WorldWideScience

Sample records for active transport advocate

  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. Advocating Green Transport and Promoting Healthy Urban Development: Strategies for Bicycle Transport Development in Jinan

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>As a green transport means,the bicycle has a history of over two hundred years.Since the 1970s,due to the inf luence of energy crisis and the consciousness of environment protection,the bicycle has regained its popularity in the public for its

  3. Three perspectives on bedload transport at a sandy gravel beach (Advocate Harbour, Nova Scotia) with focus on sediment properties

    Science.gov (United States)

    Stark, N.; Hay, A. E.; Guest, T.; Hatcher, M. G.; Cheel, R. A.; Barclay, D. J.; Zedel, L. J.; Lake, C. B.

    2012-12-01

    Bedload transport is the major transport mode for coarse sediment in coastal zones. Understanding its mechanisms requires knowledge of the driving force (hydrodynamics), the stabilizing force (sediment properties), and the bed characteristics (bed roughness, bed slope, bedforms). During a 3-week-long field experiment at Advocate Beach, Nova Scotia, bedload transport was targeted from three perspectives: (i) The water column: using a new acoustic Doppler profiler (MFDop), 3D flow velocities were monitored to assess bed shear stress over a range of conditions. Additionally, sediment concentrations close to the bed (~10 cm) were determined by water sampling under calm conditions (0.15-0.6 g/l) and within the shorebreak (1-50 g/l). (ii) The bed: rotary sonars were used to observe the development of ripples and bed elevation change as a measure of ongoing sediment transport. Also, the net displacement of 20 marked cobbles on the seabed surface was measured, revealing significant changes in transport direction and distance (ranging from 0 to 50 m). (iii) The sediment properties: grain size ranged from medium sand to small cobbles. The finer-grained particles were rounded, but showed an elliptic to plate-like shape. Grain size distributions varied significantly across the shoreface as well as under different hydrodynamic conditions. Observed beach cusps were strongly sorted (coarse pebbles at the horns, coarse sand in the bays). Direct shear tests were carried out to determine peak shear strengths of the sediment and friction angles. Peak shear strengths under low normal stress (0.47 kPa) can be compared best to surficial sediment conditions, and did not exceed 9 kPa in the case of the sands. The sediment showed a surprisingly strong dilative behavior during shearing and high friction angles considering the grain size, the low load and low density conditions during the tests. Thus, grain shape and the particle re-organization under shearing played important roles. Finally

  4. Advocating for active living on the rural-urban fringe: a case study of planning in the Portland, Oregon, metropolitan area.

    Science.gov (United States)

    Adler, Sy; Dobson, Noelle; Fox, Karen Perl; Weigand, Lynn

    2008-06-01

    This case study is about the politics of incorporating active-living elements into a concept plan for a new community of about 68,000 people on the edge of the Portland, Oregon, metropolitan area. Development on the rural-urban fringe is ongoing in metropolitan areas around the United States. In this article, we evaluate the product of the concept-planning process from the standpoint of the extent to which environmental elements conducive to active living were included. We also analyze four issues in which challenges to the incorporation of active-living features surfaced: choices related to transportation facilities, the design and location of retail stores, the location of schools and parks, and the location of a new town center. Overall, the Damascus/Boring Concept Plan positions the area well to promote active living. Analyses of the challenges that emerged yielded lessons for advocates regarding ways to deal with conflicts between facilitating active living and local economic development and related tax-base concerns and between active-living elements and school-district planning autonomy as well as the need for advocates to have the capacity to present alternatives to the usual financial and design approaches taken by private- and public-sector investors.

  5. Snowballing movement. Legislators are now active advocates regarding population and development.

    Science.gov (United States)

    De Leon, B D

    1992-08-01

    Newly industrializing economies (NIEs) in East Asia have demonstrated that the population programs were part of their economic success, such as in Thailand and Indonesia where family planning (FP) was made a way of life. The population growth in the Philippines has put pressure on the environment by migration to uplands where slash-and-burn agriculture adds to deforestation. The Global Committee of Parliamentarians of Population and Development headquartered in New York serves as a liaison for 56 legislative groups sponsoring meetings and seminars. In October 1981 the Asian Conference on Parliamentarians on Population and Development was held in Beijing with the participation of legislators from 19 countries. It set up the Asian Forum for Parliamentarians on Population and Development to contribute and promote activities that facilitate population and development, and to improve the living standards and welfare of people in Asia. The Secretariat is located in Bangkok, Thailand. In October 1987 in Beijing and in October 1990 follow-up regional conferences were organized. The latter was attended by 21 Asian parliamentarians who endorsed the stabilization of population growth to achieve a 1% growth rate for Asia by 2000. The Philippine population numbered 63.9 million in mid-1992 with an annual growth rate of 2.3%. The Philippine House of Representatives started an inquiry about the disturbing demographic trends with implications on economic growth. In 1987 a movement commenced that hosted the Philippine Parliamentarians Conference on Human Survival, Population and Development (PARLCON '88) in Manila. It focused on sustainable development, the conditions of women and children, the environment, and the promotion of FP which was adopted by the House and involved a major segment of legislators.

  6. Advocate: 2014 Annual Report

    Science.gov (United States)

    Association of Governing Boards of Universities and Colleges, 2014

    2014-01-01

    The Association of Governing Boards of Universities and Colleges (AGB) strives to continuously advance the practice of governance by designing and instilling best practices and advocating nationally on issues that affect higher education. AGB shares vital information and knowledge with members and provides customized consulting services to help…

  7. CCCT - Patient Advocate Steering Committee

    Science.gov (United States)

    The Patient Advocate Steering Committee (PASC) works to ensure advocates involved with the Scientific Steering Committees (SSCs) are completely integrated in the development, implementation, and monitoring of clinical trials within those groups.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. Nuclear physicist, arms control advocate

    CERN Multimedia

    Chang, K

    2002-01-01

    Victor F. Weisskopf, a nuclear physicist who worked on the Manhattan Project to build the first atomic bomb in World War II and later became an ardent advocate of arms control, died Monday at his home in Newton, MA, USA. He was 93 (1 page).

  13. Strategies for Training Citizen Advocates.

    Science.gov (United States)

    Nader, Ralph

    1990-01-01

    Training of citizen advocates should include legal rights and remedies; how to get information from corporations and governments; freedom of information laws; use of media; and how to write letters to editors and public officials. Adult educators can help create networks for sharing experience in dealing with community problems. (SK)

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. A Follow-Up Study of Former Student Health Advocates

    Science.gov (United States)

    Streng, Nancy J.

    2007-01-01

    Student health advocates (SHAs) are high school students who, under the supervision of the school nurse, provide health education and health promotion activities to other students via a peer education model. This 3-year follow-up study explored how the SHA experience influences career choice and attitudes of the participants. It also examined what…

  20. 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.

  1. 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.

  2. Ira P. Gunn: educator, advocate, legend.

    Science.gov (United States)

    McAuliffe, Maura S; Koch, Faan Kathy J

    2011-12-01

    This column examines the contributions of nurse anesthetist Ira P. Gunn, CRNA, MLN, FAAN (1927-2011), widely recognized as a visionary and tireless advocate for the profession of nurse anesthesia. Her contributions to nurse anesthesia practice, research, education, publication, consultation, credentialing, and government relations have significantly contributed to the preservation and advancement of nursing and nurse anesthesia.

  3. Advocating for Grade-Based Acceleration

    Science.gov (United States)

    Guilbault, Keri M.

    2014-01-01

    Parents often struggle with the decision to accelerate their child and may worry about social and emotional issues, although research indicates positive effects on the social and emotional adjustment of carefully selected accelerants. As children's advocates, parents can work effectively with a school system to secure an appropriate academic…

  4. 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.

  5. 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

  6. 39 CFR 3002.14 - Office of the Consumer Advocate.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Office of the Consumer Advocate. 3002.14 Section... Consumer Advocate. (a) The Office of the Consumer Advocate provides representation for the interests of the... pendency of a proceeding, personnel serving in the Office of the Consumer Advocate are prohibited...

  7. 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

  8. The neonatal nurse: advocating for breastfeeding mothers.

    Science.gov (United States)

    Darby, Colm; Nurse, Sharon

    2016-02-01

    Accurate information and support from healthcare professionals as well as respect for parental choice are all factors which contribute to effective breastfeeding in the neonatal unit; with this in mind, Colm Darby and Sharon Nurse discuss the potential problems in expressing breast milk and the interventions which might be effective in avoiding them. Advocacy is an inherent part of neonatal nurses' role whilst caring for sick, vulnerable babies. Colm Darby is a male neonatal nurse working in a predominantly female environment and passionately believes in supporting and advocating for mothers who want to provide breast milk for their babies. In this article, CoIm uses Borton's model of reflection to discuss how he acted as an effective advocate for such a mother.

  9. 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.

  10. An Advocates' Guide to Advocating...or A Good Offense without Being Offensive.

    Science.gov (United States)

    Monson, Jay A.

    1984-01-01

    A policy maker offers guidelines for people wishing to advocate for gifted education. Suggestions touch on such aspects as the need for apathy, the role of telephone and letter advocacy, and the appropriate target of advocacy efforts. (CL)

  11. The PRO nurse: advocate for quality care.

    Science.gov (United States)

    Carroll, M; Maichele, J

    1993-01-01

    Since the inception of the Social Security Amendments of 1983, nurses have assumed expanded roles in ensuring the monitoring of the quality of care received by Medicare beneficiaries. This unique area of nursing practice offers new challenges and employment opportunities for the nurse as a patient advocate. Nurses who are interested in this role may contact state PRO directors or watch for specific recruitment advertisements in nursing magazines.

  12. 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...

  13. 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

  14. Autoethnographic Mother-Writing: Advocating Radical Specificity

    Directory of Open Access Journals (Sweden)

    Patty Sotirin

    2010-01-01

    Full Text Available In considering the similarities between "momoirs"--popular memoirs written by mothers about motherhood experiences--and evocative autoethnographic mother-writing, I argue that differentiating these two forms of intimate observation and personal narrative requires a rethinking of autoethnographic practice. Specifically, I draw on the work of Gilles Deleuze to advocate for a radical specificity in autoethnographic writing. Thinking the autoethnographic narrative in terms of specificities and differences encourages us to think creatively about personal experiences and cultural relations beyond what is shared and communicable.

  15. 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.

  16. 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.

  17. 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)

  18. 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.

  19. An Abiotic Glass-Bead Collector Exhibiting Active Transport

    Science.gov (United States)

    Goto, Youhei; Kanda, Masato; Yamamoto, Daigo; Shioi, Akihisa

    2015-09-01

    Animals relocate objects as needed by active motion. Active transport is ubiquitous in living organisms but has been difficult to realize in abiotic systems. Here we show that a self-propelled droplet can gather scattered beads toward one place on a floor and sweep it clean. This is a biomimetic active transport with loadings and unloadings, because the transport was performed by a carrier and the motion of the carrier was maintained by the energy of the chemical reaction. The oil droplet produced fluctuation of the local number density of the beads on the floor, followed by its autocatalytic growth. This mechanism may inspire the technologies based on active transport wherein chemical and physical substances migrate as in living organisms.

  20. 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

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. John Dique: dialysis pioneer and political advocate.

    Science.gov (United States)

    George, Charles R P

    2016-02-01

    John Dique (1915-1995) epitomized the internationalism of medicine, the intellectual and manual dexterity of many pioneers of dialysis, and the social concern evinced by many nephrologists. Born in Burma of French, German, British and Indian ancestry; educated in India; an Anglo-Indian who described himself as British without ever having visited Britain; he moved to Australia in 1948 to escape the murderous inter-ethnic conflict that befell multicultural India as it and Pakistan became independent. Settling in Brisbane, he pioneered several novel medical techniques. After inventing some simple equipment to facilitate intravenous therapy, he established a neonatal exchange blood transfusion programme. Then, between 1954 and 1963, he personally constructed and operated two haemodialysis machines with which to treat patients suffering from acute renal failure, the first such treatment performed in Australasia. His patients survival results were, for the era, remarkable. He subsequently helped found the Royal Australasian College of Pathologists and went on to establish a successful private pathology practice. The latter years of his life, however, saw him become a social and political advocate. He fiercely opposed the emerging ideologies of multiculturalism and social liberalism that, he predicted, would seriously damage the national fabric of Western society. Public vilification ensued, his medical achievements disregarded. It does seem likely, however, that in none of the areas that he touched - whether medical, social, or political - has the last word yet been said.

  9. 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...

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Role of professional organizations in advocating for the nursing profession.

    Science.gov (United States)

    Matthews, Jennifer H

    2012-01-31

    Professional organizations and associations in nursing are critical for generating the energy, flow of ideas, and proactive work needed to maintain a healthy profession that advocates for the needs of its clients and nurses, and the trust of society. In this article the author discusses the characteristics of a profession, reviews the history of professional nursing organizations, and describes the advocacy activities of professional nursing organizations. Throughout, she explains how the three foundational documents of the nursing profession emphasize nursing advocacy by the professional organizations as outlined in the American Nurses Association Code of Ethics for Nurses With Interpretive Statements. The author concludes by encouraging all nurses to engage in their professional organizations and associations, noting how these organizations contribute to the accountability and voice of the profession to society.

  15. 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)

  16. 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

  17. Coaching mental health peer advocates for rural LGBTQ people.

    Science.gov (United States)

    Willging, Cathleen E; Israel, Tania; Ley, David; Trott, Elise M; DeMaria, Catherine; Joplin, Aaron; Smiley, Verida

    Lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ) people are affected by mental health disparities, especially in rural communities. We trained peer advocates in rural areas in the fundamentals of mental health, outreach, education, and support for this population. The peer advocates were coached by licensed mental health professionals. We evaluated this process through iterative qualitative analysis of semi-structured interviews and written logs from coaches and advocates. The six major themes comprising the results centered on (1) coaching support, (2) peer advocate skills and preparation, (3) working with help seekers, (4) negotiating diversity, (5) logistical challenges in rural contexts, and (6) systemic challenges. We concluded that peer advocacy for LGBTQ people with mental distress offers an affirmative, community-based strategy to assist the underserved. To be successful, however, peer advocates will likely require ongoing training, coaching, and infrastructural support to negotiate contextual factors that can influence provision of community resources and support to LGBTQ people within rural communities.

  18. Police officers' collaboration with rape victim advocates: barriers and facilitators.

    Science.gov (United States)

    Rich, Karen; Seffrin, Patrick

    2013-01-01

    Secondary victimization may occur when rape victims make police reports. This can compromise the quality of official statements and jeopardize criminal cases. Rape reporters receive better treatment by police officers when advocates are involved and best practice police work includes such collaboration. Studies of advocates have described tension, role confusion, and poor communication with police officers. Many variables, including rape myth acceptance (RMA) and training on sexual assault dynamics, may affect officers' collaboration with advocates. There were 429 police officers who responded to a survey measuring their victim interviewing skill, formal training about rape, years on the job, number of victims known personally, number of recent rape cases, RMA, and collaboration with advocates. Results suggest that officers' interviewing skill, years on the job, and specific training are related to collaboration with victim advocates on rape cases. Professional, rather than personal, variables were most predictive of collaboration. Implications for officer selection and training are explored.

  19. Family victim advocates: the importance of critical job duties

    Directory of Open Access Journals (Sweden)

    Teresa H. Young

    Full Text Available Child advocacy centers across the United States intervened in more than 250,000 child abuse cases in 2011(National Children's Alliance, 2012. Understanding the work of family victim advocates is imperative to helping children and families in child abuse cases. In this exploratory study, we surveyed advocates and program directors from child advocacy centers (CACs across the United States to compare their perceptions of the critical job duties of family victim advocates. Data analysis revealed that CAC directors rated the importance of these duties significantly higher than family victim advocates. Results suggest the need for additional training to ensure that family victim advocates understand the importance of critical job duties to meet the needs of children and families in child abuse cases.

  20. 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

  1. 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...

  2. Civil society: a critical new advocate for vaccination in Europe.

    Science.gov (United States)

    Laurent-Ledru, Vanina; Thomson, Angus; Monsonego, Joseph

    2011-01-17

    The vaccinology landscape has changed, with national authorities now being increasingly accountable to new stakeholders such as health insurers, regional regulatory bodies, the media, and civil society. Here, we discuss how civil society organisations (CSOs), such as patient and women's groups, have become important drivers in the introduction and sustainability of new vaccination programs. This shift in public implication in vaccine policy has been well illustrated in the recent introduction of human papillomavirus (HPV) vaccination in Europe. Patient and women's groups which were traditionally focused on advocacy of treatments have also become advocates for prevention with the advent of HPV vaccination. Civil society advocacy at the European level supported key resolutions and white papers which in turn informed national recommendations on cervical cancer vaccination. CSOs were also active at the national level, supporting national policy makers. These organisations may bring innovative and effective new approaches to communication on vaccination benefits, using public events, celebrities and various social media. Working with experts, CSOs can also be an important bridge from the science to the lay public. This may provide a vital counterbalance to media hype and antivaccination groups, although CSOs may also be active and vocal opponents of immunization. The successful implementation and sustainability of future vaccination programs against infections such as HIV will be dependent upon the active participation of civil society to inform, to reassure and to maintain public trust.

  3. 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.

  4. The Importance of Playing Devil's Advocate.

    Science.gov (United States)

    Schwenk, Charles; Cosier, Richard

    1990-01-01

    A "devil's advocacy" approach is proposed for the management of higher education conflict and ultimate improvement in the quality of decisions. Research supporting the value of active questioning of a preferred plan or strategy is summarized and its application is described. (DB)

  5. 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.

  6. 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...

  7. 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

  8. 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.

  9. 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

  10. Platelet serotonin transporter function predicts default-mode network activity.

    Directory of Open Access Journals (Sweden)

    Christian Scharinger

    Full Text Available The serotonin transporter (5-HTT is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence.A functional magnetic resonance study was performed in 48 healthy subjects and maximal 5-HT uptake velocity (Vmax was assessed in blood platelets. We used a mixed-effects multilevel analysis technique (MEMA to test for linear relationships between whole-brain, blood-oxygen-level dependent (BOLD activity and platelet Vmax.The present study demonstrates that increases in platelet Vmax significantly predict default-mode network (DMN suppression in healthy subjects independent of genetic variation within SLC6A4. Furthermore, functional connectivity analyses indicate that platelet Vmax is related to global DMN activation and not intrinsic DMN connectivity.This study provides evidence that platelet Vmax predicts global DMN activation changes in healthy subjects. Given previous reports on platelet-synaptosomal Vmax coupling, results further suggest an important role of neuronal 5-HT reuptake in DMN regulation.

  11. 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.

  12. 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.

  13. 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.

  14. The Development and Evaluation of a Parent Empowerment Program for Family Peer Advocates.

    Science.gov (United States)

    Rodriguez, James; Olin, S S; Hoagwood, Kimberly E; Shen, Sa; Burton, Geraldine; Radigan, Marleen; Jensen, Peter S

    2011-08-01

    Family-to-family services are emerging as an important adjunctive service to traditional mental health care and a vehicle for improving parent engagement and service use in children's mental health services. In New York State, a growing workforce of Family Peer Advocates (FPA) is delivering family-to-family services. We describe the development and evaluation of a professional program to enhance Family Peer Advocate professional skills, called the Parent Engagement and Empowerment Program (PEP). We detail the history and content of PEP and provide data from a pre/post and 6-month follow up evaluation of 58 FPA who participated in the first Statewide regional training effort. Self-efficacy, empowerment, and skills development were assessed at 3 time points: baseline, post-training, and 6-month follow-up. The largest changes were in self-efficacy and empowerment. Regional differences suggest differences in Family Peer Advocate workforce across areas of the state. This evaluation also provides the first systematic documentation of Family Peer Advocate activities over a six-month period. Consistent with peer specialists within the adult health care field, FPA in the children's mental health field primarily focused on providing emotional support and service access issues. Implications for expanding family-to-family services and integrating it more broadly into provider organizations are described.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. Gendered violence and restorative justice: the views of victim advocates.

    Science.gov (United States)

    Curtis-Fawley, Sarah; Daly, Kathleen

    2005-05-01

    The use of restorative justice for gendered violence has been debated in the feminist literature for some time. Critics warn that it is inappropriate because the process and outcomes are not sufficiently formal or stringent, and victims may be revictimized. Proponents assert that a restorative justice process may be better for victims than court because it holds offenders accountable and gives victims greater voice. This article presents what victim advocates in two Australian states think about using restorative justice for gendered violence. We find that although victim advocates have concerns and reservations about restorative justice, most saw positive elements.

