance-associated protein (MRP) 2, breast cancer resistance protein (BCRP), organic anion transporter polypeptide (OATP) 1B1, organic anion transporter (OAT) 3, multidrug and toxin extrusion transporter (MATE) 1, organic cation transporter (OCT) 1 and OCT2, with IC50 values however ranging from 2.6 μM (OCT1 inhibition by allethrin) to 77.6 μM (OAT3 inhibition by tetramethrin) and thus much higher than pyrethroid concentrations (in the nM range) reached in environmentally pyrethroid-exposed humans. By contrast, allethrin and tetramethrin cis-stimulated OATP2B1 activity and failed to alter activities of OATP1B3, OAT1 and MATE2-K, whereas P-glycoprotein activity was additionally moderately inhibited. Twelve other pyrethoids used at 100 μM did not block activities of the various investigated transporters, or only moderately inhibited some of them (inhibition by less than 50%). In silico analysis of structure-activity relationships next revealed that molecular parameters, including molecular weight and lipophilicity, are associated with transporter inhibition by allethrin/tetramethrin and successfully predicted transporter inhibition by the pyrethroids imiprothrin and prallethrin. Taken together, these data fully demonstrated that two pyrethoids, i.e., allethrin and tetramethrin, can

  14. Inhibition of Human Drug Transporter Activities by the Pyrethroid Pesticides Allethrin and Tetramethrin

    Science.gov (United States)

    Chedik, Lisa; Bruyere, Arnaud; Le Vee, Marc; Stieger, Bruno; Denizot, Claire; Parmentier, Yannick; Potin, Sophie; Fardel, Olivier

    2017-01-01

    Pyrethroids are widely-used chemical insecticides, to which humans are commonly exposed, and known to alter functional expression of drug metabolizing enzymes. Limited data have additionally suggested that drug transporters, that constitute key-actors of the drug detoxification system, may also be targeted by pyrethroids. The present study was therefore designed to analyze the potential regulatory effects of these pesticides towards activities of main ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, using transporter-overexpressing cells. The pyrethroids allethrin and tetramethrin were found to inhibit various ABC and SLC drug transporters, including multidrug resistance-associated protein (MRP) 2, breast cancer resistance protein (BCRP), organic anion transporter polypeptide (OATP) 1B1, organic anion transporter (OAT) 3, multidrug and toxin extrusion transporter (MATE) 1, organic cation transporter (OCT) 1 and OCT2, with IC50 values however ranging from 2.6 μM (OCT1 inhibition by allethrin) to 77.6 μM (OAT3 inhibition by tetramethrin) and thus much higher than pyrethroid concentrations (in the nM range) reached in environmentally pyrethroid-exposed humans. By contrast, allethrin and tetramethrin cis-stimulated OATP2B1 activity and failed to alter activities of OATP1B3, OAT1 and MATE2-K, whereas P-glycoprotein activity was additionally moderately inhibited. Twelve other pyrethoids used at 100 μM did not block activities of the various investigated transporters, or only moderately inhibited some of them (inhibition by less than 50%). In silico analysis of structure-activity relationships next revealed that molecular parameters, including molecular weight and lipophilicity, are associated with transporter inhibition by allethrin/tetramethrin and successfully predicted transporter inhibition by the pyrethroids imiprothrin and prallethrin. Taken together, these data fully demonstrated that two pyrethoids, i.e., allethrin and tetramethrin, can

  15. Are characteristics of the school district associated with active transportation to school in Danish adolescents?

    DEFF Research Database (Denmark)

    Stock, Christiane; Bloomfield, Kim; Ejstrud, Bo;

    2012-01-01

    BACKGROUND: This study sought to determine the influence of individual factors on active transportation to school among Danish seventh graders and whether school district factors are associated with such behaviour independently of individual factors. METHODS: Mixed effects logistic regression...

  16. Dopamine Transporter Genotype Conveys Familial Risk of Attention-Deficit/Hyperactivity Disorder through Striatal Activation

    Science.gov (United States)

    Durston, Sarah; Fossella, John A.; Mulder, Martijn J.; Casey B. J.; Ziermans, Tim B.; Vessaz, M. Nathalie; Van Engeland, Herman

    2008-01-01

    The study examines the effect of the dopamine transporter (DAT1) genotype in attention-deficit/hyperactivity disorder (ADHD). The results confirm that DAT1 translates the genetic risk of ADHD through striatal activation.

  17. Dopamine Transporter Genotype Conveys Familial Risk of Attention-Deficit/Hyperactivity Disorder through Striatal Activation

    Science.gov (United States)

    Durston, Sarah; Fossella, John A.; Mulder, Martijn J.; Casey B. J.; Ziermans, Tim B.; Vessaz, M. Nathalie; Van Engeland, Herman

    2008-01-01

    The study examines the effect of the dopamine transporter (DAT1) genotype in attention-deficit/hyperactivity disorder (ADHD). The results confirm that DAT1 translates the genetic risk of ADHD through striatal activation.

  18. 76 FR 73020 - Agency Information Collection (Request for Transportation Expense Reimbursement): Activity Under...

    Science.gov (United States)

    2011-11-28

    ... unable to pursue training or employment without travel assistance. An agency may not conduct or sponsor... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF VETERANS AFFAIRS Agency Information Collection (Request for Transportation Expense Reimbursement): Activity...

  19. OPTIMIZATION METHOD AND SOFTWARE FOR FUEL COST REDUCTION IN CASE OF ROAD TRANSPORT ACTIVITY

    Directory of Open Access Journals (Sweden)

    György Kovács

    2017-06-01

    Full Text Available The transport activity is one of the most expensive processes in the supply chain and the fuel cost is the highest cost among the cost components of transportation. The goal of the research is to optimize the transport costs in case of a given transport task both by the selecting the optimal petrol station and by determining the optimal amount of the refilled fuel. Recently, in practice, these two decisions have not been made centrally at the forwarding company, but they depend on the individual decision of the driver. The aim of this study is to elaborate a precise and reliable mathematical method for selecting the optimal refuelling stations and determining the optimal amount of the refilled fuel to fulfil the transport demands. Based on the elaborated model, new decision-supporting software is developed for the economical fulfilment of transport trips.

  20. Ciprofloxacin Is Actively Transported across Bronchial Lung Epithelial Cells Using a Calu-3 Air Interface Cell Model

    Science.gov (United States)

    Ong, Hui Xin; Traini, Daniela; Bebawy, Mary

    2013-01-01

    Ciprofloxacin is a well-established broad-spectrum fluoroquinolone antibiotic that penetrates well into the lung tissues; still, the mechanisms of its transepithelial transport are unknown. The contributions of specific transporters, including multidrug efflux transporters, organic cation transporters, and organic anion-transporting polypeptide transporters, to the uptake of ciprofloxacin were investigated in vitro using an air interface bronchial epithelial model. Our results demonstrate that ciprofloxacin is subject to predominantly active influx and a slight efflux component. PMID:23507281

  1. Borreliacidal activity of Borrelia metal transporter A (BmtA binding small molecules by manganese transport inhibition

    Directory of Open Access Journals (Sweden)

    Wagh D

    2015-02-01

    Full Text Available Dhananjay Wagh,* Venkata Raveendra Pothineni,* Mohammed Inayathullah, Song Liu, Kwang-Min Kim, Jayakumar Rajadas Biomaterials and Advanced Drug Delivery Laboratory, Stanford Cardiovascular Pharmacology Division, Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, CA, USA *These authors contributed equally to this work  Abstract: Borrelia burgdorferi, the causative agent of Lyme disease, utilizes manganese (Mn for its various metabolic needs. We hypothesized that blocking Mn transporter could be a possible approach to inhibit metabolic activity of this pathogen and eliminate the infection. We used a combination of in silico protein structure prediction together with molecular docking to target the Borrelia metal transporter A (BmtA, a single known Mn transporter in Borrelia and screened libraries of FDA approved compounds that could potentially bind to the predicted BmtA structure with high affinity. Tricyclic antihistamines such as loratadine, desloratadine, and 3-hydroxydesloratadine as well as yohimbine and tadalafil demonstrated a tight binding to the in silico folded BmtA transporter. We, then, tested borreliacidal activity and dose response of the shortlisted compounds from this screen using a series of in vitro assays. Amongst the probed compounds, desloratadine exhibited potent borreliacidal activity in vitro at and above 78 µg/mL (250 µM. Borrelia treated with lethal doses of desloratadine exhibited a significant loss of intracellular Mn specifically and a severe structural damage to the bacterial cell wall. Our results support the possibility of developing a novel, targeted therapy to treat Lyme disease by targeting specific metabolic needs of Borrelia.  Keywords: Lyme disease, BmtA, Borrelia burgdorferi, desloratadine, Bac Titer-Glo assay

  2. Diagnosis of Transport Activity as a Component of the Enterprise Logistical System

    Directory of Open Access Journals (Sweden)

    Skrynkovskyy Ruslan M.

    2016-05-01

    Full Text Available The article reveals the essence of the concept of “diagnosis of the enterprise transport activity”, by which there should be meant a process of evaluating the state of movement (transportation, carrying of freight (material resources, work in process or finished products by one type of transport facilities or their combination in accordance with the applied transport system and trends of its changes as well as determining the future prospects on the basis of sound management decisions in order to ensure a successful operation and development of the enterprise in the competitive environment. It has been found that the key business-indicators of the diagnosis system of transport activity as a component of the enterprise logistical system are: the coefficient of timeliness of freight transportation (delivery; coefficient of completeness of transportation; coefficient of freight safety conditions; coefficient of efficiency of freight transportation; coefficient of complexity of servicing freight owners; coefficient of satisfaction of freight owners’ demand, coefficient of readiness to operation of transport facilities per working day; coefficient of using vehicle kilometers travelled; coefficient of extensity of transport facility packing.

  3. Active patterning and asymmetric transport in a model actomyosin network

    Science.gov (United States)

    Wang, Shenshen; Wolynes, Peter G.

    2013-12-01

    Cytoskeletal networks, which are essentially motor-filament assemblies, play a major role in many developmental processes involving structural remodeling and shape changes. These are achieved by nonequilibrium self-organization processes that generate functional patterns and drive intracellular transport. We construct a minimal physical model that incorporates the coupling between nonlinear elastic responses of individual filaments and force-dependent motor action. By performing stochastic simulations we show that the interplay of motor processes, described as driving anti-correlated motion of the network vertices, and the network connectivity, which determines the percolation character of the structure, can indeed capture the dynamical and structural cooperativity which gives rise to diverse patterns observed experimentally. The buckling instability of individual filaments is found to play a key role in localizing collapse events due to local force imbalance. Motor-driven buckling-induced node aggregation provides a dynamic mechanism that stabilizes the two-dimensional patterns below the apparent static percolation limit. Coordinated motor action is also shown to suppress random thermal noise on large time scales, the two-dimensional configuration that the system starts with thus remaining planar during the structural development. By carrying out similar simulations on a three-dimensional anchored network, we find that the myosin-driven isotropic contraction of a well-connected actin network, when combined with mechanical anchoring that confers directionality to the collective motion, may represent a novel mechanism of intracellular transport, as revealed by chromosome translocation in the starfish oocyte.

  4. Webcams, crowdsourcing, and enhanced crosswalks: Developing a novel method to analyze active transportation

    Directory of Open Access Journals (Sweden)

    J. Aaron eHipp

    2016-05-01

    Full Text Available Introduction: Active transportation opportunities and infrastructure are an important component of a community’s design, livability, and health. Features of the built environment influence active transportation, but objective study of the natural experiment effects of built environment improvements on active transportation is challenging. The purpose of this study was to develop and present a novel method of active transportation research using webcams and crowdsourcing, and to determine if crosswalk enhancement was associated with changes in active transportation rates, including across a variety of weather conditions. Methods: 20,529 publicly available webcam images from two street intersections in Washington, D.C., were used to examine the impact of an improved crosswalk on active transportation. A crowdsource, Amazon Mechanical Turk, annotated image data. Temperature data was collected from the National Oceanic and Atmospheric Administration, and precipitation data was annotated from images by trained research assistants. Results: Summary analyses demonstrated slight, bi-directional differences in the percent of images with pedestrians and bicyclists captured before and after the enhancement of the crosswalks. Chi-square analyses revealed these changes were not significant. In general, pedestrian presence increased in images captured during moderate temperatures compared to images captured during hot or cold temperatures. Chi-square analyses indicated the crosswalk improvement may have encouraged walking and biking in uncomfortable outdoor conditions (p<0.5. Conclusion: The methods employed provide an objective, cost-effective alternative to traditional means of examining the effects of built environment changes on active transportation. The use of webcams to collect active transportation data has applications for community policymakers, planners, and health professionals. Future research will work to validate this method in a variety of

  5. Stress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein

    Directory of Open Access Journals (Sweden)

    Eva Klinman

    2015-07-01

    Full Text Available Axonal transport is essential for neuronal function, and defects in transport are associated with multiple neurodegenerative diseases. Aberrant cyclin-dependent kinase 5 (CDK5 activity, driven by the stress-induced activator p25, also is observed in these diseases. Here we show that elevated CDK5 activity increases the frequency of nonprocessive events for a range of organelles, including lysosomes, autophagosomes, mitochondria, and signaling endosomes. Transport disruption induced by aberrant CDK5 activation depends on the Lis1/Ndel1 complex, which directly regulates dynein activity. CDK5 phosphorylation of Ndel1 favors a high affinity Lis1/Ndel/dynein complex that blocks the ATP-dependent release of dynein from microtubules, inhibiting processive motility of dynein-driven cargo. Similar transport defects observed in neurons from a mouse model of amyotrophic lateral sclerosis are rescued by CDK5 inhibition. Together, these studies identify CDK5 as a Lis1/Ndel1-dependent regulator of transport in stressed neurons, and suggest that dysregulated CDK5 activity contributes to the transport deficits observed during neurodegeneration.

  6. Activity-Based Costing Application in an Urban Mass Transport Company

    Directory of Open Access Journals (Sweden)

    Popesko Boris

    2011-12-01

    Full Text Available The purpose of this paper is to provide a basic overview of the application of Activity-Based Costing in an urban mass transport company which operates land public transport via buses and trolleys within the city. The case study was conducted using the Activity-Based Methodology in order to calculate the true cost of individual operations and to measure the profitability of particular transport lines. The case study analysis showed the possible effects of the application of the Activity-Based Costing for an urban mass transport company as well as the limitations of using the ABC methodology in the service industry. With regards to the application of the ABC methodology, the primary limitation of the accuracy of the conclusions is the quality of the non-financial information which had to be gathered throughout the implementation process. A basic limitation of the accurate data acquisition is the nature of the fare system of the transport company which does not allow the identification of the route that is taken by an individual passenger. The study illustrates the technique of ABC in urban mass transport and provides a real company example of information outputs of the ABC system. The users indicated that, the ABC model is very useful for profitability reporting and profit management. Also, the paper shows specific application of the Activity-Based Methodology in conditions of urban mass transport companies with regional specifics.

  7. Active transportation to school in Canadian youth: should injury be a concern?

    Science.gov (United States)

    Gropp, Kathleen; Janssen, Ian; Pickett, William

    2013-02-01

    Active transportation to school provides a means for youth to incorporate physical activity into their daily routines, and this has obvious benefits for child health. Studies of active transportation have rarely focused on the negative health effects in terms of injury. This cross-sectional study is based on the 2009/10 Canadian Health Behaviour in School-Aged Children survey. A sample of children aged 11-15 years (n=20 076) was studied. Multi-level logistic regression was used to examine associations between walking or bicycling to school and related injury. Regular active transportation to school at larger distances (approximately >1.6 km; 1.0 miles) was associated with higher relative odds of active transportation injury (OR: 1.52; 95% CI 1.08 to 2.15), with a suggestion of a dose-response relationship between longer travel distances and injury (p=0.02). Physical activity interventions for youth should encourage participation in active transportation to school, while also recognising the potential for unintentional injury.

  8. Activated human CD4 T cells express transporters for both cysteine and cystine

    DEFF Research Database (Denmark)

    Levring, Trine Bøegh; Hansen, Ann Kathrine; Nielsen, Bodil Lisbeth;

    2012-01-01

    Because naïve T cells are unable to import cystine due to the absence of cystine transporters, it has been suggested that T cell activation is dependent on cysteine generated by antigen presenting cells. The aim of this study was to determine at which phases during T cell activation exogenous...... cystine/cysteine is required and how T cells meet this requirement. We found that early activation of T cells is independent of exogenous cystine/cysteine, whereas T cell proliferation is strictly dependent of uptake of exogenous cystine/cysteine. Naïve T cells express no or very low levels of both...... cystine and cysteine transporters. However, we found that these transporters become strongly up-regulated during T cell activation and provide activated T cells with the required amount of cystine/cysteine needed for T cell proliferation. Thus, T cells are equipped with mechanisms that allow T cell...

  9. Demand-responsive public transportation re-scheduling for adjusting to the joint leisure activity demand

    Directory of Open Access Journals (Sweden)

    Konstantinos Gkiotsalitis

    2016-10-01

    Full Text Available Fixed daily trips such as trips to work/school have fixed departure/arrival times and destination points. The recurrent nature of fixed activities facilitates individuals on making more well-informed decisions about the transport mode selection. On the contrary, selecting a transportation mode for non-recurrent leisure trips, which can account for up to 60% of trips in some cities (Transport for London, 2014, is a more complex task due to the fact that individuals have little knowledge about the alternative modal options. In this paper, we try to improve the operations of demand-responsive public transportation systems by increasing their service quality and their ridership related to joint-leisure-trips via timetable rescheduling. First, we model the public transport service re-scheduling problem considering operational regulations and the quality of service. Then, a sequential heuristic method is introduced for re-scheduling the timetables of demand-responsive public transport modes in near-real time and accommodating the joint leisure activity demand without deteriorating the quality of service. The public transport re-scheduling for increasing the joint leisure activity ridership was tested in a case study using user-generated data from social media in Stockholm and the General Transit Feed Specification (GTFS data from Sweden focusing especially on central bus lines 1 and 4.

  10. Active transmembrane drug transport in microgravity: a validation study using an ABC transporter model [v1; ref status: indexed, http://f1000r.es/41n

    Directory of Open Access Journals (Sweden)

    Sergi Vaquer

    2014-08-01

    Full Text Available Abstract Microgravity has been shown to influence the expression of ABC (ATP-Binding Cassette transporters in bacteria, fungi and mammals, but also to modify the activity of certain cellular components with structural and functional similarities to ABC transporters. Changes in activity of ABC transporters could lead to important metabolic disorders and undesired pharmacological effects during spaceflights. However, no current means exist to study the functionality of these transporters in microgravity. To this end, a Vesicular Transport Assay® (Solvo Biotechnology, Hungary was adapted to evaluate multi-drug resistance-associated protein 2 (MRP2 trans-membrane estradiol-17-β-glucuronide (E17βG transport activity, when activated by adenosine-tri-phosphate (ATP during parabolic flights. Simple diffusion, ATP-independent transport and benzbromarone inhibition were also evaluated. A high accuracy engineering system was designed to perform, monitor and synchronize all procedures. Samples were analysed using a validated high sensitivity drug detection protocol. Experiments were performed in microgravity during parabolic flights, and compared to 1g on ground results using identical equipment and procedures in all cases. Our results revealed that sufficient equipment accuracy and analytical sensitivity were reached to detect transport activity in both gravitational conditions. Additionally, transport activity levels of on ground samples were within commercial transport standards, proving the validity of the methods and equipment used. MRP2 net transport activity was significantly reduced in microgravity, so was signal detected in simple diffusion samples. Ultra-structural changes induced by gravitational stress upon vesicle membranes or transporters could explain the current results, although alternative explanations are possible. Further research is needed to provide a conclusive answer in this regard. Nevertheless, the present validated technology

  11. Regulation of human hepatic drug transporter activity and expression by diesel exhaust particle extract.

    Directory of Open Access Journals (Sweden)

    Marc Le Vee

    Full Text Available Diesel exhaust particles (DEPs are common environmental air pollutants primarily affecting the lung. DEPs or chemicals adsorbed on DEPs also exert extra-pulmonary effects, including alteration of hepatic drug detoxifying enzyme expression. The present study was designed to determine whether organic DEP extract (DEPe may target hepatic drug transporters that contribute in a major way to drug detoxification. Using primary human hepatocytes and transporter-overexpressing cells, DEPe was first shown to strongly inhibit activities of the sinusoidal solute carrier (SLC uptake transporters organic anion-transporting polypeptides (OATP 1B1, 1B3 and 2B1 and of the canalicular ATP-binding cassette (ABC efflux pump multidrug resistance-associated protein 2, with IC50 values ranging from approximately 1 to 20 μg/mL and relevant to environmental exposure situations. By contrast, 25 μg/mL DEPe failed to alter activities of the SLC transporter organic cation transporter (OCT 1 and of the ABC efflux pumps P-glycoprotein and bile salt export pump (BSEP, whereas it only moderately inhibited those of sodium taurocholate co-transporting polypeptide and of breast cancer resistance protein (BCRP. Treatment by 25 μg/mL DEPe was next demonstrated to induce expression of BCRP at both mRNA and protein level in cultured human hepatic cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B3, OATP2B1, OCT1 and BSEP. Such changes in transporter expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a reference activator of the aryl hydrocarbon receptor (AhR pathway. This suggests that DEPe, which is enriched in known ligands of AhR like polycyclic aromatic hydrocarbons, alters drug transporter expression via activation of the AhR cascade. Taken together, these data established human hepatic transporters as targets of organic chemicals containing in DEPs, which may contribute

  12. Transport of Optically Active Particles from the Surface Mixed Layer

    Science.gov (United States)

    2005-09-30

    aragonite in the form of abundant coccoliths and coccospheres, and occasional forams, pteropods and larval gastropods . The δ18O signature of the 2003... APPLICATIONS These experiments were designed to identify the major loss terms of optically-active particles. This indeed was accomplished. Such

  13. Activity transport models for PWR primary circuits; PWR-ydinvoimalaitoksen primaeaeripiirin aktiivisuuskulkeutumismallit

    Energy Technology Data Exchange (ETDEWEB)

    Tanner, V.; Rosenberg, R. [VTT Chemical Technology, Otaniemi (Finland)

    1995-03-01

    The corrosion products activated in the primary circuit form a major source of occupational radiation dose in the PWR reactors. Transport of corrosion activity is a complex process including chemistry, reactor physics, thermodynamics and hydrodynamics. All the mechanisms involved are not known and there is no comprehensive theory for the process, so experimental test loops and plant data are very important in research efforts. Several activity transport modelling attempts have been made to improve the water chemistry control and to minimise corrosion in PWR`s. In this research report some of these models are reviewed with special emphasis on models designed for Soviet VVER type reactors. (51 refs., 16 figs., 4 tabs.).

  14. Prolactin increases hepatic Na+/taurocholate co-transport activity and messenger RNA post partum.

    Science.gov (United States)

    Ganguly, T C; Liu, Y; Hyde, J F; Hagenbuch, B; Meier, P J; Vore, M

    1994-01-01

    We have shown that Na+/taurocholate co-transport activity is decreased in pregnancy, but rebounds post partum relative to non-pregnant controls, and that activity can be increased by treatment with ovine prolactin [Ganguly, Hyde and Vore (1993) J. Pharmacol. Exp. Ther. 267, 82-87]. To determine the basis for these effects, Na+/taurocholate co-transport was determined in purified basolateral liver plasma-membrane (bLPM) vesicles and compared with steady-state mRNA levels encoding the Na+/taurocholate-co-transporting polypeptide (Ntcp) in non-pregnant controls, pregnant rats (19-20 days pregnant), rats post partum (48 h post partum) and rats post partum treated with bromocriptine to inhibit prolactin secretion. Na+/taurocholate co-transport activity (nmol/5 s per mg of protein) in bLPM was decreased from 10.4 +/- 1.8 in non-pregnant controls to 7.9 +/- 0.6 in bLPM in pregnant rats, but rebounded to 17.5 +/- 1.3 post partum; treatment of rats post partum with bromocriptine to inhibit prolactin secretion decreased activity to 14.1 +/- 0.9. Northern and slot-blot analyses revealed similar changes in mRNA for Ntcp, so that a positive correlation was observed between Na+/taurocholate co-transport activity and Ntcp mRNA. Furthermore, treatment of ovariectomized rats with ovine prolactin increased Ntcp mRNA 10-fold compared with solvent-treated controls, consistent with the 2-fold increase in Vmax, for Na+/taurocholate co-transport in isolated hepatocytes. These data are the first to demonstrate endogenous physiological regulation by prolactin of Ntcp mRNA in parallel with Na+/taurocholate co-transport activity. Images Figure 2 PMID:7945260

  15. Polystyrene nanoparticles activate ion transport in human airway epithelial cells

    Directory of Open Access Journals (Sweden)

    McCarthy J

    2011-06-01

    Full Text Available J McCarthy1, X Gong2, D Nahirney2, M Duszyk2, MW Radomski11School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 2Department of Physiology, University of Alberta, Edmonton, Alberta, CanadaBackground: Over the last decade, nanotechnology has provided researchers with new nanometer materials, such as nanoparticles, which have the potential to provide new therapies for many lung diseases. In this study, we investigated the acute effects of polystyrene nanoparticles on epithelial ion channel function.Methods: Human submucosal Calu-3 cells that express cystic fibrosis transmembrane conductance regulator (CFTR and baby hamster kidney cells engineered to express the wild-type CFTR gene were used to investigate the actions of negatively charged 20 nm polystyrene nanoparticles on short-circuit current in Calu-3 cells by Ussing chamber and single CFTR Cl- channels alone and in the presence of known CFTR channel activators by using baby hamster kidney cell patches.Results: Polystyrene nanoparticles caused sustained, repeatable, and concentration-dependent increases in short-circuit current. In turn, these short-circuit current responses were found to be biphasic in nature, ie, an initial peak followed by a plateau. EC50 values for peak and plateau short-circuit current responses were 1457 and 315.5 ng/mL, respectively. Short-circuit current was inhibited by diphenylamine-2-carboxylate, a CFTR Cl- channel blocker. Polystyrene nanoparticles activated basolateral K+ channels and affected Cl- and HCO3- secretion. The mechanism of short-circuit current activation by polystyrene nanoparticles was found to be largely dependent on calcium-dependent and cyclic nucleotide-dependent phosphorylation of CFTR Cl- channels. Recordings from isolated inside-out patches using baby hamster kidney cells confirmed the direct activation of CFTR Cl- channels by the nanoparticles.Conclusion: This is the first study to identify

  16. Mechanism of active transport: free energy dissipation and free energy transduction.

    OpenAIRE

    Tanford, C

    1982-01-01

    The thermodynamic pathway for "chemiosmotic" free energy transduction in active transport is discussed with an ATP-driven Ca2+ pump as an illustrative example. Two innovations are made in the analysis. (i) Free energy dissipated as heat is rigorously excluded from overall free energy bookkeeping by focusing on the dynamic equilibrium state of the chemiosmotic process. (ii) Separate chemical potential terms for free energy donor and transported ions are used to keep track of the thermodynamic ...

  17. Glycoforms of UT-A3 urea transporter with poly-N-acetyllactosamine glycosylation have enhanced transport activity.

    Science.gov (United States)

    Su, Hua; Carter, Conner B; Fröhlich, Otto; Cummings, Richard D; Chen, Guangping

    2012-07-15

    Urea transporters UT-A1 and UT-A3 are both expressed in the kidney inner medulla. However, the function of UT-A3 remains unclear. Here, we found that UT-A3, which comprises only the NH(2)-terminal half of UT-A1, has a higher urea transport activity than UT-A1 in the oocyte and that this difference was associated with differences in N-glycosylation. Heterologously expressed UT-A3 is fully glycosylated with two glycoforms of 65 and 45 kDa. By contrast, UT-A1 expressed in HEK293 cells and oocytes exhibits only a 97-kDa glycosylation form. We further found that N-glycans of UT-A3 contain a large amount of poly-N-acetyllactosamine. This highly glycosylated UT-A3 is more stable and is enriched in lipid raft domains on the cell membrane. Kifunensine, an inhibitor of α-mannosidase that inhibits N-glycan processing beyond high-mannose-type N-glycans, significantly reduced UT-A3 urea transport activity. We then examined the native UT-A1 and UT-A3 glycosylation states from kidney inner medulla and found the ratio of 65 to 45 kDa in UT-A3 is higher than that of 117 to 97 kDa in UT-A1. The highly stable expression of highly glycosylated UT-A3 on the cell membrane in kidney inner medulla suggests that UT-A3 may have an important function in urea reabsorption.

  18. Glucose elevates NITRATE TRANSPORTER2.1 protein levels and nitrate transport activity independently of its HEXOKINASE1-mediated stimulation of NITRATE TRANSPORTER2.1 expression.

    Science.gov (United States)

    de Jong, Femke; Thodey, Kate; Lejay, Laurence V; Bevan, Michael W

    2014-01-01

    Mineral nutrient uptake and assimilation is closely coordinated with the production of photosynthate to supply nutrients for growth. In Arabidopsis (Arabidopsis thaliana), nitrate uptake from the soil is mediated by genes encoding high- and low-affinity transporters that are transcriptionally regulated by both nitrate and photosynthate availability. In this study, we have studied the interactions of nitrate and glucose (Glc) on gene expression, nitrate transport, and growth using glucose-insensitive2-1 (gin2-1), which is defective in sugar responses. We confirm and extend previous work by showing that HEXOKINASE1-mediated oxidative pentose phosphate pathway (OPPP) metabolism is required for Glc-mediated NITRATE TRANSPORTER2.1 (NRT2.1) expression. Treatment with pyruvate and shikimate, two products derived from intermediates of the OPPP that are destined for amino acid production, restores wild-type levels of NRT2.1 expression, suggesting that metabolites derived from OPPP metabolism can, together with Glc, directly stimulate high levels of NRT2.1 expression. Nitrate-mediated NRT2.1 expression is not influenced by gin2-1, showing that Glc does not influence NRT2.1 expression through nitrate-mediated mechanisms. We also show that Glc stimulates NRT2.1 protein levels and transport activity independently of its HEXOKINASE1-mediated stimulation of NRT2.1 expression, demonstrating another possible posttranscriptional mechanism influencing nitrate uptake. In gin2-1 plants, nitrate-responsive biomass growth was strongly reduced, showing that the supply of OPPP metabolites is essential for assimilating nitrate for growth.

  19. Packaging design criteria (onsite) project W-520 immobilized low-activity waste transportation system

    Energy Technology Data Exchange (ETDEWEB)

    BOEHNKE, W.M.

    2001-10-16

    A plan is currently in place to process the high-level radioactive wastes that resulted from uranium and plutonium recovery operations from Spent Nuclear Fuel at the Hanford Site, Richland, Washington. Currently, millions of gallons of high-level radioactive waste in the form of liquids, sludges, and saltcake are stored in many large underground tanks onsite. This waste will be processed and separated into high-level and low-activity fractions. Both fractions will then be vitrified (i.e., blended with molten borosilicate glass) in order to encapsulate the toxic radionuclides. The immobilized low-activity waste (ILAW) glass will be poured into LAW canisters, allowed to cool and harden to solid form, sealed by welding, and then transported to a double-lined trench in the 200 East Area for permanent disposal. This document presents the packaging design criteria (PDC) for an onsite LAW transportation system, which includes the ILAW canister, ILAW package, and transport vehicle and defines normal and accident conditions. This PDC provides the basis for the ILAW onsite transportation system design and fabrication and establishes the transportation safety criteria that the design will be evaluated against in the Package Specific Safety Document (PSSD). It provides the criteria for the ILAW canister, cask and transport vehicles and defines normal and accident conditions. The LAW transportation system is designed to transport stabilized waste from the vitrification facility to the ILAW disposal facility developed by Project W-520. All ILAW transport will take place within the 200 East Area (all within the Hanford Site).

  20. Metal dispersion and transportational activities using food crops as biomonitors.

    Science.gov (United States)

    Ward, N I; Savage, J M

    1994-05-23

    The multielement (Al, Ca, Cd, Ce, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Si, and Zn) levels of various common vegetables (bean, broccoli, cabbage, cauliflower, lettuce, marrow, onion, parsnip, spinach, sprouts, sweet corn, and tomato); fruits (grape and strawberry); herbs (garlic, lemon balm, marjoram, mint, rosemary and tarragon); local pasture species and surface soils collected from a commercial garden centre located within a distance of 30 m of the London Orbital Motorway (M25) is presented. Comparative values are given from a background area, namely a domestic garden located in the North Yorkshire Dales National Park area. Analysis was undertaken by inductively coupled plasma optical emission spectrometry (ICP-OES) and inductively coupled plasma-source mass spectrometry (ICP-MS) with quality control assessment using four international biological reference materials; BCR:CRM 62 Olive Leaves, NIST 1575 Pine Needles, NIST 1573 Tomato Leaves, and NIST 1572 Citrus Leaves. Inter-analytical method comparison is given using two methods of ICP-MS; namely conventional pneumatic nebulisation of sample solution, and direct solids analysis by laser ablation; and neutron activation analysis methods (NAA). For the elements listed there is a good precision obtained by ICP-MS and NAA. In particular levels of herbs > vegetables > cereals > fruits. Measured values are in good agreement with reported literature values. The lowest Pb values are for marrow, lettuce, tomato and sweet corn samples (approximately 0.001-0.021 microgram/g). 'Green' leaf material levels were approximately 0.02-0.10 microgram/g (i.e. sprouts and cabbage). Root vegetables contain higher levels, approximately 0.02-0.125 microgram/g (especially carrot), reflecting possible metal uptake from soil. The highest vegetable Pb values are for leek and onion (approximately 0.35 microgram/g). Background values are also provided for nineteen elements (Al, As, B, Ba, Br, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Rb, Se, Sr, V, and Zn

  1. Neuronal Activity and Glutamate Uptake Decrease Mitochondrial Mobility in Astrocytes and Position Mitochondria Near Glutamate Transporters

    Science.gov (United States)

    Jackson, Joshua G.; O'Donnell, John C.; Takano, Hajime; Coulter, Douglas A.

    2014-01-01

    Within neurons, mitochondria are nonuniformly distributed and are retained at sites of high activity and metabolic demand. Glutamate transport and the concomitant activation of the Na+/K+-ATPase represent a substantial energetic demand on astrocytes. We hypothesized that mitochondrial mobility within astrocytic processes might be regulated by neuronal activity and glutamate transport. We imaged organotypic hippocampal slice cultures of rat, in which astrocytes maintain their highly branched morphologies and express glutamate transporters. Using time-lapse confocal microscopy, the mobility of mitochondria within individual astrocytic processes and neuronal dendrites was tracked. Within neurons, a greater percentage of mitochondria were mobile than in astrocytes. Furthermore, they moved faster and farther than in astrocytes. Inhibiting neuronal activity with tetrodotoxin (TTX) increased the percentage of mobile mitochondria in astrocytes. Mitochondrial movement in astrocytes was inhibited by vinblastine and cytochalasin D, demonstrating that this mobility depends on both the microtubule and actin cytoskeletons. Inhibition of glutamate transport tripled the percentage of mobile mitochondria in astrocytes. Conversely, application of the transporter substrate d-aspartate reversed the TTX-induced increase in the percentage of mobile mitochondria. Inhibition of reversed Na+/Ca2+ exchange also increased the percentage of mitochondria that were mobile. Last, we demonstrated that neuronal activity increases the probability that mitochondria appose GLT-1 particles within astrocyte processes, without changing the proximity of GLT-1 particles to VGLUT1. These results imply that neuronal activity and the resulting clearance of glutamate by astrocytes regulate the movement of astrocytic mitochondria and suggest a mechanism by which glutamate transporters might retain mitochondria at sites of glutamate uptake. PMID:24478345

  2. Active transport improves the precision of linear long distance molecular signalling

    Science.gov (United States)

    Godec, Aljaž; Metzler, Ralf

    2016-09-01

    Molecular signalling in living cells occurs at low copy numbers and is thereby inherently limited by the noise imposed by thermal diffusion. The precision at which biochemical receptors can count signalling molecules is intimately related to the noise correlation time. In addition to passive thermal diffusion, messenger RNA and vesicle-engulfed signalling molecules can transiently bind to molecular motors and are actively transported across biological cells. Active transport is most beneficial when trafficking occurs over large distances, for instance up to the order of 1 metre in neurons. Here we explain how intermittent active transport allows for faster equilibration upon a change in concentration triggered by biochemical stimuli. Moreover, we show how intermittent active excursions induce qualitative changes in the noise in effectively one-dimensional systems such as dendrites. Thereby they allow for significantly improved signalling precision in the sense of a smaller relative deviation in the concentration read-out by the receptor. On the basis of linear response theory we derive the exact mean field precision limit for counting actively transported molecules. We explain how intermittent active excursions disrupt the recurrence in the molecular motion, thereby facilitating improved signalling accuracy. Our results provide a deeper understanding of how recurrence affects molecular signalling precision in biological cells and novel medical-diagnostic devices.

  3. Influence of excipients on drug absorption via modulation of intestinal transporters activity

    Directory of Open Access Journals (Sweden)

    Hetal P Thakkar

    2015-01-01

    Full Text Available One of the major factors affecting oral drug bioavailability is the activity of intestinal transport proteins, particularly for the drugs that undergo absorption by active transport mechanism. Many of the active pharmacological agents and the excipients used in their formulation are reported to modulate the activity of these transporters thereby either enhancing or decreasing the drug absorption and its systemic availability. These excipients are considered pharmacologically "inert" and have been used since years in pharmaceutical formulations. Appreciable interest is developing on the data demonstrating the role of excipients in altering the drug absorption across the intestine. Careful selection of the excipients thus is very important. A correctly chosen excipient can enhance the drug bioavailability and thus its therapeutic efficacy without increasing its dose. For locally acting drugs having systemic side effects, a proper excipient could lead to a decrease in its systemic absorption, thus reducing its side effects. This review focuses on the current findings of the excipients identified to modulate the activity of transporters, their mechanism of modulating the transporter′s activity and various formulation strategies using these excipients to enhance drug absorption.

  4. The transports in the French Plutonium Industry. A high risk activity

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-02-01

    This study throws light on the scale of transport of plutonium in France nuclear industry, an activity involving quantities of high risk materials often unknown to the public. The study is a significantly extended update of the one carried out by WISE-Paris in 1995 for the Plutonium Forum. It was motivated by important developments in the French plutonium industry and the publication of numerous data concerning transport activities since 1995. The 2003 study presents, in particular, all of the flows of plutonium crossing France every year, as well as analysis of the risks associated with this particular transport activity. Putting these data into perspective in terms of a rapidly and permanently changing political and industrial context, and a description of the regulatory framework within which shipments of plutonium take place, serve as a guide and source of reference to help readers better understand the issues. The importance of transport in the plutonium ''chain'', i.e. the stages corresponding to various industrial processes, is often under-estimated, even by the nuclear industry itself. Transport is, in fact, the activity which involves the greatest quantities of plutonium in the entire nuclear chain. Plutonium, produced during the fission reactions in the cores of nuclear reactors, is transported, contained in the irradiated fuel, to the facilities at La Hague where reprocessing separates it from the other radioactive components of the spent fuel. Part of the plutonium, now isolated in powder form, is then shipped to one of the three plants able to produce the fuel known as MOX. These are located at Cadarache and Marcoule, in France, and at Dessel in Belgium. Once in the MOX form, this plutonium has to be re-transported to reactor sites to be used. Once irradiated, the spent MOX will return to the La Hague installations to be stored for an unknown period; the plutonium contained in the spent MOX is not, at present, destined to be re

  5. Hydrogen peroxide stimulates the active transport of serotonin into human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Bosin, T.R. (Indiana Univ., Bloomington (United States))

    1991-03-11

    The effect of hydrogen peroxide on the active transport of serotonin (5-HT) by human platelets was investigated. Platelets were exposed to either a single dose of H{sub 2}O{sub 2} or to H{sub 2}O{sub 2} generated by the glucose/glucose oxidase or xanthine/xanthine oxidase enzyme systems. H{sub 2}{sub 2} produced a rapid, dose-dependent and time-dependent increase in 5-HT transport which was maximal after a 2 min incubation and decreased with continued incubation. Catalase completely prevented H{sub 2}O{sub 2}-induced stimulation and fluoxetine totally blocked 5-HT uptake into stimulated platelets. The glucose/glucose oxidase and the xanthine/xanthine oxidase generating systems produced a similar response to that of H{sub 2}O{sub 2}. In the xanthine/xanthine oxidase system, superoxide dismutase failed to alter the stimulation, while catalase effectively prevented the response. The kinetics of 5-HT transport indicated that H{sub 2}O{sub 2} treatment did not alter the K{sub m} of 5-HT transport but significantly increased the maximal rate of 5-HT transport. These data demonstrated that exposure of human platelets to H{sub 2}O{sub 2} resulted in a stimulation of the active transport of 5-HT and suggested that H{sub 2}O{sub 2} may function to regulate this process.

  6. Pancreatic lipase activity in overnight effluent predicts high transport status in peritoneal dialysis patients.

    Science.gov (United States)

    Idei, Mayumi; Tabe, Yoko; Hamada, Chieko; Miyake, Kazunori; Takemura, Hiroyuki; Io, Hiroaki; Wakita, Mitsuru; Horii, Takashi; Tomino, Yasuhiko; Ohsaka, Akimichi; Miida, Takashi

    2016-11-01

    Long-term peritoneal dialysis (PD) causes peritoneal morphological and functional changes, resulting in high transport status featuring increased peritoneal permeability. High transport status is diagnosed by peritoneal equilibration test (PET), a reliable but time-consuming method. We identifed a reliable biomarker in peritoneal effluent to predict high transport status in PD patients. We collected peritoneal effluent and serum from 33 PD patients and measured common laboratory test parameters. High transport status was determined by PET if the dialysate/plasma ratio of creatinine at 4h dwell (D/P Cr 4h) was ≥0.81. There were significant correlations between D/P Cr 4h and some laboratory parameters in overnight effluent (pancreatic lipase activity, r=0.65, povernight effluent was identified as an independent predictor of high transport status even after adjusting for age, PD duration, and glomerular filtration rate [OR=1.43 (95% CI: 1.11-1.83), p=0.005]. The pancreatic lipase activity in overnight effluent is an independent predictor of high transport status in PD patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Active intracellular transport in metastatic cells studied by spatial light interference microscopy.

    Science.gov (United States)

    Ceballos, Silvia; Kandel, Mikhail; Sridharan, Shamira; Majeed, Hassaan; Monroy, Freddy; Popescu, Gabriel

    2015-01-01

    Spatiotemporal patterns of intracellular transport are very difficult to quantify and, consequently, continue to be insufficiently understood. While it is well documented that mass trafficking inside living cells consists of both random and deterministic motions, quantitative data over broad spatiotemporal scales are lacking. We studied the intracellular transport in live cells using spatial light interference microscopy, a high spatiotemporal resolution quantitative phase imaging tool. The results indicate that in the cytoplasm, the intracellular transport is mainly active (directed, deterministic), while inside the nucleus it is both active and passive (diffusive, random). Furthermore, we studied the behavior of the two-dimensional mass density over 30 h in HeLa cells and focused on the active component. We determined the standard deviation of the velocity distribution at the point of cell division for each cell and compared the standard deviation velocity inside the cytoplasm and the nucleus. We found that the velocity distribution in the cytoplasm is consistently broader than in the nucleus, suggesting mechanisms for faster transport in the cytosol versus the nucleus. Future studies will focus on improving phase measurements by applying a fluorescent tag to understand how particular proteins are transported inside the cell.

  8. Central Hemodynamics and Oxygen Transport in Various Activation of Patients Operated On Under Extracorporeal Circulation

    Directory of Open Access Journals (Sweden)

    Ye. V. Dzybinskaya

    2009-01-01

    Full Text Available Objective: to study central hemodynamics, the determinants of myocardial oxygen balance, and the parameters of oxygen transport in various activation of patients after surgery under extracorporeal circulation. Subjects and methods. Thirty-four patients aged 57.8±2.5 years who had coronary heart disease were divided into 2 groups: 1 those with late activation (artificial ventilation time 157±9 min and 2 those with immediate activation (artificial ventilation time 33±6 min. Group 2 patients were, if required, given fentanyl, midazolam, or myorelaxants. Results. During activation, there were no intergroup differences in the mean levels of the major parameters of cardiac pump function, in the determinants of coronary blood flow (coronary perfusion gradients and myocardial oxygen demand (the product of heart rate by systolic blood pressure, and in the parameters of oxygen transport, including arterial lactatemia. After tracheal extubation, the left ventricular pump coefficient was increased considerably (up to 3.8±0.2 and 4.4±0.2 gm/mm Hg/m2 in Groups 1 and 2, respectively; p<0.05 with minimum inotropic support (dopamine and/or dobutamine being used at 2.7±0.3 and 2.4±0.3 mg/kg/min, respectively. In both groups, there were no close correlations between the indices of oxygen delivery and consumption at all stages of the study, which was indicative of no transport-dependent oxygen uptake. Conclusion. When the early activation protocol was followed up, the maximum acceleration of early activation, including that using specific antagonists of anesthetics, has no negative impact on central hemodynamics, the determinants of myocardial oxygen balance and transport in patients operated on under extracorporeal circulation. Key words: early activation, surgery under extracorporeal circulation, tracheal extubation in the operating-room, central hemodynamics, oxygen transport.

  9. A fully resolved active musculo-mechanical model for esophageal transport

    Science.gov (United States)

    Kou, Wenjun; Bhalla, Amneet Pal Singh; Griffith, Boyce E.; Pandolfino, John E.; Kahrilas, Peter J.; Patankar, Neelesh A.

    2015-10-01

    Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multi-layered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, and the esophagus is modeled as an actively contracting, fiber-reinforced tube. Before considering the full model of the esophagus, however, we first consider a standard benchmark problem of flow past a cylinder. Next a simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Finally, three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall resulting from the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function.

  10. Individual public transportation accessibility is positively associated with self-reported active commuting

    DEFF Research Database (Denmark)

    Djurhuus, Sune; Hansen, Henning Sten; Aadahl, Mette;

    2014-01-01

    BACKGROUND: Active commuters have lower risk of chronic disease. Understanding which of the, to some extent, modifiable characteristics of public transportation that facilitate its use is thus important in a public health perspective. The aim of the study was to examine the association between...... individual public transportation accessibility and self-reported active commuting, and whether the associations varied with commute distance, age, and gender. METHODS: Twenty-eight thousand nine hundred twenty-eight commuters in The Capital Region of Denmark reported self-reported time spent either walking...... or cycling to work or study each day and the distance to work or study. Data were obtained from the Danish National Health Survey collected in February to April 2010. Individual accessibility by public transportation was calculated using a multi-modal network in a GIS. Multilevel logistic regression was used...

  11. Mathematical modeling of the intracellular protein dynamics: the importance of active transport along microtubules.

    Science.gov (United States)

    Szymańska, Zuzanna; Parisot, Martin; Lachowicz, Mirosław

    2014-12-21

    In this paper we propose a mathematical model of protein and mRNA transport inside a cell. The spatio-temporal model takes into account the active transport along microtubules in the cytoplasm as well as diffusion and is able to reproduce the oscillatory changes in protein concentration observed in many experimental data. In the model the protein and the mRNA interact with each other that allows us to classify the model as a simple gene regulatory network. The proposed model is generic and may be adapted to specific signaling pathways. On the basis of numerical simulations, we formulate a new hypothesis that the oscillatory dynamics is allowed by the mRNA active transport along microtubules from the nucleus to distant locations.

  12. Children's route choice during active transportation to school : difference between shortest and actual route

    NARCIS (Netherlands)

    Dessing, D.; Vries, S.I. (Sanne); Hegeman, G.; Mechelen, W. van; Pierik, F.H.

    2016-01-01

    Background: The purpose of this study is to increase our understanding of environmental correlates that are associated with route choice during active transportation to school (ATS) by comparing characteristics of actual walking and cycling routes between home and school with the shortest possible r

  13. The Association Between the Physical Environment of Primary Schools and Active School Transport

    NARCIS (Netherlands)

    Kann, D.H.H. van; Kremers, S.P.J.; Gubbels, J.S.; Bartelink, N.H.M.; Vries, S.I. de; Vries, N.K. de; Jansen, M.W.J.

    2015-01-01

    This study examined the relationship between the physical environment characteristics of primary schools and active school transport among 3,438 5- to 12-year-old primary school children in the Netherlands. The environmental characteristics were categorized into four theory-based clusters (function,

  14. En-route mechanical activation of viscous oil and oil products transported in railroad tank cars

    Directory of Open Access Journals (Sweden)

    Yerlan MYRZAKHMETOV

    2012-01-01

    Full Text Available The authors of this document are aiming to substantiate the advantages of en-route mechanical activation technology as aids for railroad transportation of viscous oil and oil products in tank cars. The conceptual design implies the use of momentum generated by brake action. This document also contains preliminary data of laboratory research confirming the validity of the developed concept.

  15. Inhibition of Activity of GABA Transporter GAT1 by δ-Opioid Receptor

    Directory of Open Access Journals (Sweden)

    Lu Pu

    2012-01-01

    Full Text Available Analgesia is a well-documented effect of acupuncture. A critical role in pain sensation plays the nervous system, including the GABAergic system and opioid receptor (OR activation. Here we investigated regulation of GABA transporter GAT1 by δOR in rats and in Xenopus oocytes. Synaptosomes of brain from rats chronically exposed to opiates exhibited reduced GABA uptake, indicating that GABA transport might be regulated by opioid receptors. For further investigation we have expressed GAT1 of mouse brain together with mouse δOR and μOR in Xenopus oocytes. The function of GAT1 was analyzed in terms of Na+-dependent [3H]GABA uptake as well as GAT1-mediated currents. Coexpression of δOR led to reduced number of fully functional GAT1 transporters, reduced substrate translocation, and GAT1-mediated current. Activation of δOR further reduced the rate of GABA uptake as well as GAT1-mediated current. Coexpression of μOR, as well as μOR activation, affected neither the number of transporters, nor rate of GABA uptake, nor GAT1-mediated current. Inhibition of GAT1-mediated current by activation of δOR was confirmed in whole-cell patch-clamp experiments on rat brain slices of periaqueductal gray. We conclude that inhibition of GAT1 function will strengthen the inhibitory action of the GABAergic system and hence may contribute to acupuncture-induced analgesia.

  16. Statement of work for the immobilized low-activity waste transportation system -- Project W-465

    Energy Technology Data Exchange (ETDEWEB)

    Mouette, P.

    1998-06-19

    The objective of this Statement of Work (SOW) is to present the scope, the deliverables, the organization, the technical and schedule expectations for the development of a Package Design Criteria (PDC), cost and schedule estimate for the acquisition of a transportation system for the Immobilized Low-Activity Waste (ILAW).

  17. Potential Activity of Subglacial Microbiota Transported to Anoxic River Delta Sediments

    DEFF Research Database (Denmark)

    Cameron, Karen A.; Stibal, Marek; Olsen, Nikoline S.

    2017-01-01

    The Watson River drains a portion of the SW Greenland ice sheet, transporting microbial communities from subglacial environments to a delta at the head of Søndre Strømfjord. This study investigates the potential activity and community shifts of glacial microbiota deposited and buried under layers...

  18. Cargo-towing synthetic nanomachines: towards active transport in microchip devices.

    Science.gov (United States)

    Wang, Joseph

    2012-05-08

    This review article discusses the use of synthetic catalytic nano motors for cargo manipulations and for developing miniaturized lab-on-chip systems based on autonomous transport. The ability of using chemically-powered artificial nanomotors to capture, transport and release therapeutic payloads or nanostructured biomaterials represents one of the next major prospects for nanomotor development. The increased cargo-towing force of such self-propelled nanomotors, along with their precise motion control within microchannel networks, versatility and facile functionalization, pave the way to new integrated functional lab-on-a-chip powered by active transport and perform a series of tasks. Such use of cargo-towing artificial nanomotors has been inspired by on-chip kinesin molecular shuttles. Functionalized nano/microscale motors can thus be used to pick a selected nano/microscale chemical or biological payload target at the right place, transport and deliver them to a target location in a timely manner. Key challenges for using synthetic nanomachines for driving transport processes along microchannel networks are discussed, including loading and unloading of cargo and precise motion control, along with recent examples of related cargo manipulation processes and guided transport in lab-on-a-chip formats. The exciting research area of cargo-carrying catalytic man-made nanomachines is expected to grow rapidly, to lead to new lab-on-a-chip formats and to provide a wide range of future microchip opportunities.

  19. Suppression of adenosine-activated chloride transport by ethanol in airway epithelia.

    Directory of Open Access Journals (Sweden)

    Sammeta V Raju

    Full Text Available Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (I(SC in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR, a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A(2B adenosine receptor (A(2BAR, largely abolished the adenosine-stimulated chloride transport, suggesting that A(2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections.

  20. Riluzole and gabapentinoids activate glutamate transporters to facilitate glutamate-induced glutamate release from cultured astrocytes

    OpenAIRE

    Yoshizumi, Masaru; Eisenach, James C.; Hayashida, Ken-ichiro

    2011-01-01

    We have recently demonstrated that the glutamate transporter activator riluzole paradoxically enhanced glutamate-induced glutamate release from cultured astrocytes. We further showed that both riluzole and the α2δ subunit ligand gabapentin activated descending inhibition in rats by increasing glutamate receptor signaling in the locus coeruleus and hypothesized that these drugs share common mechanisms to enhance glutamate release from astrocytes. In the present study, we examined the effects o...

  1. Neutron transport calculation for Activation Evaluation for Decommissioning of PET cyclotron Facility

    Science.gov (United States)

    Nobuhara, Fumiyoshi; Kuroyanagi, Makoto; Masumoto, Kazuyoshi; Nakamura, Hajime; Toyoda, Akihiro; Takahashi, Katsuhiko

    2017-09-01

    In order to evaluate the state of activation in a cyclotron facility used for the radioisotope production of PET diagnostics, we measured the neutron flux by using gold foils and TLDs. Then, the spatial distribution of neutrons and induced activity inside the cyclotron vault were simulated with the Monte Calro calculation code for neutron transport and DCHAIN-SP for activation calculation. The calculated results are in good agreement with measured values within factor 3. Therefore, the adaption of the advanced evaluation procedure for activation level is proved to be important for the planning of decommissioning of these facilities.

  2. Supply chain and innovation activity in transport related enterprises in Eastern Poland

    Directory of Open Access Journals (Sweden)

    Giuseppe Ioppolo

    2016-12-01

    Full Text Available  Background: One of the development strategies uses R&D activity as the main source of innovation, which is often carried out in cooperation with other units, but in particular in the supply chain, and therefore applies to cooperation between enterprises and their customers and suppliers. The aim of the study was to identify the variable determinants of the impact of the character of relationships among enterprises and their suppliers and customers on their innovative performance, within regional industrial systems and to define the constraints for a model regional structure of innovation network tailored to the needs of Poland and its regions. Methods: 167 enterprises belonging to the transport sector and operating in the area of Eastern Poland took part. In order to determine the impact of relationships with suppliers and customers on innovation activity, models based on probability analysis - probit models - were used. Results: It can be clearly stated that the cooperation of industrial enterprises in the transport sector with customers and suppliers activates innovation activity and its specified attributes. However, the probability varies depending on the test variable adopted. Conclusions: The cooperation with suppliers and customers is the cognitive aspect in the development of innovation activity in industrial enterprises representing the transport-related sector. Such cooperation has a stimulating effect on expenditures on innovation activity and on the implementation of innovative solutions in the field of technological innovation (products and processes.  

  3. Activated human CD4+ T cells express transporters for both cysteine and cystine.

    Science.gov (United States)

    Levring, Trine Bøegh; Hansen, Ann Kathrine; Nielsen, Bodil Lisbeth; Kongsbak, Martin; von Essen, Marina Rode; Woetmann, Anders; Odum, Niels; Bonefeld, Charlotte Menné; Geisler, Carsten

    2012-01-01

    Because naïve T cells are unable to import cystine due to the absence of cystine transporters, it has been suggested that T cell activation is dependent on cysteine generated by antigen presenting cells. The aim of this study was to determine at which phases during T cell activation exogenous cystine/cysteine is required and how T cells meet this requirement. We found that early activation of T cells is independent of exogenous cystine/cysteine, whereas T cell proliferation is strictly dependent of uptake of exogenous cystine/cysteine. Naïve T cells express no or very low levels of both cystine and cysteine transporters. However, we found that these transporters become strongly up-regulated during T cell activation and provide activated T cells with the required amount of cystine/cysteine needed for T cell proliferation. Thus, T cells are equipped with mechanisms that allow T cell activation and proliferation independently of cysteine generated by antigen presenting cells.

  4. Promoting better health through public transit use : another step towards active, sustainable transportation

    Energy Technology Data Exchange (ETDEWEB)

    Noxon, G. [Noxon Associates Ltd., Ottawa, ON (Canada)

    2001-07-01

    A study was conducted on behalf of the Canadian Urban Transit Association and the Federation of Canadian Municipalities, aimed at determining the contribution of public transit to public health in Canada. Health and transportation are linked together in their impact on air quality, climate change and safety, to name a few. The author defined sustainable transportation, limited growth, modal shift and modal efficiency. The benefits to be derived from sustainable transportation include health, with the emphasis being placed on urban transportation. Transportation in Toronto causes 90 per cent of carbon dioxide emissions, 83 per cent of nitrogen oxide emissions, and 60 per cent of sulphur dioxide emissions. Air quality is vastly improved and pollution reduced through the use of public transit. Alternative fuels, such as clean diesel, natural gas and biomass pollute a lot less. The use of auto and urban travel represent major sources of greenhouse gases and have an effect on global climate change. Some of the measures being considered involve the use of fare technologies, tax-exempt transit benefits, pricing strategies, service improvements, vehicle/fuel technologies. Road safety has improved but vehicle accidents still represent the major cause of death among young people. Canadians are not active enough, and physical activity is critical to good health. It was recommended that walking and cycling be used for short trips. Health also improves with income and social standing. Low income families end up spending more on transportation than they do on food. Some of the challenges facing equity in access to public transit are route elimination, fare increases, and paratransit demand. More research is needed to better address public transit contribution to public health, especially air quality, climate change, safety, physical activity (multimodal lifestyles and trips) and equity of access. figs.

  5. Genetic and chemical reductions in protein phosphatase activity alter auxin transport, gravity response, and lateral root growth

    Science.gov (United States)

    Rashotte, A. M.; DeLong, A.; Muday, G. K.; Brown, C. S. (Principal Investigator)

    2001-01-01

    Auxin transport is required for important growth and developmental processes in plants, including gravity response and lateral root growth. Several lines of evidence suggest that reversible protein phosphorylation regulates auxin transport. Arabidopsis rcn1 mutant seedlings exhibit reduced protein phosphatase 2A activity and defects in differential cell elongation. Here we report that reduced phosphatase activity alters auxin transport and dependent physiological processes in the seedling root. Root basipetal transport was increased in rcn1 or phosphatase inhibitor-treated seedlings but showed normal sensitivity to the auxin transport inhibitor naphthylphthalamic acid (NPA). Phosphatase inhibition reduced root gravity response and delayed the establishment of differential auxin-induced gene expression across a gravity-stimulated root tip. An NPA treatment that reduced basipetal transport in rcn1 and cantharidin-treated wild-type plants also restored a normal gravity response and asymmetric auxin-induced gene expression, indicating that increased basipetal auxin transport impedes gravitropism. Increased auxin transport in rcn1 or phosphatase inhibitor-treated seedlings did not require the AGR1/EIR1/PIN2/WAV6 or AUX1 gene products. In contrast to basipetal transport, root acropetal transport was normal in phosphatase-inhibited seedlings in the absence of NPA, although it showed reduced NPA sensitivity. Lateral root growth also exhibited reduced NPA sensitivity in rcn1 seedlings, consistent with acropetal transport controlling lateral root growth. These results support the role of protein phosphorylation in regulating auxin transport and suggest that the acropetal and basipetal auxin transport streams are differentially regulated.

