EST2Prot: Mapping EST sequences to proteins

Directory of Open Access Journals (Sweden)

Lin David M

2006-03-01

Full Text Available Abstract Background EST libraries are used in various biological studies, from microarray experiments to proteomic and genetic screens. These libraries usually contain many uncharacterized ESTs that are typically ignored since they cannot be mapped to known genes. Consequently, new discoveries are possibly overlooked. Results We describe a system (EST2Prot that uses multiple elements to map EST sequences to their corresponding protein products. EST2Prot uses UniGene clusters, substring analysis, information about protein coding regions in existing DNA sequences and protein database searches to detect protein products related to a query EST sequence. Gene Ontology terms, Swiss-Prot keywords, and protein similarity data are used to map the ESTs to functional descriptors. Conclusion EST2Prot extends and significantly enriches the popular UniGene mapping by utilizing multiple relations between known biological entities. It produces a mapping between ESTs and proteins in real-time through a simple web-interface. The system is part of the Biozon database and is accessible at http://biozon.org/tools/est/.

UniProtKB amid the turmoil of plant proteomics research

Directory of Open Access Journals (Sweden)

Michel eSchneider

2012-12-01

Full Text Available The UniProt knowledgebase (UniProtKB provides a single, centralized, authoritative resource for protein sequences and functional information. The majority of its records is based on automatic translation of coding sequences (CDS provided by submitters at the time of initial deposition to the nucleotide sequence databases (INSDC. More and more frequently, only the raw sequence of a complete genome is deposited to the nucleotide sequence databases and the gene model predictions and annotations are kept in separate, specialized model organism databases (MODs. In order to be able to provide the complete proteome of model organisms, UniProtKB had to implement pipelines for import of protein sequences from Ensembl and EnsemblGenomes.A single genome can be the target of several unrelated sequencing projects and the final assembly and gene model predictions may diverge quite significantly. In addition, several cultivars of the same species are often sequenced -1001 Arabidopsis cultivars are currently under way- and the resulting proteomes are far from being identical. Therefore, one challenge for UniProtKB is to store and organize these data in a convenient way and to clearly defined reference proteomes that should be made available to users. Manual annotation is one of the landmarks of the Swiss-Prot section of UniProtKB. Besides adding functional annotation, curators are checking, and often correcting, gene model predictions. For plants, this task is limited to Arabidopsis thaliana and Oryza sativa subsp japonica. Proteomics data providing experimental evidences confirming the existence of proteins or identifying sequence features such as post translational modifications are also imported into UniProtKB records and the knowledgebase is cross-referenced to numerous proteomics resources.

Organisation and standardisation of information in SWISS-PROT and TrEMBL

Directory of Open Access Journals (Sweden)

Michele Magrane

2006-01-01

Full Text Available SWISS-PROT is a curated, non-redundant protein sequence database which provides a high level of annotation and is integrated with a large number of other biological databases. It is supplemented by TrEMBL, a computer-annotated database which contains translations of all coding sequences in the EMBL Nucleotide Sequence Database which are not yet in SWISS-PROT. Each fully curated SWISS-PROT entry contains as much up-to-date information as possible from a variety of sources and the high quality of the annotation in SWISS-PROT provides the basis for the procedure which is used to automatically annotate the TrEMBL database. The large amounts of different data types found in both databases are stored in a highly structured and uniform manner and this structured organisation means that SWISS-PROT and TrEMBL together provide a comprehensive resource with data that are readily accessible for users and easily retrievable by computer programs.

48 CFR 1852.219-77 - NASA Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true NASA Mentor-ProtégÃ... and Clauses 1852.219-77 NASA Mentor-Protégé Program. As prescribed in 1819.7215, insert the following clause: NASA Mentor-Protégé Program (MAY 2009) (a) Prime contractors are encouraged to participate in the...

48 CFR 752.219-70 - USAID Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false USAID Mentor-ProtégÃ....219-70 USAID Mentor-Protégé Program. As prescribed in 719.273-11(a), insert the following provision: USAID Mentor-Protégé Program (July 13, 2007) (a) Large and small business are encouraged to participate...

48 CFR 552.219-75 - GSA Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false GSA Mentor-ProtégÃ....219-75 GSA Mentor-Protégé Program. As prescribed in 519.7017(a), insert the following clause: GSA Mentor-ProtéGé Program (SEP 2009) (a) Prime contractors, including small businesses, are encouraged to...

enDNA-Prot: Identification of DNA-Binding Proteins by Applying Ensemble Learning

Directory of Open Access Journals (Sweden)

Ruifeng Xu

2014-01-01

Full Text Available DNA-binding proteins are crucial for various cellular processes, such as recognition of specific nucleotide, regulation of transcription, and regulation of gene expression. Developing an effective model for identifying DNA-binding proteins is an urgent research problem. Up to now, many methods have been proposed, but most of them focus on only one classifier and cannot make full use of the large number of negative samples to improve predicting performance. This study proposed a predictor called enDNA-Prot for DNA-binding protein identification by employing the ensemble learning technique. Experiential results showed that enDNA-Prot was comparable with DNA-Prot and outperformed DNAbinder and iDNA-Prot with performance improvement in the range of 3.97–9.52% in ACC and 0.08–0.19 in MCC. Furthermore, when the benchmark dataset was expanded with negative samples, the performance of enDNA-Prot outperformed the three existing methods by 2.83–16.63% in terms of ACC and 0.02–0.16 in terms of MCC. It indicated that enDNA-Prot is an effective method for DNA-binding protein identification and expanding training dataset with negative samples can improve its performance. For the convenience of the vast majority of experimental scientists, we developed a user-friendly web-server for enDNA-Prot which is freely accessible to the public.

48 CFR 719.273-9 - Obligations under the Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... Mentor-Protégé Program. 719.273-9 Section 719.273-9 Federal Acquisition Regulations System AGENCY FOR... Development (USAID) Mentor-Protégé Program 719.273-9 Obligations under the Mentor-Protégé Program. (a) A Mentor or Protégé may voluntarily withdraw from the Program. However, in no event shall such withdrawal...

48 CFR 3052.219-71 - DHS mentor-protégé program.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false DHS mentor-protégÃ... CONTRACT CLAUSES Text of Provisions and Clauses 3052.219-71 DHS mentor-protégé program. As prescribed in (HSAR) 48 CFR 3019.708-70(b), insert the following clause: DHS Mentor-Protégé Program (JUN 2006) (a...

Membrane Transporters as Mediators of Cisplatin Effects and Side Effects

Directory of Open Access Journals (Sweden)

Giuliano Ciarimboli

2012-01-01

Full Text Available Transporters are important mediators of specific cellular uptake and thus, not only for effects, but also for side effects, metabolism, and excretion of many drugs such as cisplatin. Cisplatin is a potent cytostatic drug, whose use is limited by its severe acute and chronic nephro-, oto-, and peripheral neurotoxicity. For this reason, other platinum derivatives, such as carboplatin and oxaliplatin, with less toxicity but still with antitumoral action have been developed. Several transporters, which are expressed on the cell membranes, have been associated with cisplatin transport across the plasma membrane and across the cell: the copper transporter 1 (Ctr1, the copper transporter 2 (Ctr2, the P-type copper-transporting ATPases ATP7A and ATP7B, the organic cation transporter 2 (OCT2, and the multidrug extrusion transporter 1 (MATE1. Some of these transporters are also able to accept other platinum derivatives as substrate. Since membrane transporters display a specific tissue distribution, they can be important molecules that mediate the entry of platinum derivatives in target and also nontarget cells possibly mediating specific effects and side effects of the chemotherapeutic drug. This paper summarizes the literature on toxicities of cisplatin compared to that of carboplatin and oxaliplatin and the interaction of these platinum derivatives with membrane transporters.

A mentor-protégé program for new faculty, Part II: Stories of mentors.

Science.gov (United States)

Wilson, Carol B; Brannan, Jane; White, Anne

2010-12-01

Mentorship has been identified as an influential factor in retaining new nursing faculty. A mentor-protégé program for novice faculty was implemented to promote development of the protégés in their role as nurse educators. A qualitative research study conducted to illuminate the meaning of experiences of mentors led to the emergence of four patterns: The Significance of the Mentor-Protégé Relationship, Communication as Important Between Mentor and Protégé, The Mentor-Protégé Program-Protégé's Perspectives, and The Mentoring Role as Expert Educator. The data from the study support the significance of providing mentorship to novice or new nurse educators. The data suggest that mentors benefit from participation in a mentor-protégé program as much as the protégés. Similar programs are needed in nursing if we are to mentor and encourage faculty to begin and remain in the role of educators to combat the future nurse educator shortage. Copyright 2010, SLACK Incorporated.

ChemProt-3.0: a global chemical biology diseases mapping

DEFF Research Database (Denmark)

Kringelum, Jens Vindahl; Kjærulff, Sonny Kim; Brunak, Søren

2016-01-01

ChemProt is a publicly available compilation of chemical-protein-disease annotation resources that enables the study of systems pharmacology for a small molecule across multiple layers of complexity from molecular to clinical levels. In this third version, ChemProt has been updated to more than 1...

Water Transport Mediated by Other Membrane Proteins.

Science.gov (United States)

Huang, Boyue; Wang, Hongkai; Yang, Baoxue

2017-01-01

Water transport through membrane is so intricate that there are still some debates. (Aquaporins) AQPs are entirely accepted to allow water transmembrane movement depending on osmotic gradient. Cotransporters and uniporters , however, are also concerned in water homeotatsis. Urea transporter B (UT-B) has a single-channel water permeability that is similar to AQP1. Cystic fibrosis transmembrane conductance regulator (CFTR ) was initially thought as a water channel but now not believed to transport water directly. By cotranporters, water is transported by water osmosis coupling with substrates, which explains how water is transported across the isolated small intestine. This chapter provides information about water transport mediated by other membrane proteins except AQPs .

48 CFR 352.219-71 - Mentor-protégé program reporting requirements.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Mentor-protégé program... Clauses 352.219-71 Mentor-protégé program reporting requirements. As prescribed in 319.270-1(b), the Contracting Officer shall insert the following clause: Mentor-Protégé Program Reporting Requirements (January...

Protein sequence annotation in the genome era: the annotation concept of SWISS-PROT+TREMBL.

Science.gov (United States)

Apweiler, R; Gateau, A; Contrino, S; Martin, M J; Junker, V; O'Donovan, C; Lang, F; Mitaritonna, N; Kappus, S; Bairoch, A

1997-01-01

SWISS-PROT is a curated protein sequence database which strives to provide a high level of annotation, a minimal level of redundancy and high level of integration with other databases. Ongoing genome sequencing projects have dramatically increased the number of protein sequences to be incorporated into SWISS-PROT. Since we do not want to dilute the quality standards of SWISS-PROT by incorporating sequences without proper sequence analysis and annotation, we cannot speed up the incorporation of new incoming data indefinitely. However, as we also want to make the sequences available as fast as possible, we introduced TREMBL (TRanslation of EMBL nucleotide sequence database), a supplement to SWISS-PROT. TREMBL consists of computer-annotated entries in SWISS-PROT format derived from the translation of all coding sequences (CDS) in the EMBL nucleotide sequence database, except for CDS already included in SWISS-PROT. While TREMBL is already of immense value, its computer-generated annotation does not match the quality of SWISS-PROTs. The main difference is in the protein functional information attached to sequences. With this in mind, we are dedicating substantial effort to develop and apply computer methods to enhance the functional information attached to TREMBL entries.

Fermi arc mediated entropy transport in topological semimetals

Science.gov (United States)

McCormick, Timothy M.; Watzman, Sarah J.; Heremans, Joseph P.; Trivedi, Nandini

2018-05-01

The low-energy excitations of topological Weyl semimetals are composed of linearly dispersing Weyl fermions that act as monopoles of Berry curvature in the bulk momentum space. Furthermore, on the surface there exist topologically protected Fermi arcs at the projections of these Weyl points. We propose a pathway for entropy transport involving Fermi arcs on one surface connecting to Fermi arcs on the other surface via the bulk Weyl monopoles. We present results for the temperature and magnetic field dependence of the magnetothermal conductance of this conveyor belt channel. The circulating currents result in a net entropy transport without any net charge transport. We provide results for the Fermi arc mediated magnetothermal conductivity in the low-field semiclassical limit as well as in the high-field ultraquantum limit, where only chiral Landau levels are involved. Our work provides a proposed signature of Fermi arc mediated magnetothermal transport and sets the stage for utilizing and manipulating the topological Fermi arcs in thermal applications.

Interactivity between protégés and scientists in an electronic mentoring program

DEFF Research Database (Denmark)

Bonnett, Cara; Wildemuth, Barbara M.; Sonnenwald, Diane H.

2006-01-01

Interactivity is defined by Henri (1992) as a three-step process involving communication of information, a response to this information, and a reply to that first response. It is a key dimension of computer-mediated communication, particularly in the one-on-one communication involved in an electr...... for successful interaction. Not only are there a variety of factors at play in developing an online relationship in this context, but mentor-protégé pairs can falter at various stages in the process and in various ways.......Interactivity is defined by Henri (1992) as a three-step process involving communication of information, a response to this information, and a reply to that first response. It is a key dimension of computer-mediated communication, particularly in the one-on-one communication involved...

48 CFR 719.273-4 - Eligibility of Mentor and Protégé firms.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Eligibility of Mentor and... Development (USAID) Mentor-Protégé Program 719.273-4 Eligibility of Mentor and Protégé firms. Eligible business entities approved as Mentors may enter into agreements (hereafter referred to as “Mentor-Protégé...

DeltaProt: a software toolbox for comparative genomics

Directory of Open Access Journals (Sweden)

Willassen Nils P

2010-11-01

Full Text Available Abstract Background Statistical bioinformatics is the study of biological data sets obtained by new micro-technologies by means of proper statistical methods. For a better understanding of environmental adaptations of proteins, orthologous sequences from different habitats may be explored and compared. The main goal of the DeltaProt Toolbox is to provide users with important functionality that is needed for comparative screening and studies of extremophile proteins and protein classes. Visualization of the data sets is also the focus of this article, since visualizations can play a key role in making the various relationships transparent. This application paper is intended to inform the reader of the existence, functionality, and applicability of the toolbox. Results We present the DeltaProt Toolbox, a software toolbox that may be useful in importing, analyzing and visualizing data from multiple alignments of proteins. The toolbox has been written in MATLAB™ to provide an easy and user-friendly platform, including a graphical user interface, while ensuring good numerical performance. Problems in genome biology may be easily stated thanks to a compact input format. The toolbox also offers the possibility of utilizing structural information from the SABLE or other structure predictors. Different sequence plots can then be viewed and compared in order to find their similarities and differences. Detailed statistics are also calculated during the procedure. Conclusions The DeltaProt package is open source and freely available for academic, non-commercial use. The latest version of DeltaProt can be obtained from http://services.cbu.uib.no/software/deltaprot/. The website also contains documentation, and the toolbox comes with real data sets that are intended for training in applying the models to carry out bioinformatical and statistical analyses of protein sequences. Equipped with the new algorithms proposed here, DeltaProt serves as an auxiliary

48 CFR 1019.202-70-8 - Protégé firms.

Science.gov (United States)

2010-10-01

... multiple mentors unless approved, in writing, by the Director, Office of Small Business Development (OSBD... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 1019.202-70-8 Protégé firms. (a) For selection as a protégé, a firm must be: (1) A small business, women-owned small business, small disadvantaged business...

48 CFR 1052.219-73 - Department of the Treasury Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... Mentor-Protégé Program. 1052.219-73 Section 1052.219-73 Federal Acquisition Regulations System... and Clauses 1052.219-73 Department of the Treasury Mentor-Protégé Program. As described in DTAR 1019.202-70, insert the following provision: Department of the Treasury Mentor-Protégé Program (JAN 2000...

ChemProt-2.0: visual navigation in a disease chemical biology database

DEFF Research Database (Denmark)

Kjærulff, Sonny Kim; Wich, Louis; Kringelum, Jens Vindahl

2013-01-01

ChemProt-2.0 (http://www.cbs.dtu.dk/services/ChemProt-2.0) is a public available compilation of multiple chemical-protein annotation resources integrated with diseases and clinical outcomes information. The database has been updated to > 1.15 million compounds with 5.32 millions bioactivity measu...

48 CFR 619.202-70 - The Department of State Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... Mentor-Protégé Program. 619.202-70 Section 619.202-70 Federal Acquisition Regulations System DEPARTMENT... Mentor-Protégé Program. (a) Purpose. The Mentor-Protégé Program is designed to motivate and encourage... service-disabled veteran-owned small business (SDVOSB) are the same as found in FAR 2.101. Mentor means a...

MultitaskProtDB: a database of multitasking proteins.

Science.gov (United States)

Hernández, Sergio; Ferragut, Gabriela; Amela, Isaac; Perez-Pons, JosepAntoni; Piñol, Jaume; Mozo-Villarias, Angel; Cedano, Juan; Querol, Enrique

2014-01-01

We have compiled MultitaskProtDB, available online at http://wallace.uab.es/multitask, to provide a repository where the many multitasking proteins found in the literature can be stored. Multitasking or moonlighting is the capability of some proteins to execute two or more biological functions. Usually, multitasking proteins are experimentally revealed by serendipity. This ability of proteins to perform multitasking functions helps us to understand one of the ways used by cells to perform many complex functions with a limited number of genes. Even so, the study of this phenomenon is complex because, among other things, there is no database of moonlighting proteins. The existence of such a tool facilitates the collection and dissemination of these important data. This work reports the database, MultitaskProtDB, which is designed as a friendly user web page containing >288 multitasking proteins with their NCBI and UniProt accession numbers, canonical and additional biological functions, monomeric/oligomeric states, PDB codes when available and bibliographic references. This database also serves to gain insight into some characteristics of multitasking proteins such as frequencies of the different pairs of functions, phylogenetic conservation and so forth.

The SWISS-PROT protein sequence data bank

OpenAIRE

Bairoch, Amos; Boeckmann, Brigitte

1992-01-01

SWISS-PROT is an annotated protein sequence database established in 1986 and maintained collaboratively, since 1988, by the Department of Medical Biochemistry of the University of Geneva and the EMBL Data Library

FireProt: web server for automated design of thermostable proteins

Science.gov (United States)

Musil, Milos; Stourac, Jan; Brezovsky, Jan; Prokop, Zbynek; Zendulka, Jaroslav; Martinek, Tomas

2017-01-01

Abstract There is a continuous interest in increasing proteins stability to enhance their usability in numerous biomedical and biotechnological applications. A number of in silico tools for the prediction of the effect of mutations on protein stability have been developed recently. However, only single-point mutations with a small effect on protein stability are typically predicted with the existing tools and have to be followed by laborious protein expression, purification, and characterization. Here, we present FireProt, a web server for the automated design of multiple-point thermostable mutant proteins that combines structural and evolutionary information in its calculation core. FireProt utilizes sixteen tools and three protein engineering strategies for making reliable protein designs. The server is complemented with interactive, easy-to-use interface that allows users to directly analyze and optionally modify designed thermostable mutants. FireProt is freely available at http://loschmidt.chemi.muni.cz/fireprot. PMID:28449074

Genes and proteins of Escherichia coli (GenProtEc).

Science.gov (United States)

Riley, M; Space, D B

1996-01-01

GenProtEc is a database of Escherichia coli genes and their gene products, classified by type of function and physiological role and with citations to the literature for each. Also present are data on sequence similarities among E.coli proteins with PAM values, percent identity of amino acids, length of alignment and percent aligned. The database is available as a PKZip file by ftp from mbl.edu/pub/ecoli.exe. The program runs under MS-DOS on IMB-compatible machines. GenProtEc can also be accessed through the World Wide Web at URL http://mbl.edu/html/ecoli.html.

Avaliação da qualidade protéica de dois suplementos alimentares em ratos Wistar

Directory of Open Access Journals (Sweden)

M. M. V. NAVES

2008-10-01

Full Text Available

O objetivo da pesquisa foi avaliar a qualidade protéica de dois suplementos alimentares - um, formulado protéico em pó (produto em fase de teste e gelatina. Seis grupos de seis ratos machos Wistar recém-desmamados foram alimentados durante catorze dias com as seguintes dietas: controle (C10 - caseína, formulado protéico (FP10 e gelatina (G10 ao nível de 10 % de proteína; misturas de caseíma com formulado protéico (C7 FP3 ou gelatina (C7G3 (7:3 em base protéica, respectivamente; e dieta aprotéica. As dietas contendo o formulado protéico apresentaram boa qualidade protéica, segundo os índices NPR (Net Protein Ratio e NPU (Net Protein Utilization, sem diferenças significativas entre C7 FP3 e C10 (NPR= 4,00 e 4,11, e NPU= 65% e 67%, respectivamente. Os animais alimentados com gelatina (G10 e com dieta aprotéica perderam peso corpóreo e apresentaram pesos semelhantes dos fígados e inferiores aos dos demais grupos de ratos. O valor protéico da mistura caseína-gelatina (C7G3 foi menor que o da caseína (NPR relativo= 77 %, p<0,05. O formulado protéico constitui uma fonte de proteína de boa qualidade e seu uso como suplemento alimentar pode ser indicado em situações especiais. A gelatina, por sua vez, não pode ser considerada um complemento ou suplemento nutricional, pois não atende às necessidades protéicas do organismo e pode prejudicar a disponibilidade biológica de proteínas de boa qualidade.

Genes and proteins of Escherichia coli K-12 (GenProtEC).

Science.gov (United States)

Riley, M

1997-01-01

GenProtEC is a database of Escherichia coli genes and their gene products, classified by type of function and physiological role and with citations to the literature for each. Also present are data on sequence similarities amongE.coliproteins with PAM values, percent identity of amino acids, length of alignment and percent aligned. GenProtEC can also be accessed through the World Wide Web at URL http://mbl.edu/html/ecoli.html .

ChemProt-3.0: a global chemical biology diseases mapping

DEFF Research Database (Denmark)

Kringelum, Jens Vindahl; Kjærulff, Sonny Kim; Brunak, Søren

2016-01-01

ChemProt is a publicly available compilation of chemical-protein-disease annotation resources that enables the study of systems pharmacology for a small molecule across multiple layers of complexity from molecular to clinical levels. In this third version, ChemProt has been updated to more than 1...... properties. In addition, the user has the possibility to search by compound, target, pathway, disease and clinical effect. Genetic variations associated to target proteins were integrated, making it possible to plan pharmacogenetic studies and to suggest human response variability to drug. Finally...

48 CFR 819.7106 - Eligibility of Mentor and Protégé firms.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Eligibility of Mentor and... VETERANS AFFAIRS SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS VA Mentor-Protégé Program 819.7106 Eligibility of Mentor and Protégé firms. Eligible business entities approved as mentors may enter into...

48 CFR 719.273 - The U.S. Agency for International Development (USAID) Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... International Development (USAID) Mentor-Protégé Program. 719.273 Section 719.273 Federal Acquisition.... Agency for International Development (USAID) Mentor-Protégé Program 719.273 The U.S. Agency for International Development (USAID) Mentor-Protégé Program. ...

Transporter-mediated natural product–drug interactions for the treatment of cardiovascular diseases

Directory of Open Access Journals (Sweden)

Weibin Zha

2018-04-01

Full Text Available The growing use of natural products in cardiovascular (CV patients has been greatly raising the concerns about potential natural product–CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product–CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product–drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins have been identified to be substrates and inhibitors of the solute carrier (SLC transporters and the ATP-binding cassette (ABC transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product–CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product–CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product–CV drug interactions and help public and physicians understand these type of interactions. Keywords: Cardiovascular drugs, Natural products, Drug transporters, Natural product–drug interaction, Pharmacokinetics

Turgor-mediated transport of sugars

International Nuclear Information System (INIS)

Daie, J.

1986-01-01

Membrane associated processes have been suggested to be modulated by cellular turgor. The nature of this regulation is not, however, clearly understood. Evidence is presented that active but not passive transport of sugars is turgor regulated. Isolated phloem tissue, vascular bundles or storage parenchyma of celery were incubated in buffered solutions adjusted to 100, 200 or 400 m osmolal that contained various concentrations of 14 C-sugars. Cellular turgor was manipulated by using the non-permeating PEG (3350). Saturating carrier-mediated sucrose transport which is present only in phloem-containing tissue was enhanced under low turgor conditions. Sucrose diffusion, the predominant mode of uptake in non-phloem parenchyma tissue was not affected by cellular turgor. Furthermore, GA and IAA seem to interact with cellular turgor to bring about modified rates of sucrose uptake. The data are consistent with observations that sucrose loading is enhanced under mild water deficit conditions

Transporter-mediated natural product-drug interactions for the treatment of cardiovascular diseases.

Science.gov (United States)

Zha, Weibin

2018-04-01

The growing use of natural products in cardiovascular (CV) patients has been greatly raising the concerns about potential natural product-CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product-CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product-drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins) have been identified to be substrates and inhibitors of the solute carrier (SLC) transporters and the ATP-binding cassette (ABC) transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients) are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product-CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product-CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product-CV drug interactions and help public and physicians understand these type of interactions. Copyright © 2017. Published by Elsevier B.V.

Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins

NARCIS (Netherlands)

Neumann, S.

2008-01-01

Proteins mediating intra- and intercellular transport of lipids and lipid-modified proteins In this thesis, I studied the intra- and intercellular transport of lipidic molecules, in particular glycosphingolipids and lipid-modified proteins. The first part focuses on the intracellular transport of

Infrastructure for the life sciences: design and implementation of the UniProt website.

Science.gov (United States)

Jain, Eric; Bairoch, Amos; Duvaud, Severine; Phan, Isabelle; Redaschi, Nicole; Suzek, Baris E; Martin, Maria J; McGarvey, Peter; Gasteiger, Elisabeth

2009-05-08

The UniProt consortium was formed in 2002 by groups from the Swiss Institute of Bioinformatics (SIB), the European Bioinformatics Institute (EBI) and the Protein Information Resource (PIR) at Georgetown University, and soon afterwards the website http://www.uniprot.org was set up as a central entry point to UniProt resources. Requests to this address were redirected to one of the three organisations' websites. While these sites shared a set of static pages with general information about UniProt, their pages for searching and viewing data were different. To provide users with a consistent view and to cut the cost of maintaining three separate sites, the consortium decided to develop a common website for UniProt. Following several years of intense development and a year of public beta testing, the http://www.uniprot.org domain was switched to the newly developed site described in this paper in July 2008. The UniProt consortium is the main provider of protein sequence and annotation data for much of the life sciences community. The http://www.uniprot.org website is the primary access point to this data and to documentation and basic tools for the data. These tools include full text and field-based text search, similarity search, multiple sequence alignment, batch retrieval and database identifier mapping. This paper discusses the design and implementation of the new website, which was released in July 2008, and shows how it improves data access for users with different levels of experience, as well as to machines for programmatic access.http://www.uniprot.org/ is open for both academic and commercial use. The site was built with open source tools and libraries. Feedback is very welcome and should be sent to help@uniprot.org. The new UniProt website makes accessing and understanding UniProt easier than ever. The two main lessons learned are that getting the basics right for such a data provider website has huge benefits, but is not trivial and easy to underestimate

Infrastructure for the life sciences: design and implementation of the UniProt website

Directory of Open Access Journals (Sweden)

Suzek Baris E

2009-05-01

Full Text Available Abstract Background The UniProt consortium was formed in 2002 by groups from the Swiss Institute of Bioinformatics (SIB, the European Bioinformatics Institute (EBI and the Protein Information Resource (PIR at Georgetown University, and soon afterwards the website http://www.uniprot.org was set up as a central entry point to UniProt resources. Requests to this address were redirected to one of the three organisations' websites. While these sites shared a set of static pages with general information about UniProt, their pages for searching and viewing data were different. To provide users with a consistent view and to cut the cost of maintaining three separate sites, the consortium decided to develop a common website for UniProt. Following several years of intense development and a year of public beta testing, the http://www.uniprot.org domain was switched to the newly developed site described in this paper in July 2008. Description The UniProt consortium is the main provider of protein sequence and annotation data for much of the life sciences community. The http://www.uniprot.org website is the primary access point to this data and to documentation and basic tools for the data. These tools include full text and field-based text search, similarity search, multiple sequence alignment, batch retrieval and database identifier mapping. This paper discusses the design and implementation of the new website, which was released in July 2008, and shows how it improves data access for users with different levels of experience, as well as to machines for programmatic access. http://www.uniprot.org/ is open for both academic and commercial use. The site was built with open source tools and libraries. Feedback is very welcome and should be sent to help@uniprot.org. Conclusion The new UniProt website makes accessing and understanding UniProt easier than ever. The two main lessons learned are that getting the basics right for such a data provider website has

Protótipo do primeiro interferômetro brasileiro - BDA

Science.gov (United States)

Cecatto, J. R.; Fernandes, F. C. R.; Neri, J. A. C. F.; Bethi, N.; Felipini, N. S.; Madsen, F. R. H.; Andrade, M. C.; Soares, A. C.; Alonso, E. M. B., Sawant, H. S.

2004-04-01

A interferometria é uma poderosa ferramenta usada para investigar estruturas espaciais de fontes astrofísicas fornecendo uma riqueza de detalhes inatingível pelas técnicas convencionais de imageamento. Em particular, a interferometria com ondas de rádio abre o horizonte de conhecimento do Universo nesta ampla banda do espectro eletromagnético, que vai de cerca de 20 kHz até centenas de GHz já próximo ao infravermelho, e que está acessível a partir de instrumentos instalados em solo. Neste trabalho, apresentamos o interferômetro designado por Arranjo Decimétrico Brasileiro (BDA). Trata-se do primeiro interferômetro a ser desenvolvido no Brasil e América Latina que já está em operação na fase de protótipo. Apresentamos o desenvolvimento realizado até o momento, o sítio de instalação do instrumento, o protótipo e os principais resultados dos testes de sua operação, as perspectivas futuras e a ciência a ser desenvolvida com o instrumento nas fases II e III. Neste trabalho é dada ênfase ao desenvolvimento, testes de operação e principais resultados do protótipo. É discutida brevemente a ciência que pode ser feita com o instrumento. Tanto os detalhes técnicos quanto os principais parâmetros estimados para o instrumento nas próximas fases de desenvolvimento e o desempenho do protótipo serão publicados em breve.

Comparison of the Impacts of Telementoring Services on Protégés’ Academic Achievements and Opinions

Directory of Open Access Journals (Sweden)

Necmi Eşgi

2011-04-01

Full Text Available The aim of the research is to compare the impacts of telementoring services, delivered using chat with video, chat with instant message, mobile phone, discussion board and video conference on protégés’ academic achievements and opinions. Telementoring services, made up with five different instruments, were administered to a group of protégés, composed of 38 university students. In the research, the multiple-choice achievement test, which consisted of twenty-four 4point Likert items, was utilized in order to determine protégés’ academic achievements. On the other hand, protégés’ opinions were determined through open-ended questions. The research findings demonstrated that telementoring services formed through using different instruments do not significantly differentiate student achievements between groups. Moreover, positive and negative characteristics regarding the communication instruments used were defined based on protégés’ opinions

Comparison of the Impacts of Telementoring Services on Protégés' Academic Achievements and Opinions

Directory of Open Access Journals (Sweden)

Necmi Eşgi

2011-10-01

Full Text Available The aim of the research is to compare the impacts of telementoring services, delivered using chat with video, chat with instant message, mobile phone, discussion board and video conference on protégés’ academic achievements and opinions. Telementoring services, made up with five different instruments, were administered to a group of protégés, composed of 38 university students. In the research, the multiple-choice achievement test, which consisted of twenty-four 4-point Likert items, was utilized in order to determine protégés’ academic achievements. On the other hand, protégés’ opinions were determined through open-ended questions. The research findings demonstrated that telementoring services formed through using different instruments do not significantly differentiate student achievements between groups. Moreover, positive and negative characteristics regarding the communication instruments used were defined based on protégés’ opinions.

48 CFR 852.219-72 - Evaluation factor for participation in the VA mentor-protégé program.

Science.gov (United States)

2010-10-01

... participation in the VA mentor-protégé program. 852.219-72 Section 852.219-72 Federal Acquisition Regulations... Texts of Provisions and Clauses 852.219-72 Evaluation factor for participation in the VA mentor-protégé... the VA Mentor-Protégé Program (DEC2009) This solicitation contains an evaluation factor or sub-factor...

In it for the long-term: defining the mentor-protégé relationship in a clinical research training program.

Science.gov (United States)

Santoro, Nanette; McGinn, Aileen P; Cohen, Hillel W; Kaskel, Frederick; Marantz, Paul R; Mulvihill, Michael; Schoenbaum, Ellie

2010-06-01

To define the characteristics of effective mentor-protégé relationships in a Clinical Research Training Program (CRTP) and to assess the agreement among mentors and protégés regarding those attributes. The authors administered an anonymous survey to protégés who completed the Albert Einstein College of Medicine's CRTP during its first seven years (2000-2006) and their mentors. Statements included aspects of mentoring thought to be important within the program, such as availability (Statement 1) and oversight of the thesis process (Statements 2-4). Additional statements were related both to career development (e.g., looking out for the best interests of the scholar and assisting in negotiations for a faculty position after program completion [Statements 5 and 6]) and to the expectation that the mentor would continue to be a resource for the protégé in years to come (Statement 7). The authors assessed overall agreement among mentors and protégés, using matched pair analysis. Overall response was 70.7% (133/188), with fewer matched pairs (n = 50, 50%). Seventy-five percent of respondents agreed strongly or somewhat with all statements. Analysis indicated significant agreement with Statements 2, 4, 6, and 7. Median scores from protégés did not differ whether their mentor responded (paired) or not (unpaired); however, mentor-protégé pairs had significantly greater agreement with Statements 3-7 than unpaired mentors and protégés (P Mentors and protégés seemed to agree that mentors within a CRTP demonstrated effective mentor attributes, including fostering a long-term relationship with the protégé.

48 CFR 652.219-72 - Department of State Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Department of State Mentor....219-72 Department of State Mentor-Protégé Program. As prescribed in 619.202-70(o)(1), insert the following provision: Department of State Mentor-Protégé Program (APR 2004) (a) Large and small businesses...

76 FR 1658 - 60-Day Notice of Proposed Information Collection: DS 4053, Department of State Mentor-Protégé...

Science.gov (United States)

2011-01-11

... 4053, Department of State Mentor-Prot[eacute]g[eacute] Program Application, OMB 1405-0161 ACTION... Collection: Department of State Mentor-Prot[eacute]g[eacute] Program Application. OMB Control Number: OMB...: Small and large for-profit companies planning to team together in an official mentor-prot[eacute]g...

48 CFR 3052.219-72 - Evaluation of prime contractor participation in the DHS mentor-protégé program.

Science.gov (United States)

2010-10-01

... contractor participation in the DHS mentor-protégé program. 3052.219-72 Section 3052.219-72 Federal... Evaluation of prime contractor participation in the DHS mentor-protégé program. As prescribed in (HSAR) 48... the DHS Mentor-Protégé Program (JUN 2006) This solicitation contains a source selection factor or...

48 CFR 653.219-71 - DOS form DS-4053, Department of State Mentor-Protégé Program Application.

Science.gov (United States)

2010-10-01

..., Department of State Mentor-Protégé Program Application. 653.219-71 Section 653.219-71 Federal Acquisition...-4053, Department of State Mentor-Protégé Program Application. As prescribed in 619.102-70(i), DS-4053 is prescribed for use in applying for an agreement under the Department of State Mentor-Protégé...

Pertes alimentaires dans la filière protéagineuse

OpenAIRE

Duc, Gérard; Anton, Marc; Baranger, Alain; Biarnes, Véronique; Buitink, Julia; Carrouée, B.; Georget, Martine; Jeuffroy, Marie-Helene; Lessire, Michel; Magrini, Marie-Benoît; Pinochet, Xavier; Walrand, Stéphane

2015-01-01

La filière française des protéagineux (espèces pois, féverole et lupins), développée dans les années 1980 à 1990, avait pour premier objectif de répondre aux besoins de l’alimentation animale. A partir des années 2000, un marché significatif vers l’alimentation humaine s’est aussi développé. Sur la base d’une estimation à 370 000 t de protéagineux actuellement destinées à l’alimentation humaine (export + marché intérieur), les pertes sont surtout situées à la récolte et représenteraient 22 00...

Carrier-mediated system for transport of biotin in rat intestine in vitro

International Nuclear Information System (INIS)

Said, H.M.; Redha, R.

1987-01-01

Transport of biotin was examined in rat intestine using the everted sac technique. Transport of 0.1 μM biotin was linear with time for at least 30 min of incubation and occurred at a rate 3.7 pmol g initial tissue wet wt -1 min -1 . Transport of biotin was higher in the jejunum than the ileum and was minimum in the colon (85 +/- 6, 36 +/- 6, and 2.8 +/- 0.6 pmol x g initial tissue wet wt -1 x 25 min -1 , respectively). In the jejunum, transport of biotin was saturable at low concentrations but linear at higher concentrations. The transport of low concentrations of biotin was 1) inhibited by structural analogues (desthiobiotin, biotin methyl ester, diaminobiotin, and biocytin), 2) Na + dependent, 3) energy dependent, 4) temperature dependent, and 5) proceeded against a concentration gradient in the serosal compartment. No metabolic alteration occurs to the biotin molecule during transport. This study demonstrates that biotin transport in rat intestine occurs by a carrier-mediated process at low concentrations and by simple diffusion at high concentrations. Furthermore, the carrier-mediated process is Na + , energy, and temperature dependent

SGLT1-mediated transport in Caco-2 cells is highly dependent on cell bank origin

DEFF Research Database (Denmark)

Steffansen, B; Pedersen, Maria; Laghmoch, A M

2017-01-01

The Caco-2 cell line is a well-established in vitro model for studying transport phenomena for prediction of intestinal nutrient and drug absorption. However, for substances depending on transporters such predictions are complicated due to variable transporter expression and limited knowledge about...... transporter function during multiple cell passaging and cell thawings. In the case of SGLT1, a key transporter of oral absorption of D-glucose, one reason for compromised prediction could be inadequate expression of SGLT1 in Caco-2 cells and thereby limited sensitivity in the determination of SGLT1-mediated...... permeability (PSGLT1). Here, the objective was to characterize and compare SGLT1-mediated uptake in Caco-2 cells obtained from different cell banks. SGLT1-mediated uptake of the standard SGLT1 substrate, α-MDG, in Caco-2 cells was shown to be highly dependent on cell bank origin. The most robust and reliable...

Quasi-equilibrium analysis of the ion-pair mediated membrane transport of low-permeability drugs.

Science.gov (United States)

Miller, Jonathan M; Dahan, Arik; Gupta, Deepak; Varghese, Sheeba; Amidon, Gordon L

2009-07-01

The aim of this research was to gain a mechanistic understanding of ion-pair mediated membrane transport of low-permeability drugs. Quasi-equilibrium mass transport analyses were developed to describe the ion-pair mediated octanol-buffer partitioning and hydrophobic membrane permeation of the model basic drug phenformin. Three lipophilic counterions were employed: p-toluenesulfonic acid, 2-naphthalenesulfonic acid, and 1-hydroxy-2-naphthoic acid (HNAP). Association constants and intrinsic octanol-buffer partition coefficients (Log P(AB)) of the ion-pairs were obtained by fitting a transport model to double reciprocal plots of apparent octanol-buffer distribution coefficients versus counterion concentration. All three counterions enhanced the lipophilicity of phenformin, with HNAP providing the greatest increase in Log P(AB), 3.7 units over phenformin alone. HNAP also enhanced the apparent membrane permeability of phenformin, 27-fold in the PAMPA model, and 4.9-fold across Caco-2 cell monolayers. As predicted from a quasi-equilibrium analysis of ion-pair mediated membrane transport, an order of magnitude increase in phenformin flux was observed per log increase in counterion concentration, such that log-log plots of phenformin flux versus HNAP concentration gave linear relationships. These results provide increased understanding of the underlying mechanisms of ion-pair mediated membrane transport, emphasizing the potential of this approach to enable oral delivery of low-permeability drugs.

GLTP mediated non-vesicular GM1 transport between native membranes.

Directory of Open Access Journals (Sweden)

Ines Lauria

Full Text Available Lipid transfer proteins (LTPs are emerging as key players in lipid homeostasis by mediating non-vesicular transport steps between two membrane surfaces. Little is known about the driving force that governs the direction of transport in cells. Using the soluble LTP glycolipid transfer protein (GLTP, we examined GM1 (monosialotetrahexosyl-ganglioside transfer to native membrane surfaces. With artificial GM1 donor liposomes, GLTP can be used to increase glycolipid levels over natural levels in either side of the membrane leaflet, i.e., external or cytosolic. In a system with native donor- and acceptor-membranes, we find that GLTP balances highly variable GM1 concentrations in a population of membranes from one cell type, and in addition, transfers lipids between membranes from different cell types. Glycolipid transport is highly efficient, independent of cofactors, solely driven by the chemical potential of GM1 and not discriminating between the extra- and intracellular membrane leaflet. We conclude that GLTP mediated non-vesicular lipid trafficking between native membranes is driven by simple thermodynamic principles and that for intracellular transport less than 1 µM GLTP would be required in the cytosol. Furthermore, the data demonstrates the suitability of GLTP as a tool for artificially increasing glycolipid levels in cellular membranes.

Glucose Elevates NITRATE TRANSPORTER2.1 Protein Levels and Nitrate Transport Activity Independently of Its HEXOKINASE1-Mediated Stimulation of NITRATE TRANSPORTER2.1 Expression1[W][OPEN

Science.gov (United States)

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

2014-01-01

Mineral nutrient uptake and assimilation is closely coordinated with the production of photosynthate to supply nutrients for growth. In Arabidopsis (Arabidopsis thaliana), nitrate uptake from the soil is mediated by genes encoding high- and low-affinity transporters that are transcriptionally regulated by both nitrate and photosynthate availability. In this study, we have studied the interactions of nitrate and glucose (Glc) on gene expression, nitrate transport, and growth using glucose-insensitive2-1 (gin2-1), which is defective in sugar responses. We confirm and extend previous work by showing that HEXOKINASE1-mediated oxidative pentose phosphate pathway (OPPP) metabolism is required for Glc-mediated NITRATE TRANSPORTER2.1 (NRT2.1) expression. Treatment with pyruvate and shikimate, two products derived from intermediates of the OPPP that are destined for amino acid production, restores wild-type levels of NRT2.1 expression, suggesting that metabolites derived from OPPP metabolism can, together with Glc, directly stimulate high levels of NRT2.1 expression. Nitrate-mediated NRT2.1 expression is not influenced by gin2-1, showing that Glc does not influence NRT2.1 expression through nitrate-mediated mechanisms. We also show that Glc stimulates NRT2.1 protein levels and transport activity independently of its HEXOKINASE1-mediated stimulation of NRT2.1 expression, demonstrating another possible posttranscriptional mechanism influencing nitrate uptake. In gin2-1 plants, nitrate-responsive biomass growth was strongly reduced, showing that the supply of OPPP metabolites is essential for assimilating nitrate for growth. PMID:24272701

ProtDCal: A program to compute general-purpose-numerical descriptors for sequences and 3D-structures of proteins.

Science.gov (United States)

Ruiz-Blanco, Yasser B; Paz, Waldo; Green, James; Marrero-Ponce, Yovani

2015-05-16

The exponential growth of protein structural and sequence databases is enabling multifaceted approaches to understanding the long sought sequence-structure-function relationship. Advances in computation now make it possible to apply well-established data mining and pattern recognition techniques to these data to learn models that effectively relate structure and function. However, extracting meaningful numerical descriptors of protein sequence and structure is a key issue that requires an efficient and widely available solution. We here introduce ProtDCal, a new computational software suite capable of generating tens of thousands of features considering both sequence-based and 3D-structural descriptors. We demonstrate, by means of principle component analysis and Shannon entropy tests, how ProtDCal's sequence-based descriptors provide new and more relevant information not encoded by currently available servers for sequence-based protein feature generation. The wide diversity of the 3D-structure-based features generated by ProtDCal is shown to provide additional complementary information and effectively completes its general protein encoding capability. As demonstration of the utility of ProtDCal's features, prediction models of N-linked glycosylation sites are trained and evaluated. Classification performance compares favourably with that of contemporary predictors of N-linked glycosylation sites, in spite of not using domain-specific features as input information. ProtDCal provides a friendly and cross-platform graphical user interface, developed in the Java programming language and is freely available at: http://bioinf.sce.carleton.ca/ProtDCal/ . ProtDCal introduces local and group-based encoding which enhances the diversity of the information captured by the computed features. Furthermore, we have shown that adding structure-based descriptors contributes non-redundant additional information to the features-based characterization of polypeptide systems. This

neXtProt: organizing protein knowledge in the context of human proteome projects.

Science.gov (United States)

Gaudet, Pascale; Argoud-Puy, Ghislaine; Cusin, Isabelle; Duek, Paula; Evalet, Olivier; Gateau, Alain; Gleizes, Anne; Pereira, Mario; Zahn-Zabal, Monique; Zwahlen, Catherine; Bairoch, Amos; Lane, Lydie

2013-01-04

About 5000 (25%) of the ~20400 human protein-coding genes currently lack any experimental evidence at the protein level. For many others, there is only little information relative to their abundance, distribution, subcellular localization, interactions, or cellular functions. The aim of the HUPO Human Proteome Project (HPP, www.thehpp.org ) is to collect this information for every human protein. HPP is based on three major pillars: mass spectrometry (MS), antibody/affinity capture reagents (Ab), and bioinformatics-driven knowledge base (KB). To meet this objective, the Chromosome-Centric Human Proteome Project (C-HPP) proposes to build this catalog chromosome-by-chromosome ( www.c-hpp.org ) by focusing primarily on proteins that currently lack MS evidence or Ab detection. These are termed "missing proteins" by the HPP consortium. The lack of observation of a protein can be due to various factors including incorrect and incomplete gene annotation, low or restricted expression, or instability. neXtProt ( www.nextprot.org ) is a new web-based knowledge platform specific for human proteins that aims to complement UniProtKB/Swiss-Prot ( www.uniprot.org ) with detailed information obtained from carefully selected high-throughput experiments on genomic variation, post-translational modifications, as well as protein expression in tissues and cells. This article describes how neXtProt contributes to prioritize C-HPP efforts and integrates C-HPP results with other research efforts to create a complete human proteome catalog.

Insulin modulates hippocampally-mediated spatial working memory via glucose transporter-4.

Science.gov (United States)

Pearson-Leary, J; Jahagirdar, V; Sage, J; McNay, E C

2018-02-15

The insulin-regulated glucose transporter, GluT4, is a key molecule in peripheral insulin signaling. Although GluT4 is abundantly expressed in neurons of specific brain regions such as the hippocampus, the functional role of neuronal GluT4 is unclear. Here, we used pharmacological inhibition of GluT4-mediated glucose uptake to determine whether GluT4 mediates insulin-mediated glucose uptake in the hippocampus. Consistent with previous reports, we found that glucose utilization increased in the dorsal hippocampus of male rats during spontaneous alternation (SA), a hippocampally-mediated spatial working memory task. We previously showed that insulin signaling within the hippocampus is required for processing this task, and that administration of exogenous insulin enhances performance. At baseline levels of hippocampal insulin, inhibition of GluT4-mediated glucose uptake did not affect SA performance. However, inhibition of an upstream regulator of GluT4, Akt, did impair SA performance. Conversely, when a memory-enhancing dose of insulin was delivered to the hippocampus prior to SA-testing, inhibition of GluT4-mediated glucose transport prevented cognitive enhancement. These data suggest that baseline hippocampal cognitive processing does not require functional hippocampal GluT4, but that cognitive enhancement by supra-baseline insulin does. Consistent with these findings, we found that in neuronal cell culture, insulin increases glucose utilization in a GluT4-dependent manner. Collectively, these data demonstrate a key role for GluT4 in transducing the procognitive effects of elevated hippocampal insulin. Copyright © 2017 Elsevier B.V. All rights reserved.

protoDUNE-Single Phase and protDUNE-DualPhase

CERN Multimedia

Brice, Maximilien

2016-01-01

At the EHN1 two big 8m x 8m x8m detector prototypes (protoDUNE-Single Phase and protDUNE-DualPhase) are being constructed. The aim is to test technologies and detector performances for DUNE, a new generation of LBN neutr

Evidence for a role of transporter-mediated currents in the depletion of brain serotonin induced by serotonin transporter substrates.

Science.gov (United States)

Baumann, Michael H; Bulling, Simon; Benaderet, Tova S; Saha, Kusumika; Ayestas, Mario A; Partilla, John S; Ali, Syed F; Stockner, Thomas; Rothman, Richard B; Sandtner, Walter; Sitte, Harald H

2014-05-01

Serotonin (5-HT) transporter (SERT) substrates like fenfluramine and 3,4-methylenedioxymethamphetamine cause long-term depletion of brain 5-HT, while certain other substrates do not. The 5-HT deficits produced by SERT substrates are dependent upon transporter proteins, but the exact mechanisms responsible are unclear. Here, we compared the pharmacology of several SERT substrates: fenfluramine, d-fenfluramine, 1-(m-chlorophenyl)piperazine (mCPP) and 1-(m-trifluoromethylphenyl)piperainze (TFMPP), to establish relationships between acute drug mechanisms and the propensity for long-term 5-HT depletions. In vivo microdialysis was carried out in rat nucleus accumbens to examine acute 5-HT release and long-term depletion in the same subjects. In vitro assays were performed to measure efflux of [(3)H]5-HT in rat brain synaptosomes and transporter-mediated ionic currents in SERT-expressing Xenopus oocytes. When administered repeatedly to rats (6 mg/kg, i.p., four doses), all drugs produce large sustained elevations in extracellular 5-HT (>5-fold) with minimal effects on dopamine. Importantly, 2 weeks after dosing, only rats exposed to fenfluramine and d-fenfluramine display depletion of brain 5-HT. All test drugs evoke fluoxetine-sensitive efflux of [(3)H]5-HT from synaptosomes, but d-fenfluramine and its bioactive metabolite d-norfenfluramine induce significantly greater SERT-mediated currents than phenylpiperazines. Our data confirm that drug-induced 5-HT release probably does not mediate 5-HT depletion. However, the magnitude of transporter-mediated inward current may be a critical factor in the cascade of events leading to 5-HT deficits. This hypothesis warrants further study, especially given the growing popularity of designer drugs that target SERT.

The inhibitory effects of five alkaloids on the substrate transport mediated through human organic anion and cation transporters.

Science.gov (United States)

Shams, Tahiatul; Lu, Xiaoxi; Zhu, Ling; Zhou, Fanfan

2018-02-01

1. Human solute carrier transporters (SLCs) are important membrane proteins mediate the cellular transport of many endogenous and exogenous substances. Organic anion/cation transporters (OATs/OCTs) and organic anion transporting polypeptides (OATPs) are essential SLCs involved in drug influx. Drug-drug/herb interactions through competing for specific SLCs often lead to unsatisfied therapeutic outcomes and/or unwanted side effects. In this study, we comprehensively investigated the inhibitory effects of five clinically relevant alkaloids (dendrobine, matrine, oxymatrine, tryptanthrin and chelerythrine) on the substrate transport through several OATs/OCTs and OATPs. 2. We performed transport functional assay and kinetic analysis on the HEK-293 cells over-expressing each SLC gene. 3. Our data showed tryptanthrin significantly inhibited the transport activity of OAT3 (IC 50  = 0.93 ± 0.22 μM, K i  = 0.43 μM); chelerythrine acted as a potent inhibitor to the substrate transport mediated through OATP1A2 (IC 50  = 0.63 ± 0.43 μM, K i  = 0.60 μM), OCT1 (IC 50  = 13.60 ± 2.81 μM) and OCT2 (IC 50  =10.80 ± 1.16 μM). 4. Our study suggested tryptanthrin and chelerythrine could potently impact on the drug transport via specific OATs/OCTs. Therefore, the co-administration of these alkaloids with drugs could have clinical consequences due to drug-drug/herb interactions. Precautions should be warranted in the multi-drug therapies involving these alkaloids.

Ebullition, Plant-Mediated Transport, and Subsurface Horizontal Water Flow Dominate Methane Transport in an Arctic Sphagnum Bog

Science.gov (United States)

Wehr, R. A.; McCalley, C. K.; Logan, T. A.; Chanton, J.; Crill, P. M.; Rich, V. I.; Saleska, S. R.

2017-12-01

Emission of the greenhouse gas methane from wetlands is of prime concern in the prediction of climate change - especially emission associated with thawing permafrost, which may drive a positive feedback loop of emission and warming. In addition to the biochemistry of methane production and consumption, wetland methane emission depends critically on the transport mechanisms by which methane moves through and out of the ecosystem. We therefore developed a model of methane biochemistry and transport for a sphagnum bog representing an intermediate permafrost thaw stage in Stordalen Mire, Sweden. In order to simultaneously reproduce measured profiles of both the concentrations and isotopic compositions of both methane and carbon dioxide in the peat pore water (Fig. 1) - as well as the surface methane emission - it was necessary for the model to include ebullition, plant-mediated transport via aerenchyma, and subsurface horizontal water flow. Diffusion of gas through the pore water was relatively unimportant. As a result, 90% of the produced methane escaped the wetland rather than being consumed by methanotrophic organisms in the near-surface pore water. Our model provides a comprehensive picture of methane emission from this bog site by quantifying the vertical profiles of: acetoclastic methanogenesis, hydrogenotrophic methanogenesis, methane oxidation, aerobic respiration, ebullition, plant-mediated transport, subsurface horizontal water flow, and diffusion.

48 CFR 1819.7205 - Mentor-protégé agreements.

Science.gov (United States)

2010-10-01

... in— (i) General business management, including organizational management, financial management, personnel management, marketing, business development, and overall business planning; (ii) Engineering... ADMINISTRATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS NASA Mentor-Protégé Program 1819.7205 Mentor...

protVirt: protein dosage simulation by spectrometry assisting Biochemistry practical class

Directory of Open Access Journals (Sweden)

Gabriel Gerber Hornink

2016-07-01

Full Text Available The practical classes in the teaching of biochemistry could provide great contributions to the process of teaching and learning, and the understanding of these by students depend on, generally,  previous concepts about the experiment and procedures performed. It is presented in this paper the educational software protVirt, which could be used as a pedagogical innovation in the method of practical classes involving dosage of proteins, focusing on the development of skills for understanding the activities. The software was developed in Adobe Flash, with the possibility of online or offline use. Despite the possibilities of using protVirt in various modalities of education, highlights the use in online courses, in which students develop, commonly, the practical class without the teacher centers, accompanied by monitors and tutors.

Enterobactin-mediated iron transport in Pseudomonas aeruginosa.

Science.gov (United States)

Poole, K; Young, L; Neshat, S

1990-01-01

A pyoverdine-deficient strain of Pseudomonas aeruginosa was unable to grow in an iron-deficient minimal medium in the presence of the nonmetabolizable iron chelator ethylene diamine-di(omega-hydroxyphenol acetic acid) (EDDHA), although addition of enterobactin to EDDHA-containing minimal media did restore growth of the pyoverdine-deficient P. aeruginosa. Consistent with the apparent ability of enterobactin to provide iron to P. aeruginosa, enterobactin-dependent 55Fe3+ uptake was observed in cells of P. aeruginosa previously grown in an iron-deficient medium containing enterobactin (or enterobactin-containing Escherichia coli culture supernatant). This uptake was energy dependent, was observable at low concentrations (60 nM) of FeCl3, and was absent in cells cultured without enterobactin. A novel protein with a molecular weight of approximately 80,000 was identified in the outer membranes of cells grown in iron-deficient minimal medium containing enterobactin, concomitant with the induction of enterobactin-dependent iron uptake. A Tn501 insertion mutant lacking this protein was isolated and shown to be deficient in enterobactin-mediated iron transport at 60 nM FeCl3, although it still exhibited enterobactin-dependent growth in iron-deficient medium containing EDDHA. It was subsequently observed that the mutant was, however, capable of enterobactin-mediated iron transport at much higher concentrations (600 nM) of FeCl3. Indeed, enterobactin-dependent iron uptake at this concentration of iron was observed in both the mutant and parent strains irrespective of whether they had been cultured in the presence of enterobactin.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:2174865

FireProt: Energy- and Evolution-Based Computational Design of Thermostable Multiple-Point Mutants.

Science.gov (United States)

Bednar, David; Beerens, Koen; Sebestova, Eva; Bendl, Jaroslav; Khare, Sagar; Chaloupkova, Radka; Prokop, Zbynek; Brezovsky, Jan; Baker, David; Damborsky, Jiri

2015-11-01

There is great interest in increasing proteins' stability to enhance their utility as biocatalysts, therapeutics, diagnostics and nanomaterials. Directed evolution is a powerful, but experimentally strenuous approach. Computational methods offer attractive alternatives. However, due to the limited reliability of predictions and potentially antagonistic effects of substitutions, only single-point mutations are usually predicted in silico, experimentally verified and then recombined in multiple-point mutants. Thus, substantial screening is still required. Here we present FireProt, a robust computational strategy for predicting highly stable multiple-point mutants that combines energy- and evolution-based approaches with smart filtering to identify additive stabilizing mutations. FireProt's reliability and applicability was demonstrated by validating its predictions against 656 mutations from the ProTherm database. We demonstrate that thermostability of the model enzymes haloalkane dehalogenase DhaA and γ-hexachlorocyclohexane dehydrochlorinase LinA can be substantially increased (ΔTm = 24°C and 21°C) by constructing and characterizing only a handful of multiple-point mutants. FireProt can be applied to any protein for which a tertiary structure and homologous sequences are available, and will facilitate the rapid development of robust proteins for biomedical and biotechnological applications.

FireProt: Energy- and Evolution-Based Computational Design of Thermostable Multiple-Point Mutants.

Directory of Open Access Journals (Sweden)

David Bednar

2015-11-01

Full Text Available There is great interest in increasing proteins' stability to enhance their utility as biocatalysts, therapeutics, diagnostics and nanomaterials. Directed evolution is a powerful, but experimentally strenuous approach. Computational methods offer attractive alternatives. However, due to the limited reliability of predictions and potentially antagonistic effects of substitutions, only single-point mutations are usually predicted in silico, experimentally verified and then recombined in multiple-point mutants. Thus, substantial screening is still required. Here we present FireProt, a robust computational strategy for predicting highly stable multiple-point mutants that combines energy- and evolution-based approaches with smart filtering to identify additive stabilizing mutations. FireProt's reliability and applicability was demonstrated by validating its predictions against 656 mutations from the ProTherm database. We demonstrate that thermostability of the model enzymes haloalkane dehalogenase DhaA and γ-hexachlorocyclohexane dehydrochlorinase LinA can be substantially increased (ΔTm = 24°C and 21°C by constructing and characterizing only a handful of multiple-point mutants. FireProt can be applied to any protein for which a tertiary structure and homologous sequences are available, and will facilitate the rapid development of robust proteins for biomedical and biotechnological applications.