  20. Remembering Albert deutsch, an advocate for mental health.

    Science.gov (United States)

    Weiss, Kenneth J

    2011-12-01

    Albert Deutsch, journalist, advocate for the mentally ill, and honorary APA Fellow died 50 years ago. Author of The Mentally Ill in America and The Shame of the States, he believed in the obligation of individuals and institutions to advocate for patients. In 1961, he was in the midst of a vast project to assess the state of the art in psychiatric research. This article recalls aspects of Deutsch's life and work and places him in the historical context of individuals who have shown great compassion for disabled persons.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. A Rhythm Recognition Computer Program to Advocate Interactivist Perception

    Science.gov (United States)

    Buisson, Jean-Christophe

    2004-01-01

    This paper advocates the main ideas of the interactive model of representation of Mark Bickhard and the assimilation/accommodation framework of Jean Piaget, through a rhythm recognition demonstration program. Although completely unsupervised, the program progressively learns to recognize more and more complex rhythms struck on the user's keyboard.…

  6. 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

  7. 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 ...

  8. 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.

  9. 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...

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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...

  16. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  18. The challenge of gun control for mental health advocates.

    Science.gov (United States)

    Pandya, Anand

    2013-09-01

    Mass shootings, such as the 2012 Newtown massacre, have repeatedly led to political discourse about limiting access to guns for individuals with serious mental illness. Although the political climate after such tragic events poses a considerable challenge to mental health advocates who wish to minimize unsympathetic portrayals of those with mental illness, such media attention may be a rare opportunity to focus attention on risks of victimization of those with serious mental illness and barriers to obtaining psychiatric care. Current federal gun control laws may discourage individuals from seeking psychiatric treatment and describe individuals with mental illness using anachronistic, imprecise, and gratuitously stigmatizing language. This article lays out potential talking points that may be useful after future gun violence.

  19. 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...

  20. FISCAL AND ACCOUNTANCY ASPECTS CONCERNING THE ECONOMIC ACTIVITY OF INTRA-COMMUNITARIAN GOODS TRANSPORT

    Directory of Open Access Journals (Sweden)

    BOTEZ DANIEL

    2009-05-01

    Full Text Available As general type of activity, transport is framed in the vast category of services. However, from a fiscal point of view, transport services are treated as an exception, in comparison with the manner in which the services are approached, in general. In t

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. Drones a Safe Way to Transport Blood

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_162471.html Drones a Safe Way to Transport Blood: Study Finding ... t seem to suffer damage when transported by drones, researchers report. The findings lend support to advocates ...

  6. 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.

  7. 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...

  8. 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...

  9. 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

  10. 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

  11. 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.

  12. Empowering natural clinical trial advocates: nurses and outreach workers.

    Science.gov (United States)

    Mitschke, Diane B; Cassel, Kevin; Higuchi, Paula

    2007-03-01

    Cancer clinical trials are essential to advancing the prevention and treatment of cancer, yet adult participation rates in clinical trials remain abysmal. Despite the essential contributions of clinical trials to science and medicine, adult participation in clinical trials remains exceedingly low, with only 2%-4% of all adult patients with cancer in the U.S. participating in clinical trials. Clinical trials accrual rates in Hawai'i follow this national trend of less than 3% of eligible patients participating in trials. Recognizing the need to increase awareness about clinical trials, the National Cancer Institute's Cancer Information Service-Pacific Region, through the Hawai'i Clinical Trials Education Coalition, has employed strategic dissemination plans to train and educate key target audiences, including registered nurses, nursing students, and community outreach workers about the availability of over 90 cancer clinical trials in Hawai'i. Previous research suggests that nurses often play a vital role in increasing a patient's understanding of clinical trials and may also act as a patient advocate in regards to participation in a clinical trial. A train-the-trainer model curriculum was developed using the Clinical Trials Education Series (CTES), a collection of multi-level resources designed by the National Cancer Institute, to educate various constituents about clinical trials. The training curriculum and workshop format is adapted based on both formal and informal needs assessments conducted with audiences prior to the planned training, yet key elements remain central to the training model. In addition, an interactive, internet-based case study was developed using local place names and cultural cues to allow training participants to engage in realistic and practical methods for locating and sharing information about clinical trials with patients and the public. This training model has been implemented in a variety of settings including three statewide nursing

  13. 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.

  14. Pere Albert: Barcelona Canon, Royal Advocate, Feudal Theorist

    Directory of Open Access Journals (Sweden)

    Kagay, Donald K.

    2002-06-01

    Full Text Available In this article, the life and career of one of Catalonia's greatest medieval legists is discussed. Using notarial and court documentation, the author explores the work of Pere Albert as judge and advocate. The Customs of Catalonia and other of Pere Albert's treatises form the basis for the review of the legist's career as a theorist in feudal law. The basis for this article is the collection of documents pertaining to Pere Albert, which the author includes in an appendix.

    En este artículo se estudia la vida y la carrera de uno de los jurisconsultos medievales más importantes de Cataluña. Utilizando la documentación notarial y judicial, el autor analiza la labor de Pere Albert como juez y abogado. ElsCostums de Catalunya y otros tratados de Pere Albert constituyen la base para el estudio de la carrera del jurisconsulto, como teórico en ley feudal y real. El artículo se basa en una colección de documentos originales relativos a Pere Albert, que el autor incluye en un apéndice.

  15. 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.

  16. 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...

  17. 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

  18. 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

  19. 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

  20. Advocate's Viewpoint on Hereditary Breast/Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Kolling-Dandrieu Francisca

    2004-08-01

    Full Text Available Abstract This paper discusses the presentation I held at the symposium on genetics during the 4th European Breast Cancer Conference held in Hamburg in March 2004. Primarily, the goals and working methods of the advocacy group specialised in Hereditary Breast/Ovarian Cancer of the Dutch Breast Cancer Patient Organisation known as BorstkankerVereniging Nederland (BVN are explained. Furthermore, some specific individual problems that mutation carriers might encounter before and after BRCA1/2 susceptibility testing are discussed. These include: dilemmas in choosing preventive interventions, dealing with the psychological impact of knowing you are a mutation carrier, dealing with the social implications of being genetically at risk, an example of insurance discrimination. In addition, some controversial social and ethical issues that are currently under debate are highlighted, such as the issue of the European patenting of the breast cancer susceptibility genes BRCA1 and BRCA2. Since this topic could also become relevant for other gene-related diseases, society as a whole has to consider the ethical and social implications related to the patenting of human genes in general. Another ethical area of debate is the controversial issue of prenatal BRCA testing and the choice of pregnancy termination. Finally, the Working Party pleads for the international co-operation and exchange of data and experience among professionals as well as patients. It appears that professionals in different European countries tend to advise on different risk management strategies and treatments and as such, the Working Party strongly advocates the international standardisation of risk management and treatment of mutation carriers. In this respect, specific attention should be given to a group that has had a non-informative or negative BRCA test result, because this group is still considered to be at high risk to develop the disease.

  1. Planning for the next generation of public health advocates: evaluation of an online advocacy mentoring program.

    Science.gov (United States)

    O'Connell, Emily; Stoneham, Melissa; Saunders, Julie

    2016-04-01

    Issue addressed Despite being viewed as a core competency for public health professionals, public health advocacy lacks a prominent place in the public health literature and receives minimal coverage in university curricula. The Public Health Advocacy Institute of Western Australia (PHAIWA) sought to fill this gap by establishing an online e-mentoring program for public health professionals to gain knowledge through skill-based activities and engaging in a mentoring relationship with an experienced public health advocate. This study is a qualitative evaluation of the online e-mentoring program. Methods Semi-structured interviews were conducted with program participants at the conclusion of the 12-month program to examine program benefits and determine the perceived contribution of individual program components to overall advocacy outcomes. Results Increased mentee knowledge, skills, level of confidence and experience, and expanded public health networks were reported. Outcomes were dependent on participants' level of commitment, time and location barriers, mentoring relationship quality, adaptability to the online format and the relevance of activities for application to participants' workplace context. Program facilitators had an important role through the provision of timely feedback and maintaining contact with participants. Conclusion An online program that combines public health advocacy content via skill-based activities with mentoring from an experienced public health advocate is a potential strategy to build advocacy capacity in the public health workforce. So what? Integrating advocacy as a core component of professional development programs will help counteract current issues surrounding hesitancy by public health professionals to proactively engage in advocacy, and ensure that high quality, innovative and effective advocacy leadership continues in the Australian public health workforce.

  2. 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

  3. 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

  4. 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 ...

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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...

  16. 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

  17. 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,

  18. 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.

  19. 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...

  20. 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).

  1. 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.

  2. 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...

  3. 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.

  4. 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.

  5. 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.  

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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...

  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. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. Conceptions of Speech Acts in the Theory and Practice of Argumentation: A Case Study of a Debate About Advocating

    Directory of Open Access Journals (Sweden)

    Goodwin Jean

    2014-03-01

    Full Text Available Far from being of interest only to argumentation theorists, conceptions of speech acts play an important role in practitioners’ self-reflection on their own activities. After a brief review of work by Houtlosser, Jackson and Kauffeld on the ways that speech acts provide normative frameworks for argumentative interactions, this essay examines an ongoing debate among scientists in natural resource fields as to the appropriateness of the speech act of advocating in policy settings. Scientists’ reflections on advocacy align well with current scholarship, and the scholarship in turn can provide a deeper understanding of how to manage the communication challenges scientists face.

  1. 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.

  2. Youth and caregiver access to peer advocates and satisfaction with mental health services.

    Science.gov (United States)

    Radigan, Marleen; Wang, Rui; Chen, Yu; Xiang, Jiani

    2014-11-01

    Access to peer advocates is increasingly available to youth and their caregivers who are receiving services in the public mental health system. This study examines associations between reported access to a youth or family advocate and perceptions of satisfaction with mental health services. A cross-sectional survey of youth (N = 768) and caregivers (N = 1,231) who utilized public mental health services in New York State in 2012 was conducted. The survey includes items on access to youth or family advocates and degree of satisfaction with mental health services. A greater proportion of youth or caregivers with access to peer advocates compared to those without access responded positively on the satisfaction domains of access to services, appropriateness of services, participation in services and overall/global satisfaction. Access to peer advocates was also positively associated with agreement on the psychotropic medication comprehension domain for youth and on perceptions of child functioning and social connectedness for caregivers compared to those without access. This study adds to the growing understanding of the important role peer advocates play in engaging youth with mental health needs and their caregivers in mental health services.

  3. 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.

  4. 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.

  5. 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

    when benomyl was applied to the HC at 10 µg g-1 soil, whereas the uptake of 32P from RHC I roots + hyphae) was reduced only at the highest dose of application to the RHC (100 µ g g-1 soil). In contrast to the marked reduction of benomyl on fungal P transport, the activity of fungal alkaline phosphatase......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...

  6. 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.

  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. 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...

  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. 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.

  11. 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.

  12. 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

  13. Dog fight: Darwin as animal advocate in the antivivisection controversy of 1875.

    Science.gov (United States)

    Feller, David Allan

    2009-12-01

    The traditional characterization of Charles Darwin as a strong advocate of physiological experimentation on animals was posited in Richard French's Antivivisection and medical science in Victorian England (1975), where French portrayed him as a soldier in Thomas Huxley's efforts to preserve anatomical experimentation on animals unfettered by government regulation. That interpretation relied too much on, inter alia, Huxley's own description of the legislative battles of 1875, and shared many historians' propensity to foster a legacy of Darwin as a leader among a new wave of scientists, even where personal interests might indicate a conflicting story. Animal rights issues concerned more than mere science for Darwin, however, and where debates over other scientific issues failed to inspire Darwin to become publicly active, he readily joined the battle over vivisection, helping to draft legislation which, in many ways, was more protective of animal rights than even the bills proposed by his friend and anti-vivisectionist, Frances Power Cobbe. Darwin may not have officially joined Cobbe's side in the fight, but personal correspondence of the period between 1870 and 1875 reveals a man whose first interest was to protect animals from inhumane treatment, and second to protect the reputations of those men and physiologists who were his friends, and who he believed incapable of inhumane acts. On this latter point he and Cobbe never did reach agreement, but they certainly agreed on the humane treatment of animals, and the need to proscribe various forms of animal experimentation.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. [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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. 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.

  14. 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.)

  15. 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)

  16. Building confidence into communication of bad news: The role of the patient advocate.

    Science.gov (United States)

    Sullivan, Ruth P; Waldemayer, Carol R; Bunting, Robert F

    2010-01-01

    The need for a patient advocate is greater than ever as medical errors continue to occur. News media quickly capture the egregious errors, but more errors are experienced by patients who suffer quietly. These patients know something wrong occurred during their hospitalization, but they choose to refrain from pursuing litigation against the providers. There also are thousands of individuals who never realize that a medical error occurred. In a patient- and family-centered care environment, patient advocates can bridge these issues by participating on the healthcare team that is involved with the initial disclosure of the event and by providing a caring relationship to assure the patient's voice is heard and understood.

  17. 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...

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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)

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. 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.

  14. 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

  15. Social values and solar energy policy: the policy maker and the advocate

    Energy Technology Data Exchange (ETDEWEB)

    Shama, A.; Jacobs, K.

    1980-07-01

    Solar energy policy makers and advocates have significantly different hierarchies (clusters) of values upon which they evaluate the adoption of solar technologies. Content analysis, which examines the frequency with which policy makers identify different types of values, indicates that they hold economic values to be of primary importance. Environmental, social, and national security values are also substantial elements of the policy makers' value clusters associated with solar energy. This finding is confirmed by a qualitative analysis of policy makers' values. Advocates, on the other hand, assign almost equal weights (33%) to economic values and social values, slightly less weight to environmental values, and significant attention to ethical and security values as well. These results of frequency analysis are made somewhat more complicated by a qualitative interpretation of the advocates' positions. As part of their more holistic approach, several of the advocates indicated that all values discussed by them are instrumental toward achieving higher-order, ethical and environmental values. In addition, our preliminary investigation indicates that neither group is entirely homogeneous. Testing this and other propositions, as well as obtaining a similar picture of the values which the public associates with solar energy, are topics of future research.

  16. Professional School Counselors as Social Justice Advocates for Undocumented Immigrant Students in Group Work

    Science.gov (United States)

    Chen, Eric C.; Budianto, Lina; Wong, Kimberly

    2010-01-01

    Due to cultural and linguistic barriers, as well as a fear of deportation, undocumented immigrant students have remained an invisible group face in the existing school system. We provide specific strategies for school counselors to consider in advocating social justice and in facilitating empowerment of undocumented immigrant students through…

  17. Content-Specific Strategies to Advocate for Lesbian, Gay, Bisexual, and Transgender Youth: An Exploratory Study

    Science.gov (United States)

    Graybill, Emily C.; Varjas, Kris; Meyers, Joel; Watson, Laurel B.

    2009-01-01

    Researchers suggest that supportive school personnel may decrease some of the challenges encountered by lesbian, gay, bisexual, and transgender (LGBT) youth in schools (Russell, Seif, & Truong, 2001); however, little is known about the approaches used by school-based advocates for LGBT youth. This exploratory study investigated the strategies used…

  18. Researcher-Advocate Collaborations to End Violence Against Women: Toward Liberating Methodologies for Action Research

    Science.gov (United States)

    Williams, Linda M.

    2004-01-01

    This article relies on literature from the field and on research conducted by the National Violence Against Women Prevention Research Center to describe the difficulties encountered in collaborations between researchers and advocates working on the prevention of violence against women. The article summarizes guidelines for collaboration that have…

  19. Professional School Counseling Evaluation Rubric: Advocating for the Profession through Awareness and Accountability

    Science.gov (United States)

    Morris, Carrie A. Wachter; Slaten, Christopher D.

    2014-01-01

    Professional school counselors have been advocating for their role as counselors in the schools for decades (Galassi & Akos, 2007; Gysbers, 2002; Slaten & Baskin, 2013). Although researchers have addressed this concern through advocacy in service and writing, school counselors continue to perform a significant amount of non-counseling…

  20. Advancement Staff and Alumni Advocates: Cultivating LGBTQ Alumni by Promoting Individual and Community Uplift

    Science.gov (United States)

    Garvey, Jason C.; Drezner, Noah D.

    2013-01-01

    Using a constructivist case-study analysis, we explore philanthropy toward higher education among lesbian, gay, bisexual, transgender, and queer (LGBTQ) alumni, examining the role of advancement staff and alumni advocates in engaging LGBTQ alumni to promote individual and community uplift. Data come from focus groups with 37 advancement staff and…

  1. Peer Assessment and Compliance Review (PACR) Innovative Strategies Report. California Court Appointed Special Advocates (CASA) Programs

    Science.gov (United States)

    Macro, Bronwen; Huang, Lee Ann

    2005-01-01

    This report focuses on the innovative strategies study component of the Peer Assessment and Compliance Review (PACR) project. California (Court Appointed Special Advocates) CASA programs have developed many innovative strategies to serve children in their communities. At each of the programs visited during the PACR project, the team identified at…

  2. Perspectives of Social Justice Activists: Advocating against Native-Themed Mascots, Nicknames, and Logos

    Science.gov (United States)

    Steinfeldt, Jesse A.; Foltz, Brad D.; LaFollette, Julie R.; White, Mattie R.; Wong, Y. Joel; Steinfeldt, Matthew Clint

    2012-01-01

    This study investigated perspectives of social justice activists who directly advocate for eliminating Native-themed mascots, nicknames, and logos. Using consensual qualitative research methodology, the research team analyzed transcripts of interviews conducted with 11 social justice activists to generate themes, categories, and domains within the…

  3. Women in History--Pearl Buck: An Advocate for Women and Children

    Science.gov (United States)

    Watts, Lynette

    2008-01-01

    This article profiles Pearl Buck, an advocate for women's rights and minority children, an author of Chinese history, and a pioneer in many ways. Buck established the Welcome House in 1949 in order to help unadoptable children find families (Conn, 1996). In 1964, Buck founded the Pearl S. Buck Foundation, now Pearl S. Buck International, which…

  4. Seven Guidelines for Parents of Gifted: How to Advocate Intelligently in a Tough Economy

    Science.gov (United States)

    Mersino, Deborah

    2010-01-01

    Almost every day, another gifted education program bites the proverbial dust. Parents all across the country feel both apprehensive and anxious about the cuts. They are concerned about the educational and social emotional well-being of these students. They also wonder if it is even possible to advocate for gifted education in today's bleak…

  5. Using Action Research to Assess and Advocate for Innovative School Library Design

    Science.gov (United States)

    Harper, Meghan; Deskins,Liz

    2015-01-01

    This article describes a collaborative project designed to use action research to assess and advocate for innovative design changes in a school library. The high school library was in its fifth year of service, and yet the layout of the library was not meeting the learning and technological needs of 21st-century high school students. The purpose…

  6. Be Your Own Best Advocate. PACER Center ACTion Information Sheets. PHP-c116

    Science.gov (United States)

    PACER Center, 2006

    2006-01-01

    Being a self-advocate means asking for what one needs while respecting the needs of others. Self-advocacy is asking for what is needed in a direct, respectful manner. It is an important skill to acquire because self-advocacy helps: (1) Obtain what is needed; (2) People make personal choices; (3) Learn to say no without feeling guilty; and (4)…

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. Reconstructing Parents’ Meetings in Primary Schools: The Teacher as Expert, the Parent as Advocate and the Pupil as Self-Advocate

    Directory of Open Access Journals (Sweden)

    Gillian Inglis

    2012-01-01

    Full Text Available The efficacy of parents’ meetings in primary schools in the UK is anarea in need of research. This article uses an approach informed by grounded theory to explore the experiences and satisfaction of parents, teachers and pupils regarding bi-annual meetings to discuss pupil progress. A two-phase approach was utilised, with diary-interviews with parents and teachers and group pupil interviews in Phase 1, followed by a parents’ questionnaire in Phase 2 derived from Phase 1 data. The findings from a doctoral study provide an overall more positive depiction of these meetings compared to existing research in the secondary sector. A model of the teacher as the expert and information-giver persists, but a consumerist ideology appears evident as parents seek to participate and advocate on behalf of their child. As parents become more proactive and teachers act to retain their professional authority, the interaction of the professional and advocate has excluded the perspective of the child. This leaves pupils in search of self-advocacy at meetings in which they are the object of discussion, but cannot be present. While pupils generally favour involvement, adults express a protectionist perspective on pupil exclusion with exceptional factors indicated as being the age of the child and the content of the meeting.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

    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...

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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...