  6. Myoelectrical activity and transport of unfertilized ova in the oviduct of the mouse in vitro.

    Science.gov (United States)

    Talo, A

    1980-09-01

    The relationship of myoelectrical activity to locations and movements of eggs was analysed in 12 mouse oviducts in vitro. When the eggs were in the ampulla the ampullary activity did not spread through the ampullary-isthmic junction (AIJ), and a narrow region of activity of lower frequency separated the ampullary and isthmic activities. When the eggs were in the isthmus the activity beginning on the isthmic side of the AIJ spread towards the uterus for progressively longer distances. Eggs were near or at the front of the plateau formed by this activity. A separate activity arising in one or more areas of the uterine side of the plateau often spread in the ovarian direction, thus opposing movements of eggs and fluid in the uterine direction. Transport of unfertilized eggs appears to be regulated by a small number of relatively stable pacemakers in the mouse oviduct.

  7. Effects of Some Management Practices on Electron Transport System (ETS) Activity in Paddy Soil

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Electron transport system (ETS)/dehydrogenase activity in a paddy field soil was measured under a variety of incubation conditions using the reduction of 2-(p-iodophenyl-3-(p-nitrophenyl)-5-phenyl tetrazolium chloride (INT) to iodonitrotetrazolium formazan (INTF). The results exhibited a high positive correlation between the ETS activity and the incubation temperature and soil moisture. Dehydrogenase/ETS activity displayed a negative correlation with insecticide concentrations, and the activity affected adversely as the concentration of the insecticide increased. The higher doses, 5 and 10 field rates (1 field rate = 1500 mL ha-1), of insecticide significantly inhibited ETS activity, while lower rates failed to produce any significant reducing effect. Inorganic N (as urea) of concentrations from 0 to 100 μg N g-1 soil showed a positive response to ETS activity. However, at concentrations of 200 and 400μg N g-1, the activity was reduced significantly.

  8. Ratchet transport of an active-passive mixture chain in confined structures

    Science.gov (United States)

    Lu, Shi-cai; Ou, Ya-li; Ai, Bao-quan

    2017-09-01

    Rectified transport of the active-passive mixture chain is numerically investigated in periodic confined structures. Due to the out-of-equilibrium property of active particles in the chain, the whole chain can be rectified. It is found that the interaction between particles can significantly affect the rectified transport. When all particles in the chain are active, the directed velocity decreases monotonously with increasing the interaction strength. When the particles are mixture, on increasing the interaction strength, the directed velocity firstly decreases to its minimal value, then increases to its maximal value, and finally decreases to zero. In addition, there exist optimal parameters (self-propelled velocity, the natural length of the spring) at which the average velocity is maximal.

  9. Measurement of multiple drug resistance transporter activity in putative cancer stem/progenitor cells.

    Science.gov (United States)

    Donnenberg, Vera S; Meyer, E Michael; Donnenberg, Albert D

    2009-01-01

    Multiple drug resistance, mediated by the expression and activity of ABC-transporters, is a major obstacle to antineoplastic therapy. Normal tissue stem cells and their malignant counterparts share MDR transporter activity as a major mechanism of self-protection. Although MDR activity is upregulated in response to substrate chemotherapeutic agents, it is also constitutively expressed on both normal tissue stem cells and a subset of tumor cells prior to the initiation of therapy, representing a built-in obstacle to therapeutic ratio. Constitutive and induced MDR activity can be detected in cellular subsets of disaggregated tissues, using the fluorescent substrates Rhodamine 123 and Hoechst 33342 for ABCB1 (also known as P-gp and MDR1) and ABCG2 (BCRP1). In this chapter, we will describe the complete procedure for the detection of MDR activity, including: (1) Preparing single-cell suspensions from tumor and normal tissue specimens; (2) An efficient method to perform cell surface marker staining on large numbers of cells; (3) Flow cytometer setup and controls; (4) Simultaneous measurement of Hoechst 33342 and Rhodamine123 transport; and (5) Data acquisition and analysis.

  10. Na+- and Cl−-coupled active transport of carnitine by the amino acid transporter ATB0,+ from mouse colon expressed in HRPE cells and Xenopus oocytes

    Science.gov (United States)

    Nakanishi, Takeo; Hatanaka, Takahiro; Huang, Wei; Prasad, Puttur D; Leibach, Frederick H; Ganapathy, Malliga E; Ganapathy, Vadivel

    2001-01-01

    ATB0,+ is an amino acid transporter energized by transmembrane gradients of Na+ and Cl− and membrane potential. We cloned this transporter from mouse colon and expressed the clone functionally in mammalian (human retinal pigment epithelial, HRPE) cells and Xenopus laevis oocytes to investigate the interaction of carnitine and its acyl esters with the transporter. When expressed in mammalian cells, the cloned ATB0,+ was able to transport carnitine, propionylcarnitine and acetylcarnitine. The transport process was Na+ and Cl− dependent and inhibitable by the amino acid substrates of the transporter. The Michaelis constant for carnitine was 0.83 ± 0.08 mm and the Hill coefficient for Na+ activation was 1.6 ± 0.1. When expressed in Xenopus laevis oocytes, the cloned ATB0,+ was able to induce inward currents in the presence of carnitine and propionylcarnitine under voltage-clamped conditions. There was no detectable current in the presence of acetylcarnitine. Carnitine-induced currents were obligatorily dependent on the presence of Na+ and Cl−. The currents were saturable with carnitine and the Michaelis constant was 1.8 ± 0.4 mm. The analysis of Na+- and Cl−-activation kinetics revealed that 2 Na+ and 1 Cl− were involved in the transport of carnitine via the transporter. These studies describe the identification of a novel function for the amino acid transporter ATB0,+. Since this transporter is expressed in the intestinal tract, lung and mammary gland, it is likely to play a significant role in the handling of carnitine in these tissues. A Na+-dependent transport system for carnitine has already been described. This transporter, known as OCTN2 (novel organic cation transporter 2), is expressed in most tissues and transports carnitine with high affinity. It is energized, however, only by a Na+ gradient and membrane potential. In contrast, ATB0,+ is a low-affinity transporter for carnitine, but exhibits much higher concentrative capacity than OCTN2 because

  11. Variations in active transport behavior among different neighborhoods and across adult life stages

    DEFF Research Database (Denmark)

    Christiansen, Lars Breum; Madsen, Thomas; Schipperijn, Jasper;

    2014-01-01

    OBJECTIVE: Built environment characteristics are closely related to transport behavior, but observed variations could be due to residents own choice of neighborhood called residential self-selection. The aim of this study was to investigate differences in neighborhood walkability and residential...... self-selection across life stages in relation to active transport behavior. METHODS: The IPEN walkability index, which consists of four built environment characteristics, was used to define 16 high and low walkable neighborhoods in Aarhus, Denmark (250.000 inhabitants). Transport behavior was assessed...... using the IPAQ questionnaire. Life stages were categorized in three groups according to age and parental status. A factor analysis was conducted to investigate patterns of self-selection. Multivariable logistic regression analyses were carried out to evaluate the association between walkability...

  12. Light-activated amino acid transport in Halobacterium halobium envelope vesicles

    Science.gov (United States)

    Macdonald, R. E.; Lanyi, J. K.

    1977-01-01

    Vesicles prepared from Halobacterium halobium cell envelopes accumulate amino acids in response to light-induced electrical and chemical gradients. Nineteen of 20 commonly occurring amino acids have been shown to be actively accumulated by these vesicles in response to illumination or in response to an artificially created Na+ gradient. On the basis of shared common carriers the transport systems can be divided into eight classes, each responsible for the transport of one or several amino acids: arginine, lysine, histidine; asparagine, glutamine; alanine, glycine, threonine, serine; leucine, valine, isoleucine, methionine; phenylalanine, tyrosine, tryptophan; aspartate; glutamate; proline. Available evidence suggests that these carriers are symmetrical in that amino acids can be transported equally well in both directions across the vesicle membranes. A tentative working model to account for these observations is presented.

  13. Estimating active transportation behaviors to support health impact assessment in the United States

    Directory of Open Access Journals (Sweden)

    Theodore J Mansfield

    2016-05-01

    Full Text Available Health impact assessment (HIA has been promoted as a means to encourage transportation and city planners to incorporate health considerations into their decision-making. Ideally, HIAs would include quantitative estimates of the population health effects of alternative planning scenarios, such as scenarios with and without infrastructure to support walking and cycling. However, the lack of baseline estimates of time spent walking or biking for transportation (together known as active transportation, which are critically related to health, often prevents planners from developing such quantitative estimates. To address this gap, we use data from the 2009 US National Household Travel Survey to develop a statistical model that estimates baseline time spent walking and biking as a function of the type of transportation used to commute to work along with demographic and built environment variables. We validate the model using survey data from the Raleigh-Durham-Chapel Hill, NC, metropolitan area. We illustrate how the validated model could be used to support transportation-related HIAs by estimating the potential health benefits of built environment modifications that support walking and cycling. Our statistical model estimates that on average, individuals who commute on foot spend an additional 19.8 (95% CI 16.9–23.2 minutes per day walking compared to automobile commuters. Public transit riders walk an additional 5.0 (95% CI 3.5–6.4 minutes per day compared to automobile commuters. Bicycle commuters cycle for an additional 28.0 (95% CI 17.5–38.1 minutes per day compared to automobile commuters. The statistical model was able to predict observed transportation physical activity in the Raleigh-Durham-Chapel Hill region to within 0.5 MET-hours per day (equivalent to about 9 minutes of daily walking time for 83% of observations. Across the Raleigh-Durham-Chapel Hill region, an estimated 38 (95% CI 15–59 premature deaths potentially could be

  14. Estimating Active Transportation Behaviors to Support Health Impact Assessment in the United States.

    Science.gov (United States)

    Mansfield, Theodore J; Gibson, Jacqueline MacDonald

    2016-01-01

    Health impact assessment (HIA) has been promoted as a means to encourage transportation and city planners to incorporate health considerations into their decision-making. Ideally, HIAs would include quantitative estimates of the population health effects of alternative planning scenarios, such as scenarios with and without infrastructure to support walking and cycling. However, the lack of baseline estimates of time spent walking or biking for transportation (together known as "active transportation"), which are critically related to health, often prevents planners from developing such quantitative estimates. To address this gap, we use data from the 2009 US National Household Travel Survey to develop a statistical model that estimates baseline time spent walking and biking as a function of the type of transportation used to commute to work along with demographic and built environment variables. We validate the model using survey data from the Raleigh-Durham-Chapel Hill, NC, USA, metropolitan area. We illustrate how the validated model could be used to support transportation-related HIAs by estimating the potential health benefits of built environment modifications that support walking and cycling. Our statistical model estimates that on average, individuals who commute on foot spend an additional 19.8 (95% CI 16.9-23.2) minutes per day walking compared to automobile commuters. Public transit riders walk an additional 5.0 (95% CI 3.5-6.4) minutes per day compared to automobile commuters. Bicycle commuters cycle for an additional 28.0 (95% CI 17.5-38.1) minutes per day compared to automobile commuters. The statistical model was able to predict observed transportation physical activity in the Raleigh-Durham-Chapel Hill region to within 0.5 MET-hours per day (equivalent to about 9 min of daily walking time) for 83% of observations. Across the Raleigh-Durham-Chapel Hill region, an estimated 38 (95% CI 15-59) premature deaths potentially could be avoided if the entire

  15. Benzotropolone moiety in theaflavins is responsiblefor inhibitingpeptide-transport and activating AMP-activated protein kinase in Caco-2 cells

    Directory of Open Access Journals (Sweden)

    Ha-Young Park

    2013-05-01

    Full Text Available ABSTRACTObjective:In the small intestine, peptide transporter 1 (PEPT1 plays a role in the transport of di- and tri-peptides. Recently, we found that theaflavins (TFs, dimeric catechins, inhibitedthe transport of di-peptides across Caco-2 monolayersby suppressingthe expression of PEPT1 through AMP-activated protein kinase (AMPK activation. In this study, we investigated the structural requirement of theaflavinsfor the effect, and the mechanism(sunderling theaflavin-induced AMPK activation.Methods:Theaflavin-3’-O-gallate (TF3’G was used forthis study, since it possessed the most potent inhibition power for peptide-transport among theaflavins. Absorption ability was measured with Caco-2 cell monolayers treated with or without 20 M sample (TF3’G or its related compounds in an Ussing Chamber. The amountof Gly-Sar (a model of PEPT1-transporing peptide transportat fixed time-pointsto 60min wasdeterminedby fluorescent naphthalene-2,3-dicarboxaldehyde-derivatized assay(Ex/Em: 405 nm/460 nm. The apparent permeability coefficient(Papp wasused to evaluate the permeability. Expression of PEPT1 protein in Caco-2 cells treated with or without 20 M TF3’G in the presence or absence of inhibitor (10 μM compound C as AMPK inhibitor or 25 μMSTO-609 as CaMKK inhibitor wasevaluated by Western blot.Results:The Pappvalue of Gly-Sar significantly (P<0.05 decreasedin 20 μM purprogallin-treated Caco-2 cellsas well asin TF3’G-treated cells, together with the reduction of PEPT1 expression, while their monomeric catechins did not show any Pappreduction. In TF3’G-treated Caco-2 cells, the recovery of the reduced PEPT1 expression was found by 10 μM compound C,but not STO-609.Conclusion:The study demonstrated that the benzotropolone moiety in theaflavins was a crucial structural requirement for exerting the inhibition of intestinal peptide-transport,and the suppression of PEPT1 expression by theaflavins would be caused by activating LKB1/AMPK pathway

  16. Modulation of LAT1 (SLC7A5) transporter activity and stability by membrane cholesterol

    Science.gov (United States)

    Dickens, David; Chiduza, George N.; Wright, Gareth S. A.; Pirmohamed, Munir; Antonyuk, Svetlana V.; Hasnain, S. Samar

    2017-01-01

    LAT1 (SLC7A5) is a transporter for both the uptake of large neutral amino acids and a number of pharmaceutical drugs. It is expressed in numerous cell types including T-cells, cancer cells and brain endothelial cells. However, mechanistic knowledge of how it functions and its interactions with lipids are unknown or limited due to inability of obtaining stable purified protein in sufficient quantities. Our data show that depleting cellular cholesterol reduced the Vmax but not the Km of the LAT1 mediated uptake of a model substrate into cells (L-DOPA). A soluble cholesterol analogue was required for the stable purification of the LAT1 with its chaperon CD98 (4F2hc,SLC3A2) and that this stabilised complex retained the ability to interact with a substrate. We propose cholesterol interacts with the conserved regions in the LAT1 transporter that have been shown to bind to cholesterol/CHS in Drosophila melanogaster dopamine transporter. In conclusion, LAT1 is modulated by cholesterol impacting on its stability and transporter activity. This novel finding has implications for other SLC7 family members and additional eukaryotic transporters that contain the LeuT fold. PMID:28272458

  17. Symplasmic networks in secondary vascular tissues: parenchyma distribution and activity supporting long-distance transport.

    Science.gov (United States)

    Spicer, Rachel

    2014-04-01

    Stems that develop secondary vascular tissue (i.e. xylem and phloem derived from the vascular cambium) have unique demands on transport owing to their mass and longevity. Transport of water and assimilates must occur over long distances, while the increasing physical separation of xylem and phloem requires radial transport. Developing secondary tissue is itself a strong sink positioned between xylem and phloem along the entire length of the stem, and the integrity of these transport tissues must be maintained and protected for years if not decades. Parenchyma cells form an interconnected three-dimensional lattice throughout secondary xylem and phloem and perform critical roles in all of these tasks, yet our understanding of their physiology, the nature of their symplasmic connections, and their activity at the symplast-apoplast interface is very limited. This review highlights key historical work as well as current research on the structure and function of parenchyma in secondary vascular tissue in the hopes of spurring renewed interest in this area, which has important implications for whole-plant transport processes and resource partitioning.

  18. Community Vision and Interagency Alignment: A Community Planning Process to Promote Active Transportation.

    Science.gov (United States)

    DeGregory, Sarah Timmins; Chaudhury, Nupur; Kennedy, Patrick; Noyes, Philip; Maybank, Aletha

    2016-04-01

    In 2010, the Brooklyn Active Transportation Community Planning Initiative launched in 2 New York City neighborhoods. Over a 2-year planning period, residents participated in surveys, school and community forums, neighborhood street assessments, and activation events-activities that highlighted the need for safer streets locally. Consensus among residents and key multisectoral stakeholders, including city agencies and community-based organizations, was garnered in support of a planned expansion of bicycling infrastructure. The process of building on community assets and applying a collective impact approach yielded changes in the built environment, attracted new partners and resources, and helped to restore a sense of power among residents.

  19. Criterion distances and correlates of active transportation to school in Belgian older adolescents

    Directory of Open Access Journals (Sweden)

    De Bourdeaudhuij Ilse

    2010-12-01

    Full Text Available Abstract Background Since physical activity levels in older adolescents have the potential to be increased by stimulating active transportation to school (ATS, the most important correlates of ATS should be determined before developing interventions, especially in those adolescents for whom the distance to school is feasible for active commuting. The main aims of this study were to determine criterion distances for ATS in Belgian older adolescents, to examine multidimensional correlates of ATS in adolescents living within a feasible distance from school and to investigate the associations of ATS with total physical activity and with other physical activities besides ATS. Methods In total, 1281 older adolescents (17-18 years from 20 general secondary schools in East- and West-Flanders completed a questionnaire on physical activity behaviors, demographic factors and psychosocial and physical environmental correlates of physical activity. Distance to school was objectively measured using Routenet online route planner. Results In total, 58.4% of the participants commuted actively to school. The criterion distance for ATS could be set at eight kilometers for cycling and two kilometers for walking. For those adolescents living within a feasible distance for ATS, gender, smoking status, walkability of the neighborhood and social modeling were associated with transportation mode choice. ATS was positively associated with total physical activity, but not significantly related to min/week of other physical activities. Conclusions For older adolescents living within eight kilometers of their school, interventions taking into account the correlates found to be related to ATS could possibly be effective to enhance ATS and to increase total physical activity levels. In the context of the overall physical activity decline in adolescence, also interventions targeting physical activity behaviors of adolescents living further away from school might be needed, but

  20. The contribution of SNAT1 to system A amino acid transporter activity in human placental trophoblast

    Energy Technology Data Exchange (ETDEWEB)

    Desforges, M., E-mail: michelle.desforges@manchester.ac.uk [Maternal and Fetal Health Research Centre, Developmental Biomedicine, School of Medicine, Manchester Academic Health Sciences Centre, University of Manchester, St. Mary' s Hospital, Level 5-Research, Oxford Road, Manchester M13 9WL (United Kingdom); Greenwood, S.L.; Glazier, J.D.; Westwood, M.; Sibley, C.P. [Maternal and Fetal Health Research Centre, Developmental Biomedicine, School of Medicine, Manchester Academic Health Sciences Centre, University of Manchester, St. Mary' s Hospital, Level 5-Research, Oxford Road, Manchester M13 9WL (United Kingdom)

    2010-07-16

    Research highlights: {yields} mRNA levels for SNAT1 are higher than other system A subtype mRNAs in primary human cytotrophoblast. {yields} SNAT1 knockdown in cytotrophoblast cells significantly reduces system A activity. {yields} SNAT1 is a key contributor to system A-mediated amino acid transport in human placenta. -- Abstract: System A-mediated amino acid transport across the placenta is important for the supply of neutral amino acids needed for fetal growth. All three system A subtypes (SNAT1, 2, and 4) are expressed in human placental trophoblast suggesting there is an important biological role for each. Placental system A activity increases as pregnancy progresses, coinciding with increased fetal nutrient demands. We have previously shown SNAT4-mediated system A activity is higher in first trimester than at term, suggesting that SNAT1 and/or SNAT2 are responsible for the increased system A activity later in gestation. However, the relative contribution of each subtype to transporter activity in trophoblast at term has yet to be evaluated. The purpose of this study was to identify the predominant subtype of system A in cytotrophoblast cells isolated from term placenta, maintained in culture for 66 h, by: (1) measuring mRNA expression of the three subtypes and determining the Michaelis-Menten constants for uptake of the system A-specific substrate, {sup 14}C-MeAIB, (2) investigating the contribution of SNAT1 to total system A activity using siRNA. Results: mRNA expression was highest for the SNAT1 subtype of system A. Kinetic analysis of {sup 14}C-MeAIB uptake revealed two distinct transport systems; system 1: K{sub m} = 0.38 {+-} 0.12 mM, V{sub max} = 27.8 {+-} 9.0 pmol/mg protein/20 min, which resembles that reported for SNAT1 and SNAT2 in other cell types, and system 2: K{sub m} = 45.4 {+-} 25.0 mM, V{sub max} = 1190 {+-} 291 pmol/mg protein/20 min, which potentially represents SNAT4. Successful knockdown of SNAT1 mRNA using target-specific si

  1. Sediment transport in an active erodible channel bend of Brahmaputra river

    Indian Academy of Sciences (India)

    Tapas Karmaker; Y Ramprasad; Subashisa Dutta

    2010-12-01

    Spatial variation of sediment transport in an alluvial sand-bed river bend needs to be understood with its influencing factors such as bank erosion, secondary current formation, land spur and bed-material characteristics. In this study, detailed hydrographic surveys with Acoustic Doppler Current Profiler (ADCP) were conducted at an active erodible river bend to measure suspended load, velocity, bathymetric profile and characteristics of the bed material. Study indicates the presence of multi-thread flow in the channel bend. Local variation of sediment transport is primarily controlled by active bank erosion, land spur and sand bar formation. Vertical distribution of suspended sediment concentration follows a power function with normalized depth. Average bed-material concentration at the reach level is computed from observed sediment profiles, and is compared against various sediment transport functions. Results show that the sediment transport function suggested by Yang gives better predictions for this reach. Transverse bed slopes at critical survey transects were computed from the bathymetric data and evaluated with analytical approaches. Out of three analytical approaches used, Odgaard’s approach estimates the bed slopes fairly close to the observed one. These two functions are suitable in the Brahmaputra river for further morphological studies.

  2. Quantification of ionic transport within thermally-activated batteries using electron probe micro-analysis

    Science.gov (United States)

    Humplik, Thomas; Stirrup, Emily K.; Grillet, Anne M.; Grant, Richard P.; Allen, Ashley N.; Wesolowski, Daniel E.; Roberts, Christine C.

    2016-07-01

    The transient transport of electrolytes in thermally-activated batteries is studied using electron probe micro-analysis (EPMA), demonstrating the robust capability of EPMA as a useful tool for studying and quantifying mass transport within porous materials, particularly in difficult environments where classical flow measurements are challenging. By tracking the mobility of bromine and potassium ions from the electrolyte stored within the separator into the lithium silicon anode and iron disulfide cathode, we are able to quantify the transport mechanisms and physical properties of the electrodes including permeability and tortuosity. Due to the micron to submicron scale porous structure of the initially dry anode, a fast capillary pressure driven flow is observed into the anode from which we are able to set a lower bound on the permeability of 10-1 mDarcy. The transport into the cathode is diffusion-limited because the cathode originally contained some electrolyte before activation. Using a transient one-dimensional diffusion model, we estimate the tortuosity of the cathode electrode to be 2.8 ± 0.8.

  3. A fully resolved fluid-structure-muscle-activation model for esophageal transport

    Science.gov (United States)

    Kou, Wenjun; Bhalla, Amneet P. S.; Griffith, Boyce E.; Johnson, Mark; Patankar, Neelesh A.

    2013-11-01

    Esophageal transport is a mechanical and physiological process that transfers the ingested food bolus from the pharynx to the stomach through a multi-layered esophageal tube. The process involves interactions between the bolus, esophageal wall composed of mucosal, circular muscle (CM) and longitudinal muscle (LM) layers, and neurally coordinated muscle activation including CM contraction and LM shortening. In this work, we present a 3D fully-resolved model of esophageal transport based on the immersed boundary method. The model describes the bolus as a Newtonian fluid, the esophageal wall as a multi-layered elastic tube represented by springs and beams, and the muscle activation as a traveling wave of sequential actuation/relaxation of muscle fibers, represented by springs with dynamic rest lengths. Results on intraluminal pressure profile and bolus shape will be shown, which are qualitatively consistent with experimental observations. Effects of activating CM contraction only, LM shortening only or both, for the bolus transport, are studied. A comparison among them can help to identify the role of each type of muscle activation. The support of grant R01 DK56033 and R01 DK079902 from NIH is gratefully acknowledged.

  4. Home transport and wastage: environmentally relevant household activities in the life cycle of food.

    Science.gov (United States)

    Sonesson, Ulf; Anteson, Frida; Davis, Jennifer; Sjödén, Per-Olow

    2005-06-01

    In environmental systems analysis of food production systems, the consumer phase (home transport, cooking, storing, and wastage) is an important contributor to the total life-cycle environmental impact. However, households are the least investigated part of the food chain. Information gathering about households involves difficulties; the number of households is large, and food-related activities are embedded in other household activities. In cooperation between researchers from environmental systems analysis and consumer research, Swedish households were surveyed by questionnaire, diary, and interviews. Data on home transport of food and wastage were collected. The average weekly driving distance was 28 to 63 km per household, depending on how trips made in conjunction with other errands are allocated. The wastage of prepared food ranged between 0 and 34% for different food categories, and wastage from storing between 0 and 164% (more food was discarded, e.g. by cleaning out a cupboard, than consumed). In both cases dairy products scored highest.

  5. Experimental thermal transport evolution of silane activated nano-clay reinforced styrene butadiene elastomeric nanocomposites

    Science.gov (United States)

    Iqbal, S. S.; Iqbal, N.; Jamil, T.; Bashir, A.; Shahid, M.

    2016-08-01

    In this study, silane activated nanoclay was reinforced in styrene butadiene rubber (SBR) to enhance the thermal resistance/stability and mechanical properties of SBR. silane activated nanoclay with variant concentrations was impregnated in the rubber matrix to fabricate polymer nanocomposites under control processing conditions. Experimental thermal transport, thermal oxidation, phase transition study, and mechanical properties of the nanocomposite specimens were carried out. Thermal insulation, thermal stability, and heat flow response were remarkably enhanced with the addition of nanokaolinite in the polymer matrix. Phase transition temperatures, their corresponding enthalpies, tensile strength, elastic modulus, elongation at break and hardness of the rubber composites were positively influenced with the filler incorporation into the host matrix. The Even dispersion of nanoreinforcements, morphological and compositional analyses of the thermal transport tested specimens were performed using scanning electron microscopy and energy dispersive spectroscopy, respectively.

  6. Dynamic defect correlations dominate activated electronic transport in SrTiO3

    Science.gov (United States)

    Snijders, Paul C.; Şen, Cengiz; McConnell, Michael P.; Ma, Ying-Zhong; May, Andrew F.; Herklotz, Andreas; Wong, Anthony T.; Ward, T. Zac

    2016-07-01

    Strontium titanate (SrTiO3, STO) is a critically important material for the study of emergent electronic phases in complex oxides, as well as for the development of applications based on their heterostructures. Despite the large body of knowledge on STO, there are still many uncertainties regarding the role of defects in the properties of STO, including their influence on ferroelectricity in bulk STO and ferromagnetism in STO-based heterostructures. We present a detailed analysis of the decay of persistent photoconductivity in STO single crystals with defect concentrations that are relatively low but significantly affect their electronic properties. The results show that photo-activated electron transport cannot be described by a superposition of the properties due to independent point defects as current models suggest but is, instead, governed by defect complexes that interact through dynamic correlations. These results emphasize the importance of defect correlations for activated electronic transport properties of semiconducting and insulating perovskite oxides.

  7. Nanoscale charge transport in cytochrome c3/DNA network: Comparative studies between redox-active molecules

    Science.gov (United States)

    Yamaguchi, Harumasa; Che, Dock-Chil; Hirano, Yoshiaki; Suzuki, Masayuki; Higuchi, Yoshiki; Matsumoto, Takuya

    2015-09-01

    The redox-active molecule of a cytochrome c3/DNA network exhibits nonlinear current-voltage (I-V) characteristics with a threshold bias voltage at low temperature and zero-bias conductance at room temperature. I-V curves for the cytochrome c3/DNA network are well matched with the Coulomb blockade network model. Comparative studies of the Mn12 cluster, cytochrome c, and cytochrome c3, which have a wide variety of redox potentials, indicate no difference in charge transport, which suggests that the conduction mechanism is not directly related to the redox states. The charge transport mechanism has been discussed in terms of the newly-formed electronic energy states near the Fermi level, induced by the ionic interaction between redox-active molecules with the DNA network.

  8. Impact of travel mode shift and trip distance on active and non-active transportation in the São Paulo Metropolitan Area in Brazil

    Directory of Open Access Journals (Sweden)

    Thiago Hérick de Sá

    2015-01-01

    Conclusion: Transport and urban planning policies to reduce individual motorized trips and the number of long trips might produce important health benefits, both by increasing population levels of active transportation and reducing the non-active and the total time of daily trips.

  9. Interactions of ( sup 3 H)amphetamine with rat brain synaptosomes. II. Active transport

    Energy Technology Data Exchange (ETDEWEB)

    Zaczek, R.; Culp, S.; De Souza, E.B. (Addiction Research Center, Baltimore, MD (USA))

    1991-05-01

    The accumulation of 5 nM d-({sup 3}H)amphetamine (d-({sup 3}H)AMPH) into rat brain synaptosomes was examined using physiological buffer conditions. The accumulation of d-({sup 3}H)AMPH into striatal synaptosomes was saturable, of high affinity, ouabain-sensitive and temperature-dependent, suggesting an active transport phenomenon. Eadee-Hofstee analysis of striatal d-({sup 3}H)AMPH transport (AMT) saturation isotherms indicated an apparent Km of 97 nM and a Vmax of 3.0 fmol/mg tissue/min. Lesion of the striatal dopaminergic innervation led to equivalent decreases of ({sup 3}H) dopamine (DA) transport and AMT, indicating that AMT occurs in DA terminals. Furthermore, AMT was not evident in cerebral cortex, a brain region with a paucity of DA terminals. In competition studies, AMT was stereospecific; d-AMPH (IC50 = 60 nM) was an 8-fold more potent inhibitor of the transport than its I-isomer (IC50 = 466 nM). DA(IC50 = 257 nM), DA uptake blockers and substrates were found to be potent inhibitors of AMT: GBR12909 IC50 = 5 nM; methamphetamine IC50 = 48 nM; methylphenidate IC50 = 53 nM; and cocaine IC50 = 172 nM. In contrast, serotonin was relatively weak in inhibiting AMT (IC50 = 7.9 microM). There was a highly significant (P less than .001; slope = 1.2) linear correlation between the AMT-inhibiting potencies of AMPH analogs and their potencies in stimulating locomotor activity in rodents. AMT may be important in the low dose effects of AMPH such as increased locomotor activity in rodents and stimulant activity in man. Differences between AMT and d-({sup 3}H)AMPH sequestration described earlier, as well as their possible relevance to behavioral and neurochemical sequelae of AMPH administration are also discussed.

  10. System Studies on Active Thermal Protection of a Hypersonic Suborbital Passenger Transport Vehicle

    OpenAIRE

    Schwanekamp, Tobias; Meyer, Frank; Reimer, Thomas; Petkov, Ivaylo; Tröltzsch, Anke; Siggel, Martin

    2014-01-01

    Aerodynamic heating is a critical design aspect for the development of reusable hypersonic transport and reentry vehicles. The reliability in terms of thermal resistance is one of the major driving factors with respect to the design margins, the mass balance and finally the total costs of a configuration. Potential designs of active cooling systems for critical regions such as the vehicle nose and leading edges are presented as well as preliminary approaches for their impact on the total mass...

  11. By your own two feet: factors associated with active transportation in Canada.

    Science.gov (United States)

    Butler, Gregory P; Orpana, Heather M; Wiens, Alexander J

    2007-01-01

    The purpose of this study is to examine socio-demographic, geographic and physical activity correlates of walking and cycling for non-leisure purposes, i.e., to work, school, or errands, in Canada. Cross-sectional data from the Canadian Community Health Survey (CCHS) 2003 (n = 127,610) were analyzed using logistic regression to identify factors associated with active transportation. The dependent variables were walking 6+ hours per week and any cycling per week. Independent variables were based on age; marital, education, working and immigrant status; income; geographic location; smoking; and other physical activity. Age and income were associated with both walking and cycling, as was geographic location and other physical activity. The results demonstrated that, while similar, walking and cycling are associated with different factors, and that socio-demographic, geographic and health behaviour variables must be taken into consideration when modelling these transportation modes. Although walking and cycling are relatively easy means to incorporate physical activity in daily life, these results suggest that it is the young and the physically active who engage in them. This research points to a need to address barriers among those who could benefit the most from increased use of both modes of travel.

  12. Association of serotonin transporter promoter regulatory region polymorphism and cerebral activity to visual presentation of food.

    Science.gov (United States)

    Kaurijoki, Salla; Kuikka, Jyrki T; Niskanen, Eini; Carlson, Synnöve; Pietiläinen, Kirsi H; Pesonen, Ullamari; Kaprio, Jaakko M; Rissanen, Aila; Tiihonen, Jari; Karhunen, Leila

    2008-07-01

    Recent functional magnetic resonance imaging (fMRI) studies have revealed links between genetic polymorphisms and cognitive and behavioural processes. Serotonin is a classical neurotransmitter of central nervous system, and it is connected to the control of appetite and satiety. In this study, the relationship between the functional variation in the serotonin transporter gene and the activity in the left posterior cingulate cortex (PCC), a brain area activated by visual food stimuli was explored. Thirty subjects underwent serial fMRI studies and provided DNA for genetic analyses. Subjects homozygous for the long allele exhibited greater left PCC activity in the comparison food > non-food compared with individuals heterozygous or homozygous for the short allele. The association between genotype and activation was linear, the subjects with two copies of the long allele variant having the strongest activation. These results demonstrate the possible genetically driven variation in the response of the left PCC to visual presentation of food in humans.

  13. Mixing it up: Corals take an active role in mass transport

    Science.gov (United States)

    Fernandez, Vicente; Shapiro, Orr; Brumley, Douglas; Garren, Melissa; Guasto, Jeffrey; Kramarski-Winter, Esti; Vardi, Assaf; Stocker, Roman

    2014-11-01

    The growth and health of reef-building corals are limited by corals' ability to exchange nutrients and oxygen with the surrounding, sometimes quiescent, seawater. Mass transport in coral systems has long been considered to occur passively as a result of molecular diffusion and the ambient fluid flow over the coral. Through a combination of microscale visualization experiments and numerical modeling, we demonstrate instead that motile cilia densely covering the coral surface - previously thought to serve cleaning and feeding purposes- actively stir the coral boundary layer by generating persistent vortices above the coral surface. This active mixing was observed over a variety of corals with differing surface geometries. We have quantified the contribution of ciliary surface vortices to mass transport, finding oxygen flux enhancements of 2 to 3 orders of magnitude under environmentally relevant ambient flow conditions. These results reveal a new, active role of the coral animal in regulating its mass transport by engineering its local hydrodynamic environment, an ability that may have an important role in the evolutionary success of reef corals.

  14. Schools, Air Pollution, and Active Transportation: An Exploratory Spatial Analysis of Calgary, Canada.

    Science.gov (United States)

    Bertazzon, Stefania; Shahid, Rizwan

    2017-07-25

    An exploratory spatial analysis investigates the location of schools in Calgary (Canada) in relation to air pollution and active transportation options. Air pollution exhibits marked spatial variation throughout the city, along with distinct spatial patterns in summer and winter; however, all school locations lie within low to moderate pollution levels. Conversely, the study shows that almost half of the schools lie in low walkability locations; likewise, transitability is low for 60% of schools, and only bikability is widespread, with 93% of schools in very bikable locations. School locations are subsequently categorized by pollution exposure and active transportation options. This analysis identifies and maps schools according to two levels of concern: schools in car-dependent locations and relatively high pollution; and schools in locations conducive of active transportation, yet exposed to relatively high pollution. The findings can be mapped and effectively communicated to the public, health practitioners, and school boards. The study contributes with an explicitly spatial approach to the intra-urban public health literature. Developed for a moderately polluted city, the methods can be extended to more severely polluted environments, to assist in developing spatial public health policies to improve respiratory outcomes, neurodevelopment, and metabolic and attention disorders in school-aged children.

  15. Schools, Air Pollution, and Active Transportation: An Exploratory Spatial Analysis of Calgary, Canada

    Science.gov (United States)

    Bertazzon, Stefania; Shahid, Rizwan

    2017-01-01

    An exploratory spatial analysis investigates the location of schools in Calgary (Canada) in relation to air pollution and active transportation options. Air pollution exhibits marked spatial variation throughout the city, along with distinct spatial patterns in summer and winter; however, all school locations lie within low to moderate pollution levels. Conversely, the study shows that almost half of the schools lie in low walkability locations; likewise, transitability is low for 60% of schools, and only bikability is widespread, with 93% of schools in very bikable locations. School locations are subsequently categorized by pollution exposure and active transportation options. This analysis identifies and maps schools according to two levels of concern: schools in car-dependent locations and relatively high pollution; and schools in locations conducive of active transportation, yet exposed to relatively high pollution. The findings can be mapped and effectively communicated to the public, health practitioners, and school boards. The study contributes with an explicitly spatial approach to the intra-urban public health literature. Developed for a moderately polluted city, the methods can be extended to more severely polluted environments, to assist in developing spatial public health policies to improve respiratory outcomes, neurodevelopment, and metabolic and attention disorders in school-aged children. PMID:28757577

  16. EarthScope Transportable Array Siting Outreach Activities in Alaska and Western Canada

    Science.gov (United States)

    Gardine, L.; Dorr, P. M.; Tape, C.; McQuillan, P.; Taber, J.; West, M. E.; Busby, R. W.

    2014-12-01

    The EarthScopeTransportable Array is working to locate over 260 stations in Alaska and western Canada. In this region, new tactics and partnerships are needed to increase outreach exposure. IRIS and EarthScope are partnering with the Alaska Earthquake Center, part of University of Alaska Geophysical Institute, to spread awareness of Alaska earthquakes and the benefits of the Transportable Array for Alaskans. Nearly all parts of Alaska are tectonically active. The tectonic and seismic variability of Alaska requires focused attention at the regional level, and the remoteness and inaccessibility of most Alaska villages and towns often makes frequent visits difficult. For this reason, Alaska outreach most often occurs at community events. When a community is accessible, every opportunity to engage the residents is made. Booths at state fairs and large cultural gatherings, such as the annual convention of the Alaska Federation of Natives, are excellent venues to distribute earthquake information and to demonstrate a wide variety of educational products and web-based applications related to seismology and the Transportable Array that residents can use in their own communities. Region-specific publications have been developed to tie in a sense of place for residents of Alaska. The Alaska content for IRIS's Active Earth Monitor will emphasize the widespread tectonic and seismic features and offer not just Alaska residents, but anyone interested in Alaska, a glimpse into what is going on beneath their feet. The concerted efforts of the outreach team will have lasting effects on Alaskan understanding of the seismic hazard and tectonics of the region. Efforts to publicize the presence of the Transportable Array in Alaska, western Canada, and the Lower 48 also continue. There have been recent articles published in university, local and regional newspapers; stories appearing in national and international print and broadcast media; and documentaries produced by some of the world

  17. Peptides actively transported across the tympanic membrane: Functional and structural properties

    Science.gov (United States)

    Kurabi, Arwa; Beasley, Kerry A.; Chang, Lisa; McCann, James; Pak, Kwang; Ryan, Allen F.

    2017-01-01

    Otitis media (OM) is the most common infectious disease of children under six, causing more antibiotic prescriptions and surgical procedures than any other pediatric condition. By screening a bacteriophage (phage) library genetically engineered to express random peptides on their surfaces, we discovered unique peptides that actively transport phage particles across the intact tympanic membrane (TM) and into the middle ear (ME). Herein our goals were to characterize the physiochemical peptide features that may underlie trans-TM phage transport; assess morphological and functional effects of phage peptides on the ME and inner ear (IE); and determine whether peptide-bearing phage transmigrate from the ME into the IE. Incubation of five peptide-bearing phage on the TM for over 4hrs resulted in demonstrably superior transport of one peptide, in level and in exponential increase over time. This suggests a preferred peptide motif for TM active transport. Functional and structural comparisons revealed unique features of this peptide: These include a central lysine residue, isoelectric point of 0.0 at physiological pH and a hydrophobic C-terminus. When the optimal peptide was applied to the TM independent of phage, similar transport was observed, indicating that integration into phage is not required. When 109 particles of the four different trans-TM phage were applied directly into the ME, no morphological effects were detected in the ME or IE when compared to saline or wild-type (WT) phage controls. Comparable, reversible hearing loss was observed for saline controls, WT phage and trans-TM peptide phage, suggesting a mild conductive hearing loss due to ME fluid. Perilymph titers after ME incubation established that few copies of trans-TM peptide phage crossed into the IE. The results suggest that, within the parameters tested, trans-TM peptides are safe and could be used as potential agents for noninvasive delivery of drugs, particles and gene therapy vectors to the ME

  18. Evaluation of Activity Concentration Values and Doses due to the Transport of Low Level Radioactive Material

    Energy Technology Data Exchange (ETDEWEB)

    Rawl, Richard R [ORNL; Scofield, Patricia A [ORNL; Leggett, Richard Wayne [ORNL; Eckerman, Keith F [ORNL

    2010-04-01

    The International Atomic Energy Agency (IAEA) initiated an international Coordinated Research Project (CRP) to evaluate the safety of transport of naturally occurring radioactive material (NORM). This report presents the United States contribution to that IAEA research program. The focus of this report is on the analysis of the potential doses resulting from the transport of low level radioactive material. Specific areas of research included: (1) an examination of the technical approach used in the derivation of exempt activity concentration values and a comparison of the doses associated with the transport of materials included or not included in the provisions of Paragraph 107(e) of the IAEA Safety Standards, Regulations for the Safe Transport of Radioactive Material, Safety Requirements No. TS-R-1; (2) determination of the doses resulting from different treatment of progeny for exempt values versus the A{sub 1}/A{sub 2} values; and (3) evaluation of the dose justifications for the provisions applicable to exempt materials and low specific activity materials (LSA-I). It was found that the 'previous or intended use' (PIU) provision in Paragraph 107(e) is not risk informed since doses to the most highly exposed persons (e.g., truck drivers) are comparable regardless of intended use of the transported material. The PIU clause can also have important economic implications for co-mined ores and products that are not intended for the fuel cycle but that have uranium extracted as part of their industrial processing. In examination of the footnotes in Table 2 of TS-R-1, which identifies the progeny included in the exempt or A1/A2 values, there is no explanation of how the progeny were selected. It is recommended that the progeny for both the exemption and A{sub 1}/A{sub 2} values should be similar regardless of application, and that the same physical information should be used in deriving the limits. Based on the evaluation of doses due to the transport of low

  19. Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity.

    Science.gov (United States)

    Williard, Robin L; Middaugh, Lawrence D; Zhu, Hao-Jie B; Patrick, Kennerly S

    2007-02-01

    Ethylphenidate is formed by metabolic transesterification of methylphenidate and ethanol. Study objectives were to (a) establish that ethylphenidate is formed in C57BL/6 (B6) mice; (b) compare the stimulatory effects of ethylphenidate and methylphenidate enantiomers; (c) determine methylphenidate and ethylphenidate plasma and brain distribution and (d) establish in-vitro effects of methylphenidate and ethylphenidate on monoamine transporter systems. Experimental results were that: (a) coadministration of ethanol with the separate methylphenidate isomers enantioselectively produced l-ethylphenidate; (b) d and dl-forms of methylphenidate and ethylphenidate produced dose-responsive increases in motor activity with stimulation being less for ethylphenidate; (c) plasma and whole-brain concentrations were greater for ethylphenidate than methylphenidate and (d) d and DL-methylphenidate and ethylphenidate exhibited comparably potent low inhibition of the dopamine transporter, whereas ethylphenidate was a less potent norepinephrine transporter inhibitor. These experiments establish the feasibility of the B6 mouse model for examining the interactive effects of ethanol and methylphenidate. As reported for humans, concurrent exposure of B6 mice to methylphenidate and ethanol more readily formed l-ethylphenidate than d-ethylphenidate, and the l-isomers of both methylphenidate and ethylphenidate were biologically inactive. The observed reduced stimulatory effect of d-ethylphenidate relative to d-methylphenidate appears not to be the result of brain dispositional factors, but rather may be related to its reduced inhibition of the norepinephrine transporter, perhaps altering the interaction of dopaminergic and noradrenergic neural systems.

  20. Does modulation of organic cation transporters improve pralidoxime activity in an animal model of organophosphate poisoning?

    Science.gov (United States)

    Kayouka, Maya; Houzé, Pascal; Baud, Frederic J; Cisternino, Salvatore; Debray, Marcel; Risède, Patricia; Schinkel, Alfred H; Warnet, Jean-Michel

    2011-04-01

    Pralidoxime is an organic cation used as an antidote in addition to atropine to treat organophosphate poisoning. Pralidoxime is rapidly eliminated by the renal route and thus has limited action. The objectives of this work were as follows. 1) Study the role of organic cation transporters in the renal secretion of pralidoxime using organic cation transporter substrates (tetraethylammonium) and knockout mice (Oct1/2⁻/⁻; Oct3⁻/⁻). 2) Assess whether sustained high plasma concentrations increase pralidoxime antidotal activity toward paraoxon-induced respiratory toxicity. INSERM U705, Faculté de Pharmacie, Université Paris Descartes, 4 Avenue de l'Observatoire, 75006 Paris, France. Rodents: Knockout mice (Oct1/2⁻/⁻; Oct3⁻/⁻) and Sprague-Dawley rats. None. In rats, the renal clearance of pralidoxime was 3.6-fold higher than the creatinine clearance. Pretreatment with tetraethylammonium (75 mg/kg) in rats or deficiencies in organic cation transporters 1 and 2 in mice (Oct1/2⁻/⁻) resulted in a significant increase in plasma pralidoxime concentrations. Lack of Oct3 did not alter plasma pralidoxime concentrations. The antidotal activity of pralidoxime (50 mg/kg intramuscularly) was longer and with greater effect, resulting in a return to normal values when administered to rats pretreated with tetraethylammonium. Pralidoxime is secreted in rats and mice by renal Oct1 and/or Oct2 but not by Oct3. Modulation of organic cation transporter activity increased the plasma pralidoxime concentrations and the antidotal effect of pralidoxime with sustained return within the normal range of respiratory variables in paraoxon-poisoned rats. These results suggest a promising approach in an animal model toward the increase in efficiency of pralidoxime. However, further studies are needed before these results are extended to human poisoning.

  1. Interaction of ABC transport proteins with toxic metals at the level of gene and transport activity in the PLHC-1 fish cell line.

    Science.gov (United States)

    Della Torre, Camilla; Zaja, Roko; Loncar, Jovica; Smital, Tvrtko; Focardi, Silvano; Corsi, Ilaria

    2012-06-25

    The aim of this study was to investigate the interaction of four toxic metals with ABC transport proteins in piscine cell line PLHC-1. Cells were exposed for 24 h to 0.01-1 μM of CdCl(2), HgCl(2), As(2)O(3), or K(2)Cr(2)O(7) and the expression of a series of ABC genes (abcb1, abcc1-4) was determined using qRT-PCR. Using the fluorescent model substrates calcein-AM and monochlorbimane we measured interaction of metals with the transport activity of ABC transporters. P-glycoprotein (P-gp) activity was measured in PLHC-1/dox (P-gp overexpressing cells) while activity and interactions of metals with MRPs was measured in PLHC-1/wt cells. After 24 h exposure, abcc2-4 genes were dose-dependently up-regulated by all metals, while abcb1 and abcc1 were less affected. Up-regulation of abcc2 was more pronounced, with up to 8-fold increase in expression. Abcc3 and abcc4 were moderately inducible by HgCl(2) with 3.3-fold and 2.2-fold, respectively. All metals caused a significant inhibition of both P-gp (2.9- to 4-fold vs. controls) and MRP (1.3- to 1.8-fold) transport activities. Modulation of ABC genes and transport activities was further investigated in PLHC-1/wt cells exposed to 1 μM HgCl(2) for 72 h and in Hg resistant cells selected by long term cultivation of PLHC-1/wt cells in increasing concentrations of HgCl(2). Exposure to HgCl(2) for 72 h induced MRP genes expression and efflux activity. The long term cultivation of PLHC-1/wt cells in HgCl(2), did not cause prolonged up-regulation of the tested abc genes but resulted in higher MRP transport activities as determined by the increased sensitivity of these cells to MK571 (MRP specific inhibitor). Results of the present study indicated specific interaction of metals with selected ABC transport proteins. Modulation of ABC transporters takes place at both transcriptional and functional level. An active involvement of efflux pumps in Hg clearance in fish is suggested. Copyright © 2012 Elsevier Ireland Ltd. All rights

  2. Physical Activity during Work, Transport and Leisure in Germany - Prevalence and Socio-Demographic Correlates

    Science.gov (United States)

    Wallmann-Sperlich, Birgit; Froboese, Ingo

    2014-01-01

    Background This study aimed 1) to provide data estimates concerning overall moderate- and vigorous-intensity physical activity (MVPA) as well as MVPA during work, transport and leisure in Germany and 2) to investigate MVPA and possible associations with socio-demographic correlates. Methods A cross-sectional telephone survey interviewed 2248 representative participants in the age of 18–65 years (1077 men; 42.4±13.4 years; body mass index: 25.3±4.5kg•m−2) regarding their self-reported physical activity across Germany. The Global Physical Activity Questionnaire was applied to investigate MVPA during work, transport and leisure and questions were answered concerning their demographics. MVPA was stratified by gender, age, body mass index, residential setting, educational and income level. To identify socio-demographic correlates of overall MVPA as well as in the domains, we used a series of linear regressions. Results 52.8% of the sample achieved physical activity recommendations (53.7% men/52.1% women). Overall MVPA was highest in the age group 18–29 years (psocio-demographic variables, residential setting as well as the physical activity domain in Germany. PMID:25390071

  3. Activity-dependent transport of the transcriptional coactivator CRTC1 from synapse to nucleus.

    Science.gov (United States)

    Ch'ng, Toh Hean; Uzgil, Besim; Lin, Peter; Avliyakulov, Nuraly K; O'Dell, Thomas J; Martin, Kelsey C

    2012-07-01

    Long-lasting changes in synaptic efficacy, such as those underlying long-term memory, require transcription. Activity-dependent transport of synaptically localized transcriptional regulators provides a direct means of coupling synaptic stimulation with changes in transcription. The CREB-regulated transcriptional coactivator (CRTC1), which is required for long-term hippocampal plasticity, binds CREB to potently promote transcription. We show that CRTC1 localizes to synapses in silenced hippocampal neurons but translocates to the nucleus in response to localized synaptic stimulation. Regulated nuclear translocation occurs only in excitatory neurons and requires calcium influx and calcineurin activation. CRTC1 is controlled in a dual fashion with activity regulating CRTC1 nuclear translocation and cAMP modulating its persistence in the nucleus. Neuronal activity triggers a complex change in CRTC1 phosphorylation, suggesting that CRTC1 may link specific types of stimuli to specific changes in gene expression. Together, our results indicate that synapse-to-nuclear transport of CRTC1 dynamically informs the nucleus about synaptic activity.

  4. Momentum Transport in DIII-D Discharges with and Without Magnetohydrodynamics (MHD) Activity

    Institute of Scientific and Technical Information of China (English)

    REN Qilong; J.M.PARK; J.S.DEGRASSIE; M.S.CHU; L.L.LAO; H.St.JOHN; R.LAHAYE; Y.M.JEON; ZHANG Cheng; ZHOU Deng; LI Guoqiang

    2009-01-01

    Two phases of a DIII-D discharge with and without magnetohydrodynamics(MHD)activity are analysed using ONETWO code.The toroidal momentum flux is extracted from experimental data and compared with the predictions by neoclassical theory,Gyro-Landau fluid transport model (GLF23) and Multi-Mode model(MMM95). It iS found that without MHD activities GLF23 and MMM95 provide a reasonable description while with MHD activity no model alone can fully describe the experimental momentum flux.For the phase with MHD activity a simple model of resonant magnetic drag is tested and it cannot fully explain the plasma slowing down observed in experiment.

  5. Active diffusion and microtubule-based transport oppose myosin forces to position organelles in cells

    Science.gov (United States)

    Lin, Congping; Schuster, Martin; Guimaraes, Sofia Cunha; Ashwin, Peter; Schrader, Michael; Metz, Jeremy; Hacker, Christian; Gurr, Sarah Jane; Steinberg, Gero

    2016-06-01

    Even distribution of peroxisomes (POs) and lipid droplets (LDs) is critical to their role in lipid and reactive oxygen species homeostasis. How even distribution is achieved remains elusive, but diffusive motion and directed motility may play a role. Here we show that in the fungus Ustilago maydis ~95% of POs and LDs undergo diffusive motions. These movements require ATP and involve bidirectional early endosome motility, indicating that microtubule-associated membrane trafficking enhances diffusion of organelles. When early endosome transport is abolished, POs and LDs drift slowly towards the growing cell end. This pole-ward drift is facilitated by anterograde delivery of secretory cargo to the cell tip by myosin-5. Modelling reveals that microtubule-based directed transport and active diffusion support distribution, mobility and mixing of POs. In mammalian COS-7 cells, microtubules and F-actin also counteract each other to distribute POs. This highlights the importance of opposing cytoskeletal forces in organelle positioning in eukaryotes.

  6. Benomyl inhibits phosphorus transport but not fungal alkaline phosphatase activity in a Glomus–cucumber symbiosis

    DEFF Research Database (Denmark)

    Larsen, John; Thingstrup, Ida; Jakobsen, Iver

    1996-01-01

    Short-term effects of benomyl on the arbuscular mycorrhizal fungus Glomus caledonium (Nicol. & Gerd.) Trappe and Gerdeman associated with Cucumis sativus L. were studied by measuring effects on fungal P transport and on fungal alkaline phosphatase activity. Mycorrhizal plants were grown in three...... compartment systems where nylon mesh was used to separate n root-free hyphal compartment (HC) and a root + hyphal compartment(RHC) from The main root compartment (RC). Non-mycorrhizal control plants were grown in similar growth units. After 6 wk benomyl was applied to the plants in three ways: as soil...... drenches to RHC or HC, or as u spray to the leaves. Benomyl was added in three concentrations. Equal amounts of 32P and 33P were added to the HC and to the RHC respectively, immediately after the application of benomyl. Plants were harvested 4–6 d later. Hyphal transport of 32P from the HC was inhibited...

  7. Can clouds enhance long-range transport of low volatile, ionizable and surface-active chemicals?

    DEFF Research Database (Denmark)

    Franco, Antonio; Trapp, Stefan

    2011-01-01

    Atmospheric partitioning and transport of low volatile organic compounds is strongly influenced by the presence of water (e.g. clouds) and its deposition velocity (e.g. rainfall, snow). It was identified that the assumption of continuous rainfall underestimates the residence time and the transport...... substances. A modified version of the regional multimedia activity model for ionics MAMI, including twolayered atmosphere with atmospheric boundary layer (ABL) and lower/middle troposphere (LMT), interface partitioning, intermittent rainfall and variable cloud coverage was applied to a selection of ten low...... were run for a constant emission to the atmospheric boundary layer to identify key model inputs. The degradation rate, the duration of dry and wet periods and the parameters describing air-water bulk partitioning (KAW and T) and ionization (pKa and pH) determine the residence time in the ABL...

  8. Active diffusion and microtubule-based transport oppose myosin forces to position organelles in cells

    Science.gov (United States)

    Lin, Congping; Schuster, Martin; Guimaraes, Sofia Cunha; Ashwin, Peter; Schrader, Michael; Metz, Jeremy; Hacker, Christian; Gurr, Sarah Jane; Steinberg, Gero

    2016-01-01

    Even distribution of peroxisomes (POs) and lipid droplets (LDs) is critical to their role in lipid and reactive oxygen species homeostasis. How even distribution is achieved remains elusive, but diffusive motion and directed motility may play a role. Here we show that in the fungus Ustilago maydis ∼95% of POs and LDs undergo diffusive motions. These movements require ATP and involve bidirectional early endosome motility, indicating that microtubule-associated membrane trafficking enhances diffusion of organelles. When early endosome transport is abolished, POs and LDs drift slowly towards the growing cell end. This pole-ward drift is facilitated by anterograde delivery of secretory cargo to the cell tip by myosin-5. Modelling reveals that microtubule-based directed transport and active diffusion support distribution, mobility and mixing of POs. In mammalian COS-7 cells, microtubules and F-actin also counteract each other to distribute POs. This highlights the importance of opposing cytoskeletal forces in organelle positioning in eukaryotes. PMID:27251117

  9. [Important application of intestinal transporters and metabolism enzymes on gastrointestinal disposal of active ingredients of Chinese materia medica].

    Science.gov (United States)

    Bi, Xiaolin; Du, Qiu; Di, Liuqing

    2010-02-01

    Oral drug bioavailability depends on gastrointestinal absorption, intestinal transporters and metabolism enzymes are the important factors in drug gastrointestinal absorption and they can also be induced or inhibited by the active ingredients of Chinese materia medica. This article presents important application of intestinal transporters and metabolism enzymes on gastrointestinal disposal of the active ingredients of Chinese materia medica, and points out the importance of research on transport and metabolism of the active ingredients of Chinese materia medica in Chinese extract and Chinese medicinal formulae.

  10. Influence of different host associations on glutamine synthetase activity and ammonium transporter in Santalumalbum L.

    Science.gov (United States)

    Deepa, P; Yusuf, A

    2016-07-01

    The present study was aimed at understanding the role of different hosts in ammonium transporter1;2 expressions and glutamine synthetase(GS) activity and their effects on the growth parameters in the sandal. Sandal plant associated with leguminous host expressed better growth parameters. GS activity of leguminous hosts alone and in host associated sandals was analyzed using GS transferase assay. Highest GS activity was expressed in Mimosa pudica-sandal association compared to other leguminous and non-leguminous host associations. The association of N2 fixing host with sandal enhanced C and N levels in order to maintain the C/N value. The role of ammonium transporters in N nutrition of sandal-host association was elucidated by cloning AMT1;2 from the leaves, haustoria and roots of host associated sandal and quantifying the relative expression by the [Formula: see text] method. SaAMT1;2 was strongly up-regulated in leaves, roots and haustoria of leguminous host associated sandal compared to non-leguminous host associations. The relative increase in SaAMT1;2 expressions and up-regulated GS activity positively affected the growth parameters in sandal when associated with leguminous hosts.

  11. E17110 promotes reverse cholesterol transport with liver X receptor β agonist activity in vitro

    Directory of Open Access Journals (Sweden)

    Ni Li

    2016-05-01

    Full Text Available Liver X receptor (LXR plays an important role in reverse cholesterol transport (RCT, and activation of LXR could reduce atherosclerosis. In the present study we used a cell-based screening method to identify new potential LXRβ agonists. A novel benzofuran-2-carboxylate derivative was identified with LXRβ agonist activity: E17110 showed a significant activation effect on LXRβ with an EC50 value of 0.72 μmol/L. E17110 also increased the expression of ATP-binding cassette transporter A1 (ABCA1 and G1 (ABCG1 in RAW264.7 macrophages. Moreover, E17110 significantly reduced cellular lipid accumulation and promoted cholesterol efflux in RAW264.7 macrophages. Interestingly, we found that the key amino acids in the LXRβ ligand-binding domain had distinct interactions with E17110 as compared to TO901317. These results suggest that E17110 was identified as a novel compound with LXRβ agonist activity in vitro via screening, and could be developed as a potential anti-atherosclerotic lead compound.