78 FR 69171 - 60-Day Notice of Proposed Information Collection: Department of State Mentor Protégé Program...

Science.gov (United States)

2013-11-18

...: Department of State Mentor Prot[eacute]g[eacute] Program Application ACTION: Notice of request for public... [email protected] . SUPPLEMENTARY INFORMATION: Title of Information Collection: Department of State Mentor... planning to team together in an official mentor-prot[eacute]g[eacute] capacity to enhance the capabilities...

ProtPOS: a python package for the prediction of protein preferred orientation on a surface.

Science.gov (United States)

Ngai, Jimmy C F; Mak, Pui-In; Siu, Shirley W I

2016-08-15

Atomistic molecular dynamics simulation is a promising technique to investigate the energetics and dynamics in the protein-surface adsorption process which is of high relevance to modern biotechnological applications. To increase the chance of success in simulating the adsorption process, favorable orientations of the protein at the surface must be determined. Here, we present ProtPOS which is a lightweight and easy-to-use python package that can predict low-energy protein orientations on a surface of interest. It combines a fast conformational sampling algorithm with the energy calculation of GROMACS. The advantage of ProtPOS is it allows users to select any force fields suitable for the system at hand and provide structural output readily available for further simulation studies. ProtPOS is freely available for academic and non-profit uses at http://cbbio.cis.umac.mo/software/protpos Supplementary data are available at Bioinformatics online. shirleysiu@umac.mo. © The Author 2016. Published by Oxford University Press.

RaftProt: mammalian lipid raft proteome database.

Science.gov (United States)

Shah, Anup; Chen, David; Boda, Akash R; Foster, Leonard J; Davis, Melissa J; Hill, Michelle M

2015-01-01

RaftProt (http://lipid-raft-database.di.uq.edu.au/) is a database of mammalian lipid raft-associated proteins as reported in high-throughput mass spectrometry studies. Lipid rafts are specialized membrane microdomains enriched in cholesterol and sphingolipids thought to act as dynamic signalling and sorting platforms. Given their fundamental roles in cellular regulation, there is a plethora of information on the size, composition and regulation of these membrane microdomains, including a large number of proteomics studies. To facilitate the mining and analysis of published lipid raft proteomics studies, we have developed a searchable database RaftProt. In addition to browsing the studies, performing basic queries by protein and gene names, searching experiments by cell, tissue and organisms; we have implemented several advanced features to facilitate data mining. To address the issue of potential bias due to biochemical preparation procedures used, we have captured the lipid raft preparation methods and implemented advanced search option for methodology and sample treatment conditions, such as cholesterol depletion. Furthermore, we have identified a list of high confidence proteins, and enabled searching only from this list of likely bona fide lipid raft proteins. Given the apparent biological importance of lipid raft and their associated proteins, this database would constitute a key resource for the scientific community. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Calixarene-mediated liquid membrane transport of choline conjugates 3: The effect of handle variation on neurotransmitter transport.

Science.gov (United States)

Collins, James L; Fujii, Ayu; Roshandel, Sahar; To, Cuong-Alexander; Schramm, Michael P

2017-07-01

Upper rim phosphonic acid functionalized calix[4]arene affects selective transport of multiple molecular payloads through a liquid membrane. The secret is in the attachment of a receptor-complementary handle to the payload. We find that the trimethylammonium ethylene group present in choline is one of several general handles for the transport of drug and drug-like species. Herein we compare the effect of handle variation against the transport of serotonin and dopamine. We find that several ionizable amine termini handles are sufficient for transport and identify two ideal candidates. Their performance is significantly enhanced in HEPES buffered solutions. This inquiry completes a series of 3 studies aimed at optimization of this strategy. In completion a new approach towards synthetic receptor mediated selective small molecule transport has emerged; future work in vesicular and cellular systems will follow. Copyright © 2017 Elsevier Ltd. All rights reserved.

Etude et fonctionnalisation de protéines végétales en vue de leur application en microencapsulation

OpenAIRE

Nesterenko, Alla

2012-01-01

Les protéines extraites des végétaux sont des matériaux relativement peu coûteux, non toxiques, biocompatibles et biodégradables. Elles représentent une bonne alternative aux protéines d’origine animale et aux polymères dérivés du pétrole. Dans le cadre de cette étude, les protéines extraites de graines de soja et de tournesol ont été utilisées en tant que matériaux enrobants pour la microencapsulation de la matière active hydrophobe (α-tocophérol) ou hydrophile (acide ascorbique) par le proc...

Trap-mediated electronic transport properties of gate-tunable pentacene/MoS2 p-n heterojunction diodes.

Science.gov (United States)

Kim, Jae-Keun; Cho, Kyungjune; Kim, Tae-Young; Pak, Jinsu; Jang, Jingon; Song, Younggul; Kim, Youngrok; Choi, Barbara Yuri; Chung, Seungjun; Hong, Woong-Ki; Lee, Takhee

2016-11-10

We investigated the trap-mediated electronic transport properties of pentacene/molybdenum disulphide (MoS 2 ) p-n heterojunction devices. We observed that the hybrid p-n heterojunctions were gate-tunable and were strongly affected by trap-assisted tunnelling through the van der Waals gap at the heterojunction interfaces between MoS 2 and pentacene. The pentacene/MoS 2 p-n heterojunction diodes had gate-tunable high ideality factor, which resulted from trap-mediated conduction nature of devices. From the temperature-variable current-voltage measurement, a space-charge-limited conduction and a variable range hopping conduction at a low temperature were suggested as the gate-tunable charge transport characteristics of these hybrid p-n heterojunctions. Our study provides a better understanding of the trap-mediated electronic transport properties in organic/2-dimensional material hybrid heterojunction devices.

Organic anion transporter 3- and organic anion transporting polypeptides 1B1- and 1B3-mediated transport of catalposide

Directory of Open Access Journals (Sweden)

Jeong HU

2015-01-01

Full Text Available Hyeon-Uk Jeong,1 Mihwa Kwon,2 Yongnam Lee,3 Ji Seok Yoo,3 Dae Hee Shin,3 Im-Sook Song,2 Hye Suk Lee1 1College of Pharmacy, The Catholic University of Korea, Bucheon 420-743, Korea; 2College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Korea; 3Central R&D Institute, Yungjin Pharm Co., Ltd., Suwon 443-270, Korea Abstract: We investigated the in vitro transport characteristics of catalposide in HEK293 cells overexpressing organic anion transporter 1 (OAT1, OAT3, organic anion transporting polypeptide 1B1 (OATP1B1, OATP1B3, organic cation transporter 1 (OCT1, OCT2, P-glycoprotein (P-gp, and breast cancer resistance protein (BCRP. The transport mechanism of catalposide was investigated in HEK293 and LLC-PK1 cells overexpressing the relevant transporters. The uptake of catalposide was 319-, 13.6-, and 9.3-fold greater in HEK293 cells overexpressing OAT3, OATP1B1, and OATP1B3 transporters, respectively, than in HEK293 control cells. The increased uptake of catalposide via the OAT3, OATP1B1, and OATP1B3 transporters was decreased to basal levels in the presence of representative inhibitors such as probenecid, furosemide, and cimetidine (for OAT3 and cyclosporin A, gemfibrozil, and rifampin (for OATP1B1 and OATP1B3. The concentration-dependent OAT3-mediated uptake of catalposide revealed the following kinetic parameters: Michaelis constant (Km =41.5 µM, maximum uptake rate (Vmax =46.2 pmol/minute, and intrinsic clearance (CLint =1.11 µL/minute. OATP1B1- and OATP1B3-mediated catalposide uptake also showed concentration dependency, with low CLint values of 0.035 and 0.034 µL/minute, respectively. However, the OCT1, OCT2, OAT1, P-gp, and BCRP transporters were apparently not involved in the uptake of catalposide into cells. In addition, catalposide inhibited the transport activities of OAT3, OATP1B1, and OATP1B3 with half-maximal inhibitory concentration values of 83, 200, and 235 µ

Avaliação da estomatite protética em portadores de próteses totais

Directory of Open Access Journals (Sweden)

CARVALHO de OLIVEIRA Terezinha Rezende

2000-01-01

Full Text Available As próteses muco-suportadas são consideradas facilitadoras em potencial da estomatite protética (EP, lesão comumente observada sob a base das próteses, caracterizada por aspectos eritematosos difusos ou pontilhados na mucosa de suporte. Sua etiologia é controversa, podendo estar relacionada principalmente a fatores locais. Diversos aspectos funcionais associam-se a estes fatores representados pela oclusão, dimensão vertical, retenção, estabilidade dinâmica e estática além de aspectos qualitativos relacionados às condições encontradas no desdentado. Foram levados em consideração o período de edentulismo, número e tempo de uso das próteses, uso contínuo, conservação, presença de placa e higiene bucal. Os fatores foram avaliados, visando esclarecer a possível relação dos aspectos funcionais e protéticos com a EP. Exame clínico foi realizado em 116 pacientes de ambos os sexos, desdentados bimaxilares, que utilizavam as duas próteses muco-suportadas, portadores ou não de estomatite protética (EP. Os resultados indicaram que a maioria dos pacientes examinados tinha EP frente ao menor número de pacientes sem EP, havendo nos dois grupos equivalência nos resultados da avaliação clínica e protética. Os fatores funcionais e qualitativos das próteses, avaliados isoladamente, não puderam ser considerados responsáveis pela ocorrência dessa patologia, constatando-se que um único fator protético não demonstrou, de per si, ser responsável pela presença da EP, embora possa ser um facilitador para o seu desenvolvimento.

76 FR 25733 - 30-Day Notice of Proposed Information Collection DS 4053, Department of State Mentor-Protégé...

Science.gov (United States)

2011-05-05

... Collection DS 4053, Department of State Mentor-Prot[eacute]g[eacute] Program Application ACTION: Notice of... Information Collection: Department of State Mentor-Prot[eacute]g[eacute] Program Application. OMB Control...-4053. Respondents: Small and large for-profit companies planning to team together in an official mentor...

BioInfra.Prot: A comprehensive proteomics workflow including data standardization, protein inference, expression analysis and data publication.

Science.gov (United States)

Turewicz, Michael; Kohl, Michael; Ahrens, Maike; Mayer, Gerhard; Uszkoreit, Julian; Naboulsi, Wael; Bracht, Thilo; Megger, Dominik A; Sitek, Barbara; Marcus, Katrin; Eisenacher, Martin

2017-11-10

The analysis of high-throughput mass spectrometry-based proteomics data must address the specific challenges of this technology. To this end, the comprehensive proteomics workflow offered by the de.NBI service center BioInfra.Prot provides indispensable components for the computational and statistical analysis of this kind of data. These components include tools and methods for spectrum identification and protein inference, protein quantification, expression analysis as well as data standardization and data publication. All particular methods of the workflow which address these tasks are state-of-the-art or cutting edge. As has been shown in previous publications, each of these methods is adequate to solve its specific task and gives competitive results. However, the methods included in the workflow are continuously reviewed, updated and improved to adapt to new scientific developments. All of these particular components and methods are available as stand-alone BioInfra.Prot services or as a complete workflow. Since BioInfra.Prot provides manifold fast communication channels to get access to all components of the workflow (e.g., via the BioInfra.Prot ticket system: bioinfraprot@rub.de) users can easily benefit from this service and get support by experts. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Protégés' Personality Traits, Expectations, the Quality of the Mentoring Relationship and Adjustment: A Big Five Analysis

Science.gov (United States)

Goldner, Limor

2016-01-01

Background: Community-based mentoring interventions can benefit high-risk youth. However, meta-analyses suggest that these benefits may be conditioned by protégés' personality. Objectives: Associations between protégés' personality traits and mentoring expectations, the quality of the mentoring relationship, the perceived mentoring contribution,…

Qualidade protéica do soro de leite fermentado pela levedura Kluyveromyces fragilis

OpenAIRE

Silva,Caio Abércio da; Hernan-Gomez,Raul Castro

2000-01-01

O soro de leite fermentado pela levedura Kluyveromyces fragilis, após secagem em spray drier, foi submetido à avaliação da qualidade protéica através de uma análise aminoacídica e de um estudo biológico pelos métodos: Relação da Eficiência Protéica (PER), Relação da Eficiência Líquida da Proteína (NPR) e Utilização Líquida da Proteína (NPU). Na análise aminoacídica, foram utilizadas como comparativo a composição de aminoácidos das proteínas padrão do ovo e da FAO. Os resultados indicaram um a...

The neXtProt peptide uniqueness checker: a tool for the proteomics community.

Science.gov (United States)

Schaeffer, Mathieu; Gateau, Alain; Teixeira, Daniel; Michel, Pierre-André; Zahn-Zabal, Monique; Lane, Lydie

2017-11-01

The neXtProt peptide uniqueness checker allows scientists to define which peptides can be used to validate the existence of human proteins, i.e. map uniquely versus multiply to human protein sequences taking into account isobaric substitutions, alternative splicing and single amino acid variants. The pepx program is available at https://github.com/calipho-sib/pepx and can be launched from the command line or through a cgi web interface. Indexing requires a sequence file in FASTA format. The peptide uniqueness checker tool is freely available on the web at https://www.nextprot.org/tools/peptide-uniqueness-checker and from the neXtProt API at https://api.nextprot.org/. lydie.lane@sib.swiss. © The Author(s) 2017. Published by Oxford University Press.

TWISTED DWARF1 Mediates the Action of Auxin Transport Inhibitors on Actin Cytoskeleton Dynamics

Science.gov (United States)

Bailly, Aurelien; Zwiewka, Marta; Sovero, Valpuri; Ge, Pei; Aryal, Bibek; Hao, Pengchao; Linnert, Miriam; Burgardt, Noelia Inés; Lücke, Christian; Weiwad, Matthias; Michel, Max; Weiergräber, Oliver H.; Pollmann, Stephan; Azzarello, Elisa; Fukao, Yoichiro; Hoffmann, Céline; Wedlich-Söldner, Roland

2016-01-01

Plant growth and architecture is regulated by the polar distribution of the hormone auxin. Polarity and flexibility of this process is provided by constant cycling of auxin transporter vesicles along actin filaments, coordinated by a positive auxin-actin feedback loop. Both polar auxin transport and vesicle cycling are inhibited by synthetic auxin transport inhibitors, such as 1-N-naphthylphthalamic acid (NPA), counteracting the effect of auxin; however, underlying targets and mechanisms are unclear. Using NMR, we map the NPA binding surface on the Arabidopsis thaliana ABCB chaperone TWISTED DWARF1 (TWD1). We identify ACTIN7 as a relevant, although likely indirect, TWD1 interactor, and show TWD1-dependent regulation of actin filament organization and dynamics and that TWD1 is required for NPA-mediated actin cytoskeleton remodeling. The TWD1-ACTIN7 axis controls plasma membrane presence of efflux transporters, and as a consequence act7 and twd1 share developmental and physiological phenotypes indicative of defects in auxin transport. These can be phenocopied by NPA treatment or by chemical actin (de)stabilization. We provide evidence that TWD1 determines downstream locations of auxin efflux transporters by adjusting actin filament debundling and dynamizing processes and mediating NPA action on the latter. This function appears to be evolutionary conserved since TWD1 expression in budding yeast alters actin polarization and cell polarity and provides NPA sensitivity. PMID:27053424

OntoCheck: verifying ontology naming conventions and metadata completeness in Protégé 4.

Science.gov (United States)

Schober, Daniel; Tudose, Ilinca; Svatek, Vojtech; Boeker, Martin

2012-09-21

Although policy providers have outlined minimal metadata guidelines and naming conventions, ontologies of today still display inter- and intra-ontology heterogeneities in class labelling schemes and metadata completeness. This fact is at least partially due to missing or inappropriate tools. Software support can ease this situation and contribute to overall ontology consistency and quality by helping to enforce such conventions. We provide a plugin for the Protégé Ontology editor to allow for easy checks on compliance towards ontology naming conventions and metadata completeness, as well as curation in case of found violations. In a requirement analysis, derived from a prior standardization approach carried out within the OBO Foundry, we investigate the needed capabilities for software tools to check, curate and maintain class naming conventions. A Protégé tab plugin was implemented accordingly using the Protégé 4.1 libraries. The plugin was tested on six different ontologies. Based on these test results, the plugin could be refined, also by the integration of new functionalities. The new Protégé plugin, OntoCheck, allows for ontology tests to be carried out on OWL ontologies. In particular the OntoCheck plugin helps to clean up an ontology with regard to lexical heterogeneity, i.e. enforcing naming conventions and metadata completeness, meeting most of the requirements outlined for such a tool. Found test violations can be corrected to foster consistency in entity naming and meta-annotation within an artefact. Once specified, check constraints like name patterns can be stored and exchanged for later re-use. Here we describe a first version of the software, illustrate its capabilities and use within running ontology development efforts and briefly outline improvements resulting from its application. Further, we discuss OntoChecks capabilities in the context of related tools and highlight potential future expansions. The OntoCheck plugin facilitates

[Carrier-mediated Transport of Cationic Drugs across the Blood-Tissue Barrier].

Science.gov (United States)

Kubo, Yoshiyuki

2015-01-01

Studies of neurological dysfunction have revealed the neuroprotective effect of several cationic drugs, suggesting their usefulness in the treatment of neurological diseases. In the brain and retina, blood-tissue barriers such as blood-brain barrier (BBB) and blood-retinal barrier (BRB) are formed to restrict nonspecific solute transport between the circulating blood and neural tissues. Therefore study of cationic drug transport at these barriers is essential to achieve systemic delivery of neuroprotective agents into the neural tissues. In the retina, severe diseases such as diabetic retinopathy and macular degeneration can cause neurological dysfunction that dramatically affects patients' QOL. The BRB is formed by retinal capillary endothelial cells (inner BRB) and retinal pigment epithelial cells (outer BRB). Blood-to-retina transport of cationic drugs was investigated at the inner BRB, which is known to nourish two thirds of the retina. Blood-to-retinal transport of verapamil suggested that the barrier function of the BRB differs from that of the BBB. Moreover, carrier-mediated transport of verapamil and pyrilamine revealed the involvement of novel organic cation transporters at the inner BRB. The identified transport systems for cationic drugs are sensitive to several cationic neuroprotective and anti-angiogenic agents such as clonidine and propranolol, and the involvement of novel transporters was also suggested in their blood-to-retina transport across the inner BRB.

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

DEFF Research Database (Denmark)

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

2016-01-01

, in addition, Na+ /K+ -ATPase-mediated K+ clearance could be governed by astrocytic [Na+ ]i . During most neuronal activity, glutamate is released in the synaptic cleft and is re-absorbed by astrocytic Na+ -coupled glutamate transporters, thereby elevating [Na+ ]i . It thus remains unresolved whether...... the different Na+ /K+ -ATPase isoforms are controlled by [K+ ]o or [Na+ ]i during neuronal activity. Hippocampal slice recordings of stimulus-induced [K+ ]o transients with ion-sensitive microelectrodes revealed reduced Na+ /K+ -ATPase-mediated K+ management upon parallel inhibition of the glutamate transporter......+ affinity to the α1 and α2 isoforms than the β2 isoform. In summary, enhanced astrocytic Na+ /K+ -ATPase-dependent K+ clearance was obtained with parallel glutamate transport activity. The astrocytic Na+ /K+ -ATPase isoform constellation α2β1 appeared to be specifically geared to respond to the [Na+ ]i...

ChemProt: A disease chemical biology database

DEFF Research Database (Denmark)

Taboureau, Olivier; Oprea, Tudor I.

2013-01-01

The integration of chemistry, biology, and informatics to study drug actions across multiple biological targets, pathways, and biological systems is an emerging paradigm in drug discovery. Rather than reducing a complex system to simplistic models, fields such as chemogenomics and translational...... informatics are seeking to build a holistic model for a better understanding of the drug pharmacology and clinical effects. Here we will present a webserver called ChemProt that can assist, in silico, the drug actions in the context of cellular and disease networks and contribute in the field of disease...... chemical biology, drug repurposing, and off-target effects prediction....

SVM-Prot 2016: A Web-Server for Machine Learning Prediction of Protein Functional Families from Sequence Irrespective of Similarity.

Science.gov (United States)

Li, Ying Hong; Xu, Jing Yu; Tao, Lin; Li, Xiao Feng; Li, Shuang; Zeng, Xian; Chen, Shang Ying; Zhang, Peng; Qin, Chu; Zhang, Cheng; Chen, Zhe; Zhu, Feng; Chen, Yu Zong

2016-01-01

Knowledge of protein function is important for biological, medical and therapeutic studies, but many proteins are still unknown in function. There is a need for more improved functional prediction methods. Our SVM-Prot web-server employed a machine learning method for predicting protein functional families from protein sequences irrespective of similarity, which complemented those similarity-based and other methods in predicting diverse classes of proteins including the distantly-related proteins and homologous proteins of different functions. Since its publication in 2003, we made major improvements to SVM-Prot with (1) expanded coverage from 54 to 192 functional families, (2) more diverse protein descriptors protein representation, (3) improved predictive performances due to the use of more enriched training datasets and more variety of protein descriptors, (4) newly integrated BLAST analysis option for assessing proteins in the SVM-Prot predicted functional families that were similar in sequence to a query protein, and (5) newly added batch submission option for supporting the classification of multiple proteins. Moreover, 2 more machine learning approaches, K nearest neighbor and probabilistic neural networks, were added for facilitating collective assessment of protein functions by multiple methods. SVM-Prot can be accessed at http://bidd2.nus.edu.sg/cgi-bin/svmprot/svmprot.cgi.

Effect of COPD treatments on MRP1-mediated transport in bronchial epithelial cells

Directory of Open Access Journals (Sweden)

Margaretha van der Deen

2008-10-01

Full Text Available Margaretha van der Deen1, Sandra Homan1, Hetty Timmer-Bosscha1, Rik J Scheper2, Wim Timens3, Dirkje S Postma4, Elisabeth G de Vries1Departments of 1Medical Oncology, 3Pathology, 4Pulmonary Diseases, University Medical Center Groningen and University of Groningen, The Netherlands; 2Department of Pathology, VU University Medical Center, Amsterdam, The NetherlandsBackground: Smoking is the principle risk factor for development of chronic obstructive pulmonary disease (COPD. Multidrug resistance-associated protein 1 (MRP1 is known to protect against toxic compounds and oxidative stress, and might play a role in protection against smoke-induced disease progression. We questioned whether MRP1-mediated transport is influenced by pulmonary drugs that are commonly prescribed in COPD.Methods: The immortalized human bronchial epithelial cell line 16HBE14o- was used to analyze direct in vitro effects of budesonide, formoterol, ipratropium bromide and N-acetylcysteine (NAC on MRP1-mediated transport. Carboxyfluorescein (CF was used as a model MRP1 substrate and was measured with functional flow cytometry.Results: Formoterol had a minor effect, whereas budesonide concentration-dependently decreased CF transport by MRP1. Remarkably, addition of formoterol to the highest concentration of budesonide increased CF transport. Ipratropium bromide inhibited CF transport at low concentrations and tended to increase CF transport at higher levels. NAC increased CF transport by MRP1 in a concentration-dependent manner.Conclusions: Our data suggest that, besides their positive effects on respiratory symptoms, budesonide, formoterol, ipratropium bromide, and NAC modulate MRP1 activity in bronchial epithelial cells. Further studies are required to assess whether stimulation of MRP1 activity is beneficial for long-term treatment of COPD.Keywords: bronchus epithelium, COPD, drugs, MRP1, multidrug resistance, oxidative stress

Effect of zolpidem on human cytochrome P450 activity, and on transport mediated by P-glycoprotein.

Science.gov (United States)

von Moltke, Lisa L; Weemhoff, James L; Perloff, Michael D; Hesse, Leah M; Harmatz, Jerold S; Roth-Schechter, Barbara F; Greenblatt, David J

2002-12-01

The influence of high concentrations of zolpidem (100 microM, corresponding to approximately 200 times maximum therapeutic concentrations) on the activity of six human Cytochrome P450 (CYP) enzymes was evaluated in a model system using human liver microsomes. Zolpidem produced negligible or weak inhibition of human CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A. Transport of rhodamine 123, presumed to be mediated mainly by the energy-dependent efflux transport protein P-glycoprotein, was studied in a cell culture system using a human intestinal cell line. High concentrations of zolpidem (100 microM), exceeding the usual therapeutic range by more than 100-fold, produced only modest impairment of rhodamine 123 transport. The findings indicate that zolpidem is very unlikely to cause clinical drug interactions attributable to impairment of CYP activity or P-gp mediated transport. Copyright 2002 John Wiley & Sons, Ltd.

Heptachlor induced mitochondria-mediated cell death via impairing electron transport chain complex III

International Nuclear Information System (INIS)

Hong, Seokheon; Kim, Joo Yeon; Hwang, Joohyun; Shin, Ki Soon; Kang, Shin Jung

2013-01-01

Highlights: •Heptachlor inhibited mitochondrial electron transport chain complex III activity. •Heptachlor promoted generation of reactive oxygen species. •Heptachlor induced Bax activation. •Heptachlor induced mitochondria-mediated and caspase-dependent apoptosis. -- Abstract: Environmental toxins like pesticides have been implicated in the pathogenesis of Parkinson’s disease (PD). Epidemiological studies suggested that exposures to organochlorine pesticides have an association with an increased PD risk. In the present study, we examined the mechanism of toxicity induced by an organochlorine pesticide heptachlor. In a human dopaminergic neuroblastoma SH-SY5Y cells, heptachlor induced both morphological and functional damages in mitochondria. Interestingly, the compound inhibited mitochondrial electron transport chain complex III activity. Rapid generation of reactive oxygen species and the activation of Bax were then detected. Subsequently, mitochondria-mediated, caspase-dependent apoptosis followed. Our results raise a possibility that an organochlorine pesticide heptachlor can act as a neurotoxicant associated with PD

Heptachlor induced mitochondria-mediated cell death via impairing electron transport chain complex III

Energy Technology Data Exchange (ETDEWEB)

Hong, Seokheon; Kim, Joo Yeon; Hwang, Joohyun [Department of Molecular Biology, Sejong University, Seoul 143-747 (Korea, Republic of); Shin, Ki Soon [Department of Biology, Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kang, Shin Jung, E-mail: sjkang@sejong.ac.kr [Department of Molecular Biology, Sejong University, Seoul 143-747 (Korea, Republic of)

2013-08-09

Highlights: •Heptachlor inhibited mitochondrial electron transport chain complex III activity. •Heptachlor promoted generation of reactive oxygen species. •Heptachlor induced Bax activation. •Heptachlor induced mitochondria-mediated and caspase-dependent apoptosis. -- Abstract: Environmental toxins like pesticides have been implicated in the pathogenesis of Parkinson’s disease (PD). Epidemiological studies suggested that exposures to organochlorine pesticides have an association with an increased PD risk. In the present study, we examined the mechanism of toxicity induced by an organochlorine pesticide heptachlor. In a human dopaminergic neuroblastoma SH-SY5Y cells, heptachlor induced both morphological and functional damages in mitochondria. Interestingly, the compound inhibited mitochondrial electron transport chain complex III activity. Rapid generation of reactive oxygen species and the activation of Bax were then detected. Subsequently, mitochondria-mediated, caspase-dependent apoptosis followed. Our results raise a possibility that an organochlorine pesticide heptachlor can act as a neurotoxicant associated with PD.

Rancang Bangun Plugin Protégé Menggunakan Ekspresi SPARQL-DL Dengan Masukan Bahasa Alami

Directory of Open Access Journals (Sweden)

Muhammad Fahrurrozi

2017-07-01

Full Text Available Semantic web is a technology that allows us to build a knowledge base or ontology for the information of the web page can be understood by computers. One software for building ontology-based semantic web is a protégé. Protege allows developers to develop an ontology with an expression of logic description. Protégé provides a plugin such as DL-Query and SPARQL-Query to display information that involve expression of class, property and individual in the ontology. The problem that then arises is DL-plugin Query only able to process the rules that involve expression of class to any object property, despite being equipped with the function of reasoning. while the SPARQL-Query plugin does not have reasoning abilities such as DL-Query plugin although the SPARQL-Query plugin can query memperoses rules involving class, property and individual. This research resulted in a new plugin using SPARQL-DL with input natural language as a protégé not provide a plugin with input natural language to see results from the combined expression-expression contained in the ontology that allows developers to view information ontology language that is easier to understand without having think of SPARQL query structure is complicated.

Facilitating Protégé Career Development through Skills of Mentors

Science.gov (United States)

Balu, L.; James, Leena

2017-01-01

The success of protégé contribution in any organisation today depends more on the type of relationship that an organisation establishes with the support of mentors. Research shows that individuals who are mentored have an increased likelihood of career success as a result of the targeted developmental support they receive. Mentors serve as trusted…

Predicting transporter-mediated drug interactions: Commentary on: "Pharmacokinetic evaluation of a drug transporter cocktail consisting of digoxin, furosemide, metformin and rosuvastatin" and "Validation of a microdose probe drug cocktail for clinical drug interaction assessments for drug transporters and CYP3A".

Science.gov (United States)

Zhang, L; Sparreboom, A

2017-04-01

Transporters, expressed in various tissues, govern the absorption, distribution, metabolism, and excretion of drugs, and consequently their inherent safety and efficacy profiles. Drugs may interact with a transporter as a substrate and/or an inhibitor. Understanding transporter-mediated drug-drug interactions (DDIs), in addition to enzyme-mediated DDIs, is an integral part of risk assessment in drug development and regulatory review because the concomitant use of more than one medication in patients is common. © 2016 ASCPT.

COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport

International Nuclear Information System (INIS)

Wang, Ying-Nai; Wang, Hongmei; Yamaguchi, Hirohito; Lee, Hong-Jen; Lee, Heng-Huan; Hung, Mien-Chie

2010-01-01

Research highlights: → ARF1 activation is involved in the EGFR transport to the ER and the nucleus. → Assembly of γ-COP coatomer mediates EGFR transport to the ER and the nucleus. → Golgi-to-ER retrograde trafficking regulates nuclear transport of EGFR. -- Abstract: Emerging evidence indicates that cell surface receptors, such as the entire epidermal growth factor receptor (EGFR) family, have been shown to localize in the nucleus. A retrograde route from the Golgi to the endoplasmic reticulum (ER) is postulated to be involved in the EGFR trafficking to the nucleus; however, the molecular mechanism in this proposed model remains unexplored. Here, we demonstrate that membrane-embedded vesicular trafficking is involved in the nuclear transport of EGFR. Confocal immunofluorescence reveals that in response to EGF, a portion of EGFR redistributes to the Golgi and the ER, where its NH 2 -terminus resides within the lumen of Golgi/ER and COOH-terminus is exposed to the cytoplasm. Blockage of the Golgi-to-ER retrograde trafficking by brefeldin A or dominant mutants of the small GTPase ADP-ribosylation factor, which both resulted in the disassembly of the coat protein complex I (COPI) coat to the Golgi, inhibit EGFR transport to the ER and the nucleus. We further find that EGF-dependent nuclear transport of EGFR is regulated by retrograde trafficking from the Golgi to the ER involving an association of EGFR with γ-COP, one of the subunits of the COPI coatomer. Our findings experimentally provide a comprehensive pathway that nuclear transport of EGFR is regulated by COPI-mediated vesicular trafficking from the Golgi to the ER, and may serve as a general mechanism in regulating the nuclear transport of other cell surface receptors.

A stromal cell free culture system generates mouse pro-T cells that can reconstitute T-cell compartments in vivo.

Science.gov (United States)

Gehre, Nadine; Nusser, Anja; von Muenchow, Lilly; Tussiwand, Roxane; Engdahl, Corinne; Capoferri, Giuseppina; Bosco, Nabil; Ceredig, Rhodri; Rolink, Antonius G

2015-03-01

T-cell lymphopenia following BM transplantation or diseases such as AIDS result in immunodeficiency. Novel approaches to ameliorate this situation are urgently required. Herein, we describe a novel stromal cell free culture system in which Lineage(-) Sca1(+)c-kit(+) BM hematopoietic progenitors very efficiently differentiate into pro-T cells. This culture system consists of plate-bound Delta-like 4 Notch ligand and the cytokines SCF and IL-7. The pro-T cells developing in these cultures express CD25, CD117, and partially CD44; express cytoplasmic CD3ε; and have their TCRβ locus partially D-J rearranged. They could be expanded for over 3 months and used to reconstitute the T-cell compartments of sublethally irradiated T-cell-deficient CD3ε(-/-) mice or lethally irradiated WT mice. Pro-T cells generated in this system could partially correct the T-cell lymphopenia of pre-Tα(-/-) mice. However, reconstituted CD3ε(-/-) mice suffered from a wasting disease that was prevented by co-injection of purified CD4(+) CD25(high) WT Treg cells. In a T-cell-sufficient or T-lymphopenic setting, the development of disease was not observed. Thus, this in vitro culture system represents a powerful tool to generate large numbers of pro-T cells for transplantation and possibly with clinical applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Flavonoids Are Inhibitors of Human Organic Anion Transporter 1 (OAT1)–Mediated Transport

Science.gov (United States)

An, Guohua; Wang, Xiaodong

2014-01-01

Organic anion transporter 1 (OAT1) has been reported to be involved in the nephrotoxicity of many anionic xenobiotics. As current clinically used OAT1 inhibitors are often associated with safety issues, identifying potent OAT1 inhibitors with little toxicity is of great value in reducing OAT1-mediated drug nephrotoxicity. Flavonoids are a class of polyphenolic compounds with exceptional safety records. Our objective was to evaluate the effects of 18 naturally occurring flavonoids, and some of their glycosides, on the uptake of para-aminohippuric acid (PAH) in both OAT1-expressing and OAT1-negative LLC-PK1 cells. Most flavonoid aglycones produced substantial decreases in PAH uptake in OAT1-expressing cells. Among the flavonoids screened, fisetin, luteolin, morin, and quercetin exhibited the strongest effect and produced complete inhibition of OAT1-mediated PAH uptake at a concentration of 50 μM. Further concentration-dependent studies revealed that both morin and luteolin are potent OAT1 inhibitors, with IC50 values of flavonoid aglycones, all flavonoid glycosides had negligible or small effects on OAT1. In addition, the role of OAT1 in the uptake of fisetin, luteolin, morin, and quercetin was investigated and fisetin was found to be a substrate of OAT1. Taken together, our results indicate that flavonoids are a novel class of OAT1 modulators. Considering the high consumption of flavonoids in the diet and in herbal products, OAT1-mediated flavonoid-drug interactions may be clinically relevant. Further investigation is warranted to evaluate the nephroprotective role of flavonoids in relation to drug-induced nephrotoxicity mediated by the OAT1 pathway. PMID:25002746

Reactive Transport Modeling of Microbe-mediated Fe (II) Oxidation for Enhanced Oil Recovery

Science.gov (United States)

Surasani, V.; Li, L.

2011-12-01

Microbially Enhanced Oil Recovery (MEOR) aims to improve the recovery of entrapped heavy oil in depleted reservoirs using microbe-based technology. Reservoir ecosystems often contain diverse microbial communities those can interact with subsurface fluids and minerals through a network of nutrients and energy fluxes. Microbe-mediated reactions products include gases, biosurfactants, biopolymers those can alter the properties of oil and interfacial interactions between oil, brine, and rocks. In addition, the produced biomass and mineral precipitates can change the reservoir permeability profile and increase sweeping efficiency. Under subsurface conditions, the injection of nitrate and Fe (II) as the electron acceptor and donor allows bacteria to grow. The reaction products include minerals such as Fe(OH)3 and nitrogen containing gases. These reaction products can have large impact on oil and reservoir properties and can enhance the recovery of trapped oil. This work aims to understand the Fe(II) oxidation by nitrate under conditions relevant to MEOR. Reactive transport modeling is used to simulate the fluid flow, transport, and reactions involved in this process. Here we developed a complex reactive network for microbial mediated nitrate-dependent Fe (II) oxidation that involves both thermodynamic controlled aqueous reactions and kinetic controlled Fe (II) mineral reaction. Reactive transport modeling is used to understand and quantify the coupling between flow, transport, and reaction processes. Our results identify key parameter controls those are important for the alteration of permeability profile under field conditions.

Protein Kinases C-Mediated Regulations of Drug Transporter Activity, Localization and Expression

Directory of Open Access Journals (Sweden)

Abdullah Mayati

2017-04-01

Full Text Available Drug transporters are now recognized as major actors in pharmacokinetics, involved notably in drug–drug interactions and drug adverse effects. Factors that govern their activity, localization and expression are therefore important to consider. In the present review, the implications of protein kinases C (PKCs in transporter regulations are summarized and discussed. Both solute carrier (SLC and ATP-binding cassette (ABC drug transporters can be regulated by PKCs-related signaling pathways. PKCs thus target activity, membrane localization and/or expression level of major influx and efflux drug transporters, in various normal and pathological types of cells and tissues, often in a PKC isoform-specific manner. PKCs are notably implicated in membrane insertion of bile acid transporters in liver and, in this way, are thought to contribute to cholestatic or choleretic effects of endogenous compounds or drugs. The exact clinical relevance of PKCs-related regulation of drug transporters in terms of drug resistance, pharmacokinetics, drug–drug interactions and drug toxicity remains however to be precisely determined. This issue is likely important to consider in the context of the development of new drugs targeting PKCs-mediated signaling pathways, for treating notably cancers, diabetes or psychiatric disorders.

Field distribution and DNA transport in solid tumors during electric field-mediated gene delivery.

Science.gov (United States)

Henshaw, Joshua W; Yuan, Fan

2008-02-01

Gene therapy has a great potential in cancer treatment. However, the efficacy of cancer gene therapy is currently limited by the lack of a safe and efficient means to deliver therapeutic genes into the nucleus of tumor cells. One method under investigation for improving local gene delivery is based on the use of pulsed electric field. Despite repeated demonstration of its effectiveness in vivo, the underlying mechanisms behind electric field-mediated gene delivery remain largely unknown. Without a thorough understanding of these mechanisms, it will be difficult to further advance the gene delivery. In this review, the electric field-mediated gene delivery in solid tumors will be examined by following individual transport processes that must occur in vivo for a successful gene transfer. The topics of examination include: (i) major barriers for gene delivery in the body, (ii) distribution of electric fields at both cell and tissue levels during the application of external fields, and (iii) electric field-induced transport of genes across each of the barriers. Through this approach, the review summarizes what is known about the mechanisms behind electric field-mediated gene delivery and what require further investigations in future studies.

Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms.

Science.gov (United States)

Feyerabend, Thorsten B; Terszowski, Grzegorz; Tietz, Annette; Blum, Carmen; Luche, Hervé; Gossler, Achim; Gale, Nicholas W; Radtke, Freddy; Fehling, Hans Jörg; Rodewald, Hans-Reimer

2009-01-16

Notch1 signaling is required for T cell development and has been implicated in fate decisions in the thymus. We showed that Notch1 deletion in progenitor T cells (pro-T cells) revealed their latent developmental potential toward becoming conventional and plasmacytoid dendritic cells. In addition, Notch1 deletion in pro-T cells resulted in large numbers of thymic B cells, previously explained by T-to-B cell fate conversion. Single-cell genotyping showed, however, that the majority of these thymic B cells arose from Notch1-sufficient cells by a cell-extrinsic pathway. Fate switching nevertheless exists for a subset of thymic B cells originating from Notch1-deleted pro-T cells. Chimeric mice lacking the Notch ligand delta-like 4 (Dll4) in thymus epithelium revealed an essential role for Dll4 in T cell development. Thus, Notch1-Dll4 signaling fortifies T cell commitment by suppressing non-T cell lineage potential in pro-T cells, and normal Notch1-driven T cell development repels excessive B cells in the thymus.

Sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle

OpenAIRE

Koh, Ho-Jin; Toyoda, Taro; Fujii, Nobuharu; Jung, Michelle M.; Rathod, Amee; Middelbeek, R. Jan-Willem; Lessard, Sarah J.; Treebak, Jonas T.; Tsuchihara, Katsuya; Esumi, Hiroyasu; Richter, Erik A.; Wojtaszewski, Jørgen F. P.; Hirshman, Michael F.; Goodyear, Laurie J.

2010-01-01

The signaling mechanisms that mediate the important effects of contraction to increase glucose transport in skeletal muscle are not well understood, but are known to occur through an insulin-independent mechanism. Muscle-specific knockout of LKB1, an upstream kinase for AMPK and AMPK-related protein kinases, significantly inhibited contraction-stimulated glucose transport. This finding, in conjunction with previous studies of ablated AMPKα2 activity showing no effect on contraction-stimulated...

Isoflavonas em isolados e concentrados protéicos de soja Isoflavones in soy protein isolate and soy protein concentrate

Directory of Open Access Journals (Sweden)

Maria Cristina Y. Lui

2003-12-01

Full Text Available Isolados e concentrados protéicos de soja são ingredientes largamente utilizados na indústria de panificação, confeitaria, bebidas e embutidos. As isoflavonas presentes na soja podem sofrer alterações em quantidade e perfil de distribuição dependendo das condições de processamento. O objetivo deste estudo foi verificar o balanço de massa de isoflavonas e proteína em processamento de isolados e de concentrados protéicos de soja (tratamento com ácido e com álcool. A maior parte das isoflavonas presentes na matéria-prima (farinha desengordurada de soja é perdida nos sobrenadantes de processo (90% para extração com etanol 60%, 52% para processamento de isolado protéico e 47% para extração com ácido. O teor de isoflavonas nos produtos obtidos foi de 686µg/g base seca (b.s. para isolado protéico, 871µ g/g b.s. para concentrado protéico obtido por tratamento ácido e apenas 153µg/g b.s. para concentrado protéico obtido por tratamento com álcool. Não foi observada alteração no perfil de distribuição das isoflavonas nesse último processo, enquanto que nos dois primeiros notou-se diminuição da quantidade das formas malonil glicosídeos e aumento da quantidade das formas beta-glicosiladas e gliconas.Soy protein isolate (SPI and soy protein concentrate (SPC are largely used in bakery, confectionary, meat and beverage products. Isoflavones present in soybeans products can undergo changes in quantity and profile depending on the processing conditions. The objective of this work was to conduct mass balance studies of isoflavones and protein during the processing of SPI and SPC (acid and alcohol leach. The majority of isoflavones present in the raw material is lost in the supernatants (90% for SPC treated with alcohol, 52% for SPI and 47% for SPC treated with acid. Total concentration of isoflavones was 652µg/g for SPI, 838µg/g for SPC (acid leach, and only 147µg/g for SPC (alcohol leach. There were no changes in the

Utilisation de la Technique D\\'électrophorèse des Protéines Totales ...

African Journals Online (AJOL)

Utilisation de la Technique D\\'électrophorèse des Protéines Totales sur Gel de Polyacrylamide-SDS (SDS-PAGE) pour L\\'étude de la Diversité des Rhizobiums D\\'Acacia tortilis (Forsk.) Hayne Subsp. Raddiana (Savi) Brenan.

48 CFR 1019.202-70 - The Treasury Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false The Treasury Mentor-Protégé Program. 1019.202-70 Section 1019.202-70 Federal Acquisition Regulations System DEPARTMENT OF THE TREASURY SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Policies 1019.202-70 The Treasury Mentor...

Efeitos da desnutrição protéica pós-natal no desempenho de ratos em diferentes tarefas de aprendizagem e memória

OpenAIRE

Camila Tavares Valadares

2006-01-01

A desnutrição protéica em estágios iniciais da vida produz alterações estruturais, neuroquímicas e funcionais no sistema nervoso central, podendo causar prejuízos no desenvolvimento cognitivo e comportamental. Assim, o objetivo do presente estudo foi o de investigar os efeitos da desnutrição protéica pós-natal em tarefas que avaliam a aprendizagem e memória. Estas investigações foram feitas comparando o desempenho de ratos Wistar, submetidos à desnutrição protéica (6% de proteína) durante a l...

Simulating kinetic parameters in transporter mediated permeability across Caco-2 cells. A case study on estrange-3-sulphate

DEFF Research Database (Denmark)

Rolsted, Kamilla; Rapin, Nicolas; Steffansen, Bente

2011-01-01

Substances that compete for the same saturable intestinal transporters may when dosed together lead to altered permeability and hence influence bioavailability. The aim was to simulate kinetic parameters, i.e. K(m) and J(max), for transporter mediated E(1)S permeability across Caco-2 cells...

Functional characterisation of an intron retaining K+ transporter of barley reveals intron-mediated alternate splicing

KAUST Repository

Shahzad, K.; Rauf, M.; Ahmed, M.; Malik, Z. A.; Habib, I.; Ahmed, Z.; Mahmood, K.; Ali, R.; Masmoudi, K.; Lemtiri-Chlieh, Fouad; Gehring, Christoph A; Berkowitz, G. A.; Saeed, N. A.

2015-01-01

Intron retention in transcripts and the presence of 5 and 3 splice sites within these introns mediate alternate splicing, which is widely observed in animals and plants. Here, functional characterisation of the K+ transporter, HvHKT2;1, with stably

The Swiss-Prot protein knowledgebase and ExPASy: providing the plant community with high quality proteomic data and tools.

Science.gov (United States)

Schneider, Michel; Tognolli, Michael; Bairoch, Amos

2004-12-01

The Swiss-Prot protein knowledgebase provides manually annotated entries for all species, but concentrates on the annotation of entries from model organisms to ensure the presence of high quality annotation of representative members of all protein families. A specific Plant Protein Annotation Program (PPAP) was started to cope with the increasing amount of data produced by the complete sequencing of plant genomes. Its main goal is the annotation of proteins from the model plant organism Arabidopsis thaliana. In addition to bibliographic references, experimental results, computed features and sometimes even contradictory conclusions, direct links to specialized databases connect amino acid sequences with the current knowledge in plant sciences. As protein families and groups of plant-specific proteins are regularly reviewed to keep up with current scientific findings, we hope that the wealth of information of Arabidopsis origin accumulated in our knowledgebase, and the numerous software tools provided on the Expert Protein Analysis System (ExPASy) web site might help to identify and reveal the function of proteins originating from other plants. Recently, a single, centralized, authoritative resource for protein sequences and functional information, UniProt, was created by joining the information contained in Swiss-Prot, Translation of the EMBL nucleotide sequence (TrEMBL), and the Protein Information Resource-Protein Sequence Database (PIR-PSD). A rising problem is that an increasing number of nucleotide sequences are not being submitted to the public databases, and thus the proteins inferred from such sequences will have difficulties finding their way to the Swiss-Prot or TrEMBL databases.

Levelling The Playing Field: Reducing Barriers To Mentoring For Women Protégés In The South African Organisational Context

OpenAIRE

Kevin Stone; Melinda Coetzee

2005-01-01

The purpose of this study was to investigate the impediments to effective mentoring faced by women protégés at two South African organisations. The purposive sampling method was used to identify female employees who had participated as protégés in a mentoring relationship (N=17). Qualitative methods were used to collect and analyse data on the respondents’ experiences of the mentoring relationship. The findings indicated numerous barriers to mentoring for women. A basic taxonomy of recommenda...

HKT transporters mediate salt stress resistance in plants: from structure and function to the field.

Science.gov (United States)

Hamamoto, Shin; Horie, Tomoaki; Hauser, Felix; Deinlein, Ulrich; Schroeder, Julian I; Uozumi, Nobuyuki

2015-04-01

Plant cells are sensitive to salinity stress and do not require sodium as an essential element for their growth and development. Saline soils reduce crop yields and limit available land. Research shows that HKT transporters provide a potent mechanism for mediating salt tolerance in plants. Knowledge of the molecular ion transport and regulation mechanisms and the control of HKT gene expression are crucial for understanding the mechanisms by which HKT transporters enhance crop performance under salinity stress. This review focuses on HKT transporters in monocot plants and in Arabidopsis as a dicot plant, as a guide to efforts toward improving salt tolerance of plants for increasing the production of crops and bioenergy feedstocks. Copyright © 2014 Elsevier Ltd. All rights reserved.

Parasitic nematodes modulate PIN-mediated auxin transport to facilitate infection.

Directory of Open Access Journals (Sweden)

Wim Grunewald

2009-01-01

Full Text Available Plant-parasitic nematodes are destructive plant pathogens that cause significant yield losses. They induce highly specialized feeding sites (NFS in infected plant roots from which they withdraw nutrients. In order to establish these NFS, it is thought that the nematodes manipulate the molecular and physiological pathways of their hosts. Evidence is accumulating that the plant signalling molecule auxin is involved in the initiation and development of the feeding sites of sedentary plant-parasitic nematodes. Intercellular transport of auxin is essential for various aspects of plant growth and development. Here, we analysed the spatial and temporal expression of PIN auxin transporters during the early events of NFS establishment using promoter-GUS/GFP fusion lines. Additionally, single and double pin mutants were used in infection studies to analyse the role of the different PIN proteins during cyst nematode infection. Based on our results, we postulate a model in which PIN1-mediated auxin transport is needed to deliver auxin to the initial syncytial cell, whereas PIN3 and PIN4 distribute the accumulated auxin laterally and are involved in the radial expansion of the NFS. Our data demonstrate that cyst nematodes are able to hijack the auxin distribution network in order to facilitate the infection process.

Parasitic nematodes modulate PIN-mediated auxin transport to facilitate infection.

Science.gov (United States)

Grunewald, Wim; Cannoot, Bernard; Friml, Jirí; Gheysen, Godelieve

2009-01-01

Plant-parasitic nematodes are destructive plant pathogens that cause significant yield losses. They induce highly specialized feeding sites (NFS) in infected plant roots from which they withdraw nutrients. In order to establish these NFS, it is thought that the nematodes manipulate the molecular and physiological pathways of their hosts. Evidence is accumulating that the plant signalling molecule auxin is involved in the initiation and development of the feeding sites of sedentary plant-parasitic nematodes. Intercellular transport of auxin is essential for various aspects of plant growth and development. Here, we analysed the spatial and temporal expression of PIN auxin transporters during the early events of NFS establishment using promoter-GUS/GFP fusion lines. Additionally, single and double pin mutants were used in infection studies to analyse the role of the different PIN proteins during cyst nematode infection. Based on our results, we postulate a model in which PIN1-mediated auxin transport is needed to deliver auxin to the initial syncytial cell, whereas PIN3 and PIN4 distribute the accumulated auxin laterally and are involved in the radial expansion of the NFS. Our data demonstrate that cyst nematodes are able to hijack the auxin distribution network in order to facilitate the infection process.

Plant-mediated CH4 transport and C gas dynamics quantified in-situ in a Phalaris arundinacea-dominant wetland

DEFF Research Database (Denmark)

Jensen, Louise Askær; Elberling, Bo; Friborg, Thomas

2011-01-01

passive. Thus, diurnal variations are less important in contrast to wetland vascular plants facilitating convective gas flow. Despite of plant-dominant CH4 transport, net CH4 fluxes were low (–0.005–0.016 µmol m-2 s-1) and annually less than 1% of the annual C-CO2 assimilation. This is considered a result......±35% of ecosystem CH4 emissions were plant-mediated, but data show no evidence of significant diurnal variations related to convective gas flow regardless of season or plant growth stages. Therefore, despite a high percentage of arenchyma, P. arundinacea-mediated CH4 transport is interpreted to be predominantly...

Maize ZmALMT2 is a root anion transporter that mediates constitutive root malate efflux.

Science.gov (United States)

Ligaba, Ayalew; Maron, Lyza; Shaff, Jon; Kochian, Leon; Piñeros, Miguel

2012-07-01

Root efflux of organic acid anions underlies a major mechanism of plant aluminium (Al) tolerance on acid soils. This efflux is mediated by transporters of the Al-activated malate transporter (ALMT) or the multi-drug and toxin extrusion (MATE) families. ZmALMT2 was previously suggested to be involved in Al tolerance based on joint association-linkage mapping for maize Al tolerance. In the current study, we functionally characterized ZmALMT2 by heterologously expressing it in Xenopus laevis oocytes and transgenic Arabidopsis. In oocytes, ZmALMT2 mediated an Al-independent electrogenic transport product of organic and inorganic anion efflux. Ectopic overexpression of ZmALMT2 in an Al-hypersensitive Arabidopsis KO/KD line lacking the Al tolerance genes, AtALMT1 and AtMATE, resulted in Al-independent constitutive root malate efflux which partially restored the Al tolerance phenotype. The lack of correlation between ZmALMT2 expression and Al tolerance (e.g., expression not localized to the root tip, not up-regulated by Al, and higher in sensitive versus tolerance maize lines) also led us to question ZmALMT2's role in Al tolerance. The functional properties of the ZmALMT2 transporter presented here, along with the gene expression data, suggest that ZmALMT2 is not involved in maize Al tolerance but, rather, may play a role in mineral nutrient acquisition and transport. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

Walkability parameters, active transportation and objective physical activity: moderating and mediating effects of motor vehicle ownership in a cross-sectional study.

Science.gov (United States)

Eriksson, Ulf; Arvidsson, Daniel; Gebel, Klaus; Ohlsson, Henrik; Sundquist, Kristina

2012-10-05

Neighborhood walkability has been associated with physical activity in several studies. However, as environmental correlates of physical activity may be context specific, walkability parameters need to be investigated separately in various countries and contexts. Furthermore, the mechanisms by which walkability affects physical activity have been less investigated. Based on previous research, we hypothesized that vehicle ownership is a potential mediator. We investigated the associations between walkability parameters and physical activity, and the mediating and moderating effects of vehicle ownership on these associations in a large sample of Swedish adults. Residential density, street connectivity and land use mix were assessed within polygon-based network buffers (using Geographic Information Systems) for 2,178 men and women. Time spent in moderate to vigorous physical activity was assessed by accelerometers, and walking and cycling for transportation were assessed by the International Physical Activity Questionnaire. Associations were examined by linear regression and adjusted for socio-demographic characteristics. The product of coefficients approach was used to investigate the mediating effect of vehicle ownership. Residential density and land use mix, but not street connectivity, were significantly associated with time spent in moderate to vigorous physical activity and walking for transportation. Cycling for transportation was not associated with any of the walkability parameters. Vehicle ownership mediated a significant proportion of the association between the walkability parameters and physical activity outcomes. For residential density, vehicle ownership mediated 25% of the association with moderate to vigorous physical activity and 20% of the association with the amount of walking for transportation. For land use mix, the corresponding proportions were 34% and 14%. Vehicle ownership did not moderate any of the associations between the walkability

Walkability parameters, active transportation and objective physical activity: moderating and mediating effects of motor vehicle ownership in a cross-sectional study

Science.gov (United States)

2012-01-01

Background Neighborhood walkability has been associated with physical activity in several studies. However, as environmental correlates of physical activity may be context specific, walkability parameters need to be investigated separately in various countries and contexts. Furthermore, the mechanisms by which walkability affects physical activity have been less investigated. Based on previous research, we hypothesized that vehicle ownership is a potential mediator. We investigated the associations between walkability parameters and physical activity, and the mediating and moderating effects of vehicle ownership on these associations in a large sample of Swedish adults. Methods Residential density, street connectivity and land use mix were assessed within polygon-based network buffers (using Geographic Information Systems) for 2,178 men and women. Time spent in moderate to vigorous physical activity was assessed by accelerometers, and walking and cycling for transportation were assessed by the International Physical Activity Questionnaire. Associations were examined by linear regression and adjusted for socio-demographic characteristics. The product of coefficients approach was used to investigate the mediating effect of vehicle ownership. Results Residential density and land use mix, but not street connectivity, were significantly associated with time spent in moderate to vigorous physical activity and walking for transportation. Cycling for transportation was not associated with any of the walkability parameters. Vehicle ownership mediated a significant proportion of the association between the walkability parameters and physical activity outcomes. For residential density, vehicle ownership mediated 25% of the association with moderate to vigorous physical activity and 20% of the association with the amount of walking for transportation. For land use mix, the corresponding proportions were 34% and 14%. Vehicle ownership did not moderate any of the associations

ChemProt: a disease chemical biology database

DEFF Research Database (Denmark)

Taboureau, Olivier; Nielsen, Sonny Kim; Audouze, Karine Marie Laure

2011-01-01

Systems pharmacology is an emergent area that studies drug action across multiple scales of complexity, from molecular and cellular to tissue and organism levels. There is a critical need to develop network-based approaches to integrate the growing body of chemical biology knowledge with network...... biology. Here, we report ChemProt, a disease chemical biology database, which is based on a compilation of multiple chemical-protein annotation resources, as well as disease-associated protein-protein interactions (PPIs). We assembled more than 700 000 unique chemicals with biological annotation for 30...... evaluation of environmental chemicals, natural products and approved drugs, as well as the selection of new compounds based on their activity profile against most known biological targets, including those related to adverse drug events. Results from the disease chemical biology database associate citalopram...

Levelling The Playing Field: Reducing Barriers To Mentoring For Women Protégés In The South African Organisational Context

Directory of Open Access Journals (Sweden)

Kevin Stone

2005-11-01

Full Text Available The purpose of this study was to investigate the impediments to effective mentoring faced by women protégés at two South African organisations. The purposive sampling method was used to identify female employees who had participated as protégés in a mentoring relationship (N=17. Qualitative methods were used to collect and analyse data on the respondents’ experiences of the mentoring relationship. The findings indicated numerous barriers to mentoring for women. A basic taxonomy of recommendations for reducing these barriers in the workplace is recommended.

Protótipos físicos e virtuais (CAD 3D: uma pesquisa descritiva sobre o processo de construção de uma saia godê

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Gisely Andressa Pires

2016-08-01

Full Text Available Este artigo discute sobre a prática da construção de protótipos na indústria do vestuário. O protótipo refere-se à construção de um modelo que está em processo de planejamento e teste para ser comercializado. Atualmente a forma mais difundida é realizando a construção efetiva das peças, porém existe disponível no mercado softwares que realizam essa atividade virtualmente. Assim, esse estudo tem como objetivo investigar o processo construção de protótipos por meio de software CAD 3D de prototipagem de vestuário e das técnicas tradicionais manuais utilizadas atualmente na indústria a fim de verificar as caraterísticas de cada etapa e os resultados alcançados. Para tanto, foi desenvolvida uma pesquisa descritiva, como forma de abordagem do problema foram realizados dois experimentos que compreendem a construção de protótipos de uma saia godê orientados pela técnica virtual e a manual. Os resultados permitiram compreender que as duas possibilidades para a elaboração de protótipos produzem resultados similares, são eficientes e uma valiosa ferramenta para avaliar uma peça de vestuário antes de ser produzida a venda.