  9. 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

  10. Advocates, interest groups and Australian news coverage of alcohol advertising restrictions: content and framing analysis

    Directory of Open Access Journals (Sweden)

    Fogarty Andrea S

    2012-08-01

    Full Text Available Abstract Background Legislating restrictions on alcohol advertising is a cost-effective measure to reduce consumption of alcohol. Yet Australia relies upon industry self-regulation through voluntary codes of practice regarding the content, timing and placement of alcohol advertising. Ending industry self-regulation was recommended by the National Preventative Health Taskforce; a suggestion contested by the drinks industry. Debates about emerging alcohol-control policies regularly play out in the news media, with various groups seeking to influence the discussion. This paper examines news coverage of recommendations to restrict alcohol advertising to see how supporters and opponents frame the debate, with a view to providing some suggestions for policy advocates to advance the discussion. Methods We used content and framing analyses to examine 329 Australian newspaper items mentioning alcohol advertising restrictions over 24 months. All items were coded for mentions of specific types of advertising and types of advertising restrictions, the presence of news frames that opposed or endorsed advertising restrictions, statements made within each frame and the news-actors who appeared. Results Restrictions were the main focus in only 36% of 329 items. Alcohol advertising was conceived of as television (47% and sport-related (56%. Restrictions were mentioned in non-specific terms (45%, or specified as restrictions on timing and placement (49%, or content (22%. Public health professionals (47% appeared more frequently than drinks industry representatives (18%. Five supportive news frames suggested the policy is a sensible public health response, essential to protect children, needed to combat the drinks industry, required to stop pervasive branding, or as only an issue in sport. Four unsupportive frames positioned restrictions as unnecessary for a responsible industry, an attack on legitimate commercial activities, ineffective and ‘nannyist’, or

  11. 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.

  12. 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.

  13. 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.

  14. Together Everyone Achieves More: Leadership Networks and Interagency Relationships of the Judge Advocate Generals Corps

    Science.gov (United States)

    2017-02-22

    leadership networks may be formal or informal in nature, but share the trait that all of the nodes of the network create products or perform services ...information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services , Directorate for Information...Together Everyone Achieves More: Leadership Networks and Interagency Relationships of the Judge Advocate General’s Corps SSG Kenneth Conklin and SSG

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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...

  9. 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...

  10. 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.

  11. 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

  12. 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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Lee Na-Young

    2010-08-01

    Full Text Available Abstract 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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...... for transendothelial protein transport....

  20. 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

  1. Advocating self-advocacy: board membership in a statewide mental health consumer organization.

    Science.gov (United States)

    Tanenbaum, Sandra J

    2014-08-01

    Until 2008 Ohio Advocates for Mental Health was a statewide mental health advocacy organization run by mental health consumers and supportive of consumer-run organizations around the state. The author's tenure on the board entailed repeated engagement with questions of identity - self-identity, peer support through personal identification, and negotiation of public identities with provider groups and the state agency. These are fundamental to defining and legitimating the claims of mentally ill people not just for health care resources but for full participation as citizens in the public sphere.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Development and Evaluation of Training for Rural LGBTQ Mental Health Peer Advocates.

    Science.gov (United States)

    Israel, Tania; Willging, Cathleen; Ley, David

    2016-01-01

    Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) people in rural areas experience negative mental health consequences of minority stress, and encounter multiple barriers to accessing mental health and substance use treatment services. As part of a larger intervention study, we developed and piloted a unique training program to prepare peer advocates for roles as paraprofessionals who assist rural LGBTQ people with mental health needs. Thirty-seven people in New Mexico took part in either the initial training or a second revised training to improve their knowledge and skills to address LGBTQ mental health needs. Evaluation of this training consisted of self-administered structured assessments, focus groups, and open-ended interviews. Results for the initial training showed no significant increases from pre- and post-test scores on knowledge about LGBTQ people and their mental health issues, whereas significant increases were detected for the revised training. There also were significant increases in self-efficacy to perform tasks associated with the peer advocate role for all but a subset of tasks for the revised training. Qualitative data reveal that participants appreciated the opportunity to increase information and skills, especially concerning bisexual and transgender persons, and the opportunity to connect with others in the community who want to support LGBTQ people.

  8. The Role of Non-Governmental Organization (NGO in Advocating the National Security Bill

    Directory of Open Access Journals (Sweden)

    Yusa Djuyandi

    2016-05-01

    Full Text Available The role run by a coalition of NGOs in advocating the National Security Bill aimed at encouraging the birth of national security policy to appropriate to the purpose of reform. However, until now the role of NGOs in advocating National Security Bill has not been able to encourage the authorities to reconstruct the draft of national security policy that is consistent with the objectives of security sector reform. This study is conducted to analyze the role of NGOs in the security sector reform in Indonesia, particularly through the advocacy of the National Security Bill. The method used in this study is a qualitative method. The result shows that NGOs, which are members of the KMSRK, have been running the multiple roles, such as: popularly involved in policy making, providing political education to the community, promoting or encouraging reform, and promoting the interests of the community. The study also suggests the existence of new findings of the role of NGOs, which is forming a coherent unity of interests.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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....

  14. 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 ...

  15. 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.

  16. 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.

  17. 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.

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. HESS Opinions: Advocating process modeling and de-emphasizing parameter estimation

    Science.gov (United States)

    Bahremand, Abdolreza

    2016-04-01

    Since its origins as an engineering discipline, with its widespread use of "black box" (empirical) modeling approaches, hydrology has evolved into a scientific discipline that seeks a more "white box" (physics-based) modeling approach to solving problems such as the description and simulation of the rainfall-runoff responses of a watershed. There has been much recent debate regarding the future of the hydrological sciences, and several publications have voiced opinions on this subject. This opinion paper seeks to comment and expand upon some recent publications that have advocated an increased focus on process-based modeling while de-emphasizing the focus on detailed attention to parameter estimation. In particular, it offers a perspective that emphasizes a more hydraulic (more physics-based and less empirical) approach to development and implementation of hydrological models.

  8. Biological processes for advancing lignocellulosic waste biorefinery by advocating circular economy.

    Science.gov (United States)

    Liguori, Rossana; Faraco, Vincenza

    2016-09-01

    The actualization of a circular economy through the use of lignocellulosic wastes as renewable resources can lead to reduce the dependence from fossil-based resources and contribute to a sustainable waste management. The integrated biorefineries, exploiting the overall lignocellulosic waste components to generate fuels, chemicals and energy, are the pillar of the circular economy. The biological treatment is receiving great attention for the biorefinery development since it is considered an eco-friendly alternative to the physico-chemical strategies to increase the biobased product recovery from wastes and improve saccharification and fermentation yields. This paper reviews the last advances in the biological treatments aimed at upgrading lignocellulosic wastes, implementing the biorefinery concept and advocating circular economy.

  9. Coleman Advocates for Children And Youth: a pioneering child advocacy organization (1974-2008).

    Science.gov (United States)

    Carnochan, Sarah; Austin, Michael J

    2011-01-01

    Coleman Advocates for Youth and Children is a pioneering 30-year-old child advocacy organization founded by several affluent community members and children's service professionals to stop housing abused and neglected children in juvenile hall. Today, low-income youth and parents in families of color are now assuming leadership in developing a unique hybrid approach that integrates community organizing with more traditional child advocacy strategies and focuses on increasing affordable housing and improving the city's educational system. The strategies employed by Coleman have also evolved, shifting from insider advocacy with administrative officials to public campaigns targeting the city budget process, to local initiative campaigns, and most recently to electoral politics. This organizational history features the issues mission and structure, leadership, managing issues, advocacy strategies and community relations, and funding.

  10. Patient Abuse in the Health Care Setting: The Nurse as Patient Advocate.

    Science.gov (United States)

    Albina, Julie K

    2016-01-01

    Incidents of verbal and physical patient abuse in health care settings continue to occur, with some making headline news. Nurses have a professional and ethical responsibility to advocate for their patients when incidents of abuse occur. Tolerating or ignoring inappropriate behaviors occurs for multiple reasons, including ignorance, fear of retaliation, the need for peer acceptance, and concerns for personal advancement. Nurses need to reflect on their biases before they can truly respect patients' autonomy. Through the examination of reported cases of patient abuse, the need for a change in hospital culture becomes evident. The primary steps in eliminating patient abuse are opening communication, providing education, establishing competency, eliminating tolerance of unacceptable behavior, and creating a code of mutual respect. A change in culture to one of mutual respect and dignity for staff members and patients will lead to the best outcomes for all involved.

  11. 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

  12. 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.…

  13. 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

  14. 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

  15. 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…

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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....

  6. 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.

  7. 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...

  8. 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.

  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. 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.

  11. 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

  12. 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).

  13. 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

  14. 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 (...

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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 (-).

  1. 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

  2. Loyalty and positive word-of-mouth: patients and hospital personnel as advocates of a customer-centric health care organization.

    Science.gov (United States)

    Ferguson, Ronald J; Paulin, Michele; Leiriao, Elizabeth

    2006-01-01

    The ability to attract and retain loyal customers depends on the successful implementation of a customer-centric strategy. Customer loyalty is an attitude about an organization and its' services that is manifested by intentions and behaviors of re-patronization and recommendation. In the context of many medical services, loyalty through repeat patronization is not pertinent, whereas loyalty through positive word-of mouth (WOM) recommendation can be a powerful marketing tool. The Shouldice Hospital, a well-known institution for the surgical correction of hernias, instituted a marketing plan to develop a stable base of patients by creating positive WOM advocacy. This study focused on the consequences of both hernia patient overall satisfaction (and overall service quality) and hospital personnel satisfaction on the level of positive WOM advocacy. Using a commitment ladder of positive WOM advocacy, respondents were divided into three categories described as passive supporters, active advocates and ambassador advocates. Patient assessments of overall satisfaction and service quality were significantly related to these progressive levels of WOM for recommending the hospital to potential patients. Similarly, the satisfaction of the hospital employees was also significantly related to these progressive levels of positive WOM about recommending the hospital to potential patients and to potential employees. High levels of satisfaction are required to create true ambassadors of a service organization.

  3. 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.

  4. 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.

  5. 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...

  6. 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....

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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...

  16. 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.

  17. 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.

  18. Caring, Advocating, and Legislating for Children: Addressing the Paradox Inherent in 'Being Born in Privacy to Live in Society'.

    Science.gov (United States)

    Ranck, Edna Runnels

    The purpose of this paper is to show how child care practitioners and public policymakers can function in the seemingly disparate and often overlapping roles of professional caregiver, participating advocate, and public policymaker. Described are: (1) the recent expansion of and anticipated future need for child day care programs, focusing on…

  19. A Little Help from Their Friends: Institutions Build Armies of Alumni Advocates to Influence Legislators and Shape Public Opinion

    Science.gov (United States)

    Simonetti, Kristin

    2013-01-01

    Institutions build armies of alumni advocates to influence legislators and shape public opinion. This article describes two types of alumni advocacy: grasstops and grassroots. Grasstops advocacy engages smaller, targeted groups of alumni who have a stronger, more influential connection with legislators and other public officeholders. Grassroots…

  20. The Education of Homeless Children: Rules, Rights and Practical Solutions. A Training Manual for Shelter Providers, Staff, Advocates and Parents.

    Science.gov (United States)

    Heybach, Laurene M.; Nix-Hodes, Patricia; Price, Sarah

    These training materials provide advocates with the tools needed to help families obtain a stable and effective education for their children despite the condition of homelessness and the trauma that accompanies it. Nine sections include: (1) "Introduction"; (2) "How Mobility Hurts Homeless Children and Schools"; (3) "Laws…

  1. History of Science in the Science Curriculum: An Historical Perspective. Part I: Early Interest and Roles Advocated.

    Science.gov (United States)

    Sherratt, W. J.

    1982-01-01

    Discusses some of the factors underlying early calls for history of science in the science curriculum of English secondary schools. These factors focus on attacks on science, disquiet among science teachers, and parallelism between intellectual and historical development. Also discusses roles seen for historial materials advocated up to World War…

  2. Assessing and Addressing the "Testing Backlash": Practical Advice and Current Public Opinion Research for Business Coalitions and Standards Advocates.

    Science.gov (United States)

    Business Roundtable, Washington, DC.

    As states and communities across the United States work to raise expectations for student learning, many are challenged by concerns and questions from increasingly vocal parents and teachers. This report summarizes the best advice for business coalitions and standards advocates on how to address the testing backlash. It also features an analysis…

  3. How You Can Help Your Child Learn to Be a Good Self Advocate. PHP-c95

    Science.gov (United States)

    PACER Center, 2004

    2004-01-01

    It is never too early for parents to start teaching children how they can advocate for themselves. Like many other important life skills, self-advocacy is a critical tool children need in order to achieve goals, increase self-sufficiency, and become successful young adults. It is a life long process that begins with children learning by watching…

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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....

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. 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

  2. Awareness and predictors of female genital mutilation/cutting among young health advocates

    Directory of Open Access Journals (Sweden)

    Abolfotouh SM

    2015-02-01

    Full Text Available Sherif M Abolfotouh,1,2 Ahmed Z Ebrahim,1,3 Mostafa A Abolfotouh4 On Behalf of IFMSA-Egypt 1IFMSA-Egypt, Alexandria, Egypt; 2Oulu University Hospital, Oulu, Finland; 3Alexandria Faculty of Medicine, Alexandria, Egypt; 4King Abdullah International Medical Research Center (KAIMRC, King Saud bin-Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia Abstract: The act of female genital mutilation/cutting (FGM/C is considered internationally as a violent act against girls and women and a violation of their human rights. This study sought to assess the awareness and predictors of FGM/C in young Egyptian health advocates. A cross-sectional study of 600 medical students from a total of 2,500 members of the International Federation of Medical Students’ Associations (IFMSA-Egypt, across all Egyptian medical schools, was conducted using a previously validated online Google survey. The overall prevalence of circumcision was 14.7/100 female students, with a significantly higher prevalence in students from rural areas (25% than in non-rural areas (10.8%, P=0.001, and in those residing in Upper (southern Egypt (20.6% than in Lower (northern Egypt (8.7%, P=0.003. The students’ mean percentage score for knowledge about the negative health consequences of FGM/C was 53.50±29.07, reflecting a modest level of knowledge; only 30.5% had a good level of knowledge. The mean percentage score for the overall attitude toward discontinuation of the practice of FGM/C was 76.29±17.93, reflecting a neutral attitude; 58.7% had a favorable attitude/norms toward discontinuation of the practice. Of circumcised students, approximately one-half (46.8% were unwilling to have their daughters circumcised, and 60% reported no harm from being circumcised. After controlling for confounders, a negative attitude toward FGM/C was significantly (P<0.001 in all cases associated with male sex, residency in Upper Egypt, rural origin, previous circumcision, and the preclinical

  3. 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

  4. Breast Cancer Survivor Advocacy at a University Hospital: Development of a Peer Support Program with Evaluation by Patients, Advocates, and Clinicians.

    Science.gov (United States)

    Mirrielees, Jennifer A; Breckheimer, Kayla R; White, Teresa A; Denure, Deb A; Schroeder, Michelle M; Gaines, Martha E; Wilke, Lee G; Tevaarwerk, Amye J

    2017-03-01

    Peer-to-peer support programs provide unique psychosocial and educational support for breast cancer patients. A Patient Survivor Advocacy (PSA) program was developed by the University of Wisconsin Breast Center (UWBC) to provide support for newly diagnosed patients from peers who had completed primary treatment. In this study, we evaluated patient, advocate, and clinician experience with the PSA program. A program matching volunteer peer advocates at least 1 year removed from primary treatment with newly diagnosed patients was developed. Peer advocates were recruited from the practices of UWBC clinicians and received in-person training on six dimensions of peer advocacy. Trained advocates were then paired based on demographic and medical history with new patients referred to the program. Survey assessment tools were distributed to assess peer advocate and patient satisfaction, as well as clinician experience. Forty patients have been matched with seven advocates, with contact largely by email (53 %) or phone (36 %). Patients and peer advocates reported satisfaction with the program. The majority of patients (92.9 %) reported that the program was "helpful" and that they would recommend the PSA program to another woman with breast cancer. All peer advocates (100 %) responded with a sense of achievement in their advocate roles. Clinicians noted challenges in referral to the program. Peer advocates can provide key emotional and psychosocial support to newly diagnosed breast cancer patients. The peer advocate, patient, and clinician feedback collected in this study will inform the future development of this program at our and peer institutions.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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).

  10. 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

  11. 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

  12. Towards optimised information about clinical trials; identification and validation of key issues in collaboration with cancer patient advocates

    DEFF Research Database (Denmark)

    Dellson, P; Nilbert, M; Bendahl, P-O;

    2011-01-01

    the possibility to discontinue treatment were perceived as the most important issues. Patients' views of the information in clinical trials provide new insights and identify key issues to consider in optimising future written information and may improve recruitment to clinical cancer trials.......Clinical trials are crucial to improve cancer treatment but recruitment is difficult. Optimised patient information has been recognised as a key issue. In line with the increasing focus on patients' perspectives in health care, we aimed to study patients' opinions about the written information used...... in three clinical trials for breast cancer. Primary data collection was done in focus group interviews with breast cancer patient advocates. Content analysis identified three major themes: comprehensibility, emotions and associations, and decision making. Based on the advocates' suggestions...

  13. 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.

  14. Comparison of Research Framing Preferences and Information Use of State Legislators and Advocates Involved in Cancer Control, United States, 2012–2013

    Science.gov (United States)

    Dodson, Elizabeth A.; Tabak, Rachel G.; Brownson, Ross C.

    2017-01-01

    Introduction Evidence-based policy plays an important role in prevention of cancer and other chronic diseases. The needs of actors involved in policy decision-making should inform knowledge translation strategies. This study examines the differences between state legislators and advocates in how they seek and use information and what their preferences are for how research information is framed. Methods We conducted a cross-sectional comparison of survey responses by US advocates (n = 77) and state legislators (n = 265) working on issues related to cancer control. Results Advocates differed significantly from legislators on all demographic characteristics. Advocates reported seeking and using information more frequently than legislators, though legislators used legislative research bureaus more often (0.45 point difference, P = .004). Both legislators and advocates prioritized the presentation and timeliness of research information similarly but reported different preferences for source (information bias, information relevance, delivery of information by trusted person) of research information. Several differences between advocates and legislators were modified by participant age. Conclusion Our study provides insights for development of knowledge translation strategies to enhance evidence-based policy making for cancer control that are tailored to state-level legislators and advocates. Additional research efforts should evaluate the effectiveness of such knowledge translation strategies, particularly among advocates. PMID:28152363

  15. 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

  16. 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.

  17. A health impact assessment of proposed public transportation service cuts and fare increases in Boston, Massachusetts (U.S.A.).

    Science.gov (United States)

    James, Peter; Ito, Kate; Buonocore, Jonathan J; Levy, Jonathan I; Arcaya, Mariana C

    2014-08-07

    Transportation decisions have health consequences that are often not incorporated into policy-making processes. Health Impact Assessment (HIA) is a process that can be used to evaluate health effects of transportation policy. We present a rapid HIA, conducted over eight weeks, evaluating health and economic effects of proposed fare increases and service cuts to Boston, Massachusetts' public transportation system. We used transportation modeling in concert with tools allowing for quantification and monetization of multiple pathways. We estimated health and economic costs of proposed public transportation system changes to be hundreds of millions of dollars per year, exceeding the budget gap the public transportation authority was required to close. Significant health pathways included crashes, air pollution, and physical activity. The HIA enabled stakeholders to advocate for more modest fare increases and service cuts, which were eventually adopted by decision makers. This HIA was among the first to quantify and monetize multiple pathways linking transportation decisions with health and economic outcomes, using approaches that could be applied in different settings. Including health costs in transportation decisions can lead to policy choices with both economic and public health benefits.

  18. A Health Impact Assessment of Proposed Public Transportation Service Cuts and Fare Increases in Boston, Massachusetts (U.S.A.

    Directory of Open Access Journals (Sweden)

    Peter James

    2014-08-01

    Full Text Available Transportation decisions have health consequences that are often not incorporated into policy-making processes. Health Impact Assessment (HIA is a process that can be used to evaluate health effects of transportation policy. We present a rapid HIA, conducted over eight weeks, evaluating health and economic effects of proposed fare increases and service cuts to Boston, Massachusetts’ public transportation system. We used transportation modeling in concert with tools allowing for quantification and monetization of multiple pathways. We estimated health and economic costs of proposed public transportation system changes to be hundreds of millions of dollars per year, exceeding the budget gap the public transportation authority was required to close. Significant health pathways included crashes, air pollution, and physical activity. The HIA enabled stakeholders to advocate for more modest fare increases and service cuts, which were eventually adopted by decision makers. This HIA was among the first to quantify and monetize multiple pathways linking transportation decisions with health and economic outcomes, using approaches that could be applied in different settings. Including health costs in transportation decisions can lead to policy choices with both economic and public health benefits.

  19. 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...

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. SENSITIVE TO PROTON RHIZOTOXICITY1, CALMODULIN BINDING TRANSCRIPTION ACTIVATOR2, and other transcription factors are involved in ALUMINUM-ACTIVATED MALATE TRANSPORTER1 expression.