  12. Conductance and activation energy for electron transport in series and parallel intramolecular circuits.

    Science.gov (United States)

    Hsu, Liang-Yan; Wu, Ning; Rabitz, Herschel

    2016-11-30

    We investigate electron transport through series and parallel intramolecular circuits in the framework of the multi-level Redfield theory. Based on the assumption of weak monomer-bath couplings, the simulations depict the length and temperature dependence in six types of intramolecular circuits. In the tunneling regime, we find that the intramolecular circuit rule is only valid in the weak monomer coupling limit. In the thermally activated hopping regime, for circuits based on two different molecular units Ma and Mb with distinct activation energies Eact,a > Eact,b, the activation energies of Ma and Mb in series are nearly the same as Eact,a while those in parallel are nearly the same as Eact,b. This study gives a comprehensive description of electron transport through intramolecular circuits from tunneling to thermally activated hopping. We hope that this work can motivate additional studies to design intramolecular circuits based on different types of building blocks, and to explore the corresponding circuit laws and the length and temperature dependence of conductance.

  13. Blonanserin, a novel atypical antipsychotic agent not actively transported as substrate by P-glycoprotein.

    Science.gov (United States)

    Inoue, Tomoko; Osada, Kenichi; Tagawa, Masaaki; Ogawa, Yuriko; Haga, Toshiaki; Sogame, Yoshihisa; Hashizume, Takanori; Watanabe, Takashi; Taguchi, Atsushi; Katsumata, Takashi; Yabuki, Masashi; Yamaguchi, Noboru

    2012-10-01

    Although blonanserin, a novel atypical antipsychotic agent with dopamine D(2)/serotonin 5-HT(2A) antagonistic properties, displays good brain distribution, the mechanism of this distribution has not been clarified. P-glycoprotein [(P-gp) or multidrug resistance protein 1 (MDR1)] is an efflux transporter expressed in the brain and plays an important role in limiting drug entry into the central nervous system (CNS). In particular, P-gp can affect the pharmacokinetics and efficacy of antipsychotics, and exacerbate or soothe their adverse effects. In this study, we conducted in vitro and in vivo experiments to determine whether blonanserin is a P-gp substrate. Risperidone and its active metabolite 9-hydroxyrisperidone, both of which are P-gp substrates, were used as reference drugs. Affinity of blonanserin, risperidone, and 9-hydroxyrisperidone for P-gp was evaluated by in vitro transcellular transport across LLC-PK1, human MDR1 cDNA-transfected LLC-PK1 (LLC-MDR1), and mouse Mdr1a cDNA-transfected LLC-PK1 (LLC-Mdr1a). In addition, pharmacokinetic parameters in the brain and plasma (B/P ratio) of test compounds were measured in mdr1a/1b knockout (KO) and wild-type (WT) mice. The results of in vitro experiments revealed that P-gp does not actively transport blonanserin as a substrate in humans or mice. In addition, blonanserin displayed comparable B/P ratios in KO and WT mice, whereas B/P ratios of risperidone and 9-hydroxyrisperidone differed markedly in these animals. Our results indicate that blonanserin is not a P-gp substrate and therefore its brain distribution is unlikely to be affected by this transporter. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Impairment of GABA transporter GAT-1 terminates cortical recurrent network activity via enhanced phasic inhibition

    Directory of Open Access Journals (Sweden)

    Daniel Simon Razik

    2013-09-01

    Full Text Available In the central nervous system, GABA transporters (GATs very efficiently clear synaptically released GABA from the extracellular space, and thus exert a tight control on GABAergic inhibition. In neocortex, GABAergic inhibition is heavily recruited during recurrent phases of spontaneous action potential activity which alternate with neuronally quiet periods. Therefore, such activity should be quite sensitive to minute alterations of GAT function. Here, we explored the effects of a gradual impairment of GAT-1 and GAT-2/3 on spontaneous recurrent network activity – termed network bursts and silent periods – in organotypic slice cultures of rat neocortex. The GAT-1 specific antagonist NO-711 depressed activity already at nanomolar concentrations (IC50 for depression of spontaneous multiunit firing rate of 42 nM, reaching a level of 80% at 500-1000 nM. By contrast, the GAT-2/3 preferring antagonist SNAP-5114 had weaker and less consistent effects. Several lines of evidence pointed towards an enhancement of phasic GABAergic inhibition as the dominant activity-depressing mechanism: network bursts were drastically shortened, phasic GABAergic currents decayed slower, and neuronal excitability during ongoing activity was diminished. In silent periods, NO-711 had little effect on neuronal excitability or membrane resistance, quite in contrast to the effects of muscimol, a GABA mimetic which activates GABAA receptors tonically. Our results suggest that an enhancement of phasic GABAergic inhibition efficiently curtails cortical recurrent activity and may mediate antiepileptic effects of therapeutically relevant concentrations of GAT-1 antagonists.

  15. Transmembrane Segment 6 of the Glut1 Glucose Transporter Is an Outer Helix and Contains Amino Acid Side Chains Essential for Transport Activity*

    Science.gov (United States)

    Mueckler, Mike; Makepeace, Carol

    2008-01-01

    Experimental data and homology modeling suggest a structure for the exofacial configuration of the Glut1 glucose transporter in which 8 transmembrane helices form an aqueous cavity in the bilayer that is stabilized by four outer helices. The role of transmembrane segment 6, predicted to be an outer helix in this model, was examined by cysteine-scanning mutagenesis and the substituted cysteine accessibility method using the membrane-impermeant, sulfhydryl-specific reagent, p-chloromercuribenzene-sulfonate (pCMBS). A fully functional Glut1 molecule lacking all 6 native cysteine residues was used as a template to produce a series of 21 Glut1 point mutants in which each residue along helix 6 was individually changed to cysteine. These mutants were expressed in Xenopus oocytes, and their expression levels, functional activities, and sensitivities to inhibition by pCMBS were determined. Cysteine substitutions at Leu204 and Pro205 abolished transport activity, whereas substitutions at Ile192, Pro196, Gln200, and Gly201 resulted in inhibition of activity that ranged from ∼35 to ∼80%. Cysteine substitutions at Leu188, Ser191, and Leu199 moderately augmented specific transport activity relative to the control. These results were dramatically different from those previously reported for helix 12, the structural cognate of helix 6 in the pseudo-symmetrical structural model, for which none of the 21 single-cysteine mutants exhibited reduced activity. Only the substitution at Leu188 conferred inhibition by pCMBS, suggesting that most of helix 6 is not exposed to the external solvent, consistent with its proposed role as an outer helix. These data suggest that helix 6 contains amino acid side chains that are critical for transport activity and that structurally analogous outer helices may play distinct roles in the function of membrane transporters. PMID:18245775

  16. Transport dynamics of molecular motors that switch between an active and inactive state.

    Science.gov (United States)

    Pinkoviezky, I; Gov, N S

    2013-08-01

    Molecular motors are involved in key transport processes in the cell. Many of these motors can switch from an active to a nonactive state, either spontaneously or depending on their interaction with other molecules. When active, the motors move processively along the filaments, while when inactive they are stationary. We treat here the simple case of spontaneously switching motors, between the active and inactive states, along an open linear track. We use our recent analogy with vehicular traffic, where we go beyond the mean-field description. We map the phase diagram of this system, and find that it clearly breaks the symmetry between the different phases, as compared to the standard total asymmetric exclusion process. We make several predictions that may be testable using molecular motors in vitro and in living cells.

  17. Quantitative Prediction of Human Renal Clearance and Drug-Drug Interactions of Organic Anion Transporter Substrates Using In Vitro Transport Data: A Relative Activity Factor Approach.

    Science.gov (United States)

    Mathialagan, Sumathy; Piotrowski, Mary A; Tess, David A; Feng, Bo; Litchfield, John; Varma, Manthena V

    2017-04-01

    Organic anion transporters (OATs) are important in the renal secretion, and thus, the clearance, of many drugs; and their functional change can result in pharmacokinetic variability. In this study, we applied transport rates measured in vitro using OAT-transfected human embryonic kidney cells to predict human renal secretory and total renal clearance of 31 diverse drugs. Selective substrates to OAT1 (tenofovir), OAT2 (acyclovir and ganciclovir), and OAT3 (benzylpenicillin, oseltamivir acid) were used to obtain relative activity factors (RAFs) for these individual transporters by relating in vitro transport clearance (after physiologic scaling) to in vivo secretory clearance. Using the estimated RAFs (0.64, 7.3, and 4.1, respectively, for OAT1, OAT2, and OAT3, respectively) and the in vitro active clearances, renal secretory clearance and total renal clearance were predicted with average fold errors (AFEs) of 1.89 and 1.40, respectively. The results show that OAT3-mediated transport play a predominant role in renal secretion for 22 of the 31 drugs evaluated. This mechanistic static approach was further applied to quantitatively predict renal drug-drug interactions (AFE ∼1.6) of the substrate drugs with probenecid, a clinical probe OAT inhibitor. In conclusion, the proposed in vitro-in vivo extrapolation approach is the first comprehensive attempt toward mechanistic modeling of renal secretory clearance based on routinely employed in vitro cell models.

  18. Ceramide 1-Phosphate Increases P-Glycoprotein Transport Activity at the Blood-Brain Barrier via Prostaglandin E2 Signaling.

    Science.gov (United States)

    Mesev, Emily V; Miller, David S; Cannon, Ronald E

    2017-04-01

    P-glycoprotein, an ATP-driven efflux pump, regulates permeability of the blood-brain barrier (BBB). Sphingolipids, endogenous to brain tissue, influence inflammatory responses and cell survival in vitro. Our laboratory has previously shown that sphingolipid signaling by sphingosine 1-phosphate decreases basal P-glycoprotein transport activity. Here, we investigated the potential for another sphingolipid, ceramide 1-phosphate (C1P), to modulate efflux pumps at the BBB. Using confocal microscopy and measuring luminal accumulation of fluorescent substrates, we assessed the transport activity of several efflux pumps in isolated rat brain capillaries. C1P treatment induced P-glycoprotein transport activity in brain capillaries rapidly and reversibly. In contrast, C1P did not affect transport activity of two other major efflux transporters, multidrug resistance protein 2 and breast cancer resistance protein. C1P induced P-glycoprotein transport activity without changing transporter protein expression. Inhibition of the key signaling components in the cyclooxygenase-2 (COX-2)/prostaglandin E2 signaling cascade (phospholipase A2, COX-2, multidrug resistance protein 4, and G-protein-coupled prostaglandin E2 receptors 1 and 2), abolished P-glycoprotein induction by C1P. We show that COX-2 and prostaglandin E2 are required for C1P-mediated increases in P-glycoprotein activity independent of transporter protein expression. This work describes how C1P activates a signaling cascade to dynamically regulate P-glycoprotein transport at the BBB and offers potential clinical targets to modulate neuroprotection and drug delivery to the CNS.

  19. Cannabinoid receptor 1 signalling dampens activity and mitochondrial transport in networks of enteric neurones.

    Science.gov (United States)

    Boesmans, W; Ameloot, K; van den Abbeel, V; Tack, J; Vanden Berghe, P

    2009-09-01

    Cannabinoid (CB) receptors are expressed in the enteric nervous system (ENS) and CB(1) receptor activity slows down motility and delays gastric emptying. This receptor system has become an important target for GI-related drug development such as in obesity treatment. The aim of the study was to investigate how CB(1) ligands and antagonists affect ongoing activity in enteric neurone networks, modulate synaptic vesicle cycling and influence mitochondrial transport in nerve processes. Primary cultures of guinea-pig myenteric neurones were loaded with different fluorescent markers: Fluo-4 to measure network activity, FM1-43 to image synaptic vesicles and Mitotracker green to label mitochondria. Synaptic vesicle cluster density was assessed by immunohistochemistry and expression of CB(1) receptors was confirmed by RT-PCR. Spontaneous network activity, displayed by both excitatory and inhibitory neurones, was significantly increased by CB(1) receptor antagonists (AM-251 and SR141716), abolished by CB(1) activation (methanandamide, mAEA) and reduced by two different inhibitors (arachidonylamide serotonin, AA-5HT and URB597) of fatty acid amide hydrolase. Antagonists reduced the number of synaptic vesicles that were recycled during an electrical stimulus. CB(1) agonists (mAEA and WIN55,212) reduced and antagonists enhanced the fraction of transported mitochondria in enteric nerve fibres. We found immunohistochemical evidence for an enhancement of synaptophysin-positive release sites with SR141716, while WIN55,212 caused a reduction. The opposite effects of agonists and antagonists suggest that enteric nerve signalling is under the permanent control of CB(1) receptor activity. Using inhibitors of the endocannabinoid degrading enzyme, we were able to show there is endogenous production of a CB ligand in the ENS.

  20. Differential regulation of glucose transport activity in yeast by specific cAMP signatures.

    Science.gov (United States)

    Bermejo, Clara; Haerizadeh, Farzad; Sadoine, Mayuri S C; Chermak, Diane; Frommer, Wolf B

    2013-06-15

    Successful colonization and survival in variable environments require a competitive advantage during the initial growth phase after experiencing nutrient changes. Starved yeast cells anticipate exposure to glucose by activating the Hxt5p (hexose transporter 5) glucose transporter, which provides an advantage during early phases after glucose resupply. cAMP and glucose FRET (fluorescence resonance energy transfer) sensors were used to identify three signalling pathways that co-operate in the anticipatory Hxt5p activity in glucose-starved cells: as expected the Snf1 (sucrose nonfermenting 1) AMP kinase pathway, but, surprisingly, the sugar-dependent G-protein-coupled Gpr1 (G-protein-coupled receptor 1)/cAMP/PKA (protein kinase A) pathway and the Pho85 (phosphate metabolism 85)/Plc (phospholipase C) 6/7 pathway. Gpr1/cAMP/PKA are key elements of a G-protein-coupled sugar response pathway that produces a transient cAMP peak to induce growth-related genes. A novel function of the Gpr1/cAMP/PKA pathway was identified in glucose-starved cells: during starvation the Gpr1/cAMP/PKA pathway is required to maintain Hxt5p activity in the absence of glucose-induced cAMP spiking. During starvation, cAMP levels remain low triggering expression of HXT5, whereas cAMP spiking leads to a shift to the high capacity Hxt isoforms.

  1. Subpopulations of rat dorsal root ganglion neurons express active vesicular acetylcholine transporter.

    Science.gov (United States)

    Tata, Ada Maria; De Stefano, M Egle; Tomassy, Giulio Srubek; Vilaró, M Teresa; Levey, Allan I; Biagioni, Stefano

    2004-01-15

    The vesicular acetylcholine transporter (VAChT) is a transmembrane protein required, in cholinergic neurons, for selective storage of acetylcholine into synaptic vesicles. Although dorsal root ganglion (DRG) neurons utilize neuropeptides and amino acids for neurotransmission, we have previously demonstrated the presence of a cholinergic system. To investigate whether, in sensory neurons, the vesicular accumulation of acetylcholine relies on the same mechanisms active in classical cholinergic neurons, we investigated VAChT presence, subcellular distribution, and activity. RT-PCR and Western blot analysis demonstrated the presence of VAChT mRNA and protein product in DRG neurons and in the striatum and cortex, used as positive controls. Moreover, in situ hybridization and immunocytochemistry showed VAChT staining located mainly in the medium/large-sized subpopulation of the sensory neurons. A few small neurons were also faintly labeled by immunocytochemistry. In the electron microscope, immunolabeling was associated with vesicle-like elements distributed in the neuronal cytoplasm and in both myelinated and unmyelinated intraganglionic nerve fibers. Finally, [(3)H]acetylcholine active transport, evaluated either in the presence or in the absence of ATP, also demonstrated that, as previously reported, the uptake of acetylcholine by VAChT is ATP dependent. This study suggests that DRG neurons not only are able to synthesize and degrade ACh and to convey cholinergic stimuli but also are capable of accumulating and, possibly, releasing acetylcholine by the same mechanism used by the better known cholinergic neurons.

  2. Evaluation of multiple-frequency, active and passive acoustics as surrogates for bedload transport

    Science.gov (United States)

    Wood, Molly S.; Fosness, Ryan L.; Pachman, Gregory; Lorang, Mark; Tonolla, Diego

    2015-01-01

    The use of multiple-frequency, active acoustics through deployment of acoustic Doppler current profilers (ADCPs) shows potential for estimating bedload in selected grain size categories. The U.S. Geological Survey (USGS), in cooperation with the University of Montana (UM), evaluated the use of multiple-frequency, active and passive acoustics as surrogates for bedload transport during a pilot study on the Kootenai River, Idaho, May 17-18, 2012. Four ADCPs with frequencies ranging from 600 to 2000 kHz were used to measure apparent moving bed velocities at 20 stations across the river in conjunction with physical bedload samples. Additionally, UM scientists measured the sound frequencies of moving particles with two hydrophones, considered passive acoustics, along longitudinal transects in the study reach. Some patterns emerged in the preliminary analysis which show promise for future studies. Statistically significant relations were successfully developed between apparent moving bed velocities measured by ADCPs with frequencies 1000 and 1200 kHz and bedload in 0.5 to 2.0 mm grain size categories. The 600 kHz ADCP seemed somewhat sensitive to the movement of gravel bedload in the size range 8.0 to 31.5 mm, but the relation was not statistically significant. The passive hydrophone surveys corroborated the sample results and could be used to map spatial variability in bedload transport and to select a measurement cross-section with moving bedload for active acoustic surveys and physical samples.

  3. Tissue Plasminogen Activator Alters Intracellular Sequestration of Zinc through Interaction with the Transporter ZIP4

    Energy Technology Data Exchange (ETDEWEB)

    Emmetsberger, Jaime; Mirrione, Martine M.; Zhou, Chun; Fernandez-Monreal, Monica; Siddiq, Mustafa M.; Ji, Kyungmin; Tsirka, Stella E. (SBU)

    2010-09-17

    Glutamatergic neurons contain free zinc packaged into neurotransmitter-loaded synaptic vesicles. Upon neuronal activation, the vesicular contents are released into the synaptic space, whereby the zinc modulates activity of postsynaptic neurons though interactions with receptors, transporters and exchangers. However, high extracellular concentrations of zinc trigger seizures and are neurotoxic if substantial amounts of zinc reenter the cells via ion channels and accumulate in the cytoplasm. Tissue plasminogen activator (tPA), a secreted serine protease, is also proepileptic and excitotoxic. However, tPA counters zinc toxicity by promoting zinc import back into the neurons in a sequestered form that is nontoxic. Here, we identify the zinc influx transporter, ZIP4, as the pathway through which tPA mediates the zinc uptake. We show that ZIP4 is upregulated after excitotoxin stimulation of the mouse, male and female, hippocampus. ZIP4 physically interacts with tPA, correlating with an increased intracellular zinc influx and lysosomal sequestration. Changes in prosurvival signals support the idea that this sequestration results in neuroprotection. These experiments identify a mechanism via which neurons use tPA to efficiently neutralize the toxic effects of excessive concentrations of free zinc.

  4. Gastrointestinal Hormone Cholecystokinin Increases P-Glycoprotein Membrane Localization and Transport Activity in Caco-2 Cells.

    Science.gov (United States)

    Yano, Kentaro; Shimizu, Saori; Tomono, Takumi; Ogihara, Takuo

    2017-09-01

    It was reported that stimulation of taste receptor type 2 member 38 by a bitter substance, phenylthiocarbamide (PTC), increased P-glycoprotein (P-gp) mRNA level and transport activity via release of the gastrointestinal hormone cholecystokinin-8 (CCK-8) at 9 h. Therefore, we hypothesized that CCK-8 and PTC might also regulate P-gp activity more rapidly via a different mechanism. As a result, we found that the pretreatment of human colon adenocarcinoma (Caco-2) cells with 10-mM PTC significantly decreased the intracellular accumulation of P-gp substrate rhodamine 123 (Rho123) compared with the control after 90-min incubation. Moreover, CCK-8 treatments significantly reduced the accumulation of Rho123 within 30 min, compared with the control. On the other hand, when Caco-2 cells were pretreated with PTC, the efflux ratio of Rho123 was significantly increased compared with control. The efflux ratio of Rho123 in CCK-8 treatment cells was also significantly increased compared with control. Furthermore, CCK-8 increased the phosphorylation of the scaffold proteins ezrin, radixin, and moesin, which regulate translocation of P-gp to the plasma membrane. Therefore, our results indicate that PTC induced release of CCK-8, which in turn induced the phosphorylation of ezrin, radixin, and moesin proteins, leading to upregulation of P-gp transport activity via increased membrane localization of P-gp. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  5. Trends in CO2 Emissions from China-Oriented International Marine Transportation Activities and Policy Implications

    Directory of Open Access Journals (Sweden)

    Hualong Yang

    2017-07-01

    Full Text Available The demand for marine transportation and its associated CO2 emissions are growing rapidly as a result of increasing international trade and economic growth. An activity-based approach is developed for forecasting CO2 emissions from the China-oriented international seaborne trade sector. To accurately estimate the aggregated emissions, CO2 emissions are calculated individually for five categories of vessels: crude oil tanker, product tanker, chemical tanker, bulk carrier, and container. A business-as-usual (BAU scenario was developed to describe the current situation without additional mitigation policies, whilst three alternative scenarios were developed to describe scenarios with various accelerated improvements of the key factors. The aggregated CO2 emissions are predicted to reach 419.97 Mt under the BAU scenario, and 258.47 Mt under the optimal case, AD3. These predictions are 4.5 times and 2.8 times that of the aggregated emissions in 2007. Our analysis suggests that regulations for monitoring, reporting, and verifying the activities of vessels should be proposed, in order to quantify the CO2 emissions of marine transportation activities in Chinese territorial waters. In the long-term future, mitigation policies should be employed to reduce CO2 emissions from the marine trade sector and to address the climatic impact of shipping.

  6. RAFT: A simulator for ReActive Flow and Transport of groundwater contaminants

    Energy Technology Data Exchange (ETDEWEB)

    Chilakapati, A

    1995-07-01

    This report documents the use of the simulator RAFT for the ReActive flow and Transport of groundwater contaminants. RAFT can be used as a predictive tool in the design and analysis of laboratory and field experiments or it can be used for the estimation of model/process parameters from experiments. RAFT simulates the reactive transport of groundwater contaminants in one, two-, or three-dimensions and it can model user specified source/link configurations and arbitrary injection strategies. A suite of solvers for transport, reactions and regression are employed so that a combination of numerical methods best suited for a problem can be chosen. User specified coupled equilibrium and kinetic reaction systems can be incorporated into RAFT. RAFT is integrated with a symbolic computational language MAPLE, to automate code generation for arbitrary reaction systems. RAFT is expected to be used as a simulator for engineering design for field experiments in groundwater remediation including bioremediation, reactive barriers and redox manipulation. As an integrated tool with both the predictive ability and the ability to analyze experimental data, RAFT can help in the development of remediation technologies, from laboratory to field.

  7. Facilitated transport of Hg(II) through novel activated composite membranes

    Energy Technology Data Exchange (ETDEWEB)

    Paez-Hernandez, M.E. [Universidad Autonoma Metropolitana-Azcapotzalco, Departamento de Materiales, Area de Ciencia de los Materiales, Col. Reynosa-Tamaulipas (Mexico); Universidad Autonoma del Estado de Hidalgo, Centro de Investigaciones Quimicas, Pachuca, Hidalgo (Mexico); Aguilar-Arteaga, K. [Universidad Autonoma del Estado de Hidalgo, Centro de Investigaciones Quimicas, Pachuca, Hidalgo (Mexico); Valiente, M. [Universitat Autonoma de Barcelona, Departament de Quimica, Unitat Analitica, Centre GTS, Facultat de Ciencies, Bellaterra, Barcelona (Spain); Ramirez-Silva, M.T. [Universidad Autonoma Metropolitana-Iztapalapa, Departamento de Quimica, Area de Quimica Analitica, Laboratorio R-105, Col. Vicentina, Mexico D.F. (Mexico); Romero-Romo, M.; Palomar-Pardave, M. [Universidad Autonoma Metropolitana-Azcapotzalco, Departamento de Materiales, Area de Ciencia de los Materiales, Col. Reynosa-Tamaulipas (Mexico)

    2004-10-01

    The results presented in this work deal with the prime application of activated composite membranes (ACMs) for the transport of Hg(II) ions in a continuous extraction-re-extraction system using di-(2-ethylhexyl)dithiophosphoric acid (DTPA) as carrier. The effects of variables such as the pH, the nature of the acid and the concentration of the casting solutions on the transport of Hg(II) are also investigated. When the ACM was prepared with a 0.5 M DTPA solution and when the feed solution contained 2.5 x 10{sup -4} M Hg(II) in 0.1 M HCl, the amount of mercury extracted was greater than 76%. The re-extracted mercury was subsequently recovered by means of a stripping phase comprising 0.3 M thiourea solution in 2 M H{sub 2}SO{sub 4}, yielding 54% of the initial amount of mercury after transport had taken place for 180 min. (orig.)

  8. Activity of erdosteine on mucociliary transport in patients affected by chronic bronchitis.

    Science.gov (United States)

    Olivieri, D; Del Donno, M; Casalini, A; D'Ippolito, R; Fregnan, G B

    1991-01-01

    The influence of erdosteine (a mucomodulator endowed with mucolytic and antioxidant properties) on human mucociliary transport (MCT) was investigated in a double-blind placebo controlled study. Sixteen former smokers affected by chronic bronchitis, preselected for their mucociliary responsiveness to an inhaled beta 2-agonist, were divided into two groups (matched by number, sex, age and FEV1%) and orally treated with placebo or erdosteine (300 mg t.i.d.) for 8 days. Their MCT was assessed by the bronchofiberscopy technique just before starting the treatment and at the end of the treatment. The pretreatment mucus transport velocity in these patients was significantly decreased with respect to healthy subjects. The erdosteine treatment induced a significant improvement of MCT while placebo was inactive (mean % variation +/- SE against their baseline values being +60.4 +/- 18.4 and -3.0 +/- 5.9, respectively). This peculiar activity of erdosteine on mucus transport may be of clinical usefulness in chronic bronchitic patients and it can be added to beta 2-agonist to restore the decreased MCT.

  9. Activity of the respiratory electron transport system and respiration rates within the oxygen minimum layer of the Arabian Sea

    Digital Repository Service at National Institute of Oceanography (India)

    Naqvi, S.W.A.; Shailaja, M.S.

    Measurements of the activity of the respirtory electron transport system (ETS) at 15 stations in the Arabian Sea during the northeast monsoon (December 1988) yield high respiration rates that do not correlate with the trends in primary productivity...

  10. Generation of an activating Zn(2+) switch in the dopamine transporter

    DEFF Research Database (Denmark)

    Loland, Claus Juul; Norregaard, Lene; Litman, Thomas

    2002-01-01

    Binding of Zn(2+) to the endogenous Zn(2+) binding site in the human dopamine transporter leads to potent inhibition of [(3)H]dopamine uptake. Here we show that mutation of an intracellular tyrosine to alanine (Y335A) converts this inhibitory Zn(2+) switch into an activating Zn(2+) switch, allowing......-type levels of surface expression, Y335A displayed a dramatic decrease in [(3)H]dopamine uptake velocity (V(max)) to less than 1% of the wild type. In addition, Y335A showed up to 150-fold decreases in the apparent affinity for cocaine, mazindol, and related inhibitors whereas the apparent affinity...

  11. A New Synthesis Method and GABA Transporters Inhibitory Activities of Tiagabine and Its Analogues

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A new synthetic method and GABA transporter inhibitory activities of Tiagabine and its analogues are described.The key intermediates 4-tosyl-1,1-diaryl/heteroaryl-1-butene 10a-10e were synthesized by Wittig reaction, and followed by N-alkylation with (R)-3-piperidinecarboxylate. The resultingN-diheterocyclylalkenylpiperidine-3-carboxylic acid ester 11a-11e were saponified and then acidified toget the target compounds 1a-1e. The preliminary bioassays show that compound 1a-1e exhibited excellent inhibition of [3H]-GABA uptake in vitro of culture cells.

  12. Endocrine control of active sodium transport across frog skin; Le controle endocrinien du transport actif de sodium a travers la peau de grenouille

    Energy Technology Data Exchange (ETDEWEB)

    Maetz, J. [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1959-07-01

    I. Action of the neurohypophyseal peptides on sodium transport. 1) On Rana Esculenta, oxytocin alone is active on the sodium transport (not vaso pressin). 2) The post hypophysis of R.e. contains an hormonal factor even more specific on Na transport (12 times more active than oxytocin). 3) This new factor must be closely related to oxytocin. II. Action of the adrenal corticoids. 1) The skin of frogs adapted to a salt-rich external medium, shows a considerable diminution in sodium uptake. 2) This decreased sodium uptake is brought back to normal by the injections of aldosterone. 3) This suggests that salt loading of amphibians (as well as mammals) inhibits the mineralocorticoid activity of the adrenals. (author) [French] I. Action des peptides neurohypophysaires chez Rana esculenta. 1) Le transport actif de Na est sensible a l'action de l'ocytocine mais non a l'hormone antidiuretique. 2) La posthypophyse de ces grenouilles contient un facteur plus specifique encore, puisque 12 fois plus actif que l'ocytocine. 3) Ce facteur est cependant tres voisin de l'ocytocine au point de vue chimique. lI. Action des corticoides surrenaliens chez Rana Esculenta. 1) L'adaptation des grenouilles a un milieu riche en sel a pour effet une diminution considerable du transport actif de sodium, visible in vivo et in vitro. 2) L'injection d'aldosterone a des grenouilles adaptees dans ces conditions restaure le transport actif a un niveau comparable a celui que l'on observe chez les animaux conserves dans de l'eau courante. 3) Ces faits suggerent que la surcharge en NaCI produirait chez les amphibiens, comme chez les mammiferes, une mise au repos de la fonction mineralotrope de la surrenale. (auteur)

  13. Activity and travel choice(s) in multimodal public transport systems

    NARCIS (Netherlands)

    Krygsman, Stephan

    2004-01-01

    Transport planners and policymakers are increasingly considering multimodal public transport and travel demand management (TDM) strategies to stem the unsustainable travel behaviour trends associated with modern-day, car-dominated travel. Multimodal public transport, however, implies that people cha

  14. Private farmers’ annual exposure to whole body vibration from the aspect of the type of agricultural and transport activities performed

    OpenAIRE

    Leszek Solecki

    2012-01-01

    The objective of the study was hygienic evaluation of farmers’ exposure to whole body vibration from the aspect of the type of agricultural and transport activities performed during the whole year. Twenty farms were selected for the study using arable land of over 10 ha, engaged in mixed production (plant-animal). The scope of the study covered measurements of mechanical vibration (acceleration) on seats of agricultural vehicles while performing various field and transport activities, t...

  15. Visualization of glutamine transporter activities in living cells using genetically encoded glutamine sensors.

    Directory of Open Access Journals (Sweden)

    Katrin Gruenwald

    Full Text Available Glutamine plays a central role in the metabolism of critical biological molecules such as amino acids, proteins, neurotransmitters, and glutathione. Since glutamine metabolism is regulated through multiple enzymes and transporters, the cellular glutamine concentration is expected to be temporally dynamic. Moreover, differentiation in glutamine metabolism between cell types in the same tissue (e.g. neuronal and glial cells is often crucial for the proper function of the tissue as a whole, yet assessing cell-type specific activities of transporters and enzymes in such heterogenic tissue by physical fractionation is extremely challenging. Therefore, a method of reporting glutamine dynamics at the cellular level is highly desirable. Genetically encoded sensors can be targeted to a specific cell type, hence addressing this knowledge gap. Here we report the development of Föster Resonance Energy Transfer (FRET glutamine sensors based on improved cyan and yellow fluorescent proteins, monomeric Teal Fluorescent Protein (mTFP1 and venus. These sensors were found to be specific to glutamine, and stable to pH-changes within a physiological range. Using cos7 cells expressing the human glutamine transporter ASCT2 as a model, we demonstrate that the properties of the glutamine transporter can easily be analyzed with these sensors. The range of glutamine concentration change in a given cell can also be estimated using sensors with different affinities. Moreover, the mTFP1-venus FRET pair can be duplexed with another FRET pair, mAmetrine and tdTomato, opening up the possibility for real-time imaging of another molecule. These novel glutamine sensors will be useful tools to analyze specificities of glutamine metabolism at the single-cell level.

  16. Development of Microorganisms with Improved Transport and Biosurfactant Activity for Enhanced Oil Recovery

    Energy Technology Data Exchange (ETDEWEB)

    M.J. McInerney; K.E. Duncan; N. Youssef; T. Fincher; S.K. Maudgalya; M.J. Folmsbee; R. Knapp; Randy R. Simpson; N.Ravi; D. Nagle

    2005-08-15

    growth at elevated salt concentrations to obtain candidates most suitable for microbial oil recovery. Seventy percent of the 205 strains tested, mostly strains of Bacillus mojavensis, Bacillus subtilis, Bacillus licheniformis, and Bacillus sonorensis, produced biosurfactants aerobically and 41% of the strains had biosurfactant activity greater than Bacillus mojavensis JF-2, the current candidate for oil recovery. Biosurfactant activity varied with the percentage of the 3-hydroxy-tetradecanoate isomers in the fatty acid portion of the biosurfactant. Changing the medium composition by incorporation of different precursors of 3-hydroxy tetradecanoate increased the activity of biosurfactant. The surface tension and critical micelle concentration of 15 different, biosurfactant-producing Bacillus strains was determined individually and in combination with other biosurfactants. Some biosurfactant mixtures were found to have synergistic effect on surface tension (e.g. surface tension was lowered from 41 to 31 mN/m in some cases) while others had a synergistic effect on CMD-1 values. We compared the transport abilities of spores from three Bacillus strains using a model porous system to study spore recovery and transport. Sand-packed columns were used to select for spores or cells with the best transport abilities through brine-saturated sand. Spores of Bacillus mojavensis strains JF-2 and ROB-2 and a natural recombinant, strain C-9, transported through sand at very high efficiencies. The earliest cells/spores that emerged from the column were regrown, allowed to sporulate, and applied to a second column. This procedure greatly enhanced the transport of strain C-9. Spores with enhanced transport abilities can be easily obtained and that the preparation of inocula for use in MEOR is feasible. We conducted a push-pull test to study in-situ biosurfactant production by exogenous biosurfactant producers to aid in oil recovery from depleted reservoirs. Five wells from the same

  17. Inhibition of dopamine transporter activity by G protein βγ subunits.

    Directory of Open Access Journals (Sweden)

    Jennie Garcia-Olivares

    Full Text Available Uptake through the Dopamine Transporter (DAT is the primary mechanism of terminating dopamine signaling within the brain, thus playing an essential role in neuronal homeostasis. Deregulation of DAT function has been linked to several neurological and psychiatric disorders including ADHD, schizophrenia, Parkinson's disease, and drug addiction. Over the last 15 years, several studies have revealed a plethora of mechanisms influencing the activity and cellular distribution of DAT; suggesting that fine-tuning of dopamine homeostasis occurs via an elaborate interplay of multiple pathways. Here, we show for the first time that the βγ subunits of G proteins regulate DAT activity. In heterologous cells and brain tissue, a physical association between Gβγ subunits and DAT was demonstrated by co-immunoprecipitation. Furthermore, in vitro pull-down assays using purified proteins established that this association occurs via a direct interaction between the intracellular carboxy-terminus of DAT and Gβγ. Functional assays performed in the presence of the non-hydrolyzable GTP analog GTP-γ-S, Gβγ subunit overexpression, or the Gβγ activator mSIRK all resulted in rapid inhibition of DAT activity in heterologous systems. Gβγ activation by mSIRK also inhibited dopamine uptake in brain synaptosomes and dopamine clearance from mouse striatum as measured by high-speed chronoamperometry in vivo. Gβγ subunits are intracellular signaling molecules that regulate a multitude of physiological processes through interactions with enzymes and ion channels. Our findings add neurotransmitter transporters to the growing list of molecules regulated by G-proteins and suggest a novel role for Gβγ signaling in the control of dopamine homeostasis.

  18. Electron transport chain inhibitors induce microglia activation through enhancing mitochondrial reactive oxygen species production.

    Science.gov (United States)

    Ye, Junli; Jiang, Zhongxin; Chen, Xuehong; Liu, Mengyang; Li, Jing; Liu, Na

    2016-01-15

    Reactive oxygen species (ROS) are believed to be mediators of excessive microglial activation, yet the resources and mechanism are not fully understood. Here we stimulated murine microglial BV-2 cells and primary microglial cells with different inhibitors of electron transport chain (ETC), rotenone, thenoyltrifluoroacetone (TTFA), antimycin A, and NaN3 to induce mitochondrial ROS production and we observed the role of mitochondrial ROS in microglial activation. Our results showed that ETC inhibitors resulted in significant changes in cell viability, microglial morphology, cell cycle arrest and mitochondrial ROS production in a dose-dependent manner in both primary cultural microglia and BV-2 cell lines. Moreover, ETC inhibitors, especially rotenone and antimycin A stimulated secretion of interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 12 (IL-12) and tumor necrosis factor α (TNF-α) by microglia with marked activation of mitogen-activated proteinkinases (MAPKs) and nuclear factor κB (NF-κB), which could be blocked by specific inhibitors of MAPK and NF-κB and mitochondrial antioxidants, Mito-TEMPO. Taken together, our results demonstrated that inhibition of mitochondrial respiratory chain in microglia led to production of mitochondrial ROS and therefore may activate MAPK/NF-кB dependent inflammatory cytokines release in microglia, which indicated that mitochondrial-derived ROS were contributed to microglial activation.

  19. Cannabinoid-Induced Changes in the Activity of Electron Transport Chain Complexes of Brain Mitochondria.

    Science.gov (United States)

    Singh, Namrata; Hroudová, Jana; Fišar, Zdeněk

    2015-08-01

    The aim of this study was to investigate changes in the activity of individual mitochondrial respiratory chain complexes (I, II/III, IV) and citrate synthase induced by pharmacologically different cannabinoids. In vitro effects of selected cannabinoids on mitochondrial enzymes were measured in crude mitochondrial fraction isolated from pig brain. Both cannabinoid receptor agonists, Δ(9)-tetrahydrocannabinol, anandamide, and R-(+)-WIN55,212-2, and antagonist/inverse agonists of cannabinoid receptors, AM251, and cannabidiol were examined in pig brain mitochondria. Different effects of these cannabinoids on mitochondrial respiratory chain complexes and citrate synthase were found. Citrate synthase activity was decreased only by Δ(9)-tetrahydrocannabinol and AM251. Significant increase in the complex I activity was induced by anandamide. At micromolar concentration, all the tested cannabinoids inhibited the activity of electron transport chain complexes II/III and IV. Stimulatory effect of anandamide on activity of complex I may participate on distinct physiological effects of endocannabinoids compared to phytocannabinoids or synthetic cannabinoids. Common inhibitory effect of cannabinoids on activity of complex II/III and IV confirmed a non-receptor-mediated mechanism of cannabinoid action on individual components of system of oxidative phosphorylation.

  20. Alteration of natural (37)Ar activity concentration in the subsurface by gas transport and water infiltration.

    Science.gov (United States)

    Guillon, Sophie; Sun, Yunwei; Purtschert, Roland; Raghoo, Lauren; Pili, Eric; Carrigan, Charles R

    2016-05-01

    High (37)Ar activity concentration in soil gas is proposed as a key evidence for the detection of underground nuclear explosion by the Comprehensive Nuclear Test-Ban Treaty. However, such a detection is challenged by the natural background of (37)Ar in the subsurface, mainly due to Ca activation by cosmic rays. A better understanding and improved capability to predict (37)Ar activity concentration in the subsurface and its spatial and temporal variability is thus required. A numerical model integrating (37)Ar production and transport in the subsurface is developed, including variable soil water content and water infiltration at the surface. A parameterized equation for (37)Ar production in the first 15 m below the surface is studied, taking into account the major production reactions and the moderation effect of soil water content. Using sensitivity analysis and uncertainty quantification, a realistic and comprehensive probability distribution of natural (37)Ar activity concentrations in soil gas is proposed, including the effects of water infiltration. Site location and soil composition are identified as the parameters allowing for a most effective reduction of the possible range of (37)Ar activity concentrations. The influence of soil water content on (37)Ar production is shown to be negligible to first order, while (37)Ar activity concentration in soil gas and its temporal variability appear to be strongly influenced by transient water infiltration events. These results will be used as a basis for practical CTBTO concepts of operation during an OSI.

  1. Opposite temperature effect on transport activity of KCC2/KCC4 and N(KCCs in HEK-293 cells

    Directory of Open Access Journals (Sweden)

    Hartmann Anna-Maria

    2011-12-01

    Full Text Available Abstract Background Cation chloride cotransporters play essential roles in many physiological processes such as volume regulation, transepithelial salt transport and setting the intracellular chloride concentration in neurons. They consist mainly of the inward transporters NCC, NKCC1, and NKCC2, and the outward transporters KCC1 to KCC4. To gain insight into regulatory and structure-function relationships, precise determination of their activity is required. Frequently, these analyses are performed in HEK-293 cells. Recently the activity of the inward transporters NKCC1 and NCC was shown to increase with temperature in these cells. However, the temperature effect on KCCs remains largely unknown. Findings Here, we determined the temperature effect on KCC2 and KCC4 transport activity in HEK-293 cells. Both transporters demonstrated significantly higher transport activity (2.5 fold for KCC2 and 3.3 fold for KCC4 after pre-incubation at room temperature compared to 37°C. Conclusions These data identify a reciprocal temperature dependence of cation chloride inward and outward cotransporters in HEK-293 cells. Thus, lower temperature should be used for functional characterization of KCC2 and KCC4 and higher temperatures for N(KCCs in heterologous mammalian expression systems. Furthermore, if this reciprocal effect also applies to neurons, the action of inhibitory neurotransmitters might be more affected by changes in temperature than previously thought.

  2. DEVELOPMENT OF MICROORGANISMS WITH IMPROVED TRANSPORT AND BIOSURFACTANT ACTIVITY FOR ENHANCED OIL RECOVERY

    Energy Technology Data Exchange (ETDEWEB)

    M.J. McInerney; N. Youssef; T. Fincher; S.K. Maudgalya; M.J. Folmsbee; R. Knapp; D. Nagle

    2004-05-31

    Diverse microorganisms were screened for biosurfactant production and anaerobic growth at elevated salt concentrations to obtain candidates most suitable for microbial oil recovery. Seventy percent of the 205 strains tested, mostly strains of Bacillus mojavensis, Bacillus subtilis, Bacillus licheniformis, and Bacillus sonorensis, produced biosurfactants aerobically and 41% of the strains had biosurfactant activity greater than Bacillus mojavensis JF-2, the current candidate for oil recovery. Biosurfactant activity varied with the percentage of the 3-hydroxy-tetradecanoate isomers in the fatty acid portion of the biosurfactant. Changing the medium composition by incorporation of different precursors of 3-hydroxy tetradecanoate increased the activity of biosurfactant. The surface tension and critical micelle concentration of 15 different, biosurfactant-producing Bacillus strains was determined individually and in combination with other biosurfactants. Some biosurfactant mixtures were found to have synergistic effect on surface tension (e.g. surface tension was lowered from 41 to 31 mN/m in some cases) while others had a synergistic effect on CMD-1 values. We compared the transport abilities of spores from three Bacillus strains using a model porous system to study spore recovery and transport. Sand-packed columns were used to select for spores or cells with the best transport abilities through brine-saturated sand. Spores of Bacillus mojavensis strains JF-2 and ROB-2 and a natural recombinant, strain C-9, transported through sand at very high efficiencies. The earliest cells/spores that emerged from the column were re-grown, allowed to sporulate, and applied to a second column. This procedure greatly enhanced the transport of strain C-9. Spores with enhanced transport abilities can be easily obtained and that the preparation of inocula for use in MEOR is feasible. Tertiary oil recovery experiments showed that 10 to 40 mg/l of JF-2 biosurfactant in the presence of 0

  3. Modulation of kidney urea transporter UT-A3 activity by alpha2,6-sialylation.

    Science.gov (United States)

    Qian, Xiaoqian; Sands, Jeff M; Song, Xiang; Chen, Guangping

    2016-07-01

    Two urea transporters, UT-A1 and UT-A3, are expressed in the kidney terminal inner medullary collecting duct (IMCD) and are important for the production of concentrated urine. UT-A1, as the largest isoform of all UT-A urea transporters, has gained much attention and been extensively studied; however, the role and the regulation of UT-A3 are less explored. In this study, we investigated UT-A3 regulation by glycosylation modification. A site-directed mutagenesis verified a single glycosylation site in UT-A3 at Asn279. Loss of the glycosylation reduced forskolin-stimulated UT-A3 cell membrane expression and urea transport activity. UT-A3 has two glycosylation forms, 45 and 65 kDa. Using sugar-specific binding lectins, the UT-A3 glycosylation profile was examined. The 45-kDa form was pulled down by lectin concanavalin A (Con A) and Galant husnivalis lectin (GNL), indicating an immature glycan with a high amount of mannose (Man), whereas the 65-kDa form is a mature glycan composed of acetylglucosamine (GlcNAc) and poly-N-acetyllactosame (poly-LacNAc) that was pulled down by wheat germ agglutinin (WGA) and tomato lectin, respectively. Interestingly, the mature form of UT-A3 glycan contains significant amounts of sialic acid. We explored the enzymes responsible for directing UT-A3 sialylation. Sialyltransferase ST6GalI, but not ST3GalIV, catabolizes UT-A3 α2,6-sialylation. Activation of protein kinase C (PKC) by PDB treatment promoted UT-A3 glycan sialylation and membrane surface expression. The PKC inhibitor chelerythrine blocks ST6GalI-induced UT-A3 sialylation. Increased sialylation by ST6GalI increased UT-A3 protein stability and urea transport activity. Collectively, our study reveals a novel mechanism of UT-A3 regulation by ST6GalI-mediated sialylation modification that may play an important role in kidney urea reabsorption and the urinary concentrating mechanism.

  4. Na(+)-K(+)-ATPase expression in alveolar epithelial cells: upregulation of active ion transport by KGF.

    Science.gov (United States)

    Borok, Z; Danto, S I; Dimen, L L; Zhang, X L; Lubman, R L

    1998-01-01

    We evaluated the effects of keratinocyte growth factor (KGF) on alveolar epithelial cell (AEC) active ion transport and on rat epithelial Na channel (rENaC) subunit and Na(+)-K(+)-adenosinetriphosphatase (ATPase) subunit isoform expression using monolayers of AEC grown in primary culture. Rat alveolar type II cells were plated on polycarbonate filters in serum-free medium, and KGF (10 ng/ml) was added to confluent AEC monolayers on day 4 in culture. Exposure of AEC monolayers to KGF on day 4 resulted in dose-dependent increases in short-circuit current (Isc) compared with controls by day 5, with further increases occurring through day 8. Relative Na(+)-K(+)-ATPase alpha 1-subunit mRNA abundance was increased by 41% on days 6 and 8 after exposure to KGF, whereas alpha 2-subunit mRNA remained only marginally detectable in both the absence and presence of KGF. Levels of mRNA for the beta 1-subunit of Na(+)-K(+)-ATPase did not increase, whereas cellular alpha 1- and beta 1-subunit protein increased 70 and 31%, respectively, on day 6. mRNA for alpha-, beta-, and gamma-rENaC all decreased in abundance after treatment with KGF. These results indicate that KGF upregulates active ion transport across AEC monolayers via a KGF-induced increase in Na pumps, primarily due to increased Na(+)-K(+)-ATPase alpha 1-subunit mRNA expression. We conclude that KGF may enhance alveolar fluid clearance after acute lung injury by upregulating Na pump expression and transepithelial Na transport across the alveolar epithelium.

  5. Activation energy spectra: insights into transport limitations of organic semiconductors and photovoltaic cells

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Ziqi; Nardes, Alexandre M.; Van de Lagemaat, Jao; Gregg, Brian A. [National Renewable Energy Laboratory, Golden, CO (United States)

    2012-03-07

    Some mechanisms of charge transport in organic semiconductors and organic photovoltaic (OPV) cells can be distinguished by their predicted change in activation energy for the current, E{sub a}, versus applied field, F. E{sub a} versus F is measured first in pure films of commercially available regioregular poly(3-hexylthiophene) (P3HT) and in the same P3HT treated to reduce its charged defect density. The former shows a Poole-Frenkel (PF)-like decrease in E{sub a} at low F, which then plateaus at higher F. The low defect material does not exhibit PF behavior and E{sub a} remains approximately constant. Upon addition of [6,6]-phenyl-C{sub 61}-butyric acid methyl ester (PCBM), however, both materials show a large increase in E{sub a} and exhibit PF-like behavior over the entire field range. These results are explained with a previously proposed model of transport that considers both the localized random disorder in the energy levels and the long-range electrostatic fluctuations resulting from charged defects. Activation energy spectra in working OPV cells show that the current is injection-limited over most of the voltage range but becomes transport-limited, with a large peak in E{sub a}, near the open circuit photovoltage. This causes a decrease in fill factor, which may be a general limitation in such solar cells. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  6. Effects of noradrenaline on the cell-surface glucose transporters in cultured brown adipocytes: novel mechanism for selective activation of GLUT1 glucose transporters.

    Science.gov (United States)

    Shimizu, Y; Satoh, S; Yano, H; Minokoshi, Y; Cushman, S W; Shimazu, T

    1998-01-01

    Glucose transport into rat brown adipocytes has been shown to be stimulated directly by the sympathetic neurotransmitter, noradrenaline, without a significant increase in the protein content of either GLUT1 or GLUT4 glucose transporter in the plasma membrane [Shimizu, Kielar, Minokoshi and Shimazu (1996) Biochem. J. 314, 485-490]. In the present study, we labelled the exofacial glucose-binding sites of GLUT1 and GLUT4 with a membrane-impermeant photoaffinity reagent, 2-N-[4-(1-azitrifluoroethyl)benzoyl]-[2-3H]1,3-bis- (D-mannos-4-yloxy)-2-propylamine (ATB-[3H]BMPA), to determine which isoform is responsible for the noradrenaline-induced increase in glucose transport into intact brown adipocytes in culture. Insulin stimulated the rate of hexose transport by increasing ATB-[3H]BMPA-labelled cell-surface GLUT4. In contrast, the noradrenaline-induced increase in glucose transport was not accompanied by an increased ATB-[3H]BMPA labelling of GLUT4, nor with an increased amount of GLUT4 in the plasma membrane fraction as assessed by Western blotting, indicating that noradrenaline does not promote the translocation of GLUT4. However, noradrenaline induced an increase in photoaffinity labelling of cell-surface GLUT1 without an apparent increase in the immunoreactive GLUT1 protein in the plasma membrane. This is suggestive of an increased affinity of GLUT1 for the ligand. In fact, the Ki value of non-radioactive ATB-BMPA for 2-deoxy-D-glucose uptake was significantly decreased after treatment of the cells with noradrenaline. The increased photoaffinity labelling of GLUT1 and increased glucose transport caused by noradrenaline were inhibited by a cAMP antagonist, cAMP-S Rp-isomer. These results demonstrate that noradrenaline stimulates glucose transport in brown adipocytes by enhancing the functional activity of GLUT1 through a cAMP-dependent mechanism. PMID:9461536

  7. A Mathematical Model of Solute Coupled Water Transport in Toad Intestine Incorporating Recirculation of the Actively Transported Solute

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Sørensen, Jakob Balslev; Sørensen, Jens Nørkær

    2000-01-01

    A mathematical model of an absorbing leaky epithelium is developed for analysis of solute coupled water transport. The non-charged driving solute diffuses into cells and is pumped from cells into the lateral intercellular space (lis). All membranes contain water channels with the solute passing...... concentration of fluid emerging from lis is then significantly larger than the concentration in lis. Thus, in absence of external driving forces the model generates isotonic transport provided a component of the solute flux emerging downstream lis is taken up by cells through the serosal membrane and pumped...... back into lis, i.e., the solute would have to be recirculated. With input variables from toad intestine (Nedergaard, S., E.H. Larsen, and H.H. Ussing, J. Membr. Biol. 168:241-251), computations predict that 60-80% of the pumped flux stems from serosal bath in agreement with the experimental estimate...

  8. Single-fluorophore membrane transport activity sensors with dual-emission read-out.

    Science.gov (United States)

    Ast, Cindy; De Michele, Roberto; Kumke, Michael U; Frommer, Wolf B

    2015-06-19

    We recently described a series of genetically encoded, single-fluorophore-based sensors, termed AmTrac and MepTrac, which monitor membrane transporter activity in vivo (De Michele et al., 2013). However, being intensiometric, AmTrac and Meptrac are limited in their use for quantitative studies. Here, we characterized the photophysical properties (steady-state and time-resolved fluorescence spectroscopy as well as anisotropy decay analysis) of different AmTrac sensors with diverging fluorescence properties in order to generate improved, ratiometric sensors. By replacing key amino acid residues in AmTrac we constructed a set of dual-emission AmTrac sensors named deAmTracs. deAmTracs show opposing changes of blue and green emission with almost doubled emission ratio upon ammonium addition. The response ratio of the deAmTracs correlated with transport activity in mutants with altered capacity. Our results suggest that partial disruption of distance-dependent excited-state proton transfer is important for the successful generation of single-fluorophore-based dual-emission sensors.

  9. Tamoxifen and its active metabolites inhibit dopamine transporter function independently of the estrogen receptors.

    Science.gov (United States)

    Mikelman, Sarah R; Guptaroy, Bipasha; Gnegy, Margaret E

    2017-04-01

    As one of the primary mechanisms by which dopamine signaling is regulated, the dopamine transporter (DAT) is an attractive pharmacological target for the treatment of diseases based in dopaminergic dysfunction. In this work we demonstrate for the first time that the commonly prescribed breast cancer therapeutic tamoxifen and its major metabolites, 4-hydroxytamoxifen and endoxifen, inhibit DAT function. Tamoxifen inhibits [(3) H]dopamine uptake into human DAT (hDAT)-N2A cells via an uncompetitive or mixed mechanism. Endoxifen, an active metabolite of tamoxifen, asymmetrically inhibits DAT function in hDAT-N2A cells, showing a preference for the inhibition of amphetamine-stimulated dopamine efflux as compared to dopamine uptake. Importantly, we demonstrate that the effects of tamoxifen and its metabolites on the DAT occur independently of its activity as selective estrogen receptor modulators. This work suggests that tamoxifen is inhibiting DAT function through a previously unidentified mechanism. © 2017 International Society for Neurochemistry.

  10. Guanidinylated neomycin mediates heparan sulfate-dependent transport of active enzymes to lysosomes.

    Science.gov (United States)

    Sarrazin, Stéphane; Wilson, Beth; Sly, William S; Tor, Yitzhak; Esko, Jeffrey D

    2010-07-01

    Guanidinylated neomycin (GNeo) can transport bioactive, high molecular weight cargo into the interior of cells in a process that depends on cell surface heparan sulfate proteoglycans. In this report, we show that GNeo-modified quantum dots bind to cell surface heparan sulfate, undergo endocytosis and eventually reach the lysosomal compartment. An N-hydroxysuccinimide activated ester of GNeo (GNeo-NHS) was prepared and conjugated to two lysosomal enzymes, beta-D-glucuronidase (GUS) and alpha-L-iduronidase. Conjugation did not interfere with enzyme activity and enabled binding of the enzymes to heparin-Sepharose and heparan sulfate on primary human fibroblasts. Cells lacking the corresponding lysosomal enzyme took up sufficient amounts of the conjugated enzymes to restore normal turnover of glycosaminoglycans. The high capacity of proteoglycan-mediated uptake suggests that this method of delivery might be used for enzyme replacement or introduction of foreign enzymes into cells.

  11. Modeling Coronal Response in Decaying Active Regions with Magnetic Flux Transport and Steady Heating

    Science.gov (United States)

    Ugarte-Urra, Ignacio; Warren, Harry P.; Upton, Lisa A.; Young, Peter R.

    2017-09-01

    We present new measurements of the dependence of the extreme ultraviolet (EUV) radiance on the total magnetic flux in active regions as obtained from the Atmospheric Imaging Assembly (AIA) and the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory. Using observations of nine active regions tracked along different stages of evolution, we extend the known radiance—magnetic flux power-law relationship (I\\propto {{{Φ }}}α ) to the AIA 335 Å passband, and the Fe xviii 93.93 Å spectral line in the 94 Å passband. We find that the total unsigned magnetic flux divided by the polarity separation ({{Φ }}/D) is a better indicator of radiance for the Fe xviii line with a slope of α =3.22+/- 0.03. We then use these results to test our current understanding of magnetic flux evolution and coronal heating. We use magnetograms from the simulated decay of these active regions produced by the Advective Flux Transport model as boundary conditions for potential extrapolations of the magnetic field in the corona. We then model the hydrodynamics of each individual field line with the Enthalpy-based Thermal Evolution of Loops model with steady heating scaled as the ratio of the average field strength and the length (\\bar{B}/L) and render the Fe xviii and 335 Å emission. We find that steady heating is able to partially reproduce the magnitudes and slopes of the EUV radiance—magnetic flux relationships and discuss how impulsive heating can help reconcile the discrepancies. This study demonstrates that combined models of magnetic flux transport, magnetic topology, and heating can yield realistic estimates for the decay of active region radiances with time.

  12. Coordinative modulation of human zinc transporter 2 gene expression through active and suppressive regulators.

    Science.gov (United States)

    Lu, Yu-Ju; Liu, Ya-Chuan; Lin, Meng-Chieh; Chen, Yi-Ting; Lin, Lih-Yuan

    2015-04-01

    Zinc transporter 2 (ZnT2) is one of the cellular factors responsible for Zn homeostasis. Upon Zn overload, ZnT2 reduces cellular Zn by transporting it into excretory vesicles. We investigated the molecular mechanism that regulates human ZnT2 (hZnT2) gene expression. Zn induces hZnT2 expression in dose- and time-dependent manners. Overexpression of metal-responsive transcription factor 1 (MTF-1) increases hZnT2 transcription, whereas depletion of MTF-1 reduces hZnT2 expression. There are five putative metal response elements (MREs) within 1kb upstream of the hZnT2 gene. A serial deletion of the hZnT2 promoter region (from 5' to 3') shows that the two MREs proximal to the gene are essential for Zn-induced promoter activity. Further mutation analysis concludes that the penultimate MRE (MREb) supports the metal-induced promoter activity. The hZnT2 promoter has also a zinc finger E-box binding homeobox (ZEB) binding element. Mutation or deletion of this ZEB binding element elevates the basal and Zn-induced hZnT2 promoter activities. Knockdown of ZEB1 mRNA enhances the hZnT2 transcript level in HEK-293 cells. In MCF-7 (ZEB-deficient) cells, expression of ZEB proteins attenuates the Zn-induced hZnT2 expression. However, expressions of MTF-1 target genes such as human ZnT1 and metallothionein IIA were not affected. Our study shows the expression of the hZnT2 gene is coordinately regulated via active and suppressive modulators.