Protótipos físicos e virtuais (CAD 3d: uma pesquisa descritiva sobre o processo de construção de uma saia godê

Directory of Open Access Journals (Sweden)

Gisely Andressa Pires

2016-10-01

Full Text Available Este artigo discute sobre a prática da construção de protótipos na indústria do vestuário. O protótipo refere-se à construção de um modelo que está em processo de planejamento e teste para ser comercializado. Atualmente a forma mais difundida é realizando a construção efetiva das peças, porém existe disponível no mercado softwares que realizam essa atividade virtualmente. Assim, esse estudo tem como objetivo investigar o processo construção de protótipos por meio de software CAD 3D de prototipagem de vestuário e das técnicas tradicionais manuais utilizadas atualmente na indústria a fim de verificar as caraterísticas de cada etapa e os resultados alcançados. Para tanto, foi desenvolvida uma pesquisa descritiva, como forma de abordagem do problema foram realizados dois experimentos que compreendem a construção de protótipos de uma saia godê orientados pela técnica virtual e a manual. Os resultados permitiram compreender que as duas possibilidades para a elaboração de protótipos produzem resultados similares, são eficientes e uma valiosa ferramenta para avaliar uma peça de vestuário antes de ser produzida a venda.

Electroacupuncture preconditioning-induced neuroprotection may be mediated by glutamate transporter type 2

OpenAIRE

Zhu, Xiaoling; Yin, Jinbo; Li, Liaoliao; Ma, Lei; Tan, Hongying; Deng, Jiao; Chen, Shaoyang; Zuo, Zhiyi

2013-01-01

Electroacupuncture has been shown to induce a preconditioning effect in the brain. The mechanisms for this protection are not fully elucidated. We hypothesize that this protection is mediated by excitatory amino acid transporters (EAATs) that have been shown to be neuroprotective. To test this hypothesis, two-month old male Sprague-Dawley rats and EAAT type 3 (EAAT3) knockout mice received or did not receive 30-min electroacupuncture once a day for 5 consecutive days. They were subjected to a...

La rehabilitación protésica en las lesiones bucales del adulto mayor

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Yaimara Pérez Hernández

2015-02-01

Full Text Available Introducción: las lesiones en la mucosa bucal relacionadas con el uso de prótesis constituyen un problema importante de salud, fundamentalmente en pacientes geriátricos. Objetivo: caracterizar las lesiones bucales en pacientes geriátricos rehabilitados protésicamente. Material y método: se realizó un estudio descriptivo, transversal y prospectivo en los consultorios médicos #9 y 47 de la Clínica Estomatológica Hermanos Saiz, municipio San Juan y Martínez, Pinar del Río, de septiembre de 2012 a septiembre de 2013. El universo estuvo conformado por 165 pacientes rehabilitados protésicamente, de los cuales 98 constituyeron la muestra, siendo pacientes que presentaron lesiones bucales producto del uso de prótesis. Como medida de resumen se utilizaron el número absoluto y el porcentaje. Resultados: el mayor número de pacientes se encontraban en edades entre 65 y 69 años, el sexo más afectado fue el femenino y las lesiones se encontraron principalmente en el maxilar y en pacientes que usaban prótesis totales de acrílico. Los pacientes que presentaban mala higiene de la prótesis eran más propensos a lesiones bucales. El mayor número de lesiones se encontró en pacientes que no practicaban el hábito de fumar. Conclusiones: se caracterizaron las lesiones bucales en pacientes geriátricos rehabilitados protésicamente, lo que posibilita proponer nuevas investigaciones sobre factores relacionados con el origen y prevención de dichas lesiones producto del uso de prótesis, y así mantener la comunicación necesaria de los implicados en el diagnóstico y atención de las personas longevas.

Processus ultra-rapides associés à la dynamique d'émission de la protéine GFP

Science.gov (United States)

Didier, P.; Guidoni, L.; Schwalbach, G.; Bigot, J.-Y.

2002-06-01

La protéine GFP (Green Fluorescent Protein) est un marqueur très efficace, utilisable en milieu vivant. La spectroscopie femtoseconde est particulièrement bien adaptée pour comprendre les mécanismes d'émission de cette protéine, étant donné la rapidité des processus de transfert mis en jeu. Nous-présentons des résultats sur la dynamique spectro-temporelle d'émission du mutant GFPuv résolue à l'échelle de la centaine de femtosecondes. Une transition Raman à 3300 cm^{-1} ainsi que la dynamique d'etablissement du gain avec un temps caractéristique d'environ 1.5 ps ont été mis en évidence.

基于不完全信息博弈的PROT项目融资模型研究%PROT Project Financing Model Based on Incomplete Information Game

Institute of Scientific and Technical Information of China (English)

王艳伟; 刘艳慧; 程静; 高鑫; 张仙

2015-01-01

以中小水电项目为代表的经营性公共基础设施项目，在采用 PROT 项目融资模式经营运行过程中，由于涉及的利益相关方之间存在信息不对称的情况，致使各方在博弈过程中存在“道德风险”，从而损害PROT项目的整体利益。将不完全信息博弈和熵理论引入 PROT 项目融资模式当中，分析社会投资者、政府以及公众三方的支付函数、期望收益以及项目融资系统熵的大小，建立了基于不完全信息博弈的 PROT 项目融资模型，通过该模型可以深入了解各利益相关方博弈的内在机理，并通过项目融资系统熵的变化来有效防范和监控产生的“道德风险”。经实例验证表明该模型具有较好的适用性。%Because of the existence of information asymmetry between the stakeholders,small and medium hydropower project will result "moral hazard",which may damage the whole benefit of PROT project in the operation process of PROT project. This paper introduces game theory and entropy theory into PROT project financing model. Firstly,through the analysis of payoff function,expected revenue of three parties and project financing system entropy,the paper established the PROT project financing model based on incomplete information game. The model can understand the intrinsic mechanism of the stakeholders’ game and effectively prevent and control the moral hazard through the changes of project financing system entropy. Finally,through the examples,it has better effect.

Development, implementation and evaluation of a peer review of teaching (PRoT) initiative in nursing education.

Science.gov (United States)

Mager, Diana R; Kazer, Meredith W; Conelius, Jaclyn; Shea, Joyce; Lippman, Doris T; Torosyan, Roben; Nantz, Kathryn

2014-06-03

For many years, an area of research in higher education has been emerging around the development and implementation of fair and effective peer evaluation programs. Recently, a new body of knowledge has developed regarding the development and implementation of fair and effective peer evaluation programs resulting in formative and summative evaluations. The purpose of this article is to describe the development, implementation, and evaluation of a peer review of teaching (PRoT) program for nursing faculty, initiated at one small comprehensive university in the northeastern United States. Pairs of nursing faculty evaluated each other's teaching, syllabi, and course materials after collaborating in a pre-evaluation conference to discuss goals of the classroom visit. Qualitative data gathered in post project focus groups revealed that faculty found their modified PRoT process to be a mutually beneficial experience that was more useful, flexible and collegial, and less stressful than their previous evaluation process.

Organic anion transporter (Slc22a) family members as mediators of toxicity

International Nuclear Information System (INIS)

Sweet, Douglas H.

2005-01-01

Exposure of the body to toxic organic anions is unavoidable and occurs from both intentional and unintentional sources. Many hormones, neurotransmitters, and waste products of cellular metabolism, or their metabolites, are organic anions. The same is true for a wide variety of medications, herbicides, pesticides, plant and animal toxins, and industrial chemicals and solvents. Rapid and efficient elimination of these substances is often the body's best defense for limiting both systemic exposure and the duration of their pharmacological or toxicological effects. For organic anions, active transepithelial transport across the renal proximal tubule followed by elimination via the urine is a major pathway in this detoxification process. Accordingly, a large number of organic anion transport proteins belonging to several different gene families have been identified and found to be expressed in the proximal nephron. The function of these transporters, in combination with the high volume of renal blood flow, predisposes the kidney to increased toxic susceptibility. Understanding how the kidney mediates the transport of organic anions is integral to achieving desired therapeutic outcomes in response to drug interactions and chemical exposures, to understanding the progression of some disease states, and to predicting the influence of genetic variation upon these processes. This review will focus on the organic anion transporter (OAT) family and discuss the known members, their mechanisms of action, subcellular localization, and current evidence implicating their function as a determinant of the toxicity of certain endogenous and xenobiotic agents

Anastomose cavo-pulmonar total sem uso de material protético

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Valdester C. PINTO Jr.

1998-07-01

Full Text Available Objetivo: Demonstrar a viabilidade na feitura de túnel cava inferior-cava superior com retalho da parede atrial direita, evitando o emprego de material protético. Casuística e Métodos: Foram operados 2 pacientes nos quais se empregou a técnica de anastomose cavo-pulmonar total, sem uso de material protético. O primeiro caso, A.L.M., masc, 4 anos, 15 kg, era portador de atresia tricúspide (EP, com comunicação interventricular (CIV restritiva. O segundo caso, M.E.N.O., fem, 15 anos, 47 kg, tinha doença de Ebstein. O controle pós-operatório dos pacientes foi feito com ecocardiograma e cateterismo cardíaco. As operações foram realizadas com o emprego de circulação extracorpórea (CEC, e cardioplegia sangüínea como método de proteção miocárdica. A canulação das cavas foi o mais distal possível. A tunelização foi realizada com retalho de tecido atrial direito, suturado ao septo interatrial, deixando-se o seio coronariano e a comunicação interatrial (CIA para a esquerda. Resultados: Ambos os pacientes evoluíram, sem complicações, na UTI. O primeiro apresentou derrame pleural discreto à direita, e o segundo mantém-se em estimulação artificial (VVI,R. Conclusões: A tunelização intra-atrial para anastomose cavo-pulmonar total pode ser realizada sem o uso de material protético, evitando-se os riscos advindos do seu emprego (calcificação, retração, embolização.The authors describe two cases (one tricuspid atresia without TGA or pulmonary stenosis, but with a restrictive IVC: the second of an Ebstein disease of total cavo-pulmonary anastomosis using only the tissue of the atrial wall, avoiding any prosthetic material. Both cases were done under cardiopulmonary bypass and cold blood cardioplegia. A flap of the right atrial wall was used to re-direct the blood flow. Pleural effusion in one patient and complete AV block in the other were the complications found. They conclude that right intra-atrial tunneling for

76 FR 70828 - Proposed Information Collection (Mentor-Protégé Program Application and Reports) Activity...

Science.gov (United States)

2011-11-15

... DEPARTMENT OF VETERANS AFFAIRS [OMB Control No. 2900-0723] Proposed Information Collection (Mentor... in response to the notice. This notice solicits comments on information needed to establish a mentor... will be used to institute a mentor-prot[eacute]g[eacute] program whereby large businesses agree to...

Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-κB Signaling Pathway.

Science.gov (United States)

Saito, Shoko; Cigdem, Sadik; Okuwaki, Mitsuru; Nagata, Kyosuke

2016-07-01

Nuclear-cytoplasmic transport through nuclear pore complexes is mediated by nuclear transport receptors. Previous reports have suggested that aberrant nuclear-cytoplasmic transport due to mutations or overexpression of nuclear pore complexes and nuclear transport receptors is closely linked to diseases. Nup214, a component of nuclear pore complexes, has been found as chimeric fusion proteins in leukemia. Among various Nup214 fusion proteins, SET-Nup214 and DEK-Nup214 have been shown to be engaged in tumorigenesis, but their oncogenic mechanisms remain unclear. In this study, we examined the functions of the Nup214 fusion proteins by focusing on their effects on nuclear-cytoplasmic transport. We found that SET-Nup214 and DEK-Nup214 interact with exportin-1 (XPO1)/CRM1 and nuclear RNA export factor 1 (NXF1)/TAP, which mediate leucine-rich nuclear export signal (NES)-dependent protein export and mRNA export, respectively. SET-Nup214 and DEK-Nup214 decreased the XPO1-mediated nuclear export of NES proteins such as cyclin B and proteins involved in the NF-κB signaling pathway by tethering XPO1 onto nuclear dots where Nup214 fusion proteins are localized. We also demonstrated that SET-Nup214 and DEK-Nup214 expression inhibited NF-κB-mediated transcription by abnormal tethering of the complex containing p65 and its inhibitor, IκB, in the nucleus. These results suggest that SET-Nup214 and DEK-Nup214 perturb the regulation of gene expression through alteration of the nuclear-cytoplasmic transport system. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

La rehabilitación protésica implantomucosoportada en el desdentado total

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Marlys Suse Sixto Iglesias

2015-04-01

Full Text Available Introducción: la rehabilitación sobre implantes con sobredentaduras mejora la calidad de vida de los pacientes y las técnicas para la rehabilitación son simples y preserva mayor cantidad de tejido dentario. Objetivo: caracterizar el comportamiento de la rehabilitación protésica implantomucosoportada en el desdentado total. Material y método: se realizó un estudio descriptivo, longitudinal y retrospectivo en los pacientes rehabilitados con sobredentaduras implantomucosoportadas en la Clínica Estomatológica "Antonio Briones Montoto" de Pinar del Río, en el período comprendido entre el año 2013 y 2014. El universo estuvo constituido por 28 pacientes, coincidente con la muestra. La información se recopiló a través de datos obtenidos en la historia clínica. Resultados: se encontró la mayor cantidad de implantes en la mandíbula. Se comprobó que la mayoría de los pacientes con mucositis perimplantaria el 14,3%, presentaban una higiene bucal regular o mala. Existió una dependencia estadísticamente significativa entre los períodos de tiempo en que les fue necesario el cambio de la cápsula de teflón. Conclusiones: se caracterizó el comportamiento de la rehabilitación protésica implantomucosoportada en el desdentado total.

Prediction of Metabolic Pathway Involvement in Prokaryotic UniProtKB Data by Association Rule Mining

KAUST Repository

Boudellioua, Imene; Saidi, Rabie; Hoehndorf, Robert; Martin, Maria J.; Solovyev, Victor

2016-01-01

The widening gap between known proteins and their functions has encouraged the development of methods to automatically infer annotations. Automatic functional annotation of proteins is expected to meet the conflicting requirements of maximizing annotation coverage, while minimizing erroneous functional assignments. This trade-off imposes a great challenge in designing intelligent systems to tackle the problem of automatic protein annotation. In this work, we present a system that utilizes rule mining techniques to predict metabolic pathways in prokaryotes. The resulting knowledge represents predictive models that assign pathway involvement to UniProtKB entries. We carried out an evaluation study of our system performance using cross-validation technique. We found that it achieved very promising results in pathway identification with an F1-measure of 0.982 and an AUC of 0.987. Our prediction models were then successfully applied to 6.2 million UniProtKB/TrEMBL reference proteome entries of prokaryotes. As a result, 663,724 entries were covered, where 436,510 of them lacked any previous pathway annotations.

Prediction of Metabolic Pathway Involvement in Prokaryotic UniProtKB Data by Association Rule Mining

KAUST Repository

Boudellioua, Imene

2016-07-08

The widening gap between known proteins and their functions has encouraged the development of methods to automatically infer annotations. Automatic functional annotation of proteins is expected to meet the conflicting requirements of maximizing annotation coverage, while minimizing erroneous functional assignments. This trade-off imposes a great challenge in designing intelligent systems to tackle the problem of automatic protein annotation. In this work, we present a system that utilizes rule mining techniques to predict metabolic pathways in prokaryotes. The resulting knowledge represents predictive models that assign pathway involvement to UniProtKB entries. We carried out an evaluation study of our system performance using cross-validation technique. We found that it achieved very promising results in pathway identification with an F1-measure of 0.982 and an AUC of 0.987. Our prediction models were then successfully applied to 6.2 million UniProtKB/TrEMBL reference proteome entries of prokaryotes. As a result, 663,724 entries were covered, where 436,510 of them lacked any previous pathway annotations.

Simultaneous Assessment of Transporter-Mediated Drug-Drug Interactions Using a Probe Drug Cocktail in Cynomolgus Monkey.

Science.gov (United States)

Kosa, Rachel E; Lazzaro, Sarah; Bi, Yi-An; Tierney, Brendan; Gates, Dana; Modi, Sweta; Costales, Chester; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena V

2018-06-07

We aim to establish an in vivo preclinical model to enable simultaneous assessment of inhibition potential of an investigational drug on clinically relevant drug transporters, organic anion transporting polypeptide (OATP)1B, breast cancer resistance protein (BCRP), P-glycoprotein (P-gp) and organic anion transporter (OAT)3. Pharmacokinetics of substrate cocktail consisting of pitavastatin (OATP1B substrate), rosuvastatin (OATP1B/BCRP/OAT3), sulfasalazine (BCRP) and talinolol (P-gp) were obtained in cynomolgus monkey - alone or in combination with transporter inhibitors. Single dose rifampicin (30 mg/kg) significantly (pdrugs, with a marked effect on pitavastatin and rosuvastatin (AUC ratio ~21-39). Elacridar, BCRP/P-gp inhibitor, increased the AUC of sulfasalazine, talinolol, as well as rosuvastatin and pitavastatin. An OAT1/3 inhibitor (probenecid) significantly (pdrug-drug interaction risk assessment, before advancing a new molecular entity into clinical development, as well as providing mechanistic insights on transporter-mediated interactions. The American Society for Pharmacology and Experimental Therapeutics.

Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice.

Science.gov (United States)

Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M; Gautier, Emmanuel L; Westerterp, Marit; Bittman, Robert; Tall, Alan R; Chen, Shu-Hsia; Thomas, Michael J; Kreisel, Daniel; Swartz, Melody A; Sorci-Thomas, Mary G; Randolph, Gwendalyn J

2013-04-01

Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin--1 surgical and the other genetic--to quantitatively track RCT following injection of [3H]-cholesterol-loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [2H]6-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [2H]-Cholesterol was retained in aortae of anti-VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis.

Hepatic ZIP14-mediated zinc transport is required for adaptation to endoplasmic reticulum stress.

Science.gov (United States)

Kim, Min-Hyun; Aydemir, Tolunay B; Kim, Jinhee; Cousins, Robert J

2017-07-18

Extensive endoplasmic reticulum (ER) stress damages the liver, causing apoptosis and steatosis despite the activation of the unfolded protein response (UPR). Restriction of zinc from cells can induce ER stress, indicating that zinc is essential to maintain normal ER function. However, a role for zinc during hepatic ER stress is largely unknown despite important roles in metabolic disorders, including obesity and nonalcoholic liver disease. We have explored a role for the metal transporter ZIP14 during pharmacologically and high-fat diet-induced ER stress using Zip14 -/- (KO) mice, which exhibit impaired hepatic zinc uptake. Here, we report that ZIP14-mediated hepatic zinc uptake is critical for adaptation to ER stress, preventing sustained apoptosis and steatosis. Impaired hepatic zinc uptake in Zip14 KO mice during ER stress coincides with greater expression of proapoptotic proteins. ER stress-induced Zip14 KO mice show greater levels of hepatic steatosis due to higher expression of genes involved in de novo fatty acid synthesis, which are suppressed in ER stress-induced WT mice. During ER stress, the UPR-activated transcription factors ATF4 and ATF6α transcriptionally up-regulate Zip14 expression. We propose ZIP14 mediates zinc transport into hepatocytes to inhibit protein-tyrosine phosphatase 1B (PTP1B) activity, which acts to suppress apoptosis and steatosis associated with hepatic ER stress. Zip14 KO mice showed greater hepatic PTP1B activity during ER stress. These results show the importance of zinc trafficking and functional ZIP14 transporter activity for adaptation to ER stress associated with chronic metabolic disorders.

Placental Drug Transport-on-a-Chip: A Microengineered In Vitro Model of Transporter-Mediated Drug Efflux in the Human Placental Barrier.

Science.gov (United States)

Blundell, Cassidy; Yi, Yoon-Suk; Ma, Lin; Tess, Emily R; Farrell, Megan J; Georgescu, Andrei; Aleksunes, Lauren M; Huh, Dongeun

2018-01-01

The current lack of knowledge about the effect of maternally administered drugs on the developing fetus is a major public health concern worldwide. The first critical step toward predicting the safety of medications in pregnancy is to screen drug compounds for their ability to cross the placenta. However, this type of preclinical study has been hampered by the limited capacity of existing in vitro and ex vivo models to mimic physiological drug transport across the maternal-fetal interface in the human placenta. Here the proof-of-principle for utilizing a microengineered model of the human placental barrier to simulate and investigate drug transfer from the maternal to the fetal circulation is demonstrated. Using the gestational diabetes drug glyburide as a model compound, it is shown that the microphysiological system is capable of reconstituting efflux transporter-mediated active transport function of the human placental barrier to limit fetal exposure to maternally administered drugs. The data provide evidence that the placenta-on-a-chip may serve as a new screening platform to enable more accurate prediction of drug transport in the human placenta. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transporter-mediated interaction of indican and methotrexate in rats

Directory of Open Access Journals (Sweden)

Shiuan-Pey Lin

2018-04-01

Full Text Available Indican (indoxyl-β-D-glucoside is present in several Chinese herbs e.g. Isatis indigotica, Polygonum tinctorium and Polygonum perfoliatum. The major metabolite of indican was indoxyl sulfate (IS, an uremic toxin which was a known substrate/inhibitor of organic anion transporter (OAT 1, OAT 3 and multidrug resistance-associated protein (MRP 4. Methotrexate (MTX, an important immunosuppressant with narrow therapeutic window, is a substrate of OAT 1, 2, 3, 4 and MRP 1, 2, 3, 4. We hypothesized that IS, the major metabolite of oral indican, might inhibit the renal excretion of MTX mediated by OAT 1, OAT 3 and MRP 4. Therefore, this study investigated the effect of oral indican on the pharmacokinetics of MTX. Rats were orally given MTX with and without indican (20.0 and 40.0 mg/kg in a parallel design. The serum MTX concentration was determined by a fluorescence polarization immunoassay. For mechanism clarification, phenolsulfonphthalein (PSP, 5.0 mg/kg, a probe substrate of OAT 1, OAT 3, MRP 2 and MRP 4, was intravenously given to rats with and without a intravenous bolus of IS (10.0 mg/kg to measure the effect of IS on the elimination of PSP. The results indicated that 20.0 and 40.0 mg/kg of oral indican significantly increased the area under concentration–time curve0-t (AUC0-t of MTX by 231% and 259%, prolonged the mean residence time (MRT by 223% and 204%, respectively. Furthermore, intravenous IS significantly increased the AUC0-t of PSP by 204% and decreased the Cl by 68%. In conclusion, oral indican increased the systemic exposure and MRT of MTX through inhibition on multiple anion transporters including OAT 1, OAT 3 and MRP 4 by the major metabolite IS. Keywords: Indican, Indoxyl sulfate, Methotrexate, Anion transporters, Pharmacokinetics

Unc-51/ATG1 controls axonal and dendritic development via kinesin-mediated vesicle transport in the Drosophila brain.

Directory of Open Access Journals (Sweden)

Hiroaki Mochizuki

2011-05-01

Full Text Available Members of the evolutionary conserved Ser/Thr kinase Unc-51 family are key regulatory proteins that control neural development in both vertebrates and invertebrates. Previous studies have suggested diverse functions for the Unc-51 protein, including axonal elongation, growth cone guidance, and synaptic vesicle transport.In this work, we have investigated the functional significance of Unc-51-mediated vesicle transport in the development of complex brain structures in Drosophila. We show that Unc-51 preferentially accumulates in newly elongating axons of the mushroom body, a center of olfactory learning in flies. Mutations in unc-51 cause disintegration of the core of the developing mushroom body, with mislocalization of Fasciclin II (Fas II, an IgG-family cell adhesion molecule important for axonal guidance and fasciculation. In unc-51 mutants, Fas II accumulates in the cell bodies, calyx, and the proximal peduncle. Furthermore, we show that mutations in unc-51 cause aberrant overshooting of dendrites in the mushroom body and the antennal lobe. Loss of unc-51 function leads to marked accumulation of Rab5 and Golgi components, whereas the localization of dendrite-specific proteins, such as Down syndrome cell adhesion molecule (DSCAM and No distributive disjunction (Nod, remains unaltered. Genetic analyses of kinesin light chain (Klc and unc-51 double heterozygotes suggest the importance of kinesin-mediated membrane transport for axonal and dendritic development. Moreover, our data demonstrate that loss of Klc activity causes similar axonal and dendritic defects in mushroom body neurons, recapitulating the salient feature of the developmental abnormalities caused by unc-51 mutations.Unc-51 plays pivotal roles in the axonal and dendritic development of the Drosophila brain. Unc-51-mediated membrane vesicle transport is important in targeted localization of guidance molecules and organelles that regulate elongation and compartmentalization of

7-ketocholesteryl-9-carboxynonanoate enhances ATP binding cassette transporter A1 expression mediated by PPARγ in THP-1 macrophages.

Science.gov (United States)

Chi, Yan; Wang, Le; Liu, Yuanyuan; Ma, Yanhua; Wang, Renjun; Han, Xiaofei; Qiao, Hui; Lin, Jiabin; Matsuura, Eiji; Liu, Shuqian; Liu, Qingping

2014-06-01

ATP binding cassette transporter A1 (ABCA1) is a member of the ATP-binding cassette transporter family. It plays an essential role in mediating the efflux of excess cholesterol. It is known that peroxisome proliferator-activated receptor gamma (PPARγ) promoted ABCA1 expression. We previously found 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) upregulated ABCA1 partially through CD36 mediated signals. In the present study, we intended to test if PPARγ signally is involved in the upregulation mediated by oxLig-1. First, we docked oxLig-1 and the ligand-binding domain (LBD) of PPARγ by using AutoDock 3.05 and subsequently confirmed the binding by ELISA assay. Western blotting analyses showed that oxLig-1 induces liver X receptor alpha (LXRα), PPARγ and consequently ABCA1 expression. Furthermore, oxLig-1 significantly enhanced ApoA-I-mediated cholesterol efflux. Pretreatment with an inhibitor for PPARγ (GW9662) or/and LXRα (GGPP) attenuated oxLig-1-induced ABCA1 expression. Under PPARγ knockdown by using PPARγ-shRNA, oxLig-1-induced ABCA1 expression and cholesterol efflux in THP-1 macrophages was blocked by 62% and 25% respectively. These observations suggest that oxLig-1 is a novel PPARγ agonist, promoting ApoA-I-mediated cholesterol efflux from THP-1 macrophages by increasing ABCA1 expression via induction of PPARγ. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Carrier-Mediated Transport of Nicotine Across the Inner Blood-Retinal Barrier: Involvement of a Novel Organic Cation Transporter Driven by an Outward H(+) Gradient.

Science.gov (United States)

Tega, Yuma; Kubo, Yoshiyuki; Yuzurihara, Chihiro; Akanuma, Shin-Ichi; Hosoya, Ken-Ichi

2015-09-01

The present study was carried out to investigate the blood-to-retina transport of nicotine across the inner blood-retinal barrier (BRB). Using the in vivo vascular injection method, the blood-to-retina influx clearance of nicotine across the BRB was determined as 131 μL/(min?g retina), which is much higher than that of a nonpermeable paracellular marker, and blood-to-retina transport of nicotine was inhibited by organic cations such as pyrilamine and verapamil. The nicotine uptake by a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells), an in vitro model of the inner BRB, exhibited time, temperature, and concentration dependence with a Km of 492 μM. These results suggest the involvement of a carrier-mediated transport process in nicotine transport in the inner BRB. The nicotine uptake by TR-iBRB2 cells was stimulated by an outwardly directed H(+) gradient, and the uptake was significantly inhibited by bulky and hydrophobic cationic drugs, whereas inhibitors of organic cation transporters did not show inhibitory effect. These results suggest that the novel organic cation transport system driven by an outwardly directed H(+) gradient is involved in the blood-to-retina transport of nicotine across the inner BRB. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

77 FR 3842 - Agency Information Collection (Mentor-Protégé Program Application and Reports) Activities Under...

Science.gov (United States)

2012-01-25

... DEPARTMENT OF VETERANS AFFAIRS [OMB Control No. 2900-0723] Agency Information Collection (Mentor... will be used to institute a mentor-prot[eacute]g[eacute] program whereby large businesses agree to... developmental plan contained in the approved agreement and to report the specific actions taken by the mentor to...

Desempenho estrutural de protótipo de alvenaria construída com blocos de terra crua estabilizada

Directory of Open Access Journals (Sweden)

Aluísio Braz Melo

Full Text Available Uma das dificuldades na difusão de tecnologias de construção não convencionais é a ausência de informações técnicas sobre os sistemas construtivos existentes. Exemplos de construção eco-eficiente, em pequena escala, feita com blocos de terra crua, desenvolvidos pelo Prof. Roberto Mattone, do Politecnico di Torino, Itália, podem ser encontrados no Brasil, Itália e Argentina. Estes blocos feitos com prensa manual apresentam intertravamentos entre si que melhoram a resistência e a rigidez da alvenaria. Testes em protótipos construídos com eles são necessários para atender as exigências técnicas e se obter credibilidade nas agências governamentais financiadoras. Este artigo apresenta resultados referentes a avaliação de desempenho estrutural de alvenaria (protótipo construído em escala real feita com blocos de terra crua estabilizada, mecânicamente por prensagem e químicamente por adição de cimento Portland. As avaliações de cargas de ocupação e impactos na alvenaria foram realizadas através de ensaios de impactos de corpo mole e de corpo duro, solicitações transmitidas por fechamentos bruscos de porta e solicitações de cargas provenientes de peças suspensas. A partir dos resultados pode-se afirmar que o protótipo apresentou desempenho satisfatório em relação à segurança estrutural. Destaca-se que os blocos avaliados tem grande potencial para reduzir o impacto ambiental das edificações.

Electrocatalizadores para pilas de combustible de membrana de intercambio protónico

OpenAIRE

Lázaro Elorri, María Jesús; Moliner Álvarez, Rafael; Calvillo Lamana, Laura; Pastor Ferrer, Elsa

2008-01-01

Electrocatalizadores para pilas de combustible de membrana de intercambio protónico. Procedimiento de obtención de un material de carbono mesoporoso (SMC) que comprende: la adición de sílice coloidal a un precursor polimérico de carbono; el curado térmico; el carbonizado del compuesto obtenido; lavado del compuesto carbonizado con ácido fluorhídrico (HF) o NaOH; y la oxidación del material lavado. Además la invención se refiere a un catalizador para pilas de combustibl...

Receptor-mediated mechanism for the transport of prolactin from blood to cerebrospinal fluid

International Nuclear Information System (INIS)

Walsh, R.J.; Slaby, F.J.; Posner, B.I.

1987-01-01

Prolactin (PRL) interacts with areas of the central nervous system which reside behind the blood-brain barrier. While vascular PRL does not cross this barrier, it is readily accessible to the cerebrospinal fluid (CSF) from which it may gain access to the PRL-responsive areas of the brain. Studies were undertaken to characterize the mechanism responsible for the translocation of PRL from blood to CSF. Rats were given external jugular vein injections of [ 125 -I]iodo-PRL in the presence or absence of an excess of unlabeled ovine PRL (oPRL), human GH, bovine GH, or porcine insulin. CSF and choroid plexus were removed 60 min later. CSF samples were electrophoresed on sodium dodecyl sulfate-polyacrylamide slab gels and resultant autoradiographs were analyzed with quantitative microdensitometry. The data revealed that unlabeled lactogenic hormones, viz. oPRL and human GH, caused a statistically significant inhibition of [ 125 I]iodo-PRL transport from blood to CSF. In contrast, nonlactogenic hormones, viz bovine GH and insulin, had no effect on [ 125 I]iodo-PRL transport into the CSF. An identical pattern of competition was observed in the binding of hormone to the choroid plexus. Furthermore, vascular injections of [ 125 I]iodo-PRL administered with a range of concentrations of unlabeled oPRL revealed a dose-response inhibition in the transport of [ 125 I]iodo-PRL from blood to CSF. The study demonstrates that PRL enters the CSF by a specific, PRL receptor-mediated transport mechanism. The data is consistent with the hypothesis that the transport mechanism resides at the choroid plexus. The existence of this transport mechanism reflects the importance of the cerebroventricular system in PRL-brain interactions

Mechanistic kinetic modeling generates system-independent P-glycoprotein mediated transport elementary rate constants for inhibition and, in combination with 3D SIM microscopy, elucidates the importance of microvilli morphology on P-glycoprotein mediated efflux activity.

Science.gov (United States)

Ellens, Harma; Meng, Zhou; Le Marchand, Sylvain J; Bentz, Joe

2018-06-01

In vitro transporter kinetics are typically analyzed by steady-state Michaelis-Menten approximations. However, no clear evidence exists that these approximations, applied to multiple transporters in biological membranes, yield system-independent mechanistic parameters needed for reliable in vivo hypothesis generation and testing. Areas covered: The classical mass action model has been developed for P-glycoprotein (P-gp) mediated transport across confluent polarized cell monolayers. Numerical integration of the mass action equations for transport using a stable global optimization program yields fitted elementary rate constants that are system-independent. The efflux active P-gp was defined by the rate at which P-gp delivers drugs to the apical chamber, since as much as 90% of drugs effluxed by P-gp partition back into nearby microvilli prior to reaching the apical chamber. The efflux active P-gp concentration was 10-fold smaller than the total expressed P-gp for Caco-2 cells, due to their microvilli membrane morphology. The mechanistic insights from this analysis are readily extrapolated to P-gp mediated transport in vivo. Expert opinion: In vitro system-independent elementary rate constants for transporters are essential for the generation and validation of robust mechanistic PBPK models. Our modeling approach and programs have broad application potential. They can be used for any drug transporter with minor adaptations.

Lucius Septimius Petronianus and Tiberius Claudius Proculus Cornelianus: Two protégés of Gnaeus Iulius Verus

Directory of Open Access Journals (Sweden)

Šajin Željka

2017-01-01

Full Text Available This article discusses the careers of Lucius Septimius Petronianus and Tiberius Claudius Proculus Cornelianus, who successively held the post of procurator of the mining districts situated in the valley of the lower Drina river during the second half of the 2nd century A.D. It aims to point out a connection between both procurators and Gnaeus Iulius Verus, a famous senator and general originating from the Roman colony of Aequum, in Dalmatia and one of Marcus Aurelius’ amici in the early years of the latter’s reign. The presence of the protégés of Gnaeus Iulius Verus in the richest mining region of Illyricum is indicative of two things: the emperor’s willingness to entrust these mines to the protégés of his closest associate at a time when this region was under constant threat from barbarian attacks, and also the possible intention of Gnaeus Iulius Verus to protect his own investment in mining.

Basolateral P2X receptors mediate inhibition of NaCl transport in mouse medullary thick ascending limb (mTAL)

DEFF Research Database (Denmark)

Marques, Rita D; de Bruijn, Pauline I.A.; Sørensen, Mads Vaarby

2012-01-01

Extracellular nucleotides regulate epithelial transport via luminal and basolateral P2 receptors. Renal epithelia express multiple P2 receptors, which mediate significant inhibition of solute absorption. Recently, we identified several P2 receptors in the medullary thick ascending limb (m...

MISS-Prot: web server for self/non-self discrimination of protein residue networks in parasites; theory and experiments in Fasciola peptides and Anisakis allergens.

Science.gov (United States)

González-Díaz, Humberto; Muíño, Laura; Anadón, Ana M; Romaris, Fernanda; Prado-Prado, Francisco J; Munteanu, Cristian R; Dorado, Julián; Sierra, Alejandro Pazos; Mezo, Mercedes; González-Warleta, Marta; Gárate, Teresa; Ubeira, Florencio M

2011-06-01

Infections caused by human parasites (HPs) affect the poorest 500 million people worldwide but chemotherapy has become expensive, toxic, and/or less effective due to drug resistance. On the other hand, many 3D structures in Protein Data Bank (PDB) remain without function annotation. We need theoretical models to quickly predict biologically relevant Parasite Self Proteins (PSP), which are expressed differentially in a given parasite and are dissimilar to proteins expressed in other parasites and have a high probability to become new vaccines (unique sequence) or drug targets (unique 3D structure). We present herein a model for PSPs in eight different HPs (Ascaris, Entamoeba, Fasciola, Giardia, Leishmania, Plasmodium, Trypanosoma, and Toxoplasma) with 90% accuracy for 15 341 training and validation cases. The model combines protein residue networks, Markov Chain Models (MCM) and Artificial Neural Networks (ANN). The input parameters are the spectral moments of the Markov transition matrix for electrostatic interactions associated with the protein residue complex network calculated with the MARCH-INSIDE software. We implemented this model in a new web-server called MISS-Prot (MARCH-INSIDE Scores for Self-Proteins). MISS-Prot was programmed using PHP/HTML/Python and MARCH-INSIDE routines and is freely available at: . This server is easy to use by non-experts in Bioinformatics who can carry out automatic online upload and prediction with 3D structures deposited at PDB (mode 1). We can also study outcomes of Peptide Mass Fingerprinting (PMFs) and MS/MS for query proteins with unknown 3D structures (mode 2). We illustrated the use of MISS-Prot in experimental and/or theoretical studies of peptides from Fasciola hepatica cathepsin proteases or present on 10 Anisakis simplex allergens (Ani s 1 to Ani s 10). In doing so, we combined electrophoresis (1DE), MALDI-TOF Mass Spectroscopy, and MASCOT to seek sequences, Molecular Mechanics + Molecular Dynamics (MM/MD) to

Les sources de protéines dans l’alimentation du bétail en France : la place des oléoprotéagineux

Directory of Open Access Journals (Sweden)

Peyronnet Corinne

2014-07-01

Full Text Available En France, les aliments concentrés totalisent 30 millions de tonnes de matières premières parmi lesquelles 64 % sont des céréales et 22 % des tourteaux d’oléagineux. Le déficit français en matières riches en protéines (dosant plus de 15 % de protéines qui était d’environ 70 % dans les années 1980 a baissé en dessous de 40 % successivement grâce au développement du pois dans les années 1990 puis du colza depuis les années 2000 avec des surfaces totales cultivées de 2,5 millions d’hectares environ. Le tourteau de soja reste le premier tourteau utilisé en France mais ses importations baissent, notamment depuis 2009, et il n’a représenté que 3,3 millions de tonnes sur la campagne 2012/2013. L’utilisation du tourteau de soja non OGM diminue également avec 0,6 million de tonnes en 2012 contre 1,2 en 2002. Les tourteaux de colza et tournesol ont quant à eux atteint respectivement 2,3 et 1,4 millions de tonnes en 2012/2013 parmi lesquels 700 000 tonnes de tourteau de tournesol High pro (à 36 % de protéines importées de la zone Mer noire et 600 000 tonnes de différentes qualités produites en France. Depuis 2013, des tourteaux de tournesol High pro sont également produits en France à Bassens. Les prix des MRP suivent le marché mondial du tourteau de soja mais la demande française pour des matières premières non OGM permet une meilleure valorisation des sources de protéines locales.

Quid de l’utilisation des protéines d’origine végétale en aquaculture ?

Directory of Open Access Journals (Sweden)

Burel Christine

2014-07-01

Full Text Available Au cours des 30 dernières années, l’aquaculture mondiale n’a cessé de croître pour répondre à la demande croissante de poisson pour la consommation humaine qui ne peut plus être satisfaite par les seules captures de pêche. En conséquence, la demande de matières premières pour les aliments aquacoles augmente, tandis que le volume disponible de farine de poisson, ingrédient traditionnellement majoritaire dans ces aliments, reste stable. Cela a conduit à une substitution des ressources marines par des produits végétaux comme ingrédients pour les aliments pour poissons. La proportion de farine de poisson dans les aliments piscicoles a été réduite d’un tiers et est remplacée par une combinaison de sources protéiques végétales qui fournissent les acides aminés indispensables en quantité suffisante pour répondre aux besoins des poissons. Une large gamme de produits végétaux a été prospectée pour remplacer la farine de poisson. Sur la base de leur composition et de leur disponibilité sur le marché, les produits végétaux les plus utilisés en Europe sont des graines d’oléagineux (soja, colza, tournesol sous forme de tourteaux ou de concentrés protéiques, des protéagineux (lupin, féverole, pois, des céréales (maïs, blé ou des extraits de protéines obtenus à partir de céréales, comme par exemple les glutens. Néanmoins, les études ayant porté sur des taux de substitution très élevés (peu ou pas de farine de poisson ont mis en évidence des verrous physiologiques bien que les régimes contenaient tous les nutriments nécessaires : une baisse de la consommation alimentaire, de l’efficacité alimentaire et du taux de croissance des poissons, ainsi que des modifications métaboliques. Les travaux de recherche doivent être poursuivis afin d’améliorer l’efficacité nutritionnelle des produits végétaux via une réduction de leurs facteurs antinutritionnels et des toxines qu’ils contiennent

l-Arginine Uptake by Cationic Amino Acid Transporter Promotes Intra-Macrophage Survival of Leishmania donovani by Enhancing Arginase-Mediated Polyamine Synthesis

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Abhishek Mandal

2017-07-01

Full Text Available The survival of intracellular protozoan parasite, Leishmania donovani, the causative agent of Indian visceral leishmaniasis (VL, depends on the activation status of macrophages. l-Arginine, a semi-essential amino acid plays a crucial regulatory role for activation of macrophages. However, the role of l-arginine transport in VL still remains elusive. In this study, we demonstrated that intra-macrophage survival of L. donovani depends on the availability of extracellular l-arginine. Infection of THP-1-derived macrophage/human monocyte-derived macrophage (hMDM with Leishmania, resulted in upregulation of l-arginine transport. While investigating the involvement of the transporters, we observed that Leishmania survival was greatly impaired when the transporters were blocked either using inhibitor or siRNA-mediated downregulation. CAT-2 was found to be the main isoform associated with l-arginine transport in L. donovani-infected macrophages. l-arginine availability and its transport regulated the host arginase in Leishmania infection. Arginase and inducible nitric oxide synthase (iNOS expression were reciprocally regulated when assayed using specific inhibitors and siRNA-mediated downregulation. Interestingly, induction of iNOS expression and nitric oxide production were observed in case of inhibition of arginase in infected macrophages. Furthermore, inhibition of l-arginine transport as well as arginase resulted in decreased polyamine production, limiting parasite survival inside macrophages. l-arginine availability and transport regulated Th1/Th2 cytokine levels in case of Leishmania infection. Upregulation of l-arginine transport, induction of host arginase, and enhanced polyamine production were correlated with increased level of IL-10 and decreased level of IL-12 and TNF-α in L. donovani-infected macrophages. Our findings provide clear evidence for targeting the metabolism of l-arginine and l-arginine-metabolizing enzymes as an important

Genet mosai tic vari ic virus iability s in Pa y in coa akistan s at prot n ...

African Journals Online (AJOL)

SAM

Saccharum hybrid cultivar. Punjab, Pakistan. KC200152. This study ... Saccharum hybrid cultivar BO 72. Bihar, India. DQ842502 ...... Fan ZF geno. Chin. Farrag. Lesi. 48(1. Frenke. War term virus. Frenke poty regio. Frenke sequ mos. 2783. Garcia plan. Gemec. Lers prot from. Gopal. (Sac. Gopal suga. 7:11. Gotz R. Coc. 147(.

Determination of Unbound Partition Coefficient and in Vitro-in Vivo Extrapolation for SLC13A Transporter-Mediated Uptake.

Science.gov (United States)

Riccardi, Keith; Li, Zhenhong; Brown, Janice A; Gorgoglione, Matthew F; Niosi, Mark; Gosset, James; Huard, Kim; Erion, Derek M; Di, Li

2016-10-01

Unbound partition coefficient (Kpuu) is important to an understanding of the asymmetric free drug distribution of a compound between cells and medium in vitro, as well as between tissue and plasma in vivo, especially for transporter-mediated processes. Kpuu was determined for a set of compounds from the SLC13A family that are inhibitors and substrates of transporters in hepatocytes and transporter-transfected cell lines. Enantioselectivity was observed, with (R)-enantiomers achieving much higher Kpuu (>4) than the (S)-enantiomers (<1) in human hepatocytes and SLC13A5-transfected human embryonic 293 cells. The intracellular free drug concentration correlated directly with in vitro pharmacological activity rather than the nominal concentration in the assay because of the high Kpuu mediated by SLC13A5 transporter uptake. Delivery of the diacid PF-06649298 directly or via hydrolysis of the ethyl ester prodrug PF-06757303 resulted in quite different Kpuu values in human hepatocytes (Kpuu of 3 for diacid versus 59 for prodrug), which was successfully modeled on the basis of passive diffusion, active uptake, and conversion rate from ester to diacid using a compartmental model. Kpuu values changed with drug concentrations; lower values were observed at higher concentrations possibly owing to a saturation of transporters. Michaelis-Menten constant (Km) of SLC13A5 was estimated to be 24 μM for PF-06649298 in human hepatocytes. In vitro Kpuu obtained from rat suspension hepatocytes supplemented with 4% fatty acid free bovine serum albumin showed good correlation with in vivo Kpuu of liver-to-plasma, illustrating the potential of this approach to predict in vivo Kpuu from in vitro systems. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells

International Nuclear Information System (INIS)

Fuchs, Dominik; Daniel, Volker; Sadeghi, Mahmoud; Opelz, Gerhard; Naujokat, Cord

2010-01-01

Leukemia stem cells are known to exhibit multidrug resistance by expression of ATP-binding cassette (ABC) transporters which constitute transmembrane proteins capable of exporting a wide variety of chemotherapeutic drugs from the cytosol. We show here that human promyeloblastic leukemia KG-1a cells exposed to the histone deacetylase inhibitor phenylbutyrate resemble many characteristics of leukemia stem cells, including expression of functional ABC transporters such as P-glycoprotein, BCRP and MRP8. Consequently, KG-1a cells display resistance to the induction of apoptosis by various chemotherapeutic drugs. Resistance to apoptosis induction by chemotherapeutic drugs can be reversed by cyclosporine A, which effectively inhibits the activity of P-glycoprotein and BCRP, thus demonstrating ABC transporter-mediated drug resistance in KG-1a cells. However, KG-1a are highly sensitive to apoptosis induction by salinomycin, a polyether ionophore antibiotic that has recently been shown to kill human breast cancer stem cell-like cells and to induce apoptosis in human cancer cells displaying multiple mechanisms of drug and apoptosis resistance. Whereas KG-1a cells can be adapted to proliferate in the presence of apoptosis-inducing concentrations of bortezomib and doxorubicin, salinomycin does not permit long-term adaptation of the cells to apoptosis-inducing concentrations. Thus, salinomycin should be regarded as a novel and effective agent for the elimination of leukemia stem cells and other tumor cells exhibiting ABC transporter-mediated multidrug resistance.

Interactive ion-mediated sap flow regulation in olive and laurel stems: physicochemical characteristics of water transport via the pit structure.

Science.gov (United States)

Ryu, Jeongeun; Ahn, Sungsook; Kim, Seung-Gon; Kim, TaeJoo; Lee, Sang Joon

2014-01-01

Sap water is distributed and utilized through xylem conduits, which are vascular networks of inert pipes important for plant survival. Interestingly, plants can actively regulate water transport using ion-mediated responses and adapt to environmental changes. However, ionic effects on active water transport in vascular plants remain unclear. In this report, the interactive ionic effects on sap transport were systematically investigated for the first time by visualizing the uptake process of ionic solutions of different ion compositions (K+/Ca2+) using synchrotron X-ray and neutron imaging techniques. Ionic solutions with lower K+/Ca2+ ratios induced an increased sap flow rate in stems of Olea europaea L. and Laurus nobilis L. The different ascent rates of ionic solutions depending on K+/Ca2+ ratios at a fixed total concentration increases our understanding of ion-responsiveness in plants from a physicochemical standpoint. Based on these results, effective structural changes in the pit membrane were observed using varying ionic ratios of K+/Ca2+. The formation of electrostatically induced hydrodynamic layers and the ion-responsiveness of hydrogel structures based on Hofmeister series increase our understanding of the mechanism of ion-mediated sap flow control in plants.

Assessment of ABCG2-mediated transport of pesticides across the rabbit placenta barrier using a novel MDCKII in vitro model

International Nuclear Information System (INIS)

Halwachs, Sandra; Schäfer, Ingo; Kneuer, Carsten; Seibel, Peter; Honscha, Walther

2016-01-01

In humans, the ATP-binding cassette efflux transporter ABCG2 contributes to the fetoprotective barrier function of the placenta, potentially limiting the toxicity of transporter substrates to the fetus. During testing of chemicals including pesticides, developmental toxicity studies are performed in rabbit. Despite its toxicological relevance, ABCG2-mediated transport of pesticides in rabbit placenta has not been yet elucidated. We therefore generated polarized MDCK II cells expressing the ABCG2 transporter from rabbit placenta (rbABCG2) and evaluated interaction of the efflux transporter with selected insecticides, fungicides, and herbicides. The Hoechst H33342 accumulation assay indicated that 13 widely used pesticidal active substances including azoxystrobin, carbendazim, chlorpyrifos, chlormequat, diflufenican, dimethoate, dimethomorph, dithianon, ioxynil, methiocarb, propamocarb, rimsulfuron and toclofos-methyl may be rbABCG2 inhibitors and/or substrates. No such evidence was obtained for chlorpyrifos-methyl, epoxiconazole, glyphosate, imazalil and thiacloprid. Moreover, chlorpyrifos (CPF), dimethomorph, tolclofos-methyl and rimsulfuron showed concentration-dependent inhibition of H33342 excretion in rbABCG2-transduced MDCKII cells. To further evaluate the role of rbABCG2 in pesticide transport across the placenta barrier, we generated polarized MDCKII-rbABCG2 monolayers. Confocal microscopy confirmed correct localization of rbABCG2 protein in the apical plasma membrane. In transepithelial flux studies, we showed the time-dependent preferential basolateral to apical (B > A) directed transport of [ 14 C] CPF across polarized MDCKII-rbABCG2 monolayers which was significantly inhibited by the ABCG2 inhibitor fumitremorgin C (FTC). Using this novel in vitro cell culture model, we altogether showed functional secretory activity of the ABCG2 transporter from rabbit placenta and identified several pesticides like the insecticide CPF as potential rbABCG2 substrates

Assessment of ABCG2-mediated transport of pesticides across the rabbit placenta barrier using a novel MDCKII in vitro model

Energy Technology Data Exchange (ETDEWEB)

Halwachs, Sandra [Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Universität Leipzig, Leipzig (Germany); Schäfer, Ingo [Molecular Cell Therapy, Center for Biotechnology and Biomedicine, Faculty of Medicine, Universität Leipzig, Leipzig (Germany); Kneuer, Carsten [Federal Institute for Risk Assessment (BfR), Pesticide Safety, Max-Dohrn-Straße 8-10, D-10589 Berlin (Germany); Seibel, Peter [Molecular Cell Therapy, Center for Biotechnology and Biomedicine, Faculty of Medicine, Universität Leipzig, Leipzig (Germany); Honscha, Walther, E-mail: honscha@vetmed.uni-leipzig.de [Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Universität Leipzig, Leipzig (Germany)

2016-08-15

In humans, the ATP-binding cassette efflux transporter ABCG2 contributes to the fetoprotective barrier function of the placenta, potentially limiting the toxicity of transporter substrates to the fetus. During testing of chemicals including pesticides, developmental toxicity studies are performed in rabbit. Despite its toxicological relevance, ABCG2-mediated transport of pesticides in rabbit placenta has not been yet elucidated. We therefore generated polarized MDCK II cells expressing the ABCG2 transporter from rabbit placenta (rbABCG2) and evaluated interaction of the efflux transporter with selected insecticides, fungicides, and herbicides. The Hoechst H33342 accumulation assay indicated that 13 widely used pesticidal active substances including azoxystrobin, carbendazim, chlorpyrifos, chlormequat, diflufenican, dimethoate, dimethomorph, dithianon, ioxynil, methiocarb, propamocarb, rimsulfuron and toclofos-methyl may be rbABCG2 inhibitors and/or substrates. No such evidence was obtained for chlorpyrifos-methyl, epoxiconazole, glyphosate, imazalil and thiacloprid. Moreover, chlorpyrifos (CPF), dimethomorph, tolclofos-methyl and rimsulfuron showed concentration-dependent inhibition of H33342 excretion in rbABCG2-transduced MDCKII cells. To further evaluate the role of rbABCG2 in pesticide transport across the placenta barrier, we generated polarized MDCKII-rbABCG2 monolayers. Confocal microscopy confirmed correct localization of rbABCG2 protein in the apical plasma membrane. In transepithelial flux studies, we showed the time-dependent preferential basolateral to apical (B > A) directed transport of [{sup 14}C] CPF across polarized MDCKII-rbABCG2 monolayers which was significantly inhibited by the ABCG2 inhibitor fumitremorgin C (FTC). Using this novel in vitro cell culture model, we altogether showed functional secretory activity of the ABCG2 transporter from rabbit placenta and identified several pesticides like the insecticide CPF as potential rbABCG2

Molecular cloning and characterization of a gene encoding the proline transporter protein in common bean (Phaseolus vulgaris L.

Directory of Open Access Journals (Sweden)

Jibao Chen

2016-10-01

Full Text Available As a typical compatible solute, proline is accumulated in plants under environmental stresses. Proline transporter (ProT plays an important role in proline distribution between plant organs. Using a candidate gene approach, we cloned a cDNA sequence for ProT from common bean (Phaseolus vulgaris L. and designated the gene PvProT. The deduced amino acid sequence of PvProT showed high similarity to Bet/ProT proteins from other leguminous plants, and the highest similarity was observed with mothbean (Vigna aconitifolia L. VuProT. Relative quantification of the mRNA level of PvProT using real-time PCR analysis showed that the PvProT transcript level was higher in leaves than in stems and roots of common bean plants subjected to drought and salt stress. Under 20% (w/w PEG-6000 treatment, drought-resistant plants expressed a higher level of PvProT transcripts than drought-sensitive plants. Although heterologous expression of PvProT in the Escherichia coli mutant mkh13 showed that PvProT exhibited uptake activities for proline and betaine, no betaine content was detected in the common bean. These findings suggest that PvProT plays an important role in the transportation of proline in common bean plants exposed to drought and salt stress.

Heat-shock stress activates a novel nuclear import pathway mediated by Hikeshi

OpenAIRE

Imamoto, Naoko; Kose, Shingo

2012-01-01

Cellular stresses significantly affect nuclear transport systems. Nuclear transport pathways mediated by importin β-family members, which are active under normal conditions, are downregulated. During thermal stress, a nuclear import pathway mediated by a novel carrier, which we named Hikeshi, becomes active. Hikeshi is not a member of the importin β family and mediates the nuclear import of Hsp70s. Unlike importin β family-mediated nuclear transport, the Hikeshi-mediated nuclear import of Hsp...

Polar transport in plants mediated by membrane transporters: focus on mechanisms of polar auxin transport.

Science.gov (United States)

Naramoto, Satoshi

2017-12-01

Directional cell-to-cell transport of functional molecules, called polar transport, enables plants to sense and respond to developmental and environmental signals. Transporters that localize to plasma membranes (PMs) in a polar manner are key components of these systems. PIN-FORMED (PIN) auxin efflux carriers, which are the most studied polar-localized PM proteins, are implicated in the polar transport of auxin that in turn regulates plant development and tropic growth. In this review, the regulatory mechanisms underlying polar localization of PINs, control of auxin efflux activity, and PIN abundance at PMs are considered. Up to date information on polar-localized nutrient transporters that regulate directional nutrient movement from soil into the root vasculature is also discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Teachable Agents and the Protégé Effect: Increasing the Effort Towards Learning

Science.gov (United States)

Chase, Catherine C.; Chin, Doris B.; Oppezzo, Marily A.; Schwartz, Daniel L.

2009-08-01

Betty's Brain is a computer-based learning environment that capitalizes on the social aspects of learning. In Betty's Brain, students instruct a character called a Teachable Agent (TA) which can reason based on how it is taught. Two studies demonstrate the protégé effect: students make greater effort to learn for their TAs than they do for themselves. The first study involved 8th-grade students learning biology. Although all students worked with the same Betty's Brain software, students in the TA condition believed they were teaching their TAs, while in another condition, they believed they were learning for themselves. TA students spent more time on learning activities (e.g., reading) and also learned more. These beneficial effects were most pronounced for lower achieving children. The second study used a verbal protocol with 5th-grade students to determine the possible causes of the protégé effect. As before, students learned either for their TAs or for themselves. Like study 1, students in the TA condition spent more time on learning activities. These children treated their TAs socially by attributing mental states and responsibility to them. They were also more likely to acknowledge errors by displaying negative affect and making attributions for the causes of failures. Perhaps having a TA invokes a sense of responsibility that motivates learning, provides an environment in which knowledge can be improved through revision, and protects students' egos from the psychological ramifications of failure.

Praxedes: protótipo de um kit educacional de robótica baseado na plataforma Arduino

Directory of Open Access Journals (Sweden)

Francisco Ioneiton da Silva

2013-09-01

Full Text Available Este artigo descreve a criação de um protótipo de um robô móvel, com finalidade educacional utilizando a plataforma Arduino, tendo como principal finalidade simplificar o uso desta plataforma, eliminando a necessidade de conhecimentos complexos em determinados níveis de ensino como bem como de oferecer uma alternativa a os kits disponíveis no mercado com custos relativamente acessíveis.

Comment les aires protégées structurent les écosystèmes des ...

African Journals Online (AJOL)

1 mars 2009 ... Cette étude menée a pour but de montrer l'influence des aires protégées sur la structuration des écosystèmes périphériques. Pour cela, une étude diachronique par images satellitaires Landsat de 1985 à 2013 a été faite et une collecte de données de terrain a été réalisée dans les villages autour du Parc ...

Efeito do desajuste marginal, tipo de soldagem e material do parafuso sobre a força de destorque de parafusos protéticos e tensões induzidas aos pilares

OpenAIRE

Sabrina Alessandra Rodrigues

2012-01-01

Resumo: O objetivo neste estudo foi analisar as tensões induzidas aos análogos de pilares protéticos, utilizando-se strain gauges; e avaliar a força de destorque de parafusos protéticos (ouro e titânio) em infraestruturas fundidas em titânio comercialmente puro (Ti cp), antes e após os procedimentos de soldagem laser e TIG (tungsten inert gas). Foram confeccionadas vinte infraestruturas fundidas em titânio comercialmente puro (Ti cp), simulando uma prótese fixa de três elementos; vinte modelo...