    Science.gov (United States)

    Tokizawa, Mutsutomo; Kobayashi, Yuriko; Saito, Tatsunori; Kobayashi, Masatomo; Iuchi, Satoshi; Nomoto, Mika; Tada, Yasuomi; Yamamoto, Yoshiharu Y; Koyama, Hiroyuki

    2015-03-01

    In Arabidopsis (Arabidopsis thaliana) the root apex is protected from aluminum (Al) rhizotoxicity by excretion of malate, an Al chelator, by ALUMINUM-ACTIVATED MALATE TRANSPORTER1 (AtALMT1). AtALMT1 expression is fundamentally regulated by the SENSITIVE TO PROTON RHIZOTOXICITY1 (STOP1) zinc finger protein, but other transcription factors have roles that enable Al-inducible expression with a broad dynamic range. In this study, we characterized multiple cis-elements in the AtALMT1 promoter that interact with transcription factors. In planta complementation assays of AtALMT1 driven by 5' truncated promoters of different lengths showed that the promoter region between -540 and 0 (the first ATG) restored the Al-sensitive phenotype of atalm1 and thus contains cis-elements essential for AtALMT1 expression for Al tolerance. Computation of overrepresented octamers showed that eight regions in this promoter region contained potential cis-elements involved in Al induction and STOP1 regulation. Mutation in a position around -297 from the first ATG completely inactivated AtALMT1 expression and Al response. In vitro binding assays showed that this region contained the STOP1 binding site, which accounted for the recognition by four zinc finger domains of the protein. Other positions were characterized as cis-elements that regulated expression by repressors and activators and a transcription factor that determines root tip expression of AtALMT1. From the consensus of known cis-elements, we identified CALMODULIN-BINDING TRANSCRIPTION ACTIVATOR2 to be an activator of AtALMT1 expression. Al-inducible expression of AtALMT1 changed transcription starting sites, which increased the abundance of transcripts with a shortened 5' untranslated region. The present analyses identified multiple mechanisms that regulate AtALMT1 expression.

  7. 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

  8. 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.

  9. Fentanyl Enhances Hepatotoxicity of Paclitaxel via Inhibition of CYP3A4 and ABCB1 Transport Activity in Mice.

    Directory of Open Access Journals (Sweden)

    Jing-Dun Xie

    Full Text Available Fentanyl, a potent opioid analgesic that is used to treat cancer pain, is commonly administered with paclitaxel in advanced tumors. However, the effect of fentanyl on the hepatotoxicity of paclitaxel and its potential mechanism of action is not well studied. The purpose of this study was to investigate the effect of fentanyl on the hepatotoxicity of paclitaxel and its potential mechanisms of action. Pharmacokinetic parameters of paclitaxel were tested using reversed phase high-performance liquid chromatography (RP-HPLC. Aspartate transaminase (AST, alanine aminotransferase (ALT, and mouse liver histopathology were examined. Moreover, the cytotoxicity of anti-carcinogens was examined using 1-(4, 5-dimethylthiazol-2-yl-3,5-diphenylformazan (MTT, and the intracellular accumulation of doxorubicin and rhodamine 123 was detected by flow cytometry. Furthermore, the expression of ABCB1 and the activity of ABCB1 ATPase and CYP3A4 were also examined. In this study, the co-administration of fentanyl and paclitaxel prolonged the half-life (t1/2 of paclitaxel from 1.455 hours to 2.344 hours and decreased the clearance (CL from 10.997 ml/h to 7.014 ml/h in mice. Fentanyl significantly increased the levels of ALT in mice to 88.2 U/L, which is more than 2-fold higher than the level detected in the control group, and it increased the histological damage in mouse livers. Furthermore, fentanyl enhanced the cytotoxicity of anti-carcinogens that are ABCB1 substrates and increased the accumulation of doxorubicin and rhodamine 123. Additionally, fentanyl stimulated ABCB1 ATPase activity and inhibited CYP3A4 activity in the liver microsomes of mice. Our study indicates that the obvious hepatotoxicity during this co-administration was due to the inhibition of CYP3A4 activity and ABCB1 transport activity. These findings suggested that the accumulation-induced hepatotoxicity of paclitaxel when it is combined with fentanyl should be avoided.

  10. Structure/activity Relationship of Thapsigargin Inhibition on the Purified Golgi/secretory Pathway Ca2+/Mn2+ Transport ATPase (SPCA1a)

    DEFF Research Database (Denmark)

    Jialin, Chen; de Raeymaecker, Joren; Hovgaard, Jannik Brøndsted

    2017-01-01

    The Golgi/secretory pathway Ca2+/Mn2+ transport ATPase (SPCA1a) is implicated in breast cancer and Hailey-Hailey disease. Here, we purified recombinant human SPCA1a from Saccharomyces cerevisiae and measured Ca2+ dependent ATPase activity following reconstitution in proteoliposomes. The purified...

  11. DEVELOPMENT OF A TECHNIQUE OF DETERMINATION OF ECONOMIC BENEFIT OF ACTIVITY OF A CONGLOMERATE «THE INNOVATIVE-TECHNOLOGICAL CENTER OF DEVELOPMENT OF TRANSPORT SYSTEM OF UKRAINE»

    OpenAIRE

    Tolstova, A.

    2010-01-01

    In the clause the basic advantages of creation of an innovative conglomerate «The is innovative-technological center of development of transport system of Ukraine» are considered, the technique of determination of economic benefit of its activity is developed.

  12. Monitoring cholinergic activity during attentional performance in mice heterozygous for the choline transporter: a model of cholinergic capacity limits.

    Science.gov (United States)

    Paolone, Giovanna; Mallory, Caitlin S; Koshy Cherian, Ajeesh; Miller, Thomas R; Blakely, Randy D; Sarter, Martin

    2013-12-01

    Reductions in the capacity of the human choline transporter (SLC5A7, CHT) have been hypothesized to diminish cortical cholinergic neurotransmission, leading to risk for cognitive and mood disorders. To determine the acetylcholine (ACh) release capacity of cortical cholinergic projections in a mouse model of cholinergic hypofunction, the CHT+/- mouse, we assessed extracellular ACh levels while mice performed an operant sustained attention task (SAT). We found that whereas SAT-performance-associated increases in extracellular ACh levels of CHT+/- mice were significantly attenuated relative to wildtype littermates, performance on the SAT was normal. Tetrodotoxin-induced blockade of neuronal excitability reduced both dialysate ACh levels and SAT performance similarly in both genotypes. Likewise, lesions of cholinergic neurons abolished SAT performance in both genotypes. However, cholinergic activation remained more vulnerable to the reverse-dialyzed muscarinic antagonist atropine in CHT+/- mice. Additionally, CHT+/- mice displayed greater SAT-disrupting effects of reverse dialysis of the nAChR antagonist mecamylamine. Receptor binding assays revealed a higher density of α4β2* nAChRs in the cortex of CHT+/- mice compared to controls. These findings reveal compensatory mechanisms that, in the context of moderate cognitive challenges, can overcome the performance deficits expected from the significantly reduced ACh capacity of CHT+/- cholinergic terminals. Further analyses of molecular and functional compensations in the CHT+/- model may provide insights into both risk and resiliency factors involved in cognitive and mood disorders.

  13. R. Tait McKenzie: Inspirational Sculptor and a Pioneer Advocate of Physical Activity for People with Disabilities

    Science.gov (United States)

    Reid, Greg; Jobling, Ian F.

    2012-01-01

    The London 2012 Summer Paralympics Mascot, "Mandeville", is named after the village of Stoke Mandeville, near Aylesbury in Buckinghamshire, England. This was where the inaugural Stoke Mandeville Games were held in 1948. On 28 July 1948, men and women who had been injured throughout the Second World War assembled in Stoke Mandeville for archery…

  14. Apparent receptor-mediated activation of Ca2+-dependent conductive Cl- transport by shark-derived polyaminosterols.

    Science.gov (United States)

    Chernova, Marina N; Vandorpe, David H; Clark, Jeffrey S; Williams, Jon I; Zasloff, Michael A; Jiang, Lianwei; Alper, Seth L

    2005-12-01

    The shark liver antimicrobial polyaminosterol squalamine is an angiogenesis inhibitor under clinical investigation as an anti-cancer agent and as a treatment for the choroidal neovascularization associated with macular degeneration of the retina. The related polyaminosterol MSI-1436 is an appetite suppressant that decreases systemic insulin resistance. However, the mechanisms of action of these polyaminosterols are unknown. We report effects of MSI-1436 on Xenopus oocytes consistent with the existence of a receptor for polyaminosterols. MSI-1436 activates bidirectional, trans-chloride-independent Cl- flux in Xenopus oocytes. At least part of this DIDS-sensitive Cl- flux is conductive, as measured using two-electrode voltage-clamp and on-cell patch-clamp techniques. MSI-1436 also elevates cytosolic Ca2+ concentration ([Ca2+]) and increases bidirectional 45Ca2+ flux. Activation of Cl- flux and elevation of cytosolic [Ca2+] by MSI-1436 both are accelerated by lowering bath Ca2+ and are not acutely inhibited by extracellular EGTA. Elevation of cytosolic [Ca2+] by MSI-1436 requires heparin-sensitive intracellular Ca2+ stores. Although injected EGTA abolishes the increased conductive Cl- flux, that Cl- flux is not dependent on heparin-sensitive stores. In low-bath Ca2+ conditions, several structurally related polyaminosterols act as strong agonists or weak agonists of conductive Cl- flux in oocytes. Weak agonist polyaminosterols antagonize the strong agonist, MSI-1436, but upon addition of the conductive Cl- transport inhibitor DIDS, they are converted into strong agonists. Together, these properties operationally define a polyaminosterol receptor at or near the surface of the Xenopus oocyte, provide an initial description of receptor signaling, and suggest routes toward further understanding of a novel class of appetite suppressants and angiogenesis inhibitors.

  15. Probing the putative active site of YjdL: an unusual proton-coupled oligopeptide transporter from E. coli.

    Directory of Open Access Journals (Sweden)

    Johanne Mørch Jensen

    Full Text Available YjdL from E. coli is an unusual proton-coupled oligopeptide transporter (POT. Unlike prototypical POTs, dipeptides are preferred over tripeptides, in particular dipeptides with a positively charged C-terminal residue. To further understand this difference in peptide specificity, the sequences of YjdL and YdgR, a prototypical E. coli POT, were compared in light of the crystal structure of a POT from Shewanella oneidensis. Several residues found in the putative active site were mutated and the activities of the mutated variants were assessed in terms of substrate uptake assays, and changes in specificity in terms of uptake inhibition. Most strikingly, changing the YjdL specific Asp392 to the conserved Ser in YjdL obliterated the preference for a positively charged C-terminal residue. Based on this unique finding and previously published results indicating that the dipeptide N-terminus may interact with Glu388, a preliminary orientation model of a dipeptide in the YjdL cavity is presented. Single site mutations of particularly Ala281 and Trp278 support the presented orientation. A dipeptide bound in the cavity of YjdL appears to be oriented such that the N-terminal side chain protrudes into a sub pocket that opens towards the extracellular space. The C-terminal side chain faces in the opposite direction into a sub pocket that faces the cytoplasm. These data indicated a stabilizing effect on a bulky N-terminal residue by an Ala281Phe variant and on the dipeptide backbone by Trp278. In the presented orientation model, Tyr25 and Tyr58 both appear to be in proximity of the dipeptide backbone while Lys117 appears to be in proximity of the peptide C-terminus. Mutational studies of these conserved residues highlight their functional importance.

  16. HIV-1 Protein Nef Inhibits Activity of ATP-binding Cassette Transporter A1 by Targeting Endoplasmic Reticulum Chaperone Calnexin*

    Science.gov (United States)

    Jennelle, Lucas; Hunegnaw, Ruth; Dubrovsky, Larisa; Pushkarsky, Tatiana; Fitzgerald, Michael L.; Sviridov, Dmitri; Popratiloff, Anastas; Brichacek, Beda; Bukrinsky, Michael

    2014-01-01

    HIV-infected patients are at increased risk of developing atherosclerosis, in part due to an altered high density lipoprotein profile exacerbated by down-modulation and impairment of ATP-binding cassette transporter A1 (ABCA1) activity by the HIV-1 protein Nef. However, the mechanisms of this Nef effect remain unknown. Here, we show that Nef interacts with an endoplasmic reticulum chaperone calnexin, which regulates folding and maturation of glycosylated proteins. Nef disrupted interaction between calnexin and ABCA1 but increased affinity and enhanced interaction of calnexin with HIV-1 gp160. The Nef mutant that did not bind to calnexin did not affect the calnexin-ABCA1 interaction. Interaction with calnexin was essential for functionality of ABCA1, as knockdown of calnexin blocked the ABCA1 exit from the endoplasmic reticulum, reduced ABCA1 abundance, and inhibited cholesterol efflux; the same effects were observed after Nef overexpression. However, the effects of calnexin knockdown and Nef on cholesterol efflux were not additive; in fact, the combined effect of these two factors together did not differ significantly from the effect of calnexin knockdown alone. Interestingly, gp160 and ABCA1 interacted with calnexin differently; although gp160 binding to calnexin was dependent on glycosylation, glycosylation was of little importance for the interaction between ABCA1 and calnexin. Thus, Nef regulates the activity of calnexin to stimulate its interaction with gp160 at the expense of ABCA1. This study identifies a mechanism for Nef-dependent inactivation of ABCA1 and dysregulation of cholesterol metabolism. PMID:25170080

  17. Serotonin/dopamine interactions in a hyperactive mouse: reduced serotonin receptor 1B activity reverses effects of dopamine transporter knockout.

    Directory of Open Access Journals (Sweden)

    Frank Scott Hall

    Full Text Available Knockout (KO mice that lack the dopamine transporter (SL6A3; DAT display increased locomotion that can be attenuated, under some circumstances, by administration of drugs that normally produce psychostimulant-like effects, such as amphetamine and methylphenidate. These results have led to suggestions that DAT KO mice may model features of attention deficit hyperactivity disorder (ADHD and that these drugs may act upon serotonin (5-HT systems to produce these unusual locomotor decreasing effects. Evidence from patterns of brain expression and initial pharmacologic studies led us to use genetic and pharmacologic approaches to examine the influence of altered 5-HT1B receptor activity on hyperactivity in DAT KO mice. Heterozygous 5-HT1B KO and pharmacologic 5-HT1B antagonism both attenuated locomotor hyperactivity in DAT KO mice. Furthermore, DAT KO mice with reduced, but not eliminated, 5-HT1B receptor expression regained cocaine-stimulated locomotion, which was absent in DAT KO mice with normal levels of 5-HT1B receptor expression. Further experiments demonstrated that the degree of habituation to the testing apparatus determined whether cocaine had no effect on locomotion in DAT KO or reduced locomotion, helping to resolve differences among prior reports. These findings of complementation of the locomotor effects of DAT KO by reducing 5-HT1B receptor activity underscore roles for interactions between specific 5-HT receptors and dopamine (DA systems in basal and cocaine-stimulated locomotion and support evaluation of 5-HT1B antagonists as potential, non-stimulant ADHD therapeutics.

  18. Effects of hypobaric hypoxia on adenine nucleotide pools, adenine nucleotide transporter activity and protein expression in rat liver

    Institute of Scientific and Technical Information of China (English)

    Cong-Yang Li; Jun-Ze Liu; Li-Ping Wu; Bing Li; Li-Fen Chen

    2006-01-01

    AIM: To explore the effect of hypobaric hypoxia on mitochondrial energy metabolism in rat liver.METHODS: Adult male Wistar rats were exposed to a hypobaric chamber simulating 5000 m high altitude for 23 h every day for 0 (HO), 1 (H1), 5 (HS), 15 (H15) and 30 d (H30) respectively. Rats were sacrificed by decapitation and liver was removed. Liver mitochondria were isolated by differential centrifugation program. The size of adenine nucleotide pool (ATP, ADP, and AMP) in tissue and mitochondria was separated and measured by high performance liquid chromatography (HPLC). The adenine nucleotide transporter (ANT) activity was determined by isotopic technique. The ANT total protein level was determined by Western blot. RESULTS: Compared with HO group, intra-mitochondrial ATP content decreased in all hypoxia groups. However,the H5 group reached the lowest point (70.6%) (P< 0.01)when compared to the control group. Intra-mitochondrial ADP and AMP level showed similar change in all hypoxia groups and were significantly lower than that in HO group. In addition, extra-mitochondrial ATP and ADP content decreased significantly in all hypoxia groups.Furthermore, extra-mitochondrial AMP in groups H5, H15and H30 was significantly lower than that in HO group,whereas H1 group had no marked change compared to the control situation. The activity of ANT in hypoxia groups decreased significantly, which was the lowest in H5 group (55.7%) (P<0.01) when compared to HO group. ANT activity in H30 group was higher than in H15 group, but still lower than that in HO group. ANT protein level in H5, H15, H30 groups, compared with HO group decreased significantly, which in H5 group was the lowest, being 27.1% of that in HO group (P<0.01). ANT protein level in H30 group was higher than in H15 group,but still lower than in HO group.CONCLUSION: Hypobaric hypoxia decreases the mitochondrial ATP content in rat liver, while mitochondrial ATP level recovers during long-term hypoxia exposure.The lower

  19. Tom, Huck, and Oliver Stone as advocates in Kohlberg's just community: theory-based strategies for moral education.

    Science.gov (United States)

    Harding, C G; Snyder, K

    1991-01-01

    Kohlberg's studies of moral reasoning provide a good theoretical framework for describing the developmental process that may serve as the basis for programs of moral education for adolescents. Kohlberg viewed moral education, particularly during adolescence, as the stimulation of the natural developmental process which leads to mature moral reasoning. Building on Kohlberg's work, specifically his concept of the just community approach where the teacher and more advanced peers serve as advocates of mature moral reasoning, this article presents the educator with a theoretical rationale for implementing procedures that can foster moral development. A case is made for using contemporary films and literature as mechanisms for stimulating moral development among adolescents.

  20. Promoter activity of a putative pollen monosaccharide transporter in Petunia hybrida and characterisation of a transposon insertion mutant

    NARCIS (Netherlands)

    Garrido, D.; Busscher-Lange, J.; Tunen, van A.J.

    2006-01-01

    For the growth of the male reproductive cells of plants, the pollen, the presence of sufficient sucrose or monosaccharides is of vital importance. From Petunia hybrida a pollen-specific putative monosaccharide transporter designated PMT1 (for petunia monosaccharide transporter) has been identified p

  1. Study of supported bilayer lipid membranes for use in chemo-electric energy conversion via active proton transport

    Science.gov (United States)

    Sarles, Stephen A.; Sundaresan, Vishnu B.; Leo, Donald J.

    2007-09-01

    Bilayer lipid membranes (BLMs) have been studied extensively due to functional and structural similarities to cell membranes, fostering research to understand ion-channel protein functions, measure bilayer mechanical properties, and identify self-assembly mechanisms. BLMs have traditionally been formed across single pores in substrates such as PTFE (Teflon). The incorporation of ion-channel proteins into the lipid bilayer enables the selective transfer of ions and fluid through the BLM. Processes of this nature have led to the measurement of ion current flowing across the lipid membrane and have been used to develop sensors that signal the presence of a particular reactant (glucose, urea, penicillin), improve drug recognition in cells, and develop materials capable of creating chemical energy from light. Recent research at Virginia Tech has shown that the incorporation of proton transporters in a supported BLM formed across an array of pores can convert chemical energy available in the adenosine triphosphate (ATP) into electricity. Experimental results from this work show that the system-named Biocell-is capable of developing 2µW/cm2 of membrane area with 15μl of ATPase. Efforts to increase the power output and conversion efficiency of this process while moving toward a packaged device present a unique engineering problem. The bilayer, as host to the active proton transporters, must therefore be formed evenly across a porous substrate, remain stable and yet fluid-like for protein interaction, and exhibit a large seal resistance. This article presents the ongoing work to characterize the Biocell using impedance analysis. Electrical impedance spectroscopy (EIS) is used to study the effect of adding ATPase proteins to POPS:POPE bilayer lipid membranes and correlate structural changes evident in the impedance data to the energy-conversion capability of various partial and whole Biocell assemblies. The specific membrane resistance of a pure BLM drops from 40-120k

  2. NATURAL GAS TRANSPORTATION

    OpenAIRE

    Stanis³aw Brzeziñski

    2007-01-01

    In the paper, Author presents chosen aspects of natural gas transportation within global market. Natural gas transportation is a technicaly complicated and economicly expensive process; in infrastructure construction and activities costs. The paper also considers last and proposed initiatives in natural gas transportation.

  3. "Media Mediators": Advocating an Alternate Paradigm for Critical Adult Education ICT Policy

    Science.gov (United States)

    Remtulla, Karim A.

    2010-01-01

    This article explores the efficacy of current education program approaches to prepare instructors to achieve critical thinking and active learning from their students by integrating ICTs with traditional adult education practices. An argument is put forward that the increasing presence and influence of ICTs in education necessitates a paradigmatic…

  4. Neuroprotection Promoted by Guanosine Depends on Glutamine Synthetase and Glutamate Transporters Activity in Hippocampal Slices Subjected to Oxygen/Glucose Deprivation.

