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Sample records for cationic lipid-based transduction

  1. Drug loading to lipid-based cationic nanoparticles

    International Nuclear Information System (INIS)

    Cavalcanti, Leide P.; Konovalov, Oleg; Torriani, Iris L.; Haas, Heinrich

    2005-01-01

    Lipid-based cationic nanoparticles are a new promising option for tumor therapy, because they display enhanced binding and uptake at the neo-angiogenic endothelial cells, which a tumor needs for its nutrition and growth. By loading suitable cytotoxic compounds to the cationic carrier, the tumor endothelial and consequently also the tumor itself can be destroyed. For the development of such novel anti-tumor agents, the control of drug loading and drug release from the carrier matrix is essential. We have studied the incorporation of the hydrophobic anti-cancer agent Paclitaxel (PXL) into a variety of lipid matrices by X-Ray reflectivity measurements. Liposome suspensions from cationic and zwitterionic lipids, comprising different molar fractions of Paclitaxel, were deposited on planar glass substrates. After drying at controlled humidity, well ordered, oriented multilayer stacks were obtained, as proven by the presence of bilayer Bragg peaks to several orders in the reflectivity curves. The presence of the drug induced a decrease of the lipid bilayer spacing, and with an excess of drug, also Bragg peaks of drug crystals could be observed. From the results, insight into the solubility of Paclitaxel in the model membranes was obtained and a structural model of the organization of the drug in the membrane was derived. Results from subsequent pressure/area-isotherm and grazing incidence diffraction (GID) measurements performed with drug/lipid Langmuir monolayers were in accordance with these conjectures

  2. Correlation between cationic lipid-based transfection and cell division

    Energy Technology Data Exchange (ETDEWEB)

    Kirchenbuechler, Inka; Kirchenbuechler, David; Elbaum, Michael, E-mail: michael@elbaum.ac.il

    2016-07-01

    We evaluate the temporal relation between protein expression by cationic lipid-mediated transfection and cell division using time lapse fluorescence microscopy. Detailed image analysis provides new insights on the single cell level while simultaneously achieving appropriate statistics. Earlier evidence by less direct methods such as flow cytometry indicates a primary route for transfection involving nuclear envelope breakdown, but also suggests the existence of a pathway independent of mitosis. We confirm and quantify both mechanisms. We found the timing for successful transfection to be unexpectedly flexible, contrary to assertions of a narrow time window. Specifically, cells dividing more than 24 h after exposure to the transfection medium express the probed protein at a comparable level to cells in a mitotic state during or shortly after transfection. This finding can have a profound impact on the guidance and development of non-viral gene delivery materials. - Highlights: • Cationic lipid-based transfection supports protein expression without cell division. • Protein expression is unrelated to cell cycle status at the time of transfection. • Time-lapse imaging provides direct evaluation without statistical averaging. • Lipoplex dissociation is a likely target for improvement of transfection efficiency.

  3. Cationic lipid-based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects

    Directory of Open Access Journals (Sweden)

    Brody LP

    2017-09-01

    Full Text Available Leigh P Brody,1,* Meliz Sahuri-Arisoylu,1,* James R Parkinson,1 Harry G Parkes,2 Po Wah So,3 Nabil Hajji,4 E Louise Thomas,1 Gary S Frost,5 Andrew D Miller,6,* Jimmy D Bell1,* 1Department of Life Sciences, Faculty of Science and Technology, University of Westminster, 2CR-UK Clinical MR Research Group, Institute of Cancer Research, Sutton, Surrey, 3Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 4Department of Medicine, Division of Experimental Medicine, Centre for Pharmacology & Therapeutics, Toxicology Unit, Imperial College London, 5Faculty of Medicine, Nutrition and Dietetic Research Group, Division of Diabetes, Endocrinology and Metabolism, Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6Institute of Pharmaceutical Science, King’s College London, London, UK *These authors contributed equally to this work Abstract: Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a unique and novel application to the treatment of malignancy using a short-chain fatty acid (SCFA-encapsulated lipid-based delivery system – liposome-encapsulated acetate nanoparticles for cancer applications (LITA-CAN. We assessed chronic in vivo administration of our nanoparticle in three separate murine models of colorectal cancer. We demonstrated a substantial reduction in tumor growth in the xenograft model of colorectal cancer cell lines HT-29, HCT-116 p53+/+ and HCT-116 p53-/-. Nanoparticle-induced reductions in histone deacetylase gene expression indicated a potential mechanism for these anti-proliferative effects. Together, these results indicated that LITA-CAN could be used as an effective direct or adjunct therapy to treat malignant transformation in vivo. Keywords: lipid-based nanoparticles, liposomes

  4. Multifunctional Cationic Lipid-Based Nanoparticles Facilitate Endosomal Escape and Reduction-Triggered Cytosolic siRNA Release

    Science.gov (United States)

    Gujrati, Maneesh; Malamas, Anthony; Shin, Tesia; Jin, Erlei; Sun, Lulu; Lu, Zheng-Rong

    2015-01-01

    Small interfering RNA (siRNA) has garnered much attention in recent years as a promising avenue for cancer gene therapy due to its ability to silence disease-related genes. Effective gene silencing is contingent upon the delivery of siRNA into the cytosol of target cells and requires the implementation of delivery systems possessing multiple functionalities to overcome delivery barriers. The present work explores the multifunctional properties and biological activity of a recently developed cationic lipid carrier, (1-aminoethyl)iminobis[N-(oleicylcysteinyl-1-amino-ethyl)propionamide]) (ECO). The physicochemical properties and biological activity of ECO/siRNA nanoparticles were assessed over a range of N/P ratios to optimize the formulation. Potent and sustained luciferase silencing in a U87 glioblastoma cell line was observed, even in the presence of serum proteins. ECO/siRNA nanoparticles exhibited pH-dependent membrane disruption at pH levels corresponding to various stages of the intracellular trafficking pathway. It was found that disulfide linkages created during nanoparticle formation enhanced the protection of siRNA from degradation and facilitated site-specific siRNA release in the cytosol by glutathione-mediated reduction. Confocal microscopy confirmed that ECO/siRNA nanoparticles readily escaped from late endosomes prior to cytosolic release of the siRNA cargo. These results demonstrate that the rationally designed multifunctionality of ECO/siRNA nanoparticles is critical for intracellular siRNA delivery and the continuing development of safe and effective delivery systems. PMID:25020033

  5. Protein Transduction Based Therapies for Breast Cancer

    National Research Council Canada - National Science Library

    Robbins, Paul D

    2004-01-01

    We have demonstrated that certain transduction peptides such as 12 lysines and 12 arginines can facilitate internalization into breast tumor lines with higher efficiency than smaller polymers of cationic amino acids...

  6. Protein Transduction Based Therapies for Breast Cancer

    National Research Council Canada - National Science Library

    Robbins, Paul D

    2005-01-01

    We have demonstrated that certain transduction peptides such as 12 lysines and 12 arginines can facilitate internalization into breast tumor lines with higher efficiency than smaller polymers of cationic amino acids...

  7. Structure-function relationships of Na+, K+, ATP, or Mg2+ binding and energy transduction in Na,K-ATPase

    DEFF Research Database (Denmark)

    Jorgensen, Peter L.; Pedersen, Per Amstrup

    2000-01-01

    Na,K-ATPase; Mutagenesis; Na+ binding; K+ binding; Tl+ binding; Mg2+ binding; ATP binding; Cation binding site; Energy transduction......Na,K-ATPase; Mutagenesis; Na+ binding; K+ binding; Tl+ binding; Mg2+ binding; ATP binding; Cation binding site; Energy transduction...

  8. Actinide cation-cation complexes

    International Nuclear Information System (INIS)

    Stoyer, N.J.; Seaborg, G.T.

    1994-12-01

    The +5 oxidation state of U, Np, Pu, and Am is a linear dioxo cation (AnO 2 + ) with a formal charge of +1. These cations form complexes with a variety of other cations, including actinide cations. Other oxidation states of actinides do not form these cation-cation complexes with any cation other than AnO 2 + ; therefore, cation-cation complexes indicate something unique about AnO 2 + cations compared to actinide cations in general. The first cation-cation complex, NpO 2 + ·UO 2 2+ , was reported by Sullivan, Hindman, and Zielen in 1961. Of the four actinides that form AnO 2 + species, the cation-cation complexes of NpO 2 + have been studied most extensively while the other actinides have not. The only PuO 2 + cation-cation complexes that have been studied are with Fe 3+ and Cr 3+ and neither one has had its equilibrium constant measured. Actinides have small molar absorptivities and cation-cation complexes have small equilibrium constants; therefore, to overcome these obstacles a sensitive technique is required. Spectroscopic techniques are used most often to study cation-cation complexes. Laser-Induced Photacoustic Spectroscopy equilibrium constants for the complexes NpO 2 + ·UO 2 2+ , NpO 2 + ·Th 4+ , PuO 2 + ·UO 2 2+ , and PuO 2 + ·Th 4+ at an ionic strength of 6 M using LIPAS are 2.4 ± 0.2, 1.8 ± 0.9, 2.2 ± 1.5, and ∼0.8 M -1

  9. Lipid-based Transfection Reagents Exhibit Cryo-induced Increase in Transfection Efficiency

    Directory of Open Access Journals (Sweden)

    Helena Sork

    2016-01-01

    Full Text Available The advantages of lipid-based transfection reagents have permitted their widespread use in molecular biology and gene therapy. This study outlines the effect of cryo-manipulation of a cationic lipid-based formulation, Lipofectamine 2000, which, after being frozen and thawed, showed orders of magnitude higher plasmid delivery efficiency throughout eight different cell lines, without compromising cell viability. Increased transfection efficiency with the freeze-thawed reagent was also seen with 2'-O-methyl phosphorothioate oligonucleotide delivery and in a splice-correction assay. Most importantly, a log-scale improvement in gene delivery using the freeze-thawed reagent was seen in vivo. Using three different methods, we detected considerable differences in the polydispersity of the different nucleic acid complexes as well as observed a clear difference in their surface spreading and sedimentation, with the freeze-thawed ones displaying substantially higher rate of dispersion and deposition on the glass surface. This hitherto overlooked elevated potency of the freeze-thawed reagent facilitates the targeting of hard-to-transfect cells, accomplishes higher transfection rates, and decreases the overall amount of reagent needed for delivery. Additionally, as we also saw a slight increase in plasmid delivery using other freeze-thawed transfection reagents, we postulate that freeze-thawing might prove to be useful for an even wider variety of transfection reagents.

  10. Lipid-Based Liquid Crystalline Nanoparticles Facilitate Cytosolic Delivery of siRNA via Structural Transformation.

    Science.gov (United States)

    He, Shufang; Fan, Weiwei; Wu, Na; Zhu, Jingjing; Miao, Yunqiu; Miao, Xiaran; Li, Feifei; Zhang, Xinxin; Gan, Yong

    2018-04-11

    RNA interference (RNAi) technology has shown great promise for the treatment of cancer and other genetic disorders. Despite the efforts to increase the target tissue distribution, the safe and effective delivery of siRNA to the diseased cells with sufficient cytosolic transport is another critical factor for successful RNAi clinical application. Here, the constructed lipid-based liquid crystalline nanoparticles, called nano-Transformers, can transform thestructure in the intracellular acidic environment and perform high-efficient siRNA delivery for cancer treatment. The developed nano-Transformers have satisfactory siRNA loading efficiency and low cytotoxicity. Different from the traditional cationic nanocarriers, the endosomal membrane fusion induced by the conformational transition of lipids contributes to the easy dissociation of siRNA from nanocarriers and direct release of free siRNA into cytoplasm. We show that transfection with cyclin-dependent kinase 1 (CDK1)-siRNA-loaded nano-Transformers causes up to 95% reduction of relevant mRNA in vitro and greatly inhibits the tumor growth without causing any immunogenic response in vivo. This work highlights that the lipid-based nano-Transformers may become the next generation of siRNA delivery system with higher efficacy and improved safety profiles.

  11. Recent developments in oral lipid-based drug delivery

    DEFF Research Database (Denmark)

    Thomas, N.; Rades, T.; Müllertz, A.

    2013-01-01

    The increasing number of poorly water-soluble drugs in development in the pharmaceutical industry has sparked interest in novel drug delivery options such as lipid-based drug delivery systems (LbDDS). Several LbDDS have been marketed successfully and have shown superior and more reliable...... bioavailability compared to conventional formulations. However, some reluctance in the broader application of LbDDS still appears, despite the growing commercial interest in lipids as a drug delivery platform. This reluctance might at least in part be related to the complexity associated with the development...... and characterization of LbDDS. In particular, the lack of standardized test protocols can be identified as the major obstacles for the broader application of LbDDS. This review seeks to summarize recent approaches in the field of lipid-based drug delivery that try to elucidate some critical steps in their development...

  12. Lipid Based Nanosystems for Curcumin: Past, Present and Future.

    Science.gov (United States)

    Nayak, Aditya P; Mills, Tom; Norton, Ian

    2016-01-01

    Curcumin is one of the principle bioactive compounds used in the ayurvedic medicine system that has the history of over 5000 years for human use. Curcumin an "Indian Gold" is used to treat simple ailments like the common cold to severe life threatening diseases like cancer, and HIV. Though its contribution is immense for the health protection and disease prevention, its clinical use is limited due to its susceptible nature to alkaline pH, high temperature, presence of oxygen and light. Hence it becomes extremely difficult to maintain its bioactivity during processing, storage and consumption. Recent advancements in the application of nanotechnology to curcumin offer an opportunity to enhance its stability, bioactivity and to overcome its pharmacokinetic mismatch. This in turn helps to bridge the gaps that exist between its bench top research data to its clinical findings. Among the various types of nano/micro delivery systems, lipid based delivery systems are well studied and are the best suited delivery systems to enhance the stability and pharmacokinetic profile of curcumin both for pharma and the food application. In the current review, effort will be made to recapitulate the work done in the past to use lipid based delivery systems (liposomes, solid lipid nanoparticles, and emulsions) to enhance the application of curcumin for health promotion and disease prevention. Further, future prospects for the utilization of these lipid-based delivery systems will be discussed in detail.

  13. Pharmaceutical and biomedical applications of lipid-based nanocarriers.

    Science.gov (United States)

    Carbone, Claudia; Leonardi, Antonio; Cupri, Sarha; Puglisi, Giovanni; Pignatello, Rosario

    2014-03-01

    Increasing attention is being given to lipid nanocarriers (LNs) as drug delivery systems, due to the advantages offered of a higher biocompatibility and lower toxicity compared with polymeric nanoparticles. Many administration routes are being investigated for LNs, including topical, oral and parenteral ones. LNs are also proposed for specific applications such as cancer treatment, gene therapy, diagnosis and medical devices production. However, the high number of published research articles does not match an equal amount of patents. A recent Review of ours, published in Pharmaceutical Patent Analyst, reported the patents proposing novel methods for the production of LNs. This review work discusses recent patents, filed in 2007-2013 and dealing with the industrial applications of lipid-based nanocarriers for the vectorization of therapeutically relevant molecules, as well as biotech products such as proteins, gene material and vaccines, in the pharmaceutical, diagnostic and biomedical areas.

  14. Enzymes as Biocatalysts for Lipid-based Bioproducts Processing

    DEFF Research Database (Denmark)

    Cheong, Ling-Zhi; Guo, Zheng; Fedosov, Sergey

    2012-01-01

    Bioproducts are materials, chemicals and energy derived from renewable biological resources such as agriculture, forestry, and biologically-derived wastes. To date, the use of enzymes as biocatalysts for lipid-based bioproducts processing has shown marked increase. This is mainly due to the fact...... that cost benefit derived from enzymatic processing such as enzyme specificity, higher product purity and lesser or none toxic waste disposal has surpassed the cost of biocatalysts itself. This chapter provided insights into distinct enzymes characteristics essential in industrial processing especially...... enzymes kinetics. Understanding of enzyme kinetics is important especially in designing efficient reaction set-ups including type of bioreactors, reaction conditions and reusability of biocatalysts to ensure efficient running cost. A brief review of state-of-the-art in industrial applications of enzymes...

  15. Nucleoside-Lipid-Based Nanocarriers for Sorafenib Delivery

    Science.gov (United States)

    Benizri, Sebastien; Ferey, Ludivine; Alies, Bruno; Mebarek, Naila; Vacher, Gaelle; Appavoo, Ananda; Staedel, Cathy; Gaudin, Karen; Barthélémy, Philippe

    2018-01-01

    Although the application of sorafenib, a small inhibitor of tyrosine protein kinases, to cancer treatments remains a worldwide option in chemotherapy, novel strategies are needed to address the low water solubility (drug. In this context, the use of nanocarriers is currently investigated in order to overcome these drawbacks. In this contribution, we report a new type of sorafenib-based nanoparticles stabilized by hybrid nucleoside-lipids. The solid lipid nanoparticles (SLNs) showed negative or positive zeta potential values depending on the nucleoside-lipid charge. Transmission electron microscopy of sorafenib-loaded SLNs revealed parallelepiped nanoparticles of about 200 nm. Biological studies achieved on four different cell lines, including liver and breast cancers, revealed enhanced anticancer activities of Sorafenib-based SLNs compared to the free drug. Importantly, contrast phase microscopy images recorded after incubation of cancer cells in the presence of SLNs at high concentration in sorafenib (> 80 μM) revealed a total cancer cell death in all cases. These results highlight the potential of nucleoside-lipid-based SLNs as drug delivery systems.

  16. Quantum Transduction with Adaptive Control

    Science.gov (United States)

    Zhang, Mengzhen; Zou, Chang-Ling; Jiang, Liang

    2018-01-01

    Quantum transducers play a crucial role in hybrid quantum networks. A good quantum transducer can faithfully convert quantum signals from one mode to another with minimum decoherence. Most investigations of quantum transduction are based on the protocol of direct mode conversion. However, the direct protocol requires the matching condition, which in practice is not always feasible. Here we propose an adaptive protocol for quantum transducers, which can convert quantum signals without requiring the matching condition. The adaptive protocol only consists of Gaussian operations, feasible in various physical platforms. Moreover, we show that the adaptive protocol can be robust against imperfections associated with finite squeezing, thermal noise, and homodyne detection, and it can be implemented to realize quantum state transfer between microwave and optical modes.

  17. Cellular semiotics and signal transduction

    DEFF Research Database (Denmark)

    Bruni, Luis Emilio

    2007-01-01

    Semiosis, the processes of production, communication and interpretation of signs - coding and de-coding - takes place within and between organisms. The term "endosemiosis" refers to the processes of interpretation and sign transmission inside an organism (as opposed to "exosemiosis", which refers...... to the processes of sign interpretation and transmission between organisms of the same or different species). In Biosemiotics it is customary to recognise the cell as the most elementary integration unit for semiosis. Therefore intra and intercellular communication constitute the departure point for the study...... considering semiotic logic in order to construct our understanding of living phenomena. Given the central integrating role of signal transduction in physiological and ecological studies, this chapter outlines its semiotic implications. The multi-modality and modularity of signal molecules and relative...

  18. Quantum Transduction with Adaptive Control.

    Science.gov (United States)

    Zhang, Mengzhen; Zou, Chang-Ling; Jiang, Liang

    2018-01-12

    Quantum transducers play a crucial role in hybrid quantum networks. A good quantum transducer can faithfully convert quantum signals from one mode to another with minimum decoherence. Most investigations of quantum transduction are based on the protocol of direct mode conversion. However, the direct protocol requires the matching condition, which in practice is not always feasible. Here we propose an adaptive protocol for quantum transducers, which can convert quantum signals without requiring the matching condition. The adaptive protocol only consists of Gaussian operations, feasible in various physical platforms. Moreover, we show that the adaptive protocol can be robust against imperfections associated with finite squeezing, thermal noise, and homodyne detection, and it can be implemented to realize quantum state transfer between microwave and optical modes.

  19. Oral delivery of peptides and proteins using lipid-based drug delivery systems

    DEFF Research Database (Denmark)

    Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette

    2012-01-01

    INTRODUCTION: In order to successfully develop lipid-based drug delivery systems (DDS) for oral administration of peptides and proteins, it is important to gain an understanding of the colloid structures formed by these DDS, the mode of peptide and protein incorporation as well as the mechanism...... by which intestinal absorption of peptides and proteins is promoted. AREAS COVERED: The present paper reviews the literature on lipid-based DDS, employed for oral delivery of peptides and proteins and highlights the mechanisms by which the different lipid-based carriers are expected to overcome the two...... and proteins. EXPERT OPINION: Lipid-based DDS are safe and suitable for oral delivery of peptides and proteins. Significant progress has been made in this area with several technologies on clinical trials. However, a better understanding of the mechanism of action in vivo is needed in order to improve...

  20. Applications of lipid based formulation technologies in the delivery of biotechnology-based therapeutics.

    Science.gov (United States)

    du Plessis, Lissinda H; Marais, Etienne B; Mohammed, Faruq; Kotzé, Awie F

    2014-01-01

    In the last decades several new biotechnologically-based therapeutics have been developed due to progress in genetic engineering. A growing challenge facing pharmaceutical scientists is formulating these compounds into oral dosage forms with adequate bioavailability. An increasingly popular approach to formulate biotechnology-based therapeutics is the use of lipid based formulation technologies. This review highlights the importance of lipid based drug delivery systems in the formulation of oral biotechnology based therapeutics including peptides, proteins, DNA, siRNA and vaccines. The different production procedures used to achieve high encapsulation efficiencies of the bioactives are discussed, as well as the factors influencing the choice of excipient. Lipid based colloidal drug delivery systems including liposomes and solid lipid nanoparticles are reviewed with a focus on recent advances and updates. We further describe microemulsions and self-emulsifying drug delivery systems and recent findings on bioactive delivery. We conclude the review with a few examples on novel lipid based formulation technologies.

  1. Platform for Lipid Based Nanocarriers' Formulation Components and their Potential Effects: A Literature Review.

    Science.gov (United States)

    Farid, Ragwa Mohamed; Youssef, Nancy Abdel Hamid Abou; Kassem, Abeer Ahmed

    2017-11-27

    Lipid based nanocarriers have gained recently enormous interest for pharmaceutical application. They have the potential to provide controlled drug release and to target the drug to a specific area. In addition, lipid based nanocarriers can improve the bioavailability of drugs suffering from high hepatic first-pass metabolism, by enhancing their transport via the lymphatic system. The main components of lipid based nanocarriers are lipids and surfactants. Both have great influence on the prepared lipid based systems characteristics. The criteria for their selection are much related to physicochemical properties of the drug and the required administration route. This work gives an overview on the effect of both the type and amount of lipids and surfactants used in the manufacture of lipid based nanocarriers on their behavior and characteristics. Recent studies revealed that the properties of the final product including; particle size, homogeneity, drug loading capacity, zeta potential, drug release profile, stability, permeability, pharmacokinetic properties, crystallinity and cytotoxicity, may be significantly influenced not only by the type but also the amount of the lipids and/or surfactants included in the formulation of the lipid based nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Architectures and representations for string transduction

    NARCIS (Netherlands)

    Chrupala, Grzegorz

    2015-01-01

    String transduction problems are ubiquitous in natural language processing: they include transliteration, grapheme-to-phoneme conversion, text normalization and translation. String transduction can be reduced to the simpler problems of sequence labeling by expressing the target string as a sequence

  3. Human hematopoietic cell culture, transduction, and analyses

    DEFF Research Database (Denmark)

    Bonde, Jesper; Wirthlin, Louisa; Kohn, Donald B

    2008-01-01

    This unit provides methods for introducing genes into human hematopoietic progenitor cells. The Basic Protocol describes isolation of CD34(+) cells, transduction of these cells with a retroviral vector on fibronectin-coated plates, assaying the efficiency of transduction, and establishing long-te...

  4. Oral delivery of peptides and proteins using lipid-based drug delivery systems.

    Science.gov (United States)

    Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette

    2012-10-01

    In order to successfully develop lipid-based drug delivery systems (DDS) for oral administration of peptides and proteins, it is important to gain an understanding of the colloid structures formed by these DDS, the mode of peptide and protein incorporation as well as the mechanism by which intestinal absorption of peptides and proteins is promoted. The present paper reviews the literature on lipid-based DDS, employed for oral delivery of peptides and proteins and highlights the mechanisms by which the different lipid-based carriers are expected to overcome the two most important barriers (extensive enzymatic degradation and poor transmucosal permeability). This paper also gives a clear-cut idea about advantages and drawbacks of using different lipidic colloidal carriers ((micro)emulsions, solid lipid core particles and liposomes) for oral delivery of peptides and proteins. Lipid-based DDS are safe and suitable for oral delivery of peptides and proteins. Significant progress has been made in this area with several technologies on clinical trials. However, a better understanding of the mechanism of action in vivo is needed in order to improve the design and development of lipid-based DDS with the desired bioavailability and therapeutic profile.

  5. Assessing cellular toxicities in fibroblasts upon exposure to lipid-based nanoparticles: a high content analysis approach

    Science.gov (United States)

    Solmesky, Leonardo J.; Shuman, Michal; Goldsmith, Meir; Weil, Miguel; Peer, Dan

    2011-12-01

    Lipid-based nanoparticles (LNPs) are widely used for the delivery of drugs and nucleic acids. Although most of them are considered safe, there is confusing evidence in the literature regarding their potential cellular toxicities. Moreover, little is known about the recovery process cells undergo after a cytotoxic insult. We have previously studied the systemic effects of common LNPs with different surface charge (cationic, anionic, neutral) and revealed that positively charged LNPs ((+)LNPs) activate pro-inflammatory cytokines and induce interferon response by acting as an agonist of Toll-like receptor 4 on immune cells. In this study, we focused on the response of human fibroblasts exposed to LNPs and their cellular recovery process. To this end, we used image-based high content analysis (HCA). Using this strategy, we were able to show simultaneously, in several intracellular parameters, that fibroblasts can recover from the cytotoxic effects of (+)LNPs. The use of HCA opens new avenues in understanding cellular response and nanotoxicity and may become a valuable tool for screening safe materials for drug delivery and tissue engineering.

  6. Assessing cellular toxicities in fibroblasts upon exposure to lipid-based nanoparticles: a high content analysis approach

    International Nuclear Information System (INIS)

    Solmesky, Leonardo J; Weil, Miguel; Shuman, Michal; Goldsmith, Meir; Peer, Dan

    2011-01-01

    Lipid-based nanoparticles (LNPs) are widely used for the delivery of drugs and nucleic acids. Although most of them are considered safe, there is confusing evidence in the literature regarding their potential cellular toxicities. Moreover, little is known about the recovery process cells undergo after a cytotoxic insult. We have previously studied the systemic effects of common LNPs with different surface charge (cationic, anionic, neutral) and revealed that positively charged LNPs ((+)LNPs) activate pro-inflammatory cytokines and induce interferon response by acting as an agonist of Toll-like receptor 4 on immune cells. In this study, we focused on the response of human fibroblasts exposed to LNPs and their cellular recovery process. To this end, we used image-based high content analysis (HCA). Using this strategy, we were able to show simultaneously, in several intracellular parameters, that fibroblasts can recover from the cytotoxic effects of (+)LNPs. The use of HCA opens new avenues in understanding cellular response and nanotoxicity and may become a valuable tool for screening safe materials for drug delivery and tissue engineering.

  7. Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3

    DEFF Research Database (Denmark)

    Williams, Hywel D; Sassene, Philip; Kleberg, Karen

    2013-01-01

    PURPOSE: Recent studies have shown that digestion of lipid-based formulations (LBFs) can stimulate both supersaturation and precipitation. The current study has evaluated the drug, formulation and dose-dependence of the supersaturation - precipitation balance for a range of LBFs. METHODS: Type I,...

  8. Lipid-based liquid biofuels from autotrophic microalgae: energetic and environmental performance

    NARCIS (Netherlands)

    Reijnders, L.

    2013-01-01

    Commercial cultivation of autotrophic microalgae for food production dates back to the 1950s. Autotrophic microalgae have also been proposed as a source for lipid-based liquid biofuels. As yet, there is no commercial production of such biofuels and estimated near-term prices are far in excess of

  9. Purinergic mechanosensory transduction and visceral pain

    Directory of Open Access Journals (Sweden)

    Burnstock Geoffrey

    2009-11-01

    Full Text Available Abstract In this review, evidence is presented to support the hypothesis that mechanosensory transduction occurs in tubes and sacs and can initiate visceral pain. Experimental evidence for this mechanism in urinary bladder, ureter, gut, lung, uterus, tooth-pulp and tongue is reviewed. Potential therapeutic strategies are considered for the treatment of visceral pain in such conditions as renal colic, interstitial cystitis and inflammatory bowel disease by agents that interfere with mechanosensory transduction in the organs considered, including P2X3 and P2X2/3 receptor antagonists that are orally bioavailable and stable in vivo and agents that inhibit or enhance ATP release and breakdown.

  10. Isomerization of propargyl cation to cyclopropenyl cation ...

    Indian Academy of Sciences (India)

    step) for isomeri- zation of the linear propargyl cation to ..... C3, C4 and C5. The ZPE corrections in each case are derived from the. B3LYP calculations. ..... the converse of which gives the relative capacity of the. LPD's to stabilize TS6 with respect ...

  11. Cationic polymeric gene delivery of beta-glucuronidase for doxorubicin prodrug therapy

    NARCIS (Netherlands)

    Fonseca, MJ; Storm, G; Hennink, WE; Gerritsen, WR; Haisma, HJ

    1999-01-01

    Background An approach to improve current chemotherapy is the selective transduction of tumor cells with suicide genes to sensitize these cells to prodrugs of cytostatic agents; Methods In this study, gene transfer was accomplished with the cationic polymer poly(2-(dimethylamino)ethyl methacrylate)

  12. Mechanical transduction via a single soft polymer

    Science.gov (United States)

    Hou, Ruizheng; Wang, Nan; Bao, Weizhu; Wang, Zhisong

    2018-04-01

    Molecular machines from biology and nanotechnology often depend on soft structures to perform mechanical functions, but the underlying mechanisms and advantages or disadvantages over rigid structures are not fully understood. We report here a rigorous study of mechanical transduction along a single soft polymer based on exact solutions to the realistic three-dimensional wormlike-chain model and augmented with analytical relations derived from simpler polymer models. The results reveal surprisingly that a soft polymer with vanishingly small persistence length below a single chemical bond still transduces biased displacement and mechanical work up to practically significant amounts. This "soft" approach possesses unique advantages over the conventional wisdom of rigidity-based transduction, and potentially leads to a unified mechanism for effective allosterylike transduction and relay of mechanical actions, information, control, and molecules from one position to another in molecular devices and motors. This study also identifies an entropy limit unique to the soft transduction, and thereby suggests a possibility of detecting higher efficiency for kinesin motor and mutants in future experiments.

  13. Current and emerging lipid-based systems for transdermal drug delivery.

    Science.gov (United States)

    Singla, Sumeet K; Sachdeva, Vishal

    2015-01-01

    Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.

  14. Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea

    Directory of Open Access Journals (Sweden)

    Bu M

    2015-11-01

    Full Text Available Meng Bu,1,2 Jingling Tang,3 Yinghui Wei,4 Yanhui Sun,1 Xinyu Wang,1 Linhua Wu,2 Hongzhuo Liu1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Department of Pharmacy, the Second Affiliated Hospital, 3School of Pharmacy, Harbin Medical University, Harbin, People’s Republic of China; 4College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China Purpose: Supplementation of exogenous nerve growth factor (NGF into the cochlea of deafened animals rescues spiral ganglion cells from degeneration. However, a safe and potent delivery of therapeutic proteins, such as NGF, to spiral ganglion cells remains one of the greatest challenges. This study presents the development of self-assembled cubic lipid-based crystalline nanoparticles to enhance inner ear bioavailability of bioactive NGF via a round window membrane route.Methods: A novel nanocarrier-entrapped NGF was developed based on phytantriol by a liquid precursor dilution, with Pluronic® F127 and propylene glycol as the surfactant and solubilizer, respectively. Upon dilution of the liquid lipid precursors, monodispersed submicron-sized particles with a slight negative charge formed spontaneously.Results: Biological activity of entrapped NGF was assessed using pheochromocytoma cells with NGF-loaded reservoirs to induce significant neuronal outgrowth, similar to that seen in free NGF-treated controls. Finally, a 3.28-fold increase in inner ear bioavailability was observed after administration of phytantriol lipid-based crystalline nanoparticles as compared to free drug, contributing to an enhanced drug permeability of the round window membrane. Conclusion: Data presented here demonstrate the potential of lipid-based crystalline nanoparticles to improve the outcomes of patients bearing cochlear implants. Keywords: nerve growth factor, lipid-based crystalline nanoparticles, PC12 cells, inner ear drug

  15. Regulation of Cation Balance in Saccharomyces cerevisiae

    Science.gov (United States)

    Cyert, Martha S.; Philpott, Caroline C.

    2013-01-01

    All living organisms require nutrient minerals for growth and have developed mechanisms to acquire, utilize, and store nutrient minerals effectively. In the aqueous cellular environment, these elements exist as charged ions that, together with protons and hydroxide ions, facilitate biochemical reactions and establish the electrochemical gradients across membranes that drive cellular processes such as transport and ATP synthesis. Metal ions serve as essential enzyme cofactors and perform both structural and signaling roles within cells. However, because these ions can also be toxic, cells have developed sophisticated homeostatic mechanisms to regulate their levels and avoid toxicity. Studies in Saccharomyces cerevisiae have characterized many of the gene products and processes responsible for acquiring, utilizing, storing, and regulating levels of these ions. Findings in this model organism have often allowed the corresponding machinery in humans to be identified and have provided insights into diseases that result from defects in ion homeostasis. This review summarizes our current understanding of how cation balance is achieved and modulated in baker’s yeast. Control of intracellular pH is discussed, as well as uptake, storage, and efflux mechanisms for the alkali metal cations, Na+ and K+, the divalent cations, Ca2+ and Mg2+, and the trace metal ions, Fe2+, Zn2+, Cu2+, and Mn2+. Signal transduction pathways that are regulated by pH and Ca2+ are reviewed, as well as the mechanisms that allow cells to maintain appropriate intracellular cation concentrations when challenged by extreme conditions, i.e., either limited availability or toxic levels in the environment. PMID:23463800

  16. Cation Exchange Water Softeners

    Science.gov (United States)

    WaterSense released a notice of intent to develop a specification for cation exchange water softeners. The program has made the decision not to move forward with a spec at this time, but is making this information available.

  17. Signal transduction and chemotaxis in mast cells

    Czech Academy of Sciences Publication Activity Database

    Dráber, Petr; Hálová, Ivana; Polakovičová, Iva; Kawakami, T.

    2016-01-01

    Roč. 778, jaro (2016), s. 11-23 ISSN 0014-2999 R&D Projects: GA ČR(CZ) GA14-09807S; GA ČR(CZ) GBP302/12/G101; GA ČR(CZ) GA14-00703S Institutional support: RVO:68378050 Keywords : Mast cell * IgE receptor * KIT receptor * Signal transduction * Chemotaxis * Plasma membrane Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.896, year: 2016

  18. Macro-Fiber Composite Based Transduction

    Science.gov (United States)

    2016-03-01

    substrate Material properties of single crystal macro fiber composite actuators for active twist rotor blades Park, Jae-Sang (Seoul National...Passive Smart Structures and Integrated Systems 2007 Material properties of single crystal macro fiber composite actuators for active twist rotor ...19b. TELEPHONE NUMBER (Include area code) 10-03-20 16 Final Report 01 Jan 2013 - 31 Dec 2015 Macro-Fiber Composite Based Transduction N000-14-13-1-0212

  19. Presence of Ca2+-dependent K+ channels in chemosensory cilia support a role in odor transduction.

    Science.gov (United States)

    Delgado, Ricardo; Saavedra, M Veronica; Schmachtenberg, Oliver; Sierralta, Jimena; Bacigalupo, Juan

    2003-09-01

    Olfactory receptor neurons (ORNs) respond to odorants with changes in the action potential firing rate. Excitatory responses, consisting of firing increases, are mediated by a cyclic AMP cascade that leads to the activation of cationic nonselective cyclic nucleotide-gated (CNG) channels and Ca2+-dependent Cl- (ClCa) channels. This process takes place in the olfactory cilia, where all protein components of this cascade are confined. ORNs from various vertebrate species have also been shown to generate inhibitory odor responses, expressed as decreases in action potential discharges. Odor inhibition appears to rely on Ca2+-dependent K+ (KCa) channels, but the underlying transduction mechanism remains unknown. If these channels are involved in odor transduction, they are expected to be present in the olfactory cilia. We found that a specific antibody against a large conductance KCa recognized a protein of approximately 116 kDa in Western blots of purified rat olfactory ciliary membranes. Moreover, the antibody labeled ORN cilia in isolated ORNs from rat and toad (Caudiverbera caudiverbera). In addition, single-channel recordings from inside-out membrane patches excised from toad chemosensory cilia showed the presence of 4 different types of KCa channels, with unitary conductances of 210, 60, 12, and 29 and 60 pS, high K+-selectivity, and Ca2+ sensitivities in the low micromolar range. Our work demonstrates the presence of K+ channels in the ORN cilia and supports their participation in odor transduction.

  20. A Biosensor for Urea from Succinimide-Modified Acrylic Microspheres Based on Reflectance Transduction

    Directory of Open Access Journals (Sweden)

    Musa Ahmad

    2011-08-01

    Full Text Available New acrylic microspheres were synthesised by photopolymerisation where the succinimide functional group was incorporated during the microsphere preparation. An optical biosensor for urea based on reflectance transduction with a large linear response range to urea was successfully developed using this material. The biosensor utilized succinimide-modified acrylic microspheres immobilized with a Nile blue chromoionophore (ETH 5294 for optical detection and urease enzyme was immobilized on the surface of the microspheres via the succinimide groups. No leaching of the enzyme or chromoionophore was observed. Hydrolysis of the urea by urease changes the pH and leads to a color change of the immobilized chromoionophore. When the color change was monitored by reflectance spectrophotometry, the linear response range of the biosensor to urea was from 0.01 to 1,000 mM (R2 = 0.97 with a limit of detection of 9.97 mM. The biosensor response showed good reproducibility (relative standard deviation = 1.43%, n = 5 with no interference by major cations such as Na+, K+, NH4+ and Mg2+. The use of reflectance as a transduction method led to a large linear response range that is better than that of many urea biosensors based on other optical transduction methods.

  1. Lipid-based formulations for oral administration of poorly water-soluble drugs

    DEFF Research Database (Denmark)

    Mu, Huiling; Holm, René; Müllertz, Anette

    2013-01-01

    Lipid-based drug delivery systems have shown great potentials in oral delivery of poorly water-soluble drugs, primarily for lipophilic drugs, with several successfully marketed products. Pre-dissolving drugs in lipids, surfactants, or mixtures of lipids and surfactants omits the dissolving....../dissolution step, which is a potential rate limiting factor for oral absorption of poorly water-soluble drugs. Lipids not only vary in structures and physiochemical properties, but also in their digestibility and absorption pathway; therefore selection of lipid excipients and dosage form has a pronounced effect...

  2. Clinical studies with oral lipid based formulations of poorly soluble compounds

    DEFF Research Database (Denmark)

    Fatouros, Dimitrios; Karpf, Ditte M; Nielsen, Flemming S

    2007-01-01

    . Several drug products intended for oral administration have been marketed utilizing lipid and surfactant based formulations. Sandimmune((R)) and Sandimmune Neoral((R)) (cyclosporin A, Novartis), Norvir((R)) (ritonavir), and Fortovase((R)) (saquinavir) have been formulated in self-emulsifying drug delivery...... systems (SEDDS). This review summarizes published pharmacokinetic studies of orally administered lipid based formulations of poorly aqueous soluble drugs in human subjects. Special attention has been paid to the physicochemical characteristics of the formulations, when available and the impact...

  3. Lipid-Based Nanovectors for Targeting of CD44-Overexpressing Tumor Cells

    Directory of Open Access Journals (Sweden)

    Silvia Arpicco

    2013-01-01

    Full Text Available Hyaluronic acid (HA is a naturally occurring glycosaminoglycan that exists in living systems, and it is a major component of the extracellular matrix. The hyaluronic acid receptor CD44 is found at low levels on the surface of epithelial, haematopoietic, and neuronal cells and is overexpressed in many cancer cells particularly in tumour initiating cells. HA has been therefore used as ligand attached to HA-lipid-based nanovectors for the active targeting of small or large active molecules for the treatment of cancer. This paper describes the different approaches employed for the preparation, characterization, and evaluation of these potent delivery systems.

  4. Calibrating passive sampling and passive dosing techniques to lipid based concentrations

    DEFF Research Database (Denmark)

    Mayer, Philipp; Schmidt, Stine Nørgaard; Annika, A.

    2011-01-01

    Equilibrium sampling into various formats of the silicone polydimethylsiloxane (PDMS) is increasingly used to measure the exposure of hydrophobic organic chemicals in environmental matrices, and passive dosing from silicone is increasingly used to control and maintain their exposure in laboratory...... coated vials and with Head Space Solid Phase Microextraction (HS-SPME) yielded lipid based concentrations that were in good agreement with each other, but about a factor of two higher than measured lipid-normalized concentrations in the organisms. Passive dosing was applied to bioconcentration...

  5. Cation radicals of xanthophylls.

    Science.gov (United States)

    Galinato, Mary Grace I; Niedzwiedzki, Dariusz; Deal, Cailin; Birge, Robert R; Frank, Harry A

    2007-10-01

    Carotenes and xanthophylls are well known to act as electron donors in redox processes. This ability is thought to be associated with the inhibition of oxidative reactions in reaction centers and light-harvesting pigment-protein complexes of photosystem II (PSII). In this work, cation radicals of neoxanthin, violaxanthin, lutein, zeaxanthin, beta-cryptoxanthin, beta-carotene, and lycopene were generated in solution using ferric chloride as an oxidant and then studied by absorption spectroscopy. The investigation provides a view toward understanding the molecular features that determine the spectral properties of cation radicals of carotenoids. The absorption spectral data reveal a shift to longer wavelength with increasing pi-chain length. However, zeaxanthin and beta-cryptoxanthin exhibit cation radical spectra blue-shifted compared to that of beta-carotene, despite all of these molecules having 11 conjugated carbon-carbon double bonds. CIS molecular orbital theory quantum computations interpret this effect as due to the hydroxyl groups in the terminal rings selectively stabilizing the highest occupied molecular orbitals of preferentially populated s-trans-isomers. The data are expected to be useful in the analysis of spectral results from PSII pigment-protein complexes seeking to understand the role of carotene and xanthophyll cation radicals in regulating excited state energy flow, in protecting PSII reaction centers against photoinhibition, and in dissipating excess light energy absorbed by photosynthetic organisms but not used for photosynthesis.

  6. Identifi cation of Sectarianism

    Directory of Open Access Journals (Sweden)

    Martinovich Vladimir

    2016-03-01

    Full Text Available «New religious movements and society» is traditionally one of the most sophisticated topics in the area of new religions studies. Its problem field is so huge that up to now by far not all important research themes where even touched by scientists from all over the world. The problem of the process of the identification of sectarianism by diff erent societal institutions is one of such untouched themes that is taken as the main subject of this article. This process by itself is an inseparable part of the every societal deliberate reaction to the very existence of unconventional religiosity, its unstructured and mainly structured types. The focal point of the article is step-by-step analysis of the general structure elements of the process of the identification of sectarianism without any reference to the specific time and place of its flow. Special attention is paid to the analysis of the subjects of the identification of sectarianism, to the criteria for religious groups to be qualified as new religious movements, and to the specific features of the process of documents filtration. The causes of selective perception of sectarianism are disclosed. Some main consequences and unpredictable outcomes of the process of the identification of sectarianism are described.

  7. Development of New Lipid-Based Paclitaxel Nanoparticles Using Sequential Simplex Optimization

    Science.gov (United States)

    Dong, Xiaowei; Mattingly, Cynthia A.; Tseng, Michael; Cho, Moo; Adams, Val R.; Mumper, Russell J.

    2008-01-01

    The objective of these studies was to develop Cremophor-free lipid-based paclitaxel (PX) nanoparticle formulations prepared from warm microemulsion precursors. To identify and optimize new nanoparticles, experimental design was performed combining Taguchi array and sequential simplex optimization. The combination of Taguchi array and sequential simplex optimization efficiently directed the design of paclitaxel nanoparticles. Two optimized paclitaxel nanoparticles (NPs) were obtained: G78 NPs composed of glyceryl tridodecanoate (GT) and polyoxyethylene 20-stearyl ether (Brij 78), and BTM NPs composed of Miglyol 812, Brij 78 and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). Both nanoparticles successfully entrapped paclitaxel at a final concentration of 150 μg/ml (over 6% drug loading) with particle sizes less than 200 nm and over 85% of entrapment efficiency. These novel paclitaxel nanoparticles were stable at 4°C over three months and in PBS at 37°C over 102 hours as measured by physical stability. Release of paclitaxel was slow and sustained without initial burst release. Cytotoxicity studies in MDA-MB-231 cancer cells showed that both nanoparticles have similar anticancer activities compared to Taxol®. Interestingly, PX BTM nanocapsules could be lyophilized without cryoprotectants. The lyophilized powder comprised only of PX BTM NPs in water could be rapidly rehydrated with complete retention of original physicochemical properties, in-vitro release properties, and cytotoxicity profile. Sequential Simplex Optimization has been utilized to identify promising new lipid-based paclitaxel nanoparticles having useful attributes. PMID:19111929

  8. Prenatal Alcohol Exposure Damages Brain Signal Transduction Systems

    National Research Council Canada - National Science Library

    Caldwell, Kevin

    2001-01-01

    .... One and twenty-four hours following fear conditioning this learning deficit is associated with altered brain signal transduction mechanisms that are dependent on an enzyme termed phosphatidylinositol...

  9. Toward the establishment of standardized in vitro tests for lipid-based formulations, part 4

    DEFF Research Database (Denmark)

    Williams, Hywel D; Sassene, Philip; Kleberg, Karen

    2014-01-01

    The Lipid Formulation Classification System Consortium looks to develop standardized in vitro tests and to generate much-needed performance criteria for lipid-based formulations (LBFs). This article highlights the value of performing a second, more stressful digestion test to identify LBFs near...... a performance threshold and to facilitate lead formulation selection in instances where several LBF prototypes perform adequately under standard digestion conditions (but where further discrimination is necessary). Stressed digestion tests can be designed based on an understanding of the factors that affect LBF...... development, and facilitate dialogue with the regulatory authorities. This classification system is based on the concept that performance evaluations across three in vitro tests, designed to subject a LBF to progressively more challenging conditions, will enable effective LBF discrimination and performance...

  10. Lipidomics in translational research and the clinical significance of lipid-based biomarkers.

    Science.gov (United States)

    Stephenson, Daniel J; Hoeferlin, L Alexis; Chalfant, Charles E

    2017-11-01

    Lipidomics is a rapidly developing field of study that focuses on the identification and quantitation of various lipid species in the lipidome. Lipidomics has now emerged in the forefront of scientific research due to the importance of lipids in metabolism, cancer, and disease. Using both targeted and untargeted mass spectrometry as a tool for analysis, progress in the field has rapidly progressed in the last decade. Having the ability to assess these small molecules in vivo has led to better understanding of several lipid-driven mechanisms and the identification of lipid-based biomarkers in neurodegenerative disease, cancer, sepsis, wound healing, and pre-eclampsia. Biomarker identification and mechanistic understanding of specific lipid pathways linked to a disease's pathologies can form the foundation in the development of novel therapeutics in hopes of curing human disease. Published by Elsevier Inc.

  11. Implications of formulation design on lipid-based nanostructured carrier system for drug delivery to brain.

    Science.gov (United States)

    Salunkhe, Sachin S; Bhatia, Neela M; Bhatia, Manish S

    2016-05-01

    The aim of present investigation was to formulate and develop lipid-based nanostructured carriers (NLCs) containing Idebenone (IDE) for delivery to brain. Attempts have been made to evaluate IDE NLCs for its pharmacokinetic and pharmacodynamic profile through the objective of enhancement in bioavailability and effectivity of drug. Nanoprecipitation technique was used for development of drug loaded NLCs. The components solid lipid Precirol ATO 5, oil Miglyol 840, surfactants Tween 80 and Labrasol have been screened out for formulation development by consideration of preformulation parameters including solubility, Required Hydrophilic lipophilic balance (HLB) of lipids and stability study. Developed IDE NLCs were subjected for particle size, zeta potential, entrapment efficiency (%EE), crystallographic investigation, transmission electron microscopy, in vitro drug release, pharmacokinetics, in vivo and stability study. Formulation under investigation has particle size 174.1 ± 2.6 nm, zeta potential -18.65 ± 1.13 mV and% EE 90.68 ± 2.90. Crystallographic studies exemplified for partial amorphization of IDE by molecularly dispersion within lipid crust. IDE NLCs showed drug release 93.56 ± 0.39% at end of 24 h by following Higuchi model which necessitates for appropriate drug delivery with enhancement in bioavailability of drug by 4.6-fold in plasma and 2.8-fold in brain over plain drug loaded aqueous dispersions. In vivo studies revealed that effect of drug was enhanced by prepared lipid nanocarriers. IDE lipid-based nanostructured carriers could have potential for efficient drug delivery to brain with enhancement in bioavailability of drug over the conventional formulations.

  12. A novel lipid-based nanomicelle of docetaxel: evaluation of antitumor activity and biodistribution

    Directory of Open Access Journals (Sweden)

    Ma M

    2012-07-01

    Full Text Available Mingshu Ma,1 Yanli Hao,1 Nan Liu,1 Zhe Yin,1 Lan Wang,1 Xingjie Liang,2 Xiaoning Zhang11Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing, China; 2National Center for Nanoscience and Technology, Beijing, ChinaPurpose: A lipid-based, nanomicelle-loaded docetaxel (M-DOC was designed and characterized. Optical imaging was employed to evaluate the pharmacokinetics and antitumor efficacy of docetaxel in vivo.Materials and methods: The M-DOC was prepared using the emulsion-diffusion method. Transmission electron microscopy and dynamic light scattering were used to assess the morphology and particle size of the M-DOC. Critical micelle concentrations, their stability under physiological conditions, and their encapsulation efficiency – as measured by high-performance liquid chromatography – were assessed. Pharmacological features were evaluated in two different animal models by comparing M-DOC treatments with docetaxel injections (I-DOC. Bioluminescence imaging was used to assess antitumor activity and docetaxel distribution in vivo, using nude mice injected with luciferase-expressing MDA-MB-231 human breast tumor cells. In addition, animals injected with B16 melanoma cells were used to measure survival time and docetaxel distribution.Results: The M-DOC was prepared as round, uniform spheres with an effective diameter of 20.8 nm. The critical micelle concentration of the original emulsion was 0.06%. Satisfactory encapsulation efficiency (87.6% ± 3.0% and 12-hour stability were achieved. Xenograft results demonstrated that the M-DOC was more effective in inhibiting tumor growth, without significantly changing body weight. Survival was prolonged by 12.6% in the M-DOC group. Tumor growth inhibitory rates in the M-DOC and I-DOC groups were 91.2% and 57.8% in volume and 71.8% and 44.9% in weight, respectively. Optical bioluminescence imaging of tumor growths yielded similar results. Area under the

  13. High-Throughput Lipolysis in 96-Well Plates for Rapid Screening of Lipid-Based Drug Delivery Systems

    DEFF Research Database (Denmark)

    Mosgaard, Mette D; Sassene, Philip J; Mu, Huiling

    2017-01-01

    The high-throughput in vitro intestinal lipolysis model (HTP) applicable for rapid and low-scale screening of lipid-based drug delivery systems (LbDDSs) was optimized and adjusted as to be conducted in 96-well plates (HTP-96). Three different LbDDSs (I-III) loaded with danazol or cinnarizine were...

  14. Endothelial cell oxidative stress and signal transduction

    Directory of Open Access Journals (Sweden)

    ROCIO FONCEA

    2000-01-01

    Full Text Available Endothelial dysfunction (ED is an early event in atherosclerotic disease, preceding clinical manifestations and complications. Increased reactive oxygen species (ROS have been implicated as important mechanisms that contribute to ED, and ROS’s may function as intracellular messengers that modulate signaling pathways. Several intracellular signal events stimulated by ROS have been defined, including the identification of two members of the mitogen activated protein kinase family (ERK1/2 and big MAP kinase, BMK1, tyrosine kinases (Src and Syk and different isoenzymes of PKC as redox-sensitive kinases. ROS regulation of signal transduction components include the modification in the activity of transcriptional factors such as NFkB and others that result in changes in gene expression and modifications in cellular responses. In order to understand the intracellular mechanisms induced by ROS in endothelial cells (EC, we are studying the response of human umbilical cord vein endothelial cells to increased ROS generation by different pro-atherogenic stimuli. Our results show that Homocysteine (Hcy and oxidized LDL (oxLDL enhance the activity and expression of oxidative stress markers, such as NFkB and heme oxygenase 1. These results suggest that these pro-atherogenic stimuli increase oxidative stress in EC, and thus explain the loss of endothelial function associated with the atherogenic process

  15. Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals.

    Science.gov (United States)

    Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

    2017-01-01

    Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations.

  16. In-vitro release of diclofenac diethylammonium from lipid-based formulations.

    Science.gov (United States)

    Parsaee, Siamak; Sarbolouki, Mohammad N; Parnianpour, Mohamad

    2002-07-08

    This article presents the preparation and topical performance of some new lipid-based formulations of diclofenac, namely (a) a diclofenac aqueous gel containing mixed micelles (sodium cholate:egg lecithin molar ratio 0.55); (b) diclofenac lotion that contains soya lecithin, ethanol and buffer; and (c) diclofenac lipogel containing egg lecithin, isopropyl myristate, propylene glycol and ethanol. Gel formulations were prepared using Carbomer 934. Release of diclofenac from all formulations was monitored via dialysis through Spectra/por membrane into phosphate buffer (0.2 M pH=7.4) using a Franz cell. Drug release profile and diffusion coefficients were compared with brand formulation (Geigy's Vlotaren Emulgel). Statistical analysis of data show that the diffusion coefficient of the drug from these formulations rank according to the following order: Diclofenac lotion (D=5.308x10(-7) cm(2)/s) >lipogel (D=2.102 x 10(-7) cm(2)/s) >Voltaren Emulgel (1.518 x 10(-7) cm(2)/s) >aqueous gel mixed micelle (0.966 x 10(-7) cm(2)/s). These results show that diclofenac lotion and lipogel maybe more suitable formulations than the conventional topical dosage form.

  17. Lipid Based Formulations of Biopharmaceutics Classification System (BCS Class II Drugs: Strategy, Formulations, Methods and Saturation

    Directory of Open Access Journals (Sweden)

    Šoltýsová I.

    2016-12-01

    Full Text Available Active ingredients in pharmaceuticals differ by their physico-chemical properties and their bioavailability therefore varies. The most frequently used and most convenient way of administration of medicines is oral, however many drugs are little soluble in water. Thus they are not sufficiently effective and suitable for such administration. For this reason a system of lipid based formulations (LBF was developed. Series of formulations were prepared and tested in water and biorelevant media. On the basis of selection criteria, there were selected formulations with the best emulsification potential, good dispersion in the environment and physical stability. Samples of structurally different drugs included in the Class II of the Biopharmaceutics classification system (BCS were obtained, namely Griseofulvin, Glibenclamide, Carbamazepine, Haloperidol, Itraconazol, Triclosan, Praziquantel and Rifaximin, for testing of maximal saturation in formulations prepared from commercially available excipients. Methods were developed for preparation of formulations, observation of emulsification and its description, determination of maximum solubility of drug samples in the respective formulation and subsequent analysis. Saturation of formulations with drugs showed that formulations 80 % XA and 20 % Xh, 35 % XF and 65 % Xh were best able to dissolve the drugs which supports the hypothesis that it is desirable to identify limited series of formulations which could be generally applied for this purpose.

  18. Relevance of Lipid-Based Products in the Management of Dry Eye Disease.

    Science.gov (United States)

    Garrigue, Jean-Sébastien; Amrane, Mourad; Faure, Marie-Odile; Holopainen, Juha M; Tong, Louis

    2017-11-01

    Components of the ocular surface synergistically contribute to maintaining and protecting a smooth refractive layer to facilitate the optimal transmission of light. At the air-water interface, the tear film lipid layer (TFLL), a mixture of lipids and proteins, plays a key role in tear surface tension and is important for the physiological hydration of the ocular surface and for ocular homeostasis. Alterations in tear fluid rheology, differences in lipid composition, or downregulation of specific tear proteins are found in most types of ocular surface disease, including dry eye disease (DED). Artificial tears have long been a first line of treatment in DED and aim to replace or supplement tears. More recently, lipid-containing eye drops have been developed to more closely mimic the combination of aqueous and lipid layers of the TFLL. Over the last 2 decades, our understanding of the nature and importance of lipids in the tear film in health and disease has increased substantially. The aim of this article is to provide a brief overview of our current understanding of tear film properties and review the effectiveness of lipid-based products in the treatment of DED. Liposome lid sprays, emulsion eye drops, and other lipid-containing formulations are discussed.

  19. Why Fish Oil Fails: A Comprehensive 21st Century Lipids-Based Physiologic Analysis

    Directory of Open Access Journals (Sweden)

    B. S. Peskin

    2014-01-01

    Full Text Available The medical community suffered three significant fish oil failures/setbacks in 2013. Claims that fish oil’s EPA/DHA would stop the progression of heart disease were crushed when The Risk and Prevention Study Collaborative Group (Italy released a conclusive negative finding regarding fish oil for those patients with high risk factors but no previous myocardial infarction. Fish oil failed in all measures of CVD prevention—both primary and secondary. Another major 2013 setback occurred when fish oil’s DHA was shown to significantly increase prostate cancer in men, in particular, high-grade prostate cancer, in the Selenium and Vitamin E Cancer Prevention Trial (SELECT analysis by Brasky et al. Another monumental failure occurred in 2013 whereby fish oil’s EPA/DHA failed to improve macular degeneration. In 2010, fish oil’s EPA/DHA failed to help Alzheimer’s victims, even those with low DHA levels. These are by no means isolated failures. The promise of fish oil and its so-called active ingredients EPA / DHA fails time and time again in clinical trials. This lipids-based physiologic review will explain precisely why there should have never been expectation for success. This review will focus on underpublicized lipid science with a focus on physiology.

  20. Why fish oil fails: a comprehensive 21st century lipids-based physiologic analysis.

    Science.gov (United States)

    Peskin, B S

    2014-01-01

    The medical community suffered three significant fish oil failures/setbacks in 2013. Claims that fish oil's EPA/DHA would stop the progression of heart disease were crushed when The Risk and Prevention Study Collaborative Group (Italy) released a conclusive negative finding regarding fish oil for those patients with high risk factors but no previous myocardial infarction. Fish oil failed in all measures of CVD prevention-both primary and secondary. Another major 2013 setback occurred when fish oil's DHA was shown to significantly increase prostate cancer in men, in particular, high-grade prostate cancer, in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) analysis by Brasky et al. Another monumental failure occurred in 2013 whereby fish oil's EPA/DHA failed to improve macular degeneration. In 2010, fish oil's EPA/DHA failed to help Alzheimer's victims, even those with low DHA levels. These are by no means isolated failures. The promise of fish oil and its so-called active ingredients EPA / DHA fails time and time again in clinical trials. This lipids-based physiologic review will explain precisely why there should have never been expectation for success. This review will focus on underpublicized lipid science with a focus on physiology.

  1. Spray drying of lipid-based systems loaded with Camellia sinensis polyphenols.

    Science.gov (United States)

    Secolin, Vanessa A; Souza, Claudia R F; Oliveira, Wanderley P

    2017-03-01

    In this work, spray-dried lipid systems based on soy phosphatidylcholine, cholesterol and lauroyl polyoxylglycerides for entrapping Green tea polyphenols were produced. The aim was to study the effects of the encapsulating composition and spray drying conditions on the system performance and physicochemical product properties. The spray dryer powder production yield falls around 50.7 ± 2.8%, which is typical for lab scale spray dryers. Wrinkled and rounded particles, with low surface porosities were generated, independent of the drying carriers (trehalose or lactose) used. The product showed high encapsulation efficiency of Green tea polyphenols, which was promptly redispersible in water. It presented low density, and good compressive and flow properties. The results herein reported confirm the feasibility of the entrapment of Green tea polyphenols in lipid-based compositions by spray drying in presence of the drying carriers evaluated. The spray-dried microparticles show high potential to be used as additive in food, nutraceutical and pharmaceutical products.

  2. Optimization and characterization of stable lipid-based, oxygen-filled microbubbles by mixture design.

    Science.gov (United States)

    Polizzotti, Brian D; Thomson, Lindsay M; O'Connell, Daniel W; McGowan, Francis X; Kheir, John N

    2014-08-01

    Tissue hypoxia is a final common pathway that leads to cellular injury and death in a number of critical illnesses. Intravenous injections of self-assembling, lipid-based oxygen microbubbles (LOMs) can be used to deliver oxygen gas, preventing organ injury and death from systemic hypoxemia. However, current formulations exhibit high polydispersity indices (which may lead to microvascular obstruction) and poor shelf-lives, limiting the translational capacity of LOMs. In this study, we report our efforts to optimize LOM formulations using a mixture response surface methodology (mRSM). We study the effect of changing excipient proportions (the independent variables) on microbubble diameter and product loss (the dependent variables). By using mRSM analysis, the experimental data were fit using a reduced Scheffé linear mixture model. We demonstrate that formulations manufactured from 1,2-distearoyl-sn-glycero-3-phosphocholine, corn syrup, and water produce micron-sized microbubbles with low polydispersity indices, and decreased product loss (relative to previously described formulations) when stored at room temperature over a 30-day period. Optimized LOMs were subsequently tested for their oxygen-releasing ability and found to have similar release kinetics as prior formulations. © 2014 Wiley Periodicals, Inc.

  3. Sorption by cation exchange

    International Nuclear Information System (INIS)

    Bradbury, M.H.; Baeyens, B.

    1994-04-01

    A procedure for introducing exchange into geochemical/surface complexation codes is described. Beginning with selectivity coefficients, K c , defined in terms of equivalent fractional ion occupancies, a general expression for the molar based exchange code input parameters, K ex , is derived. In natural systems the uptake of nuclides onto complex sorbents often occurs by more than one mechanism. The incorporation of cation exchange and surface complexation into a geochemical code therefore enables sorption by both mechanisms to be calculated simultaneously. The code and model concepts are tested against sets of experimental data from widely different sorption studies. A proposal is made to set up a data base of selectivity coefficients. Such a data base would form part of a more general one consisting of sorption mechanism specific parameters to be used in conjunction with geochemical/sorption codes to model and predict sorption. (author) 6 figs., 6 tabs., 26 refs

  4. Signal transduction in the footsteps of goethe and schiller.

    Science.gov (United States)

    Friedrich, Karlheinz; Lindquist, Jonathan A; Entschladen, Frank; Serfling, Edgar; Thiel, Gerald; Kieser, Arnd; Giehl, Klaudia; Ehrhardt, Christina; Feller, Stephan M; Ullrich, Oliver; Schaper, Fred; Janssen, Ottmar; Hass, Ralf

    2009-02-04

    The historical town of Weimar in Thuringia, the "green heart of Germany" was the sphere of Goethe and Schiller, the two most famous representatives of German literature's classic era. Not yet entirely as influential as those two cultural icons, the Signal Transduction Society (STS) has nevertheless in the last decade established within the walls of Weimar an annual interdisciplinary Meeting on "Signal Transduction - Receptors, Mediators and Genes", which is well recognized as a most attractive opportunity to exchange results and ideas in the field.The 12th STS Meeting was held from October 28 to 31 and provided a state-of-the-art overview of various areas of signal transduction research in which progress is fast and discussion lively. This report is intended to share with the readers of CCS some highlights of the Meeting Workshops devoted to specific aspects of signal transduction.

  5. Falsification of the ionic channel theory of hair cell transduction.

    Science.gov (United States)

    Rossetto, Michelangelo

    2013-11-01

    The hair cell provides the transduction of mechanical vibrations in the balance and acoustic sense of all vertebrates that swim, walk, or fly. The current theory places hair cell transduction in a mechanically controlled ion channel. Although the theory of a mechanical input modulating the flow of ions through an ion pore has been a useful tool, it is falsified by experimental data in the literature and can be definitively falsified by a proposed experiment.

  6. Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals

    Directory of Open Access Journals (Sweden)

    Rajabalaya R

    2017-02-01

    Full Text Available Rajan Rajabalaya, Muhammad Nuh Musa, Nurolaini Kifli, Sheba R David PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Brunei Darussalam Abstract: Liquid crystal (LC dosage forms, particularly those using lipid-based lyotropic LCs (LLCs, have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations. Keywords: liquid crystal, drug delivery, controlled release, lyotropic, surfactants, drug localization

  7. Providing lipid-based nutrient supplements does not affect developmental milestones among Malawian children.

    Science.gov (United States)

    Mangani, Charles; Cheung, Yin Bun; Maleta, Kenneth; Phuka, John; Thakwalakwa, Chrissie; Dewey, Kathryn; Manary, Mark; Puumalainen, Taneli; Ashorn, Per

    2014-01-01

    To assess whether using lipid-based nutrient supplements (LNS) to complement the diets of infants and young children affected when they achieved selected developmental milestones. In rural Malawi, 840 6-month-old healthy infants were enrolled to a randomised trial. Control participants received no supplements, others were provided with milk-containing LNS, soy-containing LNS or corn-soy blend (CSB) for 12 months. Outcomes were the age at which they achieved key milestone: motor (walking with assistance, standing and walking alone, running), social (drinking from a cup and eating by themselves) and language (saying single comprehensible words and waving goodbye). The mean age at which the subjects walked with assistance was 42.5, 42.3, 42.7 and 43.2 weeks in the control, milk-LNS, soy-LNS and CSB groups, respectively (p = 0.748). There were also no significant differences in the mean age at standing alone (45.0, 44.9, 45.1 and 46.3 weeks), walking alone (54.6, 55.1, 55.3, 56.5 weeks), running (64.6, 63.7, 64.8, 65.9 weeks) or any other social or language milestones (each p > 0.10). The findings do not support a hypothesis that providing tested formulations and doses of micronutrient-fortified LNS or CSB would have an impact on when young children in rural Malawi achieved selected developmental milestones. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  8. Impact of change of matrix crystallinity and polymorphism on ovalbumin release from lipid-based implants.

    Science.gov (United States)

    Duque, Luisa; Körber, Martin; Bodmeier, Roland

    2018-05-30

    The objectives of this study were to prepare lipid-based implants by hot melt extrusion (HME) for the prolonged release of ovalbumin (OVA), and to relate protein release to crystallinity and polymorphic changes of the lipid matrix. Two lipids, glycerol tristearate and hydrogenated palm oil, with different composition and degree of crystallinity were studied. Solid OVA was dispersed within the lipid matrixes, which preserved its stability during extrusion. This was partially attributed to a protective effect of the lipidic matrix. The incorporation of OVA decreased the mechanical strength of the implants prepared with the more crystalline matrix, glycerol tristearate, whereas it remained comparable for the hydrogenated palm oil because of stronger physical and non-covalent interactions between the protein and this lipid. This was also the reason for the faster release of OVA from the glycerol tristearate matrix when compared to the hydrogenated palm oil (8 vs. 28 weeks). Curing induced and increased crystallinity, and changes in the release rate, especially for the more crystalline matrix. In this case, both an increase and a decrease in release, were observed depending on the tempering condition. Curing at higher temperatures induced a melt-mediated crystallization and solid state transformation of the glycerol tristearate matrix and led to rearrangements of the inner structure with the formation of larger pores, which accelerated the release. In contrast, changes in the hydrogenated palm oil under the same curing conditions were less noticeable leading to a more robust formulation, because of less polymorphic changes over time. This study helps to understand the effect of lipid matrix composition and crystallinity degree on the performance of protein-loaded implants, and to establish criteria for the selection of a lipid carrier depending on the release profile desired. Copyright © 2018. Published by Elsevier B.V.

  9. Combination of adenovirus and cross-linked low molecular weight PEI improves efficiency of gene transduction

    International Nuclear Information System (INIS)

    Han Jianfeng; Zhao Dong; Zhong Zhirong; Zhang Zhirong; Gong Tao; Sun Xun

    2010-01-01

    Recombinant adenovirus (Ad)-mediated gene therapy is an exciting novel strategy in cancer treatment. However, poor infection efficiency with coxsackievirus and adenovirus receptor (CAR) down-regulated cancer cell lines is one of the major challenges for its practical and extensive application. As an alternative method of viral gene delivery, a non-viral carrier using cationic materials could compensate for the limitation of adenovirus. In our study, adenovectors were complexed with a new synthetic polymer PEI-DEG-bis-NPC (PDN) based on polyethylenimine (PEI), and then the properties of the vehicle were characterized by measurement of size distribution, zeta potential and transmission electron microscopy (TEM). Enhancement of gene transduction by Ad/PDN complexes was observed in both CAR-overexpressing cell lines (A549) and CAR-lacking cell lines (MDCK, CHO, LLC), as a result of facilitating binding and cell uptake of adenoviral particles by the cationic component. Ad/PDN complexes also promoted the inhibition of tumor growth in vivo and prolonged the survival time of tumor-bearing mice. These data suggest that a combination of viral and non-viral gene delivery methods may offer a new approach to successful cancer gene therapy.

  10. TRP channel proteins and signal transduction.

    Science.gov (United States)

    Minke, Baruch; Cook, Boaz

    2002-04-01

    TRP channel proteins constitute a large and diverse family of proteins that are expressed in many tissues and cell types. This family was designated TRP because of a spontaneously occurring Drosophila mutant lacking TRP that responded to a continuous light with a transient receptor potential (hence TRP). In addition to responses to light, TRPs mediate responses to nerve growth factor, pheromones, olfaction, mechanical, chemical, temperature, pH, osmolarity, vasorelaxation of blood vessels, and metabolic stress. Furthermore, mutations in several members of TRP-related channel proteins are responsible for several diseases, such as several tumors and neurodegenerative disorders. TRP-related channel proteins are found in a variety of organisms, tissues, and cell types, including nonexcitable, smooth muscle, and neuronal cells. The large functional diversity of TRPs is also reflected in their diverse permeability to ions, although, in general, they are classified as nonselective cationic channels. The molecular domains that are conserved in all members of the TRP family constitute parts of the transmembrane domains and in most members also the ankyrin-like repeats at the NH2 terminal of the protein and a "TRP domain" at the COOH terminal, which is a highly conserved 25-amino acid stretch with still unknown function. All of the above features suggest that members of the TRP family are "special assignment" channels, which are recruited to diverse signaling pathways. The channels' roles and characteristics such as gating mechanism, regulation, and permeability are determined by evolution according to the specific functional requirements.