Caveolin-1 enhances resveratrol-mediated cytotoxicity and transport in a hepatocellular carcinoma model

Directory of Open Access Journals (Sweden)

Yang Hui-ling

2009-03-01

Full Text Available Abstract Background Resveratrol (RES, an estrogen analog, is considered as a potential cancer chemo-preventive agent. However, it remains unclear how RES is transported into cells. In this study, we observed that Caveolin-1(CAV1 expression can increase the cytotoxic and pro-apoptotic activity of RES in a dose- and time-dependent manner both in vitro and in vivo in a Hepatocellular Carcinoma animal model. Methods High performance liquid chromatography (HPLC demonstrated that RES intra-cellular concentration is increased about 2-fold in cells stably expressing CAV1 or CAVM1 (a scaffolding domain (81-101AA-defective CAV1 mutant compared to the untransduced human Hepatoblastoma cell line (HepG2 or after transduction with the green fluorescent protein (GFP control vector. The increased intra-cellular transport of RES was abolished in cells stably expressing CAVM2 (a cholesterol shuttle domain (143-156AA-defective CAV1 mutant or CAVRNAi. In order to further characterize CAV1-dependent RES transport, we synthesized RES-dansyl chloride derivatives as fluorescent probes to visualize the transport process, which demonstrated a distribution consistent with that of CAV1 in HepG2 cells. Results In addition, RES endocytosis was not mediated by estrogen receptor (ER α and β, as suggested by lack of competitive inhibition by estrogen or Tamoxifen. Pathway analysis showed that RES can up-regulate the expression of endogenous CAV1; this activates further the MAPK pathway and caspase-3 expression. Discussion This study provides novel insights about the role played by CAV1 in modulating cellular sensitivity to RES through enhancement of its internalization and trafficking.

基于Netlogo平台的PROT项目融资管理仿真模型研究%Research on Simulation Model of PROT Project Financing Based on Netlogo

Institute of Scientific and Technical Information of China (English)

王艳伟; 黄宜

2016-01-01

PROT project financing is a complex and dynamic process.It is difficult to use the conventional meth-od to describe it vividly and clearly.The internal mechanism of PROT project cannot be explored.This paper at-tempts to use the netlogo simulation tool and means of system entropy to dynamically simulate,and to establish PROT project financing management simulation model based on netlogo.The simulation model can describe the change of the system entropy and the income status of the interests real-time dynamically,so as to promote the PROT project financing completed scientific and reasonable successfully.%PROT项目融资管理过程是一个复杂的、动态的多方博弈的过程，很难通过常规的研究方法全面而形象的将其清晰描述，也无法深入探究PROT项目管理的内在机理。本文尝试利用netl-ogo仿真工具，借助系统熵进行动态仿真模拟，建立基于netlogo的PROT项目融资管理仿真模型。通过该仿真模型能够实时动态的描述系统熵的变化以及各利益主体的收益状况，从而促进PROT项目科学合理的顺利完成。

Intracellular Na+ concentration influences short-term plasticity of glutamate transporter-mediated currents in neocortical astrocytes.

Science.gov (United States)

Unichenko, Petr; Myakhar, Olga; Kirischuk, Sergei

2012-04-01

Fast synaptic transmission requires a rapid clearance of the released neurotransmitter from the extracellular space. Glial glutamate transporters (excitatory amino acid transporters, EAATs) strongly contribute to glutamate removal. In this work, we investigated the paired-pulse plasticity of synaptically activated, glutamate transporter-mediated currents (STCs) in cortical layer 2/3 astrocytes. STCs were elicited by local electrical stimulation in layer 4 in the presence of ionotropic glutamate (AMPA and NMDA), GABAA, and GABAB receptor antagonists. In experiments with low [Na(+)]i (5 mM) intrapipette solution, STCs elicited by paired-pulse stimulation demonstrated paired-pulse facilitation (PPF) at short (astrocytic [Na(+)]i, reduced the mean STC amplitude, decreased PPF at short ISIs, and slowed STC kinetics. All GABA-induced changes were blocked by NO-711 and SNAP-5114, GABA transporter (GATs) antagonists. In experiments with the low intrapipette solution, GAT blockade under control conditions decreased PPF at short ISIs both at room and at near physiological temperatures. Dialysis of single astrocyte with low [Na(+)]i solution increased the amplitude and reduced PPR of evoked field potentials recorded in the vicinity of the astrocyte. We conclude that (1) endogenous GABA via GATs may influence EAAT functioning and (2) astrocytic [Na(+)]i modulates the short-term plasticity of STCs and in turn the efficacy of glutamate removal. Copyright © 2012 Wiley Periodicals, Inc.

Carrier-mediated transport of actinides and rare earth elements through liquid and plasticized membranes

International Nuclear Information System (INIS)

Kopunec, R.; Ngo Manh, Th.

1994-01-01

The first works in this field were realized approximately 25 years ago, when BLOCK et al. reported their studies about carrier-mediated transport (also called pertraction or membrane extraction) of uranium through plasticized membranes with neutral esters derived from phosphoric acid. At this time, the methodical principles of selective pertraction of ionic compounds through so-called bulk liquid membranes containing carriers were known. However, these membranes, similarly as plasticized membranes, have not achieved a broader use. This is probably because bulk liquid membranes are from a technical point of view fairly distant from the idea of a typical membrane system, and plasticized membranes (sometimes also called gel membranes) present great resistance. By the end of the 1960's and at the beginning of the 1970's, LI and CUSSLER worked out the principles for two widely used pertraction techniques, called pertraction through emulsion liquid and supported liquid membranes (ELM and SLM). These two techniques not only have greatest significance in laboratory practice, but they also are interesting for technological aims because of the attainable large phase boundaries, e.g. 10 3 -10 4 m 2 /m 3 . Many ways to arrange membrane systems are described in papers. Recently, the significance of carrier-mediated transport through liquid membranes has grown to have (since 1980) separate section at the International Solvent Extraction Conference. This paper does not deal with mathematical models and the mechanism of pertraction in general, but it gives an overview of results obtained in publications referring to pertraction of two related element groups - actinoids and rare earth elements - using various membrane types. (author) 154 refs

Electroacupuncture preconditioning-induced neuroprotection may be mediated by glutamate transporter type 2.

Science.gov (United States)

Zhu, Xiaoling; Yin, Jinbo; Li, Liaoliao; Ma, Lei; Tan, Hongying; Deng, Jiao; Chen, Shaoyang; Zuo, Zhiyi

2013-10-01

Electroacupuncture has been shown to induce a preconditioning effect in the brain. The mechanisms for this protection are not fully elucidated. We hypothesize that this protection is mediated by excitatory amino acid transporters (EAATs) that have been shown to be neuroprotective. To test this hypothesis, two-month old male Sprague-Dawley rats and EAAT type 3 (EAAT3) knockout mice received or did not receive 30-min electroacupuncture once a day for five consecutive days. They were subjected to a 120-min middle cerebral arterial occlusion (MCAO) at 24h after the last electroacupuncture. Neurological outcome was assessed 2days after the MCAO. Brain tissues were harvested at 24h after the last electroacupuncture for Western blotting. Rats subjected to electroacupuncture at the Baihui acupoint had smaller brain infarct volumes and better neurological deficit scores than control rats. Electroacupuncture increased EAAT type 2 (EAAT2) in the cerebral cortex, tended to increase EAAT3 in the hippocampus, and had no effect on EAAT type 1 expression. Dihydrokainate, an EAAT2 inhibitor, worsened the neurological outcome of rats with electroacupuncture pretreatment. Electroacupuncture pretreatment at the Baihui acupoint increased EAAT2 in the cerebral cortex and improved the neurological outcome of EAAT3 knockout mice. Together, our results suggest that EAAT2 may mediate the electroacupuncture preconditioning-induced neuroprotection. Copyright © 2013 Elsevier Ltd. All rights reserved.

Lysosomal putative RNA transporter SIDT2 mediates direct uptake of RNA by lysosomes.

Science.gov (United States)

Aizawa, Shu; Fujiwara, Yuuki; Contu, Viorica Raluca; Hase, Katsunori; Takahashi, Masayuki; Kikuchi, Hisae; Kabuta, Chihana; Wada, Keiji; Kabuta, Tomohiro

2016-01-01

Lysosomes are thought to be the major intracellular compartment for the degradation of macromolecules. We recently identified a novel type of autophagy, RNautophagy, where RNA is directly taken up by lysosomes in an ATP-dependent manner and degraded. However, the mechanism of RNA translocation across the lysosomal membrane and the physiological role of RNautophagy remain unclear. In the present study, we performed gain- and loss-of-function studies with isolated lysosomes, and found that SIDT2 (SID1 transmembrane family, member 2), an ortholog of the Caenorhabditis elegans putative RNA transporter SID-1 (systemic RNA interference deficient-1), mediates RNA translocation during RNautophagy. We also observed that SIDT2 is a transmembrane protein, which predominantly localizes to lysosomes. Strikingly, knockdown of Sidt2 inhibited up to ˜50% of total RNA degradation at the cellular level, independently of macroautophagy. Moreover, we showed that this impairment is mainly due to inhibition of lysosomal RNA degradation, strongly suggesting that RNautophagy plays a significant role in constitutive cellular RNA degradation. Our results provide a novel insight into the mechanisms of RNA metabolism, intracellular RNA transport, and atypical types of autophagy.

Hacking interdit découvrez les techniques des hackers pour mieux vous protéger

CERN Document Server

Gomez-Urbina, Alexandre

2010-01-01

Aujourd'hui, impossible de surfer sur Internet sans protection efficace ! Mais même avec des logiciels appropriés, nul n'est à l'abri du danger ! Virus, usurpations d'adresse IP, troyens, intrusions dans votre système, attaques par phishing : l'imagination des pirates est sans limite ! La seule solution est de vous protéger efficacement et pour cela, un moyen : connaître les techniques des hackers pour mieux déjouer leurs pièges ! Un internaute averti en vaut deux !

Carrier-mediated γ-aminobutyric acid transport across the basolateral membrane of human intestinal Caco-2 cell monolayers.

Science.gov (United States)

Nielsen, Carsten Uhd; Carstensen, Mette; Brodin, Birger

2012-06-01

The aim of the present study was to investigate the transport of γ-aminobutyric acid (GABA) across the basolateral membrane of intestinal cells. The proton-coupled amino acid transporter, hPAT1, mediates the influx of GABA and GABA mimetic drug substances such as vigabatrin and gaboxadol and the anticancer prodrug δ-aminolevulinic acid across the apical membrane of small intestinal enterocytes. Little is however known about the basolateral transport of these substances. We investigated basolateral transport of GABA in mature Caco-2 cell monolayers using isotope studies. Here we report that, at least two transporters seem to be involved in the basolateral transport of GABA. The basolateral uptake consisted of a high-affinity system with a K(m) of 290 μM and V(max) of 75 pmol cm(-2) min(-1) and a low affinity system with a K(m) of approximately 64 mM and V(max) of 1.6 nmol cm(-2) min(-1). The high-affinity transporter is Na(+) and Cl(-) dependent. The substrate specificity of the high-affinity transporter was further studied and Gly-Sar, Leucine, gaboxadol, sarcosine, lysine, betaine, 5-hydroxythryptophan, proline and glycine reduced the GABA uptake to approximately 44-70% of the GABA uptake in the absence of inhibitor. Other substances such as β-alanine, GABA, 5-aminovaleric acid, taurine and δ-aminolevulinic acid reduced the basolateral GABA uptake to 6-25% of the uptake in the absence of inhibitor. Our results indicate that the distance between the charged amino- and acid-groups is particular important for inhibition of basolateral GABA uptake. Thus, there seems to be a partial substrate overlap between the basolateral GABA transporter and hPAT1, which may prove important for understanding drug interactions at the level of intestinal transport. Copyright © 2012 Elsevier B.V. All rights reserved.

A SNX3-dependent retromer pathway mediates retrograde transport of the Wnt sorting receptor Wntless and is required for Wnt secretion

NARCIS (Netherlands)

Harterink, M.; Port, F.; Lorenowicz, M.J.; McGough, I.J.; Silhankova, M.; Betist, M.C.; van Weering, J.R.; van Heesbeen, R.G.; Middelkoop, T.C.; Basler, K.; Cullen, P.J.; Korswagen, H.C.

2011-01-01

Wnt proteins are lipid-modified glycoproteins that play a central role in development, adult tissue homeostasis and disease. Secretion of Wnt proteins is mediated by the Wnt-binding protein Wntless (Wls), which transports Wnt from the Golgi network to the cell surface for release. It has recently

Membrane transporters mediating root signalling and adaptive responses to oxygen deprivation and soil flooding.

Science.gov (United States)

Shabala, Sergey; Shabala, Lana; Barcelo, Juan; Poschenrieder, Charlotte

2014-10-01

This review provides a comprehensive assessment of a previously unexplored topic: elucidating the role that plasma- and organelle-based membrane transporters play in plant-adaptive responses to flooding. We show that energy availability and metabolic shifts under hypoxia and anoxia are critical in regulating membrane-transport activity. We illustrate the high tissue and time dependence of this regulation, reveal the molecular identity of transporters involved and discuss the modes of their regulation. We show that both reduced oxygen availability and accumulation of transition metals in flooded roots result in a reduction in the cytosolic K(+) pool, ultimately determining the cell's fate and transition to programmed cell death (PCD). This process can be strongly affected by hypoxia-induced changes in the amino acid pool profile and, specifically, ϒ-amino butyric acid (GABA) accumulation. It is suggested that GABA plays an important regulatory role, allowing plants to proceed with H2 O2 signalling to activate a cascade of genes that mediate plant adaptation to flooding while at the same time, preventing the cell from entering a 'suicide program'. We conclude that progress in crop breeding for flooding tolerance can only be achieved by pyramiding the numerous physiological traits that confer efficient energy maintenance, cytosolic ion homeostasis, and reactive oxygen species (ROS) control and detoxification. © 2014 John Wiley & Sons Ltd.

COPA mutations impair ER-Golgi transport causing hereditary autoimmune-mediated lung disease and arthritis

Science.gov (United States)

Watkin, Levi B.; Jessen, Birthe; Wiszniewski, Wojciech; Vece, Timothy; Jan, Max; Sha, Youbao; Thamsen, Maike; Santos-Cortez, Regie L. P.; Lee, Kwanghyuk; Gambin, Tomasz; Forbes, Lisa; Law, Christopher S.; Stray-Petersen, Asbjørg; Cheng, Mickie H.; Mace, Emily M.; Anderson, Mark S.; Liu, Dongfang; Tang, Ling Fung; Nicholas, Sarah K.; Nahmod, Karen; Makedonas, George; Canter, Debra; Kwok, Pui-Yan; Hicks, John; Jones, Kirk D.; Penney, Samantha; Jhangiani, Shalini N.; Rosenblum, Michael D.; Dell, Sharon D.; Waterfield, Michael R.; Papa, Feroz R.; Muzny, Donna M.; Zaitlen, Noah; Leal, Suzanne M.; Gonzaga-Jauregui, Claudia; Boerwinkle, Eric; Eissa, N. Tony; Gibbs, Richard A.; Lupski, James R.; Orange, Jordan S.; Shum, Anthony K.

2015-01-01

Advances in genomics have allowed unbiased genetic studies of human disease with unexpected insights into the molecular mechanisms of cellular immunity and autoimmunity1. We performed whole exome sequencing (WES) and targeted sequencing in patients with an apparent Mendelian syndrome of autoimmune disease characterized by high-titer autoantibodies, inflammatory arthritis and interstitial lung disease (ILD). In five families, we identified four unique deleterious variants in the Coatomer subunit alpha (COPA) gene all located within the same functional domain. We hypothesized that mutant COPA leads to a defect in intracellular transport mediated by coat protein complex I (COPI)2–4. We show that COPA variants impair binding of proteins targeted for retrograde Golgi to ER transport and demonstrate that expression of mutant COPA leads to ER stress and the upregulation of Th17 priming cytokines. Consistent with this pattern of cytokine expression, patients demonstrated a significant skewing of CD4+ T cells toward a T helper 17 (Th17) phenotype, an effector T cell population implicated in autoimmunity5,6. Our findings uncover an unexpected molecular link between a vesicular transport protein and a syndrome of autoimmunity manifested by lung and joint disease. These findings provide a unique opportunity to understand how alterations in cellular homeostasis caused by a defect in the intracellular trafficking pathway leads to the generation of human autoimmune disease. PMID:25894502

Characterization of rPEPT2-mediated Gly-Sar transport parameters in the rat kidney proximal tubule cell line SKPT-0193 cl.2 cultured in basic growth media

DEFF Research Database (Denmark)

Bravo, Silvina A; Nielsen, Carsten Uhd; Frokjaer, Sven

2005-01-01

The rat proximal kidney tubule cell line SKPT-0193 cl.2 (SKPT) expresses the di-/tripeptide transporter PEPT2 (rPEPT2) and has been used to study PEPT2-mediated transport. Traditionally, SKPT cells have been cultured in growth media supplemented with epidermal growth factor (EGF), apotransferrin,...

Streptococcus mutans in denture stomatitis patients under antifungal therapy = Streptococcus mutans em pacientes com estomatite protética submetidos à terapia antifúngica

Directory of Open Access Journals (Sweden)

Vasconcelos, Laurylene César de S.

2010-01-01

Full Text Available Objetivo: Verificar o número de Streptococcus mutans em saliva de pacientes com estomatite protética antes e após a terapia antifúngica. Metodologia: Após exame clínico de 93 pacientes, 47 foram selecionados para exame micológico e desta amostra foram selecionados trinta pacientes: 15 com diagnóstico positivo e 15 com diagnóstico negativo de candidose foram avaliados para contagem de S. mutans, determinação de fluxo salivar e capacidade tampão. Higiene bucal e da prótese, tempo de confecção, tipo de lesão e dados salivares foram relacionados com características clínicas e laboratoriais de Candida. Resultados: As lesões frequentes foram dos tipos I (43,5% e II (53,5%. A quantidade de S. mutans foi seis vezes maior em pacientes com candidose e foi associada com baixo fluxo salivar e higiene oral deficiente. Após a terapia, a redução de S. mutans foi verificada particularmente em pacientes com fluxo salivar normal. Os valores variaram de 0,01 a 3,88 UFC/ml x 104. Conclusão: Os dados sugerem que os Streptococcus colaboram com Candida spp na etiopatogenia da estomatite protética. O uso de agentes antimicrobianos orais pode propiciar efeito benéfico para pacientes com estomatite protética submetidos à terapia antifúngica e que apresentam higiene oral deficiente e parâmetros salivares desfavoráveis

iELM—a web server to explore short linear motif-mediated interactions

Science.gov (United States)

Weatheritt, Robert J.; Jehl, Peter; Dinkel, Holger; Gibson, Toby J.

2012-01-01

The recent expansion in our knowledge of protein–protein interactions (PPIs) has allowed the annotation and prediction of hundreds of thousands of interactions. However, the function of many of these interactions remains elusive. The interactions of Eukaryotic Linear Motif (iELM) web server provides a resource for predicting the function and positional interface for a subset of interactions mediated by short linear motifs (SLiMs). The iELM prediction algorithm is based on the annotated SLiM classes from the Eukaryotic Linear Motif (ELM) resource and allows users to explore both annotated and user-generated PPI networks for SLiM-mediated interactions. By incorporating the annotated information from the ELM resource, iELM provides functional details of PPIs. This can be used in proteomic analysis, for example, to infer whether an interaction promotes complex formation or degradation. Furthermore, details of the molecular interface of the SLiM-mediated interactions are also predicted. This information is displayed in a fully searchable table, as well as graphically with the modular architecture of the participating proteins extracted from the UniProt and Phospho.ELM resources. A network figure is also presented to aid the interpretation of results. The iELM server supports single protein queries as well as large-scale proteomic submissions and is freely available at http://i.elm.eu.org. PMID:22638578

The organic anion transport polypeptide 1d1 (Oatp1d1) mediates hepatocellular uptake of phalloidin and microcystin into skate liver.

Science.gov (United States)

Meier-Abt, F; Hammann-Hänni, A; Stieger, B; Ballatori, N; Boyer, J L

2007-02-01

Organic anion transporting polypeptides (rodent Oatp; human OATP) mediate cellular uptake of numerous organic compounds including xenobiotic toxins into mammalian hepatocytes. In the little skate Leucoraja erinacea a liver-specific Oatp (Oatp1d1, also called sOatp) has been identified and suggested to represent an evolutionarily ancient precursor of the mammalian liver OATP1B1 (human), Oatp1b2 (rat), and OATP1B3 (human). The present study tested whether Oatp1d1 shares functional transport activity of the xenobiotic oligopeptide toxins phalloidin and microcystin with the mammalian liver Oatps/OATPs. The phalloidin analogue [(3)H]-demethylphalloin was taken up into skate hepatocytes with high affinity (Km approximately 0.4 microM), and uptake could be inhibited by phalloidin and a variety of typical Oatp/OATP substrates such as bromosulfophthalein, bile salts, estrone-3-sulfate, cyclosporine A and high concentrations of microcystin-LR (Ki approximately 150 microM). When expressed in Xenopus laevis oocytes Oatp1d1 increased uptake of demethylphalloin (Km approximately 2.2 microM) and microcystin-LR (Km approximately 27 microM) 2- to 3-fold over water-injected oocytes, whereas the alternative skate liver organic anion transporter, the dimeric Ostalpha/beta, exhibited no phalloidin and only minor microcystin-LR transport. Also, the closest mammalian Oatp1d1 orthologue, the human brain and testis OATP1C1, did not show any phalloidin transport activity. These results demonstrate that the evolutionarily ancient Oatp1d1 is able to mediate uptake of cyclic oligopeptide toxins into skate liver. The findings support the notion that Oatp1d1 is a precursor of the liver-specific mammalian Oatps/OATPs and that its transport properties are closely associated with certain forms of toxic liver injury such as for example protein phosphatase inhibition by the water-borne toxin microcystin.

The organic anion transport polypeptide 1d1 (Oatp1d1) mediates hepatocellular uptake of phalloidin and microcystin into skate liver

International Nuclear Information System (INIS)

Meier-Abt, F.; Hammann-Haenni, A.; Stieger, B.; Ballatori, N.; Boyer, J.L.

2007-01-01

Organic anion transporting polypeptides (rodent Oatp; human OATP) mediate cellular uptake of numerous organic compounds including xenobiotic toxins into mammalian hepatocytes. In the little skate Leucoraja erinacea a liver-specific Oatp (Oatp1d1, also called sOatp) has been identified and suggested to represent an evolutionarily ancient precursor of the mammalian liver OATP1B1 (human), Oatp1b2 (rat), and OATP1B3 (human). The present study tested whether Oatp1d1 shares functional transport activity of the xenobiotic oligopeptide toxins phalloidin and microcystin with the mammalian liver Oatps/OATPs. The phalloidin analogue [ 3 H]-demethylphalloin was taken up into skate hepatocytes with high affinity (Km ∼ 0.4 μM), and uptake could be inhibited by phalloidin and a variety of typical Oatp/OATP substrates such as bromosulfophthalein, bile salts, estrone-3-sulfate, cyclosporine A and high concentrations of microcystin-LR (Ki ∼ 150 μM). When expressed in Xenopus laevis oocytes Oatp1d1 increased uptake of demethylphalloin (Km ∼ 2.2 μM) and microcystin-LR (Km ∼ 27 μM) 2- to 3-fold over water-injected oocytes, whereas the alternative skate liver organic anion transporter, the dimeric Ostα/β, exhibited no phalloidin and only minor microcystin-LR transport. Also, the closest mammalian Oatp1d1 orthologue, the human brain and testis OATP1C1, did not show any phalloidin transport activity. These results demonstrate that the evolutionarily ancient Oatp1d1 is able to mediate uptake of cyclic oligopeptide toxins into skate liver. The findings support the notion that Oatp1d1 is a precursor of the liver-specific mammalian Oatps/OATPs and that its transport properties are closely associated with certain forms of toxic liver injury such as for example protein phosphatase inhibition by the water-borne toxin microcystin

Cirugía biológica pre protésica en artrosis temprana de rodilla

Directory of Open Access Journals (Sweden)

Wainer E. Mauricio, DR

2014-09-01

Full Text Available La artrosis (OA de rodilla es una condición progresiva, incapacitante en distintos grados en sus etapas, terminando en el colapso y destrucción articular que requiere de cirugía protésica en las etapas más avanzadas. La cirugía biológica pre-protésica, concepto que hoy en día se implementa en el manejo de las etapas precoces de la OA, se basa en el diagnóstico precoz de esta condición y de los factores de riesgo que aseguran el progreso a estados más avanzados. Su objetivo es prolongar la vida útil de la articulación nativa y retardar o eliminar la necesidad de una prótesis de rodilla. Esto ha motivado innumerables estudios preclínicos y clínicos en base al uso de nuevos elementos de ingeniería de tejidos, uso de implantes de condrocitos autólogos y manejo de células madre. Los resultados en el corto y mediano plazo son auspiciosos, pero se requieren mejores niveles de evidencia científica de estos estudios y seguimientos más prolongados. En el presente artículo se analiza el concepto de la artrosis temprana, la detección de las lesiones de cartílago y los factores de riesgo de los pacientes que los llevan a una artrosis y los protocolos actuales de tratamiento biológico de Clínica Las Condes.

Protótipo de um sistema de gerenciamento de protocolos de câncer colorretal Management system prototype of colorectal cancer protocols

Directory of Open Access Journals (Sweden)

Huei Diana Lee

2011-03-01

Full Text Available OBJETIVO: desenvolvimento de um protótipo de sistema de cadastro e controle de protocolos de Câncer Colorretal, com a finalidade de armazenar um conjunto abrangente de dados de forma estruturada para posterior aplicação de métodos de análise inteligente de dados. MATERIAL E MÉTODO: o protótipo foi construído em cinco etapas: análise do domínio de Câncer Colorretal, definição de requisitos básicos (operacionais e informacionais, projeto do sistema, construção do sistema usando tecnologias open source e avaliação do sistema com o apoio de especialistas. RESULTADOS E DISCUSSÃO: durante o desenvolvimento, o protótipo foi avaliado por especialistas quanto à estrutura do conjunto de dados, à coerência de organização das informações, à validade das funcionalidades implementadas e ao atendimento aos requisitos básicos definidos. CONCLUSÃO: de acordo com os especialistas usuários, o desenvolvimento do protótipo completou a primeira etapa do projeto de desenvolvimento de um sistema em nível de 100% de satisfação e, atualmente, está sendo aplicado em cadastros de dados reais. Na próxima etapa será consolidado e implantado o sistema completo, atendendo a requisitos de segurança com suporte a multiusuáriosOBJECTIVE: to develop a prototype of a Colorectal Cancer records management system, aiming to store an embracing structured dataset for later application of intelligent data analysis methods. MATERIAL AND METHOD: the prototype was developed in five stages: Colorectal Cancer domain analysis, definition of basic requirements (operational and informational, system design, system construction using open source technologies and system evaluation supported by domain experts. RESULTS AND DISCUSSION: during development, the prototype dataset structure, coherence of information structure, validity of functions implemented and the attendance to the basic requirements define, were evaluated by domain experts. CONCLUSION

Estrone-1-sulphate (E1S) has impact on the kinetics parameters of transporter mediated taurine and glutamate influx in Caco-2 cells

DEFF Research Database (Denmark)

Steffansen, Bente; El-Sayed, F

Previously, we have suggested estrone-1-sulfate (E1S) to be intercalated into the phospholipid membrane 1,2-dipalmitoyl-sn-glycero-3-phospho-choline (DPPC). The overall hypothesis of the present study was that E1S intercalation in the cell membrane of Caco-2 cells may changes the functionality...... of membrane transporters. The aim was therefore to investigate if addition of E1S to the growth medium of Caco-2 cells before but not during the influx study, change the kinetic parameters of transporter-mediated influx of taurine and glutamate by respective TAUT and EAAT transporters. The results show that 4...

Lipopolysaccharide inhibits colonic biotin uptake via interference with membrane expression of its transporter: a role for a casein kinase 2-mediated pathway.

Science.gov (United States)

Lakhan, Ram; Said, Hamid M

2017-04-01

Biotin (vitamin B7), an essential micronutrient for normal cellular functions, is obtained from both dietary sources as well as gut microbiota. Absorption of biotin in both the small and large intestine is via a carrier-mediated process that involves the sodium-dependent multivitamin transporter (SMVT). Although different physiological and molecular aspects of intestinal biotin uptake have been delineated, nothing is known about the effect of LPS on the process. We addressed this issue using in vitro (human colonic epithelial NCM460 cells) and in vivo (mice) models of LPS exposure. Treating NCM460 cells with LPS was found to lead to a significant inhibition in carrier-mediated biotin uptake. Similarly, administration of LPS to mice led to a significant inhibition in biotin uptake by native colonic tissue. Although no changes in total cellular SMVT protein and mRNA levels were observed, LPS caused a decrease in the fraction of SMVT expressed at the cell surface. A role for casein kinase 2 (CK2) (whose activity was also inhibited by LPS) in mediating the endotoxin effects on biotin uptake and on membrane expression of SMVT was suggested by findings that specific inhibitors of CK2, as well as mutating the putative CK2 phosphorylation site (Thr 78 Ala) in the SMVT protein, led to inhibition in biotin uptake and membrane expression of SMVT. This study shows for the first time that LPS inhibits colonic biotin uptake via decreasing membrane expression of its transporter and that these effects likely involve a CK2-mediated pathway.

Involvement of Multiple Transporters-mediated Transports in Mizoribine and Methotrexate Pharmacokinetics

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Teruo Murakami

2012-08-01

Full Text Available Mizoribine is administered orally and excreted into urine without being metabolized. Many research groups have reported a linear relationship between the dose and peak serum concentration, between the dose and AUC, and between AUC and cumulative urinary excretion of mizoribine. In contrast, a significant interindividual variability, with a small intraindividual variability, in oral bioavailability of mizoribine is also reported. The interindividual variability is mostly considered to be due to the polymophisms of transporter genes. Methotrexate (MTX is administered orally and/or by parenteral routes, depending on the dose. Metabolic enzymes and multiple transporters are involved in the pharmacokinetics of MTX. The oral bioavailability of MTX exhibits a marked interindividual variability and saturation with increase in the dose of MTX, with a small intraindividual variability, where the contribution of gene polymophisms of transporters and enzymes is suggested. Therapeutic drug monitoring of both mizoribine and MTX is expected to improve their clinical efficacy in the treatment of rheumatoid arthritis.

SwissProt search result: AK102305 [KOME

Lifescience Database Archive (English)

Full Text Available AK102305 J033089P03 (Q9US45) RNA polymerase II mediator complex protein pmc5 (RNA polymerase II mediator... complex protein med6) (RNA polymerase II transcriptional regulation mediator 6) PMC5_SCHPO 1e-11 ...

Evaluation of a potential transporter-mediated drug interaction between rosuvastatin and pradigastat, a novel DGAT-1 inhibitor.

Science.gov (United States)

Kulmatycki, Kenneth; Hanna, Imad; Meyers, Dan; Salunke, Atish; Movva, Aishwarya; Majumdar, Tapan; Natrillo, Adrienne; Vapurcuyan, Arpine; Rebello, Sam; Sunkara, Gangadhar; Chen, Jin

2015-05-01

An in vitro drugdrug interaction (DDI) study was performed to assess the potential for pradigastat to inhibit breast cancer resistance protein (BCRP), organic anion-transporting polypeptide (OATP), and organic anion transporter 3 (OAT3) transport activities. To understand the relevance of these in vitro findings, a clinical pharmacokinetic DDI study using rosuvastatin as a BCRP, OATP, and OAT3 probe substrate was conducted. The study used cell lines that stably expressed or over-expressed the respective transporters. The clinical study was an open-label, single sequence study where subjects (n = 36) received pradigastat (100 mg once daily x 3 days thereafter 40 mg once daily) and rosuvastatin (10 mg once daily), alone and in combination. Pradigastat inhibited BCRP-mediated efflux activity in a dose-dependent fashion in a BCRP over-expressing human ovarian cancer cell line with an IC(50) value of 5 μM. Similarly, pradigastat inhibited OATP1B1, OATP1B3 (estradiol 17β glucuronide transport), and OAT3 (estrone 3 sulfate transport) activity in a concentrationdependent manner with estimated IC(50) values of 1.66 ± 0.95 μM, 3.34 ± 0.64 μM, and 0.973 ± 0.11 μM, respectively. In the presence of steady state pradigastat concentrations, AUC(τ, ss) of rosuvastatin was unchanged and its Cmax,ss decreased by 14% (5.30 and 4.61 ng/mL when administered alone and coadministered with pradigastat, respectively). Pradigastat AUC(τ, ss) and C(max, ss) were unchanged when coadministered with rosuvastatin at steady state. Both rosuvastatin and pradigastat were well tolerated. These data indicate no clinically relevant pharmacokinetic interaction between pradigastat and rosuvastatin.

AcEST: DK950047 [AcEST

Lifescience Database Archive (English)

Full Text Available .5 >sp|Q91502|SC6A8_TORMA Creatine transporter OS=Torpedo marmorata PE=2 SV=1 Length = 611 Score = 31.2 bits...n sp|Q91502|SC6A8_TORMA Creatine transporter OS=Torpedo marmorata Align length 44 Score (bit) 31.2 E-value 5...atine transporter OS=Torpedo marmorata ... 31 5.5 sp|Q6P.........................................done Score E Sequences producing significant alignments: (bits) Value sp|Q91502|SC6A8_TORMA Cre... search results ■■ - Swiss-Prot (release 56.9) Link to BlastX Result : Swiss-Prot sp_hit_id Q91502 Definitio

Speed Limits for Nonvesicular Intracellular Sterol Transport.

Science.gov (United States)

Dittman, Jeremy S; Menon, Anant K

2017-02-01

Sterol transport between the endoplasmic reticulum (ER) and plasma membrane (PM) occurs by nonvesicular mechanisms requiring sterol transport proteins (STPs). Here we examine the idea that transport is enhanced at membrane contact sites where the ER is closely apposed to the PM. We conclude that sterol desorption from the membrane, rather than STP-mediated diffusion, is rate limiting in the cellular context, so there is no apparent kinetic benefit to having STP-mediated sterol transfer occur at contact sites. Contact sites may instead compartmentalize lipid synthesis or transport machinery, providing opportunities for regulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Protocolo protésico - quirúrgico en temporización inmediata de dientes unitarios, utilizando una cubeta multifuncional desmontable Prosthetic protocol - surgery in the immediate temporization of a single tooth using a multifunctional removable tray

OpenAIRE

Y Leighton; JC Carvajal; A Wolnitzky; R Silva; A Von Marttens

2010-01-01

Propósito: El presente reporte clínico es la descripción de un protocolo protésico - quirúrgico que permite la visualización directa del sitio operatorio y el correcto posicionamiento protésico - implantario de una corona temporal atornillada, construida inmediatamente de insertado el implante. Material y métodos: Se seleccionaron 10 pacientes del programa de especialización en implantologia bucomaxilofacial de la Universidad de Chile, cuyo criterio de inclusión principal fue ser desdentado p...

Carrier mediated transport through supported liquid membranes; determination of transport parameters from a single transport experiment

NARCIS (Netherlands)

Chrisstoffels, L.A.J.; Struijk, Wilhelmina; de Jong, Feike; Reinhoudt, David

1996-01-01

This paper describes a time-dependent transport model for carrier assisted cation transport through supported liquid membranes. The model describes the flux of salt as a function of time and two parameters viz. the diffusion coefficient of the cation complex (D), and the extraction constant (Kex).

Efeito do soro de leite no teor protéico e na qualidade tecnológica e sensorial de pães

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Elessandra da Rosa Zavareze

2008-08-01

Full Text Available O trabalho teve como objetivo utilizar soro de leite in natura, concentrado e desidratado na formulação de pão e avaliar a influência deste ingrediente nas características tecnológicas e sensoriais do produto, assim como o aumento no teor protéico. Os resultados foram avaliados por análise de variância e as médias comparadas por teste de Tukey (p < 0,05. Os dados foram submetidos à correlação de Pearson. Os pães com soro de leite apresentaram maior teor protéico e notas tecnológicas superiores ao pão padrão, com exceção do pão com soro desidratado que apresentou menor volume específico. Na avaliação sensorial, os pães com adição de soro não apresentaram diferença significativa em relação ao pão padrão.

Determinação da solubilidade protéica de farinhas de subproduto de aves com a pepsina em baixa concentração Determination of solubility of poultry by-product with pepsin in low concentration

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Claudio Bellaver

2004-10-01

Full Text Available Foi proposto recentemente que a solubilidade protéica in vitro com pepsina na concentração de 0,0002% é melhor que em concentrações maiores, para melhor classificar a qualidade protéica de farinhas de origem animal (FOA. Entretanto, nessa concentração, desconhece-se qual é o intervalo que melhor exprime a qualidade por meio da solubilidade protéica das FOA. Este trabalho foi conduzido com o objetivo de identificar os valores da solubilidade protéica de farinhas de subprodutos do abate de aves (FSA, utilizadas como modelo experimental. As fontes protéicas foram duas FSA e caseína (considerada padrão com 100% de solubilidade protéica. Todas as farinhas foram autoclavadas a 120ºC, durante 0, 10, 20, 40 e 80 minutos. As concentrações utilizadas da pepsina em solução de HCl 0,0744N foram de 0,0002 e 0,02%. O delineamento experimental foi o de blocos casualizados em esquema fatorial 3 (fontes x 5 (temperaturas x 2 (concentrações, com quatro repetições para a enzima na concentração de 0,0002% e duas repetições para a concentração de 0,02%. Foram determinados os valores de solubilidade protéica in vitro em solução ácido/pepsina e energia metabolizável in vivo das FSA. Os resultados indicaram que, na concentração de pepsina de 0,0002%, os valores de boa qualidade das FSA estão acima de 55%. Da mesma forma, solubilidades próximas a 84% podem ser consideradas boas, mas decaem em solubilidade e são consideradas ruins se tiverem em torno de 67% de solubilidade protéica em pepsina a 0,02%.It was recently proposed that the in vitro protein solubility is better to classify animal by-product meals (ABP using pepsin concentration of .0002% than with higher concentrations. However on this concentration no reference value exists to express ABP quality based on protein solubility. The objective of this study was to obtain protein solubility values for poultry by-product meals (PBP, as model to ABP. Two PBP and casein

Estudo da biomassa de aguapé, para a produção do seu concentrado protéico

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MEDEIROS Rosalina M. L.

1999-01-01

Full Text Available Na produção de concentrado protéico de aguapé (C. P. A., utilizou-se para extração da fração protéica solução de hidróxido de sódio (50mM na proporção (3:1 sendo três volumes de solução de hidróxido de sódio para um volume de planta desintegrada. A precipitação da proteína foi realizada utilizando solução de ácido clorídrico (100mM à temperatura de 80° C, o pH foi sendo corrigido até atingir o ponto isoelétrico da proteína, que ocorreu em pH 3,5. O teor de proteína encontrado no C. P. A. foi superior ao encontrado em outros vegetais e produtos de origem vegetal tais como alfafa e farinha de soja por exemplo. A presença de todos aminoácidos essenciais no C. P. A. mostra que sua utilização é viável na produção não só de ração animal, mas também, como suplementação alimentar na dieta humana.

Expression and regulation of transmembrane transporters in healthy intestine and gastrointestinal diseases

OpenAIRE

Hruz, Petr

2006-01-01

Transmembrane transporters mediate energy dependent or independent translocation of drugs, potentially toxic compounds, and of various endogenous substrates such as bile acids and bilirubin across membranes. In this thesis the focus is on two classes of transporters, the ATPbinding cassette (ABC) transporters, which mediate ATP dependent transport and the solute carriers (SLC) which use electrochemical gradients for their transport. The transporters are expressed on membranes o...

ROTUNDA3 function in plant development by phosphatase 2A-mediated regulation of auxin transporter recycling.

Science.gov (United States)

Karampelias, Michael; Neyt, Pia; De Groeve, Steven; Aesaert, Stijn; Coussens, Griet; Rolčík, Jakub; Bruno, Leonardo; De Winne, Nancy; Van Minnebruggen, Annemie; Van Montagu, Marc; Ponce, María Rosa; Micol, José Luis; Friml, Jiří; De Jaeger, Geert; Van Lijsebettens, Mieke

2016-03-08

The shaping of organs in plants depends on the intercellular flow of the phytohormone auxin, of which the directional signaling is determined by the polar subcellular localization of PIN-FORMED (PIN) auxin transport proteins. Phosphorylation dynamics of PIN proteins are affected by the protein phosphatase 2A (PP2A) and the PINOID kinase, which act antagonistically to mediate their apical-basal polar delivery. Here, we identified the ROTUNDA3 (RON3) protein as a regulator of the PP2A phosphatase activity in Arabidopsis thaliana. The RON3 gene was map-based cloned starting from the ron3-1 leaf mutant and found to be a unique, plant-specific gene coding for a protein with high and dispersed proline content. The ron3-1 and ron3-2 mutant phenotypes [i.e., reduced apical dominance, primary root length, lateral root emergence, and growth; increased ectopic stages II, IV, and V lateral root primordia; decreased auxin maxima in indole-3-acetic acid (IAA)-treated root apical meristems; hypergravitropic root growth and response; increased IAA levels in shoot apices; and reduced auxin accumulation in root meristems] support a role for RON3 in auxin biology. The affinity-purified PP2A complex with RON3 as bait suggested that RON3 might act in PIN transporter trafficking. Indeed, pharmacological interference with vesicle trafficking processes revealed that single ron3-2 and double ron3-2 rcn1 mutants have altered PIN polarity and endocytosis in specific cells. Our data indicate that RON3 contributes to auxin-mediated development by playing a role in PIN recycling and polarity establishment through regulation of the PP2A complex activity.

Composição centesimal e aceitação de lingüiça elaborada com reduzido teor de gordura e adicionada de concentrados protéicos de soro de leite

OpenAIRE

Ferreira,Ana Cláudia Brandi; Fonseca,Leorges Moraes da; Santos,Wagner Luiz Moreira dos

2009-01-01

Este trabalho objetivou avaliar a composição centesimal e aceitação de lingüiças de carne suína fabricadas com Concentrado Protéico do Soro (WPC) ou com concentrado protéico, com elevado teor de b-lactoglobulina, como substitutos da gordura. Foram realizados sete tratamentos, um grupo controle, contendo 20% de gordura, e seis tratamentos com reduzido teor de gordura, contendo diferentes níveis de adição de WPC ou de fração de b-lactoglobulina, a saber, três tratamentos com 10% de gordura e ad...

Regulation of organic anion transport in the liver

NARCIS (Netherlands)

Roelofsen, H; Jansen, PLM

1997-01-01

In several liver diseases the biliary transport is disturbed, resulting in, for example, jaundice and cholestasis. Many of these symptoms can be attributed to altered regulation of hepatic transporters. Organic anion transport, mediated by the canalicular multispecific organic anion transporter

Reconstrucción del maxilar superior mediante transporte del proceso alveolar: Presentación de un caso Reconstruction of the maxilla by means of transport of the alveolar process: A case report

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A. Bilbao

2006-02-01

Full Text Available La osteogénesis mediante distracción aplicada a la reconstrucción del proceso alveolar es una técnica sobradamente contrastada en la literatura, al igual que la utilización del transporte óseo en la reconstrucción de defectos segmentarios mandibulares. Presentamos en este artículo un caso de reconstrucción de un defecto segmentario del maxilar superior mediante transporte de proceso alveolar y su posterior rehabilitación protésica implantosoportada. Mostramos tanto la técnica quirúrgica como el manejo de del vector de distracción utilizando elásticos de ortodoncia y tornillos de bloqueo intermaxilar.Osteogenesis by means of distraction applied to the reconstruction of the alveolar process is a well-documented technique in the literature, as is the use of bone transport in the reconstruction of mandibular segment defects. In the present article we report on a case of reconstruction of a segment defect in the maxilla using the alveolar transport process, and on the subsequent rehabilitation by means of an implant-supported prosthesis. Both the surgical technique and the handling of the distraction vector using orthodontic bands and inter-maxillary fixation screws are shown.

Características de carcaça de cordeiros terminados em confinamento, com dietas contendo diferentes níveis protéicos

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Zundt Marilice

2003-01-01

Full Text Available Trinta e dois cordeiros (¹/2 Texel + ¼ Bergamácia + ¼ Corriedale, 16 machos inteiros e 16 fêmeas, foram alimentados durante 71 dias com dietas isoenergéticas (72% NDT, variando os níveis protéicos (12, 16, 20 e 24 % PB em baias individuais, com avaliação de carcaça após abate. O rendimento verdadeiro médio da carcaça foi 54%, enquanto o rendimento comercial médio foi 48%. Verificou-se que os níveis protéicos entre 12 e 24% não afetaram o peso da carcaça quente e fria; o rendimento comercial da carcaça, o índice de compacidade da carcaça e do pernil, bem como a condição corporal, conformação, cobertura de gordura, consistência da gordura, cor da carne, espessura de gordura e deposição de gordura. Os animais terminados com dietas com 12% de proteína bruta foram os que apresentaram maior rendimento verdadeiro de carcaça.

Efeito da dieta hiperlipídico-protéica no metabolismo de ratos wistar adultos

OpenAIRE

Borba, Alberto José de

2008-01-01

O consumo de dietas com pouco carboidrato e rica em proteínas e gorduras faz parte do rol de dietas usadas para a perda de peso. A princípio, essas dietas levam à mobilização de triglicerídeos para a produção de corpos cetônicos e manutenção das funções corporais. O presente trabalho testou o efeito de uma dieta hiperlipídico-protéica (HLP) com baixo teor de carboidrato sobre o peso corporal, peso dos órgãos, consumo de ração, parâmetros bioquímicos séricos e alterações histopatológicas...

Recobrimento de laranja 'Pêra' com filme de concentrado protéico de soro de leite associado a plastificantes.

OpenAIRE

ALLEONI, A.C.C.; JACOMINO, A.P.; ROSA, A.S.

2006-01-01

O objetivo desse estudo foi avaliar o efeito de coberturas à base de concentrado protéico de soro de leite (CPSL), associadas a dois tipos de plastificantes (glicerol e sorbitol), em laranja 'Pêra'. As frutas foram lavadas e higienizadas de acordo com os padrões comerciais e submetidas à aplicação das coberturas. As coberturas à base de CPSL não foram eficientes na redução da perda de massa fresca da laranja 'Pera', independentemente do plastificante utilizado. Depois de 11 dias de armazenage...

DNA-Mediated Electrochemistry

Science.gov (United States)

Gorodetsky, Alon A.; Buzzeo, Marisa C.

2009-01-01

The base pair stack of DNA has been demonstrated as a medium for long range charge transport chemistry both in solution and at DNA-modified surfaces. This chemistry is exquisitely sensitive to structural perturbations in the base pair stack as occur with lesions, single base mismatches, and protein binding. We have exploited this sensitivity for the development of reliable electrochemical assays based on DNA charge transport at self-assembled DNA monolayers. Here we discuss the characteristic features, applications, and advantages of DNA-mediated electrochemistry. PMID:18980370

An ATP Binding Cassette Transporter Mediates the Uptake of α-(1,6)-Linked Dietary Oligosaccharides in Bifidobacterium and Correlates with Competitive Growth on These Substrates

DEFF Research Database (Denmark)

Hansen, Morten Ejby; Fredslund, Folmer; Andersen, Joakim Mark

2016-01-01

that the dominant HGM commensal Bacteroides ovatus was out-competed by B. animalis subsp. lactis Bl-04 in mixed cultures growing on raffinose, the preferred ligand for the BlG16BP. By comparison, B. ovatus mono-cultures grew very efficiently on this trisaccharide. These findings suggest that the ABC-mediated uptake...... of raffinose provides an important competitive advantage, particularly against dominant Bacteroides that lack glycan-specific ABC-transporters. This novel insight highlights the role of glycan transport in defining the metabolic specialization of gut bacteria....

Caracterización de la trombosis protésica en el servicio de cardiología de Las Tunas. 2006-2011

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Maikel Santos Medina

2015-11-01

Full Text Available Se realizó un estudio descriptivo y transversal en el Servicio de Cardiología del Hospital “Dr. Ernesto Guevara de la Serna” de la provincia de Las Tunas, con el objetivo de caracterizar la trombosis de prótesis valvular en el período entre 2006 y 2011. El universo estuvo conformado por los 34 pacientes ingresados en el servicio por sospecha de trombosis protésica y la muestra por los 29 casos con diagnóstico definitivo de trombosis valvular protésica. Se utilizó la estadística descriptiva a través del análisis porcentual. La edad promedio de los casos fue de 47 años. Predominaron los pacientes del sexo femenino, con prótesis en posición mitral, con anticoagulación inadecuada y con ritmo sinusal en el electrocardiograma al ingreso. El edema agudo del pulmón fue la forma de presentación de disfunción ventricular izquierda que predominó. La mayoría de los pacientes fueron tratados con estreptoquinasa, lográndose resolución de la trombosis en la mayoría de los casos, con un número escaso de complicaciones tras el tratamiento trombolítico.

Yarrowia lipolytica vesicle-mediated protein transport pathways

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Beckerich Jean-Marie

2007-11-01

Full Text Available Abstract Background Protein secretion is a universal cellular process involving vesicles which bud and fuse between organelles to bring proteins to their final destination. Vesicle budding is mediated by protein coats; vesicle targeting and fusion depend on Rab GTPase, tethering factors and SNARE complexes. The Génolevures II sequencing project made available entire genome sequences of four hemiascomycetous yeasts, Yarrowia lipolytica, Debaryomyces hansenii, Kluyveromyces lactis and Candida glabrata. Y. lipolytica is a dimorphic yeast and has good capacities to secrete proteins. The translocation of nascent protein through the endoplasmic reticulum membrane was well studied in Y. lipolytica and is largely co-translational as in the mammalian protein secretion pathway. Results We identified S. cerevisiae proteins involved in vesicular secretion and these protein sequences were used for the BLAST searches against Génolevures protein database (Y. lipolytica, C. glabrata, K. lactis and D. hansenii. These proteins are well conserved between these yeasts and Saccharomyces cerevisiae. We note several specificities of Y. lipolytica which may be related to its good protein secretion capacities and to its dimorphic aspect. An expansion of the Y. lipolytica Rab protein family was observed with autoBLAST and the Rab2- and Rab4-related members were identified with BLAST against NCBI protein database. An expansion of this family is also found in filamentous fungi and may reflect the greater complexity of the Y. lipolytica secretion pathway. The Rab4p-related protein may play a role in membrane recycling as rab4 deleted strain shows a modification of colony morphology, dimorphic transition and permeability. Similarly, we find three copies of the gene (SSO encoding the plasma membrane SNARE protein. Quantification of the percentages of proteins with the greatest homology between S. cerevisiae, Y. lipolytica and animal homologues involved in vesicular

Astrocytic GABA Transporters

DEFF Research Database (Denmark)

Schousboe, Arne; Wellendorph, Petrine; Frølund, Bente

2017-01-01

, and several of these compounds have been shown to exhibit pronounced anticonvulsant activity in a variety of animal seizure models. As proof of concept of the validity of this drug development approach, one GABA-transport inhibitor, tiagabine, has been developed as a clinically active antiepileptic drug......Inactivation of GABA-mediated neurotransmission is achieved by high-affinity transporters located at both GABAergic neurons and the surrounding astrocytes. Early studies of the pharmacological properties of neuronal and glial GABA transporters suggested that different types of transporters might...... be expressed in the two cell types, and such a scenario was confirmed by the cloning of four distinctly different GABA transporters from a number of different species. These GABA-transport entities have been extensively characterized using a large number of GABA analogues of restricted conformation...

Considering a Threshold Energy in Reactive Transport Modeling of Microbially Mediated Redox Reactions in an Arsenic-Affected Aquifer

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Marco Rotiroti

2018-01-01

Full Text Available The reductive dissolution of Fe-oxide driven by organic matter oxidation is the primary mechanism accepted for As mobilization in several alluvial aquifers. These processes are often mediated by microorganisms that require a minimum Gibbs energy available to conduct the reaction in order to sustain their life functions. Implementing this threshold energy in reactive transport modeling is rarely used in the existing literature. This work presents a 1D reactive transport modeling of As mobilization by the reductive dissolution of Fe-oxide and subsequent immobilization by co-precipitation in iron sulfides considering a threshold energy for the following terminal electron accepting processes: (a Fe-oxide reduction, (b sulfate reduction, and (c methanogenesis. The model is then extended by implementing a threshold energy on both reaction directions for the redox reaction pairs Fe(III reduction/Fe(II oxidation and methanogenesis/methane oxidation. The optimal threshold energy fitted in 4.50, 3.76, and 1.60 kJ/mol e− for sulfate reduction, Fe(III reduction/Fe(II oxidation, and methanogenesis/methane oxidation, respectively. The use of models implementing bidirectional threshold energy is needed when a redox reaction pair can be transported between domains with different redox potentials. This may often occur in 2D or 3D simulations.

Role of Sphingosine Kinase 1 and S1P Transporter Spns2 in HGF-mediated Lamellipodia Formation in Lung Endothelium.

Science.gov (United States)

Fu, Panfeng; Ebenezer, David L; Berdyshev, Evgeny V; Bronova, Irina A; Shaaya, Mark; Harijith, Anantha; Natarajan, Viswanathan

2016-12-30

Hepatocyte growth factor (HGF) signaling via c-Met is known to promote endothelial cell motility and angiogenesis. We have previously reported that HGF stimulates lamellipodia formation and motility of human lung microvascular endothelial cells (HLMVECs) via PI3K/Akt signal transduction and reactive oxygen species generation. Here, we report a role for HGF-induced intracellular sphingosine-1-phosphate (S1P) generation catalyzed by sphingosine kinase 1 (SphK1), S1P transporter, spinster homolog 2 (Spns2), and S1P receptor, S1P 1 , in lamellipodia formation and perhaps motility of HLMVECs. HGF stimulated SphK1 phosphorylation and enhanced intracellular S1P levels in HLMVECs, which was blocked by inhibition of SphK1. HGF enhanced co-localization of SphK1/p-SphK1 with actin/cortactin in lamellipodia and down-regulation or inhibition of SphK1 attenuated HGF-induced lamellipodia formation in HLMVECs. In addition, down-regulation of Spns2 also suppressed HGF-induced lamellipodia formation, suggesting a key role for inside-out S1P signaling. The HGF-mediated phosphorylation of SphK1 and its localization in lamellipodia was dependent on c-Met and ERK1/2 signaling, but not the PI3K/Akt pathway; however, blocking PI3K/Akt signaling attenuated HGF-mediated phosphorylation of Spns2. Down-regulation of S1P 1 , but not S1P 2 or S1P 3 , with specific siRNA attenuated HGF-induced lamellipodia formation. Further, HGF enhanced association of Spns2 with S1P 1 that was blocked by inhibiting SphK1 activity with PF-543. Moreover, HGF-induced migration of HLMVECs was attenuated by down-regulation of Spns2 . Taken together, these results suggest that HGF/c-Met-mediated lamellipodia formation, and perhaps motility is dependent on intracellular generation of S1P via activation and localization of SphK1 to cell periphery and Spns2-mediated extracellular transportation of S1P and its inside-out signaling via S1P 1 . © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Hernia incisional grande: Resultado del tratamiento quirúrgico con material protésico

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Juan Francisco Puerta Alvarez

1996-12-01

Full Text Available Se realizó un estudio observacional y prospectivo para evaluar el tratamiento quirúrgico de las grandes hernias incisionales, con material protésico en 75 pacientes operados en el Hospital Militar Docente "Joaquín Castillo Duany" de Santiago de Cuba, desde febrero de 1990 hasta julio de 1994. Se conformaron 2 grupos: de estudio con 50 pacientes (subdividido en 2 de 25 cada uno y testigo con 25. En este último la pared abdominal se cerró por planos con sutura irreabsorbible y sin material protésico, y al del estudio, en uno se practicó igual procedimiento pero utilizando malla de Mersilene y en el otro se sustituyó por duramadre homóloga. Las hernias incisionales grandes fueron más frecuentes en mujeres de 40 a 60 años con incisiones primarias medias; la mayoría de ellas obesas y diabéticas. Se comprobó que no hubo rechazo a la duramadre homóloga, grupo éste que mostró el menor índice de recidivas y complicaciones, y con los mejores resultados a los 5 años de seguimiento posoperatorioAn observation and prospective study was carried out to assess the surgical treatment of the big incisional hernias with prosthetic material in 75 operated patients in the "Joaquín Castillo Duany" Educational Military Hospital, at Santiago de Cuba, from February 1990 to July 1994. Two groups were formed: a study group with 50 patients, subdivided in two groups of 25 each, and a witness group with 25 patients. In this last group the abdominal wall was closed by planes with non reabsorbable suture and without prosthetic material, and in the study group, in one 25 patients subgroup the same procedure was carried out, but using Mersilene mesh, and in the other subgroup the mesh was substituted with homologous duramater. The big incisional hernias were more frequent in women from 40 to 60 years old with partial primary incision, mostly obese and diabetic. There was a confirmation of no reject to the homologous duramater. This group showed the smallets

The vacuolar transport of aleurain-GFP and 2S albumin-GFP fusions is mediated by the same pre-vacuolar compartments in tobacco BY-2 and Arabidopsis suspension cultured cells.

Science.gov (United States)

Miao, Yansong; Li, Kwun Yee; Li, Hong-Ye; Yao, Xiaoqiang; Jiang, Liwen

2008-12-01

Soluble proteins reach vacuoles because they contain vacuolar sorting determinants (VSDs) that are recognized by vacuolar sorting receptor (VSR) proteins. Pre-vacuolar compartments (PVCs), defined by VSRs and GFP-VSR reporters in tobacco BY-2 cells, are membrane-bound intermediate organelles that mediate protein traffic from the Golgi apparatus to the vacuole in plant cells. Multiple pathways have been demonstrated to be responsible for vacuolar transport of lytic enzymes and storage proteins to the lytic vacuole (LV) and the protein storage vacuole (PSV), respectively. However, the nature of PVCs for LV and PSV pathways remains unclear. Here, we used two fluorescent reporters, aleurain-GFP and 2S albumin-GFP, that represent traffic of lytic enzymes and storage proteins to LV and PSV, respectively, to study the PVC-mediated transport pathways via transient expression in suspension cultured cells. We demonstrated that the vacuolar transport of aleurain-GFP and 2S albumin-GFP was mediated by the same PVC populations in both tobacco BY-2 and Arabidopsis suspension cultured cells. These PVCs were defined by the seven GFP-AtVSR reporters. In wortmannin-treated cells, the vacuolated PVCs contained the mRFP-AtVSR reporter in their limiting membranes, whereas the soluble aleurain-GFP or 2S albumin-GFP remained in the lumen of the PVCs, indicating a possible in vivo relationship between receptor and cargo within PVCs.

A lower isoelectric point increases signal sequence-mediated secretion of recombinant proteins through a bacterial ABC transporter.