    Science.gov (United States)

    Dal-Cim, Tharine; Martins, Wagner C; Thomaz, Daniel T; Coelho, Victor; Poluceno, Gabriela Godoy; Lanznaster, Débora; Vandresen-Filho, Samuel; Tasca, Carla I

    2016-05-01

    Guanosine (GUO) has been shown to act as a neuroprotective agent against glutamatergic excitotoxicity by increasing glutamate uptake and decreasing its release. In this study, a putative effect of GUO action on glutamate transporters activity modulation was assessed in hippocampal slices subjected to oxygen and glucose deprivation (OGD), an in vitro model of brain ischemia. Slices subjected to OGD showed increased excitatory amino acids release (measured by D-[(3)H]aspartate release) that was prevented in the presence of GUO (100 µM). The glutamate transporter blockers, DL-TBOA (10 µM), DHK (100 µM, selective inhibitor of GLT-1), and sulfasalazine (SAS, 250 µM, Xc(-) system inhibitor) decreased OGD-induced D-aspartate release. Interestingly, DHK or DL-TBOA blocked the decrease in glutamate release induced by GUO, whereas SAS did not modify the GUO effect. GUO protected hippocampal slices from cellular damage by modulation of glutamate transporters, however selective blockade of GLT-1 or Xc- system only did not affect this protective action of GUO. OGD decreased hippocampal glutamine synthetase (GS) activity and GUO recovered GS activity to control levels without altering the kinetic parameters of GS activity, thus suggesting GUO does not directly interact with GS. Additionally, the pharmacological inhibition of GS activity with methionine sulfoximine abolished the effect of GUO in reducing D-aspartate release and cellular damage evoked by OGD. Altogether, results in hippocampal slices subjected to OGD show that GUO counteracts the release of excitatory amino acids, stimulates the activity of GS, and decreases the cellular damage by modulation of glutamate transporters activity.

  5. Sodium-dependent vitamin C transporter 2 (SVCT2 expression and activity in brain capillary endothelial cells after transient ischemia in mice.

    Directory of Open Access Journals (Sweden)

    Burkhard Gess

    Full Text Available Expression and transport activity of Sodium-dependent Vitamin C Transporter 2 (SVCT2 was shown in various tissues and organs. Vitamin C was shown to be cerebroprotective in several animal models of stroke. Data on expression, localization and transport activity of SVCT2 after cerebral ischemia, however, has been scarce so far. Thus, we studied the expression of SVCT2 after middle cerebral artery occlusion (MCAO in mice by immunohistochemistry. We found an upregulation of SVCT2 after stroke. Co-stainings with Occludin, Von-Willebrand Factor and CD34 demonstrated localization of SVCT2 in brain capillary endothelial cells in the ischemic area after stroke. Time-course analyses of SVCT2 expression by immunohistochemistry and western blots showed upregulation in the subacute phase of 2-5 days. Radioactive uptake assays using (14C-labelled ascorbic acid showed a significant increase of ascorbic acid uptake into the brain after stroke. Taken together, these results provide evidence for the expression and transport activity of SVCT2 in brain capillary endothelial cells after transient ischemia in mice. These results may lead to the development of novel neuroprotective strategies in stroke therapy.

  6. Serum biochemical activities and muscular soreness in transported goats administered with ascorbic acid during the hot-dry season

    Directory of Open Access Journals (Sweden)

    Ndazo S Minka

    2010-12-01

    Full Text Available The effects of handling, loading and 12 h of road transportation during the hot-dry season on muscular metabolism of 20 experimental goats administered orally with 100 mg/kg body weight of ascorbic acid (AA dissolved in 10 ml of sterile water, and other 20 control goats given equivalent of sterile water 40 min prior to transportation were investigated. The result obtained post-transportation showed that handling, loading and transportation were stressful to the goats, especially the control goats and resulted into muscular damage and the development of delayed-onset-muscular-soreness (DOMS, which may lead to dark-firm-dry (DFD syndrome meat with undesirable effects on its quality. In the experimental goats administered AA such transportation effects were minimal or completely abolished. The result demonstrated that AA reduced the incidence of DOMS and muscular damage in transported goats, therefore it may be used to improve the welfare and quality of meat obtained from goats subjected to long period of road transportation under adverse climatic conditions.

  7. Potential respiration estimated by electron transport system activity in deep-sea suprabenthic crustaceans off Balearic Islands (Western Mediterranean)

    Science.gov (United States)

    Herrera, A.; Gómez, M.; Packard, T. T.; Reglero, P.; Blanco, E.; Barberá-Cebrián, C.

    2014-10-01

    ETS is an acronym for the activity of the respiratory electron transport system; the ETS assay is a biochemical method for estimating the “potential” respiration (Φ). We apply this technique to suprabenthic species captured at three depths (250 m, 650 m and 850 m) in two different locations: Cabrera (Algerian subbasin) and Sóller (Balearic subbasin) during the IDEADOS survey during summer 2010. The aim of this study was to compare specific Φ between areas and between three depths to identify differences in the suprabenthos physiological state related to nutritional conditions. Specific Φ, expressed in unit of μl O2 h- 1 mg prot- 1 was not significantly different between species. Mean values were for the decapods: Plesionika heterocarpus, 8.4 ± 7.9; Gennadas elegans, 8.3 ± 2.9; and Sergestes arcticus 7.3 ± 4.6. Within the euphausiids specific Φ averaged 6.5 ± 4.2 for Thysanopoda aequalis and 9.8 ± 5.1 for Meganyctiphanes norvegica; while for the mysids it ranged from 7.7 ± 4.4 for Boreomysis arctica and 2.1 ± 0.6 for Eucopia unguiculata. The comparison of specific potential respiration (Φ), with the pooling of the data of all the species, showed differences between the two locations, being higher in Cabrera. However, no significant differences between the different depths of each locality were found. The slope of the log Φ-log biomass plot was 0.93 ± 0.09 for Cabrera and 0.64 ± 0.11 in Sóller. We interpret these differences as indicating that the suprabenthos in the Cabrera area, as compared to the Sóller area, has been well-nourished.

  8. Promotores As Advocates for Community Improvement: Experiences of the Western States REACH Su Comunidad Consortium.

    Science.gov (United States)

    Kutcher, Rachel; Moore-Monroy, Martha; Bello, Elizur; Doyle, Seth; Ibarra, Jorge; Kunz, Susan; Munoz, Rocio; Patton-Lopez, Megan; Sharkey, Joseph R; Wilger, Susan; Alfero, Charlie

    2015-01-01

    The REACH Su Comunidad Consortium worked with 10 communities to address disparities in access to healthy food and physical activity opportunities among Hispanic populations through policy, systems, and environmental (PSE) strategies. Community health workers took leadership roles in the implementation of PSE strategies in partnership with local multisector coalitions. This article describes the role of community health workers in PSE change, the technical and professional development support provided to the REACH Su Comunidad Communities, and highlights professional development needs of community health workers engaging in PSE strategies.

  9. Activation of melatonin receptor (MT1/2) promotes P-gp transporter in methamphetamine-induced toxicity on primary rat brain microvascular endothelial cells.

    Science.gov (United States)

    Jumnongprakhon, Pichaya; Sivasinprasasn, Sivanan; Govitrapong, Piyarat; Tocharus, Chainarong; Tocharus, Jiraporn

    2017-02-20

    Melatonin has been known as a neuroprotective agent for the central nervous system (CNS) and the blood-brain barrier (BBB), which is the primary structure that comes into contact with several neurotoxins including methamphetamine (METH). Previous studies have reported that the activation of melatonin receptors (MT1/2) by melatonin could protect against METH-induced toxicity in brain endothelial cells via several mechanisms. However, its effects on the P-glycoprotein (P-gp) transporter, the active efflux pump involved in cell homeostasis, are still unclear. Thus, this study investigated the role of melatonin and its receptors on the METH-impaired P-gp transporter in primary rat brain microvascular endothelial cells (BMVECs). The results showed that METH impaired the function of the P-gp transporter, significantly decreasing the efflux of Rho123 and P-gp expression, which caused a significant increase in the intracellular accumulation of Rho123, and these responses were reversed by the interaction of melatonin with its receptors. Blockade of the P-gp transporter by verapamil caused oxidative stress, apoptosis, and cell integrity impairment after METH treatment, and these effects could be reversed by melatonin. Our results, together with previous findings, suggest that the interaction of melatonin with its receptors protects against the effects of the METH-impaired P-gp transporter and that the protective role in METH-induced toxicity was at least partially mediated by the regulation of the P-gp transporter. Thus, melatonin and its receptors (MT1/2) are essential for protecting against BBB impairment caused by METH.

  10. Inhibition of serotonin transporters by cocaine and meprylcaine through 5-TH2C receptor stimulation facilitates their seizure activities.

    Science.gov (United States)

    Morita, Katsuya; Hamamoto, Masahiro; Arai, Shigeaki; Kitayama, Shigeo; Irifune, Masahiro; Kawahara, Michio; Kihira, Kenji; Dohi, Toshihiro

    2005-09-28

    The present study examined whether the inhibition of serotonin transporters (SERT) contributes to cocaine- and other local anesthetics-induced convulsions, and which subtypes of 5-HT receptor are involved in the convulsions. For this purpose, cocaine, meprylcaine and lidocaine, all of which have different effects on SERT, were used as convulsants and the effects of serotonin reuptake inhibitors (SSRIs), specific agonists and antagonists for 5-HT receptor subtypes were evaluated in mice. Administration of SSRI, zimelidine, citalopram and fluoxetine, 5-HT(2A,2C) receptor agonist, R(-)-DOI and the 5-HT2C receptor agonists, mCPP, and MK212 resulted in a marked increase in incidence of convulsions and a reduction in the threshold of lidocaine-induced convulsions, while the 5-HT2B receptor agonist, BW723C86, had little influence. On the other hand, SSRI did not affect the measured parameters in meprylcaine- and cocaine-induced convulsions. R(-)-DOI, mCPP, and MK212 reduced the threshold of meprylcaine or cocaine with less extent than the reduction of lidocaine threshold. Incidence of cocaine- and meprylcaine-induced convulsions was significantly reduced by 5-HT(2A,2B,2C) antagonist, LY-53857, and 5-HT2C antagonist, RS 102221. The threshold of cocaine and meprylcaine was significantly increased by both antagonists. 5-HT2A antagonists MDL 11,939 and ketanserin, and 5-HT2B antagonist SB 204741 except at high doses had little effect on cocaine- and meprylcaine-induced convulsions. None of these antagonists altered the parameters of lidocaine-induced convulsions. Pretreatment with fluoxetine but not citalopram increased the plasma concentration of lidocaine. These results suggest that the increase of serotonergic neuronal activity through 5-HT2C receptor stimulation was responsible for increased activity of local anesthetics-induced convulsions and support the involvement of this mechanism in cocaine- and meprylcaine- but not in lidocaine-induced convulsions through their

  11. Understanding the Transport of Patagonian Dust and Its Influence on Marine Biological Activity in the South Atlantic Ocean

    Science.gov (United States)

    Johnson, Matthew; Meskhidze, Nicholas; Kiliyanpilakkil, Praju; Gasso, Santiago

    2010-01-01

    Modeling and remote sensing techniques were applied to examine the horizontal and vertical transport pathways of Patagonian dust and quantify the effect of soluble-iron- laden mineral dust deposition on marine primary productivity in the South Atlantic Ocean (SAO) surface waters. The global chemistry transport model GEOS-Chem, implemented with an iron dissolution scheme, was applied to evaluate the atmospheric transport and deposition of mineral dust and bioavailable iron during two dust outbreaks originating in the source regions of Patagonia. In addition to this "rapidly released" iron, offline calculations were also carried out to estimate the amount of bioavailable iron leached during the residence time of dust in the ocean mixed layer. Model simulations showed that the horizontal and vertical transport pathways of Patagonian dust plumes were largely influenced by the synoptic meteorological patterns of high and low pressure systems. Model-predicted horizontal and vertical transport pathways of Patagonian dust over the SAO were in reasonable agreement with remotely-sensed data. Comparison between remotely-sensed and offline calculated ocean surface chlorophyll-a concentrations indicated that, for the two dust outbreaks examined in this study, the deposition of bioavailable iron in the SAO through atmospheric pathways was insignificant. As the two dust transport episodes examined here represent typical outflows of mineral dust from South American sources, our study suggests that the atmospheric deposition of mineral dust is unlikely to induce large scale marine primary productivity and carbon sequestration in the South Atlantic sector of the Southern Ocean.

  12. Preparation of faculty members and students to be citizen leaders and pharmacy advocates.

    Science.gov (United States)

    Ross, Leigh Ann; Janke, Kristin K; Boyle, Cynthia J; Gianutsos, Gerald; Lindsey, Cameron C; Moczygemba, Leticia R; Whalen, Karen

    2013-12-16

    To identify characteristics and quality indicators of best practices for leadership and advocacy development in pharmacy education, a national task force on leadership development in pharmacy invited colleges and schools to complete a phone survey to characterize the courses, processes, and noteworthy practices for leadership and advocacy development at their institution. The literature was consulted to corroborate survey findings and identify additional best practices. Recommendations were derived from the survey results and literature review, as well as from the experience and expertise of task force members. Fifty-four institutions provided information about lecture-based and experiential curricular and noncurricular components of leadership and advocacy development. Successful programs have a supportive institutional culture, faculty and alumni role models, administrative and/or financial support, and a cocurricular thread of activities. Leadership and advocacy development for student pharmacists is increasingly important. The recommendations and suggestions provided can facilitate leadership and advocacy development at other colleges and schools of pharmacy.

  13. Interaction of the transcription start site core region and transcription factor YY1 determine ascorbate transporter SVCT2 exon 1a promoter activity.

    Directory of Open Access Journals (Sweden)

    Huan Qiao

    Full Text Available Transcription of the ascorbate transporter, SVCT2, is driven by two distinct promoters in exon 1 of the transporter sequence. The exon 1a promoter lacks a classical transcription start site and little is known about regulation of promoter activity in the transcription start site core (TSSC region. Here we present evidence that the TSSC binds the multifunctional initiator-binding protein YY1. Electrophoresis shift assays using YY1 antibody showed that YY1 is present as one of two major complexes that specifically bind to the TSSC. The other complex contains the transcription factor NF-Y. Mutations in the TSSC that decreased YY1 binding also impaired the exon 1a promoter activity despite the presence of an upstream activating NF-Y/USF complex, suggesting that YY1 is involved in the regulation of the exon 1a transcription. Furthermore, YY1 interaction with NF-Y and/or USF synergistically enhanced the exon 1a promoter activity in transient transfections and co-activator p300 enhanced their synergistic activation. We propose that the TSSC plays a vital role in the exon 1a transcription and that this function is partially carried out by the transcription factor YY1. Moreover, co-activator p300 might be able to synergistically enhance the TSSC function via a "bridge" mechanism with upstream sequences.

  14. Engaging parliamentarians as advocates for women's health: findings from Kenya and Namibia.

    Science.gov (United States)

    Caffrey, P; Weiss, E; Wood, L; Connor, E; Orza, L; Trasi, R

    2009-01-01

    Members of parliament (MPs) are well placed to promote national health policies that improve women's access to quality health care, including HIV services. To catalyse political will and leadership, the International Centre for Research on Women, Centre for the Study of AIDS at the University of Pretoria, International Community of Women Living with HIV/AIDS and Realising Rights: The Ethical Globalization Initiative, conducted the Parliamentarians for Women's Health project in select African countries. This paper focus on participatory community assessments - a methodology used by the project to improve MPs' understanding of women's health issues, particularly HIV/AIDS, and to increase their engagement with civil society in order to better represent women's health needs and concerns. In-depth interviews with eight MPs from Kenya and Namibia highlight the value of the assessments in identifying women's health problems and service gaps. The MPs reported that they undertook various activities after the assessments, including gathering more information about women's health from local communities, pushing for new parliamentary committees to be a platform for health issues, using the information from the assessments to inform policy, more carefully reviewing budget allocations and establishing relationships with civil society. Participatory methods can be used to meet political leaders' needs for information and communities' needs to influence policymaking that affects their lives.

  15. Systems and methods for solar energy storage, transportation, and conversion utilizing photochemically active organometallic isomeric compounds and solid-state catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Vollhardt, K. Peter C.; Segalman, Rachel A; Majumdar, Arunava; Meier, Steven

    2015-02-10

    A system for converting solar energy to chemical energy, and, subsequently, to thermal energy includes a light-harvesting station, a storage station, and a thermal energy release station. The system may include additional stations for converting the released thermal energy to other energy forms, e.g., to electrical energy and mechanical work. At the light-harvesting station, a photochemically active first organometallic compound, e.g., a fulvalenyl diruthenium complex, is exposed to light and is photochemically converted to a second, higher-energy organometallic compound, which is then transported to a storage station. At the storage station, the high-energy organometallic compound is stored for a desired time and/or is transported to a desired location for thermal energy release. At the thermal energy release station, the high-energy organometallic compound is catalytically converted back to the photochemically active organometallic compound by an exothermic process, while the released thermal energy is captured for subsequent use.

  16. Caregivers, school liaisons, and agency advocates speak out about the educational needs of children and youths in foster care.

    Science.gov (United States)

    Zetlin, Andrea; Weinberg, Lois; Shea, Nancy M

    2010-07-01

    Children in foster care comprise a population of students at great risk for school failure. The child welfare agency, schools, and home must all work together to provide the services and supports required to achieve better results. The purpose of this study was to conduct focus groups with participants from each sector to discuss their views on the educational problems and needs of students in foster care and their recommendations for what is needed to improve the academic prospects of foster students. The article provides details of the distinct themes identified by caregivers, school liaisons, and agency advocates and reveals how each group-while recognizing that foster students face substantial school problems-operates independent of each other and lacks a shared view on what is needed. The article concludes with recommendations for designing a model program that involves all the sectors and provides an arena for strategically addressing barriers to school success.

  17. As child survival and development advocates: the PFA/UNICEF experience.

    Science.gov (United States)

    Tirol, V G

    1989-07-01

    The Press Foundation of Asia was founded in 1968 by editors and publishers in Asia and the Pacific. Its activities include an editorial program which publishes several editions of DEPTHnews and a training program for training journalists and other communicators in the skills needed to report news stories in different fields, including child survival and development. The Press Foundation's programs are coordinated by the Foundation secretariate in Manila in coordination with national and regional associates throughout Asia and the Pacific. The UN Childrens Fund selected the Asian Press Foundation as its partner in the Communication Training Project in Support of Child Survival and Development. The objectives of the Project are to make journalists aware of child survival issues, to win the involvement of governments and nongovernmental organizations in child survival, and to create a desire for more information on the subject. The Project conducted a total of 21 workshops for training communicators and produces a monthly newsletter "Asian Women and Children." The workshops concentrate on the presentation of facts related to child survival, the conduction of discussion groups and field trips, and exercises in writing features for newspapers and radio, based on what was learned and seen. As a result of the Foundation's efforts, the city of Tacloban in the Philippines achieved 80% child immunization coverage, and comic book editors and publishers in the Philippines began running health features in comic book format. In order for the media to help in child survival, they must know of the plight of mothers and children, they must be given information in ready-to-use format, they must be dealt with openly, they must be made aware of contrary messages in the media, such as those of the milk companies, they must be given recognition and acknowledgment of their contributions, and they must get feedback.

  18. DISCUSSIONS ON ADVOCATING LOW CARBON AGRICULTURE%提倡低碳的几个问题

    Institute of Scientific and Technical Information of China (English)

    刘巽浩

    2012-01-01

    Low carbon agriculture is a historical necessity. However, it should conform to the reasonable principles and avoid extremalization. Chinese agriculture with a big population and shortage of cultivated land needs to implement the intensive sustainable farming systems that combined high yield with environmental protection. What is called " agriculture low - carbonization" should not be recommended blindly. Based on the author's practice and on - the - spot investigation both in domestic and foreign countries, the relationship between low carbon expenditure and four main agricultural activities, i. e. , farming systems, fertilization, tillage, and forestation, were analyzed and discussed.%农业提倡低碳是历史的必然.提倡低碳必须符合适度、合情、合理的原则,避免极端化.中国农业的特点是人多地少,必须实行高产高效与资源环境兼顾的集约持续农作制,不可盲目地推行所谓“农业低碳化”.该文根据作者多年的实践研究以及国内外考察,围绕着如何适度合情合理提倡低碳的问题,对涉及碳流的4个主要领域,即农作制、施肥、耕作和造林,进行具体的分析与讨论.

  19. Using accelerometers and global positioning system devices to assess gender and age differences in children's school, transport, leisure and home based physical activity

    DEFF Research Database (Denmark)

    Klinker, Charlotte D; Schipperijn, Jasper; Christian, Hayley

    2014-01-01

    Knowledge on domain-specific physical activity (PA) has the potential to advance public health interventions and inform new policies promoting children's PA. The purpose of this study is to identify and assess domains (leisure, school, transport, home) and subdomains (e.g., recess, playgrounds......, and urban green space) for week day moderate to vigorous PA (MVPA) using objective measures and investigate gender and age differences....