  11. The Precipitation Behavior of Poorly Water-Soluble Drugs with an Emphasis on the Digestion of Lipid Based Formulations

    DEFF Research Database (Denmark)

    Khan, Jamal; Rades, Thomas; Boyd, Ben

    2016-01-01

    digestion and drug solubilisation during gastrointestinal transit have been explored in detail, but the implications of drug precipitation beyond the potential adverse effect on bioavailability have received attention only in recent years. Specifically, these implications are that different solid forms...... the events that lead to drug precipitation during the dispersion and digestion of lipid based formulations, common methods used to inhibit precipitation, as well as conventional and newly emerging characterization techniques for studying the solid state form of the precipitated drug. Moreover, selected case...... studies are discussed where drug precipitation has ensued from the digestion of lipid based formulations, as well as the apparent link between drug ionisability and altered solid forms on precipitation, culminating in a discussion about the importance of the solid form on precipitation with relevance...

  12. Cationic polymers and porous materials

    KAUST Repository

    Han, Yu

    2017-04-27

    According to one or more embodiments, cationic polymers may be produced which include one or more monomers containing cations. Such cationic polymers may be utilized as structure directing agents to form mesoporous zeolites. The mesoporous zeolites may include micropores as well as mesopores, and may have a surface area of greater than 350 m2/g and a pore volume of greater than 0.3 cm3/g. Also described are core/shell zeolites, where at least the shell portion includes a mesoporous zeolite material.

  13. Cationic polymers and porous materials

    KAUST Repository

    Han, Yu; Tian, Qiwei; Dong, Xinglong; Liu, Zhaohui; Basset, Jean-Marie; Saih, Youssef; Sun, Miao; Xu, Wei; Shaikh, Sohel

    2017-01-01

    According to one or more embodiments, cationic polymers may be produced which include one or more monomers containing cations. Such cationic polymers may be utilized as structure directing agents to form mesoporous zeolites. The mesoporous zeolites may include micropores as well as mesopores, and may have a surface area of greater than 350 m2/g and a pore volume of greater than 0.3 cm3/g. Also described are core/shell zeolites, where at least the shell portion includes a mesoporous zeolite material.

  14. The cation-π interaction.

    Science.gov (United States)

    Dougherty, Dennis A

    2013-04-16

    The chemistry community now recognizes the cation-π interaction as a major force for molecular recognition, joining the hydrophobic effect, the hydrogen bond, and the ion pair in determining macromolecular structure and drug-receptor interactions. This Account provides the author's perspective on the intellectual origins and fundamental nature of the cation-π interaction. Early studies on cyclophanes established that water-soluble, cationic molecules would forego aqueous solvation to enter a hydrophobic cavity if that cavity was lined with π systems. Important gas phase studies established the fundamental nature of the cation-π interaction. The strength of the cation-π interaction (Li(+) binds to benzene with 38 kcal/mol of binding energy; NH4(+) with 19 kcal/mol) distinguishes it from the weaker polar-π interactions observed in the benzene dimer or water-benzene complexes. In addition to the substantial intrinsic strength of the cation-π interaction in gas phase studies, the cation-π interaction remains energetically significant in aqueous media and under biological conditions. Many studies have shown that cation-π interactions can enhance binding energies by 2-5 kcal/mol, making them competitive with hydrogen bonds and ion pairs in drug-receptor and protein-protein interactions. As with other noncovalent interactions involving aromatic systems, the cation-π interaction includes a substantial electrostatic component. The six (four) C(δ-)-H(δ+) bond dipoles of a molecule like benzene (ethylene) combine to produce a region of negative electrostatic potential on the face of the π system. Simple electrostatics facilitate a natural attraction of cations to the surface. The trend for (gas phase) binding energies is Li(+) > Na(+) > K(+) > Rb(+): as the ion gets larger the charge is dispersed over a larger sphere and binding interactions weaken, a classical electrostatic effect. On other hand, polarizability does not define these interactions. Cyclohexane is

  15. Synthetic cation-selective nanotube: permeant cations chaperoned by anions.

    Science.gov (United States)

    Hilder, Tamsyn A; Gordon, Dan; Chung, Shin-Ho

    2011-01-28

    The ability to design ion-selective, synthetic nanotubes which mimic biological ion channels may have significant implications for the future treatment of bacteria, diseases, and as ultrasensitive biosensors. We present the design of a synthetic nanotube made from carbon atoms that selectively allows monovalent cations to move across and rejects all anions. The cation-selective nanotube mimics some of the salient properties of biological ion channels. Before practical nanodevices are successfully fabricated it is vital that proof-of-concept computational studies are performed. With this in mind we use molecular and stochastic dynamics simulations to characterize the dynamics of ion permeation across a single-walled (10, 10), 36 Å long, carbon nanotube terminated with carboxylic acid with an effective radius of 5.08 Å. Although cations encounter a high energy barrier of 7 kT, its height is drastically reduced by a chloride ion in the nanotube. The presence of a chloride ion near the pore entrance thus enables a cation to enter the pore and, once in the pore, it is chaperoned by the resident counterion across the narrow pore. The moment the chaperoned cation transits the pore, the counterion moves back to the entrance to ferry another ion. The synthetic nanotube has a high sodium conductance of 124 pS and shows linear current-voltage and current-concentration profiles. The cation-anion selectivity ratio ranges from 8 to 25, depending on the ionic concentrations in the reservoirs.

  16. Effects of lipophilic components on the compatibility of lipid-based formulations with hard gelatin capsules.

    Science.gov (United States)

    Chen, Feng-Jing; Etzler, Frank M; Ubben, Johanna; Birch, Amy; Zhong, Li; Schwabe, Robert; Dudhedia, Mayur S

    2010-01-01

    The present study investigated the effect of lipophilic components on the compatibility of propylene glycol (PG)-containing lipid-based drug delivery system (LBDDS) formulations with hard gelatin capsules. The presence of a lipophilic active pharmaceutical ingredient (API) (log P approximately 6.1) and an additional lipophilic excipient (Capmul MCM) significantly affected the activity of PG in the fills and the equilibrium of PG between capsule shells and fills. These changes in activity and equilibrium of PG were furthermore correlated to the mechanical and thermal properties of the liquid-filled capsules and subsequently linked to the shelf-life of the capsules on stability with respect to capsule deformation. The present study also investigated the mechanism by which lipophilic component(s) might affect the activity of PG in the fill formulations and the equilibrium of PG between capsule shells and fills. The activities of PG in two series of "binary" mixtures with Capmul MCM and with Cremophor EL were measured, respectively. The mixtures of PG containing Capmul MCM were found to be more nearly ideal than those containing Cremophor EL. The observed negative deviation from Rauolt's law indicates that the excess free energies of mixing are less then zero indicating favorable interaction between PG and the other component. It is speculated that enhanced hydrogen bonding opportunities with Cremophor EL are responsible for the decreased excess free energy of mixing. Replacement of Cremophor EL with lipophilic API also reduces the hydrogen bonding opportunities for PG in the mixtures. This hypothesis may further explain the increased activity of PG in the fills and the shifted equilibrium of PG toward the capsule shells. Activity determination utilizing headspace gas chromatography (GC) using short 30 min incubation time seems to be a time-efficient approach for assessing capsule-fill compatibility. Direct measurements of PG migration and other physical properties of

  17. Simultaneous anionic and cationic redox

    Science.gov (United States)

    Jung, Sung-Kyun; Kang, Kisuk

    2017-12-01

    It is challenging to unlock anionic redox activity, accompanied by full utilization of available cationic redox process, to boost capacity of battery cathodes. Now, material design by tuning the metal-oxygen interaction is shown to be a promising solution.

  18. Reciprocity and gyrotropism in magnetic resonance transduction

    International Nuclear Information System (INIS)

    Tropp, James

    2006-01-01

    We give formulas for transduction in magnetic resonance - i.e., the appearance of an emf due to Larmor precession of spins - based upon the modified Lorentz reciprocity principle for gyrotropic (also called 'nonreciprocal') media, i.e., in which a susceptibility tensor is carried to its transpose by reversal of an external static field [cf., R. F. Harrington and A. T. Villeneuve IRE Trans. Microwave Theory and Technique MTT6, 308 (1958)]. Prior applications of reciprocity to magnetic resonance, despite much success, have ignored the gyrotropism which necessarily arises due to nuclear and/or unpaired electronic spins. For detection with linearly polarized fields, oscillating at the Larmor frequency, the emf is written in terms of a volume integral containing a product of two factors which we define as the antenna patterns, i.e. (H 1x ±iH 1y ), where, e.g., for a single transceive antenna, the H's are just the spatially dependent oscillatory magnetic field strengths, per the application of some reference current at the antenna terminals, with the negative sign obtaining for transmission, and the positive for reception. Similar expressions hold for separate transmit and receive antennas; expressions are also given for circular polarization of the fields. We then exhibit a receive-only array antenna of two elements for magnetic resonance imaging of protons, which, due an intensity artifact arising from stray reactive coupling of the elements, produces, despite its own bilateral symmetry, asymmetric proton NMR images of a symmetric cylindrical phantom containing aqueous saline solution [J. Tropp and T. Schirmer, J. Magn. Reson. 151, 146 (2001)]. Modification of this two-port antenna, to function in transmit-receive mode, allows us to demonstrate highly nonreciprocal behavior: that is, to record images (of cylindrical test phantoms containing aqueous saline solution) whose appearance dramatically changes, when the roles of transmission and reception are swapped between

  19. Cation disorder in Ga1212.

    Science.gov (United States)

    Greenwood, K B; Ko, D; Vander Griend, D A; Sarjeant, G M; Milgram, J W; Garrity, E S; DeLoach, D I; Poeppelmeier, K R; Salvador, P A; Mason, T O

    2000-07-24

    Substitution of calcium for strontium in LnSr2-xCaxCu2GaO7 (Ln = La, Pr, Nd, Gd, Ho, Er, Tm, and Yb) materials at ambient pressure and 975 degrees C results in complete substitution of calcium for strontium in the lanthanum and praseodymium systems and partial substitution in the other lanthanide systems. The calcium saturation level depends on the size of the Ln cation, and in all cases, a decrease in the lattice parameters with calcium concentration was observed until a common, lower bound, average A-cation size is reached. Site occupancies from X-ray and neutron diffraction experiments for LnSr2-xCaxCu2GaO7 (x = 0 and x = 2) confirm that the A-cations distribute between the two blocking-layer sites and the active-layer site based on size. A quantitative link between cation distribution and relative site-specific cation enthalpy for calcium, strontium, and lanthanum within the gallate structure is derived. The cation distribution in other similar materials can potentially be modeled.

  20. Magnetic concentration of a retroviral vector using magnetite cationic liposomes.

    Science.gov (United States)

    Ito, Akira; Takahashi, Tetsuya; Kameyama, Yujiro; Kawabe, Yoshinori; Kamihira, Masamichi

    2009-03-01

    For tissue engineering purposes, retroviral vectors represent an efficient method of delivering exogenous genes such as growth factors to injured tissues because gene-transduced cells can produce stable and constant levels of the gene product. However, retroviral vector technology suffers from low yields. In the present study, we used magnetite nanoparticles and magnetic force to concentrate the retroviral vectors to enhance the transduction efficiency and to enable their magnetic manipulation. Magnetite nanoparticles modified with cationic liposomes were added to a solution containing a retroviral vector pseudotyped with vesicular stomatitis virus glycoprotein. The magnetic particles that captured the viral vectors were collected using a magnetic force and seeded into mouse neuroblastoma Neuro2a cells. The viral titer was up to 55 times greater (up to 3 x 10(8) infectious units/mL). Additionally, the magnetically labeled retroviral vectors can be directed to the desired regions for infection by applying magnetic fields, and micro-patterns of gene-transduced cell regions could be created on a cellular monolayer using micro-patterned magnetic concentrators. These results suggest that this technique provides a promising approach to capturing and concentrating viral vectors, thus achieving high transduction efficiency and the ability to deliver genes to a specific injured site by applying a magnetic field.

  1. Theory and modeling of cylindrical thermo-acoustic transduction

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Lihong, E-mail: lhtong@ecjtu.edu.cn [School of Civil Engineering and Architecture, East China Jiaotong University, Nanchang, Jiangxi (China); Lim, C.W. [Department of Architecture and Civil Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR (China); Zhao, Xiushao; Geng, Daxing [School of Civil Engineering and Architecture, East China Jiaotong University, Nanchang, Jiangxi (China)

    2016-06-03

    Models both for solid and thinfilm-solid cylindrical thermo-acoustic transductions are proposed and the corresponding acoustic pressure solutions are obtained. The acoustic pressure for an individual carbon nanotube (CNT) as a function of input power is investigated analytically and it is verified by comparing with the published experimental data. Further numerical analysis on the acoustic pressure response and characteristics for varying input frequency and distance are also examined both for solid and thinfilm-solid cylindrical thermo-acoustic transductions. Through detailed theoretical and numerical studies on the acoustic pressure solution for thinfilm-solid cylindrical transduction, it is concluded that a solid with smaller thermal conductivity favors to improve the acoustic performance. In general, the proposed models are applicable to a variety of cylindrical thermo-acoustic devices performing in different gaseous media. - Highlights: • Theory and modeling both for solid and thinfilm-solid cylindrical thermo-acoustic transductions are proposed. • The modeling is verified by comparing with the published experimental data. • Acoustic response characteristics of cylindrical thermo-acoustic transductions are predicted by the proposed model.

  2. Integrated Electromechanical Transduction Schemes for Polymer MEMS Sensors

    Directory of Open Access Journals (Sweden)

    Damien Thuau

    2018-04-01

    Full Text Available Polymer Micro ElectroMechanical Systems (MEMS have the potential to constitute a powerful alternative to silicon-based MEMS devices for sensing applications. Although the use of commercial photoresists as structural material in polymer MEMS has been widely reported, the integration of functional polymer materials as electromechanical transducers has not yet received the same amount of interest. In this context, we report on the design and fabrication of different electromechanical schemes based on polymeric materials ensuring different transduction functions. Piezoresistive transduction made of carbon nanotube-based nanocomposites with a gauge factor of 200 was embedded within U-shaped polymeric cantilevers operating either in static or dynamic modes. Flexible resonators with integrated piezoelectric transduction were also realized and used as efficient viscosity sensors. Finally, piezoelectric-based organic field effect transistor (OFET electromechanical transduction exhibiting a record sensitivity of over 600 was integrated into polymer cantilevers and used as highly sensitive strain and humidity sensors. Such advances in integrated electromechanical transduction schemes should favor the development of novel all-polymer MEMS devices for flexible and wearable applications in the future.

  3. Liquid-solid extraction of cationic metals by cationic amphiphiles

    International Nuclear Information System (INIS)

    Muller, W.

    2010-01-01

    In the field of selective separation for recycling of spent nuclear fuel, liquid-liquid extraction processes are widely used (PUREX, DIAMEX..) in industrial scale. In order to guarantee a sustainable nuclear energy for the forthcoming generations, alternative reprocessing techniques are under development. One of them bases on the studies from Heckmann et al in the 80's and consists in selectively precipitating actinides from aqueous waste solutions by cationic surfactants (liquid-solid extraction). This technique has some interesting advantages over liquid-liquid extraction techniques, because several steps are omitted like stripping or solvent washing. Moreover, the amount of waste is decreased considerably, since no contaminated organic solvent is produced. In this thesis, we have carried out a physico-chemical study to understand the specific interactions between the metallic cations with the cationic surfactant. First, we have analysed the specific effect of the different counter-ions (Cl - , NO 3 - , C 2 O 4 2- ) and then the effect of alkaline cations on the structural properties of the surfactant aggregation in varying thermodynamical conditions. Finally, different multivalent cations (Cu 2+ , Zn 2+ , UO 2 2+ , Fe 3+ , Nd 3+ , Eu 3+ , Th 4+ ) were considered; we have concluded that depending on the anionic complex of these metals formed in acidic media, we can observe either an adsorption at the micellar interface or not. This adsorption has a large influence of the surfactant aggregation properties and determines the limits of the application in term of ionic strength, temperature and surfactant concentration. (author) [fr

  4. Microenvironment Dependent Photobiomodulation on Function-Specific Signal Transduction Pathways

    Directory of Open Access Journals (Sweden)

    Timon Cheng-Yi Liu

    2014-01-01

    Full Text Available Cellular photobiomodulation on a cellular function has been shown to be homeostatic. Its function-specific pathway mechanism would be further discussed in this paper. The signal transduction pathways maintaining a normal function in its function-specific homeostasis (FSH, resisting the activation of many other irrelative signal transduction pathways, are so sparse that it can be supposed that there may be normal function-specific signal transduction pathways (NSPs. A low level laser irradiation or monochromatic light may promote the activation of partially activated NSP and/or its redundant NSP so that it may induce the second-order phase transition of a function from its dysfunctional one far from its FSH to its normal one in a function-specific microenvironment and may also induce the first-order functional phase transition of the normal function from low level to high level.

  5. Willingness-to-Pay for Lipid-Based Nutrient Supplements in Burkina Faso

    International Nuclear Information System (INIS)

    Guissou, Rosemonde; Adams, Katherine; Xu Yingying; Vosti, Stephen; Hess, Sonja; Ouedraogo, Jean Bosco

    2014-01-01

    Full text: Supplementing young children’s diets with small-quantity lipid-based nutrient supplements (SQ-LNS) is a promising strategy to prevent growth restriction and improve development. It is uncertain how best to scale up the distribution of SQ-LNS and both private and public approaches are being considered. This paper reports on the willingness-to-pay (WTP) by households in rural Burkina Faso for SQ-LNS designed to prevent childhood undernutrition. In a recent randomized controlled nutrition efficacy trial in the Dandé Health District in rural Burkina Faso, 20 g of SQ-LNS per day along with selected health care services have been shown to increase the linear growth and weight gain of children who received the supplement daily from 9-18 months of age. Given the frequency and duration of prescribed consumption of SQ-LNS (one sachet per day, per child) and inter-household differences in poverty, a hybrid distribution system that reaches target consumers through both public channels and retail markets may be recommended; the viability of the latter will hinge on demand. Therefore, policy makers will need to consider household-level demand for SQ-LNS and the factors that influence demand to guide decisions regarding the cost burden borne by recipients versus public sector programs. Using a contingent valuation approach, we solicited, at baseline and six months later, the hypothetical WTP for a daily dose of 20 g of SQ-LNS and a traditional substitute, herbal teas, from a subsample (N = 319) of households participating in the efficacy trial. WTP for SQ-LNS is positive for almost all households, but WTP for SQ-LNS is, on average, lower than WTP for herbal teas. At baseline, average WTP for a day’s supply of SQ-LNS is $0.22 (4th quarter 2011 USD), while average WTP for herbal teas is $0.28. Approximately six months later, average WTP for LNS and for herbal teas, respectively, are $0.21 and $0.25. These results suggest that while households do value SQ

  6. Physical aspects of sensory transduction on seeing, hearing and smelling.

    Science.gov (United States)

    Yoshioka, Tohru; Sakakibara, Manabu

    2013-01-01

    What is the general principle of sensory transduction? Sensory transduction is defined as energy transformation from the external world to the internal world. The energy of the external world, such as thermal energy (heat), electro-magnetic energy (light), mechanical energy (sound) and the energy from molecules (chemicals), is converted into electrochemical events in the animal nervous system. The following five classes of special sense receptors are utilized for energy conversion: vision (photo); audition (sound); taste and smell (chemo); and tactile (mechano). There are also other special sense receptors, including thermo and noxious receptors. The focus of this study is on photoreceptors, sound-receptors and odorant-receptors because the transduction mechanisms of these receptors are explained biochemically and understood by a common physical principle; these biochemical models are well known in neuroscience. The following notable problems are inherent in these biochemical models: the cGMP ionophore model of the vertebrate photoreceptor cannot explain the fast photo-response (∼msec); the tip links connection model of stereocilia in the basilar membrane for opening the K(+) channel on the tip of a hair has difficulty explaining the high frequency vibration of hair cells without a damping of the oscillation, and the odorant shape-specific receptor model for olfactory transduction has difficulty in discriminating the minute differences among similar fragrant smells of essential oils with different molecular shapes. These difficulties might arise from a lack of the physical sense when the transduction models were proposed. This article will reconsider these problems and propose rational models for visual, olfactory and auditory transduction.

  7. Signal transduction pathways involved in mechanotransduction in bone cells

    International Nuclear Information System (INIS)

    Liedert, Astrid; Kaspar, Daniela; Blakytny, Robert; Claes, Lutz; Ignatius, Anita

    2006-01-01

    Several in vivo and in vitro studies with different loading regimens showed that mechanical stimuli have an influence on proliferation and differentiation of bone cells. Prerequisite for this influence is the transduction of mechanical signals into the cell, a phenomenon that is termed mechanotransduction, which is essential for the maintenance of skeletal homeostasis in adults. Mechanoreceptors, such as the integrins, cadherins, and stretch-activated Ca 2+ channels, together with various signal transduction pathways, are involved in the mechanotransduction process that ultimately regulates gene expression in the nucleus. Mechanotransduction itself is considered to be regulated by hormones, the extracellular matrix of the osteoblastic cells and the mode of the mechanical stimulus

  8. In vivo evaluation of lipid-based formulations for oral delivery of apomorphine and its diester prodrugs

    DEFF Research Database (Denmark)

    Borkar, Nrupa Nitin; Holm, René; Yang, Mingshi

    2016-01-01

    .05) than after DLA-w/o administration, indicating that triglycerides and surfactants improved the oral absorption of DLA. Similarly, Cmax and AUC after dosing apomorphine-o/w were significantly higher (p≤0.05) than that of aqueous suspension. This suggested that lipids and lipolysis products possibly aided......In the present study, the differences in oral absorption of apomorphine and its diester prodrugs and the effect of lipid-based formulations on the absorption of apomorphine or its prodrugs were investigated. Apomorphine, dilauroyl apomorphine (DLA) and dipalmitoyl apomorphine (DPA) were orally...

  9. Coating with spermine-pullulan polymer enhances adenoviral transduction of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Wan L

    2016-12-01

    Full Text Available Li Wan,1,* Xinglei Yao,1–3,* Francesco Faiola,3 Bojun Liu,4 Tianyuan Zhang,2 Yasuhiko Tabata,5 Hiroyuki Mizuguchi,6 Shinsaku Nakagawa,7 Jian-Qing Gao,2 Robert Chunhua Zhao1 1Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing, 2Institute of Pharmaceutics, Zhejiang University, Hangzhou, 3State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 4YouAn Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, 6Department of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 7Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan *These authors contributed equally to this work Abstract: Mesenchymal stem cells (MSCs are adult stem cells with multilineage potential, which makes them attractive tools for regenerative medicine applications. Efficient gene transfer into MSCs is essential not only for basic research in developmental biology but also for therapeutic applications involving gene-modification in regenerative medicine. Adenovirus vectors (Advs can efficiently and transiently introduce an exogenous gene into many cell types via their primary receptors, the coxsackievirus and adenovirus receptors, but not into MSCs, which are deficient in coxsackievirus and adenovirus receptors expression. To overcome this problem, we developed an Adv coated with a spermine-pullulan (SP cationic polymer and investigated its physicochemical properties and internalization mechanisms. We demonstrated that the SP

  10. Multi-signalling cation sensing behaviour of a bis(pyridin-2-yl methyl)aniline based hetarylazo dye

    International Nuclear Information System (INIS)

    Kaur, Paramjit; Sareen, Divya; Kaur, Mandeep; Singh, Kamaljit

    2013-01-01

    Graphical abstract: The chromogenic and electrochemical behaviour of bis(pyridine-2-yl methyl)aniline based hetarylazo dye gets perturbed in the presence of cations, most effective being Cu 2+ . The conversion of ICT to ICT/MLCT is witnessed by TD-DFT calculations. -- Highlights: •Cation sensing of hetarylazo dye based upon visual, absorption and electrochemical changes is described. •Sensing mechanism is based upon perturbation in intramolecular charge-transfer upon interaction with cations. •Sensing protocol is supported by 1 H NMR studies as well as theoretical calculations. •Hetarylazo dye acts as a multichannel sensor. •Response of the dye towards various cations has also been explored in acidic pH window. -- Abstract: We investigated the cation sensing behaviour of a bis(pyridin-2-yl methyl)aniline appended hetarylazo dye via chromogenic and electrochemical transduction channels. The binding pocket constituting both the pyridyl as well as aniline nitrogen atoms acts as recognition site for the cations and consequent perturbation in the intramolecular charge-transfer prevailing in the dye results in the chromogenic response manifested in the form of hypsochromic shift in the intramolecular charge-transfer band and the attendant naked-eye color changes. The dye exhibits significant changes in its electrochemical behaviour in the presence of cations. The experimental results are also rationalized by time-dependent density functional theory (TD-DFT) calculations

  11. Mitogen-activated protein kinase and abscisic acid signal transduction

    NARCIS (Netherlands)

    Heimovaara-Dijkstra, S.; Testerink, C.; Wang, M.

    1998-01-01

    The phytohormone abscisic acid (ABA) is a classical plant hormone, responsible for regulation of abscission, diverse aspects of plant and seed development, stress responses and germination. It was found that ABA signal transduction in plants can involve the activity of type 2C-phosphatases (PP2C),

  12. Molecular methods for the study of signal transduction in plants

    KAUST Repository

    Irving, Helen R.; Gehring, Christoph A

    2013-01-01

    as well as at the systems level where transcriptomics and particularly phosphoproteomics afford a window into complex biological responses. Here we review the role of the cyclic nucleotides cAMP and cGMP in plant signal transduction as well

  13. Cell biology symposium: Membrane trafficking and signal transduction

    Science.gov (United States)

    In general, membrane trafficking is a broad group of processes where proteins and other large molecules are distributed throughout the cell as well as adjacent extracellular spaces. Whereas signal transduction is a process where signals are transmitted through a series of chemical or molecular event...

  14. Olfactory transduction pathways in the Senegalese sole Solea senegalensis.

    Science.gov (United States)

    Velez, Z; Hubbard, P C; Barata, E N; Canário, A V M

    2013-09-01

    This study tested whether differences in sensitivity between the upper and lower olfactory epithelia of Solea senegalensis are associated with different odorant receptors and transduction pathways, using the electro-olfactogram. Receptor mechanisms were assessed by cross-adaptation with amino acids (L-cysteine, L-phenylalanine and 1-methyl-L-tryptophan) and bile acids (taurocholic acid and cholic acid). This suggested that relatively specific receptors exist for 1-methyl-L-tryptophan and L-phenylalanine (food-related odorants) in the lower epithelium, and for taurocholic acid (conspecific-derived odorant) in the upper. Inhibition by U73122 [a phospholipase C (PLC) inhibitor] suggested that olfactory responses to amino acids were mediated mostly, but not entirely, by PLC-mediated transduction (IC50 ; 15-55 nM), whereas bile acid responses were mediated by both PLC and adenylate cyclase-cyclic adenosine monophosphate (AC-cAMP) (using SQ-22536; an AC inhibitor). Simultaneous application of both drugs rarely inhibited responses completely, suggesting possible involvement of non-PLC and non-AC mediated mechanisms. For aromatic amino acids and bile acids, there were differences in the contribution of each transduction pathway (PLC, AC and non-PLC and non-AC) between the two epithelia. These results suggest that differences in sensitivity of the two epithelia are associated with differences in odorant receptors and transduction mechanisms. © 2013 The Fisheries Society of the British Isles.

  15. Protein phosphorylation and its role in archaeal signal transduction

    Science.gov (United States)

    Esser, Dominik; Hoffmann, Lena; Pham, Trong Khoa; Bräsen, Christopher; Qiu, Wen; Wright, Phillip C.; Albers, Sonja-Verena; Siebers, Bettina

    2016-01-01

    Reversible protein phosphorylation is the main mechanism of signal transduction that enables cells to rapidly respond to environmental changes by controlling the functional properties of proteins in response to external stimuli. However, whereas signal transduction is well studied in Eukaryotes and Bacteria, the knowledge in Archaea is still rather scarce. Archaea are special with regard to protein phosphorylation, due to the fact that the two best studied phyla, the Euryarchaeota and Crenarchaeaota, seem to exhibit fundamental differences in regulatory systems. Euryarchaeota (e.g. halophiles, methanogens, thermophiles), like Bacteria and Eukaryotes, rely on bacterial-type two-component signal transduction systems (phosphorylation on His and Asp), as well as on the protein phosphorylation on Ser, Thr and Tyr by Hanks-type protein kinases. Instead, Crenarchaeota (e.g. acidophiles and (hyper)thermophiles) only depend on Hanks-type protein phosphorylation. In this review, the current knowledge of reversible protein phosphorylation in Archaea is presented. It combines results from identified phosphoproteins, biochemical characterization of protein kinases and protein phosphatases as well as target enzymes and first insights into archaeal signal transduction by biochemical, genetic and polyomic studies. PMID:27476079

  16. Expression of SMAD signal transduction molecules in the pancreas

    DEFF Research Database (Denmark)

    Brorson, Michael; Hougaard, D.; Nielsen, Jens Høiriis

    2001-01-01

    Members of the TGF-beta superfamily of cytokines have been implicated in pancreatic cancer, pancreatitis and in regulation and differentiation of pancreatic endocrine and exocrine cells. Different TGF-beta members signal through phosphorylation of different signal transduction proteins, which eve...

  17. The sugarcane signal transduction (SUCAST catalogue: prospecting signal transduction in sugarcane

    Directory of Open Access Journals (Sweden)

    Glaucia Mendes Souza

    2001-12-01

    Full Text Available EST sequencing has enabled the discovery of many new genes in a vast array of organisms, and the utility of this approach to the scientific community is greatly increased by the establishment of fully annotated databases. The present study aimed to identify sugarcane ESTs sequenced in the sugarcane expressed sequence tag (SUCEST project (http://sucest.lad.ic.unicamp.br that corresponded to signal transduction components. We also produced a sugarcane signal transduction (SUCAST catalogue (http://sucest.lad.ic.unicamp.br/private/mining-reports/QG/QG-mining.htm that covered the main categories and pathways. Expressed sequence tags (ESTs encoding enzymes for hormone (gibberellins, ethylene, auxins, abscisic acid and jasmonic acid biosynthetic pathways were found and tissue specificity was inferred from their relative frequency of occurrence in the different libraries. Whenever possible, transducers of hormones and plant peptide signaling were catalogued to the respective pathway. Over 100 receptors were found in sugarcane, which contains a large family of Ser/Thr kinase receptors and also photoreceptors, histidine kinase receptors and their response regulators. G-protein and small GTPases were analyzed and compared to known members of these families found in mammalian and plant systems. Major kinase and phosphatase pathways were mapped, with special attention being given to the MAP kinase and the inositol pathway, both of which are well known in plants.O sequenciamento de ESTs (etiquetas de sequencias transcritas tem possibilitado a descoberta de muitos novos genes em uma ampla variedade de organismos. Um aumento do aproveitamento desta informação pela comunidade científica tem sido possível graças ao desenvolvimento de base de dados contendo seqüências completamente anotadas. O trabalho aqui relatado teve como objetivo a identificação de ESTs de cana de açúcar seqüenciadas através do projeto SUCEST (http://sucest.lad.ic. unicamp.br que

  18. The Precipitation Behavior of Poorly Water-Soluble Drugs with an Emphasis on the Digestion of Lipid Based Formulations.

    Science.gov (United States)

    Khan, Jamal; Rades, Thomas; Boyd, Ben

    2016-03-01

    An increasing number of newly discovered drugs are poorly water-soluble and the use of natural and synthetic lipids to improve the oral bioavailability of these drugs by utilizing the digestion pathway in-vivo has proved an effective formulation strategy. The mechanisms responsible for lipid digestion and drug solubilisation during gastrointestinal transit have been explored in detail, but the implications of drug precipitation beyond the potential adverse effect on bioavailability have received attention only in recent years. Specifically, these implications are that different solid forms of drug on precipitation may affect the total amount of drug absorbed in-vivo through their different physico-chemical properties, and the possibility that the dynamic environment of the small intestine may afford re-dissolution of precipitated drug if present in a high-energy form. This review describes the events that lead to drug precipitation during the dispersion and digestion of lipid based formulations, common methods used to inhibit precipitation, as well as conventional and newly emerging characterization techniques for studying the solid state form of the precipitated drug. Moreover, selected case studies are discussed where drug precipitation has ensued from the digestion of lipid based formulations, as well as the apparent link between drug ionisability and altered solid forms on precipitation, culminating in a discussion about the importance of the solid form on precipitation with relevance to the total drug absorbed.

  19. Protective Effect of a Lipid-Based Preparation from Mycobacterium smegmatis in a Murine Model of Progressive Pulmonary Tuberculosis

    Directory of Open Access Journals (Sweden)

    Maria de los Angeles García

    2014-01-01

    Full Text Available A more effective vaccine against tuberculosis (TB is urgently needed. Based on its high genetic homology with Mycobacterium tuberculosis (Mtb, the nonpathogenic mycobacteria, Mycobacterium smegmatis (Ms, could be an attractive source of potential antigens to be included in such a vaccine. We evaluated the capability of lipid-based preparations obtained from Ms to provide a protective response in Balb/c mice after challenge with Mtb H37Rv strain. The intratracheal model of progressive pulmonary TB was used to assess the level of protection in terms of bacterial load as well as the pathological changes in the lungs of immunized Balb/c mice following challenge with Mtb. Mice immunized with the lipid-based preparation from Ms either adjuvanted with Alum (LMs-AL or nonadjuvanted (LMs showed significant reductions in bacterial load (P<0.01 compared to the negative control group (animals immunized with phosphate buffered saline (PBS. Both lipid formulations showed the same level of protection as Bacille Calmette and Guerin (BCG. Regarding the pathologic changes in the lungs, mice immunized with both lipid formulations showed less pneumonic area when compared with the PBS group (P<0.01 and showed similar results compared with the BCG group. These findings suggest the potential of LMs as a promising vaccine candidate against TB.

  20. [Transduction peptides, the useful face of a new signaling mechanism].

    Science.gov (United States)

    Joliot, Alain; Prochiantz, Alain

    2005-03-01

    Transduction peptides that cross the plasma membrane of live cells are commonly used for the in vitro and in vivo targeting of hydrophilic drugs into the cell interior. Although this family of peptides has recently increased and will probably continue to do so, the two mainly used peptides are derived from transcription factors. Indeed, TAT is a 12 amino acid long arginine-rich peptide present in the HIV transcription factor, and penetratin - or its variants - corresponds to 16 amino acids that define the highly conserved third helix of the DNA-binding domain (homeodomain) of homeoprotein transcription factors. In this review, we shall recall the different steps that have led to the discovery of transduction peptides and present the most likely hypotheses concerning the mechanisms involved in their internalization. At the risk of being incomplete or, even, biased, we shall concentrate on penetratins and TAT. The reason is that these peptides have been studied for over ten years leading to the edification of robust knowledge regarding their properties. This attitude will not preclude comparisons with other peptides, if necessary. Our goal is to describe the mode of action of these transduction peptides, their range of activity in term of cell types that accept them and cargoes that they can transport, and, also, some of the limitations that one can encounter in their use. Finally, based on the idea that peptide transduction is the technological face of a physiological property of some transcription factors, we shall discuss the putative physiological function of homeoprotein transduction, and, as a consequence, the possibility to use these factors as therapeutic proteins.

  1. New double-cation borohydrides

    Energy Technology Data Exchange (ETDEWEB)

    Lindemann, Inge; Domenech Ferrer, Roger; Schultz, Ludwig; Gutfleisch, Oliver [IFW Dresden, Institute for Metallic Materials, P.O. Box 270016, 01171 Dresden (Germany); Filinchuk, Yaroslav [Swiss-Norwegian Beam Lines at ESRF, BP-220, 38043 Grenoble (France); Hagemann, Hans; Cerny, Radovan [Department of Physical Chemistry and Crystallography, University of Geneva, 1211 Geneva (Switzerland)

    2011-07-01

    Complex hydrides are under consideration for on-board hydrogen storage due to their high hydrogen density. However, up to now conventional borohydrides are either too stable or unstable for applications as in PEM fuel cells (60-120 C). Recently, double-cation borohydride systems have attracted great interest. The desorption temperature of the borohydrides decreases with increasing electronegativity of the cation. Consequently, it is possible to tailor a feasible on-board hydrogen storage material by the combination of appropriate cations. The stability was found to be intermediate between the single-cation borohydride systems. Two combinations were sucessfully synthesised by metathesis reaction via high energy ball milling. Al-Li-borohydride shows desorption at about 70 C combined with a very high hydrogen density (17.2 wt.%) and the Na-Al-borohydride (14.2 wt.%) decomposes around 90 C. Both desorption temperatures are in the target range for applications. The decomposition pathways were observed by in-situ-Raman spectroscopy, DSC (Differential Scanning Calorimetry), TG (Thermogravimetry) and thermal desorption measurements.

  2. Liquid-solid extraction of metallic cations by cationic amphiphiles

    International Nuclear Information System (INIS)

    Mueller, Wolfram; Sievers, Torsten K.; Zemb, Thomas; Diat, Olivier; Sievers, Torsten K.; Dejugnat, Christophe

    2012-01-01

    In the field of selective metal ion separation, liquid-liquid extraction is usually conducted through an emulsion mixing of hydrophobic complexants dispersed in an organic phase and acidic water containing the ionic species. Recently, it has been shown that amphiphilic complexants could influence strongly extraction efficiency by enhancing the interfacial interaction between the metal ion in the aqueous and the complexant in the organic phase. Moreover, these amphiphiles can also substitute the organic phase if an appropriate aliphatic chain is chosen. The dispersion of such amphiphilic complexants in an aqueous solution of salt mixtures is not only attractive for studying specific interactions but also to better the understanding of complex formation in aqueous solution of multivalent metal ions, such as lanthanides and actinides. This understanding is of potential interest for a broad range of industries including purification of rare earth metals and pollute treatment e.g. of fission byproducts. This principle can also be applied to liquid-solid extraction, where the final state of the separation is a solid phase containing the selectively extracted ions. Indeed, a novel solid-liquid extraction method exploits the selective precipitation of metal ions from an aqueous salt mixture using a cationic surfactant, below its Krafft point (temperature below which the long aliphatic chains of surfactant crystallize). This technique has been proven to be highly efficient for the separation of actinides and heavy metal using long chain ammonium or pyridinium amphiphiles. The most important point in this process is the recognition of cationic metal ions by cationic surfactants. By computing the free energy of the polar head group per micelle as a function of the different counter-anions, we have demonstrated for the first time that different interactions exist between the micellar surface and the ions. These interactions depend on the nature of the cation but also on

  3. Characterization of sur-2, a Novel Ras-Mediated Signal Transduction Component in C. elegans

    National Research Council Canada - National Science Library

    DesJardins, Edward

    1998-01-01

    ... (oncogenes). A subset of proto-oncogenes comprise the RAS signal transduction pathway. Vulval development in the nematode worm Caenorhabditis elegans is controlled by a RAS signal transduction pathway...

  4. Characterization of sur-2, a Novel Ras-Mediated Signal Transduction Component in C. elegans

    National Research Council Canada - National Science Library

    DesJardins, Edward

    1999-01-01

    ... (oncogenes). A subset of proto-oncogenes comprise the RAS signal transduction pathway. Vulval development in the nematode worm Caenorhabditis elegans is controlled by a RAS signal transduction pathway. C...

  5. Tripodal receptors for cation and anion sensors

    NARCIS (Netherlands)

    Kuswandi, Bambang; Nuriman, [Unknown; Verboom, Willem; Reinhoudt, David

    2006-01-01

    This review discusses different types of artificial tripodal receptors for the selectiverecognition and sensing of cations and anions. Examples on the relationship between structure andselectivity towards cations and anions are described. Furthermore, their applications as potentiometricion sensing

  6. Heavy metal cations permeate the TRPV6 epithelial cation channel.

    Science.gov (United States)

    Kovacs, Gergely; Danko, Tamas; Bergeron, Marc J; Balazs, Bernadett; Suzuki, Yoshiro; Zsembery, Akos; Hediger, Matthias A

    2011-01-01

    TRPV6 belongs to the vanilloid family of the transient receptor potential channel (TRP) superfamily. This calcium-selective channel is highly expressed in the duodenum and the placenta, being responsible for calcium absorption in the body and fetus. Previous observations have suggested that TRPV6 is not only permeable to calcium but also to other divalent cations in epithelial tissues. In this study, we tested whether TRPV6 is indeed also permeable to cations such as zinc and cadmium. We found that the basal intracellular calcium concentration was higher in HEK293 cells transfected with hTRPV6 than in non-transfected cells, and that this difference almost disappeared in nominally calcium-free solution. Live cell imaging experiments with Fura-2 and NewPort Green DCF showed that overexpression of human TRPV6 increased the permeability for Ca(2+), Ba(2+), Sr(2+), Mn(2+), Zn(2+), Cd(2+), and interestingly also for La(3+) and Gd(3+). These results were confirmed using the patch clamp technique. (45)Ca uptake experiments showed that cadmium, lanthanum and gadolinium were also highly efficient inhibitors of TRPV6-mediated calcium influx at higher micromolar concentrations. Our results suggest that TRPV6 is not only involved in calcium transport but also in the transport of other divalent cations, including heavy metal ions, which may have toxicological implications. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Transforming lipid-based oral drug delivery systems into solid dosage forms: an overview of solid carriers, physicochemical properties, and biopharmaceutical performance.

    Science.gov (United States)

    Tan, Angel; Rao, Shasha; Prestidge, Clive A

    2013-12-01

    The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.

  8. Cationic electrodepositable coating composition comprising lignin

    Science.gov (United States)

    Fenn, David; Bowman, Mark P; Zawacky, Steven R; Van Buskirk, Ellor J; Kamarchik, Peter

    2013-07-30

    A cationic electrodepositable coating composition is disclosed. The present invention in directed to a cationic electrodepositable coating composition comprising a lignin-containing cationic salt resin, that comprises (A) the reaction product of: lignin, an amine, and a carbonyl compound; (B) the reaction product of lignin, epichlorohydrin, and an amine; or (C) combinations thereof.

  9. Molecular methods for the study of signal transduction in plants

    KAUST Repository

    Irving, Helen R.

    2013-09-03

    Novel and improved analytical methods have led to a rapid increase in our understanding of the molecular mechanism underlying plant signal transduction. Progress has been made both at the level of single-component analysis and in vivo imaging as well as at the systems level where transcriptomics and particularly phosphoproteomics afford a window into complex biological responses. Here we review the role of the cyclic nucleotides cAMP and cGMP in plant signal transduction as well as the discovery and biochemical and biological characterization of an increasing number of complex multi-domain nucleotide cyclases that catalyze the synthesis of cAMP and cGMP from ATP and GTP, respectively. © Springer Science+Business Media New York 2013.

  10. Asymmetric cation-binding catalysis

    DEFF Research Database (Denmark)

    Oliveira, Maria Teresa; Lee, Jiwoong

    2017-01-01

    The employment of metal salts is quite limited in asymmetric catalysis, although it would provide an additional arsenal of safe and inexpensive reagents to create molecular functions with high optical purity. Cation chelation by polyethers increases the salts' solubility in conventional organic...... solvents, thus increasing their applicability in synthesis. The expansion of this concept to chiral polyethers led to the emergence of asymmetric cation-binding catalysis, where chiral counter anions are generated from metal salts, particularly using BINOL-based polyethers. Alkali metal salts, namely KF...... highly enantioselective silylation reactions in polyether-generated chiral environments, and leading to a record-high turnover in asymmetric organocatalysis. This can lead to further applications by the asymmetric use of other inorganic salts in various organic transformations....

  11. Tuning piezoresistive transduction in nanomechanical resonators by geometrical asymmetries

    Energy Technology Data Exchange (ETDEWEB)

    Llobet, J.; Sansa, M.; Lorenzoni, M.; Pérez-Murano, F., E-mail: francesc.perez@csic.es [Institut de Microelectrònica de Barcelona (IMB-CNM CSIC), Campus UAB, 08193 Bellaterra (Spain); Borrisé, X. [Institut Català de Nanociència i Nanotecnologia (ICN2), Campus UAB, 08193 Bellaterra Spain (Spain); San Paulo, A. [Instituto de Microelectrónica de Madrid (IMM-CSIC), 28760 Tres Cantos, Madrid (Spain)

    2015-08-17

    The effect of geometrical asymmetries on the piezoresistive transduction in suspended double clamped beam nanomechanical resonators is investigated. Tapered silicon nano-beams, fabricated using a fast and flexible prototyping method, are employed to determine how the asymmetry affects the transduced piezoresistive signal for different mechanical resonant modes. This effect is attributed to the modulation of the strain in pre-strained double clamped beams, and it is confirmed by means of finite element simulations.

  12. Efficiency of Energy Transduction in a Molecular Chemical Engine

    OpenAIRE

    Sasaki, Kazuo; Kanada, Ryo; Amari, Satoshi

    2006-01-01

    A simple model of the two-state ratchet type is proposed for molecular chemical engines that convert chemical free energy into mechanical work and vice versa. The engine works by catalyzing a chemical reaction and turning a rotor. Analytical expressions are obtained for the dependences of rotation and reaction rates on the concentrations of reactant and product molecules, from which the performance of the engine is analyzed. In particular, the efficiency of energy transduction is discussed in...

  13. Dynamic Testing of Signal Transduction Deregulation During Breast Cancer Initiation

    Science.gov (United States)

    2012-07-01

    Std. Z39.18 Victoria Seewaldt, M.D. Dynamic Testing of Signal Transduction Deregulation During Breast Cancer Initiation Duke University Durham...attomole- zeptomole range. Internal dilution curves insure a high-dynamic calibration range. DU -26 8L DU -26 6L DU -29 5R DU -22 9.2 L DU...3: Nanobiosensor technology is translated to test for pathway deregulation in RPFNA cytology obtained from 10 high-risk women with cytological

  14. Lipid-based nutrient supplements do not affect efavirenz but lower plasma nevirapine concentrations in Ethiopian adult HIV patients

    DEFF Research Database (Denmark)

    Abdissa, A; Olsen, Mette Frahm; Yilma, D

    2015-01-01

    OBJECTIVES: Lipid-based nutrient supplements (LNSs) are increasingly used in HIV programmes in resource-limited settings. However, the possible effects of LNSs on the plasma concentrations of antiretroviral drugs have not been assessed. Here, we aimed to assess the effects of LNSs on plasma...... efavirenz and nevirapine trough concentrations in Ethiopian adult HIV-infected patients. METHODS: The effects of LNSs were studied in adults initiating antiretroviral therapy (ART) in a randomized trial. Patients with body mass index (BMI) > 17 kg/m(2) (n = 282) received daily supplementation of an LNS.......9; -0.9 μg/mL; P = 0.01), respectively, compared with the group not receiving supplements. There were no differences between groups with respect to efavirenz plasma concentrations. The CYP2B6 516 G>T polymorphism was associated with a 5 μg/mL higher plasma efavirenz concentration compared with the wild...

  15. Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading

    Science.gov (United States)

    Streck, Letícia; Sarmento, Víctor H. V.; Machado, Paula R. L.; Farias, Kleber J. S.; Fernandes-Pedrosa, Matheus F.; da Silva-Júnior, Arnóbio Antônio

    2016-01-01

    Previous studies reported low benznidazole (BNZ) loading in conventional emulsions due to the weak interaction of the drug with the most common oils used to produce foods or pharmaceuticals. In this study, we focused on how the type of surfactant, surfactant-to-oil ratio w/w (SOR) and oil-to-water ratio w/w (OWR) change the phase behavior of different lipid-based drug delivery systems (LBDDS) produced by emulsion phase inversion. The surfactant mixture composed of soy phosphatidylcholine and sodium oleate (1:7, w/w, hydrophilic lipophilic balance = 16) stabilized medium chain triglyceride in water. Ten formulations with the clear aspect or less turbid dispersions (five with the SOR ranging from 0.5 to 2.5 and five with the OWR from 0.06 to 0.4) were selected from the phase behavior diagram to assess structural features and drug-loading capacity. The rise in the SOR induced the formation of distinct lipid-based drug delivery systems (nanoemulsions and liquid crystal lamellar type) that were identified using rheological measurements and cross-polarized light microscopy images. Clear dispersions of small and narrow droplet-sized liquid-like nanoemulsions, Newtonian flow-type, were produced at SOR from 0.5 to 1.5 and OWR from 0.12 to 0.4, while clear liquid or gel-like liquid crystals were produced at SOR from 1.5 to 2.5. The BNZ loading was improved according to the composition and type of LBDDS produced, suggesting possible drug location among surfactant layers. The cell viability assays proved the biocompatibility for all of the prepared nanoemulsions at SOR less than 1.5 and liquid crystals at SOR less than 2.5, demonstrating their promising features for the oral or parenteral colloidal delivery systems containing benznidazole for Chagas disease treatment. PMID:27376278

  16. Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading

    Directory of Open Access Journals (Sweden)

    Letícia Streck

    2016-06-01

    Full Text Available Previous studies reported low benznidazole (BNZ loading in conventional emulsions due to the weak interaction of the drug with the most common oils used to produce foods or pharmaceuticals. In this study, we focused on how the type of surfactant, surfactant-to-oil ratio w/w (SOR and oil-to-water ratio w/w (OWR change the phase behavior of different lipid-based drug delivery systems (LBDDS produced by emulsion phase inversion. The surfactant mixture composed of soy phosphatidylcholine and sodium oleate (1:7, w/w, hydrophilic lipophilic balance = 16 stabilized medium chain triglyceride in water. Ten formulations with the clear aspect or less turbid dispersions (five with the SOR ranging from 0.5 to 2.5 and five with the OWR from 0.06 to 0.4 were selected from the phase behavior diagram to assess structural features and drug-loading capacity. The rise in the SOR induced the formation of distinct lipid-based drug delivery systems (nanoemulsions and liquid crystal lamellar type that were identified using rheological measurements and cross-polarized light microscopy images. Clear dispersions of small and narrow droplet-sized liquid-like nanoemulsions, Newtonian flow-type, were produced at SOR from 0.5 to 1.5 and OWR from 0.12 to 0.4, while clear liquid or gel-like liquid crystals were produced at SOR from 1.5 to 2.5. The BNZ loading was improved according to the composition and type of LBDDS produced, suggesting possible drug location among surfactant layers. The cell viability assays proved the biocompatibility for all of the prepared nanoemulsions at SOR less than 1.5 and liquid crystals at SOR less than 2.5, demonstrating their promising features for the oral or parenteral colloidal delivery systems containing benznidazole for Chagas disease treatment.

  17. State–time spectrum of signal transduction logic models

    International Nuclear Information System (INIS)

    MacNamara, Aidan; Terfve, Camille; Henriques, David; Bernabé, Beatriz Peñalver; Saez-Rodriguez, Julio

    2012-01-01

    Despite the current wealth of high-throughput data, our understanding of signal transduction is still incomplete. Mathematical modeling can be a tool to gain an insight into such processes. Detailed biochemical modeling provides deep understanding, but does not scale well above relatively a few proteins. In contrast, logic modeling can be used where the biochemical knowledge of the system is sparse and, because it is parameter free (or, at most, uses relatively a few parameters), it scales well to large networks that can be derived by manual curation or retrieved from public databases. Here, we present an overview of logic modeling formalisms in the context of training logic models to data, and specifically the different approaches to modeling qualitative to quantitative data (state) and dynamics (time) of signal transduction. We use a toy model of signal transduction to illustrate how different logic formalisms (Boolean, fuzzy logic and differential equations) treat state and time. Different formalisms allow for different features of the data to be captured, at the cost of extra requirements in terms of computational power and data quality and quantity. Through this demonstration, the assumptions behind each formalism are discussed, as well as their advantages and disadvantages and possible future developments. (paper)

  18. Signal Transduction Pathways of TNAP: Molecular Network Analyses.

    Science.gov (United States)

    Négyessy, László; Györffy, Balázs; Hanics, János; Bányai, Mihály; Fonta, Caroline; Bazsó, Fülöp

    2015-01-01

    Despite the growing body of evidence pointing on the involvement of tissue non-specific alkaline phosphatase (TNAP) in brain function and diseases like epilepsy and Alzheimer's disease, our understanding about the role of TNAP in the regulation of neurotransmission is severely limited. The aim of our study was to integrate the fragmented knowledge into a comprehensive view regarding neuronal functions of TNAP using objective tools. As a model we used the signal transduction molecular network of a pyramidal neuron after complementing with TNAP related data and performed the analysis using graph theoretic tools. The analyses show that TNAP is in the crossroad of numerous pathways and therefore is one of the key players of the neuronal signal transduction network. Through many of its connections, most notably with molecules of the purinergic system, TNAP serves as a controller by funnelling signal flow towards a subset of molecules. TNAP also appears as the source of signal to be spread via interactions with molecules involved among others in neurodegeneration. Cluster analyses identified TNAP as part of the second messenger signalling cascade. However, TNAP also forms connections with other functional groups involved in neuronal signal transduction. The results indicate the distinct ways of involvement of TNAP in multiple neuronal functions and diseases.

  19. Exploring Transduction Mechanisms of Protein Transduction Domains (PTDs in Living Cells Utilizing Single-Quantum Dot Tracking (SQT Technology

    Directory of Open Access Journals (Sweden)

    Yasuhiro Suzuki

    2012-01-01

    Full Text Available Specific protein domains known as protein transduction domains (PTDs can permeate cell membranes and deliver proteins or bioactive materials into living cells. Various approaches have been applied for improving their transduction efficacy. It is, therefore, crucial to clarify the entry mechanisms and to identify the rate-limiting steps. Because of technical limitations for imaging PTD behavior on cells with conventional fluorescent-dyes, how PTDs enter the cells has been a topic of much debate. Utilizing quantum dots (QDs, we recently tracked the behavior of PTD that was derived from HIV-1 Tat (TatP in living cells at the single-molecule level with 7-nm special precision. In this review article, we initially summarize the controversy on TatP entry mechanisms; thereafter, we will focus on our recent findings on single-TatP-QD tracking (SQT, to identify the major sequential steps of intracellular delivery in living cells and to discuss how SQT can easily provide direct information on TatP entry mechanisms. As a primer for SQT study, we also discuss the latest findings on single particle tracking of various molecules on the plasma membrane. Finally, we discuss the problems of QDs and the challenges for the future in utilizing currently available QD probes for SQT. In conclusion, direct identification of the rate-limiting steps of PTD entry with SQT should dramatically improve the methods for enhancing transduction efficiency.

  20. Cation-Coupled Bicarbonate Transporters

    OpenAIRE

    Aalkjaer, Christian; Boedtkjer, Ebbe; Choi, Inyeong; Lee, Soojung

    2014-01-01

    Cation-coupled HCO3− transport was initially identified in the mid-1970s when pioneering studies showed that acid extrusion from cells is stimulated by CO2/HCO3− and associated with Na+ and Cl− movement. The first Na+-coupled bicarbonate transporter (NCBT) was expression-cloned in the late 1990s. There are currently five mammalian NCBTs in the SLC4-family: the electrogenic Na,HCO3-cotransporters NBCe1 and NBCe2 (SLC4A4 and SLC4A5 gene products); the electroneutral Na,HCO3-cotransporter NBCn1 ...

  1. Cation disorder in shocked orthopyroxene.

    Science.gov (United States)

    Dundon, R. W.; Hafner, S. S.

    1971-01-01

    The study of cation distributions over nonequivalent lattice sites in minerals may reveal information on the history of temperature and pressure in rocks. Chemically homogeneous orthopyroxene specimens were shocked under well-controlled conditions in the laboratory in order to provide a basis for the interpretation of more complex natural materials. As a result of the investigation it is concluded that the distribution of magnesium and iron over the M1 and M2 positions in Bamle enstatite shocked at 1 megabar is highly disordered. It corresponds to an equilibrium distribution of at least 1000 C.

  2. Cation coordination in oxychloride glasses

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, J A [Energy Technology Division, Argonne National Laboratory, Argonne, IL (United States); Holland, D [Physics Department, Warwick University, Coventry (United Kingdom); Bland, J [Physics Department, University of Liverpool, PO Box 147, Liverpool (United Kingdom); Johnson, C E [Physics Department, Northern Illinois University, DeKalb, IL (United States); Thomas, M F [Physics Department, University of Liverpool, PO Box 147, Liverpool (United Kingdom)

    2003-02-19

    Glasses containing mixtures of cations and anions of nominal compositions [Sb{sub 2}O{sub 3}]{sub x} - [ZnCl{sub 2}]{sub 1-x} where x = 0.25, 0.50, 0.75, and 1.00, have been studied by means of neutron diffraction and Raman and Moessbauer spectroscopy. There is preferential bonding within the system with the absence of Sb-Cl bonds. Antimony is found to be threefold coordinated to oxygen, and zinc fourfold coordinated. The main contributing species are of the form [Sb(OSb){sub 2}(OZn)] and [Zn(ClZn){sub 2}(OSb){sub 2}].

  3. Cation coordination in oxychloride glasses

    International Nuclear Information System (INIS)

    Johnson, J A; Holland, D; Bland, J; Johnson, C E; Thomas, M F

    2003-01-01

    Glasses containing mixtures of cations and anions of nominal compositions [Sb 2 O 3 ] x - [ZnCl 2 ] 1-x where x = 0.25, 0.50, 0.75, and 1.00, have been studied by means of neutron diffraction and Raman and Moessbauer spectroscopy. There is preferential bonding within the system with the absence of Sb-Cl bonds. Antimony is found to be threefold coordinated to oxygen, and zinc fourfold coordinated. The main contributing species are of the form [Sb(OSb) 2 (OZn)] and [Zn(ClZn) 2 (OSb) 2

  4. The Free Tricoordinated Silyl Cation Problem

    Directory of Open Access Journals (Sweden)

    Čičak, H.

    2010-03-01

    Full Text Available As the importance and abundance of silicon in our environment is large, it has been thought that silicon might take the place of carbon in forming a host of similar compounds and silicon-based life. However, until today there is no experimental evidence for such a hypothesis and carbon is still unique among the elements in the vast number and variety of compounds it can form. Also, the corresponding derivatives of the two elements show considerable differences in their chemical properties.The essential debate concerning organosilicon chemistry relates to the existence of the free planar tricoordinated silyl cations in condensed phase (R3Si+, in analogy to carbocations (R3C+ which have been known and characterized as free species. Although silyl cations are thermodynamically more stable than their carbon analogs, they are very reactive due to their high inherent electrophilicity and the ability of hypervalent coordination. On the other hand, stabilization by inductive and hyperconjugative effects and larger steric effects of carbocations make them less sensitive to solvation or other environmental effects than silyl cations. Hence, observation of free silyl cations in the condensed phase proved extremely difficult and the actual problem is the question of the degree of the (remaining silyl cation character.The first free silyl cation, trimesitylsilyl cation, and in analogy with it tridurylsilyl cation, were synthesized by Lambert et al. Free silyl cations based on analogy to aromatic ions (homocyclopropenylium and tropylium have also been prepared. However, in these silyl cations the cationic character is reduced by internal π -conjugation. Čičak et al. prepared some silyl-cationic intermediates (Me3Si--CH≡CR+in solid state. With the help of quantum-mechanical calculations it was concluded that these adducts have much more silyl cation than carbocation character.

  5. FY1995 transduction method and CAD database systems for integrated design; 1995 nendo transduction ho to CAD database togo sekkei shien system

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    Transduction method developed by the research coordinator and Prof. Muroga is one of the most popular methods to design large-scale integrated circuits, and thus used by major design tool companies in USA and Japan. The major objectives of the research is to improve capability and utilize its reusable property by combining with CAD databases. Major results of the project is as follows, (1) Improvement of Transduction method : Efficiency, capability and the maximum circuit size are improved. Error compensation method is also improved. (2) Applications to new logic elements : Transduction method is modified to cope with wired logic and FPGAs. (3) CAD databases : One of the major advantages of Transduction methods is 'reusability' of already designed circuits. It is suitable to combine with CAD databases. We design CAD databases suitable for cooperative design using Transduction method. (4) Program development : Programs for Windows95 and developed for distribution. (NEDO)

  6. FY1995 transduction method and CAD database systems for integrated design; 1995 nendo transduction ho to CAD database togo sekkei shien system

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    Transduction method developed by the research coordinator and Prof. Muroga is one of the most popular methods to design large-scale integrated circuits, and thus used by major design tool companies in USA and Japan. The major objectives of the research is to improve capability and utilize its reusable property by combining with CAD databases. Major results of the project is as follows, (1) Improvement of Transduction method : Efficiency, capability and the maximum circuit size are improved. Error compensation method is also improved. (2) Applications to new logic elements : Transduction method is modified to cope with wired logic and FPGAs. (3) CAD databases : One of the major advantages of Transduction methods is 'reusability' of already designed circuits. It is suitable to combine with CAD databases. We design CAD databases suitable for cooperative design using Transduction method. (4) Program development : Programs for Windows95 and developed for distribution. (NEDO)

  7. Reduced modeling of signal transduction – a modular approach

    Directory of Open Access Journals (Sweden)

    Ederer Michael

    2007-09-01

    Full Text Available Abstract Background Combinatorial complexity is a challenging problem in detailed and mechanistic mathematical modeling of signal transduction. This subject has been discussed intensively and a lot of progress has been made within the last few years. A software tool (BioNetGen was developed which allows an automatic rule-based set-up of mechanistic model equations. In many cases these models can be reduced by an exact domain-oriented lumping technique. However, the resulting models can still consist of a very large number of differential equations. Results We introduce a new reduction technique, which allows building modularized and highly reduced models. Compared to existing approaches further reduction of signal transduction networks is possible. The method also provides a new modularization criterion, which allows to dissect the model into smaller modules that are called layers and can be modeled independently. Hallmarks of the approach are conservation relations within each layer and connection of layers by signal flows instead of mass flows. The reduced model can be formulated directly without previous generation of detailed model equations. It can be understood and interpreted intuitively, as model variables are macroscopic quantities that are converted by rates following simple kinetics. The proposed technique is applicable without using complex mathematical tools and even without detailed knowledge of the mathematical background. However, we provide a detailed mathematical analysis to show performance and limitations of the method. For physiologically relevant parameter domains the transient as well as the stationary errors caused by the reduction are negligible. Conclusion The new layer based reduced modeling method allows building modularized and strongly reduced models of signal transduction networks. Reduced model equations can be directly formulated and are intuitively interpretable. Additionally, the method provides very good

  8. Polybrene inhibits human mesenchymal stem cell proliferation during lentiviral transduction.

    Directory of Open Access Journals (Sweden)

    Paul Lin

    Full Text Available Human mesenchymal stem cells (hMSCs can be engineered to express specific genes, either for their use in cell-based therapies or to track them in vivo over long periods of time. To obtain long-term expression of these genes, a lentivirus- or retrovirus-mediated cell transduction is often used. However, given that the efficiency with these viruses is typically low in primary cells, additives such as polybrene are always used for efficient viral transduction. Unfortunately, as presented here, exposure to polybrene alone at commonly used concentratons (1-8 µg/mL negatively impacts hMSC proliferation in a dose-dependent manner as measured by CyQUANT, EdU incorporation, and cell cycle analysis. This inhibition of proliferation was observable in culture even 3 weeks after exposure. Culturing the cells in the presence of FGF-2, a potent mitogen, did not abrogate this negative effect of polybrene. In fact, the normally sharp increase in hMSC proliferation that occurs during the first days of exposure to FGF-2 was absent at 4 µg/mL or higher concentrations of polybrene. Similarly, the effect of stimulating cell proliferation under simulated hypoxic conditions was also decreased when cells were exposed to polybrene, though overall proliferation rates were higher. The negative influence of polybrene was, however, reduced when the cells were exposed to polybrene for a shorter period of time (6 hr vs 24 hr. Thus, careful evaluation should be done when using polybrene to aid in lentiviral transduction of human MSCs or other primary cells, especially when cell number is critical.

  9. Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3: understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations.

    Science.gov (United States)

    Williams, Hywel D; Sassene, Philip; Kleberg, Karen; Calderone, Marilyn; Igonin, Annabel; Jule, Eduardo; Vertommen, Jan; Blundell, Ross; Benameur, Hassan; Müllertz, Anette; Pouton, Colin W; Porter, Christopher J H

    2013-12-01

    Recent studies have shown that digestion of lipid-based formulations (LBFs) can stimulate both supersaturation and precipitation. The current study has evaluated the drug, formulation and dose-dependence of the supersaturation - precipitation balance for a range of LBFs. Type I, II, IIIA/B LBFs containing medium-chain (MC) or long-chain (LC) lipids, and lipid-free Type IV LBF incorporating different doses of fenofibrate or tolfenamic acid were digested in vitro in a simulated intestinal medium. The degree of supersaturation was assessed through comparison of drug concentrations in aqueous digestion phases (APDIGEST) during LBF digestion and the equilibrium drug solubility in the same phases. Increasing fenofibrate or tolfenamic acid drug loads (i.e., dose) had negligible effects on LC LBF performance during digestion, but promoted drug crystallization (confirmed by XRPD) from MC and Type IV LBF. Drug crystallization was only evident in instances when the calculated maximum supersaturation ratio (SR(M)) was >3. This threshold SR(M) value was remarkably consistent across all LBF and was also consistent with previous studies with danazol. The maximum supersaturation ratio (SR(M)) provides an indication of the supersaturation 'pressure' exerted by formulation digestion and is strongly predictive of the likelihood of drug precipitation in vitro. This may also prove effective in discriminating the in vivo performance of LBFs.

  10. Lipid-based oral delivery systems for skin deposition of a potential chemopreventive DIM derivative: characterization and evaluation.

    Science.gov (United States)

    Boakye, Cedar H A; Patel, Ketan; Patel, Apurva R; Faria, Henrique A M; Zucolotto, Valtencir; Safe, Stephen; Singh, Mandip

    2016-10-01

    The objective of this study was to explore the oral route as a viable potential for the skin deposition of a novel diindolylmethane derivative (DIM-D) for chemoprevention activity. Various lipid-based oral delivery systems were optimized and compared for enhancing DIM-D's oral bioavailability and skin deposition. Preformulation studies were performed to evaluate the log P and solubility of DIM-D. Microsomal metabolism, P-glycoprotein efflux, and caco-2 monolayer permeability of DIM-D were determined. Comparative evaluation of the oral absorption and skin deposition of DIM-D-loaded various lipid-based formulations was performed in rats. DIM-D showed pH-dependent solubility and a high log P value. It was not a strong substrate of microsomal degradation and P-glycoprotein. SMEDDs comprised of medium chain triglycerides, monoglycerides, and kolliphor-HS15 (36.70 ± 0.42 nm). SNEDDs comprised of long chain triglycerides, cremophor RH40, labrasol, and TPGS (84.00 ± 14.14 nm). Nanostructured lipid carriers (NLC) consisted of compritol, miglyol, and surfactants (116.50 ± 2.12 nm). The blank formulations all showed >70 % cell viability in caco-2 cells. Differential Scanning Calorimetry confirmed the amorphization of DIM-D within the lipid matrices while Atomic Force Microscopy showed particle size distribution similar to the dynamic light scattering data. DIM-D also showed reduced permeation across caco-2 monolayer that was enhanced (p < 0.05) by SNEDDs in comparison to SMEDDs and NLC. Fabsolute for DIM-D SNEDDs, SMEDDs, and NLC was 0.14, 0.04, and 0.007, respectively. SNEDDs caused 53.90, 11.32, and 15.08-fold more skin deposition of DIM-D than the free drug, SMEDDs, and NLC, respectively, at 2 h following oral administration and shows a viable potential for use in skin cancer chemoprevention. Graphical Abstract ᅟ.

  11. Feeding behaviors during home-based treatment of moderate acute malnutrition using corn-soy blends or lipid-based nutrient supplements

    DEFF Research Database (Denmark)

    Iuel-Brockdorff, Ann-Sophie Julie D; Ouedraogo, Albertine; Ritz, Christian

    2017-01-01

    Feeding behaviors have an important impact on children's nutritional status and are essential to consider when implementing nutrition programs. The objective of this study was to explore and compare feeding behaviors related to supplementary feeding with corn-soy blends (CSB) and lipid-based nutr...

  12. Modeling evolution of crosstalk in noisy signal transduction networks

    Science.gov (United States)

    Tareen, Ammar; Wingreen, Ned S.; Mukhopadhyay, Ranjan

    2018-02-01

    Signal transduction networks can form highly interconnected systems within cells due to crosstalk between constituent pathways. To better understand the evolutionary design principles underlying such networks, we study the evolution of crosstalk for two parallel signaling pathways that arise via gene duplication. We use a sequence-based evolutionary algorithm and evolve the network based on two physically motivated fitness functions related to information transmission. We find that one fitness function leads to a high degree of crosstalk while the other leads to pathway specificity. Our results offer insights on the relationship between network architecture and information transmission for noisy biomolecular networks.

  13. Signal transduction by the major histocompatibility complex class I molecule

    DEFF Research Database (Denmark)

    Pedersen, A E; Skov, Svend; Bregenholt, S

    1999-01-01

    Ligation of cell surface major histocompatibility class I (MHC-I) proteins by antibodies, or by their native counter receptor, the CD8 molecule, mediates transduction of signals into the cells. MHC-I-mediated signaling can lead to both increased and decreased activity of the MHC-I-expressing cell...... and functioning, MHC-I molecules might be of importance for the maintenance of cellular homeostasis not only within the immune system, but also in the interplay between the immune system and other organ systems....

  14. Signaling transduction pathways involved in basophil adhesion and histamine release

    DEFF Research Database (Denmark)

    Sha, Quan; Poulsen, Lars K.; Gerwien, Jens

    2006-01-01

    Little is known about basophil with respect to the different signaling transduction pathways involved in spontaneous, cytokine or anti-IgE induced adhesion and how this compares to IgE-dependent and IgE-independent mediator secretion. The purpose of the present study was to investigate the roles...... of beta1 and beta2 integrins in basophil adhesion as well as hosphatidylinositol 3-kinase (PI3K), src-kinases and extracellular signal regulated kinase (ERK) 1/2 in basophil adhesion and histamine release (HR)....

  15. ADSORPTION METHOD FOR SEPARATING METAL CATIONS

    Science.gov (United States)

    Khym, J.X.

    1959-03-10

    The chromatographic separation of fission product cations is discussed. By use of this method a mixture of metal cations containing Zr, Cb, Ce, Y, Ba, and Sr may be separated from one another. Mentioned as preferred exchange adsorbents are resins containing free sulfonic acid groups. Various eluants, such as tartaric acid, HCl, and citric acid, used at various acidities, are employed to effect the selective elution and separation of the various fission product cations.