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Byun, Hyunjong; Park, Jiyeon; Kim, Sun Chang; Ahn, Jung Hoon

2017-12-01

Efficient protein production for industrial and academic purposes often involves engineering microorganisms to produce and secrete target proteins into the culture. Pseudomonas fluorescens has a TliDEF ATP-binding cassette transporter, a type I secretion system, which recognizes C-terminal LARD3 signal sequence of thermostable lipase TliA. Many proteins are secreted by TliDEF in vivo when recombined with LARD3, but there are still others that cannot be secreted by TliDEF even when LARD3 is attached. However, the factors that determine whether or not a recombinant protein can be secreted through TliDEF are still unknown. Here, we recombined LARD3 with several proteins and examined their secretion through TliDEF. We found that the proteins secreted via LARD3 are highly negatively charged with highly-acidic isoelectric points (pI) lower than 5.5. Attaching oligo-aspartate to lower the pI of negatively-charged recombinant proteins improved their secretion, and attaching oligo-arginine to negatively-charged proteins blocked their secretion by LARD3. In addition, negatively supercharged green fluorescent protein (GFP) showed improved secretion, whereas positively supercharged GFP did not secrete. These results disclosed that proteins' acidic pI and net negative charge are major factors that determine their secretion through TliDEF. Homology modeling for TliDEF revealed that TliD dimer forms evolutionarily-conserved positively-charged clusters in its pore and substrate entrance site, which also partially explains the pI dependence of the TliDEF-dependent secretions. In conclusion, lowering the isoelectric point improved LARD3-mediated protein secretion, both widening the range of protein targets for efficient production via secretion and signifying an important aspect of ABC transporter-mediated secretions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Neuroactivity of detonation nanodiamonds: dose-dependent changes in transporter-mediated uptake and ambient level of excitatory/inhibitory neurotransmitters in brain nerve terminals.

Science.gov (United States)

Pozdnyakova, Natalia; Pastukhov, Artem; Dudarenko, Marina; Galkin, Maxim; Borysov, Arsenii; Borisova, Tatiana

2016-03-31

Nanodiamonds are one of the most perspective nano-sized particles with superb physical and chemical properties, which are mainly composed of carbon sp(3) structures in the core with sp(2) and disorder/defect carbons on the surface. The research team recently demonstrated neuromodulatory properties of carbon nanodots with other than nanodiamonds hybridization types, i.e., sp(2) hybridized graphene islands and diamond-like sp(3) hybridized elements. In this study, neuroactive properties of uncoated nanodiamonds produced by detonation synthesis were assessed basing on their effects on transporter-mediated uptake and the ambient level of excitatory and inhibitory neurotransmitters, glutamate and γ-aminobutyric acid (GABA), in isolated rat brain nerve terminals. It was shown that nanodiamonds in a dose-dependent manner attenuated the initial velocity of Na(+)-dependent transporter-mediated uptake and accumulation of L-[(14)C]glutamate and [(3)H]GABA by nerve terminals and increased the ambient level of these neurotransmitters. Also, nanodiamonds caused a weak reduction in acidification of synaptic vesicles and depolarization of the plasma membrane of nerve terminals. Therefore, despite different types of hybridization in nanodiamonds and carbon dots, they exhibit very similar effects on glutamate and GABA transport in nerve terminals and this common feature of both nanoparticles is presumably associated with their nanoscale size. Observed neuroactive properties of pure nanodiamonds can be used in neurotheranostics for simultaneous labeling/visualization of nerve terminals and modulation of key processes of glutamate- and GABAergic neurotransmission. In comparison with carbon dots, wider medical application involving hypo/hyperthermia, external magnetic fields, and radiolabel techniques can be perspective for nanodiamonds.

Complicações cirúrgicas e protéticas em implantodontia = Prosthetic and surgical complications in dental implantology

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Lourenço, Simone Vessecchi

2007-01-01

Full Text Available Os implantes osseointegrados e as próteses implanto-suportadas têm sido utilizados na substituição de dentes perdidos. Com a descoberta da Osseointegração o índice de sucesso em Implantodontia aumentou acarretando no desenvolvimento de vários sistemas e marcas de implantes. Entretanto, toda essa evolução na Implantodontia, não permitiu aos Cirurgiões Dentistas que eximisse o tratamento de complicações cirúrgicas e protéticas. Com o intuito de confirmar o alto número de complicações que ocorrem durante o tratamento com implantes, assim como o surgimento de constrangimentos entre profissionais e pacientes e o descuido de informar o paciente da ocorrência das complicações, foi realizado esse estudo. Os resultados informaram que 100% dos entrevistados já tiveram alguma complicação durante o tratamento e de 1810 complicações citadas pela amostra as complicações cirúrgicas que mais ocorreram foram edema e equimose (898. De acordo com o resultado somente 42% da amostra utilizavam documento escrito informando ao paciente que poderiam ocorrer complicações. Observou-se que 59 dentistas já tiveram algum constrangimento com o paciente e 13 (22,03% destes dentistas tiveram constrangimento relacionado a ocorrência das complicações cirúrgicas e protéticas. Ressalta-se a necessidade de informar aos pacientes antes da realização do tratamento da ocorrência das complicações e solucioná-las quando ocorram evitando assim as lides judiciais

Projeto cartográfico e implementação de um protótipo de atlas escolar interativo

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Fernanda Puga Santos

Full Text Available Este trabalho tem por objetivo apresentar o desenvolvimento de um protótipo de Atlas Escolar Interativo para alunos do 4º ciclo do ensino fundamental. A abordagem metodológica baseou-se na teoria de desenvolvimento cognitivo com a finalidade de produzir um material que possa ser compreendido e utilizado pelo público alvo. Para tanto, analisou-se as necessidades dos usuários com base nos Parâmetros Curriculares Nacionais relacionados à disciplina de Geografia e nos livros didáticos utilizados em algumas escolas do ensino fundamental. Além disso, aplicou-se recursos multimídia de animação e interatividade, de acordo com a teoria de comunicação cartográfica, para facilitar a leitura e compreensão de mapas e assim, o conhecimento dos fenômenos geográficos. O desenvolvimento do protótipo subdividiu-se em duas grandes etapas: projeto cartográfico e produção do Atlas. Para a implementação do Atlas utilizou-se os aplicativos Macromedia Flash MX, Visual Basic e a biblioteca MapObjects-ESRI. Embora o Atlas não tenha sido avaliado, vale ressaltar que foi projetado com base no conhecimento teóricometodológico do desenvolvimento cognitivo, e é importante que no futuro, esse produto seja testado com um grupo de alunos do referido ciclo para avaliar a real contribuição da animação e interatividade no ensino da Geografia.

Physical control of carrier-mediated ion-transporters by entrainment of their turnover rate

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Chen, Wei; Mathis, Clausell; Fang, Zhihui; Mast, Jason; Hamidi, Karim; Kelly, Patrick; Eve, Max

2012-02-01

In the past, tremendous efforts have been made to physically activate carrier-mediated ion-transporters, such as Na/K pumps. However, the outcome is not significant. Recently, we developed a new technique which can effectively and efficiently control the pumping rate by introducing a concept of an electronic synchrotron accelerator to the biological system. The approach consists of two steps. First, a specially designed oscillating electric field is used to force or synchronize individual pump molecules to run at the same turnover rate and phase as the field oscillation frequency. Then, by gradually changing the field frequency and carefully keeping the pump synchronization we can entrain the pump molecules so that their pumping rate can be progressively modulated, either decelerated or accelerated, following the field frequency to a defined value. Based on theoretical analysis of the underlying mechanisms involved in the technique, computer simulation of the entrainment process, and intensive experimental studies we have realized significant activation of the Na/K pumping rate up to ten-folds quickly in less than ten seconds.

Analyse des cadres juridiques des aires marines protégées des pays ouest africains

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Marie Cuq

2013-06-01

Full Text Available En analysant de manière transversale les droits nationaux relatifs aux aires protégées de sept pays d'Afrique de l'Ouest (le Cap Vert, la Gambie, la Guinée, la Guinée-Bissau, la Mauritanie, le Sénégal et la Sierra Leone, cette étude tend à apporter des éléments de connaissances de ces droits nationaux, tant sur le plan normatif qu'institutionnel, et à s'interroger sur le contenu, la mise en oeuvre et l'adaptabilité de ceux-ci à la lumière des enjeux environnementaux, sociaux et économiques de la sous-région ouest-africaine.

Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters

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Walker, Aisha L.; Franke, Ryan M.; Sparreboom, Alex; Ware, Russell E.

2015-01-01

Objective Hydroxyurea has proven laboratory and clinical therapeutic benefits for sickle cell anemia (SCA) and other diseases, yet many questions remain regarding its in vivo pharmacokinetic and pharmacodynamic profiles. Previous reports suggest that hydroxyurea passively diffuses across cells, but its observed rapid absorption and distribution are more consistent with facilitated or active transport. We investigated the potential role of solute carrier (SLC) transporters in cellular uptake and accumulation of hydroxyurea. Materials and Methods Passive diffusion of hydroxyurea across cell membranes was determined using the parallel artificial membrane permeability assay. SLC transporter screens were conducted using in vitro intracellular drug accumulation and transcellular transport assays in cell lines and oocytes overexpressing SLC transporters. Gene expression of SLC transporters was measured by real-time PCR in human tissues and cell lines. Results Hydroxyurea had minimal diffusion across a lipid bilayer but was a substrate for 5 different SLC transporters belonging to the OCTN and OATP families of transporters and urea transporters A and B. Further characterization of hydroxyurea transport revealed that cellular uptake by OATP1B3 is time and temperature dependent and inhibited by known substrates of OATP1B3. Urea transporters A and B are expressed differentially in human tissues and erythroid cells, and transport hydroxyurea bidirectionally via facilitated diffusion. Conclusions These studies provide new insight into drug transport proteins that may be involved in the in vivo absorption, cellular distribution, and elimination of hydroxyurea. Elucidation of hydroxyurea transcellular movement should improve our understanding of its pharmacokinetics and pharmacodynamics, and may help explain some of the inter-patient drug variability observed in patients with SCA. PMID:21256917

Propranolol transport across the inner blood-retinal barrier: potential involvement of a novel organic cation transporter.

Science.gov (United States)

Kubo, Yoshiyuki; Shimizu, Yoshimi; Kusagawa, Yusuke; Akanuma, Shin-Ichi; Hosoya, Ken-Ichi

2013-09-01

The influx transport of propranolol across the inner blood-retinal barrier (BRB) was investigated. In the in vivo analysis of carotid artery single-injection method, [(3) H]propranolol uptake by the retina was greater than that of an internal reference compound, and was reduced by several organic cations. In the in vitro uptake study, TR-iBRB2 cells, an in vitro model of the inner BRB, showed a time-, concentration-, pH- and temperature-dependent [(3) H]propranolol uptake, suggesting the involvement of a carrier-mediated transport process in the influx of propranolol across the inner BRB. In the inhibition study, various organic cations, including drugs and candidates for the treatment of the retinal diseases, inhibited the [(3) H]propranolol uptake by TR-iBRB2 cells with no significant effects by the substrates and inhibitors of well-characterized organic cation transporters, suggesting that the influx transport of propranolol is performed by a novel transporter at the inner BRB. An analysis of the relationship between the inhibitory effect and the lipophilicity of inhibitors suggests a lipophilicity-dependent inhibitory effect of amines on the [(3) H]propranolol uptake by TR-iBRB2 cells. These results showed that influx transport of propranolol across the inner BRB is performed by a carrier-mediated transport process, suggesting the involvement of a novel organic cation transporter. Copyright © 2013 Wiley Periodicals, Inc.

Characterization of cesium uptake mediated by a potassium transport system of bacteria in a soil conditioner

International Nuclear Information System (INIS)

Zhang, Pengyao; Idota, Yoko; Yano, Kentaro; Negishi, Masayuki; Kawabata, Hideaki; Arakawa, Hiroshi; Ogihara, Takuo; Morimoto, Kaori; Tsuji, Akira

2014-01-01

We found that bacteria in a commercial soil conditioner sold in Ishinomaki, Miyagi, exhibited concentrative and saturable cesium ion (Cs + ) uptake in the natural range of pH and temperature. The concentration of intracellular Cs + could be condensed at least a few times higher compared with the outside medium of the cells. This uptake appeared to be mediated by a K + transport system, since Cs + uptake was dose-dependently inhibited by potassium ion (K + ). Eadie-Hofstee plot analysis indicated that the Cs + uptake involved a single saturable process. The maximum uptake amount (J max ) was the same in the presence and absence of K + , suggesting that Cs + and K + uptakes were competitive with respect to each other. These bacteria might be useful for bioremediation of cesium-contaminated soil. (author)

Structural Basis for a Ribofuranosyl Binding Protein: Insights into the Furanose Specific Transport

Energy Technology Data Exchange (ETDEWEB)

Bagaria, A.; Swaminathan, S.; Kumaran, D.; Burley, S. K.

2011-04-01

The ATP-binding cassette transporters (ABC-transporters) are members of one of the largest protein superfamilies, with representatives in all extant phyla. These integral membrane proteins utilize the energy of ATP hydrolysis to carry out certain biological processes, including translocation of various substrates across membranes and non-transport related processes such as translation of RNA and DNA repair. Typically, such transport systems in bacteria consist of an ATP binding component, a transmembrane permease, and a periplasmic receptor or binding protein. Soluble proteins found in the periplasm of gram-negative bacteria serve as the primary receptors for transport of many compounds, such as sugars, small peptides, and some ions. Ligand binding activates these periplasmic components, permitting recognition by the membrane spanning domain, which supports for transport and, in some cases, chemotaxis. Transport and chemotaxis processes appear to be independent of one another, and a few mutants of bifunctional periplasmic components reveal the absence of one or the other function. Previously published high-resolution X-ray structures of various periplasmic ligand binding proteins include Arabinose binding protein (ABP), Allose binding protein (ALBP), Glucose-galactose binding protein (GBP) and Ribose binding protein (RBP). Each of these proteins consists of two structurally similar domains connected by a three-stranded hinge region, with ligand buried between the domains. Upon ligand binding and release, various conformational changes have been observed. For RBP, open (apo) and closed (ligand bound) conformations have been reported and so for MBP. The closed/active form of the protein interacts with the integral membrane component of the system in both transport and chemotaxis. Herein, we report 1.9{angstrom} resolution X-ray structure of the R{sub f}BP periplasmic component of an ABC-type sugar transport system from Hahella chejuensis (UniProt Id Q2S7D2) bound to

Polymer-mediated tunneling transport between carbon nanotubes in nanocomposites.

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Derosa, Pedro A; Michalak, Tyler

2014-05-01

Electron transport in nanocomposites has attracted a good deal of attention for some time now; furthermore, the ability to control its characteristics is a necessary step in the design of multifunctional materials. When conductive nanostructures (for example carbon nanotubes) are inserted in a non-conductive matrix, electron transport below the percolation threshold is dominated by tunneling and thus the conductive characteristics of the composite depends heavily on the characteristics of the tunneling currents between nanoinserts. A parameter-free approach to study tunneling transport between carbon nanotubes across a polymer matrix is presented. The calculation is done with a combination of Density Functional Theory and Green functions (an approach heavily used in molecular electronics) which is shown here to be effective in this non-resonant transport condition. The results show that the method can effectively capture the effect of a dielectric layer in tunneling transport. The current is found to exponentially decrease with the size of the gap for both vacuum and polymer, and that the polymer layer lowers the tunneling barrier enhancing tunneling conduction. For a polyacrylonitrile matrix, a four-fold decrease in the tunneling constant, compared to tunneling in vacuum, is observed, a result that is consistent with available information. The method is very versatile as any DFT functional (or any other quantum mechanics method) can be used and thus the most accurate method for each particular system can be chosen. Furthermore as more methods become available, the calculations can be revised and improved. This approach can be used to design functional materials for fine-tunning the tunneling transport, for instance, the effect of modifying the nanoinsert-matrix interface (for example, by adding functional groups to carbon nanotubes) can be captured and the comparative performance of each interface predicted by simulation.

Proposta de um software-protótipo para uso na assistência a pacientes com cateter central de inserção periférica (PICC Proposal for a software-prototype to assist patients with peripherally inserted central catheter (PICC

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Luiz Célio Martins Freitas

2017-04-01

Full Text Available Objetivo: Propor um software-protótipo como estratégia para melhorar o processo de comunicação e os registros relativos ao cuidado de enfermagem a pacientes com cateter central de inserção periférica (PICC e descrever os passos para a construção de um protótipo de software. Método: Utilizou-se da Pesquisa de Intervenções, na modalidade de Processo de Intervenção e como método de operacionalização a Prototipação associados a instrumentos de informática. Resultado: Foi criado um modelo computadorizado de interface gráfica simples e projetado para uso em redes abertas ou fechadas. Conclusão: O desenvolvimento do software-protótipo para funcionar em rede web tornará o processo de implantação mais prático. Acrescenta-se que validação com equipe de saúde será realizada antes da utilização.

Podocyte expression of membrane transporters involved in puromycin aminonucleoside-mediated injury.

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Cristina Zennaro

Full Text Available Several complex mechanisms contribute to the maintenance of the intricate ramified morphology of glomerular podocytes and to interactions with neighboring cells and the underlying basement membrane. Recently, components of small molecule transporter families have been found in the podocyte membrane, but expression and function of membrane transporters in podocytes is largely unexplored. To investigate this complex field of investigation, we used two molecules which are known substrates of membrane transporters, namely Penicillin G and Puromycin Aminonucleoside (PA. We observed that Penicillin G pre-administration prevented both in vitro and in vivo podocyte damage caused by PA, suggesting the engagement of the same membrane transporters by the two molecules. Indeed, we found that podocytes express a series of transporters which are known to be used by Penicillin G, such as members of the Organic Anion Transporter Polypeptides (OATP/Oatp family of influx transporters, and P-glycoprotein, a member of the MultiDrug Resistance (MDR efflux transporter family. Expression of OATP/Oatp transporters was modified by PA treatment. Similarly, in vitro PA treatment increased mRNA and protein expression of P-glycoprotein, as well as its activity, confirming the engagement of the molecule upon PA administration. In summary, we have characterized some of the small molecule transporters present at the podocyte membrane, focusing on those used by PA to enter and exit the cell. Further investigation will be needed to understand precisely the role of these transporter families in maintaining podocyte homeostasis and in the pathogenesis of podocyte injury.

Strain-mediated magnetic and transport properties of epitaxial LuxFe3-xO4 films

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Wang, P.; Jin, C.; Zheng, D. X.; Bai, H. L.

2015-10-01

Strain mediated structure, magnetic, and transport properties of spinel ferrites were investigated by growing epitaxial LuxFe3-xO4 (LFO, 0 ≤ x ≤ 0.26 ) films on SrTiO3 and MgO substrates with in-plane compressive and tensile strains, respectively. The lattice parameter of LFO films decreases on SrTiO3 substrates, while increases on MgO substrates with the increasing Lu content. The LFO films on SrTiO3 substrates exhibit larger saturation magnetization and smaller exchange bias and coercive field. Phase shift of anisotropic magnetoresistance is also observed in the LFO films on SrTiO3 substrates. In addition, the nonmagnetic Lu3+ ions in spinel ferrites enhance the spin canting, which further increases the exchange bias and coercive field and strengthens the four-fold symmetry of anisotropic magnetoresistance and the two-fold symmetry of planar Hall effect.

Evaluation of transporters in drug development: Current status and contemporary issues.

Science.gov (United States)

Lee, Sue-Chih; Arya, Vikram; Yang, Xinning; Volpe, Donna A; Zhang, Lei

2017-07-01

Transporters govern the access of molecules to cells or their exit from cells, thereby controlling the overall distribution of drugs to their intracellular site of action. Clinically relevant drug-drug interactions mediated by transporters are of increasing interest in drug development. Drug transporters, acting alone or in concert with drug metabolizing enzymes, can play an important role in modulating drug absorption, distribution, metabolism and excretion, thus affecting the pharmacokinetics and/or pharmacodynamics of a drug. The drug interaction guidance documents from regulatory agencies include various decision criteria that may be used to predict the need for in vivo assessment of transporter-mediated drug-drug interactions. Regulatory science research continues to assess the prediction performances of various criteria as well as to examine the strength and limitations of each prediction criterion to foster discussions related to harmonized decision criteria that may be used to facilitate global drug development. This review discusses the role of transporters in drug development with a focus on methodologies in assessing transporter-mediated drug-drug interactions, challenges in both in vitro and in vivo assessments of transporters, and emerging transporter research areas including biomarkers, assessment of tissue concentrations, and effect of diseases on transporters. Published by Elsevier B.V.

Role of glutathione transport processes in kidney function

International Nuclear Information System (INIS)

Lash, Lawrence H.

2005-01-01

The kidneys are highly dependent on an adequate supply of glutathione (GSH) to maintain normal function. This is due, in part, to high rates of aerobic metabolism, particularly in the proximal tubules. Additionally, the kidneys are potentially exposed to high concentrations of oxidants and reactive electrophiles. Renal cellular concentrations of GSH are maintained by both intracellular synthesis and transport from outside the cell. Although function of specific carriers has not been definitively demonstrated, it is likely that multiple carriers are responsible for plasma membrane transport of GSH. Data suggest that the organic anion transporters OAT1 and OAT3 and the sodium-dicarboxylate 2 exchanger (SDCT2 or NaDC3) mediate uptake across the basolateral plasma membrane (BLM) and that the organic anion transporting polypeptide OATP1 and at least one of the multidrug resistance proteins mediate efflux across the brush-border plasma membrane (BBM). BLM transport may be used pharmacologically to provide renal proximal tubular cells with exogenous GSH to protect against oxidative stress whereas BBM transport functions physiologically in turnover of cellular GSH. The mitochondrial GSH pool is derived from cytoplasmic GSH by transport into the mitochondrial matrix and is mediated by the dicarboxylate and 2-oxoglutarate exchangers. Maintenance of the mitochondrial GSH pool is critical for cellular and mitochondrial redox homeostasis and is important in determining susceptibility to chemically induced apoptosis. Hence, membrane transport processes are critical to regulation of renal cellular and subcellular GSH pools and are determinants of susceptibility to cytotoxicity induced by oxidants and electrophiles

Protótipo de sistema de documentação em enfermagem no puerpério Documentation system prototype for postpartum nursing

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Regina Célia Sales Santos Veríssimo

2013-01-01

Full Text Available OBJETIVO: Desenvolver protótipo de sistema de documentação em enfermagem no puerpério. MÉTODOS: Planejamento de software utilizou modelo baseado em orientação a objetos, que englobou: compreensão e definição do contexto e dos modos de utilização projeto de arquitetura do sistema, identificação dos principais objetos do sistema, desenvolvimento dos modelos do projeto, especificação das interfaces dos objetos. Foram utilizadas as linguagem Structured Query Language (SQL, MySQL e Hypertext Preprocessor (php. RESULTADOS: O protótipo apresenta os requisitos planejados, entre eles: uso da Classificação Internacional para a Prática de Enfermagem (CIPE® versão 1.0 como código de apoio para execução do processo de enfermagem; apresentação dos eixos da CIPE® versão 1.0 em ordem de uso; geração de relatórios sobre a prática de uso dos processos de enfermagem. CONCLUSÃO: O protótipo de sistema de documentação proposto foi desenvolvido com sucesso com possibilidade de registros de enfermagem por meio de linguagem padronizada.OBJECTIVE: To develop a documentation system prototype for postpartum nursing. METHODS: For the software planning, a model based on object orientation was used, which included: understanding and definition of the context and usage modes of the system design project, identification of the main objects of the system, development of project models, specification of object interfaces. The languages Structured Query Language (SQL, MySQL and Hypertext Preprocessor (php were used. RESULTS: The prototype shows the planned requirements, among them: use of the International Classification For Nursing Practice (ICNP® version 1.0 as support code to perform the nursing process; presentation of the axes of ICNP® version 1.0 in order of use; elaboration of reports about the usage practice of nursing processes. CONCLUSION: The proposed documentation system prototype was successfully developed, allowing professional

Activation of CFTR by ASBT-mediated bile salt absorption

NARCIS (Netherlands)

Bijvelds, MJC; Jorna, H; Verkade, HJ; Bot, AGM; Hofmann, F; Agellon, LB; Sinaasappel, M; de Jonge, HR

2005-01-01

In cholangiocytes, bile salt (BS) uptake via the apical sodium-dependent bile acid transporter (ASBT) may evoke ductular flow by enhancing cAMP-mediated signaling to the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. We considered that ASBT-mediated BS uptake in the distal

Plasma Transport at the Magnetospheric Flank Boundary. Final report

International Nuclear Information System (INIS)

Otto, Antonius

2012-01-01

Progress is highlighted in these areas: 1. Model of magnetic reconnection induced by three-dimensional Kelvin Helmholtz (KH) modes at the magnetospheric flank boundary; 2. Quantitative evaluation of mass transport from the magnetosheath onto closed geomagnetic field for northward IMF; 3. Comparison of mass transfer by cusp reconnection and Flank Kelvin Helmholtz modes; 4. Entropy constraint and plasma transport in the magnetotail - a new mechanism for current sheet thinning; 5. Test particle model for mass transport onto closed geomagnetic field for northward IMF; 6. Influence of density asymmetry and magnetic shear on (a) the linear and nonlinear growth of 3D Kelvin Helmholtz (KH) modes, and (b) three-dimensional KH mediated mass transport; 7. Examination of entropy and plasma transport in the magnetotail; 8. Entropy change and plasma transport by KH mediated reconnection - mixing and heating of plasma; 9. Entropy and plasma transport in the magnetotail - tail reconnection; and, 10. Wave coupling at the magnetospheric boundary and generation of kinetic Alfven waves

Protótipo de um sistema de aquecimento de água para população de baixa renda usando energia solar e elétrica, com reaproveitamento de calor

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Marco Antônio Silva Pereira

2016-01-01

Full Text Available Este artigo consiste em uma pesquisa sobre os vários meios de aquecimento de água para o banho, buscando o uso de alternativas para viabilizar o acesso da população de baixa renda a esses benefícios. A ideia principal é fazer uma combinação dos vários sistemas existentes a fim de produzir um protótipo eficiente e de baixo custo. O protótipo constitui-se de um sistema de aquecimento solar, recuperador de calor e de um misturador de água automatizado. A representação do sistema foi obtida por meio de uma maquete do protótipo ecológico de chuveiro, englobando as diversas tecnologias estudadas.Palavras-chave: Aquecedor solar. Recuperador de calor. Misturador automatizado. Microcontrolador.Prototype of a water heating system for low-income population using solar energy and power, with reuse of heatAbstractThis paper consists of a survey on the various means of heating water for the bath, trying to use of alternatives to allow access of the low-income population. The main idea is to make a blend of various existing systems in order to produce an efficient and cost effective prototype. The prototype consists of a system of solar heating, heat recovery and an automated water mixer. The representation of the system was obtained through a model of the ecological prototype shower encompassing the several studied technologies.Keywords: Solar heating. Heat recovery. Automated mixer. Microcontroller.

Desnutrição protéico-energética no paciente gastrectomizado Protein-energy deficiency in the gastrectomized patient

Directory of Open Access Journals (Sweden)

Silvia Justina PAPINI-BERTO

2002-03-01

Full Text Available Racional - A gastrectomia traz conseqüências nutricionais inevitáveis mas atenuáveis, dependendo da dietoterapia pós-operatória. Embora observada, essa desnutrição protéico-energética é pouco dimensionada, provavelmente, pela falta de consenso metodológico. Objetivo - Avaliar o grau de desnutrição protéico-energética do paciente gastrectomizado, utilizando-se de indicadores isolados ou combinados. Pacientes e Métodos - Foram estudados 71 pacientes com gastrectomia parcial (n = 53 ou total (n =18 em pós-operatório de 6 a 24 meses e 24-60 meses. Os dados dietéticos, composição corporal e bioquímicos foram analisados de acordo com o tipo de gastrectomia e tempo pós-operatório. Resultados - A cirurgia foi conseqüência de complicações de úlcera péptica (68% ou a câncer gástrico (32%. A perda de peso foi referida por 70% dos pacientes, sendo maior no grupo gastrectomia total (16 ± 5 kg do que no grupo gastrectomia parcial (10 ± 6 kg. Em geral, os pacientes apresentaram déficit antropométrico, albuminemia normal e baixa ingestão calórica, sugerindo deficiência energética crônica. A redução de hemoglobina, hematócrito e ferro ocorreu em maior intensidade e mais precocemente no grupo gastrectomia total. Assim, quando se associou hemoglobina aos indicadores albumina, linfócitos circunferência do braço e prega cutânea subescapular, a prevalência de desnutrição protéico-energética foi maior e em maior intensidade do que na ausência da hemoglobina. Conclusão - A gastrectomia resultou em desnutrição protéico-energética do tipo marasmática, acompanhada de anemia, mais intensa e precoce na gastrectomia total e gradativa na gastrectomia parcial, assemelhando-se à gastrectomia total no pós-operatório tardio.Background - Gastrectomy leads to nutritional consequences that although expected, are not usually measured due to methodological limitations. Aim - To assess the protein-energy deficiency degrees

Localization of the placental BCRP/ABCG2 transporter to lipid rafts: Role for cholesterol in mediating efflux activity.

Science.gov (United States)

Szilagyi, John T; Vetrano, Anna M; Laskin, Jeffrey D; Aleksunes, Lauren M

2017-07-01

The breast cancer resistance protein (BCRP/ABCG2) is an efflux transporter in the placental barrier. By transporting chemicals from the fetal to the maternal circulation, BCRP limits fetal exposure to a range of drugs, toxicants, and endobiotics such as bile acids and hormones. The purpose of the present studies was to 1) determine whether BCRP localizes to highly-ordered, cholesterol-rich lipid raft microdomains in placenta microvillous membranes, and 2) determine the impact of cholesterol on BCRP-mediated placental transport in vitro. BCRP expression was analyzed in lipid rafts isolated from placentas from healthy, term pregnancies and BeWo trophoblasts by density gradient ultracentrifugation. BeWo cells were also tested for their ability to efflux BCRP substrates after treatment with the cholesterol sequestrant methyl-β-cyclodextrin (MβCD, 5 mM, 1 h) or the cholesterol synthesis inhibitor pravastatin (200 μM, 48 h). BCRP was found to co-localize with lipid raft proteins in detergent-resistant, lipid raft-containing fractions from placental microvillous membranes and BeWo cells. Treatment of BeWo cells with MβCD redistributed BCRP protein into higher density non-lipid raft fractions. Repletion of the cells with cholesterol restored BCRP localization to lipid raft-containing fractions. Treatment of BeWo cells with MβCD or pravastatin increased cellular retention of two BCRP substrates, the fluorescent dye Hoechst 33342 and the mycotoxin zearalenone. Repletion with cholesterol restored BCRP transporter activity. Taken together, these data demonstrate that cholesterol may play a critical role in the post-translational regulation of BCRP in placental lipid rafts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Retirada do tegumento e da extração dos pigmentos na qualidade protéica do feijão-preto Effect of removal of tegument and extraction of pigments on protein quality of black beans

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Ana Cristina Nascimento Chiaradia

1999-08-01

Full Text Available O feijão é cultivado e consumido mundialmente e é a leguminosa mais consumida na América Latina. O baixo valor biológico das proteínas do feijão pode ser resultante, dentre outros, da presença de fatores antinutricionais presentes no tegumento do grão. Este trabalho visou avaliar, através de ensaios biológicos, o efeito da retirada do tegumento e das antocianinas e outros polifenóis do feijão-preto, na qualidade de suas proteínas. Foram analisados o quociente de eficiência protéica, o quociente de eficiência líquida protéica e a utilização líquida da proteína, e digestibilidade. Os resultados obtidos mostraram que a eliminação parcial do tegumento dos grãos cozidos e secagem em estufa diminuíram significativamente o valor do quociente de eficiência protéica comparativamente ao do grão integral cozido e secado nas mesmas condições. A extração, com etanol acidificado, de 27,5% dos polifenóis não influiu significativamente no valor protéico do feijão-preto. Concluiu-se que a retirada do tegumento e a extração parcial de polifenóis do feijão não elevaram a sua qualidade protéica.Bean seeds (Phaseolus vulgaris, L. are cultivated and consumed all over the world and are a staple food in most countries of South America. The low biological value of bean proteins may be due to, among others, the effect of antinutritional factors on the tegument. The objective of this work was to evaluate, through biological assays, the effect of removal of black bean tegument, anthocyanins and other polyphenols on protein quality. The protein efficiency ratio, the protein liquid efficiency ratio, the protein liquid utilization and the digestibility were analyzed. The results indicated that removal of the tegument of cooked beans reduced their protein value (PER when compared to whole cooked beans. The ethanolic extraction of 27.5% of polyphenols did not increase the protein quality of beans. It was concluded that removal of the

ZmPUMP encodes a fully functional monocot plant uncoupling mitochondrial protein whose affinity to fatty acid is increased with the introduction of a His pair at the second matrix loop

International Nuclear Information System (INIS)

Favaro, Regiane Degan; Borecky, Jiri; Colombi, Debora; Maia, Ivan G.

2006-01-01

Uncoupling proteins (UCPs) are specialized mitochondrial transporter proteins that uncouple respiration from ATP synthesis. In this study, cDNA encoding maize uncoupling protein (ZmPUMP) was expressed in Escherichia coli and recombinant ZmPUMP reconstituted in liposomes. ZmPUMP activity was associated with a linoleic acid (LA)-mediated H + efflux with K m of 56.36 ± 0.27 μM and V max of 66.9 μmol H + min -1 (mg prot) -1 . LA-mediated H + fluxes were sensitive to ATP inhibition with K i of 2.61 ± 0.36 mM (at pH 7.2), a value similar to those for dicot UCPs. ZmPUMP was also used to investigate the importance of a histidine pair present in the second matrix loop of mammalian UCP1 and absent in plant UCPs. ZmPUMP with introduced His pair (Lys155His and Ala157His) displayed a 1.55-fold increase in LA-affinity while its activity remained unchanged. Our data indicate conserved properties of plant UCPs and suggest an enhancing but not essential role of the histidine pair in proton transport mechanism

Transport of amino acids and GABA analogues via the human proton-coupled amino acid transporter, hPAT1

DEFF Research Database (Denmark)

Larsen, Mie; Larsen, Birger Brodin; Frølund, Bente

2008-01-01

The objective of this study was to investigate transepithelial amino acid transport as a function of Caco-2 cell culture time. Furthermore, the objective was to investigate apical uptake characteristics of hPAT1-mediated transport under various experimental conditions. Apical amino acid uptake......, which has been shown to function as a carboxylic acid bioisostere for substrates of the GABA receptor and transport systems....

ATP-induced conformational changes of nucleotide-binding domains in an ABC transporter. Importance of the water-mediated entropic force.

Science.gov (United States)

Hayashi, Tomohiko; Chiba, Shuntaro; Kaneta, Yusuke; Furuta, Tadaomi; Sakurai, Minoru

2014-11-06

ATP binding cassette (ABC) proteins belong to a superfamily of active transporters. Recent experimental and computational studies have shown that binding of ATP to the nucleotide binding domains (NBDs) of ABC proteins drives the dimerization of NBDs, which, in turn, causes large conformational changes within the transmembrane domains (TMDs). To elucidate the active substrate transport mechanism of ABC proteins, it is first necessary to understand how the NBD dimerization is driven by ATP binding. In this study, we selected MalKs (NBDs of a maltose transporter) as a representative NBD and calculated the free-energy change upon dimerization using molecular mechanics calculations combined with a statistical thermodynamic theory of liquids, as well as a method to calculate the translational, rotational, and vibrational entropy change. This combined method is applied to a large number of snapshot structures obtained from molecular dynamics simulations containing explicit water molecules. The results suggest that the NBD dimerization proceeds with a large gain of water entropy when ATP molecules bind to the NBDs. The energetic gain arising from direct NBD-NBD interactions is canceled by the dehydration penalty and the configurational-entropy loss. ATP hydrolysis induces a loss of the shape complementarity between the NBDs, which leads to the dissociation of the dimer, due to a decrease in the water-entropy gain and an increase in the configurational-entropy loss. This interpretation of the NBD dimerization mechanism in concert with ATP, especially focused on the water-mediated entropy force, is potentially applicable to a wide variety of the ABC transporters.

Ligand-Receptor Interaction-Mediated Transmembrane Transport of Dendrimer-like Soft Nanoparticles: Mechanisms and Complicated Diffusive Dynamics.

Science.gov (United States)

Liang, Junshi; Chen, Pengyu; Dong, Bojun; Huang, Zihan; Zhao, Kongyin; Yan, Li-Tang

2016-05-09

Nearly all nanomedical applications of dendrimer-like soft nanoparticles rely on the functionality of attached ligands. Understanding how the ligands interact with the receptors in cell membrane and its further effect on the cellular uptake of dendrimer-like soft nanoparticles is thereby a key issue for their better application in nanomedicine. However, the essential mechanism and detailed kinetics for the ligand-receptor interaction-mediated transmembrane transport of such unconventional nanoparticles remain poorly elucidated. Here, using coarse-grained simulations, we present the very first study of molecular mechanism and kinetics behaviors for the transmembrane transport of dendrimer-like soft nanoparticles conjugated with ligands. A phase diagram of interaction states is constructed through examining ligand densities and membrane tensions that allows us to identify novel endocytosis mechanisms featured by the direct wrapping and the penetration-extraction vesiculation. The results provide an in-depth insight into the diffusivity of receptors and dendrimer in the membrane plane and demonstrate how the ligand density influences receptor diffusion and uptake kinetics. It is interesting to find that the ligand-conjugated dendrimers present superdiffusive behaviors on a membrane, which is revealed to be driven by the random fluctuation dynamics of the membrane. The findings facilitate our understanding of some recent experimental observations and could establish fundamental principles for the future development of such important nanomaterials for widespread nanomedical applications.

The molecular mechanism for overcoming the rate-limiting step in monoamine neurotransmitter transport

DEFF Research Database (Denmark)

Sinning, Steffen; Said, Saida; Malinauskaite, Lina

The monoamine transporter family consists of dopamine (DAT), norepinephrine (NET) and serotonin transporters (SERT) that mediate the reuptake of the monoamine neurotransmitters after their release during neurotransmission. These transporters play prominent roles in psychiatric disorders and are t......The monoamine transporter family consists of dopamine (DAT), norepinephrine (NET) and serotonin transporters (SERT) that mediate the reuptake of the monoamine neurotransmitters after their release during neurotransmission. These transporters play prominent roles in psychiatric disorders...... membrane. The rate-limiting step in monoamine reuptake is the return of the empty transporter from an inward-facing to an outward-facing conformation without neurotransmitter and sodium bound. The molecular mechanism underlying this important conformational transition has not been described. Crystal...

Inter-cellular transport of ran GTPase.

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Deepak Khuperkar

Full Text Available Ran, a member of the Ras-GTPase superfamily, has a well-established role in regulating the transport of macromolecules across the nuclear envelope (NE. Ran has also been implicated in mitosis, cell cycle progression, and NE formation. Over-expression of Ran is associated with various cancers, although the molecular mechanism underlying this phenomenon is unclear. Serendipitously, we found that Ran possesses the ability to move from cell-to-cell when transiently expressed in mammalian cells. Moreover, we show that the inter-cellular transport of Ran is GTP-dependent. Importantly, Ran displays a similar distribution pattern in the recipient cells as that in the donor cell and co-localizes with the Ran binding protein Nup358 (also called RanBP2. Interestingly, leptomycin B, an inhibitor of CRM1-mediated export, or siRNA mediated depletion of CRM1, significantly impaired the inter-cellular transport of Ran, suggesting a function for CRM1 in this process. These novel findings indicate a possible role for Ran beyond nucleo-cytoplasmic transport, with potential implications in inter-cellular communication and cancers.

Seeking effective dyes for a mediated glucose-air alkaline battery/fuel cell

Science.gov (United States)

Eustis, Ross; Tsang, Tsz Ming; Yang, Brigham; Scott, Daniel; Liaw, Bor Yann

2014-02-01

A significant level of power generation from an abiotic, air breathing, mediated reducing sugar-air alkaline battery/fuel cell has been achieved in our laboratories at room temperature without complicated catalysis or membrane separation in the reaction chamber. Our prior studies suggested that mass transport limitation by the mediator is a limiting factor in power generation. New and effective mediators were sought here to improve charge transfer and power density. Forty-five redox dyes were studied to identify if any can facilitate mass transport in alkaline electrolyte solution; namely, by increasing the solubility and mobility of the dye, and the valence charge carried per molecule. Indigo dyes were studied more closely to understand the complexity involved in mass transport. The viability of water-miscible co-solvents was also explored to understand their effect on solubility and mass transport of the dyes. Using a 2.0 mL solution, 20% methanol by volume, with 100 mM indigo carmine, 1.0 M glucose and 2.5 M sodium hydroxide, the glucose-air alkaline battery/fuel cell attained 8 mA cm-2 at short-circuit and 800 μW cm-2 at the maximum power point. This work shall aid future optimization of mediated charge transfer mechanism in batteries or fuel cells.

Current rectification by mediating electroactive polymers

Energy Technology Data Exchange (ETDEWEB)

Ybarra, Gabriel; Moina, Carlos [Centro de Investigacion sobre Electrodeposicion y Procesos Superficiales, Instituto Nacional de Tecnologia Industrial, CC 157, (1650) San Martin (Argentina); Florit, M. Ines [INIFTA, Facultad de Ciencias Exactas, UNLP, Suc. 4, CC 16, (1900) La Plata (Argentina); Posadas, Dionisio [INIFTA, Facultad de Ciencias Exactas, UNLP, Suc. 4, CC 16, (1900) La Plata (Argentina)], E-mail: dposadas@inifta.unlp.edu.ar

2008-04-20

In this work we briefly review the theoretical basis for the electrochemical rectification in mediated redox reactions at redox polymer modified electrodes. Electrochemical rectification may have two distinct origins. It is either caused by a slow kinetics of the reaction between the external redox couple and the mediator or it is originated by a slow electronic transport within the film under an unfavorable thermodynamic condition. We show experimental results for the redox mediation reaction of poly(o-aminophenol) (POAP) on the Fe{sup 2+/3+} and on the Fe(CN){sub 6}{sup 3-/4-} redox couples in solution that prove the proposed mechanisms of electrochemical rectification.

Current rectification by mediating electroactive polymers

International Nuclear Information System (INIS)

Ybarra, Gabriel; Moina, Carlos; Florit, M. Ines; Posadas, Dionisio

2008-01-01

In this work we briefly review the theoretical basis for the electrochemical rectification in mediated redox reactions at redox polymer modified electrodes. Electrochemical rectification may have two distinct origins. It is either caused by a slow kinetics of the reaction between the external redox couple and the mediator or it is originated by a slow electronic transport within the film under an unfavorable thermodynamic condition. We show experimental results for the redox mediation reaction of poly(o-aminophenol) (POAP) on the Fe 2+/3+ and on the Fe(CN) 6 3-/4- redox couples in solution that prove the proposed mechanisms of electrochemical rectification

Di/tri-peptide transporters as drug delivery targets

DEFF Research Database (Denmark)

Nielsen, C U; Brodin, Birger

2003-01-01

-dependent, and the transporters thus belong to the Proton-dependent Oligopeptide Transporter (POT)-family. The transporters are not drug targets per se, however due to their uniquely broad substrate specificity; they have proved to be relevant drug targets at the level of drug transport. Drug molecules such as oral active beta....../tri-peptide transporters from vesicular storages 3) changes in gene transcription/mRNA stability. The aim of the present review is to discuss physiological, patho-physiological and drug-induced regulation of di/tri-peptide transporter mediated transport....

The TULIP superfamily of eukaryotic lipid-binding proteins as a mediator of lipid sensing and transport.

Science.gov (United States)

Alva, Vikram; Lupas, Andrei N

2016-08-01

The tubular lipid-binding (TULIP) superfamily has emerged in recent years as a major mediator of lipid sensing and transport in eukaryotes. It currently encompasses three protein families, SMP-like, BPI-like, and Takeout-like, which share a common fold. This fold consists of a long helix wrapped in a highly curved anti-parallel β-sheet, enclosing a central, lipophilic cavity. The SMP-like proteins, which include subunits of the ERMES complex and the extended synaptotagmins (E-Syts), appear to be mainly located at membrane contacts sites (MCSs) between organelles, mediating inter-organelle lipid exchange. The BPI-like proteins, which include the bactericidal/permeability-increasing protein (BPI), the LPS (lipopolysaccharide)-binding protein (LBP), the cholesteryl ester transfer protein (CETP), and the phospholipid transfer protein (PLTP), are either involved in innate immunity against bacteria through their ability to sense lipopolysaccharides, as is the case for BPI and LBP, or in lipid exchange between lipoprotein particles, as is the case for CETP and PLTP. The Takeout-like proteins, which are comprised of insect juvenile hormone-binding proteins and arthropod allergens, transport, where known, lipid hormones to target tissues during insect development. In all cases, the activity of these proteins is underpinned by their ability to bind large, hydrophobic ligands in their central cavity and segregate them away from the aqueous environment. Furthermore, where they are involved in lipid exchange, recent structural studies have highlighted their ability to establish lipophilic, tubular channels, either between organelles in the case of SMP domains or between lipoprotein particles in the case of CETP. Here, we review the current knowledge on the structure, versatile functions, and evolution of the TULIP superfamily. We propose a deep evolutionary split in this superfamily, predating the Last Eukaryotic Common Ancestor, between the SMP-like proteins, which act on

Psychostimulants affect dopamine transmission through both dopamine transporter-dependent and independent mechanisms

Science.gov (United States)

dela Peña, Ike; Gevorkiana, Ruzanna; Shi, Wei-Xing

2015-01-01

The precise mechanisms by which cocaine and amphetamine-like psychostimulants exert their reinforcing effects are not yet fully defined. It is widely believed, however, that these drugs produce their effects by enhancing dopamine neurotransmission in the brain, especially in limbic areas such as the nucleus accumbens, by inducing dopamine transporter-mediated reverse transport and/or blocking dopamine reuptake though the dopamine transporter. Here, we present the evidence that aside from dopamine transporter, non-dopamine transporter-mediated mechanisms also participate in psychostimulant-induced dopamine release and contribute to the behavioral effects of these drugs, such as locomotor activation and reward. Accordingly, psychostimulants could increase norepinephrine release in the prefrontal cortex, the latter then alters the firing pattern of dopamine neurons resulting in changes in action potential-dependent dopamine release. These alterations would further affect the temporal pattern of dopamine release in the nucleus accumbens, thereby modifying information processing in that area. Hence, a synaptic input to a nucleus accumbens neuron may be enhanced or inhibited by dopamine depending on its temporal relationship to dopamine release. Specific temporal patterns of dopamine release may also be required for certain forms of synaptic plasticity in the nucleus accumbens. Together, these effects induced by psychostimulants, mediated through a non-dopamine transporter-mediated mechanism involving norepinephrine and the prefrontal cortex, may also contribute importantly to the reinforcing properties of these drugs. PMID:26209364

Energetics of Transport through the Nuclear Pore Complex

NARCIS (Netherlands)

Ghavami, Ali; van der Giessen, Erik; Onck, Patrick R

2016-01-01

Molecular transport across the nuclear envelope in eukaryotic cells is solely controlled by the nuclear pore complex (NPC). The NPC provides two types of nucleocytoplasmic transport: passive diffusion of small molecules and active chaperon-mediated translocation of large molecules. It has been shown

Composição centesimal e valor protéico de levedura residual da fermentação etanólica e de seus derivados Centesimal composition and protein nutritive value of yeast from ethanol fermentation and of yeast derivatives

Directory of Open Access Journals (Sweden)

Eunice Akemi Yamada

2003-12-01

Full Text Available Este trabalho teve por objetivo promover a autólise e o fracionamento da levedura (Saccharomyces sp. para produção de autolisado e extrato, bem como para produção de concentrado protéico fosforilado, a partir da levedura residual das destilarias de álcool etílico. Foram estudados a composição centesimal, o perfil de aminoácidos essenciais e o valor protéico dos três derivados comparativamente à levedura íntegra não processada. Proteína e carboidrato (fibra alimentar foram os principais componentes da levedura íntegra e do autolisado. No extrato e no concentrado protéico predominaram proteína e minerais (cinzas. O autolisado e a levedura íntegra apresentaram os melhores índices de aminoácidos essenciais, seguidos pelo concentrado protéico e pelo extrato. A digestibilidade da proteína variou de 68% para a levedura íntegra a 91% para o extrato. Os índices de quociente de utilização líquida da proteína variaram de 2,1 para a levedura íntegra a 4,3 para a caseína (referência. Não houve diferença estatística no quociente de utilização líquida da proteína entre o autolisado (4,1, o extrato (3,9 e o concentrado protéico (4,2. O concentrado protéico promoveu o maior crescimento no período (21 dias, seguido do extrato e o autolisado. As células íntegras apresentaram a menor capacidade para promover crescimento em rato.The objective of this work was to promote the autolysis and the fractionation of the yeast (Saccharomyces sp. for the production of autolysate and extract, as well as phosphorylated protein concentrate, from ethanol distillery yeast. Comparative studies of centesimal composition, essential amino acid profiles and protein nutritive value were performed for the unprocessed integral cells, and for autolysate, extract and phosphorylated protein concentrate. Protein and carbohydrate (dietary fiber were the main components for the integral cells and autolysate. For the extract and the protein

78 FR 29071 - Assessment of Mediation and Arbitration Procedures

Science.gov (United States)

2013-05-17

... Processors Association (NOPA), RSTAC, Transportation Arbitration and Mediation, P.L.L.C. (TAM), the Western.... FOR FURTHER INFORMATION CONTACT: Amy C. Ziehm at 202-245-0391. [Assistance for the hearing impaired is... Transportation are ex officio, nonvoting RSTAC members. (49 U.S.C. 726.) \\5\\ The Board received comments from the...

High resolution respirometry analysis of polyethylenimine-mediated mitochondrial energy crisis and cellular stress

DEFF Research Database (Denmark)

Hall, Arnaldur; Larsen, Anna Karina; Parhamifar, Ladan

2013-01-01

and spectrophotometry analysis of cytochrome c oxidase activity we were able to identify complex IV (cytochrome c oxidase) as a likely specific site of PEI mediated inhibition within the electron transport system. Unraveling the mechanisms of PEI-mediated mitochondrial energy crisis is central for combinatorial design...... of PEI-mediated plasma membrane damage and subsequent ATP leakage to the extracellular medium. Studies with freshly isolated mouse liver mitochondria corroborated with bioenergetic findings and demonstrated parallel polycation concentration- and time-dependent changes in state 2 and state 4o oxygen flux...... as well as lowered ADP phosphorylation (state 3) and mitochondrial ATP synthesis. Polycation-mediated reduction of electron transport system activity was further demonstrated in 'broken mitochondria' (freeze-thawed mitochondrial preparations). Moreover, by using both high-resolution respirometry...

Tratamento clínico de endocardite em prótese valvar complicada por abscesso para-protético Successful medical management of prosthetic-valve endocarditis complicated by perivalvular abscess

Directory of Open Access Journals (Sweden)

Maria do Carmo Pereira Nunes

2009-09-01

Full Text Available O presente artigo relata o caso de um paciente do sexo masculino, 44 anos, com endocardite em prótese aórtica complicada por abscesso para-protético. Evoluiu com melhora do processo infeccioso apenas com o tratamento clínico. História prévia de doença reumática, submetido a três cirurgias cardíacas para troca valvar por disfunção de prótese e endocardite prévia. Neste relato de caso, discutiremos as características principais do abscesso para-protético como complicação de endocarditeWe present a case of a 44-year-old man with prosthetic aortic endocarditis complicated by a perivalvular abscess. He evolved with improvement of the infectious process only under clinical treatment. The patient presented a prior history of rheumatic fever and had previously been undergone three valve replacements due to prosthesis dysfunction and previous endocarditis. In this case report we discuss the main features of perivalvular abscess complicating infective endocarditis

An in vitro and in silico study on the flavonoid-mediated modulation of the transport of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through Caco-2 monolayers

International Nuclear Information System (INIS)

Schutte, Maaike E.; Freidig, Andreas P.; Sandt, Johannes J.M. van de; Alink, Gerrit M.; Rietjens, Ivonne M.C.M.; Groten, John P.

2006-01-01

The present study describes the effect of different flavonoids on the absorption of the pro-carcinogen PhIP through Caco-2 monolayers and the development of an in silico model describing this process taking into account passive diffusion and active transport of PhIP. Various flavonoids stimulated the apical to basolateral PhIP transport. Using the in silico model for flavone, kaempferol and chrysoeriol, the apparent Ki value for inhibition of the active transport to the apical side was estimated to be below 53 μM and for morin, robinetin and taxifolin between 164 and 268 μM. For myricetin, luteolin, naringenin and quercetin, the apparent Ki values were determined more accurately and amounted to 37.3, 12.2, 11.7 and 5.6 μM respectively. Additional experiments revealed that the apical to basolateral PhIP transport was also increased in the presence of a typical BCRP or MRP inhibitor with apparent Ki values in the same range as those of the flavonoids. This observation together with the fact that flavonoids are known to be inhibitors of MRPs and BCRP, corroborates that inhibition of these apical membrane transporters is involved in the flavonoid-mediated increased apical to basolateral PhIP transport. Based on the apparent Ki values obtained, it is concluded that the flavonols, at the levels present in the regular Western diet, are capable of stimulating the transport of PhIP through Caco-2 monolayers from the apical to the basolateral compartment. This points to flavonoid-mediated stimulation of the bioavailability of PhIP and, thus, a possible adverse effect of these supposed beneficial food ingredients

Functional characterisation of an intron retaining K+ transporter of barley reveals intron-mediated alternate splicing

KAUST Repository

Shahzad, K.

2015-01-01

Intron retention in transcripts and the presence of 5 and 3 splice sites within these introns mediate alternate splicing, which is widely observed in animals and plants. Here, functional characterisation of the K+ transporter, HvHKT2;1, with stably retained introns from barley (Hordeum vulgare) in yeast (Saccharomyces cerevisiae), and transcript profiling in yeast and transgenic tobacco (Nicotiana tabacum) is presented. Expression of intron-retaining HvHKT2;1 cDNA (HvHKT2;1-i) in trk1, trk2 yeast strain defective in K+ uptake restored growth in medium containing hygromycin in the presence of different concentrations of K+ and mediated hypersensitivity to Na+. HvHKT2;1-i produces multiple transcripts via alternate splicing of two regular introns and three exons in different compositions. HKT isoforms with retained introns and exon skipping variants were detected in relative expression analysis of (i) HvHKT2;1-i in barley under native conditions, (ii) in transgenic tobacco plants constitutively expressing HvHKT2;1-i, and (iii) in trk1, trk2 yeast expressing HvHKT2;1-i under control of an inducible promoter. Mixed proportions of three HKT transcripts: HvHKT2;1-e (first exon region), HvHKT2;1-i1 (first intron) and HvHKT2;1-i2 (second intron) were observed. The variation in transcript accumulation in response to changing K+ and Na+ concentrations was observed in both heterologous and plant systems. These findings suggest a link between intron-retaining transcripts and different splice variants to ion homeostasis, and their possible role in salt stress.

Validation of a new fiber electrode prototype for clinical electroretinography Validação de protótipo de um novo eletrodo de fibra para eletrorretinografia clínica

Directory of Open Access Journals (Sweden)

Adriana Berezovsky

2008-06-01

prototype provided stable and safe recordings of corneal electroretinograms compared to the commercially availabe DTL® electrode in healthy human subjects. The prototype is a feasible alternative instrument for clinical electroretinography recording to assess retinal function, however further analysis is recommended to validate its clinical usefulness in patients with retinal disorders.OBJETIVO: Validar um novo protótipo de um eletrodo de fibra para eletrorretinografia clínica (ERG. MÉTODOS: Foi testado em um grupo de 20 voluntários saudáveis (17-31 anos; média 22,7 ± 4,5; 8 homens, um protótipo de eletrodo de fibra com referência acoplado descartável recentemente desenvolvido (depósito de patente no Instituto Nacional de Propriedade Intelectual # PI0602186-7, constando de uma fibra de sinais corneanos e uma segunda fibra servindo como referência. Após 30 minutos de adaptação ao escuro, as respostas de cones e bastonetes da eletrorretinografia foram registradas simultaneamente com dilatação completa das pupilas em ambos os olhos, com o protótipo de eletrodo de fibra com referência acoplado em um olho escolhido ao acaso e um eletrodo DTL® no outro olho. Após a apresentação dos estímulos escotópicos e fotópicos cada resposta foi analisada em amplitude e tempo de culminação das ondas a e b. O sistema VERIS 5.1.9 foi usado para a aquisição e análise dos dados. Os resultados da eletrorretinografia foram analisados pelo teste de Mann-Whitney. Após a sessão da eletrorretinografia foi feito exame em lâmpada de fenda para avaliar possíveis eventos adversos. RESULTADOS: As respostas obtidas com o protótipo de eletrodo de fibra com referência acoplado foram comparáveis às do eletrodo DTL® comercialmente disponível. Numa análise qualitativa, o eletrodo de fibra com referência acoplado produziu sinais com menos ruído. Na média, a amplitude escotópica da eletrorretinografia e o tempo de culminação da onda-b usando o eletrodo DTL® foram

Detergent-Mediated Reconstitution of Membrane Proteins

NARCIS (Netherlands)

Knol, J; Sjollema, K.A; Poolman, B.