  20. Ontogenic Changes of Villus Growth, Lactase Activity, and Intestinal Glucose Transporters in Preterm and Term Born Calves with or without Prolonged Colostrum Feeding.

    Science.gov (United States)

    Steinhoff-Wagner, Julia; Schönhusen, Ulrike; Zitnan, Rudolf; Hudakova, Monika; Pfannkuche, Helga; Hammon, Harald M

    2015-01-01

    Oral glucose supply is important for neonatal calves to stabilize postnatal plasma glucose concentration. The objective of this study was to investigate ontogenic development of small intestinal growth, lactase activity, and glucose transporter in calves (n = 7 per group) that were born either preterm (PT; delivered by section 9 d before term) or at term (T; spontaneous vaginal delivery) or spontaneously born and fed colostrum for 4 days (TC). Tissue samples from duodenum and proximal, mid, and distal jejunum were taken to measure villus size and crypt depth, protein concentration of mucosa and brush border membrane vesicles (BBMV), total DNA and RNA concentration of mucosa, mRNA expression and activity of lactase, and mRNA expression of sodium-dependent glucose co-transporter-1 (SGLT1) and facilitative glucose transporter 2 (GLUT2) in mucosal tissue. Additionally, protein expression of SGLT1 in BBMV and GLUT2 in crude mucosal membranes and immunochemical localization of GLUT2 in the enterocytes were determined. Villus height in distal jejunum was lower in TC than in T. Crypt depth in all segments was largest and the villus height/crypt depth ratio in jejunum was smallest in TC calves. Concentration of RNA was highest in duodenal mucosa of TC calves, but neither lactase mRNA and activity nor SGLT1 and GLUT2 mRNA and protein expression differed among groups. Localization of GLUT2 in the apical membrane was greater, whereas in the basolateral membrane was lower in TC than in T and PT calves. Our study indicates maturation processes after birth for mucosal growth and trafficking of GLUT2 from the basolateral to the apical membrane. Minor differences of mucosal growth, lactase activity, and intestinal glucose transporters were seen between PT and T calves, pointing at the importance of postnatal maturation and feeding for mucosal growth and GLUT2 trafficking.

  1. Ontogenic Changes of Villus Growth, Lactase Activity, and Intestinal Glucose Transporters in Preterm and Term Born Calves with or without Prolonged Colostrum Feeding.

    Directory of Open Access Journals (Sweden)

    Julia Steinhoff-Wagner

    Full Text Available Oral glucose supply is important for neonatal calves to stabilize postnatal plasma glucose concentration. The objective of this study was to investigate ontogenic development of small intestinal growth, lactase activity, and glucose transporter in calves (n = 7 per group that were born either preterm (PT; delivered by section 9 d before term or at term (T; spontaneous vaginal delivery or spontaneously born and fed colostrum for 4 days (TC. Tissue samples from duodenum and proximal, mid, and distal jejunum were taken to measure villus size and crypt depth, protein concentration of mucosa and brush border membrane vesicles (BBMV, total DNA and RNA concentration of mucosa, mRNA expression and activity of lactase, and mRNA expression of sodium-dependent glucose co-transporter-1 (SGLT1 and facilitative glucose transporter 2 (GLUT2 in mucosal tissue. Additionally, protein expression of SGLT1 in BBMV and GLUT2 in crude mucosal membranes and immunochemical localization of GLUT2 in the enterocytes were determined. Villus height in distal jejunum was lower in TC than in T. Crypt depth in all segments was largest and the villus height/crypt depth ratio in jejunum was smallest in TC calves. Concentration of RNA was highest in duodenal mucosa of TC calves, but neither lactase mRNA and activity nor SGLT1 and GLUT2 mRNA and protein expression differed among groups. Localization of GLUT2 in the apical membrane was greater, whereas in the basolateral membrane was lower in TC than in T and PT calves. Our study indicates maturation processes after birth for mucosal growth and trafficking of GLUT2 from the basolateral to the apical membrane. Minor differences of mucosal growth, lactase activity, and intestinal glucose transporters were seen between PT and T calves, pointing at the importance of postnatal maturation and feeding for mucosal growth and GLUT2 trafficking.

  2. Diet effects on glucose absorption in the small intestine of neonatal calves: importance of intestinal mucosal growth, lactase activity, and glucose transporters.

    Science.gov (United States)

    Steinhoff-Wagner, Julia; Zitnan, Rudolf; Schönhusen, Ulrike; Pfannkuche, Helga; Hudakova, Monika; Metges, Cornelia C; Hammon, Harald M

    2014-10-01

    Colostrum (C) feeding in neonatal calves improves glucose status and stimulates intestinal absorptive capacity, leading to greater glucose absorption when compared with milk-based formula feeding. In this study, diet effects on gut growth, lactase activity, and glucose transporters were investigated in several gut segments of the small intestine. Fourteen male German Holstein calves received either C of milkings 1, 3, and 5 (d 1, 2, and 3 in milk) or respective formulas (F) twice daily from d 1 to d 3 after birth. Nutrient content, and especially lactose content, of C and respective F were the same. On d 4, calves were fed C of milking 5 or respective F and calves were slaughtered 2h after feeding. Tissue samples from duodenum and proximal, mid-, and distal jejunum were taken to measure villus size and crypt depth, mucosa and brush border membrane vesicles (BBMV) were taken to determine protein content, and mRNA expression and activity of lactase and mRNA expression of sodium-dependent glucose co-transporter-1 (SGLT1) and facilitative glucose transporter (GLUT2) were determined from mucosal tissue. Additionally, protein expression of SGLT1 in BBMV and GLUT2 in crude mucosal membranes and BBMV were determined, as well as immunochemically localized GLUT2 in the intestinal mucosa. Villus circumference, area, and height were greater, whereas crypt depth was smaller in C than in F. Lactase activity tended to be greater in C than in F. Protein expression of SGLT1 was greater in F than in C. Parameters of villus size, lactase activity, SGLT1 protein expression, as well as apical and basolateral GLUT2 localization in the enterocytes differed among gut segments. In conclusion, C feeding, when compared with F feeding, enhances glucose absorption in neonatal calves primarily by stimulating mucosal growth and increasing absorptive capacity in the small intestine, but not by stimulating abundance of intestinal glucose transporters.

  3. Caffeine and contraction synergistically stimulate 5'-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscle.

    Science.gov (United States)

    Tsuda, Satoshi; Egawa, Tatsuro; Kitani, Kazuto; Oshima, Rieko; Ma, Xiao; Hayashi, Tatsuya

    2015-10-01

    5'-Adenosine monophosphate-activated protein kinase (AMPK) has been identified as a key mediator of contraction-stimulated insulin-independent glucose transport in skeletal muscle. Caffeine acutely stimulates AMPK in resting skeletal muscle, but it is unknown whether caffeine affects AMPK in contracting muscle. Isolated rat epitrochlearis muscle was preincubated and then incubated in the absence or presence of 3 mmol/L caffeine for 30 or 120 min. Electrical stimulation (ES) was used to evoke tetanic contractions during the last 10 min of the incubation period. The combination of caffeine plus contraction had additive effects on AMPKα Thr(172) phosphorylation, α-isoform-specific AMPK activity, and 3-O-methylglucose (3MG) transport. In contrast, caffeine inhibited basal and contraction-stimulated Akt Ser(473) phosphorylation. Caffeine significantly delayed muscle fatigue during contraction, and the combination of caffeine and contraction additively decreased ATP and phosphocreatine contents. Caffeine did not affect resting tension. Next, rats were given an intraperitoneal injection of caffeine (60 mg/kg body weight) or saline, and the extensor digitorum longus muscle was dissected 15 min later. ES of the sciatic nerve was performed to evoke tetanic contractions for 5 min before dissection. Similar to the findings from isolated muscles incubated in vitro, the combination of caffeine plus contraction in vivo had additive effects on AMPK phosphorylation, AMPK activity, and 3MG transport. Caffeine also inhibited basal and contraction-stimulated Akt phosphorylation in vivo. These findings suggest that caffeine and contraction synergistically stimulate AMPK activity and insulin-independent glucose transport, at least in part by decreasing muscle fatigue and thereby promoting energy consumption during contraction.

  4. Phosphatidylinositol- and phosphatidylcholine-transfer activity of PITPβ is essential for COPI-mediated retrograde transport from the Golgi to the endoplasmic reticulum

    OpenAIRE

    Carvou, Nicolas; Holic, Roman; Li, Michelle; Futter, Clare; Skippen, Alison; Cockcroft, Shamshad

    2010-01-01

    Vesicles formed by the COPI complex function in retrograde transport from the Golgi to the endoplasmic reticulum (ER). Phosphatidylinositol transfer protein β (PITPβ), an essential protein that possesses phosphatidylinositol (PtdIns) and phosphatidylcholine (PtdCho) lipid transfer activity is known to localise to the Golgi and ER but its role in these membrane systems is not clear. To examine the function of PITPβ at the Golgi-ER interface, RNA interference (RNAi) was used to knockdown PITPβ ...

  5. Active Hydrophilic Components of the Medicinal Herb Salvia miltiorrhiza (Danshen Potently Inhibit Organic Anion Transporters 1 (Slc22a6 and 3 (Slc22a8

    Directory of Open Access Journals (Sweden)

    Li Wang

    2012-01-01

    Full Text Available Many active components of herbal products are small organic anions, and organic anion transporters were previously demonstrated to be a potential site of drug-drug interactions. In this study, we assessed the inhibitory effects of six hydrophilic components of the herbal medicine Danshen, lithospermic acid, protocatechuic acid, rosmarinic acid, salvianolic acid A, salvianolic acid B, and tanshinol, on the function of the murine organic anion transporters, mOat1 and mOat3. All of Danshen components significantly inhibited mOat1- and mOat3-mediated substrate uptake (<0.001 with lithospermic acid (LSA, protocatechuic acid, rosmarinic acid (RMA, and salvianolic acid A (SAA producing virtually complete inhibition under test conditions. Kinetic analysis demonstrated that LSA, RMA, and SAA were competitive inhibitors. As such, values were estimated as 14.9±4.9 μM for LSA, 5.5±2.2 μM for RMA, and 4.9±2.2 μM for SAA on mOat1-mediated transport, and as 31.1±7.0 μM for LSA, 4.3±0.2 μM for RMA, and 21.3±7.7 μM for SAA on mOat3-mediated transport. These data suggest that herb-drug interactions may occur in vivo on the human orthologs of these transporters in situations of polypharmacy involving Danshen and clinical therapeutics known to be organic anion transporter substrates.

  6. UNC-16 (JIP3) Acts Through Synapse-Assembly Proteins to Inhibit the Active Transport of Cell Soma Organelles to Caenorhabditis elegans Motor Neuron Axons.

    Science.gov (United States)

    Edwards, Stacey L; Morrison, Logan M; Yorks, Rosalina M; Hoover, Christopher M; Boominathan, Soorajnath; Miller, Kenneth G

    2015-09-01

    The conserved protein UNC-16 (JIP3) inhibits the active transport of some cell soma organelles, such as lysosomes, early endosomes, and Golgi, to the synaptic region of axons. However, little is known about UNC-16's organelle transport regulatory function, which is distinct from its Kinesin-1 adaptor function. We used an unc-16 suppressor screen in Caenorhabditis elegans to discover that UNC-16 acts through CDK-5 (Cdk5) and two conserved synapse assembly proteins: SAD-1 (SAD-A Kinase), and SYD-2 (Liprin-α). Genetic analysis of all combinations of double and triple mutants in unc-16(+) and unc-16(-) backgrounds showed that the three proteins (CDK-5, SAD-1, and SYD-2) are all part of the same organelle transport regulatory system, which we named the CSS system based on its founder proteins. Further genetic analysis revealed roles for SYD-1 (another synapse assembly protein) and STRADα (a SAD-1-interacting protein) in the CSS system. In an unc-16(-) background, loss of the CSS system improved the sluggish locomotion of unc-16 mutants, inhibited axonal lysosome accumulation, and led to the dynein-dependent accumulation of lysosomes in dendrites. Time-lapse imaging of lysosomes in CSS system mutants in unc-16(+) and unc-16(-) backgrounds revealed active transport defects consistent with the steady-state distributions of lysosomes. UNC-16 also uses the CSS system to regulate the distribution of early endosomes in neurons and, to a lesser extent, Golgi. The data reveal a new and unprecedented role for synapse assembly proteins, acting as part of the newly defined CSS system, in mediating UNC-16's organelle transport regulatory function.

  7. Halotolerant Cyanobacterium Aphanothece halophytica Contains a Betaine Transporter Active at Alkaline pH and High Salinity

    OpenAIRE

    2006-01-01

    Aphanothece halophytica is a halotolerant alkaliphilic cyanobacterium which can grow in media of up to 3.0 M NaCl and pH 11. This cyanobacterium can synthesize betaine from glycine by three-step methylation using S-adenosylmethionine as a methyl donor. To unveil the mechanism of betaine uptake and efflux in this alkaliphile, we isolated and characterized a betaine transporter. A gene encoding a protein (BetTA. halophytica) that belongs to the betaine-choline-carnitine transporter (BCCT) famil...

  8. Higher concentrations of nanoscale zero-valent iron (nZVI) in soil induced rice chlorosis due to inhibited active iron transportation.

    Science.gov (United States)

    Wang, Jie; Fang, Zhanqiang; Cheng, Wen; Yan, Xiaomin; Tsang, Pokeung Eric; Zhao, Dongye

    2016-03-01

    In this study, the effects of concentrations 0, 100, 250, 500, 750 and 1000 mg kg(-1) of nanoscale zero-valent iron (nZVI) on germination, seedlings growth, physiology and toxicity mechanisms were investigated. The results showed that nZVI had no effect on germination, but inhibited the rice seedlings growth in higher concentrations (>500 mg kg(-1) nZVI). The highest suppression rate of the length of roots and shoots reached 46.9% and 57.5%, respectively. The 1000mg kg(-1) nZVI caused the highest suppression rates for chlorophyll and carotenoids, at 91.6% and 85.2%, respectively. In addition, the activity of antioxidant enzymes was altered by the translocation of nanoparticles and changes in active iron content. Visible symptoms of iron deficiency were observed at higher concentrations, at which the active iron content decreased 61.02% in the shoots, but the active iron content not decreased in roots. Interestingly, the total and available amounts of iron in the soil were not less than those in the control. Therefore, the plants iron deficiency was not caused by (i) deficiency of available iron in the soil and (ii) restraint of the absorption that plant takes in the available iron, while induced by (ⅲ) the transport of active iron from the root to the shoot was blocked. The cortex tissues were seriously damaged by nZVI which was transported from soil to the root, these were proved by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). This current study shows that the mechanism of iron deficiency in rice seedling was due to transport of active iron from the root to the shoot blocked, which was caused by the uptake of nZVI.

  9. Liposome reconstitution and transport assay for recombinant transporters.

    Science.gov (United States)

    Johnson, Zachary Lee; Lee, Seok-Yong

    2015-01-01

    Secondary active transporters are responsible for the cellular uptake of many biologically important molecules, including neurotransmitters, nutrients, and drugs. Because of their physiological and clinical importance, a method for assessing their transport activity in vitro is necessary to gain a better understanding of how these transporters function at the molecular level. In this chapter, we describe a protocol for reconstituting the concentrative nucleoside transporter from Vibrio cholerae into proteoliposomes. We then describe a radiolabeled substrate uptake assay that can be used to functionally characterize the transporter. These methods are relatively common and can be applied to other secondary active transporters, with or without some modification.

  10. Development of a Novel Method for in vivo Determination of Activation Energy of Glucose Transport Across S. cerevisiae Cellular Membranes. A Biosensor-like Approach.

    Science.gov (United States)

    Kormes, Diego J; Cortón, Eduardo

    2009-01-01

    Whereas biosensors have been usually proposed as analytical tools, used to investigate the surrounding media pursuing an analytical answer, we have used a biosensor-like device to characterize the microbial cells immobilized on it. We have studied the kinetics of transport and degradation of glucose at different concentrations and temperatures. When glucose concentrations of 15 and 1.5 mM were assayed, calculated activation energies were 25.2 and 18.4 kcal mol(-1), respectively, in good agreement with previously published data. The opportunity and convenience of using Arrhenius plots to estimate the activation energy in metabolic-related processes is also discussed.

  11. Developmental and hormone-induced changes of mitochondrial electron transport chain enzyme activities during the last instar larval development of maize stem borer, Chilo partellus (Lepidoptera: Crambidae).

    Science.gov (United States)

    VenkatRao, V; Chaitanya, R K; Naresh Kumar, D; Bramhaiah, M; Dutta-Gupta, A

    2016-12-01

    The energy demand for structural remodelling in holometabolous insects is met by cellular mitochondria. Developmental and hormone-induced changes in the mitochondrial respiratory activity during insect metamorphosis are not well documented. The present study investigates activities of enzymes of mitochondrial electron transport chain (ETC) namely, NADH:ubiquinone oxidoreductase or complex I, Succinate: ubiquinone oxidoreductase or complex II, Ubiquinol:ferricytochrome c oxidoreductase or complex III, cytochrome c oxidase or complex IV and F1F0ATPase (ATPase), during Chilo partellus development. Further, the effect of juvenile hormone (JH) analog, methoprene, and brain and corpora-allata-corpora-cardiaca (CC-CA) homogenates that represent neurohormones, on the ETC enzyme activities was monitored. The enzymatic activities increased from penultimate to last larval stage and thereafter declined during pupal development with an exception of ATPase which showed high enzyme activity during last larval and pupal stages compared to the penultimate stage. JH analog, methoprene differentially modulated ETC enzyme activities. It stimulated complex I and IV enzyme activities, but did not alter the activities of complex II, III and ATPase. On the other hand, brain homogenate declined the ATPase activity while the injected CC-CA homogenate stimulated complex I and IV enzyme activities. Cumulatively, the present study is the first to show that mitochondrial ETC enzyme system is under hormone control, particularly of JH and neurohormones during insect development.

  12. Bibliography for acid-rock drainage and selected acid-mine drainage issues related to acid-rock drainage from transportation activities

    Science.gov (United States)

    Bradley, Michael W.; Worland, Scott C.

    2015-01-01

    Acid-rock drainage occurs through the interaction of rainfall on pyrite-bearing formations. When pyrite (FeS2) is exposed to oxygen and water in mine workings or roadcuts, the mineral decomposes and sulfur may react to form sulfuric acid, which often results in environmental problems and potential damage to the transportation infrastructure. The accelerated oxidation of pyrite and other sulfidic minerals generates low pH water with potentially high concentrations of trace metals. Much attention has been given to contamination arising from acid mine drainage, but studies related to acid-rock drainage from road construction are relatively limited. The U.S. Geological Survey, in cooperation with the Tennessee Department of Transportation, is conducting an investigation to evaluate the occurrence and processes controlling acid-rock drainage and contaminant transport from roadcuts in Tennessee. The basic components of acid-rock drainage resulting from transportation activities are described and a bibliography, organized by relevant categories (remediation, geochemical, microbial, biological impact, and secondary mineralization) is presented.

  13. Mechanistic Coupling of Transport and Phosphorylation Activity by Enzyme IImtl of the Escherichia coli Phosphoenolpyruvate-Dependent Phosphotransferase System

    NARCIS (Netherlands)

    Lolkema, Juke S.; Duurkens, Hinderika; Swaving Dijkstra, Dolf; Robillard, George T.

    1991-01-01

    Mannitol bound to enzyme II(mtl) could be trapped specifically by rapid phosphorylation with P-HPr. The assay was used to demonstrate transport of mannitol across the cytoplasmic membrane with and without phosphorylation of mannitol. The latter was 2-3 orders of magnitude slower. The fraction of bou

  14. D6 PROTEIN KINASE activates auxin transport-dependent growth and PIN-FORMED phosphorylation at the plasma membrane.

    Science.gov (United States)

    Barbosa, Inês C R; Zourelidou, Melina; Willige, Björn C; Weller, Benjamin; Schwechheimer, Claus

    2014-06-23

    The directed cell-to-cell transport of the phytohormone auxin by efflux and influx transporters is essential for proper plant growth and development. Like auxin efflux facilitators of the PIN-FORMED (PIN) family, D6 PROTEIN KINASE (D6PK) from Arabidopsis thaliana localizes to the basal plasma membrane of many cells, and evidence exists that D6PK may directly phosphorylate PINs. We find that D6PK is a membrane-bound protein that is associated with either the basal domain of the plasma membrane or endomembranes. Inhibition of the trafficking regulator GNOM leads to a rapid internalization of D6PK to endomembranes. Interestingly, the dissociation of D6PK from the plasma membrane is also promoted by auxin. Surprisingly, we find that auxin transport-dependent tropic responses are critically and reversibly controlled by D6PK and D6PK-dependent PIN phosphorylation at the plasma membrane. We conclude that D6PK abundance at the plasma membrane and likely D6PK-dependent PIN phosphorylation are prerequisites for PIN-mediated auxin transport.