  16. Electronic spectra of astrophysically interesting cations

    Energy Technology Data Exchange (ETDEWEB)

    Maier, John P., E-mail: j.p.maier@unibas.ch; Rice, Corey A., E-mail: j.p.maier@unibas.ch; Mazzotti, Fabio J., E-mail: j.p.maier@unibas.ch; Johnson, Anatoly, E-mail: j.p.maier@unibas.ch [Department of Chemistry, University of Basel, Klingelbergstr. 80, CH-4056 Basel (Switzerland)

    2015-01-22

    The electronic spectra of polyacetylene cations were recorded at 20K in the laboratory in an ion trap instrument. These can then be compared with diffuse interstellar band (DIB) absorptions. Examination of recently published data shows that the attribution of a weak DIB at ∼506.9 nm to diacetylene cation is not justified. Study of the higher excited electronic states of polyacetylene cations shows that their widths can still be sufficiently narrow for consideration as DIB carriers.

  17. Uranium isotope separation using styrene cation exchangers

    International Nuclear Information System (INIS)

    Kahovec, J.

    1980-01-01

    The separation of 235 U and 238 U isotopes is carried out either by simple isotope exchange in the system uranium-cation exchanger (sulphonated styrene divinylbenzene resin), or by combination of isotope exchange in a uranium-cation exchanger (Dowex 50, Amberlite IR-120) system and a chemical reaction. A review is presented of elution agents used, the degree of cation exchanger cross-linking, columns length, and 235 U enrichment. The results are described of the isotope effect study in a U(IV)-U(VI)-cation exchanger system conducted by Japanese and Romanian authors (isotope exchange kinetics, frontal analysis, reverse (indirect) frontal analysis). (H.S.)

  18. Cation-π interactions in structural biology

    OpenAIRE

    Gallivan, Justin P.; Dougherty, Dennis A.

    1999-01-01

    Cation-pi interactions in protein structures are identified and evaluated by using an energy-based criterion for selecting significant sidechain pairs. Cation-pi interactions are found to be common among structures in the Protein Data Bank, and it is clearly demonstrated that, when a cationic sidechain (Lys or Arg) is near an aromatic sidechain (Phe, Tyr, or Trp), the geometry is biased toward one that would experience a favorable cation-pi interaction. The sidechain of Arg is more likely tha...

  19. Simultaneous anion and cation mobility in polypyrrole

    DEFF Research Database (Denmark)

    Skaarup, Steen; Bay, Lasse; Vidanapathirana, K.

    2003-01-01

    and the expulsion of anions; a broad anodic peak centered at ca. - 0.5 V representing the expulsion of cations; and a second broad peak at +0.2 to +0.5 V corresponding to anions being inserted. Although the motion of cations is the most important, as expected, there is a significant anion contribution, thereby...... complicating reproducibility when employing PPy(DBS) polymers as actuators. When the cation is doubly charged, it enters the film less readily, and anions dominate the mobility. Using a large and bulky cation switches the mechanism to apparently total anion motion. The changes in area of the three peaks...

  20. Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid-State Lipid-Based Drug Delivery Systems.

    Science.gov (United States)

    Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

    2016-01-01

    Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs. Despite the successful commercialization of several LBDDS products over the years, a large discrepancy exists between the number of poorly water-soluble drugs displaying suboptimal in vivo performances and the application of LBDDS to mitigate their various delivery challenges. Conventional LBDDS, including lipid solutions and suspensions, emulsions, and self-emulsifying formulations, suffer from various drawbacks limiting their widespread use and commercialization. Accordingly, solid-state LBDDS, fabricated by adsorbing LBDDS onto a chemically inert solid carrier material, have attracted substantial interest as a viable means of stabilizing LBDDS whilst eliminating some of the various limitations. This review describes the impact of solid carrier choice on LBDDS performance and highlights the importance of appropriate solid carrier material selection when designing hybrid solid-state LBDDS. Specifically, emphasis is placed on discussing the ability of the specific solid carrier to modulate drug release, control lipase action and lipid digestion, and enhance biopharmaceutical performance above the original liquid-state LBDDS. To encourage the interested reader to consider their solid carrier choice on a higher level, various novel materials with the potential for future use as solid carriers for LBDDS are described. This review is highly significant in guiding future research directions in the solid-state LBDDS field and fostering the translation of these delivery systems to the pharmaceutical marketplace.

  1. Effect of lipid-based dry eye supplements on the tear film in wearers of eye cosmetics.

    Science.gov (United States)

    Wang, Michael T M; Cho, Irene Sung Hee; Jung, Soo Hee; Craig, Jennifer P

    2017-08-01

    To compare the effects on tear film parameters and contamination in cosmetic eyeliner wearers, after single application of two lipid-based dry eye treatments: a lipid-containing lubricant eye drop and a phospholipid liposomal spray. Fifty participants were enrolled in a prospective, randomised, paired-eye, investigator-masked trial. Pencil eyeliner (Body Shop ® Crayon Eye Definer) was applied to the upper eyelid periocular skin of both eyes, anterior to the lash line. Baseline tear film quality was assessed fifteen minutes after eyeliner application. A lubricant drop (Systane ® Balance) was then applied to one eye (randomised), and liposomal spray (Tears Again ® ) to the contralateral eye. Tear film contamination, lipid layer grade, non-invasive tear film break-up time and tear evaporation rate were evaluated fifteen minutes post-treatment and compared to pre-treatment values. Pre-treatment measurements did not differ between eyes assigned to lubricant drop and liposomal spray. Tear film contamination was observed in a greater proportion of eyes following both treatments (both p0.05). Changes in tear film parameters did not differ between treatments (all p>0.05). Both the lipid-containing lubricant eye drop and phospholipid liposomal spray result in clinically apparent tear film contamination in eyeliner cosmetic wearers. Although both treatments effected an increase in lipid layer thickness, neither displayed clinical efficacy in improving tear film stability. Copyright © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  2. Preventative lipid-based nutrient supplements (LNS) and young child feeding practices: findings from qualitative research in Haiti.

    Science.gov (United States)

    Lesorogol, Carolyn; Jean-Louis, Sherlie; Green, Jamie; Iannotti, Lora

    2015-12-01

    To prevent undernutrition in an urban slum in Haiti, a lipid-based nutrient supplement (LNS) was introduced through a randomised control trial. Food supplementation for young child nutrition has a long history in Haiti, but there is little empirical information regarding the effects of supplementation on young child feeding practices. One of the concerns raised by supplementation is that it may disrupt other positive feeding practices such as breastfeeding and use of other complementary foods, with negative consequences for child nutrition. We conducted 29 in-depth interviews with mother-baby pairs from the three comparison groups: control, 3-month LNS supplementation and 6-month LNS supplementation. Findings from those in the LNS groups indicated high acceptance and satisfaction with LNS and perceptions that it positively affects child health and development. LNS was integrated into and enhanced ongoing complementary feeding practices. The effects of LNS use on duration and perceived quantity of breastfeeding were variable, but generally, breastfeeding was maintained during and after the intervention. Interviews generated insights into beliefs regarding infant and young child feeding practices such as introduction and use of complementary foods, and breastfeeding duration, exclusivity and cessation. Implications for the use of LNS in public health nutrition programmes are discussed. © 2014 John Wiley & Sons Ltd.

  3. Polar Quassinoids in Standardized Eurycoma longifolia Extract Formulated into a Lipid-Based Solid Dispersion to Improve Rat Sperm Count.

    Science.gov (United States)

    Ma, Hai-Qiu; Ebrahimi, Forough; Low, Bin-Seng; Khan, Nurzalina Abdul Karim; Chan, Kit-Lam

    2017-12-01

    Eurycoma longifolia Jack is popularly sought in Southeast Asian countries for traditional remedies to improve sexual performance and fertility. 13α(21)-Epoxyeurycomanone and eurycomanone, two major quassinoids in a root extract (TAF2) were reported to improve rat spermatogenesis and fertility. Unfortunately, these quassinoids possess low bioavailability because of high aqueous solubility and low lipid membrane permeability. Often, other possible barriers may be P-glycoprotein (P-gp) efflux in the gut and presystemic hepatic metabolism. The present study attempted to solve these problems by formulating a lipid-based solid dispersion (TAF2-SD) of optimized mixture of TAF2 and emulsifiers, which was then orally administered to rats prior to sperm count analysis. The TAF2-SD-treated rats showed significantly twofold (p < 0.001) and fourfold (p < 0.001) higher sperm count than did TAF2-treated and vehicle-treated (control) rats, respectively. The study also demonstrated no significant in vitro ileal absorption changes of the quassinoids by P-gp efflux inhibitors and concentration change or secondary metabolite formation upon in vitro incubation with rat liver homogenates, suggesting that P-gp-mediated efflux and presystemic metabolism were not limiting their bioavailability. Further study on orally TAF2-treated rats confirmed that the area under the curve and bioavailability curve of each quassinoid in the absence and presence of ketoconazole were unchanged. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Analysis and logical modeling of biological signaling transduction networks

    Science.gov (United States)

    Sun, Zhongyao

    The study of network theory and its application span across a multitude of seemingly disparate fields of science and technology: computer science, biology, social science, linguistics, etc. It is the intrinsic similarities embedded in the entities and the way they interact with one another in these systems that link them together. In this dissertation, I present from both the aspect of theoretical analysis and the aspect of application three projects, which primarily focus on signal transduction networks in biology. In these projects, I assembled a network model through extensively perusing literature, performed model-based simulations and validation, analyzed network topology, and proposed a novel network measure. The application of network modeling to the system of stomatal opening in plants revealed a fundamental question about the process that has been left unanswered in decades. The novel measure of the redundancy of signal transduction networks with Boolean dynamics by calculating its maximum node-independent elementary signaling mode set accurately predicts the effect of single node knockout in such signaling processes. The three projects as an organic whole advance the understanding of a real system as well as the behavior of such network models, giving me an opportunity to take a glimpse at the dazzling facets of the immense world of network science.

  5. Signal perception, transduction, and gene expression involved in anthocyanin biosynthesis

    International Nuclear Information System (INIS)

    Mol, J.; Jenkins, G.; Schäfer, E.; Weiss, D.

    1996-01-01

    Anthocyanin pigments provide fruits and flowers with their bright red and blue colors and are induced in vegetative tissues by various signals. The biosynthetic pathway probably represents one of the best‐studied examples of higher plant secondary metabolism. It has attracted much attention of plant geneticists because of the dispensable nature of the compounds it produces. Not unexpectedly, several excellent reviews on anthocyanin biosynthesis have been published over the last 5 years (Dooner et al., 1991; Martin and Gerats, 1993a, 1993b; Koes et al., 1994; Holton and Cornish, 1995). These reviews emphasize the late steps of pigment biosynthesis rather than the early and intermediate events of signal perception and transduction. This review is broader and not only covers the identification of components of the anthocyanin signal perception/transduction networks but also provides a description of our current understanding of how they evoke the responses that they do. Progress has derived from a combination of biochemical, molecular and genetic studies. We discuss a range of relevant research to highlight the different experimental approaches being used and the diverse biological systems under investigation. (author)

  6. Discriminative clustering on manifold for adaptive transductive classification.

    Science.gov (United States)

    Zhang, Zhao; Jia, Lei; Zhang, Min; Li, Bing; Zhang, Li; Li, Fanzhang

    2017-10-01

    In this paper, we mainly propose a novel adaptive transductive label propagation approach by joint discriminative clustering on manifolds for representing and classifying high-dimensional data. Our framework seamlessly combines the unsupervised manifold learning, discriminative clustering and adaptive classification into a unified model. Also, our method incorporates the adaptive graph weight construction with label propagation. Specifically, our method is capable of propagating label information using adaptive weights over low-dimensional manifold features, which is different from most existing studies that usually predict the labels and construct the weights in the original Euclidean space. For transductive classification by our formulation, we first perform the joint discriminative K-means clustering and manifold learning to capture the low-dimensional nonlinear manifolds. Then, we construct the adaptive weights over the learnt manifold features, where the adaptive weights are calculated through performing the joint minimization of the reconstruction errors over features and soft labels so that the graph weights can be joint-optimal for data representation and classification. Using the adaptive weights, we can easily estimate the unknown labels of samples. After that, our method returns the updated weights for further updating the manifold features. Extensive simulations on image classification and segmentation show that our proposed algorithm can deliver the state-of-the-art performance on several public datasets. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Fetus Sound Stimulation: Cilia Memristor Effect of Signal Transduction

    Directory of Open Access Journals (Sweden)

    Svetlana Jankovic-Raznatovic

    2014-01-01

    Full Text Available Background. This experimental study evaluates fetal middle cerebral artery (MCA circulation after the defined prenatal acoustical stimulation (PAS and the role of cilia in hearing and memory and could explain signal transduction and memory according to cilia optical-acoustical properties. Methods. PAS was performed twice on 119 no-risk term pregnancies. We analyzed fetal MCA circulation before, after first and second PAS. Results. Analysis of the Pulsatility index basic (PIB and before PAS and Pulsatility index reactive after the first PAS (PIR 1 shows high statistical difference, representing high influence on the brain circulation. Analysis of PIB and Pulsatility index reactive after the second PAS (PIR 2 shows no statistical difference. Cilia as nanoscale structure possess magnetic flux linkage that depends on the amount of charge that has passed between two-terminal variable resistors of cilia. Microtubule resistance, as a function of the current through and voltage across the structure, leads to appearance of cilia memory with the “memristor” property. Conclusion. Acoustical and optical cilia properties play crucial role in hearing and memory processes. We suggest that fetuses are getting used to sound, developing a kind of memory patterns, considering acoustical and electromagnetically waves and involving cilia and microtubules and try to explain signal transduction.

  8. Molecular mechanisms of root gravity sensing and signal transduction.

    Science.gov (United States)

    Strohm, Allison K; Baldwin, Katherine L; Masson, Patrick H

    2012-01-01

    Plants use gravity as a guide to direct their roots down into the soil to anchor themselves and to find resources needed for growth and development. In higher plants, the columella cells of the root tip form the primary site of gravity sensing, and in these cells the sedimentation of dense, starch-filled plastids (amyloplasts) triggers gravity signal transduction. This generates an auxin gradient across the root cap that is transmitted to the elongation zone where it promotes differential cell elongation, allowing the root to direct itself downward. It is still not well understood how amyloplast sedimentation leads to auxin redistribution. Models have been proposed to explain how mechanosensitive ion channels or ligand-receptor interactions could connect these events. Although their roles are still unclear, possible second messengers in this process include protons, Ca(2+), and inositol 1,4,5-triphosphate. Upon gravistimulation, the auxin efflux facilitators PIN3 and PIN7 relocalize to the lower side of the columella cells and mediate auxin redistribution. However, evidence for an auxin-independent secondary mechanism of gravity sensing and signal transduction suggests that this physiological process is quite complex. Furthermore, plants must integrate a variety of environmental cues, resulting in multifaceted relationships between gravitropism and other directional growth responses such as hydro-, photo-, and thigmotropism. Copyright © 2011 Wiley Periodicals, Inc.

  9. Genetic analysis of gravity signal transduction in roots

    Science.gov (United States)

    Masson, Patrick; Strohm, Allison; Baldwin, Katherine

    To grow downward into the soil, roots use gravity as a guide. Specialized cells, named stato-cytes, enable this directional growth response by perceiving gravity. Located in the columella region of the cap, these cells sense a reorientation of the root within the gravity field through the sedimentation of, and/or tension/pressure exerted by, dense amyloplasts. This process trig-gers a gravity signal transduction pathway that leads to a fast alkalinization of the cytoplasm and a change in the distribution of the plasma membrane-associated auxin-efflux carrier PIN3. The latter protein is uniformly distributed within the plasma membrane on all sides of the cell in vertically oriented roots. However, it quickly accumulates at the bottom side upon gravis-timulation. This process correlates with a preferential transport of auxin to the bottom side of the root cap, resulting in a lateral gradient across the tip. This gradient is then transported to the elongation zone where it promotes differential cellular elongation, resulting in downward curvature. We isolated mutations that affect gravity signal transduction at a step that pre-cedes cytoplasmic alkalinization and/or PIN3 relocalization and lateral auxin transport across the cap. arg1 and arl2 mutations identify a common genetic pathway that is needed for all three gravity-induced processes in the cap statocytes, indicating these genes function early in the pathway. On the other hand, adk1 affects gravity-induced PIN3 relocalization and lateral auxin transport, but it does not interfere with cytoplasmic alkalinization. ARG1 and ARL2 encode J-domain proteins that are associated with membranes of the vesicular trafficking path-way whereas ADK1 encodes adenosine kinase, an enzyme that converts adenosine derived from nucleic acid metabolism and the AdoMet cycle into AMP, thereby alleviating feedback inhibi-tion of this important methyl-donor cycle. Because mutations in ARG1 (and ARL2) do not completely eliminate

  10. Genetic Analysis of Gravity Signal Transduction in Arabidopsis Roots

    Science.gov (United States)

    Masson, Patrick; Strohm, Allison; Barker, Richard; Su, Shih-Heng

    Like most other plant organs, roots use gravity as a directional guide for growth. Specialized cells within the columella region of the root cap (the statocytes) sense the direction of gravity through the sedimentation of starch-filled plastids (amyloplasts). Amyloplast movement and/or pressure on sensitive membranes triggers a gravity signal transduction pathway within these cells, which leads to a fast transcytotic relocalization of plasma-membrane associated auxin-efflux carrier proteins of the PIN family (PIN3 and PIN7) toward the bottom membrane. This leads to a polar transport of auxin toward the bottom flank of the cap. The resulting lateral auxin gradient is then transmitted toward the elongation zones where it triggers a curvature that ultimately leads to a restoration of vertical downward growth. Our laboratory is using strategies derived from genetics and systems biology to elucidate the molecular mechanisms that modulate gravity sensing and signal transduction in the columella cells of the root cap. Our previous research uncovered two J-domain-containing proteins, ARG1 and ARL2, as contributing to this process. Mutations in the corresponding paralogous genes led to alterations of root and hypocotyl gravitropism accompanied by an inability for the statocytes to develop a cytoplasmic alkalinization, relocalize PIN3, and transport auxin laterally, in response to gravistimulation. Both proteins are associated peripherally to membranes belonging to various compartments of the vesicular trafficking pathway, potentially modulating the trafficking of defined proteins between plasma membrane and endosomes. MAR1 and MAR2, on the other end, are distinct proteins of the plastidic outer envelope protein import TOC complex (the transmembrane channel TOC75 and the receptor TOC132, respectively). Mutations in the corresponding genes enhance the gravitropic defects of arg1. Using transformation-rescue experiments with truncated versions of TOC132 (MAR2), we have shown

  11. Protein phylogenetic analysis of Ca2+/cation antiporters and insights into their evolution in plants

    Directory of Open Access Journals (Sweden)

    Laura eEmery

    2012-01-01

    Full Text Available Cation transport is a critical process in all organisms and is essential for mineral nutrition, ion stress tolerance, and signal transduction. Transporters that are members of the Ca2+/Cation Antiporter (CaCA superfamily are involved in the transport of Ca2+ and/or other cations using the counter exchange of another ion such as H+ or Na+. The CaCA superfamily has been previously divided into five transporter families: the YRBG, NCX, NCKX, CAX and CCX families, which include the well-characterized Na+/Ca2+ exchanger (NCX and H+/cation exchanger (CAX transporters. To examine the evolution of CaCA transporters within higher plants and the green plant lineage, CaCA genes were identified from the genomes of sequenced flowering plants, a bryophyte, lycophyte, and freshwater and marine algae, and compared with those from non-plant species. We found evidence of the expansion and increased diversity of flowering plant genes within the CAX and CCX families. Genes related to the NCX family are present in land plant though they encode distinct MHX homologs which probably have an altered transport function. In contrast, the NCX and NCKX genes which are absent in land plants have been retained in many species of algae, especially the marine algae, indicating that these organisms may share ‘animal-like’ characteristics of Ca2+ homeostasis and signaling. A group of genes encoding novel CAX-like proteins containing an EF hand domain were identified from plants and selected algae but appeared to be lacking in any other species. Lack of functional data for most of the CaCA proteins make it impossible to reliably predict substrate specificity and function for many of the groups or individual proteins. The abundance and diversity of CaCA genes throughout all branches of life indicates the importance of this class of cation transporter, and that many transporters with novel functions are waiting to be discovered.

  12. Afrikaans Syllabification Patterns

    Directory of Open Access Journals (Sweden)

    Tilla Fick

    2010-01-01

    Full Text Available In contrast to English, automatic hyphenation by computer of Afrikaans words is a problem that still needs to be addressed, since errors are still often encountered in printed text. An initial step in this task is the ability to automatically syllabify words. Since new words are created continuously by joining words, it is necessary to develop an “intelligent” technique for syllabification. As a first phase of the research, we consider only the orthographic information of words, and disregard both syntactic and morphological information. This approach allows us to use machine-learning techniques such as artificial neural networks and decision trees that are known for their pattern recognition abilities. Both these techniques are trained with isolated patterns consisting of input patterns and corresponding outputs (or targets that indicate whether the input pattern should be split at a certain position, or not. In the process of compiling a list of syllabified words from which to generate training data for the  syllabification problem, irregular patterns were identified. The same letter patterns are split differently in different words and complete words that are spelled identically are split differently due to meaning. We also identified irregularities in and between  the different dictionaries that we used. We examined the influence range of letters that are involved in irregularities. For example, for their in agter-ente and vaste-rente we have to consider three letters to the left of r to be certain where the hyphen should be inserted. The influence range of the k in verstek-waarde and kleinste-kwadrate is four to the left and three to the right. In an analysis of letter patterns in Afrikaans words we found that the letter e has the highest frequency overall (16,2% of all letters in the word list. The frequency of words starting with s is the highest, while the frequency of words ending with e is the highest. It is important to

  13. Staurosporine Increases Lentiviral Vector Transduction Efficiency of Human Hematopoietic Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Gretchen Lewis

    2018-06-01

    Full Text Available Lentiviral vector (LVV-mediated transduction of human CD34+ hematopoietic stem and progenitor cells (HSPCs holds tremendous promise for the treatment of monogenic hematological diseases. This approach requires the generation of a sufficient proportion of gene-modified cells. We identified staurosporine, a serine/threonine kinase inhibitor, as a small molecule that could be added to the transduction process to increase the proportion of genetically modified HSPCs by overcoming a LVV entry barrier. Staurosporine increased vector copy number (VCN approximately 2-fold when added to mobilized peripheral blood (mPB CD34+ cells prior to transduction. Limited staurosporine treatment did not affect viability of cells post-transduction, and there was no difference in in vitro colony formation compared to vehicle-treated cells. Xenotransplantation studies identified a statistically significant increase in VCN in engrafted human cells in mouse bone marrow at 4 months post-transplantation compared to vehicle-treated cells. Prostaglandin E2 (PGE2 is known to increase transduction efficiency of HSPCs through a different mechanism. Combining staurosporine and PGE2 resulted in further enhancement of transduction efficiency, particularly in short-term HSPCs. The combinatorial use of small molecules, such as staurosporine and PGE2, to enhance LVV transduction of human CD34+ cells is a promising method to improve transduction efficiency and subsequent potential therapeutic benefit of gene therapy drug products. Keywords: lentiviral, HSPC, transduction

  14. Polymerase chain reaction-based detection of myc transduction in feline leukemia virus-infected cats.

    Science.gov (United States)

    Sumi, Ryosuke; Miyake, Ariko; Endo, Taiji; Ohsato, Yoshiharu; Ngo, Minh Ha; Nishigaki, Kazuo

    2018-04-01

    Feline lymphomas are associated with the transduction and activation of cellular proto-oncogenes, such as c-myc, by feline leukemia virus (FeLV). We describe a polymerase chain reaction assay for detection of myc transduction usable in clinical diagnosis. The assay targets c-myc exons 2 and 3, which together result in a FeLV-specific fusion gene following c-myc transduction. When this assay was conducted on FeLV-infected feline tissues submitted for clinical diagnosis of tumors, myc transduction was detected in 14% of T-cell lymphoma/leukemias. This newly established system could become a useful diagnostic tool in veterinary medicine.

  15. Third colloquium in biological sciences: Cellular signal transduction

    International Nuclear Information System (INIS)

    Strand, F.L.

    1987-01-01

    This book contains over 100 papers. Some of the paper titles are: Characterization of Antibodies to DNA by Immunoadsorption on Cation-Complexed DNA; Simultaneous Evaluation of Radiochromatography Strips Using Gamma Camera Interfaced to a Computer; Simultaneous Quantification of Procine Myocardial Adenine Nucleotides and Creatine Phosphate by Ion-Pair Reverse-Phase High-Performance Liquid Chromatography; HPLC Analysis of Proteins from Alzheimer Paired Helical Filaments; and Internal Dosimetry Evaluations of Various Organs in Humans Using a Computerized Model

  16. Cationic polymers and their therapeutic potential

    NARCIS (Netherlands)

    Samal, S.K.; Dash, M.; van Vlierberghe, S.; Kaplan, D.; Chiellini, E.; van Blitterswijk, Clemens; Moroni, Lorenzo; Dubruel, P.

    2012-01-01

    The last decade has witnessed enormous research focused on cationic polymers. Cationic polymers are the subject of intense research as non-viral gene delivery systems, due to their flexible properties, facile synthesis, robustness and proven gene delivery efficiency. Here, we review the most recent

  17. Tripodal Receptors for Cation and Anion Sensors

    Directory of Open Access Journals (Sweden)

    David N. Reinhoudt

    2006-08-01

    Full Text Available This review discusses different types of artificial tripodal receptors for the selectiverecognition and sensing of cations and anions. Examples on the relationship between structure andselectivity towards cations and anions are described. Furthermore, their applications as potentiometricion sensing are emphasised, along with their potential applications in optical sensors or optodes.

  18. Asymmetric Aminalization via Cation-Binding Catalysis

    DEFF Research Database (Denmark)

    Park, Sang Yeon; Liu, Yidong; Oh, Joong Suk

    2018-01-01

    Asymmetric cation-binding catalysis, in principle, can generate "chiral" anionic nucleophiles, where the counter cations are coordinated within chiral environments. Nitrogen-nucleophiles are intrinsically basic, therefore, its use as nucleophiles is often challenging and limiting the scope of the...

  19. Structural and energetic study of cation-π-cation interactions in proteins.

    Science.gov (United States)

    Pinheiro, Silvana; Soteras, Ignacio; Gelpí, Josep Lluis; Dehez, François; Chipot, Christophe; Luque, F Javier; Curutchet, Carles

    2017-04-12

    Cation-π interactions of aromatic rings and positively charged groups are among the most important interactions in structural biology. The role and energetic characteristics of these interactions are well established. However, the occurrence of cation-π-cation interactions is an unexpected motif, which raises intriguing questions about its functional role in proteins. We present a statistical analysis of the occurrence, composition and geometrical preferences of cation-π-cation interactions identified in a set of non-redundant protein structures taken from the Protein Data Bank. Our results demonstrate that this structural motif is observed at a small, albeit non-negligible frequency in proteins, and suggest a preference to establish cation-π-cation motifs with Trp, followed by Tyr and Phe. Furthermore, we have found that cation-π-cation interactions tend to be highly conserved, which supports their structural or functional role. Finally, we have performed an energetic analysis of a representative subset of cation-π-cation complexes combining quantum-chemical and continuum solvation calculations. Our results point out that the protein environment can strongly screen the cation-cation repulsion, leading to an attractive interaction in 64% of the complexes analyzed. Together with the high degree of conservation observed, these results suggest a potential stabilizing role in the protein fold, as demonstrated recently for a miniature protein (Craven et al., J. Am. Chem. Soc. 2016, 138, 1543). From a computational point of view, the significant contribution of non-additive three-body terms challenges the suitability of standard additive force fields for describing cation-π-cation motifs in molecular simulations.

  20. Willingness to pay for lipid-based nutrient supplements for young children in four urban sites of Ethiopia.

    Science.gov (United States)

    Segrè, Joel; Winnard, Kim; Abrha, Teweldebrhan Hailu; Abebe, Yewelsew; Shilane, David; Lapping, Karin

    2015-12-01

    Malnutrition in children under 5 years of age is pervasive in Ethiopia across all wealth quintiles. The objective of this study was to determine the willingness to pay (WTP) for a week's supply of Nutributter® (a lipid-based nutrient supplement, or LNS) through typical urban Ethiopian retail channels. In February, 2012, 128 respondents from 108 households with 6-24-month-old children had the opportunity to sample Nutributter® for 2 days in their homes as a complementary food. Respondents were asked directly and indirectly what they were willing to pay for the product, and then participated in market simulation where they could demonstrate their WTP through an exchange of real money for real product. Nearly all (96%) of the respondents had a positive WTP, and 25% were willing to pay the equivalent of at least $1.05, which we calculated as the likely minimum, unsubsidised Ethiopian retail price of Nutributter® for 1 week for one child. Respondents willing to pay at least $1.05 included urban men and women with children 6-24 months old from low-, middle- and high-wealth groups from four study sites across three cities. Additionally, we estimated the initial annual market size for Nutributter® in the cities where the study took place to be around $500 000. The study has important implications for retail distribution of LNS in Ethiopia, showing who the most likely customers could be, and also suggesting why the initial market may be too small to be of interest to food manufacturers seeking profit maximisation. © 2012 Blackwell Publishing Ltd.

  1. Prenatal lipid-based nutrient supplements increase cord leptin concentration in pregnant women from rural Burkina Faso.

    Science.gov (United States)

    Huybregts, Lieven; Roberfroid, Dominique; Lanou, Hermann; Meda, Nicolas; Taes, Youri; Valea, Innocent; D'Alessandro, Umberto; Kolsteren, Patrick; Van Camp, John

    2013-05-01

    In developing countries, prenatal lipid-based nutrient supplements (LNSs) were shown to increase birth size; however, the mechanism of this effect remains unknown. Cord blood hormone concentrations are strongly associated with birth size. Therefore, we hypothesize that LNSs increase birth size through a change in the endocrine regulation of fetal development. We compared the effect of daily prenatal LNSs with multiple micronutrient tablets on cord blood hormone concentrations using a randomized, controlled design including 197 pregnant women from rural Burkina Faso. Insulin-like growth factors (IGF) I and II, their binding proteins IGFBP-1 and IGFBP-3, leptin, cortisol, and insulin were quantified in cord sera using immunoassays. LNS was associated with higher cord blood leptin mainly in primigravidae (+57%; P = 0.02) and women from the highest tertile of BMI at study inclusion (+41%; P = 0.02). We did not find any significant LNS effects on other measured cord hormones. The observed increase in cord leptin was associated with a significantly higher birth weight. Cord sera from small-for-gestational age newborns had lower median IGF-I (-9 μg/L; P = 0.003), IGF-II (-79 μg/L; P = 0.003), IGFBP-3 (-0.7 μg/L; P = 0.007), and leptin (-1.0 μg/L; P = 0.016) concentrations but higher median cortisol (+18 μg/L; P = 0.037) concentrations compared with normally grown newborns. Prenatal LNS resulted in increased cord leptin concentrations in primigravidae and mothers with higher BMI at study inclusion. The elevated leptin concentrations could point toward a higher neonatal fat mass.

  2. Drug Solubility in Fatty Acids as a Formulation Design Approach for Lipid-Based Formulations: A Technical Note.

    Science.gov (United States)

    Lee, Yung-Chi; Dalton, Chad; Regler, Brian; Harris, David

    2018-06-06

    Lipid-based drug delivery systems have been intensively investigated as a means of delivering poorly water-soluble drugs. Upon ingestion, the lipases in the gastrointestinal tract digest lipid ingredients, mainly triglycerides, within the formulation into monoglycerides and fatty acids. While numerous studies have addressed the solubility of drugs in triglycerides, comparatively few publications have addressed the solubility of drugs in fatty acids, which are the end product of digestion and responsible for the solubility of drug within mixed micelles. The objective of this investigation was to explore the solubility of a poorly water-soluble drug in fatty acids and raise the awareness of the importance of drug solubility in fatty acids. The model API (active pharmaceutical ingredient), a weak acid, is considered a BCS II compound with an aqueous solubility of 0.02 μg/mL and predicted partition coefficient >7. The solubility of API ranged from 120 mg/mL to over 1 g/mL in fatty acids with chain lengths across the range C18 to C6. Hydrogen bonding was found to be the main driver of the solubilization of API in fatty acids. The solubility of API was significantly reduced by water uptake in caprylic acid but not in oleic acid. This report demonstrates that solubility data generated in fatty acids can provide an indication of the solubility of the drug after lipid digestion. This report also highlights the importance of measuring the solubility of drugs in fatty acids in the course of lipid formulation development.

  3. Mechanistic Insights in Ethylene Perception and Signal Transduction1

    Science.gov (United States)

    Ju, Chuanli; Chang, Caren

    2015-01-01

    The gaseous hormone ethylene profoundly affects plant growth, development, and stress responses. Ethylene perception occurs at the endoplasmic reticulum membrane, and signal transduction leads to a transcriptional cascade that initiates diverse responses, often in conjunction with other signals. Recent findings provide a more complete picture of the components and mechanisms in ethylene signaling, now rendering a more dynamic view of this conserved pathway. This includes newly identified protein-protein interactions at the endoplasmic reticulum membrane, as well as the major discoveries that the central regulator ETHYLENE INSENSITIVE2 (EIN2) is the long-sought phosphorylation substrate for the CONSTITUTIVE RESPONSE1 protein kinase, and that cleavage of EIN2 transmits the signal to the nucleus. In the nucleus, hundreds of potential gene targets of the EIN3 master transcription factor have been identified and found to be induced in transcriptional waves, and transcriptional coregulation has been shown to be a mechanism of ethylene cross talk. PMID:26246449

  4. Piezoelectric Multilayer-Stacked Hybrid Actuation/Transduction System

    Science.gov (United States)

    Xu, Tian-Bing (Inventor); Jiang, Xiaoning (Inventor); Su, Ji (Inventor)

    2014-01-01

    A novel full piezoelectric multilayer stacked hybrid actuation/transduction system. The system demonstrates significantly-enhanced electromechanical performance by utilizing the cooperative contributions of the electromechanical responses of multilayer stacked negative and positive strain components. Both experimental and theoretical studies indicate that for this system, the displacement is over three times that of a same-sized conventional flextensional actuator/transducer. The system consists of at least 2 layers which include electromechanically active components. The layers are arranged such that when electric power is applied, one layer contracts in a transverse direction while the second layer expands in a transverse direction which is perpendicular to the transverse direction of the first layer. An alternate embodiment includes a third layer. In this embodiment, the outer two layers contract in parallel transverse directions while the middle layer expands in a transverse direction which is perpendicular to the transverse direction of the outer layers.

  5. Exploring backbone-cation alkyl spacers for multi-cation side chain anion exchange membranes

    Science.gov (United States)

    Zhu, Liang; Yu, Xuedi; Hickner, Michael A.

    2018-01-01

    In order to systematically study how the arrangement of cations on the side chain and length of alkyl spacers between cations impact the performance of multi-cation AEMs for alkaline fuel cells, a series of polyphenylene oxide (PPO)-based AEMs with different cationic side chains were synthesized. This work resulted in samples with two or three cations in a side chain pendant to the PPO backbone. More importantly, the length of the spacer between cations varied from 3 methylene (-CH2-) (C3) groups to 8 methylene (C8) groups. The highest conductivity, up to 99 mS/cm in liquid water at room temperature, was observed for the triple-cation side chain AEM with pentyl (C5) or hexyl (C6) spacers. The multi-cation AEMs were found to have decreased water uptake and ionic conductivity when the spacer chains between cations were lengthened from pentyl (C5) or hexyl (C6) to octyl (C8) linking groups. The triple-cation membranes with pentyl (C5) or hexyl (C6) groups between cations showed greatest stability after immersion in 1 M NaOH at 80 °C for 500 h.

  6. Influence of Unweighting on Insulin Signal Transduction in Muscle

    Science.gov (United States)

    Tischler, Marc E.

    2002-01-01

    Unweighting of the juvenile soleus muscle is characterized by an increased binding capacity for insulin relative to muscle mass due to sparing of the receptors during atrophy. Although carbohydrate metabolism and protein degradation in the unweighted muscle develop increased sensitivity to insulin in vivo, protein synthesis in vivo and system A amino acid transport in vitro do not appear to develop such an enhanced response. The long-term goal is to identify the precise nature of this apparent resistance in the insulin signal transduction pathway and to consider how reduced weight-bearing may elicit this effect, by evaluating specific components of the insulin signalling pathway. Because the insulin-signalling pathway has components in common with the signal transduction pathway for insulin-like growth factor (IGF-1) and potentially other growth factors, the study could have important implications in the role of weight-bearing function on muscle growth and development. Since the insulin signalling pathway diverges following activation of insulin receptor tyrosine kinase, the immediate specific aims will be to study the receptor tyrosine kinase (IRTK) and those branches, which lead to phosphorylation of insulin receptor substrate-1 (IRS-1) and of Shc protein. To achieve these broader objectives, we will test in situ, by intramuscular injection, the responses of glucose transport, system A amino acid transport and protein synthesis to insulin analogues for which the receptor has either a weaker or much stronger binding affinity compared to insulin. Studies will include: (1) estimation of the ED(sub 50) for each analogue for these three processes; (2) the effect of duration (one to four days) of unweighting on the response of each process to all analogues tested; (3) the effect of unweighting and the analogues on IRTK activity; and (4) the comparative effects of unweighting and analogue binding on the tyrosine phosphorylation of IRTK, IRS-1, and Shc protein.

  7. [Effects of a lipid-based nutrient supplement on hemoglobin levels and anthropometric indicators in children from five districts in Huánuco Peru].

    Science.gov (United States)

    Vargas-Vásquez, Alejandro; Bado, Ricardo; Alcázar, Lorena; Aquino, Oscar; Rodríguez, Amelia; Novalbos, José Pedro

    2015-01-01

    Objectives . To determine the effect of consumption of a lipid-based nutrient supplement (LNS) on hemoglobin levels, anemia and anthropometric indicators in children aged six to eleven months old in five districts in the province of Ambo in the region of Huanuco, Peru. A pre-experimental, pre-post study was performed. The study population included children aged six to eleven months old in 19 health facilities in five districts with very high vulnerability to chronic malnutrition in the province of Ambo, Huanuco. Data from 147 children who received the lipid-based nutrient supplement (LNS) from six to eleven months old were obtained. The mean hemoglobin significantly increased by 0.67 g/dL (panemia dropped by 27 percentage points (panemia in children under twelve months, which might constitute an effective alternative to prevent and control childhood anemia.

  8. The Use of Quasi-Isothermal Modulated Temperature Differential Scanning Calorimetry for the Characterization of Slow Crystallization Processes in Lipid-Based Solid Self-Emulsifying Systems

    OpenAIRE

    Otun, Sarah O.; Meehan, Elizabeth; Qi, Sheng; Craig, Duncan Q. M.

    2014-01-01

    Purpose Slow or incomplete crystallization may be a significant manufacturing issue for solid lipid-based dosage forms, yet little information is available on this phenomenon. In this investigation we suggest a novel means by which slow solidification may be monitored in Gelucire 44/14 using quasi-isothermal modulated temperature DSC (QiMTDSC). Methods Conventional linear heating and cooling DSC methods were employed, along with hot stage microscopy (HSM), for basic thermal profiling of Geluc...

  9. Cation transport in isomeric pentanes

    International Nuclear Information System (INIS)

    Gyoergy, Istvan; Gee, Norman; Freeman, G.R.

    1985-01-01

    The cation mobility μsub(+) is measured in n-pentane, isopentane, neo-pentane, and mixtures of n- and neo-pentane over conditions from the normal liquid, through the critical fluid, to the low density gas. Most of the liquid data correlate with the reduced temperature T/Tsub(c). The T/Tsub(c) reflects free volume and viscosity changes. Comparison is made to neutral molecule diffusion. The transition from viscosity control of mobility in the liquid to density control in the dilute gas occurs over the reduced viscosity region 3 > eta/etasub(c) > 0.6, which corresponds to the reduced density region 1.9 > eta/etasub(c) > 0.5. In the saturated gas etaμsub(+) is similar in all pentanes, but iso- approximately> n- > neo-pentane. At constant density dμsub(+)/dT >= 0 for gases. The average gas nμsub(+) is similar in all pentanes, but iso- approximately> n- > neo-pentane. At constant density dμsub(+)/dT >= 0 for gases. The average momentum transfer cross sections in the n-/neo-pentane mixtures are similar to those in neo-pentane at low T but similar to those in n-pentane at high T. The present findings are combined with previous electron mobility data in addressing the effect of hydrocarbon molecular (external) shape on the electric breakdown strength of gases

  10. Cationic Bolaamphiphiles for Gene Delivery

    Science.gov (United States)

    Tan, Amelia Li Min; Lim, Alisa Xue Ling; Zhu, Yiting; Yang, Yi Yan; Khan, Majad

    2014-05-01

    Advances in medical research have shed light on the genetic cause of many human diseases. Gene therapy is a promising approach which can be used to deliver therapeutic genes to treat genetic diseases at its most fundamental level. In general, nonviral vectors are preferred due to reduced risk of immune response, but they are also commonly associated with low transfection efficiency and high cytotoxicity. In contrast to viral vectors, nonviral vectors do not have a natural mechanism to overcome extra- and intracellular barriers when delivering the therapeutic gene into cell. Hence, its design has been increasingly complex to meet challenges faced in targeting of, penetration of and expression in a specific host cell in achieving more satisfactory transfection efficiency. Flexibility in design of the vector is desirable, to enable a careful and controlled manipulation of its properties and functions. This can be met by the use of bolaamphiphile, a special class of lipid. Unlike conventional lipids, bolaamphiphiles can form asymmetric complexes with the therapeutic gene. The advantage of having an asymmetric complex lies in the different purposes served by the interior and exterior of the complex. More effective gene encapsulation within the interior of the complex can be achieved without triggering greater aggregation of serum proteins with the exterior, potentially overcoming one of the great hurdles faced by conventional single-head cationic lipids. In this review, we will look into the physiochemical considerations as well as the biological aspects of a bolaamphiphile-based gene delivery system.

  11. Multidrug resistance and retroviral transduction potential in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Theilade, M D; Gram, G J; Jensen, P B

    1999-01-01

    of blue colonies after X-Gal staining of the cells grown in soft agar. All examined SCLC cell lines were transducible with either vector. Transduction efficiencies varied from 5.7% to 33.5% independent of the presence of MDR. These results indicate that MDR does not severely impair transduction of SCLC...

  12. Stressor states and the cation crossroads.

    Science.gov (United States)

    Weber, Karl T; Bhattacharya, Syamal K; Newman, Kevin P; Soberman, Judith E; Ramanathan, Kodangudi B; McGee, Jesse E; Malik, Kafait U; Hickerson, William L

    2010-12-01

    Neurohormonal activation involving the hypothalamic-pituitary-adrenal axis and adrenergic nervous and renin-angiotensin-aldosterone systems is integral to stressor state-mediated homeostatic responses. The levels of effector hormones, depending upon the degree of stress, orchestrate the concordant appearance of hypokalemia, ionized hypocalcemia and hypomagnesemia, hypozincemia, and hyposelenemia. Seemingly contradictory to homeostatic responses wherein the constancy of extracellular fluid would be preserved, upregulation of cognate-binding proteins promotes coordinated translocation of cations to injured tissues, where they participate in wound healing. Associated catecholamine-mediated intracellular cation shifts regulate the equilibrium between pro-oxidants and antioxidant defenses, a critical determinant of cell survival. These acute and chronic stressor-induced iterations in extracellular and intracellular cations are collectively referred to as the cation crossroads. Intracellular cation shifts, particularly excessive accumulation of Ca2+, converge on mitochondria to induce oxidative stress and raise the opening potential of their inner membrane permeability transition pores (mPTPs). The ensuing loss of cationic homeostasis and adenosine triphosphate (ATP) production, together with osmotic swelling, leads to organellar degeneration and cellular necrosis. The overall impact of iterations in extracellular and intracellular cations and their influence on cardiac redox state, cardiomyocyte survival, and myocardial structure and function are addressed herein.

  13. The Role of Cgrp-Receptor Component Protein (Rcp in Cgrp-Mediated Signal Transduction

    Directory of Open Access Journals (Sweden)

    M. A. Prado

    2001-01-01

    Full Text Available The calcitonin gene-related peptide (CGRP-receptor component protein (RCP is a 17-kDa intracellular peripheral membrane protein required for signal transduction at CGRP receptors. To determine the role of RCP in CGRP-mediated signal transduction, RCP was depleted from NIH3T3 cells using antisense strategy. Loss of RCP protein correlated with loss of cAMP production by CGRP in the antisense cells. In contrast, loss of RCP had no effect on CGRP-mediated binding; therefore RCP is not acting as a chaperone for the CGRP receptor. Instead, RCP is a novel signal transduction molecule that couples the CGRP receptor to the cellular signal transduction machinery. RCP thus represents a prototype for a new class of signal transduction proteins that are required for regulation of G protein-coupled receptors.

  14. Cation distributions on rapidly solidified cobalt ferrite

    Science.gov (United States)

    De Guire, Mark R.; Kalonji, Gretchen; O'Handley, Robert C.

    1990-01-01

    The cation distributions in two rapidly solidified cobalt ferrites have been determined using Moessbauer spectroscopy at 4.2 K in an 8-T magnetic field. The samples were obtained by gas atomization of a Co0-Fe2O3-P2O5 melt. The degree of cation disorder in both cases was greater than is obtainable by cooling unmelted cobalt ferrite. The more rapidly cooled sample exhibited a smaller departure from the equilibrium cation distribution than did the more slowly cooled sample. This result is explained on the basis of two competing effects of rapid solidification: high cooling rate of the solid, and large undercooling.

  15. Radioimmunoassay of human eosinophil cationic protein

    International Nuclear Information System (INIS)

    Venge, P.; Roxin, L.E.; Olsson, I.

    1977-01-01

    A radioimmunosorbent assay has been developed which allows the detection in serum of a cationic protein derived from eosinophil granulocytes. In 34 healthy individuals the mean level was 31 μg/l. with a range of 5 to 55 μg/l. The serum concentration of 'eosinophil' cationic protein was correlated (P<0.001) to the number of eosinophil granulocytes in peripheral blood. Quantitiation of 'eosinophil' cationic protein in serum might be useful in the study of eosinophil granulocyte turnover and function in vivo. (author)

  16. Elucidation of the outer membrane proteome of Salmonella enterica serovar Typhimurium utilising a lipid-based protein immobilization technique

    Directory of Open Access Journals (Sweden)

    Appleton Hazel

    2010-02-01

    Full Text Available Abstract Background Salmonella enterica serovar Typhimurium (S. Typhimurium is a major cause of human gastroenteritis worldwide. The outer membrane proteins expressed by S. Typhimurium mediate the process of adhesion and internalisation within the intestinal epithelium of the host thus influencing the progression of disease. Since the outer membrane proteins are surface-exposed, they provide attractive targets for the development of improved antimicrobial agents and vaccines. Various techniques have been developed for their characterisation, but issues such as carryover of cytosolic proteins still remain a problem. In this study we attempted to characterise the surface proteome of S. Typhimurium using Lipid-based Protein Immobilisation technology in the form of LPI™ FlowCells. No detergents are required and no sample clean up is needed prior to downstream analysis. The immobilised proteins can be digested with proteases in multiple steps to increase sequence coverage, and the peptides eluted can be characterised directly by liquid chromatography - tandem mass spectrometry (LC-MS/MS and identified from mass spectral database searches. Results In this study, 54 outer membrane proteins, were identified with two or more peptide hits using a multi-step digest approach. Out of these 28 were lipoproteins, nine were involved in transport and three with enzyme activity These included the transporters BtuB which is responsible for the uptake of vitamin B12, LamB which is involved in the uptake of maltose and maltodextrins and LolB which is involved in the incorporation of lipoproteins in the outer membrane. Other proteins identified included the enzymes MltC which may play a role in cell elongation and division and NlpD which is involved in catabolic processes in cell wall formation as well as proteins involved in virulence such as Lpp1, Lpp2 and OmpX. Conclusion Using a multi-step digest approach the LPI™ technique enables the incorporation of a

  17. Outcomes associated with conventional versus lipid-based formulations of amphotericin B in propensity-matched groups

    Directory of Open Access Journals (Sweden)

    Campbell RS

    2013-10-01

    Full Text Available Rebecca S Campbell,1 Paresh Chaudhari,2 Harlen D Hays,1 Robert J Taylor,1 Brian H Nathanson,3 Samuel A Bozzette,1 David Horn4 1Cerner Research, Culver City, CA, USA; 2Astellas Scientific and Medical Affairs, Inc., Northbrook, IL, USA; 3OptiStatim, LLC, Longmeadow, MA, USA; 4David Horn LLC, Doylestown, PA, USA Background: Lipid-based formulations of amphotericin B (LF-AMB are indicated for treatment of invasive fungal infections in patients intolerant to conventional amphotericin B (CAB or with refractory infections. Physicians still may choose to administer CAB to such patients. We described the use of CAB and LF-AMB in this population and quantified differences in post-amphotericin B length of stay (LOS among survivors and hospital mortality in matched patients. Methods: Data were extracted from Health Facts (Cerner Corporation, Kansas City, MO, USA for a retrospective cohort analysis. Inpatients aged ≥18 years with evidence of fungal infection and with orders for LF-AMB or CAB on  ≥2 days from January 2001 to June 2010 were identified. Patients were required to have renal insufficiency or other relative contraindications to use of CAB, exposure to nephrotoxic agents, or evidence of a CAB-refractory infection. Multilevel (hierarchical mixed-effects logistic regression was used to determine factors associated with initial exposure to LF-AMB versus CAB. Multivariate adjustment of outcomes was done using propensity score matching. Results: 655 patients were identified: 322 patients initiated therapy with CAB and 333 initiated treatment with LF-AMB. Compared to those initiating CAB, patients initiating LF-AMB had greater acuity and underlying disease severity. In unadjusted analyses, hospital mortality was significantly higher in the LF-AMB group (32.2% versus 23.7%; P = 0.02. After propensity score matching and covariate adjustment, mortality equalized and observed differences in LOS after amphotericin B initiation decreased. Conclusion

  18. Genetic Analysis of Gravity Signal Transduction in Arabidopsis thaliana Seedlings

    Science.gov (United States)

    Boonsirichai, K.; Harrison, B.; Stanga, J.; Young, L.-S.; Neal, C.; Sabat, G.; Murthy, N.; Harms, A.; Sedbrook, J.; Masson, P.

    The primary roots of Arabidopsis thaliana seedlings respond to gravity stimulation by developing a tip curvature that results from differential cellular elongation on opposite flanks of the elongation zone. This curvature appears modulated by a lateral gradient of auxin that originates in the gravity-perceiving cells (statocytes) of the root cap through an apparent lateral repositioning of a component the auxin efflux carrier complex within these cells (Friml et al, 2002, Nature 415: 806-809). Unfortunately, little is known about the molecular mechanisms that govern early phases of gravity perception and signal transduction within the root-cap statocytes. We have used a molecular genetic approach to uncover some of these mechanisms. Mutations in the Arabidopsis ARG1 and ARL2 genes, which encode J-domain proteins, resulted in specific alterations in root and hypocotyl gravitropism, without pleiotropic phenotypes. Interestingly, ARG1 and ARL2 appear to function in the same genetic pathway. A combination of molecular genetic, biochemical and cell-biological approaches were used to demonstrate that ARG1 functions in early phases of gravity signal transduction within the root and hypocotyl statocytes, and is needed for efficient lateral auxin transport within the cap. The ARG1 protein is associated with components of the secretory and/or endosomal pathways, suggesting its role in the recycling of components of the auxin efflux carrier complex between plasma membrane and endosome (Boonsirichai et al, 2003, Plant Cell 15:2612-2625). Genetic modifiers of arg1-2 were isolated and shown to enhance the gravitropic defect of arg1-2, while resulting in little or no gravitropic defects in a wild type ARG1 background. A slight tendency for arg1-2;mar1-1 and arg1-2;mar2-1 double-mutant organs to display an opposite gravitropic response compared to wild type suggests that all three genes contribute to the interpretation of the gravity-vector information by seedling organs. The

  19. Cationization of heparin for film applications

    Czech Academy of Sciences Publication Activity Database

    Šimkovic, I.; Mendichi, R.; Kelnar, Ivan; Filip, J.; Hricovíni, M.

    2015-01-01

    Roč. 115, 22 January (2015), s. 551-558 ISSN 0144-8617 Institutional support: RVO:61389013 Keywords : heparin * cationization * NMR Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.219, year: 2015

  20. Test procedure for cation exchange chromatography

    International Nuclear Information System (INIS)

    Cooper, T.D.

    1994-01-01

    The purpose of this test plan is to demonstrate the synthesis of inorganic antimonate ion exchangers and compare their performance against the standard organic cation exchangers. Of particular interest is the degradation rate of both inorganic and organic cation exchangers. This degradation rate will be tracked by determining the ion exchange capacity and thermal stability as a function of time, radiation dose, and chemical reaction

  1. Cycloaliphatic epoxide resins for cationic UV - cure

    International Nuclear Information System (INIS)

    Verschueren, K.; Balwant Kaur

    1999-01-01

    This paper introduces the cyclo - aliphatic epoxide resins used for the various applications of radiation curing and their comparison with acrylate chemistry. Radiation curable coatings and inks are pre - dominantly based on acrylate chemistry but over the last few years, cationic chemistry has emerged successfully with the unique properties inherent with cyclo - aliphatic epoxide ring structures. Wide variety of cationic resins and diluents, the formulation techniques to achieve the desired properties greatly contributes to the advancement of UV - curing technology

  2. Chemical reactivity of cation-exchanged zeolites

    OpenAIRE

    Pidko, E.A.

    2008-01-01

    Zeolites modified with metal cations have been extensively studied during the last two decades because of their wide application in different technologically important fields such as catalysis, adsorption and gas separation. Contrary to the well-understood mechanisms of chemical reactions catalyzed by Brønsted acid sites in the hydrogen forms of zeolites, the nature of chemical reactivity, and related, the structure of the metal-containing ions in cation-exchanged zeolites remains the subject...

  3. Restructuring of a peat in interaction with multivalent cations: effect of cation type and aging time.

    Science.gov (United States)

    Kunhi Mouvenchery, Yamuna; Jaeger, Alexander; Aquino, Adelia J A; Tunega, Daniel; Diehl, Dörte; Bertmer, Marko; Schaumann, Gabriele Ellen

    2013-01-01

    It is assumed to be common knowledge that multivalent cations cross-link soil organic matter (SOM) molecules via cation bridges (CaB). The concept has not been explicitly demonstrated in solid SOM by targeted experiments, yet. Therefore, the requirements for and characteristics of CaB remain unidentified. In this study, a combined experimental and molecular modeling approach was adopted to investigate the interaction of cations on a peat OM from physicochemical perspective. Before treatment with salt solutions of Al(3+), Ca(2+) or Na(+), respectively, the original exchangeable cations were removed using cation exchange resin. Cation treatment was conducted at two different values of pH prior to adjusting pH to 4.1. Cation sorption is slower (>2 h) than deprotonation of functional groups (cation addition and decreased with increasing cation valency. Sorption coefficients were similar for all cations and at both pH. This contradicts the general expectations for electrostatic interactions, suggesting that not only the interaction chemistry but also spatial distribution of functional groups in OM determines binding of cations in this peat. The reaction of contact angle, matrix rigidity due to water molecule bridges (WaMB) and molecular mobility of water (NMR analysis) suggested that cross-linking via CaB has low relevance in this peat. This unexpected finding is probably due to the low cation exchange capacity, resulting in low abundance of charged functionalities. Molecular modeling demonstrates that large average distances between functionalities (∼3 nm in this peat) cannot be bridged by CaB-WaMB associations. However, aging strongly increased matrix rigidity, suggesting successive increase of WaMB size to connect functionalities and thus increasing degree of cross-linking by CaB-WaMB associations. Results thus demonstrated that the physicochemical structure of OM is decisive for CaB and aging-induced structural reorganisation can enhance cross-link formation.

  4. Formation of radical cations of diaryloxadiazoles

    International Nuclear Information System (INIS)

    Helmstreit, W.

    1988-01-01

    The nature of the formation of the radical cation of the 2,5-bis-(p-diethylaminophenyl)-1,3,4-oxadiazole (PC) in liquid n-butyl chloride and acetonitrile has been investigated by observing excited state fluorescence and transient absorption using nanosecond pulse radiolysis and laser flash photolysis. The formation of solute oxonium ions has also been observed. At concentrations -4 mol dm -3 the growth time at which the transient absorption of the radical cation reaches the maximum follows the rise time of the electron pulse ( 2 laser yields the solute radical cation in an acetonitrile solution of 2 x 10 -4 mol dm -3 PC via an electronically excited state. Here, the generation time was smaller than 5 ns. The yield of the cation is increased by addition of CCl 4 . A reaction mechanism is proposed that explains the fast cation formation in terms of an exciplex formed by interaction between an electronically excited state of diaryloxadiazole and the ground state of the solvent. This exciplex yields the solute radical cation. (author)

  5. Luminescent sulfides of monovalent and trivalent cations

    International Nuclear Information System (INIS)

    1975-01-01

    The invention discloses a family of luminescent materials or phosphors having a rhombohedral crystal structure and consisting essentially of a mixed host sulfide of at least one monovalent host cation and at least one trivalent host cation, and containing, for each mole of phosphor, 0.0005 to 0.05 mole of at least one activating cation. The monovalent host cations may be Na, K or Rb and Cs. The trivalent host cations may be Gd, La, Lu, Sc and Y. The activating cations may be one or more of trivalent As, Bi, Ce, Dy, Er, Pr, Sb, Sm, Tb and Tm; divalent Lu, Mn, Pb and Sn; and monovalent Ag, Cu and Tl. The novel phosphors may be used in devices to convert electron-beam, ultraviolet or x-ray energy to light in the visible spectrum. Such energy conversion can be employed for example in fluoroscopic screens, and in viewing screens of cathode-ray tubes and other electron tubes

  6. Divalent cation shrinks DNA but inhibits its compaction with trivalent cation.

    Science.gov (United States)

    Tongu, Chika; Kenmotsu, Takahiro; Yoshikawa, Yuko; Zinchenko, Anatoly; Chen, Ning; Yoshikawa, Kenichi

    2016-05-28

    Our observation reveals the effects of divalent and trivalent cations on the higher-order structure of giant DNA (T4 DNA 166 kbp) by fluorescence microscopy. It was found that divalent cations, Mg(2+) and Ca(2+), inhibit DNA compaction induced by a trivalent cation, spermidine (SPD(3+)). On the other hand, in the absence of SPD(3+), divalent cations cause the shrinkage of DNA. As the control experiment, we have confirmed the minimum effect of monovalent cation, Na(+) on the DNA higher-order structure. We interpret the competition between 2+ and 3+ cations in terms of the change in the translational entropy of the counterions. For the compaction with SPD(3+), we consider the increase in translational entropy due to the ion-exchange of the intrinsic monovalent cations condensing on a highly charged polyelectrolyte, double-stranded DNA, by the 3+ cations. In contrast, the presence of 2+ cation decreases the gain of entropy contribution by the ion-exchange between monovalent and 3+ ions.

  7. Mannotriose regulates learning and memory signal transduction in the hippocampus

    Institute of Scientific and Technical Information of China (English)

    Lina Zhang; Weiwei Dai; Xueli Zhang; Zhangbin Gong; Guoqin Jin

    2013-01-01

    Rehmannia is a commonly used Chinese herb, which improves learning and memory. However, the crucial components of the signal transduction pathway associated with this effect remain elusive. Pri-mary hippocampal neurons were cultured in vitro, insulted with high-concentration (1 × 10-4 mol/L) cor-ticosterone, and treated with 1 × 10-4 mol/L mannotriose. Thiazolyl blue tetrazolium bromide assay and western blot analysis showed that hippocampal neuron survival rates and protein levels of glucocorti-coid receptor, serum and glucocorticoid-regulated protein kinase, and brain-derived neurotrophic factor were al dramatical y decreased after high-concentration corticosterone-induced injury. This effect was reversed by mannotriose, to a similar level as RU38486 and donepezil. Our findings indicate that mannotriose could protect hippocampal neurons from high-concentration corticosterone-induced injury. The mechanism by which this occurred was associated with levels of glucocorticoid receptor protein, serum and glucocorticoid-regulated protein kinase, and brain-derived neurotrophic factor.

  8. The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

    Science.gov (United States)

    Keegan, A D; Pierce, J H

    1994-02-01

    Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

  9. Modulation of signal transduction by tea catechins and related phytochemicals

    International Nuclear Information System (INIS)

    Shimizu, Masahito; Weinstein, I. Bernard

    2005-01-01

    Epidemiologic studies in human populations and experimental studies in rodents provide evidence that green tea and its constituents can inhibit both the development and growth of tumors at a variety of tissue sites. In addition, EGCG, a major biologically active component of green tea, inhibits growth and induces apoptosis in a variety of cancer cell lines. The purpose of this paper is to review evidence that these effects are mediated, at least in part, through inhibition of the activity of specific receptor tyrosine kinases (RTKs) and related downstream pathways of signal transduction. We also review evidence indicating that the antitumor effects of the related polyphenolic phytochemicals resveratrol, genistein, curcumin, and capsaicin are exerted via similar mechanisms. Some of these agents (EGCG, genistein, and curcumin) appear to directly target specific RTKs, and all of these compounds cause inhibition of the activity of the transcription factors AP-1 and NF-κB, thus inhibiting cell proliferation and enhancing apoptosis. Critical areas of future investigation include: (1) identification of the direct molecular target(s) of EGCG and related polyphenolic compounds in cells; (2) the in vivo metabolism and bioavailability of these compounds; (3) the ancillary effects of these compounds on tumor-stromal interactions; (4) the development of synergistic combinations with other antitumor agents to enhance efficacy in cancer prevention and therapy, and also minimize potential toxicities

  10. Fenspiride and membrane transduction signals in rat alveolar macrophages.

    Science.gov (United States)

    Féray, J C; Mohammadi, K; Taouil, K; Brunet, J; Garay, R P; Hannaert, P

    1997-07-15

    Fenspiride inhibits the calcium signal evoked by the inflammatory peptide formyl-Met-Leu-Phe (fMLP) in peritoneal macrophages, but at concentrations (approximately 1 mM) far above the therapeutic range (approximately 1 microM). Here, in rat alveolar macrophages, high fenspiride concentrations (1 mM) were required to inhibit the calcium signals evoked by the calcium agonist Bay K8644 or by ionomycin. Moreover, fenspiride (1 mM) was a poor inhibitor of the cell membrane depolarization induced by gramicidine D. By contrast, fenspiride blocked Na+-H+ antiport activation by (i) fMLP with an IC50 = 3.1 +/- 1.9 nM and (ii) PMA (phorbol 12-myristate 13-acetate) with an IC50 = 9.2 +/- 3.1 nM. Finally, protein kinase C (PKC) activity of macrophage homogenate was not significantly modified by 10 or 100 microM fenspiride (at 100 microM: 2.57 +/- 1.60 vs. 2.80 +/- 1.71 pmol/10(6) cells/min). In conclusion, fenspiride inhibits fMLP- and PMA-induced pH signals in rat alveolar macrophages, probably by acting distally on the PKC transduction signal. This pH antagonistic action may be relevant for the antiinflammatory mechanism of fenspiride and requires further investigation.

  11. Structural basis for energy transduction by respiratory alternative complex III.

    Science.gov (United States)

    Sousa, Joana S; Calisto, Filipa; Langer, Julian D; Mills, Deryck J; Refojo, Patrícia N; Teixeira, Miguel; Kühlbrandt, Werner; Vonck, Janet; Pereira, Manuela M

    2018-04-30

    Electron transfer in respiratory chains generates the electrochemical potential that serves as energy source for the cell. Prokaryotes can use a wide range of electron donors and acceptors and may have alternative complexes performing the same catalytic reactions as the mitochondrial complexes. This is the case for the alternative complex III (ACIII), a quinol:cytochrome c/HiPIP oxidoreductase. In order to understand the catalytic mechanism of this respiratory enzyme, we determined the structure of ACIII from Rhodothermus marinus at 3.9 Å resolution by single-particle cryo-electron microscopy. ACIII presents a so-far unique structure, for which we establish the arrangement of the cofactors (four iron-sulfur clusters and six c-type hemes) and propose the location of the quinol-binding site and the presence of two putative proton pathways in the membrane. Altogether, this structure provides insights into a mechanism for energy transduction and introduces ACIII as a redox-driven proton pump.

  12. Signal transduction in cells of the immune system in microgravity

    Directory of Open Access Journals (Sweden)

    Huber Kathrin

    2008-10-01

    Full Text Available Abstract Life on Earth developed in the presence and under the constant influence of gravity. Gravity has been present during the entire evolution, from the first organic molecule to mammals and humans. Modern research revealed clearly that gravity is important, probably indispensable for the function of living systems, from unicellular organisms to men. Thus, gravity research is no more or less a fundamental question about the conditions of life on Earth. Since the first space missions and supported thereafter by a multitude of space and ground-based experiments, it is well known that immune cell function is severely suppressed in microgravity, which renders the cells of the immune system an ideal model organism to investigate the influence of gravity on the cellular and molecular level. Here we review the current knowledge about the question, if and how cellular signal transduction depends on the existence of gravity, with special focus on cells of the immune system. Since immune cell function is fundamental to keep the organism under imnological surveillance during the defence against pathogens, to investigate the effects and possible molecular mechanisms of altered gravity is indispensable for long-term space flights to Earth Moon or Mars. Thus, understanding the impact of gravity on cellular functions on Earth will provide not only important informations about the development of life on Earth, but also for therapeutic and preventive strategies to cope successfully with medical problems during space exploration.

  13. Signal transduction by the platelet-derived growth factor receptor

    International Nuclear Information System (INIS)

    Williams, L.T.; Escobedo, J.A.; Keating, M.T.; Coughlin, S.R.

    1988-01-01

    The mitogenic effects of platelet-derived growth factor (PDGF) are mediated by the PDGF receptor. The mouse PDGF receptor was recently purified on the basis of its ability to become tyrosine phosphorylated in response to the A-B human platelet form of PDGF, and the receptor amino acid sequence was determined from a full-length cDNA clone. Both the human and mouse receptor cDNA sequences have been expressed in Chinese hamster ovary fibroblast (CHO) cells that normally lack PDGF receptors. This paper summarizes recent results using this system to study signal transduction by the PDGF receptor. Some of the findings show that the KI domain of the PDGF receptor plays an important role in the stimulation of DNA synthesis by PDGF. Surprisingly, the kinase insert region is not essential for PDGF stimulation of PtdIns turnover, pH change, increase in cellular calcium, and receptor autophosphorylation. In addition, PDGF stimulates a conformational change in the receptor

  14. Metformin selectively targets redox control of complex I energy transduction

    Directory of Open Access Journals (Sweden)

    Amy R. Cameron

    2018-04-01

    Full Text Available Many guanide-containing drugs are antihyperglycaemic but most exhibit toxicity, to the extent that only the biguanide metformin has enjoyed sustained clinical use. Here, we have isolated unique mitochondrial redox control properties of metformin that are likely to account for this difference. In primary hepatocytes and H4IIE hepatoma cells we found that antihyperglycaemic diguanides DG5-DG10 and the biguanide phenformin were up to 1000-fold more potent than metformin on cell signalling responses, gluconeogenic promoter expression and hepatocyte glucose production. Each drug inhibited cellular oxygen consumption similarly but there were marked differences in other respects. All diguanides and phenformin but not metformin inhibited NADH oxidation in submitochondrial particles, indicative of complex I inhibition, which also corresponded closely with dehydrogenase activity in living cells measured by WST-1. Consistent with these findings, in isolated mitochondria, DG8 but not metformin caused the NADH/NAD+ couple to become more reduced over time and mitochondrial deterioration ensued, suggesting direct inhibition of complex I and mitochondrial toxicity of DG8. In contrast, metformin exerted a selective oxidation of the mitochondrial NADH/NAD+ couple, without triggering mitochondrial deterioration. Together, our results suggest that metformin suppresses energy transduction by selectively inducing a state in complex I where redox and proton transfer domains are no longer efficiently coupled. Keywords: Diabetes, Metformin, Mitochondria, NADH, NAD+

  15. Phosphoproteomics-based systems analysis of signal transduction networks

    Directory of Open Access Journals (Sweden)

    Hiroko eKozuka-Hata

    2012-01-01

    Full Text Available Signal transduction systems coordinate complex cellular information to regulate biological events such as cell proliferation and differentiation. Although the accumulating evidence on widespread association of signaling molecules has revealed essential contribution of phosphorylation-dependent interaction networks to cellular regulation, their dynamic behavior is mostly yet to be analyzed. Recent technological advances regarding mass spectrometry-based quantitative proteomics have enabled us to describe the comprehensive status of phosphorylated molecules in a time-resolved manner. Computational analyses based on the phosphoproteome dynamics accelerate generation of novel methodologies for mathematical analysis of cellular signaling. Phosphoproteomics-based numerical modeling can be used to evaluate regulatory network elements from a statistical point of view. Integration with transcriptome dynamics also uncovers regulatory hubs at the transcriptional level. These omics-based computational methodologies, which have firstly been applied to representative signaling systems such as the epidermal growth factor receptor pathway, have now opened up a gate for systems analysis of signaling networks involved in immune response and cancer.

  16. Signal transduction around thymic stromal lymphopoietin (TSLP in atopic asthma

    Directory of Open Access Journals (Sweden)

    Kuepper Michael

    2008-08-01

    Full Text Available Abstract Thymic stromal lymphopoietin (TSLP, a novel interleukin-7-like cytokine, triggers dendritic cell-mediated inflammatory responses ultimately executed by T helper cells of the Th2 subtype. TSLP emerged as a central player in the development of allergic symptoms, especially in the airways, and is a prime regulatory cytokine at the interface of virus- or antigen-exposed epithelial cells and dendritic cells (DCs. DCs activated by epithelium-derived TSLP can promote naïve CD4+ T cells to adopt a Th2 phenotype, which in turn recruite eosinophilic and basophilic granulocytes as well as mast cells into the airway mucosa. These different cells secrete inflammatory cytokines and chemokines operative in inducing an allergic inflammation and atopic asthma. TSLP is, thus, involved in the control of both an innate and an adaptive immune response. Since TSLP links contact of allergen with the airway epithelium to the onset and maintainance of the asthmatic syndrome, defining the signal transduction underlying TSLP expression and function is of profound interest for a better understandimg of the disease and for the development of new therapeutics.

  17. Defect in radiation signal transduction in ataxia-telangiectasia

    International Nuclear Information System (INIS)

    Lavin, M.F.