  13. Expression and functional activity of nucleoside transporters in human choroid plexus

    Directory of Open Access Journals (Sweden)

    Grujicic Danica

    2010-01-01

    Full Text Available Abstract Background Human equilibrative nucleoside transporters (hENTs 1-3 and human concentrative nucleoside transporters (hCNTs 1-3 in the human choroid plexus (hCP play a role in the homeostasis of adenosine and other naturally occurring nucleosides in the brain; in addition, hENT1, hENT2 and hCNT3 mediate membrane transport of nucleoside reverse transcriptase inhibitors that could be used to treat HIV infection, 3'-azido-3'-deoxythymidine, 2'3'-dideoxycytidine and 2'3'-dideoxyinosine. This study aimed to explore the expression levels and functional activities of hENTs 1-3 and hCNTs 1-3 in human choroid plexus. Methods Freshly-isolated pieces of lateral ventricle hCP, removed for various clinical reasons during neurosurgery, were obtained under Local Ethics Committee approval. Quantification of mRNAs that encoded hENTs and hCNTs was performed by the hydrolysis probes-based reverse transcription real time-polymerase chain reaction (RT-qPCR; for each gene of interest and for 18 S ribosomal RNA, which was an endogenous control, the efficiency of PCR reaction (E and the quantification cycle (Cq were calculated. The uptake of [3H]inosine by the choroid plexus pieces was investigated to explore the functional activity of hENTs and hCNTs in the hCP. Results RT-qPCR revealed that the mRNA encoding the intracellularly located transporter hENT3 was the most abundant, with E-Cq value being only about 40 fold less that the E-Cq value for 18 S ribosomal RNA; mRNAs encoding hENT1, hENT2 and hCNT3 were much less abundant than mRNA for the hENT3, while mRNAs encoding hCNT1 and hCNT2 were of very low abundance and not detectable. Uptake of [3H]inosine by the CP samples was linear and consisted of an Na+-dependent component, which was probably mediated by hCNT3, and Na+-independent component, mediated by hENTs. The latter component was not sensitive to inhibition by S-(4-nitrobenzyl-6-thioinosine (NBMPR, when used at a concentration of 0.5 μM, a finding that

  14. Activity-based concept for transport and partitioning of ionizing organics.

    Science.gov (United States)

    Trapp, Stefan; Franco, Antonio; Mackay, Don

    2010-08-15

    Ionizing chemicals, including pesticides, pharmaceuticals, and personal care products, are care products, are widely used chemicals of commerce and have been detected in the environment in large numbers. These "ionics" are subject to a variety of processes, such as dissociation, ion trap, and electrical interactions with organic matter and biota. Conventional chemodynamic concepts and models designed to treat neutral compounds do not necessarily address these processes. A new system of equations, based on activity and analogous to the fugacity approach, is suggested to describe the fate of organic ionics. The total concentration of all molecule species in a bulk compartment is determined from the product of activity 'a' and a bulk activity capacity 'B'. The concentration ratio between compartments in equilibrium depends on the activity ratio and the capacity ratio. Changes in partitioning due to pH, ionic strength, and the ion trap effect are quantified. The calculation is illustrated for two pharmaceuticals, namely the monovalent acid ibuprofen and the monovalent base trimethoprim, in a multimedia lake system. Trimethoprim is neutral at high pH but ionized at low pH, while ibuprofen exhibits the opposite. The concentration ratios of air and biota to water are shown to depend on pH. The activity approach may be used to describe transport and partitioning of multivalent ionizable organic compounds and to build multimedia fate models.

  15. Inhibition of fast axonal transport by pathogenic SOD1 involves activation of p38 MAP kinase.

    Directory of Open Access Journals (Sweden)

    Gerardo A Morfini

    Full Text Available Dying-back degeneration of motor neuron axons represents an established feature of familial amyotrophic lateral sclerosis (FALS associated with superoxide dismutase 1 (SOD1 mutations, but axon-autonomous effects of pathogenic SOD1 remained undefined. Characteristics of motor neurons affected in FALS include abnormal kinase activation, aberrant neurofilament phosphorylation, and fast axonal transport (FAT deficits, but functional relationships among these pathogenic events were unclear. Experiments in isolated squid axoplasm reveal that FALS-related SOD1 mutant polypeptides inhibit FAT through a mechanism involving a p38 mitogen activated protein kinase pathway. Mutant SOD1 activated neuronal p38 in mouse spinal cord, neuroblastoma cells and squid axoplasm. Active p38 MAP kinase phosphorylated kinesin-1, and this phosphorylation event inhibited kinesin-1. Finally, vesicle motility assays revealed previously unrecognized, isoform-specific effects of p38 on FAT. Axon-autonomous activation of the p38 pathway represents a novel gain of toxic function for FALS-linked SOD1 proteins consistent with the dying-back pattern of neurodegeneration characteristic of ALS.

  16. Electron Transport Controls Glutamine Synthetase Activity in the Facultative Heterotrophic Cyanobacterium Synechocystis sp. PCC 6803.

    Science.gov (United States)

    Reyes, J. C.; Crespo, J. L.; Garcia-Dominguez, M.; Florencio, F. J.

    1995-11-01

    Glutamine synthetase (GS) from Synechocystis sp. PCC 6803 was inactivated in vivo by transferring cells from light to darkness or by incubation with the photosynthetic inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea but not with 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone. Addition of glucose prevented both dark and 3-(3,4-dichlorophenyl)-1,1-dimethylurea GS inactivation. In a Synechocystis psbE-psbF mutant (T1297) lacking photosystem II, glucose was required to maintain active GS, even in the light. However, in nitrogen-starved T1297 cells the removal of glucose did not affect GS activity. The fact that dark-inactivated GS was reactivated in vitro by the same treatments that reactivate the ammonium-inactivated GS points out that both nitrogen metabolism and redox state of the cells lead to the same molecular regulatory mechanism in the control of GS activity. Using GS antibodies we detected that dark-inactivated GS displayed a different electrophoretic migration with respect to the active form in nondenaturing polyacrylamide gel electrophoresis but not in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The possible pathway to modulate GS activity by the electron transport flow in Synechocystis cells is discussed.

  17. A needs assessment for DOE`s packaging and transportation activities - a look into the twenty-first century

    Energy Technology Data Exchange (ETDEWEB)

    Pope, R. [Oak Ridge National Lab., TN (United States); Turi, G.; Brancato, R.; Blalock, L. [Department of Energy, Germantown, MD (United States); Merrill, O. [Scientific Applications International Corp., Gaithersburg, MD (United States)

    1995-12-31

    The U.S. Department of Energy (DOE) has performed a department-wide scoping of its packaging and transportation needs and has arrived at a projection of these needs for well into the twenty-first century. The assessment, known as the Transportation Needs Assessment (TNA) was initiated during August 1994 and completed in December 1994. The TNA will allow DOE to better prepare for changes in its transportation requirements in the future. The TNA focused on projected, quantified shipping needs based on forecasts of inventories of materials which will ultimately require transport by the DOE for storage, treatment and/or disposal. In addition, experts provided input on the growing needs throughout DOE resulting from changes in regulations, in DOE`s mission, and in the sociopolitical structure of the United States. Through the assessment, DOE`s transportation needs have been identified for a time period extending from the present through the first three decades of the twenty-first century. The needs assessment was accomplished in three phases: (1) defining current packaging, shipping, resource utilization, and methods of managing packaging and transportation activities; (2) establishing the inventory of materials which DOE will need to transport on into the next century and scenarios which project when, from where, and to where these materials will need to be transported; and (3) developing requirements and projected changes for DOE to accomplish the necessary transport safely and economically.

  18. Multi-level examination of correlates of active transportation to school among youth living within 1 mile of their school

    Directory of Open Access Journals (Sweden)

    Gropp Kathleen M

    2012-10-01

    Full Text Available Abstract Background Active transportation to school is a method by which youth can build physical activity into their daily routines. We examined correlates of active transportation to school at both individual- (characteristics of the individual and family and area- (school and neighborhood levels amongst youth living within 1 mile (1.6 km of their school. Methods Using the 2009/10 Canadian Health Behaviour in School-Aged Children (HBSC survey, we selected records of students (n = 3 997 from 161 schools that resided in an urban setting and lived within 1 mile from their school. Student records were compiled from: (1 individual-level HBSC student questionnaires; (2 area-level administrator (school questionnaires; and (3 area-level geographic information system data sources. The outcome, active transportation to school, was determined via a questionnaire item describing the method of transportation that individual students normally use to get to school. Analyses focused on factors at multiple levels that potentially contribute to student decisions to engage in active transportation. Multi-level logistic regression analyses were employed. Results Approximately 18% of the variance in active transportation was accounted for at the area-level. Several individual and family characteristics were associated with engagement in active transportation to school including female gender (RR vs. males = 0.86, 95% CI: 0.80-0.91, having ≥2 cars in the household (RR vs. no cars = 0.87, 0.74-0.97, and family socioeconomic status (RR for ‘not well off’ vs. ‘very well off’ = 1.14, 1.01-1.26. Neighborhood characteristics most strongly related to active transportation were: the length of roads in the 1 km buffer (RR in quartile 4 vs. quartile 1 = 1.23, 1.00-1.42, the amount of litter in the neighborhood (RR for ‘major problem’ vs. ‘no problem’ = 1.47, 1.16-1.57, and relatively hot climates (RR in quartile 4 vs. quartile 1

  19. Molecular physiology of the insect K-activated amino acid transporter 1 (KAAT1) and cation-anion activated amino acid transporter/channel 1 (CAATCH1) in the light of the structure of the homologous protein LeuT.

    Science.gov (United States)

    Castagna, M; Bossi, E; Sacchi, V F

    2009-06-01

    K-activated amino acid transporter 1 (KAAT1) and cation-anion-activated amino acid transporter/channel 1 (CAATCH1) are amino acid cotransporters, belonging to the Na/Cl-dependent neurotransmitter transporter family (also called SLC6/NSS), that have been cloned from Manduca sexta midgut. They have been thoroughly studied by expression in Xenopus laevis oocytes, and structure/function analyses have made it possible to identify the structural determinants of their cation and amino acid selectivity. About 40 mutants of these proteins have been studied by measuring amino acid uptake and current/voltage relationships. The results obtained since the cloning of KAAT1 and CAATCH1 are here discussed in the light of the 3D model of the first crystallized member of the family, the leucine transporter LeuT.

  20. Intestinal Serotonin Transporter Inhibition by Toll-Like Receptor 2 Activation. A Feedback Modulation

    Science.gov (United States)

    Layunta, Elena; Grasa, Laura; Castro, Marta; Pardo, Julián; Gomollón, Fernando; Mesonero, José E.

    2016-01-01

    TLR2 is a microbiota recognition receptor that has been described to contribute to intestinal homeostasis and to ameliorate inflammatory intestinal injury. In this context, serotonin (5-HT) has shown to be an essential intestinal physiological neuromodulator that is also involved in intestinal inflammatory diseases. Since the interaction between TLR2 activation and the intestinal serotoninergic system remains non-investigated, our main aim was to analyze the effect of TLR2 on intestinal serotonin transporter (SERT) activity and expression and the intracellular pathways involved. Caco-2/TC7 cells were used to analyze SERT and TLR2 molecular expression and SERT activity by measuring 5-HT uptake. The results showed that apical TLR2 activation inhibits SERT activity in Caco-2/TC7 cells mainly by reducing SERT protein level either in the plasma membrane, after short-term TLR2 activation or in both the plasma membrane and cell lysate, after long-term activation. cAMP/PKA pathway appears to mediate short-term inhibitory effect of TLR2 on SERT; however, p38 MAPK pathway has been shown to be involved in both short- and long-term TLR2 effect. Reciprocally, 5-HT long-term treatment yielded TLR2 down regulation in Caco-2/TC7 cells. Finally, results from in vivo showed an augmented intestinal SERT expression in mice Tlr2-/-, thus confirming our inhibitory effect of TLR2 on intestinal SERT in vitro. The present work infers that TLR2 may act in intestinal pathophysiology, not only by its inherent innate immune role, but also by regulating the intestinal serotoninergic system. PMID:28033388

  1. Extracellular Microvesicles from Astrocytes Contain Functional Glutamate Transporters: Regulation by Protein Kinase C and Cell Activation

    Directory of Open Access Journals (Sweden)

    Romain-Daniel eGosselin

    2013-12-01

    Full Text Available Glutamate transport through astrocytic excitatory amino-acid transporters (EAAT-1 and EAAT-2 is paramount for neural homeostasis. EAAT-1 has been reported in secreted extracellular microvesicles (eMV, such as exosomes and because the Protein Kinase C (PKC family controls the sub-cellular distribution of EAATs, we have explored whether PKCs drive EAATs into eMV. Using rat primary astrocytes, confocal immunofluorescence and ultracentrifugation on sucrose gradient we here report that PKC activation by phorbol myristate acetate (PMA reorganizes EAAT-1 distribution and reduces functional [3H]-aspartate reuptake. Western-blots show that EAAT-1 is present in eMV from astrocyte conditioned medium, together with NaK ATPase and glutamine synthetase all being further increased after PMA treatment. However, nanoparticle tracking analysis reveals that PKC activation did not change particle concentration. Functional analysis indicates that eMV have the capacity to reuptake [3H]-aspartate. In vivo, we demonstrate that spinal astrocytic reaction induced by peripheral nerve lesion (spared nerve injury, SNI is associated with a phosphorylation of PKC δ together with a shift of EAAT distribution ipsilaterally. Ex vivo, spinal explants from SNI rats release eMV with an increased content of NaK ATPase, EAAT-1 and EAAT-2. These data indicate PKC and cell activation as important regulators of EAAT-1 incorporation in eMV, and raise the possibility that microvesicular EAAT-1 may exert extracellular functions. Beyond a putative role in neuropathic pain, this phenomenon may be important for understanding neural homeostasis and a wide range of neurological diseases associated with astrocytic reaction as well as non-neurological diseases linked to eMV release.

  2. Adult active transportation: adding habit strength to the theory of planned behavior.

    Science.gov (United States)

    de Bruijn, Gert-Jan; Kremers, Stef P J; Singh, Amika; van den Putte, Bas; van Mechelen, Willem

    2009-03-01

    Many health behaviors have a history of repetition and, as a result, may become habitual. Because including a measure of habit strength may add depth to current theoretical models on health behavior, the present study explored the issue of habit strength within the context of the theory of planned behavior regarding adult bicycle use as a means of transportation. Cross-sectional data were gathered in a Dutch adult sample (n=317; mean age=42.09 years; 46.7% men) in 2006 using self-administered questionnaires. Variables for the theory of planned behavior were assessed regarding bicycle use as a means of transportation; habit strength regarding bicycle use as a means of transportation was assessed with the validated Self-Reported Habit Index. Hierarchical regression analyses and interaction analyses using simple slope analyses were conducted. After controlling for variables for the theory of planned behavior, habit strength was the strongest predictor of bicycle use. In addition, simple slope analyses based on a significant interaction term, intention x habit, showed that intention was a significant predictor of bicycle use among those at low levels of habit strength for bicycle use (beta=0.67, pstrength (beta=0.10, p=0.136). Habit strength is a moderator of the intention-behavior relationship regarding bicycle use, with intention becoming less relevant when bicycle use increases in habit strength. Future determinant and intervention studies on physical activity may benefit from including a measure of habit strength--for instance, by identifying the differential effects of informational and environmental interventions.

  3. Cationic amino acid transporter-2 regulates immunity by modulating arginase activity.

    Directory of Open Access Journals (Sweden)

    Robert W Thompson

    2008-03-01

    Full Text Available Cationic amino acid transporters (CAT are important regulators of NOS2 and ARG1 activity because they regulate L-arginine availability. However, their role in the development of Th1/Th2 effector functions following infection has not been investigated. Here we dissect the function of CAT2 by studying two infectious disease models characterized by the development of polarized Th1 or Th2-type responses. We show that CAT2(-/- mice are significantly more susceptible to the Th1-inducing pathogen Toxoplasma gondii. Although T. gondii infected CAT2(-/- mice developed stronger IFN-gamma responses, nitric oxide (NO production was significantly impaired, which contributed to their enhanced susceptibility. In contrast, CAT2(-/- mice infected with the Th2-inducing pathogen Schistosoma mansoni displayed no change in susceptibility to infection, although they succumbed to schistosomiasis at an accelerated rate. Granuloma formation and fibrosis, pathological features regulated by Th2 cytokines, were also exacerbated even though their Th2 response was reduced. Finally, while IL-13 blockade was highly efficacious in wild-type mice, the development of fibrosis in CAT2(-/- mice was largely IL-13-independent. Instead, the exacerbated pathology was associated with increased arginase activity in fibroblasts and alternatively activated macrophages, both in vitro and in vivo. Thus, by controlling NOS2 and arginase activity, CAT2 functions as a potent regulator of immunity.

  4. Serotonin transporter genotype modulates the association between depressive symptoms and amygdala activity among psychiatrically healthy adults.

    Science.gov (United States)

    Gillihan, Seth J; Rao, Hengyi; Brennan, Lauretta; Wang, Danny J J; Detre, John A; Sankoorikal, Geena Mary V; Brodkin, Edward S; Farah, Martha J

    2011-09-30

    Recent attempts to understand the biological bases of depression vulnerability have revealed that both the short allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) and activity in the amygdala are associated with depression. Other studies have reported amygdala hyperactivity associated with the 5-HTTLPR short allele, linking the genetic and neuroimaging lines of research and suggesting a mechanism whereby the short allele confers depression risk. However, fewer investigations have examined the associations among depression, 5-HTTLPR variability, and amygdala activation in a single study. The current study thus investigated whether 5-HTTLPR genotype modulates the association between depressive symptoms and amygdala activity among psychiatrically healthy adults. Regional cerebral blood flow was measured with perfusion fMRI during a task-free scan. We hypothesized differential associations between depressive symptoms and amygdala activity among individuals homozygous for the short allele and individuals homozygous for the long allele. Both whole brain analyses and region-of-interest analyses confirmed this prediction, revealing a significant negative association among the long allele group and a trend of positive association among the short allele group. These results complement existing reports of short allele related amygdala hyperactivity and suggest an additional neurobiological mechanism whereby the 5-HTTLPR is associated with psychiatric outcomes.

  5. SELECTED ASPECTS OF THE IMPLEMENTATION OF ACTIVE MARKETING CAMPAIGN TO RAISE AWARENESS AND PROMOTE PUBLIC TRANSPORT SERVICES IN RURAL AREAS

    Directory of Open Access Journals (Sweden)

    Katarzyna NOSAL

    2016-09-01

    Full Text Available The article presents selected aspects of the implementation of the EU’s SmartMove project, which aims to promote feeder public transport systems in rural areas through the implementation of an active marketing campaign (AMC. Campaigns of this type are connected with providing general and personalized information concerning the functioning of public transport services. In the article, characteristics of one of the implementation areas of the project are presented, namely, the Liszki district near Cracow. Transport services were also evaluated. In addition, selected results are presented from a survey that was conducted among residents of the area from the point of view of the implementation of the AMC. The results concerned data about the means of transport that were currently used for travelling, the knowledge of bus services, the reasons for their use and the factors that might encourage residents to use public transport

  6. A Natural Chimeric Pseudomonas Bacteriocin with Novel Pore-Forming Activity Parasitizes the Ferrichrome Transporter.

    Science.gov (United States)

    Ghequire, Maarten G K; Kemland, Lieselore; Anoz-Carbonell, Ernesto; Buchanan, Susan K; De Mot, René

    2017-02-21

    Modular bacteriocins represent a major group of secreted protein toxins with a narrow spectrum of activity, involved in interference competition between Gram-negative bacteria. These antibacterial proteins include a domain for binding to the target cell and a toxin module at the carboxy terminus. Self-inhibition of producers is provided by coexpression of linked immunity genes that transiently inhibit the toxin's activity through formation of bacteriocin-immunity complexes or by insertion in the inner membrane, depending on the type of toxin module. We demonstrate strain-specific inhibitory activity for PmnH, a Pseudomonas bacteriocin with an unprecedented dual-toxin architecture, hosting both a colicin M domain, potentially interfering with peptidoglycan synthesis, and a novel colicin N-type domain, a pore-forming module distinct from the colicin Ia-type domain in Pseudomonas aeruginosa pyocin S5. A downstream-linked gene product confers PmnH immunity upon susceptible strains. This protein, ImnH, has a transmembrane topology similar to that of Pseudomonas colicin M-like and pore-forming immunity proteins, although homology with either of these is essentially absent. The enhanced killing activity of PmnH under iron-limited growth conditions reflects parasitism of the ferrichrome-type transporter for entry into target cells, a strategy shown here to be used as well by monodomain colicin M-like bacteriocins from pseudomonads. The integration of a second type of toxin module in a bacteriocin gene could offer a competitive advantage against bacteria displaying immunity against only one of both toxic activities.IMPORTANCE In their continuous struggle for ecological space, bacteria face a huge load of contenders, including phylogenetically related strains that compete for the same niche. One important group of secreted antibacterial proteins assisting in eliminating these rivals are modular bacteriocins of Gram-negative bacteria, comprising a domain for docking onto the

  7. Psychosocial and environmental correlates of active and passive transport behaviors in college educated and non-college educated working young adults.

    Science.gov (United States)

    Simons, Dorien; De Bourdeaudhuij, Ilse; Clarys, Peter; De Cocker, Katrien; de Geus, Bas; Vandelanotte, Corneel; Van Cauwenberg, Jelle; Deforche, Benedicte

    2017-01-01

    This study aimed to examine potential differences in walking, cycling, public transport and passive transport (car/moped/motorcycle) to work and to other destinations between college and non-college educated working young adults. Secondly, we aimed to investigate which psychosocial and environmental factors are associated with the four transport modes and whether these associations differ between college and non-college educated working young adults. In this cross-sectional study, 224 working young adults completed an online questionnaire assessing socio-demographic variables (8 items), psychosocial variables (6 items), environmental variables (10 items) and transport mode (4 types) and duration to work/other destinations. Zero-inflated negative binomial regression models were performed in R. A trend (ppassive transport trips were shorter in non-college compared to college educated working young adults. In all working young adults, high self-efficacy towards active transport, and high perceived benefits and low perceived barriers towards active and public transport were related to more active and public transport. High social support/norm/modeling towards active, public and passive transport was related to more active, public and passive transport. High neighborhood walkability was related to more walking and less passive transport. Only in non-college educated working young adults, feeling safe from traffic and crime in their neighborhood was related to more active and public transport and less passive transport. Educational levels should be taken into account when promoting healthy transport behaviors in working young adults. Among non-college educated working young adults, focus should be on increasing active and public transport participation and on increasing neighborhood safety to increase active and public transport use. Among college educated working young adults, more minutes of active transport should be encouraged.

  8. CFD Lagrangian Modeling of Water Droplet Transport for ISS Hygiene Activity Application

    Science.gov (United States)

    Son, Chang H.

    2013-01-01

    The goal of this study was to assess the impacts of free water propagation in the Waste and Hygiene Compartment (WHC) installed in Node 3. Free water can be generated inside the WHC in small quantities due to crew hygiene activity. To mitigate potential impact of free water in Node 3 cabin the WHC doorway is enclosed by a waterproof bump-out, Kabin, with openings at the top and bottom. At the overhead side of the rack, there is a screen that prevents large drops of water from exiting. However, as the avionics fan in the WHC causes airflow toward the deck side of the rack, small quantities of free water may exit at the bottom of the Kabin. A Computational Fluid Dynamics (CFD) analysis of Node 3 cabin airflow enable identifying the paths of water transport. To simulate the droplet transport the Lagrangian discrete phase approach was used. Various initial droplet distributions were considered in the study. The droplet diameter was varied in the range of 5-20 mm. The results of the computations showed that most of the drops fall to the rack surface not far from the WHC curtain.

  9. Study on transport of powdered activated carbon using a rotating circular flume

    Institute of Scientific and Technical Information of China (English)

    尹海龙; 邱敏燕; 徐祖信

    2013-01-01

    This study employed a rotating flume to examine the Powdered Activated Carbon (PAC) transport with water flow. The initial PAC concentration was 10 mg/L-30 mg/L, and PAC concentration versus time under a specified cross-sectional averaging fluid shear was observed. Results show that compared with PAC deposition in still water, PAC is depleted to zero faster under a fluid shear of 0.02 Pa, due to PAC agglomeration with the fluid shear. However, since PAC floc size only ranges from a single particle (2mm) to approximate 6mm, an increasing of instantaneous turbulent fluctuations could counteract the force of PAC floc settling downward, and as a result the steady PAC concentration increases with the increase of shear stress. It is found that the critical shear stress for PAC deposition is about 0.60 Pa, and further the PAC deposition probability is presented according to the experimental scenarios between 0.02 Pa and 0.60 Pa. Combining the PAC transport and deposition formula with PAC-pollutant removal model provides an insight into PAC deployment in raw water aqueduct for sudden open water source pollution.

  10. MAGNETIC HELICITY TRANSPORTED BY FLUX EMERGENCE AND SHUFFLING MOTIONS IN SOLAR ACTIVE REGION NOAA 10930

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y. [Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Chaoyang District, Beijing 100012 (China); Kitai, R.; Takizawa, K., E-mail: zhangyin@kwasan.kyoto-u.ac.jp, E-mail: zhangyin@bao.ac.cn [Kwasan and Hida Observatories, Kyoto University, Yamashina-ku, Kyoto 607-8471 (Japan)

    2012-06-01

    We present a new methodology which can determine magnetic helicity transport by the passage of helical magnetic field lines from the sub-photosphere and the shuffling motions of footpoints of preexisting coronal field lines separately. It is well known that only the velocity component, which is perpendicular to the magnetic field ({upsilon}{sub B}), has contributed to the helicity accumulation. Here, we demonstrate that {upsilon}{sub B} can be deduced from a horizontal motion and vector magnetograms under a simple relation of {upsilon}{sub t} = {mu}{sub t} + ({upsilon}{sub n}/B{sub n} ) B{sub t}, as suggested by Demoulin and Berger. Then after dividing {upsilon}{sub B} into two components, as one is tangential and the other is normal to the solar surface, we can determine both terms of helicity transport. Active region (AR) NOAA 10930 is analyzed as an example during its solar disk center passage by using data obtained by the Spectropolarimeter and the Narrowband Filter Imager of Solar Optical Telescope on board Hinode. We find that in our calculation the helicity injection by flux emergence and shuffling motions have the same sign. During the period we studied, the main contribution of helicity accumulation comes from the flux emergence effect, while the dynamic transient evolution comes from the shuffling motions effect. Our observational results further indicate that for this AR the apparent rotational motion in the following sunspot is the real shuffling motions on the solar surface.

  11. Synthesis and serotonin transporter activity of sulphur-substituted alpha-alkyl phenethylamines as a new class of anticancer agents

    DEFF Research Database (Denmark)

    Cloonan, Suzanne M.; Keating, John J.; Butler, Stephen G.

    2009-01-01

    The discovery that some serotonin reuptake transporter (SERT) ligands have the potential to act as pro-apoptotic agents in the treatment of cancer adds greatly to their diverse pharmacological application. 4-Methylthioamphetamine (MTA) is a selective ligand for SERT over other monoamine transport......The discovery that some serotonin reuptake transporter (SERT) ligands have the potential to act as pro-apoptotic agents in the treatment of cancer adds greatly to their diverse pharmacological application. 4-Methylthioamphetamine (MTA) is a selective ligand for SERT over other monoamine...... transporters. In this study, a novel library of structurally diverse 4-MTA analogues were synthesised with or without N-alkyl and/or C-alpha methyl or ethyl groups so that their potential SERT-dependent antiproliferative activity could be assessed. Many of the compounds displayed SERT-binding activity as well...

  12. Transforming growth factor β signaling upregulates the expression of human GDP-fucose transporter by activating transcription factor Sp1.

    Science.gov (United States)

    Xu, Yu-Xin; Ma, Anna; Liu, Li

    2013-01-01

    GDP-fucose transporter plays a crucial role in fucosylation of glycoproteins by providing activated fucose donor, GDP-fucose, for fucosyltransferases in the lumen of the Golgi apparatus. Fucose-containing glycans are involved in many biological processes, which are essential for growth and development. Mutations in the GDP-fucose transporter gene cause leukocyte adhesion deficiency syndrome II, a disease characterized by slow growth, mental retardation and immunodeficiency. However, no information is available regarding its transcriptional regulation. Here, by using human cells, we show that TGF-β1 specifically induces the GDP-fucose transporter expression, but not other transporters tested such as CMP-sialic acid transporter, suggesting a diversity of regulatory pathways for the expression of these transporters. The regulatory elements that are responsive to the TGF-β1 stimulation are present in the region between bp -330 and -268 in the GDP-fucose transporter promoter. We found that this region contains two identical octamer GC-rich motifs (GGGGCGTG) that were demonstrated to be essential for the transporter expression. We also show that the transcription factor Sp1 specifically binds to the GC-rich motifs in vitro and Sp1 coupled with phospho-Smad2 is associated with the promoter region covering the Sp1-binding motifs in vivo using chromatin immunoprecipitation (ChIP) assays. In addition, we further confirmed that Sp1 is essential for the GDP-fucose transporter expression stimulated by TGF-β1 using a luciferase reporter system. These results highlight the role of TGF-β signaling in regulation of the GDP-fucose transporter expression via activating Sp1. This is the first transcriptional study for any nucleotide sugar transporters that have been identified so far. Notably, TGF-β1 receptor itself is known to be modified by fucosylation. Given the essential role of GDP-fucose transporter in fucosylation, the finding that TGF-β1 stimulates the expression of

  13. Experimental Investigation of Active Feedback Control of Turbulent Transport in a Magnetized Plasma

    Energy Technology Data Exchange (ETDEWEB)

    Gilmore, Mark Allen [University of New Mexico

    2013-07-07

    A new and unique basic plasma science laboratory device - the HelCat device (HELicon-CAThode) - has been constructed and is operating at the University of New Mexico. HelCat is a 4 m long, 0.5 m diameter device, with magnetic field up to 2.2 kG, that has two independent plasmas sources - an RF helicon source, and a thermionic cathode. These two sources, which can operate independently or simultaneously, are capable of producing plasmas with a wide range of parameters and turbulence characteristics, well suited to a variety of basic plasma physics experiments. An extensive set of plasma diagnostics is also operating. Experiments investigating the active feedback control of turbulent transport of particles and heat via electrode biasing to affect plasma ExB flows are underway, and ongoing.

  14. The varied functions of aluminium-activated malate transporters-much more than aluminium resistance.

    Science.gov (United States)

    Palmer, Antony J; Baker, Alison; Muench, Stephen P

    2016-06-15

    The ALMT (aluminium-activated malate transporter) family comprises a functionally diverse but structurally similar group of ion channels. They are found ubiquitously in plant species, expressed throughout different tissues, and located in either the plasma membrane or tonoplast. The first family member identified was TaALMT1, discovered in wheat root tips, which was found to be involved in aluminium resistance by means of malate exudation into the soil. However, since this discovery other family members have been shown to have many other functions such as roles in stomatal opening, general anionic homoeostasis, and in economically valuable traits such as fruit flavour. Recent evidence has also shown that ALMT proteins can act as key molecular actors in GABA (γ-aminobutyric acid) signalling, the first evidence that GABA can act as a signal transducer in plants. © 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  15. School site walkability and active school transport - association, mediation and moderation

    DEFF Research Database (Denmark)

    Breum, Lars; Toftager, M.; Schipperijn, J.

    2014-01-01

    Increasing active school transport (AST) can improve population health, but its association with the urban form is not fully clear. This study investigated the association of an objective school walkability index with AST and how this association is mediated by the perceived physical and social...... environment. 1250 Danish students aged 11-13. years completed a commuting diary and a questionnaire. The walkability index was constituted of measures of road connectivity, traffic exposure and residential density. AST's share in all school trips was 85.4% with little difference between genders. The school...... walkability index was significantly associated with AST (Medium vs. Low OR 2.68; High vs. Low OR 2.49). Adding the perceived physical and social environment variables improved the model prediction of AST, with no change in the association with the school walkability index. Furthermore, distance to school...

  16. Disposition and transportation of surplus radioactive low specific activity nitric acid. Volume 1, Environmental Assessment

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-05-01

    DOE is deactivating the PUREX plant at Hanford; this will involve the disposition of about 692,000 liters (183,000 gallons) of surplus nitric acid contaminated with low levels of U and other radionuclides. The nitric acid, designated as low specific activity, is stored in 4 storage tanks at PUREX. Five principal alternatives were evaluated: transfer for reuse (sale to BNF plc), no action, continued storage in Hanford upgraded or new facility, consolidation of DOE surplus acid, and processing the LSA nitric acid as waste. The transfer to BNF plc is the preferred alternative. From the analysis, it is concluded that the proposed disposition and transportation of the acid does not constitute a major federal action significantly affecting the quality of the human environment within the meaning of NEPA; therefore an environmental impact statement is not required.

  17. Pharmacological and behavioral characterization of D-473, an orally active triple reuptake inhibitor targeting dopamine, serotonin and norepinephrine transporters.

    Directory of Open Access Journals (Sweden)

    Aloke K Dutta

    Full Text Available Major depressive disorder (MDD is a debilitating disease affecting a wide cross section of people around the world. The current therapy for depression is less than adequate and there is a considerable unmet need for more efficacious treatment. Dopamine has been shown to play a significant role in depression including production of anhedonia which has been one of the untreated symptoms in MDD. It has been hypothesized that drugs acting at all three monoamine transporters including dopamine transporter should provide more efficacious antidepressants activity. This has led to the development of triple reuptake inhibitor D-473 which is a novel pyran based molecule and interacts with all three monoamine transporters. The monoamine uptake inhibition activity in the cloned human transporters expressed in HEK-293 cells (70.4, 9.18 and 39.7 for DAT, SERT and NET, respectively indicates a serotonin preferring triple reuptake inhibition profile for this drug. The drug D-473 exhibited good brain penetration and produced efficacious activity in rat forced swim test under oral administration. The optimal efficacy dose did not produce any locomotor activation. Microdialysis experiment demonstrated that systemic administration of D-473 elevated extracellular level of the three monoamines DA, 5-HT, and NE efficaciously in the dorsal lateral striatum (DLS and the medial prefrontal cortex (mPFC area, indicating in vivo blockade of all three monoamine transporters by D-473. Thus, the current biological data from D-473 indicate potent antidepressant activity of the molecule.

  18. Toolkit for high performance Monte Carlo radiation transport and activation calculations for shielding applications in ITER

    Energy Technology Data Exchange (ETDEWEB)

    Serikov, A.; Fischer, U.; Grosse, D.; Leichtle, D.; Majerle, M., E-mail: arkady.serikov@kit.edu [Karlsruhe Institute of Technology (KIT), Eggenstein-Leopoldshafen (Germany)

    2011-07-01

    The Monte Carlo (MC) method is the most suitable computational technique of radiation transport for shielding applications in fusion neutronics. This paper is intended for sharing the results of long term experience of the fusion neutronics group at Karlsruhe Institute of Technology (KIT) in radiation shielding calculations with the MCNP5 code for the ITER fusion reactor with emphasizing on the use of several ITER project-driven computer programs developed at KIT. Two of them, McCad and R2S, seem to be the most useful in radiation shielding analyses. The McCad computer graphical tool allows to perform automatic conversion of the MCNP models from the underlying CAD (CATIA) data files, while the R2S activation interface couples the MCNP radiation transport with the FISPACT activation allowing to estimate nuclear responses such as dose rate and nuclear heating after the ITER reactor shutdown. The cell-based R2S scheme was applied in shutdown photon dose analysis for the designing of the In-Vessel Viewing System (IVVS) and the Glow Discharge Cleaning (GDC) unit in ITER. Newly developed at KIT mesh-based R2S feature was successfully tested on the shutdown dose rate calculations for the upper port in the Neutral Beam (NB) cell of ITER. The merits of McCad graphical program were broadly acknowledged by the neutronic analysts and its continuous improvement at KIT has introduced its stable and more convenient run with its Graphical User Interface. Detailed 3D ITER neutronic modeling with the MCNP Monte Carlo method requires a lot of computation resources, inevitably leading to parallel calculations on clusters. Performance assessments of the MCNP5 parallel runs on the JUROPA/HPC-FF supercomputer cluster permitted to find the optimal number of processors for ITER-type runs. (author)

  19. P-glycoprotein in sheep liver and small intestine: gene expression and transport efflux activity.

    Science.gov (United States)

    Ballent, M; Wilkens, M R; Maté, L; Muscher, A S; Virkel, G; Sallovitz, J; Schröder, B; Lanusse, C; Lifschitz, A

    2013-12-01

    The role of the transporter P-glycoprotein (P-gp) in the disposition kinetics of different drugs therapeutically used in veterinary medicine has been demonstrated. Considering the anatomo-physiological features of the ruminant species, the constitutive expression of P-gp (ABCB1) along the sheep gastrointestinal tract was studied. Additionally, the effect of repeated dexamethasone (DEX) administrations on the ABCB1 gene expression in the liver and small intestine was also assessed. The ABCB1 mRNA expression was determined by real-time quantitative PCR. P-gp activity was evaluated in diffusion chambers to determine the efflux of rhodamine 123 (Rho 123) in the ileum from experimental sheep. The constitutive ABCB1 expression was 65-fold higher in the liver than in the intestine (ileum). The highest ABCB1 mRNA expression along the small intestine was observed in the ileum (between 6- and 120-fold higher). The treatment with DEX did not elicit a significant effect on the P-gp gene expression levels in any of the investigated gastrointestinal tissues. Consistently, no significant differences were observed in the intestinal secretion of Rho 123, between untreated control (Peff S-M = 3.99 × 10(-6)  ± 2.07 × 10(-6) ) and DEX-treated animals (Peff S-M = 6.00 × 10(-6)  ± 2.5 × 10(-6) ). The understanding of the efflux transporters expression and activity along the digestive tract may help to elucidate clinical implications emerging from drug interactions in livestock.

  20. Ceruloplasmin ferroxidase activity stimulates cellular iron uptake by a trivalent cation-specific transport mechanism

    Science.gov (United States)

    Attieh, Z. K.; Mukhopadhyay, C. K.; Seshadri, V.; Tripoulas, N. A.; Fox, P. L.

    1999-01-01

    The balance required to maintain appropriate cellular and tissue iron levels has led to the evolution of multiple mechanisms to precisely regulate iron uptake from transferrin and low molecular weight iron chelates. A role for ceruloplasmin (Cp) in vertebrate iron metabolism is suggested by its potent ferroxidase activity catalyzing conversion of Fe2+ to Fe3+, by identification of yeast copper oxidases homologous to Cp that facilitate high affinity iron uptake, and by studies of "aceruloplasminemic" patients who have extensive iron deposits in multiple tissues. We have recently shown that Cp increases iron uptake by cultured HepG2 cells. In this report, we investigated the mechanism by which Cp stimulates cellular iron uptake. Cp stimulated the rate of non-transferrin 55Fe uptake by iron-deficient K562 cells by 2-3-fold, using a transferrin receptor-independent pathway. Induction of Cp-stimulated iron uptake by iron deficiency was blocked by actinomycin D and cycloheximide, consistent with a transcriptionally induced or regulated transporter. Cp-stimulated iron uptake was completely blocked by unlabeled Fe3+ and by other trivalent cations including Al3+, Ga3+, and Cr3+, but not by divalent cations. These results indicate that Cp utilizes a trivalent cation-specific transporter. Cp ferroxidase activity was required for iron uptake as shown by the ineffectiveness of two ferroxidase-deficient Cp preparations, copper-deficient Cp and thiomolybdate-treated Cp. We propose a model in which iron reduction and subsequent re-oxidation by Cp are essential for an iron uptake pathway with high ion specificity.

  1. Accelerated ovum transport in rabbits induced by endotoxin II. Changes in oviductal smooth muscle activity.

    Science.gov (United States)

    Hodgson, B J; Harper, M J; Valenzuela, G

    1978-01-01

    Oviductal mortility, measured with open-ended perfused catheters in anesthetized animals injected with human Chorionic Gonadotropin (hCG), is depressed 2 h following endotoxin injection and returns to control levels by 3 h after endotoxin injection. This decrease in motility is prevented by indomethacin. Endotoxin did not affect spontaneous or phenylephrine (PE)-induced contractions of oviduct when it was added to the bathing medium of in vitro tissues. Oviductal segments removed 2 h after endotoxin (26 h after hCG) showed electrical activity confined to the ampullary-isthmic-junction (AIJ), where ova were located; the dose-response curve for PE was shifted to the right and the maximum contraction was depressed. Activity of tissues removed 4 h after endotoxin more closely resembled control tissues except that the maximum contraction to PE was depressed, ova had passed out of the oviduct and a proovarian bias in the isthmus was not present. The response of the oviduct to prostaglandins (PGs) in vivo is critically dependent on the previous exposure to PGs. In endotoxin-treated animals PGE then PGF levels increase and the decrease in motility coincides with increased PGE levels, but accelerated ovum transport with the return of motility and activation of the isthmus.

  2. Development of Microorganisms with Improved Transport and Biosurfactant Activity for Enhanced Oil Recovery

    Energy Technology Data Exchange (ETDEWEB)

    M.J. McInerney; K.E. Duncan; N. Youssef; T. Fincher; S.K. Maudgalya; M.J. Folmsbee; R. Knapp; Randy R. Simpson; N.Ravi; D. Nagle

    2005-08-15

    growth at elevated salt concentrations to obtain candidates most suitable for microbial oil recovery. Seventy percent of the 205 strains tested, mostly strains of Bacillus mojavensis, Bacillus subtilis, Bacillus licheniformis, and Bacillus sonorensis, produced biosurfactants aerobically and 41% of the strains had biosurfactant activity greater than Bacillus mojavensis JF-2, the current candidate for oil recovery. Biosurfactant activity varied with the percentage of the 3-hydroxy-tetradecanoate isomers in the fatty acid portion of the biosurfactant. Changing the medium composition by incorporation of different precursors of 3-hydroxy tetradecanoate increased the activity of biosurfactant. The surface tension and critical micelle concentration of 15 different, biosurfactant-producing Bacillus strains was determined individually and in combination with other biosurfactants. Some biosurfactant mixtures were found to have synergistic effect on surface tension (e.g. surface tension was lowered from 41 to 31 mN/m in some cases) while others had a synergistic effect on CMD-1 values. We compared the transport abilities of spores from three Bacillus strains using a model porous system to study spore recovery and transport. Sand-packed columns were used to select for spores or cells with the best transport abilities through brine-saturated sand. Spores of Bacillus mojavensis strains JF-2 and ROB-2 and a natural recombinant, strain C-9, transported through sand at very high efficiencies. The earliest cells/spores that emerged from the column were regrown, allowed to sporulate, and applied to a second column. This procedure greatly enhanced the transport of strain C-9. Spores with enhanced transport abilities can be easily obtained and that the preparation of inocula for use in MEOR is feasible. We conducted a push-pull test to study in-situ biosurfactant production by exogenous biosurfactant producers to aid in oil recovery from depleted reservoirs. Five wells from the same

  3. Transportation use in community-dwelling older adults: association with participation and leisure activities.

    Science.gov (United States)

    Dahan-Oliel, Noémi; Mazer, Barbara; Gélinas, Isabelle; Dobbs, Bonnie; Lefebvre, Hélène

    2010-12-01

    This article presents a study that compared participation by elderly individuals living in the community according to primary transportation mode used, and estimated the association between transportation, personal factors, and environmental factors. Participants included 90 adults aged 65 and older (M=76.3 years; SD=7.7). They were classified according to their primary transportation mode: driver, passenger, public transport user, walk, or adapted transport/taxi user. Participation was measured with the Craig Handicap Assessment and Reporting Technique (CHART) and the Nottingham Leisure Questionnaire (NLQ). Overall, results indicated that drivers, public transport users, and walkers had higher participation levels compared to passengers and adapted transport/taxi users. This study suggests that clinicians should consider older adults' use of transportation in an attempt to encourage and maximize their participation.

  4. Diagnosis of Transport Activity as a Component of the Enterprise Logistical System

    OpenAIRE

    Skrynkovskyy Ruslan M.; Kostiuk Nataliia R.; Koval Nataliya M.; Haleliuk Mykola M.

    2016-01-01

    The article reveals the essence of the concept of “diagnosis of the enterprise transport activity”, by which there should be meant a process of evaluating the state of movement (transportation, carrying) of freight (material resources, work in process or finished products) by one type of transport facilities or their combination in accordance with the applied transport system and trends of its changes as well as determining the future prospects on the basis of sound manageme...

  5. Living City: community mobilization to build active transport policies and programs in Santiago, Chile

    Directory of Open Access Journals (Sweden)

    L. Sagaris

    2010-09-01

    Full Text Available Although the usefulness of walking and cycling to promote health is increasingly recognized, the importance of civil society leadership in developing new policies and activities is often overlooked. This case study, of Living City (Ciudad Viva a community-based organization in Santiago, Chile, examines how several communities used knowledge about transport’s impact on the environment and health, gained through opposition to a major highway project, to build effective sustainable urban transport initiatives.Inspired by urban reforms in Bogot´a, Living City now focuses mainly on “active transport” (formerly nonmotorized, building the policies, attitudes and infrastructure necessary to encourage walking and cycling, and the inclusion of the differently abled. It has won two major awards for innovation and now partners with NGOs in The Netherlands and elsewhere in Chile and Latin America.Moreover, Living City now organizes cycling-inclusive training programs, design charrettes and participatory processes in cooperation with Santiago’s regional and national authorities. Its publication, La Voz de La Chimba, distributed free throughout the city by volunteers, has helped to open people’s eyes to the implications of active transport for social equality and health, and provided support to other citizens’ initiatives, struggling to get off the ground.This experience illustrates how citizens’ and community organizations acquire important knowledge and practical experience in learning by doing situations, and how they can learn to reach out to ordinary people and key policymakers, building bridges across the citizen-policy divide to produce innovative, win-win programs that simultaneously bring change at micro- and macro-levels.Bien que la nécessité de marcher et de faire du vélo pour rester en bonne santé soit de plus en plus reconnue, l’importance du rôle prépondérant de la société civile dans le développement de nouvelles

  6. Fluorescent sensors for activity and regulation of the nitrate transceptor CHL1/NRT1.1 and oligopeptide transporters.

    Science.gov (United States)

    Ho, Cheng-Hsun; Frommer, Wolf B

    2014-03-12

    To monitor nitrate and peptide transport activity in vivo, we converted the dual-affinity nitrate transceptor CHL1/NRT1.1/NPF6.3 and four related oligopeptide transporters PTR1, 2, 4, and 5 into fluorescence activity sensors (NiTrac1, PepTrac). Substrate addition to yeast expressing transporter fusions with yellow fluorescent protein and mCerulean triggered substrate-dependent donor quenching or resonance energy transfer. Fluorescence changes were nitrate/peptide-specific, respectively. Like CHL1, NiTrac1 had biphasic kinetics. Mutation of T101A eliminated high-affinity transport and blocked the fluorescence response to low nitrate. NiTrac was used for characterizing side chains considered important for substrate interaction, proton coupling, and regulation. We observed a striking correlation between transport activity and sensor output. Coexpression of NiTrac with known calcineurin-like proteins (CBL1, 9; CIPK23) and candidates identified in an interactome screen (CBL1, KT2, WNKinase 8) blocked NiTrac1 responses, demonstrating the suitability for in vivo analysis of activity and regulation. The new technology is applicable in plant and medical research. DOI: http://dx.doi.org/10.7554/eLife.01917.001.

  7. The TORC1 effector kinase Npr1 fine tunes the inherent activity of the Mep2 ammonium transport protein.

    Science.gov (United States)

    Boeckstaens, Mélanie; Llinares, Elisa; Van Vooren, Pascale; Marini, Anna Maria

    2014-01-01

    The TORC1 complex controls cell growth upon integrating nutritional signals including amino-acid availability. TORC1 notably adapts the plasma membrane protein content by regulating arrestin-mediated endocytosis of amino-acid transporters. Here we demonstrate that TORC1 further fine tunes the inherent activity of the ammonium transport protein, Mep2, a yeast homologue of mammalian Rhesus factors, independently of arrestin-mediated endocytosis. The TORC1 effector kinase Npr1 and the upstream TORC1 regulator Npr2 control Mep2 transport activity by phospho-silencing a carboxy-terminal autoinhibitory domain. Under poor nitrogen supply, Npr1 enables Mep2 S457 phosphorylation and thus ammonium transport activity. Supplementation of the preferred nitrogen source glutamine leads to Mep2 inactivation and instant S457 dephosphorylation via plasma membrane Psr1 and Psr2 redundant phosphatases. This study underscores that TORC1 also adjusts nutrient permeability to regulate cell growth in a fast and flexible response to environmental perturbation, establishing a hierarchy in the transporters to be degraded, inactivated or maintained active at the plasma membrane.

  8. The importance of gradients in particle activity during sediment transport: Insights from a probabilistic description of particle motions

    Science.gov (United States)

    Furbish, D. J.

    2009-04-01

    Sediment particles transported by rainsplash, by bioturbation, and as bedload in turbulent flows, undergo motions that are quasi-random in magnitude and direction. Moreover, these motions characteristically are intermittent, in that particles are mostly at rest most of the time, and heterogeneous, in that the volumetric or areal concentration of particles in motion at any instant is spatially patchy. These particle motions can be formulated as a stochastic processes involving both advective and dispersive parts. By taking into account the intermittent activity of particles, and separating this activity from the physics of motion in the parametric description of transport, the formulation indicates that gradients in particle activity can have a key role in transport. The formulation illustrates, for example, how the growth of soil mounds beneath desert shrubs involves differential rainsplash that initially causes more grains to be splashed inward beneath protective shrub canopies than outward. This ‘harvesting' of nearby soil material, including nutrients, means that shrubs locally participate in regulating the rate sediment transport down a hillslope. With soil bioturbation, spatial variations in the disturbance frequency strongly influence the mixing of soil constituents, including distinct particle fractions (such as specific size or mineral fractions, seeds, or debitage), or elements and compounds adsorbed to particles. The formulation also provides a probabilistic version of the Exner equation. During bedload transport, gradients in particle activity, through both advective and dispersive effects, may contribute importantly to the local divergence of the particle flux, thereby influencing initial bedform growth.

  9. Resveratrol Prevents Retinal Dysfunction by Regulating Glutamate Transporters, Glutamine Synthetase Expression and Activity in Diabetic Retina.

    Science.gov (United States)

    Zeng, Kaihong; Yang, Na; Wang, Duozi; Li, Suping; Ming, Jian; Wang, Jing; Yu, Xuemei; Song, Yi; Zhou, Xue; Yang, Yongtao

    2016-05-01

    This study investigated the effects of resveratrol (RSV) on retinal functions, glutamate transporters (GLAST) and glutamine synthetase (GS) expression in diabetic rats retina, and on glutamate uptake, GS activity, GLAST and GS expression in high glucose-cultured Müller cells. The electroretinogram was used to evaluate retinal functions. Müller cells cultures were prepared from 5- to 7-day-old Sprague-Dawley rats. The expression of GLAST and GS was examined by qRT-PCR, ELISA and western-blotting. Glutamate uptake was measured as (3)H-glutamate contents of the lysates. GS activity was assessed by a spectrophotometric assay. 1- to 7-month RSV administrations (5 and 10 mg/kg/day) significantly alleviated hyperglycemia and weight loss in diabetic rats. RSV administrations also significantly attenuated diabetes-induced decreases in amplitude of a-wave in rod response, decreases in amplitude of a-, and b-wave in cone and rod response and decreases in amplitude of OP2 in oscillatory potentials. 1- to 7-month RSV treatments also significantly inhibited diabetes-induced delay in OP2 implicit times in scotopic 3.0 OPS test. The down-regulated mRNA and protein expression of GLAST and GS in diabetic rats retina was prevented by RSV administrations. In high glucose-treated cultures, Müller cells' glutamate uptake, GS activity, GLAST and GS expression were decreased significantly compared with normal control cultures. RSV (10, 20, and 30 mmol/l) significantly inhibited the HG-induced decreases in glutamate uptake, GS activity, GLAST and GS expression (at least P < 0.05). These beneficial results suggest that RSV may be considered as a therapeutic option to prevent from diabetic retinopathy.

  10. Gender differences in association between serotonin transporter gene polymorphism and resting-state EEG activity.

    Science.gov (United States)

    Volf, N V; Belousova, L V; Knyazev, G G; Kulikov, A V

    2015-01-22

    Human brain oscillations represent important features of information processing and are highly heritable. Gender has been observed to affect association between the 5-HTTLPR (serotonin-transporter-linked polymorphic region) polymorphism and various endophenotypes. This study aimed to investigate the effects of 5-HTTLPR on the spontaneous electroencephalography (EEG) activity in healthy male and female subjects. DNA samples extracted from buccal swabs and resting EEG recorded at 60 standard leads were collected from 210 (101 men and 109 women) volunteers. Spectral EEG power estimates and cortical sources of EEG activity were investigated. It was shown that effects of 5-HTTLPR polymorphism on electrical activity of the brain vary as a function of gender. Women with the S/L genotype had greater global EEG power compared to men with the same genotype. In men, current source density was markedly different among genotype groups in only alpha 2 and alpha 3 frequency ranges: S/S allele carriers had higher current source density estimates in the left inferior parietal lobule in comparison with the L/L group. In women, genotype difference in global power asymmetry was found in the central-temporal region. Contrasting L/L and S/L genotype carriers also yielded significant effects in the right hemisphere inferior parietal lobule and the right postcentral gyrus with L/L genotype carriers showing lower current source density estimates than S/L genotype carriers in all but gamma bands. So, in women, the effects of 5-HTTLPR polymorphism were associated with modulation of the EEG activity in a wide range of EEG frequencies. The significance of the results lies in the demonstration of gene by sex interaction with resting EEG that has implications for understanding sex-related differences in affective states, emotion and cognition.

  11. Bundling dynamics regulates the active mechanics and transport in carbon nanotube networks and their nanocomposites

    Science.gov (United States)

    Hahm, Myung Gwan; Wang, Hailong; Jung, Hyun Young; Hong, Sanghyun; Lee, Sung-Goo; Kim, Sung-Ryong; Upmanyu, Moneesh; Jung, Yung Joon

    2012-05-01

    High-density carbon nanotube networks (CNNs) continue to attract interest as active elements in nanoelectronic devices, nanoelectromechanical systems (NEMS) and multifunctional nanocomposites. The interplay between the network nanostructure and its properties is crucial, yet current understanding remains limited to the passive response. Here, we employ a novel superstructure consisting of millimeter-long vertically aligned single walled carbon nanotubes (SWCNTs) sandwiched between polydimethylsiloxane (PDMS) layers to quantify the effect of two classes of mechanical stimuli, film densification and stretching, on the electronic and thermal transport across the network. The network deforms easily with an increase in the electrical and thermal conductivities, suggestive of a floppy yet highly reconfigurable network. Insight from atomistically informed coarse-grained simulations uncover an interplay between the extent of lateral assembly of the bundles, modulated by surface zipping/unzipping, and the elastic energy associated with the bent conformations of the nanotubes/bundles. During densification, the network becomes highly interconnected yet we observe a modest increase in bundling primarily due to the reduced spacing between the SWCNTs. The stretching, on the other hand, is characterized by an initial debundling regime as the strain accommodation occurs via unzipping of the branched interconnects, followed by rapid rebundling as the strain transfers to the increasingly aligned bundles. In both cases, the increase in the electrical and thermal conductivity is primarily due to the increase in bundle size; the changes in network connectivity have a minor effect on the transport. Our results have broad implications for filamentous networks of inorganic nanoassemblies composed of interacting tubes, wires and ribbons/belts.High-density carbon nanotube networks (CNNs) continue to attract interest as active elements in nanoelectronic devices, nanoelectromechanical systems

  12. Tissue Specific Expression of Cre in Rat Tyrosine Hydroxylase and Dopamine Active Transporter-Positive Neurons.

    Directory of Open Access Journals (Sweden)

    Zhenyi Liu

    Full Text Available The rat is a preferred model system over the mouse for neurological studies, and cell type-specific Cre expression in the rat enables precise ablation of gene function in neurons of interest, which is especially valuable for neurodegenerative disease modeling and optogenetics. Yet, few such Cre rats are available. Here we report the characterization of two Cre rats, tyrosine hydroxylase (TH-Cre and dopamine active transporter (DAT or Slc6a3-Cre, by using a combination of immunohistochemistry (IHC and mRNA fluorescence in situ hybridization (FISH as well as a fluorescent reporter for Cre activity. We detected Cre expression in expected neurons in both Cre lines. Interestingly, we also found that in Th-Cre rats, but not DAT-Cre rats, Cre is expressed in female germ cells, allowing germline excision of the floxed allele and hence the generation of whole-body knockout rats. In summary, our data demonstrate that targeted integration of Cre cassette lead to faithful recapitulation of expression pattern of the endogenous promoter, and mRNA FISH, in addition to IHC, is an effective method for the analysis of the spatiotemporal gene expression patterns in the rat brain, alleviating the dependence on high quality antibodies that are often not available against rat proteins. The Th-Cre and the DAT-Cre rat lines express Cre in selective subsets of dopaminergic neurons and should be particularly useful for researches on Parkinson's disease.

  13. INVESTIGATION OF HELICITY AND ENERGY FLUX TRANSPORT IN THREE EMERGING SOLAR ACTIVE REGIONS

    Energy Technology Data Exchange (ETDEWEB)

    Vemareddy, P., E-mail: vemareddy@iiap.res.in [Indian Institute of Astrophysics, II Block, Koramangala, Bangalore-560 034 (India)

    2015-06-20

    We report the results of an investigation of helicity and energy flux transport from three emerging solar active regions (ARs). Using time sequence vector magnetic field observations obtained from the Helioseismic Magnetic Imager, the velocity field of plasma flows is derived by the differential affine velocity estimator for vector magnetograms. In three cases, the magnetic fluxes evolve to pump net positive, negative, and mixed-sign helicity flux into the corona. The coronal helicity flux is dominantly coming from the shear term that is related to horizontal flux motions, whereas energy flux is dominantly contributed by the emergence term. The shear helicity flux has a phase delay of 5–14 hr with respect to absolute magnetic flux. The nonlinear curve of coronal energy versus relative helicity identifies the configuration of coronal magnetic fields, which is approximated by a fit of linear force-free fields. The nature of coronal helicity related to the particular pattern of evolving magnetic fluxes at the photosphere has implications for the generation mechanism of two kinds of observed activity in the ARs.

  14. Tissue Specific Expression of Cre in Rat Tyrosine Hydroxylase and Dopamine Active Transporter-Positive Neurons.

    Science.gov (United States)

    Liu, Zhenyi; Brown, Andrew; Fisher, Dan; Wu, Yumei; Warren, Joe; Cui, Xiaoxia

    2016-01-01

    The rat is a preferred model system over the mouse for neurological studies, and cell type-specific Cre expression in the rat enables precise ablation of gene function in neurons of interest, which is especially valuable for neurodegenerative disease modeling and optogenetics. Yet, few such Cre rats are available. Here we report the characterization of two Cre rats, tyrosine hydroxylase (TH)-Cre and dopamine active transporter (DAT or Slc6a3)-Cre, by using a combination of immunohistochemistry (IHC) and mRNA fluorescence in situ hybridization (FISH) as well as a fluorescent reporter for Cre activity. We detected Cre expression in expected neurons in both Cre lines. Interestingly, we also found that in Th-Cre rats, but not DAT-Cre rats, Cre is expressed in female germ cells, allowing germline excision of the floxed allele and hence the generation of whole-body knockout rats. In summary, our data demonstrate that targeted integration of Cre cassette lead to faithful recapitulation of expression pattern of the endogenous promoter, and mRNA FISH, in addition to IHC, is an effective method for the analysis of the spatiotemporal gene expression patterns in the rat brain, alleviating the dependence on high quality antibodies that are often not available against rat proteins. The Th-Cre and the DAT-Cre rat lines express Cre in selective subsets of dopaminergic neurons and should be particularly useful for researches on Parkinson's disease.