1998-01-01

The efficiency of reconstitution of the lactose transport protein (LacS) of Streptococcus thermophilus is markedly higher with Triton X-100 than with other detergents commonly employed to mediate the membrane insertion. To rationalize these differences, the lipid/detergent structures that are formed

Mercury toxicokinetics of the healthy human term placenta involve amino acid transporters and ABC transporters

International Nuclear Information System (INIS)

Straka, Elisabeth; Ellinger, Isabella; Balthasar, Christina; Scheinast, Matthias; Schatz, Jasmin; Szattler, Tamara; Bleichert, Sonja; Saleh, Leila; Knöfler, Martin; Zeisler, Harald; Hengstschläger, Markus; Rosner, Margit; Salzer, Hans; Gundacker, Claudia

2016-01-01

Highlights: • It is known that MeHg is able to pass the placenta and to affect fetal brain development. • Uptake and efflux transporters were examined in human primary trophoblast cells and BeWo cells. • Involvement in mercury transfer was assessed by measurement of cellular mercury content upon siRNA mediated gene knockdown. • Localization of transporters was determined by immunofluorescence microscopy. • LAT1 and rBAT at the apical membrane of the syncytiotrophoblast (STB) are involved in MeHg uptake. • MRP1 located at basal membrane of STB mediates mercury efflux. - Abstract: Background: The capacity of the human placenta to handle exogenous stressors is poorly understood. The heavy metal mercury is well-known to pass the placenta and to affect brain development. An active transport across the placenta has been assumed. The underlying mechanisms however are virtually unknown. Objectives: Uptake and efflux transporters (17 candidate proteins) assumed to play a key role in placental mercury transfer were examined for expression, localization and function in human primary trophoblast cells and the trophoblast-derived choriocarcinoma cell line BeWo. Methods: To prove involvement of the transporters, we used small interfering RNA (siRNA) and exposed cells to methylmercury (MeHg). Total mercury contents of cells were analyzed by Cold vapor-atomic fluorescence spectrometry (CV-AFS). Localization of the proteins in human term placenta sections was determined via immunofluorescence microscopy. Results: We found the amino acid transporter subunits L-type amino acid transporter (LAT)1 and rBAT (related to b 0,+ type amino acid transporter) as well as the efflux transporter multidrug resistance associated protein (MRP)1 to be involved in mercury kinetics of trophoblast cells (t-test P < 0.05). Conclusion: The amino acid transporters located at the apical side of the syncytiotrophoblast (STB) manage uptake of MeHg. Mercury conjugated to glutathione (GSH) is

The high risk HPV16 L2 minor capsid protein has multiple transport signals that mediate its nucleocytoplasmic traffic

International Nuclear Information System (INIS)

Mamoor, Shahan; Onder, Zeynep; Karanam, Balasubramanyam; Kwak, Kihyuck; Bordeaux, Jennifer; Crosby, Lauren; Roden, Richard B.S.; Moroianu, Junona

2012-01-01

In this study we examined the transport signals contributing to HPV16 L2 nucleocytoplasmic traffic using confocal microscopy analysis of enhanced green fluorescent protein—L2 (EGFP-L2) fusions expressed in HeLa cells. We confirmed that both nuclear localization signals (NLSs), the nNLS (1MRHKRSAKRTKR12) and cNLS (456RKRRKR461), previously characterized in vitro (Darshan et al., 2004), function independently in vivo. We discovered that a middle region rich in arginine residues (296SRRTGIRYSRIGNKQTLRTRS316) functions as a nuclear retention sequence (NRS), as mutagenesis of critical arginine residues within this NRS reduced the fraction of L2 in the nucleus despite the presence of both NLSs. Significantly, the infectivity of HPV16 pseudoviruses containing either RR297AA or RR297EE within the L2 NRS was strongly reduced both in HaCaT cells and in a murine challenge model. Experiments using Ratjadone A nuclear export inhibitor and mutation-localization analysis lead to the discovery of a leucine-rich nuclear export signal ( 462 LPYFFSDVSL) mediating 16L2 nuclear export. These data indicate that HPV16 L2 nucleocytoplasmic traffic is dependent on multiple functional transport signals.

The high risk HPV16 L2 minor capsid protein has multiple transport signals that mediate its nucleocytoplasmic traffic

Energy Technology Data Exchange (ETDEWEB)

Mamoor, Shahan; Onder, Zeynep [Biology Department, Boston College, Chestnut Hill, MA 02467 (United States); Karanam, Balasubramanyam; Kwak, Kihyuck [Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231 (United States); Bordeaux, Jennifer; Crosby, Lauren [Biology Department, Boston College, Chestnut Hill, MA 02467 (United States); Roden, Richard B.S. [Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231 (United States); Moroianu, Junona, E-mail: moroianu@bc.edu [Biology Department, Boston College, Chestnut Hill, MA 02467 (United States)

2012-01-20

In this study we examined the transport signals contributing to HPV16 L2 nucleocytoplasmic traffic using confocal microscopy analysis of enhanced green fluorescent protein-L2 (EGFP-L2) fusions expressed in HeLa cells. We confirmed that both nuclear localization signals (NLSs), the nNLS (1MRHKRSAKRTKR12) and cNLS (456RKRRKR461), previously characterized in vitro (Darshan et al., 2004), function independently in vivo. We discovered that a middle region rich in arginine residues (296SRRTGIRYSRIGNKQTLRTRS316) functions as a nuclear retention sequence (NRS), as mutagenesis of critical arginine residues within this NRS reduced the fraction of L2 in the nucleus despite the presence of both NLSs. Significantly, the infectivity of HPV16 pseudoviruses containing either RR297AA or RR297EE within the L2 NRS was strongly reduced both in HaCaT cells and in a murine challenge model. Experiments using Ratjadone A nuclear export inhibitor and mutation-localization analysis lead to the discovery of a leucine-rich nuclear export signal ({sub 462}LPYFFSDVSL) mediating 16L2 nuclear export. These data indicate that HPV16 L2 nucleocytoplasmic traffic is dependent on multiple functional transport signals.

Inhibition of the MRP1-mediated transport of the menadione-glutathione conjugate (thiodione) in HeLa cells as studied by SECM.

Science.gov (United States)

Koley, Dipankar; Bard, Allen J

2012-07-17

Oxidative stress induced in live HeLa cells by menadione (2-methyl-1,4-napthaquinone) was studied in real time by scanning electrochemical microscopy (SECM). The hydrophobic molecule menadione diffuses through a living cell membrane where it is toxic to the cell. However, in the cell it is conjugated with glutathione to form thiodione. Thiodione is then recognized and transported across the cell membrane via the ATP-driven MRP1 pump. In the extracellular environment, thiodione was detected by the SECM tip at levels of 140, 70, and 35 µM upon exposure of the cells to menadione concentrations of 500, 250, and 125 µM, respectively. With the aid of finite element modeling, the kinetics of thiodione transport was determined to be 1.6 10(-7) m/s, about 10 times faster than menadione uptake. Selective inhibition of these MRP1 pumps inside live HeLa cells by MK571 produced a lower thiodione concentration of 50 µM in presence of 500 µM menadione and 50 µM MK571. A similar reduced (50% drop) thiodione efflux was observed in the presence of monoclonal antibody QCRL-4, a selective blocking agent of the MRP1 pumps. The reduced thiodione flux confirmed that thiodione was transported by MRP1, and that glutathione is an essential substrate for MRP1-mediated transport. This finding demonstrates the usefulness of SECM in quantitative studies of MRP1 inhibitors and suggests that monoclonal antibodies can be a useful tool in inhibiting the transport of these MDR pumps, and thereby aiding in overcoming multidrug resistance.

Amphetamine activates Rho GTPase signaling to mediate dopamine transporter internalization and acute behavioral effects of amphetamine

Science.gov (United States)

Wheeler, David S.; Underhill, Suzanne M.; Stolz, Donna B.; Murdoch, Geoffrey H.; Thiels, Edda; Romero, Guillermo; Amara, Susan G.

2015-01-01

Acute amphetamine (AMPH) exposure elevates extracellular dopamine through a variety of mechanisms that include inhibition of dopamine reuptake, depletion of vesicular stores, and facilitation of dopamine efflux across the plasma membrane. Recent work has shown that the DAT substrate AMPH, unlike cocaine and other nontransported blockers, can also stimulate endocytosis of the plasma membrane dopamine transporter (DAT). Here, we show that when AMPH enters the cytoplasm it rapidly stimulates DAT internalization through a dynamin-dependent, clathrin-independent process. This effect, which can be observed in transfected cells, cultured dopamine neurons, and midbrain slices, is mediated by activation of the small GTPase RhoA. Inhibition of RhoA activity with C3 exotoxin or a dominant-negative RhoA blocks AMPH-induced DAT internalization. These actions depend on AMPH entry into the cell and are blocked by the DAT inhibitor cocaine. AMPH also stimulates cAMP accumulation and PKA-dependent inactivation of RhoA, thus providing a mechanism whereby PKA- and RhoA-dependent signaling pathways can interact to regulate the timing and robustness of AMPH’s effects on DAT internalization. Consistent with this model, the activation of D1/D5 receptors that couple to PKA in dopamine neurons antagonizes RhoA activation, DAT internalization, and hyperlocomotion observed in mice after AMPH treatment. These observations support the existence of an unanticipated intracellular target that mediates the effects of AMPH on RhoA and cAMP signaling and suggest new pathways to target to disrupt AMPH action. PMID:26553986

Arabidopsis CDS blastp result: AK072551 [KOME

Lifescience Database Archive (English)

Full Text Available AK072551 J023131N19 At3g05000.1 transport protein particle (TRAPP) component Bet3 f...amily protein similar to Transport protein particle 33 kDa subunit (TRAPP 33 kDa subunit) (Swiss-Prot:Q99394...) [Saccharomyces cerevisiae]; contains Pfam profile PF04051: Transport protein particle (TRAPP) component, Bet3 3e-75 ...

Arabidopsis CDS blastp result: AK061918 [KOME

Lifescience Database Archive (English)

Full Text Available AK061918 001-042-B03 At3g05000.1 transport protein particle (TRAPP) component Bet3 ...family protein similar to Transport protein particle 33 kDa subunit (TRAPP 33 kDa subunit) (Swiss-Prot:Q9939...4) [Saccharomyces cerevisiae]; contains Pfam profile PF04051: Transport protein particle (TRAPP) component, Bet3 3e-75 ...

Arabidopsis CDS blastp result: AK099662 [KOME

Lifescience Database Archive (English)

Full Text Available AK099662 J013066M10 At3g05000.1 transport protein particle (TRAPP) component Bet3 f...amily protein similar to Transport protein particle 33 kDa subunit (TRAPP 33 kDa subunit) (Swiss-Prot:Q99394...) [Saccharomyces cerevisiae]; contains Pfam profile PF04051: Transport protein particle (TRAPP) component, Bet3 1e-71 ...

Arabidopsis CDS blastp result: AK063779 [KOME

Lifescience Database Archive (English)

Full Text Available AK063779 001-121-D05 At3g05000.1 transport protein particle (TRAPP) component Bet3 ...family protein similar to Transport protein particle 33 kDa subunit (TRAPP 33 kDa subunit) (Swiss-Prot:Q9939...4) [Saccharomyces cerevisiae]; contains Pfam profile PF04051: Transport protein particle (TRAPP) component, Bet3 6e-75 ...

Arabidopsis CDS blastp result: AK099703 [KOME

Lifescience Database Archive (English)

Full Text Available AK099703 J013075G21 At3g05000.1 transport protein particle (TRAPP) component Bet3 f...amily protein similar to Transport protein particle 33 kDa subunit (TRAPP 33 kDa subunit) (Swiss-Prot:Q99394...) [Saccharomyces cerevisiae]; contains Pfam profile PF04051: Transport protein particle (TRAPP) component, Bet3 1e-74 ...

Glucose transporter 1 localisation throughout pregnancy in the carnivore placenta

DEFF Research Database (Denmark)

Wooding, F.B.P.; Dantzer, Vibeke; Klisch, K.

2007-01-01

Glucose is one of the major fetal nutrients. Maternofetal transfer requires transport across the several placental membranes. This transfer is mediated by one or more of the fourteen known isoforms of glucose transporter. So far only Glucose Transporters 1 and 3 (GT1, GT3) have been shown to be l...

A systemic study of stepwise chlorination-chemical vapor transport characteristics of pure rare earth oxides from Sc2O3 to Lu2O3 mediated by alkaline chlorides as complex former

International Nuclear Information System (INIS)

Sun Yanhui; He Peng; Chen Huani

2007-01-01

A systematic study has been carried out for the stepwise chlorination-chemical vapor transport (SC-CVT) characteristics of pure rare earth oxides from Sc 2 O 3 to Lu 2 O 3 mediated by the vapor complexes KLnCl 4 and NaLnCl 4 (Ln = Sc, Y and La-Lu) used NaCl and KCl as complex former, respectively. The results showed that the SC-CVT characteristics are similarly for NaCl and KCl as complex former, the main deposition temperature of the rare earth chlorides LnCl 3 is in the increasing order ScCl 3 3 3 , and then with a systematically decreasing trend from the early lanthanide chlorides to the end one. The results also showed that the total transported amount of the produced chlorides is YCl 3 > ScCl 3 , and they are much higher than that of most lanthanoid chlorides. For lanthanoids, the total transported amount of chloride increases systematically from the early lanthanoid chlorides to the end one except for EuCl 3 and GdCl 3 mediated by KCl and NaCl as complex former, respectively, which showed the divergence effect of Gd in the total transport efficiency. But there are some differences in SC-CVT characteristics of pure rare earth oxide mediated by KCl and NaCl as complex former, that is the main deposition temperature region for the same rare earth element was lower for KCl than that for NaCl as complex former except for LaCl 3 , CeCl 3 , YbCl 3 and LuCl 3 , while the total transport amount of rare earth chloride for KCl as complex former is higher than that for NaCl except for LaCl 3 and EuCl 3 . More over, the discussion was carried out for Sc and Y on the one hand and the lanthanides contain 4f electron as another hand based on the 4f electron hybridization assumption. Further more, the transport characteristics of rare earth oxides with alkaline chlorides as complex former in this study were compared to that with AlCl 3 as complex former

Multidrug and toxin extrusion proteins mediate cellular transport of cadmium

International Nuclear Information System (INIS)

Yang, Hong; Guo, Dong; Obianom, Obinna N.; Su, Tong; Polli, James E.; Shu, Yan

2017-01-01

Cadmium (Cd) is an environmentally prevalent toxicant posing increasing risk to human health worldwide. As compared to the extensive research in Cd tissue accumulation, little was known about the elimination of Cd, particularly its toxic form, Cd ion (Cd 2+ ). In this study, we aimed to examine whether Cd 2+ is a substrate of multidrug and toxin extrusion proteins (MATEs) that are important in renal xenobiotic elimination. HEK-293 cells overexpressing the human MATE1 (HEK-hMATE1), human MATE2-K (HEK-hMATE2-K) and mouse Mate1 (HEK-mMate1) were used to study the cellular transport and toxicity of Cd 2+ . The cells overexpressing MATEs showed a 2–4 fold increase of Cd 2+ uptake that could be blocked by the MATE inhibitor cimetidine. A saturable transport profile was observed with the Michaelis-Menten constant (K m ) of 130 ± 15.8 μM for HEK-hMATE1; 139 ± 21.3 μM for HEK-hMATE2-K; and 88.7 ± 13.5 μM for HEK-mMate1, respectively. Cd 2+ could inhibit the uptake of metformin, a substrate of MATE transporters, with the half maximal inhibitory concentration (IC 50 ) of 97.5 ± 6.0 μM, 20.2 ± 2.6 μM, and 49.9 ± 6.9 μM in HEK-hMATE1, HEK-hMATE2-K, and HEK-mMate1 cells, respectively. In addition, hMATE1 could transport preloaded Cd 2+ out of the HEK-hMATE1 cells, thus resulting in a significant decrease of Cd 2+ -induced cytotoxicity. The present study has provided the first evidence supporting that MATEs transport Cd 2+ and may function as cellular elimination machinery in Cd intoxication. - Highlights: • Cadmium is an environmentally prevalent toxicant. • Little was known regarding the elimination and detoxification of cadmium. • Cadmium ion is here demonstrated as a substrate of MATE transporters. • MATEs may function as cellular elimination machinery in cadmium detoxification.

Passive scalar transport mediated by laminar vortex rings

Energy Technology Data Exchange (ETDEWEB)

Hernández, R H; Rodríguez, G, E-mail: rohernan@ing.uchile.cl [LEAF-NL, Depto. Ingeniería Civil Mecánica, Universidad de Chile, Casilla 2777, Santiago (Chile)

2017-04-15

Numerical simulations were used to study the dynamics of a passive conserved scalar quantity entrained by a self-propelling viscous vortex ring. The transport and mixing process of the passive scalar variable were studied considering two initial scalar distributions: (i) The scalar substance was introduced into the ring during its formation, further focusing in the shedding into the wake of the ring; (ii) A disk-like scalar layer was placed in the ring’s path where the entrainment of the scalar substance into the ring bubble was studied as a function of the ring strength. In both cases, the scalar concentration inside the vortex bubble exhibits a steady decay with time. In the second case, it was shown that the entrained scalar mass grows with both the Reynolds number of the ring and the thickness of the scalar layer in the propagation direction. The ring can be viewed as a mechanism for scalar transportation along important distances. (paper)

An evolved xylose transporter from Zymomonas mobilis enhances sugar transport in Escherichia coli

Directory of Open Access Journals (Sweden)

Zhang Jingqing

2009-12-01

tests revealed that 2-RD5 was advantageous in xylose and glucose uptakes, while no obvious advantage was seen for xylose co-consumption when co-fermented with glucose. Further efforts could focus on reducing CCR-mediated repression of intracellular metabolism of xylose. Glf should also serve as a useful model to further exploit the molecular mechanism of xylose transport and the CCR-mediated inhibition.

Lansoprazole Exacerbates Pemetrexed-Mediated Hematologic Toxicity by Competitive Inhibition of Renal Basolateral Human Organic Anion Transporter 3.

Science.gov (United States)

Ikemura, Kenji; Hamada, Yugo; Kaya, Chinatsu; Enokiya, Tomoyuki; Muraki, Yuichi; Nakahara, Hiroki; Fujimoto, Hajime; Kobayashi, Tetsu; Iwamoto, Takuya; Okuda, Masahiro

2016-10-01

Pemetrexed, a multitargeted antifolate, is eliminated by tubular secretion via human organic anion transporter 3 (hOAT3). Although proton pump inhibitors (PPIs) are frequently used in cancer patients, the drug interaction between PPIs and pemetrexed remains to be clarified. In this study, we examined the drug interaction between pemetrexed and PPIs in hOAT3-expressing cultured cells, and retrospectively analyzed the impact of PPIs on the development of hematologic toxicity in 108 patients who received pemetrexed and carboplatin treatment of nonsquamous non-small cell lung cancer for the first time between January 2011 and June 2015. We established that pemetrexed was transported via hOAT3 (Km = 68.3 ± 11.1 µM). Lansoprazole, rabeprazole, pantoprazole, esomeprazole, omeprazole, and vonoprazan inhibited hOAT3-mediated uptake of pemetrexed in a concentration-dependent manner. The inhibitory effect of lansoprazole was much greater than those of other PPIs and the apparent IC50 value of lansoprazole against pemetrexed transport via hOAT3 was 0.57 ± 0.17 µM. The inhibitory type of lansoprazole was competitive. In a retrospective study, multivariate analysis revealed that coadministration of lansoprazole, but not other PPIs, with pemetrexed and carboplatin was an independent risk factor significantly contributing to the development of hematologic toxicity (odds ratio: 10.004, P = 0.005). These findings demonstrated that coadministration of lansoprazole could exacerbate the hematologic toxicity associated with pemetrexed, at least in part, by competitive inhibition of hOAT3. Our results would aid clinicians to make decisions of coadministration drugs to avoid drug interaction-induced side effects for achievement of safe and appropriate chemotherapy with pemetrexed. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Extracellular vesicles provide a means for tissue crosstalk during exercise

DEFF Research Database (Denmark)

Whitham, Martin; Parker, Benjamin L; Friedrichsen, Martin

2018-01-01

Exercise stimulates the release of molecules into the circulation, supporting the concept that inter-tissue signaling proteins are important mediators of adaptations to exercise. Recognizing that many circulating proteins are packaged in extracellular vesicles (EVs), we employed quantitative prot...

Role of NH3 and NH4+ transporters in renal acid-base transport.

Science.gov (United States)

Weiner, I David; Verlander, Jill W

2011-01-01

Renal ammonia excretion is the predominant component of renal net acid excretion. The majority of ammonia excretion is produced in the kidney and then undergoes regulated transport in a number of renal epithelial segments. Recent findings have substantially altered our understanding of renal ammonia transport. In particular, the classic model of passive, diffusive NH3 movement coupled with NH4+ "trapping" is being replaced by a model in which specific proteins mediate regulated transport of NH3 and NH4+ across plasma membranes. In the proximal tubule, the apical Na+/H+ exchanger, NHE-3, is a major mechanism of preferential NH4+ secretion. In the thick ascending limb of Henle's loop, the apical Na+-K+-2Cl- cotransporter, NKCC2, is a major contributor to ammonia reabsorption and the basolateral Na+/H+ exchanger, NHE-4, appears to be important for basolateral NH4+ exit. The collecting duct is a major site for renal ammonia secretion, involving parallel H+ secretion and NH3 secretion. The Rhesus glycoproteins, Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg), are recently recognized ammonia transporters in the distal tubule and collecting duct. Rhcg is present in both the apical and basolateral plasma membrane, is expressed in parallel with renal ammonia excretion, and mediates a critical role in renal ammonia excretion and collecting duct ammonia transport. Rhbg is expressed specifically in the basolateral plasma membrane, and its role in renal acid-base homeostasis is controversial. In the inner medullary collecting duct (IMCD), basolateral Na+-K+-ATPase enables active basolateral NH4+ uptake. In addition to these proteins, several other proteins also contribute to renal NH3/NH4+ transport. The role and mechanisms of these proteins are discussed in depth in this review.

Functional Expression of P-glycoprotein and Organic Anion Transporting Polypeptides at the Blood-Brain Barrier: Understanding Transport Mechanisms for Improved CNS Drug Delivery?

Science.gov (United States)

Abdullahi, Wazir; Davis, Thomas P; Ronaldson, Patrick T

2017-07-01

Drug delivery to the central nervous system (CNS) is greatly limited by the blood-brain barrier (BBB). Physical and biochemical properties of the BBB have rendered treatment of CNS diseases, including those with a hypoxia/reoxygenation (H/R) component, extremely difficult. Targeting endogenous BBB transporters from the ATP-binding cassette (ABC) superfamily (i.e., P-glycoprotein (P-gp)) or from the solute carrier (SLC) family (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents)) has been suggested as a strategy that can improve delivery of drugs to the brain. With respect to P-gp, direct pharmacological inhibition using small molecules or selective regulation by targeting intracellular signaling pathways has been explored. These approaches have been largely unsuccessful due to toxicity issues and unpredictable pharmacokinetics. Therefore, our laboratory has proposed that optimization of CNS drug delivery, particularly for treatment of diseases with an H/R component, can be achieved by targeting Oatp isoforms at the BBB. As the major drug transporting Oatp isoform, Oatp1a4 has demonstrated blood-to-brain transport of substrate drugs with neuroprotective properties. Furthermore, our laboratory has shown that targeting Oatp1a4 regulation (i.e., TGF-β signaling mediated via the ALK-1 and ALK-5 transmembrane receptors) represents an opportunity to control Oatp1a4 functional expression for the purpose of delivering therapeutics to the CNS. In this review, we will discuss limitations of targeting P-gp-mediated transport activity and the advantages of targeting Oatp-mediated transport. Through this discussion, we will also provide critical information on novel approaches to improve CNS drug delivery by targeting endogenous uptake transporters expressed at the BBB.

Action de I'AlA sur la teneur en azote total et protéinique des graines de céréales cultivées à different niveau de la capacité capillaire en eau

Directory of Open Access Journals (Sweden)

Wiesław Nowakowski

2015-06-01

Full Text Available L'action de I'AIA sur la teneur en azote total et en azote protéinique des graines du Triticum vulgare, d'Hordeum vulgare et d'Avena sativa cultivés a 30%, 60% et 90% de la capacité capillaire en eau du sable a tété étudiée au cours de trois ans (1969, 1970, 1971. La teneur en g-protéines totales liée au rendement des graines de céréales examinees a été plus élevée dans les conditions de sécheresse (30% de la capacite capillaire en eau à la suite d'un traitement auxinique. La teneur (% en azote total et proteinique ne semble pas etre tellement modifiee dans les graines de cereales à la suite d'un traitement auxinique.

Schisandra chinensis regulates drug metabolizing enzymes and drug transporters via activation of Nrf2-mediated signaling pathway

Directory of Open Access Journals (Sweden)

He JL

2014-12-01

increase in the intracellular level of glutathione and total glutathione S-transferase content. SCE significantly elevated the messenger ribonucleic acid and protein levels of P-glycoprotein and multidrug resistance-associated protein 2 and 4, whereas the expression of organic anion transporting peptide 1A2 and 1B1 was significantly downregulated by SCE. Knockdown of Nrf2 by small interfering ribonucleic acid attenuated the regulatory effect of SCE on these DMEs and drug transporters. SCE significantly upregulated Nrf2 and promoted the translocation of Nrf2 from cytoplasm to the nuclei. Additionally, SCE significantly suppressed the expression of cytosolic Kelch-like ECH-associated protein 1 (the repressor of Nrf2 and remarkably increased Nrf2 stability in HepG2 cells. Taken together, our findings suggest that the hepatoprotective effects of SCE may be partially ascribed to the modulation of DMEs and drug transporters via Nrf2-mediated signaling pathway. SCE may alter the pharmacokinetics of other coadministered drugs that are substrates of these DMEs and transporters and thus cause unfavorable herb–drug interactions. Keywords: Nrf2, Keap1, HepG2 cell, drug metabolizing enzyme, drug transporter, P-gp, MRP, OATP, Schisandra chinensis

Multidrug and toxin extrusion proteins mediate cellular transport of cadmium

Energy Technology Data Exchange (ETDEWEB)

Yang, Hong; Guo, Dong; Obianom, Obinna N. [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Su, Tong [Department of Oral Maxillofacial Surgery, the First Affiliated Hospital, Xiangya Medical School, Central South University, Hunan 410007 (China); Polli, James E. [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Shu, Yan, E-mail: yshu@rx.umaryland.edu [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States)

2017-01-01

Cadmium (Cd) is an environmentally prevalent toxicant posing increasing risk to human health worldwide. As compared to the extensive research in Cd tissue accumulation, little was known about the elimination of Cd, particularly its toxic form, Cd ion (Cd{sup 2+}). In this study, we aimed to examine whether Cd{sup 2+} is a substrate of multidrug and toxin extrusion proteins (MATEs) that are important in renal xenobiotic elimination. HEK-293 cells overexpressing the human MATE1 (HEK-hMATE1), human MATE2-K (HEK-hMATE2-K) and mouse Mate1 (HEK-mMate1) were used to study the cellular transport and toxicity of Cd{sup 2+}. The cells overexpressing MATEs showed a 2–4 fold increase of Cd{sup 2+} uptake that could be blocked by the MATE inhibitor cimetidine. A saturable transport profile was observed with the Michaelis-Menten constant (K{sub m}) of 130 ± 15.8 μM for HEK-hMATE1; 139 ± 21.3 μM for HEK-hMATE2-K; and 88.7 ± 13.5 μM for HEK-mMate1, respectively. Cd{sup 2+} could inhibit the uptake of metformin, a substrate of MATE transporters, with the half maximal inhibitory concentration (IC{sub 50}) of 97.5 ± 6.0 μM, 20.2 ± 2.6 μM, and 49.9 ± 6.9 μM in HEK-hMATE1, HEK-hMATE2-K, and HEK-mMate1 cells, respectively. In addition, hMATE1 could transport preloaded Cd{sup 2+} out of the HEK-hMATE1 cells, thus resulting in a significant decrease of Cd{sup 2+}-induced cytotoxicity. The present study has provided the first evidence supporting that MATEs transport Cd{sup 2+} and may function as cellular elimination machinery in Cd intoxication. - Highlights: • Cadmium is an environmentally prevalent toxicant. • Little was known regarding the elimination and detoxification of cadmium. • Cadmium ion is here demonstrated as a substrate of MATE transporters. • MATEs may function as cellular elimination machinery in cadmium detoxification.

Solitary BioY Proteins Mediate Biotin Transport into Recombinant Escherichia coli

Science.gov (United States)

Finkenwirth, Friedrich; Kirsch, Franziska

2013-01-01

Energy-coupling factor (ECF) transporters form a large group of vitamin uptake systems in prokaryotes. They are composed of highly diverse, substrate-specific, transmembrane proteins (S units), a ubiquitous transmembrane protein (T unit), and homo- or hetero-oligomeric ABC ATPases. Biotin transporters represent a special case of ECF-type systems. The majority of the biotin-specific S units (BioY) is known or predicted to interact with T units and ABC ATPases. About one-third of BioY proteins, however, are encoded in organisms lacking any recognizable T unit. This finding raises the question of whether these BioYs function as transporters in a solitary state, a feature ascribed to certain BioYs in the past. To address this question in living cells, an Escherichia coli K-12 derivative deficient in biotin synthesis and devoid of its endogenous high-affinity biotin transporter was constructed as a reference strain. This organism is particularly suited for this purpose because components of ECF transporters do not naturally occur in E. coli K-12. The double mutant was viable in media containing either high levels of biotin or a precursor of the downstream biosynthetic path. Importantly, it was nonviable on trace levels of biotin. Eight solitary bioY genes of proteobacterial origin were individually expressed in the reference strain. Each of the BioYs conferred biotin uptake activity on the recombinants, which was inferred from uptake assays with [3H]biotin and growth of the cells on trace levels of biotin. The results underscore that solitary BioY transports biotin across the cytoplasmic membrane. PMID:23836870

Ammonia transport in the kidney by Rhesus glycoproteins

Science.gov (United States)

Verlander, Jill W.

2014-01-01

Renal ammonia metabolism is a fundamental element of acid-base homeostasis, comprising a major component of both basal and physiologically altered renal net acid excretion. Over the past several years, a fundamental change in our understanding of the mechanisms of renal epithelial cell ammonia transport has occurred, replacing the previous model which was based upon diffusion equilibrium for NH3 and trapping of NH4+ with a new model in which specific and regulated transport of both NH3 and NH4+ across renal epithelial cell membranes via specific membrane proteins is required for normal ammonia metabolism. A major advance has been the recognition that members of a recently recognized transporter family, the Rhesus glycoprotein family, mediate critical roles in renal and extrarenal ammonia transport. The erythroid-specific Rhesus glycoprotein, Rh A Glycoprotein (Rhag), was the first Rhesus glycoprotein recognized as an ammonia-specific transporter. Subsequently, the nonerythroid Rh glycoproteins, Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg), were cloned and identified as ammonia transporters. They are expressed in specific cell populations and membrane domains in distal renal epithelial cells, where they facilitate ammonia secretion. In this review, we discuss the distribution of Rhbg and Rhcg in the kidney, the regulation of their expression and activity in physiological disturbances, the effects of genetic deletion on renal ammonia metabolism, and the molecular mechanisms of Rh glycoprotein-mediated ammonia transport. PMID:24647713

The dopamine transporter: role in neurotoxicity and human disease

International Nuclear Information System (INIS)

Bannon, Michael J.

2005-01-01

The dopamine transporter (DAT) is a plasma membrane transport protein expressed exclusively within a small subset of CNS neurons. It plays a crucial role in controlling dopamine-mediated neurotransmission and a number of associated behaviors. This review focuses on recent data elucidating the role of the dopamine transporter in neurotoxicity and a number of CNS disorders, including Parkinson disease, drug abuse, and attention deficit hyperactivity disorder (ADHD)

The dopamine transporter: role in neurotoxicity and human disease

Energy Technology Data Exchange (ETDEWEB)

Bannon, Michael J [Department of Psychiatry and Behavioral Neuroscience, Pharmacology, and Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201 (United States)

2005-05-01

The dopamine transporter (DAT) is a plasma membrane transport protein expressed exclusively within a small subset of CNS neurons. It plays a crucial role in controlling dopamine-mediated neurotransmission and a number of associated behaviors. This review focuses on recent data elucidating the role of the dopamine transporter in neurotoxicity and a number of CNS disorders, including Parkinson disease, drug abuse, and attention deficit hyperactivity disorder (ADHD)

The multidrug ABC transporter BmrC/BmrD of Bacillus subtilis is regulated via a ribosome-mediated transcriptional attenuation mechanism.

Science.gov (United States)

Reilman, Ewoud; Mars, Ruben A T; van Dijl, Jan Maarten; Denham, Emma L

2014-10-01

Expression of particular drug transporters in response to antibiotic pressure is a critical element in the development of bacterial multidrug resistance, and represents a serious concern for human health. To obtain a better understanding of underlying regulatory mechanisms, we have dissected the transcriptional activation of the ATP-binding cassette (ABC) transporter BmrC/BmrD of the Gram-positive model bacterium Bacillus subtilis. By using promoter-GFP fusions and live cell array technology, we demonstrate a temporally controlled transcriptional activation of the bmrCD genes in response to antibiotics that target protein synthesis. Intriguingly, bmrCD expression only occurs during the late-exponential and stationary growth stages, irrespective of the timing of the antibiotic challenge. We show that this is due to tight transcriptional control by the transition state regulator AbrB. Moreover, our results show that the bmrCD genes are co-transcribed with bmrB (yheJ), a small open reading frame immediately upstream of bmrC that harbors three alternative stem-loop structures. These stem-loops are apparently crucial for antibiotic-induced bmrCD transcription. Importantly, the antibiotic-induced bmrCD expression requires translation of bmrB, which implies that BmrB serves as a regulatory leader peptide. Altogether, we demonstrate for the first time that a ribosome-mediated transcriptional attenuation mechanism can control the expression of a multidrug ABC transporter. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Solid-state Water-mediated Transport Reduction of Nanostructured Iron Oxides

International Nuclear Information System (INIS)

Smirnov, Vladimir M.; Povarov, Vladimir G.; Voronkov, Gennadii P.; Semenov, Valentin G.; Murin, Igor' V.; Gittsovich, Viktor N.; Sinel'nikov, Boris M.

2001-01-01

The Fe 2+ /Fe 3+ ratio in two-dimensional iron oxide nanosructures (nanolayers with a thickness of 0.3-1.5 nm on silica surface) may be precisely controlled using the transport reduction (TR) technique. The species ≡-O-Fe(OH) 2 and (≡Si-O-) 2 -FeOH forming the surface monolayer are not reduced at 400-600 deg. C because of their covalent bonding to the silica surface, as demonstrated by Moessbauer spectroscopy. Iron oxide microparticles (microstructures) obtained by the impregnation technique, being chemically unbound to silica, are subjected to reduction at T ≥ 500 deg. C with formation of metallic iron in the form of α-Fe. Transport reduction of supported nanostructures (consisting of 1 or 4 monolayers) at T ≥ 600 deg. C produces bulk iron(II) silicate and metallic iron phases. The structural-chemical transformations occurring in transport reduction of supported iron oxide nanolayers are proved to be governed by specific phase processes in the nanostructures themselves

KIF20A-Mediated RNA Granule Transport System Promotes the Invasiveness of Pancreatic Cancer Cells

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Keisuke Taniuchi

2014-12-01

Full Text Available Pancreatic cancers are aggressive because they are highly invasive and highly metastatic; moreover, effective treatments for aggressive pancreatic cancers are lacking. Here, we report that the motor kinesin protein KIF20A promoted the motility and invasiveness of pancreatic cancer cells through transporting the RNA-binding protein IGF2BP3 and IGF2BP3-bound transcripts toward cell protrusions along microtubules. We previously reported that IGF2BP3 and its target transcripts are assembled into cytoplasmic stress granules of pancreatic cancer cells, and that IGF2BP3 promotes the motility and invasiveness of pancreatic cancer cells through regulation of localized translation of IGF2BP3-bound transcripts in cell protrusions. We show that knockdown of KIF20A inhibited accumulation of IGF2BP3-containing stress granules in cell protrusions and suppressed local protein expression from specific IGF2BP3-bound transcripts, ARF6 and ARHGEF4, in the protrusions. Our results provide insight into the link between regulation of KIF20A-mediated trafficking of IGF2BP3-containing stress granules and modulation of the motility and invasiveness in pancreatic cancers.

Comparison between s - and d -electron mediated transport in a photoswitching dithienylethene molecule using ab initio transport methods

KAUST Repository

Odell, Anders; Delin, Anna; Johansson, Bö rje; Ulman, Kanchan; Narasimhan, Shobhana; Rungger, Ivan; Sanvito, Stefano

2011-01-01

The influence of the electrode's Fermi surface on the transport properties of a photoswitching molecule is investigated with state-of-the-art ab initio transport methods. We report results for the conducting properties of the two forms

In vivo analysis of post space sealing with different adhesive materials Análise in vivo do selamento do canal protéico com diferentes materais adesivos

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Carlos Alexandre Souza Bier

2003-09-01

Full Text Available This in vivo study analyzed the sealing ability of two adhesives in post spaces, cyanoacrylate (Super Bonder® - Henkel Loctite Adesivos Ltda., Itapevi, SP, Brazil and ScotchbondTM Multi-Purpose (3M Dental Products, St. Paul, MN, USA, testing the hypothesis that their use would result in a decreased leakage through the remaining filling material. Forty extracted premolars (80 root canals of dogs were used. The root canals were cleaned, shaped and filled by the lateral condensation technique using Sealer 26TM. The post space was created removing two thirds of the filling material within the root canal. The canals were randomly divided in three groups, which were treated as follows: Group A received the ScotchbondTM Multi-Purpose adhesive system; for Group B the cyanoacrylate adhesive, Super BonderTM, was employed; and no adhesive was applied into the post space for Group C (control group. A glass ionomer provisional restoration was placed allowing the sealer to set for 72 hours. Then the restoration was removed and the root canal was exposed to the oral environment for 45 days. The dogs were then killed and their jaws were removed. The post spaces were filled with India ink and the teeth were restored for 96 hours. Afterwards, the teeth were extracted and the roots were sectioned at the furcation for allocation to their specific groups. The teeth were turned transparent and the quantitative analysis of leakage was performed using light microscopy. The results showed no significant differences between groups, rejecting the initial hypothesis. Leakage occurred in a great extent in all specimens. Therefore, sealing post spaces with the adhesives used in this study was not an effective method to prevent microleakage.Esse estudo in vivo analisou a capacidade de selamento do canal protético com dois adesivos, o Super Bonder® (Henkel Loctite Adesivos Ltda., Itapevi, SP e o Scotchbond® Multi-Purpose (3M Dental Products, St. Paul, MN, EUA, testando a

Importin 8 regulates the transport of mature microRNAs into the cell nucleus.

Science.gov (United States)

Wei, Yao; Li, Limin; Wang, Dong; Zhang, Chen-Yu; Zen, Ke

2014-04-11

Mature microRNAs (miRNAs), ∼ 22-nucleotide noncoding RNAs regulating target gene expression at the post-transcriptional level, have been recently shown to be transported into the nucleus where they modulate the biogenesis of other miRNAs or their own expression. However, the mechanism that governs the transport of mature miRNAs from cytoplasm to nucleus remains unknown. Here, we report that importin 8 (IPO8), a member of the karyopherin β (also named the protein import receptor importin β) family, plays a critical role in mediating the cytoplasm-to-nucleus transport of mature miRNAs. Specifically knocking down IPO8 but not other karyopherin β family proteins via siRNA significantly decreases the nuclear transport of various known nucleus-enriched miRNAs without affecting their total cellular levels. IPO8-mediated nuclear transport of mature miRNAs is also dependent on the association of IPO8 with the Argonaute 2 (Ago2) complex. Cross-immunoprecipitation and Western blot analysis show that IPO8 is physically associated with Ago2. Knocking down IPO8 via siRNA markedly decreases the nuclear transport of Ago2 but does not affect the total cellular Ago2 level. Furthermore, dissociating the binding of miRNAs with Ago2 by trypaflavine strongly reduces the IPO8-mediated nuclear transport of miRNAs.

Hepcidin Protects Neuron from Hemin-Mediated Injury by Reducing Iron

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Yu-Fu Zhou

2017-05-01

Full Text Available Hemin plays a key role in mediating secondary neuronal injury after intracerebral hemorrhage (ICH and the cell toxicity of hemin is thought to be due to iron that is liberated when hemin is degraded. In a recent study, we demonstrated the iron regulatory hormone hepcidin reduces brain iron in iron-overloaded rats. Therefore, we hypothesized that hepcidin might be able to reduce iron and then protect neurons from hemin or iron-mediated neurotoxicity in hemin-treated neuronal cells. Here, we tested the hypothesis and demonstrated that ad-hepcidin and hepcidin peptide both have the ability to suppress the hemin-induced increase in LDH release and apoptotic cell numbers, to reduce cell iron and ferritin contents, and to inhibit expression of transferrin receptor 1, divalent metal transporter 1, and ferroportin 1 in hemin-treated neurons. We conclude that hepcidin protects neuron from hemin-mediated injury by reducing iron via inhibition of expression of iron transport proteins.

Membrane-traversing mechanism of thyroid hormone transport by monocarboxylate transporter 8.

Science.gov (United States)

Protze, Jonas; Braun, Doreen; Hinz, Katrin Manuela; Bayer-Kusch, Dorothea; Schweizer, Ulrich; Krause, Gerd

2017-06-01

Monocarboxylate transporter 8 (MCT8) mediates thyroid hormone (TH) transport across the plasma membrane in many cell types. In order to better understand its mechanism, we have generated three new MCT8 homology models based on sugar transporters XylE in the intracellular opened (PDB ID: 4aj4) and the extracellular partly occluded (PDB ID: 4gby) conformations as well as FucP (PDB ID: 3o7q) and GLUT3 (PDB ID: 4zwc) in the fully extracellular opened conformation. T 3 -docking studies from both sides revealed interactions with His192, His415, Arg445 and Asp498 as previously identified. Selected mutations revealed further transport-sensitive positions mainly at the discontinuous transmembrane helices TMH7 and 10. Lys418 is potentially involved in neutralising the charge of the TH substrate because it can be replaced by charged, but not by uncharged, amino acids. The side chain of Thr503 was hypothesised to stabilise a helix break at TMH10 that undergoes a prominent local shift during the transport cycle. A T503V mutation accordingly affected transport. The aromatic Tyr419, the polar Ser313 and Ser314 as well as the charged Glu422 and Glu423 lining the transport channel have been studied. Based on related sugar transporters, we suggest an alternating access mechanism for MCT8 involving a series of amino acid positions previously and newly identified as critical for transport.

Hydrogen vacancies facilitate hydrogen transport kinetics in sodium hydride nanocrystallites

NARCIS (Netherlands)

Singh, S.; Eijt, S.W.H.

2008-01-01

We report ab initio calculations based on density-functional theory, of the vacancy-mediated hydrogen migration energy in bulk NaH and near the NaH(001) surface. The estimated rate of the vacancy mediated hydrogen transport, obtained within a hopping diffusion model, is consistent with the reaction

Transepithelial transport of flavanone in intestinal Caco-2 cell monolayers

International Nuclear Information System (INIS)

Kobayashi, Shoko; Konishi, Yutaka

2008-01-01

Our recent study [S. Kobayashi, S. Tanabe, M. Sugiyama, Y. Konishi, Transepithelial transport of hesperetin and hesperidin in intestinal Caco-2 cell monolayers, Biochim. Biophys. Acta, 1778 (2008) 33-41] shows that the mechanism of absorption of hesperetin involves both proton-coupled active transport and transcellular passive diffusion. Here, as well as analyzing the cell permeability of hesperetin, we also study the transport of other flavanones, naringenin and eriodictyol, using Caco-2 cell monolayers. Similar to hesperetin mentioned, naringenin and eriodictyol showed proton-coupled polarized transport in apical-to-basolateral direction in non-saturable manner, constant permeation in the apical-to-basolateral direction (J ap→bl ) irrespective of the transepithelial electrical resistance (TER), and preferable distribution into the basolateral side after apical loading in the presence of a proton gradient. Furthermore, the proton-coupled J ap→bl of hesperetin, naringenin and eriodictyol, were inhibited by substrates of the monocarboxylic acid transporter (MCT), such as benzoic acid, but not by ferulic acid. In contrast, both benzoic and ferulic acids have no stimulatory effect on J ap→bl of each flavanone by trans-stimulation analysis. These results indicates that proton-driven active transport is commonly participated in the absorption of flavanone in general, and that its transport is presumed to be unique other than MCT-mediated transport for absorption of phenolic acids (PAs), sodium-dependent MCT (SMCT) nor anion exchanger-mediated transport

Influence of multidrug resistance and drug transport proteins on chemotherapy drug metabolism.

Science.gov (United States)

Joyce, Helena; McCann, Andrew; Clynes, Martin; Larkin, Annemarie

2015-05-01

Chemotherapy involving the use of anticancer drugs remains an important strategy in the overall management of patients with metastatic cancer. Acquisition of multidrug resistance remains a major impediment to successful chemotherapy. Drug transporters in cell membranes and intracellular drug metabolizing enzymes contribute to the resistance phenotype and determine the pharmacokinetics of anticancer drugs in the body. ATP-binding cassette (ABC) transporters mediate the transport of endogenous metabolites and xenobiotics including cytotoxic drugs out of cells. Solute carrier (SLC) transporters mediate the influx of cytotoxic drugs into cells. This review focuses on the substrate interaction of these transporters, on their biology and what role they play together with drug metabolizing enzymes in eliminating therapeutic drugs from cells. The majority of anticancer drugs are substrates for the ABC transporter and SLC transporter families. Together, these proteins have the ability to control the influx and the efflux of structurally unrelated chemotherapeutic drugs, thereby modulating the intracellular drug concentration. These interactions have important clinical implications for chemotherapy because ultimately they determine therapeutic efficacy, disease progression/relapse and the success or failure of patient treatment.

Efeitos da correção da acidose metabólica com bicarbonato de sódio sobre o catabolismo protéico na insuficiência renal crônica The effects of the correction of metabolic acidosis with sodium bicarbonate on protein catabolism in chronic kidney failure

Directory of Open Access Journals (Sweden)

Denise MAFRA

2001-04-01

Full Text Available A desnutrição protéico-energética constitui problema comum aos pacientes com insuficiência renal crônica, influenciando diretamente na sua morbi-mortalidade. A acidose metabólica tem papel no catabolismo protéico, ativando a via proteolítica proteasoma-ubiquitina, dependente de adenosina trifosfato, e conjuntamente com glicocorticóides induz uma maior atividade na desidrogenase que degrada os aminoácidos de cadeia ramificada. Esta revisão teve como objetivo descrever o mecanismo pelo qual a acidose metabólica nos pacientes com insuficiência renal crônica promove o catabolismo protéico, favorecendo assim a desnutrição, bem como avaliar os efeitos do uso de bicarbonato de sódio na correção da acidose e conseqüentemente redução do catabolismo protéico. Pesquisas mostram melhora da acidose pelo uso de bicarbonato de sódio e conseqüente redução do catabolismo protéico na insuficiência renal crônica, podendo ser esta uma conduta promissora na atenuação da desnutrição nestes pacientes.Protein-Energy Malnutrition is common among patients with chronic kidney failure, thus increasing morbidity and mortality. Several studies have shown that metabolic acidosis is a major cause of muscle protein breakdown, and recently it was attributed to ATP-dependent ubiquitin-proteasome proteolytic pathway. Acidosis, plus glucocorticoids, also respond to increasing branched-chain amino acids oxidation. In this review, the impact of metabolic acidosis on protein and amino acid metabolism is examined in order to understand its effect on lean body mass and the nutritional status of patients with chronic kidney failure. The study also observes whether or not sodium bicarbonate supplementation is beneficial to chronic kidney failure patients. In summary, there is a preliminary evidence suggesting that the correction of acidosis using sodium bicarbonate reduces protein degradation in chronic kidney failure patients, thus emerging as a

Protein concentrate obtainment from leaves and aerial part cassava (ManihotesculentaCrantzObtenção de concentrado protéico de folhas e parte aérea da mandioca (ManihotesculentaCrantz

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Janaina Lima da Silva

2012-12-01

Full Text Available The aerial parts of cassava, constituted by leaves, stalk sand stems, are considered as agro-industrial waste, so, they are thrown away during roots crop. This material has content of protein, vitamin and mineral; therefore, it can be used as a dietary supplement for food industries. Thus, alternatives have come to extract protein from leaves and remove toxic agent sand anti-nutrients that make part of their composition. In this context, this study aimed at evaluating yield, mineral composition and functional properties of protein concentrates from leaves and aerial part of cassava. During the extraction of proteins, the following tested methods were:(1 isoelectric precipitation; (2 natural fermentation for five days; (3 fermentation for 48 hours and (4 fermentation for 48 hours, followed by pH adjustment. A 2 x 4 factorial design was used, the studied factors were the products (leaves and shoots and the method of protein extraction (four methods, with three replications. From the results, it was observed that Method1 provided the highest yields of protein concentrate and protein extraction for cassava leaves, however, there was no significant difference among the extraction methods for the aerial part of cassava. The values of Fe, Mn and Zn increased in protein concentrates obtained both in leaves and the aerial part of cassava, especially for Method 3. The capacities of absorbing water and oil from protein concentrates were considered high for the four studied methods, thus, indicating a good application in food products.As partes aéreas da mandioca, representadas pelas folhas, hastes e caules, constituem-se como resíduos agroindustriais por serem desperdiçadas na colheita das raízes. Esse material possui valor protéico, vitaminas e mineiras, propiciando sua utilização como suplemento alimentar nas indústrias alimentícias. Alternativas neste sentido surgem para extrair a proteína das folhas e eliminar os agentes tóxicos e

Trombosis protésica obstructiva: un enemigo latente: Revisión del tema, a propósito de tres casos clínicos

OpenAIRE

ABREU, RODRIGO; BARRANCO, DANIELA; PIÑEYRO, HUGO; CASALES, DANIEL

2011-01-01

RESUMEN La trombosis protésica obstructiva es una complicación temida y de mal pronóstico aun con un tratamiento rápido. Sus diversas formas de presentación hacen necesario un alto nivel de sospecha clínica y la rápida utilización de métodos diagnósticos en vistas a un tratamiento correcto y mejorar la evolución. Se analizan tres casos clínicos de nuestro centro que ejemplifican las diferentes formas de presentación y tienen un desenlace diferente. Posteriormente se realiza una revisión de la...

Hummingbirds rely on both paracellular and carrier-mediated intestinal glucose absorption to fuel high metabolism

Science.gov (United States)

McWhorter, Todd J; Bakken, Bradley Hartman; Karasov, William H; del Rio, Carlos Martínez

2005-01-01

Twenty years ago, the highest active glucose transport rate and lowest passive glucose permeability in vertebrates were reported in Rufous and Anna's hummingbirds (Selasphorus rufus, Calypte anna). These first measurements of intestinal nutrient absorption in nectarivores provided an unprecedented physiological foundation for understanding their foraging ecology. They showed that physiological processes are determinants of feeding behaviour. The conclusion that active, mediated transport accounts for essentially all glucose absorption in hummingbirds influenced two decades of subsequent research on the digestive physiology and nutritional ecology of nectarivores. Here, we report new findings demonstrating that the passive permeability of hummingbird intestines to glucose is much higher than previously reported, suggesting that not all sugar uptake is mediated. Even while possessing the highest active glucose transport rates measured in vertebrates, hummingbirds must rely partially on passive non-mediated intestinal nutrient absorption to meet their high mass-specific metabolic demands. PMID:17148346

Arsenic tolerance in Arabidopsis is mediated by two ABCC-type phytochelatin transporters

Science.gov (United States)

Song, Won-Yong; Park, Jiyoung; Mendoza-Cózatl, David G.; Suter-Grotemeyer, Marianne; Shim, Donghwan; Hörtensteiner, Stefan; Geisler, Markus; Weder, Barbara; Rea, Philip A.; Rentsch, Doris; Schroeder, Julian I.; Lee, Youngsook; Martinoia, Enrico

2010-01-01

Arsenic is an extremely toxic metalloid causing serious health problems. In Southeast Asia, aquifers providing drinking and agricultural water for tens of millions of people are contaminated with arsenic. To reduce nutritional arsenic intake through the consumption of contaminated plants, identification of the mechanisms for arsenic accumulation and detoxification in plants is a prerequisite. Phytochelatins (PCs) are glutathione-derived peptides that chelate heavy metals and metalloids such as arsenic, thereby functioning as the first step in their detoxification. Plant vacuoles act as final detoxification stores for heavy metals and arsenic. The essential PC–metal(loid) transporters that sequester toxic metal(loid)s in plant vacuoles have long been sought but remain unidentified in plants. Here we show that in the absence of two ABCC-type transporters, AtABCC1 and AtABCC2, Arabidopsis thaliana is extremely sensitive to arsenic and arsenic-based herbicides. Heterologous expression of these ABCC transporters in phytochelatin-producing Saccharomyces cerevisiae enhanced arsenic tolerance and accumulation. Furthermore, membrane vesicles isolated from these yeasts exhibited a pronounced arsenite [As(III)]–PC2 transport activity. Vacuoles isolated from atabcc1 atabcc2 double knockout plants exhibited a very low residual As(III)–PC2 transport activity, and interestingly, less PC was produced in mutant plants when exposed to arsenic. Overexpression of AtPCS1 and AtABCC1 resulted in plants exhibiting increased arsenic tolerance. Our findings demonstrate that AtABCC1 and AtABCC2 are the long-sought and major vacuolar PC transporters. Modulation of vacuolar PC transporters in other plants may allow engineering of plants suited either for phytoremediation or reduced accumulation of arsenic in edible organs. PMID:21078981

Lysosomes as mediators of drug resistance in cancer.

Science.gov (United States)

Zhitomirsky, Benny; Assaraf, Yehuda G

2016-01-01

Drug resistance remains a leading cause of chemotherapeutic treatment failure and cancer-related mortality. While some mechanisms of anticancer drug resistance have been well characterized, multiple mechanisms remain elusive. In this respect, passive ion trapping-based lysosomal sequestration of multiple hydrophobic weak-base chemotherapeutic agents was found to reduce the accessibility of these drugs to their target sites, resulting in a markedly reduced cytotoxic effect and drug resistance. Recently we have demonstrated that lysosomal sequestration of hydrophobic weak base drugs triggers TFEB-mediated lysosomal biogenesis resulting in an enlarged lysosomal compartment, capable of enhanced drug sequestration. This study further showed that cancer cells with an increased number of drug-accumulating lysosomes are more resistant to lysosome-sequestered drugs, suggesting a model of drug-induced lysosome-mediated chemoresistance. In addition to passive drug sequestration of hydrophobic weak base chemotherapeutics, other mechanisms of lysosome-mediated drug resistance have also been reported; these include active lysosomal drug sequestration mediated by ATP-driven transporters from the ABC superfamily, and a role for lysosomal copper transporters in cancer resistance to platinum-based chemotherapeutics. Furthermore, lysosomal exocytosis was suggested as a mechanism to facilitate the clearance of chemotherapeutics which highly accumulated in lysosomes, thus providing an additional line of resistance, supplementing the organelle entrapment of chemotherapeutics away from their target sites. Along with these mechanisms of lysosome-mediated drug resistance, several approaches were recently developed for the overcoming of drug resistance or exploiting lysosomal drug sequestration, including lysosomal photodestruction and drug-induced lysosomal membrane permeabilization. In this review we explore the current literature addressing the role of lysosomes in mediating cancer drug

Adenoviral-mediated placental gene transfer of IGF-1 corrects placental insufficiency via enhanced placental glucose transport mechanisms.

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Helen N Jones

Full Text Available Previous work in our laboratory demonstrated that over-expression of human insulin-like growth factor -1 (hIGF-1 in the placenta corrects fetal weight deficits in mouse, rat, and rabbit models of intrauterine growth restriction without changes in placental weight. The underlying mechanisms of this effect have not been elucidated. To investigate the effect of intra-placental IGF-1 over-expression on placental function we examined glucose transporter expression and localization in both a mouse model of IUGR and a model of human trophoblast, the BeWo Choriocarcinoma cell line.At gestational day 18, animals were divided into four groups; sham-operated controls, uterine artery branch ligation (UABL, UABL+Ad-hIGF-1 (10(8 PFU, UABL+Ad-LacZ (10(8 PFU. At gestational day 20, pups and placentas were harvested by C-section. For human studies, BeWo choriocarcinoma cells were grown in F12 complete medium +10%FBS. Cells were incubated in serum-free control media ± Ad-IGF-1 or Ad-LacZ for 48 hours. MOIs of 10∶1 and 100∶1 were utilized. The RNA, protein expression and localization of glucose transporters GLUT1, 3, 8, and 9 were analyzed by RT-PCR, Western blot and immunohistochemistry.In both the mouse placenta and BeWo, GLUT1 regulation was linked to altered protein localization. GLUT3, localized to the mouse fetal endothelial cells, was reduced in placental insufficiency but maintained with Ad-I GF-1 treatment. Interestingly, GLUT8 expression was reduced in the UABL placenta but up-regulated following Ad-IGF-1 in both mouse and human systems. GLUT9 expression in the mouse was increased by Ad-IGF-1 but this was not reflected in the BeWo, where Ad-IGF-1 caused moderate membrane relocalization.Enhanced GLUT isoform transporter expression and relocalization to the membrane may be an important mechanism in Ad-hIGF-1mediated correction of placental insufficiency.

Boron transport in plants: co-ordinated regulation of transporters

Science.gov (United States)

Miwa, Kyoko; Fujiwara, Toru

2010-01-01

Background The essentiality of boron (B) for plant growth was established >85 years ago. In the last decade, it has been revealed that one of the physiological roles of B is cross-linking the pectic polysaccharide rhamnogalacturonan II in primary cell walls. Borate cross-linking of pectic networks serves both for physical strength of cell walls and for cell adhesion. On the other hand, high concentrations of B are toxic to plant growth. To avoid deficiency and toxicity problems, it is important for plants to maintain their tissue B concentrations within an optimum range by regulating transport processes. Boron transport was long believed to be a passive, unregulated process, but the identification of B transporters has suggested that plants sense and respond to the B conditions and regulate transporters to maintain B homeostasis. Scope Transporters responsible for efficient B uptake by roots, xylem loading and B distribution among leaves have been described. These transporters are required under B limitation for efficient acquisition and utilization of B. Transporters important for tolerating high B levels in the environment have also been identified, and these transporters export B from roots back to the soil. Two types of transporters are involved in these processes: NIPs (nodulin-26-like intrinsic proteins), boric acid channels, and BORs, B exporters. It is demonstrated that the expression of genes encoding these transporters is finely regulated in response to B availability in the environment to ensure tissue B homeostasis. Furthermore, plants tolerant to stress produced by low B or high B in the environment can be generated through altered expression of these transporters. Conclusions The identification of the first B transporter led to the discovery that B transport was a process mediated not only by passive diffusion but also by transporters whose activity was regulated in response to B conditions. Now it is evident that plants sense internal and external B

Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport

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Nobuhiko Satoh

2015-01-01

Full Text Available A serine/threonine kinase Akt is a key mediator in various signaling pathways including regulation of renal tubular transport. In proximal tubules, Akt mediates insulin signaling via insulin receptor substrate 2 (IRS2 and stimulates sodium-bicarbonate cotransporter (NBCe1, resulting in increased sodium reabsorption. In insulin resistance, the IRS2 in kidney cortex is exceptionally preserved and may mediate the stimulatory effect of insulin on NBCe1 to cause hypertension in diabetes via sodium retention. Likewise, in distal convoluted tubules and cortical collecting ducts, insulin-induced Akt phosphorylation mediates several hormonal signals to enhance sodium-chloride cotransporter (NCC and epithelial sodium channel (ENaC activities, resulting in increased sodium reabsorption. Serum- and glucocorticoid-inducible kinase 1 (SGK1 mediates aldosterone signaling. Insulin can stimulate SGK1 to exert various effects on renal transporters. In renal cortical collecting ducts, SGK1 regulates the expression level of ENaC through inhibition of its degradation. In addition, SGK1 and Akt cooperatively regulate potassium secretion by renal outer medullary potassium channel (ROMK. Moreover, sodium-proton exchanger 3 (NHE3 in proximal tubules is possibly activated by SGK1. This review focuses on recent advances in understanding of the roles of Akt and SGK1 in the regulation of renal tubular transport.

Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice

NARCIS (Netherlands)

Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M.; Gautier, Emmanuel L.; Westerterp, Marit; Bittman, Robert; Tall, Alan R.; Chen, Shu-Hsia; Thomas, Michael J.; Kreisel, Daniel; Swartz, Melody A.; Sorci-Thomas, Mary G.; Randolph, Gwendalyn J.

2013-01-01

Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic

Students' Conceptions of Water Transport

Science.gov (United States)

Rundgren, Carl-Johan; Rundgren, Shu-Nu Chang; Schonborn, Konrad J.

2010-01-01

Understanding diffusion of water into and out of the cell through osmosis is fundamental to the learning and teaching of biology. Although this process is thought of as occurring directly across the lipid bilayer, the majority of water transport is actually mediated by specialised transmembrane water-channels called aquaporins. This study…

Lactate/H+ transport kinetics in rat skeletal muscle related to fibre type and changes in transport capacity

DEFF Research Database (Denmark)

Juel; Pilegaard

1998-01-01

muscles, muscles of old rats and rats that had been subjected to high-intensity training, endurance training, repeated exposure to hypoxia, and hypothyroid or hyperthyroid treatments. The lactate/H+ transport capacity of red muscles was greater than that of white muscles, and this difference...... and hypothyroidism was due to a decrease in Vmax. The denervation-induced decline in lactate/H+ transport capacity resulted from both an increased Km and a reduced Vmax. The present data show that muscle type differences and most changes in the lactate/H+ transport capacity are mediated by modifications in Vmax......, which is expected to represent the number of membrane transporter molecules. Km is unaffected by most treatments and appears to be independent of fibre type....

The rheology of non-suspended sediment transport mediated by a Newtonian fluid

Science.gov (United States)

Pähtz, Thomas; Durán, Orencio

2017-04-01

Using a coupled DEM/RANS numerical model of non-suspended sediment transport in a Newtonian fluid (Durán et al., POF 103306, 2012), we find that the gas-like part of the granular transport flow can be described by a universal condition that constrains the average geometry of interparticle collisions. We show that this condition corresponds to a constant sliding friction coefficient μ at an appropriately defined bed surface, thus explaining the success of Bagnold's old idea to describe the sediment transport in analogy to sliding friction. We are currently exploring whether this rheology applies to gas-like granular flows in general. We further find a transition of the gas-like flow to either a solid-like flow (solid-to-gas transition), which is typical for aeolian sediment transport ('saltation'), or a liquid-like flow (liquid-to-gas transition), which is typical for subaqueous sediment transport ('bedload'). The transition occurs at about the location of maximal particle collision frequency. If there is a liquid-like flow below the transition, we find that it can be described by a μ(I) rheology, where I is the visco-intertial number, an appropriately defined average of the viscous and intertial number.

New Insight Into the Diversity of SemiSWEET Sugar Transporters and the Homologs in Prokaryotes

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Baolei Jia

2018-05-01

Full Text Available Sugars will eventually be exported transporters (SWEETs and SemiSWEETs represent a family of sugar transporters in eukaryotes and prokaryotes, respectively. SWEETs contain seven transmembrane helices (TMHs, while SemiSWEETs contain three. The functions of SemiSWEETs are less studied. In this perspective article, we analyzed the diversity and conservation of SemiSWEETs and further proposed the possible functions. 1,922 SemiSWEET homologs were retrieved from the UniProt database, which is not proportional to the sequenced prokaryotic genomes. However, these proteins are very diverse in sequences and can be classified into 19 clusters when >50% sequence identity is required. Moreover, a gene context analysis indicated that several SemiSWEETs are located in the operons that are related to diverse carbohydrate metabolism. Several proteins with seven TMHs can be found in bacteria, and sequence alignment suggested that these proteins in bacteria may be formed by the duplication and fusion. Multiple sequence alignments showed that the amino acids for sugar translocation are still conserved and coevolved, although the sequences show diversity. Among them, the functions of a few amino acids are still not clear. These findings highlight the challenges that exist in SemiSWEETs and provide future researchers the foundation to explore these uncharted areas.

Lysosome Transport as a Function of Lysosome Diameter

Science.gov (United States)

Bandyopadhyay, Debjyoti; Cyphersmith, Austin; Zapata, Jairo A.; Kim, Y. Joseph; Payne, Christine K.

2014-01-01

Lysosomes are membrane-bound organelles responsible for the transport and degradation of intracellular and extracellular cargo. The intracellular motion of lysosomes is both diffusive and active, mediated by motor proteins moving lysosomes along microtubules. We sought to determine how lysosome diameter influences lysosome transport. We used osmotic swelling to double the diameter of lysosomes, creating a population of enlarged lysosomes. This allowed us to directly examine the intracellular transport of the same organelle as a function of diameter. Lysosome transport was measured using live cell fluorescence microscopy and single particle tracking. We find, as expected, the diffusive component of intracellular transport is decreased proportional to the increased lysosome diameter. Active transport of the enlarged lysosomes is not affected by the increased lysosome diameter. PMID:24497985

Mediator-assisted photocurrent extraction from the thylakoids

International Nuclear Information System (INIS)

Yu, Yue; Zuo, Fulin; Li, Chen-Zhong

2014-01-01

Photocurrent extracted from the thylakoids has been studied as a function of electron mediator concentration. Phenazine methosulfate is used to facilitate the charge transfer from the thylakoid's charge transport chain to the outside medium. The photocurrent has been shown to originate from the photosynthesis on the thylakoid membranes. Comparing with a previous study using para-Benzoquinone as the mediator, a similar peak effect in the photocurrent as a function of concentration is observed, but the magnitude of the current is nearly a thousand times greater. A semi-quantitative analysis is presented to explain the data found in those systems

Image transport through a disordered optical fibre mediated by transverse Anderson localization

Science.gov (United States)

Karbasi, Salman; Frazier, Ryan J.; Koch, Karl W.; Hawkins, Thomas; Ballato, John; Mafi, Arash

2014-02-01

Transverse Anderson localization of light allows localized optical-beam-transport through a transversely disordered and longitudinally invariant medium. Its successful implementation in disordered optical fibres recently resulted in the propagation of localized beams of radii comparable to that of conventional optical fibres. Here we demonstrate optical image transport using transverse Anderson localization of light. The image transport quality obtained in the polymer disordered optical fibre is comparable to or better than some of the best commercially available multicore image fibres with less pixelation and higher contrast. It is argued that considerable improvement in image transport quality can be obtained in a disordered fibre made from a glass matrix with near wavelength-size randomly distributed air-holes with an air-hole fill-fraction of 50%. Our results open the way to device-level implementation of the transverse Anderson localization of light with potential applications in biological and medical imaging.

In Vitro Analysis of Metabolite Transport Proteins.

Science.gov (United States)

Roell, Marc-Sven; Kuhnert, Franziska; Zamani-Nour, Shirin; Weber, Andreas P M

2017-01-01

The photorespiratory cycle is distributed over four cellular compartments, the chloroplast, peroxisomes, cytoplasm, and mitochondria. Shuttling of photorespiratory intermediates between these compartments is essential to maintain the function of photorespiration. Specific transport proteins mediate the transport across biological membranes and represent important components of the cellular metabolism. Although significant progress was made in the last years on identifying and characterizing new transport proteins, the overall picture of intracellular metabolite transporters is still rather incomplete. The photorespiratory cycle requires at least 25 transmembrane transport steps; however to date only plastidic glycolate/glycerate transporter and the accessory 2-oxoglutarate/malate and glutamate/malate transporters as well as the mitochondrial transporter BOU1 have been identified. The characterization of transport proteins and defining their substrates and kinetics are still major challenges.Here we present a detailed set of protocols for the in vitro characterization of transport proteins. We provide protocols for the isolation of recombinant transport protein expressed in E. coli or Saccharomyces cerevisiae and the extraction of total leaf membrane protein for in vitro analysis of transporter proteins. Further we explain the process of reconstituting transport proteins in artificial lipid vesicles and elucidate the details of transport assays.

Regulation of transport in the connecting tubule and cortical collecting duct

Science.gov (United States)

Staruschenko, Alexander

2012-01-01

The central goal of this overview article is to summarize recent findings in renal epithelial transport, focusing chiefly on the connecting tubule (CNT) and the cortical collecting duct (CCD). Mammalian CCD and CNT are involved in fine tuning of electrolyte and fluid balance through reabsorption and secretion. Specific transporters and channels mediate vectorial movements of water and solutes in these segments. Although only a small percent of the glomerular filtrate reaches the CNT and CCD, these segments are critical for water and electrolyte homeostasis since several hormones, e.g. aldosterone and arginine vasopressin, exert their main effects in these nephron sites. Importantly, hormones regulate the function of the entire nephron and kidney by affecting channels and transporters in the CNT and CCD. Knowledge about the physiological and pathophysiological regulation of transport in the CNT and CCD and particular roles of specific channels/transporters has increased tremendously over the last two decades. Recent studies shed new light on several key questions concerning the regulation of renal transport. Precise distribution patterns of transport proteins in the CCD and CNT will be reviewed, and their physiological roles and mechanisms mediating ion transport in these segments will be also covered. Special emphasis will be given to pathophysiological conditions appearing as a result of abnormalities in renal transport in the CNT and CCD. PMID:23227301

Species differences in ligand specificity of auxin-controlled elongation and auxin transport: comparing Zea and Vigna

Science.gov (United States)

Zhao, Hu; Hertel, Rainer; Ishikawa, Hideo; Evans, Michael L.

2002-01-01

The plant hormone auxin affects cell elongation in both roots and shoots. In roots, the predominant action of auxin is to inhibit cell elongation while in shoots auxin, at normal physiological levels, stimulates elongation. The question of whether the primary receptor for auxin is the same in roots and shoots has not been resolved. In addition to its action on cell elongation in roots and shoots, auxin is transported in a polar fashion in both organs. Although auxin transport is well characterized in both roots and shoots, there is relatively little information on the connection, if any, between auxin transport and its action on elongation. In particular, it is not clear whether the protein mediating polar auxin movement is separate from the protein mediating auxin action on cell elongation or whether these two processes might be mediated by one and the same receptor. We examined the identity of the auxin growth receptor in roots and shoots by comparing the response of roots and shoots of the grass Zea mays L. and the legume Vigna mungo L. to indole-3-acetic acid, 2-naphthoxyacetic acid, 4,6-dichloroindoleacetic acid, and 4,7-dichloroindoleacetic acid. We also studied whether or not a single protein might mediate both auxin transport and auxin action by comparing the polar transport of indole-3-acetic acid and 2-naphthoxyacetic acid through segments from Vigna hypocotyls and maize coleoptiles. For all of the assays performed (root elongation, shoot elongation, and polar transport) the action and transport of the auxin derivatives was much greater in the dicots than in the grass species. The preservation of ligand specificity between roots and shoots and the parallels in ligand specificity between auxin transport and auxin action on growth are consistent with the hypothesis that the auxin receptor is the same in roots and shoots and that this protein may mediate auxin efflux as well as auxin action in both organ types.

Reparación protésica de hernias inguinales con técnica de Lichtenstein

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Ernesto Simón Enríquez Weinmann

2003-03-01

Full Text Available Se presentan los resultados de un estudio prospectivo que trata de la colocación de prótesis por vía anterior en la reparación de hernias inguinales con la utilización de variantes técnicas propuestas por Lichtenstein. Se incluye un total de 150 pacientes, a los que se les realizó operación, desde septiembre de 1996 hasta febrero de 2001; en 100 de éstos se practicó la técnica de reforzamiento protésico inicialmente descrita por Lichtenstein, y en 50, la técnica libre de tensión. Se realizaron 93 herniorrafias primarias, y 57 en hernias recidivadas, 10 de ellas iteradas. El tipo de hernia más frecuentemente operado según la clasificación de Gilbert modificada, fue la tipo III; 8 pacientes presentaban hernia en pantalón (tipo VI. La anestesia más frecuentemente usada fue la regional, y le siguió en frecuencia la anestesia general, local y analgesia acupuntural. Las complicaciones se comportaron de manera similar a las técnicas tradicionales, donde 26 pacientes presentaron complicaciones inmediatas menores. Ocurrió sepsis de la herida en un caso (0,6 %, y hasta la fecha no se han verificado recidivas, con un seguimiento promedio de 39 meses (12-66 del 100 % de los casos. Se sustenta la enseñanza del reforzamiento protésico para el cirujano en formaciónThe results of a prospective study dealing with the placement of prostheses by anterior route in the repair of inguinal hernias by using the technical variants proposed by Lichtenstein were presented. 150 patients who were operated on from September, 1996, to February, 2001, were included. The prosthetic reinforcement technique initially described by Lichtenstein was performed in 100, whereas the free-tension technique was used in 50 patients. 93 primary herniorraphies were performed. 57 were carried out in recurrent hernias, 10 of them iterated. Type III was the type of hernia most commonly operated on, according to Gilbert classification. 8 patients presented type VI hernia

Polyamines mediate abnormal Ca2+ transport and Ca2+-induced cardiac cell injury in the calcium paradox

International Nuclear Information System (INIS)

Trout, J.J.; Koenig, H.; Goldstone, A.D.; Lu, C.Y.; Fan, C.C.

1986-01-01

Ca 2+ -free perfusion renders heart cells Ca 2+ -sensitive so that readmission of Ca 2+ causes a sudden massive cellular injury attributed to abnormal entry of Ca 2+ into cells (Ca paradox). Hormonal stimulation of Ca 2+ fluxes was earlier shown to be mediated by polyamines (PA). 5 min perfusion of rat heart with Ca 2+ -free medium induce a prompt 40-50% decline in levels of the PA putrescine (PUT), spermidine and spermine and their rate-regulatory synthetic enzyme ornithine decarboxylase (ODC), and readmission of Ca 2+ -containing medium abruptly ( 2+ reperfusion-induced increases in ODC and PA and also prevented increased 45 Ca 2+ uptake and heart injury, manifested by loss of contractility, release of enzymes (CPK, LDH), myoglobin and protein, and E.M. lesions (contracture bands, mitochondrial changes). 1 mM PUT negated DFMO inhibition, repleted heart PA and restored Ca 2+ reperfusion-induced 45 Ca 2+ influx and cell injury. These data indicate that the Ca 2+ -directed depletion-repletion cycle of ODC and PA triggers excessive transsarcolemmal Ca 2+ transport leading to the calcium paradox

Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate cotransporting polypeptide and organic anion transporting polypeptides and modulated by intestinal sensing of plasma bile acid levels in mice.

Science.gov (United States)

Slijepcevic, Davor; Roscam Abbing, Reinout L P; Katafuchi, Takeshi; Blank, Antje; Donkers, Joanne M; van Hoppe, Stéphanie; de Waart, Dirk R; Tolenaars, Dagmar; van der Meer, Jonathan H M; Wildenberg, Manon; Beuers, Ulrich; Oude Elferink, Ronald P J; Schinkel, Alfred H; van de Graaf, Stan F J

2017-11-01

The Na + -taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport proteins mediate the hepatic uptake of conjugated bile acids and demonstrated intestinal sensing of elevated bile acid levels in plasma in mice. Mice or healthy volunteers were treated with myrcludex B. Hepatic bile acid uptake kinetics were determined in wild-type (WT), organic anion transporting polypeptide (OATP) knockout mice (lacking Slco1a/1b isoforms), and human OATP1B1-transgenic mice. Effects of fibroblast growth factor 19 (FGF19) on hepatic transporter mRNA levels were assessed in rat hepatoma cells and in mice by peptide injection or adeno-associated virus-mediated overexpression. NTCP inhibition using myrcludex B had only moderate effects on bile acid kinetics in WT mice, but completely inhibited active transport of conjugated bile acid species in OATP knockout mice. Cholesterol 7α-hydroxylase Cyp7a1 expression was strongly down-regulated upon prolonged inhibition of hepatic uptake of conjugated bile acids. Fgf15 (mouse counterpart of FGF19) expression was induced in hypercholanemic OATP and NTCP knockout mice, as well as in myrcludex B-treated cholestatic mice, whereas plasma FGF19 was not induced in humans treated with myrcludex B. Fgf15/FGF19 expression was induced in polarized human enterocyte-models and mouse organoids by basolateral incubation with a high concentration (1 mM) of conjugated bile acids. NTCP and OATPs contribute to hepatic uptake of conjugated bile acids in mice, whereas the predominant uptake in humans is NTCP mediated. Enterocytes sense highly elevated levels of (conjugated) bile acids in the systemic circulation to induce FGF15/19, which modulates hepatic bile acid synthesis and uptake. (Hepatology 2017;66:1631-1643). �

Influence of norepinephrine transporter inhibition on hemodynamic response to hypergravitation

OpenAIRE

Strempel, Sebastian

2011-01-01

Background: Sympathetically-mediated tachycardia and vasoconstriction maintain blood pressure during hypergravitational stress, thereby preventing gravitation-induced loss of consciousness (g-LOC). Norepinephrine transporter (NET) inhibition prevents neurally-mediated (pre)syncope during gravitational stress imposed by head-up tilt testing. Thus, it seems reasonable that NET inhibition could increase tolerance to hypergravitational stress. Methods. We performed a double-blind, randomized...

Exigência protéica de juvenis de tambaqui (Colossoma macropomum após privação alimentar Protein requirement of tambaqui juveniles (Colossoma macropomum after feed deprivation

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Luciana Santos

2010-09-01

Full Text Available O objetivo deste trabalho foi avaliar a exigência protéica de juvenis de tambaqui (Colossoma macropomum após a privação alimentar. Os peixes (50,3 ± 0,26g foram submetidos a quatro rações isoenergéticas com diferentes concentrações protéicas (28, 32, 36 e 40% proteína bruta e dois regimes alimentares (com privação e sem privação durante 60 dias. O delineamento experimental foi inteiramente casualizado, em esquema fatorial 4x2, em triplicata. Avaliaram-se os parâmetros de qualidade de água e de desempenho no 1º, 15º e 60º dia de experimento. Os parâmetros da qualidade da água permaneceram dentro dos padrões de cultivo. Não houve mortalidade nos tratamentos testados. Foram observados diferenças entre os tratamentos para os índices de desempenho analisados: taxa de crescimento específico, eficiência alimentar, consumo diário de ração, consumo de proteína bruta, taxa de eficiência protéica e ganho de peso relativo, com exceção do índice hepatossomático. Houve hiperfagia, indicando a existência de crescimento compensatório. Os peixes realimentados com 36% proteína bruta tiveram incremento no teor de gordura visceral e maior deposição de proteína corporal. Estes resultados explicam uma melhora nos dados de ganho de peso, duração da hiperfagia, taxa de crescimento e eficiência alimentar. A privação alimentar não influencia a exigência protéica em juvenis de tambaqui.The aim of this work was evaluate protein requirement of tambaqui (Colossoma macropomum juveniles after feed deprivation. During 60 days, fish (50,3 ± 0,26 g were fed on four isoenergetics diets with different protein content (28, 32, 36 and 40% crude protein at two feeding regimes (with and without feed deprivation under completely random factorial design (4x2 in triplicate. Water quality parameters and performance index were evaluated at 1º, 15º and 60º days. Water quality parameters were kept at normal fish cultivation patterns

The emerging physiological roles of the SLC14A family of urea transporters

Science.gov (United States)

Stewart, Gavin

2011-01-01

In mammals, urea is the main nitrogenous breakdown product of protein catabolism and is produced in the liver. In certain tissues, the movement of urea across cell membranes is specifically mediated by a group of proteins known as the SLC14A family of facilitative urea transporters. These proteins are derived from two distinct genes, UT-A (SLC14A2) and UT-B (SLC14A1). Facilitative urea transporters play an important role in two major physiological processes – urinary concentration and urea nitrogen salvaging. Although UT-A and UT-B transporters both have a similar basic structure and mediate the transport of urea in a facilitative manner, there are a number of significant differences between them. UT-A transporters are mainly found in the kidney, are highly specific for urea, have relatively lower transport rates and are highly regulated at both gene expression and cellular localization levels. In contrast, UT-B transporters are more widespread in their tissue location, transport both urea and water, have a relatively high transport rate, are inhibited by mercurial compounds and currently appear to be less acutely regulated. This review details the fundamental research that has so far been performed to investigate the function and physiological significance of these two types of urea transporters. PMID:21449978

Exploring the human plasma proteome for humoral mediators of remote ischemic preconditioning--a word of caution.

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Erik Helgeland

Full Text Available Despite major advances in early revascularization techniques, cardiovascular diseases are still the leading cause of death worldwide, and myocardial infarctions contribute heavily to this. Over the past decades, it has become apparent that reperfusion of blood to a previously ischemic area of the heart causes damage in and of itself, and that this ischemia reperfusion induced injury can be reduced by up to 50% by mechanical manipulation of the blood flow to the heart. The recent discovery of remote ischemic preconditioning (RIPC provides a non-invasive approach of inducing this cardioprotection at a distance. Finding its endogenous mediators and their operative mode is an important step toward increasing the ischemic tolerance. The release of humoral factor(s upon RIPC was recently demonstrated and several candidate proteins were published as possible mediators of the cardioprotection. Before clinical applicability, these potential biomarkers and their efficiency must be validated, a task made challenging by the large heterogeneity in reported data and results. Here, in an attempt to reproduce and provide more experimental data on these mediators, we conducted an unbiased in-depth analysis of the human plasma proteome before and after RIPC. From the 68 protein markers reported in the literature, only 28 could be mapped to manually reviewed (Swiss-Prot protein sequences. 23 of them were monitored in our untargeted experiment. However, their significant regulation could not be reproducibly estimated. In fact, among the 394 plasma proteins we accurately quantified, no significant regulation could be confidently and reproducibly assessed. This indicates that it is difficult to both monitor and reproduce published data from experiments exploring for RIPC induced plasma proteomic regulations, and suggests that further work should be directed towards small humoral factors. To simplify this task, we made our proteomic dataset available via Proteome

Exploring the Human Plasma Proteome for Humoral Mediators of Remote Ischemic Preconditioning - A Word of Caution

Science.gov (United States)

Helgeland, Erik; Breivik, Lars Ertesvåg; Vaudel, Marc; Svendsen, Øyvind Sverre; Garberg, Hilde; Nordrehaug, Jan Erik; Berven, Frode Steingrimsen; Jonassen, Anne Kristine

2014-01-01

Despite major advances in early revascularization techniques, cardiovascular diseases are still the leading cause of death worldwide, and myocardial infarctions contribute heavily to this. Over the past decades, it has become apparent that reperfusion of blood to a previously ischemic area of the heart causes damage in and of itself, and that this ischemia reperfusion induced injury can be reduced by up to 50% by mechanical manipulation of the blood flow to the heart. The recent discovery of remote ischemic preconditioning (RIPC) provides a non-invasive approach of inducing this cardioprotection at a distance. Finding its endogenous mediators and their operative mode is an important step toward increasing the ischemic tolerance. The release of humoral factor(s) upon RIPC was recently demonstrated and several candidate proteins were published as possible mediators of the cardioprotection. Before clinical applicability, these potential biomarkers and their efficiency must be validated, a task made challenging by the large heterogeneity in reported data and results. Here, in an attempt to reproduce and provide more experimental data on these mediators, we conducted an unbiased in-depth analysis of the human plasma proteome before and after RIPC. From the 68 protein markers reported in the literature, only 28 could be mapped to manually reviewed (Swiss-Prot) protein sequences. 23 of them were monitored in our untargeted experiment. However, their significant regulation could not be reproducibly estimated. In fact, among the 394 plasma proteins we accurately quantified, no significant regulation could be confidently and reproducibly assessed. This indicates that it is difficult to both monitor and reproduce published data from experiments exploring for RIPC induced plasma proteomic regulations, and suggests that further work should be directed towards small humoral factors. To simplify this task, we made our proteomic dataset available via ProteomeXchange, where

Evidence for aquaporin-mediated water transport in nematocytes of the jellyfish Pelagia noctiluca.

Science.gov (United States)

Marino, Angela; Morabito, Rossana; La Spada, Giuseppina; Adragna, Norma C; Lauf, Peter K

2011-01-01

Nematocytes, the stinging cells of Cnidarians, have a cytoplasm confined to a thin rim. The main cell body is occupied by an organoid, the nematocyst, containing the stinging tubule and venom. Exposed to hypotonic shock, nematocytes initially swell during an osmotic phase (OP) and then undergo regulatory volume decrease (RVD) driven by K(+), Cl(-) and obligatory water extrusion mechanisms. The purpose of this report is to characterize the OP. Nematocytes were isolated by the NaSCN/Ca(2+) method from tentacles of the jellyfish Pelagia noctiluca, collected in the Strait of Messina, Italy. Isolated nematocytes were subjected to hyposmotic shock in 65% artificial seawater (ASW) for 15 min. The selective aquaporin water channel inhibitor HgCl(2) (0.1-25 μM) applied prior to osmotic shock prevented the OP and thus RVD. These effects were attenuated in the presence of 1mM dithiothreitol (DTT), a mercaptide bond reducing agent. AgNO(3) (1 μM) and TEA (tetraethylammonium, 100 μM), also reported to inhibit water transport, did not alter the OP but significantly diminished RVD, suggesting different modes of action for the inhibitors tested. Based on estimates of the nematocyte surface area and volume, and OP duration, a relative water permeability of ~10(-7) cm/sec was calculated and the number of putative aquaporin molecules mediating the OP was estimated. This water permeability is 3-4 orders of magnitude lower in comparison to higher order animals and may constitute an evolutionary advantage for Cnidarian survival. Copyright © 2011 S. Karger AG, Basel.

Co-treatment with grapefruit juice inhibits while chronic administration activates intestinal P-glycoprotein-mediated drug efflux.

Science.gov (United States)

Panchagnula, R; Bansal, T; Varma, M V S; Kaul, C L

2005-12-01

P-Glycoprotein (P-gp) mediated efflux is recognized as a significant biochemical barrier affecting oral absorption for a number of drugs. Various conflicting reports have been published regarding the effects of grapefruit juice (GFJ) on P-gp-mediated drug efflux, in which GFJ has been shown both to inhibit and activate it. Hence, the present study adopted a two-way approach, involving both co-treatment and chronic administration. Bi-directional transport of paclitaxel (PCL) was carried out in the absence and presence of GFJ extract, in rat everted ileum sac. Further, the effect of chronic administration of GFJ to rats was characterized by permeability studies with indinavir (INDI). Co-treatment of GFJ extract at 100% concentration reduced the asymmetric transport of PCL (efflux ratio = 20.8) by increasing absorptive (A --> B) transport by 921% and reducing secretory (B --> A) transport by 41%. Further, GFJ showed a concentration dependent effect on PCL permeability. Imipramine, a passive permeability marker with absorptive permeability of 15.33 +/- 4.26 x 10(-6) cm/s showed no asymmetric transport and also no significant (P extract inhibited P-gp-mediated efflux in co-treatment, whereas chronic administration led to increased levels of P-gp expression, thus having a profound effect on intestinal absorption and GFJ-drug interactions in vivo.

Anion transport and GABA signaling

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Christian Andreas Huebner

2013-10-01

Full Text Available Whereas activation of GABAA receptors by GABA usually results in a hyperpolarizing influx of chloride into the neuron, the reversed chloride driving force in the immature nervous system results in a depolarizing efflux of chloride. This GABAergic depolarization is deemed to be important for the maturation of the neuronal network. The concept of a developmental GABA switch has mainly been derived from in vitro experiments and reliable in vivo evidence is still missing. As GABAA receptors are permeable for both chloride and bicarbonate, the net effect of GABA also critically depends on the distribution of bicarbonate. Whereas chloride can either mediate depolarizing or hyperpolarizing currents, bicarbonate invariably mediates a depolarizing current under physiological conditions. Intracellular bicarbonate is quickly replenished by cytosolic carbonic anhydrases. Intracellular bicarbonate levels also depend on different bicarbonate transporters expressed by neurons. The expression of these proteins is not only developmentally regulated but also differs between cell types and even subcellular regions. In this review we will summarize current knowledge about the role of some of these transporters for brain development and brain function.

Fontes protéicas vegetais na alimentação da carpa húngara Plant protein sources on common carp feeding

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Giovani Taffarel Bergamin

2011-09-01

Full Text Available A substituição parcial da farinha de carne suína por farelos vegetais em dietas para juvenis de carpa húngara (Cyprinus carpio foi avaliada em cinco dietas experimentais: um controle (farinha de carne suína (FCS como fonte protéica e quatro dietas vegetais: farelo de soja (FS, farelo de canola (FC, farelo de girassol (FG ou farelo de linhaça (FL, substituindo 50% da proteína proveniente da FCS. 195 juvenis (43,4±0,4g foram alimentados duas vezes ao dia (9 e 15 horas durante 71 dias. Ao final do experimento, maior peso (205,69g, ganho em peso (2,29g dia-1, taxa de crescimento específico (2,2% dia-1 e conversão alimentar (1,74 foram obtidos nas dietas com FCS, seguido dos tratamentos FC e FS que não diferiram entre si. Os peixes alimentados com FCS, FG e FS apresentaram maior gordura corporal. A dieta FL apresentou piores resultados de desempenho, coeficiente de retenção protéica, deposição de proteína e gordura corporal e no filé. Pode-se concluir que a dieta à base de farinha de carne suína proporciona maior crescimento e deposição de proteína em juvenis de carpa húngara, comparada às dietas com farelos vegetais; os parâmetros de carcaça (rendimentos e índices digestivos não são afetados pelas fontes protéicas da dieta.This study was conducted to evaluate the partial replacement of porcine meat meal by plant-protein meals in diets for common carp (Cyprinus carpio. Five experimental diets were evaluated: control (FCS, only porcine meat meal as protein source, and four plant-based diets: soybean meal (FS, canola meal (FC, sunflower meal (FG or linseed meal (FL replacing 50% of protein from porcine meat meal. Juveniles (195, 43.4±0.4g were fed twice daily (9:00 am and 03:00pm for 71 days. At the end of the trial, the best weight (205,69g, weight gain (2,29g day-1, specific growth rate (2,2% day-1 and food conversion ratio (1,74 were obtained in FCS, followed by FC and FS, that did not differ among each other. Fish

Electric Field Mediated Ion Transport Through Charged Mesoporous Membranes

NARCIS (Netherlands)

Schmuhl, R.; de Lint, W.B.S.; Keizer, Klaas; van den Berg, Albert; ten Elshof, Johan E.; Burganos, Vasilis N.; Noble, Richard D.; Asaeda, Masashi; Ayral, Andre; LeRoux, Johann D.

2003-01-01

The transport of ions from aqueous solutions through a stacked Au/alpha-alumina/gamma-alumina/Au membrane under the influence of a dc potential difference is reported. The membrane shows high cation permselectivity at ionic strengths of ~1 mM at pH 4.3-6.5, which is associated with a combination of

Sugar and Glycerol Transport in Saccharomyces cerevisiae.

Science.gov (United States)

Bisson, Linda F; Fan, Qingwen; Walker, Gordon A

2016-01-01

In Saccharomyces cerevisiae the process of transport of sugar substrates into the cell comprises a complex network of transporters and interacting regulatory mechanisms. Members of the large family of hexose (HXT) transporters display uptake efficiencies consistent with their environmental expression and play physiological roles in addition to feeding the glycolytic pathway. Multiple glucose-inducing and glucose-independent mechanisms serve to regulate expression of the sugar transporters in yeast assuring that expression levels and transporter activity are coordinated with cellular metabolism and energy needs. The expression of sugar transport activity is modulated by other nutritional and environmental factors that may override glucose-generated signals. Transporter expression and activity is regulated transcriptionally, post-transcriptionally and post-translationally. Recent studies have expanded upon this suite of regulatory mechanisms to include transcriptional expression fine tuning mediated by antisense RNA and prion-based regulation of transcription. Much remains to be learned about cell biology from the continued analysis of this dynamic process of substrate acquisition.

Mechanism of ochratoxin A transport in kidney

International Nuclear Information System (INIS)

Sokol, P.P.; Ripich, G.; Holohan, P.D.; Ross, C.R.

1988-01-01

The effect of the fungal metabolite (mycotoxin) Ochratoxin A (OTA) on the transport of p-amino[ 3 H]hippurate (PAH), a prototypic organic anion, was examined in renal brush border (BBMV) and basolateral membrane vesicles (BLMV). OTA was as effective an inhibitor of PAH uptake in both membranes as probenecid. The dose response curves for OTA in BBMV and BLMV gave IC50 values of 20 +/- 6 and 32 +/- 7 microM, respectively. The effect was specific since the transport of the organic cation N1-methylnicotinamide was not affected. The phenomenon of counterflow was studied to establish that OTA is translocated. OTA produced trans stimulation of PAH transport in both BBMV and BLMV, demonstrating that OTA is transported across both these membranes. The data suggest that OTA interacts with the PAH transport system in both BBMV and BLMV. We conclude that OTA transport in the kidney is mediated via the renal organic anion transport system

Electric field-mediated transport of plasmid DNA in tumor interstitium in vivo.

Science.gov (United States)

Henshaw, Joshua W; Zaharoff, David A; Mossop, Brian J; Yuan, Fan

2007-11-01

Local pulsed electric field application is a method for improving non-viral gene delivery. Mechanisms of the improvement include electroporation and electrophoresis. To understand how electrophoresis affects pDNA delivery in vivo, we quantified the magnitude of electric field-induced interstitial transport of pDNA in 4T1 and B16.F10 tumors implanted in mouse dorsal skin-fold chambers. Four different electric pulse sequences were used in this study, each consisted of 10 identical pulses that were 100 or 400 V/cm in strength and 20 or 50 ms in duration. The interval between consecutive pulses was 1 s. The largest distance of transport was obtained with the 400 V/cm and 50 ms pulse, and was 0.23 and 0.22 microm/pulse in 4T1 and B16.F10 tumors, respectively. There were no significant differences in transport distances between 4T1 and B16.F10 tumors. Results from in vivo mapping and numerical simulations revealed an approximately uniform intratumoral electric field that was predominantly in the direction of the applied field. The data in the study suggested that interstitial transport of pDNA induced by a sequence of ten electric pulses was ineffective for macroscopic delivery of genes in tumors. However, the induced transport was more efficient than passive diffusion.

Bioensayo preclínico de nuevos adhesivos tisulares sintéticos (cianoacrilatos) en implantes de materiales protésicos destinados a reparar defectos de parted abdominal

OpenAIRE

Kühnhardt Barrantes, Andrée Wolfgang

2016-01-01

Una de las indicaciones de los adhesivos tisulares (AT), es su empleo para la fijación de materiales protésicos en la reparación herniaria. El propósito de este trabajo de Tesis, ha sido analizar de forma experimental, el comportamiento intraperitoneal y extraperitoneal un nuevo AT de cianoacrilato (n-octilo), comparándolo con un AT comercial (Ifabond®). En el modelo intraperitoneal, se fijaron fragmentos de prótesis de PTFEe de 3x3 cm sobre el peritoneo parietal del animal de experimentació...

Solute carrier transporters: potential targets for digestive system neoplasms.

Science.gov (United States)

Xie, Jing; Zhu, Xiao Yan; Liu, Lu Ming; Meng, Zhi Qiang

2018-01-01

Digestive system neoplasms are the leading causes of cancer-related death all over the world. Solute carrier (SLC) superfamily is composed of a series of transporters that are ubiquitously expressed in organs and tissues of digestive systems and mediate specific uptake of small molecule substrates in facilitative manner. Given the important role of SLC proteins in maintaining normal functions of digestive system, dysregulation of these protein in digestive system neoplasms may deliver biological and clinical significance that deserves systemic studies. In this review, we critically summarized the recent advances in understanding the role of SLC proteins in digestive system neoplasms. We highlighted that several SLC subfamilies, including metal ion transporters, transporters of glucose and other sugars, transporters of urea, neurotransmitters and biogenic amines, ammonium and choline, inorganic cation/anion transporters, transporters of nucleotide, amino acid and oligopeptide organic anion transporters, transporters of vitamins and cofactors and mitochondrial carrier, may play important roles in mediating the initiation, progression, metastasis, and chemoresistance of digestive system neoplasms. Proteins in these SLC subfamilies may also have diagnostic and prognostic values to particular cancer types. Differential expression of SLC proteins in tumors of digestive system was analyzed by extracting data from human cancer database, which revealed that the roles of SLC proteins may either be dependent on the substrates they transport or be tissue specific. In addition, small molecule modulators that pharmacologically regulate the functions of SLC proteins were discussed for their possible application in the treatment of digestive system neoplasms. This review highlighted the potential of SLC family proteins as drug target for the treatment of digestive system neoplasms.

Desarrollo por ultrafiltración de un concentrado protéico a partir de lactosuero / Protein concentrate from whey developed by ultrafiltration

OpenAIRE

Riquelme Gymesy, Luis Felipe

2010-01-01

Esta monografía se centra en la operación de un sistema de ultrafiltración con miras a la obtención de un concentrado protéico a partir del subproducto de la elaboración de quesos: el suero lácteo. Se propone la metodología de operación del equipo con que cuenta el Instituto de Ciencia y Tecnología de Alimentos (ICTA), el cual mediante unos ajustes, podría entrar en operación en el corto plazo. Se hace una exhaustiva revisión, de acuerdo a los manuales de operación proveídos por el fabricante...

Identification and characterization of jasmonate transporters

DEFF Research Database (Denmark)

Lambertz, Sophie Konstanze

of the stimulus but also in distal tissues. The systemic accumulation has been the focus of many studies, which proposed that jasmonate is transported over long and short distances to induce defense responses. However, our knowledge of jasmonate transporting elements is marginal. In this thesis, two jasmonate...... Spodoptera littoralis and the fungus Botrytis cinerea was tested. Wounding assays indicate that the JEFFs are involved in systemic induction of the defense compounds glucosinolates, which may be caused by a JEFF mediated shift of jasmonate precursors to the biologically active form of jasmonates. Further...

Polycyclic Aromatic Hydrocarbons (PAHs) Mediate Transcriptional Activation of the ATP Binding Cassette Transporter ABCB6 Gene via the Aryl Hydrocarbon Receptor (AhR)*

Science.gov (United States)

Chavan, Hemantkumar; Krishnamurthy, Partha

2012-01-01

Liver is endowed with a mechanism to induce hepatic cytochromes P450 (CYP450s) in response to therapeutic drugs and environmental contaminants, leading to increased detoxification and elimination of the xenobiotics. Each CYP450 is composed of an apoprotein moiety and a heme prosthetic group, which is required for CYP450 activity. Thus, under conditions of CYP450 induction, there is a coordinate increase in heme biosynthesis to compensate for the increased expression of CYP450s. ABCB6, a mitochondrial ATP binding cassette transporter, which regulates coproporphyrinogen transport from the cytoplasm into the mitochondria to complete heme biosynthesis, represents a previously unrecognized rate-limiting step in heme biosynthesis. However, it is not known if exposure to drugs and environmental contaminants induces ABCB6 expression, to assure an adequate and apparently coordinated supply of heme for the generation of functional cytochrome holoprotein. In the present study, we demonstrate that polycyclic aromatic hydrocarbons (PAHs), the widely distributed environmental toxicants shown to induce porphyrin accumulation causing hepatic porphyria, up-regulate ABCB6 expression in both mice and humans. Using siRNA technology and Abcb6 knock-out mice, we demonstrate that PAH-mediated increase in hepatic porphyrins is compromised in the absence of ABCB6. Moreover, in vivo studies in aryl hydrocarbon receptor (AhR) knock-out mice demonstrate that PAH induction of ABCB6 is mediated by AhR. Promoter activation studies combined with electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrate direct interactions between the AhR binding sites in the ABCB6 promoter and the AhR receptor, implicating drug activation mechanisms for ABCB6 similar to those found in inducible cytochrome P450s. These studies are the first to describe direct transcriptional activation of both mouse and human ABCB6 by xenobiotics. PMID:22761424

Identificação de peptídeos hipocolesterolemizantes do isolado protéico do grão de amaranto (Amaranthus cruentus L. BRS-Alegria)

OpenAIRE

Rosana Aparecida Manolio Soares

2008-01-01

Introdução: Dentre os distúrbios relacionados à alimentação, o aumento do colesterol e, conseqüentemente, a incidência de doenças cardiovasculares, representa um importante problema de Saúde Pública. A proteína do amaranto reduz o colesterol plasmático, possivelmente pela presença de peptídeos bioativos, liberados durante sua digestão parcial. Objetivo: Verificar a ocorrência de peptídeos hipocolesterolemizantes após digestão in vitro do isolado protéico de amaranto. Métodos: Proteína isola...

LiZIP3 is a cellular zinc transporter that mediates the tightly regulated import of zinc in Leishmania infantum parasites

Science.gov (United States)

Carvalho, Sandra; da Silva, Rosa Barreira; Shawki, Ali; Castro, Helena; Lamy, Márcia; Eide, David; Costa, Vítor; Mackenzie, Bryan; Tomás, Ana M.

2016-01-01

Summary Cellular zinc homeostasis ensures that the intracellular concentration of this element is kept within limits that enable its participation in critical physiological processes without exerting toxic effects. We report here the identification and characterization of the first mediator of zinc homeostasis in Leishmania infantum, LiZIP3, a member of the ZIP family of divalent metal-ion transporters. The zinc transporter activity of LiZIP3 was first disclosed by its capacity to rescue the growth of Saccharomyces cerevisiae strains deficient in zinc acquisition. Subsequent expression of LiZIP3 in Xenopus laevis oocytes was shown to stimulate the uptake of a broad range of metal ions, among which Zn2+ was the preferred LiZIP3 substrate (K0.5 ≈ 0.1 μM). Evidence that LiZIP3 functions as a zinc importer in L. infantum came from the observations that the protein locates to the cell membrane and that its overexpression leads to augmented zinc internalization. Importantly, expression and cell-surface location of LiZIP3 are lost when parasites face high zinc bioavailability. LiZIP3 decline in response to zinc is regulated at the mRNA level in a process involving (a) short-lived protein(s). Collectively, our data reveal that LiZIP3 enables L. infantum to acquire zinc in a highly regulated manner, hence contributing to zinc homeostasis. PMID:25644708

Innovative bio-mediated particulate materials for sustainable maritime transportation infrastructure.

Science.gov (United States)

2017-08-15

The mechanical properties of sandy soils in the coastal area and beach sands often do not satisfy construction expectation for maritime transportation infrastructure. The salty, loose sand makes it difficult for quick construction of port, building a...

Sulfur-Mediated-Alleviation of Aluminum-Toxicity in Citrus grandis Seedlings

Directory of Open Access Journals (Sweden)

Peng Guo

2017-12-01

Full Text Available Limited data are available on the sulfur (S-mediated-alleviation of aluminum (Al-toxicity in higher plants. Citrus grandis seedlings were irrigated for 18 weeks with 0.5 mM MgSO4 or 0.5 mM MgSO4 + 0.5 mM Na2SO4, and 0 (−Al or 1 mM AlCl3·6H2O (+Al, Al-toxicity. Under Al-toxicity, S decreased the level of Al in leaves; increased the relative water content (RWC of roots and leaves, the contents of phosphorus (P, calcium (Ca and magnesium (Mg per plant, the dry weights (DW of roots and shoots, the ratios of root DW/shoot DW, and the Al-induced secretion of citrate from root; and alleviated the Al-induced inhibition of photosynthesis via mitigating the Al-induced decrease of electron transport capacity resulting from the impaired photosynthetic electron transport chain. In addition to decreasing the Al-stimulated H2O2 production, the S-induced upregulation of both S metabolism-related enzymes and antioxidant enzymes also contributed to the S-mediated-alleviation of oxidative damage in Al-treated roots and leaves. Decreased transport of Al from roots to shoots and relatively little accumulation of Al in leaves, and increased leaf and root RWC and P, Ca, and Mg contents per plant might also play a role in the S-mediated-alleviation of Al-toxicity.

Further characterization of cadmium uptake by rat liver sinusoidal plasma membrane vesicles as a carrier mediated process

International Nuclear Information System (INIS)

Eastman, H.B.; Frazier, J.M.

1990-01-01

Previously we have reported that cadmium (Cd) transport by rat hepatic sinusoidal plasma membrane vesicles (SPMV's) occurs by both carrier mediated process and simple diffusion. This study was undertaken in order to further characterize the carrier mediated component of Cd transport as a carrier mediated process. Efflux of Cd from SPMV's was measured by first loading the vesicles with 1 μM Cd, containing 109 Cd (Amersham, 0.25 mCi/ml, carrier free) as a tracer, and then diluting the vesicles 1 to 5 into efflux buffer containing 0.25 M sucrose, 150 mM NaCl and 50 mM Tris/HCl (pH 7.4). Under standard conditions, no efflux of Cd from the vesicles was observed. However, the presence of 4mM CdCl 2 or 4.0% BSA in the efflux buffer was able to release 109 Cd from the vesicles. When the vesicles were lysed with 0.1% Triton X-100, approximately 75% of the internalized Cd could be released from the vesicles. Efflux of Cd from the vesicles was also determined to be a temperature dependent process. At 0 C the efflux of Cd from the vesicles, in the presence of a 4 mM CdCl 2 or 4.0% BSA chase, was blocked. The specificity of the carrier mediated component of Cd transport for Cd was investigated by determining whether other metals could compete for Cd uptake. Zinc was a competitive inhibitor of the carrier mediated component of Cd uptake while calcium had no effect on Cd uptake. Using this system, we have demonstrated that one component of Cd transport exhibits the basic characteristics of a carrier mediated process: saturation, reversibility, specificity and temperature dependence

The homeobox protein CEH-23 mediates prolonged longevity in response to impaired mitochondrial electron transport chain in C. elegans.

Directory of Open Access Journals (Sweden)

Ludivine Walter

2011-06-01

Full Text Available Recent findings indicate that perturbations of the mitochondrial electron transport chain (METC can cause extended longevity in evolutionarily diverse organisms. To uncover the molecular basis of how altered METC increases lifespan in C. elegans, we performed an RNAi screen and revealed that three predicted transcription factors are specifically required for the extended longevity of mitochondrial mutants. In particular, we demonstrated that the nuclear homeobox protein CEH-23 uniquely mediates the longevity but not the slow development, reduced brood size, or resistance to oxidative stress associated with mitochondrial mutations. Furthermore, we showed that ceh-23 expression levels are responsive to altered METC, and enforced overexpression of ceh-23 is sufficient to extend lifespan in wild-type background. Our data point to mitochondria-to-nucleus communications to be key for longevity determination and highlight CEH-23 as a novel longevity factor capable of responding to mitochondrial perturbations. These findings provide a new paradigm for how mitochondria impact aging and age-dependent diseases.

Altered carnitine transport in pressure-overload hypertrophied rat hearts

International Nuclear Information System (INIS)

O'Rourke, B.; Foster, K.; Reibel, D.K.

1986-01-01

The authors have previously observed reduced carnitine levels in hypertrophied hearts of rats subjected to aortic constriction. In an attempt to determine the mechanism for reduced myocardial carnitine content, carnitine transport was examined in isolated perfused hearts. Hearts were excised from sham-operated and aortic-constricted rats 3 weeks following surgery and perfused at 60 mm Hg aortic pressure with buffer containing various concentrations of L- 14 C-carnitine. Carnitine uptake by control and hypertrophied hearts was linear throughout 30 minutes of perfusion with 40 μM carnitine. Total carnitine uptake was significantly reduced by 25% in hypertrophied hearts at each time point examined. The reduction in uptake by hypertrophied hearts was also evident when hearts were perfused with 100 or 200 μM carnitine. When 0.05 mM mersalyl acid was included in the buffer to inhibit the carrier-mediated component of transport, no difference in carnitine uptake was observed indicating that the transport of carnitine by diffusion was unaltered in the hypertrophied myocardium. Carrier-mediated carnitine uptake (total uptake - uptake by diffusion) was significantly reduced by approximately 40% in hypertrophied hearts at all concentrations examined. Thus, the reduction in carnitine content in the pressure-overload hypertrophied rat heart appears to be due to a reduction in carrier-mediated carnitine uptake by the heart

Neuronal and non-neuronal GABA transporters as targets for antiepileptic drugs

DEFF Research Database (Denmark)

Madsen, Karsten K; White, H Steve; Schousboe, Arne

2010-01-01

of transmembrane transport and enzymatic degradation. The development of tiagabine selectively inhibiting the GABA transporter GAT1 constitutes a proof of concept that the GABA transporters are interesting drug targets in the context of antiepileptic drugs. The review provides a detailed analysis of the role......,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol) has been shown to possess a novel anticonvulsant profile in animal models of epilepsy, involving the ability to inhibit GABA transport mediated by GAT1 and BGT1 at the same time....

The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter

Science.gov (United States)

Abplanalp, Jeannette; Laczko, Endre; Philp, Nancy J.; Neidhardt, John; Zuercher, Jurian; Braun, Philipp; Schorderet, Daniel F.; Munier, Francis L.; Verrey, François; Berger, Wolfgang; Camargo, Simone M.R.; Kloeckener-Gruissem, Barbara

2013-01-01

Creatine transport has been assigned to creatine transporter 1 (CRT1), encoded by mental retardation associated SLC6A8. Here, we identified a second creatine transporter (CRT2) known as monocarboxylate transporter 12 (MCT12), encoded by the cataract and glucosuria associated gene SLC16A12. A non-synonymous alteration in MCT12 (p.G407S) found in a patient with age-related cataract (ARC) leads to a significant reduction of creatine transport. Furthermore, Slc16a12 knockout (KO) rats have elevated creatine levels in urine. Transport activity and expression characteristics of the two creatine transporters are distinct. CRT2 (MCT12)-mediated uptake of creatine was not sensitive to sodium and chloride ions or creatine biosynthesis precursors, breakdown product creatinine or creatine phosphate. Increasing pH correlated with increased creatine uptake. Michaelis–Menten kinetics yielded a Vmax of 838.8 pmol/h/oocyte and a Km of 567.4 µm. Relative expression in various human tissues supports the distinct mutation-associated phenotypes of the two transporters. SLC6A8 was predominantly found in brain, heart and muscle, while SLC16A12 was more abundant in kidney and retina. In the lens, the two transcripts were found at comparable levels. We discuss the distinct, but possibly synergistic functions of the two creatine transporters. Our findings infer potential preventive power of creatine supplementation against the most prominent age-related vision impaired condition. PMID:23578822

Unifying Concept of Serotonin Transporter-associated Currents*

Science.gov (United States)

Schicker, Klaus; Uzelac, Zeljko; Gesmonde, Joan; Bulling, Simon; Stockner, Thomas; Freissmuth, Michael; Boehm, Stefan; Rudnick, Gary; Sitte, Harald H.; Sandtner, Walter

2012-01-01

Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter-associated currents. PMID:22072712

Unifying concept of serotonin transporter-associated currents.

Science.gov (United States)

Schicker, Klaus; Uzelac, Zeljko; Gesmonde, Joan; Bulling, Simon; Stockner, Thomas; Freissmuth, Michael; Boehm, Stefan; Rudnick, Gary; Sitte, Harald H; Sandtner, Walter

2012-01-02

Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter-associated currents.

Improving L-arabinose utilization of pentose fermenting Saccharomyces cerevisiae cells by heterologous expression of L-arabinose transporting sugar transporters

Directory of Open Access Journals (Sweden)

Boles Eckhard

2011-10-01

Full Text Available Abstract Background Hydrolysates of plant biomass used for the production of lignocellulosic biofuels typically contain sugar mixtures consisting mainly of D-glucose and D-xylose, and minor amounts of L-arabinose. The yeast Saccharomyces cerevisiae is the preferred microorganism for the fermentative production of ethanol but is not able to ferment pentose sugars. Although D-xylose and L-arabinose fermenting S. cerevisiae strains have been constructed recently, pentose uptake is still a limiting step in mixed sugar fermentations. Results Here we described the cloning and characterization of two sugar transporters, AraT from the yeast Scheffersomyces stipitis and Stp2 from the plant Arabidopsis thaliana, which mediate the uptake of L-arabinose but not of D-glucose into S. cerevisiae cells. A yeast strain lacking all of its endogenous hexose transporter genes and expressing a bacterial L-arabinose utilization pathway could no longer take up and grow with L-arabinose as the only carbon source. Expression of the heterologous transporters supported uptake and utilization of L-arabinose especially at low L-arabinose concentrations but did not, or only very weakly, support D-glucose uptake and utilization. In contrast, the S. cerevisiae D-galactose transporter, Gal2, mediated uptake of both L-arabinose and D-glucose, especially at high concentrations. Conclusions Using a newly developed screening system we have identified two heterologous sugar transporters from a yeast and a plant which can support uptake and utilization of L-arabinose in L-arabinose fermenting S. cerevisiae cells, especially at low L-arabinose concentrations.

Mediation Analysis with Multiple Mediators.

Science.gov (United States)

VanderWeele, T J; Vansteelandt, S

2014-01-01

Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

Multidrug and toxin extrusion proteins as transporters of antimicrobial drugs.

Science.gov (United States)

Nies, Anne T; Damme, Katja; Schaeffeler, Elke; Schwab, Matthias

2012-12-01

Antimicrobial drugs are essential in the treatment of infectious diseases. A better understanding of transport processes involved in drug disposition will improve the predictability of drug-drug interactions with consequences for drug response. Multidrug And Toxin Extrusion (MATE; SLC47A) proteins are efflux transporters mediating the excretion of several antimicrobial drugs as well as other organic compounds into bile and urine, thereby contributing to drug disposition. This review summarizes current knowledge of the structural and molecular features of human MATE transporters including their functional role in drug transport with a specific focus on antimicrobial drugs. The PubMed database was searched using the terms "MATE1," "MATE-2K," "MATE2," "SLC47A1," "SLC47A2," and "toxin extrusion protein" (up to June 2012). MATE proteins have been recognized as important transporters mediating the final excretion step of cationic drugs into bile and urine. These include the antiviral drugs acyclovir, amprenavir, and ganciclovir, the antibiotics cephalexin, cephradine and levofloxacin, as well as the antimalarial agents chloroquine and quinine. It is therefore important to enhance our understanding of the role of MATEs in drug extrusion with particular emphasis on the functional consequences of genetic variants on disposition of these antimicrobial drugs.

Lactate transport and receptor actions in cerebral malaria

DEFF Research Database (Denmark)

Mariga, Shelton T; Kolko, Miriam; Gjedde, Albert

2014-01-01

in order to identify therapeutic targets. Here, we argue that cerebral energy metabolic defects are probable etiological factors in CM pathogenesis, because malaria parasites consume large amounts of glucose metabolized mostly to lactate. Monocarboxylate transporters (MCTs) mediate facilitated transfer...

Efficiency, selectivity, and robustness of nucleocytoplasmic transport.

Directory of Open Access Journals (Sweden)

Anton Zilman

2007-07-01

Full Text Available All materials enter or exit the cell nucleus through nuclear pore complexes (NPCs, efficient transport devices that combine high selectivity and throughput. NPC-associated proteins containing phenylalanine-glycine repeats (FG nups have large, flexible, unstructured proteinaceous regions, and line the NPC. A central feature of NPC-mediated transport is the binding of cargo-carrying soluble transport factors to the unstructured regions of FG nups. Here, we model the dynamics of nucleocytoplasmic transport as diffusion in an effective potential resulting from the interaction of the transport factors with the flexible FG nups, using a minimal number of assumptions consistent with the most well-established structural and functional properties of NPC transport. We discuss how specific binding of transport factors to the FG nups facilitates transport, and how this binding and competition between transport factors and other macromolecules for binding sites and space inside the NPC accounts for the high selectivity of transport. We also account for why transport is relatively insensitive to changes in the number and distribution of FG nups in the NPC, providing an explanation for recent experiments where up to half the total mass of the FG nups has been deleted without abolishing transport. Our results suggest strategies for the creation of artificial nanomolecular sorting devices.

Rat organic solute carrier protein 1 (rOscp1) mediated the transport of organic solutes in Xenopus laevis oocytes: isolation and pharmacological characterization of rOscp1.

Science.gov (United States)

Izuno, Hisanori; Kobayashi, Yasuna; Sanada, Yutaka; Nihei, Daisuke; Suzuki, Masako; Kohyama, Noriko; Ohbayashi, Masayuki; Yamamoto, Toshinori

2007-09-22

Rat organic solute carrier protein 1 (rOscp1) was isolated from a rat testis cDNA library. Isolated rOscp1 cDNA consisted of 1089 base pairs that encoded a 363-amino acid protein, and the amino acid sequence was 88% and 93% identical to that of human OSCP1 (hOSCP1) and mouse Oscp1 (mOscp1), respectively. The message for rOscp1 is highly detected in rat testis. When expressed in X. oocytes, rOscp1 mediated the high affinity transport of p-aminohippurate (PAH) with a Km value of 15.7+/-1.9 microM, and rOscp1-mediated organic solutes were exhibited in time- and Na+-independent manners. rOscp1 also transported various structurally heterogenous compounds such as testosterone, dehydroepiandrosterone sulfate (DHEA-S), and taurocholate with some differences in substrate specificity compared with hOSCP1. Immunohistochemical analysis revealed that the rOscp1 protein is localized in the basal membrane side of Sertoli cells as observed in mouse testis [Kobayashi et al., 2007; Kobayashi, Y., Tsuchiya, A., Hayashi, T., Kohyama, N., Ohbayashi, M., Yamamoto, T., 2007. Isolation and characterization of polyspecific mouse organic solute carrier protein 1 (mOscp1). Drug Metabolism and Disposition 35 (7), 1239-1245]. Thus, the present results indicate that a newly isolated cDNA clone, rOscp1, is a polyspecific organic solute carrier protein with some differences in substrate specificity compared with human and mouse OSCP1.

Comparison between s - and d -electron mediated transport in a photoswitching dithienylethene molecule using ab initio transport methods

KAUST Repository

Odell, Anders

2011-10-03

The influence of the electrode\\'s Fermi surface on the transport properties of a photoswitching molecule is investigated with state-of-the-art ab initio transport methods. We report results for the conducting properties of the two forms of dithienylethene attached either to Ag or to nonmagnetic Ni leads. The I-V curves of the Ag/dithienylethene/Ag device are found to be very similar to those reported previously for Au. In contrast, when Ni is used as the electrode material the zero-bias transmission coefficient is profoundly different as a result of the role played by the Ni d bands in the bonding between the molecule and the electrodes. Intriguingly, despite these differences the overall conducting properties depend little on the electrode material. We thus conclude that electron transport in dithienylethene is, for the cases studied, mainly governed by the intrinsic electronic structure of the molecule. © 2011 American Physical Society.