    1994-01-01

    Exposure of mammalian cells to ionizing radiation causes a delay in progression through the cycle at several checkpoints. Cells from patients with ataxia-telangiectasia (A-T) ignore these checkpoint controls postirradiation. The tumour suppressor gene product p53 plays a key role at the G 1 /S checkpoint preventing the progression of cells into S phase. The induction of p53 by radiation is reduced and/or delayed in A-T cells, which appears to account for the failure of delay at the G 1 /S checkpoint. We have investigated further this defect in radiation signal transduction in A-T. While the p53 response was defective after radiation, agents that interfered with cell cycle progression such as mimosine, aphidicolin and deprivation of serum led to a normal p53 response in A-T cells. None of these agents caused breaks in DNA, as determined by pulse-field gel electrophoresis, in order to elicit the response. Since this pathway is mediated by protein kinases, we investigated the activity of several of these enzymes in control and A-T cells. Ca +2 -dependent and -independent protein kinase C activities were increased by radiation to the same extent in the two cell types, a variety of serine/threonine protein kinase activities were approximately the same and anti-tyrosine antibodies failed to reveal any differences in protein phosphorylation between A-T and control cells. (author)

  18. Load-induced modulation of signal transduction networks.

    Science.gov (United States)

    Jiang, Peng; Ventura, Alejandra C; Sontag, Eduardo D; Merajver, Sofia D; Ninfa, Alexander J; Del Vecchio, Domitilla

    2011-10-11

    Biological signal transduction networks are commonly viewed as circuits that pass along information--in the process amplifying signals, enhancing sensitivity, or performing other signal-processing tasks--to transcriptional and other components. Here, we report on a "reverse-causality" phenomenon, which we call load-induced modulation. Through a combination of analytical and experimental tools, we discovered that signaling was modulated, in a surprising way, by downstream targets that receive the signal and, in doing so, apply what in physics is called a load. Specifically, we found that non-intuitive changes in response dynamics occurred for a covalent modification cycle when load was present. Loading altered the response time of a system, depending on whether the activity of one of the enzymes was maximal and the other was operating at its minimal rate or whether both enzymes were operating at submaximal rates. These two conditions, which we call "limit regime" and "intermediate regime," were associated with increased or decreased response times, respectively. The bandwidth, the range of frequency in which the system can process information, decreased in the presence of load, suggesting that downstream targets participate in establishing a balance between noise-filtering capabilities and a circuit's ability to process high-frequency stimulation. Nodes in a signaling network are not independent relay devices, but rather are modulated by their downstream targets.

  19. Signal transduction in mitogenesis: Further evidence for multiple pathways

    International Nuclear Information System (INIS)

    Rozengurt, E.; Erusalimsky, J.; Mehmet, H.; Morris, C.; Nanberg, E.; Sinnett-Smith, J.

    1988-01-01

    Growth factors are implicated in a wide variety of physiological and pathological processes, including embryogenesis, hematopoiesis, would healing, immune responses, atherosclerosis, and neoplasia. An important link between growth factors and their receptors and oncogene products has also been established. Thus, the elucidation of the mechanism of action of growth factors has emerged as one of the fundamental problems in biology and may prove crucial for understanding the unrestrained proliferation of cancer cells. A new and intriguing development is the discovery that neuropeptides localized in neural and neuroendocrine cells of mammalian tissue can also act as growth factors for cells in culture. Furthermore, indirect evidence is accumulating that the mitogenic effects of neuropeptides may be relevant for a variety of long-term biological processes, including development and oncogenesis. In this context, the peptides of the bombesin family are of particular significance. These peptides are potent mitogens for Swiss 3T3 cells and may act as autocrine growth factors for small cell lung cancer. Here, the authors summarize their recent studies using bombesin-like peptides for elucidating the signal transduction pathways leading to mitogenesis and compare these pathways with those elicited by other growth factors

  20. Disruption of Microtubules Post-Virus Entry Enhances Adeno-Associated Virus Vector Transduction

    Science.gov (United States)

    Xiao, Ping-Jie; Mitchell, Angela M.; Huang, Lu; Li, Chengwen; Samulski, R. Jude

    2016-01-01

    Perinuclear retention of viral particles is a poorly understood phenomenon observed during many virus infections. In this study, we investigated whether perinuclear accumulation acts as a barrier to limit recombinant adeno-associated virus (rAAV) transduction. After nocodazole treatment to disrupt microtubules at microtubule-organization center (MT-MTOC) after virus entry, we observed higher rAAV transduction. To elucidate the role of MT-MTOC in rAAV infection and study its underlying mechanisms, we demonstrated that rAAV's perinuclear localization was retained by MT-MTOC with fluorescent analysis, and enhanced rAAV transduction from MT-MTOC disruption was dependent on the rAAV capsid's nuclear import signals. Interestingly, after knocking down RhoA or inhibiting its downstream effectors (ROCK and Actin), MT-MTOC disruption failed to increase rAAV transduction or nuclear entry. These data suggest that enhancement of rAAV transduction is the result of increased trafficking to the nucleus via the RhoA-ROCK-Actin pathway. Ten-fold higher rAAV transduction was also observed by disrupting MT-MTOC in brain, liver, and tumor in vivo. In summary, this study indicates that virus perinuclear accumulation at MT-MTOC is a barrier-limiting parameter for effective rAAV transduction and defines a novel defense mechanism by which host cells restrain viral invasion. PMID:26942476

  1. Microfluidic Transduction Harnesses Mass Transport Principles to Enhance Gene Transfer Efficiency.

    Science.gov (United States)

    Tran, Reginald; Myers, David R; Denning, Gabriela; Shields, Jordan E; Lytle, Allison M; Alrowais, Hommood; Qiu, Yongzhi; Sakurai, Yumiko; Li, William C; Brand, Oliver; Le Doux, Joseph M; Spencer, H Trent; Doering, Christopher B; Lam, Wilbur A

    2017-10-04

    Ex vivo gene therapy using lentiviral vectors (LVs) is a proven approach to treat and potentially cure many hematologic disorders and malignancies but remains stymied by cumbersome, cost-prohibitive, and scale-limited production processes that cannot meet the demands of current clinical protocols for widespread clinical utilization. However, limitations in LV manufacture coupled with inefficient transduction protocols requiring significant excess amounts of vector currently limit widespread implementation. Herein, we describe a microfluidic, mass transport-based approach that overcomes the diffusion limitations of current transduction platforms to enhance LV gene transfer kinetics and efficiency. This novel ex vivo LV transduction platform is flexible in design, easy to use, scalable, and compatible with standard cell transduction reagents and LV preparations. Using hematopoietic cell lines, primary human T cells, primary hematopoietic stem and progenitor cells (HSPCs) of both murine (Sca-1 + ) and human (CD34 + ) origin, microfluidic transduction using clinically processed LVs occurs up to 5-fold faster and requires as little as one-twentieth of LV. As an in vivo validation of the microfluidic-based transduction technology, HSPC gene therapy was performed in hemophilia A mice using limiting amounts of LV. Compared to the standard static well-based transduction protocols, only animals transplanted with microfluidic-transduced cells displayed clotting levels restored to normal. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Protein Phylogenetic Analysis of Ca2+/cation Antiporters and Insights into their Evolution in Plants

    Science.gov (United States)

    Emery, Laura; Whelan, Simon; Hirschi, Kendal D.; Pittman, Jon K.

    2012-01-01

    Cation transport is a critical process in all organisms and is essential for mineral nutrition, ion stress tolerance, and signal transduction. Transporters that are members of the Ca2+/cation antiporter (CaCA) superfamily are involved in the transport of Ca2+ and/or other cations using the counter exchange of another ion such as H+ or Na+. The CaCA superfamily has been previously divided into five transporter families: the YRBG, Na+/Ca2+ exchanger (NCX), Na+/Ca2+, K+ exchanger (NCKX), H+/cation exchanger (CAX), and cation/Ca2+ exchanger (CCX) families, which include the well-characterized NCX and CAX transporters. To examine the evolution of CaCA transporters within higher plants and the green plant lineage, CaCA genes were identified from the genomes of sequenced flowering plants, a bryophyte, lycophyte, and freshwater and marine algae, and compared with those from non-plant species. We found evidence of the expansion and increased diversity of flowering plant genes within the CAX and CCX families. Genes related to the NCX family are present in land plant though they encode distinct MHX homologs which probably have an altered transport function. In contrast, the NCX and NCKX genes which are absent in land plants have been retained in many species of algae, especially the marine algae, indicating that these organisms may share “animal-like” characteristics of Ca2+ homeostasis and signaling. A group of genes encoding novel CAX-like proteins containing an EF-hand domain were identified from plants and selected algae but appeared to be lacking in any other species. Lack of functional data for most of the CaCA proteins make it impossible to reliably predict substrate specificity and function for many of the groups or individual proteins. The abundance and diversity of CaCA genes throughout all branches of life indicates the importance of this class of cation transporter, and that many transporters with novel functions are waiting to be discovered. PMID:22645563

  3. Graph Regularized Meta-path Based Transductive Regression in Heterogeneous Information Network.

    Science.gov (United States)

    Wan, Mengting; Ouyang, Yunbo; Kaplan, Lance; Han, Jiawei

    2015-01-01

    A number of real-world networks are heterogeneous information networks, which are composed of different types of nodes and links. Numerical prediction in heterogeneous information networks is a challenging but significant area because network based information for unlabeled objects is usually limited to make precise estimations. In this paper, we consider a graph regularized meta-path based transductive regression model ( Grempt ), which combines the principal philosophies of typical graph-based transductive classification methods and transductive regression models designed for homogeneous networks. The computation of our method is time and space efficient and the precision of our model can be verified by numerical experiments.

  4. Accelerators for forming cationic technetium complexes useful as radiodiagnostic images

    International Nuclear Information System (INIS)

    Tweedle, M.F.

    1985-01-01

    This invention relates to compositions for making cationic radiodiagnostic agents and, in particular, to accelerator compounds for labelling such cationic radiodiagnostic agents, kits for preparing such 99m Tc-labelled cationic radiodiagnostic agents with technetium, and methods for labelling such cationic radiodiagnostic agents with technetium

  5. Evaluation of conformity of a first prescription of lipid-based formulation of amphotericin B in a university-teaching pediatric hospital.

    Science.gov (United States)

    Agogué, Claire; Bussières, Jean-François; Dehaut, Catherine; Lebel, Denis; Brochet, Marie-Sophie

    2006-04-01

    Invasive fungal infections are an important cause of morbidity and mortality in immunodeficient children. Amphotericin B is an important therapeutic agent for the treatment of invasive fungal infections but is associated with significant toxicities and high acquisition costs. The purpose of this study was to evaluate physician adherence to a local guideline for the use of lipid-based amphotericin B. The study was approved through Pharmacology & Therapeutics (P&T) committee activities. A retrospective drug utilization review (DUR) was conducted. All orders written between January 1, 2003, and December 31, 2004, were reviewed. Demographic and descriptive clinical data were collected as well as variables related to the drug order process. Conformity rates were calculated for the primary objective criteria (authorized prescribers - infectious disease members; recommended drug of choice-Abelcet; accepted indications; and presence of underlying conditions). A total of 109 orders for 70 patients were reviewed by a single research assistant for a 2-year period. Global conformity rate for all four criteria was calculated at 7.3%. Non-conformity was mostly associated with the absence of underlying conditions (e.g., prerenal insufficiency or presence of nephrotoxicity due to amphotericin B desoxycholate) in 84.5% of the cases. Infusionrelated adverse drug reactions partly explained a switch to a non-formulary lipid-based amphotericin B product. External factors (newly published results since the adoption of the guideline and continuous marketing practices) and internal factors (availability of non-formulary process, inefficient DUR process) could have contributed to non-adherence to a local guideline. This study shows low adherence to P&T committee drug guidelines on lipid-based amphotericin B. Continuous and efficient DUR processes should be in place to monitor drug guideline adherence.

  6. Signal transduction through the IL-4 and insulin receptor families.

    Science.gov (United States)

    Wang, L M; Keegan, A; Frankel, M; Paul, W E; Pierce, J H

    1995-07-01

    Activation of tyrosine kinase-containing receptors and intracellular tyrosine kinases by ligand stimulation is known to be crucial for mediating initial and subsequent events involved in mitogenic signal transduction. Receptors for insulin and insulin-like growth factor 1 (IGF-1) contain cytoplasmic tyrosine kinase domains that undergo autophosphorylation upon ligand stimulation. Activation of these receptors also leads to pronounced and rapid tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in cells of connective tissue origin. A related substrate, designated 4PS, is similarly phosphorylated by insulin and IGF-1 stimulation in many hematopoietic cell types. IRS-1 and 4PS possess a number of tyrosine phosphorylation sites that are within motifs that bind specific SH2-containing molecules known to be involved in mitogenic signaling such as PI-3 kinase, SHPTP-2 (Syp) and Grb-2. Thus, they appear to act as docking substrates for a variety of signaling molecules. The majority of hematopoietic cytokines bind to receptors that do not possess intrinsic kinase activity, and these receptors have been collectively termed as members of the hematopoietin receptor superfamily. Despite their lack of tyrosine kinase domains, stimulation of these receptors has been demonstrated to activate intracellular kinases leading to tyrosine phosphorylation of multiple substrates. Recent evidence has demonstrated that activation of different members of the Janus family of tyrosine kinases is involved in mediating tyrosine phosphorylation events by specific cytokines. Stimulation of the interleukin 4 (IL-4) receptor, a member of the hematopoietin receptor superfamily, is thought to result in activation of Jak1, Jak3, and/or Fes tyrosine kinases.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Computational study of noise in a large signal transduction network

    Directory of Open Access Journals (Sweden)

    Ruohonen Keijo

    2011-06-01

    Full Text Available Abstract Background Biochemical systems are inherently noisy due to the discrete reaction events that occur in a random manner. Although noise is often perceived as a disturbing factor, the system might actually benefit from it. In order to understand the role of noise better, its quality must be studied in a quantitative manner. Computational analysis and modeling play an essential role in this demanding endeavor. Results We implemented a large nonlinear signal transduction network combining protein kinase C, mitogen-activated protein kinase, phospholipase A2, and β isoform of phospholipase C networks. We simulated the network in 300 different cellular volumes using the exact Gillespie stochastic simulation algorithm and analyzed the results in both the time and frequency domain. In order to perform simulations in a reasonable time, we used modern parallel computing techniques. The analysis revealed that time and frequency domain characteristics depend on the system volume. The simulation results also indicated that there are several kinds of noise processes in the network, all of them representing different kinds of low-frequency fluctuations. In the simulations, the power of noise decreased on all frequencies when the system volume was increased. Conclusions We concluded that basic frequency domain techniques can be applied to the analysis of simulation results produced by the Gillespie stochastic simulation algorithm. This approach is suited not only to the study of fluctuations but also to the study of pure noise processes. Noise seems to have an important role in biochemical systems and its properties can be numerically studied by simulating the reacting system in different cellular volumes. Parallel computing techniques make it possible to run massive simulations in hundreds of volumes and, as a result, accurate statistics can be obtained from computational studies.

  8. Transduction-like gene transfer in the methanogen Methanococcus voltae

    Science.gov (United States)

    Bertani, G.

    1999-01-01

    Strain PS of Methanococcus voltae (a methanogenic, anaerobic archaebacterium) was shown to generate spontaneously 4.4-kbp chromosomal DNA fragments that are fully protected from DNase and that, upon contact with a cell, transform it genetically. This activity, here called VTA (voltae transfer agent), affects all markers tested: three different auxotrophies (histidine, purine, and cobalamin) and resistance to BES (2-bromoethanesulfonate, an inhibitor of methanogenesis). VTA was most effectively prepared by culture filtration. This process disrupted a fraction of the M. voltae cells (which have only an S-layer covering their cytoplasmic membrane). VTA was rapidly inactivated upon storage. VTA particles were present in cultures at concentrations of approximately two per cell. Gene transfer activity varied from a minimum of 2 x 10(-5) (BES resistance) to a maximum of 10(-3) (histidine independence) per donor cell. Very little VTA was found free in culture supernatants. The phenomenon is functionally similar to generalized transduction, but there is no evidence, for the time being, of intrinsically viral (i.e., containing a complete viral genome) particles. Consideration of VTA DNA size makes the existence of such viral particles unlikely. If they exist, they must be relatively few in number;perhaps they differ from VTA particles in size and other properties and thus escaped detection. Digestion of VTA DNA with the AluI restriction enzyme suggests that it is a random sample of the bacterial DNA, except for a 0.9-kbp sequence which is amplified relative to the rest of the bacterial chromosome. A VTA-sized DNA fraction was demonstrated in a few other isolates of M. voltae.

  9. Transduction on Directed Graphs via Absorbing Random Walks.

    Science.gov (United States)

    De, Jaydeep; Zhang, Xiaowei; Lin, Feng; Cheng, Li

    2017-08-11

    In this paper we consider the problem of graph-based transductive classification, and we are particularly interested in the directed graph scenario which is a natural form for many real world applications.Different from existing research efforts that either only deal with undirected graphs or circumvent directionality by means of symmetrization, we propose a novel random walk approach on directed graphs using absorbing Markov chains, which can be regarded as maximizing the accumulated expected number of visits from the unlabeled transient states. Our algorithm is simple, easy to implement, and works with large-scale graphs on binary, multiclass, and multi-label prediction problems. Moreover, it is capable of preserving the graph structure even when the input graph is sparse and changes over time, as well as retaining weak signals presented in the directed edges. We present its intimate connections to a number of existing methods, including graph kernels, graph Laplacian based methods, and interestingly, spanning forest of graphs. Its computational complexity and the generalization error are also studied. Empirically our algorithm is systematically evaluated on a wide range of applications, where it has shown to perform competitively comparing to a suite of state-of-the-art methods. In particular, our algorithm is shown to work exceptionally well with large sparse directed graphs with e.g. millions of nodes and tens of millions of edges, where it significantly outperforms other state-of-the-art methods. In the dynamic graph setting involving insertion or deletion of nodes and edge-weight changes over time, it also allows efficient online updates that produce the same results as of the batch update counterparts.

  10. Radiation-induced adaptive response and intracellular signal transduction pathways

    International Nuclear Information System (INIS)

    Tachibana, Akira

    2009-01-01

    As an essential biological function, cells can sense the radiation even at low dose and respond to it, and which is one of bases of the radiation-induced adaptive response (AR) where effects caused by high dose radiation are reduced by prior exposure to low dose radiation (LDR). Here described are studies of AR in well established m5S cells on the intracellular signal transduction that involves sensing of LDR and transmitting of its signal within the cell network. The first signal for AR yielded by LDR on the cell membrane is exactly unknown though hydrogen peroxide and phorbol ester (PMA) can reportedly cause AR. As PMA activates protein kinase C (PKC) and its inhibitors suppress AR, participation of PKC in AR has been suggested and supported by studies showing PKCα activation by LDR. In addition, p38 mitogen-activated protein kinase (MAPK) is shown to participate in AR by those facts that the enzyme is activated by LDR, a p38 MAPK inhibitor suppresses AR, and PKC inhibitors suppress the enzyme activation, which also suggesting that the signaling from PKC to p38 MAPK can become operative by LDR. However, the possible reverse signaling is also suggested, and thus the activation of positive feedback mechanism is postulated in PKC/p38 MAPK/phospholipase δ1/ PKC pathway. Cells introduced with siRNA against Prkca gene (coding PKCs) produce reduced amount of the enzyme, particularly, of PKCα. In those cells, AR by 5 Gy X-ray is not observed and thereby PKCα is involved in AR. The signaling in AR is only partly elucidated at present as above, and more detailed studies including identification of more PKC subtypes and signaling to DNA repair system are considered necessary. (K.T.)

  11. Second-chance signal transduction explains cooperative flagellar switching.

    Science.gov (United States)

    Zot, Henry G; Hasbun, Javier E; Minh, Nguyen Van

    2012-01-01

    The reversal of flagellar motion (switching) results from the interaction between a switch complex of the flagellar rotor and a torque-generating stationary unit, or stator (motor unit). To explain the steeply cooperative ligand-induced switching, present models propose allosteric interactions between subunits of the rotor, but do not address the possibility of a reaction that stimulates a bidirectional motor unit to reverse direction of torque. During flagellar motion, the binding of a ligand-bound switch complex at the dwell site could excite a motor unit. The probability that another switch complex of the rotor, moving according to steady-state rotation, will reach the same dwell site before that motor unit returns to ground state will be determined by the independent decay rate of the excited-state motor unit. Here, we derive an analytical expression for the energy coupling between a switch complex and a motor unit of the stator complex of a flagellum, and demonstrate that this model accounts for the cooperative switching response without the need for allosteric interactions. The analytical result can be reproduced by simulation when (1) the motion of the rotor delivers a subsequent ligand-bound switch to the excited motor unit, thereby providing the excited motor unit with a second chance to remain excited, and (2) the outputs from multiple independent motor units are constrained to a single all-or-none event. In this proposed model, a motor unit and switch complex represent the components of a mathematically defined signal transduction mechanism in which energy coupling is driven by steady-state and is regulated by stochastic ligand binding. Mathematical derivation of the model shows the analytical function to be a general form of the Hill equation (Hill AV (1910) The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves. J Physiol 40: iv-vii).

  12. Gas phase chemistry of N-benzylbenzamides with silver(I) cations: characterization of benzylsilver cation.

    Science.gov (United States)

    Sun, Hezhi; Jin, Zhe; Quan, Hong; Sun, Cuirong; Pan, Yuanjiang

    2015-03-07

    The benzylsilver cation which emerges from the collisional dissociation of silver(I)-N-benzylbenzamide complexes was characterized by deuterium-labeling experiments, theoretical calculations, breakdown curves and substituent effects. The nucleophilic attack of the carbonyl oxygen on an α-hydrogen results in the generation of the benzylsilver cation, which is competitive to the AgH loss with the α-hydrogen.

  13. Toward the Establishment of Standardized In Vitro Tests for Lipid-Based Formulations. 5. Lipolysis of Representative Formulations by Gastric Lipase

    DEFF Research Database (Denmark)

    Bakala-N'Goma, Jean-Claude; Williams, Hywel D.; Sassene, Philip J.

    2015-01-01

    Purpose Lipid-based formulations (LBF) are substrates for digestive lipases and digestion can significantly alter their properties and potential to support drug absorption. LBFs have been widely examined for their behaviour in the presence of pancreatic enzymes. Here, the impact of gastric lipase...... on the digestion of representative formulations from the Lipid Formulation Classification System has been investigated. Methods The pHstat technique was used to measure the lipolysis by recombinant dog gastric lipase (rDGL) of eight LBFs containing either medium (MC) or long (LC) chain triglycerides and a range...

  14. Effect of Divalent Cations on RED Performance and Cation Exchange Membrane Selection to Enhance Power Densities.

    Science.gov (United States)

    Rijnaarts, Timon; Huerta, Elisa; van Baak, Willem; Nijmeijer, Kitty

    2017-11-07

    Reverse electrodialysis (RED) is a membrane-based renewable energy technology that can harvest energy from salinity gradients. The anticipated feed streams are natural river and seawater, both of which contain not only monovalent ions but also divalent ions. However, RED using feed streams containing divalent ions experiences lower power densities because of both uphill transport and increased membrane resistance. In this study, we investigate the effects of divalent cations (Mg 2+ and Ca 2+ ) on RED and demonstrate the mitigation of those effects using both novel and existing commercial cation exchange membranes (CEMs). Monovalent-selective Neosepta CMS is known to block divalent cations transport and can therefore mitigate reductions in stack voltage. The new multivalent-permeable Fuji T1 is able to transport divalent cations without a major increase in resistance. Both strategies significantly improve power densities compared to standard-grade CEMs when performing RED using streams containing divalent cations.

  15. Multidrug resistance and retroviral transduction potential in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Theilade, M D; Gram, G J; Jensen, P B

    1999-01-01

    Multidrug resistance (MDR) remains a major problem in the successful treatment of small cell lung cancer (SCLC). New treatment strategies are needed, such as gene therapy specifically targeting the MDR cells in the tumor. Retroviral LacZ gene-containing vectors that were either pseudotyped...... for the gibbon ape leukemia virus (GALV-1) receptor or had specificity for the amphotropic murine leukemia virus (MLV-A) receptor were used for transduction of five SCLC cell lines differing by a range of MDR mechanisms. Transduction efficiencies in these cell lines were compared by calculating the percentage...... of blue colonies after X-Gal staining of the cells grown in soft agar. All examined SCLC cell lines were transducible with either vector. Transduction efficiencies varied from 5.7% to 33.5% independent of the presence of MDR. These results indicate that MDR does not severely impair transduction of SCLC...

  16. Efficient, Broadband and Wide-Angle Hot-Electron Transduction using Metal-Semiconductor Hyperbolic Metamaterials

    KAUST Repository

    Sakhdari, Maryam; Hajizadegan, Mehdi; Farhat, Mohamed; Chen, Pai-Yen

    2016-01-01

    Hot-electron devices are emerging as promising candidates for the transduction of optical radiation into electrical current, as they enable photodetection and solar/infrared energy harvesting at sub-bandgap wavelengths. Nevertheless, poor

  17. [Cellular adhesion signal transduction network of tumor necrosis factor-alpha induced hepatocellular carcinoma cells].

    Science.gov (United States)

    Zheng, Yongchang; Du, Shunda; Xu, Haifeng; Xu, Yiyao; Zhao, Haitao; Chi, Tianyi; Lu, Xin; Sang, Xinting; Mao, Yilei

    2014-11-18

    To systemically explore the cellular adhesion signal transduction network of tumor necrosis factor-alpha (TNF-α)-induced hepatocellular carcinoma cells with bioinformatics tools. Published microarray dataset of TNF-α-induced HepG2, human transcription factor database HTRI and human protein-protein interaction database HPRD were used to construct and analyze the signal transduction network. In the signal transduction network, MYC and SP1 were the key nodes of signaling transduction. Several genes from the network were closely related with cellular adhesion.Epidermal growth factor receptor (EGFR) is a possible key gene of effectively regulating cellular adhesion during the induction of TNF-α. EGFR is a possible key gene for TNF-α-induced metastasis of hepatocellular carcinoma.

  18. Investigation of the charge effect on the electrochemical transduction in a quinone-based DNA sensor

    DEFF Research Database (Denmark)

    Reisberg, S.; Piro, B.; Noel, V.

    2008-01-01

    To elucidate the mechanism involved in the electrochemical transduction process of a conducting polymer-based DNA sensor, peptide nucleic acids (PNA) were used. PNA are DNA analogues having similar hybridization properties but are neutral. This allows to discriminate the electrostatic effect of D...... strands from the steric hindrance generated on the bioelectrode upon hybridization. It can be concluded that DNA conformational changes are determinant in the transduction process and that the electrostatic effect is negligible....

  19. Cavity opto-electromechanical system combining strong electrical actuation with ultrasensitive transduction

    OpenAIRE

    McRae, Terry G.; Lee, Kwan H.; Harris, Glen I.; Knittel, Joachim; Bowen, Warwick P.

    2010-01-01

    A cavity opto-electromechanical system is reported which combines the ultrasensitive transduction of cavity optomechanical systems with the electrical actuation of nanoelectromechanical systems. Ultrasensitive mechanical transduction is achieved via opto-mechanical coupling. Electrical gradient forces as large as 0.40 $\\mu$N are realized, facilitating strong actuation with ultralow dissipation. A scanning probe microscope is implemented, capable of characterizing the mechanical modes. The int...

  20. Forging Colloidal Nanostructures via Cation Exchange Reactions.

    Science.gov (United States)

    De Trizio, Luca; Manna, Liberato

    2016-09-28

    Among the various postsynthesis treatments of colloidal nanocrystals that have been developed to date, transformations by cation exchange have recently emerged as an extremely versatile tool that has given access to a wide variety of materials and nanostructures. One notable example in this direction is represented by partial cation exchange, by which preformed nanocrystals can be either transformed to alloy nanocrystals or to various types of nanoheterostructures possessing core/shell, segmented, or striped architectures. In this review, we provide an up to date overview of the complex colloidal nanostructures that could be prepared so far by cation exchange. At the same time, the review gives an account of the fundamental thermodynamic and kinetic parameters governing these types of reactions, as they are currently understood, and outlines the main open issues and possible future developments in the field.

  1. Forging Colloidal Nanostructures via Cation Exchange Reactions

    Science.gov (United States)

    2016-01-01

    Among the various postsynthesis treatments of colloidal nanocrystals that have been developed to date, transformations by cation exchange have recently emerged as an extremely versatile tool that has given access to a wide variety of materials and nanostructures. One notable example in this direction is represented by partial cation exchange, by which preformed nanocrystals can be either transformed to alloy nanocrystals or to various types of nanoheterostructures possessing core/shell, segmented, or striped architectures. In this review, we provide an up to date overview of the complex colloidal nanostructures that could be prepared so far by cation exchange. At the same time, the review gives an account of the fundamental thermodynamic and kinetic parameters governing these types of reactions, as they are currently understood, and outlines the main open issues and possible future developments in the field. PMID:26891471

  2. Polyploidization without mitosis improves in vivo liver transduction with lentiviral vectors.

    Science.gov (United States)

    Pichard, Virginie; Couton, Dominique; Desdouets, Chantal; Ferry, Nicolas

    2013-02-01

    Lentiviral vectors are efficient gene delivery vehicles for therapeutic and research applications. In contrast to oncoretroviral vectors, they are able to infect most nonproliferating cells. In the liver, induction of cell proliferation dramatically improved hepatocyte transduction using all types of retroviral vectors. However, the precise relationship between hepatocyte division and transduction efficiency has not been determined yet. Here we compared gene transfer efficiency in the liver after in vivo injection of recombinant lentiviral or Moloney murine leukemia viral (MoMuLV) vectors in hepatectomized rats treated or not with retrorsine, an alkaloid that blocks hepatocyte division and induces megalocytosis. Partial hepatectomy alone resulted in a similar increase in hepatocyte transduction using either vector. In retrorsine-treated and partially hepatectomized rats, transduction with MoMuLV vectors dropped dramatically. In contrast, we observed that retrorsine treatment combined with partial hepatectomy increased lentiviral transduction to higher levels than hepatectomy alone. Analysis of nuclear ploidy in single cells showed that a high level of transduction was associated with polyploidization. In conclusion, endoreplication could be exploited to improve the efficiency of liver-directed lentiviral gene therapy.

  3. Evidence that membrane transduction of oligoarginine does not require vesicle formation

    International Nuclear Information System (INIS)

    Zaro, Jennica L.; Shen Weichiang

    2005-01-01

    The involvement of vesicular formation processes in the membrane transduction and nuclear transport of oligoarginine is currently a subject of controversy. In this report, a novel quantitative method which allows for the selective measurement of membrane transduction excluding concurrent endocytosis was used to determine the effects of temperature, endosomal acidification, endosomolysis, and several known inhibitors of endocytic pathways on the internalization of oligoarginine. The results show that, unlike endocytosis, transduction of oligoarginine was not affected by incubation at 16 deg. C as compared to the 37 deg. C control, and was only partially inhibited at 4 deg. C incubation. Additionally, membrane transduction was not inhibited to the same extent as endocytosis following treatment with ammonium chloride, hypertonic medium, amiloride, or filipin. The endosomolytic activity of oligoarginine was investigated by examining the leakage of FITC-dextran into the cytosolic compartment, which was not higher in the presence of oligoarginine. Furthermore, ammonium chloride showed no effect on the nuclear transport of oligoarginine. The data presented in this report indicate that membrane transduction is likely to occur at the plasma membrane without the formation of membrane vesicles, and the nuclear localization involves membrane transduction, rather than endocytosis of oligoarginine

  4. Formulation and characterization of lipid-based drug delivery system of raloxifene-microemulsion and self-microemulsifying drug delivery system

    Science.gov (United States)

    Thakkar, Hetal; Nangesh, Jitesh; Parmar, Mayur; Patel, Divyakant

    2011-01-01

    Background: Raloxifene, a second-generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women is administered orally in the form of a tablet. The absolute bioavailability of the drug is only 2% because of extensive hepatic first-pass metabolism. Lipid-based formulations are reported to reduce the first-pass metabolism by promoting its lymphatic uptake. Materials and Methods: In the present investigation, microemulsion and Self-Microemulsifying Drug Delivery System (SMEDDS) formulations of Raloxifene were prepared. The prepared formulations were characterized for drug loading, size, transparency, zeta potential, Transmission Electron Microscopy (TEM) and in vitro intestinal permeability. Results: The results indicated that high drug loading, optimum size and desired zeta potential and transparency could be achieved with both SMEDDS and microemulsion. The TEM studies indicated the absence of aggregation with both the systems. The in vitro intestinal permeability results showed that the permeation of the drug from the microemulsion and SMEDDs was significantly higher than that obtained from the drug dispersion and marketed formulation. Conclusion: Lipid based formulations such as microemulsion and Self Microemulsifying drug delivery systems are expected to increase the oral bioavailability as evidenced by the increased intestinal permeation. PMID:21966167

  5. Dissolution of Lipid-Based Matrices in Simulated Gastrointestinal Solutions to Evaluate Their Potential for the Encapsulation of Bioactive Ingredients for Foods.

    Science.gov (United States)

    Raymond, Yves; Champagne, Claude P

    2014-01-01

    The goal of the study was to compare the dissolution of chocolate to other lipid-based matrices suitable for the microencapsulation of bioactive ingredients in simulated gastrointestinal solutions. Particles having approximately 750 μm or 2.5 mm were prepared from the following lipid-based matrices: cocoa butter, fractionated palm kernel oil (FPKO), chocolate, beeswax, carnauba wax, and paraffin. They were added to solutions designed to simulate gastric secretions (GS) or duodenum secretions (DS) at 37°C. Paraffin, carnauba wax, and bees wax did not dissolve in either the GS or DS media. Cocoa butter, FPKO, and chocolate dissolved in the DS medium. Cocoa butter, and to a lesser extent chocolate, also dissolved in the GS medium. With chocolate, dissolution was twice as fast as that with small particles (750 μm) as compared to the larger (2.5 mm) ones. With 750 μm particle sizes, 90% dissolution of chocolate beads was attained after only 60 minutes in the DS medium, while it took 120 minutes for 70% of FPKO beads to dissolve in the same conditions. The data are discussed from the perspective of controlled release in the gastrointestinal tract of encapsulated ingredients (minerals, oils, probiotic bacteria, enzymes, vitamins, and peptides) used in the development of functional foods.

  6. Dissolution of Lipid-Based Matrices in Simulated Gastrointestinal Solutions to Evaluate Their Potential for the Encapsulation of Bioactive Ingredients for Foods

    Directory of Open Access Journals (Sweden)

    Yves Raymond

    2014-01-01

    Full Text Available The goal of the study was to compare the dissolution of chocolate to other lipid-based matrices suitable for the microencapsulation of bioactive ingredients in simulated gastrointestinal solutions. Particles having approximately 750 μm or 2.5 mm were prepared from the following lipid-based matrices: cocoa butter, fractionated palm kernel oil (FPKO, chocolate, beeswax, carnauba wax, and paraffin. They were added to solutions designed to simulate gastric secretions (GS or duodenum secretions (DS at 37°C. Paraffin, carnauba wax, and bees wax did not dissolve in either the GS or DS media. Cocoa butter, FPKO, and chocolate dissolved in the DS medium. Cocoa butter, and to a lesser extent chocolate, also dissolved in the GS medium. With chocolate, dissolution was twice as fast as that with small particles (750 μm as compared to the larger (2.5 mm ones. With 750 μm particle sizes, 90% dissolution of chocolate beads was attained after only 60 minutes in the DS medium, while it took 120 minutes for 70% of FPKO beads to dissolve in the same conditions. The data are discussed from the perspective of controlled release in the gastrointestinal tract of encapsulated ingredients (minerals, oils, probiotic bacteria, enzymes, vitamins, and peptides used in the development of functional foods.

  7. Formulation and characterization of lipid-based drug delivery system of raloxifene-microemulsion and self-microemulsifying drug delivery system

    Directory of Open Access Journals (Sweden)

    Hetal Thakkar

    2011-01-01

    Full Text Available Background : Raloxifene, a second-generation selective estrogen receptor modulator (SERM used to prevent osteoporosis in postmenopausal women is administered orally in the form of a tablet. The absolute bioavailability of the drug is only 2% because of extensive hepatic first-pass metabolism. Lipid-based formulations are reported to reduce the first-pass metabolism by promoting its lymphatic uptake. Materials and Methods : In the present investigation, microemulsion and Self-Microemulsifying Drug Delivery System (SMEDDS formulations of Raloxifene were prepared. The prepared formulations were characterized for drug loading, size, transparency, zeta potential, Transmission Electron Microscopy (TEM and in vitro intestinal permeability. Results : The results indicated that high drug loading, optimum size and desired zeta potential and transparency could be achieved with both SMEDDS and microemulsion. The TEM studies indicated the absence of aggregation with both the systems. The in vitro intestinal permeability results showed that the permeation of the drug from the microemulsion and SMEDDs was significantly higher than that obtained from the drug dispersion and marketed formulation. Conclusion : Lipid based formulations such as microemulsion and Self Microemulsifying drug delivery systems are expected to increase the oral bioavailability as evidenced by the increased intestinal permeation.

  8. Computational Models of the Gastrointestinal Environment. 2. Phase Behavior and Drug Solubilization Capacity of a Type I Lipid-Based Drug Formulation after Digestion.

    Science.gov (United States)

    Birru, Woldeamanuel A; Warren, Dallas B; Han, Sifei; Benameur, Hassan; Porter, Christopher J H; Pouton, Colin W; Chalmers, David K

    2017-03-06

    Lipid-based drug formulations can greatly enhance the bioavailability of poorly water-soluble drugs. Following the oral administration of formulations containing tri- or diglycerides, the digestive processes occurring within the gastrointestinal (GI) tract hydrolyze the glycerides to mixtures of free fatty acids and monoglycerides that are, in turn, solubilized by bile. The behavior of drugs within the resulting colloidal mixtures is currently not well characterized. This work presents matched in vitro experimental and molecular dynamics (MD) theoretical models of the GI microenvironment containing a digested triglyceride-based (Type I) drug formulation. Both the experimental and theoretical models consist of molecular species representing bile (glycodeoxycholic acid), digested triglyceride (1:2 glyceryl-1-monooleate and oleic acid), and water. We have characterized the phase behavior of the physical system using nephelometry, dynamic light scattering, and polarizing light microscopy and compared these measurements to phase behavior observed in multiple MD simulations. Using this model microenvironment, we have investigated the dissolution of the poorly water-soluble drug danazol experimentally using LC-MS and theoretically by MD simulation. The results show how the formulation lipids alter the environment of the GI tract and improve the solubility of danazol. The MD simulations successfully reproduce the experimental results showing the utility of MD in modeling the fate of drugs after digestion of lipid-based formulations within the intestinal lumen.

  9. Full Piezoelectric Multilayer-Stacked Hybrid Actuation/Transduction Systems

    Science.gov (United States)

    Su, Ji; Jiang, Xiaoning; Zu, Tian-Bing

    2011-01-01

    The Stacked HYBATS (Hybrid Actuation/Transduction system) demonstrates significantly enhanced electromechanical performance by using the cooperative contributions of the electromechanical responses of multilayer, stacked negative strain components and positive strain components. Both experimental and theoretical studies indicate that, for Stacked HYBATS, the displacement is over three times that of a same-sized conventional flextensional actuator/transducer. The coupled resonance mode between positive strain and negative strain components of Stacked HYBATS is much stronger than the resonance of a single element actuation only when the effective lengths of the two kinds of elements match each other. Compared with the previously invented hybrid actuation system (HYBAS), the multilayer Stacked HYBATS can be designed to provide high mechanical load capability, low voltage driving, and a highly effective piezoelectric constant. The negative strain component will contract, and the positive strain component will expand in the length directions when an electric field is applied on the device. The interaction between the two elements makes an enhanced motion along the Z direction for Stacked-HYBATS. In order to dominate the dynamic length of Stacked-HYBATS by the negative strain component, the area of the cross-section for the negative strain component will be much larger than the total cross-section areas of the two positive strain components. The transverse strain is negative and longitudinal strain positive in inorganic materials, such as ceramics/single crystals. Different piezoelectric multilayer stack configurations can make a piezoelectric ceramic/single-crystal multilayer stack exhibit negative strain or positive strain at a certain direction without increasing the applied voltage. The difference of this innovation from the HYBAS is that all the elements can be made from one-of-a-kind materials. Stacked HYBATS can provide an extremely effective piezoelectric

  10. The dynamic basis of energy transduction in enzymes.

    Science.gov (United States)

    Somogyi, B; Welch, G R; Damjanovich, S

    1984-09-06

    The most important idea underlying our treatment herein is the unity of the enzyme molecule and the medium. Appreciation of this relationship is vital, if enzymology is to graduate from its present reductionistic status to a more holistic posture. Enzymes are biological entities firstly, and isolated objects of physicochemical analysis secondly. Perhaps the most crucial 'biological lesson', particularly apropos of enzymes in intermediary metabolism, concerns the 'cytosociology' of enzyme action in vivo [94,128]. The natural habitat of many enzymes in the living cell is far different from that in bulk aqueous solution in vitro. In order to obtain a real grasp of the nature of enzyme function, one must ultimately couch enzymology in concepts emerging from contemporary cell biology [95]. Notwithstanding, analysis precedes synthesis; and one must needs begin with the individual enzyme molecule. The trenchant efforts of the physical chemist and the organic chemist have produced a wealth of information on the nature of the binding and catalytic events at the enzyme active site. While it is not yet possible to explain precisely the complete sequence of events in the catalytic process, nevertheless, the basic mechanisms by which enzymes effect catalysis (i.e., reduce activation energy) now seem apparent [81,129]. The new frontier is to be found, in exploring the dynamic role of the protein matrix [17]. Not only does the protein provide the 3-D scaffolding for active-site processes, but, more importantly, it serves as the local solvent for the bound chemical subsystem. Thus, the dynamical aspects of enzyme catalysis (for thermally based systems) must arise from the fluctuational properties of the protein molecule. This notion is the common denominator in all of the models in subsection IIC. It is the anisotropic nature of this fluctuational behavior, which would characterize the energy-transduction phenomenon leading to localized catalytic events at the active-site. In

  11. Signal transduction, receptors, mediators and genes: younger than ever - the 13th meeting of the Signal Transduction Society focused on aging and immunology

    Directory of Open Access Journals (Sweden)

    Klotz Lars-Oliver

    2010-02-01

    Full Text Available Abstract The 13th meeting of the Signal Transduction Society was held in Weimar, from October 28 to 30, 2009. Special focus of the 2009 conference was "Aging and Senescence", which was co-organized by the SFB 728 "Environmentally-Induced Aging Processes" of the University of Düsseldorf and the study group 'Signal Transduction' of the German Society for Cell Biology (DGZ. In addition, several other areas of signal transduction research were covered and supported by different consortia associated with the Signal Transduction Society including the long-term associated study groups of the German Society for Immunology and the Society for Biochemistry and Molecular Biology, and for instance the SFB/Transregio 52 "Transcriptional Programming of Individual T Cell Subsets" located in Würzburg, Mainz and Berlin. The different research areas that were introduced by outstanding keynote speakers attracted more than 250 scientists, showing the timeliness and relevance of the interdisciplinary concept and exchange of knowledge during the three days of the scientific program. This report gives an overview of the presentations of the conference.

  12. Restructuring of a peat in interaction with multivalent cations: effect of cation type and aging time.

    Directory of Open Access Journals (Sweden)

    Yamuna Kunhi Mouvenchery

    Full Text Available It is assumed to be common knowledge that multivalent cations cross-link soil organic matter (SOM molecules via cation bridges (CaB. The concept has not been explicitly demonstrated in solid SOM by targeted experiments, yet. Therefore, the requirements for and characteristics of CaB remain unidentified. In this study, a combined experimental and molecular modeling approach was adopted to investigate the interaction of cations on a peat OM from physicochemical perspective. Before treatment with salt solutions of Al(3+, Ca(2+ or Na(+, respectively, the original exchangeable cations were removed using cation exchange resin. Cation treatment was conducted at two different values of pH prior to adjusting pH to 4.1. Cation sorption is slower (>>2 h than deprotonation of functional groups (<2 h and was described by a Langmuir model. The maximum uptake increased with pH of cation addition and decreased with increasing cation valency. Sorption coefficients were similar for all cations and at both pH. This contradicts the general expectations for electrostatic interactions, suggesting that not only the interaction chemistry but also spatial distribution of functional groups in OM determines binding of cations in this peat. The reaction of contact angle, matrix rigidity due to water molecule bridges (WaMB and molecular mobility of water (NMR analysis suggested that cross-linking via CaB has low relevance in this peat. This unexpected finding is probably due to the low cation exchange capacity, resulting in low abundance of charged functionalities. Molecular modeling demonstrates that large average distances between functionalities (∼3 nm in this peat cannot be bridged by CaB-WaMB associations. However, aging strongly increased matrix rigidity, suggesting successive increase of WaMB size to connect functionalities and thus increasing degree of cross-linking by CaB-WaMB associations. Results thus demonstrated that the physicochemical structure of OM is

  13. Adsorption of cationic amylopectin on microcrystalline cellulose.

    NARCIS (Netherlands)

    Steeg, van de H.G.M.; Keizer, de A.; Cohen Stuart, M.A.; Bijsterbosch, B.H.

    1993-01-01

    The effects of electrolyte concentration and pH on the adsorption of cationic amylopectin on microcrystalline cellulose were investigated. The adsorbed amount in the pseudo-plateau of the isotherm showed a maximum as a function of the electrolyte concentration. We compared the data with a recent

  14. Alkynylcarbenium ions and related unsaturated cations

    Energy Technology Data Exchange (ETDEWEB)

    Lukyanov, Sergey M; Koblik, Alla V; Muradyan, Lyudmila A [Institute of Physical and Organic Chemistry, Rostov State University, Rostov-on-Don (Russian Federation)

    1998-10-31

    Published data on carbenium ions containing carbon-carbon triple bonds both directly conjugated with the carbenium centre and separated from it are surveyed and described systematically. Ammonium, diazonium, iminium, phosphonium and iodonium cations containing alkynyl groups, which can be regarded as heteroanalogues of alkynylcarbenium ions, are also considered. The bibliography includes 283 references.

  15. Alkynylcarbenium ions and related unsaturated cations

    International Nuclear Information System (INIS)

    Lukyanov, Sergey M; Koblik, Alla V; Muradyan, Lyudmila A

    1998-01-01

    Published data on carbenium ions containing carbon-carbon triple bonds both directly conjugated with the carbenium centre and separated from it are surveyed and described systematically. Ammonium, diazonium, iminium, phosphonium and iodonium cations containing alkynyl groups, which can be regarded as heteroanalogues of alkynylcarbenium ions, are also considered. The bibliography includes 283 references

  16. Effect of cations on the hydrated proton.

    Science.gov (United States)

    Ottosson, Niklas; Hunger, Johannes; Bakker, Huib J

    2014-09-17

    We report on a strong nonadditive effect of protons and other cations on the structural dynamics of liquid water, which is revealed using dielectric relaxation spectroscopy in the frequency range of 1-50 GHz. For pure acid solutions, protons are known to have a strong structuring effect on water, leading to a pronounced decrease of the dielectric response. We observe that this structuring is reduced when protons are cosolvated with salts. This reduction is exclusively observed for combinations of protons with other ions; for all studied solutions of cosolvated salts, the effect on the structural dynamics of water is observed to be purely additive, even up to high concentrations. We derive an empirical model that quantitatively describes the nonadditive effect of cosolvated protons and cations. We argue that the effect can be explained from the special character of the proton in water and that Coulomb fields exerted by other cations, in particular doubly charged cations like Mg(2+)aq and Ca(2+)aq, induce a localization of the H(+)aq hydration structures.

  17. Mixed cation effect in sodium aluminosilicate glasses

    DEFF Research Database (Denmark)

    Kjeldsen, Jonas; Smedskjær, Morten Mattrup; Mauro, John C.

    , network structure, and the resistances associated with the deformation processes in mixed cation glasses by partially substituting magnesium for calcium and calcium for lithium in sodium aluminosilicate glasses. We use Raman and 27Al NMR spectroscopies to obtain insights into the structural...

  18. Cationic flotation of some lithium ores

    International Nuclear Information System (INIS)

    Valadao, G.E.S.; Peres, A.E.C.; Silva, H.C. da

    1984-01-01

    The cationic flotation of some lithium ores (spodumene, amblygonite, petalite, lepidolite) is studied by the measure of zeta potential and micro-flotation tests in Hallimond tube. The effect of some modifier agents (corn starch, meta sodium silicate) on the lithium flotation is studied. (M.A.C.) [pt

  19. Letter: OCCO*+, NNCO*+ and NNNN*+ radical cations.

    Science.gov (United States)

    Flammang, R; Srinivas, R; Nguyen, M T; Gerbaux, P

    2007-01-01

    Chemical ionization of a mixture of nitrogen and carbon monoxide produces three stable isobaric species at m/z 56: OCCO, OCNN and NNNN radical cations. Separated at increased resolution, these ions are readily identified by collisional activation. Neutralization-reionization experiments performed on two different mass spectrometers have not allowed the detection of any recovery signals for the corresponding neutrals.

  20. Al cation induces aggregation of serum proteins.

    Science.gov (United States)

    Chanphai, P; Kreplak, L; Tajmir-Riahi, H A

    2017-07-15

    Al cation is known to induce protein fibrillation and causes several neurodegenerative disorders. We report the spectroscopic, thermodynamic analysis and AFM imaging for the Al cation binding process with human serum albumin (HSA), bovine serum albumin (BSA) and milk beta-lactoglobulin (b-LG) in aqueous solution at physiological pH. Hydrophobicity played a major role in Al-protein interactions with more hydrophobic b-LG forming stronger Al-protein complexes. Thermodynamic parameters ΔS, ΔH and ΔG showed Al-protein bindings occur via hydrophobic and H-bonding contacts for b-LG, while van der Waals and H-bonding interactions prevail in HSA and BSA adducts. AFM clearly indicated that aluminum cations are able to force BSA and b-LG into larger or more robust aggregates than HSA, with HSA 4±0.2 (SE, n=801) proteins per aggregate, for BSA 17±2 (SE, n=148), and for b-LG 12±3 (SE, n=151). Thioflavin T test showed no major protein fibrillation in the presence of Al cation. Al complexation induced major alterations of protein conformations with the order of perturbations b-LG>BSA>HSA. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Chemical reactivity of cation-exchanged zeolites

    NARCIS (Netherlands)

    Pidko, E.A.

    2008-01-01

    Zeolites modified with metal cations have been extensively studied during the last two decades because of their wide application in different technologically important fields such as catalysis, adsorption and gas separation. Contrary to the well-understood mechanisms of chemical reactions catalyzed

  2. Selective crystallization of cations with crown ethers

    International Nuclear Information System (INIS)

    Heffels, Dennis Egidius

    2014-01-01

    The aim of this work was to study the selectivity and preferences of the incorporation of differently sized cations in the cavities of various crown ethers and the characterization of the resulting compounds. The coordination preferences of crown ethers with different cavities have long been known, and the impact of other effects on the structure formation have increasingly become the focus of attention. In this work a comparative overview of the coordination preferences depending on various factors was undertaken. The focus was mainly on the variation of the cavity of the crown ether in the presence of differently sized cations. In addition, the effects of the solvent and differently coordinating anions have been investigated. Within the framework of this work, basic coordination preferences could be detected with rare earth nitrates, which are affected particularly by the choice of the solvent. The formation of different types of structures could be controlled by varying the conditions such that the incorporation of the cation in the cavity of the crown ether was influenced and the formation of a particular type of structure can be influenced partly by the choice of solvent. In this case no direct preferences for the incorporation into the cavity of the crown ether in relation to the cation size were observed for rare earth cations. However, the coordination of the crown ether leads in each case - for lanthanides - to rather high coordination numbers. A total of five new rare earth complexes and two structural variants could be observed with crown ethers. In the study of the selectivity of the incorporation into the cavity, known structures were also reproduced and further structures were characterized but the crystal structures not entirely solved. With the use of monovalent cations such as potassium, lithium or silver a total of nine new compounds could be synthesized, while no clear preferences for the incorporation of certain cations were detected. The

  3. Single Amino Acid Modification of Adeno-Associated Virus Capsid Changes Transduction and Humoral Immune Profiles

    Science.gov (United States)

    Diprimio, Nina; Bowles, Dawn E.; Hirsch, Matthew L.; Monahan, Paul E.; Asokan, Aravind; Rabinowitz, Joseph; Agbandje-McKenna, Mavis

    2012-01-01

    Adeno-associated virus (AAV) vectors have the potential to promote long-term gene expression. Unfortunately, humoral immunity restricts patient treatment and in addition provides an obstacle to the potential option of vector readministration. In this study, we describe a comprehensive characterization of the neutralizing antibody (NAb) response to AAV type 1 (AAV1) through AAV5 both in vitro and in vivo. These results demonstrated that NAbs generated from one AAV type are unable to neutralize the transduction of other types. We extended this observation by demonstrating that a rationally engineered, muscle-tropic AAV2 mutant containing 5 amino acid substitutions from AAV1 displayed a NAb profile different from those of parental AAV2 and AAV1. Here we found that a single insertion of Thr from AAV1 into AAV2 capsid at residue 265 preserved high muscle transduction, while also changing the immune profile. To better understand the role of Thr insertion at position 265, we replaced all 20 amino acids and evaluated both muscle transduction and the NAb response. Of these variants, 8 mutants induced higher muscle transduction than AAV2. Additionally, three classes of capsid NAb immune profile were defined based on the ability to inhibit transduction from AAV2 or mutants. While no relationship was found between transduction, amino acid properties, and NAb titer or its cross-reactivity, these studies map a critical capsid motif involved in all steps of AAV infectivity. Our results suggest that AAV types can be utilized not only as templates to generate mutants with enhanced transduction efficiency but also as substrates for repeat administration. PMID:22593151

  4. [Noncovalent cation-π interactions--their role in nature].

    Science.gov (United States)

    Fink, Krzysztof; Boratyński, Janusz

    2014-11-07

    Non-covalent interactions play an extremely important role in organisms. The main non-covalent interactions in nature are: ion-ion interactions, dipole-dipole interactions, hydrogen bonds, and van der Waals interactions. A new kind of intermolecular interactions--cation-π interactions--is gaining increasing attention. These interactions occur between a cation and a π system. The main contributors to cation-π interactions are electrostatic, polarization and, to a lesser extent, dispersion interactions. At first, cation-π interactions were studied in a gas phase, with metal cation-aromatic system complexes. The characteristics of these complexes are as follows: an increase of cation atomic number leads to a decrease of interaction energy, and an increase of cation charge leads to an increase of interaction energy. Aromatic amino acids bind with metal cations mainly through interactions with their main chain. Nevertheless, cation-π interaction with a hydrophobic side chain significantly enhances binding energy. In water solutions most cations preferentially interact with water molecules rather than aromatic systems. Cation-π interactions occur in environments with lower accessibility to a polar solvent. Cation-π interactions can have a stabilizing role on the secondary, tertiary and quaternary structure of proteins. These interactions play an important role in substrate or ligand binding sites in many proteins, which should be taken into consideration when the screening of effective inhibitors for these proteins is carried out. Cation-π interactions are abundant and play an important role in many biological processes.

  5. Structure relationship of cationic lipids on gene transfection mediated by cationic liposomes.

    Science.gov (United States)

    Paecharoenchai, Orapan; Niyomtham, Nattisa; Apirakaramwong, Auayporn; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Yingyongnarongkul, Boon-ek; Opanasopit, Praneet

    2012-12-01

    The aim of this study was to investigate the transfection efficiency of cationic liposomes formulated with phosphatidylcholine (PC) and novel synthesized diethanolamine-based cationic lipids at a molar ratio of 5:1 in comparison with Lipofectamine™ 2000. Factors affecting transfection efficiency and cell viability, including the chemical structure of the cationic lipids, such as different amine head group (diamine and polyamine; and non-spermine and spermine) and acyl chain lengths (C14, C16, and C18) and the weight ratio of liposomes to DNA were evaluated on a human cervical carcinoma cell line (HeLa cells) using the pDNA encoding green fluorescent protein (pEGFP-C2). Characterizations of these lipoplexes in terms of size and charge measurement and agarose gel electrophoresis were performed. The results from this study revealed that almost no transfection was observed in the liposome formulations composed of cationic lipids with a non-spermine head group. In addition, the transfection efficiency of these cationic liposomes was in the following order: spermine-C14 > spermine-C16 > spermine-C18. The highest transfection efficiency was observed in the formulation of spermine-C14 liposomes at a weight ratio of 25; furthermore, this formulation was safe for use in vitro. In conclusion, cationic liposomes containing spermine head groups demonstrated promising potential as gene carriers.

  6. MRP-1/CD9 gene transduction regulates the actin cytoskeleton through the downregulation of WAVE2.

    Science.gov (United States)

    Huang, C-L; Ueno, M; Liu, D; Masuya, D; Nakano, J; Yokomise, H; Nakagawa, T; Miyake, M

    2006-10-19

    Motility-related protein-1 (MRP-1/CD9) is involved in cell motility. We studied the change in the actin cytoskeleton, and the expression of actin-related protein (Arp) 2 and Arp3 and the Wiskott-Aldrich syndrome protein (WASP) family according to MRP-1/CD9 gene transduction into HT1080 cells. The frequency of cells with lamellipodia was significantly lower in MRP-1/CD9-transfected HT1080 cells than in control HT1080 cells (PMRP-1/CD9 gene transduction affected the subcellular localization of Arp2 and Arp3 proteins. Furthermore, MRP-1/CD9 gene transduction induced a downregulation of WAVE2 expression (PMRP-1/CD9 monoclonal antibody inhibited downregulation of WAVE2 in MRP-1/CD9-transfected HT1080 cells (PMRP-1/CD9 gene transduction. Furthermore, downregulation of WAVE2 by transfection of WAVE2-specific small interfering RNA (siRNA) mimicked the morphological effects of MRP-1/CD9 gene transduction and suppressed cell motility. However, transfection of each siRNA for Wnt1, Wnt2b1 or Wnt5a did not affect WAVE2 expression. Transfection of WAVE2-specific siRNA also did not affect expressions of these Wnts. These results indicate that MRP-1/CD9 regulates the actin cytoskeleton by downregulating of the WAVE2, through the Wnt-independent signal pathway.

  7. Effects of the TAT peptide orientation and relative location on the protein transduction efficiency.

    Science.gov (United States)

    Guo, Qingguo; Zhao, Guojie; Hao, Fengjin; Guan, Yifu

    2012-05-01

    To understand the protein transduction domain (PTD)-mediated protein transduction behavior and to explore its potential in delivering biopharmaceutic drugs, we prepared four TAT-EGFP conjugates: TAT(+)-EGFP, TAT(-)-EGFP, EGFP-TAT(+) and EGFP-TAT(-), where TAT(+) and TAT(-) represent the original and the reversed TAT sequence, respectively. These four TAT-EGFP conjugates were incubated with HeLa and PC12 cells for in vitro study as well as injected intraperitoneally to mice for in vivo study. Flow cytometric results showed that four TAT-EGFP conjugates were able to traverse HeLa and PC12 cells with almost equal transduction efficiency. The in vivo study showed that the TAT-EGFP conjugates could be delivered into different organs of mice with different transduction capabilities. Bioinformatic analyses and CD spectroscopic data revealed that the TAT peptide has no defined secondary structure, and conjugating the TAT peptide to the EGFP cargo protein would not alter the native structure and the function of the EGFP protein. These results conclude that the sequence orientation, the spatial structure, and the relative location of the TAT peptide have much less effect on the TAT-mediated protein transduction. Thus, the TAT-fused conjugates could be constructed in more convenient and flexible formats for a wide range of biopharmaceutical applications. © 2011 John Wiley & Sons A/S.

  8. Discovery of intramolecular signal transduction network based on a new protein dynamics model of energy dissipation.

    Directory of Open Access Journals (Sweden)

    Cheng-Wei Ma

    Full Text Available A novel approach to reveal intramolecular signal transduction network is proposed in this work. To this end, a new algorithm of network construction is developed, which is based on a new protein dynamics model of energy dissipation. A key feature of this approach is that direction information is specified after inferring protein residue-residue interaction network involved in the process of signal transduction. This enables fundamental analysis of the regulation hierarchy and identification of regulation hubs of the signaling network. A well-studied allosteric enzyme, E. coli aspartokinase III, is used as a model system to demonstrate the new method. Comparison with experimental results shows that the new approach is able to predict all the sites that have been experimentally proved to desensitize allosteric regulation of the enzyme. In addition, the signal transduction network shows a clear preference for specific structural regions, secondary structural types and residue conservation. Occurrence of super-hubs in the network indicates that allosteric regulation tends to gather residues with high connection ability to collectively facilitate the signaling process. Furthermore, a new parameter of propagation coefficient is defined to determine the propagation capability of residues within a signal transduction network. In conclusion, the new approach is useful for fundamental understanding of the process of intramolecular signal transduction and thus has significant impact on rational design of novel allosteric proteins.

  9. Rapid lentiviral transduction preserves the engraftment potential of Fanca(-/-) hematopoietic stem cells.

    Science.gov (United States)

    Müller, Lars U W; Milsom, Michael D; Kim, Mi-Ok; Schambach, Axel; Schuesler, Todd; Williams, David A

    2008-06-01

    Fanconi anemia (FA) is a rare recessive syndrome, characterized by congenital anomalies, bone marrow failure, and predisposition to cancer. Two earlier clinical trials utilizing gamma-retroviral vectors for the transduction of autologous FA hematopoietic stem cells (HSCs) required extensive in vitro manipulation and failed to achieve detectable long-term engraftment of transduced HSCs. As a strategy for minimizing ex vivo manipulation, we investigated the use of a "rapid" lentiviral transduction protocol in a murine Fanca(-/-) model. Importantly, while this and most murine models of FA fail to completely mimic the human hematopoietic phenotype, we observed a high incidence of HSC transplant engraftment failure and low donor chimerism after conventional transduction (CT) of Fanca(-/-) donor cells. In contrast, rapid transduction (RT) of Fanca(-/-) HSCs preserved engraftment to the level achieved in wild-type cells, resulting in long-term multilineage engraftment of gene-modified cells. We also demonstrate the correction of the characteristic hypersensitivity of FA cells against the cross-linking agent mitomycin C (MMC), and provide evidence for the advantage of using pharmacoselection as a means of further increasing gene-modified cells after RT. Collectively, these data support the use of rapid lentiviral transduction for gene therapy in FA.

  10. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis

    Directory of Open Access Journals (Sweden)

    Gareth W. Fearnley

    2016-05-01

    Full Text Available Vascular endothelial growth factor A (VEGF-A binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A–VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor–ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145 promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes.

  11. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis.

    Science.gov (United States)

    Fearnley, Gareth W; Smith, Gina A; Abdul-Zani, Izma; Yuldasheva, Nadira; Mughal, Nadeem A; Homer-Vanniasinkam, Shervanthi; Kearney, Mark T; Zachary, Ian C; Tomlinson, Darren C; Harrison, Michael A; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

    2016-05-15

    Vascular endothelial growth factor A (VEGF-A) binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A-VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor-ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145) promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes. © 2016. Published by The Company of Biologists Ltd.

  12. Fluconazole affects the alkali-metal-cation homeostasis and susceptibility to cationic toxic compounds of Candida glabrata.

    Science.gov (United States)

    Elicharova, Hana; Sychrova, Hana

    2014-08-01

    Candida glabrata is a salt-tolerant and fluconazole (FLC)-resistant yeast species. Here, we analyse the contribution of plasma-membrane alkali-metal-cation exporters, a cation/proton antiporter and a cation ATPase to cation homeostasis and the maintenance of membrane potential (ΔΨ). Using a series of single and double mutants lacking CNH1 and/or ENA1 genes we show that the inability to export potassium and toxic alkali-metal cations leads to a slight hyperpolarization of the plasma membrane of C. glabrata cells; this hyperpolarization drives more cations into the cells and affects cation homeostasis. Surprisingly, a much higher hyperpolarization of C. glabrata plasma membrane was produced by incubating cells with subinhibitory concentrations of FLC. FLC treatment resulted in a substantially increased sensitivity of cells to various cationic drugs and toxic cations that are driven into the cell by negative-inside plasma-membrane potential. The effect of the combination of FLC plus cationic drug treatment was enhanced by the malfunction of alkali-metal-cation transporters that contribute to the regulation of membrane potential and cation homeostasis. In summary, we show that the combination of subinhibitory concentrations of FLC and cationic drugs strongly affects the growth of C. glabrata cells. © 2014 The Authors.

  13. (4 + 3) Cycloadditions of Nitrogen-Stabilized Oxyallyl Cations

    Science.gov (United States)

    Lohse, Andrew G.; Hsung, Richard P.

    2011-01-01

    The use of heteroatom-substituted oxyallyl cations in (4 + 3) cycloadditions has had a tremendous impact on the development of cycloaddition chemistry. Extensive efforts have been exerted toward investigating the effect of oxygen-, sulfur-, and halogen-substituents on the reactivity of oxyallyl cations. Most recently, the use of nitrogen-stabilized oxyallyl cations has gained prominence in the area of (4 + 3) cycloadditions. The following article will provide an overview of this concept utilizing nitrogen-stabilized oxyallyl cations. PMID:21384451

  14. Comparative physical-chemical characterization of encapsulated lipid-based isotretinoin products assessed by particle size distribution and thermal behavior analyses

    Energy Technology Data Exchange (ETDEWEB)

    Guimaraes, Carla Aiolfi, E-mail: carlaaiolfi@usp.br [Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP 05508-000 (Brazil); Menaa, Farid [Department of Dermatology, School of Medicine Wuerzburg, Wuerzburg 97080 (Germany); Fluorotronics, Inc., 1425 Russ Bvld, San Diego Technology Incubator, San Diego, CA 92101 (United States); Menaa, Bouzid, E-mail: bouzid.menaa@gmail.com [Fluorotronics, Inc., 1425 Russ Bvld, San Diego Technology Incubator, San Diego, CA 92101 (United States); Quenca-Guillen, Joyce S. [Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP 05508-000 (Brazil); Matos, Jivaldo do Rosario [Department of Fundamental Chemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP 05508-000 (Brazil); Mercuri, Lucildes Pita [Department of Exact and Earth Sciences, Federal University of Sao Paulo, Diadema, SP 09972-270 (Brazil); Braz, Andre Borges [Department of Engineering of Mines and Oil, Polytechnical School, University of Sao Paulo, SP 05508-900 (Brazil); Rossetti, Fabia Cristina [Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP 14015-120 (Brazil); Kedor-Hackmann, Erika Rosa Maria; Santoro, Maria Ines Rocha Miritello [Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP 05508-000 (Brazil)

    2010-06-10

    Isotretinoin is the drug of choice for the management of severe recalcitrant nodular acne. Nevertheless, some of its physical-chemical properties are still poorly known. Hence, the aim of our study consisted to comparatively evaluate the particle size distribution (PSD) and characterize the thermal behavior of the three encapsulated isotretinoin products in oil suspension (one reference and two generics) commercialized in Brazil. Here, we show that the PSD, estimated by laser diffraction and by polarized light microscopy, differed between the generics and the reference product. However, the thermal behavior of the three products, determined by thermogravimetry (TGA), differential thermal (DTA) analyses and differential scanning calorimetry (DSC), displayed no significant changes and were more thermostable than the isotretinoin standard used as internal control. Thus, our study suggests that PSD analyses in isotretinoin lipid-based formulations should be routinely performed in order to improve their quality and bioavailability.

  15. Acceptability of new formulations of corn-soy blends and lipid-based nutrient supplements in Province du Passoré, Burkina Faso

    DEFF Research Database (Denmark)

    Iuel-Brockdorff, Ann-Sophie Julie D; Dræbel, Tania; Fabiansen, Christian

    2015-01-01

    The objective of this study was to evaluate the acceptability of new formulations of six corn-soy blended flours (CSB) and six lipid-based nutrient supplements (LNS) with different quantities of milk and qualities of soy to be used for the treatment of moderate acute malnutrition (MAM). Furthermore......, we wanted to explore the acceptability of foods currently used for the prevention and treatment of malnutrition in Burkina Faso to identify possible barriers that could affect the acceptability of the new formulations of supplementary foods. The study was carried out prior to a randomized controlled...... trial evaluating the effectiveness of these new formulations. The study involved an observed test-meal and a three-day take-home ration of the experimental food supplements to 6-30-months-old healthy children, followed by questionnaire-based interviews about the acceptability of these supplements...

  16. Lipid-Based Formulations Can Enable the Model Poorly Water-Soluble Weakly Basic Drug Cinnarizine to Precipitate in an Amorphous-Salt Form during in Vitro Digestion

    DEFF Research Database (Denmark)

    Khan, Jamal; Rades, Thomas; Boyd, Ben J

    2016-01-01

    The tendency for poorly water-soluble weakly basic drugs to precipitate in a noncrystalline form during the in vitro digestion of lipid-based formulations (LBFs) was linked to an ionic interaction between drug and fatty acid molecules produced upon lipid digestion. Cinnarizine was chosen as a model...... from the starting free base crystalline material to the hydrochloride salt, thus supporting the case that ionic interactions between weak bases and fatty acid molecules during digestion are responsible for producing amorphous-salts upon precipitation. The conclusion has wide implications...... weakly basic drug and was dissolved in a medium-chain (MC) LBF, which was subject to in vitro lipolysis experiments at various pH levels above and below the reported pKa value of cinnarizine (7.47). The solid-state form of the precipitated drug was analyzed using X-ray diffraction (XRD), Fourier...

  17. Cloning of a two-component signal transduction system of Xanthomonas campestris pv. phaseoli var. fuscans strain BXPF65

    DEFF Research Database (Denmark)

    Chan, JWYF; Maynard, Scott; Goodwin, PH

    1998-01-01

    A putative two-component signal transduction system was amplified and cloned from the plant pathogenic bacterium Xanthomonas campestris pv. phaseoli var. fuscans isolate BXPF65. The 620 bp amplified fragment was sequenced and analyzed with the BLAST Enhanced Alignment Utility (BEAUTY). BEAUTY...... that the putative histidine kinase has homology with conserved “transmitter” domains of sensor proteins in two-component signal transduction systems. RFLP analysis using the putative signal transduction system showed polymorphisms among the strains....