  15. P-gp Protein Expression and Transport Activity in Rodent Seizure Models and Human Epilepsy.

    Science.gov (United States)

    Hartz, Anika M S; Pekcec, Anton; Soldner, Emma L B; Zhong, Yu; Schlichtiger, Juli; Bauer, Bjoern

    2017-03-02

    A cure for epilepsy is currently not available, and seizure genesis, seizure recurrence, and resistance to antiseizure drugs remain serious clinical problems. Studies show that the blood-brain barrier is altered in animal models of epilepsy and in epileptic patients. In this regard, seizures increase expression of blood-brain barrier efflux transporters such as P-glycoprotein (P-gp), which is thought to reduce brain uptake of antiseizure drugs, and thus, contribute to antiseizure drug resistance. The goal of the current study was to assess the viability of combining in vivo and ex vivo preparations of isolated brain capillaries from animal models of seizures and epilepsy as well as from patients with epilepsy to study P-gp at the blood-brain barrier. Exposing isolated rat brain capillaries to glutamate ex vivo upregulated P-gp expression to levels that were similar to those in capillaries isolated from rats that had status epilepticus or chronic epilepsy. Moreover, the fold-increase in P-gp protein expression seen in animal models is consistent with the fold-increase in P-gp observed in human brain capillaries isolated from patients with epilepsy compared to age-matched control individuals. Overall, the in vivo/ex vivo approach presented here allows detailed analysis of the mechanisms underlying seizure-induced changes of P-gp expression and transport activity at the blood-brain barrier. This approach can be extended to other blood-brain barrier proteins that might contribute to drug-resistant epilepsy or other CNS disorders as well.

  16. Bundling dynamics regulates the active mechanics and transport in carbon nanotube networks and their nanocomposites.

    Science.gov (United States)

    Hahm, Myung Gwan; Wang, Hailong; Jung, Hyun Young; Hong, Sanghyun; Lee, Sung-Goo; Kim, Sung-Ryong; Upmanyu, Moneesh; Jung, Yung Joon

    2012-06-01

    High-density carbon nanotube networks (CNNs) continue to attract interest as active elements in nanoelectronic devices, nanoelectromechanical systems (NEMS) and multifunctional nanocomposites. The interplay between the network nanostructure and its properties is crucial, yet current understanding remains limited to the passive response. Here, we employ a novel superstructure consisting of millimeter-long vertically aligned single walled carbon nanotubes (SWCNTs) sandwiched between polydimethylsiloxane (PDMS) layers to quantify the effect of two classes of mechanical stimuli, film densification and stretching, on the electronic and thermal transport across the network. The network deforms easily with an increase in the electrical and thermal conductivities, suggestive of a floppy yet highly reconfigurable network. Insight from atomistically informed coarse-grained simulations uncover an interplay between the extent of lateral assembly of the bundles, modulated by surface zipping/unzipping, and the elastic energy associated with the bent conformations of the nanotubes/bundles. During densification, the network becomes highly interconnected yet we observe a modest increase in bundling primarily due to the reduced spacing between the SWCNTs. The stretching, on the other hand, is characterized by an initial debundling regime as the strain accommodation occurs via unzipping of the branched interconnects, followed by rapid rebundling as the strain transfers to the increasingly aligned bundles. In both cases, the increase in the electrical and thermal conductivity is primarily due to the increase in bundle size; the changes in network connectivity have a minor effect on the transport. Our results have broad implications for filamentous networks of inorganic nanoassemblies composed of interacting tubes, wires and ribbons/belts.

  17. Active Solute Transport across Frog Skin and Epithelial Cell Systems According to the Association-Induction Hypothesis,

    Science.gov (United States)

    1980-01-01

    AD A136 163 ACTIVE SOLUTE TRANSPORT ACROSS FROG SKIN AND EPITHELIAL 1/1 CELL SYSTEMS ACCO..(U) PENNSYLVANIA HOSPITAL PHILADELPHIA DEPT OF MOLECULAR...TEST CHART fi4TIOtM4. @I*AU OF STA’dAftOS. 43- A ACTIVE SOWTE TRANSPORT ACROSS FROG SKIN AND EPITH-IAL CELL SYSTEMS AC:ORC:NG TO THE ASSOCIATION...taken full account of the difference between unifacial solid cells typified by human red blood cells, frog muscle and squid awn, and bifacial hollow

  18. The implications of megatrends in information and communication technology and transportation for changes in global physical activity.

    Science.gov (United States)

    Pratt, Michael; Sarmiento, Olga L; Montes, Felipe; Ogilvie, David; Marcus, Bess H; Perez, Lilian G; Brownson, Ross C

    2012-07-21

    Physical inactivity accounts for more than 3 million deaths per year, most from non-communicable diseases in low-income and middle-income countries. We used reviews of physical activity interventions and a simulation model to examine how megatrends in information and communication technology and transportation directly and indirectly affect levels of physical activity across countries of low, middle, and high income. The model suggested that the direct and potentiating eff ects of information and communication technology, especially mobile phones, are nearly equal in magnitude to the mean eff ects of planned physical activity interventions. The greatest potential to increase population physical activity might thus be in creation of synergistic policies in sectors outside health including communication and transportation. However, there remains a glaring mismatch between where studies on physical activity interventions are undertaken and where the potential lies in low-income and middle-income countries for population-level effects that will truly affect global health.

  19. Direct observations of active school transportation and stroller use in kindergarten children

    Directory of Open Access Journals (Sweden)

    Linda Rothman

    2016-12-01

    Full Text Available Little is known about kindergarten students' active school transportation (AST and stroller/wagon use as sedentary travel devices. The primary objective of this cross-sectional study was to determine the prevalence of kindergarten children arriving to school by active and sedentary modes, including strollers, in Toronto elementary schools and compare to students in kindergarten to grade 6 (K–6. The secondary objective was to examine factors associated with AST in kindergarten and K–6 students. School travel mode was counted using direct observations at elementary schools in the City of Toronto in 2015. Two samples were observed: 1 Kindergarten sample: a random sample of schools with separate kindergarten entrances (n = 26 schools, 1069 children; 2 Kindergarten to grade 6 sample: observations were conducted at arrival locations at 50% of eligible elementary schools for students of all ages (n = 88 schools, 17,224 children. Proportions arriving by different travel modes were compared using Chi-square analysis. Negative binomial regression was conducted to examine the association between school characteristics and AST. AST was lower in the kindergarten compared to the K–6 sample (60% versus 74%, χ2 = 91.37, p < 0.001. The predominant sedentary mode for kindergarten students was by vehicle (38%, with <2% using strollers/wagons. Recent immigrant status was related to higher AST in kindergarten students; higher social disadvantage, crossing guards, school population and collision rates were related to higher AST in the K–6 sample. Factors influencing AST in young students require further investigation to influence the development of healthy active lifestyles at an early age.

  20. Fate and Transport of Methane Formed in the Active Layer of Alaskan Permafrost

    Science.gov (United States)

    Conrad, M. E.; Curtis, J. B.; Smith, L. J.; Bill, M.; Torn, M. S.

    2015-12-01

    Over the past 2 years a series of tracer tests designed to estimate rates of methane formation via acetoclastic methanogenesis in the active layer of permafrost soils were conducted at the Barrow Environmental Observatory (BEO) in northernmost Alaska. The tracer tests consisted of extracting 0.5 to 1.0 liters of soil water in gas-tight bags from different features of polygons at the BEO, followed by addition of a tracer cocktail including acetate with a 13C-labeled methyl group and D2O (as a conservative tracer) into the soil water and injection of the mixture back into the original extraction site. Samples were then taken at depths of 30 cm (just above the bottom of the active layer), 20 cm, 10 cm and surface flux to determine the fate of the 13C-labeled acetate. During 2014 (2015 results are pending) water, soil gas, and flux gas were sampled for 60 days following injection of the tracer solution. Those samples were analyzed for concentrations and isotopic compositions of CH4, DIC/CO2 and water. At one site (the trough of a low-centered polygon) the 13C acetate was completely converted to 13CH4 within the first 2 days. The signal persisted for throughout the entire monitoring period at the injection depth with little evidence of transport or oxidation in any of the other sampling depths. In the saturated center of the same polygon, the acetate was also rapidly converted to 13CH4, but water turnover caused the signal to rapidly dissipate. High δ13C CO2 in flux samples from the polygon center indicate oxidation of the 13CH4 in near-surface waters. Conversely, CH4 production in the center of an unsaturated, flat-centered polygon was relatively small 13CH4 and dissipated rapidly without any evidence of either 13CH4 transport to shallower levels or oxidation. At another site in the edge of that polygon no 13CH4 was produced, but significant 13CO2/DIC was observed indicating direct aerobic oxidation of the acetate was occurring at this site. These results suggest that

  1. Shoe leather epidemiology: active travel and transport infrastructure in the urban landscape

    Directory of Open Access Journals (Sweden)

    Mutrie Nanette

    2010-05-01

    Full Text Available Abstract Background Building new transport infrastructure could help to promote changes in patterns of mobility, physical activity, and other determinants of population health such as economic development. However, local residents may not share planners' goals or assumptions about the benefits of such interventions. A particularly contentious example is the construction of major roads close to deprived residential areas. We report the qualitative findings of the baseline phase of a longitudinal mixed-method study of a new urban section of the M74 motorway in Glasgow, Scotland, that aims to combine quantitative epidemiological and spatial data with qualitative interview data from local residents. Methods We interviewed 12 residents purposively sampled from a larger study cohort of 1322 to include men and women, different age groups, and people with and without cars, all living within 400 metres of the proposed route of the new motorway. We elicited their views and experiences of the local urban environment and the likely impact of the new motorway using a topic guide based on seven key environmental constructs (aesthetics, green space, convenience of routes, access to amenities, traffic, road danger and personal danger reflecting an overall ecological model of walking and cycling. Results Traffic was widely perceived to be heavy despite a low local level of car ownership. Few people cycled, and cycling on the roads was widely perceived to be dangerous for both adults and children. Views about the likely impacts of the new motorway on traffic congestion, pollution and the pleasantness of the local environment were polarised. A new motorway has potential to cause inequitable psychological or physical severance of routes to local amenities, and people may not necessarily use local walking routes or destinations such as parks and shops if these are considered undesirable, unsafe or 'not for us'. Public transport may have the potential to promote or

  2. GABA transporter subtype 1 and GABA transporter subtype 3 modulate glutamatergic transmission via activation of presynaptic GABA(B) receptors in the rat globus pallidus.

    Science.gov (United States)

    Jin, Xiao-Tao; Paré, Jean-Francois; Smith, Yoland

    2012-08-01

    The intra-pallidal application of γ-aminobutyric acid (GABA) transporter subtype 1 (GAT-1) or GABA transporter subtype 3 (GAT-3) transporter blockers [1-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid hydrochloride (SKF 89976A) or 1-[2-[tris(4-methoxyphenyl)methoxy]ethyl]-(S)-3-piperidinecarboxylic acid (SNAP 5114)] reduces the activity of pallidal neurons in monkey. This effect could be mediated through the activation of presynaptic GABA(B) heteroreceptors in glutamatergic terminals by GABA spillover following GABA transporter (GAT) blockade. To test this hypothesis, we applied the whole-cell recording technique to study the effects of SKF 89976A and SNAP 5114 on evoked excitatory postsynaptic currents (eEPSCs) in the presence of gabazine, a GABA(A) receptor antagonist, in rat globus pallidus slice preparations. Under the condition of postsynaptic GABA(B) receptor blockade by the intra-cellular application of N-(2,6-dimethylphenylcarbamoylmethyl)-triethylammonium bromide (OX314), bath application of SKF 89976A (10 μM) or SNAP 5114 (10 μM) decreased the amplitude of eEPSCs, without a significant effect on its holding current and whole cell input resistance. The inhibitory effect of GAT blockade on eEPSCs was blocked by (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl](phenylmethyl)phosphinic acid, a GABA(B) receptor antagonist. The paired-pulse ratio of eEPSCs was increased, whereas the frequency, but not the amplitude, of miniature excitatory postsynaptic currents was reduced in the presence of either GAT blocker, demonstrating a presynaptic effect. These results suggest that synaptically released GABA can inhibit glutamatergic transmission through the activation of presynaptic GABA(B) heteroreceptors following GAT-1 or GAT-3 blockade. In conclusion, our findings demonstrate that presynaptic GABA(B) heteroreceptors in putative glutamatergic subthalamic afferents to the globus pallidus are sensitive to increases in extracellular GABA induced

  3. Phenformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) activation of AMP-activated protein kinase inhibits transepithelial Na+ transport across H441 lung cells.

    Science.gov (United States)

    Woollhead, Alison M; Scott, John W; Hardie, D Grahame; Baines, Deborah L

    2005-08-01

    Active re-absorption of Na+ across the alveolar epithelium is essential to maintain lung fluid balance. Na+ entry at the luminal membrane is predominantly via the amiloride-sensitive Na+ channel (ENaC) down its electrochemical gradient. This gradient is generated and maintained by basolateral Na+ extrusion via Na+,K+-ATPase an energy-dependent process. Several kinases and factors that activate them are known to regulate these processes; however, the role of AMP-activated protein kinase (AMPK) in the lung is unknown. AMPK is an ultra-sensitive cellular energy sensor that monitors energy consumption and down-regulates ATP-consuming processes when activated. The biguanide phenformin has been shown to independently decrease ion transport processes, influence cellular metabolism and activate AMPK. The AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) also activates AMPK in intact cells. Western blotting revealed that both the alpha1 and alpha2 catalytic subunits of AMPK are present in Na+ transporting H441 human lung epithelial cells. Phenformin and AICAR increased AMPK activity in H441 cells in a dose-dependent fashion, stimulating the kinase maximally at 5-10 mm (P = 0.001, n = 3) and 2 mm (P < 0.005, n = 3), respectively. Both agents significantly decreased basal ion transport (measured as short circuit current) across H441 monolayers by approximately 50% compared with that of controls (P < 0.05, n = 4). Neither treatment altered the resistance of the monolayers. Phenformin and AICAR significantly reduced amiloride-sensitive transepithelial Na+ transport compared with controls (P < 0.05, n = 4). This was a result of both decreased Na+,K+-ATPase activity and amiloride-sensitive apical Na+ conductance. Transepithelial Na+ transport decreased with increasing concentrations of phenformin (0.1-10 mm) and showed a significant correlation with AMPK activity. Taken together, these results show that phenformin and AICAR suppress amiloride

  4. The biological activity of Coccinia indica on glucose transporter 1 (GLUT1 promoter

    Directory of Open Access Journals (Sweden)

    Juntipa Purintrapiban

    2009-08-01

    Full Text Available Plant derivatives with purported hypoglycemic properties have been used in traditional medicine around the world. Coccinia indica (ivy gourd is used in traditional medicine to treat diabetics in many countries. C. indica is able to cause a reduction in blood glucose level and has shown hypoglycemic activity in vitro and in vivo. However, the mechanism of this effect remains unknown. In this study, we generated the pGL3-glucose transporter 1 (GLUT1 promoter to elucidate the molecular mechanism of the regulation of GLUT1 gene expression in response to a water extract of C. indica stem (CIextract. A fragment of 2.1 kb of rat GLUT1 promoter, located at -2,106 to +134, was linked to firefly luciferase. The regulating transcription was analyzed in transient expression assay after transfection and exposure of L6 myocytes with the GLUT1 promoter system and CI extract, respectively. Under normal condition (5 mM glucose, promoter activity induced by 0.15 mg CI extract was markedly increased by 5.71 fold from the basal value. CI extract was more effective than 2 mM metformin. Surprisingly, promoter activity in hyperglycemic condition (15 mM glucose induced by 0.50 mg CI was increased by 1.63 fold from the basal value. In addition, CI extract increased the 2-deoxyglucose (2-DG uptake in L6myocytes in a dose-dependent manner in both conditions, 5 mM and 15 mM glucose. GLUT1 protein was determined by Western blot analysis and the level also increased in a dose-dependent fashion. Interestingly, the activity of the -273 to +134 of GLUT1 promoter was increased by 2.12 fold from the basal value. This site is the transcription initiation site containing GC box and TATA box. These observations suggest that the hypoglycemic action of C. indica may regulate through the activation of GLUT1 promoter resulting in an increase of the GLUT1 protein expression.

  5. Functional identification of activity-regulated, high-affinity glutamine transport in hippocampal neurons inhibited by riluzole.

    Science.gov (United States)

    Erickson, Jeffrey D

    2017-07-01

    Glutamine (Gln) is considered the preferred precursor for the neurotransmitter pool of glutamate (Glu), the major excitatory transmitter in the mammalian CNS. Here, an activity-regulated, high-affinity Gln transport system is described in developing and mature neuron-enriched hippocampal cultures that is potently inhibited by riluzole (IC50 1.3 ± 0.5 μM), an anti-glutamatergic drug, and is blocked by low concentrations of 2-(methylamino)isobutyrate (MeAIB), a system A transport inhibitor. K(+) -stimulated MeAIB transport displays an affinity (Km ) for MeAIB of 37 ± 1.2 μM, saturates at ~ 200 μM, is dependent on extracellular Ca(2+) , and is blocked by inhibition of voltage-gated Ca(2+) channels. Spontaneous MeAIB transport is also dependent on extracellullar Ca(2+) and voltage-gated calcium channels, but is also blocked by the Na(+) channel blocker tetrodotoxin, by Glu receptor antagonists, and by GABA indicating its dependence on intact neural circuits driven by endogenous glutamatergic activity. The transport of MeAIB itself does not rely on Ca(2+) , but on Na(+) ions, and is pH sensitive. Activity-regulated, riluzole-sensitive spontaneous and K(+) -stimulated transport is minimal at 7-8 days in vitro, coordinately induced during the next 2 weeks and is maximally expressed by days in vitro > 20; the known period for maturation of the Glu/Gln cycle and regulated pre-synaptic Glu release. Competition analyses with various amino acids indicate that Gln is the most likely physiological substrate. Activity-regulated Gln/MeAIB transport is not observed in astrocytes. The functional identification of activity-regulated, high-affinity, riluzole-sensitive Gln/MeAIB transport in hippocampal neurons may have important ramifications in the neurobiology of activity-stimulated pre-synaptic Glu release, the Glu/Gln cycle between astrocytes and neurons, and neuronal Glu-induced excitotoxicity. Cover Image for this issue: doi: 10.1111/jnc.13805. © 2017

  6. Effect of graded Nrf2 activation on phase-I and -II drug metabolizing enzymes and transporters in mouse liver.

    Directory of Open Access Journals (Sweden)

    Kai Connie Wu

    Full Text Available Nuclear factor erythroid 2-related factor 2 (Nrf2 is a transcription factor that induces a battery of cytoprotective genes in response to oxidative/electrophilic stress. Kelch-like ECH associating protein 1 (Keap1 sequesters Nrf2 in the cytosol. The purpose of this study was to investigate the role of Nrf2 in regulating the mRNA of genes encoding drug metabolizing enzymes and xenobiotic transporters. Microarray analysis was performed in livers of Nrf2-null, wild-type, Keap1-knockdown mice with increased Nrf2 activation, and Keap1-hepatocyte knockout mice with maximum Nrf2 activation. In general, Nrf2 did not have a marked effect on uptake transporters, but the mRNAs of organic anion transporting polypeptide 1a1, sodium taurocholate cotransporting polypeptide, and organic anion transporter 2 were decreased with Nrf2 activation. The effect of Nrf2 on cytochrome P450 (Cyp genes was minimal, with only Cyp2a5, Cyp2c50, Cyp2c54, and Cyp2g1 increased, and Cyp2u1 decreased with enhanced Nrf2 activation. However, Nrf2 increased mRNA of many other phase-I enzymes, such as aldo-keto reductases, carbonyl reductases, and aldehyde dehydrogenase 1. Many genes involved in phase-II drug metabolism were induced by Nrf2, including glutathione S-transferases, UDP- glucuronosyltransferases, and UDP-glucuronic acid synthesis enzymes. Efflux transporters, such as multidrug resistance-associated proteins, breast cancer resistant protein, as well as ATP-binding cassette g5 and g8 were induced by Nrf2. In conclusion, Nrf2 markedly alters hepatic mRNA of a large number of drug metabolizing enzymes and xenobiotic transporters, and thus Nrf2 plays a central role in xenobiotic metabolism and detoxification.

  7. Alternative electron transports participate in the maintenance of violaxanthin De-epoxidase activity of Ulva sp. under low irradiance.

    Directory of Open Access Journals (Sweden)

    Xiujun Xie

    Full Text Available The xanthophyll cycle (Xc, which involves violaxanthin de-epoxidase (VDE and the zeaxanthin epoxidase (ZEP, is one of the most rapid and efficient responses of plant and algae to high irradiance. High light intensity can activate VDE to convert violaxanthin (Vx to zeaxanthin (Zx via antheraxanthin (Ax. However, it remains unclear whether VDE remains active under low light or dark conditions when there is no significant accumulation of Ax and Zx, and if so, how the ΔpH required for activation of VDE is built. In this study, we used salicylaldoxime (SA to inhibit ZEP activity in the intertidal macro-algae Ulva sp. (Ulvales, Chlorophyta and then characterized VDE under low light and dark conditions with various metabolic inhibitors. With inhibition of ZEP by SA, VDE remained active under low light and dark conditions, as indicated by large accumulations of Ax and Zx at the expense of Vx. When PSII-mediated linear electron transport systems were completely inhibited by SA and DCMU, alternative electron transport systems (i.e., cyclic electron transport and chlororespiration could maintain VDE activity. Furthermore, accumulations of Ax and Zx decreased significantly when SA, DCMU, or DBMIB together with an inhibitor of chlororespiration (i.e., propyl gallate (PG were applied to Ulva sp. This result suggests that chlororespiration not only participates in the build-up of the necessary ΔpH, but that it also possibly influences VDE activity indirectly by diminishing the oxygen level in the chloroplast.

  8. 49 CFR 173.427 - Transport requirements for low specific activity (LSA) Class 7 (radioactive) materials and...

    Science.gov (United States)

    2010-10-01

    ... (LSA) Class 7 (radioactive) materials and surface contaminated objects (SCO). 173.427 Section 173.427... SHIPMENTS AND PACKAGINGS Class 7 (Radioactive) Materials § 173.427 Transport requirements for low specific activity (LSA) Class 7 (radioactive) materials and surface contaminated objects (SCO). (a) In addition...

  9. Child dopamine active transporter 1 genotype and parenting: evidence for evocative gene-environment correlations.

    Science.gov (United States)

    Hayden, Elizabeth P; Hanna, Brigitte; Sheikh, Haroon I; Laptook, Rebecca S; Kim, Jiyon; Singh, Shiva M; Klein, Daniel N

    2013-02-01

    The dopamine active transporter 1 (DAT1) gene is implicated in psychopathology risk. Although the processes by which this gene exerts its effects on risk are poorly understood, a small body of research suggests that the DAT1 gene influences early emerging negative emotionality, a marker of children's psychopathology risk. As child negative emotionality evokes negative parenting practices, the DAT1 gene may also play a role in gene-environment correlations. To test this model, children (N = 365) were genotyped for the DAT1 gene and participated in standardized parent-child interaction tasks with their primary caregiver. The DAT1 gene 9-repeat variant was associated with child negative affect expressed toward the parent during parent-child interactions, and parents of children with a 9-repeat allele exhibited more hostility and lower guidance/engagement than parents of children without a 9-repeat allele. These gene-environment associations were partially mediated by child negative affect toward the parent. The findings implicate a specific polymorphism in eliciting negative parenting, suggesting that evocative associations play a role in elevating children's risk for emotional trajectories toward psychopathology risk.

  10. Structure activity relationships of benzylproline-derived inhibitors of the glutamine transporter ASCT2

    Science.gov (United States)

    Singh, Kurnvir; Tanui, Rose; Gameiro, Armanda; Eisenberg, Gilad; Colas, Claire; Schlessinger, Avner; Grewer, Christof

    2017-01-01

    The glutamine transporter ASCT2 has been identified as a promising target to inhibit rapid growth of cancer cells. However, ASCT2 pharmacology is not well established. In this report, we performed a systematic structure activity analysis of a series of substituted benzylproline derivatives. Substitutions on the phenyl ring resulted in compounds with characteristics of ASCT2 inhibitors. Apparent binding affinity increased with increasing hydrophobicity of the side chain. In contrast, interaction of the ASCT2 binding site with specific positions on the phenyl ring was not observed. The most potent compound inhibits the ASCT2 anion conductance with a Ki of 3 μM, which is in the same range as that of more bulky and higher molecular weight inhibitors recently reported by others. The experimental results are consistent with computational analysis based on docking of the inhibitors against an ASCT2 homology model. The benzylproline scaffold provides a valuable tool for further improving binding potency of future ASCT2 inhibitors. PMID:28057420

  11. Robust active noise control in the loadmaster area of a military transport aircraft.

    Science.gov (United States)

    Kochan, Kay; Sachau, Delf; Breitbach, Harald

    2011-05-01

    The active noise control (ANC) method is based on the superposition of a disturbance noise field with a second anti-noise field using loudspeakers and error microphones. This method can be used to reduce the noise level inside the cabin of a propeller aircraft. However, during the design process of the ANC system, extensive measurements of transfer functions are necessary to optimize the loudspeaker and microphone positions. Sometimes, the transducer positions have to be tailored according to the optimization results to achieve a sufficient noise reduction. The purpose of this paper is to introduce a controller design method for such narrow band ANC systems. The method can be seen as an extension of common transducer placement optimization procedures. In the presented method, individual weighting parameters for the loudspeakers and microphones are used. With this procedure, the tailoring of the transducer positions is replaced by adjustment of controller parameters. Moreover, the ANC system will be robust because of the fact that the uncertainties are considered during the optimization of the controller parameters. The paper describes the necessary theoretic background for the method and demonstrates the efficiency in an acoustical mock-up of a military transport aircraft.

  12. Potential Activity of Subglacial Microbiota Transported to Anoxic River Delta Sediments.

    Science.gov (United States)

    Cameron, Karen A; Stibal, Marek; Olsen, Nikoline S; Mikkelsen, Andreas B; Elberling, Bo; Jacobsen, Carsten S

    2017-07-01

    The Watson River drains a portion of the SW Greenland ice sheet, transporting microbial communities from subglacial environments to a delta at the head of Søndre Strømfjord. This study investigates the potential activity and community shifts of glacial microbiota deposited and buried under layers of sediments within the river delta. A long-term (12-month) incubation experiment was established using Watson River delta sediment under anaerobic conditions, with and without CO2/H2 enrichment. Within CO2/H2-amended incubations, sulphate depletion and a shift in the microbial community to a 52% predominance of Desulfosporosinus meridiei by day 371 provides evidence for sulphate reduction. We found evidence of methanogenesis in CO2/H2-amended incubations within the first 5 months, with production rates of ~4 pmol g(-1) d(-1), which was likely performed by methanogenic Methanomicrobiales- and Methanosarcinales-related organisms. Later, a reduction in methane was observed to be paired with the depletion of sulphate, and we hypothesise that sulphate reduction out competed hydrogenotrophic methanogenesis. The structure and diversity of the original CO2/H2-amended incubation communities changed dramatically with a major shift in predominant community members and a decline in diversity and cell abundance. These results highlight the need for further investigations into the fate of subglacial microbiota within downstream environments.

  13. The implications of megatrends in information and communication technology and transportation for changes in global physical activity

    DEFF Research Database (Denmark)

    Pratt, Michael; Sarmiento, Olga L; Montes, Felipe

    2012-01-01

    Physical inactivity accounts for more than 3 million deaths per year, most from non-communicable diseases in low-income and middle-income countries. We used reviews of physical activity interventions and a simulation model to examine how megatrends in information and communication technology...... and transportation directly and indirectly aff ect levels of physical activity across countries of low, middle, and high income. The model suggested that the direct and potentiating eff ects of information and communication technology, especially mobile phones, are nearly equal in magnitude to the mean eff ects...... of planned physical activity interventions. The greatest potential to increase population physical activity might thus be in creation of synergistic policies in sectors outside health including communication and transportation. However, there remains a glaring mismatch between where studies on physical...

  14. Allelic differences in Medicago truncatula NIP/LATD mutants correlate with their encoded proteins' transport activities in planta.

    Science.gov (United States)

    Salehin, Mohammad; Huang, Ying-Sheng; Bagchi, Rammyani; Sherrier, D Janine; Dickstein, Rebecca

    2013-02-01

    Medicago truncatula NIP/LATD gene, required for symbiotic nitrogen fixing nodule and root architecture development, encodes a member of the NRT1(PTR) family that demonstrates high-affinity nitrate transport in Xenopus laevis oocytes. Of three Mtnip/latd mutant proteins, one retains high-affinity nitrate transport in oocytes, while the other two are nitrate-transport defective. To further examine the mutant proteins' transport properties, the missense Mtnip/latd alleles were expressed in Arabidopsis thaliana chl1-5, resistant to the herbicide chlorate because of a deletion spanning the nitrate transporter AtNRT1.1(CHL1) gene. Mtnip-3 expression restored chlorate sensitivity in the Atchl1-5 mutant, similar to wild type MtNIP/LATD, while Mtnip-1 expression did not. The high-affinity nitrate transporter AtNRT2.1 gene was expressed in Mtnip-1 mutant roots; it did not complement, which could be caused by several factors. Together, these findings support the hypothesis that MtNIP/LATD may have another biochemical activity.

  15. Modular electron-transport chains from eukaryotic organelles function to support nitrogenase activity.

    Science.gov (United States)

    Yang, Jianguo; Xie, Xiaqing; Yang, Mingxuan; Dixon, Ray; Wang, Yi-Ping

    2017-03-21

    A large number of genes are necessary for the biosynthesis and activity of the enzyme nitrogenase to carry out the process of biological nitrogen fixation (BNF), which requires large amounts of ATP and reducing power. The multiplicity of the genes involved, the oxygen sensitivity of nitrogenase, plus the demand for energy and reducing power, are thought to be major obstacles to engineering BNF into cereal crops. Genes required for nitrogen fixation can be considered as three functional modules encoding electron-transport components (ETCs), proteins required for metal cluster biosynthesis, and the "core" nitrogenase apoenzyme, respectively. Among these modules, the ETC is important for the supply of reducing power. In this work, we have used Escherichia coli as a chassis to study the compatibility between molybdenum and the iron-only nitrogenases with ETC modules from target plant organelles, including chloroplasts, root plastids, and mitochondria. We have replaced an ETC module present in diazotrophic bacteria with genes encoding ferredoxin-NADPH oxidoreductases (FNRs) and their cognate ferredoxin counterparts from plant organelles. We observe that the FNR-ferredoxin module from chloroplasts and root plastids can support the activities of both types of nitrogenase. In contrast, an analogous ETC module from mitochondria could not function in electron transfer to nitrogenase. However, this incompatibility could be overcome with hybrid modules comprising mitochondrial NADPH-dependent adrenodoxin oxidoreductase and the Anabaena ferredoxins FdxH or FdxB. We pinpoint endogenous ETCs from plant organelles as power supplies to support nitrogenase for future engineering of diazotrophy in cereal crops.

  16. Insulin-increased L-arginine transport requires A(2A adenosine receptors activation in human umbilical vein endothelium.

    Directory of Open Access Journals (Sweden)

    Enrique Guzmán-Gutiérrez

    Full Text Available Adenosine causes vasodilation of human placenta vasculature by increasing the transport of arginine via cationic amino acid transporters 1 (hCAT-1. This process involves the activation of A(2A adenosine receptors (A(2AAR in human umbilical vein endothelial cells (HUVECs. Insulin increases hCAT-1 activity and expression in HUVECs, and A(2AAR stimulation increases insulin sensitivity in subjects with insulin resistance. However, whether A(2AAR plays a role in insulin-mediated increase in L-arginine transport in HUVECs is unknown. To determine this, we first assayed the kinetics of saturable L-arginine transport (1 minute, 37°C in the absence or presence of nitrobenzylthioinosine (NBTI, 10 µmol/L, adenosine transport inhibitor and/or adenosine receptors agonist/antagonists. We also determined hCAT-1 protein and mRNA expression levels (Western blots and quantitative PCR, and SLC7A1 (for hCAT-1 reporter promoter activity. Insulin and NBTI increased the extracellular adenosine concentration, the maximal velocity for L-arginine transport without altering the apparent K(m for L-arginine transport, hCAT-1 protein and mRNA expression levels, and SLC7A1 transcriptional activity. An A2AAR antagonist ZM-241385 blocked these effects. ZM241385 inhibited SLC7A1 reporter transcriptional activity to the same extent in cells transfected with pGL3-hCAT-1(-1606 or pGL3-hCAT-1(-650 constructs in the presence of NBTI + insulin. However, SLC7A1 reporter activity was increased by NBTI only in cells transfected with pGL3-hCAT-1(-1606, and the ZM-241385 sensitive fraction of the NBTI response was similar in the absence or in the presence of insulin. Thus, insulin modulation of hCAT-1 expression and activity requires functional A(2AAR in HUVECs, a mechanism that may be applicable to diseases associated with fetal insulin resistance, such as gestational diabetes.

  17. Regulation of taurine transport at the blood-placental barrier by calcium ion, PKC activator and oxidative stress conditions

    Science.gov (United States)

    2010-01-01

    Background In the present study, we investigated the changes of uptake and efflux transport of taurine under various stress conditions using rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT cells), as in vitro blood-placental barrier (BPB) model. Methods The transport of taurine in TR-TBT cells were characterized by cellular uptake study using radiolabeled taurine. The efflux of taurine was measured from the amount of radiolabeled taurine remaining in the cells after the uptake of radiolabeled taurine for 60 min. Results Taurine uptake was significantly decreased by phosphorylation of protein kinase C (PKC) activator in TR-TBT cells. Also, calcium ion (Ca2+) was involved in taurine transport in TR-TBT cells. Taurine uptake was inhibited and efflux was enhanced under calcium free conditions in the cells. In addition, oxidative stress induced the change of taurine transport in TR-TBT cells, but the changes were different depending on the types of oxidative stress inducing agents. Tumor necrosis factor-α (TNF-α), lipopolysaccharide (LPS) and diethyl maleate (DEM) significantly increased taurine uptake, but H2O2 and nitric oxide (NO) donor decreased taurine uptake in the cells. Taurine efflux was down-regulated by TNF-α in TR-TBT cells. Conclusion Taurine transport in TR-TBT cells were regulated diversely at extracellular Ca2+ level, PKC activator and oxidative stress conditions. It suggested that variable stresses affected the taurine supplies from maternal blood to fetus and taurine level of fetus. PMID:20804613

  18. Ethanolic extract of Allium cepa stimulates glucose transporter typ 4-mediated glucose uptake by the activation of insulin signaling.

    Science.gov (United States)

    Gautam, Sudeep; Pal, Savita; Maurya, Rakesh; Srivastava, Arvind K

    2015-02-01

    The present work was undertaken to investigate the effects and the molecular mechanism of the standardized ethanolic extract of Allium cepa (onion) on the glucose transport for controlling diabetes mellitus. A. cepa stimulates glucose uptake by the rat skeletal muscle cells (L6 myotubes) in both time- and dose-dependent manners. This effect was shown to be mediated by the increased translocation of glucose transporter typ 4 protein from the cytoplasm to the plasma membrane as well as the synthesis of glucose transporter typ 4 protein. The effect of A. cepa extract on glucose transport was stymied by wortmannin, genistein, and AI½. In vitro phosphorylation analysis revealed that, like insulin, A. cepa extract also enhances the tyrosine phosphorylation of the insulin receptor-β, insulin receptor substrate-1, and the serine phosphorylation of Akt under both basal and insulin-stimulated conditions without affecting the total amount of these proteins. Furthermore, it is also shown that the activation of Akt is indispensable for the A. cepa-induced glucose uptake in L6 myotubes. Taken together, these findings provide ample evidence that the ethanolic extract of A. cepa stimulates glucose transporter typ 4 translocation-mediated glucose uptake by the activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt dependent pathway.

  19. Crossover from band-like to thermally activated charge transport in organic transistors due to strain-induced traps

    KAUST Repository

    Mei, Yaochuan

    2017-08-02

    The temperature dependence of the charge-carrier mobility provides essential insight into the charge transport mechanisms in organic semiconductors. Such knowledge imparts critical understanding of the electrical properties of these materials, leading to better design of high-performance materials for consumer applications. Here, we present experimental results that suggest that the inhomogeneous strain induced in organic semiconductor layers by the mismatch between the coefficients of thermal expansion (CTE) of the consecutive device layers of field-effect transistors generates trapping states that localize charge carriers. We observe a universal scaling between the activation energy of the transistors and the interfacial thermal expansion mismatch, in which band-like transport is observed for similar CTEs, and activated transport otherwise. Our results provide evidence that a high-quality semiconductor layer is necessary, but not sufficient, to obtain efficient charge-carrier transport in devices, and underline the importance of holistic device design to achieve the intrinsic performance limits of a given organic semiconductor. We go on to show that insertion of an ultrathin CTE buffer layer mitigates this problem and can help achieve band-like transport on a wide range of substrate platforms.

  20. Influence of muscle activation and mucosal material property on esophageal transport: study based on a fully-resolved computational model

    Science.gov (United States)

    Kou, Wenjun; Pandolfino, John; Kahrilas, Peter; Patankar, Neelesh

    2014-11-01

    Esophageal transport involves interactions between food (bolus), the esophageal walls (composed of mucosal, circular muscle (CM) and longitudinal muscle (LM) layers), and neurally coordinated muscle activation including CM contraction and LM shortening. Due to the complexity of these interactions, few studies have been conducted on the mechanical role of the mucosal layer in esophageal transport. Also poorly understood are the collaborative roles of CM contraction and LM shortening and the influence of their synchronization. Here, based on a fully-resolved computational model that we developed, we investigated the individual roles of CM contraction and LM shortening, compared bolus transport with various levels of discoordination between CM and LM activation, and studied the role of the mucosa and how its stiffening influenced transport. These preliminary findings should help understand the synergy between LM, CM, and the mucosal layer in facilitating bolus transport, thereby providing insight into related physiology and pathophysiology. The support of Grant R01 DK56033 and R01 DK079902 from NIH is gratefully acknowledged.

  1. Suppressed intrinsic catalytic activity of GLUT1 glucose transporters in insulin-sensitive 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, S.A.; Buxton, J.M.; Czech, M.P. (Univ. of Massachusetts Medical Center, Worcester (United States))

    1991-09-01

    Previous studies indicated that the erythroid-type (GLUT1) glucose transporter isoform contributes to basal but not insulin-stimulated hexose transport in mouse 3T3-L1 adipocytes. In the present studies it was found that basal hexose uptake in 3T3-L1 adipocytes was about 50% lower than that in 3T3-L1 or CHO-K1 fibroblasts. Intrinsic catalytic activities of GLUT1 transporters in CHO-K1 and 3T3-L1 cells were compared by normalizing these hexose transport rates to GLUT1 content on the cell surface, as measured by two independent methods. Cell surface GLUT1 levels in 3T3-L1 fibroblasts and adipocytes were about 10- and 25-fold higher, respectively, than in CHO-K1 fibroblasts, as assessed with an anti-GLUT1 exofacial domain antiserum, delta. The large excess of cell surface GLUT1 transporters in 3T3-L1 adipocytes relative to CHO-K1 fibroblasts was confirmed by GLUT1 protein immunoblot analysis and by photoaffinity labeling (with 3-({sup 125}I)iodo-4-azidophenethylamido-7-O-succinyldeacetylforskolin) of glucose transporters in isolated plasma membranes. Thus, GLUT1 intrinsic activity is markedly reduced in 3T3-L1 fibroblasts compared with the CHO-K1 fibroblasts, and further reduction occurs upon differentiation to adipocytes. The authors conclude that a mechanism that markedly suppresses basal hexose transport catalyzed by GLUT1 is a major contributor to the dramatic insulin sensitivity of glucose uptake in 3T3-L1 adipocytes.

  2. Repeat-swap homology modeling of secondary active transporters: updated protocol and prediction of elevator-type mechanisms.

    Science.gov (United States)

    Vergara-Jaque, Ariela; Fenollar-Ferrer, Cristina; Kaufmann, Desirée; Forrest, Lucy R

    2015-01-01

    Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to one or other side of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, GltPh, in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (a)symmetry of these systems has been successfully used as a bioinformatic tool, called "repeat-swap modeling" to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeat-swap homology modeling protocol, and calibrate the accuracy of the method using GltPh, for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of GltPh. The repeat-swapped model of VcCNT predicts that nucleoside transport also

  3. An Activity-Based Multimodal Model Structure to assess Transportation Management Strategies for Urban Emergencies

    NARCIS (Netherlands)

    Van der Gun, J.P.T.; Pel, A.J.; Van Arem, B.

    2014-01-01

    There are many kinds of disasters that can severely impact the transportation system of an urbanized region. Transportation authorities therefore need to develop management strategies to adequately deal with such emergencies. In this paper, we discuss the structure of a simulation model that can be

  4. Active transportation among elementary-aged students: walking or biking to and from school

    Science.gov (United States)

    Whitney Knollenberg; Pavlina Latkova; Christine Vogt; Ariel Rodriguez

    2009-01-01

    Heightened attention is being drawn to the health conditions linked to physical inactivity, particularly in children. Encouraging students to walk and bike to school encourages them to develop healthier lifestyles and to choose nonmotorized transportation at other times. The Safe Routes to School program, administered by the U.S. Department of Transportation National...

  5. An Activity-Based Multimodal Model Structure to assess Transportation Management Strategies for Urban Emergencies

    NARCIS (Netherlands)

    Van der Gun, J.P.T.; Pel, A.J.; Van Arem, B.

    2014-01-01

    There are many kinds of disasters that can severely impact the transportation system of an urbanized region. Transportation authorities therefore need to develop management strategies to adequately deal with such emergencies. In this paper, we discuss the structure of a simulation model that can be

  6. Structures and properties of sulfonated ionomers probed by transport and mechanical measurements: The role of solute activity

    Science.gov (United States)

    Zhao, Qiao

    This work is focused on advancing the understanding of the structures and properties of sulfonated ionomer membranes in the context of Polymer Electrolyte Membrane Fuel Cell applications by transport and mechanical measurements. Transport and mechanical properties are two critical elements of ionomer membranes that govern the performance and longevity of fuel cells. Additionally, transport and mechanical property measurements can also provide valuable information about the structure of the ionomer membranes. It is essential to develop a comprehensive understanding of them under well controlled environmental conditions. The mechanism of water transport through Nafion membranes was found to be governed by water diffusivity, swelling of the hydrophilic phase and the interfacial transport across membrane/vapor interface. A transport model incorporating these parameters was developed and successfully employed to resolve water activity profiles in the membrane and make quantitative predictions under steady state and dynamic conditions. Experimental results of diffusivity, volume of mixing and tortuosity also provided hints about the hydration shell structure around in the hydrophilic domains of Nafion. The alcohol sorption and transport was found to be qualitatively similar to the behavior of water and the quantitative differences were attributed to the difference in molecular size. The transport of alcohol water mixtures through Nafion displayed significant non-ideality which was connected to the abnormal swelling and incomplete mixing within the hydrophilic domains. The mechanical properties of several perfluoro-sulfonated ionomer (PFSI) membranes were studied as functions of temperature and solute activity. The thermal transition found between 60-100°C was described as an order-disorder transition of the ionic clusters. Water and other polar solutes were found to plasticize PFSI below the transition but stiffen PFSI above the transition. The stiffening effect was

  7. Outer membrane active transport: structure of the BtuB:TonB complex.

    Science.gov (United States)

    Shultis, David D; Purdy, Michael D; Banchs, Christian N; Wiener, Michael C

    2006-06-02

    In Gram-negative bacteria, the import of essential micronutrients across the outer membrane requires a transporter, an electrochemical gradient of protons across the inner membrane, and an inner membrane protein complex (ExbB, ExbD, TonB) that couples the proton-motive force to the outer membrane transporter. The inner membrane protein TonB binds directly to a conserved region, called the Ton-box, of the transporter. We solved the structure of the cobalamin transporter BtuB in complex with the C-terminal domain of TonB. In contrast to its conformations in the absence of TonB, the Ton-box forms a beta strand that is recruited to the existing beta sheet of TonB, which is consistent with a mechanical pulling model of transport.

  8. Glial and Neuronal Glutamate Transporters Differ in the Na+ Requirements for Activation of the Substrate-Independent Anion Conductance

    Directory of Open Access Journals (Sweden)

    Christopher B. Divito

    2017-05-01

    Full Text Available Excitatory amino acid transporters (EAATs are secondary active transporters of L-glutamate and L- or D-aspartate. These carriers also mediate a thermodynamically uncoupled anion conductance that is gated by Na+ and substrate binding. The activation of the anion channel by binding of Na+ alone, however, has only been demonstrated for mammalian EAAC1 (EAAT3 and EAAT4. To date, no difference has been observed for the substrate dependence of anion channel gating between the glial, EAAT1 and EAAT2, and the neuronal isoforms EAAT3, EAAT4 and EAAT5. Here we describe a difference in the Na+-dependence of anion channel gating between glial and neuronal isoforms. Chloride flux through transporters without glutamate binding has previously been described as substrate-independent or “leak” channel activity. Choline or N-methyl-D-glucamine replacement of external Na+ ions significantly reduced or abolished substrate-independent EAAT channel activity in EAAT3 and EAAT4 yet has no effect on EAAT1 or EAAT2. The interaction of Na+ with the neuronal carrier isoforms was concentration dependent, consistent with previous data. The presence of substrate and Na+-independent open states in the glial EAAT isoforms is a novel finding in the field of EAAT function. Our results reveal an important divergence in anion channel function between glial and neuronal glutamate transporters and highlight new potential roles for the EAAT-associated anion channel activity based on transporter expression and localization in the central nervous system.

  9. Sustainable Transportation

    DEFF Research Database (Denmark)

    Hall, Ralph P.; Gudmundsson, Henrik; Marsden, Greg

    2014-01-01

    The transportation system is the backbone of economic and social progress and the means by which humans access goods and services and connect with one another. Yet, as the scale of transportation activities has grown worldwide, so too have the negative environmental, social, and economic impacts...... that relate to the construction and maintenance of transportation infrastructure and the operation or use of the different transportation modes. The concept of sustainable transportation emerged in response to these concerns as part of the broader notion of sustainable development. Given the transportation...... sector’s significant contribution to global challenges such as climate change, it is often said that sustainable development cannot be achieved without sustainable transportation....

  10. Effect of collection, transport, processing and storage of blood specimens on the activity of lysosomal enzymes in plasma and leukocytes

    Directory of Open Access Journals (Sweden)

    Burin M.

    2000-01-01

    Full Text Available This study was designed to evaluate the effect of different conditions of collection, transport and storage on the quality of blood samples from normal individuals in terms of the activity of the enzymes ß-glucuronidase, total hexosaminidase, hexosaminidase A, arylsulfatase A and ß-galactosidase. The enzyme activities were not affected by the different materials used for collection (plastic syringes or vacuum glass tubes. In the evaluation of different heparin concentrations (10% heparin, 5% heparin, and heparinized syringe in the syringes, it was observed that higher doses resulted in an increase of at least 1-fold in the activities of ß-galactosidase, total hexosaminidase and hexosaminidase A in leukocytes, and ß-glucuronidase in plasma. When the effects of time and means of transportation were studied, samples that had been kept at room temperature showed higher deterioration with time (72 and 96 h before processing, and in this case it was impossible to isolate leukocytes from most samples. Comparison of heparin and acid citrate-dextrose (ACD as anticoagulants revealed that ß-glucuronidase and hexosaminidase activities in plasma reached levels near the lower normal limits when ACD was used. In conclusion, we observed that heparin should be used as the preferable anticoagulant when measuring these lysosomal enzyme activities, and we recommend that, when transport time is more than 24 h, samples should be shipped by air in a styrofoam box containing wet ice.

  11. Earliest Results in the Use of Activated Composite Membranes for the Transport of Silver Ions from Aqueous Solutions

    Directory of Open Access Journals (Sweden)

    Yucundo Mendoza-Tolentino

    2014-01-01

    Full Text Available This paper presents the results concerning the first use of activated composite membranes (ACMs for the facilitated transport of silver ions containing di-(2-ethylhexyl-dithiophosphoric acid (DTPA as the carrier. DTPA was immobilized by interfacial polymerization in a dense layer that was deposited in a porous layer, which was prepared on a nonwoven fabric support by phase inversion. The influence of fundamental parameters affecting the transport of silver ion as the carrier concentration in the membrane phase and stripping agent variation of the stripping solution have been studied. In the optimal conditions, the amount of silver transported across the ACMs was greater than 50%, whereas if the content of the carrier is modified, more than the 90% of the initial silver is removed from the feed phase.

  12. Geodetic monitoring (TLS of a steel transport trestle bridge located in an active mining exploitation site

    Directory of Open Access Journals (Sweden)

    Skoczylas Arkadiusz

    2016-09-01

    Full Text Available Underground mining exploitation causes, in general, irregular vertical and horizontal shifts in the superficial layer of the rock mass. In the case of construction objects seated on this layer, a deformation of the object’s foundation can be observed. This leads to additional loads and deformations. Identification of surface geometry changes in construction objects located within the premises of underground mining exploitation areas is an important task as far as safety of mining sites is concerned. Surveys targeting shifts and deformations in engineering objects preformed with the use of classic methods are of a selective nature and do not provide the full image of the phenomenon being the subject of the observation. This paper presents possibilities of terrestrial laser scanning technology application in the monitoring of engineering objects that allows for a complete spatial documentation of an object subjected to the influence of an active mining exploitation. This paper describes an observation of a 100 m section of a steel transport trestle bridge located on the premises of hard coal mine Lubelski Węgiel “Bogdanka” S.A. carried out in 2015. Measurements were carried out using a Z+F Imager 5010C scanner at an interval of 3.5 months. Changes in the structure’s geometry were determined by comparing the point clouds recorded during the two measurement periods. The results of the analyses showed shifts in the trestle bridge towards the exploited coal wall accompanied by object deformation. The obtained results indicate the possibility of of terrestrial laser scanning application in studying the aftereffects of underground mining exploitation on surface engineering objects.

  13. GIS measured environmental correlates of active school transport: A systematic review of 14 studies

    Directory of Open Access Journals (Sweden)

    Faulkner Guy

    2011-05-01

    Full Text Available Abstract Background Emerging frameworks to examine active school transportation (AST commonly emphasize the built environment (BE as having an influence on travel mode decisions. Objective measures of BE attributes have been recommended for advancing knowledge about the influence of the BE on school travel mode choice. An updated systematic review on the relationships between GIS-measured BE attributes and AST is required to inform future research in this area. The objectives of this review are: i to examine and summarize the relationships between objectively measured BE features and AST in children and adolescents and ii to critically discuss GIS methodologies used in this context. Methods Six electronic databases, and websites were systematically searched, and reference lists were searched and screened to identify studies examining AST in students aged five to 18 and reporting GIS as an environmental measurement tool. Fourteen cross-sectional studies were identified. The analyses were classified in terms of density, diversity, and design and further differentiated by the measures used or environmental condition examined. Results Only distance was consistently found to be negatively associated with AST. Consistent findings of positive or negative associations were not found for land use mix, residential density, and intersection density. Potential modifiers of any relationship between these attributes and AST included age, school travel mode, route direction (e.g., to/from school, and trip-end (home or school. Methodological limitations included inconsistencies in geocoding, selection of study sites, buffer methods and the shape of zones (Modifiable Areal Unit Problem [MAUP], the quality of road and pedestrian infrastructure data, and school route estimation. Conclusions The inconsistent use of spatial concepts limits the ability to draw conclusions about the relationship between objectively measured environmental attributes and AST. Future

  14. Cost-effectiveness of active transport for primary school children - Walking School Bus program

    Directory of Open Access Journals (Sweden)

    Swinburn Boyd

    2009-09-01

    Full Text Available Abstract Background To assess from a societal perspective the incremental cost-effectiveness of the Walking School Bus (WSB program for Australian primary school children as an obesity prevention measure. The intervention was modelled as part of the ACE-Obesity study, which evaluated, using consistent methods, thirteen interventions targeting unhealthy weight gain in Australian children and adolescents. Methods A logic pathway was used to model the effects on body mass index [BMI] and disability-adjusted life years [DALYs] of the Victorian WSB program if applied throughout Australia. Cost offsets and DALY benefits were modelled until the eligible cohort reached 100 years of age or death. The reference year was 2001. Second stage filter criteria ('equity', 'strength of evidence', 'acceptability', feasibility', sustainability' and 'side-effects' were assessed to incorporate additional factors that impact on resource allocation decisions. Results The modelled intervention reached 7,840 children aged 5 to 7 years and cost $AUD22.8M ($16.6M; $30.9M. This resulted in an incremental saving of 30 DALYs (7:104 and a net cost per DALY saved of $AUD0.76M ($0.23M; $3.32M. The evidence base was judged as 'weak' as there are no data available documenting the increase in the number of children walking due to the intervention. The high costs of the current approach may limit sustainability. Conclusion Under current modelling assumptions, the WSB program is not an effective or cost-effective measure to reduce childhood obesity. The attribution of some costs to non-obesity objectives (reduced traffic congestion and air pollution etc. is justified to emphasise the other possible benefits. The program's cost-effectiveness would be improved by more comprehensive implementation within current infrastructure arrangements. The importance of active transport to school suggests that improvements in WSB or its variants need to be developed and fully evaluated.

  15. Sustainable Transportation

    DEFF Research Database (Denmark)

    Hall, Ralph P.; Gudmundsson, Henrik; Marsden, Greg

    2014-01-01

    The transportation system is the backbone of economic and social progress and the means by which humans access goods and services and connect with one another. Yet, as the scale of transportation activities has grown worldwide, so too have the negative environmental, social, and economic impacts ...... sector’s significant contribution to global challenges such as climate change, it is often said that sustainable development cannot be achieved without sustainable transportation....

  16. Conserved charged amino acid residues in the extracellular region of sodium/iodide symporter are critical for iodide transport activity

    Directory of Open Access Journals (Sweden)

    Liang Ji-An

    2010-11-01

    Full Text Available Abstract Background Sodium/iodide symporter (NIS mediates the active transport and accumulation of iodide from the blood into the thyroid gland. His-226 located in the extracellular region of NIS has been demonstrated to be critical for iodide transport in our previous study. The conserved charged amino acid residues in the extracellular region of NIS were therefore characterized in this study. Methods Fourteen charged residues (Arg-9, Glu-79, Arg-82, Lys-86, Asp-163, His-226, Arg-228, Asp-233, Asp-237, Arg-239, Arg-241, Asp-311, Asp-322, and Asp-331 were replaced by alanine. Iodide uptake abilities of mutants were evaluated by steady-state and kinetic analysis. The three-dimensional comparative protein structure of NIS was further modeled using sodium/glucose transporter as the reference protein. Results All the NIS mutants were expressed normally in the cells and targeted correctly to the plasma membrane. However, these mutants, except R9A, displayed severe defects on the iodide uptake. Further kinetic analysis revealed that mutations at conserved positively charged amino acid residues in the extracellular region of NIS led to decrease NIS-mediated iodide uptake activity by reducing the maximal rate of iodide transport, while mutations at conserved negatively charged residues led to decrease iodide transport by increasing dissociation between NIS mutants and iodide. Conclusions This is the first report characterizing thoroughly the functional significance of conserved charged amino acid residues in the extracellular region of NIS. Our data suggested that conserved charged amino acid residues, except Arg-9, in the extracellular region of NIS were critical for iodide transport.

  17. Atovaquone and quinine anti-malarials inhibit ATP binding cassette transporter activity

    NARCIS (Netherlands)

    Rijpma, S.R.; Heuvel, J.J.; Velden, M. van der; Sauerwein, R.W.; Russel, F.G.; Koenderink, J.B.

    2014-01-01

    BACKGROUND: Therapeutic blood plasma concentrations of anti-malarial drugs are essential for successful treatment. Pharmacokinetics of pharmaceutical compounds are dependent of adsorption, distribution, metabolism, and excretion. ATP binding cassette (ABC) transport proteins are particularly involve

  18. Electron transport system activity of microfouling material: Relationships with biomass parameters

    Digital Repository Service at National Institute of Oceanography (India)

    Bhosle, N.B.; Tulaskar, A.; Wagh, A.B.

    Microfouling material developed on aluminium panels immersed in surface waters of the Dona Paula Bay, Goa India was analysed for biomass (measured as dry weight, organic crabon, protein and chlorophyll @ia@@) and electron transport system actitity...

  19. Nuclear Choline Acetyltransferase Activates Transcription of a High-affinity Choline Transporter*

    OpenAIRE

    Matsuo, Akinori; Bellier, Jean-Pierre; Nishimura, Masaki; YASUHARA, Osamu; Saito, Naoaki; Kimura, Hiroshi

    2010-01-01

    Choline acetyltransferase (ChAT) synthesizes the neurotransmitter, acetylcholine, at cholinergic nerve terminals. ChAT contains nuclear localization signals and is also localized in the nuclei of neural and non-neuronal cells. Nuclear ChAT might have an as yet unidentified function, such as transcriptional regulation. In this study, we investigated the alteration of candidate gene transcription by ChAT. We chose high affinity choline transporter (CHT1) and vesicular acetylcholine transporter ...

  20. The influence of serotonin transporter polymorphisms on cortical activity: A resting EEG study

    Directory of Open Access Journals (Sweden)

    Hong Chen-Jee

    2011-04-01

    Full Text Available Abstract Background The serotonin transporter gene (5-HTT is a key regulator of serotonergic neurotransmission and has been linked to various psychiatric disorders. Among the genetic variants, polymorphisms in the 5-HTT gene-linked polymorphic region (5-HTTLPR and variable-number-of-tandem-repeat in the second intron (5-HTTVNTR have functional consequences. However, their genetic impact on cortical oscillation remains unclear. This study examined the modulatory effects of 5-HTTLPR (L-allele carriers vs. non-carriers and 5-HTTVNTR (10-repeat allele carriers vs. non-carriers polymorphism on regional neural activity in a young female population. Methods Blood samples and resting state eyes-closed electroencephalography (EEG signals were collected from 195 healthy women and stratified into 2 sets of comparisons of 2 groups each: L-allele carriers (N = 91 vs. non-carriers for 5-HTTLPR and 10-repeat allele carriers (N = 25 vs. non-carriers for 5-HTTVNTR. The mean power of 18 electrodes across theta, alpha, beta, gamma, gamma1, and gamma2 frequencies was analyzed. Between-group statistics were performed by an independent t-test, and global trends of regional power were quantified by non-parametric analyses. Results Among 5-HTTVNTR genotypes, 10-repeat allele carriers showed significantly low regional power at gamma frequencies across the brain. We noticed a consistent global trend that carriers with low transcription efficiency of 5-HTT possessed low regional powers, regardless of frequency bands. The non-parametric analyses confirmed this observation, with P values of 3.071 × 10-8 and 1.459 × 10-12 for 5-HTTLPR and 5-HTTVNTR, respectively. Conclusions and Limitations Our analyses showed that genotypes with low 5-HTT activity are associated with less local neural synchronization during relaxation. The implication with respect to genetic vulnerability of 5-HTT across a broad range of psychiatric disorders is discussed. Given the low frequency of 10

  1. Summary report for ITER task - D10: Update and implementation of neutron transport and activation codes and processed libraries

    Energy Technology Data Exchange (ETDEWEB)

    Attaya, H.

    1995-01-01

    The primary goal of this task is to provide the capabilities in the activation code RACC, to treat pulsed operation modes. In addition, it is required that the code utilizes the same spatial mesh and geometrical models as employed in the one or multidimensional neutron transport codes used in ITER design. This would ensure the use of the same neutron flux generated by those codes to calculate the different activation parameters. It is also required to have the capabilities for generating graphical outputs for the calculated activation parameters.