  15. Effect of vanadate on glucose transporter (GLUT4) intrinsic activity in skeletal muscle plasma membrane giant vesicles

    DEFF Research Database (Denmark)

    Kristiansen, S; Youn, J; Richter, Erik

    1996-01-01

    for 1.5 h with concentrations of vanadate ranging from 3 to 40 mmol l-1 at 34 degrees C before being used for determination of glucose transport. The dose-response curve showed that vanadate decreased the specific D-glucose uptake by a maximum of 70% compared with a control preparation. The vanadate...

  16. Pentamidine exerts in vitro and in vivo anti Trypanosoma cruzi activity and inhibits the polyamine transport in Trypanosoma cruzi.

    Science.gov (United States)

    Díaz, María V; Miranda, Mariana R; Campos-Estrada, Carolina; Reigada, Chantal; Maya, Juan D; Pereira, Claudio A; López-Muñoz, Rodrigo

    2014-06-01

    Pentamidine is an antiprotozoal and fungicide drug used in the treatment of leishmaniasis and African trypanosomiasis. Despite its extensive use as antiparasitic drug, little evidence exists about the effect of pentamidine in Trypanosoma cruzi, the etiological agent of Chagas' disease. Recent studies have shown that pentamidine blocks a polyamine transporter present in Leishmania major; consequently, its might also block these transporters in T. cruzi. Considering that T. cruzi lacks the ability to synthesize putrescine de novo, the inhibition of polyamine transport can bring a new therapeutic target against the parasite. In this work, we show that pentamidine decreases, not only the viability of T. cruzi trypomastigotes, but also the parasite burden of infected cells. In T. cruzi-infected mice pentamidine decreases the inflammation and parasite burden in hearts from infected mice. The treatment also decreases parasitemia, resulting in an increased survival rate. In addition, pentamidine strongly inhibits the putrescine and spermidine transport in T. cruzi epimastigotes and amastigotes. Thus, this study points to reevaluate the utility of pentamidine and introduce evidence of a potential new action mechanism. In the quest of new therapeutic strategies against Chagas disease, the extensive use of pentamidine in human has led to a well-known clinical profile, which could be an advantage over newly synthesized molecules that require more comprehensive trials prior to their clinical use.

  17. Zinc transporter 7 deficiency affects lipid synthesis in adipocytes by inhibiting insulin-dependent Akt activity and glucose uptake

    Science.gov (United States)

    Mice deficient for zinc transporter 7 (Znt7) are mildly zinc deficient, accompanied with low body weight gain and body fat accumulation. To investigate the underlying mechanism of Znt7 deficiency in body adiposity, we investigated fatty acid composition and insulin sensitivity in visceral (epididyma...

  18. Binding of PDZ-RhoGEF to ATP-binding cassette transporter A1 (ABCA1) induces cholesterol efflux through RhoA activation and prevention of transporter degradation.

    Science.gov (United States)

    Okuhira, Keiichiro; Fitzgerald, Michael L; Tamehiro, Norimasa; Ohoka, Nobumichi; Suzuki, Kazuhiro; Sawada, Jun-ichi; Naito, Mikihiko; Nishimaki-Mogami, Tomoko

    2010-05-21

    ATP-binding cassette transporter A1 (ABCA1)-mediated lipid efflux to apolipoprotein A1 (apoA-I) initiates the biogenesis of high density lipoprotein. Here we show that the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG bind to the C terminus of ABCA1 by a PDZ-PDZ interaction and prevent ABCA1 protein degradation by activating RhoA. ABCA1 is a protein with a short half-life, and apoA-I stabilizes ABCA1 protein; however, depletion of PDZ-RhoGEF/LARG by RNA interference suppressed the apoA-I stabilization of ABCA1 protein in human primary fibroblasts. Exogenous PDZ-RhoGEF expression activated RhoA and increased ABCA1 protein levels and cholesterol efflux activity. Likewise, forced expression of a constitutively active RhoA mutant significantly increased ABCA1 protein levels, whereas a dominant negative RhoA mutant decreased them. The constitutively active RhoA retarded ABCA1 degradation, thus accounting for its ability to increase ABCA1 protein. Moreover, stimulation with apoA-I transiently activated RhoA, and the pharmacological inhibition of RhoA or the dominant negative RhoA blocked the ability of apoA-I to stabilize ABCA1. Finally, depletion of RhoA or RhoGEFs/RhoA reduces the cholesterol efflux when transcriptional regulation via PPARgamma is eliminated. Taken together, our results have identified a novel physical and functional interaction between ABCA1 and PDZ-RhoGEF/LARG, which activates RhoA, resulting in ABCA1 stabilization and cholesterol efflux activity.

  19. Molecular characterization of an ice nucleation protein variant (inaQ) from Pseudomonas syringae and the analysis of its transmembrane transport activity in Escherichia coli.

    Science.gov (United States)

    Li, Qianqian; Yan, Qi; Chen, Jinsi; He, Yan; Wang, Jing; Zhang, Hongxing; Yu, Ziniu; Li, Lin

    2012-01-01

    The ice nucleation protein (INP) of Pseudomonas syringae has gained scientific interest not only because of its pathogenicity of foliar necroses but also for its wide range of potential applications, such as in snow making, frozen food preparation, and surface-display system development. However, studies on the transport activity of INP remain lacking. In the present study, a newly identified INP-gene variant, inaQ, from a P. syringae MB03 strain was cloned. Its structural domains, signal sequences, and the hydrophilicity or hydrophobicity of each domain, were then characterized. The deduced amino acid sequence of InaQ shares similar protein domains with three P. syringae INPs, namely, InaK, InaZ, and InaV, which were identified as an N-terminal domain, a central repeating domain, and a C-terminal domain. The expression of the full-length InaQ and of various truncated variants was induced in Escherichia coli to analyze their transmembrane transport and surface-binding activities, while using the green fluorescence protein (GFP) as the fusion partner. With two transmembrane segments and a weak secretion signal, the N-terminal domain (InaQ-N) alone was found to be responsible for the transport process as well as for the binding to the outer membrane, whereas the C-terminal region was nonfunctional in protein transport. Increased membrane transport and surface-binding capacities were induced by a low isopropyl-β-D-thiogalactoside concentration (0.1 mmol/l) but not by culture temperatures (15 ºC to 37 ºC). Furthermore, by constructing the GFP-fused proteins with a single InaQ-N, as well as two and three tandemly aligned InaQ-N molecules, the transport and membrane-binding activities of these proteins were compared using Western blot analysis, immmunofluorescence microscopy, and assays of the GFP specific fluorescence intensity of subcellular fractions and flow cytometry, which showed that the increase of InaQ-N repeats resulted in a coordinated increase of the

  20. Molecular Characterization of an Ice Nucleation Protein Variant (InaQ from Pseudomonas syringae and the Analysis of Its Transmembrane Transport Activity in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Qianqian Li, Qi Yan, Jinsi Chen, Yan He, Jing Wang, Hongxing Zhang, Ziniu Yu, Lin Li

    2012-01-01

    Full Text Available The ice nucleation protein (INP of Pseudomonas syringae has gained scientific interest not only because of its pathogenicity of foliar necroses but also for its wide range of potential applications, such as in snow making, frozen food preparation, and surface-display system development. However, studies on the transport activity of INP remain lacking. In the present study, a newly identified INP-gene variant, inaQ, from a P. syringae MB03 strain was cloned. Its structural domains, signal sequences, and the hydrophilicity or hydrophobicity of each domain, were then characterized. The deduced amino acid sequence of InaQ shares similar protein domains with three P. syringae INPs, namely, InaK, InaZ, and InaV, which were identified as an N-terminal domain, a central repeating domain, and a C-terminal domain. The expression of the full-length InaQ and of various truncated variants was induced in Escherichia coli to analyze their transmembrane transport and surface-binding activities, while using the green fluorescence protein (GFP as the fusion partner. With two transmembrane segments and a weak secretion signal, the N-terminal domain (InaQ-N alone was found to be responsible for the transport process as well as for the binding to the outer membrane, whereas the C-terminal region was nonfunctional in protein transport. Increased membrane transport and surface-binding capacities were induced by a low isopropyl-β-D-thiogalactoside concentration (0.1 mmol/l but not by culture temperatures (15 ºC to 37 ºC. Furthermore, by constructing the GFP-fused proteins with a single InaQ-N, as well as two and three tandemly aligned InaQ-N molecules, the transport and membrane-binding activities of these proteins were compared using Western blot analysis, immmunofluorescence microscopy, and assays of the GFP specific fluorescence intensity of subcellular fractions and flow cytometry, which showed that the increase of InaQ-N repeats resulted in a coordinated

  1. Radiation Transport

    Energy Technology Data Exchange (ETDEWEB)

    Urbatsch, Todd James [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-06-15

    We present an overview of radiation transport, covering terminology, blackbody raditation, opacities, Boltzmann transport theory, approximations to the transport equation. Next we introduce several transport methods. We present a section on Caseology, observing transport boundary layers. We briefly broach topics of software development, including verification and validation, and we close with a section on high energy-density experiments that highlight and support radiation transport.

  2. Glutamate transporters combine transporter- and channel-like features

    NARCIS (Netherlands)

    Slotboom, DJ; Konings, WN; Lolkema, JS

    2001-01-01

    Glutamate transporters in the mammalian central nervous system have a unique position among secondary transport proteins as they exhibit glutamate-gated chloride-channel activity in addition to glutamate-transport activity. In this article, the available data on the structure of the glutamate transp

  3. A replacement of the active-site aspartic acid residue 293 in mouse cathepsin D affects its intracellular stability, processing and transport in HEK-293 cells.

    Science.gov (United States)

    Partanen, Sanna; Storch, Stephan; Löffler, Hans-Gerhard; Hasilik, Andrej; Tyynelä, Jaana; Braulke, Thomas

    2003-01-01

    The substitution of an active-site aspartic acid residue by asparagine in the lysosomal protease cathepsin D (CTSD) results in a loss of enzyme activity and severe cerebrocortical atrophy in a novel form of neuronal ceroid lipofuscinosis in sheep [Tyynelä, Sohar, Sleat, Gin, Donnelly, Baumann, Haltia and Lobel (2000) EMBO J. 19, 2786-2792]. In the present study we have introduced the corresponding mutation by replacing aspartic acid residue 293 with asparagine (D293N) into the mouse CTSD cDNA to analyse its effect on synthesis, transport and stability in transfected HEK-293 cells. The complete inactivation of mutant D293N mouse CTSD was confirmed by a newly developed fluorimetric quantification system. Moreover, in the heterologous overexpression systems used, mutant D293N mouse CTSD was apparently unstable and proteolytically modified during early steps of the secretory pathway, resulting in a loss of mass by about 1 kDa. In the affected sheep, the endogenous mutant enzyme was stable but also showed the shift in its molecular mass. In HEK-293 cells, the transport of the mutant D293N mouse CTSD to the lysosome was delayed and associated with a low secretion rate compared with wild-type CTSD. These data suggest that the mutation may result in a conformational change which affects stability, processing and transport of the enzyme. PMID:12350228

  4. The Next Generation Non-competitive Active Polyester Nanosystems for Transferrin Receptor-mediated Peroral Transport Utilizing Gambogic Acid as a Ligand.

    Science.gov (United States)

    Saini, P; Ganugula, R; Arora, M; Kumar, M N V Ravi

    2016-01-01

    The current methods for targeted drug delivery utilize ligands that must out-compete endogenous ligands in order to bind to the active site facilitating the transport. To address this limitation, we present a non-competitive active transport strategy to overcome intestinal barriers in the form of tunable nanosystems (NS) for transferrin receptor (TfR) utilizing gambogic acid (GA), a xanthanoid, as its ligand. The NS made using GA conjugated poly(lactide-co-glycolide) (PLGA) have shown non-competitive affinity to TfR evaluated in cell/cell-free systems. The fluorescent PLGA-GA NS exhibited significant intestinal transport and altered distribution profile compared to PLGA NS in vivo. The PLGA-GA NS loaded with cyclosporine A (CsA), a model peptide, upon peroral dosing to rodents led to maximum plasma concentration of CsA at 6 h as opposed to 24 h with PLGA-NS with at least 2-fold higher levels in brain at 72 h. The proposed approach offers new prospects for peroral drug delivery and beyond.

  5. Phosphatidylinositol- and phosphatidylcholine-transfer activity of PITPβ is essential for COPI-mediated retrograde transport from the Golgi to the endoplasmic reticulum

    Science.gov (United States)

    Carvou, Nicolas; Holic, Roman; Li, Michelle; Futter, Clare; Skippen, Alison; Cockcroft, Shamshad

    2010-01-01

    Vesicles formed by the COPI complex function in retrograde transport from the Golgi to the endoplasmic reticulum (ER). Phosphatidylinositol transfer protein β (PITPβ), an essential protein that possesses phosphatidylinositol (PtdIns) and phosphatidylcholine (PtdCho) lipid transfer activity is known to localise to the Golgi and ER but its role in these membrane systems is not clear. To examine the function of PITPβ at the Golgi-ER interface, RNA interference (RNAi) was used to knockdown PITPβ protein expression in HeLa cells. Depletion of PITPβ leads to a decrease in PtdIns(4)P levels, compaction of the Golgi complex and protection from brefeldin-A-mediated dispersal to the ER. Using specific transport assays, we show that anterograde traffic is unaffected but that KDEL-receptor-dependent retrograde traffic is inhibited. This phenotype can be rescued by expression of wild-type PITPβ but not by mutants defective in docking, PtdIns transfer and PtdCho transfer. These data demonstrate that the PtdIns and PtdCho exchange activity of PITPβ is essential for COPI-mediated retrograde transport from the Golgi to the ER. PMID:20332109

  6. Phosphatidylinositol- and phosphatidylcholine-transfer activity of PITPbeta is essential for COPI-mediated retrograde transport from the Golgi to the endoplasmic reticulum.

    Science.gov (United States)

    Carvou, Nicolas; Holic, Roman; Li, Michelle; Futter, Clare; Skippen, Alison; Cockcroft, Shamshad

    2010-04-15

    Vesicles formed by the COPI complex function in retrograde transport from the Golgi to the endoplasmic reticulum (ER). Phosphatidylinositol transfer protein beta (PITPbeta), an essential protein that possesses phosphatidylinositol (PtdIns) and phosphatidylcholine (PtdCho) lipid transfer activity is known to localise to the Golgi and ER but its role in these membrane systems is not clear. To examine the function of PITPbeta at the Golgi-ER interface, RNA interference (RNAi) was used to knockdown PITPbeta protein expression in HeLa cells. Depletion of PITPbeta leads to a decrease in PtdIns(4)P levels, compaction of the Golgi complex and protection from brefeldin-A-mediated dispersal to the ER. Using specific transport assays, we show that anterograde traffic is unaffected but that KDEL-receptor-dependent retrograde traffic is inhibited. This phenotype can be rescued by expression of wild-type PITPbeta but not by mutants defective in docking, PtdIns transfer and PtdCho transfer. These data demonstrate that the PtdIns and PtdCho exchange activity of PITPbeta is essential for COPI-mediated retrograde transport from the Golgi to the ER.

  7. Advocating beyond the academy

    DEFF Research Database (Denmark)

    Mackenzie, Catrina; Christensen, Julia; Turner, Sarah

    2015-01-01

    Drawing from experiences in Northern Indigenous Canada, Uganda, and Vietnam, we discuss the challenges encountered while trying to communicate relevant results to local communities with whom we work. Wavering between participatory and advocacy research, we explore how we grapple with finding the ...

  8. Patient Advocate Foundation

    Science.gov (United States)

    ... Montana Nebraska Nevada New Hampshire New Jersey New Mexico New York North Carolina North Dakota Ohio Oklahoma ... Employment Resources Disease Specific Resources Prevention Cancer Prevention Diabetes Prevention Cardiovascular/Heart Disease Prevention Healthcare Reform Additional ...

  9. TRANSPORT/HANDLING REQUESTS

    CERN Multimedia

    Groupe ST/HM

    2002-01-01

    A new EDH document entitled 'Transport/Handling Request' will be in operation as of Monday, 11th February 2002, when the corresponding icon will be accessible from the EDH desktop, together with the application instructions. This EDH form will replace the paper-format transport/handling request form for all activities involving the transport of equipment and materials. However, the paper form will still be used for all vehicle-hire requests. The introduction of the EDH transport/handling request form is accompanied by the establishment of the following time limits for the various services concerned: 24 hours for the removal of office items, 48 hours for the transport of heavy items (of up to 6 metric tons and of standard road width), 5 working days for a crane operation, extra-heavy transport operation or complete removal, 5 working days for all transport operations relating to LHC installation. ST/HM Group, Logistics Section Tel: 72672 - 72202

  10. Chamber transport

    Energy Technology Data Exchange (ETDEWEB)

    OLSON,CRAIG L.

    2000-05-17

    Heavy ion beam transport through the containment chamber plays a crucial role in all heavy ion fusion (HIF) scenarios. Here, several parameters are used to characterize the operating space for HIF beams; transport modes are assessed in relation to evolving target/accelerator requirements; results of recent relevant experiments and simulations of HIF transport are summarized; and relevant instabilities are reviewed. All transport options still exist, including (1) vacuum ballistic transport, (2) neutralized ballistic transport, and (3) channel-like transport. Presently, the European HIF program favors vacuum ballistic transport, while the US HIF program favors neutralized ballistic transport with channel-like transport as an alternate approach. Further transport research is needed to clearly guide selection of the most attractive, integrated HIF system.

  11. Gate-induced transition between metal-type and thermally activated transport in self-catalyzed MBE-grown InAs nanowires.

    Science.gov (United States)

    Blömers, C; Rieger, T; Grap, T; Raux, M; Lepsa, M I; Lüth, H; Grützmacher, D; Schäpers, Th

    2013-08-16

    Electronic transport properties of InAs nanowires are studied systematically. The nanowires are grown by molecular beam epitaxy on a SiOx-covered GaAs wafer, without using foreign catalyst particles. Room-temperature measurements revealed relatively high resistivity and low carrier concentration values, which correlate with the low background doping obtained by our growth method. Transport parameters, such as resistivity, mobility, and carrier concentration, show a relatively large spread that is attributed to variations in surface conditions. For some nanowires the conductivity has a metal-type dependence on temperature, i.e. decreasing with decreasing temperature, while other nanowires show the opposite temperature behavior, i.e. temperature-activated characteristics. An applied gate voltage in a field-effect transistor configuration can switch between the two types of behavior. The effect is explained by the presence of barriers formed by potential fluctuations.

  12. Continuous on-line calibration of diffusive soil-atmosphere trace gas transport using vertical {sup 220}Rn- and {sup 222}Rn-activity profiles

    Energy Technology Data Exchange (ETDEWEB)

    Lehmann, B.E. [Bern Univ. (Switzerland). Physics Inst.; Neftel, A. [Inst. of Environmental Protection and Agriculture, Bern (Switzerland); Tarakanov, S.V. [Inst. of Silicate Chemistry, St. Petersburg (Russian Federation)

    2001-07-01

    Continuous monitoring of {sup 220}Rn- and {sup 222}Rn-activities above and below the soil surface combined with sporadic direct {sup 222}Rn-flux measurements is used to quantify diffusive trace gas transport in the air-filled pore space of soil, through the soil-atmosphere interface and in the lowest layers of the atmosphere. In a calm night, {sup 222}Rn-activities above the surface first build-up near the ground (z < 10 cm) and subsequently with a delay of 2-3 hours at higher altitudes (z < 5 m). Knowing (1) the {sup 222}Rn-flux from activity profiles measured in soil gas, (2) from direct flux determinations and (3) using information about atmospheric diffusion parameters from {sup 220}Rn-activities measured near the surface it is possible to model the temporal evolution of the vertical {sup 222}Rn-profiles in a night with stable weather and constant soil conditions. The system operates automatically for extended periods of time in the field enabling a better understanding of transport processes in response to changing environmental conditions (wind, rain, soil humidity). (orig.)

  13. Understanding the transport of Patagonian dust and its influence on marine biological activity in the South Atlantic Ocean

    OpenAIRE

    Johnson, M. S.; Meskhidze, N.; Kiliyanpilakkil, V. P.; Gassó, S.

    2010-01-01

    The supply of bioavailable iron to the high-nitrate low-chlorophyll (HNLC) waters of the Southern Ocean through atmospheric pathways could stimulate phytoplankton blooms and have major implications for the global carbon cycle. In this study, model results and remotely-sensed data are analyzed to examine the horizontal and vertical transport pathways of Patagonian dust and quantify the effect of iron-laden mineral dust deposition on marine biological productivity in the surface waters o...