  18. Selective alkylation by photogenerated aryl and vinyl cation

    NARCIS (Netherlands)

    Slegt, Micha

    2006-01-01

    Seven para-substituted phenyl cations and the parent phenyl cation were prepared from iodonium salt precursors. Product studies revealed remarkable chemoselectivity and regioselectivity that could be related to the spin multiplicity of the cations. Also an universal method to fingerprint singlet and

  19. Radiation chemistry of aromatic dimer radical cations

    International Nuclear Information System (INIS)

    Okamoto, Kazumasa; Tagawa, Seiichi

    2009-01-01

    π-π Interactions of aromatic molecules are paid attention much in many fields, especially biology, chemistry, and applied physics, represented as protein, DNA, electron donor-accepter complexes, charge transfers, and self assembly molecules. Aromatic molecules including benzene rings are the simplest case to study the π-π interactions. To interpret the charge resonance (CR) structure in the dimer radical cations, spectroscopic and ESR methods have been carried out. The spectroscopic study on the dimer radical ion of molecules with two chromophores would be profitable to identify the electronic and configurational properties. In this article, dynamics of the dimer radical cation of benzenes, polystyrenes, and resist polymers is described on the basis of direct observation of CR band by the nanosecond pulse radiolysis and low temperature γ-radiolysis methods. (author)

  20. Electronic spectrum of 9-methylanthracenium radical cation

    Energy Technology Data Exchange (ETDEWEB)

    O’Connor, Gerard D.; Schmidt, Timothy W., E-mail: timothy.schmidt@unsw.edu.au [School of Chemistry, UNSW Sydney, New South Wales 2052 (Australia); Sanelli, Julian A.; Dryza, Vik; Bieske, Evan J. [School of Chemistry, The University of Melbourne, Victoria 3010 (Australia)

    2016-04-21

    The predissociation spectrum of the cold, argon-tagged, 9-methylanthracenium radical cation is reported from 8000 cm{sup −1} to 44 500 cm{sup −1}. The reported spectrum contains bands corresponding to at least eight electronic transitions ranging from the near infrared to the ultraviolet. These electronic transitions are assigned through comparison with ab initio energies and intensities. The infrared D{sub 1}←D{sub 0} transitions exhibit significant vibronic activity, which is assigned through comparison with TD-B3LYP excited state frequencies and intensities, as well as modelled vibronic interactions. Dissociation of 9-methylanthracenium is also observed at high visible-photon energies, resulting in the loss of either CH{sub 2} or CH{sub 3}. The relevance of these spectra, and the spectra of other polycyclic aromatic hydrocarbon radical cations, to the largely unassigned diffuse interstellar bands, is discussed.

  1. Photodissociation of spatially aligned acetaldehyde cations.

    Science.gov (United States)

    Lee, Suk Kyoung; Silva, Ruchira; Kim, Myung Hwa; Shen, Lei; Suits, Arthur G

    2007-07-26

    Photofragment translational energy and angular distributions are reported for the photodissociation of acetaldehyde cations in the wavelength range 354-363 nm obtained using the DC slice ion imaging technique. Vibrationally selected parent ions were produced by 2+1 resonance-enhanced multiphoton ionization (REMPI) via the 3sCH3CO+, and CH4+. The angular distributions reveal that all product channels have a predominantly parallel recoil anisotropy although the lower beta2 parameter of CH3CO+ indicates the concomitant presence of a perpendicular component. Furthermore, the distinct angular distribution of the CH3CO+ fragments shows a large value of the higher order Legendre polynomial term, providing evidence that acetaldehyde cations are spatially aligned during the ionization process.

  2. Mechanism of adsorption of cations onto rocks

    International Nuclear Information System (INIS)

    Kitamura, Akira; Yamamoto, Tadashi; Fujiwara, Kenso; Nishikawa, Sataro; Moriyama, Hirotake

    1999-01-01

    Adsorption behavior of cations onto granite was investigated. The distribution coefficient (K d ) of Sr 2+ and Ba 2+ onto granite was determined in the solution of which pH was ranged from 3.5 to 11.3 and ionic strength was set at 10 -2 and 10 -1 . The K d values were found to increase with increasing pH and with deceasing ionic strength. The obtained data were successfully analyzed by applying an electrical double layer model. The optimum parameter values of the double layer electrostatics and adsorption reactions were obtained, and the mechanism of adsorption of cations onto granite was discussed. Feldspar was found to play an important role in their adsorption. (author)

  3. Information Thermodynamics of the Cell Signal Transduction as a Szilard Engine

    Directory of Open Access Journals (Sweden)

    Tatsuaki Tsuruyama

    2018-03-01

    Full Text Available A cell signaling system is in a non-equilibrium state, and it includes multistep biochemical signaling cascades (BSCs, which involve phosphorylation of signaling molecules, such as mitogen-activated protein kinase (MAPK pathways. In this study, the author considered signal transduction description using information thermodynamic theory. The ideal BSCs can be considered one type of the Szilard engine, and the presumed feedback controller, Maxwell’s demon, can extract the work during signal transduction. In this model, the mutual entropy and chemical potential of the signal molecules can be redefined by the extracted chemical work in a mechanicochemical model, Szilard engine, of BSC. In conclusion, signal transduction is computable using the information thermodynamic method.

  4. Notch2 transduction by feline leukemia virus in a naturally infected cat.

    Science.gov (United States)

    Watanabe, Shinya; Ito, Jumpei; Baba, Takuya; Hiratsuka, Takahiro; Kuse, Kyohei; Ochi, Haruyo; Anai, Yukari; Hisasue, Masaharu; Tsujimoto, Hajime; Nishigaki, Kazuo

    2014-04-01

    Feline leukemia virus (FeLV) induces neoplastic and nonneoplastic diseases in cats. The transduction of cellular genes by FeLV is sometimes observed and associated with neoplastic diseases including lymphoma and sarcoma. Here, we report the first natural case of feline Notch2 transduction by FeLV in an infected cat with multicentric lymphoma and hypercalcemia. We cloned recombinant FeLVs harboring Notch2 in the env gene. Notch2 was able to activate expression of a reporter gene, similar to what was previously reported in cats with experimental FeLV-induced thymic lymphoma. Our findings suggest that the transduction of Notch2 strongly correlates with FeLV-induced lymphoma.

  5. Double Solvent Sensing Method for Improving Sensitivity and Accuracy of Hg(II) Detection Based on Different Signal Transduction of a Tetrazine-Functionalized Pillared Metal-Organic Framework.

    Science.gov (United States)

    Razavi, Sayed Ali Akbar; Masoomi, Mohammad Yaser; Morsali, Ali

    2017-08-21

    To design a robust, π-conjugated, low-cost, and easy to synthesize metal-organic framework (MOF) for cation sensing by the photoluminescence (PL) method, 4,4'-oxybis(benzoic acid) (H 2 OBA) has been used in combination with 3,6-di(pyridin-4-yl)-1,2,4,5-tetrazine (DPT) as a tetrazine-functionalized spacer to construct [Zn(OBA)(DPT) 0.5 ]·DMF (TMU-34(-2H)). The tetrazine motif is a π-conjugated, water-soluble/stable fluorophore with relatively weak σ-donating Lewis basic sites. These characteristics of tetrazine make TMU-34(-2H) a good candidate for cation sensing. Because of hydrogen bonding between tetrazine moieties and water molecules, TMU-34(-2H) shows different PL emissions in water and acetonitrile. Cation sensing in these two solvents revealed that TMU-34(-2H) can selectively detect Hg 2+ in water (by 243% enhancement) and in acetonitrile (by 90% quenching). The contribution of electron-donating/accepting characteristics along with solvation effects on secondary interactions of the tetrazine motifs inside the TMU-34(-2H) framework results in different signal transductions. Improved sensitivity and accuracy of detection were obtained using the double solvent sensing method (DSSM), in which different signal transductions of TMU-34(-2H) in water and acetonitrile were combined simultaneously to construct a double solvent sensing curve and formulate a sensitivity factor. Calculation of sensitivity factors for all of the tested cations demonstrated that it is possible to detect Hg 2+ by DSSM with ultrahigh sensitivity. Such a tremendous distinction in the Hg 2+ sensitivity factor is visualizable in the double solvent sensing curve. Thus, by application of DSSM instead of one-dimensional sensing, the interfering effects of other cations are completely eliminated and the sensitivity toward Hg(II) is highly improved. Strong interactions between Hg 2+ and the nitrogen atoms of the tetrazine groups along with easy accessibility of Hg 2+ to the tetrazine groups lead

  6. Effects of pergolide mesylate on transduction efficiency of PEP-1-catalase protein

    International Nuclear Information System (INIS)

    Sohn, Eun Jeong; Kim, Dae Won; Kim, Young Nam; Kim, So Mi; Lim, Soon Sung; Kang, Tae-Cheon; Kwon, Hyeok Yil; Kim, Duk-Soo; Cho, Sung-Woo; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Hwang, Hyun Sook; Choi, Soo Young

    2011-01-01

    Research highlights: → We studied effects of pergolide mesylate (PM) on in vitro and in vivo transduction of PEP-1-catalase. → PEP-1-catatase inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. → PM enhanced the transduction of PEP-1-catalase into HaCaT cells and skin tissue. → PM increased anti-inflammatory activity of PEP-1-catalase. → PM stimulated therapeutic action of anti-oxidant enzyme catalase in oxidative-related diseases. -- Abstract: The low transduction efficiency of various proteins is an obstacle to their therapeutic application. However, protein transduction domains (PTDs) are well-known for a highly effective tool for exogenous protein delivery to cells. We examined the effects of pergolide mesylate (PM) on the transduction of PEP-1-catalase into HaCaT human keratinocytes and mice skin and on the anti-inflammatory activity of PEP-1-catatase against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation using Western blot and histological analysis. PM enhanced the time- and dose-dependent transduction of PEP-1-catalase into HaCaT cells without affecting the cellular toxicity. In a mouse edema model, PEP-1-catalase inhibited the increased expressions of inflammatory mediators and cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1β, and tumor necrosis factor-α induced by TPA. On the other hand, PM alone failed to exert any significant anti-inflammatory effects. However, the anti-inflammatory effect of co-treatment with PEP-1-catalase and PM was more potent than that of PEP-1-catalase alone. Our results indicate that PM may enhance the delivery of PTDs fusion therapeutic proteins to target cells and tissues and has potential to increase their therapeutic effects of such drugs against various diseases.

  7. Effects of pergolide mesylate on transduction efficiency of PEP-1-catalase protein

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Eun Jeong; Kim, Dae Won; Kim, Young Nam; Kim, So Mi [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Lim, Soon Sung [Department of Food Science and Nutrition and RIC Center, Hallym University, Chunchon 200-702 (Korea, Republic of); Kang, Tae-Cheon [Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Kwon, Hyeok Yil [Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Kim, Duk-Soo [Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-090 (Korea, Republic of); Cho, Sung-Woo [Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Hwang, Hyun Sook, E-mail: wazzup@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

    2011-03-18

    Research highlights: {yields} We studied effects of pergolide mesylate (PM) on in vitro and in vivo transduction of PEP-1-catalase. {yields} PEP-1-catatase inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. {yields} PM enhanced the transduction of PEP-1-catalase into HaCaT cells and skin tissue. {yields} PM increased anti-inflammatory activity of PEP-1-catalase. {yields} PM stimulated therapeutic action of anti-oxidant enzyme catalase in oxidative-related diseases. -- Abstract: The low transduction efficiency of various proteins is an obstacle to their therapeutic application. However, protein transduction domains (PTDs) are well-known for a highly effective tool for exogenous protein delivery to cells. We examined the effects of pergolide mesylate (PM) on the transduction of PEP-1-catalase into HaCaT human keratinocytes and mice skin and on the anti-inflammatory activity of PEP-1-catatase against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation using Western blot and histological analysis. PM enhanced the time- and dose-dependent transduction of PEP-1-catalase into HaCaT cells without affecting the cellular toxicity. In a mouse edema model, PEP-1-catalase inhibited the increased expressions of inflammatory mediators and cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1{beta}, and tumor necrosis factor-{alpha} induced by TPA. On the other hand, PM alone failed to exert any significant anti-inflammatory effects. However, the anti-inflammatory effect of co-treatment with PEP-1-catalase and PM was more potent than that of PEP-1-catalase alone. Our results indicate that PM may enhance the delivery of PTDs fusion therapeutic proteins to target cells and tissues and has potential to increase their therapeutic effects of such drugs against various diseases.

  8. Reducible cationic lipids for gene transfer.

    Science.gov (United States)

    Wetzer, B; Byk, G; Frederic, M; Airiau, M; Blanche, F; Pitard, B; Scherman, D

    2001-01-01

    One of the main challenges of gene therapy remains the increase of gene delivery into eukaryotic cells. We tested whether intracellular DNA release, an essential step for gene transfer, could be facilitated by using reducible cationic DNA-delivery vectors. For this purpose, plasmid DNA was complexed with cationic lipids bearing a disulphide bond. This reduction-sensitive linker is expected to be reduced and cleaved in the reducing milieu of the cytoplasm, thus potentially improving DNA release and consequently transfection. The DNA--disulphide-lipid complexation was monitored by ethidium bromide exclusion, and the size of complexes was determined by dynamic light scattering. It was found that the reduction kinetics of disulphide groups in DNA--lipid complexes depended on the position of the disulphide linker within the lipid molecule. Furthermore, the internal structure of DNA--lipid particles was examined by small-angle X-ray scattering before and after lipid reduction. DNA release from lipid complexes was observed after the reduction of disulphide bonds of several lipids. Cell-transfection experiments suggested that complexes formed with selected reducible lipids resulted in up to 1000-fold higher reporter-gene activity, when compared with their analogues without disulphide bonds. In conclusion, reduction-sensitive groups introduced into cationic lipid backbones potentially allow enhanced DNA release from DNA--lipid complexes after intracellular reduction and represent a tool for improved vectorization. PMID:11389682

  9. Cationic Polyamidoamine Dendrimers as Modulators of EGFR Signaling In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    Saghir Akhtar

    Full Text Available Cationic polyamidoamine (PAMAM dendrimers are branch-like spherical polymers being investigated for a variety of applications in nanomedicine including nucleic acid drug delivery. Emerging evidence suggests they exhibit intrinsic biological and toxicological effects but little is known of their interactions with signal transduction pathways. We previously showed that the activated (fragmented generation (G 6 PAMAM dendrimer, Superfect (SF, stimulated epidermal growth factor receptor (EGFR tyrosine kinase signaling-an important signaling cascade that regulates cell growth, survival and apoptosis- in cultured human embryonic kidney (HEK 293 cells. Here, we firstly studied the in vitro effects of Polyfect (PF, a non-activated (intact G6 PAMAM dendrimer, on EGFR tyrosine kinase signaling via extracellular-regulated kinase 1/2 (ERK1/2 and p38 mitogen-activated protein kinase (MAPK in cultured HEK 293 cells and then compared the in vivo effects of a single administration (10mg/kg i.p of PF or SF on EGFR signaling in the kidneys of normal and diabetic male Wistar rats. Polyfect exhibited a dose- and time-dependent inhibition of EGFR, ERK1/2 and p38 MAPK phosphorylation in HEK-293 cells similar to AG1478, a selective EGFR inhibitor. Administration of dendrimers to non-diabetic or diabetic animals for 24h showed that PF inhibited whereas SF stimulated EGFR phosphorylation in the kidneys of both sets of animals. PF-mediated inhibition of EGFR phosphorylation as well as SF or PF-mediated apoptosis in HEK 293 cells could be significantly reversed by co-treatment with antioxidants such as tempol implying that both these effects involved an oxidative stress-dependent mechanism. These results show for the first time that SF and PF PAMAM dendrimers can differentially modulate the important EGFR signal transduction pathway in vivo and may represent a novel class of EGFR modulators. These findings could have important clinical implications for the use of PAMAM

  10. Cancer classification through filtering progressive transductive support vector machine based on gene expression data

    Science.gov (United States)

    Lu, Xinguo; Chen, Dan

    2017-08-01

    Traditional supervised classifiers neglect a large amount of data which not have sufficient follow-up information, only work with labeled data. Consequently, the small sample size limits the advancement of design appropriate classifier. In this paper, a transductive learning method which combined with the filtering strategy in transductive framework and progressive labeling strategy is addressed. The progressive labeling strategy does not need to consider the distribution of labeled samples to evaluate the distribution of unlabeled samples, can effective solve the problem of evaluate the proportion of positive and negative samples in work set. Our experiment result demonstrate that the proposed technique have great potential in cancer prediction based on gene expression.

  11. Anchoring cationic amphiphiles for nucleotide delivery: significance of DNA release from cationic liposomes for transfection.

    Science.gov (United States)

    Hirashima, Naohide; Minatani, Kazuhiro; Hattori, Yoshifumi; Ohwada, Tomohiko; Nakanishi, Mamoru

    2007-06-01

    We have designed and synthesized lithocholic acid-based cationic amphiphile molecules as components of cationic liposomes for gene transfection (lipofection). To study the relationship between the molecular structures of those amphiphilic molecules, particularly the extended hydrophobic appendant (anchor) at the 3-hydroxyl group, and transfection efficiency, we synthesized several lithocholic and isolithocholic acid derivatives, and examined their transfection efficiency. We also compared the physico-chemical properties of cationic liposomes prepared from these derivatives. We found that isolithocholic acid derivatives exhibit higher transfection efficiency than the corresponding lithocholic acid derivatives. This result indicates that the orientation and extension of hydrophobic regions influence the gene transfection process. Isolithocholic acid derivatives showed a high ability to encapsulate DNA in a compact liposome-DNA complex and to protect it from enzymatic degradation. Isolithocholic acid derivatives also facilitated the release of DNA from the liposome-DNA complex, which is a crucial step for DNA entry into the nucleus. Our results show that the transfection efficiency is directly influenced by the ability of the liposome complex to release DNA, rather than by the DNA-encapsulating ability. Molecular modeling revealed that isolithocholic acid derivatives take relatively extended conformations, while the lithocholic acid derivatives take folded structures. Thus, the efficiency of release of DNA from cationic liposomes in the cytoplasm, which contributes to high transfection efficiency, appears to be dependent upon the molecular shape of the cationic amphiphiles.

  12. Comparative analysis of cation/proton antiporter superfamily in plants.

    Science.gov (United States)

    Ye, Chu-Yu; Yang, Xiaohan; Xia, Xinli; Yin, Weilun

    2013-06-01

    The cation/proton antiporter superfamily is associated with the transport of monovalent cations across membranes. This superfamily was annotated in the Arabidopsis genome and some members were functionally characterized. In the present study, a systematic analysis of the cation/proton antiporter genes in diverse plant species was reported. We identified 240 cation/proton antiporters in alga, moss, and angiosperm. A phylogenetic tree was constructed showing these 240 members are separated into three families, i.e., Na(+)/H(+) exchangers, K(+) efflux antiporters, and cation/H(+) exchangers. Our analysis revealed that tandem and/or segmental duplications contribute to the expansion of cation/H(+) exchangers in the examined angiosperm species. Sliding window analysis of the nonsynonymous/synonymous substitution ratios showed some differences in the evolutionary fate of cation/proton antiporter paralogs. Furthermore, we identified over-represented motifs among these 240 proteins and found most motifs are family specific, demonstrating diverse evolution of the cation/proton antiporters among three families. In addition, we investigated the co-expressed genes of the cation/proton antiporters in Arabidopsis thaliana. The results showed some biological processes are enriched in the co-expressed genes, suggesting the cation/proton antiporters may be involved in these biological processes. Taken together, this study furthers our knowledge on cation/proton antiporters in plants. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Radical cations of quadricyclane and norbornadiene in polar ZSM-5 matrices: Radical cation photochemical transformations without photons

    International Nuclear Information System (INIS)

    Barnabas, M.V.; Trifunac, A.D.

    1994-01-01

    Radical cations of quadricyclane (Q) and norbornadiene (NBD) are produced by γ-radiolysis in zeolites. In polar ZSM-5, only one radical cation is initially observed below 100K. Increasing the temperature above 200K gives rise to the cyclopentadiene radical cation. Higher temperatures (>360K) give rise to the cyclopenten-4-yl radical. The observation of cyclopentadiene radical cation implies the occurrence of the reverse Diels-Alder reaction. This is a thermally forbidden, photochemically allowed, process, which is made possible by the interaction of the polar zeolite matrix sites with parent NBD and Q radical cations

  14. Cationic niosomes an effective gene carrier composed of novel spermine-derivative cationic lipids: effect of central core structures.

    Science.gov (United States)

    Opanasopit, Praneet; Leksantikul, Lalita; Niyomtham, Nattisa; Rojanarata, Theerasak; Ngawhirunpat, Tanasait; Yingyongnarongkul, Boon-Ek

    2017-05-01

    Cationic niosomes formulated from Span 20, cholesterol (Chol) and novel spermine-based cationic lipids of multiple central core structures (di(oxyethyl)amino, di(oxyethyl)amino carboxy, 3-amino-1,2-dioxypropyl and 2-amino-1,3-dioxypropyl) were successfully prepared for improving transfection efficiency in vitro. The niosomes composed of spermine cationic lipid with central core structure of di(oxyethyl)amino revealed the highest gene transfection efficiency. To investigate the factors affecting gene transfection and cell viability including differences in the central core structures of cationic lipids, the composition of vesicles, molar ratio of cationic lipids in formulations and the weight ratio of niosomes to DNA. Cationic niosomes composed of nonionic surfactants (Span20), cholesterol and spermine-based cationic lipids of multiple central core structures were formulated. Gene transfection and cell viability were evaluated on a human cervical carcinoma cell line (HeLa cells) using pDNA encoding green fluorescent protein (pEGFP-C2). The morphology, size and charge were also characterized. High transfection efficiency was obtained from cationic niosomes composed of Span20:Chol:cationic lipid at the molar ratio of 2.5:2.5:0.5 mM. Cationic lipids with di(oxyethyl)amino as a central core structure exhibited highest transfection efficiency. In addition, there was also no serum effect on transfection efficiency. These novel cationic niosomes may constitute a good alternative carrier for gene transfection.

  15. Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

    Science.gov (United States)

    Ai, Jianzhong; Tai, Phillip W L; Lu, Yi; Li, Jia; Ma, Hong; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

    2017-09-01

    Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases. We produced Ad expressing enhanced green fluorescence protein (EGFP), and characterized the transduction efficiency of Ad in both human and mouse prostate cancer cell lines in vitro, as well as prostate tumor xenograft, and wild-type mouse prostate tissue in vivo. Ad transduction efficiency was determined by EGFP fluorescence using microscopy and flow cytometry. Cell type-specific transduction was examined by immunofluorescence staining of cell markers. Our data showed that Ad efficiently transduced human and mouse prostate cancer cells in vitro in a dose dependent manner. Following intratumoral and intraprostate injection, Ad could efficiently transduce prostate tumor xenograft and the major prostatic cell types in vivo, respectively. Our findings suggest that Ad can efficiently transduce prostate tumor cells in vitro as well as xenograft and normal prostate tissue in vivo, and further indicate that Ad could be a potentially powerful toolbox for future gene therapy of prostate diseases. © 2017 Wiley Periodicals, Inc.

  16. Regulation of autophagy by amino acids and MTOR-dependent signal transduction

    NARCIS (Netherlands)

    Meijer, Alfred J.; Lorin, Séverine; Blommaart, Edward F.; Codogno, Patrice

    2015-01-01

    Amino acids not only participate in intermediary metabolism but also stimulate insulin-mechanistic target of rapamycin (MTOR)-mediated signal transduction which controls the major metabolic pathways. Among these is the pathway of autophagy which takes care of the degradation of long-lived proteins

  17. Beacon Editor: Capturing Signal Transduction Pathways Using the Systems Biology Graphical Notation Activity Flow Language.

    Science.gov (United States)

    Elmarakeby, Haitham; Arefiyan, Mostafa; Myers, Elijah; Li, Song; Grene, Ruth; Heath, Lenwood S

    2017-12-01

    The Beacon Editor is a cross-platform desktop application for the creation and modification of signal transduction pathways using the Systems Biology Graphical Notation Activity Flow (SBGN-AF) language. Prompted by biologists' requests for enhancements, the Beacon Editor includes numerous powerful features for the benefit of creation and presentation.

  18. Effects of matrine on JAK-STAT signaling transduction pathways in ...

    African Journals Online (AJOL)

    The current study aims to investigate the effects of matrine on the JAK-STAT signaling transduction pathways in bleomycin (BLM)-induced pulmonary fibrosis (PF) and to explore its action mechanism. A total of 72 male C57BL/6 mice were randomized into the control, model, and treatment groups. PF models were ...

  19. Signal transduction events in aluminum-induced cell death in tomato suspension cells

    NARCIS (Netherlands)

    Iakimova, E.T.; Kapchina-Toteva, V.M.; Woltering, E.J.

    2007-01-01

    In this study, some of the signal transduction events involved in AlCl3-induced cell death in tomato (Lycopersicon esculentum Mill.) suspension cells were elucidated. Cells treated with 100 ¿M AlCl3 showed typical features of programmed cell death (PCD) such as nuclear and cytoplasmic condensation.

  20. Sensory cilia and integration of signal transduction in human health and disease

    DEFF Research Database (Denmark)

    Christensen, Søren T; Pedersen, Lotte B; Schneider, Linda

    2007-01-01

    The primary cilium is a hallmark of mammalian tissue cells. Recent research has shown that these organelles display unique sets of selected signal transduction modules including receptors, ion channels, effector proteins and transcription factors that relay chemical and physical stimuli from the ...

  1. CRISPR-cas-mediated phage resistance enhances horizontal gene transfer by transduction

    NARCIS (Netherlands)

    Watson, Bridget N.J.; Staals, Raymond H.J.; Fineran, Peter C.

    2018-01-01

    A powerful contributor to prokaryotic evolution is horizontal gene transfer (HGT) through transformation, conjugation, and transduction, which can be advantageous, neutral, or detrimental to fitness. Bacteria and archaea control HGT and phage infection through CRISPR-Cas (clustered regularly

  2. Efficient transduction of neurons using Ross River glycoprotein-pseudotyped lentiviral vectors

    DEFF Research Database (Denmark)

    Jakobsson, J; Nielsen, T Tolstrup; Staflin, K

    2006-01-01

    , including the possibility to establish stable producer cell lines. After injection of RRV-LV expressing green fluorescent protein into different structures in the rat brain we found efficient transduction of both neurons and glial cells. By using two cell-type-specific promoters, neuron-specific enolase...

  3. The role of Ryk and Ror receptor tyrosine kinases in Wnt signal transduction

    NARCIS (Netherlands)

    Green, J.; Nusse, R.; van Amerongen, R.

    2014-01-01

    Receptor tyrosine kinases of the Ryk and Ror families were initially classified as orphan receptors because their ligands were unknown. They are now known to contain functional extracellular Wnt-binding domains and are implicated in Wnt-signal transduction in multiple species. Although their

  4. Semi-Supervised Transductive Hot Spot Predictor Working on Multiple Assumptions

    KAUST Repository

    Wang, Jim Jing-Yan; Almasri, Islam; Shi, Yuexiang; Gao, Xin

    2014-01-01

    of the transductive semi-supervised algorithms takes all the three semisupervised assumptions, i.e., smoothness, cluster and manifold assumptions, together into account during learning. In this paper, we propose a novel semi-supervised method for hot spot residue

  5. Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors

    Directory of Open Access Journals (Sweden)

    Mayumi Oakland

    2013-01-01

    Full Text Available Persistent viral vector-mediated transgene expression in the airways requires delivery to cells with progenitor capacity and avoidance of immune responses. Previously, we observed that GP64-pseudotyped feline immunodeficiency virus (FIV-mediated gene transfer was more efficient in the nasal airways than the large airways of the murine lung. We hypothesized that in vivo gene transfer was limited by immunological and physiological barriers in the murine intrapulmonary airways. Here, we systematically investigate multiple potential barriers to lentiviral gene transfer in the airways of mice. We show that GP64-FIV vector transduced primary cultures of well-differentiated murine nasal epithelia with greater efficiency than primary cultures of murine tracheal epithelia. We further demonstrate that neutrophils, type I interferon (IFN responses, as well as T and B lymphocytes are not the major factors limiting the transduction of murine conducting airways. In addition, we observed better transduction of GP64-pseudotyped vesicular stomatitis virus (VSV in the nasal epithelia compared with the intrapulmonary airways in mice. VSVG glycoprotein pseudotyped VSV transduced intrapulmonary epithelia with similar efficiency as nasal epithelia. Our results suggest that the differential transduction efficiency of nasal versus intrapulmonary airways by FIV vector is not a result of immunological barriers or surface area, but rather differential expression of cellular factors specific for FIV vector transduction.

  6. Integration of adeno-associated virus vectors in CD34+ human hematopoietic progenitor cells after transduction.

    Science.gov (United States)

    Fisher-Adams, G; Wong, K K; Podsakoff, G; Forman, S J; Chatterjee, S

    1996-07-15

    Gene transfer vectors based on adeno-associated virus (AAV) appear promising because of their high transduction frequencies regardless of cell cycle status and ability to integrate into chromosomal DNA. We tested AAV-mediated gene transfer into a panel of human bone marrow or umbilical cord-derived CD34+ hematopoietic progenitor cells, using vectors encoding several transgenes under the control of viral and cellular promoters. Gene transfer was evaluated by (1) chromosomal integration of vector sequences and (2) analysis of transgene expression. Southern hybridization and fluorescence in situ hybridization analysis of transduced CD34 genomic DNA showed the presence of integrated vector sequences in chromosomal DNA in a portion of transduced cells and showed that integrated vector sequences were replicated along with cellular DNA during mitosis. Transgene expression in transduced CD34 cells in suspension cultures and in myeloid colonies differentiating in vitro from transduced CD34 cells approximated that predicted by the multiplicity of transduction. This was true in CD34 cells from different donors, regardless of the transgene or selective pressure. Comparisons of CD34 cell transduction either before or after cytokine stimulation showed similar gene transfer frequencies. Our findings suggest that AAV transduction of CD34+ hematopoietic progenitor cells is efficient, can lead to stable integration in a population of transduced cells, and may therefore provide the basis for safe and efficient ex vivo gene therapy of the hematopoietic system.

  7. FASEB summer research conference on signal transduction in plants. Final report, June 16, 1996--June 21, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Lomax, T.L.; Quatrano, R.S.

    1996-12-31

    This is the program from the second FASEB conference on Signal Transduction in Plants. Topic areas included the following: environmental signaling; perception and transduction of light signals; signaling in plant microbe interactions; signaling in plant pathogen interactions; cell, cell communication; cytoskeleton, plasma membrane, and cellwall continuum; signaling molecules in plant growth and development I and II. A list of participants is included.

  8. Cation-Cation Complexes of Pentavalent Uranyl: From Disproportionation Intermediates to Stable Clusters

    Energy Technology Data Exchange (ETDEWEB)

    Mougel, Victor; Horeglad, Pawel; Nocton, Gregory; Pecaut, Jacques; Mazzanti, Marinella [CEA, INAC, SCIB, Laboratoire de Reconnaissance Ionique et Chimie de Coordination, CEA-Grenoble, 38054 GRENOBLE, Cedex 09 (France)

    2010-07-01

    Three new cation cation complexes of pentavalent uranyl, stable with respect to the disproportionation reaction, have been prepared from the reaction of the precursor [(UO{sub 2}py{sub 5})-(KI{sub 2}py{sub 2})]{sub n} (1) with the Schiff base ligands salen{sup 2-}, acacen{sup 2-}, and salophen{sup 2-} (H{sub 2}salen N, N'-ethylene-bis(salicylidene-imine), H{sub 2}acacen=-N, N'-ethylenebis(acetylacetone-imine), H{sub 2}salophen=N, N'-phenylene-bis(salicylidene-imine)). The preparation of stable complexes requires a careful choice of counter ions and reaction conditions. Notably the reaction of 1 with salophen{sup 2-} in pyridine leads to immediate disproportionation, but in the presence of [18]crown-6 ([18]C-6) a stable complex forms. The solid-state structure of the four tetra-nuclear complexes ([UO{sub 2}-(acacen)]{sub 4}[{mu}{sub 8}-]{sub 2}[K([18]C-6)(py)]{sub 2}) (3) and ([UO{sub 2}(acacen)](4)[{mu}{sub 8}-]).2[K([222])(py)] (4) ([UO{sub 2}(salophen)](4)[{mu}{sub 8}-K]{sub 2}[mu(5)-KI]{sub 2}[(K([18]C-6)]).2 [K([18]C-6)-(thf){sub 2}].2I (5), and ([UO{sub 2}(salen)(4)][{mu}{sub 8}-Rb]{sub 2}[Rb([18]C-6)]{sub 2}) (9) ([222] = [222]cryptand, py =pyridine), presenting a T-shaped cation cation interaction has been determined by X-ray crystallographic studies. NMR spectroscopic and UV/Vis studies show that the tetra-nuclear structure is maintained in pyridine solution for the salen and acacen complexes. Stable mononuclear complexes of pentavalent uranyl are also obtained by reduction of the hexavalent uranyl Schiff base complexes with cobaltocene in pyridine in the absence of coordinating cations. The reactivity of the complex [U{sup V}O{sub 2}(salen)(py)][Cp*{sub 2}Co] with different alkali ions demonstrates the crucial effect of coordinating cations on the stability of cation cation complexes. The nature of the cation plays a key role in the preparation of stable cation cation complexes. Stable tetra-nuclear complexes form in the presence of K

  9. Complexes of natural carbohydrates with metal cations

    International Nuclear Information System (INIS)

    Alekseev, Yurii E; Garnovskii, Alexander D; Zhdanov, Yu A

    1998-01-01

    Data on the interaction of natural carbohydrates (mono-, oligo-, and poly-saccharides, amino sugars, and natural organic acids of carbohydrate origin) with metal cations are surveyed and described systematically. The structural diversity of carbohydrate metal complexes, caused by some specific features of carbohydrates as ligands, is demonstrated. The influence of complex formation on the chemical properties of carbohydrates is discussed. It is shown that the formation of metal complexes plays an important role in the configurational and conformational analysis of carbohydrates. The practical significance of the coordination interaction in the series of carbohydrate ligands is demonstrated. The bibliography includes 571 references.

  10. Complex Macromolecular Architectures by Living Cationic Polymerization

    KAUST Repository

    Alghamdi, Reem D.

    2015-05-01

    Poly (vinyl ether)-based graft polymers have been synthesized by the combination of living cationic polymerization of vinyl ethers with other living or controlled/ living polymerization techniques (anionic and ATRP). The process involves the synthesis of well-defined homopolymers (PnBVE) and co/terpolymers [PnBVE-b-PCEVE-b-PSiDEGVE (ABC type) and PSiDEGVE-b-PnBVE-b-PSiDEGVE (CAC type)] by sequential living cationic polymerization of n-butyl vinyl ether (nBVE), 2-chloroethyl vinyl ether (CEVE) and tert-butyldimethylsilyl ethylene glycol vinyl ether (SiDEGVE), using mono-functional {[n-butoxyethyl acetate (nBEA)], [1-(2-chloroethoxy) ethyl acetate (CEEA)], [1-(2-(2-(t-butyldimethylsilyloxy)ethoxy) ethoxy) ethyl acetate (SiDEGEA)]} or di-functional [1,4-cyclohexanedimethanol di(1-ethyl acetate) (cHMDEA), (VEMOA)] initiators. The living cationic polymerizations of those monomers were conducted in hexane at -20 0C using Et3Al2Cl3 (catalyst) in the presence of 1 M AcOEt base.[1] The PCEVE segments of the synthesized block terpolymers were then used to react with living macroanions (PS-DPE-Li; poly styrene diphenyl ethylene lithium) to afford graft polymers. The quantitative desilylation of PSiDEGVE segments by n-Bu4N+F- in THF at 0 °C led to graft co- and terpolymers in which the polyalcohol is the outer block. These co-/terpolymers were subsequently subjected to “grafting-from” reactions by atom transfer radical polymerization (ATRP) of styrene to afford more complex macromolecular architectures. The base assisted living cationic polymerization of vinyl ethers were also used to synthesize well-defined α-hydroxyl polyvinylether (PnBVE-OH). The resulting polymers were then modified into an ATRP macro-initiator for the synthesis of well-defined block copolymers (PnBVE-b-PS). Bifunctional PnBVE with terminal malonate groups was also synthesized and used as a precursor for more complex architectures such as H-shaped block copolymer by “grafting-from” or

  11. Homogeneous cation exchange membrane by radiation grafting

    International Nuclear Information System (INIS)

    Kolhe, Shailesh M.; G, Agathian; Ashok Kumar

    2001-01-01

    Preparation of a strong cation exchange membrane by radiation grafting of styrene on to polyethylene (LDPE) film by mutual irradiation technique in the presence of air followed by sulfonation is described. The grafting has been carried out in the presence of air and without any additive. Low dose rate has been seen to facilitate the grafting. Further higher the grafting percentage more is the exchange capacity. The addition of a swelling agent during the sulfonation helped in achieving the high exchange capacity. The TGA-MASS analysis confirmed the grafting and the sulfonation. (author)

  12. Antiretroviral therapy provided to HIV-infected Malawian women in a randomized trial diminishes the posiitive effect of lipid-based nutrient supplements on breast milk B-vitamins

    Science.gov (United States)

    Background: There is little information on B-vitamin concentrations in human milk or how they are affected by maternal B-vitamin deficiencies, antiretroviral (ARV) therapy or maternal supplementation. Objective: To evaluate effects of ARV therapy and/or lipid-based nutrient supplements (LNS) on B-v...

  13. Effect of supplementation with a lipid-based nutrient supplement on the micronutrient status of children aged 6–18 months living in the rural region of Intibucá, Honduras

    Science.gov (United States)

    Background: Lipid-based nutrient supplements (LNS) have been effective in the treatment of acute malnutrition among children. We evaluated the use of LNS supplementation for improving the micronutrient status of young children. Methods: A 12-month randomised controlled trial was conducted among chil...

  14. Maternal cortisol and stress are associated with birth outcomes, but are not affected by lipid-based micronutrient supplements during pregnancy: an analysis of data from a randomized controlled trial in rural Malawi

    Science.gov (United States)

    Background: Prenatal micronutrient supplements have been found to increase birth weight, but mechanisms for increased growth are poorly understood. Our hypotheses were that 1) women who receive lipid-based micronutrient supplements (LNS) during pregnancy would have lower salivary cortisol concentrat...

  15. Towards the systematic discovery of signal transduction networks using phosphorylation dynamics data

    Directory of Open Access Journals (Sweden)

    Yachie Nozomu

    2010-05-01

    Full Text Available Abstract Background Phosphorylation is a ubiquitous and fundamental regulatory mechanism that controls signal transduction in living cells. The number of identified phosphoproteins and their phosphosites is rapidly increasing as a result of recent mass spectrometry-based approaches. Results We analyzed time-course phosphoproteome data obtained previously by liquid chromatography mass spectrometry with the stable isotope labeling using amino acids in cell culture (SILAC method. This provides the relative phosphorylation activities of digested peptides at each of five time points after stimulating HeLa cells with epidermal growth factor (EGF. We initially calculated the correlations between the phosphorylation dynamics patterns of every pair of peptides and connected the strongly correlated pairs to construct a network. We found that peptides extracted from the same intracellular fraction (nucleus vs. cytoplasm tended to be close together within this phosphorylation dynamics-based network. The network was then analyzed using graph theory and compared with five known signal-transduction pathways. The dynamics-based network was correlated with known signaling pathways in the NetPath and Phospho.ELM databases, and especially with the EGF receptor (EGFR signaling pathway. Although the phosphorylation patterns of many proteins were drastically changed by the EGF stimulation, our results suggest that only EGFR signaling transduction was both strongly activated and precisely controlled. Conclusions The construction of a phosphorylation dynamics-based network provides a useful overview of condition-specific intracellular signal transduction using quantitative time-course phosphoproteome data under specific experimental conditions. Detailed prediction of signal transduction based on phosphoproteome dynamics remains challenging. However, since the phosphorylation profiles of kinase-substrate pairs on the specific pathway were localized in the dynamics

  16. Enrichment of human hematopoietic stem/progenitor cells facilitates transduction for stem cell gene therapy.

    Science.gov (United States)

    Baldwin, Kismet; Urbinati, Fabrizia; Romero, Zulema; Campo-Fernandez, Beatriz; Kaufman, Michael L; Cooper, Aaron R; Masiuk, Katelyn; Hollis, Roger P; Kohn, Donald B

    2015-05-01

    Autologous hematopoietic stem cell (HSC) gene therapy for sickle cell disease has the potential to treat this illness without the major immunological complications associated with allogeneic transplantation. However, transduction efficiency by β-globin lentiviral vectors using CD34-enriched cell populations is suboptimal and large vector production batches may be needed for clinical trials. Transducing a cell population more enriched for HSC could greatly reduce vector needs and, potentially, increase transduction efficiency. CD34(+) /CD38(-) cells, comprising ∼1%-3% of all CD34(+) cells, were isolated from healthy cord blood CD34(+) cells by fluorescence-activated cell sorting and transduced with a lentiviral vector expressing an antisickling form of beta-globin (CCL-β(AS3) -FB). Isolated CD34(+) /CD38(-) cells were able to generate progeny over an extended period of long-term culture (LTC) compared to the CD34(+) cells and required up to 40-fold less vector for transduction compared to bulk CD34(+) preparations containing an equivalent number of CD34(+) /CD38(-) cells. Transduction of isolated CD34(+) /CD38(-) cells was comparable to CD34(+) cells measured by quantitative PCR at day 14 with reduced vector needs, and average vector copy/cell remained higher over time for LTC initiated from CD34(+) /38(-) cells. Following in vitro erythroid differentiation, HBBAS3 mRNA expression was similar in cultures derived from CD34(+) /CD38(-) cells or unfractionated CD34(+) cells. In vivo studies showed equivalent engraftment of transduced CD34(+) /CD38(-) cells when transplanted in competition with 100-fold more CD34(+) /CD38(+) cells. This work provides initial evidence for the beneficial effects from isolating human CD34(+) /CD38(-) cells to use significantly less vector and potentially improve transduction for HSC gene therapy. © 2015 AlphaMed Press.

  17. Cationic polymers in water treatment: Part 1: Treatability of water with cationic polymers

    Czech Academy of Sciences Publication Activity Database

    Polasek, P.; Mutl, Silvestr

    2002-01-01

    Roč. 28, č. 1 (2002), s. 69-82 ISSN 0378-4738 R&D Projects: GA AV ČR KSK2067107 Keywords : cationic polymers * treatability * water quality Subject RIV: BK - Fluid Dynamics Impact factor: 0.481, year: 2002

  18. Alkali Metal Cation versus Proton and Methyl Cation Affinities: Structure and Bonding Mechanism.

    Science.gov (United States)

    Boughlala, Zakaria; Fonseca Guerra, Célia; Bickelhaupt, F Matthias

    2016-06-01

    We have analyzed the structure and bonding of gas-phase Cl-X and [HCl-X](+) complexes for X(+)= H(+), CH3 (+), Li(+), and Na(+), using relativistic density functional theory (DFT). We wish to establish a quantitative trend in affinities of the anionic and neutral Lewis bases Cl(-) and HCl for the various cations. The Cl-X bond becomes longer and weaker along X(+) = H(+), CH3 (+), Li(+), and Na(+). Our main purpose is to understand the heterolytic bonding mechanism behind the intrinsic (i.e., in the absence of solvent) alkali metal cation affinities (AMCA) and how this compares with and differs from those of the proton affinity (PA) and methyl cation affinity (MCA). Our analyses are based on Kohn-Sham molecular orbital (KS-MO) theory in combination with a quantitative energy decomposition analysis (EDA) that pinpoints the importance of the different features in the bonding mechanism. Orbital overlap appears to play an important role in determining the trend in cation affinities.

  19. Cobalt 60 cation exchange with mexican clays

    International Nuclear Information System (INIS)

    Nava Galve, R.G.

    1993-01-01

    Mexican clays can be used to remove radioactive elements from contaminated aqueous solutions. Cation exchange experiments were performed with 60 Co radioactive solution. In the present work the effect of contact time on the sorption of Co 2+ was studied. The contact time in hydrated montmorillonite was from 5 to 120 minutes and in dehydrated montmorillonite 5 to 1400 minutes. The Co 2+ uptake value was, in hydrated montmorillonite, between 0.3 to 0.85 m eq/g and in dehydrated montmorillonite, between 0.6 to 1.40 m eq/g. The experiments were done in a pH 5.1 to 5.7 and normal conditions. XRD patterns were used to characterize the samples. The crystallinity was determined by X-ray Diffraction and it was maintained before and after the cation exchange. DTA thermo grams showed the temperatures of the lost humidity and crystallization water. Finally, was observed that dehydrated montmorillonite adsorb more cobalt than hydrated montmorillonite. (Author)

  20. Cationic antimicrobial peptides in penaeid shrimp.

    Science.gov (United States)

    Tassanakajon, Anchalee; Amparyup, Piti; Somboonwiwat, Kunlaya; Supungul, Premruethai

    2011-08-01

    Penaeid shrimp aquaculture has been consistently affected worldwide by devastating diseases that cause a severe loss in production. To fight a variety of harmful microbes in the surrounding environment, particularly at high densities (of which intensive farming represents an extreme example), shrimps have evolved and use a diverse array of antimicrobial peptides (AMPs) as part of an important first-line response of the host defense system. Cationic AMPs in penaeid shrimps composed of penaeidins, crustins, and anti-lipopolysaccharide factors are comprised of multiple classes or isoforms and possess antibacterial and antifungal activities against different strains of bacteria and fungi. Shrimp AMPs are primarily expressed in circulating hemocytes, which is the main site of the immune response, and hemocytes expressing AMPs probably migrate to infection sites to fight against pathogen invasion. Indeed, most AMPs are produced as early as the nauplii developmental stage to protect shrimp larvae from infections. In this review, we discuss the sequence diversity, expression, gene structure, and antimicrobial activities of cationic AMPs in penaeid shrimps. The information available on antimicrobial activities indicates that these shrimp AMPs have potential therapeutic applications in the control of disease problems in aquaculture.

  1. Cationic Antimicrobial Polymers and Their Assemblies

    Science.gov (United States)

    Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

    2013-01-01

    Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs). The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications. PMID:23665898

  2. Cationic Antimicrobial Polymers and Their Assemblies

    Directory of Open Access Journals (Sweden)

    Ana Maria Carmona-Ribeiro

    2013-05-01

    Full Text Available Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs. The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications.

  3. Basic exchangeable cations in Finnish mineral soils

    Directory of Open Access Journals (Sweden)

    Armi Kaila

    1972-09-01

    Full Text Available The content of exchangeable Ca, Mg, K and Na replaced by neutral ammonium acetate was determined in 470 samples of mineral soils from various parts of Finland, except from Lapland. The amount of all these cations tended to increase with an increase in the clay content, but variation within each textural class was large, and the ranges usually overlapped those of the other classes. The higher acidity of virgin surface soils was connected with a lower average degree of saturation by Ca as compared with the corresponding textural classes of cultivated soils. No significant difference in the respective contents of other cations was detected. The samples of various textural groups from deeper layers were usually poorer in exchangeable Ca and K than the corresponding groups of plough layer. The mean content of exchangeable Mg was equal or even higher in the samples from deeper layers than in the samples from plough layer, except in the group of sand soils. The percentage of Mg of the effective CEC increased, as an average, from 9 in the sand and fine sand soils of plough layer to 30 in the heavy clay soils; in the heavy clay soils from deeper layers its mean value was 38 ± 4 %. In the samples of plough layer, the mean ratio of Ca to Mg in sand and fine sand soils was about 9, in silt and loam soils about 6, in the coarser clay soils about 4, and in heavy clay about 2.

  4. A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8+ T Cells

    Science.gov (United States)

    Maji, Mithun; Mazumder, Saumyabrata; Bhattacharya, Souparno; Choudhury, Somsubhra Thakur; Sabur, Abdus; Shadab, Md.; Bhattacharya, Pradyot; Ali, Nahid

    2016-06-01

    The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8+ cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4+ and CD8+ T cell responses for long-term protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4+ and CD8+ T cells. Furthermore, lymphoid CD8+ T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8+ T cell responses when compared to free and liposomal antigen. These liposomal formulations presented to CD8+ T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine.

  5. Radiochemical study of isomerization of free butyl cations

    International Nuclear Information System (INIS)

    Sinotova, E.N.; Nefedov, V.D.; Skorokhodov, S.S.; Arkhipov, Yu.M.

    1987-01-01

    Ion-molecular reactions of free butyl cations, generated by nuclear chemical method, with carbon monoxide containing small quantities of ethanol vapors are studied. Carbon monoxide was used to fix instable butyl cations in the form of corresponding acyl ions. Ester of α-methyl-butyric acid appears to be the only product of free butyl cation interaction with carbon monoxide in the presence of ethanol vapors. That means, that up to the moment of butyl cation reaction with carbon monoxide, the primary butyl cations are almost completely isomerized into secondary in agreement with results of previous investigations. This allows one to study free butyl cation isomerization process according to ion-molecular reaction product isomeric composition

  6. Willingness to pay for small-quantity lipid-based nutrient supplements for women and children: Evidence from Ghana and Malawi.

    Science.gov (United States)

    Adams, Katherine P; Vosti, Stephen A; Ayifah, Emmanuel; Phiri, Thokozani E; Adu-Afarwuah, Seth; Maleta, Kenneth; Ashorn, Ulla; Arimond, Mary; Dewey, Kathryn G

    2018-04-01

    Small-quantity lipid-based nutrient supplements (SQ-LNS) are designed to enrich maternal and child diets with the objective of preventing undernutrition during the first 1,000 days. Scaling up the delivery of supplements such as SQ-LNS hinges on understanding private demand and creatively leveraging policy-relevant factors that might influence demand. We used longitudinal stated willingness-to-pay (WTP) data from contingent valuation studies that were integrated into randomized controlled nutrition trials in Ghana and Malawi to estimate private valuation of SQ-LNS during pregnancy, postpartum, and early childhood. We found that average stated WTP for a day's supply of SQ-LNS was more than twice as high in Ghana than Malawi, indicating that demand for SQ-LNS (and by extension, the options for effective delivery of SQ-LNS) may be very context specific. We also examined factors associated with WTP, including intervention group, household socioeconomic status, birth outcomes, child growth, and maternal and child morbidity. In both sites, WTP was consistently negatively associated with household food insecurity, indicating that subsidization might be needed to permit food insecure households to acquire SQ-LNS if it is made available for purchase. In Ghana, WTP was higher among heads of household than among mothers, which may be related to control over household resources. Personal experience using SQ-LNS was not associated with WTP in either site. © 2017 The Authors. Maternal and Child Nutrition published by John Wiley & Sons, Ltd.

  7. Toward the establishment of standardized in vitro tests for lipid-based formulations, part 4: proposing a new lipid formulation performance classification system.

    Science.gov (United States)

    Williams, Hywel D; Sassene, Philip; Kleberg, Karen; Calderone, Marilyn; Igonin, Annabel; Jule, Eduardo; Vertommen, Jan; Blundell, Ross; Benameur, Hassan; Müllertz, Anette; Porter, Christopher J H; Pouton, Colin W

    2014-08-01

    The Lipid Formulation Classification System Consortium looks to develop standardized in vitro tests and to generate much-needed performance criteria for lipid-based formulations (LBFs). This article highlights the value of performing a second, more stressful digestion test to identify LBFs near a performance threshold and to facilitate lead formulation selection in instances where several LBF prototypes perform adequately under standard digestion conditions (but where further discrimination is necessary). Stressed digestion tests can be designed based on an understanding of the factors that affect LBF performance, including the degree of supersaturation generated on dispersion/digestion. Stresses evaluated included decreasing LBF concentration (↓LBF), increasing bile salt, and decreasing pH. Their capacity to stress LBFs was dependent on LBF composition and drug type: ↓LBF was a stressor to medium-chain glyceride-rich LBFs, but not more hydrophilic surfactant-rich LBFs, whereas decreasing pH stressed tolfenamic acid LBFs, but not fenofibrate LBFs. Lastly, a new Performance Classification System, that is, LBF composition independent, is proposed to promote standardized LBF comparisons, encourage robust LBF development, and facilitate dialogue with the regulatory authorities. This classification system is based on the concept that performance evaluations across three in vitro tests, designed to subject a LBF to progressively more challenging conditions, will enable effective LBF discrimination and performance grading. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  8. Providing lipid-based nutrient supplement during pregnancy does not reduce the risk of maternal P falciparum parasitaemia and reproductive tract infections: a randomised controlled trial.

    Science.gov (United States)

    Nkhoma, Minyanga; Ashorn, Per; Ashorn, Ulla; Dewey, Kathryn G; Gondwe, Austrida; Mbotwa, John; Rogerson, Stephen; Taylor, Steve M; Maleta, Kenneth

    2017-01-17

    Maternal infections are associated with maternal and foetal adverse outcomes. Nutrient supplementation during pregnancy may reduce the occurrence of infections by improving maternal immunity. We aimed to investigate the impact of small-quantity lipid-based nutrient supplement (SQ-LNS) on the occurrence of Plasmodium falciparum parasitaemia during pregnancy and trichomoniasis, vaginal candidiasis and urinary tract infection (UTI) after delivery. Pregnant Malawian women enrolled in the iLiNS-DYAD trial receiving daily supplementation with SQ-LNS, multiple micronutrients (MMN) or iron & folic acid (IFA) from UTI using urine dipstick analysis. The prevalence of each infection by intervention group was estimated at the prescribed time points and the global null hypothesis was tested using logistic regression. Adjusted analyses were performed using preselected covariates. The prevalence of P. falciparum parasitaemia was 10.7% at 32 gw, 9% at 36 gw, and 8.3% by RDT and 20.2% by PCR at delivery. After delivery the prevalence of trichomoniasis was 10.5%, vaginal candidiasis was 0.5%, and UTI was 3.1%. There were no differences between intervention groups in the prevalence of any of the infections. In this population, SQ-LNS did not influence the occurrence of maternal P. falciparum parasitaemia, trichomoniasis, vaginal candidiasis or UTI. Identifier: NCT01239693 (10 November 2010).

  9. Enhanced microemulsion formation in lipid-based drug delivery systems by combining mono-esters of mediumchain fatty acids with di- or tri-esters

    Directory of Open Access Journals (Sweden)

    Darshil P. Patel

    2012-06-01

    Full Text Available To develop strategies for selecting appropriate lipids from mono-, di- and tri-esters of medium-chain fatty acids for the development of lipid-based drug delivery systems, ternary phase diagrams of propylene glycol (PG monocaprylate (Capryol® 90; HLB~7, PG dicaprylocaprate (Labrafac™ PG; HLB~2 and glycerol tricaprylocaprate (Labrafac™ Lipophile WL1349; HLB~2 were determined in combination with a common surfactant, PEG-35 castor oil (Cremophor® EL, HLB~13, and water. Particle size and viscosity in different regions of the phase diagrams were measured, solubility of a model drug, danazol, in different lipid-surfactant mixtures was determined, and dispersion testing by diluting selected preconcentrates with 250 ml 0.01 NHCl was performed. Further, phase diagrams were constructed using binary mixtures of lipids (monoester with diester, or monoester with triester in place of single lipids. The phase diagrams of PG dicaprylocaprate and glycerol tricaprylocaprate were similar, while it was distinctly different for PG monocaprylate. The microemulsion regions in phase diagrams were rather limited for individual lipids, and additionally, the diand tri-esters showed pronounced gel regions in the phase diagrams, which could influence drug release from preconcentrates. The mixing of PG monocaprylate (monoester with PG dicaprylocaprate (diester or glycerol tricaprylocaprate (triester had dramatic effects on the performance of lipids as evidenced by the greatly reduced gel phases, much larger microemulsion regions, faster dispersion of the preconcentrates in an aqueous medium, and smaller particle size of the microemulsions subsequently formed.

  10. A new in vitro lipid digestion - in vivo absorption model to evaluate the mechanisms of drug absorption from lipid-based formulations.

    Science.gov (United States)

    Crum, Matthew F; Trevaskis, Natalie L; Williams, Hywel D; Pouton, Colin W; Porter, Christopher J H

    2016-04-01

    In vitro lipid digestion models are commonly used to screen lipid-based formulations (LBF), but in vitro-in vivo correlations are in some cases unsuccessful. Here we enhance the scope of the lipid digestion test by incorporating an absorption 'sink' into the experimental model. An in vitro model of lipid digestion was coupled directly to a single pass in situ intestinal perfusion experiment in an anaesthetised rat. The model allowed simultaneous real-time analysis of the digestion and absorption of LBFs of fenofibrate and was employed to evaluate the influence of formulation digestion, supersaturation and precipitation on drug absorption. Formulations containing higher quantities of co-solvent and surfactant resulted in higher supersaturation and more rapid drug precipitation in vitro when compared to those containing higher quantities of lipid. In contrast, when the same formulations were examined using the coupled in vitro lipid digestion - in vivo absorption model, drug flux into the mesenteric vein was similar regardless of in vitro formulation performance. For some drugs, simple in vitro lipid digestion models may underestimate the potential for absorption from LBFs. Consistent with recent in vivo studies, drug absorption for rapidly absorbed drugs such as fenofibrate may occur even when drug precipitation is apparent during in vitro digestion.

  11. The use of quasi-isothermal modulated temperature differential scanning calorimetry for the characterization of slow crystallization processes in lipid-based solid self-emulsifying systems.

    Science.gov (United States)

    Otun, Sarah O; Meehan, Elizabeth; Qi, Sheng; Craig, Duncan Q M

    2015-04-01

    Slow or incomplete crystallization may be a significant manufacturing issue for solid lipid-based dosage forms, yet little information is available on this phenomenon. In this investigation we suggest a novel means by which slow solidification may be monitored in Gelucire 44/14 using quasi-isothermal modulated temperature DSC (QiMTDSC). Conventional linear heating and cooling DSC methods were employed, along with hot stage microscopy (HSM), for basic thermal profiling of Gelucire 44/14. QiMTDSC experiments were performed on cooling from the melt, using a range of incremental decreases in temperature and isothermal measurement periods. DSC and HSM highlighted the main (primary) crystallization transition; solid fat content analysis and kinetic analysis were used to profile the solidification process. The heat capacity profile from QiMTDSC indicated that after an initial energetic primary crystallisation, the lipid underwent a slower period of crystallization which continued to manifest at much lower temperatures than indicated by standard DSC. We present evidence that Gelucire 44/14 undergoes an initial crystallization followed by a secondary, slower process. QIMTDSC appears to be a promising tool in the investigation of this secondary crystallization process.

  12. Stability and recovery of DNA origami structure with cation concentration

    Science.gov (United States)

    Chen, Yi; Wang, Ping; Liu, Yang; Liu, Ting; Xu, Yan; Zhu, Shanshan; Zhu, Jun; Ye, Kai; Huang, Guang; Dannong, He

    2018-01-01

    We synthesized triangular and rectangular DNA origami nanostructures and investigated the stability and recovery of them under low cation concentration. Our results demonstrated that the origami nanostructures would melt when incubated in low cation concentration, and recover whilst kept in the concentration for less than 10 min. However, extending the incubation time would lead to irreversible melting. Our results show the possibility of application of DNA origami nanostructures for things such as a sensor for cation concentration response, etc.

  13. Genome-wide identification and comparative analysis of the cation proton antiporters family in pear and four other Rosaceae species.

    Science.gov (United States)

    Zhou, Hongsheng; Qi, Kaijie; Liu, Xing; Yin, Hao; Wang, Peng; Chen, Jianqing; Wu, Juyou; Zhang, Shaoling

    2016-08-01

    The monovalent cation proton antiporters (CPAs) play essential roles in plant nutrition, development, and signal transduction by regulating ion and pH homeostasis of the cell. The CPAs of plants include the Na(+)/H(+) exchanger, K(+) efflux antiporter, and cation/H(+) exchanger families. However, currently, little is known about the CPA genes in Rosaceae species. In this study, 220 CPA genes were identified from five Rosaceae species (Pyrus bretschneideri, Malus domestica, Prunus persica, Fragaria vesca, and Prunus mume), and 53 of which came from P. bretschneideri. Phylogenetic, structure, collinearity, and gene expression analyses were conducted on the entire CPA genes of pear. Gene expression data showed that 35 and 37 CPA genes were expressed in pear fruit and pollen tubes, respectively. The transcript analysis of some CPA genes under abiotic stress conditions revealed that CPAs may play an important role in pollen tubes growth. The results presented here will be useful in improving understanding of the complexity of the CPA gene family and will promote functional characterization in future studies.

  14. Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes.

    OpenAIRE

    Joiner, C H; Platt, O S; Lux, S E

    1986-01-01

    The mechanism by which sickle cells and xerocytic red cells become depleted of cations in vivo has not been identified previously. Both types of cells exhibit elevated permeabilities to sodium and potassium, in the case of sickle cells, when deoxygenated. The ouabain-insensitive fluxes of sodium and potassium were equivalent, however, in both cell types under these conditions. When incubated 18 hours in vitro, sickle cells lost cations but only when deoxygenated. This cation depletion was blo...

  15. DMPD: Signal transduction pathways mediated by the interaction of CpG DNA withToll-like receptor 9. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14751759 Signal transduction pathways mediated by the interaction of CpG DNA withTo...;16(1):17-22. (.png) (.svg) (.html) (.csml) Show Signal transduction pathways mediated by the interaction of... CpG DNA withToll-like receptor 9. PubmedID 14751759 Title Signal transduction pathways media

  16. Predicting Organic Cation Sorption Coefficients: Accounting for Competition from Sorbed Inorganic Cations Using a Simple Probe Molecule.

    Science.gov (United States)

    Jolin, William C; Goyetche, Reaha; Carter, Katherine; Medina, John; Vasudevan, Dharni; MacKay, Allison A

    2017-06-06

    With the increasing number of emerging contaminants that are cationic at environmentally relevant pH values, there is a need for robust predictive models of organic cation sorption coefficients (K d ). Current predictive models fail to account for the differences in the identity, abundance, and affinity of surface-associated inorganic exchange ions naturally present at negatively charged receptor sites on environmental solids. To better understand how organic cation sorption is influenced by surface-associated inorganic exchange ions, sorption coefficients of 10 organic cations (including eight pharmaceuticals and two simple probe organic amines) were determined for six homoionic forms of the aluminosilicate mineral, montmorillonite. Organic cation sorption coefficients exhibited consistent trends for all compounds across the various homoionic clays with sorption coefficients (K d ) decreasing as follows: K d Na + > K d NH 4 + ≥ K d K + > K d Ca 2+ ≥ K d Mg 2+ > K d Al 3+ . This trend for competition between organic cations and exchangeable inorganic cations is consistent with the inorganic cation selectivity sequence, determined for exchange between inorganic ions. Such consistent trends in competition between organic and inorganic cations suggested that a simple probe cation, such as phenyltrimethylammonium or benzylamine, could capture soil-to-soil variations in native inorganic cation identity and abundance for the prediction of organic cation sorption to soils and soil minerals. Indeed, sorption of two pharmaceutical compounds to 30 soils was better described by phenyltrimethylammonium sorption than by measures of benzylamine sorption, effective cation exchange capacity alone, or a model from the literature (Droge, S., and Goss, K. Environ. Sci. Technol. 2013, 47, 14224). A hybrid approach integrating structural scaling factors derived from this literature model of organic cation sorption, along with phenyltrimethylammonium K d values, allowed for

  17. Computational study of cation substitutions in apatites

    International Nuclear Information System (INIS)

    Tamm, Toomas; Peld, Merike

    2006-01-01

    Density-functional theory plane-wave modeling of fluor- and hydroxyapatites has been performed, where one or two calcium ions per unit cell were replaced with cadmium or zinc cations. It was found that cadmium ions favor Ca(1) positions in fluorapatites and Ca(2) positions in hydroxyapatites, in agreement with experiment. A similar pattern is predicted for zinc substitutions. In the doubly substituted cases, where only hydroxyapatites were modeled, a preference for the substituting ions to be located in Ca(2) position was also observed. Displacement of the hydroxide ions from their symmetrical positions on the hexagonal axis can be used to explain the preferred configurations of substituting ions around the axis. -- Deformation of the hydroxide ion chain due to substitutions around the ion channel in substituted hydroxyapatites

  18. Retention of Cationic Starch onto Cellulose Fibres

    Science.gov (United States)

    Missaoui, Mohamed; Mauret, Evelyne; Belgacem, Mohamed Naceur

    2008-08-01

    Three methods of cationic starch titration were used to quantify its retention on cellulose fibres, namely: (i) the complexation of CS with iodine and measurement of the absorbency of the ensuing blue solution by UV-vis spectroscopy; (ii) hydrolysis of the starch macromolecules followed by the conversion of the resulting sugars to furan-based molecules and quantifying the ensuing mixture by measuring their absorbance at a Ι of 490 nm, using the same technique as previous one and; finally (iii) hydrolysis of starch macromolecules by trifluoro-acetic acid and quantification of the sugars in the resulting hydrolysates by high performance liquid chromatography. The three methods were found to give similar results within the range of CS addition from 0 to 50 mg per g of cellulose fibres.

  19. Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment

    DEFF Research Database (Denmark)

    Ellegaard, Anne-Marie; Dehlendorff, Christian; Vind, Anna C.

    2016-01-01

    Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide. In search for new NSCLC treatment options, we screened a cationic amphiphilic drug (CAD) library for cytotoxicity against NSCLC cells and identified several CAD antihistamines as inducers of lysosomal cell death. We...... then performed a cohort study on the effect of CAD antihistamine use on mortality of patients diagnosed with non-localized cancer in Denmark between 1995 and 2011. The use of the most commonly prescribed CAD antihistamine, loratadine, was associated with significantly reduced all-cause mortality among patients...... with non-localized NSCLC or any non-localized cancer when compared with use of non-CAD antihistamines and adjusted for potential confounders. Of the less frequently described CAD antihistamines, astemizole showed a similar significant association with reduced mortality as loratadine among patients with any...

  20. Use of a material conducting hydrogen cations

    International Nuclear Information System (INIS)

    Howe, A.T.; Shilton, M.G.

    1986-01-01

    The invention concerns a separator conducting hydrogenous for electrical devices, which contains at least one compound with the formula H(UO 2 )PO 4 x nH 2 O, H(UO 2 )AsO 4 x nH 2 O or H(UO 2 )IO 4 (OH) 2 x nH 2 O, where not more than 50% by weight of the H + is replaced by one or more cations, such as Li + , Na + , K + , NH 4 + , Cu 2+ , Mg 2+ , Ca 2+ , Ba 2+ , Sr 2+ , Pb 2+ , Fe 2+ , Co 2+ , Ni 2+ , Mn 2+ or Al 3+ . The electrical device having the separator can be an electrolysis cell, for example, an electro chromium cell. (H x WO 3 ), a hydrogen isotope enrichment device, a proton-sensitive electrode (eg for a pH meter), a battery or a fuel cell. (orig./MM) [de

  1. A Cationic Smart Copolymer for DNA Binding

    Directory of Open Access Journals (Sweden)

    Tânia Ribeiro

    2017-11-01

    Full Text Available A new block copolymer with a temperature-responsive block and a cationic block was prepared by reversible addition-fragmentation chain transfer (RAFT polymerization, with good control of its size and composition. The first block is composed by di(ethylene glycol methyl ether methacrylate (DEGMA and oligo(ethylene glycol methyl ether methacrylate (OEGMA, with the ratio DEGMA/OEGMA being used to choose the volume phase transition temperature of the polymer in water, tunable from ca. 25 to above 90 °C. The second block, of trimethyl-2-methacroyloxyethylammonium chloride (TMEC, is positively charged at physiological pH values and is used for DNA binding. The coacervate complexes between the block copolymer and a model single strand DNA are characterized by fluorescence correlation spectroscopy and fluorescence spectroscopy. The new materials offer good prospects for biomedical application, for example in controlled gene delivery.

  2. Hydration Structure of the Quaternary Ammonium Cations

    KAUST Repository

    Babiaczyk, Wojtek Iwo

    2010-11-25

    Two indicators of the hydropathicity of small solutes are introduced and tested by molecular dynamics simulations. These indicators are defined as probabilities of the orientation of water molecules\\' dipoles and hydrogen bond vectors, conditional on a generalized distance from the solute suitable for arbitrarily shaped molecules. Using conditional probabilities, it is possible to distinguish features of the distributions in close proximity of the solute. These regions contain the most significant information on the hydration structure but cannot be adequately represented by using, as is usually done, joint distance-angle probability densities. Our calculations show that using our indicators a relative hydropathicity scale for the interesting test set of the quaternary ammonium cations can be roughly determined. © 2010 American Chemical Society.

  3. Calixarenes synthesized for seducing and trapping cations

    International Nuclear Information System (INIS)

    Dozol, J.F.

    1997-01-01

    Calixarenes are known to be selective extractants for cesium radioactive cations. This liquid-liquid extraction is still to be studied and would allow to reduce the volume of years living radioactive wastes before they were stored and perhaps to remove then the cesium by transmutation. Calixarenes are macrocycles with phenolic units bridged by methylene groups. They have the important property to have a flexible structure. On this basic structure, all kinds of chemical functions can be branched. They thus confer particular properties to the molecule. A computerized virtual construction phase of molecules is actually studied in order to optimize the extraction. It is currently known that with small modifications it will be possible to selectively extract heavy metals (Hg, Cd..) coming from industrial pollution. (O.M.)

  4. Primary cilia modulate Ihh signal transduction in response to hydrostatic loading of growth plate chondrocytes.

    Science.gov (United States)

    Shao, Yvonne Y; Wang, Lai; Welter, Jean F; Ballock, R Tracy

    2012-01-01

    Indian hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Experimental demonstration of high fidelity entanglement distribution over decoherence channels via qubit transduction.

    Science.gov (United States)

    Lim, Hyang-Tag; Hong, Kang-Hee; Kim, Yoon-Ho

    2015-10-21

    Quantum coherence and entanglement, which are essential resources for quantum information, are often degraded and lost due to decoherence. Here, we report a proof-of-principle experimental demonstration of high fidelity entanglement distribution over decoherence channels via qubit transduction. By unitarily switching the initial qubit encoding to another, which is insensitive to particular forms of decoherence, we have demonstrated that it is possible to avoid the effect of decoherence completely. In particular, we demonstrate high-fidelity distribution of photonic polarization entanglement over quantum channels with two types of decoherence, amplitude damping and polarization-mode dispersion, via qubit transduction between polarization qubits and dual-rail qubits. These results represent a significant breakthrough in quantum communication over decoherence channels as the protocol is input-state independent, requires no ancillary photons and symmetries, and has near-unity success probability.