  2. A European perspective on GIS-based walkability and active modes of transport.

    Science.gov (United States)

    Grasser, Gerlinde; van Dyck, Delfien; Titze, Sylvia; Stronegger, Willibald J

    2017-02-01

    The association between GIS-based walkability and walking for transport is considered to be well established in USA and in Australia. Research on the association between walkability and cycling for transport in European cities is lacking. The aim of this study was to test the predictive validity of established walkability measures and to explore alternative walkability measures associated with walking and cycling for transport in a European context. Outcome data were derived from the representative cross-sectional survey ( n  = 843) ‘Radfreundliche Stadt’ of adults in the city of Graz (Austria). GIS-based walkability was measured using both established measures (e.g. gross population density, household unit density, entropy index, three-way intersection density, IPEN walkability index) and alternative measures (e.g. proportion of mixed land use, four-way intersection density, Graz walkability index). ANCOVAs were conducted to examine the adjusted association between walkability measures and outcomes. Household unit density, proportion of mixed land use, three-way intersection density and IPEN walkability index were positively associated with walking for transport, but the other measures were not. All walkability measures were positively associated with cycling for transport. The established walkability measures were applicable to a European city such as Graz. The alternative walkability measures performed well in a European context. Due to measurement issues the association between these walkability measures and walking for transport needs to be investigated further.

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

    Science.gov (United States)

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

    2017-01-03

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

  4. The PP-motif in luminal loop 2 of ZnT transporters plays a pivotal role in TNAP activation.

    Science.gov (United States)

    Fujimoto, Shigeyuki; Tsuji, Tokuji; Fujiwara, Takashi; Takeda, Taka-Aki; Merriman, Chengfeng; Fukunaka, Ayako; Nishito, Yukina; Fu, Dax; Hoch, Eitan; Sekler, Israel; Fukue, Kazuhisa; Miyamae, Yusaku; Masuda, Seiji; Nagao, Masaya; Kambe, Taiho

    2016-09-01

    Secretory and membrane-bound zinc-requiring enzymes are thought to be activated by binding zinc in the early secretory pathway. One such enzyme, tissue-non-specific alkaline phosphatase (TNAP), is activated through a two-step mechanism, via protein stabilization and subsequent enzyme activation through metalation, by ZnT5-ZnT6 heterodimers or ZnT7 homodimers. However, little is known about the molecular basis underlying the activation process. In the present study, we found that the di-proline motif (PP-motif) in luminal loop 2 of ZnT5 and ZnT7 is important for TNAP activation. TNAP activity was significantly reduced in cells lacking ZnT5-ZnT6 heterodimers and ZnT7 homodimers [triple knockout (TKO) cells]. The decreased TNAP activity was restored by expressing hZnT5 with hZnT6 or hZnT7, but significantly less so (almost 90% less) by expressing mutants thereof in which the PP-motif was mutated to alanine (PP-AA). In TKO cells, overexpressed hTNAP was not completely activated, and it was converted less efficiently into the holo form by expressing a PP-AA mutant of hZnT5 with hZnT6, whose defects were not restored by zinc supplementation. The zinc transport activity of hZnT7 was not significantly impaired by the PP-AA mutation, indicating that the PP-motif is involved in the TNAP maturation process, although it does not control zinc transport activity. The PP-motif is highly conserved in ZnT5 and ZnT7 orthologues, and its importance for TNAP activation is conserved in the Caenorhabditis elegans hZnT5 orthologue CDF5. These results provide novel molecular insights into the TNAP activation process in the early secretory pathway.

  5. Calculative activation analysis of the transport rack for CASTOR {sup registered} casks; Berechnung der Aktivierung eines Transportgestells fuer CASTOR {sup registered} -Behaelter

    Energy Technology Data Exchange (ETDEWEB)

    Tittelbach, S. [Wissenschaftlich-Technische Ingenieurberatung GmbH (WTI), Juelich (Germany); Biedermann, R. [GNS Gesellschaft fuer Nuklear-Service mbH, Essen (Germany); Schmidt-Wohlfarth, Y.; Louia, A. [EnBW Kernkraft GmbH, Philippsburg (Germany)

    2011-07-01

    The transport rack for the internal transport of loaded CASTOR {sup registered} casks before the storage in the intermediate storage facility at the site of the NPP Philippsburg is exposed to neutron irradiation from the cask inventory. Using the Monte Carlo code MCNP the activation rates of the transport rack materials are calculated for typical storage times of the casks in the rack. The long-term activation was also calculated for the continuous use of the transport rack over 10 years. Further topics were the dose rate in the near surrounding of the transport rack after long-term activation and finally the disposability of rack components according to the legal regulations. The maximum contact dose rate was calculated to be below 1 micro Sv/h after 10 years of application. The transport rack can be disposed with large safety margins to the radiation protection limits.

  6. In vitro transport activity of the fully assembled MexAB-OprM efflux pump from Pseudomonas aeruginosa

    Science.gov (United States)

    Verchère, Alice; Dezi, Manuela; Adrien, Vladimir; Broutin, Isabelle; Picard, Martin

    2015-04-01

    Antibiotic resistance is a major public health issue and many bacteria responsible for human infections have now developed a variety of antibiotic resistance mechanisms. For instance, Pseudomonas aeruginosa, a disease-causing Gram-negative bacteria, is now resistant to almost every class of antibiotics. Much of this resistance is attributable to multidrug efflux pumps, which are tripartite membrane protein complexes that span both membranes and actively expel antibiotics. Here we report an in vitro procedure to monitor transport by the tripartite MexAB-OprM pump. By combining proteoliposomes containing the MexAB and OprM portions of the complex, we are able to assay energy-dependent substrate translocation in a system that mimics the dual-membrane architecture of Gram-negative bacteria. This assay facilitates the study of pump transport dynamics and could be used to screen pump inhibitors with potential clinical use in restoring therapeutic activity of old antibiotics.

  7. A Double-Ring Algorithm for Modeling Solar Active Regions: Unifying Kinematic Dynamo Models and Surface Flux-Transport Simulations

    CERN Document Server

    Muñoz-Jaramillo, Andrés; Martens, Petrus C H; Yeates, Anthony R

    2010-01-01

    The emergence of tilted bipolar active regions and the dispersal of their flux, mediated via processes such as diffusion, differential rotation and meridional circulation is believed to be responsible for the reversal of the Sun's polar field. This process (commonly known as the Babcock-Leighton mechanism) is usually modeled as a near-surface, spatially distributed $\\alpha$-effect in kinematic mean-field dynamo models. However, this formulation leads to a relationship between polar field strength and meridional flow speed which is opposite to that suggested by physical insight and predicted by surface flux-transport simulations. With this in mind, we present an improved double-ring algorithm for modeling the Babcock-Leighton mechanism based on active region eruption, within the framework of an axisymmetric dynamo model. Using surface flux-transport simulations we first show that an axisymmetric formulation -- which is usually invoked in kinematic dynamo models -- can reasonably approximate the surface flux dy...

  8. Activation of Big Grain1 significantly improves grain size by regulating auxin transport in rice.

    Science.gov (United States)

    Liu, Linchuan; Tong, Hongning; Xiao, Yunhua; Che, Ronghui; Xu, Fan; Hu, Bin; Liang, Chengzhen; Chu, Jinfang; Li, Jiayang; Chu, Chengcai

    2015-09-01

    Grain size is one of the key factors determining grain yield. However, it remains largely unknown how grain size is regulated by developmental signals. Here, we report the identification and characterization of a dominant mutant big grain1 (Bg1-D) that shows an extra-large grain phenotype from our rice T-DNA insertion population. Overexpression of BG1 leads to significantly increased grain size, and the severe lines exhibit obviously perturbed gravitropism. In addition, the mutant has increased sensitivities to both auxin and N-1-naphthylphthalamic acid, an auxin transport inhibitor, whereas knockdown of BG1 results in decreased sensitivities and smaller grains. Moreover, BG1 is specifically induced by auxin treatment, preferentially expresses in the vascular tissue of culms and young panicles, and encodes a novel membrane-localized protein, strongly suggesting its role in regulating auxin transport. Consistent with this finding, the mutant has increased auxin basipetal transport and altered auxin distribution, whereas the knockdown plants have decreased auxin transport. Manipulation of BG1 in both rice and Arabidopsis can enhance plant biomass, seed weight, and yield. Taking these data together, we identify a novel positive regulator of auxin response and transport in a crop plant and demonstrate its role in regulating grain size, thus illuminating a new strategy to improve plant productivity.

  9. Montmorillonite enhanced ciprofloxacin transport in saturated porous media with sorbed ciprofloxacin showing antibiotic activity

    Science.gov (United States)

    Chen, Hao; Gao, Bin; Yang, Liu-Yan; Ma, Lena Q.

    2015-02-01

    Antibiotic ciprofloxacin (CIP) is immobile in the subsurface but it has been frequently detected in the aquatic system. Therefore it is important to investigate the factors impacting CIP's mobilization in aquifer. Laboratory columns packed with sand were used to test colloid-facilitated CIP transport by 1) using kaolinite or montmorillonite to mobilize presorbed-CIP in a column or 2) co-transporting with CIP by pre-mixing them before transport. The Langmuir model showed that CIP sorption by montmorillonite (23 g kg- 1) was 100 times more effective than sand or kaolinite. Even with strong CIP complexation ability to Fe/Al coating on sand surface, montmorillonite promoted CIP transport, but not kaolinite. All presorbed-CIP by sand was mobilized by montmorillonite after 3 pore volumes through co-transporting of CIP with montmorillonite. The majority of CIP was fixed onto the montmorillonite interlayer but still showed inhibition of bacteria growth. Our results suggested that montmorillonite with high CIP sorption ability can act as a carrier to enhance CIP's mobility in aquifer.

  10. Mode shifting in school travel mode: examining the prevalence and correlates of active school transport in Ontario, Canada

    Directory of Open Access Journals (Sweden)

    Buliung Ron

    2011-08-01

    Full Text Available Abstract Background Studies examining the correlates of school transport commonly fail to make the distinction between morning and afternoon school trips. The purpose of this study was to examine the prevalence and correlates of mode shift from passive in the morning to active in the afternoon among elementary and secondary school students in Ontario, Canada. Methods Data were derived from the 2009 cycle of the Ontario Student Drug Use and Health Survey (OSDUHS. 3,633 students in grades 7 through 12 completed self-administered questionnaires. Socio-demographic, behavioural, psychological, and environmental predictors of active school transport (AST were assessed using logistic regression. Results Overall, 47% and 38% of elementary school students reported AST to and from school, respectively. The corresponding figures were 23% and 32% for secondary school students. The prevalence of AST varied temporarily and spatially. There was a higher prevalence of walking/biking found for elementary school students than for secondary school students, and there was an approximate 10% increase in AST in the afternoon. Different correlates of active school transport were also found across elementary and secondary school students. For all ages, students living in urban areas, with a shorter travel time between home and school, and having some input to the decision making process, were more likely to walk to and from school. Conclusions Future research examining AST should continue to make the analytic distinction between the morning and afternoon trip, and control for the moderating effect of age and geography in predicting mode choice. In terms of practice, these variations highlight the need for school-specific travel plans rather than 'one size fits all' interventions in promoting active school transport.

  11. Universal arrhenius temperature activated charge transport in diodes from disordered organic semiconductors.

    Science.gov (United States)

    Craciun, N I; Wildeman, J; Blom, P W M

    2008-02-08

    Charge transport models developed for disordered organic semiconductors predict a non-Arrhenius temperature dependence ln(mu) proportional, variant1/T(2) for the mobility mu. We demonstrate that in space-charge limited diodes the hole mobility (micro(h)) of a large variety of organic semiconductors shows a universal Arrhenius temperature dependence micro(h)(T) = micro(0)exp(-Delta/kT) at low fields, due to the presence of extrinsic carriers from the Ohmic contact. The transport in a range of organic semiconductors, with a variation in room temperature mobility of more than 6 orders of magnitude, is characterized by a universal mobility micro(0) of 30-40 cm(2)/V s. As a result, we can predict the full temperature dependence of their charge transport properties with only the mobility at one temperature known.

  12. Chemical form of selenium affects its uptake, transport, and glutathione peroxidase activity in the human intestinal Caco-2 cell model.

    Science.gov (United States)

    Zeng, Huawei; Jackson, Matthew I; Cheng, Wen-Hsing; Combs, Gerald F

    2011-11-01

    Determining the effect of selenium (Se) chemical form on uptake, transport, and glutathione peroxidase activity in human intestinal cells is critical to assess Se bioavailability at nutritional doses. In this study, we found that two sources of L-selenomethionine (SeMet) and Se-enriched yeast each increased intracellular Se content more effectively than selenite or methylselenocysteine (SeMSC) in the human intestinal Caco-2 cell model. Interestingly, SeMSC, SeMet, and digested Se-enriched yeast were transported at comparable efficacy from the apical to basolateral sides, each being about 3-fold that of selenite. In addition, these forms of Se, whether before or after traversing from apical side to basolateral side, did not change the potential to support glutathione peroxidase (GPx) activity. Although selenoprotein P has been postulated to be a key Se transport protein, its intracellular expression did not differ when selenite, SeMSC, SeMet, or digested Se-enriched yeast was added to serum-contained media. Taken together, our data show, for the first time, that the chemical form of Se at nutritional doses can affect the absorptive (apical to basolateral side) efficacy and retention of Se by intestinal cells; but that, these effects are not directly correlated to the potential to support GPx activity.

  13. SNPs altering ammonium transport activity of human Rhesus factors characterized by a yeast-based functional assay.

    Directory of Open Access Journals (Sweden)

    Aude Deschuyteneer

    Full Text Available Proteins of the conserved Mep-Amt-Rh family, including mammalian Rhesus factors, mediate transmembrane ammonium transport. Ammonium is an important nitrogen source for the biosynthesis of amino acids but is also a metabolic waste product. Its disposal in urine plays a critical role in the regulation of the acid/base homeostasis, especially with an acid diet, a trait of Western countries. Ammonium accumulation above a certain concentration is however pathologic, the cytotoxicity causing fatal cerebral paralysis in acute cases. Alteration in ammonium transport via human Rh proteins could have clinical outcomes. We used a yeast-based expression assay to characterize human Rh variants resulting from non synonymous single nucleotide polymorphisms (nsSNPs with known or unknown clinical phenotypes and assessed their ammonium transport efficiency, protein level, localization and potential trans-dominant impact. The HsRhAG variants (I61R, F65S associated to overhydrated hereditary stomatocytosis (OHSt, a disease affecting erythrocytes, proved affected in intrinsic bidirectional ammonium transport. Moreover, this study reveals that the R202C variant of HsRhCG, the orthologue of mouse MmRhcg required for optimal urinary ammonium excretion and blood pH control, shows an impaired inherent ammonium transport activity. Urinary ammonium excretion was RHcg gene-dose dependent in mouse, highlighting MmRhcg as a limiting factor. HsRhCG(R202C may confer susceptibility to disorders leading to metabolic acidosis for instance. Finally, the analogous R211C mutation in the yeast ScMep2 homologue also impaired intrinsic activity consistent with a conserved functional role of the preserved arginine residue. The yeast expression assay used here constitutes an inexpensive, fast and easy tool to screen nsSNPs reported by high throughput sequencing or individual cases for functional alterations in Rh factors revealing potential causal variants.

  14. Heterocyclic cyclohexanone monocarbonyl analogs of curcumin can inhibit the activity of ATP-binding cassette transporters in cancer multidrug resistance.

    Science.gov (United States)

    Revalde, Jezrael L; Li, Yan; Hawkins, Bill C; Rosengren, Rhonda J; Paxton, James W

    2015-02-01

    Curcumin (CUR) is a phytochemical that inhibits the xenobiotic ABC efflux transporters implicated in cancer multidrug resistance (MDR), such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins 1 and 5 (MRP1 and MRP5). The use of CUR in the clinic however, is complicated by its instability and poor pharmacokinetic profile. Monocarbonyl analogs of CUR (MACs) are compounds without CUR's unstable β-diketone moiety and were reported to have improved stability and in vivo disposition. Whether the MACs can be used as MDR reversal agents is less clear, as the absence of a β-diketone may negatively impact transporter inhibition. In this study, we investigated 23 heterocyclic cyclohexanone MACs for inhibitory effects against P-gp, BCRP, MRP1 and MRP5. Using flow cytometry and resistance reversal assays, we found that many of these compounds inhibited the transport activity of the ABC transporters investigated, often with much greater potency than CUR. Overall the analogs were most effective at inhibiting BCRP and we identified three compounds, A12 (2,6-bis((E)-2,5-dimethoxy-benzylidene)cyclohexanone), A13 (2,6-bis((E)-4-hydroxyl-3-methoxybenzylidene)-cyclohexanone) and B11 (3,5-bis((E)-2-fluoro-4,5-dimethoxybenzylidene)-1-methylpiperidin-4-one), as the most promising BCRP inhibitors. These compounds inhibited BCRP activity in a non-cell line, non-substrate-specific manner. Their inhibition occurred by direct transporter interaction rather than modulating protein or cell surface expression. From these results, we concluded that MACs, such as the heterocyclic cyclohexanone analogs in this study, also have potential as MDR reversal agents and may be superior alternatives to the unstable parent compound, CUR.

  15. SNPs altering ammonium transport activity of human Rhesus factors characterized by a yeast-based functional assay.

    Science.gov (United States)

    Deschuyteneer, Aude; Boeckstaens, Mélanie; De Mees, Christelle; Van Vooren, Pascale; Wintjens, René; Marini, Anna Maria

    2013-01-01

    Proteins of the conserved Mep-Amt-Rh family, including mammalian Rhesus factors, mediate transmembrane ammonium transport. Ammonium is an important nitrogen source for the biosynthesis of amino acids but is also a metabolic waste product. Its disposal in urine plays a critical role in the regulation of the acid/base homeostasis, especially with an acid diet, a trait of Western countries. Ammonium accumulation above a certain concentration is however pathologic, the cytotoxicity causing fatal cerebral paralysis in acute cases. Alteration in ammonium transport via human Rh proteins could have clinical outcomes. We used a yeast-based expression assay to characterize human Rh variants resulting from non synonymous single nucleotide polymorphisms (nsSNPs) with known or unknown clinical phenotypes and assessed their ammonium transport efficiency, protein level, localization and potential trans-dominant impact. The HsRhAG variants (I61R, F65S) associated to overhydrated hereditary stomatocytosis (OHSt), a disease affecting erythrocytes, proved affected in intrinsic bidirectional ammonium transport. Moreover, this study reveals that the R202C variant of HsRhCG, the orthologue of mouse MmRhcg required for optimal urinary ammonium excretion and blood pH control, shows an impaired inherent ammonium transport activity. Urinary ammonium excretion was RHcg gene-dose dependent in mouse, highlighting MmRhcg as a limiting factor. HsRhCG(R202C) may confer susceptibility to disorders leading to metabolic acidosis for instance. Finally, the analogous R211C mutation in the yeast ScMep2 homologue also impaired intrinsic activity consistent with a conserved functional role of the preserved arginine residue. The yeast expression assay used here constitutes an inexpensive, fast and easy tool to screen nsSNPs reported by high throughput sequencing or individual cases for functional alterations in Rh factors revealing potential causal variants.

  16. Metabolic evidence that serosal sodium does not recycle through the active transepithelial transport pathway of toad bladder.

    Science.gov (United States)

    Canessa, M; Labarca, P; Leaf, A

    1976-12-25

    The possibility that sodium from the serosal bathing medium "back diffuses" into the active sodium transport pool within the mucosal epithelial cell of the isolated toad bladder was examined by determining the effect on the metabolism of the tissue of removing sodium from the serosal medium. It was expected that if recycling of serosal sodium did occur through the active transepithelial transport pathway of the isolated toad bladder, removal of sodium from the serosal medium would reduce the rate of CO2 production by the tissue and enhance of stoichiometric ratio of sodium ions transported across the bladder per molecula of sodium transport dependent CO2 produced simultaneously by the bladder (JNa/JCO2). The data revealed no significant change in this ratio (17.19 with serosal sodium and 16.13 after replacing serosal sodium with choline). Further, when transepithelial sodium transport was inhibited (a) by adding amiloride to the mucosal medium, or (b) by removing sodium from the mucosal medium, subsequent removal of sodium from the serosal medium, or (c) addition of ouabain failed to depress the basal rate of CO2 production by the bladder [(a)rate of basal, nontransport related, CO2 production (JbCO2) equals 1.54 +/- 0.52 with serosal sodium and 1.54 +/- 0.37 without serosal sodium; (b) Jb CO2 equals 2.18 +/- 0.21 with serosal sodium and 2.09 +/- 0.21 without serosal sodium; (c) 1.14 +/- 0.26 without ouabain and 1.13 +/- 0.25 with ouabain; unite of JbCO2 are nmoles mg d.w.-1 min-1]. The results support the hypothesis that little, if any, recycling of serosal sodium occurs in the total bladder.

  17. Sociospatial distribution of access to facilities for moderate and vigorous intensity physical activity in Scotland by different modes of transport

    Directory of Open Access Journals (Sweden)

    Lamb Karen E

    2012-07-01

    Full Text Available Abstract Background People living in neighbourhoods of lower socioeconomic status have been shown to have higher rates of obesity and a lower likelihood of meeting physical activity recommendations than their more affluent counterparts. This study examines the sociospatial distribution of access to facilities for moderate or vigorous intensity physical activity in Scotland and whether such access differs by the mode of transport available and by Urban Rural Classification. Methods A database of all fixed physical activity facilities was obtained from the national agency for sport in Scotland. Facilities were categorised into light, moderate and vigorous intensity activity groupings before being mapped. Transport networks were created to assess the number of each type of facility accessible from the population weighted centroid of each small area in Scotland on foot, by bicycle, by car and by bus. Multilevel modelling was used to investigate the distribution of the number of accessible facilities by small area deprivation within urban, small town and rural areas separately, adjusting for population size and local authority. Results Prior to adjustment for Urban Rural Classification and local authority, the median number of accessible facilities for moderate or vigorous intensity activity increased with increasing deprivation from the most affluent or second most affluent quintile to the most deprived for all modes of transport. However, after adjustment, the modelling results suggest that those in more affluent areas have significantly higher access to moderate and vigorous intensity facilities by car than those living in more deprived areas. Conclusions The sociospatial distributions of access to facilities for both moderate intensity and vigorous intensity physical activity were similar. However, the results suggest that those living in the most affluent neighbourhoods have poorer access to facilities of either type that can be reached on foot

  18. New Transportation Technology : Norm Activation Processes and the Intention to Switch to an Electric/Hybrid Vehicle

    OpenAIRE

    Nordlund, A.; Jansson, J.; Westin, K.

    2016-01-01

    Since humans' activities contribute to climate change it is important to change behavior. Switching to a hybrid/plugin/electric vehicle (HEV/PHEV/EV) for personal transport can be one way. In this study the intention to switch to a HEV/PHEV/EV is studied from the theoretical framework of the moral norm-activation theory of altruism (Schwartz, 1977) and the Value-Belief-Norm (VBN) Theory of environmentalism (Stern et al., 1999). Data was collected using a survey to three groups, alternative fu...

  19. Effect of transportation on fecal bacterial communities and fermentative activities in horses: impact of Saccharomyces cerevisiae CNCM I-1077 supplementation.

    Science.gov (United States)

    Faubladier, C; Chaucheyras-Durand, F; da Veiga, L; Julliand, V

    2013-04-01

    This study evaluated the effect of transportation on fecal bacterial communities and activities in horses with or without supplementation of live yeast and attempted to link those effects with changes in blood stress markers. Four mature horses were assigned to a crossover design and fed a basal diet (60:40 forage to concentrate; 1.45% BW on a DM basis), with or without supplementation, of 2 × 10(10) cfu/d of Saccharomyces cerevisiae CNCM I-1077. After a 14-d adaptation to dietary treatments, the 5-d experiment started 1 d before transportation (d -1). At d 0, horses were simultaneously transported in a truck for 2 h. Feces were sampled 4 h after the morning meal of concentrate at d -1, 0 (immediately after transportation), and 3 for enumeration of the main functional bacterial groups and determination of fermentative variables. Within each dietary treatment, feces were pooled before DNA extraction and molecular analysis of the bacterial communities, using temporal temperature gradient electrophoreses (TTGE). Blood samples were collected at the same time for determination of white blood cells (WBC) counts and glucose and total protein concentrations. Regardless of dietary treatment, the neutrophil to lymphocyte ratio increased during transportation (P horses were stressed. In both treatments, TTGE profiles were clearly different before and 3 d after transportation, and the percentage of similarity between profiles at d -1 and 3 was greater in supplemented horses compared with the controls. From d 0 to 3, the molar percentage of propionate increased and total concentration of VFA and the acetate + butyrate to propionate ratio decreased, regardless of dietary treatment (P horses (P = 0.03). Regardless of day of sampling, fecal concentrations of lactate-utilizing bacteria and cellulolytic bacteria were greater in supplemented horses than in control horses (P = 0.04 and 0.08, respectively). Our results indicate that transportation for 2 h disturbed the fecal bacterial

  20. Mixed sand and gravel beaches: accurate measurement of active layer depth and sediment transport volumes using PIT tagged tracer pebbles

    Science.gov (United States)

    Holland, A.; Moses, C.; Sear, D. A.; Cope, S.

    2016-12-01

    As sediments containing significant gravel portions are increasingly used for beach replenishment projects globally, the total number of beaches classified as `mixed sand and gravel' (MSG) increases. Calculations for required replenishment sediment volumes usually assume a uniform layer of sediment transport across and along the beach, but research into active layer (AL) depth has shown variations both across shore and according to sediment size distribution. This study addresses the need for more accurate calculations of sediment transport volumes on MSG beaches by using more precise measurements of AL depth and width, and virtual velocity of tracer pebbles. Variations in AL depth were measured along three main profile lines (from MHWS to MLWN) at Eastoke, Hayling Island (Hampshire, UK). Passive Integrated Transponder (PIT) tagged pebbles were deployed in columns, and their new locations repeatedly surveyed with RFID technology. These data were combined with daily dGPS beach profiles and sediment sampling for detailed analysis of the influence of beach morphodynamics on sediment transport volumes. Data were collected over two consecutive winter seasons: 2014-15 (relatively calm, average wave height sandy lower foreshore reduced the AL to 10% of wave height in this area. The disparity in AL depth across the beach profile indicates that traditional models are not accurately representing bulk sediment transport on MSG beaches. It is anticipated that by improving model inputs, beach managers will be better able to predict necessary volumes and sediment grain size proportions of replenishment material for effective management of MSG beaches.

  1. Universal arrhenius temperature activated charge transport in diodes from disordered organic semiconductors

    NARCIS (Netherlands)

    Craciun, N. I.; Wildeman, J.; Blom, P. W. M.

    2008-01-01

    Charge transport models developed for disordered organic semiconductors predict a non-Arrhenius temperature dependence ln(mu) proportional to 1/T(2) for the mobility mu. We demonstrate that in space-charge limited diodes the hole mobility (mu(h)) of a large variety of organic semiconductors shows a

  2. St. John's Wort constituents modulate P-glycoprotein transport activity at the blood-brain barrier.

    NARCIS (Netherlands)

    Ott, M.; Huls, M.; Cornelius, M.G.; Fricker, G.

    2010-01-01

    PURPOSE: The purpose of this study was to investigate the short-term signaling effects of St. John's Wort (SJW) extract and selected SJW constituents on the blood-brain barrier transporter P-glycoprotein and to describe the role of PKC in the signaling. METHODS: Cultured porcine brain capillary endo

  3. An Active Learning Exercise to Facilitate Understanding of Nephron Function: Anatomy and Physiology of Renal Transporters

    Science.gov (United States)

    Dirks-Naylor, Amie J.

    2016-01-01

    Renal transport is a central mechanism underlying electrolyte homeostasis, acid base balance and other essential functions of the kidneys in human physiology. Thus, knowledge of the anatomy and physiology of the nephron is essential for the understanding of kidney function in health and disease. However, students find this content difficult to…

  4. Carbon Footprint Reduction in Transportation Activity by Emphasizing the Usage of Public Bus Services Among Adolescents

    Science.gov (United States)

    Sukor, Nur Sabahiah Abdul; Khairiyah Basri, Nur; Asmah Hassan, Sitti

    2017-08-01

    Transportation is one of the sectors that contributes to the Greenhouse Gases (GHGs) emissions. In terms of carbon footprint, transportation is among the major contributors of high carbon intensity in the urban area. This study was conducted to reduce the carbon footprint contributed by the transportation sector in Penang Island by emphasizing the use of public buses. Secondary school students were the target group for this study. They were asked to report their daily travel behaviour and fuel consumption in a travel journal. The fuel consumption data from the travel journal were used to calculate each individual’s carbon emission level. After the analyses, the value of carbon emissions was revealed to the students. Next, they were encouraged to use public transport in a motivation session and were asked to record their fuel consumption in the travel journal once again. The results showed that there was a significant difference in fuel consumption before and after the motivation session, as the students preferred to use public buses instead of private vehicles after the motivation session. This indicates that the motivation programme had been successful in creating the awareness towards carbon footprint reduction among the adolescents.

  5. Evidence of active transport (filtration?) of plasma proteins across the capillary walls in muscle and subcutis

    DEFF Research Database (Denmark)

    Noer, Ivan; Lassen, N A

    1978-01-01

    Under slight lymphatic stasis (tilting the body 15 degrees) we measured the arrival of locally injected I-albumin to the plasma pool. From 30 min. to 90 min. after the injection the return rate was zero i.e. local back transport in the two tissues studied viz.muscle and subcutaneous fat is very...

  6. Evidence of active transport (filtration?) of plasma proteins across the capillary walls in muscle and subcutis

    DEFF Research Database (Denmark)

    Noer, Ivan; Lassen, N A

    1979-01-01

    Under slight lymphatic stasis (tilting the body 15 degrees) we measured the arrival of locally injected 131I-albumin in the plasma pool. From 30 min to 90 min after the injection the return rate was zero, i.e. local back transport in the two tissues studied, muscle and subcutaneous fat, is very...

  7. Mechanism of Osmotic Activation of the Quaternary Ammonium Compound Transporter (QacT) of Lactobacillus plantarum

    NARCIS (Netherlands)

    Glaasker, Erwin; Heuberger, Esther H.M.L.; Konings, Wil N.; Poolman, Bert

    1998-01-01

    The accumulation of quaternary ammonium compounds in Lactobacillus plantarum is mediated via a single transport system with a high affinity for glycine betaine (apparent Km of 18 μM) and carnitine and a low affinity for proline (apparent Km of 950 μM) and other analogues. Mutants defective in the

  8. Undergraduate Laboratory Experiment Facilitating Active Learning of Concepts in Transport Phenomena: Experiment with a Subliming Solid

    Science.gov (United States)

    Utgikar, Vivek P.

    2015-01-01

    An experiment based on the sublimation of a solid was introduced in the undergraduate Transport Phenomena course. The experiment required the students to devise their own apparatus and measurement techniques. The theoretical basis, assignment of the experiment, experimental results, and student/instructor observations are described in this paper.…

  9. Universal arrhenius temperature activated charge transport in diodes from disordered organic semiconductors

    NARCIS (Netherlands)

    Craciun, N. I.; Wildeman, J.; Blom, P. W. M.

    2008-01-01

    Charge transport models developed for disordered organic semiconductors predict a non-Arrhenius temperature dependence ln(mu) proportional to 1/T(2) for the mobility mu. We demonstrate that in space-charge limited diodes the hole mobility (mu(h)) of a large variety of organic semiconductors shows a

  10. An Active Learning Exercise to Facilitate Understanding of Nephron Function: Anatomy and Physiology of Renal Transporters

    Science.gov (United States)

    Dirks-Naylor, Amie J.

    2016-01-01

    Renal transport is a central mechanism underlying electrolyte homeostasis, acid base balance and other essential functions of the kidneys in human physiology. Thus, knowledge of the anatomy and physiology of the nephron is essential for the understanding of kidney function in health and disease. However, students find this content difficult to…

  11. Bovine neuronal vesicular glutamate transporter activity is inhibited by ergovaline and other ergopeptines

    Science.gov (United States)

    L-Glutamate (Glu) is the major excitatory neurotransmitter responsible for neurotransmission in the vertebrate central nervous system, including the gastrointestinal tract (GIT) of cattle. Vesicular Glu transporters VGLUT1 and VGLUT2 concentrate (50 mM) Glu (Km = 1 to 4 mM) into synaptic vesicles (S...

  12. Lattice-gas model for active vesicle transport by molecular motors with opposite polarities

    Science.gov (United States)

    Muhuri, Sudipto; Pagonabarraga, Ignacio

    2010-08-01

    We introduce a multispecies lattice-gas model for motor protein driven collective cargo transport on cellular filaments. We use this model to describe and analyze the collective motion of interacting vesicle cargos being carried by oppositely directed molecular motors, moving on a single biofilament. Building on a totally asymmetric exclusion process to characterize the motion of the interacting cargos, we allow for mass exchange with the environment, input, and output at filament boundaries and focus on the role of interconversion rates and how they affect the directionality of the net cargo transport. We quantify the effect of the various different competing processes in terms of nonequilibrium phase diagrams. The interplay of interconversion rates, which allow for flux reversal and evaporation-deposition processes, introduces qualitatively unique features in the phase diagrams. We observe regimes of three-phase coexistence, the possibility of phase re-entrance, and a significant flexibility in how the different phase boundaries shift in response to changes in control parameters. The moving steady-state solutions of this model allows for different possibilities for the spatial distribution of cargo vesicles, ranging from homogeneous distribution of vesicles to polarized distributions, characterized by inhomogeneities or shocks. Current reversals due to internal regulation emerge naturally within the framework of this model. We believe that this minimal model will clarify the understanding of many features of collective vesicle transport, apart from serving as the basis for building more exact quantitative models for vesicle transport relevant to various in vivo situations.

  13. Adrenergic regulation of ion transport across adult alveolar epithelial cells: effects on Cl- channel activation and transport function in cultures with an apical air interface.

    Science.gov (United States)

    Jiang, X; Ingbar, D H; O'Grady, S M

    2001-06-01

    The effect of beta-adrenergic receptor stimulation on Cl- channel activation was investigated in alveolar epithelial cells grown in monolayer culture and in freshly isolated cells. Monolayers cultured under apical air interface conditions exhibited enhanced amiloride-sensitive Na+ transport compared to apical liquid interface monolayers. Amiloride or benzamil inhibited most (66%) of the basal short circuit current (Isc) with half-maximal inhibitory concentration (IC50) values of 0.62 microm and 0.09 microm respectively. Basolateral addition of terbutaline (2 microm) produced a rapid decrease in Isc followed by a slow recovery that exceeded the basal Isc. When Cl- was replaced with methanesulfonate in either intact monolayers or basolateral membrane permeabilized monolayers, the response to terbutaline (2 microm) was completely inhibited. No effect of terbutaline on amiloride-sensitive Na+ current was detected. beta-Adrenergic agonists and 8-chlorothiophenyl cyclic adenosine monophosphate (8-ctp cAMP) directly stimulated a Cl- channel in freshly isolated alveolar epithelial cells. The current was blocked by glibenclamide (100 microm) and had a reversal potential of -22 mV. No increase in amiloride-sensitve current was detected in response to terbutaline or 8-cpt cAMP stimulation. These data support the conclusion that beta-adrenergic agonists produce acute activation of apical Cl- channels and that monolayers maintained under apical air interface conditions exhibit increased Na+ absorption.

  14. Protein Kinase C-Independent Inhibition of Organic Cation Transporter 1 Activity by the Bisindolylmaleimide Ro 31-8220.

    Directory of Open Access Journals (Sweden)

    Abdullah Mayati

    Full Text Available Ro 31-8220 is a potent protein kinase C (PKC inhibitor belonging to the chemical class of bisindolylmaleimides (BIMs. Various PKC-independent effects of Ro 31-8220 have however been demonstrated, including inhibition of the ATP-binding cassette drug transporter breast cancer resistance protein. In the present study, we reported that the BIM also blocks activity of the solute carrier organic cation transporter (OCT 1, involved in uptake of marketed drugs in the liver, in a PKC-independent manner. Ro 31-8220, in contrast to other pan-PKC inhibitors such as staurosporine and chelerythrine, was thus shown to cis-inhibit uptake of the reference OCT1 substrate tetraethylammonium in OCT1-transfected HEK293 cells in a concentration-dependent manner (IC50 = 0.18 μM and without altering membrane expression of OCT1. This blockage of OCT1 was also observed in human hepatic HepaRG cells that constitutionally express OCT1. It likely occurred through a mixed mechanism of inhibition. Ro 31-8220 additionally trans-inhibited TEA uptake in OCT1-transfected HEK293 cells, which likely discards a transport of Ro 31-8220 by OCT1. Besides Ro 31-8220, 7 additional BIMs, including the PKC inhibitor LY 333531, inhibited OCT1 activity, whereas 4 other BIMs were without effect. In silico analysis of structure-activity relationships next revealed that various molecular descriptors, especially 3D-WHIM descriptors related to total size, correspond to key physico-chemical parameters for inhibition of OCT1 activity by BIMs. In addition to activity of OCT1, Ro 31-8220 inhibited those of other organic cation transporters such as multidrug and toxin extrusion protein (MATE 1 and MATE2-K, whereas, by contrast, it stimulated that of OCT2. Taken together, these data extend the nature of cellular off-targets of the BIM Ro 31-8220 to OCT1 and other organic cation transporters, which has likely to be kept in mind when using Ro 31-8220 and other BIMs as PKC inhibitors in experimental or

  15. The response of electron transport mediated by active NADPH dehydrogenase complexes to heat stress in the cyanobacterium Synechocystis 6803

    Institute of Scientific and Technical Information of China (English)

    MA WeiMin; WEI LanZhen; WANG QuanXi

    2008-01-01

    The electron-transport machinery in photosynthetic membranes is known to be very sensitive to heat. In this study, the rate of electron transport (ETR) driven by photosystem Ⅰ (PSI) and photosystem Ⅱ (PSII) during heat stress in the wild-type Synechocystis sp. strain PCC 6803 (WT) and its ndh gene inactivation mutants △ndhB (M55) and △ndhD1/ndhD2 (D1/D2) was simultaneously assessed by using the novel Dual-PAM-100 measuring system. The rate of electron transport driven by the photosystems (ETRPSs) in the WT, M55, and D1/D2 cells incubated at 30℃ and at 55℃ for 10 min was compared. Incubation at 55℃ for 10 min significantly inhibited PSII-driven ETR (ETRPSII) in the WT, M55 and D1/D2 cells, and the extent of inhibition in both the M55 and D1/D2 cells was greater than that in the WT cells. Further, PSI-driven ETR (ETRPSI) was stimulated in both the WT and D1/D2 cells, and this rate was increased to a greater extent in the D1/D2 than in the WT cells. However, ETRPSI was considerably inhibited in the M55 cells. Analysis of the effect of heat stress on ETRPSs with regard to the alterations in the 2 active NDH-1 complexes in the WT, M55, and D1/D2 cells indicated that the active NDH-1 supercomplex and mediumcomplex are essential for alleviating the heat-induced inhibition of ETRPSII and for accelerating the heat-induced stimulation of ETRPSI, respectively. Further, it is believed that these effects are most likely brought about by the electron transport mediated by each of these 2 active NDH-1 complexes.

  16. The response of electron transport mediated by active NADPH dehydrogenase complexes to heat stress in the cyanobacterium Synechocystis 6803

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The electron-transport machinery in photosynthetic membranes is known to be very sensitive to heat. In this study, the rate of electron transport (ETR) driven by photosystem I (PSI) and photosystem II (PSII) during heat stress in the wild-type Synechocystis sp. strain PCC 6803 (WT) and its ndh gene inactiva-tion mutants △ndhB (M55) and △ndhD1/ndhD2 (D1/D2) was simultaneously assessed by using the novel Dual-PAM-100 measuring system. The rate of electron transport driven by the photosystems (ETRPSs) in the WT, M55, and D1/D2 cells incubated at 30℃ and at 55℃ for 10 min was compared. Incubation at 55 ℃ for 10 min significantly inhibited PSII-driven ETR (ETRPSII) in the WT, M55 and D1/D2 cells, and the ex-tent of inhibition in both the M55 and D1/D2 cells was greater than that in the WT cells. Further, PSI-driven ETR (ETRPSI) was stimulated in both the WT and D1/D2 cells, and this rate was increased to a greater extent in the D1/D2 than in the WT cells. However, ETRPSI was considerably inhibited in the M55 cells. Analysis of the effect of heat stress on ETRPSs with regard to the alterations in the 2 active NDH-1 complexes in the WT, M55, and D1/D2 cells indicated that the active NDH-1 supercomplex and medi-umcomplex are essential for alleviating the heat-induced inhibition of ETRPSII and for accelerating the heat-induced stimulation of ETRPSI, respectively. Further, it is believed that these effects are most likely brought about by the electron transport mediated by each of these 2 active NDH-1 complexes.

  17. Real-time, Spatially Resolved Analysis of Serotonin Transporter Activity And Regulation Using the Fluorescent Substrate, ASP+

    Science.gov (United States)

    Oz, M.; Libby, T.; Kivell, B.; Jaligam, V.; Ramamoorthy, S.; Shippenberg, T.S.

    2010-01-01

    The serotonin transporter (SERT) mediates clearance of serotonin from the synapse, thereby, regulating extracellular serotonin concentrations. Radioligand uptake techniques are typically used to assess SERT function in tissue and heterologous expression systems. The need for sufficient protein in samples, however, requires use of homogenate preparations, potentially masking effects limited to specific cell populations. 4-(4-(dimethylamino)-styryl)-N-methylpyridinium (ASP+) is a fluorescent monoamine transporter substrate that has been used for real-time monitoring of dopamine and norepinephrine transporter function in single cells. The present live cell imaging studies examine the utility of ASP+ for quantifying hSERT function in HEK-293 and neuroblastoma cells. We show rapid membrane binding and intracellular ASP+ accumulation in hSERT expressing cells. Accumulation is saturable; dependent on temperature and the presence of sodium and chloride in the media, and attenuated by serotonin. Acute or prolonged exposure of cells to serotonin re-uptake inhibitors produces a concentration-dependent decrease in accumulation. Similar effects are produced by PKC activation whereas p38MAPK activation increases ASP+ accumulation. These data demonstrate the validity of ASP+ as a probe for monitoring SERT function in living cells. Alterations in SERT binding and uptake can be quantified in the same cell and use of a within cell design permits analysis of time-related alterations in SERT function. PMID:20524964

  18. Small GTPase Rab14 down-regulates UT-A1 urea transport activity through enhanced clathrin-dependent endocytosis.

    Science.gov (United States)

    Su, Hua; Liu, Bingchen; Fröhlich, Otto; Ma, Heping; Sands, Jeff M; Chen, Guangping

    2013-10-01

    The UT-A1 urea transporter plays an important role in the urinary concentration mechanism. However, the molecular mechanisms regarding UT-A1 trafficking, endocytosis, and degradation are still unclear. In this study, we identified the small GTPase Rab14 as a binding partner to the C terminus of UT-A1 in a yeast 2-hybrid assay. Interestingly, UT-A1 binding is preferential for the GDP-bound inactive form of Rab14. Coinjection of Rab14 in Xenopus oocytes results in a decrease of UT-A1 urea transport activity, suggesting that Rab14 acts as a negative regulator of UT-A1. We subsequently found that Rab14 reduces the cell membrane expression of UT-A1, as evidenced by cell surface biotinylation. This effect is blocked by chlorpromazine, an inhibitor of the clathrin-mediated endocytic pathway, but not by filipin, an inhibitor of the caveolin-mediated endocytic pathway. In kidney, Rab14 is mainly expressed in IMCD epithelial cells with a pattern identical to UT-A1 expression. Consistent with its role in participating in clathrin-mediated endocytosis, Rab14 localizes in nonlipid raft microdomains and codistributes with Rab5, a marker of the clathrin-mediated endocytic pathway. Taken together, our study suggests that Rab14, as a novel UT-A1 partner, may have an important regulatory function for UT-A1 urea transport activity in the kidney inner medulla.

  19. IGF-I regulates redox status in breast cancer cells by activating the amino acid transport molecule xC-.

    Science.gov (United States)

    Yang, Yuzhe; Yee, Douglas

    2014-04-15

    Insulin-like growth factors (IGF) stimulate cell growth in part by increasing amino acid uptake. xCT (SLC7A11) encodes the functional subunit of the cell surface transport system xC(-), which mediates cystine uptake, a pivotal step in glutathione synthesis and cellular redox control. In this study, we show that IGF-I regulates cystine uptake and cellular redox status by activating the expression and function of xCT in estrogen receptor-positive (ER(+)) breast cancer cells by a mechanism that relies on the IGF receptor substrate-1 (IRS-1). Breast cancer cell proliferation mediated by IGF-I was suppressed by attenuating xCT expression or blocking xCT activity with the pharmacologic inhibitor sulfasalazine (SASP). Notably, SASP sensitized breast cancer cells to inhibitors of the type I IGF receptor (IGF-IR) in a manner reversed by the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine. Thus, IGF-I promoted the proliferation of ER(+) breast cancer cells by regulating xC(-) transporter function to protect cancer cells from ROS in an IRS-1-dependent manner. Our findings suggest that inhibiting xC(-) transporter function may synergize with modalities that target the IGF-IR to heighten their therapeutic effects.

  20. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria

    Science.gov (United States)

    Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

    2014-01-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UEUA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA, suggesting that SUA decreased as a result of the increase in the UEUA. The increase in UEUA was correlated with an increase in urinary d-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UEUA is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and d-glucose. It was observed that the efflux of [14C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm d-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [14C]UA by oocytes was cis-inhibited by 100 mm d-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UEUA could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose. PMID:25044127

  1. Excess Weapons Plutonium Disposition: Plutonium Packaging, Storage and Transportation and Waste Treatment, Storage and Disposal Activities

    Energy Technology Data Exchange (ETDEWEB)

    Jardine, L J; Borisov, G B

    2004-07-21

    A fifth annual Excess Weapons Plutonium Disposition meeting organized by Lawrence Livermore National Laboratory (LLNL) was held February 16-18, 2004, at the State Education Center (SEC), 4 Aerodromnya Drive, St. Petersburg, Russia. The meeting discussed Excess Weapons Plutonium Disposition topics for which LLNL has the US Technical Lead Organization responsibilities. The technical areas discussed included Radioactive Waste Treatment, Storage, and Disposal, Plutonium Oxide and Plutonium Metal Packaging, Storage and Transportation and Spent Fuel Packaging, Storage and Transportation. The meeting was conducted with a conference format using technical presentations of papers with simultaneous translation into English and Russian. There were 46 Russian attendees from 14 different Russian organizations and six non-Russian attendees, four from the US and two from France. Forty technical presentations were made. The meeting agenda is given in Appendix B and the attendance list is in Appendix C.

  2. A Review of some Critical Assumptions in the Relationship between Economic Activity and Freight Transport

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Kveiborg, Ole

    2004-01-01

    . We find that it is necessary to account for changing composition of production across industries, but that the commodity mix within each industry safely can be regarded as constant. Changing value densities account for almost a third of transport growth; however, this is attributable to the first......A number of conversion factors are often needed when projecting freight transport growth, depending on the level of detail of the projection. Here we investigate conversion factors that convert production in fixed prices in different industries into production of different commodities and further...... year of data. Otherwise, value densities could be regarded as constant with our data. Finally, we find that using import or export data to impute value densities induces unacceptably large errors....

  3. A review of some critical assumptions in the relationship between economic activity and freight transport

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Kveiborg, Ole

    2004-01-01

    . We find that it is necessary to account for changing composition of production across industries, but that the commodity mix within each industry safely can be regarded as constant. Changing value densities account for almost a third of transport growth; however, this is attributable to the first......A number of conversion factors are often needed when projecting freight transport growth, depending on the level of detail of the projection. Here we investigate conversion factors that convert production in fixed prices in different industries into production of different commodities and further...... year of data. Otherwise, value densities could be regarded as constant with our data. Finally, we find that using import or export data to impute value densities induces unacceptably large errors....

  4. Retinoids activate proton transport by the uncoupling proteins UCP1 and UCP2.

    OpenAIRE

    1999-01-01

    In mammalian brown adipose tissue, thermogenesis is explained by uncoupling mitochondrial respiration from ATP synthesis. Uncoupling protein-1 (UCP1) is responsible for this uncoupled state, because it allows proton re-entry into the matrix and thus dissipates the proton gradient generated by the respiratory chain. Proton transport by UCP1 is regulated negatively by nucleotides and positively by fatty acids. Adrenergic stimulation of brown adipocytes stimulates lipolysis and therefore enhance...

  5. Perenosins: a new class of anion transporter with anti-cancer activity.

    Science.gov (United States)

    Van Rossom, Wim; Asby, Daniel J; Tavassoli, Ali; Gale, Philip A

    2016-03-07

    A new class of anion transporter named 'perenosins' consisting of a pyrrole linked through an imine to either an indole, benzimidazole or indazole is reported. The indole containing members of the perenosin family function as effective transmembrane Cl(-)/NO3(-) antiporters and HCl cotransporters in a manner similar to the prodigiosenes. The compounds reduce the viability of MDA-MB-231 and MCF-7.

  6. A Review of some Critical Assumptions in the Relationship between Economic Activity and Freight Transport

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Kveiborg, Ole

    2004-01-01

    A number of conversion factors are often needed when projecting freight transport growth, depending on the level of detail of the projection. Here we investigate conversion factors that convert production in fixed prices in different industries into production of different commodities and further...... year of data. Otherwise, value densities could be regarded as constant with our data. Finally, we find that using import or export data to impute value densities induces unacceptably large errors....

  7. The effect of active warming in prehospital trauma care during road and air ambulance transportation - a clinical randomized trial

    Directory of Open Access Journals (Sweden)

    Naredi Peter

    2011-10-01

    Full Text Available Abstract Background Prevention and treatment of hypothermia by active warming in prehospital trauma care is recommended but scientifical evidence of its effectiveness in a clinical setting is scarce. The objective of this study was to evaluate the effect of additional active warming during road or air ambulance transportation of trauma patients. Methods Patients were assigned to either passive warming with blankets or passive warming with blankets with the addition of an active warming intervention using a large chemical heat pad applied to the upper torso. Ear canal temperature, subjective sensation of cold discomfort and vital signs were monitored. Results Mean core temperatures increased from 35.1°C (95% CI; 34.7-35.5°C to 36.0°C (95% CI; 35.7-36.3°C (p Conclusions In mildly hypothermic trauma patients, with preserved shivering capacity, adequate passive warming is an effective treatment to establish a slow rewarming rate and to reduce cold discomfort during prehospital transportation. However, the addition of active warming using a chemical heat pad applied to the torso will significantly improve thermal comfort even further and might also reduce the cold induced stress response. Trial Registration ClinicalTrials.gov: NCT01400152

  8. Dendritic transport element of human arc mRNA confers RNA degradation activity in a translation-dependent manner.

    Science.gov (United States)

    Ninomiya, Kensuke; Ohno, Mutsuhito; Kataoka, Naoyuki

    2016-11-01

    Localization of mRNA in neuronal cells is a critical process for spatiotemporal regulation of gene expression. Cytoplasmic localization of mRNA is often conferred by transport elements in 3' untranslated region (UTR). Activity-regulated cytoskeleton-associated protein (arc) mRNA is one of the localizing mRNAs in neuronal cells, and its localization is mediated by dendritic targeting element (DTE). As arc mRNA has introns in its 3' UTR, it was thought that arc mRNA is a natural target of nonsense-mediated mRNA decay (NMD). Here, we show that DTE in human arc 3' UTR has destabilizing activity of RNA independent of NMD pathway. DTE alone was able to cause instability of the reporter mRNA and this degradation was dependent on translation. Our results indicate that DTE has dual activity in mRNA transport and degradation, which suggests the novel spatiotemporal regulation mechanism of activity-dependent degradation of the mRNA.

  9. Active Transport of Phosphorylated Carbohydrates Promotes Intestinal Colonization and Transmission of a Bacterial Pathogen.

    Directory of Open Access Journals (Sweden)

    Brandon Sit

    2015-08-01

    Full Text Available Efficient acquisition of extracellular nutrients is essential for bacterial pathogenesis, however the identities and mechanisms for transport of many of these substrates remain unclear. Here, we investigate the predicted iron-binding transporter AfuABC and its role in bacterial pathogenesis in vivo. By crystallographic, biophysical and in vivo approaches, we show that AfuABC is in fact a cyclic hexose/heptose-phosphate transporter with high selectivity and specificity for a set of ubiquitous metabolites (glucose-6-phosphate, fructose-6-phosphate and sedoheptulose-7-phosphate. AfuABC is conserved across a wide range of bacterial genera, including the enteric pathogens EHEC O157:H7 and its murine-specific relative Citrobacter rodentium, where it lies adjacent to genes implicated in sugar sensing and acquisition. C. rodentium ΔafuA was significantly impaired in an in vivo murine competitive assay as well as its ability to transmit infection from an afflicted to a naïve murine host. Sugar-phosphates were present in normal and infected intestinal mucus and stool samples, indicating that these metabolites are available within the intestinal lumen for enteric bacteria to import during infection. Our study shows that AfuABC-dependent uptake of sugar-phosphates plays a critical role during enteric bacterial infection and uncovers previously unrecognized roles for these metabolites as important contributors to successful pathogenesis.

  10. Active Transport of Phosphorylated Carbohydrates Promotes Intestinal Colonization and Transmission of a Bacterial Pathogen

    Science.gov (United States)

    Sit, Brandon; Crowley, Shauna M.; Bhullar, Kirandeep; Lai, Christine Chieh-Lin; Tang, Calvin; Hooda, Yogesh; Calmettes, Charles; Khambati, Husain; Ma, Caixia; Brumell, John H.; Schryvers, Anthony B.; Vallance, Bruce A.; Moraes, Trevor F.

    2015-01-01

    Efficient acquisition of extracellular nutrients is essential for bacterial pathogenesis, however the identities and mechanisms for transport of many of these substrates remain unclear. Here, we investigate the predicted iron-binding transporter AfuABC and its role in bacterial pathogenesis in vivo. By crystallographic, biophysical and in vivo approaches, we show that AfuABC is in fact a cyclic hexose/heptose-phosphate transporter with high selectivity and specificity for a set of ubiquitous metabolites (glucose-6-phosphate, fructose-6-phosphate and sedoheptulose-7-phosphate). AfuABC is conserved across a wide range of bacterial genera, including the enteric pathogens EHEC O157:H7 and its murine-specific relative Citrobacter rodentium, where it lies adjacent to genes implicated in sugar sensing and acquisition. C. rodentium ΔafuA was significantly impaired in an in vivo murine competitive assay as well as its ability to transmit infection from an afflicted to a naïve murine host. Sugar-phosphates were present in normal and infected intestinal mucus and stool samples, indicating that these metabolites are available within the intestinal lumen for enteric bacteria to import during infection. Our study shows that AfuABC-dependent uptake of sugar-phosphates plays a critical role during enteric bacterial infection and uncovers previously unrecognized roles for these metabolites as important contributors to successful pathogenesis. PMID:26295949

  11. Novel propulsion of active colloids by self-induced field gradients with potential for cargo transport

    Science.gov (United States)

    Boymelgreen, Alicia; Yossifon, Gilad; Miloh, Touvia

    2016-11-01

    Localized electric field gradients, induced by the dual symmetry-breaking of an asymmetric particle adjacent to a wall are shown to potentially drive particle motion, even in a uniform field. Since the driving gradient is induced by the particle itself, we have termed this propulsion mechanism "self-dielectrophoresis" (sDEP), to distinguish from traditional DEP where the driving non-uniform field is externally fixed and particle direction is restricted. It is also shown that sDEP driven particles are natural cargo carriers, since the localized gradients can also trap and release targets selectively and on demand. This phenomenon is specifically characterized for Gold-Polystyrene Janus spheres, including the establishment of a non-dimensional parameter marking the critical frequency at which sDEP dominates low-frequency ICEP- evidenced by a reversal in particle direction. Additionally we demonstrate that localized gradients can transform the translating Janus particles into an externally controlled, mobile floating electrode with the ability to collect, transport and release a target sample a target 1/50 of its size. It is also shown that calculated control of the frequency enables selective sorting and transport - if the driving frequency is aligned with the positive-DEP (pDEP) response of a specific "target" and negative-DEP (nDEP) of any other contaminants, only the former will be transported with the Janus sphere. ISF,BSF,RBNI.

  12. Regulation of the high-affinity choline transporter activity and trafficking by its association with cholesterol-rich lipid rafts.

    Science.gov (United States)

    Cuddy, Leah K; Winick-Ng, Warren; Rylett, Rebecca Jane

    2014-03-01

    The sodium-coupled, hemicholinium-3-sensitive, high-affinity choline transporter (CHT) is responsible for transport of choline into cholinergic nerve terminals from the synaptic cleft following acetylcholine release and hydrolysis. In this study, we address regulation of CHT function by plasma membrane cholesterol. We show for the first time that CHT is concentrated in cholesterol-rich lipid rafts in both SH-SY5Y cells and nerve terminals from mouse forebrain. Treatment of SH-SY5Y cells expressing rat CHT with filipin, methyl-β-cyclodextrin (MβC) or cholesterol oxidase significantly decreased choline uptake. In contrast, CHT activity was increased by addition of cholesterol to membranes using cholesterol-saturated MβC. Kinetic analysis of binding of [(3)H]hemicholinium-3 to CHT revealed that reducing membrane cholesterol with MβC decreased both the apparent binding affinity (KD) and maximum number of binding sites (Bmax ); this was confirmed by decreased plasma membrane CHT protein in lipid rafts in cell surface protein biotinylation assays. Finally, the loss of cell surface CHT associated with lipid raft disruption was not because of changes in CHT internalization. In summary, we provide evidence that CHT association with cholesterol-rich rafts is critical for transporter function and localization. Alterations in plasma membrane cholesterol cholinergic nerve terminals could diminish cholinergic transmission by reducing choline availability for acetylcholine synthesis. The sodium-coupled choline transporter CHT moves choline into cholinergic nerve terminals to serve as substrate for acetylcholine synthesis. We show for the first time that CHT is concentrated in cholesterol-rich lipid rafts, and decreasing membrane cholesterol significantly reduces both choline uptake activity and cell surface CHT protein levels. CHT association with cholesterol-rich rafts is critical for its function, and alterations in plasma membrane cholesterol could diminish cholinergic

  13. Reduction of CO2 emission from transportation activities in the area of Pasar Besar in Malang City

    Science.gov (United States)

    Sari, K. E.; Sulistyo, D. E.; Utomo, D. M.

    2017-06-01

    The number of vehicles increases every year. Where vehicles are the largest contributor to air pollution up to 70%-80%, while 20%-30% caused by industrial activities. The increasing number of vehicles which perform movements will result in more emissions of vehicles in the free air of the city. Traffic is also influenced by the presence of land use. One of the types of land use that have considerable influence against the movement of traffic is trade. Along with the development of transport activities in the area of Pasar Besar Malang city (the Biggest Traditional Market in Malang), it will cause problems such as traffic jam and air pollution. Therefore, the need for proper handling of the problem of traffic jam and air pollution in the area of Pasar Besar that is to identify the performance of road traffic around area of Pasar Besar and calculate the quantity of CO2 emissions based on the footprint of transport on the area of Pasar Besar. Where is produced that level of service roads on its way around area of Pasar Besar have an average value between LOS A and B, while the quantity of CO2 emissions is based on the footprint of transport on area of Pasar Besar that is amounting to 4,551.42 tons/year. The magnitude of the emissions have exceeded the standard of composition in the air so that the need for recommendations. Recommendations in this research is in the form of simulated users of private vehicle redirects to public transportation based on the level of willingness to switch by the users of private vehicles. The selected simulation that is the second of four simulations with the output of emissions amounting to 3,952.91 tons/year in which can reduce emissions amounting to 598.51 tons/year or approximately 13.15%.