  14. Understanding the transport of Patagonian dust and its influence on marine biological activity in the South Atlantic Ocean

    OpenAIRE

    Johnson, M. S.; Meskhidze, N.; Kiliyanpilakkil, V. P.; Gassó, S.

    2011-01-01

    The supply of bioavailable iron to the high-nitrate low-chlorophyll (HNLC) waters of the Southern Ocean through atmospheric pathways could stimulate phytoplankton blooms and have major implications for the global carbon cycle. In this study, model results and remotely-sensed data are analyzed to examine the horizontal and vertical transport pathways of Patagonian dust and quantify the effect of iron-laden mineral dust deposition on marine biological productivity in the surface waters of the S...

  15. Redox status in mammalian cells and stem cells during culture in vitro: critical roles of Nrf2 and cystine transporter activity in the maintenance of redox balance.

    Science.gov (United States)

    Ishii, Tetsuro; Mann, Giovanni E

    2014-01-01

    Culturing cells and tissues in vitro has provided valuable insights into the molecular mechanisms regulating redox signaling in cells with implications for medicine. However, standard culture techniques maintain mammalian cells in vitro under an artificial physicochemical environment such as ambient air and 5% CO2. Oxidative stress is caused by the rapid oxidation of cysteine to cystine in culture media catalyzed by transition metals, leading to diminished intracellular cysteine and glutathione (GSH) pools. Some cells, such as fibroblasts and macrophages, express cystine transport activity, designated as system [Formula: see text], which enables cells to maintain these pools to counteract oxidative stress. Additionally, many cells have the ability to activate the redox sensitive transcription factor Nrf2, a master regulator of cellular defenses against oxidative stress, and to upregulate xCT, the subunit of the [Formula: see text] transport system leading to increases in cellular GSH. In contrast, some cells, including lymphoid cells, embryonic stem cells and iPS cells, express relatively low levels of xCT and cannot maintain cellular cysteine and GSH pools. Thus, fibroblasts have been used as feeder cells for the latter cell types based on their ability to supply cysteine. Other key Nrf2 regulated gene products include heme oxygenase 1, peroxiredoxin 1 and sequestosome1. In macrophages, oxidized LDL activates Nrf2 and upregulates the scavenger receptor CD36 forming a positive feedback loop to facilitate removal of the oxidant from the vascular microenvironment. This review describes cell type specific responses to oxygen derived stress, and the key roles that activation of Nrf2 and membrane transport of cystine and cysteine play in the maintenance and proliferation of mammalian cells in culture.

  16. Beta-adrenergic activation of solute coupled water uptake by toad skin epithelium results in near-isosmotic transport

    DEFF Research Database (Denmark)

    Nielsen, Robert; Larsen, Erik Hviid

    2007-01-01

    (V) decreased to 0.50+/-0.15 nL cm(-2) x s(-1), which is significantly different from zero. Isoproterenol decreased the osmotic concentration of the transported fluid, C(osm) approximately 2 x I(SC)(Eqv)/J(V), from 351+/-72 to 227+/-28 mOsm (Ringer's solution: 252.8 mOsm). J(V) depicted a saturating function......(V) with a [Na+] of the transported fluid of 130+/-24 mM ([Na+]Ringer's solution = 117.4 mM). Addition of bumetanide to the inside solution reduced J(V). Water was transported uphill and J(V) reversed at an excess outside osmotic concentration, deltaC(S,rev) = 28.9+/-3.9 mOsm, amiloride decreased delta......Transepithelial potential (V(T)), conductance (G(T)), and water flow (J(V)) were measured simultaneously with good time resolution (min) in isolated toad (Bufo bufo) skin epithelium with Ringer on both sides. Inside application of 5 microM isoproterenol resulted in the fast increase in G(T) from 1...

  17. Energy and transport.

    Science.gov (United States)

    Woodcock, James; Banister, David; Edwards, Phil; Prentice, Andrew M; Roberts, Ian

    2007-09-22

    We examine the links between fossil-fuel-based transportation, greenhouse-gas emissions, and health. Transport-related carbon emissions are rising and there is increasing consensus that the growth in motorised land vehicles and aviation is incompatible with averting serious climate change. The energy intensity of land transport correlates with its adverse health effects. Adverse health effects occur through climate change, road-traffic injuries, physical inactivity, urban air pollution, energy-related conflict, and environmental degradation. For the world's poor people, walking is the main mode of transport, but such populations often experience the most from the harms of energy-intensive transport. New energy sources and improvements in vehicle design and in information technology are necessary but not sufficient to reduce transport-related carbon emissions without accompanying behavioural change. By contrast, active transport has the potential to improve health and equity, and reduce emissions. Cities require safe and pleasant environments for active transport with destinations in easy reach and, for longer journeys, public transport that is powered by renewable energy, thus providing high levels of accessibility without car use. Much investment in major road projects does not meet the transport needs of poor people, especially women whose trips are primarily local and off road. Sustainable development is better promoted through improving walking and cycling infrastructures, increasing access to cycles, and investment in transport services for essential needs. Our model of London shows how increased active transport could help achieve substantial reductions in emissions by 2030 while improving population health. There exists the potential for a global contraction and convergence in use of fossil-fuel energy for transport to benefit health and achieve sustainability.

  18. Male-dominant activation of rat renal organic anion transporter 1 (Oat1 and 3 (Oat3 expression by transcription factor BCL6.

    Directory of Open Access Journals (Sweden)

    Waja Wegner

    Full Text Available BACKGROUND: Organic anion transporters 1 (Oat1 and 3 (Oat3 mediate the transport of organic anions, including frequently prescribed drugs, across cell membranes in kidney proximal tubule cells. In rats, these transporters are known to be male-dominant and testosterone-dependently expressed. The molecular mechanisms that are involved in the sex-dependent expression are unknown. Our aim was to identify genes that show a sex-dependent expression and could be involved in male-dominant regulation of Oat1 and Oat3. METHODOLOGY/PRINCIPAL FINDINGS: Promoter activities of Oat1 and Oat3 were analyzed using luciferase assays. Expression profiling was done using a SurePrint G3 rat GE 8 × 60K microarray. RNA was isolated from renal cortical slices of four adult rats per sex. To filter the achieved microarray data for genes expressed in proximal tubule cells, transcription database alignment was carried out. We demonstrate that predicted androgen response elements in the promoters of Oat1 and Oat3 are not functional when the promoters were expressed in OK cells. Using microarray analyses we analyzed 17,406 different genes. Out of these genes, 56 exhibit a sex-dependent expression in rat proximal tubule cells. As genes potentially involved in the regulation of Oat1 and Oat3 expression, we identified, amongst others, the male-dominant hydroxysteroid (17-beta dehydrogenase 1 (Hsd17b1, B-cell CLL/lymphoma 6 (BCL6, and polymerase (RNA III (DNA directed polypeptide G (Polr3g. Moreover, our results revealed that the transcription factor BCL6 activates promoter constructs of Oat1 and Oat3. CONCLUSION: The results indicate that the male-dominant expression of both transporters, Oat1 and Oat3, is possibly not directly regulated by the classical androgen receptor mediated transcriptional pathway but appears to be regulated by the transcription factor BCL6.

  19. Lipopolysaccharide-induced serotonin transporter up-regulation involves PKG-I and p38MAPK activation partially through A3 adenosine receptor.

    Science.gov (United States)

    Zhao, Rui; Wang, Shoubao; Huang, Zhonglin; Zhang, Li; Yang, Xiuying; Bai, Xiaoyu; Zhou, Dan; Qin, Zhizhen; Du, Guanhua

    2015-12-01

    Serotonin transporter (SERT) is a critical determinant of synaptic serotonin (5-hydroxytryptamine, 5-HT) inactivation which plays a critical role in the pathology of depression and other mood disorders. Lipopolysaccharide (LPS), a potent activator of the inflammatory system, has been reported to cause depression symptoms by the modulation of SERT in vivo and in vitro. This study is aimed to investigate the underlying mechanism of LPS-induced SERT modulation. The 4-(4-(dimethylamino) styryl)-N-methylpyridinium iodide (ASP) assay was used to detect dynamic 5-HT uptake as read out of SERT activities in RBL-2H3 cells, and cytosol Ca(2+) concentrations ([Ca(2+)]i) and nitric oxide (NO) were examined. Using specific cyclic GMP-dependent protein kinase type I (PKG-I), p38 mitogen-activated protein kinases (p38MAPK) and A3 adenosine receptor (A3AR) inhibitors, SERT expression was evaluated by western blot and immunofluorescence analysis. Results showed that 24 h treatment with LPS stimulated 5-HT transport and up-regulate plasma membrane distribution of SERT in RBL-2H3 cells. LPS treatment increased NO and [Ca(2+)]i, and led to significant increases in levels of phosphorylated calcium/calmodulin-dependent protein kinase type II (CaMK-II), inducible NOS (iNOS) and PKG-I as well as active p38 MAPK. Moreover, PKG-I inhibitor KT5823 or p38MAPK inhibitor SB203580 respectively impaired SERT activation and transposition to plasma membrane by LPS. Notably, A3 adenosine receptor inhibitor MRS1191 also hindered SERT stimulation by LPS. In conclusion, LPS-induced 5-HT uptake and transposition to plasma membrane of SERT in RBL-2H3 cells involves CaMK-II/iNOS/PKG-I and p38 MAPK activation, which may be partially mediated by A3 adenosine receptor activation. This finding provides a novel insight into the interrelationship between LPS and depression.

  20. Understanding the transport of Patagonian dust and its influence on marine biological activity in the South Atlantic Ocean

    Directory of Open Access Journals (Sweden)

    M. S. Johnson

    2011-03-01

    Full Text Available The supply of bioavailable iron to the high-nitrate low-chlorophyll (HNLC waters of the Southern Ocean through atmospheric pathways could stimulate phytoplankton blooms and have major implications for the global carbon cycle. In this study, model results and remotely-sensed data are analyzed to examine the horizontal and vertical transport pathways of Patagonian dust and quantify the effect of iron-laden mineral dust deposition on marine biological productivity in the surface waters of the South Atlantic Ocean (SAO. Model simulations for the atmospheric transport and deposition of mineral dust and bioavailable iron are carried out for two large dust outbreaks originated at the source regions of northern Patagonia during the austral summer of 2009. Model-simulated horizontal and vertical transport pathways of Patagonian dust plumes are in reasonable agreement with remotely-sensed data. Simulations indicate that the synoptic meteorological patterns of high and low pressure systems are largely accountable for dust transport trajectories over the SAO. According to model results and retrievals from the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO, synoptic flows caused by opposing pressure systems (a high pressure system located to the east or north-east of a low pressure system elevate the South American dust plumes well above the marine boundary layer. Under such conditions, the bulk concentration of mineral dust can quickly be transported around the low pressure system in a clockwise manner, follow the southeasterly advection pathway, and reach the HNLC waters of the SAO and Antarctica in ~3–4 days after emission from the source regions of northern Patagonia. Two different mechanisms for dust-iron mobilization into a bioavailable form are considered in this study. A global 3-D chemical transport model (GEOS-Chem, implemented with an iron dissolution scheme, is employed to estimate the atmospheric fluxes of soluble

  1. Understanding the transport of Patagonian dust and its influence on marine biological activity in the South Atlantic Ocean

    Directory of Open Access Journals (Sweden)

    M. S. Johnson

    2010-11-01

    Full Text Available The supply of bioavailable iron to the high-nitrate low-chlorophyll (HNLC waters of the Southern Ocean through atmospheric pathways could stimulate phytoplankton blooms and have major implications for the global carbon cycle. In this study, model results and remotely-sensed data are analyzed to examine the horizontal and vertical transport pathways of Patagonian dust and quantify the effect of iron-laden mineral dust deposition on marine biological productivity in the surface waters of the South Atlantic Ocean (SAO. Model simulations for the atmospheric transport and deposition of mineral dust and bioavailable iron are carried out for two large dust outbreaks originated at the source regions of Northern Patagonia during the austral summer of 2009. Model-simulated horizontal and vertical transport pathways of Patagonian dust plumes are in reasonable agreement with remotely-sensed data. Simulations indicate that the synoptic meteorological patterns of high and low pressure systems are largely accountable for dust transport trajectories over the SAO. According to model results and retrievals from the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO, synoptic flows caused by opposing pressure systems (a high pressure system located to the east or north-east of a low pressure system elevate the South American dust plumes well above the marine boundary layer. Under such conditions, the bulk concentration of mineral dust can quickly be transported around the low pressure system in a clockwise manner, follow the southeasterly advection pathway, and reach the HNLC waters of the SAO and Antarctica in ~3–4 days after emission from the source regions of Northern Patagonia. Two different mechanisms for dust-iron mobilization into a bioavailable form are considered in this study. A global 3-D chemical transport model (GEOS-Chem, implemented with an iron dissolution scheme, is employed to estimate the atmospheric fluxes of soluble

  2. Effects of L-carnitine administration on mitochondrial electron transport activity present in human muscle during circulatory shock.

    Science.gov (United States)

    Corbucci, G G; Gasparetto, A; Antonelli, M; Bufi, M; Crimi, G; Conti, G; De Blasi, R A; Candiani, A; Cooper, M B; Jones, D A

    1985-01-01

    Carnitine was administered to a group of patients in shock, and the activities of cytochrome oxidase and succinate cytochrome c reductase in muscle needle biopsies from these patients were compared to those activities present in a non-carnitine treated control group of patients. Carnitine seemingly exerted a significant protective action on cytochrome oxidase activity during the initial phases of shock, but not to such an extent on succinate cytochrome c reductase activities.

  3. Nitrate transport in cucumber leaves is an inducible process involving an increase in plasma membrane H+-ATPase activity and abundance

    Directory of Open Access Journals (Sweden)

    Nikolic Miroslav

    2012-05-01

    Full Text Available Abstract Background The mechanisms by which nitrate is transported into the roots have been characterized both at physiological and molecular levels. It has been demonstrated that nitrate is taken up in an energy-dependent way by a four-component uptake machinery involving high- and low- affinity transport systems. In contrast very little is known about the physiology of nitrate transport towards different plant tissues and in particular at the leaf level. Results The mechanism of nitrate uptake in leaves of cucumber (Cucumis sativus L. cv. Chinese long plants was studied and compared with that of the root. Net nitrate uptake by roots of nitrate-depleted cucumber plants proved to be substrate-inducible and biphasic showing a saturable kinetics with a clear linear non saturable component at an anion concentration higher than 2 mM. Nitrate uptake by leaf discs of cucumber plants showed some similarities with that operating in the roots (e.g. electrogenic H+ dependence via involvement of proton pump, a certain degree of induction. However, it did not exhibit typical biphasic kinetics and was characterized by a higher Km with values out of the range usually recorded in roots of several different plant species. The quantity and activity of plasma membrane (PM H+-ATPase of the vesicles isolated from leaf tissues of nitrate-treated plants for 12 h (peak of nitrate foliar uptake rate increased with respect to that observed in the vesicles isolated from N-deprived control plants, thus suggesting an involvement of this enzyme in the leaf nitrate uptake process similar to that described in roots. Molecular analyses suggest the involvement of a specific isoform of PM H+-ATPase (CsHA1 and NRT2 transporter (CsNRT2 in root nitrate uptake. At the leaf level, nitrate treatment modulated the expression of CsHA2, highlighting a main putative role of this isogene in the process. Conclusions Obtained results provide for the first time evidence that a saturable

  4. Building a Generation of Physician Advocates: The Case for Including Mandatory Training in Advocacy in Canadian Medical School Curricula.

    Science.gov (United States)

    Bhate, Tahara D; Loh, Lawrence C

    2015-12-01

    There is an increasing focus on the social accountability of physicians as individuals, and of medicine itself. This has led to increasing emphasis on physician advocacy from a wide variety of institutions. The physician advocacy concept is now part of the Health Advocacy competency mandated by the Royal College of Physicians and Surgeons of Canada. Despite its growing prominence, physician advocacy remains poorly integrated into current medical undergraduate curricula. The authors recommend how and why curricular reform should proceed; they focus on Canadian medical education, although they hope their views will be useful in other countries as well.The authors discuss conflicting definitions of physician advocacy, which have previously hampered curriculum development efforts, and suggest a way of reconciling the conflicts. They review current gaps in advocacy-related curricula, suggest that these can be addressed by incorporating practice-based and skills acquisition elements into current didactic teaching, and offer several strategies by which an advocacy curriculum could be implemented, ranging from small modifications to current curriculum to developing new competencies in medical education nationally.The authors present a case for making an advocacy curriculum mandatory for every Canadian medical trainee; they argue that teaching trainees how to fulfill their professional responsibility to advocate may also help them meet the social accountability mandate of medical school education. Finally, the authors explain why making the development and implementation of a mandatory, skill-based curriculum in advocacy should be a priority.

  5. The research subject advocate at minority Clinical Research Centers: an added resource for protection of human subjects.

    Science.gov (United States)

    Easa, David; Norris, Keith; Hammatt, Zoë; Kim, Kari; Hernandez, Esther; Kato, Kambrie; Balaraman, Venkataraman; Ho, Tammy; Shomaker, Samuel

    2005-01-01

    In early 2001, the National Institutes of Health (NIH) created the research subject advocate (RSA) position as an additional resource for human subjects protection at NIH-funded Clinical Research Centers (CRCs) to enhance the protection of human participants in clinical research studies. We describe the RSA position in the context of clinical research, with a particular emphasis on the role of the RSA in two of the five CRCs funded by the NIH Research Centers in Minority Institutions (RCMI) program. Through participation in protocol development, informed consent procedures, study implementation and follow-up with adverse events, the RSA works closely with research investigators and their staff to protect study participants. The RSA also conducts workshops, training and education sessions, and consultation with investigators to foster enhanced communication and adherence to ethical standards and safety regulations. Although we cannot yet provide substantive evidence of positive outcomes, this article illuminates the value of the RSA position in ensuring that safety of research participants is accorded the highest priority at CRCs. On the basis of initial results, we conclude that the RSA is an effective mechanism for achieving the NIH goal of maintaining the utmost scrutiny of protocols involving human subjects.

  6. Monitoring the Gamma-ray Sky through 4.5 Years of Fermi LAT Flare Advocate Service

    CERN Document Server

    Ciprini, Stefano

    2013-01-01

    The Fermi Flare Advocate (also known as Gamma-ray Sky Watcher, FA-GSW) service provides for a quick look and review of the gamma-ray sky observed daily by the Fermi Large Area Telescope (LAT). The FA-GSW service provides alerts and communicates to the external scientific community potentially new gamma-ray sources, interesting transients and source flares. A weekly digest containing the highlights about the variable LAT gamma-ray sky at E>100 MeV is published in the web ("Fermi Sky Blog"). Other news items are occasionally posted through the Fermi multiwavelength mailing list, Astronomer's Telegrams (ATels) and Gamma-ray Coordination Network notes (GCNs). From July 2008 to January 2013 about 230 ATels and some GCNs have been published by the Fermi LAT Collaboration, more than 40 target of opportunity observing programs have been triggered by the LAT Collaboration and performed though the Swift satellite, and individual observing alerts have been addressed to ground-based Cherenkov telescopes. This is helping ...

  7. Design, synthesis and structure-activity relationships of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease.

    Science.gov (United States)

    Toda, Narihiro; Tago, Keiko; Marumoto, Shinji; Takami, Kazuko; Ori, Mayuko; Yamada, Naho; Koyama, Kazuo; Naruto, Shunji; Abe, Kazumi; Yamazaki, Reina; Hara, Takao; Aoyagi, Atsushi; Abe, Yasuyuki; Kaneko, Tsugio; Kogen, Hiroshi

    2003-05-01

    We have designed and synthesized a dual inhibitor of acetylcholinesterase (AChE) and serotonin transporter (SERT) as a novel class of treatment drugs for Alzheimer's disease on the basis of a hypothetical model of the AChE active site. Dual inhibitions of AChE and SERT would bring about greater therapeutic effects than AChE inhibition alone and avoid adverse peripheral effects caused by excessive AChE inhibition. Compound (S)-6j exhibited potent inhibitory activities against AChE (IC(50)=101 nM) and SERT (IC(50)=42 nM). Furthermore, (S)-6j showed inhibitory activities of both AChE and SERT in mice brain following oral administration.

  8. Enhanced Oxygen and Hydroxide Transport in a Cathode Interface by Efficient Antibacterial Property of a Silver Nanoparticle-Modified, Activated Carbon Cathode in Microbial Fuel Cells.

    Science.gov (United States)

    Li, Da; Qu, Youpeng; Liu, Jia; Liu, Guohong; Zhang, Jie; Feng, Yujie

    2016-08-17

    A biofilm growing on an air cathode is responsible for the decreased performance of microbial fuel cells (MFCs). For t