  6. Systematic Prediction of Scaffold Proteins Reveals New Design Principles in Scaffold-Mediated Signal Transduction

    Science.gov (United States)

    Hu, Jianfei; Neiswinger, Johnathan; Zhang, Jin; Zhu, Heng; Qian, Jiang

    2015-01-01

    Scaffold proteins play a crucial role in facilitating signal transduction in eukaryotes by bringing together multiple signaling components. In this study, we performed a systematic analysis of scaffold proteins in signal transduction by integrating protein-protein interaction and kinase-substrate relationship networks. We predicted 212 scaffold proteins that are involved in 605 distinct signaling pathways. The computational prediction was validated using a protein microarray-based approach. The predicted scaffold proteins showed several interesting characteristics, as we expected from the functionality of scaffold proteins. We found that the scaffold proteins are likely to interact with each other, which is consistent with previous finding that scaffold proteins tend to form homodimers and heterodimers. Interestingly, a single scaffold protein can be involved in multiple signaling pathways by interacting with other scaffold protein partners. Furthermore, we propose two possible regulatory mechanisms by which the activity of scaffold proteins is coordinated with their associated pathways through phosphorylation process. PMID:26393507

  7. Lipid rafts generate digital-like signal transduction in cell plasma membranes.

    Science.gov (United States)

    Suzuki, Kenichi G N

    2012-06-01

    Lipid rafts are meso-scale (5-200 nm) cell membrane domains where signaling molecules assemble and function. However, due to their dynamic nature, it has been difficult to unravel the mechanism of signal transduction in lipid rafts. Recent advanced imaging techniques have revealed that signaling molecules are frequently, but transiently, recruited to rafts with the aid of protein-protein, protein-lipid, and/or lipid-lipid interactions. Individual signaling molecules within the raft are activated only for a short period of time. Immobilization of signaling molecules by cytoskeletal actin filaments and scaffold proteins may facilitate more efficient signal transmission from rafts. In this review, current opinions of how the transient nature of molecular interactions in rafts generates digital-like signal transduction in cell membranes, and the benefits this phenomenon provides, are discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Primary Cilia Modulate IHH Signal Transduction in Response to Hydrostatic Loading of Growth Plate Chondrocytes

    Science.gov (United States)

    Shao, Y, Yvonne Y.; Wang, Lai; Welter, J, Jean F.; Ballock, R. Tracy

    2011-01-01

    Indian Hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. PMID:21930256

  9. Effect of insulin resistance on intracellular signal transduction of vessels in diabetic

    International Nuclear Information System (INIS)

    Cen Rongguang; Wei Shaoying; Mo Xingju

    2003-01-01

    To investigate the relationship between the insulin resistance (IR) and the intracellular signal transduction of vessels, changes in fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), inositol triphosphate (IP 3 ), protein kinase C(PKC) and intracellular total calcium concentration in 31 diabetic patients were compared with those of 39 normal controls. The levels of FBG, FINS, TG and TC in diabetic patients were significantly higher than those of normal controls (P 3 and PKC in diabetic patients were significantly lower than those of normal controls (P<0.01). The results suggest that there is a causal relation between insulin resistance and abnormalities of cellular calcium metabolism and intracellular signal transduction of vessels

  10. Adeno-associated viral vector transduction of human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Stender, Stefan; Murphy, Mary; O'Brien, Tim

    2007-01-01

    Mesenchymal stem cells (MSCs) have received considerable attention in the emerging field of regenerative medicine. One aspect of MSC research focuses on genetically modifying the cells with the aim of enhancing their regenerative potential. Adeno-associated virus (AAV) holds promise as a vector...... in human MSCs and to assess whether AAV transduction affects MSC multipotentiality. The results indicated that human MSCs could indeed be transiently transduced in vitro by the AAV2 vector with efficiencies of up to 65%. The percentage of GFP-positive cells peaked at 4 days post-transduction and declined...... rapidly towards 0% after day 8. The level of transgene expression in the GFP-positive population increased 4-fold over a 10,000 fold viral dose increase. This dose-response contrasted with the 200-fold increase observed in similarly transduced 293-cells, indicating a relatively restricted transgene...

  11. Safety evaluation of cation-exchange resins

    International Nuclear Information System (INIS)

    Kalkwarf, D.R.

    1977-08-01

    Results are presented of a study to evaluate whether sufficient information is available to establish conservative limits for the safe use of cation-exchange resins in separating radionuclides and, if not, to recommend what new data should be acquired. The study was also an attempt to identify in-line analytical techniques for the evaluation of resin degradation during radionuclide processing. The report is based upon a review of the published literature and upon discussions with many people engaged in the use of these resins. It was concluded that the chief hazard in the use of cation-exchange resins for separating radionuclides is a thermal explosion if nitric acid or other strong oxidants are present in the process solution. Thermal explosions can be avoided by limiting process parameters so that the rates of heat and gas generation in the system do not exceed the rates for their transfer to the surroundings. Such parameters include temperature, oxidant concentration, the amounts of possible catalysts, the radiation dose absorbed by the resin and the diameter of the resin column. Current information is not sufficient to define safe upper limits for these parameters. They can be evaluated, however, from equations derived from the Frank-Kamenetskii theory of thermal explosions provided the heat capacities, thermal conductivities and rates of heat evolution in the relevant resin-oxidant mixtures are known. It is recommended that such measurements be made and the appropriate limits be evaluated. A list of additional safety precautions are also presented to aid in the application of these limits and to provide additional margins of safety. In-line evaluation of resin degradation to assess its safety hazard is considered impractical. Rather, it is recommended that the resin be removed from use before it has received the limiting radiation dose, evaluated as described above

  12. Anaerobic toxicity of cationic silver nanoparticles

    International Nuclear Information System (INIS)

    Gitipour, Alireza; Thiel, Stephen W.; Scheckel, Kirk G.; Tolaymat, Thabet

    2016-01-01

    The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag"+ under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged polyvinylpyrrolidone coated AgNPs (PVP-AgNPs) and (3) positively charged branched polyethyleneimine coated AgNPs (BPEI-AgNPs). The AgNPs investigated in this experiment were similar in size (10–15 nm), spherical in shape, but varied in surface charge which ranged from highly negative to highly positive. While, at AgNPs concentrations lower than 5 mg L"−"1, the anaerobic decomposition process was not influenced by the presence of the nanoparticles, there was an observed impact on the diversity of the microbial community. At elevated concentrations (100 mg L"−"1 as silver), only the cationic BPEI-AgNPs demonstrated toxicity similar in magnitude to that of Ag"+. Both citrate and PVP-AgNPs did not exhibit toxicity at the 100 mg L"−"1 as measured by biogas evolution. These findings further indicate the varying modes of action for nanoparticle toxicity and represent one of the few studies that evaluate end-of-life management concerns with regards to the increasing use of nanomaterials in our everyday life. These findings also highlight some of the concerns with a one size fits all approach to the evaluation of environmental health and safety concerns associated with the use of nanoparticles. - Highlights: • At concentrations -1 the anaerobic decomposition process was not impacted. • An impact on the microbial community at concentrations -1 were observed. • At high concentrations (100 mg L"−"1), the cationic BPEI-AgNPs demonstrated toxicity. • Toxicity was demonstrated without the presence of oxidative dissolution of silver. • A one size fits all approach for the evaluation of NPs may not be accurate.

  13. TRANSDUCTION OF BACILLUS LICHENIFORMIS AND BACILLUS SUBTILIS BY EACH OF TWO PHAGES1

    Science.gov (United States)

    Taylor, Martha J.; Thorne, Curtis B.

    1963-01-01

    Taylor, Martha J. (U.S. Army Biological Laboratories, Fort Detrick, Frederick, Md.) and Curtis B. Thorne. Transduction of Bacillus licheniformis and Bacillus subtilis by each of two phages. J. Bacteriol. 86:452–461. 1963.—A second transducing bacteriophage, designated SP-15, was isolated from the same soil-sample culture filtrate that supplied the Bacillus subtilis transducing phage, SP-10, reported earlier from this laboratory. SP-10 and SP-15 differ serologically and in several other respects, but share the ability to propagate on B. subtilis W-23-Sr (streptomycin-resistant) and B. licheniformis ATCC 9945a, and to mediate general transduction in either species when propagated homologously. Attempts to transduce between the species have failed. SP-10 forms plaques readily on both W-23-Sr and 9945a; SP-15 forms minute plaques on W-23-Sr and has shown no evidence of any lytic activity on 9945a. Maximal recoveries of prototrophic colonies from mixtures of SP-10 with auxotrophs of either W-23-Sr or 9945a were obtained only when excess phage was neutralized by post-transduction treatment with specific phage antiserum. Such treatment was not necessary for maximal recovery of transductants effected by SP-15. Unlike SP-10, SP-15 propagated on W-23-Sr did not transduce B. subtilis 168 (indole−). SP-15 transduced B. licheniformis more efficiently than did SP-10. Neither phage was able to transduce B. licheniformis as efficiently as it transduced B. subtilis. The differing influences of multiplicity of infection were compared for the two phages in both species. PMID:14066421

  14. 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 ...

  15. Tapping of Love waves in an isotropic surface waveguide by surface-to-bulk wave transduction.

    Science.gov (United States)

    Tuan, H.-S.; Chang, C.-P.

    1972-01-01

    A theoretical study of tapping a Love wave in an isotropic microacoustic surface waveguide is given. The surface Love wave is tapped by partial transduction into a bulk wave at a discontinuity. It is shown that, by careful design of the discontinuity, the converted bulk wave power and the radiation pattern may be controlled. General formulas are derived for the calculation of these important characteristics from a relatively general surface contour deformation.

  16. Efficient biotechnological approach for lentiviral transduction of induced pluripotent stem cells.

    Science.gov (United States)

    Zare, Mehrak; Soleimani, Masoud; Mohammadian, Mozhdeh; Akbarzadeh, Abolfazl; Havasi, Parvaneh; Zarghami, Nosratollah

    2016-01-01

    Induced pluripotent stem (iPS) cells are generated from differentiated adult somatic cells by reprogramming them. Unlimited self-renewal, and the potential to differentiate into any cell type, make iPS cells very promising candidates for basic and clinical research. Furthermore, iPS cells can be genetically manipulated for use as therapeutic tools. DNA can be introduced into iPS cells, using lentiviral vectors, which represent a helpful choice for efficient transduction and stable integration of transgenes. In this study, we compare two methods of lentiviral transduction of iPS cells, namely, the suspension method and the hanging drop method. In contrast to the conventional suspension method, in the hanging drop method, embryoid body (EB) formation and transduction occur concurrently. The iPS cells were cultured to form EBs, and then transduced with lentiviruses, using the conventional suspension method and the hanging drop method, to express miR-128 and green fluorescent protein (GFP). The number of transduced cells were assessed by fluorescent microscopy and flow cytometry. MTT assay and real-time PCR were performed to determine the cell viability and transgene expression, respectively. Morphologically, GFP+ cells were more detectable in the hanging drop method, and this finding was quantified by flow cytometric analysis. According to the results of the MTT assay, cell viability was considerably higher in the hanging drop method, and real-time PCR represented a higher relative expression of miR-128 in the iPS cells introduced with lentiviruses in drops. Altogether, it seems that lentiviral transduction of challenging iPS cells using the hanging drop method offers a suitable and sufficient strategy in their gene transfer, with less toxicity than the conventional suspension method.

  17. Signal transduction by normal isoforms and W mutant variants of the Kit receptor tyrosine kinase.

    OpenAIRE

    Reith, A D; Ellis, C; Lyman, S D; Anderson, D M; Williams, D E; Bernstein, A; Pawson, T

    1991-01-01

    Germline mutations at the Dominant White Spotting (W) and Steel (Sl) loci have provided conclusive genetic evidence that c-kit mediated signal transduction pathways are essential for normal mouse development. We have analysed the interactions of normal and mutant W/c-kit gene products with cytoplasmic signalling proteins, using transient c-kit expression assays in COS cells. In addition to the previously identified c-kit gene product (Kit+), a second normal Kit isoform (KitA+) containing an i...

  18. Role of Glycolytic Intermediates in Global Regulation and Signal Transduction. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Liao, J.C.

    2000-05-08

    The goal of this project is to determine the role of glycolytic intermediates in regulation of cell physiology. It is known that many glycolytic intermediates are involved in regulation of enzyme activities at the kinetic level. However, little is known regarding the role of these metabolites in global regulation and signal transduction. This project aims to investigate the role of glycolytic intermediates in the regulation of gene expression.

  19. Enhanced transduction of photonic crystal dye lasers for gas sensing via swelling polymer film

    DEFF Research Database (Denmark)

    Smith, Cameron; Lind, Johan Ulrik; Christiansen, Mads Brøkner

    2011-01-01

    We present the enhanced transduction of a photonic crystal dye laser for gas sensing via deposition of an additional swelling polymer film. Device operation involves swelling of the polymer film during exposure to specific gases, leading to a change in total effective refractive index. Experimental...... in its application to other intracavity-based detection schemes to enable gas sensing. © 2011 Optical Society of America....

  20. Recombinant adeno-associated virus: efficient transduction of the rat VMH and clearance from blood.

    Directory of Open Access Journals (Sweden)

    Margriet A van Gestel

    Full Text Available To promote the efficient and safe application of adeno-associated virus (AAV vectors as a gene transfer tool in the central nervous system (CNS, transduction efficiency and clearance were studied for serotypes commonly used to transfect distinct areas of the brain. As AAV2 was shown to transduce only small volumes in several brain regions, this study compares the transduction efficiency of three AAV pseudotyped vectors, namely AAV2/1, AAV2/5 and AAV2/8, in the ventromedial nucleus of the hypothalamus (VMH. No difference was found between AAV2/1 and AAV2/5 in transduction efficiency. Both AAV2/1 and AAV2/5 achieved a higher transduction rate than AAV2/8. One hour after virus administration to the brain, no viral particles could be traced in blood, indicating that no or negligible numbers of virions crossed the blood-brain barrier. In order to investigate survival of AAV in blood, clearance was determined following systemic AAV administration. The half-life of AAV2/1, AAV2/2, AAV2/5 and AAV2/8 was calculated by determining virus clearance rates from blood after systemic injection. The half-life of AAV2/2 was 4.2 minutes, which was significantly lower than the half-lives of AAV2/1, AAV2/5 and AAV2/8. With a half-life of more than 11 hours, AAV2/8 particles remained detectable in blood significantly longer than AAV2/5. We conclude that application of AAV in the CNS is relatively safe as no AAV particles are detectable in blood after injection into the brain. With a half-life of 1.67 hours of AAV2/5, a systemic injection with 1×109 genomic copies of AAV would be fully cleared from blood after 2 days.

  1. The Drosophila rolled locus encodes a MAP kinase required in the sevenless signal transduction pathway.

    OpenAIRE

    Biggs, W H; Zavitz, K H; Dickson, B; van der Straten, A; Brunner, D; Hafen, E; Zipursky, S L

    1994-01-01

    Mitogen-activated protein (MAP) kinases have been proposed to play a critical role in receptor tyrosine kinase (RTK)-mediated signal transduction pathways. Although genetic and biochemical studies of RTK pathways in Caenorhabditis elegans, Drosophila melanogaster and mammals have revealed remarkable similarities, a genetic requirement for MAP kinases in RTK signaling has not been established. During retinal development in Drosophila, the sevenless (Sev) RTK is required for development of the ...

  2. The third helix of the murine Hoxc8 homeodomain facilitates protein transduction in mammalian cells

    International Nuclear Information System (INIS)

    Kong, Kyoung-Ah; Gadi, Jogeswar; Park, Hyoung Woo; Bok, Jinwoong; Kim, Myoung Hee

    2008-01-01

    Previously, we have demonstrated that purified Hoxc8 homeoprotein has the ability to penetrate the cellular membrane and can be transduced efficiently into COS-7 cells. Moreover, the Hoxc8 protein is able to form a complex with DNA molecules in vitro and helps the DNA be delivered intracellularly, serving as a gene delivery vehicle. Here, we further analyzed the membrane transduction activity of Hoxc8 protein and provide the evidence that the 16 amino acid (a.a.191-206, 2.23 kDa) third helix of murine Hoxc8 protein is an efficient protein transduction domain (PTD). When the 16 amino acid peptide was fused at the carboxyl terminal of enhanced green fluorescence protein (EGFP), the fusion proteins were transduced efficiently into the primary pig fetal fibroblast cells. The transduction efficiency increased in a concentration-dependent manner up to 1 μM, and appeared to plateau above a concentration of 1 μM. When tandem multimers of PTD, EGFP-PTD(2), EGFP-PTD(3), EGFP-PTD(4), and EGFP-PTD(5), were analyzed at 500 nM of concentration, the penetrating efficiency increased in a dose-dependent manner. As the number of PTDs increased, the EGFP signal also increased, although the signal maintained plateau after EGFP-PTD(3). These results indicate that the 16 amino acid third helix is the key element responsible for the membrane transduction activity of Hoxc8 proteins, and further suggest that the small peptide could serve as a therapeutic delivery vehicle for large cargo proteins

  3. Decision Aggregation in Distributed Classification by a Transductive Extension of Maximum Entropy/Improved Iterative Scaling

    Directory of Open Access Journals (Sweden)

    George Kesidis

    2008-06-01

    Full Text Available In many ensemble classification paradigms, the function which combines local/base classifier decisions is learned in a supervised fashion. Such methods require common labeled training examples across the classifier ensemble. However, in some scenarios, where an ensemble solution is necessitated, common labeled data may not exist: (i legacy/proprietary classifiers, and (ii spatially distributed and/or multiple modality sensors. In such cases, it is standard to apply fixed (untrained decision aggregation such as voting, averaging, or naive Bayes rules. In recent work, an alternative transductive learning strategy was proposed. There, decisions on test samples were chosen aiming to satisfy constraints measured by each local classifier. This approach was shown to reliably correct for class prior mismatch and to robustly account for classifier dependencies. Significant gains in accuracy over fixed aggregation rules were demonstrated. There are two main limitations of that work. First, feasibility of the constraints was not guaranteed. Second, heuristic learning was applied. Here, we overcome these problems via a transductive extension of maximum entropy/improved iterative scaling for aggregation in distributed classification. This method is shown to achieve improved decision accuracy over the earlier transductive approach and fixed rules on a number of UC Irvine datasets.

  4. Adeno-associated virus vector-mediated transduction in the cat brain.

    Science.gov (United States)

    Vite, Charles H; Passini, Marco A; Haskins, Mark E; Wolfe, John H

    2003-10-01

    Adeno-associated virus (AAV) vectors are capable of delivering a therapeutic gene to the mouse brain that can result in long-term and widespread protein production. However, the human infant brain is more than 1000 times larger than the mouse brain, which will make the treatment of global neurometabolic disorders in children more difficult. In this study, we evaluated the ability of three AAV serotypes (1,2, and 5) to transduce cells in the cat brain as a model of a large mammalian brain. The human lysosomal enzyme beta-glucuronidase (GUSB) was used as a reporter gene, because it can be distinguished from feline GUSB by heat stability. The vectors were injected into the cerebral cortex, caudate nucleus, thalamus, corona radiata, internal capsule, and centrum semiovale of 8-week-old cats. The brains were evaluated for gene expression using in situ hybridization and enzyme histochemistry 10 weeks after surgery. The AAV2 vector was capable of transducing cells in the gray matter, while the AAV1 vector resulted in greater transduction of the gray matter than AAV2 as well as transduction of the white matter. AAV5 did not result in detectable transduction in the cat brain.

  5. Influence of arsenate and arsenite on signal transduction pathways: an update

    Energy Technology Data Exchange (ETDEWEB)

    Druwe, Ingrid L.; Vaillancourt, Richard R. [The University of Arizona College of Pharmacy, Department of Pharmacology and Toxicology, Tucson, AZ (United States)

    2010-08-15

    Arsenic has been a recognized contaminant and toxicant, as well as a medicinal compound throughout human history. Populations throughout the world are exposed to arsenic and these exposures have been associated with a number of human cancers. Not much is known about the role of arsenic as a human carcinogen and more recently its role in non-cancerous diseases, such as cardiovascular disease, hypertension and diabetes mellitus have been uncovered. The health effects associated with arsenic are numerous and the association between arsenic exposure and human disease has intensified the search for molecular mechanisms that describe the biological activity of arsenic in humans and leads to the aforementioned disease states. Arsenic poses a human health risk due in part to the regulation of cellular signal transduction pathways and over the last few decades, some cellular mechanisms that account for arsenic toxicity, as well as, signal transduction pathways have been discovered. However, given the ubiquitous nature of arsenic in the environment, making sense of all the data remains a challenge. This review will focus on our knowledge of signal transduction pathways that are regulated by arsenic. (orig.)

  6. Progestins alter photo-transduction cascade and circadian rhythm network in eyes of zebrafish (Danio rerio)

    Science.gov (United States)

    Zhao, Yanbin; Fent, Karl

    2016-02-01

    Environmental progestins are implicated in endocrine disruption in vertebrates. Additional targets that may be affected in organisms are poorly known. Here we report that progesterone (P4) and drospirenone (DRS) interfere with the photo-transduction cascade and circadian rhythm network in the eyes of zebrafish. Breeding pairs of adult zebrafish were exposed to P4 and DRS for 21 days with different measured concentrations of 7-742 ng/L and 99-13´650 ng/L, respectively. Of totally 10 key photo-transduction cascade genes analyzed, transcriptional levels of most were significantly up-regulated, or normal down-regulation was attenuated. Similarly, for some circadian rhythm genes, dose-dependent transcriptional alterations were also observed in the totally 33 genes analyzed. Significant alterations occurred even at environmental relevant levels of 7 ng/L P4. Different patterns were observed for these transcriptional alterations, of which, the nfil3 family displayed most significant changes. Furthermore, we demonstrate the importance of sampling time for the determination and interpretation of gene expression data, and put forward recommendations for sampling strategies to avoid false interpretations. Our results suggest that photo-transduction signals and circadian rhythm are potential targets for progestins. Further studies are required to assess alterations on the protein level, on physiology and behavior, as well as on implications in mammals.

  7. Organic cation rhodamines for screening organic cation transporters in early stages of drug development.

    Science.gov (United States)

    Ugwu, Malachy C; Oli, Angus; Esimone, Charles O; Agu, Remigius U

    The aim of this study was to investigate the suitability of rhodamine-123, rhodamine-6G and rhodamine B as non-radioactive probes for characterizing organic cation transporters in respiratory cells. Fluorescent characteristics of the compounds were validated under standard in vitro drug transport conditions (buffers, pH, and light). Uptake/transport kinetics and intracellular accumulation of the compounds were investigated. Uptake/transport mechanisms were investigated by comparing the effect of pH, temperature, concentration, polarity, OCTs/OCTNs inhibitors/substrates, and metabolic inhibitors on the cationic dyes uptake in Calu-3 cells. Fluorescence stability and intensity of the compounds were altered by buffer composition, light, and pH. Uptake of the dyes was concentration-, temperature- and pH-dependent. OCTs/OCTNs inhibitors significantly reduced intracellular accumulation of the compounds. Whereas rhodamine-B uptake was sodium-dependent, pH had no effect on rhodamine-123 and rhodamine-6G uptake. Transport of the dyes across the cells was polarized: (AP→BL>BL→AP transport) and saturable: {V max =14.08±2.074, K m =1821±380.4 (rhodamine-B); V max =6.555±0.4106, K m =1353±130.4 (rhodamine-123) and V max =0.3056±0.01402, K m =702.9±60.97 (rhodamine-6G)}. The dyes were co-localized with MitoTracker®, the mitochondrial marker. Cationic rhodamines, especially rhodamine-B and rhodamine- 6G can be used as organic cation transporter substrates in respiratory cells. During such studies, buffer selection, pH and light exposure should be taken into consideration. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Linear growth increased in young children in an urban slum of Haiti: a randomized controlled trial of a lipid-based nutrient supplement.

    Science.gov (United States)

    Iannotti, Lora L; Dulience, Sherlie Jean Louis; Green, Jamie; Joseph, Saminetha; François, Judith; Anténor, Marie-Lucie; Lesorogol, Carolyn; Mounce, Jacqueline; Nickerson, Nathan M

    2014-01-01

    Haiti has experienced rapid urbanization that has exacerbated poverty and undernutrition in large slum areas. Stunting affects 1 in 5 young children. We aimed to test the efficacy of a daily lipid-based nutrient supplement (LNS) for increased linear growth in young children. Healthy, singleton infants aged 6-11 mo (n = 589) were recruited from an urban slum of Cap Haitien and randomly assigned to receive: 1) a control; 2) a 3-mo LNS; or 3) a 6-mo LNS. The LNS provided 108 kcal and other nutrients including vitamin A, vitamin B-12, iron, and zinc at ≥80% of the recommended amounts. Infants were followed monthly on growth, morbidity, and developmental outcomes over a 6-mo intervention period and at one additional time point 6 mo postintervention to assess sustained effects. The Bonferroni multiple comparisons test was applied, and generalized least-squares (GLS) regressions with mixed effects was used to examine impacts longitudinally. Baseline characteristics did not differ by trial arm except for a higher mean age in the 6-mo LNS group. GLS modeling showed LNS supplementation for 6 mo significantly increased the length-for-age z score (±SE) by 0.13 ± 0.05 and the weight-for-age z score by 0.12 ± 0.02 compared with in the control group after adjustment for child age (P < 0.001). The effects were sustained 6 mo postintervention. Morbidity and developmental outcomes did not differ by trial arm. A low-energy, fortified product improved the linear growth of young children in this urban setting. The trial was registered at clinicaltrials.gov as NCT01552512.

  9. Feeding behaviors during home-based treatment of moderate acute malnutrition using corn-soy blends or lipid-based nutrient supplements.

    Science.gov (United States)

    Iuel-Brockdorf, Ann-Sophie; Ouedraogo, Albertine; Ritz, Christian; Draebel, Tania Aase; Ashorn, Per; Filteau, Suzanne; Michaelsen, Kim F

    2017-10-01

    Feeding behaviors have an important impact on children's nutritional status and are essential to consider when implementing nutrition programs. The objective of this study was to explore and compare feeding behaviors related to supplementary feeding with corn-soy blends (CSB) and lipid-based nutrient supplements (LNS) based on best practice feeding behaviors. The study was conducted as part of a randomized controlled trial assessing the effectiveness of new formulations of CSB and LNS and comprised 1,546 children from 6 to 23 months. The study included a mixed methods approach using questionnaires, focus group discussions and home visits and interviews with a subsample of 20 caretakers of trial participants. We found that LNS, compared to CSB, were more likely to be mixed into other foods (OR [95% CI] 1.7 [1.3-2.2], p = <.001), served with a meal (OR [95% CI] 1.6 [1.1-2.3], p = <.018)or between meals (OR [95% CI] 1.5 [1.1-1.9], p = <.005), and fed using an encouraging feeding style (mean difference in percentage points [95% CI] 23% [6%:40%], p = .01). CSB were more likely to be fed using a forced feeding style (mean difference in percentage points [95% CI] 18% [3%:33%], p = .02) and were often observed to be served unprepared. The main differences in feeding behaviors between the two diet groups were linked to how and when supplements were served. Educational instructions should therefore be adapted according to the supplement provided; when providing CSB, efforts should be made to promote an encouraging feeding style, and emphasis should be made to ensure preparations are made according to recommendations. © 2016 John Wiley & Sons Ltd.

  10. Incorporation of photosenzitizer hypericin into synthetic lipid-based nano-particles for drug delivery and large unilamellar vesicles with different content of cholesterol

    Science.gov (United States)

    Joniova, Jaroslava; Blascakova, Ludmila; Jancura, Daniel; Nadova, Zuzana; Sureau, Franck; Miskovsky, Pavol

    2014-08-01

    Low-density lipoproteins (LDL) and high-density lipoproteins (HDL) are attractive natural occurring vehicles for drug delivery and targeting to cancer tissues. The capacity of both types of the lipoproteins to bind hydrophobic drugs and their functionality as drug carriers have been examined in several studies and it has been also shown that mixing of anticancer drugs with LDL or HDL before administration led to an increase of cytotoxic effects of the drugs in the comparison when the drugs were administered alone. However, a difficult isolation of the lipoproteins in large quantity from a biological organism as well as a variability of the composition and size of these molecules makes practical application of LDL and HDL as drug delivery systems quite complicated. Synthetic LDL and HDL and large unilamellar vesicles (LUV) are potentially suitable candidates to substitute the native lipoproteins for targeted and effective drug delivery. In this work, we have studied process of an association of potent photosensitizer hypericin (Hyp) with synthetic lipid-based nano-particles (sLNP) and large unilamellar vesicles (LUV) containing various amount of cholesterol. Cholesterol is one of the main components of both LDL and HDL particles and its presence in biological membranes is known to be a determining factor for membrane properties. It was found that the behavior of Hyp incorporation into sLNP particles with diameter ca ~ 90 nm is qualitatively very similar to that of Hyp incorporation into LDL (diameter ca. 22 nm) and these particles are able to enter U-87 MG cells by endocytosis. The presence of cholesterol in LUV influences the capacity of these vesicles to incorporate Hyp into their structure.

  11. Complementary feeding messages that target cultural barriers enhance both the use of lipid-based nutrient supplements and underlying feeding practices to improve infant diets in rural Zimbabwe.

    Science.gov (United States)

    Paul, Keriann H; Muti, Monica; Chasekwa, Bernard; Mbuya, Mduduzi N N; Madzima, Rufaro C; Humphrey, Jean H; Stoltzfus, Rebecca J

    2012-04-01

    Supplementation with lipid-based nutrient supplements (LiNS) is promoted as an approach to prevent child undernutrition and growth faltering. Previous LiNS studies have not tested the effects of improving the underlying diet prior to providing LiNS. Formative research was conducted in rural Zimbabwe to develop feeding messages to improve complementary feeding with and without LiNS. Two rounds of Trials of Improved Practices were conducted with mothers of infants aged 6-12 months to assess the feasibility of improving infant diets using (1) only locally available resources and (2) locally available resources plus 20 g of LiNS as Nutributter®/day. Common feeding problems were poor dietary diversity and low energy density. Popular improved practices were to process locally available foods so that infants could swallow them and add processed local foods to enrich porridges. Consumption of beans, fruits, green leafy vegetables, and peanut/seed butters increased after counselling (P < 0.05). Intakes of energy, protein, vitamin A, folate, calcium, iron and zinc from complementary foods increased significantly after counselling with or without the provision of Nutributter (P < 0.05). Intakes of fat, folate, iron, and zinc increased only (fat) or more so (folate, iron, and zinc) with the provision of Nutributter (P < 0.05). While provision of LiNS was crucial to ensure adequate intakes of iron and zinc, educational messages that were barrier-specific and delivered directly to mothers were crucial to improving the underlying diet. © 2010 Blackwell Publishing Ltd.

  12. Responsive feeding and child interest in food vary when rural Malawian children are fed lipid-based nutrient supplements or local complementary food.

    Science.gov (United States)

    Flax, Valerie L; Mäkinen, Samppa; Ashorn, Ulla; Cheung, Yin Bun; Maleta, Kenneth; Ashorn, Per; Bentley, Margaret E

    2013-07-01

    Caregiver and child behaviours during feeding have been used to measure responsiveness, which has been recognised as important for child growth and development. The aims of this study were to understand how caregiver and child behaviours differ when feeding lipid-based nutrient supplements (LNS) vs. local complementary food and to detect associations between behaviours and child interest in food. Sixteen moderately underweight 6-17-month-old Malawian children receiving 50 g/day of supplementary LNS for 12 weeks were videotaped during LNS (n = 32) and local complementary feeding (n = 28) episodes. Behaviours were coded at the level of the intended bite (1674 total bites). The analysis used regression models adjusted for within-subject correlation. Caregivers were less likely to allow children to self-feed and more likely to use physical pressure during LNS vs. complementary food bites. Positive caregiver verbalization was infrequent and did not differ by type of food. Higher odds of accepting a bite were associated with the bite containing LNS, odds ratio (OR) 3.05; 90% confidence interval (CI) (1.98, 4.71), the child self-feeding, OR 5.70; 90% CI (2.77, 11.69), and positive caregiver verbalization, OR 2.46; 90% CI (1.26, 4.80), while lower odds of acceptance were associated with negative child verbalization during feeding, OR 0.27; 90% CI (0.17, 0.42). In this sample, caregivers used more responsive feeding practices during bites of local complementary food and were more controlling when feeding LNS. Responsive caregiver behaviours predicted child acceptance of food. These results could be used to design interventions in Malawi to improve responsive feeding practices in general and during LNS use. © 2011 John Wiley & Sons Ltd.

  13. Efficacy of an oral and tropically stable lipid-based formulation of Amphotericin B (iCo-010) in an experimental mouse model of systemic candidiasis.

    Science.gov (United States)

    Ibrahim, Fady; Sivak, Olena; Wasan, Ellen K; Bartlett, Karen; Wasan, Kishor M

    2013-10-29

    An oral lipid based formulation that exhibits tropical stability (iCo-010) was developed to enhance the absorption of orally administered amphotericin B (AmB). iCo-010 has previously shown high efficacy in an acute model of systemic candidiasis in rats, directing the focus of this study to be its efficacy in a chronic model of systemic candidiasis in mice. Mice were infected with 0.6 to 1×108 CFUs of Candida albicans ATCC 18804 strain by tail vein injection and were left for three days to develop the infection after which time treatment was initiated. The infected animals were assigned to the following treatment groups: no treatment (control) or iCo-010 at 5, 10 and 20 mg/kg administered by oral gavage once daily (QD) for 5 consecutive days. The animals were sacrificed 7 days after the last dose and the concentration of AmB and the fungal burden were assessed within the liver, kidneys, heart, lungs, spleen and brain. Although the infection was relatively low (~ 60-100 CFUs/ 1 ml tissue homogenate) in the liver, lungs and heart, the infection level was very high (70 000 CFUs / 1 ml tissue homogenate) in the kidney tissues for the control group. The highest concentrations of AmB were recovered in the kidneys and the spleen. The fungal burden in the tissues was lowered by 69-96% in the treatment groups when compared to the control group. Oral iCo-010 is an effective treatment of systemic candidiasis in the mouse model.

  14. Crossover trial to test the acceptability of a locally produced lipid-based nutrient supplement (LNS) for children under 2 years in Cambodia: a study protocol.

    Science.gov (United States)

    Borg, Bindi; Mihrshahi, Seema; Griffin, Mark; Chamnan, Chhoun; Laillou, Arnaud; Wieringa, Frank T

    2017-09-06

    The acceptability and efficacy of existing ready-to-use supplementary and therapeutic foods has been low in Cambodia, thus limiting success in preventing and treating malnutrition among Cambodian children. In that context, UNICEF and IRD have developed a locally produced, multiple micronutrient fortified lipid-based nutrient supplement. This food is innovative, in that it uses fish instead of milk as the animal source food. Very few supplementary foods have non-milk animal source foods, and in addition they have not been widely tested. This trial will assess the novel food's acceptability to children and caregivers. This is a cluster-randomised, incomplete block, 4×4 crossover design with no blinding. It will take place in four sites in a community setting in periurban Phnom Penh. Healthy children aged 9-23 months (n=100) will eat each of four foods for 3 days at a time. The amount they consume will be measured, and at the end of each 3-day set, caregivers will assess how well their child liked the food. After 12 days, caregivers themselves will do a sensory test of the 4 foods and will rank them in terms of preference. Ethical clearance was received from the University of Queensland Medical Research Ethics Committee (2014001070) and from Cambodia's National Ethics Committee for Health Research (03/8 NECHR). ClinicalTrials.gov, identifier: LNS-CAMB-INFANTS; NCT02257437. Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Effects of metallic cations in the beryl flotation

    International Nuclear Information System (INIS)

    Lima Leonel, C.M. de; Peres, A.E.C.

    1984-01-01

    The beryl zeta potential in microelectrophoretic cell is studied in the presence of neutral electrolyte, cations of calcium, magnesium and iron. The petroleum sulfonate is used how collector in Hallimond tube. Hydroxy complex of metallic cations seems activate the ore and precipitates of colloidal metallic hidroxies seems lower him when added to the mixture. (M.A.C.) [pt

  16. Stable polyfluorinated cycloalkenyl cations and their NMR spectra

    International Nuclear Information System (INIS)

    Snegirev, V.F.; Galakhov, M.V.; Makarov, K.N.; Bakhmutov, V.I.

    1986-01-01

    New stable 1-methoxyperfluoro-2-ethylcyclobutenyl, 1-methoxyperfluoro-2-methylcyclo-pentenyl, and 1-methoxyperfluoro-2-ethylcyclohexenyl cations were obtained by the action of antimony pentafluoride on the corresponding olefins. The distribution of the charges in the investigated polyfluorinated cycloalkenyl cations was investigated by 13 C NMR method

  17. Synthesis of Cationic Core-Shell Latex Particles

    NARCIS (Netherlands)

    Dziomkina, N.; Hempenius, Mark A.; Vancso, Gyula J.

    2006-01-01

    Surfactant-free seeded (core-shell) polymerization of cationic polymer colloids is presented. Polystyrene core particles with sizes between 200 nm and 500 nm were synthesized. The number average diameter of the colloidal core particles increased with increasing monomer concentration. Cationic shells

  18. Cationic antimicrobial peptides inactivate Shiga toxin-encoding bacteriophages

    Science.gov (United States)

    Del Cogliano, Manuel E.; Hollmann, Axel; Martinez, Melina; Semorile, Liliana; Ghiringhelli, Pablo D.; Maffía, Paulo C.; Bentancor, Leticia V.

    2017-12-01

    Shiga toxin (Stx) is the principal virulence factor during Shiga toxin-producing Escherichia coli (STEC) infections. We have previously reported the inactivation of bacteriophage encoding Stx after treatment with chitosan, a linear polysaccharide polymer with cationic properties. Cationic antimicrobial peptides (cAMPs) are short linear aminoacidic sequences, with a positive net charge, which display bactericidal or bacteriostatic activity against a wide range of bacterial species. They are promising novel antibiotics since they have shown bactericidal effects against multiresistant bacteria. To evaluate whether cationic properties are responsible for bacteriophage inactivation, we tested seven cationic peptides with proven antimicrobial activity as anti-bacteriophage agents, and one random sequence cationic peptide with no antimicrobial activity as a control. We observed bacteriophage inactivation after incubation with five cAMPs, but no inactivating activity was observed with the random sequence cationic peptide or with the non alpha helical cAMP Omiganan. Finally, to confirm peptide-bacteriophage interaction, zeta potential was analyzed by following changes on bacteriophage surface charges after peptide incubation. According to our results we could propose that: 1) direct interaction of peptides with phage is a necessary step for bacteriophage inactivation, 2) cationic properties are necessary but not sufficient for bacteriophage inactivation, and 3) inactivation by cationic peptides could be sequence (or structure) specific. Overall our data suggest that these peptides could be considered a new family of molecules potentially useful to decrease bacteriophage replication and Stx expression.

  19. CATION EXCHANGE METHOD FOR THE RECOVERY OF PROTACTINIUM

    Science.gov (United States)

    Studier, M.H.; Sullivan, J.C.

    1959-07-14

    A cation exchange prccess is described for separating protactinium values from thorium values whereby they are initially adsorbed together from an aqueous 0.1 to 2 N hydrochloric acid on a cation exchange resin in a column. Then selectively eluting the thorium by an ammonium sulfate solution and subsequently eluting the protactinium by an oxalate solution.

  20. pi-Dimers of end-capped oligopyrrole cation radicals

    NARCIS (Netherlands)

    Haare, van J.A.E.H.; Groenendaal, L.; Havinga, E.E.; Janssen, R.A.J.; Meijer, E.W.

    1996-01-01

    In two consecutive one-electron oxidations, oligopyrroles substituted with phenyl capping groups (PhPynPh, n = 2–4) can be oxidized reversibly to give stable cation radicals and dications. Spectroelectrochemical studies give direct evidence that diamagnetic p-dimers of cation radicals are formed in

  1. Cation exchange of 53 elements in nitric acid

    International Nuclear Information System (INIS)

    Marsh, S.F.; Alarid, J.E.; Hamond, C.F.; McLeod, M.J.; Roensch, F.R.; Rein, J.E.

    1978-02-01

    Cation-exchange distribution data are presented for 53 elements from 3 to 12M HNO 3 for three strong-acid resins, having cross-linkages of 8%, 4%, and macroporous. Data obtained by 16- to 18-h dynamic batch contacts are compared to cation-exchange distribution data from strong HCl and HClO 4

  2. Base Cation Leaching From the Canopy of a Rubber ( Hevea ...

    African Journals Online (AJOL)

    Base cations are essential to the sustainability of forest ecosystems. They are important for neutralizing the acidifying effects of atmospheric deposition. There is the need for in-depth understanding of base cation depletion and leaching from forest canopy. This is important particularly due to the increasing acidification and ...

  3. Cationic Antimicrobial Peptides Inactivate Shiga Toxin-Encoding Bacteriophages

    Directory of Open Access Journals (Sweden)

    Manuel E. Del Cogliano

    2017-12-01

    Full Text Available Shiga toxin (Stx is the principal virulence factor during Shiga toxin-producing Escherichia coli (STEC infections. We have previously reported the inactivation of bacteriophage encoding Stx after treatment with chitosan, a linear polysaccharide polymer with cationic properties. Cationic antimicrobial peptides (cAMPs are short linear aminoacidic sequences, with a positive net charge, which display bactericidal or bacteriostatic activity against a wide range of bacterial species. They are promising novel antibiotics since they have shown bactericidal effects against multiresistant bacteria. To evaluate whether cationic properties are responsible for bacteriophage inactivation, we tested seven cationic peptides with proven antimicrobial activity as anti-bacteriophage agents, and one random sequence cationic peptide with no antimicrobial activity as a control. We observed bacteriophage inactivation after incubation with five cAMPs, but no inactivating activity was observed with the random sequence cationic peptide or with the non-alpha helical cAMP Omiganan. Finally, to confirm peptide-bacteriophage interaction, zeta potential was analyzed by following changes on bacteriophage surface charges after peptide incubation. According to our results we could propose that: (1 direct interaction of peptides with phage is a necessary step for bacteriophage inactivation, (2 cationic properties are necessary but not sufficient for bacteriophage inactivation, and (3 inactivation by cationic peptides could be sequence (or structure specific. Overall our data suggest that these peptides could be considered a new family of molecules potentially useful to decrease bacteriophage replication and Stx expression.

  4. Cation substitution induced blue-shift of optical band gap

    Indian Academy of Sciences (India)

    Cation substitution induced blue-shift of optical band gap in nanocrystalline Zn ( 1 − x ) Ca x O thin films deposited by sol–gel dip coating technique ... thin films giving 13.03% enhancement in theenergy gap value due to the electronic perturbation caused by cation substitution as well as deterioration in crystallinity.

  5. In vivo toxicity of cationic micelles and liposomes

    DEFF Research Database (Denmark)

    Knudsen, Kristina Bram; Northeved, Helle; Ek, Pramod Kumar

    2015-01-01

    This study investigated toxicity of nanocarriers comprised of cationic polymer and lipid components often used in gene and drug delivery, formulated as cationic micelles and liposomes. Rats were injected intravenously with 10, 25 or 100 mg/kg and sacrificed after 24 or 48 h, or 24 h after the las...

  6. Inversion of membrane surface charge by trivalent cations probed with a cation-selective channel.

    Science.gov (United States)

    Gurnev, Philip A; Bezrukov, Sergey M

    2012-11-13

    We demonstrate that the cation-selective channel formed by gramicidin A can be used as a reliable sensor for studying the multivalent ion accumulation at the surfaces of charged lipid membranes and the "charge inversion" phenomenon. In asymmetrically charged membranes with the individual leaflets formed from pure negative and positive lipids bathed by 0.1 M CsCl solutions the channel exhibits current rectification, which is comparable to that of a typical n/p semiconductor diode. We show that even at these highly asymmetrical conditions the channel conductance can be satisfactorily described by the electrodiffusion equation in the constant field approximation but, due to predictable limitations, only when the applied voltages do not exceed 50 mV. Analysis of the changes in the voltage-dependent channel conductance upon addition of trivalent cations allows us to gauge their interactions with the membrane surface. The inversion of the sign of the effective surface charge takes place at the concentrations, which correlate with the cation size. Specifically, these concentrations are close to 0.05 mM for lanthanum, 0.25 mM for hexaamminecobalt, and 4 mM for spermidine.

  7. Cation interdiffusion in polycrystalline calcium and strontium titanate

    International Nuclear Information System (INIS)

    Butler, E.P.; Jain, H.; Smyth, D.M.

    1991-01-01

    This paper discusses a method that has been developed to study bulk lattice interdiffusion between calcium and strontium titanate by fabrication of a diffusion couple using cosintering. The measured interdiffusion coefficients, D(C), indicate that strontium impurity diffusion in calcium titanate occurs at a faster rate than calcium impurity diffusion in strontium titanate. These interdiffusion coefficients are composition independent when the concentration of the calcium cation exceeds that of the strontium cation; otherwise D(C) is strongly composition dependent. Investigations into the effect of cation nonstoichiometry give results that are consistent with a defect incorporation reaction in which excess TiO 2 , within the solid solubility limit, produces A-site cation vacancies as compensating defects. The interdiffusion coefficients increase with increasing concentrations of TiO 2 , so it is concluded that interdiffusion of these alkaline-earth cations in their titanates occurs via a vacancy mechanism

  8. Thermochemical stability of Soviet macroporous sulfonated cation-exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Rukhlyada, N.N.; Plotnikova, V.P.; Roginskaya, B.S.; Znamenskii, Yu.P.; Zavodovskaya, A.S.; Dobrova, E.I.

    1988-10-20

    The purpose of this work was to study the influence of macroporosity on the thermochemical stability of sulfonated cation-exchangers. The investigations were carried out on commercial macroporous sulfonated cation-exchangers based on styrene-divinylbenzene copolymers. Study of the thermochemical stability of macroporous sulfonated cation-exchangers in dilute hydrogen peroxide solutions showed that the type of macroporosity has virtually no influence on their stability. The determining factor in thermal stability of macroporous cation-exchangers, as of the gel type, is the degree of cross-linking of the polymer matrix. The capacity loss of macroporous cation-exchangers during oxidative thermolysis is caused by destruction of the macromolecular skeleton and elution of fragments of polar chains containing sulfo groups into the solution.

  9. Increasing Base Cations in Streams: Another Legacy of Deicing Salts?

    Science.gov (United States)

    Helton, A. M.; Barclay, J. R.; Bellucci, C.; Rittenhouse, C.

    2017-12-01

    Elevated use of deicing salts directly increases sodium chloride inputs to watersheds. Sodium can accumulate in soils over time and has the potential to leach other cations (e.g., calcium, magnesium, and potassium) from the soil through cation exchange. We hypothesize that increased use of deicing salts results in a legacy of soils depleted in non-sodium base cations with loss of cations to receiving waters. The goal of this project is to quantify temporal trends in base cations and chloride in streams and rivers across the United States. We used Weighted Regressions on Time, Discharge, and Season (WRTDS) to analyze trends in base cations. Our preliminary analysis of 10 rivers in Connecticut with chemical periods of record ranging from 24 - 64 years (median = 55 years), shows that the flux of base cations is increasing in all sites (25 - 366 103 meq ha-1 yr-1 yr-1), driven largely by increases in sodium (23 - 222 103 meq ha-1 yr-1 yr-1), the dominant cation in 7 of the sites. Chloride is also increasing at all sites (26 - 261 103 meq ha-1 yr-1 yr-1), which, in combination with salt use trends, suggests a road salt source for the increased sodium. Non-sodium cations are also increasing in 9 of the sites (8 - 54 103 meq ha-1 yr-1 yr-1), though they are not directly added with most deicing salts. We will compare these trends to other long-term sites across the United States, and quantify relationships between cation trends and land cover, road density, and snowfall.

  10. Inconsistent Transduction

    DEFF Research Database (Denmark)

    Højlund, Marie Koldkjær; Riis, Morten S.

    2017-01-01

    The growing integration of sounding art as research practice in academia is a part of the “practice turn” in humanities and social sciences, where artistic practices and artefacts themselves become a form of academic inquiry. As the process of creating art represents a valid research method...... at “not-knowing” or “not-yet-knowing” within artistic research encompassing the unexpected, the spontaneous and involuntary. We argue that the implicit human-centred perspective present in these alternative understandings of knowledge production in artistic research prevents us from fully engaging...... with the objects in question on their own premises. Therefore, tuning into the “not-knowing” requires expanding the perspective to encompass non-human forms of knowledge incorporated through an object-oriented ontological line of thinking. By switching the focus from the human perspective to that of the objects...

  11. Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes.

    Science.gov (United States)

    Joiner, C H; Platt, O S; Lux, S E

    1986-12-01

    The mechanism by which sickle cells and xerocytic red cells become depleted of cations in vivo has not been identified previously. Both types of cells exhibit elevated permeabilities to sodium and potassium, in the case of sickle cells, when deoxygenated. The ouabain-insensitive fluxes of sodium and potassium were equivalent, however, in both cell types under these conditions. When incubated 18 hours in vitro, sickle cells lost cations but only when deoxygenated. This cation depletion was blocked by ouabain, removal of external potassium, or pretreatment with 4,4'-diisothiocyanostilbene-2,2'-disulfonate, which blocks the increase in cation permeability induced by deoxygenation. The loss of cation exhibited by oxygenated xerocytes similarly incubated was also blocked by ouabain. These data support the hypothesis that the elevated "passive" cation fluxes of xerocytes and deoxygenated sickle cells are not directly responsible for cation depletion of these cells; rather, these pathologic leaks interact with the sodium pump to produce a net loss of cellular cation.

  12. Comparison of "type I" and "type II" organic cation transport by organic cation transporters and organic anion-transporting polypeptides

    NARCIS (Netherlands)

    Van Montfoort, JE; Muller, M; Groothuis, GMM; Meijer, DKF; Koepsell, H; Meier, PJ

    Previous inhibition studies with taurocholate and cardiac glycosides suggested the presence of separate uptake systems for small "type I" (system1) and for bulky "type II" (system2) organic cations in rat hepatocytes. To identify the transport systems involved in type I and type II organic cation

  13. IRMPD Action Spectroscopy of Alkali Metal Cation-Cytosine Complexes: Effects of Alkali Metal Cation Size on Gas Phase Conformation

    NARCIS (Netherlands)

    Yang, B.; Wu, R.R.; Polfer, N.C.; Berden, G.; Oomens, J.; Rodgers, M.T.

    2013-01-01

    The gas-phase structures of alkali metal cation-cytosine complexes generated by electrospray ionization are probed via infrared multiple photon dissociation (IRMPD) action spectroscopy and theoretical calculations. IRMPD action spectra of five alkali metal cation-cytosine complexes exhibit both

  14. Anaerobic toxicity of cationic silver nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Gitipour, Alireza; Thiel, Stephen W. [Biomedical, Chemical, and Environmental Engineering, University of Cincinnati, Cincinnati, OH (United States); Scheckel, Kirk G. [USEPA, Office of Research and Development, Cincinnati, OH (United States); Tolaymat, Thabet, E-mail: tolaymat.thabet@epa.gov [USEPA, Office of Research and Development, Cincinnati, OH (United States)

    2016-07-01

    The microbial toxicity of silver nanoparticles (AgNPs) stabilized with different capping agents was compared to that of Ag{sup +} under anaerobic conditions. Three AgNPs were investigated: (1) negatively charged citrate-coated AgNPs (citrate-AgNPs), (2) minimally charged polyvinylpyrrolidone coated AgNPs (PVP-AgNPs) and (3) positively charged branched polyethyleneimine coated AgNPs (BPEI-AgNPs). The AgNPs investigated in this experiment were similar in size (10–15 nm), spherical in shape, but varied in surface charge which ranged from highly negative to highly positive. While, at AgNPs concentrations lower than 5 mg L{sup −1}, the anaerobic decomposition process was not influenced by the presence of the nanoparticles, there was an observed impact on the diversity of the microbial community. At elevated concentrations (100 mg L{sup −1} as silver), only the cationic BPEI-AgNPs demonstrated toxicity similar in magnitude to that of Ag{sup +}. Both citrate and PVP-AgNPs did not exhibit toxicity at the 100 mg L{sup −1} as measured by biogas evolution. These findings further indicate the varying modes of action for nanoparticle toxicity and represent one of the few studies that evaluate end-of-life management concerns with regards to the increasing use of nanomaterials in our everyday life. These findings also highlight some of the concerns with a one size fits all approach to the evaluation of environmental health and safety concerns associated with the use of nanoparticles. - Highlights: • At concentrations -1 the anaerobic decomposition process was not impacted. • An impact on the microbial community at concentrations -1 were observed. • At high concentrations (100 mg L{sup −1}), the cationic BPEI-AgNPs demonstrated toxicity. • Toxicity was demonstrated without the presence of oxidative dissolution of silver. • A one size fits all approach for the evaluation of NPs may not be accurate.

  15. Vibrational Spectroscopy of Cation and Anion Channelrhodopsins

    Science.gov (United States)

    Yi, Adrian S.

    Optogenetics is a technique to control and monitor cell activity with light by expression of specific microbial rhodopsins. Cation channelrhodopsins (CCRs) and anion channelrhodopsins (ACRs) have been demonstrated to activate and silence cell activity, respectively. In this dissertation, the molecular mechanisms of two channelrhodopsins are studied: a CCR from Chlamydomonas augustae (CaChR1) and an ACR from Guillardia theta (GtACR1). The recently discovered GtACR1is especially interesting, as it achieves neural silencing with 1/1000th of the light intensity compared to previous microbial rhodopsin silencing ion pumps. Static and time-resolved resonance Raman, FTIR difference, and UV-visible spectroscopies were utilized in addition to various biochemical and genetic techniques to explore the molecular mechanisms of these channelrhodopsins. In CaChR1, Glu169 and Asp299 residues are located nearby the Schiff base (SB) similar to the homologous residues Asp85 and Asp212, which exist in an ionized state in unphotolyzed bacteriorhodopsin (BR) and play a key role in proton pumping. We observe significant changes in the protonation states of the SB, Glu169, and Asp299 of CaChR1 leading up to the open-channel P2 state, where all three groups exist in a charge neutral state. This unusual charge neutrality along with the position of these groups in the CaChR1 ion channel suggests that charge neutrality plays an important role in cation gating and selectivity in these low efficiency CCRs. Significant differences exist in the photocycle and protonation/hydrogen bonding states of key residues inGtACR1compared to BR and CaChR1. Resonance Raman studies reveal that in the unphotolyzed state of GtACR1, residues Glu68, Ser97 (BR Asp85 homolog), and Asp234 (BR Asp212 homolog) located near the SB exist in charge neutral states. Furthermore, upon K formation, these residues do not change their protonation states. At room temperature, a slow decay of the red-shifted K intermediate is

  16. Cation-π interaction of the univalent sodium cation with [2.2.2]paracyclophane: Experimental and theoretical study

    Science.gov (United States)

    Makrlík, Emanuel; Sýkora, David; Böhm, Stanislav; Vaňura, Petr

    2018-02-01

    By employing electrospray ionization mass spectrometry (ESI-MS), it was proven experimentally that the univalent sodium cation (Na+) forms with [2.2.2]paracyclophane (C24H24) the cationic complex [Na(C24H24)]+. Further, applying quantum chemical DFT calculations, the most probable structure of the [Na(C24H24)]+ complex was derived. In the resulting complex with a symmetry very close to C3, the "central" cation Na+, fully located in the cavity of the parent [2.2.2]paracyclophane ligand, is bound to all three benzene rings of [2.2.2]paracyclophane via cation-π interaction. Finally, the interaction energy, E(int), of the considered cation-π complex [Na(C24H24)]+ was found to be -267.3 kJ/mol, confirming the formation of this fascinating complex species as well.

  17. Towards a clinically relevant lentiviral transduction protocol for primary human CD34 hematopoietic stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Michelle Millington

    2009-07-01

    Full Text Available Hematopoietic stem cells (HSC, in particular mobilized peripheral blood stem cells, represent an attractive target for cell and gene therapy. Efficient gene delivery into these target cells without compromising self-renewal and multi-potency is crucial for the success of gene therapy. We investigated factors involved in the ex vivo transduction of CD34(+ HSCs in order to develop a clinically relevant transduction protocol for gene delivery. Specifically sought was a protocol that allows for efficient transduction with minimal ex vivo manipulation without serum or other reagents of animal origin.Using commercially available G-CSF mobilized peripheral blood (PB CD34(+ cells as the most clinically relevant target, we systematically examined factors including the use of serum, cytokine combinations, pre-stimulation time, multiplicity of infection (MOI, transduction duration and the use of spinoculation and/or retronectin. A self-inactivating lentiviral vector (SIN-LV carrying enhanced green fluorescent protein (GFP was used as the gene delivery vehicle. HSCs were monitored for transduction efficiency, surface marker expression and cellular function. We were able to demonstrate that efficient gene transduction can be achieved with minimal ex vivo manipulation while maintaining the cellular function of transduced HSCs without serum or other reagents of animal origin.This study helps to better define factors relevant towards developing a standard clinical protocol for the delivery of SIN-LV into CD34(+ cells.

  18. Removal of radiocesium using cation exchange resin

    International Nuclear Information System (INIS)

    Morita-Murase, Yuko; Mizumura, Ryosuke; Tachibana, Yoshitaka; Kanazawa, Hideko

    2013-01-01

    Cation exchange resins (calcium polystyrene sulfonate, Ca-resin and sodium polystyrene sulfonate, Na-resin) have been used as agents to improve hyperkerlemia. For removing 137 Cs from the human body, the adsorption ability of the resin for 137 Cs was examined and evaluated. Resin (0.03 g) and 137 Cs (ca.1 kBq) were introduced into 3 mL of water, the Japanese Pharmacopoeia 1st fluid for a dissolution test (pH 1.2) and 2nd fluid (pH 6.8), respectively, and shaken. After 1-3 hours, the 137 Cs adsorption (%) of Na-resin was 99% in water, 60% in a pH 1.2 fluid and, 66% in a pH 6.8 fluid. By adding potassium, the 137 Cs adsorption (%) of Ca-resin was reduced. However, the 137 Cs adsorption (%) of Na-resin was almost unchanged. These results show that both resins have adsorption ability for 137 Cs in the stomach and the intestines. Therefore, the proposed method will be an effective means in the case of a radiological emergency due to 137 Cs. (author)

  19. Cyanide ion complexation by a cationic borane.

    Science.gov (United States)

    Chiu, Ching-Wen; Gabbaï, François P

    2008-02-14

    While we have previously reported that [1-(Mes2B)-8-(Me3NCH2)-C10H6]+ ([2]+) complexes fluoride ions to form [1-(Mes2FB)-8-(Me3NCH2)-C10H6] (2-F), we now show that this cationic borane also complexes cyanide to form [1-(Mes2(NC)B)-8-(Me3NCH2)-C10H6] (2-CN). This reaction also occurs under biphasic conditions (H2O-CHCl3) and may serve to transport cyanide in organic phases. The zwitterionic cyanoborate 2-CN has been fully characterized and its crystal structure determined. UV-vis titration experiments carried out in THF indicate that [2]+ has a higher affinity for fluoride (K > 10(8) M(-1)) than cyanide (K = 8.0 (+/-0.5) x 10(5) M(-1)). Steric effects which impede cyanide binding to the sterically congested boron center of [2]+ are most likely at the origin of this selectivity. Finally, electrochemical studies indicate that [2]+ is significantly more electrophilic than its neutral precursor 1-(Mes2B)-8-(Me2NCH2)-(C10H6) (1). These studies also show that reduction of [2]+ is irreversible, possibly because of elimination of the NMe3 moiety under reductive conditions. In fact, [2]OTf reacts with NaBH4 to afford 1-(Mes2B)-8-(CH3)-(C10H6) (4) which has also been fully characterized.

  20. Interaction of cationic drugs with liposomes.

    Science.gov (United States)

    Howell, Brett A; Chauhan, Anuj

    2009-10-20

    Interactions between cationic drugs and anionic liposomes were studied by measuring binding of drugs and the effect of binding on liposome permeability. The measurements were analyzed in the context of a continuum model based on electrostatic interactions and a Langmuir isotherm. Experiments and modeling indicate that, although electrostatic interactions are important, the fraction of drug sequestered in the double-layer is negligible. The majority of drug enters the bilayer with the charged regions interacting with the charged lipid head groups and the lipophilic regions associated with the bilayer. The partitioning of the drug can be described by a Langmuir isotherm with the electrostatic interactions increasing the sublayer concentration of the drug. The binding isotherms are similar for all tricyclic antidepressants (TCA). Bupivacaine (BUP) binds significantly less compared to TCA because its structure is such that the charged region has minimal interactions with the lipid heads once the BUP molecule partitions inside the bilayer. Conversely, the TCAs are linear with distinct hydrophilic and lipophilic regions, allowing the lipophilic regions to lie inside the bilayer and the hydrophilic regions to protrude out. This conformation maximizes the permeability of the bilayer, leading to an increased release of a hydrophilic fluorescent dye from liposomes.

  1. Radical Cations and Acid Protection during Radiolysis

    Energy Technology Data Exchange (ETDEWEB)

    Mincher, Bruce J. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Zarzana, Christopher A. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mezyk, Stephen P. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-09-09

    Ligand molecules for used nuclear fuel separation schemes are exposed to high radiation fields and high concentrations of acid. Thus, an understanding of the complex interactions between extraction ligands, diluent, and acid is critical to understanding the performance of a separation process. The diglycolamides are ligands with important structural similarities to CMPO; however, previous work has shown that their radiolytic degradation has important mechanistic differences from CMPO. The DGAs do not enjoy radioprotection by HNO3 and the kinetics of DGA radiolytic degradation are different. CMPO degrades with pseudo-zero-order kinetics in linear fashion with absorbed dose while the DGAs degrade in pseudo-first-order, exponential fashion. This suggests that the DGAs degrade by simple reaction with some product of direct diluent radiolysis, while CMPO degradation is probably multi-step, with a slow step that is not dependent on the CMPO concentration, and mitigated by HNO3. It is thus believed that radio-protection and the zero-order radiolytic degradation kinetics are related, and that these phenomena are a function of either the formation of strong acid complexes with CMPO and/or to the presence of the CMPO phenyl ring. Experiments to test both these hypotheses have been designed and partially conducted. This report summarizes findings related to these phenomena for FY16, in satisfaction of milestone M3FT-16IN030104053. It also reports continued kinetic measurements for the reactions of the dodecane radical cation with solvent extraction ligands.

  2. Radical Cations and Acid Protection during Radiolysis

    International Nuclear Information System (INIS)

    Mincher, Bruce J.; Zarzana, Christopher A.; Mezyk, Stephen P.

    2016-01-01

    Ligand molecules for used nuclear fuel separation schemes are exposed to high radiation fields and high concentrations of acid. Thus, an understanding of the complex interactions between extraction ligands, diluent, and acid is critical to understanding the performance of a separation process. The diglycolamides are ligands with important structural similarities to CMPO; however, previous work has shown that their radiolytic degradation has important mechanistic differences from CMPO. The DGAs do not enjoy radioprotection by HNO3 and the kinetics of DGA radiolytic degradation are different. CMPO degrades with pseudo-zero-order kinetics in linear fashion with absorbed dose while the DGAs degrade in pseudo-first-order, exponential fashion. This suggests that the DGAs degrade by simple reaction with some product of direct diluent radiolysis, while CMPO degradation is probably multi-step, with a slow step that is not dependent on the CMPO concentration, and mitigated by HNO 3 . It is thus believed that radio-protection and the zero-order radiolytic degradation kinetics are related, and that these phenomena are a function of either the formation of strong acid complexes with CMPO and/or to the presence of the CMPO phenyl ring. Experiments to test both these hypotheses have been designed and partially conducted. This report summarizes findings related to these phenomena for FY16, in satisfaction of milestone M3FT-16IN030104053. It also reports continued kinetic measurements for the reactions of the dodecane radical cation with solvent extraction ligands.

  3. Cation exchange properties of zeolites in hyper alkaline aqueous media.

    Science.gov (United States)

    Van Tendeloo, Leen; de Blochouse, Benny; Dom, Dirk; Vancluysen, Jacqueline; Snellings, Ruben; Martens, Johan A; Kirschhock, Christine E A; Maes, André; Breynaert, Eric

    2015-02-03

    Construction of multibarrier concrete based waste disposal sites and management of alkaline mine drainage water requires cation exchangers combining excellent sorption properties with a high stability and predictable performance in hyper alkaline media. Though highly selective organic cation exchange resins have been developed for most pollutants, they can serve as a growth medium for bacterial proliferation, impairing their long-term stability and introducing unpredictable parameters into the evolution of the system. Zeolites represent a family of inorganic cation exchangers, which naturally occur in hyper alkaline conditions and cannot serve as an electron donor or carbon source for microbial proliferation. Despite their successful application as industrial cation exchangers under near neutral conditions, their performance in hyper alkaline, saline water remains highly undocumented. Using Cs(+) as a benchmark element, this study aims to assess the long-term cation exchange performance of zeolites in concrete derived aqueous solutions. Comparison of their exchange properties in alkaline media with data obtained in near neutral solutions demonstrated that the cation exchange selectivity remains unaffected by the increased hydroxyl concentration; the cation exchange capacity did however show an unexpected increase in hyper alkaline media.

  4. Effect of alkali metal cations on anodic dissolution of gold in cyanide solutions. Potentiodynamic measurement

    International Nuclear Information System (INIS)

    Bek, R.Yu.; Rogozhnikov, N.A.; Kosolapov, G.V.

    1998-01-01

    It is shown that gold dissolution rate in cyanic solutions in Li + , Na + , K + , Cs + cation series increases basically and decreases under cation concentration increasing. Cation effect on current value is caused by cations drawing in dense layer. A model of dense part of double layer with two Helmholtz planes (anion and cation) is suggested. Effect of nature and concentration of alkali metal cations on gold dissolution rate is explained on the base of the model [ru

  5. Prenatal Lipid-Based Nutrient Supplements Do Not Affect Pregnancy or Childbirth Complications or Cesarean Delivery in Bangladesh: A Cluster-Randomized Controlled Effectiveness Trial.

    Science.gov (United States)

    Mridha, Malay K; Matias, Susana L; Paul, Rina Rani; Hussain, Sohrab; Sarker, Mostofa; Hossain, Mokbul; Peerson, Janet M; Vosti, Stephen A; Dewey, Kathryn G

    2017-09-01

    Background: Pregnancy and childbirth complications and cesarean delivery are common in Bangladesh. Objective: We evaluated the effect of lipid-based nutrient supplements for pregnant and lactating women (LNS-PL) on pregnancy and childbirth complications and cesarean delivery. Methods: We conducted the Rang-Din Nutrition Study, a cluster-randomized controlled effectiveness trial within a community health program in rural Bangladesh. We enrolled 4011 pregnant women in early pregnancy. Women in 48 clusters received iron and folic acid (IFA; 60 mg Fe + 400 μg folic acid/d) and women in 16 clusters received LNS-PL (20 g/d, 118 kcal) containing essential fatty acids and 22 vitamins and minerals. Pregnancy and childbirth complications and the cesarean delivery rate were secondary outcomes of the study. Results: Women in the LNS-PL group did not differ significantly from the IFA group with respect to mean systolic blood pressure at 36 wk gestation (113 and 112 mm Hg; P = 0.17), diastolic blood pressure at 36 wk gestation (68.9 and 68.7 mmHg; P = 0.88), or mean total number of pregnancy and childbirth complications (0.32 and 0.31; P = 0.86). They also did not differ significantly with respect to the prevalence of high blood pressure at 36 wk (1.74% and 2.03%; P = 0.62), antepartum hemorrhage (0.83% and 1.39%; P = 0.21), prolonged labor (8.34% and 8.79%; P = 0.68), early rupture of membranes (9.30% and 8.45%; P = 0.43), convulsions (1.57% and 1.08%; P = 0.24), high blood pressure in labor (1.54% and 1.19%; P = 0.46), obstructed labor (2.83% and 2.91%; P = 0.90), any complications during pregnancy or childbirth (35.9% and 37.1%; P = 0.64), episiotomy (6.31% and 6.44%; P = 0.90), or cesarean delivery (15.6% and 14.2%; P = 0.48). Conclusion: Compared with IFA, antenatal LNS-PL did not increase or decrease pregnancy and childbirth complications or cesarean delivery among women in rural Bangladesh. This trial was registered at clinicaltrials.gov as NCT01715038. © 2017 American

  6. Maternal and Child Supplementation with Lipid-Based Nutrient Supplements, but Not Child Supplementation Alone, Decreases Self-Reported Household Food Insecurity in Some Settings.

    Science.gov (United States)

    Adams, Katherine P; Ayifah, Emmanuel; Phiri, Thokozani E; Mridha, Malay K; Adu-Afarwuah, Seth; Arimond, Mary; Arnold, Charles D; Cummins, Joseph; Hussain, Sohrab; Kumwenda, Chiza; Matias, Susana L; Ashorn, Ulla; Lartey, Anna; Maleta, Kenneth M; Vosti, Stephen A; Dewey, Kathryn G

    2017-12-01

    Background: It is unknown whether self-reported measures of household food insecurity change in response to food-based nutrient supplementation. Objective: We assessed the impacts of providing lipid-based nutrient supplements (LNSs) to women during pregnancy and postpartum and/or to their children on self-reported household food insecurity in Malawi [DOSE and DYAD trial in Malawi (DYAD-M)], Ghana [DYAD trial in Ghana (DYAD-G)], and Bangladesh [Rang-Din Nutrition Study (RDNS) trial]. Methods: Longitudinal household food-insecurity data were collected during 3 individually randomized trials and 1 cluster-randomized trial testing the efficacy or effectiveness of LNSs (generally 118 kcal/d). Seasonally adjusted Household Food Insecurity Access Scale (HFIAS) scores were constructed for 1127 DOSE households, 732 DYAD-M households, 1109 DYAD-G households, and 3671 RDNS households. The impact of providing LNSs to women during pregnancy and the first 6 mo postpartum and/or to their children from 6 to 18-24 mo on seasonally adjusted HFIAS scores was assessed by using negative binomial models (DOSE, DYAD-M, and DYAD-G trials) and mixed-effect negative binomial models (RDNS trial). Results: In the DOSE and DYAD-G trials, seasonally adjusted HFIAS scores were not different between the LNS and non-LNS groups. In the DYAD-M trial, the average household food-insecurity scores were 14% lower ( P = 0.01) in LNS households than in non-LNS households. In the RDNS trial, compared with non-LNS households, food-insecurity scores were 17% lower ( P = 0.02) during pregnancy and the first 6 mo postpartum and 15% lower ( P = 0.02) at 6-24 mo postpartum in LNS households. Conclusions: The daily provision of LNSs to mothers and their children throughout much of the "first 1000 d" may improve household food security in some settings, which could be viewed as an additional benefit that may accrue in households should policy makers choose to invest in LNSs to promote child growth and development

  7. Thiamin and Riboflavin in Human Milk: Effects of Lipid-Based Nutrient Supplementation and Stage of Lactation on Vitamer Secretion and Contributions to Total Vitamin Content.