  14. Analysis of different research activities and description of parties within the Swedish Knowledge Centre for Renewable Transportation Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Lundgren, Joakim [Bio4Energy, Luleaa (Sweden); Wallberg, Ola [Lund Univ., Lund (Sweden)

    2012-07-01

    The Swedish Knowledge Centre for Renewable Transportation Fuels (f3) is a nationwide centre, which through cooperation and a systems approach will contribute to the development of sustainable fossil free fuels for transportation. The centre will, through joint efforts by the centre partners, perform syntheses of current research about the production of renewable fuels as well as supplementing research, such as comparative systems analyses of fuels, processes, raw materials and plant design. f3 provides a platform for collaboration between centre partners, with a common vision of sustainable fuels for transportation and common objectives. The centre partners include Sweden's most active universities and research institutes within the field, as well as a number of highly relevant industrial companies. New fuels will be an important component of a strategy to reduce both greenhouse gas emissions and our dependence on petroleum. The Swedish Government has established a vision for the Swedish transport industry to function without fossil fuels by 2030. Such a development requires a concerted response, with participation from all stake holders. Swedish researchers in various disciplines and at various colleges and institutes have a unique breadth and they are at the forefront in several areas of knowledge appropriate for a centre for renewable fuels. Through collaboration, f3 should help to link engineering and systems research and communicate results and conclusions from these research efforts. Within the f3 centre, several parties with different research activities are represented. This document is a snapshot of the different parties at the end of 2011 where the stake holders are described and their current research is highlighted. Also, the different projects conducted by the parties have been categorized and presented at the end of the document.

  15. Methane efflux from marine sediments in passive and active margins: Estimations from bioenergetic reaction-transport simulations

    Science.gov (United States)

    Dale, A. W.; Van Cappellen, P.; Aguilera, D. R.; Regnier, P.

    2008-01-01

    A simplified version of a kinetic-bioenergetic reaction model for anaerobic oxidation of methane (AOM) in marine sediments [Dale, A.W., Regnier, P., Van Cappellen, P., 2006. Bioenergetic controls on anaerobic oxidation of methane (AOM) in coastal marine sediments: a theoretical analysis. Am. J. Sci. 306, 246-294.] is used to assess the impact of transport processes on biomass distributions, AOM rates and methane release fluxes from the sea floor. The model explicitly represents the functional microbial groups and the kinetic and bioenergetic limitations of the microbial metabolic pathways involved in AOM. Model simulations illustrate the dominant control exerted by the transport regime on the activity and abundance of AOM communities. Upward fluid flow at active seep systems restricts AOM to a narrow subsurface reaction zone and sustains high rates of methane oxidation. In contrast, pore-water transport dominated by molecular diffusion leads to deeper and broader zones of AOM, characterized by much lower rates and biomasses. Under steady-state conditions, less than 1% of the upward dissolved methane flux reaches the water column, irrespective of the transport regime. However, a sudden increase in the advective flux of dissolved methane, for example as a result of the destabilization of methane hydrates, causes a transient efflux of methane from the sediment. The benthic efflux of dissolved methane is due to the slow growth kinetics of the AOM community and lasts on the order of 60 years. This time window is likely too short to allow for a significant escape of pore-water methane following a large scale gas hydrate dissolution event such as the one that may have accompanied the Paleocene/Eocene Thermal Maximum (PETM).

  16. Potential role of tyrosine hydroxylase in the loss of psychostimulant effect of amphetamine under conditions of impaired dopamine transporter activity.

    Science.gov (United States)

    Janenaite, Egle; Vengeliene, Valentina; Bespalov, Anton; Behl, Berthold

    2017-09-15

    Amphetamine and methylphenidate are known to have stimulatory effect in healthy subjects but not in humans with attention deficit hyperactivity disorder and in rodents with impaired dopamine transporter (DAT) function. This phenomenon is called the paradoxical calming effect of psychostimulants. It has been previously demonstrated that psychostimulants may regulate the enzymatic activity of tyrosine hydroxylase (TH). Hence, the objective of the present study was to determine whether the lack of activity-stimulating effects of amphetamine in hyperactive rats is associated with changes in TH activity. To model hyperactivity in rats, acute administration of DAT inhibitor GBR12909 was used. Changes in TH activity, assessed as L-DOPA accumulation and TH phosphorylation levels, were measured in amphetamine treated rats with or without pretreatment with GBR12909. Our results showed that amphetamine treatment alone increased locomotor activity in rats, whereas pretreatment of rats with GBR12909 counteracted this effect, a finding consistent with the paradoxical calming effect. GBR12909, while having no effect on its own, blocked amphetamine-induced elevation of TH activity in dorsal striatum and nucleus accumbens, measured as increased tissue L-DOPA concentration. However, the phosphorylation levels of TH were not affected by treatment with amphetamine, GBR12909 or the combination of both. Our findings indicate that other mechanisms than phosphorylation-regulated TH activity changes are responsible for the paradoxical calming effect of amphetamine under conditions of impaired DAT activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Functional, structural and phylogenetic analysis of domains underlying the Al-sensitivity of the aluminium-activated malate/anion transporter, TaALMT1

    Science.gov (United States)

    TaALMT1 (Triticum aestivum Aluminum Activated Malate Transporter) is the founding member of a novel gene family of anion transporters (ALMTs) that mediate the efflux of organic acids. A small subgroup of root-localized ALMTs, including TaALMT1, is physiologically associated with in planta aluminum (...

  18. Meta-analysis: a functional polymorphism in the gene encoding for activity of the serotonin transporter protein is not associated with the irritable bowel syndrome.

    NARCIS (Netherlands)

    Kerkhoven, L.A.S. van; Laheij, R.J.F.; Jansen, J.B.M.J.

    2007-01-01

    BACKGROUND: Serotonin is associated with symptoms of the irritable bowel syndrome, its action is terminated by the serotonin transporter protein. AIM: To assess the association between a functional polymorphism in the gene encoding for activity of the serotonin transporter protein and the irritable

  19. Biophysics of active vesicle transport, an intermediate step that couples excitation and exocytosis of serotonin in the neuronal soma.

    Directory of Open Access Journals (Sweden)

    Francisco F De-Miguel

    Full Text Available Transmitter exocytosis from the neuronal soma is evoked by brief trains of high frequency electrical activity and continues for several minutes. Here we studied how active vesicle transport towards the plasma membrane contributes to this slow phenomenon in serotonergic leech Retzius neurons, by combining electron microscopy, the kinetics of exocytosis obtained from FM1-43 dye fluorescence as vesicles fuse with the plasma membrane, and a diffusion equation incorporating the forces of local confinement and molecular motors. Electron micrographs of neurons at rest or after stimulation with 1 Hz trains showed cytoplasmic clusters of dense core vesicles at 1.5±0.2 and 3.7±0.3 µm distances from the plasma membrane, to which they were bound through microtubule bundles. By contrast, after 20 Hz stimulation vesicle clusters were apposed to the plasma membrane, suggesting that transport was induced by electrical stimulation. Consistently, 20 Hz stimulation of cultured neurons induced spotted FM1-43 fluorescence increases with one or two slow sigmoidal kinetics, suggesting exocytosis from an equal number of vesicle clusters. These fluorescence increases were prevented by colchicine, which suggested microtubule-dependent vesicle transport. Model fitting to the fluorescence kinetics predicted that 52-951 vesicles/cluster were transported along 0.60-6.18 µm distances at average 11-95 nms(-1 velocities. The ATP cost per vesicle fused (0.4-72.0, calculated from the ratio of the ΔG(process/ΔG(ATP, depended on the ratio of the traveling velocity and the number of vesicles in the cluster. Interestingly, the distance-dependence of the ATP cost per vesicle was bistable, with low energy values at 1.4 and 3.3 µm, similar to the average resting distances of the vesicle clusters, and a high energy barrier at 1.6-2.0 µm. Our study confirms that active vesicle transport is an intermediate step for somatic serotonin exocytosis by Retzius neurons and provides a

  20. Biophysics of active vesicle transport, an intermediate step that couples excitation and exocytosis of serotonin in the neuronal soma.

    Science.gov (United States)

    De-Miguel, Francisco F; Santamaría-Holek, Iván; Noguez, Paula; Bustos, Carlos; Hernández-Lemus, Enrique; Rubí, J Miguel

    2012-01-01

    Transmitter exocytosis from the neuronal soma is evoked by brief trains of high frequency electrical activity and continues for several minutes. Here we studied how active vesicle transport towards the plasma membrane contributes to this slow phenomenon in serotonergic leech Retzius neurons, by combining electron microscopy, the kinetics of exocytosis obtained from FM1-43 dye fluorescence as vesicles fuse with the plasma membrane, and a diffusion equation incorporating the forces of local confinement and molecular motors. Electron micrographs of neurons at rest or after stimulation with 1 Hz trains showed cytoplasmic clusters of dense core vesicles at 1.5±0.2 and 3.7±0.3 µm distances from the plasma membrane, to which they were bound through microtubule bundles. By contrast, after 20 Hz stimulation vesicle clusters were apposed to the plasma membrane, suggesting that transport was induced by electrical stimulation. Consistently, 20 Hz stimulation of cultured neurons induced spotted FM1-43 fluorescence increases with one or two slow sigmoidal kinetics, suggesting exocytosis from an equal number of vesicle clusters. These fluorescence increases were prevented by colchicine, which suggested microtubule-dependent vesicle transport. Model fitting to the fluorescence kinetics predicted that 52-951 vesicles/cluster were transported along 0.60-6.18 µm distances at average 11-95 nms(-1) velocities. The ATP cost per vesicle fused (0.4-72.0), calculated from the ratio of the ΔG(process)/ΔG(ATP), depended on the ratio of the traveling velocity and the number of vesicles in the cluster. Interestingly, the distance-dependence of the ATP cost per vesicle was bistable, with low energy values at 1.4 and 3.3 µm, similar to the average resting distances of the vesicle clusters, and a high energy barrier at 1.6-2.0 µm. Our study confirms that active vesicle transport is an intermediate step for somatic serotonin exocytosis by Retzius neurons and provides a quantitative method

  1. Down-Regulation of the Na+-Coupled Phosphate Transporter NaPi-IIa by AMP-Activated Protein Kinase

    Directory of Open Access Journals (Sweden)

    Miribane Dërmaku-Sopjani

    2013-11-01

    Full Text Available Background/Aims: The Na+-coupled phosphate transporter NaPi-IIa is the main carrier accomplishing renal tubular phosphate reabsorption. It is driven by the electrochemical Na+ gradient across the apical cell membrane, which is maintained by Na+ extrusion across the basolateral cell membrane through the Na+/K+ ATPase. The operation of NaPi-IIa thus requires energy in order to avoid cellular Na+ accumulation and K+ loss with eventual decrease of cell membrane potential, Cl- entry and cell swelling. Upon energy depletion, early inhibition of Na+-coupled transport processes may delay cell swelling and thus foster cell survival. Energy depletion is sensed by the AMP-activated protein kinase (AMPK, a serine/threonine kinase stimulating several cellular mechanisms increasing energy production and limiting energy utilization. The present study explored whether AMPK influences the activity of NAPi-IIa. Methods: cRNA encoding NAPi-IIa was injected into Xenopus oocytes with or without additional expression of wild-type AMPK (AMPKα1-HA+AMPKβ1-Flag+AMPKγ1-HA, of inactive AMPKαK45R (AMPKα1K45R+AMPKβ1-Flag+AMPKγ1-HA or of constitutively active AMPKγR70Q (AMPKα1-HA+AMPKβ1-Flag+AMPKγ1R70Q. NaPi-IIa activity was estimated from phosphate-induced current in dual electrode voltage clamp experiments. Results: In NaPi-IIa-expressing, but not in water-injected Xenopus oocytes, the addition of phosphate (1 mM to the extracellular bath solution generated a current (Ip, which was significantly decreased by coexpression of wild-type AMPK and of AMPKγR70Q but not of AMPKαK45R. The phosphate-induced current in NaPi-IIa- and AMPK-expressing Xenopus ooocytes was significantly increased by AMPK inhibitor Compound C (20 µM. Kinetic analysis revealed that AMPK significantly decreased the maximal transport rate. Conclusion: The AMP-activated protein kinase AMPK is a powerful regulator of NaPi-IIa and thus of renal tubular phosphate transport.

  2. Plant Transporter Identification

    DEFF Research Database (Denmark)

    Larsen, Bo

    Membrane transport proteins (transporters) play a critical role for numerous biological processes, by controlling the movements of ions and molecules in and out of cells. In plants, transporters thus function as gatekeepers between the plant and its surrounding environment and between organs......, tissues, cells and intracellular compartments. Since plants are highly compartmentalized organisms with complex transportation infrastructures, they consequently have many transporters. However, the vast majority of predicted transporters have not yet been experimentally verified to have transport...... activity. This project contains a review of the implemented methods, which have led to plant transporter identification, and present our progress on creating a high-throughput functional genomics transporter identification platform....

  3. Plant Transporter Identification

    DEFF Research Database (Denmark)

    Larsen, Bo

    Membrane transport proteins (transporters) play a critical role for numerous biological processes, by controlling the movements of ions and molecules in and out of cells. In plants, transporters thus function as gatekeepers between the plant and its surrounding environment and between organs......, tissues, cells and intracellular compartments. Since plants are highly compartmentalized organisms with complex transportation infrastructures, they consequently have many transporters. However, the vast majority of predicted transporters have not yet been experimentally verified to have transport...... activity. This project contains a review of the implemented methods, which have led to plant transporter identification, and present our progress on creating a high-throughput functional genomics transporter identification platform....

  4. Quantitative transporter proteomics by liquid chromatography with tandem mass spectrometry: addressing methodologic issues of plasma membrane isolation and expression-activity relationship.

    Science.gov (United States)

    Kumar, Vineet; Prasad, Bhagwat; Patilea, Gabriela; Gupta, Anshul; Salphati, Laurent; Evers, Raymond; Hop, Cornelis E C A; Unadkat, Jashvant D

    2015-02-01

    To predict transporter-mediated drug disposition using physiologically based pharmacokinetic models, one approach is to measure transport activity and relate it to protein expression levels in cell lines (overexpressing the transporter) and then scale these to via in vitro to in vivo extrapolation (IVIVE). This approach makes two major assumptions. First, that the expression of the transporter is predominantly in the plasma membrane. Second, that there is a linear correlation between expression level and activity of the transporter protein. The present study was conducted to test these two assumptions. We evaluated two commercially available kits that claimed to separate plasma membrane from other cell membranes. The Qiagen Qproteome kit yielded very little protein in the fraction purported to be the plasma membrane. The Abcam Phase Separation kit enriched the plasma membrane but did not separate it from other intracellular membranes. For the Abcam method, the expression level of organic anion-transporting polypeptides (OATP) 1B1/2B1 and breast cancer resistance protein (BCRP) proteins in all subcellular fractions isolated from cells or human liver tissue tracked that of Na⁺-K⁺ ATPase. Assuming that Na⁺-K⁺ ATPase is predominantly located in the plasma membrane, these data suggest that the transporters measured are also primarily located in the plasma membrane. Using short hairpin RNA, we created clones of cell lines with varying degrees of OATP1B1 or BCRP expression level. In these clones, transport activity of OATP1B1 or BCRP was highly correlated with protein expression level (r² > 0.9). These data support the use of transporter expression level data and activity data from transporter overexpressing cell lines for IVIVE of transporter-mediated disposition of drugs.

  5. Evaluation of Hylife-II and Sombrero using 175- and 566- group neutron transport and activation cross sections

    Energy Technology Data Exchange (ETDEWEB)

    Cullen, D; Latkowski, J; Sanz, J

    1999-06-18

    Recent modifications to the TART Monte Carlo neutron and photon transport code enable calculation of 566-group neutron spectra. This expanded group structure represents a significant improvement over the 50- and 175-group structures that have been previously available. To support use of this new capability, neutron activation cross section libraries have been created in the 175- and 566-group structures starting from the FENDL/A-2.0 pointwise data. Neutron spectra have been calculated for the first walls of the HYLIFE-II and SOMBRERO inertial fusion energy power plant designs and have been used in subsequent neutron activation calculations. The results obtained using the two different group structures are compared to each other as well as to those obtained using a 175-group version of the EAF3.1 activation cross section library.

  6. Evaluation of HYLIFE-II and Sombrero using 175- and 566-group neutron transport and activation cross sections

    CERN Document Server

    Latkowski, J F; Sanz, J

    2000-01-01

    Recent modifications to the TART Monte Carlo neutron and photon transport code allow enable calculation of 566-group neutron spectra. This expanded group structure represents a significant improvement over the 50- and 175-group structures that have been previously available. To support use of this new capability, neutron activation cross-section libraries have been created in the 175- and 566-group structures starting from the FENDL/A-2.0 pointwise data. Neutron spectra have been calculated for the first walls of the HYLIFE-II and Sombrero inertial fusion energy power plant designs and have been used in subsequent neutron activation calculations. The results obtained using the two different group structures are compared with each other as well as to those obtained using a 175-group version of the EAF3.1 activation cross-section library.

  7. Role of NADH/NAD+ transport activity and glycogen store on skeletal muscle energy metabolism during exercise: in silico studies.

    Science.gov (United States)

    Li, Yanjun; Dash, Ranjan K; Kim, Jaeyeon; Saidel, Gerald M; Cabrera, Marco E

    2009-01-01

    Skeletal muscle can maintain ATP concentration constant during the transition from rest to exercise, whereas metabolic reaction rates may increase substantially. Among the key regulatory factors of skeletal muscle energy metabolism during exercise, the dynamics of cytosolic and mitochondrial NADH and NAD+ have not been characterized. To quantify these regulatory factors, we have developed a physiologically based computational model of skeletal muscle energy metabolism. This model integrates transport and reaction fluxes in distinct capillary, cytosolic, and mitochondrial domains and investigates the roles of mitochondrial NADH/NAD+ transport (shuttling) activity and muscle glycogen concentration (stores) during moderate intensity exercise (60% maximal O2 consumption). The underlying hypothesis is that the cytosolic redox state (NADH/NAD+) is much more sensitive to a metabolic disturbance in contracting skeletal muscle than the mitochondrial redox state. This hypothesis was tested by simulating the dynamic metabolic responses of skeletal muscle to exercise while altering the transport rate of reducing equivalents (NADH and NAD+) between cytosol and mitochondria and muscle glycogen stores. Simulations with optimal parameter estimates showed good agreement with the available experimental data from muscle biopsies in human subjects. Compared with these simulations, a 20% increase (or approximately 20% decrease) in mitochondrial NADH/NAD+ shuttling activity led to an approximately 70% decrease (or approximately 3-fold increase) in cytosolic redox state and an approximately 35% decrease (or approximately 25% increase) in muscle lactate level. Doubling (or halving) muscle glycogen concentration resulted in an approximately 50% increase (or approximately 35% decrease) in cytosolic redox state and an approximately 30% increase (or approximately 25% decrease) in muscle lactate concentration. In both cases, changes in mitochondrial redox state were minimal. In conclusion, the

  8. Transport and Application of Heat-Activated Persulfate for In-situ Chemical Oxidation of Residual Trichloroethylene

    Science.gov (United States)

    Quig, L.; Johnson, G. R.

    2015-12-01

    Persulfate ISCO has been shown to treat a wide range of contaminants. While persulfate ISCO can be tailored to site and pollutant specific characteristics (e.g., activation via energy or catalysis), thermal activation of persulfate is particularly promising as it can be easily controlled and requires no additional reagents. A mechanistic study of the physical and chemical processes controlling the effectiveness of this remedial approach is not well documented in the literature with much therein focused on reactions in batch systems. The purpose of this research was twofold. Initial studies characterized the overall transport behavior of unactivated and thermally-activated persulfate (20, 60, and 90°C) in one-dimensional soil column systems. Finally, experiments were conducted to investigate persulfate ISCO as a remedial approach for residual-phase trichloroethylene (TCE). At all activation temperatures investigated, persulfate exhibited ideal transport behavior in miscible displacement experiments. Moment analysis of persulfate ion breakthrough curves indicated negligible interaction of persulfate with the natural sandy material. Persulfate ISCO for residual-phase TCE was characterized at two flow rates, 0.2 mL/min and 0.5 mL/min, resulting in two degrees of persulfate activation, 39.5% and 24.6%, respectively. Both ISCO soil column systems showed an initial, long-term plateau in effluent TCE concentrations indicating steady-state dissolution of pure phase TCE. Observed effluent concentrations decreased after 75 and 100 pore volumes (normalized for the measured residual NAPL fraction) compared to 110 pore volumes in the control study. Pseudo first-order reaction rate constants for the decreasing TCE concentrations equaled 0.063/hr and 0.083/hr, respectively, compared to 0.041/hr for the control. Moment analysis of the complete dissolution of TCE in the persulfate/activated persulfate remediation systems indicated approximately 33% oxidation of TCE mass present. By

  9. Functional fluo-3/AM assay on P-glycoprotein transport activity in L1210/VCR cells by confocal microscopy.

    Science.gov (United States)

    Orlický, J; Sulová, Z; Dovinová, I; Fiala, R; Zahradníková, A; Breier, A

    2004-09-01

    Multidrug resistance (MDR) phenotype of L1210/VCR cell line, acquired by selection for vincristine (VCR), is predominantly mediated by P-glycoprotein (Pgp). Calcein/AM (Cal) was recently described as a fluorescent substrate for Pgp and may be used for measuring of transport activity of Pgp. Expression of Pgp in the cells prevents them to be loaded with the fluorescent marker. To detect the activity of Pgp, verapamil (Ver) or cyclosporine A (CsA) has to be used as Pgp inhibitors. Multidrug resistance protein (MRP), another drug efflux pump, may be inhibited by probenecid (Pro), i.e, the inhibitor of a wide variety of anion transporters. Ver, but not Pro, is able to induce the loading of L1210/CR cells by Cal that is measurable by fluorescence-activated cell sorter (FACS). Another dye, fluo-3/AM (F-3), has a similar behaviour like Cal. Using confocal microscopy we have proved that L1210/VCR cells, in contrast to parental sensitive cells, are not loaded with F-3. Marking of cells with the dye can be achieved using inhibitors of Pgp like Ver or CsA but not by Pro. These results indicate that F-3 is usable for detection of Pgp function in various MDR tissue cells.

  10. Glutamine deprivation enhances antitumor activity of 3-bromopyruvate through the stabilization of monocarboxylate transporter-1.

    Science.gov (United States)

    Cardaci, Simone; Rizza, Salvatore; Filomeni, Giuseppe; Bernardini, Roberta; Bertocchi, Fabio; Mattei, Maurizio; Paci, Maurizio; Rotilio, Giuseppe; Ciriolo, Maria Rosa

    2012-09-01

    Anticancer drug efficacy might be leveraged by strategies to target certain biochemical adaptations of tumors. Here we show how depriving cancer cells of glutamine can enhance the anticancer properties of 3-bromopyruvate, a halogenated analog of pyruvic acid. Glutamine deprival potentiated 3-bromopyruvate chemotherapy by increasing the stability of the monocarboxylate transporter-1, an effect that sensitized cells to metabolic oxidative stress and autophagic cell death. We further elucidated mechanisms through which resistance to chemopotentiation by glutamine deprival could be circumvented. Overall, our findings offer a preclinical proof-of-concept for how to employ 3-bromopyruvate or other monocarboxylic-based drugs to sensitize tumors to chemotherapy.

  11. System data communication structures for active-control transport aircraft, volume 2

    Science.gov (United States)

    Hopkins, A. L.; Martin, J. H.; Brock, L. D.; Jansson, D. G.; Serben, S.; Smith, T. B.; Hanley, L. D.

    1981-01-01

    The application of communication structures to advanced transport aircraft are addressed. First, a set of avionic functional requirements is established, and a baseline set of avionics equipment is defined that will meet the requirements. Three alternative configurations for this equipment are then identified that represent the evolution toward more dispersed systems. Candidate communication structures are proposed for each system configuration, and these are compared using trade off analyses; these analyses emphasize reliability but also address complexity. Multiplex buses are recognized as the likely near term choice with mesh networks being desirable for advanced, highly dispersed systems.

  12. Experimental investigation of the vortical activity in the close wake of a simplified military transport aircraft

    Science.gov (United States)

    Bury, Yannick; Jardin, Thierry; Klöckner, Andreas

    2013-05-01

    This paper focuses on the experimental characterization of the vortex structures that develop in the aft fuselage region and in the wake of a simplified geometry of a military transport aircraft. It comes within the framework of the military applications of airflow influence on airdrop operations. This work relies on particle image velocimetry measurements combined with a vortex-tracking approach. Complex vortex dynamics is revealed, in terms of vortex positions, intensities, sizes, shapes and fluctuation levels, for both closed and opened cargo-door and ramp airdrop configurations.

  13. Butyrate activates the monocarboxylate transporter MCT4 expression in breast cancer cells and enhances the antitumor activity of 3-bromopyruvate.

    Science.gov (United States)

    Queirós, Odília; Preto, Ana; Pacheco, António; Pinheiro, Céline; Azevedo-Silva, João; Moreira, Roxana; Pedro, Madalena; Ko, Young H; Pedersen, Peter L; Baltazar, Fátima; Casal, Margarida

    2012-02-01

    Most malignant tumors exhibit the Warburg effect, which consists in increased glycolysis rates with production of lactate, even in the presence of oxygen. Monocarboxylate transporters (MCTs), maintain these glycolytic rates, by mediating the influx and/or efflux of lactate and are overexpressed in several cancer cell types. The lactate and pyruvate analogue 3-bromopyruvate (3-BP) is an inhibitor of the energy metabolism, which has been proposed as a specific antitumor agent. In the present study, we aimed at determining the effect of 3-BP in breast cancer cells and evaluated the putative role of MCTs on this effect. Our results showed that the three breast cancer cell lines used presented different sensitivities to 3-BP: ZR-75-1 ER (+)>MCF-7 ER (+)>SK-BR-3 ER (-). We also demonstrated that 3-BP reduced lactate production, induced cell morphological alterations and increased apoptosis. The effect of 3-BP appears to be cytotoxic rather than cytostatic, as a continued decrease in cell viability was observed after removal of 3-BP. We showed that pre-incubation with butyrate enhanced significantly 3-BP cytotoxicity, especially in the most resistant breast cancer cell line, SK-BR-3. We observed that butyrate treatment induced localization of MCT1 in the plasma membrane as well as overexpression of MCT4 and its chaperone CD147. Our results thus indicate that butyrate pre-treatment potentiates the effect of 3-BP, most probably by increasing the rates of 3-BP transport through MCT1/4. This study supports the potential use of butyrate as adjuvant of 3-BP in the treatment of breast cancer resistant cells, namely ER (-).

  14. Inositol hexakisphosphate kinase 1 (IP6K1) activity is required for cytoplasmic dynein-driven transport

    Science.gov (United States)

    Chanduri, Manasa; Rai, Ashim; Malla, Aushaq Bashir; Wu, Mingxuan; Fiedler, Dorothea; Mallik, Roop; Bhandari, Rashna

    2016-01-01

    Inositol pyrophosphates, such as diphosphoinositol pentakisphosphate (IP7), are conserved eukaryotic signaling molecules that possess pyrophosphate and monophosphate moieties. Generated predominantly by inositol hexakisphosphate kinases (IP6Ks), inositol pyrophosphates can modulate protein function by posttranslational serine pyrophosphorylation. Here, we report inositol pyrophosphates as novel regulators of cytoplasmic dynein-driven vesicle transport. Mammalian cells lacking IP6K1 display defects in dynein-dependent trafficking pathways, including endosomal sorting, vesicle movement, and Golgi maintenance. Expression of catalytically active but not inactive IP6K1 reverses these defects, suggesting a role for inositol pyrophosphates in these processes. Endosomes derived from slime mold lacking inositol pyrophosphates also display reduced dynein-directed microtubule transport. We demonstrate that Ser51 in the dynein intermediate chain (IC) is a target for pyrophosphorylation by IP7, and this modification promotes the interaction of the IC N-terminus with the p150Glued subunit of dynactin. IC–p150Glued interaction is decreased, and IC recruitment to membranes is reduced in cells lacking IP6K1. Our study provides the first evidence for the involvement of IP6Ks in dynein function and proposes that inositol pyrophosphate-mediated pyrophosphorylation may act as a regulatory signal to enhance dynein-driven transport. PMID:27474409

  15. Physical, Hydraulic, and Transport Properties of Sediments and Engineered Materials Associated with Hanford Immobilized Low-Activity Waste

    Energy Technology Data Exchange (ETDEWEB)

    Rockhold, Mark L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zhang, Z. F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Meyer, Philip D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Thomle, Jonathan N. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-02-28

    Current plans for treatment and disposal of immobilized low-activity waste (ILAW) from Hanford’s underground waste storage tanks include vitrification and storage of the glass waste form in a nearsurface disposal facility. This Integrated Disposal Facility (IDF) is located in the 200 East Area of the Hanford Central Plateau. Performance assessment (PA) of the IDF requires numerical modeling of subsurface flow and reactive transport processes over very long periods (thousands of years). The models used to predict facility performance require parameters describing various physical, hydraulic, and transport properties. This report provides updated estimates of physical, hydraulic, and transport properties and parameters for both near- and far-field materials, intended for use in future IDF PA modeling efforts. Previous work on physical and hydraulic property characterization for earlier IDF PA analyses is reviewed and summarized. For near-field materials, portions of this document and parameter estimates are taken from an earlier data package. For far-field materials, a critical review is provided of methodologies used in previous data packages. Alternative methods are described and associated parameters are provided.

  16. Exogenous FABP4 increases breast cancer cell proliferation and activates the expression of fatty acid transport proteins.

    Science.gov (United States)

    Guaita-Esteruelas, Sandra; Bosquet, Alba; Saavedra, Paula; Gumà, Josep; Girona, Josefa; Lam, Eric W-F; Amillano, Kepa; Borràs, Joan; Masana, Lluís

    2017-01-01

    Adipose tissue plays an important role in tumor progression, because it provides nutrients and adipokines to proliferating cells. Fatty acid binding protein 4 (FABP4) is a key adipokine for fatty acid transport. In metabolic pathologies, plasma levels of FABP4 are increased. However, the role of this circulating protein is unknown. Recent studies have demonstrated that FABP4 might have a role in tumor progression, but the molecular mechanisms involved are still unclear. In this study, we analysed the role of eFABP4 (exogenous FABP4) in breast cancer progression. MCF-7 and MDA-MB-231 breast cancer cells did not express substantial levels of FABP4 protein, but intracellular FABP4 levels increased after eFABP4 incubation. Moreover, eFABP4 enhanced the proliferation of these breast cancer cells but did not have any effect on MCF-7 and MDA-MB-231 cell migration. Additionally, eFABP4 induced the AKT and MAPK signaling cascades in breast cancer cells, and the inhibition of these pathways reduced the eFBAP4-mediated cell proliferation. Interestingly, eFABP4 treatment in MCF-7 cells increased levels of the transcription factor FoxM1 and the fatty acid transport proteins CD36 and FABP5. In summary, we showed that eFABP4 plays a key role in tumor proliferation and activates the expression of fatty acid transport proteins in MCF-7 breast cancer cells. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Stimulation of vesicular monoamine transporter 2 activity by DJ-1 in SH-SY5Y cells

    OpenAIRE

    Ishikawa, Shizuma; Tanaka, Yuki; Takahashi-Niki, Kazuko; Niki, Takeshi; Ariga, Hiroyoshi; Iguchi-Ariga, Sanae M. M.

    2012-01-01

    Loss-of-functional mutation in the DJ-1 gene causes a subset of familial Parkinson's disease. The mechanism underlying DJ-1-related selective vulnerability in the dopaminergic pathway is, however, not known. Dopamine is synthesized by two enzymes and then packed into synaptic vesicles by vesicular monoamine transporter 2 (VMAT2). In this study, we found that knockdown of DJ-1 expression reduced the levels of mRNA and protein of VMAT2, resulting in reduced VMAT2 activity. Co-immunoprecipitatio...

  18. Preparation, characterization, biological activity, and transport study of polystyrene based calcium–barium phosphate composite membrane

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Mohammad Mujahid Ali; Rafiuddin,, E-mail: rafi_amu@rediffmail.com

    2013-10-15

    Calcium–barium phosphate (CBP) composite membrane with 25% polystyrene was prepared by co-precipitation method. Scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transformed infrared (FTIR), and Thermogravimetric analysis (TGA) were used to characterize the membrane. The membrane was found to be crystalline in nature with consistent arrangement of particles and no indication of visible cracks. The electrical potentials measured across the composite membrane in contact with univalent electrolytes (KCl, NaCl and LiCl), have been found to increase with decrease in concentrations. Thus the membrane was found to be cation-selective. Transport properties of developed membranes may be utilized for the efficient desalination of saline water and more importantly demineralization process. The antibacterial study of this composite membrane shows good results for killing the disease causing bacteria along with waste water treatment. Highlights: • Transport properties of composite membrane are evaluated. • The composite membrane was found to be stable in all media. • TMS method is used for electrochemical characterization. • The membrane was found to be cation selective. • The order of surface charge density was found to be LiCl < NaCl < KCl.

  19. ACTIVE MEASURES AS PART OF DIALOGUE MARKETING PROMOTING THE USE OF PUBLIC TRANSPORT IN RURAL AREAS

    Directory of Open Access Journals (Sweden)

    Roman KLEMENTSCHITZ

    2015-12-01

    Full Text Available The SmartMove project is working to advance innovative marketing and mobility solutions in eight rural and peripheral European regions and is co-funded by the Intelligent Energy Europe Programme of the European Union. Through tailor-made strategies, it aims to provide information and encourage people to use public transport in their region. Sparsely populated rural areas in Europe are facing tremendous social changes due to shrinking and ageing populations. Because of the scattered settlement structure in these areas, the public transport network density is low and service frequency is often poor. The problems are exacerbated by increasing private car use, which, in a vicious circle, leads to further reductions in services. However, simple tools such as dialogue marketing and minor adjustments to scheduling can help change people’s perceptions. Dialogue marketing techniques have already been shown to increase passenger numbers by as much as 10 to 15 percent. Greater demand leads to higher revenues, making it possible to improve the system and attract even more passengers, turning the vicious circle into a positive loop.

  20. A subset of annular lipids is linked to the flippase activity of an ABC transporter.

    Science.gov (United States)

    Bechara, Chérine; Nöll, Anne; Morgner, Nina; Degiacomi, Matteo T; Tampé, Robert; Robinson, Carol V

    2015-03-01

    Lipids are critical components of membranes that could affect the properties of membrane proteins, yet the precise compositions of lipids surrounding membrane-embedded protein complexes is often difficult to discern. Here we report that, for the heterodimeric ABC transporter TmrAB, the extent of delipidation can be controlled by timed exposure to detergent. We subsequently characterize the cohort of endogenous lipids that are extracted in contact with the membrane protein complex, and show that with prolonged delipidation the number of neutral lipids is reduced in favour of their negatively charged counterparts. We show that lipid A is retained by the transporter and that the extent of its binding decreases during the catalytic cycle, implying that lipid A release is linked to adenosine tri-phosphate hydrolysis. Together, these results enable us to propose that a subset of annular lipids is invariant in composition, with negatively charged lipids binding tightly to TmrAB, and imply a role for this exporter in glycolipid translocation.

  1. Schisandra chinensis regulates drug metabolizing enzymes and drug transporters via activation of Nrf2-mediated signaling pathway

    Directory of Open Access Journals (Sweden)

    He JL

    2014-12-01

    Full Text Available Jin-Lian He,1 Zhi-Wei Zhou,2,3 Juan-Juan Yin,2 Chang-Qiang He,1 Shu-Feng Zhou,2,3 Yang Yu1 1College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, Guizhou, People’s Republic of China Abstract: Drug metabolizing enzymes (DMEs and drug transporters are regulated via epigenetic, transcriptional, posttranscriptional, and translational and posttranslational modifications. Phase I and II DMEs and drug transporters play an important role in the disposition and detoxification of a large number of endogenous and exogenous compounds. The nuclear factor (erythroid-derived 2-like 2 (Nrf2 is a critical regulator of a variety of important cytoprotective genes that are involved in disposition and detoxification of xenobiotics. Schisandra chinensis (SC is a commonly used traditional Chinese herbal medicine that has been primarily used to protect the liver because of its potent antioxidative and anti-inflammatory activities. SC can modulate some DMEs and drug transporters, but the underlying mechanisms are unclear. In this study, we aimed to explore the role of Nrf2 in the regulatory effect of SC extract (SCE on selected DMEs and drug transporters in human hepatocellular liver carcinoma cell line (HepG2 cells. The results showed that SCE, schisandrin A, and schisandrin B significantly increased the expression of NAD(PH: Nicotinamide Adenine Dinucleotide Phosphate-oxidase or:quinone oxidoreductase 1, heme oxygenase-1, glutamate–cysteine ligase, and glutathione S-transferase A4 at both transcriptional and posttranscriptional levels. Incubation of HepG2 cells with SCE resulted in a significant

  2. Characterization of a Chinese hamster-human hybrid cell line with increased system L amino acid transport activity.

    Science.gov (United States)

    Lobaton, C D; Moreno, A; Oxender, D L

    1984-03-01

    We have studied leucine transport in several Chinese hamster-human hybrid cell lines obtained by fusion of a temperature-sensitive line of Chinese hamster ovary cells, ts025C1, and normal human leukocytes. A hybrid cell line exhibiting a twofold increase in L-leucine uptake over that in the parental cell line was found. This hybrid cell line, 158CnpT-1, was temperature resistant, whereas the parental Chinese hamster ovary mutant, ts025C1, contained a temperature-sensitive leucyl-tRNA synthetase mutation. An examination of the different amino acid transport systems in this hybrid cell line revealed a specific increase of system L activity with no significant changes in systems A and ASC. The Vmax for L-leucine uptake exhibited by the hybrid 158CnpT-1 was twice that in the CHO parental mutant, ts025C1. Cytogenetic analysis showed that the hybrid 158CnpT-1 contains four complete human chromosomes (numbers 4, 5, 10, and 21) and three interspecific chromosomal translocations in a total complement of 34 chromosomes. Biochemical and cytogenetic analysis of segregant clones obtained from hybrid 158CnpT-1 showed that the primary temperature resistance and high system L transport phenotypes can be segregated from this hybrid independently. The loss of the primary temperature resistance was associated with the loss of the human chromosome 5, as previously reported by other laboratories, whereas the loss of the high leucine transport phenotype, which is associated with a lesser degree of temperature resistance, was correlated with the loss of human chromosome 20.

  3. Salvinorin A inhibits colonic transit and neurogenic ion transport in mice by activating kappa-opioid and cannabinoid receptors.

    Science.gov (United States)

    Fichna, J; Schicho, R; Andrews, C N; Bashashati, M; Klompus, M; McKay, D M; Sharkey, K A; Zjawiony, J K; Janecka, A; Storr, M A

    2009-12-01

    The major active ingredient of the plant Salvia divinorum, salvinorin A (SA) has been used to treat gastrointestinal (GI) symptoms. As the action of SA on the regulation of colonic function is unknown, our aim was to examine the effects of SA on mouse colonic motility and secretion in vitro and in vivo. The effects of SA on GI motility were studied using isolated preparations of colon, which were compared with preparations from stomach and ileum. Colonic epithelial ion transport was evaluated using Ussing chambers. Additionally, we studied GI motility in vivo by measuring colonic propulsion, gastric emptying, and upper GI transit. Salvinorin A inhibited contractions of the mouse colon, stomach, and ileum in vitro, prolonged colonic propulsion and slowed upper GI transit in vivo. Salvinorin A had no effect on gastric emptying in vivo. Salvinorin A reduced veratridine-, but not forskolin-induced epithelial ion transport. The effects of SA on colonic motility in vitro were mediated by kappa-opioid receptors (KORs) and cannabinoid (CB) receptors, as they were inhibited by the antagonists nor-binaltorphimine (KOR), AM 251 (CB(1) receptor) and AM 630 (CB(2) receptor). However, in the colon in vivo, the effects were largely mediated by KORs. The effects of SA on veratridine-mediated epithelial ion transport were inhibited by nor-binaltorphimine and AM 630. Salvinorin A slows colonic motility in vitro and in vivo and influences neurogenic ion transport. Due to its specific regional action, SA or its derivatives may be useful drugs in the treatment of lower GI disorders associated with increased GI transit and diarrhoea.

  4. Transport of Schisandra chinensis extract and its biologically-active constituents across Caco-2 cell monolayers - an in-vitro model of intestinal transport.

    Science.gov (United States)

    Madgula, Vamsi L M; Avula, Bharathi; Choi, Young W; Pullela, Srinivas V; Khan, Ikhlas A; Walker, Larry A; Khan, Shabana I

    2008-03-01

    We have determined the intestinal transport of Schisandra chinensis extract and its lignans (gomisin A, gomisin N and schisandrin C) in the Caco-2 cell monolayer model. The transport across monolayers was examined for 2 h in absorptive and secretory directions. Quantitation of lignans was performed by HPLC. Out of the three lignans, gomisin A exhibited bi-directional transport, with P(app) values in the range of 25-29 x 10(-6) cm s(-1), indicating a passive diffusion. Gomisin N, mixture and Schisandra extract displayed a higher transport in the secretory direction with efflux ratios in the range of 2.2-5.2. The efflux was decreased in the presence of inhibitors of multidrug resistance protein (MRP) transporter (MK-571) and P-glycoprotein (verapamil) indicating a possible involvement of an efflux pump and MRP in the transport of Schisandra lignans. Poor transport of schisandrin C was observed which could not be quantitated. The permeability of gomisin A in the isolated form was significantly different compared with the mixture or extract.

  5. Synthetic cathinone MDPV downregulates glutamate transporter subtype I (GLT-1) and produces rewarding and locomotor-activating effects that are reduced by a GLT-1 activator.

    Science.gov (United States)

    Gregg, Ryan A; Hicks, Callum; Nayak, Sunil U; Tallarida, Christopher S; Nucero, Paul; Smith, Garry R; Reitz, Allen B; Rawls, Scott M

    2016-09-01

    Synthetic cathinones produce dysregulation of monoamine systems, but their effects on the glutamate system and the influence of glutamate on behavioral effects related to cathinone abuse are unknown. A principal regulator of glutamate homeostasis is glutamate transporter subtype 1 (GLT-1), an astrocytic protein that clears glutamate from the extracellular space and influences behavioral effects of established psychostimulants. We hypothesized that repeated administration of the synthetic cathinone, MDPV (3,4-methylenedioxypyrovalerone), would affect GLT-1 expression in the corticolimbic circuit, and that a GLT-1 activator (ceftriaxone, CTX) would reduce rewarding and locomotor-stimulant effects of MDPV in rats. GLT-1 protein expression in the nucleus accumbens (NAcc), but not prefrontal cortex (PFC), was decreased following withdrawal (2, 5 and 10 days) from repeated MDPV treatment, but not immediately after the last MDPV injection. CTX (200 mg/kg) pretreatment did not affect acute locomotor activation produced by MDPV (0.5, 1, 3 mg/kg). However, CTX (200 mg/kg) administered during a 7-day MDPV treatment paradigm attenuated the development of MDPV-induced sensitization of repetitive movements in rats challenged with MDPV following 11 days of drug abstinence. Pretreatment with CTX (200 mg/kg) during a 4-day MDPV (2 mg/kg) conditioned place preference (CPP) paradigm reduced the development of place preference produced by MDPV. The present data demonstrate dysregulation of corticolimbic glutamate transport systems during withdrawal from chronic MDPV exposure, and show that a GLT-1 transporter activator disrupts behavioral effects of MDPV that are related to synthetic cathinone abuse.

  6. Impact of redox-active polymer molecular weight on the electrochemical properties and transport across porous separators in nonaqueous solvents.

    Science.gov (United States)

    Nagarjuna, Gavvalapalli; Hui, Jingshu; Cheng, Kevin J; Lichtenstein, Timothy; Shen, Mei; Moore, Jeffrey S; Rodríguez-López, Joaquín

    2014-11-19

    Enhancing the ionic conductivity across the electrolyte separator in nonaqueous redox flow batteries (NRFBs) is essential for improving their performance and enabling their widespread utilization. Separating redox-active species by size exclusion without greatly impeding the transport of supporting electrolyte is a potentially powerful alternative to the use of poorly performing ion-exchange membranes. However, this strategy has not been explored possibly due to the lack of suitable redox-active species that are easily varied in size, remain highly soluble, and exhibit good electrochemical properties. Here we report the synthesis, electrochemical characterization, and transport properties of redox-active poly(vinylbenzyl ethylviologen) (RAPs) with molecular weights between 21 and 318 kDa. The RAPs reported here show very good solubility (up to at least 2.0 M) in acetonitrile and propylene carbonate. Ultramicroelectrode voltammetry reveals facile electron transfer with E1/2 ∼ -0.7 V vs Ag/Ag(+)(0.1 M) for the viologen 2+/+ reduction at concentrations as high as 1.0 M in acetonitrile. Controlled potential bulk electrolysis indicates that 94-99% of the nominal charge on different RAPs is accessible and that the electrolysis products are stable upon cycling. The dependence of the diffusion coefficient on molecular weight suggests the adequacy of the Stokes-Einstein formalism to describe RAPs. The size-selective transport properties of LiBF4 and RAPs across commercial off-the-shelf (COTS) separators such as Celgard 2400 and Celgard 2325 were tested. COTS porous separators show ca. 70 times higher selectivity for charge balancing ions (Li(+)BF4(-)) compared to high molecular weight RAPs. RAPs rejection across these separators showed a strong dependence on polymer molecular weight as well as the pore size; the rejection increased with both increasing polymer molecular weight and reduction in pore size. Significant rejection was observed even for rpoly/rpore (polymer

  7. Glutamate transporter activity promotes enhanced Na+/K+-ATPase -mediated extracellular K+ management during neuronal activity

    DEFF Research Database (Denmark)

    Larsen, Brian R; Holm, Rikke; Vilsen, Bente;

    2016-01-01

    , in addition, Na+ /K+ -ATPase-mediated K+ clearance could be governed by astrocytic [Na+ ]i . During most neuronal activity, glutamate is released in the synaptic cleft and is re-absorbed by astrocytic Na+ -coupled glutamate transporters, thereby elevating [Na+ ]i . It thus remains unresolved whether...... astrocytic isoform constellations in Xenopus oocytes and determined their apparent Na+ affinity in intact oocytes and isolated membranes. The Na+ /K+ -ATPase was not fully saturated at basal astrocytic [Na+ ]i , irrespective of isoform constellation, although the β1 subunit conferred lower apparent Na...

  8. Reduction of spatial distribution of risk factors for transportation of contaminants released by coal mining activities.

    Science.gov (United States)

    Karan, Shivesh Kishore; Samadder, Sukha Ranjan

    2016-09-15

    It is reported that water-energy nexus composes two of the biggest development and human health challenges. In the present study we presented a Risk Potential Index (RPI) model which encapsulates Source, Vector (Transport), and Target risks for forecasting surface water contamination. The main aim of the model is to identify critical surface water risk zones for an open cast mining environment, taking Jharia Coalfield, India as the study area. The model also helps in feasible sampling design. Based on spatial analysis various risk zones were successfully delineated. Monthly RPI distribution revealed that the risk of surface water contamination was highest during the monsoon months. Surface water samples were analysed to validate the model. A GIS based alternative management option was proposed to reduce surface water contamination risk and observed 96% and 86% decrease in the spatial distribution of very high risk areas for the months June and July respectively.

  9. Active transport on disordered microtubule networks: The generalized random velocity model

    Science.gov (United States)

    Kahana, Aviv; Kenan, Gilad; Feingold, Mario; Elbaum, Michael; Granek, Rony

    2008-11-01

    The motion of small cargo particles on microtubules by means of motor proteins in disordered microtubule networks is investigated theoretically using both analytical tools and computer simulations. Different network topologies in two and three dimensions are considered, one of which has been recently studied experimentally by Salman [Biophys. J. 89, 2134 (2005)]. A generalization of the random velocity model is used to derive the mean-square displacement of the cargo particle. We find that all cases belong to the class of anomalous superdiffusion, which is sensitive mainly to the dimensionality of the network and only marginally to its topology. Yet in three dimensions the motion is very close to simple diffusion, with sublogarithmic corrections that depend on the network topology. When details of the thermal diffusion in the bulk solution are included, no significant change to the asymptotic time behavior is found. However, a small asymmetry in the mean microtubule polarity affects the corresponding long-time behavior. We also study a three-dimensional model of the microtubule network in living animal cells. Three first-passage-time problems of intracellular transport are simulated and analyzed for different motor processivities: (i) cargo that originates near the nucleus and has to reach the membrane, (ii) cargo that originates from the membrane and has to reach the nucleus, and (iii) cargo that leaves the nucleus and has to reach a specific target in the cytoplasm. We conclude that while a higher motor processivity increases the transport efficiency in cases (i) and (ii), in case (iii) it has the opposite effect. We conjecture that the balance between the different network tasks, as manifested in cases (i) and (ii) versus case (iii), may be the reason for the evolutionary choice of a finite motor processivity.

  10. Association between low-activity serotonin transporter genotype and heroin dependence: behavioral and personality correlates.

    Science.gov (United States)

    Gerra, G; Garofano, L; Santoro, G; Bosari, S; Pellegrini, C; Zaimovic, A; Moi, G; Bussandri, M; Moi, A; Brambilla, F; Donnini, C

    2004-04-01

    In previous studies, serotonin (5-HT) system disturbance was found involved in a variety of behavioral disorders, psychopathologies, and substance use disorders. A functional polymorphism in the promoter region of the human serotonin transporter gene (5-HTTLPR) was recently identified and the presence of the short (S) allele found to be associated with a lower level of expression of the gene, lower levels of 5-HT uptake, type 2 alcoholism, violence and suicidal behavior. In the present study, 101 heroin addicts (males, West European, Caucasians) and 101 healthy control subjects matched for race and gender, with no history of substance use disorder, have been genotyped. Aggressiveness levels were measured in both heroin addicts and controls utilizing Buss-Durkee-Hostility-Inventory (BDHI). Data about suicide attempt and violent criminal behavior in subject history have been collected. The short-short (SS) genotype frequency was significantly higher among heroin dependent individuals compared with control subjects (P = 0.025). The odds ratio for the SS genotype versus the long-long (LL) genotype frequency was 0.69, 95% Cl (0.49-0.97), when heroin addicts were compared with healthy controls. The SS genotype frequency was significantly higher among violent heroin dependent individuals compared with addicted individuals without aggressive behavior (P = 0.02). BDHI mean total scores and suspiciousness and negativism subscales scores were significantly higher in SS individuals, in comparison with LL subjects, among heroin addicts. No association was found between SS genotype and suicide history. Our data suggest that a decreased expression of the gene encoding the 5-HTT transporter, due to "S" promoter polymorphism, may be associated with an increased risk for substance use disorders, particularly in the subjects with more consistent aggressiveness and impulsiveness.

  11. Nucleoside transporter expression and activity is regulated during granulocytic differentiation of NB4 cells in response to all-trans-retinoic acid.

    Science.gov (United States)

    Flanagan, Sheryl A; Meckling, Kelly A

    2007-07-01

    NB4 cells express multiple nucleoside transporters (NTs), including: hENT1 (es), and hENT2 (ei), and the CNT subtype referred to as, csg; a concentrative sensitive guanosine specific transporter. csg activity is a distinguishing feature of the NB4 cell line and its presence suggests a particular requirement of these cells for guanosine salvage. Proliferation and differentiation pathways determine, in part, the number of NTs in cells and tissues. In this study, all-trans-retinoic acid (ATRA)-induced granulocytic differentiation of NB4 cells resulted in biphasic changes in guanosine transport. Transient increases in csg and es activity, the result of an increase in V(max) (pmol/muls) of both transporter systems, served as early markers of differentiation while expression of a fully differentiated phenotype was accompanied by a selective loss of csg activity and the return of es activity to that of proliferating cells. Intracellular incorporation of [(3)H]-guanosine decreased as cells matured despite increased transport rates and suggested a reduced intracellular requirement of NB4-granulocytes compared to their proliferating counterparts. Whether a loss of csg activity could serve to assess clinical response to differentiation therapies is not known. Nitrobenzylthioinosine (NBMPR) binding sites within nuclear membrane (NM) preparations, suggested the presence of functional intracellular NTs. An increase in plasma membrane (PM) associated transporters coincided with the early increase in guanosine transport and a decrease in NBMPR binding to NM fractions and suggests that intracellular NTs may serve as a reserve pool for translocation to the (PM) when additional transport capacity is required. The modulation of transporters during differentiation could potentially regulate drug bioavailability and cytotoxicity and should be evaluated prior to combining differentiating agents with traditional nucleoside analogs in the treatment of APL.

  12. Which Socio-Ecological Factors Associate with a Switch to or Maintenance of Active and Passive Transport during the Transition from Primary to Secondary School?

    Directory of Open Access Journals (Sweden)

    Griet Vanwolleghem

    Full Text Available The aim was to investigate which individual, psychosocial and physical neighborhood environmental factors associate with children's switch to or maintenance of active/passive transport to school and to leisure time destinations during the transition from primary to secondary school.Children (n = 313 filled out a questionnaire in the last year of primary school and 2 years later to assess socio-demographic characteristics and self-reported transport. One of their parents completed a questionnaire to assess parental perceptions of psychosocial and physical neighborhood environmental factors.The increase of the home-school distance was significantly associated with children's switch to or maintenance of passive transport to school compared to a switch to (OR = 0.81; p = 0.03 and maintenance (OR = 0.87; p = 0.03 of active transport to school. Low SES was associated with children's switch to active transport to school compared to maintenance of active transport (OR = 3.67; p = 0.07. For transport to leisure time destinations, other factors such as parental perceived neighborhood safety from traffic and crime (OR = 2.78; p = 0.004, a positive social norm (OR = 1.49; p = 0.08, positive attitudes (OR = 1.39; p = 0.08 (i.e. more benefits, less barriers towards their children's physical activity and poor walking/cycling facilities in the neighborhood (OR = 0.70; p = 0.06 were associated with children's maintenance of active transport to leisure time destinations compared to a switch to or maintenance of passive transport.This longitudinal study can give directions for interventions promoting children's active transport during the transition to secondary school. It is necessary to promote different possibilities at primary school for children to use active transport when going to secondary school. Walking/cycling a part of the home-school trip can be a possible solution for children who will be living at non-feasible distances from secondary school

  13. Novel biotinylated lipid prodrugs of acyclovir for the treatment of herpetic keratitis (HK): transporter recognition, tissue stability and antiviral activity.

    Science.gov (United States)

    Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Earla, Ravinder; Sirimulla, Suman; Bailey, Jake Brain; Pal, Dhananjay; Mitra, Ashim K

    2013-08-01

    Biotinylated lipid prodrugs of acyclovir (ACV) were designed to target the sodium dependent multivitamin transporter (SMVT) on the cornea to facilitate enhanced cellular absorption of ACV. All the prodrugs were screened for in vitro cellular uptake, interaction with SMVT, docking analysis, cytotoxicity, enzymatic stability and antiviral activity. Uptake of biotinylated lipid prodrugs of ACV (B-R-ACV and B-12HS-ACV) was significantly higher than biotinylated prodrug (B-ACV), lipid prodrugs (R-ACV and 12HS-ACV) and ACV in corneal cells. Transepithelial transport across rabbit corneas indicated the recognition of the prodrugs by SMVT. Average Vina scores obtained from docking studies further confirmed that biotinylated lipid prodrugs possess enhanced affinity towards SMVT. All the prodrugs studied did not cause any cytotoxicity and were found to be safe and non-toxic. B-R-ACV and B-12HS-ACV were found to be relatively more stable in ocular tissue homogenates and exhibited excellent antiviral activity. Biotinylated lipid prodrugs demonstrated synergistic improvement in cellular uptake due to recognition of the prodrugs by SMVT on the cornea and lipid mediated transcellular diffusion. These biotinylated lipid prodrugs appear to be promising drug candidates for the treatment of herpetic keratitis (HK) and may lower ACV resistance in patients with poor clinical response.

  14. The kinetics of the partial dehydration of gibbsite to activated alumina in a reactor for pneumatic transport

    Directory of Open Access Journals (Sweden)

    NADEZDA JOVANOVIC

    2001-04-01

    Full Text Available The dehidration kinetics of gibbsite to activated alumina was investigated at four different temperatures between 883 K and 943 K in a reactor for pneumatic transport in the dilute two phase flow regime. The first order kinetic behavior of this reactionwith respect to the water content of the solid material was proved and an activation energy of 66.5 kJ/mol was calculated. The effect of residence time on the water content is given and compared with theoretical calculations. The water content and other characteristics of the products depend on two main parameters, one is the short residence time and the other is the temperature of the dehydration of gibbsite. The short residence time of the gibbsite particles in a reactor for pneumatic transport prevents crystallization into new phases, as established from XRD analysis data. Reactive amorphous alumina powder, with a specific surface area of 250 m2/g, suitable as a precursor for catalyst supports is obtained.

  15. Releasable activity and maximum permissible leakage rate within a transport cask of Tehran Research Reactor fuel samples

    Directory of Open Access Journals (Sweden)

    Rezaeian Mahdi

    2015-01-01

    Full Text Available Containment of a transport cask during both normal and accident conditions is important to the health and safety of the public and of the operators. Based on IAEA regulations, releasable activity and maximum permissible volumetric leakage rate within the cask containing fuel samples of Tehran Research Reactor enclosed in an irradiated capsule are calculated. The contributions to the total activity from the four sources of gas, volatile, fines, and corrosion products are treated separately. These calculations are necessary to identify an appropriate leak test that must be performed on the cask and the results can be utilized as the source term for dose evaluation in the safety assessment of the cask.

  16. Modulators of membrane drug transporters potentiate the activity of the DMI fungicide oxpoconazole against Botrytis cinerea

    NARCIS (Netherlands)

    Hayashi, K.; Schoonbeek, H.; Waard, de M.A.

    2003-01-01

    Modulators known to reduce multidrug resistance in tumour cells were tested for their potency to synergize the fungitoxic activity of the fungicide oxpoconazole, a sterol demethylation inhibitor (DMI), against Botrytis cinerea Pers. Chlorpromazine, a phenothiazine compound known as a calmodulin

  17. Collective transport for active matter run-and-tumble disk systems on a traveling-wave substrate

    Science.gov (United States)

    Sándor, Cs.; Libál, A.; Reichhardt, C.; Reichhardt, C. J. Olson

    2017-01-01

    We examine numerically the transport of an assembly of active run-and-tumble disks interacting with a traveling-wave substrate. We show that as a function of substrate strength, wave speed, disk activity, and disk density, a variety of dynamical phases arise that are correlated with the structure and net flux of disks. We find that there is a sharp transition into a state in which the disks are only partially coupled to the substrate and form a phase-separated cluster state. This transition is associated with a drop in the net disk flux, and it can occur as a function of the substrate speed, maximum substrate force, disk run time, and disk density. Since variation of the disk activity parameters produces different disk drift rates for a fixed traveling-wave speed on the substrate, the system we consider could be used as an efficient method for active matter species separation. Within the cluster phase, we find that in some regimes the motion of the cluster center of mass is in the opposite direction to that of the traveling wave, while when the maximum substrate force is increased, the cluster drifts in the direction of the traveling wave. This suggests that swarming or clustering motion can serve as a method by which an active system can collectively move against an external drift.

  18. μ-Opioid receptor activation and noradrenaline transport inhibition by tapentadol in rat single locus coeruleus neurons.

    Science.gov (United States)

    Sadeghi, Mahsa; Tzschentke, Thomas M; Christie, MacDonald J

    2015-01-01

    Tapentadol is a novel analgesic that combines moderate μ-opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule. Both mechanisms of action are involved in producing analgesia; however, the potency and efficacy of tapentadol in individual neurons has not been characterized. Whole-cell patch-clamp recordings of G-protein-coupled inwardly rectifying K(+) (KIR 3.x) currents were made from rat locus coeruleus neurons in brain slices to investigate the potency and relative efficacy of tapentadol and compare its intrinsic activity with other clinically used opioids. Tapentadol showed agonist activity at μ receptors and was approximately six times less potent than morphine with respect to KIR 3.x current modulation. The intrinsic activity of tapentadol was lower than [Met]enkephalin, morphine and oxycodone, but higher than buprenorphine and pentazocine. Tapentadol inhibited the noradrenaline transporter (NAT) with potency similar to that at μ receptors. The interaction between these two mechanisms of action was additive in individual LC neurons. Tapentadol displays similar potency for both µ receptor activation and NAT inhibition in functioning neurons. The intrinsic activity of tapentadol at the μ receptor lies between that of buprenorphine and oxycodone, potentially explaining the favourable profile of side effects, related to μ receptors. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2013 The British Pharmacological Society.

  19. Ssh4, Rcr2 and Rcr1 affect plasma membrane transporter activity in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kota, Jhansi; Melin-Larsson, Monika; Ljungdahl, Per O; Forsberg, Hanna

    2007-04-01

    Nutrient uptake in the yeast Saccharomyces cerevisiae is a highly regulated process. Cells adjust levels of nutrient transporters within the plasma membrane at multiple stages of the secretory and endosomal pathways. In the absence of the ER-membrane-localized chaperone Shr3, amino acid permeases (AAP) inefficiently fold and are largely retained in the ER. Consequently, shr3 null mutants exhibit greatly reduced rates of amino acid uptake due to lower levels of AAPs in their plasma membranes. To further our understanding of mechanisms affecting AAP localization, we identified SSH4 and RCR2 as high-copy suppressors of shr3 null mutations. The overexpression of SSH4, RCR2, or the RCR2 homolog RCR1 increases steady-state AAP levels, whereas the genetic inactivation of these genes reduces steady-state AAP levels. Additionally, the overexpression of any of these suppressor genes exerts a positive effect on phosphate and uracil uptake systems. Ssh4 and Rcr2 primarily localize to structures associated with the vacuole; however, Rcr2 also localizes to endosome-like vesicles. Our findings are consistent with a model in which Ssh4, Rcr2, and presumably Rcr1, function within the endosome-vacuole trafficking pathway, where they affect events that determine whether plasma membrane proteins are degraded or routed to the plasma membrane.

  20. Active lithium transport by rat renal proximal tubule: a micropuncture study

    DEFF Research Database (Denmark)

    Leyssac, P P; Frederiksen, O; Holstein-Rathlou, N H

    1994-01-01

    We tested the hypothesis that proximal tubular Li+ reabsorption is due to passive transport. Clearances of [14C]inulin (CIn) and Li+ (CLi), proximal transepithelial electrical potential difference (PD), and tubular fluid-to-plasma Li+ concentration ratios [(TF/P)Li] were measured in anesthetized...... rats before and after induction of osmotic mannitol diuresis. Late proximal (TF/P)Li was measured after acute intravenous LiCl administration and after addition of LiCl to the diet for 2 days. Glomerular filtration rate (CIn) decreased, whereas CNa and CLi increased during osmotic diuresis. Control...... early proximal PD was -0.6 mV (lumen negative); late proximal PD (PDLP) was 1.1 mV (lumen positive). PDLP decreased by 1.5 mV to -0.4 mV (lumen negative) after mannitol infusion. Late proximal (TF/P)Li was 1.01 after oral Li+, 1.16 after intravenous Li+ (P osmotic diuresis...

  1. Verification of high-energy transport codes on the basis of activation data

    CERN Document Server

    Titarenko, Yu E; Butko, M A; Dikarev, D V; Florya, S N; Pavlov, K V; Titarenko, A Yu; Tikhonov, R S; Zhivun, V M; Ignatyuk, A V; Mashnik, S G; Boudard, A; Leray, S; David, J -C; Cugnon, J; Mancusi, D; Yariv, Y; Kumawat, H; Nishihara, K; Matsuda, N; Mank, G; Gudowski, W

    2011-01-01

    Nuclide production cross sections measured at ITEP for the targets of nat-Cr, 56-Fe, nat-Ni, 93-Nb, 181-Ta, nat-W, nat-Pb, 209-Bi irradiated by protons with energies from 40 to 2600 MeV were used to estimate the predictive accuracy of several popular high-energy transport codes. A general agreement of the ITEP data with the data obtained by other groups, including the numerous GSI data measured by the inverse kinematics method was found. Simulations of the measured data were performed with the MCNPX (Bertini and ISABEL options), CEM03.02, INCL4.2+ABLA, INCL4.5+ABLA07, PHITS, and CASCADE.07 codes. Deviation factors between the calculated and experimental cross sections have been estimated for each target and for the whole energy range covered by our measurements. Two-dimensional diagrams of deviation factor values were produced for estimating the predictive power of every code for intermediate, not measured masses of nuclei-targets and bombarding energies of protons. Further improvements of all tested here cod...

  2. Action of bicyclic isoxazole GABA analogues on GABA transporters and its relation to anticonvulsant activity

    DEFF Research Database (Denmark)

    Bolvig, T; Larsson, O M; Pickering, D S;

    1999-01-01

    The inhibitory action of bicyclic isoxazole gamma-aminobutyric acid (GABA) analogues and their 4,4-diphenyl-3-butenyl (DPB) substituted derivatives has been investigated in cortical neurones and astrocytes as well as in human embryonic kidney (HEK 293) cells transiently expressing either mouse GABA...... anticonvulsant activity, lack of proconvulsant activity and the ability of THPO to increase extracellular GABA concentration, indicate that these bicyclic isoxazole GABA analogues and their DPB derivatives may be useful lead structures in future search for new antiepileptic drugs....

  3. Activity-dependent regulation of the K/Cl transporter KCC2 membrane diffusion, clustering, and function in hippocampal neurons.

    Science.gov (United States)

    Chamma, Ingrid; Heubl, Martin; Chevy, Quentin; Renner, Marianne; Moutkine, Imane; Eugène, Emmanuel; Poncer, Jean Christophe; Lévi, Sabine

    2013-09-25

    The neuronal K/Cl transporter KCC2 exports chloride ions and thereby influences the efficacy and polarity of GABA signaling in the brain. KCC2 is also critical for dendritic spine morphogenesis and the maintenance of glutamatergic transmission in cortical neurons. Because KCC2 plays a pivotal role in the function of central synapses, it is of particular importance to understand the cellular and molecular mechanisms underlying its regulation. Here, we studied the impact of membrane diffusion and clustering on KCC2 function. KCC2 forms clusters in the vicinity of both excitatory and inhibitory synapses. Using quantum-dot-based single-particle tracking on rat primary hippocampal neurons, we show that KCC2 is slowed down and confined at excitatory and inhibitory synapses compared with extrasynaptic regions. However, KCC2 escapes inhibitory synapses faster than excitatory synapses, reflecting stronger molecular constraints at the latter. Interfering with KCC2-actin interactions or inhibiting F-actin polymerization releases diffusion constraints on KCC2 at excitatory but not inhibitory synapses. Thus, F-actin constrains KCC2 diffusion at excitatory synapses, whereas KCC2 is confined at inhibitory synapses by a distinct mechanism. Finally, increased neuronal activity rapidly increases the diffusion coefficient and decreases the dwell time of KCC2 at excitatory synapses. This effect involves NMDAR activation, Ca(2+) influx, KCC2 S940 dephosphorylation and calpain protease cleavage of KCC2 and is accompanied by reduced KCC2 clustering and ion transport function. Thus, activity-dependent regulation of KCC2 lateral diffusion and clustering allows for a rapid regulation of chloride homeostasis in neurons.

  4. Mass transport deposits as witness of Holocene seismic activity on the Ligurian margin, Western Mediterranean (ASTARTE project)

    Science.gov (United States)

    Samalens, Kevin; Cattaneo, Antonio; Migeon, Sébastien

    2016-04-01

    The Ligurian Margin (Western Mediterranean) is at the transition between the Southern Alpes and the Liguro-Provençal margin and it is one of the most seismic areas of France. Several historic earthquakes have been indexed; the strongest, on February 23rd, 1887, occurred offshore Menton and Imperia and also caused a tsunami wave. Its equivalent magnitude has been estimated between 6 and 6.5. In addition, a moderate recurrent seismicity shakes the margin. The aim of this study is to understand the link between seismic activity and slope destabilization, and to identify the sedimentary deposits resulting from mass transport or turbidity currents. During Malisar (Geoazur laboratory), Prisme 2 and Prisme 3 (Ifremer) cruises, bathymetry, seafloor imagery (SAR), geophysics data (CHIRP SYSIF and high resolution seismics), and sediment cores have been acquired on the continental slope, focussing on canyons and submarine landslides, and in the basin. These data record numerous mass transport deposits (slump, debrites) in the different physiographic areas of the margin. To search for evidences of past Ligurian margin seismicity during the Holocene, we focused on the northeast part of the margin, the Finale area. We identified and sampled acoustically transparent Mass Transport Deposits up to 20-m thick in the bottom of three coaleshing canyons: Noli, Pora and Centa canyons from W to E in the area offshore Finale Ligure. We also recovered an MTD in the collecting deeper canyon system. MTDs in cores appear as sediment with different degrees of deformation (tilted blocks, slump, debrites) and are topped by hemipelagites. The radiocarbon age of the top of MTDs can be considered synchronous and centered around 4900 yr BP. Mass wasting occurring over more than 50 km of the Ligurian margin could indicate that an earthquake stroke the Finale area sector at that time.

  5. Folate concentration dependent transport activity of the Multidrug Resistance Protein 1 (ABCC1).

    NARCIS (Netherlands)

    Hooijberg, J.H.; Jansen, G.; Assaraf, Y.G.; Kathmann, I.; Pieters, R.; Laan, AC; Veerman, A.J.P.; Kaspers, G.J.L.; Peters, G.J.

    2004-01-01

    The Multidrug Resistance Protein MRP1 (ABCC1) can confer resistance to a variety of therapeutic drugs. In addition, MRP1/ABCC1 mediates cellular export of natural folates, such as folic acid and l-leucovorin. In this study we determined whether cellular folate status affected the functional activity

  6. Activation of CFTR-mediated CI-Transport by Capsaicinoids in Cell Culture Model

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xue-liang; HOU Ting-ting; GE Hong; SUN Juan-juan; YANG Hong; MA Tong-hui

    2009-01-01

    Previous studies reported that capsaicin potentiates ΔF508 mutant cystic fibrosis transmembrane conductance regulator(CFTR) channel gating defect by transfected cell-based assays.It has been postulated that orally ingested capsaicin may conceptually be used to develop a therapeutic strategy to treat gastrointestinal disorders in CF patients.We tried to reproduce and extend those pre-clinical data of previous studies.Cell-based fluorescence functional measurements in Fischer thyroid epithelial cells(FRT) expressing CFTR showed no effect of capsaicin on potentiating ΔF508-CFTR.while genistein showed a strongly positive activity.Studies show that capsaicin and dihydrocapsaicin activated cAMP-prestimulated wild-type CFTR in a dose-dependent manner with a maximal response of 70% of that activated by genistein,thus gave an apparent EC50 of (40.4±6.8)μmol/L and (150.2±7.4) μmol/L respectively.Preliminary study shows that the binding sites for capsaicin and dihydrocapsaicin may be probably partially overlapped with that for genistein because the maximal activation of wild-type CFTR with genistein is partially blocked by capsaicin and dihydrocapsaicin.

  7. Flavonol-induced changes in PIN2 polarity and auxin transport in the Arabidopsis thaliana rol1-2 mutant require phosphatase activity

    Science.gov (United States)

    Kuhn, Benjamin M.; Nodzyński, Tomasz; Errafi, Sanae; Bucher, Rahel; Gupta, Shibu; Aryal, Bibek; Dobrev, Petre; Bigler, Laurent; Geisler, Markus; Zažímalová, Eva; Friml, Jiří; Ringli, Christoph

    2017-01-01

    The phytohormone auxin is a major determinant and regulatory component important for plant development. Auxin transport between cells is mediated by a complex system of transporters such as AUX1/LAX, PIN, and ABCB proteins, and their localization and activity is thought to be influenced by phosphatases and kinases. Flavonols have been shown to alter auxin transport activity and changes in flavonol accumulation in the Arabidopsis thaliana rol1-2 mutant cause defects in auxin transport and seedling development. A new mutation in ROOTS CURL IN NPA 1 (RCN1), encoding a regulatory subunit of the phosphatase PP2A, was found to suppress the growth defects of rol1-2 without changing the flavonol content. rol1-2 rcn1-3 double mutants show wild type-like auxin transport activity while levels of free auxin are not affected by rcn1-3. In the rol1-2 mutant, PIN2 shows a flavonol-induced basal-to-apical shift in polar localization which is reversed in the rol1-2 rcn1-3 to basal localization. In vivo analysis of PINOID action, a kinase known to influence PIN protein localization in a PP2A-antagonistic manner, revealed a negative impact of flavonols on PINOID activity. Together, these data suggest that flavonols affect auxin transport by modifying the antagonistic kinase/phosphatase equilibrium. PMID:28165500

  8. Active transport, ion movements, and pH changes : I. The chemistry of pH changes.

    Science.gov (United States)

    Good, N E

    1988-10-01

    The transport of substances across cell membranes may be the most fundamental activity of living things. When the substance transported is any ion there can be a change in the concentration of hydrogen ions on the two sides of the membrane. These hydrogen ion concentration changes are not caused by fluxes of hydrogen ions although fluxes of hydrogen ions may sometimes be involved. The reason for the apparent contradiction is quite simple. All aqueous systems are subject to two constraints: (1) to maintain the charge balance, the sum of the cationic charges must equal the sum of the anionic charges and (2) the product of the molar concentration of H(+) and the molar concentration of OH(-), established and maintained by the association and the dissociation of water, remains always at 10(-14). As a consequence the concentrations of H(+) and OH(-) are determined uniquely by differences between the concentrations of the other cations and anions, with [H(+)] and [OH(-)] being dependent variables. Hydrogen ions and hydroxyl ions can be produced or consumed in local reactions whereas any strong ions such as Cl(-), Mg(2+), or K(+) can be neither produced nor consumed in biological reactions. Further consequences of these truisms are outlined here in terms of the chemistry of the kinds of reactions which can lead to pH changes.

  9. Impact of humic acid fouling on membrane performance and transport of pharmaceutically active compounds in forward osmosis.

    Science.gov (United States)

    Xie, Ming; Nghiem, Long D; Price, William E; Elimelech, Menachem

    2013-09-01

    The impact of humic acid fouling on the membrane transport of two pharmaceutically active compounds (PhACs) - namely carbamazepine and sulfamethoxazole - in forward osmosis (FO) was investigated. Deposition of humic acid onto the membrane surface was promoted by the complexation with calcium ions in the feed solution and the increase in ionic strength at the membrane surface due to the reverse transport of NaCl draw solute. The increase in the humic acid deposition on the membrane surface led to a substantial decrease in the membrane salt (NaCl) permeability coefficient but did not result in a significant decrease in the membrane pure water permeability coefficient. As the deposition of humic acid increased, the permeation of carbamazepine and sulfamethoxazole decreased, which correlated well with the decrease in the membrane salt (NaCl) permeability coefficient. It is hypothesized that the hydrated humic acid fouling layer hindered solute diffusion through the membrane pore and enhanced solute rejection by steric hindrance, but not the permeation of water molecules. The membrane water and salt (NaCl) permeability coefficients were fully restored by physical cleaning of the membrane, suggesting that humic acid did not penetrate into the membrane pores.

  10. Stormwater run-off and pollutant transport related to the activities carried out in a modern waste management park.

    Science.gov (United States)

    Marques, M; Hogland, W

    2001-02-01

    Stormwater run-off from twelve different areas and roads has been characterized in a modern waste disposal site, where several waste management activities are carried out. Using nonparametric statistics, medians and confidence intervals of the medians, 22 stormwater quality parameters were calculated. Suspended solids, chemical oxygen demand, biochemical oxygen demand, total nitrogen and total phosphorus, as well as run-off from several areas, showed measured values above standard limits for discharge into recipient waters--even higher than those of leachate from covered landfill cells. Of the heavy metals analyzed, copper, zinc and nickel were the most prevalent, being detected in every sample. Higher concentrations of metals such as zinc, nickel, cobalt, iron and cadmium were found in run-off from composting areas, compared to areas containing stored and exposed scrap metal. This suggests that factors other than the total amount of exposed material affect the concentration of metals in run-off, such as binding to organic compounds and hydrological transport efficiency. The pollutants transported by stormwater represent a significant environmental threat, comparable to leachate. Careful design, monitoring and maintenance of stormwater run-off drainage systems and infiltration elements are needed if infiltration is to be used as an on-site treatment strategy.

  11. The Great Solar Active Region NOAA 12192: Helicity Transport, Filament Formation, and Impact on the Polar Field

    Science.gov (United States)

    Petrie, Gordon; McMaken, Tyler C.

    2017-08-01

    The solar active region (AR), NOAA 12192, appeared in 2014 October as the largest AR in 24 years. Here we examine the counterintuitive nature of two diffusion-driven processes in the region: the role of helicity buildup in the formation of a major filament, and the relationship between the effects of supergranular diffusion and meridional flow on the AR and on the polar field. Quantitatively, calculations of current helicity and magnetic twist from Helioseismic and Magnetic Imager (HMI) vector magnetograms indicate that, though AR 12192 emerged with negative helicity, positive helicity from subsequent flux emergence, consistent with the hemispheric sign-preference of helicity, increased over time within large-scale, weak-field regions such as those near the polarity inversion line (PIL). Morphologically, Atmospheric Imaging Assembly observations of filament barbs, sigmoidal patterns, and bases of Fe xii stalks initially exhibited signatures of negative helicity, and the long filament that subsequently formed had a strong positive helicity consistent with the helicity buildup along the PIL. We find from full-disk HMI magnetograms that AR 12192's leading positive flux was initially closer to the equator but, owing either to the region’s magnetic surroundings or to its asymmetric flux density distribution, was transported poleward more quickly on average than its trailing negative flux, contrary to the canonical pattern of bipole flux transport. This behavior caused the AR to have a smaller effect on the polar fields than expected and enabled the formation of the very long neutral line where the filament formed.

  12. Transport of a dilute active suspension in pressure-driven channel flow

    CERN Document Server

    Ezhilan, Barath

    2015-01-01

    Confined suspensions of active particles show peculiar dynamics characterized by wall accumulation, as well as upstream swimming, centerline depletion and shear-trapping when a pressure-driven flow is imposed. We use theory and numerical simulations to investigate the effects of confinement and non-uniform shear on the dynamics of a dilute suspension of Brownian active swimmers by incorporating a detailed treatment of boundary conditions within a simple kinetic model where the configuration of the suspension is described using a conservation equation for the probability distribution function of particle positions and orientations, and where particle-particle and particle-wall hydrodynamic interactions are neglected. Based on this model, we first investigate the effects of confinement in the absence of flow, in which case the dynamics is governed by a swimming Peclet number, or ratio of the persistence length of particle trajectories over the channel width, and a second swimmer-specific parameter whose inverse...

  13. Methamphetamine Increases Locomotion and Dopamine Transporter Activity in Dopamine D5 Receptor-Deficient Mice

    OpenAIRE

    Seiji Hayashizaki; Shinobu Hirai; Yumi Ito; Yoshiko Honda; Yosefu Arime; Ichiro Sora; Haruo Okado; Tohru Kodama; Masahiko Takada

    2013-01-01

    Dopamine regulates the psychomotor stimulant activities of amphetamine-like substances in the brain. The effects of dopamine are mediated through five known dopamine receptor subtypes in mammals. The functional relevance of D5 dopamine receptors in the central nervous system is not well understood. To determine the functional relevance of D5 dopamine receptors, we created D5 dopamine receptor-deficient mice and then used these mice to assess the roles of D5 dopamine receptors in the behaviora...

  14. Outer membrane vesicles mediate transport of biologically active Vibrio cholerae cytolysin (VCC from V. cholerae strains.

    Directory of Open Access Journals (Sweden)

    Sridhar Elluri

    Full Text Available Outer membrane vesicles (OMVs released from Gram-negative bacteria can serve as vehicles for the translocation of virulence factors. Vibrio cholerae produce OMVs but their putative role in translocation of effectors involved in pathogenesis has not been well elucidated. The V. cholerae cytolysin (VCC, is a pore-forming toxin that lyses target eukaryotic cells by forming transmembrane oligomeric β-barrel channels. It is considered a potent toxin that contributes to V. cholerae pathogenesis. The mechanisms involved in the secretion and delivery of the VCC have not been extensively studied.OMVs from V. cholerae strains were isolated and purified using a differential centrifugation procedure and Optiprep centrifugation. The ultrastructure and the contents of OMVs were examined under the electron microscope and by immunoblot analyses respectively. We demonstrated that VCC from V. cholerae strain V:5/04 was secreted in association with OMVs and the release of VCC via OMVs is a common feature among V. cholerae strains. The biological activity of OMV-associated VCC was investigated using contact hemolytic assay and epithelial cell cytotoxicity test. It showed toxic activity on both red blood cells and epithelial cells. Our results indicate that the OMVs architecture might play a role in stability of VCC and thereby can enhance its biological activities in comparison with the free secreted VCC. Furthermore, we tested the role of OMV-associated VCC in host cell autophagy signalling using confocal microscopy and immunoblot analysis. We observed that OMV-associated VCC triggered an autophagy response in the target cell and our findings demonstrated for the first time that autophagy may operate as a cellular defence mechanism against an OMV-associated bacterial virulence factor.Biological assays of OMVs from the V. cholerae strain V:5/04 demonstrated that OMV-associated VCC is indeed biologically active and induces toxicity on mammalian cells and

  15. Control of Mycosphaerella graminicola on wheat seedlings by medical drugs known to modulate the activity of ATP-binding cassette transporters

    NARCIS (Netherlands)

    Roohparvar, R.; Huser, A.; Zwiers, L.H.; Waard, de M.A.

    2007-01-01

    Medical drugs known to modulate the activity of human ATP-binding cassette (ABC) transporter proteins (modulators) were tested for the ability to potentiate the activity of the azole fungicide cyproconazole against in vitro growth of Mycosphaerella graminicola and to control disease development due

  16. Breaking Out of Surveillance Silos: Integrative Geospatial Data Collection for Child Injury Risk and Active School Transport.

    Science.gov (United States)

    Schuch, Laura; Curtis, Jacqueline W; Curtis, Andrew; Hudson, Courtney; Wuensch, Heather; Sampsell, Malinda; Wiles, Erika; Infantino, Mary; Davis, Andrew J

    2016-02-01

    The preponderance of active school transport (AST) and child injury research has occurred independently, yet they are inherently related. This is particularly true in urban areas where the environmental context of AST may pose risks to safety. However, it can be difficult to make these connections due to the often segregated nature in which these veins of research operate. Spatial video presents a geospatial approach for simultaneous data collection related to both issues. This article reports on a multi-sector pilot project among researchers, a children's hospital, and a police department, using spatial video to map child AST behaviors; a geographic information system (GIS) is used to analyze these data in the environmental context of child pedestrian injury and community violence.

  17. Electron transport of photoconductive n-type liquid crystals based on a redox-active tetraazanaphthacene framework.

    Science.gov (United States)

    Isoda, Kyosuke; Abe, Tomonori; Funahashi, Masahiro; Tadokoro, Makoto

    2014-06-10

    The preparation of two liquid crystals composed of a redox-active tetraazanaphthacene (TANC) framework is reported. The materials form smectic A (SmA) thin-film liquid-crystalline (LC) phases over a wide temperature range. Cyclic voltammetry analysis revealed that LC TANCs behave as organic electron acceptors. The electron mobilities of the thin films were determined by time- of-flight (TOF) measurements, which are the order of 10(-4)  cm(2)  V(-1)  s(-1) in the SmA LC phase. This value is two orders of magnitude larger than those of amorphous organic semiconductors. To the best of our knowledge, very few reports exist on the electron-transporting behaviors of LC N-heteroacene semiconductors.

  18. Transport of uranium concentrates: low specific activity versus logistic complexity; Transporte de concentrado de uranio: baixa atividade especifica versus complexidade logistica

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Pedro L.S.; Macedo, Eclesio F.; Carvalho, Leonardo B.; Carvalho, Renata R., E-mail: pedroluis@inb.gov.b, E-mail: eclesio@inb.gov.b, E-mail: leonardobernadino@inb.gov.b, E-mail: renatarangel@inb.gov.b [Industrias Nucleares do Brasil S.A., Caetite, BA (Brazil)

    2011-10-26

    This paper describes the case of radioactive material transport, according to pertinent documentation - nuclear material specifically in the form op ammonium diuranate, produced by Industrias Nucleares do Brasil S.A. - from the mine and physic-chemical processing at Caetite, Bahia, to the port of Salvador, state of Bahia, approaching the radiological protection aspects

  19. Proposition for Research Activities in the Area of Maritime Transport in the Republic of Slovenia

    Directory of Open Access Journals (Sweden)

    Milojka Počuča

    2012-10-01

    Full Text Available The paper shows the maritime system of the Republic ofSlovenia and its weakpoints, mainly as a result of the transitionand gaining of independence. The second heading describes researchactivities in the area of the maritime system of the Republicof Slovenia during the period from 1992 to 1995. Thethird heading gives a brief review of the EU maritime policy anddescription of Research & Development projects that are intendedas guidelines of the EU maritime policy. In conclusion,the author presents a proposal of the themes and procedures ofscientific research projects in the area of maritime activities ofthe Republic of Slovenia.

  20. Neighbourhood walkability, leisure-time and transport-related physical activity in a mixed urban–rural area

    Directory of Open Access Journals (Sweden)

    Eric de Sa

    2014-07-01

    Full Text Available Objectives. To develop a walkability index specific to mixed rural/suburban areas, and to explore the relationship between walkability scores and leisure time physical activity.Methods. Respondents were geocoded with 500 m and 1,000 m buffer zones around each address. A walkability index was derived from intersections, residential density, and land-use mix according to built environment measures. Multivariable logistic regression models were used to quantify the association between the index and physical activity levels. Analyses used cross-sectional data from the 2007–2008 Canadian Community Health Survey (n = 1158; ≥18 y.Results. Respondents living in highly walkable 500 m buffer zones (upper quartiles of the walkability index were more likely to walk or cycle for leisure than those living in low-walkable buffer zones (quartile 1. When a 1,000 m buffer zone was applied, respondents in more walkable neighbourhoods were more likely to walk or cycle for both leisure-time and transport-related purposes.Conclusion. Developing a walkability index can assist in exploring the associations between measures of the built environment and physical activity to prioritize neighborhood change.

  1. Structure-activity analysis of thiourea analogs as inhibitors of UT-A and UT-B urea transporters.

    Science.gov (United States)

    Esteva-Font, Cristina; Phuan, Puay-Wah; Lee, Sujin; Su, Tao; Anderson, Marc O; Verkman, A S

    2015-05-01

    Small-molecule inhibitors of urea transporter (UT) proteins in kidney have potential application as novel salt-sparing diuretics. The urea analog dimethylthiourea (DMTU) was recently found to inhibit the UT isoforms UT-A1 (expressed in kidney tubule epithelium) and UT-B (expressed in kidney vasa recta endothelium) with IC50 of 2-3 mM, and was shown to have diuretic action when administered to rats. Here, we measured UT-A1 and UT-B inhibition activity of 36 thiourea analogs, with the goal of identifying more potent and isoform-selective inhibitors, and establishing structure-activity relationships. The analog set systematically explored modifications of substituents on the thiourea including alkyl, heterocycles and phenyl rings, with different steric and electronic features. The analogs had a wide range of inhibition activities and selectivities. The most potent inhibitor, 3-nitrophenyl-thiourea, had an IC50 of ~0.2 mM for inhibition of both UT-A1 and UT-B. Some analogs such as 4-nitrophenyl-thiourea were relatively UT-A1 selective (IC50 1.3 vs. 10 mM), and others such as thioisonicotinamide were UT-B selective (IC50>15 vs. 2.8 mM).

  2. Mutation of aspartic acid-351, lysine-352, and lysine-515 alters the Ca2+ transport activity of the Ca2+-ATPase expressed in COS-1 cells.

    Science.gov (United States)

    Maruyama, K; MacLennan, D H

    1988-01-01

    Full-length cDNAs encoding neonatal and adult isoforms of the Ca2+-ATPase of rabbit fast-twitch skeletal muscle sarcoplasmic reticulum were expressed transiently in COS-1 cells. The microsomal fraction isolated from transfected COS-1 cells contained immunoreactive Ca2+-ATPase and catalyzed Ca2+ transport at rates at least 15-fold above controls. No differences were observed in either the rates or Ca2+ dependency of Ca2+ transport catalyzed by the two isoforms. Aspartic acid-351, the site of formation of the catalytic acyl phosphate in the enzyme, was mutated to asparagine, glutamic acid, serine, threonine, histidine, or alanine. In every case, Ca2+ transport activity and Ca2+-dependent phosphorylation were eliminated. Ca2+ transport was also eliminated by mutation of lysine-352 to arginine, glutamine, or glutamic acid or by mutation of Asp351-Lys352 to Lys351-Asp352. Mutation of lysine-515, the site of fluorescein isothiocyanate modification in the enzyme, resulted in diminished Ca2+ transport activity as follows: arginine, 60%; glutamine, 25%; glutamic acid, 5%. These results demonstrate the absolute requirement of acylphosphate formation for the Ca2+ transport function and define a residue important for ATP binding. They also demonstrate the feasibility of a thorough analysis of active sites in the Ca2+-ATPase by expression and site-specific mutagenesis. Images PMID:2966962

  3. Effects of muscle activity and fiber composition on glucose transport and GLUT-4.

    Science.gov (United States)

    Megeney, L A; Neufer, P D; Dohm, G L; Tan, M H; Blewett, C A; Elder, G C; Bonen, A

    1993-04-01

    We examined glucose uptake and GLUT-4 in rat muscles [soleus (Sol), plantaris (PL), extensor digitorum longus (EDL), tibialis anterior, and the red and white gastrocnemius (WG)]. In the normally innervated perfused rat hindlimb muscles the proportion of oxidative fibers was highly correlated with the muscle's insulin-stimulated 3-O-methyl-D-glucose (3-MG) uptake (R2 = 0.78) and GLUT-4 content (r = 0.94). Insulin-stimulated 3-MG uptake and GLUT-4 were also highly correlated (R2 = 0.996). In 3-day denervated muscles, insulin-stimulated 3-MG uptake was reduced in all six muscles (-41 to -14.6%, P 0.05). A very high correlation was observed between the decrements in GLUT-4 (%) and the decrements in 3-MG uptake (%; r = 0.99). The relatively greater loss in muscle activity (%) due to denervation in the Sol compared with the PL coincided with the reductions (%) in GLUT-4 and 3-MG uptake. These studies demonstrate that glucose uptake and GLUT-4 are regulated by insulin-independent means, namely the oxidative capacity of the muscle and the normal activity level of the muscle.

  4. Thermodynamic and transport properties of some biologically active compounds in aqueous solutions at different temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Dhondge, Sudhakar S., E-mail: s_dhondge@hotmail.co [P.G. Department of Chemistry, S.K. Porwal College, Kamptee, Nagpur 441 002 (India); Zodape, Sangesh P.; Parwate, Dilip V. [Department of Chemistry, R.T.M. Nagpur University, Nagpur 440 033 (India)

    2011-01-15

    The experimental data of density and viscosity have been obtained for aqueous solutions of biologically active compounds like salbutamol sulphate (SS), diethylcarbamazine citrate (DEC), and chlorpheniramine maleate (CPM) in the concentration range (0 to 0.15) mol . kg{sup -1} at three different temperatures. The derived parameters, such as apparent molar volume of solute ({phi}{sub V})), limiting apparent molar volume of solute ({phi}{sub V}{sup 0}), limiting apparent molar expansivity ({phi}{sub E}{sup 0}), thermal expansion coefficient ({alpha}*) and Jones-Dole equation viscosity A and B coefficients, were obtained using the density and viscosity results. It has been observed that the electrolyte-salt (SS) as well as adducts exhibit a positive viscosity B coefficient having negative ((dB)/(dT)). These results are interpreted in the light of possible solute-solute and solute-solvent interactions.

  5. Caffeine inhibition of GLUT1 is dependent on the activation state of the transporter.

    Science.gov (United States)

    Gunnink, Leesha K; Busscher, Brianna M; Wodarek, Jeremy A; Rosette, Kylee A; Strohbehn, Lauren E; Looyenga, Brendan D; Louters, Larry L

    2017-06-01

    Caffeine has been shown to be a robust uncompetitive inhibitor of glucose uptake in erythrocytes. It preferentially binds to the nucleotide-binding site on GLUT1 in its tetrameric form and mimics the inhibitory action of ATP. Here we demonstrate that caffeine is also a dose-dependent, uncompetitive inhibitor of 2-deoxyglucose (2DG) uptake in L929 fibroblasts. The inhibitory effect on 2DG uptake in these cells was reversible with a rapid onset and was additive to the competitive inhibitory effects of glucose itself, confirming that caffeine does not interfere with glucose binding. We also report for the first time that caffeine inhibition was additive to inhibition by curcumin, suggesting distinct binding sites for curcumin and caffeine. In contrast, caffeine inhibition was not additive to that of cytochalasin B, consistent with previous data that reported that these two inhibitors have overlapping binding sites. More importantly, we show that the magnitude of maximal caffeine inhibition in L929 cells is much lower than in erythrocytes (35% compared to 90%). Two epithelial cell lines, HCLE and HK2, have both higher concentrations of GLUT1 and increased basal 2DG uptake (3-4 fold) compared to L929 cells, and subsequently display greater maximal inhibition by caffeine (66-70%). Interestingly, activation of 2DG uptake (3-fold) in L929 cells by glucose deprivation shifted the responsiveness of these cells to caffeine inhibition (35%-70%) without a change in total GLUT1 concentration. These data indicate that the inhibition of caffeine is dependent on the activity state of GLUT1, not merely on the concentration. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  6. Molecular Motions Involved in Na-K-Cl Cotransporter-mediated Ion Transport and Transporter Activation Revealed by Internal Cross-linking between Transmembrane Domains 10 and 11/12*

    Science.gov (United States)

    Monette, Michelle Y.; Somasekharan, Suma; Forbush, Biff

    2014-01-01

    We examined the relationship between transmembrane domain (TM) 10 and TM11/12 in NKCC1, testing homology models based on the structure of AdiC in the same transporter superfamily. We hypothesized that introduced cysteine pairs would be close enough for disulfide formation and would alter transport function: indeed, evidence for cross-link formation with low micromolar concentrations of copper phenanthroline or iodine was found in 3 of 8 initially tested pairs and in 1 of 26 additionally tested pairs. Inhibition of transport was observed with copper phenanthroline and iodine treatment of P676C/A734C and I677C/A734C, consistent with the proximity of these residues and with movement of TM10 during the occlusion step of ion transport. We also found Cu2+ inhibition of the single-cysteine mutant A675C, suggesting that this residue and Met382 of TM3 are involved in a Cu2+-binding site. Surprisingly, cross-linking of P676C/I730C was found to prevent rapid deactivation of the transporter while not affecting the dephosphorylation rate, thus uncoupling the phosphorylation and activation steps. Consistent with this, (a) cross-linking of P676C/I730C was dependent on activation state, and (b) mutants lacking the phosphoregulatory domain could still be activated by cross-linking. These results suggest a model of NKCC activation that involves movement of TM12 relative to TM10, which is likely tied to movement of the large C terminus, a process somehow triggered by phosphorylation of the regulatory domain in the N terminus. PMID:24451383

  7. Ciliary transport regulates PDGF-AA/αα signaling via elevated mammalian target of rapamycin signaling and diminished PP2A activity.

    Science.gov (United States)

    Umberger, Nicole L; Caspary, Tamara

    2015-01-15

    Primary cilia are built and maintained by intraflagellar transport (IFT), whereby the two IFT complexes, IFTA and IFTB, carry cargo via kinesin and dynein motors for anterograde and retrograde transport, respectively. Many signaling pathways, including platelet- derived growth factor (PDGF)-AA/αα, are linked to primary cilia. Active PDGF-AA/αα signaling results in phosphorylation of Akt at two residues: P-Akt(T308) and P-Akt(S473), and previous work showed decreased P-Akt(S473) in response to PDGF-AA upon anterograde transport disruption. In this study, we investigated PDGF-AA/αα signaling via P-Akt(T308) and P-Akt(S473) in distinct ciliary transport mutants. We found increased Akt phosphorylation in the absence of PDGF-AA stimulation, which we show is due to impaired dephosphorylation resulting from diminished PP2A activity toward P-Akt(T308). Anterograde transport mutants display low platelet-derived growth factor receptor (PDGFR)α levels, whereas retrograde mutants exhibit normal PDGFRα levels. Despite this, neither shows an increase in P-Akt(S473) or P-Akt(T308) upon PDGF-AA stimulation. Because mammalian target of rapamycin complex 1 (mTORC1) signaling is increased in ciliary transport mutant cells and mTOR signaling inhibits PDGFRα levels, we demonstrate that inhibition of mTORC1 rescues PDGFRα levels as well as PDGF-AA-dependent phosphorylation of Akt(S473) and Akt(T308) in ciliary transport mutant MEFs. Taken together, our data indicate that the regulation of mTORC1 signaling and PP2A activity by ciliary transport plays key roles in PDGF-AA/αα signaling.

  8. EUV-driven ionospheres and electron transport on extrasolar giant planets orbiting active stars

    CERN Document Server

    Chadney, J M; Koskinen, T T; Miller, S; Sanz-Forcada, J; Unruh, Y C; Yelle, R V

    2016-01-01

    The composition and structure of the upper atmospheres of Extrasolar Giant Planets (EGPs) are affected by the high-energy spectrum of their host stars from soft X-rays to EUV. This emission depends on the activity level of the star, which is primarily determined by its age. We focus upon EGPs orbiting K- and M-dwarf stars of different ages. XUV spectra for these stars are constructed using a coronal model. These spectra are used to drive both a thermospheric model and an ionospheric model, providing densities of neutral and ion species. Ionisation is included through photo-ionisation and electron-impact processes. We find that EGP ionospheres at all orbital distances considered and around all stars selected are dominated by the long-lived H$^+$ ion. In addition, planets with upper atmospheres where H$_2$ is not substantially dissociated have a layer in which H$_3^+$ is the major ion at the base of the ionosphere. For fast-rotating planets, densities of short-lived H$_3^+$ undergo significant diurnal variation...

  9. Targeting the lactate transporter MCT1 in endothelial cells inhibits lactate-induced HIF-1 activation and tumor angiogenesis.

    Directory of Open Access Journals (Sweden)

    Pierre Sonveaux

    Full Text Available Switching to a glycolytic metabolism is a rapid adaptation of tumor cells to hypoxia. Although this metabolic conversion may primarily represent a rescue pathway to meet the bioenergetic and biosynthetic demands of proliferating tumor cells, it also creates a gradient of lactate that mirrors the gradient of oxygen in tumors. More than a metabolic waste, the lactate anion is known to participate to cancer aggressiveness, in part through activation of the hypoxia-inducible factor-1 (HIF-1 pathway in tumor cells. Whether lactate may also directly favor HIF-1 activation in endothelial cells (ECs thereby offering a new druggable option to block angiogenesis is however an unanswered question. In this study, we therefore focused on the role in ECs of monocarboxylate transporter 1 (MCT1 that we previously identified to be the main facilitator of lactate uptake in cancer cells. We found that blockade of lactate influx into ECs led to inhibition of HIF-1-dependent angiogenesis. Our demonstration is based on the unprecedented characterization of lactate-induced HIF-1 activation in normoxic ECs and the consecutive increase in vascular endothelial growth factor receptor 2 (VEGFR2 and basic fibroblast growth factor (bFGF expression. Furthermore, using a variety of functional assays including endothelial cell migration and tubulogenesis together with in vivo imaging of tumor angiogenesis through intravital microscopy and immunohistochemistry, we documented that MCT1 blockers could act as bona fide HIF-1 inhibitors leading to anti-angiogenic effects. Together with the previous demonstration of MCT1 being a key regulator of lactate exchange between tumor cells, the current study identifies MCT1 inhibition as a therapeutic modality combining antimetabolic and anti-angiogenic activities.

  10. Effects of pharmaceuticals and personal care products (PPCPs) on multixenobiotic resistance (MXR) related efflux transporter activity in zebrafish (Danio rerio) embryos.

    Science.gov (United States)

    Cunha, V; Burkhardt-Medicke, K; Wellner, P; Santos, M M; Moradas-Ferreira, P; Luckenbach, T; Ferreira, M

    2017-02-01

    Certain ATP binding cassette (ABC) transporter proteins, such as zebrafish Abcb4, are efflux pumps acting as a cellular defence against a wide range of different, potentially toxic chemical compounds thus mediating so called multixenobiotic resistance (MXR). Certain chemicals target MXR proteins and, as so called chemosensitisers, inhibit the activity of these proteins thus increasing the toxicity of other chemicals that would normally be effluxed. In this study 14 pharmaceuticals and personal care products (PPCPs) that are being increasingly detected in aquatic systems, were assessed for interference with the MXR system of zebrafish (Danio rerio). Concentration dependent effects of test compounds were recorded with the dye accumulation assay using zebrafish embryos and in ATPase assays with recombinant zebrafish Abcb4. In the dye accumulation assay embryos at 24h post fertilisation (hpf) were exposed to 8µm rhodamine 123 along with test compounds for 2h. The rhodamine 123 tissue levels upon the exposure served as a measure for MXR transporter efflux activity of the embryo (low rhodamine levels - high activity; high levels - low activity). The known ABC protein inhibitors MK571, vinblastine and verapamil served as positive controls. All tested PPCPs affected rhodamine 123 accumulation in embryos. For seven compounds rhodamine tissue levels were either both decreased and increased depending on the compound concentration indicating both stimulation and inhibition of rhodamine 123 efflux by those compounds, only increased (inhibition, six compounds) or only decreased (stimulation, one compound). Recombinant zebrafish Abcb4 was obtained with the baculovirus expression system and PPCPs were tested for stimulation/inhibition of basal transporter ATPase activity and for inhibition of the transporter ATPase activity stimulated with verapamil. Eight of the tested PPCPs showed effects on Abcb4 ATPase activity indicating that their effects in the dye accumulation assay may

  11. Health impact modelling of active travel visions for England and Wales using an Integrated Transport and Health Impact Modelling Tool (ITHIM.

    Directory of Open Access Journals (Sweden)

    James Woodcock

    Full Text Available BACKGROUND: Achieving health benefits while reducing greenhouse gas emissions from transport offers a potential policy win-win; the magnitude of potential benefits, however, is likely to vary. This study uses an Integrated Transport and Health Impact Modelling tool (ITHIM to evaluate the health and environmental impacts of high walking and cycling transport scenarios for English and Welsh urban areas outside London. METHODS: Three scenarios with increased walking and cycling and lower car use were generated based upon the Visions 2030 Walking and Cycling project. Changes to carbon dioxide emissions were estimated by environmental modelling. Health impact assessment modelling was used to estimate changes in Disability Adjusted Life Years (DALYs resulting from changes in exposure to air pollution, road traffic injury risk, and physical activity. We compare the findings of the model with results generated using the World Health Organization's Health Economic Assessment of Transport (HEAT tools. RESULTS: This study found considerable reductions in disease burden under all three scenarios, with the largest health benefits attributed to reductions in ischemic heart disease. The pathways that produced the largest benefits were, in order, physical activity, road traffic injuries, and air pollution. The choice of dose response relationship for physical activity had a large impact on the size of the benefits. Modelling the impact on all-cause mortality rather than through individual diseases suggested larger benefits. Using the best available evidence we found fewer road traffic injuries for all scenarios compared with baseline but alternative assumptions suggested potential increases. CONCLUSIONS: Methods to estimate the health impacts from transport related physical activity and injury risk are in their infancy; this study has demonstrated an integration of transport and health impact modelling approaches. The findings add to the case for a move from

  12. Effect of Aloe vera extract on the improvement of the respiratory activity of leukocytes of matrinxã during the transport stress

    Directory of Open Access Journals (Sweden)

    Fábio Sabbadin Zanuzzo

    2012-10-01

    Full Text Available This study evaluated the effect of extract of Aloe vera in the transport water of matrinxã (Brycon amazonicus fish on stress response and leukocyte respiratory activity. Fish was transported for 4 h in water containing Aloe at levels 0; 0.02; 0.2 and 2 mg/L, and sampled before transport 2, 4, 24 and 96 h after for determination of plasma glucose and respiratory activity of leukocytes. An additional in vitro assay was conducted with another fish species, pacu (Piaractus mesopotamicus, to test the respiratory burst of leukocytes exposed to Aloe extract (0.0, phosphate-buffered saline (PBS only at 0.1, 0.2, 0.5 and 1 mg/L. Plasma glucose increased after 2 and 4 h of transport and returned to control levels within 24 h, but the addition of Aloe in the transport water did not affect the level of blood glucose. However, at 2 h of transport, Aloe enhanced the respiratory activity of leukocytes in a dose-dependent way. The highest value of respiratory burst activity of leukocytes was observed in the fish transported in water containing Aloe at 2 mg/L. The enhancing effect of the plant extract on the production of oxygen radicals was confirmed in vitro in leukocytes of pacu incubated in Aloe at concentrations 0.1 and 0.2 mg/L. The results suggest that Aloe vera is a modulator of the immune system in fish improving the innate immune response tested.

  13. Sinupret activates CFTR and TMEM16A-dependent transepithelial chloride transport and improves indicators of mucociliary clearance.

    Directory of Open Access Journals (Sweden)

    Shaoyan Zhang

    Full Text Available INTRODUCTION: We have previously demonstrated that Sinupret, an established treatment prescribed widely in Europe for respiratory ailments including rhinosinusitis, promotes transepithelial chloride (Cl- secretion in vitro and in vivo. The present study was designed to evaluate other indicators of mucociliary clearance (MCC including ciliary beat frequency (CBF and airway surface liquid (ASL depth, but also investigate the mechanisms that underlie activity of this bioflavonoid. METHODS: Primary murine nasal septal epithelial (MNSE [wild type (WT and transgenic CFTR(-/-], human sinonasal epithelial (HSNE, WT CFTR-expressing CFBE and TMEM16A-expressing HEK cultures were utilized for the present experiments. CBF and ASL depth measurements were performed. Mechanisms underlying transepithelial Cl- transport were determined using pharmacologic manipulation in Ussing chambers, Fura-2 intracellular calcium [Ca(2+]i imaging, cAMP signaling, regulatory domain (R-D phosphorylation of CFTR, and excised inside out and whole cell patch clamp analysis. RESULTS: Sinupret-mediated Cl- secretion [ΔISC(µA/cm(2] was pronounced in WT MNSE (20.7+/-0.9 vs. 5.6+/-0.9(control, p<0.05, CFTR(-/- MNSE (10.1+/-1.0 vs. 0.9+/-0.3(control, p<0.05 and HSNE (20.7+/-0.3 vs. 6.4+/-0.9(control, p<0.05. The formulation activated Ca(2+ signaling and TMEM16A channels, but also increased CFTR channel open probability (Po without stimulating PKA-dependent pathways responsible for phosphorylation of the CFTR R-domain and resultant Cl- secretion. Sinupret also enhanced CBF and ASL depth. CONCLUSION: Sinupret stimulates CBF, promotes transepithelial Cl- secretion, and increases ASL depth in a manner likely to enhance MCC. Our findings suggest that direct stimulation of CFTR, together with activation of Ca(2+-dependent TMEM16A secretion account for the majority of anion transport attributable to Sinupret. These studies provide further rationale for using robust Cl- secretagogue based

  14. Associations of occupational, transportation, household and leisure-time physical activity patterns with metabolic risk factors among middle-aged adults in a middle-income country.

    Science.gov (United States)

    Chu, Anne H Y; Moy, Foong Ming

    2013-01-01

    This study investigates physical activity in different domains and its association with metabolic risk factors among middle-aged adults. The study was performed in Kuala Lumpur, Malaysia from August 2010-August 2011. Body mass index (BMI), waist circumference, systolic/diastolic blood pressure, and fasting blood glucose/lipid profile were measured in 686 Malay participants (mean age 45.9 ± 6.5 years). Self-reported physical activity was obtained with the validated IPAQ (Malay version) and categorized into low-, moderate- and high-activity levels across occupational, transportation, household and leisure-time domains. Participants spent most of their time on household (567.5, 95% CI: 510-630 MET-minutes/week) and occupational activities (297, 95% CI: 245-330 MET-minutes/week). After adjusted for gender and smoking, participants with low-activity levels in occupational, transport and household domains were associated with significantly higher odds for metabolic syndrome (2.02, 95% CI: 1.33-3.05; 1.49, 95% CI: 1.01-2.21; 1.96, 95% CI: 1.33-2.91). Significantly higher odds for obesity and abdominal obesity were consistently reported among those with low-activity levels across all four domains. High-activity levels in occupational, transportation and household domains were each negatively associated with metabolic syndrome among our cohort. Increase participation of physical activity across all four domains (including leisure-time activity) should be encouraged. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Reprint of “Zooplankton biomass and electron transport system activity around the Balearic Islands (western Mediterranean)”

    Science.gov (United States)

    Herrera, A.; Gómez, M.; Packard, T. T.; Fernández de Puelles, M. L.

    2014-10-01

    Measuring electron transport system (ETS) activity in zooplankton provides an index of respiration, theoretically, the potential respiration rate. We apply the ETS technique to estimate potential respiration and carbon demand from the zooplankton community in the upper 200 m of the water column near the Balearic Islands. The investigation was focused on two areas with different oceanographic conditions: the Balearic and Algerian subbasins. It compared the biomass, potential respiration and specific potential respiration of different size fractions (53-200, 200-500, > 500 μm) in both areas. In these regions the largest contribution to respiration was found in the larger sizes. The specific respiration (per unit biomass) was greater in smaller fractions, indicating that they have a more active metabolism. Both biomass and potential respiration increased in the Algerian subbasin and for both regions biomass and potential respiration were greater in shallow waters over the continental shelf (< 200 m). Using Kleiber's law as a tool to investigate the relationships between these two variables, we found that the exponential relation coefficient (b) was less than 0.75, indicating that the respiration was depressed (shifted down). In cultures and in eutrophic ocean waters (upwelling areas) b normally is greater than 0.75, consequently we intuit that the low value of b over the Balearic and Algerian subbasins indicates that the zooplankton is not well fed and that they are living under oligotrophic stress.

  16. An evaluation of the active fracture concept with modelingunsaturated flow and transport in a fractured meter-sized block ofrock

    Energy Technology Data Exchange (ETDEWEB)

    Seol, Yongkoo; Kneafsey, Timothy J.; Ito, Kazumasa

    2003-05-30

    Numerical simulation is an effective and economical tool for optimally designing laboratory experiments and deriving practical experimental conditions. We executed a detailed numerical simulation study to examine the active fracture concept (AFC, Liu et al., 1998) using a cubic meter-sized block model. The numerical simulations for this study were performed by applying various experimental conditions, including different bottom flow boundaries, varying injection rates, and different fracture-matrix interaction (by increasing absolute matrix permeability at the fracture matrix boundary) for a larger fracture interaction under transient or balanced-state flow regimes. Two conceptual block models were developed based on different numerical approaches: a two-dimensional discrete-fracture-network model (DFNM) and a one-dimensional dual continuum model (DCM). The DFNM was used as a surrogate for a natural block to produce synthetic breakthrough curves of water and tracer concentration under transient or balanced-state conditions. The DCM is the approach typically used for the Yucca Mountain Project because of its computational efficiency. The AFC was incorporated into the DCM to capture heterogeneous flow patterns that occur in unsaturated fractured rocks. The simulation results from the DCM were compared with the results from the DFNM to determine whether the DCM could predict the water flow and tracer transport observed in the DFNM at the scale of the experiment. It was found that implementing the AFC in the DCM improved the prediction of unsaturated flow and that the flow and transport experiments with low injection rates in the DFNM were compared better with the AFC implemented DCM at the meter scale. However, the estimated AFC parameter varied from 0.38 to 1.0 with different flow conditions, suggesting that the AFC parameter was not a sufficient to fully capture the complexity of the flow processes in a one meter sized discrete fracture network.

  17. A role for tungsten in the biology of Campylobacter jejuni: tungstate stimulates formate dehydrogenase activity and is transported via an ultra-high affinity ABC system distinct from the molybdate transporter.

    Science.gov (United States)

    Smart, Jonathan P; Cliff, Matthew J; Kelly, David J

    2009-11-01

    The food-borne pathogen Campylobacter jejuni possesses no known tungstoenzymes, yet encodes two ABC transporters (Cj0300-0303 and Cj1538-1540) homologous to bacterial molybdate (ModABC) uptake systems and the tungstate transporter (TupABC) of Eubacterium acidaminophilum respectively. The actual substrates and physiological role of these transporters were investigated. Tryptophan fluorescence spectroscopy and isothermal titration calorimetry of the purified periplasmic binding proteins of each system revealed that while Cj0303 is unable to discriminate between molybdate and tungstate (K(D) values for both ligands of 4-8 nM), Cj1540 binds tungstate with a K(D) of 1.0 +/- 0.2 pM; 50 000-fold more tightly than molybdate. Induction-coupled plasma mass spectroscopy of single and double mutants showed that this large difference in affinity is reflected in a lower cellular tungsten content in a cj1540 (tupA) mutant compared with a cj0303c (modA) mutant. Surprisingly, formate dehydrogenase (FDH) activity was decreased approximately 50% in the tupA strain, and supplementation of the growth medium with tungstate significantly increased FDH activity in the wild type, while inhibiting known molybdoenzymes. Our data suggest that C. jejuni possesses a specific, ultra-high affinity tungstate transporter that supplies tungsten for incorporation into FDH. Furthermore, possession of two MoeA paralogues may explain the formation of both molybdopterin and tungstopterin in this bacterium.

  18. Transcriptional activation and localization of expression of Brassica juncea putative metal transport protein BjMTP1

    Directory of Open Access Journals (Sweden)

    Salt David E

    2007-06-01

    Full Text Available Abstract Background Metal hyperaccumulators, including various Thlaspi species, constitutively express the putative metal transporter MTP1 to high levels in shoots. Here we present data on the transcriptional regulation and localization of expression of the homologous gene BjMTP1 in Brassica juncea. Though B. juncea lacks the ability to hyperaccumulate metals, its relatively high biomass, rapid growth and relatedness to true metal hyperaccumulating plants makes it a promising starting point for the development of plants for phytoremediation. Our goal in this study is to determine the transcriptional regulation of MTP1 in order to start to better understanding the physiological role of MTP1 in B. juncea. Results Steady-state mRNA levels of BjMTP1 were found to be enhanced 8.8, 5.9, and 1.6-fold in five-day-old B. juncea seedlings after exposure to Ni2+, Cd2+ or Zn2+, respectively. This was also reflected in enhanced GUS activity in B. juncea seedlings transformed with BjMTP1 promoter::GUSPlus after exposure to these metals over a similar range of toxicities from mild to severe. However, no increase in GUS activity was observed after exposure of seedlings to cold or heat stress, NaCl or hydrogen peroxide. GUS expression in Ni2+ treated seedlings was localized in roots, particularly in the root-shoot transition zone. In four- week- old transgenic plants BjMTP1 promoter activity also primarily increased in roots in response to Ni2+ or Cd2+ in plants transformed with either GUS or mRFP1 as reporter genes, and expression was localized to the secondary xylem parenchyma. In leaves, BjMTP1 promoter activity in response to Ni2+ or Cd2+ spiked after 24 h then decreased. In shoots GUS expression was prominently present in the vasculature of leaves, and floral parts. Conclusion Our studies establish that a 983 bp DNA fragment upstream of the BjMTP1 translational start site is sufficient for the specific activation by Ni2+ and Cd2+ of BjMTP1 expression

  19. Transcriptional activation and localization of expression of Brassica juncea putative metal transport protein BjMTP1

    Science.gov (United States)

    Muthukumar, Balasubramaniam; Yakubov, Bakhtiyor; Salt, David E

    2007-01-01

    Background Metal hyperaccumulators, including various Thlaspi species, constitutively express the putative metal transporter MTP1 to high levels in shoots. Here we present data on the transcriptional regulation and localization of expression of the homologous gene BjMTP1 in Brassica juncea. Though B. juncea lacks the ability to hyperaccumulate metals, its relatively high biomass, rapid growth and relatedness to true metal hyperaccumulating plants makes it a promising starting point for the development of plants for phytoremediation. Our goal in this study is to determine the transcriptional regulation of MTP1 in order to start to better understanding the physiological role of MTP1 in B. juncea. Results Steady-state mRNA levels of BjMTP1 were found to be enhanced 8.8, 5.9, and 1.6-fold in five-day-old B. juncea seedlings after exposure to Ni2+, Cd2+ or Zn2+, respectively. This was also reflected in enhanced GUS activity in B. juncea seedlings transformed with BjMTP1 promoter::GUSPlus after exposure to these metals over a similar range of toxicities from mild to severe. However, no increase in GUS activity was observed after exposure of seedlings to cold or heat stress, NaCl or hydrogen peroxide. GUS expression in Ni2+ treated seedlings was localized in roots, particularly in the root-shoot transition zone. In four- week- old transgenic plants BjMTP1 promoter activity also primarily increased in roots in response to Ni2+ or Cd2+ in plants transformed with either GUS or mRFP1 as reporter genes, and expression was localized to the secondary xylem parenchyma. In leaves, BjMTP1 promoter activity in response to Ni2+ or Cd2+ spiked after 24 h then decreased. In shoots GUS expression was prominently present in the vasculature of leaves, and floral parts. Conclusion Our studies establish that a 983 bp DNA fragment upstream of the BjMTP1 translational start site is sufficient for the specific activation by Ni2+ and Cd2+ of BjMTP1 expression primarily in roots. Activation of

  20. "If You Don't Do Parking Management .. Forget Your Behaviour Change, It's Not Going to Work.": Health and Transport Practitioner Perspectives on Workplace Active Travel Promotion.

    Science.gov (United States)

    Petrunoff, Nick; Rissel, Chris; Wen, Li Ming

    2017-01-01

    After having conducted two studies of the effectiveness of workplace travel plans for promoting active travel, we investigated health and transport practitioners' perspectives on implementing workplace travel plans to share some of the lessons learnt. The objectives of this study were to describe perceived elements of effective workplace travel plans, barriers and enablers to workplace travel planning, their experiences of working with the other profession on travel plan implementation, their recommendations for workplace travel planning, and also to explore similarities and differences in transport and health practitioner perspectives. Fourteen health and ten transport practitioners who had prior involvement in workplace travel plan programs were purposefully selected from workplaces in Australia. We conducted 20 in-depth interviews since data saturation had been reached at this point, and data were subject to framework analysis. Perceived essential elements of effective workplace travel plans included parking management; leadership, organisational commitment and governance; skills and other resources like a dedicated travel plan coordinator; and, pre-conditions including supportive transport infrastructure in the surrounds. Recommendations for promoting travel plans included supportive government policy, focusing on business benefits and working at different scales of implementation (e.g. single large worksites and business precincts). Health and transport practitioner perspectives differed, with transport practitioners believing that parking management is the key action for managing travel demand at a worksite. Health practitioners implementing travel plans may require training including concepts of travel demand management, and support from transport planners on parking management strategies. Promoting an understanding of the shared travel behaviour change skills of transport and health practitioners may assist further collaboration. For take-up by