    Science.gov (United States)

    Hampel, Daniela; Shahab-Ferdows, Setareh; Adair, Linda S; Bentley, Margaret E; Flax, Valerie L; Jamieson, Denise J; Ellington, Sascha R; Tegha, Gerald; Chasela, Charles S; Kamwendo, Debbie; Allen, Lindsay H

    2016-01-01

    While thiamin and riboflavin in breast milk have been analyzed for over 50 years, less attention has been given to the different forms of each vitamin. Thiamin-monophosphate (TMP) and free thiamin contribute to total thiamin content; flavin adenine-dinucleotide (FAD) and free riboflavin are the main contributors to total riboflavin. We analyzed milk collected at 2 (n = 258) or 6 (n = 104), and 24 weeks (n = 362) from HIV-infected Malawian mothers within the Breastfeeding, Antiretrovirals and Nutrition (BAN) study, randomly assigned at delivery to lipid-based nutrient supplements (LNS) or a control group, to investigate each vitamer's contribution to total milk vitamin content and the effects of supplementation on the different thiamin and riboflavin vitamers at early and later stages of lactation, and obtain insight into the transport and distribution of these vitamers in human milk. Thiamin vitamers were derivatized into thiochrome-esters and analyzed by high-performance liquid-chromatography-fluorescence-detection (HPLC-FLD). Riboflavin and FAD were analyzed by ultra-performance liquid-chromatography-tandem-mass-spectrometry (ULPC-MS/MS). Thiamin-pyrophosphate (TPP), identified here for the first time in breast milk, contributed 1.9-4.5% to total thiamin. Free thiamin increased significantly from 2/6 to 24 weeks regardless of treatment indicating an active transport of this vitamer in milk. LNS significantly increased TMP and free thiamin only at 2 weeks compared to the control: median 170 versus 151 μg/L (TMP), 13.3 versus 10.5 μg/L (free thiamin, priboflavin was consistently and significantly increased with LNS (range: 14.8-19.6 μg/L (LNS) versus 5.0-7.4 μg/L (control), priboflavin relative amounts from 92-94:6-8% to 85:15%, indicating a preferred secretion of the free form into breast milk. The continuous presence of FAD in breast milk suggests an active transport and secretion system for this vitamer or possibly formation of this co-enymatic form in the

  8. Validation of ethnopharmacology of ayurvedic sarasvata ghrita and comparative evaluation of its neuroprotective effect with modern alcoholic and lipid based extracts in β-amyloid induced memory impairment.

    Science.gov (United States)

    Shelar, Madhuri; Nanaware, Sadhana; Arulmozhi, S; Lohidasan, Sathiyanarayanan; Mahadik, Kakasaheb

    2018-06-12

    Sarasvata ghrita (SG), a polyherbal formulation from ayurveda, an ancient medicinal system of India, has been used to improve intelligence and memory, treat speech delay, speaking difficulties and low digestion power in children. Study aimed to validate the ethno use of SG in memory enhancement through systematic scientific protocol. The effect of SG and modern extracts of ingredients of SG was compared on cognitive function and neuroprotection in amyloid-β peptide 25-35(Aβ25-35) induced memory impairment in wistar rats. Further the underlying mechanism for neuroprotective activity was investigated. SG was prepared as per traditional method, ethanolic extract (EE) was prepared by conventional method and lipid based extract was prepared by modern extraction method. All extracts were standardised by newly developed HPLC method with respect to marker compounds. SG, EE and LE were administered orally to male Wistar rats at doses of 100,200 and 400 mg/kg Body Weight by feeding needle for a period of 21 days after the intracerebroventricular administration of Aβ25-35 bilaterally. Spatial memory of rats was tested using Morris water maze (MWM) and Radial arm maze (RAM) test. The possible underlying mechanisms for the cognitive improvement exhibited by SG, EE and LE was investigated through ex-vivo brain antioxidant effect, monoamine level estimation, acetylcholine esterase (AchE) inhibitory effect and Brain-derived neurotropic factor (BDNF) levels estimation. SG, EE and LE were analyzed by HPLC method, results showed that EE extract has high percent of selected phytoconstituents as compared with SG and LE. SG and LE decrease escape latency and searching distance in a dose dependant manner during MWM test. In case of RAM significant decrease in number of errors and increase in number of correct choices indicate an elevation in retention and recall aspects of learning and memory after administration of SG an LE. SG and LE extract can efficiently prevent accumulation of

  9. Preparation, characterization, and efficient transfection of cationic liposomes and nanomagnetic cationic liposomes

    Directory of Open Access Journals (Sweden)

    Samadikhah HR

    2011-10-01

    Full Text Available Hamid Reza Samadikhah1,*, Asia Majidi2,*, Maryam Nikkhah2, Saman Hosseinkhani11Department of Biochemistry, 2Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran *These authors contributed equally to this work Purpose: Cationic liposomes (CLs are composed of phospholipid bilayers. One of the most important applications of these particles is in drug and gene delivery. However, using CLs to deliver therapeutic nucleic acids and drugs to target organs has some problems, including low transfection efficiency in vivo. The aim of this study was to develop novel CLs containing magnetite to overcome the deficiencies. Patients and methods: CLs and magnetic cationic liposomes (MCLs were prepared using the freeze-dried empty liposome method. Luciferase-harboring vectors (pGL3 were transferred into liposomes and the transfection efficiencies were determined by luciferase assay. Firefly luciferase is one of most popular reporter genes often used to measure the efficiency of gene transfer in vivo and in vitro. Different formulations of liposomes have been used for delivery of different kinds of gene reporters. Lipoplex (liposome–plasmid DNA complexes formation was monitored by gel retardation assay. Size and charge of lipoplexes were determined using particle size analysis. Chinese hamster ovary cells were transfected by lipoplexes (liposome-pGL3; transfection efficiency and gene expression level was evaluated by luciferase assay. Results: High transfection efficiency of plasmid by CLs and novel nanomagnetic CLs was achieved. Moreover, lipoplexes showed less cytotoxicity than polyethyleneimine and Lipofectamine™. Conclusion: Novel liposome compositions (1,2-dipalmitoyl-sn-glycero-3-phosphocholine [DPPC]/dioctadecyldimethylammonium bromide [DOAB] and DPPC/cholesterol/DOAB with high transfection efficiency can be useful in gene delivery in vitro. MCLs can also be used for targeted gene delivery, due to

  10. Evaluation of phenomena affecting diffusion of cations in compacted bentonite

    International Nuclear Information System (INIS)

    Muurinen, A.; Lehikoinen, J.

    1995-04-01

    In a number of diffusion studies, contradictions between the apparent diffusivities of cations and their distribution coefficients in bentonite have been found. Two principal reasons have been offered as explanations for this discrepancy; diffusion of the sorbed cations, often called surface diffusion, and the decrease of sorption in compacted clay compared to a sorption value obtained from a batch experiment. In the study the information available from the literature on sorption-diffusion mechanisms of cations in bentonite has been compiled and re-interpreted in order to improve the understanding of the diffusion process. (103 refs., 23 figs., 8 tabs.)

  11. Microscopic theory of cation exchange in CdSe nanocrystals.

    Science.gov (United States)

    Ott, Florian D; Spiegel, Leo L; Norris, David J; Erwin, Steven C

    2014-10-10

    Although poorly understood, cation-exchange reactions are increasingly used to dope or transform colloidal semiconductor nanocrystals (quantum dots). We use density-functional theory and kinetic Monte Carlo simulations to develop a microscopic theory that explains structural, optical, and electronic changes observed experimentally in Ag-cation-exchanged CdSe nanocrystals. We find that Coulomb interactions, both between ionized impurities and with the polarized nanocrystal surface, play a key role in cation exchange. Our theory also resolves several experimental puzzles related to photoluminescence and electrical behavior in CdSe nanocrystals doped with Ag.

  12. Alkali Metal Cation versus Proton and Methyl Cation Affinities: Structure and Bonding Mechanism

    OpenAIRE

    Boughlala, Z.; Guerra, C.F.; Bickelhaupt, F.M.

    2016-01-01

    Abstract We have analyzed the structure and bonding of gas?phase Cl?X and [HCl?X]+ complexes for X+=?H+, CH3 +, Li+, and Na+, using relativistic density functional theory (DFT). We wish to establish a quantitative trend in affinities of the anionic and neutral Lewis bases Cl? and HCl for the various cations. The Cl?X bond becomes longer and weaker along X+?=?H+, CH3 +, Li+, and Na+. Our main purpose is to understand the heterolytic bonding mechanism behind the intrinsic (i.e., in the absence ...

  13. Semi-Supervised Transductive Hot Spot Predictor Working on Multiple Assumptions

    KAUST Repository

    Wang, Jim Jing-Yan

    2014-05-23

    Protein-protein interactions are critically dependent on just a few residues (“hot spots”) at the interfaces. Hot spots make a dominant contribution to the binding free energy and if mutated they can disrupt the interaction. As mutagenesis studies require significant experimental efforts, there exists a need for accurate and reliable computational hot spot prediction methods. Compared to the supervised hot spot prediction algorithms, the semi-supervised prediction methods can take into consideration both the labeled and unlabeled residues in the dataset during the prediction procedure. The transductive support vector machine has been utilized for this task and demonstrated a better prediction performance. To the best of our knowledge, however, none of the transductive semi-supervised algorithms takes all the three semisupervised assumptions, i.e., smoothness, cluster and manifold assumptions, together into account during learning. In this paper, we propose a novel semi-supervised method for hot spot residue prediction, by considering all the three semisupervised assumptions using nonlinear models. Our algorithm, IterPropMCS, works in an iterative manner. In each iteration, the algorithm first propagates the labels of the labeled residues to the unlabeled ones, along the shortest path between them on a graph, assuming that they lie on a nonlinear manifold. Then it selects the most confident residues as the labeled ones for the next iteration, according to the cluster and smoothness criteria, which is implemented by a nonlinear density estimator. Experiments on a benchmark dataset, using protein structure-based features, demonstrate that our approach is effective in predicting hot spots and compares favorably to other available methods. The results also show that our method outperforms the state-of-the-art transductive learning methods.

  14. Rice PLASTOCHRON genes regulate leaf maturation downstream of the gibberellin signal transduction pathway.

    Science.gov (United States)

    Mimura, Manaki; Nagato, Yasuo; Itoh, Jun-Ichi

    2012-05-01

    Rice PLASTOCHRON 1 (PLA1) and PLA2 genes regulate leaf maturation and plastochron, and their loss-of-function mutants exhibit small organs and rapid leaf emergence. They encode a cytochrome P450 protein CYP78A11 and an RNA-binding protein, respectively. Their homologs in Arabidopsis and maize are also associated with plant development/organ size. Despite the importance of PLA genes in plant development, their molecular functions remain unknown. Here, we investigated how PLA1 and PLA2 genes are related to phytohormones. We found that gibberellin (GA) is the major phytohormone that promotes PLA1 and PLA2 expression. GA induced PLA1 and PLA2 expression, and conversely the GA-inhibitor uniconazole suppressed PLA1 and PLA2 expression. In pla1-4 and pla2-1 seedlings, expression levels of GA biosynthesis genes and the signal transduction gene were similar to those in wild-type seedlings. GA treatment slightly down-regulated the GA biosynthesis gene GA20ox2 and up-regulated the GA-catabolizing gene GA2ox4, whereas the GA biosynthesis inhibitor uniconazole up-regulated GA20ox2 and down-regulated GA2ox4 both in wild-type and pla mutants, suggesting that the GA feedback mechanism is not impaired in pla1 and pla2. To reveal how GA signal transduction affects the expression of PLA1 and PLA2, PLA expression in GA-signaling mutants was examined. In GA-insensitive mutant, gid1 and less-sensitive mutant, Slr1-d1, PLA1 and PLA2 expression was down-regulated. On the other hand, the expression levels of PLA1 and PLA2 were highly enhanced in a GA-constitutive-active mutant, slr1-1, causing ectopic overexpression. These results indicate that both PLA1 and PLA2 act downstream of the GA signal transduction pathway to regulate leaf development.

  15. Unrestricted Hepatocyte Transduction with Adeno-Associated Virus Serotype 8 Vectors in Mice

    Science.gov (United States)

    Nakai, Hiroyuki; Fuess, Sally; Storm, Theresa A.; Muramatsu, Shin-ichi; Nara, Yuko; Kay, Mark A.

    2005-01-01

    Recombinant adeno-associated virus (rAAV) vectors can mediate long-term stable transduction in various target tissues. However, with rAAV serotype 2 (rAAV2) vectors, liver transduction is confined to only a small portion of hepatocytes even after administration of extremely high vector doses. In order to investigate whether rAAV vectors of other serotypes exhibit similar restricted liver transduction, we performed a dose-response study by injecting mice with β-galactosidase-expressing rAAV1 and rAAV8 vectors via the portal vein. The rAAV1 vector showed a blunted dose-response similar to that of rAAV2 at high doses, while the rAAV8 vector dose-response remained unchanged at any dose and ultimately could transduce all the hepatocytes at a dose of 7.2 × 1012 vector genomes/mouse without toxicity. This indicates that all hepatocytes have the ability to process incoming single-stranded vector genomes into duplex DNA. A single tail vein injection of the rAAV8 vector was as efficient as portal vein injection at any dose. In addition, intravascular administration of the rAAV8 vector at a high dose transduced all the skeletal muscles throughout the body, including the diaphragm, the entire cardiac muscle, and substantial numbers of cells in the pancreas, smooth muscles, and brain. Thus, rAAV8 is a robust vector for gene transfer to the liver and provides a promising research tool for delivering genes to various target organs. In addition, the rAAV8 vector may offer a potential therapeutic agent for various diseases affecting nonhepatic tissues, but great caution is required for vector spillover and tight control of tissue-specific gene expression. PMID:15596817

  16. Transfer functions for protein signal transduction: application to a model of striatal neural plasticity.

    Directory of Open Access Journals (Sweden)

    Gabriele Scheler

    Full Text Available We present a novel formulation for biochemical reaction networks in the context of protein signal transduction. The model consists of input-output transfer functions, which are derived from differential equations, using stable equilibria. We select a set of "source" species, which are interpreted as input signals. Signals are transmitted to all other species in the system (the "target" species with a specific delay and with a specific transmission strength. The delay is computed as the maximal reaction time until a stable equilibrium for the target species is reached, in the context of all other reactions in the system. The transmission strength is the concentration change of the target species. The computed input-output transfer functions can be stored in a matrix, fitted with parameters, and even recalled to build dynamical models on the basis of state changes. By separating the temporal and the magnitudinal domain we can greatly simplify the computational model, circumventing typical problems of complex dynamical systems. The transfer function transformation of biochemical reaction systems can be applied to mass-action kinetic models of signal transduction. The paper shows that this approach yields significant novel insights while remaining a fully testable and executable dynamical model for signal transduction. In particular we can deconstruct the complex system into local transfer functions between individual species. As an example, we examine modularity and signal integration using a published model of striatal neural plasticity. The modularizations that emerge correspond to a known biological distinction between calcium-dependent and cAMP-dependent pathways. Remarkably, we found that overall interconnectedness depends on the magnitude of inputs, with higher connectivity at low input concentrations and significant modularization at moderate to high input concentrations. This general result, which directly follows from the properties of

  17. IGF-1 signaling mediated cell-specific skeletal mechano-transduction.

    Science.gov (United States)

    Tian, Faming; Wang, Yongmei; Bikle, Daniel D

    2018-02-01

    Mechanical loading preserves bone mass and stimulates bone formation, whereas skeletal unloading leads to bone loss. In addition to osteocytes, which are considered the primary sensor of mechanical load, osteoblasts, and bone specific mesenchymal stem cells also are involved. The skeletal response to mechanical signals is a complex process regulated by multiple signaling pathways including that of insulin-like growth factor-1 (IGF-1). Conditional osteocyte deletion of IGF-1 ablates the osteogenic response to mechanical loading. Similarly, osteocyte IGF-1 receptor (IGF-1R) expression is necessary for reloading-induced periosteal bone formation. Transgenic overexpression of IGF-1 in osteoblasts results in enhanced responsiveness to in vivo mechanical loading in mice, a response which is eliminated by osteoblastic conditional disruption of IGF-1 in vivo. Bone marrow derived stem cells (BMSC) from unloaded bone fail to respond to IGF-1 in vitro. IGF-1R is required for the transduction of a mechanical stimulus to downstream effectors, transduction which is lost when the IGF-1R is deleted. Although the molecular mechanisms are not yet fully elucidated, the IGF signaling pathway and its interactions with potentially interlinked signaling cascades involving integrins, the estrogen receptor, and wnt/β-catenin play an important role in regulating adaptive response of cancer bone cells to mechanical stimuli. In this review, we discuss recent advances investigating how IGF-1 and other interlinked molecules and signaling pathways regulate skeletal mechano-transduction involving different bone cells, providing an overview of the IGF-1 signaling mediated cell-specific response to mechanical stimuli. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:576-583, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  18. Converting Hg-1212 to Tl-2212 via Tl-Hg cation exchange in combination with Tl cation intercalation

    International Nuclear Information System (INIS)

    Zhao Hua; Wu, Judy Z

    2007-01-01

    In a cation exchange process developed recently for epitaxy of HgBa 2 CaCu 2 O 6 (Hg-1212) thin films, TlBa 2 CaCu 2 O 7 (Tl-1212) or Tl 2 Ba 2 CaCu 2 O 9 (Tl-2212) precursor films were employed as the precursor matrices and Hg-1212 was obtained by replacing Tl cations on the precursor lattice with Hg cations. The reversibility of the cation exchange dictates directly the underlying mechanism. Following our recent success in demonstrating a complete reversibility within '1212' structure, we show the conversion from Hg-1212 to Tl-2212 can be achieved via two steps: conversion from Hg-1212 to Tl-1212 followed by Tl intercalation to form double Tl-O plans in each unit cell. The demonstrated reversibility of the cation exchange process has confirmed the process is a thermal perturbation of weakly bonded cations on the lattice and the direction of the process is determined by the population ratio between the replacing cations and that to be replaced

  19. Endomembrane Cation Transporters and Membrane Trafficking

    Energy Technology Data Exchange (ETDEWEB)

    Sze, Heven [Univ. of Maryland, College Park, MD (United States). Dept. of Cell Biology & Molecular Genetics

    2017-04-01

    Multicellular, as well as unicellular, organisms have evolved mechanisms to regulate ion and pH homeostasis in response to developmental cues and to a changing environment. The working hypothesis is that the balance of fluxes mediated by diverse transporters at the plasma membrane and in subcellular organelles determines ionic cellular distribution, which is critical for maintenance of membrane potential, pH control, osmolality, transport of nutrients, and protein activity. An emerging theme in plant cell biology is that cells respond and adapt to diverse cues through changes of the dynamic endomembrane system. Yet we know very little about the transporters that might influence the operation of the secretory system in plants. Here we focus on transporters that influence alkali cation and pH homeostasis, mainly in the endomembrane/ secretory system. The endomembrane system of eukaryote cells serves several major functions: i) sort cargo (e.g. enzymes, transporters or receptors) to specific destinations, ii) modulate the protein and lipid composition of membrane domains through remodeling, and iii) determine and alter the properties of the cell wall through synthesis and remodeling. We had uncovered a novel family of predicted cation/H+ exchangers (CHX) and K+ efflux antiporters (KEA) that are prevalent in higher plants, but rare in metazoans. We combined phylogenetic and transcriptomic analyses with molecular genetic, cell biological and biochemical studies, and have published the first reports on functions of plant CHXs and KEAs. CHX studied to date act at the endomembrane system where their actions are distinct from the better-studied NHX (Na/K-H+ exchangers). Arabidopsis thaliana CHX20 in guard cells modulate stomatal opening, and thus is significant for vegetative survival. Other CHXs ensure reproductive success on dry land, as they participate in organizing pollen walls, targeting of pollen tubes to the ovule or promoting

  20. Resting lymphocyte transduction with measles virus glycoprotein pseudotyped lentiviral vectors relies on CD46 and SLAM

    International Nuclear Information System (INIS)

    Zhou Qi; Schneider, Irene C.; Gallet, Manuela; Kneissl, Sabrina; Buchholz, Christian J.

    2011-01-01

    The measles virus (MV) glycoproteins hemagglutinin (H) and fusion (F) were recently shown to mediate transduction of resting lymphocytes by lentiviral vectors. MV vaccine strains use CD46 or signaling lymphocyte activation molecule (SLAM) as receptor for cell entry. A panel of H protein mutants derived from vaccine strain or wild-type MVs that lost or gained CD46 or SLAM receptor usage were investigated for their ability to mediate gene transfer into unstimulated T lymphocytes. The results demonstrate that CD46 is sufficient for efficient vector particle association with unstimulated lymphocytes. For stable gene transfer into these cells, however, both MV receptors were found to be essential.

  1. Phenomenally High Transduction Air/gas Transducers for Practical Non-Contact Ultrasonic Applications

    Science.gov (United States)

    Bhardwaj, Mahesh C.

    2009-03-01

    Based on novel acoustic impedance matching layers and high coupling piezoelectric materials this paper describes exceptionally high air/gas transduction ultrasonic transducers. By providing applications oriented performance of these transducers we also usher in the era of much desired Non-Contact Ultrasound (NCU) testing and analysis of a wide range of materials including early stage formation of materials such as uncured composite prepregs, green ceramics and powder metals, plastics, elastomers, porous, hygroscopic, chemically bonded and other materials. Besides quality control, ultimately NCU offers timely opportunities for cost-effective materials production, energy savings, and environment protection.

  2. Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction

    DEFF Research Database (Denmark)

    Frödin, M; Gammeltoft, S

    1999-01-01

    ), which were among the first substrates of ERK to be discovered and which has proven to be a ubiquitous and versatile mediator of ERK signal transduction. RSK is composed of two functional kinase domains that are activated in a sequential manner by a series of phosphorylations. Recently, a family of RSK......-related kinases that are activated by ERK as well as p38 MAPK were discovered and named mitogen- and stress-activated protein kinases (MSK). A number of cellular functions of RSK have been proposed. (1) Regulation of gene expression via association and phosphorylation of transcriptional regulators including c...

  3. Transductive and matched-pair machine learning for difficult target detection problems

    Science.gov (United States)

    Theiler, James

    2014-06-01

    This paper will describe the application of two non-traditional kinds of machine learning (transductive machine learning and the more recently proposed matched-pair machine learning) to the target detection problem. The approach combines explicit domain knowledge to model the target signal with a more agnostic machine-learning approach to characterize the background. The concept is illustrated with simulated data from an elliptically-contoured background distribution, on which a subpixel target of known spectral signature but unknown spatial extent has been implanted.

  4. Cytoplasmic transduction peptide (CTP): New approach for the delivery of biomolecules into cytoplasm in vitro and in vivo

    International Nuclear Information System (INIS)

    Kim, Daeyou; Jeon, Choonju; Kim, Jeong-Hwan; Kim, Mi-Seon; Yoon, Cheol-Hee; Choi, In-Soo; Kim, Sung-Hoon; Bae, Yong-Soo

    2006-01-01

    The protein transduction domain (PTD) of HIV-1 TAT has been extensively documented with regard to its membrane transduction potential, as well as its efficient delivery of biomolecules in vivo. However, the majority of PTD and PTD-conjugated molecules translocate to the nucleus rather than to the cytoplasm after transduction, due to the functional nuclear localization sequence (NLS). Here, we report a cytoplasmic transduction peptide (CTP), which was deliberately designed to ensure the efficient cytoplasmic delivery of the CTP-fused biomolecules. In comparison with PTD, CTP and its fusion partners exhibited a clear preference for cytoplasmic localization, and also markedly enhanced membrane transduction potential. Unlike the mechanism underlying PTD-mediated transduction, CTP-mediated transduction occurs independently of the lipid raft-dependent macropinocytosis pathway. The CTP-conjugated Smac/DIABLO peptide (Smac-CTP) was also shown to be much more efficient than Smac-PTD in the blockage of the antiapoptotic properties of XIAP, suggesting that cytoplasmic functional molecules can be more efficiently targeted by CTP-mediated delivery. In in vivo trafficking studies, CTP-fused β-gal exhibited unique organ tropisms to the liver and lymph nodes when systemically injected into mice, whereas PTD-β-gal exhibited no such tropisms. Taken together, our findings implicate CTP as a novel delivery peptide appropriate for (i) molecular targeting to cytoplasmic compartments in vitro, (ii) the development of class I-associated CTL vaccines, and (iii) special drug delivery in vivo, without causing any untoward effects on nuclear genetic material

  5. Cation binding to 15-TBA quadruplex DNA is a multiple-pathway cation-dependent process.

    Science.gov (United States)

    Reshetnikov, Roman V; Sponer, Jiri; Rassokhina, Olga I; Kopylov, Alexei M; Tsvetkov, Philipp O; Makarov, Alexander A; Golovin, Andrey V

    2011-12-01

    A combination of explicit solvent molecular dynamics simulation (30 simulations reaching 4 µs in total), hybrid quantum mechanics/molecular mechanics approach and isothermal titration calorimetry was used to investigate the atomistic picture of ion binding to 15-mer thrombin-binding quadruplex DNA (G-DNA) aptamer. Binding of ions to G-DNA is complex multiple pathway process, which is strongly affected by the type of the cation. The individual ion-binding events are substantially modulated by the connecting loops of the aptamer, which play several roles. They stabilize the molecule during time periods when the bound ions are not present, they modulate the route of the ion into the stem and they also stabilize the internal ions by closing the gates through which the ions enter the quadruplex. Using our extensive simulations, we for the first time observed full spontaneous exchange of internal cation between quadruplex molecule and bulk solvent at atomistic resolution. The simulation suggests that expulsion of the internally bound ion is correlated with initial binding of the incoming ion. The incoming ion then readily replaces the bound ion while minimizing any destabilization of the solute molecule during the exchange. © The Author(s) 2011. Published by Oxford University Press.

  6. Cation binding to 15-TBA quadruplex DNA is a multiple-pathway cation-dependent process

    Science.gov (United States)

    Reshetnikov, Roman V.; Sponer, Jiri; Rassokhina, Olga I.; Kopylov, Alexei M.; Tsvetkov, Philipp O.; Makarov, Alexander A.; Golovin, Andrey V.

    2011-01-01

    A combination of explicit solvent molecular dynamics simulation (30 simulations reaching 4 µs in total), hybrid quantum mechanics/molecular mechanics approach and isothermal titration calorimetry was used to investigate the atomistic picture of ion binding to 15-mer thrombin-binding quadruplex DNA (G-DNA) aptamer. Binding of ions to G-DNA is complex multiple pathway process, which is strongly affected by the type of the cation. The individual ion-binding events are substantially modulated by the connecting loops of the aptamer, which play several roles. They stabilize the molecule during time periods when the bound ions are not present, they modulate the route of the ion into the stem and they also stabilize the internal ions by closing the gates through which the ions enter the quadruplex. Using our extensive simulations, we for the first time observed full spontaneous exchange of internal cation between quadruplex molecule and bulk solvent at atomistic resolution. The simulation suggests that expulsion of the internally bound ion is correlated with initial binding of the incoming ion. The incoming ion then readily replaces the bound ion while minimizing any destabilization of the solute molecule during the exchange. PMID:21893589

  7. Use of marker ion and cationic surfactant plastic membrane electrode for potentiometric titration of cationic polyelectrolytes.

    Science.gov (United States)

    Masadome, Takashi; Imato, Toshihiko

    2003-07-04

    A plasticized poly (vinyl chloride) (PVC) membrane electrode sensitive to stearyltrimethylammonium (STA) ion is applied to the determination of cationic polyelectrolytes such as poly (diallyldimethylammonium chloride) (Cat-floc) by potentiometric titration, using a potassium poly (vinyl sulfate) (PVSK) solution as a titrant. The end-point of the titration is detected as the potential change of the plasticized PVC membrane electrode caused by decrease in the concentration of STA ion added to the sample solution as a marker ion due to the ion association reaction between the STA ion and PVSK. The effects of the concentration of STA ion, coexisting electrolytes in the sample solution and pH of the sample on the degree of the potential change at the end-point were examined. A linear relationship between the concentration of cationic polyelectrolyte and the end-point volume of the titrant exists in the concentration range from 2x10(-5) to 4x10(-4) N for Cat-floc, glycol chitosan, and methylglycol chitosan.

  8. Opposing effects of cationic antimicrobial peptides and divalent cations on bacterial lipopolysaccharides

    Science.gov (United States)

    Smart, Matthew; Rajagopal, Aruna; Liu, Wing-Ki; Ha, Bae-Yeun

    2017-10-01

    The permeability of the bacterial outer membrane, enclosing Gram-negative bacteria, depends on the interactions of the outer, lipopolysaccharide (LPS) layer, with surrounding ions and molecules. We present a coarse-grained model for describing how cationic amphiphilic molecules (e.g., antimicrobial peptides) interact with and perturb the LPS layer in a biologically relevant medium, containing monovalent and divalent salt ions (e.g., Mg2+). In our approach, peptide binding is driven by electrostatic and hydrophobic interactions and is assumed to expand the LPS layer, eventually priming it for disruption. Our results suggest that in parameter ranges of biological relevance (e.g., at micromolar concentrations) the antimicrobial peptide magainin 2 effectively disrupts the LPS layer, even though it has to compete with Mg2+ for the layer. They also show how the integrity of LPS is restored with an increasing concentration of Mg2+. Using the approach, we make a number of predictions relevant for optimizing peptide parameters against Gram-negative bacteria and for understanding bacterial strategies to develop resistance against cationic peptides.

  9. Chemical bonding and structural ordering of cations in silicate glasses

    International Nuclear Information System (INIS)

    Calas, G.; Cormier, L.; Galoisy, L.; Ramos, A.; Rossano, St.

    1997-01-01

    The specific surrounding of cations in multicomponent silicate glasses is briefly presented. Information about interatomic distances and site geometry may be gained by using spectroscopic methods among which x-ray absorption spectroscopy may be used for the largest number of glass components. Scattering of x-rays and neutrons may also be used to determine the importance of medium range order around specific cations. All the existing data show that cations occur in sites with a well-defined geometry, which are in most cases connected to the silicate polymeric network. Medium range order has been detected around cations such as Ti, Ca and Ni, indicating that these elements have an heterogeneous distribution within the glassy matrix. (authors)

  10. Dynamics of photoexcited Ba+ cations in 4He nanodroplets

    International Nuclear Information System (INIS)

    2UB, Universitat de Barcelona, Diagonal 645, 08028 Barcelona (Spain))" data-affiliation=" (Departament ECM, Facultat de Física, and IN2UB, Universitat de Barcelona, Diagonal 645, 08028 Barcelona (Spain))" >Leal, Antonio; 2UB, Universitat de Barcelona, Diagonal 645, 08028 Barcelona (Spain))" data-affiliation=" (Departament ECM, Facultat de Física, and IN2UB, Universitat de Barcelona, Diagonal 645, 08028 Barcelona (Spain))" >Pi, Martí; Zhang, Xiaohang; Drabbels, Marcel; 2UB, Universitat de Barcelona, Diagonal 645, 08028 Barcelona (Spain); Laboratoire des Collisions, Agrégats, Réactivité, IRSAMC, UMR 5589, CNRS et Université Paul Sabatier-Toulouse 3, 118 route de Narbonne, F-31062 Toulouse Cedex 09 (France))" data-affiliation=" (Departament ECM, Facultat de Física, and IN2UB, Universitat de Barcelona, Diagonal 645, 08028 Barcelona (Spain); Laboratoire des Collisions, Agrégats, Réactivité, IRSAMC, UMR 5589, CNRS et Université Paul Sabatier-Toulouse 3, 118 route de Narbonne, F-31062 Toulouse Cedex 09 (France))" >Barranco, Manuel; Cargnoni, Fausto; Hernando, Alberto; Mateo, David; Mella, Massimo

    2016-01-01

    We present a joint experimental and theoretical study on the desolvation of Ba + cations in 4 He nanodroplets excited via the 6p ← 6s transition. The experiments reveal an efficient desolvation process yielding mainly bare Ba + cations and Ba + He n exciplexes with n = 1 and 2. The speed distributions of the ions are well described by Maxwell-Boltzmann distributions with temperatures ranging from 60 to 178 K depending on the excitation frequency and Ba + He n exciplex size. These results have been analyzed by calculations based on a time-dependent density functional description for the helium droplet combined with classical dynamics for the Ba + . In agreement with experiment, the calculations reveal the dynamical formation of exciplexes following excitation of the Ba + cation. In contrast to experimental observation, the calculations do not reveal desolvation of excited Ba + cations or exciplexes, even when relaxation pathways to lower lying states are included.

  11. Aggregation of trypsin and trypsin inhibitor by Al cation.

    Science.gov (United States)

    Chanphai, P; Kreplak, L; Tajmir-Riahi, H A

    2017-04-01

    Al cation may trigger protein structural changes such as aggregation and fibrillation, causing neurodegenerative diseases. We report the effect of Al cation on the solution structures of trypsin (try) and trypsin inhibitor (tryi), using thermodynamic analysis, UV-Visible, Fourier transform infrared (FTIR) spectroscopic methods and atomic force microscopy (AFM). Thermodynamic parameters showed Al-protein bindings occur via H-bonding and van der Waals contacts for trypsin and trypsin inhibitor. AFM showed that Al cations are able to force trypsin into larger or more robust aggregates than trypsin inhibitor, with trypsin 5±1 SE (n=52) proteins per aggregate and for trypsin inhibitor 8.3±0.7 SE (n=118). Thioflavin T test showed no major protein fibrillation in the presence of Al cation. Al complexation induced more alterations of trypsin inhibitor conformation than trypsin. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Significant role of cationic polymers in drug delivery systems.

    Science.gov (United States)

    Farshbaf, Masoud; Davaran, Soodabeh; Zarebkohan, Amir; Annabi, Nasim; Akbarzadeh, Abolfazl; Salehi, Roya

    2017-11-06

    Cationic polymers are characterized as the macromolecules that possess positive charges, which can be either inherently in the polymer side chains and/or its backbone. Based on their origins, cationic polymers are divided in two category including natural and synthetic, in which the possessed positive charges are as result of primary, secondary or tertiary amine functional groups that could be protonated in particular situations. Cationic polymers have been employed commonly as drug delivery agents due to their superior encapsulation efficacy, enhanced bioavailability, low toxicity and improved release profile. In this paper, we focus on the most prominent examples of cationic polymers which have been revealed to be applicable in drug delivery systems and we also discuss their general synthesis and surface modification methods as well as their controlled release profile in drug delivery.

  13. Changing certain dietary cationic and anionic minerals: Impact on ...

    African Journals Online (AJOL)

    Changing certain dietary cationic and anionic minerals: Impact on blood chemistry, milk ... Increased blood pH and serum HCO3 were noticed in buffaloes fed with LC ... Serum calcium and chloride increased with decreased DCAD level while ...

  14. Mercury release from deforested soils triggered by base cation enrichment

    International Nuclear Information System (INIS)

    Farella, N.; Lucotte, M.; Davidson, R.; Daigle, S.

    2006-01-01

    The Brazilian Amazon has experienced considerable colonization in the last few decades. Family agriculture based on slash-and-burn enables millions of people to live in that region. However, the poor nutrient content of most Amazonian soils requires cation-rich ashes from the burning of the vegetation biomass for cultivation to be successful, which leads to forest ecosystem degradation, soil erosion and mercury contamination. While recent studies have suggested that mercury present in soils was transferred towards rivers upon deforestation, little is known about the dynamics between agricultural land-use and mercury leaching. In this context, the present study proposes an explanation that illustrates how agricultural land-use triggers mercury loss from soils. This explanation lies in the competition between base cations and mercury in soils which are characterized by a low adsorption capacity. Since these soils are naturally very poor in base cations, the burning of the forest biomass suddenly brings high quantities of base cations to soils, destabilizing the previous equilibrium amongst cations. Base cation enrichment triggers mobility in soil cations, rapidly dislocating mercury atoms. This conclusion comes from principal component analyses illustrating that agricultural land-use was associated with base cation enrichment and mercury depletion. The overall conclusions highlight a pernicious cycle: while soil nutrient enrichment actually occurs through biomass burning, although on a temporary basis, there is a loss in Hg content, which is leached to rivers, entering the aquatic chain, and posing a potential health threat to local populations. Data presented here reflects three decades of deforestation activities, but little is known about the long-term impact of such a disequilibrium. These findings may have repercussions on our understanding of the complex dynamics of deforestation and agriculture worldwide

  15. Isomerizations of the Nitromethane Radical Cation in the Gas Phase

    DEFF Research Database (Denmark)

    Egsgaard, Helge; Carlsen, Lars; Elbel, Susanne

    1986-01-01

    The concurrent isomerizations of the nitromethane radical cation to its aci-nitromethane and methylnitrite isomers, respectively, has been established based on metastable ion studies and collision activation mass spectrometry. The energy diagram for the ionized nitromethane/aci-nitromethane tauto......The concurrent isomerizations of the nitromethane radical cation to its aci-nitromethane and methylnitrite isomers, respectively, has been established based on metastable ion studies and collision activation mass spectrometry. The energy diagram for the ionized nitromethane...

  16. Tunable states of interlayer cations in two-dimensional materials

    International Nuclear Information System (INIS)

    Sato, K.; Numata, K.; Dai, W.; Hunger, M.

    2014-01-01

    The local state of cations inside the Ångstrom-scale interlayer spaces is one of the controlling factors for designing sophisticated two-dimensional (2D) materials consisting of 2D nanosheets. In the present work, the molecular mechanism on how the interlayer cation states are induced by the local structures of the 2D nanosheets is highlighted. For this purpose, the local states of Na cations in inorganic 2D materials, in which the compositional fluctuations of a few percent are introduced in the tetrahedral and octahedral units of the 2D nanosheets, were systematically studied by means of 23 Na magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) and 23 Na multiple-quantum MAS (MQMAS) NMR spectroscopy. In contrast with an uniform distribution of Na cations expected so far, various well-defined cation states sensitive to the local structures of the 2D nanosheets were identified. The tunability of the interlayer cation states along with the local structure of the 2D nanosheets, as the smallest structural unit of the 2D material, is discussed

  17. Tunable states of interlayer cations in two-dimensional materials

    Energy Technology Data Exchange (ETDEWEB)

    Sato, K.; Numata, K. [Department of Environmental Sciences, Tokyo Gakugei University, Koganei, Tokyo 184-8501 (Japan); Dai, W. [Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), College of Chemistry, Nankai University, Tianjin 300071 (China); Hunger, M. [Institute of Chemical Technology, University of Stuttgart, 70550 Stuttgart (Germany)

    2014-03-31

    The local state of cations inside the Ångstrom-scale interlayer spaces is one of the controlling factors for designing sophisticated two-dimensional (2D) materials consisting of 2D nanosheets. In the present work, the molecular mechanism on how the interlayer cation states are induced by the local structures of the 2D nanosheets is highlighted. For this purpose, the local states of Na cations in inorganic 2D materials, in which the compositional fluctuations of a few percent are introduced in the tetrahedral and octahedral units of the 2D nanosheets, were systematically studied by means of {sup 23}Na magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) and {sup 23}Na multiple-quantum MAS (MQMAS) NMR spectroscopy. In contrast with an uniform distribution of Na cations expected so far, various well-defined cation states sensitive to the local structures of the 2D nanosheets were identified. The tunability of the interlayer cation states along with the local structure of the 2D nanosheets, as the smallest structural unit of the 2D material, is discussed.

  18. Separation of cations of heavy metalsfrom concentrated galvanic drains

    Directory of Open Access Journals (Sweden)

    L. P. Bondareva

    2018-01-01

    Full Text Available When applying galvanic coatings, soluble salts of heavy metals such as iron, copper, nickel, zinc, cadmium, chromium and other metals are used, toxic cations enter the water, with subsequent migration to the biosphere. To date, many methods have been developed for cleaning galvanic sewage, which cannot be considered sufficiently effective. The joint sorption of divalent cations of copper, nickel and cadmium from concentrated aqueous solutions was investigated. Calculation and experimental methods were used to determine the separation conditions of the bivalent ion systems that differed and close in sorption properties on the aminophosphonic polyampholyte Purolite S950 in a natrium form. It is shown that the cadmium (II cations can be isolated from solutions containing copper (II or nickel (II cations even at the height of the sorption layer of 0.13 m due to the difference in the defining characteristics of the cations. This layer height can be used not only in a chromatographic column, but also in a concentrating cartridge. Separation of the copper (II and nickel (II close to the sorption properties requires an absorbing layer of 0.76 m, which can only be used in a chromatographic column, but not for a concentrating cartridge. In this paper, the degrees of ion separation in various sorption conditions are calculated. The applicability of the conductometric method for controlling the ion exchange process is shown not only when the free cations are isolated from aqueous solutions but also bound to complexes.

  19. Two-Component Signal Transduction System SaeRS Positively Regulates Staphylococcus epidermidis Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Qiang Lou

    2014-01-01

    Full Text Available Staphylococcus epidermidis, which is a causative pathogen of nosocomial infection, expresses its virulent traits such as biofilm and autolysis regulated by two-component signal transduction system SaeRS. In this study, we performed a proteomic analysis of differences in expression between the S. epidermidis 1457 wild-type and saeRS mutant to identify candidates regulated by saeRS using two-dimensional gel electrophoresis (2-DE combined with matrix-assisted laser desorption/lonization mass spectrometry (MALDI-TOF-MS. Of 55 identified proteins that significantly differed in expression between the two strains, 15 were upregulated and 40 were downregulated. The downregulated proteins included enzymes related to glycolysis and TCA cycle, suggesting that glucose is not properly utilized in S. epidermidis when saeRS was deleted. The study will be helpful for treatment of S. epidermidis infection from the viewpoint of metabolic modulation dependent on two-component signal transduction system SaeRS.

  20. Gibberellin biosynthesis and signal transduction is essential for internode elongation in deepwater rice.

    Science.gov (United States)

    Ayano, Madoka; Kani, Takahiro; Kojima, Mikiko; Sakakibara, Hitoshi; Kitaoka, Takuya; Kuroha, Takeshi; Angeles-Shim, Rosalyn B; Kitano, Hidemi; Nagai, Keisuke; Ashikari, Motoyuki

    2014-10-01

    Under flooded conditions, the leaves and internodes of deepwater rice can elongate above the water surface to capture oxygen and prevent drowning. Our previous studies showed that three major quantitative trait loci (QTL) regulate deepwater-dependent internode elongation in deepwater rice. In this study, we investigated the age-dependent internode elongation in deepwater rice. We also investigated the relationship between deepwater-dependent internode elongation and the phytohormone gibberellin (GA) by physiological and genetic approach using a QTL pyramiding line (NIL-1 + 3 + 12). Deepwater rice did not show internode elongation before the sixth leaf stage under deepwater condition. Additionally, deepwater-dependent internode elongation occurred on the sixth and seventh internodes during the sixth leaf stage. These results indicate that deepwater rice could not start internode elongation until the sixth leaf stage. Ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS) method for the phytohormone contents showed a deepwater-dependent GA1 and GA4 accumulation in deepwater rice. Additionally, a GA inhibitor abolished deepwater-dependent internode elongation in deepwater rice. On the contrary, GA feeding mimicked internode elongation under ordinary growth conditions. However, mutations in GA biosynthesis and signal transduction genes blocked deepwater-dependent internode elongation. These data suggested that GA biosynthesis and signal transduction are essential for deepwater-dependent internode elongation in deepwater rice. © 2014 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.

  1. Analysis of signal transduction in cell-free extracts and rafts of Xenopus eggs.

    Science.gov (United States)

    Tokmakov, Alexander A; Iwasaki, Tetsushi; Sato, Ken-Ichi; Fukami, Yasuo

    2010-05-01

    Intracellular signaling during egg activation/fertilization has been extensively studied using intact eggs, which can be manipulated by microinjection of different mRNAs, proteins, or chemical drugs. Furthermore, egg extracts, which retain high CSF activity (CSF-arrested extracts), were developed for studying fertilization/activation signal transduction, which have significant advantages as a model system. The addition of calcium to CSF-arrested extracts initiates a plethora of signaling events that take place during egg activation. Hence, the signaling downstream of calcium mobilization has been successfully studied in the egg extracts. Moreover, despite disruption of membrane-associated signaling compartments and ordered compartmentalization during extract preparation, CSF-arrested extracts can be successfully used to study early signaling events, which occur upstream of calcium release during egg activation/fertilization. In combination with the CSF-arrested extracts, activated egg rafts can reproduce some events of egg activation, including PLCgamma activation, IP3 production, transient calcium release, MAPK inactivation, and meiotic exit. This becomes possible due to complementation of the sperm-induced egg activation signaling machinery present in the rafts with the components of signal transduction system localized in the extracts. Herein, we describe protocols for studying molecular mechanisms of egg fertilization/activation using cell-free extracts and membrane rafts prepared from metaphase-arrested Xenopus eggs.

  2. Effect of saw palmetto extract on PI3K cell signaling transduction in human glioma.

    Science.gov (United States)

    Yang, Yang; Hui, Lv; Yuqin, Che; Jie, Li; Shuai, Hou; Tiezhu, Zhou; Wei, Wang

    2014-08-01

    Saw palmetto extract can induce the apoptosis of prostate cancer cells. The aim of the present study was to investigate the effect of saw palmetto extract on the phosphatidylinositol 3-kinase (PI3K)/Akt signaling transduction pathway in human glioma U87 and U251 cell lines. Suspensions of U87 and U251 cells in a logarithmic growth phase were seeded into six-well plates at a density of 10 4 cells/well. In the experimental group, 1 μl/ml saw palmetto extract was added, while the control group was cultured without a drug for 24 h. The expression levels of PI3K, B-cell lymphoma-extra large (Bcl-xL) and p53 were evaluated through western blot analysis. In the experimental group, the U87 and U251 cells exhibited a lower expression level of PI3K protein as compared with the control group (t=6.849; Psaw palmetto extract induces glioma cell growth arrest and apoptosis via decreasing PI3K/Akt signal transduction.

  3. A functional TOC complex contributes to gravity signal transduction in Arabidopsis.

    Science.gov (United States)

    Strohm, Allison K; Barrett-Wilt, Greg A; Masson, Patrick H

    2014-01-01

    Although plastid sedimentation has long been recognized as important for a plant's perception of gravity, it was recently shown that plastids play an additional function in gravitropism. The Translocon at the Outer envelope membrane of Chloroplasts (TOC) complex transports nuclear-encoded proteins into plastids, and a receptor of this complex, Toc132, was previously hypothesized to contribute to gravitropism either by directly functioning as a gravity signal transducer or by indirectly mediating the plastid localization of a gravity signal transducer. Here we show that mutations in multiple genes encoding TOC complex components affect gravitropism in a genetically sensitized background and that the cytoplasmic acidic domain of Toc132 is not required for its involvement in this process. Furthermore, mutations in TOC132 enhance the gravitropic defect of a mutant whose amyloplasts lack starch. Finally, we show that the levels of several nuclear-encoded root proteins are altered in toc132 mutants. These data suggest that the TOC complex indirectly mediates gravity signal transduction in Arabidopsis and support the idea that plastids are involved in gravitropism not only through their ability to sediment but also as part of the signal transduction mechanism.

  4. Ubiquitination of basal VEGFR2 regulates signal transduction and endothelial function

    Directory of Open Access Journals (Sweden)

    Gina A. Smith

    2017-10-01

    Full Text Available Cell surface receptors can undergo recycling or proteolysis but the cellular decision-making events that sort between these pathways remain poorly defined. Vascular endothelial growth factor A (VEGF-A and vascular endothelial growth factor receptor 2 (VEGFR2 regulate signal transduction and angiogenesis, but how signaling and proteolysis is regulated is not well understood. Here, we provide evidence that a pathway requiring the E1 ubiquitin-activating enzyme UBA1 controls basal VEGFR2 levels, hence metering plasma membrane receptor availability for the VEGF-A-regulated endothelial cell response. VEGFR2 undergoes VEGF-A-independent constitutive degradation via a UBA1-dependent ubiquitin-linked pathway. Depletion of UBA1 increased VEGFR2 recycling from endosome-to-plasma membrane and decreased proteolysis. Increased membrane receptor availability after UBA1 depletion elevated VEGF-A-stimulated activation of key signaling enzymes such as PLCγ1 and ERK1/2. Although UBA1 depletion caused an overall decrease in endothelial cell proliferation, surviving cells showed greater VEGF-A-stimulated responses such as cell migration and tubulogenesis. Our study now suggests that a ubiquitin-linked pathway regulates the balance between receptor recycling and degradation which in turn impacts on the intensity and duration of VEGF-A-stimulated signal transduction and the endothelial response.

  5. Subsumed complexity: abiogenesis as a by-product of complex energy transduction

    Science.gov (United States)

    Adam, Z. R.; Zubarev, D.; Aono, M.; Cleaves, H. James

    2017-11-01

    The origins of life bring into stark relief the inadequacy of our current synthesis of thermodynamic, chemical, physical and information theory to predict the conditions under which complex, living states of organic matter can arise. Origins research has traditionally proceeded under an array of implicit or explicit guiding principles in lieu of a universal formalism for abiogenesis. Within the framework of a new guiding principle for prebiotic chemistry called subsumed complexity, organic compounds are viewed as by-products of energy transduction phenomena at different scales (subatomic, atomic, molecular and polymeric) that retain energy in the form of bonds that inhibit energy from reaching the ground state. There is evidence for an emergent level of complexity that is overlooked in most conceptualizations of abiogenesis that arises from populations of compounds formed from atomic energy input. We posit that different forms of energy input can exhibit different degrees of dissipation complexity within an identical chemical medium. By extension, the maximum capacity for organic chemical complexification across molecular and macromolecular scales subsumes, rather than emerges from, the underlying complexity of energy transduction processes that drive their production and modification. This article is part of the themed issue 'Reconceptualizing the origins of life'.

  6. New insights into the organization of plasma membrane and its role in signal transduction.

    Science.gov (United States)

    Suzuki, Kenichi G N

    2015-01-01

    Plasma membranes have heterogeneous structures for efficient signal transduction, required to perform cell functions. Recent evidence indicates that the heterogeneous structures are produced by (1) compartmentalization by actin-based membrane skeleton, (2) raft domains, (3) receptor-receptor interactions, and (4) the binding of receptors to cytoskeletal proteins. This chapter provides an overview of recent studies on diffusion, clustering, raft association, actin binding, and signal transduction of membrane receptors, especially glycosylphosphatidylinositol (GPI)-anchored receptors. Studies on diffusion of GPI-anchored receptors suggest that rafts may be small and/or short-lived in plasma membranes. In steady state conditions, GPI-anchored receptors form transient homodimers, which may represent the "standby state" for the stable homodimers and oligomers upon ligation. Furthermore, It is proposed that upon ligation, the binding of GPI-anchored receptor clusters to cytoskeletal actin filaments produces a platform for downstream signaling, and that the pulse-like signaling easily maintains the stability of the overall signaling activity. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Evidence for some signal transduction elements involved in UV-light-dependent responses in parsley protoplasts

    International Nuclear Information System (INIS)

    Frohnmeyer, H.; Bowler, C.; Schäfer, E.

    1997-01-01

    The signalling pathways used by UV-light are largely unknown. Using protoplasts from a heterotrophic parsley (Petroselinum crispum L.) cell culture that exclusively respond to UV-B light between 300 and 350 nm with a fast induction of genes encoding flavonoid biosynthetic enzymes, information was obtained about the UV-light signal transduction pathway for chalcone synthase (CHS) and phenylalanine ammonia-lyase (PAL) gene expression. Pharmacological effectors which influence intracellular calcium levels, calmodulin and the activity of serine/threonine kinases also changed the UV-light-dependent expression of these genes. This evaluation indicated the participation of these components on the UV-B-mediated signal transduction cascade to CHS. In contrast, neither membrane-permeable cyclic GMP nor the tyrosine kinase inhibitor genistein affected CHS or PAL expression. Similar results were obtained in protoplasts, which have been transiently transformed with CHS-promoter/GUS (β-glucuronidase) reporter fusion constructs. The involvement of calcium and calmodulin was further indicated in a cell-free light-responsive in vitro transcription system from evacuolated parsley protoplasts. In conclusion, there is evidence now that components of the UV-light-dependent pathway leading to the CHS-promoter are different from the previously characterized cGMP-dependent pathway to CHS utilized by phytochrome in soybean (Glycine max) and tomato seedlings (Lycopersicon esculentum). (author)

  8. Ubiquitination of basal VEGFR2 regulates signal transduction and endothelial function.

    Science.gov (United States)

    Smith, Gina A; Fearnley, Gareth W; Abdul-Zani, Izma; Wheatcroft, Stephen B; Tomlinson, Darren C; Harrison, Michael A; Ponnambalam, Sreenivasan

    2017-10-15

    Cell surface receptors can undergo recycling or proteolysis but the cellular decision-making events that sort between these pathways remain poorly defined. Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) regulate signal transduction and angiogenesis, but how signaling and proteolysis is regulated is not well understood. Here, we provide evidence that a pathway requiring the E1 ubiquitin-activating enzyme UBA1 controls basal VEGFR2 levels, hence metering plasma membrane receptor availability for the VEGF-A-regulated endothelial cell response. VEGFR2 undergoes VEGF-A-independent constitutive degradation via a UBA1-dependent ubiquitin-linked pathway. Depletion of UBA1 increased VEGFR2 recycling from endosome-to-plasma membrane and decreased proteolysis. Increased membrane receptor availability after UBA1 depletion elevated VEGF-A-stimulated activation of key signaling enzymes such as PLCγ1 and ERK1/2. Although UBA1 depletion caused an overall decrease in endothelial cell proliferation, surviving cells showed greater VEGF-A-stimulated responses such as cell migration and tubulogenesis. Our study now suggests that a ubiquitin-linked pathway regulates the balance between receptor recycling and degradation which in turn impacts on the intensity and duration of VEGF-A-stimulated signal transduction and the endothelial response. © 2017. Published by The Company of Biologists Ltd.

  9. Rab11-FIP3 Regulation of Lck Endosomal Traffic Controls TCR Signal Transduction.

    Science.gov (United States)

    Bouchet, Jérôme; Del Río-Iñiguez, Iratxe; Vázquez-Chávez, Elena; Lasserre, Rémi; Agüera-González, Sonia; Cuche, Céline; McCaffrey, Mary W; Di Bartolo, Vincenzo; Alcover, Andrés

    2017-04-01

    The role of endosomes in receptor signal transduction is a long-standing question, which remains largely unanswered. The T cell Ag receptor and various components of its proximal signaling machinery are associated with distinct endosomal compartments, but how endosomal traffic affects T cell signaling remains ill-defined. In this article, we demonstrate in human T cells that the subcellular localization and function of the protein tyrosine kinase Lck depends on the Rab11 effector FIP3 (Rab11 family interacting protein-3). FIP3 overexpression or silencing and its ability to interact with Rab11 modify Lck subcellular localization and its delivery to the immunological synapse. Importantly, FIP3-dependent Lck localization controls early TCR signaling events, such as tyrosine phosphorylation of TCRζ, ZAP70, and LAT and intracellular calcium concentration, as well as IL-2 gene expression. Interestingly, FIP3 controls both steady-state and poststimulation phosphotyrosine and calcium levels. Finally, our findings indicate that FIP3 modulates TCR-CD3 cell surface expression via the regulation of steady-state Lck-mediated TCRζ phosphorylation, which in turn controls TCRζ protein levels. This may influence long-term T cell activation in response to TCR-CD3 stimulation. Therefore, our data underscore the importance of finely regulated endosomal traffic in TCR signal transduction and T cell activation leading to IL-2 production. Copyright © 2017 by The American Association of Immunologists, Inc.

  10. Signal transduction meets vesicle traffic: the software and hardware of GLUT4 translocation.

    Science.gov (United States)

    Klip, Amira; Sun, Yi; Chiu, Tim Ting; Foley, Kevin P

    2014-05-15

    Skeletal muscle is the major tissue disposing of dietary glucose, a function regulated by insulin-elicited signals that impart mobilization of GLUT4 glucose transporters to the plasma membrane. This phenomenon, also central to adipocyte biology, has been the subject of intense and productive research for decades. We focus on muscle cell studies scrutinizing insulin signals and vesicle traffic in a spatiotemporal manner. Using the analogy of an integrated circuit to approach the intersection between signal transduction and vesicle mobilization, we identify signaling relays ("software") that engage structural/mechanical elements ("hardware") to enact the rapid mobilization and incorporation of GLUT4 into the cell surface. We emphasize how insulin signal transduction switches from tyrosine through lipid and serine phosphorylation down to activation of small G proteins of the Rab and Rho families, describe key negative regulation step of Rab GTPases through the GTPase-activating protein activity of the Akt substrate of 160 kDa (AS160), and focus on the mechanical effectors engaged by Rabs 8A and 10 (the molecular motor myosin Va), and the Rho GTPase Rac1 (actin filament branching and severing through Arp2/3 and cofilin). Finally, we illustrate how actin filaments interact with myosin 1c and α-Actinin4 to promote vesicle tethering as preamble to fusion with the membrane. Copyright © 2014 the American Physiological Society.

  11. Targeted genome editing by lentiviral protein transduction of zinc-finger and TAL-effector nucleases.

    Science.gov (United States)

    Cai, Yujia; Bak, Rasmus O; Mikkelsen, Jacob Giehm

    2014-04-24

    Future therapeutic use of engineered site-directed nucleases, like zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), relies on safe and effective means of delivering nucleases to cells. In this study, we adapt lentiviral vectors as carriers of designer nuclease proteins, providing efficient targeted gene disruption in vector-treated cell lines and primary cells. By co-packaging pairs of ZFN proteins with donor RNA in 'all-in-one' lentiviral particles, we co-deliver ZFN proteins and the donor template for homology-directed repair leading to targeted DNA insertion and gene correction. Comparative studies of ZFN activity in a predetermined target locus and a known nearby off-target locus demonstrate reduced off-target activity after ZFN protein transduction relative to conventional delivery approaches. Additionally, TALEN proteins are added to the repertoire of custom-designed nucleases that can be delivered by protein transduction. Altogether, our findings generate a new platform for genome engineering based on efficient and potentially safer delivery of programmable nucleases.DOI: http://dx.doi.org/10.7554/eLife.01911.001. Copyright © 2014, Cai et al.

  12. Transmembrane signal transduction by peptide hormones via family B G protein-coupled receptors

    Directory of Open Access Journals (Sweden)

    Kelly J Culhane

    2015-11-01

    Full Text Available Although family B G protein-coupled receptors (GPCRs contain only 15 members, they play key roles in transmembrane signal transduction of hormones. Family B GPCRs are drug targets for developing therapeutics for diseases ranging from metabolic to neurological disorders. Despite their importance, the molecular mechanism of activation of family B GPCRs remains largely unexplored due to the challenges in expression and purification of functional receptors to the quantity for biophysical characterization. Currently, there is no crystal structure available of a full-length family B GPCR. However, structures of key domains, including the extracellular ligand binding regions and seven-helical transmembrane regions, have been solved by X-ray crystallography and NMR, providing insights into the mechanisms of ligand recognition and selectivity, and helical arrangements within the cell membrane. Moreover, biophysical and biochemical methods have been used to explore functions, key residues for signaling, and the kinetics and dynamics of signaling processes. This review summarizes the current knowledge of the signal transduction mechanism of family B GPCRs at the molecular level and comments on the challenges and outlook for mechanistic studies of family B GPCRs.

  13. Repair of damage induced by ultraviolet radiation in mutator T-1 Escherichia coli transductants

    International Nuclear Information System (INIS)

    Sideropoulos, A.S.; Greenberg, J.; Warren, G.

    1975-01-01

    To ascertain whether a relationship commonly exists between azide resistance, ultraviolet (uv) resistance, and the mutator property (mut T-1), we performed uv survival and mutation frequency determinations with and without caffeine (2.571 mM) in nonmutator azide resistant (azi/sup r/) and phage mediated mut T-1 transductants of Escherichia coli K-12, B/r, B/r T-, Bs-1, and Bs-8. The strains constructed were assumed to be ''co-isogenic'' except for the mutator factor. The frequency of mutation to streptomycin resistance (str/sup r/) was relatively constant and approximated 2 x 10- 7 . Transductants carrying the azide marker with or without the mut T-1 gene had the same level of uv survival as the parent with the same mutator phenotype. Dark repair of the prelethal uv lesion is equally caffeine sensitive in the nonmutator and mutator HCR+ strains. Our results indicated that the mut T-1 strains possess an efficient dark repair system for uv damage and that the mechanism of mut T-1 action is independent of uv dark repair processes. (auth)

  14. Progression in sensing cardiac troponin biomarker charge transductions on semiconducting nanomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Fathil, M.F.M., E-mail: faris.fathil@gmail.com [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Md Arshad, M.K., E-mail: mohd.khairuddin@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); School of Microelectronic Engineering, Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Ruslinda, A.R., E-mail: ruslinda@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Nuzaihan, M.N.M., E-mail: m.nuzaihan@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Gopinath, Subash C.B., E-mail: subash@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); School of Bioprocess Engineering, Universiti Malaysia Perlis, 02600, Arau, Perlis (Malaysia); Adzhri, R., E-mail: adzhri@gmail.com [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); Hashim, U., E-mail: uda@unimap.edu.my [Institute of Nano Electronic Engineering (INEE), Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia); School of Microelectronic Engineering, Universiti Malaysia Perlis, 01000, Kangar, Perlis (Malaysia)

    2016-09-07

    A real-time ability to interpret the interaction between targeted biomolecules and the surface of semiconductors (metal transducers) into readable electrical signals, without biomolecular modification involving fluorescence dyes, redox enzymes, and radioactive labels, created by label-free biosensors has been extensively researched. Field-effect transistor (FET)- and capacitor-based biosensors are among the diverse electrical charge biosensing architectures that have drawn much attention for having charge transduction; thus, enabling the early and rapid diagnosis of the appropriate cardiac biomarkers at lower concentrations. These semiconducting material-based transducers are very suitable to be integrated with portable electronic devices for future online collection, transmission, reception, analysis, and reporting. This overview elucidates and clarifies two major electrical label-free systems (FET- and capacitor-based biosensors) with cardiac troponin (cTn) biomarker-mediated charge transduction for acute myocardial infarction (AMI) diagnosis. Advances in these systems are highlighted by their progression in bridging the laboratory and industry; the foremost technologies have made the transition from benchtop to bedside and beyond. - Highlights: • The progression of cardiac troponin detection from past to future are presented. • Electrical label-free biosensors for cardiac troponin are discussed. • The discussion focused on field-effect transistor-and capacitor-based devices. • Surface functionalization, sensitivity, and innovation of devices are highlighted. • They presented high sensitivity and specificity of real-time AMI determination.

  15. How the cation-cation π-π stacking occurs: A theoretical investigation into ionic clusters of imidazolium.

    Science.gov (United States)

    Gao, Wei; Tian, Yong; Xuan, Xiaopeng

    2015-07-01

    The cation-cation π-π stacking is uncommon but it is essential for the understanding of some supramolecular structures. We explore theoretically the nature of non-covalent interaction occurring in the stacked structure within modeled clusters of 1,3-dimethylimidazolium and halide. The evidences of the energy decomposition analysis (EDA) and reduced density gradient (RDG) approach are different from those of common π-π interaction. Isosurfaces with RDG also illustrate the strength of the titled π-π interaction and their region. Additionally, we find that the occurrence of this interaction is attributed to a few C-H···X interactions, as depicted using atom in molecule (AIM) method. This work presents a clear picture of the typical cation-cation π-π interaction and can serve to advance the understanding of this uncommon interaction. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part II: signal transduction.

    Science.gov (United States)

    Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

    2015-02-01

    The unique mechanoelectrochemical environment of cartilage has motivated researchers to investigate the effect of multiple biophysical cues, including mechanical, magnetic, and electrical stimulation, on chondrocyte biology. It is well established that biophysical stimuli promote chondrocyte proliferation, differentiation, and maturation within "biological windows" of defined dose parameters, including mode, frequency, magnitude, and duration of stimuli (see companion review Part I: Cellular Response). However, the underlying molecular mechanisms and signal transduction pathways activated in response to multiple biophysical stimuli remain to be elucidated. Understanding the mechanisms of biophysical signal transduction will deepen knowledge of tissue organogenesis, remodeling, and regeneration and aiding in the treatment of pathologies such as osteoarthritis. Further, this knowledge will provide the tissue engineer with a potent toolset to manipulate and control cell fate and subsequently develop functional replacement cartilage. The aim of this article is to review chondrocyte signal transduction pathways in response to mechanical, magnetic, and electrical cues. Signal transduction does not occur along a single pathway; rather a number of parallel pathways appear to be activated, with calcium signaling apparently common to all three types of stimuli, though there are different modes of activation. Current tissue engineering strategies, such as the development of "smart" functionalized biomaterials that enable the delivery of growth factors or integration of conjugated nanoparticles, may further benefit from targeting known signal transduction pathways in combination with external biophysical cues.

  17. Novel Reactivity Of The Cationic Complex

    International Nuclear Information System (INIS)

    Wang, J.; Dash, A.K.; Eisen, AM.; Berthet, J.C.; Ephritikhine, M.

    2002-01-01

    The catalytic chemistry of electrophilic d 0 /f organometallic complexes is nowadays under intense investigation, reaching a high level of sophistication. General aspects concerning these complexes are concentrated for most studies to the functionalization of unsaturated organic molecules. To cite an instance, the actinide-promoted oligomerization of terminal alkynes is of essential present concern since it may introduce to a diversity of organic enynes and oligoacetylene products that are valuable synthons for the synthesis of natural products. Enynes are the simplest oligomerization products of alkynes. We have demonstrated that organoactinides complexes of the type [Cp* 2 AnMe 2 AnMe 2 ] (Cp* = C 5 Me 5 ; An = U, Th) are active catalysts for the linear oligomerization of terminal alkynes and the extent of oligomerization was found to be strongly dependent on the electronic and steric properties of the alkyne substituents. Bulky alkynes were reacted with high regioselectivity toward dimer and/or trimers whereas for non-bulky alkynes, these compounds were transformed into oligomers with a total deficiency of regioselectivity. The addition of primary amines to the catalytic cycle, for An = Th, granted the chemoselective formation of dimers, chemoselectively, whereas for An = U, this control was not succeeded. In distinction to the neutral organoactinide complexes, homogeneous cationic d 0 /f n actinide complexes have been used as in the homogeneous polymerization of olefins as extremely active catalysts. Hence, the catalytic alkyne oligomerization is a opportune route to explore insertions and σ-bond metathesis reactivity of complexes. We have recently shown that the reaction of terminal alkynes (RC≡CH), promoted by [(Et 2 N) 3 U][BPh 4 ], in toluene, produces efficiently mostly the gem dimers (for R = Me, i Pr and n Bu) as the major products, whereas for bulky alkynes (R = t MS or t Bu) small amounts of the cis dimer was concomitantly obtained. A plausible

  18. Small-quantity lipid-based nutrient supplements, together with malaria and diarrhoea treatment, improve growth and prevent MAM in young Burkinabe children

    International Nuclear Information System (INIS)

    Hess, Sonja Y; Abbeddou, Souheila; Somé, Jerome W; Vosti, Stephen A; Brown, Kenneth H; Yakes Jimenez, Elizabeth; Ouédraogo, Zinéwindé P; Guissou, Rosemonde M; Ouédraogo, Jean-Bosco

    2014-01-01

    Background: Supplementing young children’s diets with small-quantity lipid-based nutrient supplements (LNS) may prevent growth restriction, but the optimal amount of zinc to include in these products is uncertain. Objectives: To assess zinc-related functional responses among young Burkinabe children who received LNS without or with varied amounts of zinc, and to compare these outcomes among children who do or do not receive LNS and selected health services. Methods: In a partially masked, placebo-controlled, randomized trial, 34 communities were assigned to immediate (II) or non-intervention (NI) cohorts. 2469 eligible II children were randomly assigned to 1 of 4 groups to receive LNS containing 0, 5 or 10 mg zinc (and placebo tablet) or LNS without zinc and 5 mg zinc tablet from 9 to 18 months of age. The daily ration of LNS was 20 g which provided 118 kcal along with 20 other micronutrients in addition to zinc. Weekly morbidity surveillance was conducted at children’s homes; malaria treatment was provided for confirmed malaria, and ORS for reported diarrhea. Children in NI (n = 797) received neither supplements nor illness treatment. At 9 and 18 months, length, weight, mid-upper arm circumference (MUAC) and hemoglobin (Hb) concentration were measured in all children. Results: Reported adherence was 97 ± 5% for LNS and tablets. Mean baseline Hb was 89 ± 15 g/L, and 91% were anemic (Hb <110 g/L). At 18 months, change in Hb was greater in II cohort than NI (+8 vs -1 g/L, p<0.0001), but 79% of II were still anemic (vs. 91% in NI). During the 9 month follow-up in the II cohort, the incidence of diarrhea and malaria was 1.15 ± 1.18 and 0.55 ± 0.54 episodes per 100 child-days, respectively and did not differ by intervention group. At baseline, mean length-for-age z-score (LAZ), weight-for-length z-score (WLZ) and MUAC were -1.21 ± 1.10, -0.99 ± 1.05 and 133 ± 12 mm, respectively, in all groups combined. Mean length, weight and MUAC were significantly greater

  19. Does the cation really matter? The effect of modifying an ionic liquid cation on an SN2 process.

    Science.gov (United States)

    Tanner, Eden E L; Yau, Hon Man; Hawker, Rebecca R; Croft, Anna K; Harper, Jason B

    2013-09-28

    The rate of reaction of a Menschutkin process in a range of ionic liquids with different cations was investigated, with temperature-dependent kinetic data giving access to activation parameters for the process in each solvent. These data, along with molecular dynamics simulations, demonstrate the importance of accessibility of the charged centre on the cation and that the key interactions are of a generalised electrostatic nature.

  20. Sorption of the organic cation metoprolol on silica gel from its aqueous solution considering the competition of inorganic cations.

    Science.gov (United States)

    Kutzner, Susann; Schaffer, Mario; Börnick, Hilmar; Licha, Tobias; Worch, Eckhard

    2014-05-01

    Systematic batch experiments with the organic monovalent cation metoprolol as sorbate and the synthetic material silica gel as sorbent were conducted with the aim of characterizing the sorption of organic cations onto charged surfaces. Sorption isotherms for metoprolol (>99% protonated in the tested pH of around 6) in competition with mono- and divalent inorganic cations (Na(+), NH4(+), Ca(2+), and Mg(2+)) were determined in order to assess their influence on cation exchange processes and to identify the role of further sorptive interactions. The obtained sorption isotherms could be described well by an exponential function (Freundlich isotherm model) with consistent exponents (about 0.8). In general, a decreasing sorption of metoprolol with increasing concentrations in inorganic cations was observed. Competing ions of the same valence showed similar effects. A significant sorption affinity of metoprolol with ion type dependent Freundlich coefficients KF,0.77 between 234.42 and 426.58 (L/kg)(0.77) could still be observed even at very high concentrations of competing inorganic cations. Additional column experiments confirm this behavior, which suggests the existence of further relevant interactions beside cation exchange. In subsequent batch experiments, the influence of mixtures with more than one competing ion and the effect of a reduced negative surface charge at a pH below the point of zero charge (pHPZC ≈ 2.5) were also investigated. Finally, the study demonstrates that cation exchange is the most relevant but not the sole mechanism for the sorption of metoprolol on silica gel. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. High-capacity cation-exchange column for enhanced resolution of adjacent peaks of cations in ion chromatography.

    Science.gov (United States)

    Rey, M A

    2001-06-22

    One of the advantages of ion chromatography [Anal Chem. 47 (1975) 1801] as compared to other analytical techniques is that several ions may be analyzed simultaneously. One of the most important contributions of cation-exchange chromatography is its sensitivity to ammonium ion, which is difficult to analyze by other techniques [J. Weiss, in: E.L. Johnson (Ed.), Handbook of Ion Chromatography, Dionex, Sunnyvale, CA, USA]. The determination of low concentrations of ammonium ion in the presence of high concentrations of sodium poses a challenge in cation-exchange chromatography [J. Weiss, Ion Chromatography, VCH, 2nd Edition, Weinheim, 1995], as both cations have similar selectivities for the common stationary phases containing either sulfonate or carboxylate functional groups. The task was to develop a new cation-exchange stationary phase (for diverse concentration ratios of adjacent peaks) to overcome limitations experienced in previous trails. Various cation-exchange capacities and column body formats were investigated to optimize this application and others. The advantages and disadvantages of two carboxylic acid columns of different cation-exchange capacities and different column formats will be discussed.

  2. FLT3 ligand preserves the uncommitted CD34+CD38- progenitor cells during cytokine prestimulation for retroviral transduction

    DEFF Research Database (Denmark)

    Nielsen, S D; Husemoen, L L; Sørensen, T U

    2000-01-01

    for transduction of CD34+ cells. The effect of cytokine prestimulation on transduction efficiency and the population of uncommitted CD34+CD38- cells was determined. CD34+ cells harvested from umbilical cord blood were kept in suspension cultures and stimulated with combinations of the cytokines stem cell factor......Before stem cell gene therapy can be considered for clinical applications, problems regarding cytokine prestimulation remain to be solved. In this study, a retroviral vector carrying the genes for the enhanced version of green fluorescent protein (EGFP) and neomycin resistance (neo(r)) was used...... in a higher percentage of cells than the EGFP gene, but there seemed to be a positive correlation between expression of the two genes. The effect of cytokine prestimulation was therefore monitored using EGFP as marker for transduction. When SCF was compared to SCF in combination with more potent cytokines...

  3. Changes in serum phosphate and potassium and their effects on mortality in malnourished African HIV-infected adults starting antiretroviral therapy and given vitamins and minerals in lipid-based nutritional supplements

    DEFF Research Database (Denmark)

    Rehman, Andrea Mary; Woodd, Susannah Louise; Heimburger, Douglas Corbett

    2017-01-01

    Malnourished HIV-infected patients starting antiretroviral therapy (ART) are at high risk of early mortality, some of which may be attributed to altered electrolyte metabolism. We used data from a randomised controlled trial of electrolyte-enriched lipid-based nutritional supplements to assess...... that changes in serum electrolytes, largely irrespective of the starting point and the direction of change, were more strongly associated with mortality than were absolute electrolyte levels. Although K and phosphate are required for tissue deposition during recovery from malnutrition, further studies...... are needed to determine whether specific supplements exacerbate physiologically adverse shifts in electrolyte levels during nutritional rehabilitation of ill malnourished HIV patients....

  4. In Situ Lipolysis and Synchrotron Small-Angle X-ray Scattering for the Direct Determination of the Precipitation and Solid-State Form of a Poorly Water-Soluble Drug During Digestion of a Lipid-Based Formulation

    DEFF Research Database (Denmark)

    Khan, Jamal; Hawley, Adrian; Rades, Thomas

    2016-01-01

    In situ lipolysis and synchrotron small-angle X-ray scattering (SAXS) were used to directly detect and elucidate the solid-state form of precipitated fenofibrate from the digestion of a model lipid-based formulation (LBF). This method was developed in light of recent findings that indicate variab...... on drugs, and experimental conditions, which are anticipated to produce altered solid-state forms upon the precipitation of drug (i.e., polymorphs, amorphous forms, and salts). © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci....

  5. Expression of the synaptic exocytosis-regulating molecule complexin 2 in taste buds and its participation in peripheral taste transduction.

    Science.gov (United States)

    Kurokawa, Azusa; Narukawa, Masataka; Ohmoto, Makoto; Yoshimoto, Joto; Abe, Keiko; Misaka, Takumi

    2015-06-01

    Taste information from type III taste cells to gustatory neurons is thought to be transmitted via synapses. However, the molecular mechanisms underlying taste transduction through this pathway have not been fully elucidated. In this study, to identify molecules that participate in synaptic taste transduction, we investigated whether complexins (Cplxs), which play roles in regulating membrane fusion in synaptic vesicle exocytosis, were expressed in taste bud cells. Among four Cplx isoforms, strong expression of Cplx2 mRNA was detected in type III taste cells. To investigate the function of CPLX2 in taste transduction, we observed taste responses in CPLX2-knockout mice. When assessed with electrophysiological and behavioral assays, taste responses to some sour stimuli in CPLX2-knockout mice were significantly lower than those in wild-type mice. These results suggested that CPLX2 participated in synaptic taste transduction from type III taste cells to gustatory neurons. A part of taste information is thought to be transmitted via synapses. However, the molecular mechanisms have not been fully elucidated. To identify molecules that participate in synaptic taste transduction, we investigated complexins (Cplxs) expression in taste bud cells. Strong expression of Cplx2 mRNA was detected in taste bud cells. Furthermore, taste responses to some sour stimuli in CPLX2- knockout mice were significantly lower than those in wild-type mice. These suggested that CPLX2 participated in synaptic taste transduction. © 2015 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of The International Society for Neurochemistry.

  6. Elucidation of the Signal Transduction Pathways Activated by the Plant Natriuretic Peptide AtPNP-A

    KAUST Repository

    Turek, Ilona

    2014-11-01

    Plant natriuretic peptides (PNPs) comprise a novel class of hormones that share some sequence similarity in the active site with their animal analogues that function as regulators of salt and water balance. A PNP present in Arabidopsis thaliana (AtPNP-A) has been assigned a role in abiotic and biotic stress responses, and the recombinant protein has been demonstrated to elicit cyclic guanosine monophosphate (cGMP)-dependent stomatal guard cell opening, regulate ion movements, and induce osmoticum-dependent water uptake. Although the importance of the hormone in maintaining ion and fluid homeostasis has been established, key components of the AtPNP-A-dependent signal transduction pathway remain unknown. Since identification of the binding partners of AtPNP-A, including its receptor(s), is fundamental to understanding the mode of its action at the molecular level, comprehensive protein-protein interaction studies, involving yeast two-hybrid screening, affinity-based assays, protein cross-linking and co-immunoprecipitation followed by mass spectrometric (MS) analyses have been performed. Several candidate binding partners of AtPNP-A identified with at least two independent methods were subsequently expressed as recombinant proteins, purified, and the specificity of their interactions with the recombinant AtPNP-A was verified using surface plasmon resonance. Several specific binary interactants of AtPNP-A were subjected to functional assays aimed at unraveling the consequences of the interactions in planta. These experiments have revealed that reactive oxygen species (ROS) are novel secondary messengers involved in the transduction of AtPNP-A signal in suspension-cultured cells of A. thaliana (Col-0). Further insight into the AtPNP-A dependent signalling events occurring in suspension-cultured cells in ROS-dependent or ROS-independent manner have been obtained from the large-scale proteomics study employing tandem mass tag (TMT) labelling followed by MS analysis to

  7. On the nanotoxicity of PAMAM dendrimers: Superfect® stimulates the EGFR-ERK1/2 signal transduction pathway via an oxidative stress-dependent mechanism in HEK 293 cells.

    Science.gov (United States)

    Akhtar, Saghir; Chandrasekhar, Bindu; Attur, Sreeja; Yousif, Mariam H M; Benter, Ibrahim F

    2013-05-01

    Polyamidoamine (PAMAM) dendrimers are cationic branch-like macromolecules that may serve as drug delivery systems for gene-based therapies such as RNA interference. For their safe use in the clinic, they should ideally only enhance drug delivery to target tissues and exhibit no adverse effects. However, little is known about their toxicological profiles in terms of their interactions with cellular signal transduction pathways such as the epidermal growth factor receptor (EGFR). The EGFR is an important signaling cascade that regulates cell growth, differentiation, migration, survival and apoptosis. Here, we investigated the impact of naked, unmodified Superfect (SF), a commercially available generation 6 PAMAM dendrimer, on the epidermal growth factor receptor (EGFR) tyrosine kinase-extracellular-regulated kinase 1/2 (ERK1/2) signaling pathway in human embryonic kidney (HEK 293) cells. At concentrations routinely used for transfection, SF exhibited time and dose-dependent stimulation of EGFR and ERK1/2 phosphorylation whereas AG1478, a selective EGFR tyrosine kinase antagonist, inhibited EGFR-ERK1/2 signaling. SF-induced phosphorylation of EGFR for 1h was partly reversible upon removal of the dendrimer and examination of cells 24 later. Co-treatment of SF with epidermal growth factor (EGF) ligand resulted in greater EGFR stimulation than either agent alone implying that the stimulatory effects of SF and the ligand are synergistic. Dendrimer-induced stimulation of EGFR-ERK1/2 signaling could be attenuated by the antioxidants apocynin, catalase and tempol implying that an oxidative stress dependent mechanism was involved. These results show for the first time that PAMAM dendrimers, aside from their ability to improve drug delivery, can modulate the important EGFR-ERK1/2 cellular signal transduction pathway - a novel finding that may have a bearing on their safe application as drug delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Efficient Generation of Functional Hepatocytes From Human Embryonic Stem Cells and Induced Pluripotent Stem Cells by HNF4α Transduction

    OpenAIRE

    Takayama, Kazuo; Inamura, Mitsuru; Kawabata, Kenji; Katayama, Kazufumi; Higuchi, Maiko; Tashiro, Katsuhisa; Nonaka, Aki; Sakurai, Fuminori; Hayakawa, Takao; Kusuda Furue, Miho; Mizuguchi, Hiroyuki

    2012-01-01

    Hepatocyte-like cells from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are expected to be a useful source of cells drug discovery. Although we recently reported that hepatic commitment is promoted by transduction of SOX17 and HEX into human ESC- and iPSC-derived cells, these hepatocyte-like cells were not sufficiently mature for drug screening. To promote hepatic maturation, we utilized transduction of the hepatocyte nuclear factor 4α (HNF4α) gene, which is kn...

  9. Cation Substitution in Earth‐Abundant Kesterite Photovoltaic Materials

    Science.gov (United States)

    Li, Jianjun; Wang, Dongxiao; Li, Xiuling; Zeng, Yu

    2018-01-01

    Abstract As a promising candidate for low‐cost and environmentally friendly thin‐film photovoltaics, the emerging kesterite‐based Cu2ZnSn(S,Se)4 (CZTSSe) solar cells have experienced rapid advances over the past decade. However, the record efficiency of CZTSSe solar cells (12.6%) is still significantly lower than those of its predecessors Cu(In,Ga)Se2 (CIGS) and CdTe thin‐film solar cells. This record has remained for several years. The main obstacle for this stagnation is unanimously attributed to the large open‐circuit voltage (V OC) deficit. In addition to cation disordering and the associated band tailing, unpassivated interface defects and undesirable energy band alignment are two other culprits that account for the large V OC deficit in kesterite solar cells. To capture the great potential of kesterite solar cells as prospective earth‐abundant photovoltaic technology, current research focuses on cation substitution for CZTSSe‐based materials. The aim here is to examine recent efforts to overcome the V OC limit of kesterite solar cells by cation substitution and to further illuminate several emerging prospective strategies, including: i) suppressing the cation disordering by distant isoelectronic cation substitution, ii) optimizing the junction band alignment and constructing a graded bandgap in absorber, and iii) engineering the interface defects and enhancing the junction band bending. PMID:29721421

  10. Cation Substitution in Earth-Abundant Kesterite Photovoltaic Materials.

    Science.gov (United States)

    Li, Jianjun; Wang, Dongxiao; Li, Xiuling; Zeng, Yu; Zhang, Yi

    2018-04-01

    As a promising candidate for low-cost and environmentally friendly thin-film photovoltaics, the emerging kesterite-based Cu 2 ZnSn(S,Se) 4 (CZTSSe) solar cells have experienced rapid advances over the past decade. However, the record efficiency of CZTSSe solar cells (12.6%) is still significantly lower than those of its predecessors Cu(In,Ga)Se 2 (CIGS) and CdTe thin-film solar cells. This record has remained for several years. The main obstacle for this stagnation is unanimously attributed to the large open-circuit voltage ( V OC ) deficit. In addition to cation disordering and the associated band tailing, unpassivated interface defects and undesirable energy band alignment are two other culprits that account for the large V OC deficit in kesterite solar cells. To capture the great potential of kesterite solar cells as prospective earth-abundant photovoltaic technology, current research focuses on cation substitution for CZTSSe-based materials. The aim here is to examine recent efforts to overcome the V OC limit of kesterite solar cells by cation substitution and to further illuminate several emerging prospective strategies, including: i) suppressing the cation disordering by distant isoelectronic cation substitution, ii) optimizing the junction band alignment and constructing a graded bandgap in absorber, and iii) engineering the interface defects and enhancing the junction band bending.

  11. THERMODYNAMICS OF ETHANOLAMMONIUM CATIONES DISSOCIATION IN AQUEOUS SOLUTIONS

    Directory of Open Access Journals (Sweden)

    R. E. Khoma

    2017-03-01

    Full Text Available The literature data on the thermodynamics of ethanolamines onium cations dissociation have been systematized and generalized. The correlation between these cations dissociation thermodynamic functions (DH and DS and physicochemical properties (Tmp., Tbp, Pp, lgPow et al. has been revealed. There was a correlation between lipophilicity determined experimentally and calculated by QSAR. For monoethanolammonium, diethanolammonium, and their N-methyl and N-ethyl derivatives it was found dissociation thermodynamic functions to depend on bases lgPow. Acid-base dissociation of TRIS and triethanolamine onium cations does not correspond to said relationship because TRIS (primary amine, TEA (tertiary amine act differently on aqueous solutions of SO2. TEA, unlike MEA, DEA and MMEA, has a salting out effect towards sulfur dioxide because of competing hydration that promotes sulfite «onium» salts hydrolysis. TRIS promotes S(IV → S(VI sulphooxidation, in contrast to another ethanolamines. Enthalpy–enthropy compensation with isothermodynamic temperature 303 K has been recorded. The revealed correlations may be useful in developing of procedures for air sanitary cleaning from acidic gases; chemisorbents immobilized for gas and ion exchange chromatography; potentiometric methods for fluorocomplex acids determinations. The use of monoethanolamine is most promising to obtain chemisorbents because the thermodynamic functions of its onium cation acid-base dissociation are least dependent on temperature compared to other etanolammonium cations.

  12. Electrospray ionization tandem mass spectrometry of ammonium cationized polyethers.

    Science.gov (United States)

    Nasioudis, Andreas; Heeren, Ron M A; van Doormalen, Irene; de Wijs-Rot, Nicolette; van den Brink, Oscar F

    2011-05-01

    Quaternary ammonium salts (Quats) and amines are known to facilitate the MS analysis of high molar mass polyethers by forming low charge state adduct ions. The formation, stability, and behavior upon collision-induced dissociation (CID) of adduct ions of polyethers with a variety of Quats and amines were studied by electrospray ionization quadrupole time-of-flight, quadrupole ion trap, and linear ion trap tandem mass spectrometry (MS/MS). The linear ion trap instrument was part of an Orbitrap hybrid mass spectrometer that allowed accurate mass MS/MS measurements. The Quats and amines studied were of different degree of substitution, structure, and size. The stability of the adduct ions was related to the structure of the cation, especially the amine's degree of substitution. CID of singly/doubly charged primary and tertiary ammonium cationized polymers resulted in the neutral loss of the amine followed by fragmentation of the protonated product ions. The latter reveals information about the monomer unit, polymer sequence, and endgroup structure. In addition, the detection of product ions retaining the ammonium ion was observed. The predominant process in the CID of singly charged quaternary ammonium cationized polymers was cation detachment, whereas their doubly charged adduct ions provided the same information as the primary and tertiary ammonium cationized adduct ions. This study shows the potential of specific amines as tools for the structural elucidation of high molar mass polyethers. © American Society for Mass Spectrometry, 2011

  13. Cation-enhanced capillary electrophoresis separation of atropoisomer anions.

    Science.gov (United States)

    Na, Yun-Cheol; Berthod, Alain; Armstrong, Daniel W

    2015-12-01

    CE was used to study the separation of the atropoisomers of four phosphoric acids and two sulfonic acids and the enantiomers of two phosphoric acids. All solutes are in their anionic forms in aqueous electrolytes. The chiral additives were two hydroxypropyl cyclodextrins (CDs) and cyclofructan 6 (CF6). The CDs were able to separate four solutes and the CF6 additive could separate only one: 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate (BHP). Since CF6 is able to bind with cations, nitrate of alkaline metals, Ba(2+) , and Pb(2+) were added, greatly improving the BHP separation at the expense of longer migration times. There seems to be a link between CF6-cation-binding constants and BHP resolution factors. Cation additions were also performed with CD selectors that are less prone to form complexes with cations. Significant improvements of enantiomer or atropoisomer separations were observed also associated with longer migration times. It is speculated that the anionic solutes associate with the added cations forming larger entities better differentiated by CDs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Cation Binding to Xanthorhodopsin: Electron Paramagnetic Resonance and Magnetic Studies.

    Science.gov (United States)

    Smolensky Koganov, Elena; Leitus, Gregory; Rozin, Rinat; Weiner, Lev; Friedman, Noga; Sheves, Mordechai

    2017-05-04

    Xanthorhodopsin (xR) is a member of the retinal protein family and acts as a proton pump in the cell membranes of the extremely halophilic eubacterium Salinibacter ruber. In addition to the retinal chromophore, xR contains a carotenoid, which acts as a light-harvesting antenna as it transfers 40% of the quanta it absorbs to the retinal. Our previous studies have shown that the CD and absorption spectra of xR are dramatically affected due to the protonation of two different residues. It is still unclear whether xR can bind cations. Electron paramagnetic resonance (EPR) spectroscopy used in the present study revealed that xR can bind divalent cations, such as Mn 2+ and Ca 2+ , to deionized xR (DI-xR). We also demonstrate that xR can bind 1 equiv of Mn 2+ to a high-affinity binding site followed by binding of ∼40 equiv in cooperative manner and ∼100 equiv of Mn 2+ that are weakly bound. SQUID magnetic studies suggest that the high cooperative binding of Mn 2+ cations to xR is due to the formation of Mn 2+ clusters. Our data demonstrate that Ca 2+ cations bind to DI-xR with a lower affinity than Mn 2+ , supporting the assumption that binding of Mn 2+ occurs through cluster formation, because Ca 2+ cations cannot form clusters in contrast to Mn 2+ .

  15. Cationic polymerization of styrene by means of pulse radiolysis

    International Nuclear Information System (INIS)

    Egusa, S.; Arai, S.; Kira, A.; Imamura, M.; Tabata, Y.

    1977-01-01

    The radiation-induced cationic polymerization of styrene has been studied by microsecond pulse radiolysis. It was possible to observe absorption bands of a monomer cation radical (St. + ) at 630 nm and at 350 nm in a mixture of isopentane and n-butyl chloride at - 165 0 C. Three absorption bands, around 1600 nm, at 600 nm and at 450 nm, grew in parallel with the decay of St. + after pulse. The 1600-nm and 600-nm bands were assigned to an associated dimer cation radical (St 2 . + ), and the 450-nm band to a bonded dimer cation radical (St-St. + ) by comparison of absorption spectra of α-methylstyrene, 1,2-dihydronaphthalene and trans-β-methylstyrene. The kinetic behaviour of these species suggests that St-St. + and a part of St 2 . + are formed by the reaction of St. + with a styrene monomer, and the rest of St 2 . + may be formed by positive charge transfer from a solvent cation radical to an auto-associated neutral dimer of styrene. A long-lived absorption band at 340 nm grew with the decay of St-St. + . This band is considered due to a growing polymer carbonium ion. (author)

  16. Cationic uremic toxins affect human renal proximal tubule cell functioning through interaction with the organic cation transporter.

    Science.gov (United States)

    Schophuizen, Carolien M S; Wilmer, Martijn J; Jansen, Jitske; Gustavsson, Lena; Hilgendorf, Constanze; Hoenderop, Joost G J; van den Heuvel, Lambert P; Masereeuw, Rosalinde

    2013-12-01

    Several organic cations, such as guanidino compounds and polyamines, have been found to accumulate in plasma of patients with kidney failure due to inadequate renal clearance. Here, we studied the interaction of cationic uremic toxins with renal organic cation transport in a conditionally immortalized human proximal tubule epithelial cell line (ciPTEC). Transporter activity was measured and validated in cell suspensions by studying uptake of the fluorescent substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium-iodide (ASP(+)). Subsequently, the inhibitory potencies of the cationic uremic toxins, cadaverine, putrescine, spermine and spermidine (polyamines), acrolein (polyamine breakdown product), guanidine, and methylguanidine (guanidino compounds) were determined. Concentration-dependent inhibition of ASP(+) uptake by TPA, cimetidine, quinidine, and metformin confirmed functional endogenous organic cation transporter 2 (OCT2) expression in ciPTEC. All uremic toxins tested inhibited ASP(+) uptake, of which acrolein required the lowest concentration to provoke a half-maximal inhibition (IC50 = 44 ± 2 μM). A Dixon plot was constructed for acrolein using three independent inhibition curves with 10, 20, or 30 μM ASP(+), which demonstrated competitive or mixed type of interaction (K i = 93 ± 16 μM). Exposing the cells to a mixture of cationic uremic toxins resulted in a more potent and biphasic inhibitory response curve, indicating complex interactions between the toxins and ASP(+) uptake. In conclusion, ciPTEC proves a suitable model to study cationic xenobiotic interactions. Inhibition of cellular uptake transport was demonstrated for several uremic toxins, which might indicate a possible role in kidney disease progression during uremia.

  17. Improved intracellular delivery of glucocerebrosidase mediated by the HIV-1 TAT protein transduction domain

    International Nuclear Information System (INIS)

    Lee, Kyun Oh; Luu, Nga; Kaneski, Christine R.; Schiffmann, Raphael; Brady, Roscoe O.; Murray, Gary J.

    2005-01-01

    Enzyme replacement therapy (ERT) for Gaucher disease designed to target glucocerebrosidase (GC) to macrophages via mannose-specific endocytosis is very effective in reversing hepatosplenomegaly, and normalizing hematologic parameters but is less effective in improving bone and lung involvement and ineffective in brain. Recombinant GCs containing an in-frame fusion to the HIV-1 trans-activator protein transduction domain (TAT) were expressed in eukaryotic cells in order to obtain active, normally glycosylated GC fusion proteins for enzyme uptake studies. Despite the absence of mannose-specific endocytic receptors on the plasma membranes of various fibroblasts, the recombinant GCs with C-terminal TAT fusions were readily internalized by these cells. Immunofluorescent confocal microscopy demonstrated the recombinant TAT-fusion proteins with a mixed endosomal and lysosomal localization. Thus, TAT-modified GCs represent a novel strategy for a new generation of therapeutic enzymes for ERT for Gaucher disease

  18. Electro-Optomechanical Transduction & Quantum Hard-Sphere Model for Dissipative Rydberg-EIT Media

    DEFF Research Database (Denmark)

    Zeuthen, Emil

    by two key parameters, the signal transfer efficiency and added noise temperature. In terms of these, we may evaluate its performance in various tasks ranging from classical signal detection to quantum state conversion between, e.g., superconducting circuitry and traveling optical signals. Having...... transduction functionality into the well-established framework of electrical engineering, thereby facilitating its implementation in potential applications such as nuclear magnetic resonance imaging and radio astronomy. We consider such optomechanical sensing of weak electrical signals and discuss how...... in a cold, optically dense cloud with light fields propagating under the condition of electromagnetically induced transparency (EIT). This can lead to strong and non-linear dissipative dynamics at the quantum level that prevent slow-light polaritons from coexisting within a blockade radius of one another...

  19. Comprehensive analysis of signal transduction in three-dimensional ECM-based tumor cell cultures

    Directory of Open Access Journals (Sweden)

    Iris Eke

    2015-11-01

    Full Text Available Analysis of signal transduction and protein phosphorylation is fundamental to understand physiological and pathological cell behavior as well as identification of novel therapeutic targets. Despite the fact that more physiological three-dimensional cell culture assays are increasingly used, particularly proteomics and phosphoproteomics remain challenging due to easy, robust and reproducible sample preparation. Here, we present an easy-to-perform, reliable and time-efficient method for the production of 3D cell lysates without compromising cell adhesion before cell lysis. The samples can be used for Western blotting as well as phosphoproteome array technology. This technique would be of interest for researchers working in all fields of biology and drug development.

  20. Development of a Modular Magnetostrictive Transducer for Torsional Guided Wave Transduction in a Cylindrical Structure

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Seung Hyun; Park, Jae Ha; Kwon, Hyu Sang; Ahn, Bong Young; Lee, Seung Seok [Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of)

    2009-10-15

    Cylindrical structures such as pipes and shafts are widely used in various industrial facilities. Recently, researches on magnetostrictive transduction of torsional waves have been actively reported for the nondestructive evaluation of those cylindrical structures. However, the existing magnetostrictive patch transducer has somewhat inconvenient and time. Consuming process like patch bonding to a structure since it should employ a magnetostrictive patch having strong magnetostriction. To overcome these limitations of the existing transducer, in this work, we develop a novel modular magnetostrictive transducer to generate and measure torsional waves to inspect a cylindrical structure. The proposed transducer can be applied as viscous liquid coupling with shear couplant or dry coupling without coupling media instead of patch bonding to a structure. We describe a detailed structure of the modular transducer and conduct some experiments to verify its performance

  1. Development of a Modular Magnetostrictive Transducer for Torsional Guided Wave Transduction in a Cylindrical Structure

    International Nuclear Information System (INIS)

    Cho, Seung Hyun; Park, Jae Ha; Kwon, Hyu Sang; Ahn, Bong Young; Lee, Seung Seok

    2009-01-01

    Cylindrical structures such as pipes and shafts are widely used in various industrial facilities. Recently, researches on magnetostrictive transduction of torsional waves have been actively reported for the nondestructive evaluation of those cylindrical structures. However, the existing magnetostrictive patch transducer has somewhat inconvenient and time. Consuming process like patch bonding to a structure since it should employ a magnetostrictive patch having strong magnetostriction. To overcome these limitations of the existing transducer, in this work, we develop a novel modular magnetostrictive transducer to generate and measure torsional waves to inspect a cylindrical structure. The proposed transducer can be applied as viscous liquid coupling with shear couplant or dry coupling without coupling media instead of patch bonding to a structure. We describe a detailed structure of the modular transducer and conduct some experiments to verify its performance

  2. Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Anna W.; Satyshur, Kenneth A.; Morales, Neydis Moreno; Forest, Katrina T. (UW)

    2016-02-01

    ABSTRACT

    Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacteriumRamlibacter tataouinensis. RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, theR. tataouinensisbacteriophytochrome response regulator (RtBRR), and a homolog, AtBRR fromAgrobacterium tumefaciens, crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRRmon) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems.

  3. Regulation of autophagy by amino acids and MTOR-dependent signal transduction.

    Science.gov (United States)

    Meijer, Alfred J; Lorin, Séverine; Blommaart, Edward F; Codogno, Patrice

    2015-10-01

    Amino acids not only participate in intermediary metabolism but also stimulate insulin-mechanistic target of rapamycin (MTOR)-mediated signal transduction which controls the major metabolic pathways. Among these is the pathway of autophagy which takes care of the degradation of long-lived proteins and of the elimination of damaged or functionally redundant organelles. Proper functioning of this process is essential for cell survival. Dysregulation of autophagy has been implicated in the etiology of several pathologies. The history of the studies on the interrelationship between amino acids, MTOR signaling and autophagy is the subject of this review. The mechanisms responsible for the stimulation of MTOR-mediated signaling, and the inhibition of autophagy, by amino acids have been studied intensively in the past but are still not completely clarified. Recent developments in this field are discussed.

  4. Expression of cDNAs in human Natural Killer cell lines by retroviral transduction.

    Science.gov (United States)

    Miah, S M Shahjahan; Campbell, Kerry S

    2010-01-01

    Human NK-like cell lines are difficult to transfect using standard mammalian expression vectors and conventional transfection protocols, but they are susceptible to retroviral transduction as a means to introduce cDNAs. Our laboratory has exploited this technique to study a number of receptors in human NK cell lines. The method utilizes a bicistronic retroviral vector that co-expresses either drug resistance or enhanced green fluorescent protein (EGFP) in parallel with the gene of interest. After a single infection with recombinant retrovirus, transduced NK cells can be sorted for expression of EGFP or the transduced cell surface marker. Alternatively, cells expressing the transduced cDNAs can be selected for by treatment with neomycin, puromycin, or hygromycin. Using this method, the sorted/selected cells uniformly express the gene of interest and the expression is stable for many weeks of culture.

  5. Effect of the opioid methionine enkephalinamide on signal transduction in human T-lymphocytes

    DEFF Research Database (Denmark)

    Sørensen, A N; Claesson, Mogens Helweg

    1998-01-01

    T cell receptor (TCR/CD3) induced fluctuations in intracellular free ionizied calcium, [Ca2+]i, was analysed in the human T leukemia cell clone, Jurkat, cultured in the presence of the opioid methionine enkephalinamide (Met-Enk) in titrated concentrations (10[-7] to 10[-15] M) or saline (PBS....... Moreover, the levels of [Ca2+]i in this particular fraction were lower than control levels prior to ligation of the TCR/CD3 complex. The data support the idea that signal transduction in T cells can be influenced by endogenous opioid. The data therefore give credit to the evolving hypothesis...... of a functional relationship between the neuroendocrine system and the immune system....

  6. Practical considerations of image analysis and quantification of signal transduction IHC staining.

    Science.gov (United States)

    Grunkin, Michael; Raundahl, Jakob; Foged, Niels T

    2011-01-01

    The dramatic increase in computer processing power in combination with the availability of high-quality digital cameras during the last 10 years has fertilized the grounds for quantitative microscopy based on digital image analysis. With the present introduction of robust scanners for whole slide imaging in both research and routine, the benefits of automation and objectivity in the analysis of tissue sections will be even more obvious. For in situ studies of signal transduction, the combination of tissue microarrays, immunohistochemistry, digital imaging, and quantitative image analysis will be central operations. However, immunohistochemistry is a multistep procedure including a lot of technical pitfalls leading to intra- and interlaboratory variability of its outcome. The resulting variations in staining intensity and disruption of original morphology are an extra challenge for the image analysis software, which therefore preferably should be dedicated to the detection and quantification of histomorphometrical end points.

  7. Creating and analyzing pathway and protein interaction compendia for modelling signal transduction networks

    Directory of Open Access Journals (Sweden)

    Kirouac Daniel C

    2012-05-01

    Full Text Available Abstract Background Understanding the information-processing capabilities of signal transduction networks, how those networks are disrupted in disease, and rationally designing therapies to manipulate diseased states require systematic and accurate reconstruction of network topology. Data on networks central to human physiology, such as the inflammatory signalling networks analyzed here, are found in a multiplicity of on-line resources of pathway and interactome databases (Cancer CellMap, GeneGo, KEGG, NCI-Pathway Interactome Database (NCI-PID, PANTHER, Reactome, I2D, and STRING. We sought to determine whether these databases contain overlapping information and whether they can be used to construct high reliability prior knowledge networks for subsequent modeling of experimental data. Results We have assembled an ensemble network from multiple on-line sources representing a significant portion of all machine-readable and reconcilable human knowledge on proteins and protein interactions involved in inflammation. This ensemble network has many features expected of complex signalling networks assembled from high-throughput data: a power law distribution of both node degree and edge annotations, and topological features of a “bow tie” architecture in which diverse pathways converge on a highly conserved set of enzymatic cascades focused around PI3K/AKT, MAPK/ERK, JAK/STAT, NFκB, and apoptotic signaling. Individual pathways exhibit “fuzzy” modularity that is statistically significant but still involving a majority of “cross-talk” interactions. However, we find that the most widely used pathway databases are highly inconsistent with respect to the actual constituents and interactions in this network. Using a set of growth factor signalling networks as examples (epidermal growth factor, transforming growth factor-beta, tumor necrosis factor, and wingless, we find a multiplicity of network topologies in which receptors couple to downstream

  8. A composite approach boosts transduction coefficients of piezoceramics for energy harvesting

    Science.gov (United States)

    Yu, Xiaole; Hou, Yudong; Zheng, Mupeng; Zhao, Haiyan; Zhu, Mankang

    2018-03-01

    Piezoelectric energy harvesting is a hotspot in the field of new energy, the core goal of which is to prepare piezoceramics with a high transduction coefficient (d33×g33). The traditional solid-solution design strategy usually causes the same variation trend of d33 and ɛr, resulting in a low d33×g33 value. In this work, a composite design strategy was proposed that uses PZN-PZT/ZnAl2O4 as an example. By introducing ZnAl2O4, which is nonferroelectric with low ɛr, to the PZN-PZT piezoelectric matrix, ɛr decreased rapidly while d33 remained relatively stable. This behavior was ascribed to the increase of Q33 caused by an interfacial effect facilitating the formation of micro-domain structure.

  9. A composite approach boosts transduction coefficients of piezoceramics for energy harvesting

    Directory of Open Access Journals (Sweden)

    Xiaole Yu

    2018-03-01

    Full Text Available Piezoelectric energy harvesting is a hotspot in the field of new energy, the core goal of which is to prepare piezoceramics with a high transduction coefficient (d33×g33. The traditional solid–solution design strategy usually causes the same variation trend of d33 and εr, resulting in a low d33×g33 value. In this work, a composite design strategy was proposed that uses PZN–PZT/ZnAl2O4 as an example. By introducing ZnAl2O4, which is nonferroelectric with low εr, to the PZN–PZT piezoelectric matrix, εr decreased rapidly while d33 remained relatively stable. This behavior was ascribed to the increase of Q33 caused by an interfacial effect facilitating the formation of micro-domain structure.

  10. Transduction of Repetitive Mechanical Stimuli by Piezo1 and Piezo2 Ion Channels

    Directory of Open Access Journals (Sweden)

    Amanda H. Lewis

    2017-06-01

    Full Text Available Several cell types experience repetitive mechanical stimuli, including vein endothelial cells during pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their innervating dorsal root ganglion (DRG neurons when sweeping across a textured surface or touching a vibrating object. While mechanosensitive Piezo ion channels have been clearly implicated in sensing static touch, their roles in transducing repetitive stimulations are less clear. Here, we perform electrophysiological recordings of heterologously expressed mouse Piezo1 and Piezo2 responding to repetitive mechanical stimulations. We find that both channels function as pronounced frequency filters whose transduction efficiencies vary with stimulus frequency, waveform, and duration. We then use numerical simulations and human disease-related point mutations to demonstrate that channel inactivation is the molecular mechanism underlying frequency filtering and further show that frequency filtering is conserved in rapidly adapting mouse DRG neurons. Our results give insight into the potential contributions of Piezos in transducing repetitive mechanical stimuli.

  11. Efficient, Broadband and Wide-Angle Hot-Electron Transduction using Metal-Semiconductor Hyperbolic Metamaterials

    KAUST Repository

    Sakhdari, Maryam

    2016-05-20

    Hot-electron devices are emerging as promising candidates for the transduction of optical radiation into electrical current, as they enable photodetection and solar/infrared energy harvesting at sub-bandgap wavelengths. Nevertheless, poor photoconversion quantum yields and low bandwidth pose fundamental challenge to fascinating applications of hot-electron optoelectronics. Based on a novel hyperbolic metamaterial (HMM) structure, we theoretically propose a vertically-integrated hot-electron device that can efficiently couple plasmonic excitations into electron flows, with an external quantum efficiency approaching the physical limit. Further, this metamaterial-based device can have a broadband and omnidirectional response at infrared and visible wavelengths. We believe that these findings may shed some light on designing practical devices for energy-efficient photodetection and energy harvesting beyond the bandgap spectral limit.

  12. A bead-based western for high-throughput cellular signal transduction analyses

    Science.gov (United States)

    Treindl, Fridolin; Ruprecht, Benjamin; Beiter, Yvonne; Schultz, Silke; Döttinger, Anette; Staebler, Annette; Joos, Thomas O.; Kling, Simon; Poetz, Oliver; Fehm, Tanja; Neubauer, Hans; Kuster, Bernhard; Templin, Markus F.

    2016-01-01

    Dissecting cellular signalling requires the analysis of large number of proteins. The DigiWest approach we describe here transfers the western blot to a bead-based microarray platform. By combining gel-based protein separation with immobilization on microspheres, hundreds of replicas of the initial blot are created, thus enabling the comprehensive analysis of limited material, such as cells collected by laser capture microdissection, and extending traditional western blotting to reach proteomic scales. The combination of molecular weight resolution, sensitivity and signal linearity on an automated platform enables the rapid quantification of hundreds of specific proteins and protein modifications in complex samples. This high-throughput western blot approach allowed us to identify and characterize alterations in cellular signal transduction that occur during the development of resistance to the kinase inhibitor Lapatinib, revealing major changes in the activation state of Ephrin-mediated signalling and a central role for p53-controlled processes. PMID:27659302

  13. Modulators of Stomatal Lineage Signal Transduction Alter Membrane Contact Sites and Reveal Specialization among ERECTA Kinases.

    Science.gov (United States)

    Ho, Chin-Min Kimmy; Paciorek, Tomasz; Abrash, Emily; Bergmann, Dominique C

    2016-08-22

    Signal transduction from a cell's surface to its interior requires dedicated signaling elements and a cellular environment conducive to signal propagation. Plant development, defense, and homeostasis rely on plasma membrane receptor-like kinases to perceive endogenous and environmental signals, but little is known about their immediate downstream targets and signaling modifiers. Using genetics, biochemistry, and live-cell imaging, we show that the VAP-RELATED SUPPRESSOR OF TMM (VST) family is required for ERECTA-mediated signaling in growth and cell-fate determination and reveal a role for ERECTA-LIKE2 in modulating signaling by its sister kinases. We show that VSTs are peripheral plasma membrane proteins that can form complexes with integral ER-membrane proteins, thereby potentially influencing the organization of the membrane milieu to promote efficient and differential signaling from the ERECTA-family members to their downstream intracellular targets. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Therapeutic peptides for cancer therapy. Part I - peptide inhibitors of signal transduction cascades.

    Science.gov (United States)

    Bidwell, Gene L; Raucher, Drazen

    2009-10-01

    Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that inhibit signal transduction cascades are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Given our current knowledge of protein sequences, structures and interaction interfaces, therapeutic peptides that inhibit interactions of interest are easily designed. These peptides are advantageous because they are highly specific for the interaction of interest, and they are much more easily developed than small molecule inhibitors of the same interactions. The main hurdle to application of peptides for cancer therapy is their poor pharmacokinetic and biodistribution parameters. Therefore, successful development of peptide delivery vectors could potentially make possible the use of this new and very promising class of anticancer agents.

  15. Auxin apical control of the auxin polar transport and its oscillation - a suggested cellular transduction mechanism

    Directory of Open Access Journals (Sweden)

    Tomasz J. Wodzicki

    2014-01-01

    Full Text Available The proposed hypothesis concerns the transduction of auxin molecular signals arriving from the apoplast at the plasma membrane or recognized by the proteineous receptors of the responding cell, to the concentration gradients oscillating in the supracellular space, associated usually with the specific plant growth and differentiation. Acting as an agonist from outside the target cell auxin stimulates in this cell: (1 the liberation of auxin from the cytosolic pool of its conjugates directly into the basipetal efflux; (2 the synthesis of new auxin which restores the cytosolic reserve of auxin conjugates. The functioning of such a system may be effective in a series of processes initiated by the changing concentration of cytosolic calcium. The hypothesis suggests a molecular mechanism for the development and effective operation of the morphogenetic field in the supracellular space of the plant body, such as the field resulting from auxin waves discovered in cambium.

  16. Drawing a Transductive Ecosophy in Process: Technological Arts, Residual Matter, Associated Milieus

    Directory of Open Access Journals (Sweden)

    Gisèle Trudel

    2015-06-01

    Full Text Available Drawing a Transductive Ecosophy in Process: Technological Arts, Residual Matter, Associated Milieus by Gisèle Trudel. NANO: New American Notes Online, Issue 7: The Aesthetics of Trash - nanocrit.com. This text examines the tetralogy of media artworks about residual matter produced by Ælab between 2008 and 2014. Taking its own title as a diagram (Deleuze and Guattari Mille Plateaux, it charts and builds on the processes of these artworks, elucidating their relations to materiality, philosophy and technicity. Technological research-creation becomes in these instances a transdisciplinary aesthetic act, emerging from an ecology of practices that combine humans, non-humans and waste matter in an effort to increase attentiveness in actions.

  17. Localization of phosphatidylinositol signaling components in rat taste cells: Role in bitter taste transduction

    International Nuclear Information System (INIS)

    Hwang, P.M.; Verma, A.; Bredt, D.S.; Snyder, S.H.

    1990-01-01

    To assess the role of phosphatidylinositol turnover in taste transduction we have visualized, in rat tongue, ATP-dependent endoplasmic reticular accumulation of 45 Ca 2+ , inositol 1,4,5-trisphosphate receptor binding sites, and phosphatidylinositol turnover monitored by autoradiography of [ 3 H]cytidine diphosphate diacylglycerol formed from [ 3 H]cytidine. Accumulated 45 Ca 2+ , inositol 1,4,5-trisphosphate receptors, and phosphatidylinositol turnover are selectively localized to apical areas of the taste buds of circumvallate papillae, which are associated with bitter taste. Further evidence for a role of phosphatidylinositol turnover in bitter taste is our observation of a rapid, selective increase in mass levels of inositol 1,4,5-trisphosphate elicited by low concentrations of denatonium, a potently bitter tastant

  18. CD4 expression on EL4 cells as an epiphenomenon of retroviral transduction and selection.

    Science.gov (United States)

    Logan, Grant J; Spinoulas, Afroditi; Alexander, Stephen I; Smythe, Jason A; Alexander, Ian E

    2004-04-01

    The EL4 murine tumour cell line, isolated from a chemically induced lymphoma over 50 years ago, has been extensively exploited in immunological research. The conclusions drawn from many of these studies have been based on the presumption that EL4 cells maintain a stable phenotype during experimental manipulation. To the contrary, we have observed 100-fold greater expression of cell surface CD4 (CD4(high)) on a subpopulation of EL4 cells following retroviral transduction and G418 selection when compared with unmodified populations. Although the mechanism responsible for this effect remains to be elucidated, the unexpected expression of CD4, a molecule that functions as both a coreceptor with the T-cell receptor and ligand for the pro-inflammatory cytokine IL-16, has the potential to influence experimental outcomes. Upregulation of CD4 should be excluded when EL4 cells are utilized in experiments requiring a consistent immuno-phenotype.

  19. Hydration of cations: a key to understanding of specific cation effects on aggregation behaviors of PEO-PPO-PEO triblock copolymers.

    Science.gov (United States)

    Lutter, Jacob C; Wu, Tsung-yu; Zhang, Yanjie

    2013-09-05

    This work reports results from the interactions of a series of monovalent and divalent cations with a triblock copolymer, poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO). Phase transition temperatures of the polymer in the presence of chloride salts with six monovalent and eight divalent cations were measured using an automated melting point apparatus. The polymer undergoes a two-step phase transition, consisting of micellization of the polymer followed by aggregation of the micelles, in the presence of all the salts studied herein. The results suggest that hydration of cations plays a key role in determining the interactions between the cations and the polymer. The modulation of the phase transition temperature of the polymer by cations can be explained as a balance between three interactions: direct binding of cations to the oxygen in the polymer chains, cations sharing one water molecule with the polymer in their hydration layer, and cations interacting with the polymer via two water molecules. Monovalent cations Na(+), K(+), Rb(+), and Cs(+) do not bind to the polymer, while Li(+) and NH4(+) and all the divalent cations investigated including Mg(2+), Ca(2+), Sr(2+), Ba(2+), Co(2+), Ni(2+), Cu(2+), and Cd(2+) bind to the polymer. The effects of the cations correlate well with their hydration thermodynamic properties. Mechanisms for cation-polymer interactions are discussed.

  20. Downstream reporter gene imaging for signal transduction pathway of dopamine type 2 receptor

    International Nuclear Information System (INIS)

    Le, Uyenchi N.; Min, Jung Joon; Moon, Sung Min; Bom, Hee Seung

    2004-01-01

    The Dopamine 2 receptor (D2R) signal pathway regulates gene expression by phosphorylation of proteins including cAMP reponse element-binding protein (CREB), a transcription factor. In this study, we developed a reporter strategy using the GAL4 fusion CREB to assess the phosphorylation of CREB, one of the targets of the D2R signal transduction pathway. We used three plasmids: GAL4 fusion transactivator (pCMV-CREB), firefly luciferase reporter with GAL4 binding sites (pG5-FLUC), and D2R plasmid (pCMV-D2R). Group 1 293T cells were transiently transfected with pCMV-CREB and pG5-FLUC, and group 2 cells were transfected with all three plasmids. Transfected cells were stimulated with different concentrations of dopamine (0-200 M). For animal studies, group 1 and 2 cells (1x10 6 ) were subcutaneously injected on the left and right thigh of six nude mice, respectively. Dopamine stimiulation was performed with intraperitoneal injection of L-DOPA incombination with carbidopa, a peripheral DOPA decarboxylase inhibitor. Bioluminescence optical imaging studies were performed before and after L-DOPA injection. In cell culture studies, group 1 cells showed strong luciferase activity which implies direct activation of the signaling pathway due to growth factors contained in culture medium. Group 2 cells showed strong luciferase activity and a further increase after administration of dopamine. In animal studies, group 1 and 2 cells showed bioluminescence signal before L-DOPA injection, but signal from group 2 cells significantly increased 12 h after L-DOPA injection. The signal from group 1 cells disappeared thereafter, but group 2 cells continued to show signal until 36 h of L-DOPA injection. This study demonstrates imaging of the D2R signal transduction pathway and should be useful for noninvasive imaging of downstream effects of G-coupled protein pathways

  1. Anagrelide represses GATA-1 and FOG-1 expression without interfering with thrombopoietin receptor signal transduction.

    Science.gov (United States)

    Ahluwalia, M; Donovan, H; Singh, N; Butcher, L; Erusalimsky, J D

    2010-10-01

     Anagrelide is a selective inhibitor of megakaryocytopoiesis used to treat thrombocytosis in patients with chronic myeloproliferative disorders. The effectiveness of anagrelide in lowering platelet counts is firmly established, but its primary mechanism of action remains elusive.  Here, we have evaluated whether anagrelide interferes with the major signal transduction cascades stimulated by thrombopoietin in the hematopoietic cell line UT-7/mpl and in cultured CD34(+) -derived human hematopoietic cells. In addition, we have used quantitative mRNA expression analysis to assess whether the drug affects the levels of known transcription factors that control megakaryocytopoiesis.  In UT-7/mpl cells, anagrelide (1μm) did not interfere with MPL-mediated signaling as monitored by its lack of effect on JAK2 phosphorylation. Similarly, the drug did not affect the phosphorylation of STAT3, ERK1/2 or AKT in either UT-7/mpl cells or primary hematopoietic cells. In contrast, during thrombopoietin-induced megakaryocytic differentiation of normal hematopoietic cultures, anagrelide (0.3μm) reduced the rise in the mRNA levels of the transcription factors GATA-1 and FOG-1 as well as those of the downstream genes encoding FLI-1, NF-E2, glycoprotein IIb and MPL. However, the drug showed no effect on GATA-2 or RUNX-1 mRNA expression. Furthermore, anagrelide did not diminish the rise in GATA-1 and FOG-1 expression during erythropoietin-stimulated erythroid differentiation. Cilostamide, an exclusive and equipotent phosphodiesterase III (PDEIII) inhibitor, did not alter the expression of these genes.  Anagrelide suppresses megakaryocytopoiesis by reducing the expression levels of GATA-1 and FOG-1 via a PDEIII-independent mechanism that is differentiation context-specific and does not involve inhibition of MPL-mediated early signal transduction events. © 2010 International Society on Thrombosis and Haemostasis.

  2. MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hong-hua Peng

    2012-01-01

    Full Text Available The matrix metalloprotease-1 (MMP-1/protease-activated receptor-1 (PAR-1 signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC, we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9% and 58 (68.2% tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM stage and regional lymph node involvement. Patients with MMP-1- and PAR-1-positive tumors, respectively, had poorer disease-free survival (DFS than those with negative ESCC (P = 0.002 and 0.003, respectively. Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR = 2.836, 95% confidence interval (CI = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068, MMP-1 expression (HR = 2.669, 95%CI = 1.229-6.127, and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883 and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681, MMP-1 expression (HR = 2.109, 95%CI = 1.293-3.279, and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881 as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC.

  3. Dual functional extracellular recording using a light-addressable potentiometric sensor for bitter signal transduction.

    Science.gov (United States)

    Du, Liping; Wang, Jian; Chen, Wei; Zhao, Luhang; Wu, Chunsheng; Wang, Ping

    2018-08-31

    This paper presents a dual functional extracellular recording biosensor based on a light-addressable potentiometric sensor (LAPS). The design and fabrication of this biosensor make it possible to record both extracellular membrane potential changes and ATP release from a single taste bud cell for the first time. For detecting ATP release, LAPS chip was functionalized with ATP-sensitive DNA aptamer by covalent immobilization. Taste bud cells isolated from rat were cultured on LAPS surface. When the desired single taste bud cell was illuminated by modulated light, ATP release from single taste bud cells can be measured by recording the shifts of bias voltage-photocurrent curves (I-V curves) when the LAPS chip is working in discrete mode. On the other hand, extracellular membrane potential changes can be monitored by recording the fluctuation of LAPS photocurrent when the LAPS chip is working in continuous mode. The results show this biosensor can effectively record the enhancive effect of the bitter substance and inhibitory effect of the carbenoxolone (CBX) on the extracellular membrane potential changes and ATP release of single taste bud cells. In addition, the inhibitory effect of CBX also confirms LAPS extracellular recordings are originated from bitter signal transduction. It is proved this biosensor is suitable for extracellular recording of ATP release and membrane potential changes of single taste bud cells. It is suggested this biosensor could be applied to investigating taste signal transduction at the single-cell level as well as applied to other types of cells which have similar functions to taste bud cells. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Immunophilin ligands demonstrate common features of signal transduction leading to exocytosis or transcription.

    Science.gov (United States)

    Hultsch, T; Albers, M W; Schreiber, S L; Hohman, R J

    1991-01-01

    Investigations of the actions and interactions of the immunophilin ligands FK506, cyclosporin A (CsA), rapamycin, and 506BD suggest that complexes of FK506 with an FK506-binding protein or of CsA with a cyclophilin (CsA-binding protein) inhibit the T-cell receptor-mediated signal transduction that results in the transcription of interleukin 2. Now we report an identical spectrum of activities of FK506, CsA, rapamycin, and 506BD on IgE receptor-mediated signal transduction that results in exocytosis of secretory granules from the rat basophilic leukemia cell line RBL-2H3, a mast cell model. Both FK506 and CsA inhibit receptor-mediated exocytosis (CsA IC50 = 200 nM; FK506 IC50 = 2 nM) without affecting early receptor-associated events (hydrolysis of phosphatidylinositol, synthesis and release of eicosanoids, uptake of Ca2+). In contrast, rapamycin and 506BD, which share common structural elements with FK506, by themselves have no effect on IgE receptor-mediated exocytosis. Both compounds, however, prevent inhibition by FK506 but not by CsA. Affinity chromatography with FK506, CsA, and rapamycin matrices indicates that the same set of immunophilins present in RBL-2H3 cells have been found in Jurkat T cells and calf thymus; however, the relative amounts of these proteins differ in the two cell types. These results suggest the existence of a common step in cytoplasmic signaling in T cells and mast cells that may be part of a general signaling mechanism. Images PMID:1712484

  5. Human HOXA5 homeodomain enhances protein transduction and its application to vascular inflammation

    International Nuclear Information System (INIS)

    Lee, Ji Young; Park, Kyoung sook; Cho, Eun Jung; Joo, Hee Kyoung; Lee, Sang Ki; Lee, Sang Do; Park, Jin Bong; Chang, Seok Jong; Jeon, Byeong Hwa

    2011-01-01

    Highlights: → We have developed an E. coli protein expression vector including human specific gene sequences for protein cellular delivery. → The plasmid was generated by ligation the nucleotides 770-817 of the homeobox A5 mRNA sequence. → HOXA5-APE1/Ref-1 inhibited TNF-alpha-induced monocyte adhesion to endothelial cells. → Human HOXA5-PTD vector provides a powerful research tools for uncovering cellular functions of proteins or for the generation of human PTD-containing proteins. -- Abstract: Cellular protein delivery is an emerging technique by which exogenous recombinant proteins are delivered into mammalian cells across the membrane. We have developed an Escherichia coli expression vector including human specific gene sequences for protein cellular delivery. The plasmid was generated by ligation the nucleotides 770-817 of the homeobox A5 mRNA sequence which was matched with protein transduction domain (PTD) of homeodomain protein A5 (HOXA5) into pET expression vector. The cellular uptake of HOXA5-PTD-EGFP was detected in 1 min and its transduction reached a maximum at 1 h within cell lysates. The cellular uptake of HOXA5-EGFP at 37 o C was greater than in 4 o C. For study for the functional role of human HOXA5-PTD, we purified HOXA5-APE1/Ref-1 and applied it on monocyte adhesion. Pretreatment with HOXA5-APE1/Ref-1 (100 nM) inhibited TNF-α-induced monocyte adhesion to endothelial cells, compared with HOXA5-EGFP. Taken together, our data suggested that human HOXA5-PTD vector provides a powerful research tools for uncovering cellular functions of proteins or for the generation of human PTD-containing proteins.

  6. Multiple signal transduction pathways in okadaic acid induced apoptosis in HeLa cells

    International Nuclear Information System (INIS)

    Jayaraj, R.; Gupta, Nimesh; Rao, P.V. Lakshmana

    2009-01-01

    Okadaic acid (OA) is the major component of diarrhetic shell fish poisoning toxins and a potent inhibitor of protein phosphatase 1 and 2A. We investigated the signal transduction pathways involved in OA induced cell death in HeLa cells. OA induced cytotoxicity and apoptosis at IC50 of 100 nM. OA treatment resulted in time dependent increase in reactive oxygen species and depleted intracellular glutathione levels. Loss of mitochondrial membrane permeability led to translocation of bax, cytochrome-c and AIF from mitochondria to cytosol. The cells under fluorescence microscope showed typical apoptotic morphology with condensed chromatin, and nuclear fragmentation. We investigated the mitochondrial-mediated caspase cascade. The time dependent activation and cleavage of of bax, caspases-8, 10, 9, 3 and 7 was observed in Western blot analysis. In addition to caspase-dependent pathway AIF mediated caspase-independent pathway was involved in OA mediated cell death. OA also caused time dependent inhibition of protein phosphatase 2A activity and phosphorylation of p38 and p42/44 MAP kinases. Inhibitor studies with Ac-DEVO-CHO and Z-VAD-FMK could not prevent the phosphorylation of p38 and p42/44 MAP kinases. Our experiments with caspase inhibitors Ac-DEVD-CHO, Z-IETD-FMK and Z-VAD-FMK inhibited capsase-3, 8 cleavages but did not prevent OA-induced apoptosis and DNA fragmentation. Similarly, pretreatment with cyclosporin-A and N-acetylcysteine could not prevent the DNA fragmentation. In summary, the results of our study show that OA induces multiple signal transduction pathways acting either independently or simultaneously leading to apoptosis

  7. Evolution of multiple phosphodiesterase isoforms in stickleback involved in cAMP signal transduction pathway.

    Science.gov (United States)

    Sato, Yukuto; Hashiguchi, Yasuyuki; Nishida, Mutsumi

    2009-02-20

    Duplicate genes are considered to have evolved through the partitioning of ancestral functions among duplicates (subfunctionalization) and/or the acquisition of novel functions from a beneficial mutation (neofunctionalization). Additionally, an increase in gene dosage resulting from duplication may also confer an advantageous effect, as has been suggested for histone, tRNA, and rRNA genes. Currently, there is little understanding of the effect of increased gene dosage on subcellular networks like signal transduction pathways. Addressing this issue may provide further insights into the evolution by gene duplication. We analyzed the evolution of multiple stickleback phosphodiesterase (PDE, EC: 3.1.4.17) 1C genes involved in the cyclic nucleotide signaling pathway. Stickleback has 8-9 copies of this gene, whereas only one or two loci exist in other model vertebrates. Our phylogenetic and synteny analyses suggested that the multiple PDE1C genes in stickleback were generated by repeated duplications of >100-kbp chromosome segments. Sequence evolution analysis did not provide strong evidence for neofunctionalization in the coding sequences of stickleback PDE1C isoforms. On the other hand, gene expression analysis suggested that the derived isoforms acquired expression in new organs, implying their neofunctionalization in terms of expression patterns. In addition, at least seven isoforms of the stickleback PDE1C were co-expressed with olfactory-type G-proteins in the nose, suggesting that PDE1C dosage is increased in the stickleback olfactory transduction (OT) pathway. In silico simulations of OT implied that the increased PDE1C dosage extends the longevity of the depolarization signals of the olfactory receptor neuron. The predicted effect of the increase in PDE1C products on the OT pathway may play an important role in stickleback behavior and ecology. However, this possibility should be empirically examined. Our analyses imply that an increase in gene product sometimes

  8. Evolution of multiple phosphodiesterase isoforms in stickleback involved in cAMP signal transduction pathway

    Directory of Open Access Journals (Sweden)

    Nishida Mutsumi

    2009-02-01

    Full Text Available Abstract Background Duplicate genes are considered to have evolved through the partitioning of ancestral functions among duplicates (subfunctionalization and/or the acquisition of novel functions from a beneficial mutation (neofunctionalization. Additionally, an increase in gene dosage resulting from duplication may also confer an advantageous effect, as has been suggested for histone, tRNA, and rRNA genes. Currently, there is little understanding of the effect of increased gene dosage on subcellular networks like signal transduction pathways. Addressing this issue may provide further insights into the evolution by gene duplication. Results We analyzed the evolution of multiple stickleback phosphodiesterase (PDE, EC: 3.1.4.17 1C genes involved in the cyclic nucleotide signaling pathway. Stickleback has 8–9 copies of this gene, whereas only one or two loci exist in other model vertebrates. Our phylogenetic and synteny analyses suggested that the multiple PDE1C genes in stickleback were generated by repeated duplications of >100-kbp chromosome segments. Sequence evolution analysis did not provide strong evidence for neofunctionalization in the coding sequences of stickleback PDE1C isoforms. On the other hand, gene expression analysis suggested that the derived isoforms acquired expression in new organs, implying their neofunctionalization in terms of expression patterns. In addition, at least seven isoforms of the stickleback PDE1C were co-expressed with olfactory-type G-proteins in the nose, suggesting that PDE1C dosage is increased in the stickleback olfactory transduction (OT pathway. In silico simulations of OT implied that the increased PDE1C dosage extends the longevity of the depolarization signals of the olfactory receptor neuron. Conclusion The predicted effect of the increase in PDE1C products on the OT pathway may play an important role in stickleback behavior and ecology. However, this possibility should be empirically examined. Our

  9. MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Hong-hua; Zhang, Xi; Cao, Pei-guo [Department of Oncology, the Third Xiangya Hospital, Central South University, Changsha, Hunan Province (China)

    2011-11-18

    The matrix metalloprotease-1 (MMP-1)/protease-activated receptor-1 (PAR-1) signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC), we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9%) and 58 (68.2%) tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM) stage and regional lymph node involvement. Patients with MMP-1- and PAR-1-positive tumors, respectively, had poorer disease-free survival (DFS) than those with negative ESCC (P = 0.002 and 0.003, respectively). Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR) = 2.836, 95% confidence interval (CI) = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068), MMP-1 expression (HR = 2.669, 95%CI = 1.229-6.127), and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883) and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681), MMP-1 expression (HR = 2.109, 95%CI = 1.293-3.279), and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881) as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC.

  10. Optimization of Liquid DiElectroPhoresis (LDEP Digital Microfluidic Transduction for Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Hiroyuki Fujita

    2011-06-01

    Full Text Available Digital microfluidic has recently been under intensive study, as an effective method to carry out liquid manipulation in Lab-On-a-Chip (LOC systems. Among droplet actuation forces, ElectroWetting on Dielectric (EWOD and Liquid DiElectroPhoresis (LDEP are powerful tools, used in many LOC platforms. Such digital microfluidic transductions do not require integration of complex mechanical components such as pumps and valves to perform the fluidic operations. However, although LDEP has been proved to be efficient to carry and manipulate biological components in insulating liquids, this microfluidic transduction requires several hundreds of volts at relatively high frequencies (kHz to MHz. With the purpose to develop integrated microsystems µ-TAS (Micro Total Analysis System or Point of Care systems, the goal here is to reduce such high actuation voltage, the power consumption, though using standard dielectric materials. This paper gives key rules to determine the best tradeoff between liquid manipulation efficiency, low-power consumption and robustness of microsystems using LDEP actuation. This study leans on an electromechanical model to describe liquid manipulation that is applied to an experimental setup, and provides precise quantification of both actuation voltage Vth and frequency fc thresholds between EWOD and LDEP regimes. In particular, several parameters will be investigated to quantify Vth and fc, such as the influence of the chip materials, the electrodes size and the device configurations. Compared to current studies in the field, significant reduction of both Vth and fc is achieved by optimization of the aforementioned parameters.

  11. Comparison contemporary methods of regeneration sodium-cationic filters

    Science.gov (United States)

    Burakov, I. A.; Burakov, A. Y.; Nikitina, I. S.; Verkhovsky, A. E.; Ilyushin, A. S.; Aladushkin, S. V.

    2017-11-01

    Regeneration plays a crucial role in the field of efficient application sodium-cationic filters for softening the water. Traditionally used as regenerant saline NaCl. However, due to the modern development of the energy industry and its close relationship with other industrial and academic sectors the opportunity to use in the regeneration of other solutions. The report estimated data and application possibilities as regenerant solution sodium-cationic filters brine wells a high mineral content, as both primary application and after balneotherapeutic use reverse osmosis and concentrates especially recycled regenerant water repeated. Comparison of the effectiveness of these solutions with the traditional use of NaCl. Developed and tested system for the processing of highly mineralized brines wells after balneological use. Recommendations for use as regeneration solutions for the sodium-cationic unit considered solutions and defined rules of brine for regeneration costs.

  12. Gamma-irradiated cationic starches: Paper surface-sizing agents

    International Nuclear Information System (INIS)

    Hofreiter, B.T.; Heath, H.D.; Schulte, M.I.; Phillips, B.S.

    1981-01-01

    Cationic starches, precisely depolymerized by gamma-irradiation ( 60 Co), were dispersed in mild alkali and evaluated as surface sizes for bond paper on a pilot paper machine. The irradiated products had excellent dispersion properties, were well retained on fibers when sized wastepaper (broke) was repulped and had an ability to enhance paper properties that was comparable to that of starch-based materials used commercially. A yellow corn flour, cationized by an essentially dry reaction process recently developed at this Center, was also radiolyzed and evaluated as a size. This latter product was unique in that all drying steps were eliminated in the preparation of a cationic ceral product of reduced viscosity. (orig.) [de

  13. Nanoscale encapsulation: the structure of cations in hydrophobic microporous aluminosilicates

    International Nuclear Information System (INIS)

    Wasserman, S.R.; Yuchs, S.E.; Giaquinta, D.; Soderholm, L.; Song, Kang.

    1996-01-01

    Hydrophobic microporous aluminosilicates, created by organic surface modification of inherently hydrophilic materials such as zeolites and clays, are currently being investigated as storage media for hazardous cations. Use of organic monolayers to modify the surface of an aluminosilicate after introducing an ion into the zeolite/clay reduces the interaction of water with the material. Resulting systems are about 20 times more resistant to leaching of stored ion. XAS spectra from the encapsulated ion demonstrate that byproducts from the organic modifier can complex with the stored cation. This complexation can result in a decreased affinity of the cation for the aluminosilicate matrix. Changing the organic modifier eliminates this problem. XAS spectra also indicate that the reactivity and speciation of the encapsulated ion may change upon application of the hydrophobic layer

  14. Radical Addition to Iminium Ions and Cationic Heterocycles

    Directory of Open Access Journals (Sweden)

    Johannes Tauber

    2014-10-01

    Full Text Available Carbon-centered radicals represent highly useful reactive intermediates in organic synthesis. Their nucleophilic character is reflected by fast additions to electron deficient C=X double bonds as present in iminium ions or cationic heterocycles. This review covers diverse reactions of preformed or in situ-generated cationic substrates with various types of C-radicals, including alkyl, alkoxyalkyl, trifluoromethyl, aryl, acyl, carbamoyl, and alkoxycarbonyl species. Despite its high reactivity, the strong interaction of the radical’s SOMO with the LUMO of the cation frequently results in a high regioselectivity. Intra- and intermolecular processes such as the Minisci reaction, the Porta reaction, and the Knabe rearrangement will be discussed along with transition metal and photoredox catalysis or electrochemical methods to generate the odd-electron species.

  15. A covalent attraction between two molecular cation TTF·~+

    Institute of Scientific and Technical Information of China (English)

    WANG FangFang; WANG Yi; WANG BingQiang; WANG YinFeng; MA Fang; Li ZhiRu

    2009-01-01

    The optimized structure of the tetrathiafulvalence radical-cation dimer (TTF·~+-TTF·~+) with all-real frequencies is obtained at MP2/6-311G level,which exhibits the attraction between two molecular cation TTF·~+.The new attraction interaction is a 20-center-2-electron intermolecular covalent π/π bonding with a telescope shape.The covalent π/π bonding has the bonding energy of about-21 kcal·mol~(-1) and is concealed by the Coulombic repulsion between two TTF·~+ cations.This intermolecular covalent attraction also influences the structure of the TTF·~+ subunit,I.e.,its molecular plane is bent by an angle θ=5.6°.This work provides new knowledge on intermolecular interaction.

  16. A covalent attraction between two molecular cation TTF·~+

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The optimized structure of the tetrathiafulvalence radical-cation dimer(TTF·+-TTF·+) with all-real frequencies is obtained at MP2/6-311G level,which exhibits the attraction between two molecular cation TTF·+.The new attraction interaction is a 20-center-2-electron intermolecular covalent π /π bonding with a telescope shape.The covalent π /π bonding has the bonding energy of about -21 kcal·mol-1 and is concealed by the Coulombic repulsion between two TTF·+ cations.This intermolecular covalent attraction also influences the structure of the TTF·+ subunit,i.e.,its molecular plane is bent by an angle θ=5.6°.This work provides new knowledge on intermolecular interaction.

  17. Intracrystalline cation order in a lunar crustal troctolite

    Science.gov (United States)

    Smyth, J. R.

    1975-01-01

    Lunar sample 76535 appears to be one of the most slowly cooled bits of silicate material yet studied. It provides, therefore, a unique opportunity for the study of ordering processes in the minerals present. A better understanding of these processes may permit better characterization of the thermal history of this and similar rocks. The cation ordering in the olivine is consistent with terrestrial olivines favoring the interpretation that ordering in olivines increases with increasing temperature. In low bronzite, the deviations from the common orthopyroxene space group appear to be caused by cation order on the basis of four M sites instead of two. The degree of cation order in each of these minerals is consistent with the rock having been excavated from its depth of formation by tectonic or impact processes without being reheated above 300 C.

  18. Structure and Intramolecular Proton Transfer of Alanine Radical Cations

    International Nuclear Information System (INIS)

    Lee, Gab Yong

    2012-01-01

    The structures of the four lowest alanine conformers, along with their radical cations and the effect of ionization on the intramolecular proton transfer process, are studied using the density functional theory and MP2 method. The energy order of the radical cations of alanine differs from that of the corresponding neutral conformers due to changes in the basicity of the NH 2 group upon ionization. Ionization favors the intramolecular proton transfer process, leading to a proton-transferred radical-cation structure, [NH 3 + -CHCH 3 -COO·], which contrasts with the fact that a proton-transferred zwitterionic conformer is not stable for a neutral alanine in the gas phase. The energy barrier during the proton transfer process is calculated to be about 6 kcal/mol

  19. Cationic mobility in polystyrene sulfone exchangers - Application to the elution of a cation on an exchange column

    International Nuclear Information System (INIS)

    Menin, Jean-Pierre

    1969-01-01

    The aim of this work is to improve elutions and separations carried out on inorganic exchangers by selective electromigration of the ionic species to be displaced. To do this, it has been found indispensable to make a fundamental study of the mobility of cations in exchangers. As the field for this research we have chosen those organic exchangers whose structure and behaviour with respect to ion-exchange are much better known that in the case of their inorganic equivalents. We have related the idea of the equivalent conductivity to that of the cation mobility in the exchanger, and this has entailed determining the specific conductivity of the exchanger and the cation concentration in the resin. The results obtained have allowed us to draw up a hypothesis concerning the cation migration mechanism in the exchanger. The third part of our work has been the application of the preceding results to an operation on an ion-exchange column, viz. the elution by an acid solution of a single fixed ion, magnesium or strontium. This work has enabled us to show that the electromigration of a cation during its elution can markedly accelerate or retard this elution. (author) [fr

  20. Effect of cation exchange of major cation chemistry in the large scale redox experiment at Aespoe. Revision 1

    International Nuclear Information System (INIS)

    Viani, B.E.; Bruton, C.J.

    1996-06-01

    Geochemical modeling was used to test the hypothesis that cation exchange with fracture-lining clays during fluid mixing in the Aespoe Hard Rock Laboratory can significantly affect major element chemistry. Conservative mixing models do not adequately account for changes in Na, Ca and Mg concentrations during mixing. Mixing between relatively dilute shallow waters and more concentrated waters at depth along fracture zones was modeled using the EQ3/6 geochemical modeling package. A cation exchange model was added to the code to describe simultaneously aqueous speciation, mineral precipitation/dissolution, and equilibration between a fluid and a cation exchanger. Fluid chemistries predicted to result from mixing were compared with those monitored from boreholes intersecting the fracture zone. Modeling results suggest that less than 0.1 equivalent of a smectite exchanger per liter of groundwater is necessary to account for discrepancies between predictions from a conservative mixing model and measured Na and Ca concentrations. This quantity of exchanger equates to an effective fracture coating thickness of 20 microm or less given a fracture aperture width of 1,000 microm or less. Trends in cation ratios in the fluid cannot be used to predict trends in cation ratios on the exchanger because of the influence of ionic strength on heterovalent exchange equilibrium. It is expected that Na for Ca exchange will dominate when shallow waters such as HBHO2 are mixed with deeper waters. In contrast, Na for Mg exchange will dominate mixing between deeper waters