Addition of proteic nitrogen during alcoholic fermentation for the production of cachaça Adição de nitrogênio protéico durante a fermentação alcoólica de caldo de cana para produção de cachaça

Directory of Open Access Journals (Sweden)

Elisangela Marques Jeronimo

2008-04-01

Full Text Available Cachaça is the denomination of a typical and exclusive Brazilian spirit produced from the distillation of fermented sugarcane juice must. The objective of this study was to evaluate the effect of adding yeast extract to the sugarcane juice used for sugarcane liquor production, because for the artisanal process no studies are available on nitrogen addition nor beverage quality, involving nitrogen complementation. Results of previous studies in the laboratory scale showed that sugarcane juice complementation with proteic nitrogen can be a beneficial practice for yeast multiplication and cellular growth, and also for the improvement of fermentation yield and liquor productivity. In this pilot scale study, using recycled yeast, the addition of proteic nitrogen influenced positively the cell viability, confirmed the yeast recycling operation, and also reduced the fermentation time. The proteic nitrogen addition did not affect the sensory acceptance of the distillate, and did not change the contents of volatile compounds, indicating that assimilable forms of proteic nitrogen can be helpfull to improve the alcoholic fermentation for cachaça production.Cachaça é a denominação de uma típica e exclusiva bebida destilada brasileira produzida a partir da destilação do caldo fermentado da cana-de-açúcar. O objetivo deste estudo foi avaliar a adição de extrato de levedura no mosto de caldo de cana para a produção de cachaça, pois em processo artesanal não há estudos específicos sobre as características fermentativas da levedura assim como sobre a qualidade da bebida, envolvendo a complementação nitrogenada e em específico a aplicação de nitrogênio protéico. Os resultados obtidos em trabalhos anteriores, conduzidos em laboratório, indicaram que nas destilarias artesanais de aguardente a complementação protéica do mosto pode constituir uma prática benéfica para a multiplicação e crescimento celular do fermento e conseq

Understanding transporter specificity and the discrete appearance of channel-like gating domains in transporters

Directory of Open Access Journals (Sweden)

GEORGE eDIALLINAS

2014-09-01

Full Text Available Transporters are ubiquitous proteins mediating the translocation of solutes across cell membranes, a biological process involved in nutrition, signaling, neurotransmission, cell communication and drug uptake or efflux. Similarly to enzymes, most transporters have a single substrate binding-site and thus their activity follows Michaelis-Menten kinetics. Substrate binding elicits a series of structural changes, which produce a transporter conformer open towards the side opposite to the one from where the substrate was originally bound. This mechanism, involving alternate outward- and inward-facing transporter conformers, has gained significant support from structural, genetic, biochemical and biophysical approaches. Most transporters are specific for a given substrate or a group of substrates with similar chemical structure, but substrate specificity and/or affinity can vary dramatically, even among members of a transporter family that show high overall amino acid sequence and structural similarity. The current view is that transporter substrate affinity or specificity is determined by a small number of interactions a given solute can make within a specific binding site. However, genetic, biochemical and in silico modeling studies with the purine transporter UapA of the filamentous ascomycete Aspergillus nidulans have challenged this dogma. This review highlights results leading to a novel concept, stating that substrate specificity, but also transport kinetics and transporter turnover, are determined by subtle intramolecular interactions between a major substrate binding site and independent outward- or cytoplasmically-facing gating domains, analogous to those present in channels. This concept is supported by recent structural evidence from several, phylogenetically and functionally distinct transporter families. The significance of this concept is discussed in relationship to the role and potential exploitation of transporters in drug action.

Isolation of ionospheres from ion transport systems and their role in energy transduction

Energy Technology Data Exchange (ETDEWEB)

Shamoo, A E; Goldstein, D A

1977-01-01

In the past twenty-five years cell membrane transport has been studied from the point of view of kinetics and the biochemical correlation of enzyme function with that of transport. Artificial lipid bilayers have been used as a model for cell membrane transport. Antibiotics, such as valinomycin have also been studied as models of ion-transport mediators. Much effort has been invested on the study of model compounds as the possible molecular bases of transport. Information derived from the study of model systems throughout the years has been valuable and worthwhile. However, if the aim is to elucidate the mechanism of cell membrane transport, the time has come to merge the two lines of research into one and to shift emphasis from the study of model systems to the study of isolated transport machine components before and after reconstitution of its components into model membranes. These studies should be augmented at all times with the biochemical correlates of the transport proteins. A review is presented of the new avenues employed to elucidate the molecular mechanism of active transport. The new avenues are those of isolation of ion-transport mediators (ionophores) from membrane transport proteins. Reconstitution of ionophores and the various membrane transport proteins into artificial systems such as bilayers and vesicles presents a powerful tool to elucidate the molecular mechanism of active transport. More importantly, the new approach provides the first glimpse of evidence for a reasonable investigation of energy transduction from ATP hydrolysis to transport of an ion.

49 CFR 1109.4 - Mandatory mediation in rate cases to be considered under the stand-alone cost methodology.

Science.gov (United States)

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Mandatory mediation in rate cases to be considered... § 1109.4 Mandatory mediation in rate cases to be considered under the stand-alone cost methodology. (a) A... methodology must engage in non-binding mediation of its dispute with the railroad upon filing a formal...

Loss of ift122, a Retrograde Intraflagellar Transport (IFT) Complex Component, Leads to Slow, Progressive Photoreceptor Degeneration Due to Inefficient Opsin Transport*

Science.gov (United States)

Boubakri, Meriam; Chaya, Taro; Hirata, Hiromi; Kajimura, Naoko; Kuwahara, Ryusuke; Ueno, Akiko; Malicki, Jarema; Furukawa, Takahisa; Omori, Yoshihiro

2016-01-01

In the retina, aberrant opsin transport from cell bodies to outer segments leads to retinal degenerative diseases such as retinitis pigmentosa. Opsin transport is facilitated by the intraflagellar transport (IFT) system that mediates the bidirectional movement of proteins within cilia. In contrast to functions of the anterograde transport executed by IFT complex B (IFT-B), the precise functions of the retrograde transport mediated by IFT complex A (IFT-A) have not been well studied in photoreceptor cilia. Here, we analyzed developing zebrafish larvae carrying a null mutation in ift122 encoding a component of IFT-A. ift122 mutant larvae show unexpectedly mild phenotypes, compared with those of mutants defective in IFT-B. ift122 mutants exhibit a slow onset of progressive photoreceptor degeneration mainly after 7 days post-fertilization. ift122 mutant larvae also develop cystic kidney but not curly body, both of which are typically observed in various ciliary mutants. ift122 mutants display a loss of cilia in the inner ear hair cells and nasal pit epithelia. Loss of ift122 causes disorganization of outer segment discs. Ectopic accumulation of an IFT-B component, ift88, is observed in the ift122 mutant photoreceptor cilia. In addition, pulse-chase experiments using GFP-opsin fusion proteins revealed that ift122 is required for the efficient transport of opsin and the distal elongation of outer segments. These results show that IFT-A is essential for the efficient transport of outer segment proteins, including opsin, and for the survival of retinal photoreceptor cells, rendering the ift122 mutant a unique model for human retinal degenerative diseases. PMID:27681595

Water-mediated interactions enable smooth substrate transport in a bacterial efflux pump.

Science.gov (United States)

Vargiu, Attilio Vittorio; Ramaswamy, Venkata Krishnan; Malvacio, Ivana; Malloci, Giuliano; Kleinekathöfer, Ulrich; Ruggerone, Paolo

2018-04-01

Efflux pumps of the Resistance-Nodulation-cell Division superfamily confer multi-drug resistance to Gram-negative bacteria. The most-studied polyspecific transporter belonging to this class is the inner-membrane trimeric antiporter AcrB of Escherichia coli. In previous studies, a functional rotation mechanism was proposed for its functioning, according to which the three monomers undergo concerted conformational changes facilitating the extrusion of substrates. However, the molecular determinants and the energetics of this mechanism still remain unknown, so its feasibility must be proven mechanistically. A computational protocol able to mimic the functional rotation mechanism in AcrB was developed. By using multi-bias molecular dynamics simulations we characterized the translocation of the substrate doxorubicin driven by conformational changes of the protein. In addition, we estimated for the first time the free energy profile associated to this process. We provided a molecular view of the process in agreement with experimental data. Moreover, we showed that the conformational changes occurring in AcrB enable the formation of a layer of structured waters on the internal surface of the transport channel. This water layer, in turn, allows for a fairly constant hydration of the substrate, facilitating its diffusion over a smooth free energy profile. Our findings reveal a new molecular mechanism of polyspecific transport whereby water contributes by screening potentially strong substrate-protein interactions. We provided a mechanistic understanding of a fundamental process related to multi-drug transport. Our results can help rationalizing the behavior of other polyspecific transporters and designing compounds avoiding extrusion or inhibitors of efflux pumps. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Chlorovirus-mediated membrane depolarization of Chlorella alters secondary active transport of solutes.

Science.gov (United States)

Agarkova, Irina; Dunigan, David; Gurnon, James; Greiner, Timo; Barres, Julia; Thiel, Gerhard; Van Etten, James L

2008-12-01

Paramecium bursaria chlorella virus 1 (PBCV-1) is the prototype of a family of large, double-stranded DNA, plaque-forming viruses that infect certain eukaryotic chlorella-like green algae from the genus Chlorovirus. PBCV-1 infection results in rapid host membrane depolarization and potassium ion release. One interesting feature of certain chloroviruses is that they code for functional potassium ion-selective channel proteins (Kcv) that are considered responsible for the host membrane depolarization and, as a consequence, the efflux of potassium ions. This report examines the relationship between cellular depolarization and solute uptake. Annotation of the virus host Chlorella strain NC64A genome revealed 482 putative transporter-encoding genes; 224 are secondary active transporters. Solute uptake experiments using seven radioactive compounds revealed that virus infection alters the transport of all the solutes. However, the degree of inhibition varied depending on the solute. Experiments with nystatin, a drug known to depolarize cell membranes, produced changes in solute uptake that are similar but not identical to those that occurred during virus infection. Therefore, these studies indicate that chlorovirus infection causes a rapid and sustained depolarization of the host plasma membrane and that this depolarization leads to the inhibition of secondary active transporters that changes solute uptake.

Are lipid rafts involved in ABC transporter-mediated drug resistance of tumor cells?

NARCIS (Netherlands)

Kok, Jan Willem; Klappe, Karin; Hummel, Ina; Kroesen, Bart-Jan; Sietsma, Hannie; Meszaros, Peter

2008-01-01

Since their discovery, lipid rafts have been implicated in several cellular functions, including protein transport in polarized cells and signal transduction. Also in multidrug resistance lipid rafts may be important with regard to the localization of ATP-binding cassette (ABC) transporters in these

Qualidade protéica de pão de sal contendo farinha de linhaça (Linum usitatissimum L.
Protein quality of “french” bread containing flaxseed flour

Directory of Open Access Journals (Sweden)

J. T. S. BORGES

2010-09-01

Full Text Available

As proteínas são moléculas essenciais aos organismos animais, devendo, portanto, estar presentes na alimentação em quantidades adequadas. Além do aspecto quantitativo deve-se considerar o aspecto qualitativo, isto é, seu valor nutricional, que dependerá da composição, digestibilidade, biodisponibilidade de aminoácidos essenciais, ausência de toxicidade e de fatores antinutricionais. O objetivo do presente estudo foi determinar a digestibilidade in vivo e a qualidade nutricional de proteínas de pães de sal obtidos com farinhas mistas de trigo e linhaça integral nas proporções de 90:10 e 85:15. Os melhores resultados para ganho de peso, coefi ciente de efi cácia alimentar, coefi ciente de efi cácia protéica e razão protéica líquida foram obtidos quando maior teor de farinha de trigo foi substituído pela farinha integral de linhaça na formulação dos pães. A lisina foi o primeiro aminoácido limitante em todos os produtos elaborados. A substituição parcial da farinha de trigo pela farinha de linhaça não melhorou a qualidade protéica dos pães estudados.

Defect-band mediated ferromagnetism in Gd-doped ZnO thin films

KAUST Repository

Venkatesh, S.; Franklin, J. B.; Ryan, M. P.; Lee, J.-S.; Ohldag, Hendrik; McLachlan, M. A.; Alford, N. M.; Roqan, Iman S.

2015-01-01

. %) at low oxygen deposition pressure (<25 mTorr) were ferromagnetic at room temperature. Negative magnetoresistance, electric transport properties showed that the ferromagnetic exchange is mediated by a spin-split defect band formed due to oxygen deficiency

Comparative study of hop-containing products on human cytochrome p450-mediated metabolism.

Science.gov (United States)

Foster, Brian C; Kearns, Nikia; Arnason, John T; Saleem, Ammar; Ogrodowczyk, Carolina; Desjardins, Suzanne

2009-06-10

Thirty-five national and international brands of beer were examined for their potential to affect human cytochrome P450 (CYP)-mediated metabolism. They represented the two main categories of beer, ales and lagers, and included a number of specialty products including bitter (porter, stout), coffee, ice, wheat, Pilsner, and hemp seed. Aliquots were examined for nonvolatile soluble solids, effect on CYP metabolism and P-glycoprotein (Pgp) transport, and major alpha- and beta-hop acids. Wide variance was detected in contents of alcohol, nonvolatile suspended solids, and hop acids and in the potential to affect CYP-mediated metabolism and Pgp-mediated efflux transport. Many of the products affected CYP2C9-mediated metabolism, and only two (NRP 306 and 307) markedly affected CYP3A4; hence, some products have the capacity to affect drug safety. CYP3A4, CYP3A5, CYP3A7, and CYP19 (aromatase) inhibition to the log concentration of beta-acid content was significant with r(2) > 0.37, suggesting that these components can account for some of the variation in inhibition of CYP metabolism.

SLC6 Neurotransmitter Transporters: Structure, Function, and Regulation

DEFF Research Database (Denmark)

Kristensen, Anders S; Andersen, Jacob; Jørgensen, Trine N

2011-01-01

The neurotransmitter transporters (NTTs) belonging to the solute carrier 6 (SLC6) gene family (also referred to as the neurotransmitter-sodium-symporter family or Na(+)/Cl(-)-dependent transporters) comprise a group of nine sodium- and chloride-dependent plasma membrane transporters...... for the monoamine neurotransmitters serotonin (5-hydroxytryptamine), dopamine, and norepinephrine, and the amino acid neurotransmitters GABA and glycine. The SLC6 NTTs are widely expressed in the mammalian brain and play an essential role in regulating neurotransmitter signaling and homeostasis by mediating uptake...... of released neurotransmitters from the extracellular space into neurons and glial cells. The transporters are targets for a wide range of therapeutic drugs used in treatment of psychiatric diseases, including major depression, anxiety disorders, attention deficit hyperactivity disorder and epilepsy...

Neurosteroid Transport in the Brain: Role of ABC and SLC Transporters

Directory of Open Access Journals (Sweden)

Markus Grube

2018-04-01

Full Text Available Neurosteroids, comprising pregnane, androstane, and sulfated steroids can alter neuronal excitability through interaction with ligand-gated ion channels and other receptors and have therefore a therapeutic potential in several brain disorders. They can be formed in brain cells or are synthesized by an endocrine gland and reach the brain by penetrating the blood–brain barrier (BBB. Especially sulfated steroids such as pregnenolone sulfate (PregS and dehydroepiandrosterone sulfate (DHEAS depend on transporter proteins to cross membranes. In this review, we discuss the involvement of ATP-binding cassette (ABC- and solute carrier (SLC-type membrane proteins in the transport of these compounds at the BBB and in the choroid plexus (CP, but also in the secretion from neurons and glial cells. Among the ABC transporters, especially BCRP (ABCG2 and several MRP/ABCC subfamily members (MRP1, MRP4, MRP8 are expressed in the brain and known to efflux conjugated steroids. Furthermore, several SLC transporters have been shown to mediate cellular uptake of steroid sulfates. These include members of the OATP/SLCO subfamily, namely OATP1A2 and OATP2B1, as well as OAT3 (SLC22A3, which have been reported to be expressed at the BBB, in the CP and in part in neurons. Furthermore, a role of the organic solute transporter OSTα-OSTβ (SLC51A/B in brain DHEAS/PregS homeostasis has been proposed. This transporter was reported to be localized especially in steroidogenic cells of the cerebellum and hippocampus. To date, the impact of transporters on neurosteroid homeostasis is still poorly understood. Further insights are desirable also with regard to the therapeutic potential of these compounds.

SwissProt search result: AK069337 [KOME

Lifescience Database Archive (English)

Full Text Available AK069337 J023014F07 (Q28727) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transpo

SwissProt search result: AK072870 [KOME

Lifescience Database Archive (English)

Full Text Available AK072870 J023142A17 (Q28727) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transpo

SwissProt search result: AK104932 [KOME

Lifescience Database Archive (English)

Full Text Available AK104932 001-047-B10 (Q28727) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transp

SwissProt search result: AK104932 [KOME

Lifescience Database Archive (English)

Full Text Available AK104932 001-047-B10 (Q60414) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transp

SwissProt search result: AK072870 [KOME

Lifescience Database Archive (English)

Full Text Available AK072870 J023142A17 (Q60414) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transpo

SwissProt search result: AK069337 [KOME

Lifescience Database Archive (English)

Full Text Available AK069337 J023014F07 (Q60414) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transpo

SwissProt search result: AK069337 [KOME

Lifescience Database Archive (English)

Full Text Available AK069337 J023014F07 (P70172) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transpo

SwissProt search result: AK072870 [KOME

Lifescience Database Archive (English)

Full Text Available AK072870 J023142A17 (P70172) Ileal sodium/bile acid cotransporter (Ileal Na(+)/bile... acid cotransporter) (Na(+) dependent ileal bile acid transporter) (Ileal sodium-dependent bile acid transpo

A study on the characteristics of colloid-associated radionuclide transport in porous media

International Nuclear Information System (INIS)

Jeong, Yun Chang

1997-02-01

Recently, the radionuclide transport in the form of colloids has been focused intensively in the safety assessment of a radioactive waste repository. As colloids are considered to be able to increase the transport rate of radionuclide through geologic media, the transport of radionuclide should be adjusted by the presence of colloids. The migration of dissolved radionuclide is expected to depend on various process such as advection, dispersion and interactions with soils, and, in addition, the transport of colloid-mediated radionuclide is considered to be more complicated because of the interactions between radionuclides and colloids. In this paper the migration behavior of colloid-associated radionuclides within subsurface are reviewed and studied in detail. The colloid-mediated transport system was modelled and simulated in order to illustrate the effects of colloids on the transport of radionuclide in the aquifer system. The transport rate of radionuclide is mainly controlled by a retardation factor which is controlled by colloidal behaviors, degree of adsorption, and the related geologic parameters. Therefore it is necessary to carefully understand the accelerating tendency of the retardation difference factor, and in this study the trends are analyzed, described and the retardation difference factor is mathematically defined, simplified and applied practically to the safety and performance assessment of a future repository

Emprego de fubá de melhor qualidade protéica em farinhas mistas para produção de biscoito Use of quality-protein maize in flour blends and in the production of cookies

Directory of Open Access Journals (Sweden)

Fátima F. P. Guilherme

2005-03-01

Full Text Available Farinhas mistas (FM à base de farinha de trigo com substituição parcial por isolado protéico de soja, soro de leite em pó e três tipos de fubá (mimoso ou de cultivares BR451 e BR2121 foram preparadas para melhorar a qualidade protéica da farinha de trigo. As características sensoriais e químicas dos biscoitos foram avaliadas, e o valor protéico em potencial foi calculado. Os resultados foram comparados com os da farinha de trigo ou seu biscoito (controles. Os teores em macronutrientes nas FM e nos biscoitos foram superiores aos dos respectivos controles, com exceção de carboidratos. Apenas na aparência o biscoito com FM BR2121 foi estatisticamente inferior à daquele com FM mimoso, sendo semelhantes ao controle e aos outros biscoitos na textura e no sabor. O biscoito com FM mimoso teve a maior aceitação. O valor calórico médio dos biscoitos foi de 436kcal. A qualidade protéica dos biscoitos com as FM - lisina e treonina como aminoácidos limitantes e C-PER em torno de 2 - foi superior a do controle. O custo (preço/kg dos biscoitos assados com as FM foi superior ao do biscoito controle, devido ao custo da FM ter sido cerca do dobro da farinha de trigo pura e de se necessitar maiores quantidades de ingredientes na formulação.Flour blends (FB based on wheat flour with partial substitution for isolated soy protein, powdered whey and three corn flour types (common or cultivar BR451 and BR2121 were prepared to improve the protein quality of wheat flour. The sensory and chemical characteristics of the cookies were evaluated and the potential proteic value was calculated. The results were compared with the wheat flour or its cookie (controls. Macronutrients levels in FB and cookies were superior than those in the respective controls, except for carbohydrates. Only in the appearance the cookie made with FB BR2121 was statistically inferior to the one with common corn FB, being similar to the control and other cookies in texture and

Transport proteins of parasitic protists and their role in nutrient salvage.

Science.gov (United States)

Dean, Paul; Major, Peter; Nakjang, Sirintra; Hirt, Robert P; Embley, T Martin

2014-01-01

The loss of key biosynthetic pathways is a common feature of important parasitic protists, making them heavily dependent on scavenging nutrients from their hosts. This is often mediated by specialized transporter proteins that ensure the nutritional requirements of the parasite are met. Over the past decade, the completion of several parasite genome projects has facilitated the identification of parasite transporter proteins. This has been complemented by functional characterization of individual transporters along with investigations into their importance for parasite survival. In this review, we summarize the current knowledge on transporters from parasitic protists and highlight commonalities and differences in the transporter repertoires of different parasitic species, with particular focus on characterized transporters that act at the host-pathogen interface.

Water transport inside carbon nanotubes mediated by phonon-induced oscillating friction.

Science.gov (United States)

Ma, Ming; Grey, François; Shen, Luming; Urbakh, Michael; Wu, Shuai; Liu, Jefferson Zhe; Liu, Yilun; Zheng, Quanshui

2015-08-01

The emergence of the field of nanofluidics in the last decade has led to the development of important applications including water desalination, ultrafiltration and osmotic energy conversion. Most applications make use of carbon nanotubes, boron nitride nanotubes, graphene and graphene oxide. In particular, understanding water transport in carbon nanotubes is key for designing ultrafiltration devices and energy-efficient water filters. However, although theoretical studies based on molecular dynamics simulations have revealed many mechanistic features of water transport at the molecular level, further advances in this direction are limited by the fact that the lowest flow velocities accessible by simulations are orders of magnitude higher than those measured experimentally. Here, we extend molecular dynamics studies of water transport through carbon nanotubes to flow velocities comparable with experimental ones using massive crowd-sourced computing power. We observe previously undetected oscillations in the friction force between water and carbon nanotubes and show that these oscillations result from the coupling between confined water molecules and the longitudinal phonon modes of the nanotube. This coupling can enhance the diffusion of confined water by more than 300%. Our results may serve as a theoretical framework for the design of new devices for more efficient water filtration and osmotic energy conversion devices.

Maternal use of drug substrates of placental transporters and the effect of transporter-mediated drug interactions on the risk of congenital anomalies.

Directory of Open Access Journals (Sweden)

Aizati N A Daud

Full Text Available A number of transporter proteins are expressed in the placenta, and they facilitate the placental transfer of drugs. The inhibition of P-glycoprotein (P-gp was previously found to be associated with an increase in the risk of congenital anomalies caused by drug substrates of this transporter. We now explore the role of other placental transporter proteins.A population-based case-referent study was performed using cases with congenital anomalies (N = 5,131 from EUROCAT Northern Netherlands, a registry of congenital anomalies. The referent population (N = 31,055 was selected from the pregnancy IADB.nl, a pharmacy prescription database.Ten placental transporters known to have comparable expression levels in the placenta to that of P-gp, were selected in this study. In total, 147 drugs were identified to be substrates, inhibitors or inducers, of these transporters. Fifty-eight of these drugs were used by at least one mother in our cases or referent population, and 28 were used in both. The highest user rate was observed for the substrates of multidrug resistance-associated protein 1, mainly folic acid (6% of cases, 8% of referents, and breast cancer resistance protein, mainly nitrofurantoin (2.3% of cases, 2.9% of referents. In contrast to P-gp, drug interactions involving substrates of these transporters did not have a significant effect on the risk of congenital anomalies.Some of the drugs which are substrates or inhibitors of placental transporters were commonly used during pregnancy. No significant effect of transporter inhibition was found on fetal drug exposure, possibly due to a limited number of exposures.

Adiponectin inhibits insulin function in primary trophoblasts by PPARα-mediated ceramide synthesis.

Science.gov (United States)

Aye, Irving L M H; Gao, Xiaoli; Weintraub, Susan T; Jansson, Thomas; Powell, Theresa L

2014-04-01

Maternal adiponectin (ADN) levels are inversely correlated with birth weight, and ADN infusion in pregnant mice down-regulates placental nutrient transporters and decreases fetal growth. In contrast to the insulin-sensitizing effects in adipose tissue and muscle, ADN inhibits insulin signaling in the placenta. However, the molecular mechanisms involved are unknown. We hypothesized that ADN inhibits insulin signaling and insulin-stimulated amino acid transport in primary human trophoblasts by peroxisome proliferator-activated receptor-α (PPARα)-mediated ceramide synthesis. Primary human term trophoblast cells were treated with ADN and/or insulin. ADN increased the phosphorylation of p38 MAPK and PPARα. ADN inhibited insulin signaling and insulin-stimulated amino acid transport. This effect was dependent on PPARα, because activation of PPARα with an agonist (GW7647) inhibited insulin signaling and function, whereas PPARα-small interfering RNA reversed the effects of ADN on the insulin response. ADN increased ceramide synthase expression and stimulated ceramide production. C2-ceramide inhibited insulin signaling and function, whereas inhibition of ceramide synthase (with Fumonisin B1) reversed the effects of ADN on insulin signaling and amino acid transport. These findings are consistent with the model that maternal ADN limits fetal growth mediated by activation of placental PPARα and ceramide synthesis, which inhibits placental insulin signaling and amino acid transport, resulting in reduced fetal nutrient availability.

Long-Distance Transport of Thiamine (Vitamin B1) Is Concomitant with That of Polyamines.

Science.gov (United States)

Martinis, Jacopo; Gas-Pascual, Elisabet; Szydlowski, Nicolas; Crèvecoeur, Michèle; Gisler, Alexandra; Bürkle, Lukas; Fitzpatrick, Teresa B

2016-05-01

Thiamine (vitamin B1) is ubiquitous and essential for cell energy supply in all organisms as a vital metabolic cofactor, known for over a century. In plants, it is established that biosynthesis de novo is taking place predominantly in green tissues and is furthermore limited to plastids. Therefore, transport mechanisms are required to mediate the movement of this polar metabolite from source to sink tissue to activate key enzymes in cellular energy generating pathways but are currently unknown. Similar to thiamine, polyamines are an essential set of charged molecules required for diverse aspects of growth and development, the homeostasis of which necessitates long-distance transport processes that have remained elusive. Here, a yeast-based screen allowed us to identify Arabidopsis (Arabidopsis thaliana) PUT3 as a thiamine transporter. A combination of biochemical, physiological, and genetic approaches permitted us to show that PUT3 mediates phloem transport of both thiamine and polyamines. Loss of function of PUT3 demonstrated that the tissue distribution of these metabolites is altered with growth and developmental consequences. The pivotal role of PUT3 mediated thiamine and polyamine homeostasis in plants, and its importance for plant fitness is revealed through these findings. © 2016 American Society of Plant Biologists. All Rights Reserved.

The second sodium site in the dopamine transporter controls cation permeability and is regulated by chloride

DEFF Research Database (Denmark)

Borre, Lars; Andreassen, Thorvald F; Shi, Lei

2014-01-01

The dopamine transporter (DAT) belongs to the family of neurotransmitter:sodium symporters (NSSs) and controls dopamine (DA) homeostasis by mediating Na(+)- and Cl(-)-dependent reuptake of DA. Here we used two-electrode voltage clamp measurements in Xenopus oocytes together with targeted mutagene......The dopamine transporter (DAT) belongs to the family of neurotransmitter:sodium symporters (NSSs) and controls dopamine (DA) homeostasis by mediating Na(+)- and Cl(-)-dependent reuptake of DA. Here we used two-electrode voltage clamp measurements in Xenopus oocytes together with targeted...

Proteoliposomes as Tool for Assaying Membrane Transporter Functions and Interactions with Xenobiotics

Directory of Open Access Journals (Sweden)

Annamaria Tonazzi

2013-09-01

Full Text Available Proteoliposomes represent a suitable and up to date tool for studying membrane transporters which physiologically mediate absorption, excretion, trafficking and reabsorption of nutrients and metabolites. Using recently developed reconstitution strategies, transporters can be inserted in artificial bilayers with the same orientation as in the cell membranes and in the absence of other interfering molecular systems. These methodologies are very suitable for studying kinetic parameters and molecular mechanisms. After the first applications on mitochondrial transporters, in the last decade, proteoliposomes obtained with optimized methodologies have been used for studying plasma membrane transporters and defining their functional and kinetic properties and structure/function relationships. A lot of information has been obtained which has clarified and completed the knowledge on several transporters among which the OCTN sub-family members, transporters for neutral amino acid, B0AT1 and ASCT2, and others. Transporters can mediate absorption of substrate-like derivatives or drugs, improving their bioavailability or can interact with these compounds or other xenobiotics, leading to side/toxic effects. Therefore, proteoliposomes have recently been used for studying the interaction of some plasma membrane and mitochondrial transporters with toxic compounds, such as mercurials, H2O2 and some drugs. Several mechanisms have been defined and in some cases the amino acid residues responsible for the interaction have been identified. The data obtained indicate proteoliposomes as a novel and potentially important tool in drug discovery.

Altered blood-brain barrier transport in neuro-inflammatory disorders.

Science.gov (United States)

Schenk, Geert J; de Vries, Helga E

2016-06-01

During neurodegenerative and neuroinflammatory disorders of the central nervous system (CNS), such as Alzheimer's disease (AD) and multiple sclerosis (MS), the protective function of the blood-brain barrier (BBB) may be severely impaired. The general neuro-inflammatory response, ranging from activation of glial cells to immune cell infiltration that is frequently associated with such brain diseases may underlie the loss of the integrity and function of the BBB. Consequentially, the delivery and disposition of drugs to the brain will be altered and may influence the treatment efficiency of such diseases. Altered BBB transport of drugs into the CNS during diseases may be the result of changes in both specific transport and non-specific transport pathways. Potential alterations in transport routes like adsorptive mediated endocytosis and receptor-mediated endocytosis may affect drug delivery to the brain. As such, drugs that normally are unable to traverse the BBB may reach their target in the diseased brain due to increased permeability. In contrast, the delivery of (targeted) drugs could be hampered during inflammatory conditions due to disturbed transport mechanisms. Therefore, the inventory of the neuro-inflammatory status of the neurovasculature (or recovery thereof) is of utmost importance in choosing and designing an adequate drug targeting strategy under disease conditions. Within this review we will briefly discuss how the function of the BBB can be affected during disease and how this may influence the delivery of drugs into the diseased CNS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ceramide transport from endoplasmic reticulum to Golgi apparatus is not vesicle-mediated

NARCIS (Netherlands)

Kok, JW; Babia, T; Klappe, K; Egea, G; Hoekstra, D

1998-01-01

Ceramide (Cer) transfer from the endoplasmic reticulum (ER) to the Golgi apparatus was measured under conditions that block vesicle-mediated protein transfer. This was done either in intact cells by reducing the incubation temperature to 15 degrees C, or in streptolysin O-permeabilized cells by

GLUT1-mediated selective tumor targeting with fluorine containing platinum(II) glycoconjugates

OpenAIRE

Liu, Ran; Fu, Zheng; Zhao, Meng; Gao, Xiangqian; Li, Hong; Mi, Qian; Liu, Pengxing; Yang, Jinna; Yao, Zhi; Gao, Qingzhi

2017-01-01

Increased glycolysis and overexpression of glucose transporters (GLUTs) are physiological characteristics of human malignancies. Based on the so-called Warburg effect, 18flurodeoxyglucose-positron emission tomography (FDG-PET) has successfully developed as clinical modality for the diagnosis and staging of many cancers. To leverage this glucose transporter mediated metabolic disparity between normal and malignant cells, in the current report, we focus on the fluorine substituted series of glu...

Transendothelial Transport and Its Role in Therapeutics

Science.gov (United States)

Upadhyay, Ravi Kant

2014-01-01

Present review paper highlights role of BBB in endothelial transport of various substances into the brain. More specifically, permeability functions of BBB in transendothelial transport of various substances such as metabolic fuels, ethanol, amino acids, proteins, peptides, lipids, vitamins, neurotransmitters, monocarbxylic acids, gases, water, and minerals in the peripheral circulation and into the brain have been widely explained. In addition, roles of various receptors, ATP powered pumps, channels, and transporters in transport of vital molecules in maintenance of homeostasis and normal body functions have been described in detail. Major role of integral membrane proteins, carriers, or transporters in drug transport is highlighted. Both diffusion and carrier mediated transport mechanisms which facilitate molecular trafficking through transcellular route to maintain influx and outflux of important nutrients and metabolic substances are elucidated. Present review paper aims to emphasize role of important transport systems with their recent advancements in CNS protection mainly for providing a rapid clinical aid to patients. This review also suggests requirement of new well-designed therapeutic strategies mainly potential techniques, appropriate drug formulations, and new transport systems for quick, easy, and safe delivery of drugs across blood brain barrier to save the life of tumor and virus infected patients. PMID:27355037

New structure–activity relationships of chalcone inhibitors of breast cancer resistance protein: polyspecificity toward inhibition and critical substitutions against cytotoxicity

Directory of Open Access Journals (Sweden)

Rangel LP

2013-09-01

Full Text Available Luciana Pereira Rangel,1,2,* Evelyn Winter,1,3,* Charlotte Gauthier,1 Raphaël Terreux,4 Louise D Chiaradia-Delatorre,5 Alessandra Mascarello,5 Ricardo J Nunes,5 Rosendo A Yunes,5 Tania B Creczynski-Pasa,3 Sira Macalou,1 Doriane Lorendeau,1 Hélène Baubichon-Cortay,1 Antonio Ferreira-Pereira,2 Attilio Di Pietro11Equipe Labellisée Ligue 2013, BMSSI UMR 5086 CNRS/Université Lyon 1, Institut de Biologie et Chimie des Protéines, Lyon, France; 2Department of General Microbiology, Institute of Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 3Department of Pharmaceutical Sciences, PPGFAR, Federal University of Santa Catarina, Florianopolis, Santa Catarina, Brazil; 4Equipe BISI, BMSSI UMR 5086 CNRS/Université Lyon 1, Institut de Biologie et Chimie des Protéines, Lyon, France; 5Department of Chemistry, Federal University of Santa Catarina, Florianopolis, Santa Catarina, Brazil*These authors contributed equally to this workAbstract: Adenosine triphosphate-binding cassette subfamily G member 2 (ABCG2 plays a major role in cancer cell multidrug resistance, which contributes to low efficacy of chemotherapy. Chalcones were recently found to be potent and specific inhibitors, but unfortunately display a significant cytotoxicity. A cellular screening against ABCG2-mediated mitoxantrone efflux was performed here by flow cytometry on 54 chalcone derivatives from three different series with a wide panel of substituents. The identified leads, with submicromolar IC50 (half maximal inhibitory concentration values, showed that the previously identified 2'-OH-4',6'-dimethoxyphenyl, as A-ring, could be efficiently replaced by a 2'-naphthyl group, or a 3',4'-methylenedioxyphenyl with lower affinity. Such a structural variability indicates polyspecificity of the multidrug transporter for inhibitors. At least two methoxyl groups were necessary on B-ring for optimal inhibition, but substitution at positions 3, 4, and 5 induced cytotoxicity

Structural basis of nanobody-mediated blocking of BtuF, the cognate substrate-binding protein of the Escherichia coli vitamin B12 transporter BtuCD.

Science.gov (United States)

Mireku, S A; Sauer, M M; Glockshuber, R; Locher, K P

2017-10-30

Bacterial ABC importers catalyze the uptake of essential nutrients including transition metals and metal-containing co-factors. Recently, an IgG antibody targeting the external binding protein of the Staphylococcus aureus Mn(II) ABC importer was reported to inhibit transport activity and reduce bacterial cell growth. We here explored the possibility of using alpaca-derived nanobodies to inhibit the vitamin B12 transporter of Escherichia coli, BtuCD-F, as a model system by generating nanobodies against the periplasmic binding protein BtuF. We isolated six nanobodies that competed with B12 for binding to BtuF, with inhibition constants between 10 -6 and 10 -9  M. Kinetic characterization of the nanobody-BtuF interactions revealed dissociation half-lives between 1.6 and 6 minutes and fast association rates between 10 4 and 10 6  M -1 s -1 . For the tightest-binding nanobody, we observed a reduction of in vitro transport activity of BtuCD-F when an excess of nanobody over B12 was used. The structure of BtuF in complex with the most effective nanobody Nb9 revealed the molecular basis of its inhibitory function. The CDR3 loop of Nb9 reached into the substrate-binding pocket of BtuF, preventing both B12 binding and BtuCD-F complex formation. Our results suggest that nanobodies can mediate ABC importer inhibition, providing an opportunity for novel antibiotic strategies.

MS transport assays for γ-aminobutyric acid transporters--an efficient alternative for radiometric assays.

Science.gov (United States)

Schmitt, Sebastian; Höfner, Georg; Wanner, Klaus T

2014-08-05

Transport assays for neurotransmitters based on radiolabeled substrates are widely spread and often indispensable in basic research and the drug development process, although the use of radioisotopes is inherently coupled to issues concerning radioactive waste and safety precautions. To overcome these disadvantages, we developed mass spectrometry (MS)-based transport assays for γ-aminobutyric acid (GABA), which is the major inhibitory neurotransmitter in the central nervous system (CNS). These "MS Transport Assays" provide all capabilities of [(3)H]GABA transport assays and therefore represent the first substitute for the latter. The performance of our approach is demonstrated for GAT1, the most important GABA transporter (GAT) subtype. As GABA is endogenously present in COS-7 cells employed as hGAT1 expression system, ((2)H6)GABA was used as a substrate to differentiate transported from endogenous GABA. To record transported ((2)H6)GABA, a highly sensitive, short, robust, and reliable HILIC-ESI-MS/MS quantification method using ((2)H2)GABA as an internal standard was developed and validated according to the Center for Drug Evaluation and Research (CDER) guidelines. Based on this LC-MS quantification, a setup to characterize hGAT1 mediated ((2)H6)GABA transport in a 96-well format was established, that enables automated processing and avoids any sample preparation. The K(m) value for ((2)H6)GABA determined for hGAT1 is in excellent agreement with results obtained from [(3)H]GABA uptake assays. In addition, the established assay format enables efficient determination of the inhibitory potency of GAT1 inhibitors, is capable of identifying those inhibitors transported as substrates, and furthermore allows characterization of efflux. The approach described here combines the strengths of LC-MS/MS with the high efficiency of transport assays based on radiolabeled substrates and is applicable to all GABA transporter subtypes.

Hypoxic tumor environments exhibit disrupted collagen I fibers and low macromolecular transport.

Directory of Open Access Journals (Sweden)

Samata M Kakkad

Full Text Available Hypoxic tumor microenvironments result in an aggressive phenotype and resistance to therapy that lead to tumor progression, recurrence, and metastasis. While poor vascularization and the resultant inadequate drug delivery are known to contribute to drug resistance, the effect of hypoxia on molecular transport through the interstitium, and the role of the extracellular matrix (ECM in mediating this transport are unexplored. The dense mesh of fibers present in the ECM can especially influence the movement of macromolecules. Collagen 1 (Col1 fibers form a key component of the ECM in breast cancers. Here we characterized the influence of hypoxia on macromolecular transport in tumors, and the role of Col1 fibers in mediating this transport using an MDA-MB-231 breast cancer xenograft model engineered to express red fluorescent protein under hypoxia. Magnetic resonance imaging of macromolecular transport was combined with second harmonic generation microscopy of Col1 fibers. Hypoxic tumor regions displayed significantly decreased Col1 fiber density and volume, as well as significantly lower macromolecular draining and pooling rates, than normoxic regions. Regions adjacent to severely hypoxic areas revealed higher deposition of Col1 fibers and increased macromolecular transport. These data suggest that Col1 fibers may facilitate macromolecular transport in tumors, and their reduction in hypoxic regions may reduce this transport. Decreased macromolecular transport in hypoxic regions may also contribute to poor drug delivery and tumor recurrence in hypoxic regions. High Col1 fiber density observed around hypoxic regions may facilitate the escape of aggressive cancer cells from hypoxic regions.

Sugar transporter genes of the brown planthopper, Nilaparvata lugens: A facilitated glucose/fructose transporter.

Science.gov (United States)

Kikuta, Shingo; Kikawada, Takahiro; Hagiwara-Komoda, Yuka; Nakashima, Nobuhiko; Noda, Hiroaki

2010-11-01

The brown planthopper (BPH), Nilaparvata lugens, attacks rice plants and feeds on their phloem sap, which contains large amounts of sugars. The main sugar component of phloem sap is sucrose, a disaccharide composed of glucose and fructose. Sugars appear to be incorporated into the planthopper body by sugar transporters in the midgut. A total of 93 expressed sequence tags (ESTs) for putative sugar transporters were obtained from a BPH EST database, and 18 putative sugar transporter genes (Nlst1-18) were identified. The most abundantly expressed of these genes was Nlst1. This gene has previously been identified in the BPH as the glucose transporter gene NlHT1, which belongs to the major facilitator superfamily. Nlst1, 4, 6, 9, 12, 16, and 18 were highly expressed in the midgut, and Nlst2, 7, 8, 10, 15, 17, and 18 were highly expressed during the embryonic stages. Functional analyses were performed using Xenopus oocytes expressing NlST1 or 6. This showed that NlST6 is a facilitative glucose/fructose transporter that mediates sugar uptake from rice phloem sap in the BPH midgut in a manner similar to NlST1. Copyright © 2010 Elsevier Ltd. All rights reserved.

Serotonin-induced down-regulation of cell surface serotonin transporter

DEFF Research Database (Denmark)

Jørgensen, Trine Nygaard; Christensen, Peter Møller; Gether, Ulrik

2014-01-01

The serotonin transporter (SERT) terminates serotonergic signaling and enables refilling of synaptic vesicles by mediating reuptake of serotonin (5-HT) released into the synaptic cleft. The molecular and cellular mechanisms controlling SERT activity and surface expression are not fully understood...

Prohibitin/annexin 2 interaction regulates fatty acid transport in adipose tissue

Science.gov (United States)

Salameh, Ahmad; Daquinag, Alexes C.; Staquicini, Daniela I.; An, Zhiqiang; Pasqualini, Renata; Kolonin, Mikhail G.

2016-01-01

We have previously identified prohibitin (PHB) and annexin A2 (ANX2) as proteins interacting on the surface of vascular endothelial cells in white adipose tissue (WAT) of humans and mice. Here, we demonstrate that ANX2 and PHB also interact in adipocytes. Mice lacking ANX2 have normal WAT vascularization, adipogenesis, and glucose metabolism but display WAT hypotrophy due to reduced fatty acid uptake by WAT endothelium and adipocytes. By using cell culture systems in which ANX2/PHB binding is disrupted either genetically or through treatment with a blocking peptide, we show that fatty acid transport efficiency relies on this protein complex. We also provide evidence that the interaction between ANX2 and PHB mediates fatty acid transport from the endothelium into adipocytes. Moreover, we demonstrate that ANX2 and PHB form a complex with the fatty acid transporter CD36. Finally, we show that the colocalization of PHB and CD36 on adipocyte surface is induced by extracellular fatty acids. Together, our results suggest that an unrecognized biochemical interaction between ANX2 and PHB regulates CD36-mediated fatty acid transport in WAT, thus revealing a new potential pathway for intervention in metabolic diseases. PMID:27468426

Hijacking membrane transporters for arsenic phytoextraction

Science.gov (United States)

LeBlanc, Melissa S.; McKinney, Elizabeth C.; Meagher, Richard B.; Smith, Aaron P.

2012-01-01

Arsenic is a toxic metalloid and recognized carcinogen. Arsenate and arsenite are the most common arsenic species available for uptake by plants. As an inorganic phosphate (Pi) analog, arsenate is acquired by plant roots through endogenous Pi transport systems. Inside the cell, arsenate is reduced to the thiol-reactive form arsenite. Glutathione (GSH)-conjugates of arsenite may be extruded from the cell or sequestered in vacuoles by members of the ATP-binding cassette (ABC) family of transporters. In the present study we sought to enhance both plant arsenic uptake through Pi transporter overexpression, and plant arsenic tolerance through ABC transporter overexpression. We demonstrate that Arabidopsis thaliana plants overexpressing the high-affinity Pi transporter family members, AtPht1;1 or AtPht1;7, are hypersensitive to arsenate due to increased arsenate uptake. These plants do not exhibit increased sensitivity to arsenite. Co-overexpression of the yeast ABC transporter YCF1 in combination with AtPht1;1 or AtPht1;7 suppresses the arsenate-sensitive phenotype while further enhancing arsenic uptake. Taken together, our results support an arsenic transport mechanism in which arsenate uptake is increased through Pi transporter overexpression, and arsenic tolerance is enhanced through YCF1-mediated vacuolar sequestration. This work substantiates the viability of coupling enhanced uptake and vacuolar sequestration as a means for developing a prototypical engineered arsenic hyperaccumulator. PMID:23108027

Insulin transport into the brain and cerebrospinal fluid.

Science.gov (United States)

Begg, Denovan P

2015-01-01

The pancreatic hormone insulin plays a well-described role in the periphery, based principally on its ability to lower circulating glucose levels via activation of glucose transporters. However, insulin also acts within the central nervous system (CNS) to alter a number of physiological outcomes ranging from energy balance and glucose homeostasis to cognitive performance. Insulin is transported into the CNS by a saturable receptor-mediated process that is proposed to be dependent on the insulin receptor. Transport of insulin into the brain is dependent on numerous factors including diet, glycemia, a diabetic state and notably, obesity. Obesity leads to a marked decrease in insulin transport from the periphery into the CNS and the biological basis of this reduction of transport remains unresolved. Despite decades of research into the effects of central insulin on a wide range of physiological functions and its transport from the periphery to the CNS, numerous questions remain unanswered including which receptor is responsible for transport and the precise mechanisms of action of insulin within the brain. © 2015 Elsevier Inc. All rights reserved.

Lysosome-related organelles as mediators of metal homeostasis.

Science.gov (United States)

Blaby-Haas, Crysten E; Merchant, Sabeeha S

2014-10-10

Metal ion assimilation is essential for all forms of life. However, organisms must properly control the availability of these nutrients within the cell to avoid inactivating proteins by mismetallation. To safeguard against an imbalance between supply and demand in eukaryotes, intracellular compartments contain metal transporters that load and unload metals. Although the vacuoles of Saccharomyces cerevisiae and Arabidopsis thaliana are well established locales for the storage of copper, zinc, iron, and manganese, related compartments are emerging as important mediators of metal homeostasis. Here we describe these compartments and review their metal transporter complement. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms

Science.gov (United States)

Widdows, Kate L.; Panitchob, Nuttanont; Crocker, Ian P.; Please, Colin P.; Hanson, Mark A.; Sibley, Colin P.; Johnstone, Edward D.; Sengers, Bram G.; Lewis, Rohan M.; Glazier, Jocelyn D.

2015-01-01

Uptake of system L amino acid substrates into isolated placental plasma membrane vesicles in the absence of opposing side amino acid (zero-trans uptake) is incompatible with the concept of obligatory exchange, where influx of amino acid is coupled to efflux. We therefore hypothesized that system L amino acid exchange transporters are not fully obligatory and/or that amino acids are initially present inside the vesicles. To address this, we combined computational modeling with vesicle transport assays and transporter localization studies to investigate the mechanisms mediating [14C]l-serine (a system L substrate) transport into human placental microvillous plasma membrane (MVM) vesicles. The carrier model provided a quantitative framework to test the 2 hypotheses that l-serine transport occurs by either obligate exchange or nonobligate exchange coupled with facilitated transport (mixed transport model). The computational model could only account for experimental [14C]l-serine uptake data when the transporter was not exclusively in exchange mode, best described by the mixed transport model. MVM vesicle isolates contained endogenous amino acids allowing for potential contribution to zero-trans uptake. Both L-type amino acid transporter (LAT)1 and LAT2 subtypes of system L were distributed to MVM, with l-serine transport attributed to LAT2. These findings suggest that exchange transporters do not function exclusively as obligate exchangers.—Widdows, K. L., Panitchob, N., Crocker, I. P., Please, C. P., Hanson, M. A., Sibley, C. P., Johnstone, E. D., Sengers, B. G., Lewis, R. M., Glazier, J. D. Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms. PMID:25761365

Excitatory amino acid transporters: recent insights into molecular mechanisms, novel modes of modulation and new therapeutic possibilities

DEFF Research Database (Denmark)

Jensen, Anders A.; Fahlke, Christoph; Bjørn-Yoshimoto, Walden Emil

2015-01-01

The five excitatory amino acid transporters (EAAT1–5) mediating the synaptic uptake of the major excitatory neurotransmitter glutamate are differently expressed throughout the CNS and at the synaptic level. Although EAATs are crucial for normal excitatory neurotransmission, explorations into the ......The five excitatory amino acid transporters (EAAT1–5) mediating the synaptic uptake of the major excitatory neurotransmitter glutamate are differently expressed throughout the CNS and at the synaptic level. Although EAATs are crucial for normal excitatory neurotransmission, explorations...

SwissProt search result: AK100483 [KOME

Lifescience Database Archive (English)

Full Text Available AK100483 J023097B04 (P23634) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_HUMAN 7e-23 ...

SwissProt search result: AK120057 [KOME

Lifescience Database Archive (English)

Full Text Available AK120057 J013000P10 (P23634) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_HUMAN 1e-88 ...

SwissProt search result: AK120057 [KOME

Lifescience Database Archive (English)

Full Text Available AK120057 J013000P10 (Q16720) Plasma membrane calcium-transporting ATPase 3 (EC 3.6....3.8) (PMCA3) (Plasma membrane calcium pump isoform 3) (Plasma membrane calcium ATPase isoform 3) AT2B3_HUMAN 2e-89 ...

SwissProt search result: AK105082 [KOME

Lifescience Database Archive (English)

Full Text Available AK105082 001-046-C08 (Q01814) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) AT2B2_HUMAN 6e-15 ...

SwissProt search result: AK241795 [KOME

Lifescience Database Archive (English)

Full Text Available AK241795 J065208E19 (Q64542) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_RAT 5e-15 ...

SwissProt search result: AK058787 [KOME

Lifescience Database Archive (English)

Full Text Available AK058787 001-002-E05 (P20020) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_HUMAN 1e-65 ...

SwissProt search result: AK120495 [KOME

Lifescience Database Archive (English)

Full Text Available AK120495 J013120H18 (P23634) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_HUMAN 1e-142 ...

SwissProt search result: AK070260 [KOME

Lifescience Database Archive (English)

Full Text Available AK070260 J023045A10 (Q64542) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_RAT 2e-78 ...

SwissProt search result: AK110494 [KOME

Lifescience Database Archive (English)

Full Text Available AK110494 002-167-C09 (P58165) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) (Fragment) AT2B2_OREMO 2e-24 ...

SwissProt search result: AK100435 [KOME

Lifescience Database Archive (English)

Full Text Available AK100435 J023088J16 (P20020) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_HUMAN 2e-24 ...

SwissProt search result: AK110177 [KOME

Lifescience Database Archive (English)

Full Text Available AK110177 002-161-G12 (P11505) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_RAT 7e-20 ...

SwissProt search result: AK100436 [KOME

Lifescience Database Archive (English)

Full Text Available AK100436 J023088M17 (Q64542) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_RAT 1e-166 ...

SwissProt search result: AK100435 [KOME

Lifescience Database Archive (English)

Full Text Available AK100435 J023088J16 (Q64568) Plasma membrane calcium-transporting ATPase 3 (EC 3.6....3.8) (PMCA3) (Plasma membrane calcium pump isoform 3) (Plasma membrane calcium ATPase isoform 3) AT2B3_RAT 3e-23 ...

SwissProt search result: AK107078 [KOME

Lifescience Database Archive (English)

Full Text Available AK107078 002-121-F06 (P20020) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_HUMAN 2e-96 ...

SwissProt search result: AK121509 [KOME

Lifescience Database Archive (English)

Full Text Available AK121509 J033023K22 (P20020) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_HUMAN 1e-77 ...

SwissProt search result: AK067259 [KOME

Lifescience Database Archive (English)

Full Text Available AK067259 J013095I07 (P11506) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) AT2B2_RAT 1e-120 ...

SwissProt search result: AK066838 [KOME

Lifescience Database Archive (English)

Full Text Available AK066838 J013084L23 (Q64542) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_RAT 8e-14 ...

SwissProt search result: AK121272 [KOME

Lifescience Database Archive (English)

Full Text Available AK121272 J023107A16 (P23634) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_HUMAN 7e-29 ...

SwissProt search result: AK109037 [KOME

Lifescience Database Archive (English)

Full Text Available AK109037 002-154-C10 (P11506) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) AT2B2_RAT 6e-81 ...

SwissProt search result: AK243441 [KOME

Lifescience Database Archive (English)

Full Text Available AK243441 J100068F13 (P20020) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_HUMAN 6e-14 ...

SwissProt search result: AK243441 [KOME

Lifescience Database Archive (English)

Full Text Available AK243441 J100068F13 (Q01814) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) AT2B2_HUMAN 4e-14 ...

SwissProt search result: AK068950 [KOME

Lifescience Database Archive (English)

Full Text Available AK068950 J023001P16 (Q64542) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_RAT 3e-25 ...

SwissProt search result: AK066864 [KOME

Lifescience Database Archive (English)

Full Text Available AK066864 J013085P21 (Q16720) Plasma membrane calcium-transporting ATPase 3 (EC 3.6....3.8) (PMCA3) (Plasma membrane calcium pump isoform 3) (Plasma membrane calcium ATPase isoform 3) AT2B3_HUMAN 1e-13 ...

SwissProt search result: AK105840 [KOME

Lifescience Database Archive (English)

Full Text Available AK105840 001-203-F07 (P23634) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_HUMAN 2e-28 ...

SwissProt search result: AK067259 [KOME

Lifescience Database Archive (English)

Full Text Available AK067259 J013095I07 (Q01814) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) AT2B2_HUMAN 1e-119 ...

SwissProt search result: AK063540 [KOME

Lifescience Database Archive (English)

Full Text Available AK063540 001-117-C05 (Q64542) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_RAT 4e-12 ...

SwissProt search result: AK070260 [KOME

Lifescience Database Archive (English)

Full Text Available AK070260 J023045A10 (P11505) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_RAT 3e-69 ...

SwissProt search result: AK100435 [KOME

Lifescience Database Archive (English)

Full Text Available AK100435 J023088J16 (P23634) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_HUMAN 7e-23 ...

SwissProt search result: AK121509 [KOME

Lifescience Database Archive (English)

Full Text Available AK121509 J033023K22 (P23634) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_HUMAN 1e-77 ...

SwissProt search result: AK100878 [KOME

Lifescience Database Archive (English)

Full Text Available AK100878 J023127C21 (Q64542) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_RAT 5e-25 ...

SwissProt search result: AK105840 [KOME

Lifescience Database Archive (English)

Full Text Available AK105840 001-203-F07 (Q16720) Plasma membrane calcium-transporting ATPase 3 (EC 3.6....3.8) (PMCA3) (Plasma membrane calcium pump isoform 3) (Plasma membrane calcium ATPase isoform 3) AT2B3_HUMAN 2e-28 ...

SwissProt search result: AK100436 [KOME

Lifescience Database Archive (English)

Full Text Available AK100436 J023088M17 (P23634) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_HUMAN 1e-168 ...

SwissProt search result: AK241795 [KOME

Lifescience Database Archive (English)

Full Text Available AK241795 J065208E19 (Q16720) Plasma membrane calcium-transporting ATPase 3 (EC 3.6....3.8) (PMCA3) (Plasma membrane calcium pump isoform 3) (Plasma membrane calcium ATPase isoform 3) AT2B3_HUMAN 6e-15 ...

SwissProt search result: AK242630 [KOME

Lifescience Database Archive (English)

Full Text Available AK242630 J090022D11 (P20020) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_HUMAN 1e-143 ...

SwissProt search result: AK121250 [KOME

Lifescience Database Archive (English)

Full Text Available AK121250 J023101G05 (Q64568) Plasma membrane calcium-transporting ATPase 3 (EC 3.6....3.8) (PMCA3) (Plasma membrane calcium pump isoform 3) (Plasma membrane calcium ATPase isoform 3) AT2B3_RAT 1e-179 ...

SwissProt search result: AK121250 [KOME

Lifescience Database Archive (English)

Full Text Available AK121250 J023101G05 (Q64542) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_RAT 1e-178 ...

SwissProt search result: AK100483 [KOME

Lifescience Database Archive (English)

Full Text Available AK100483 J023097B04 (P58165) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) (Fragment) AT2B2_OREMO 1e-20 ...

SwissProt search result: AK070260 [KOME

Lifescience Database Archive (English)

Full Text Available AK070260 J023045A10 (Q64568) Plasma membrane calcium-transporting ATPase 3 (EC 3.6....3.8) (PMCA3) (Plasma membrane calcium pump isoform 3) (Plasma membrane calcium ATPase isoform 3) AT2B3_RAT 1e-70 ...

SwissProt search result: AK100483 [KOME

Lifescience Database Archive (English)

Full Text Available AK100483 J023097B04 (Q01814) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) AT2B2_HUMAN 2e-23 ...

SwissProt search result: AK068950 [KOME

Lifescience Database Archive (English)

Full Text Available AK068950 J023001P16 (P11506) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) AT2B2_RAT 2e-24 ...

SwissProt search result: AK241795 [KOME

Lifescience Database Archive (English)

Full Text Available AK241795 J065208E19 (P11505) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_RAT 3e-15 ...

SwissProt search result: AK072909 [KOME

Lifescience Database Archive (English)

Full Text Available AK072909 J023148A19 (Q01814) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) AT2B2_HUMAN 6e-23 ...

SwissProt search result: AK072909 [KOME

Lifescience Database Archive (English)

Full Text Available AK072909 J023148A19 (P58165) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) (Fragment) AT2B2_OREMO 3e-20 ...

SwissProt search result: AK070064 [KOME

Lifescience Database Archive (English)

Full Text Available AK070064 J023041B03 (P20020) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_HUMAN 1e-135 ...

SwissProt search result: AK100415 [KOME

Lifescience Database Archive (English)

Full Text Available AK100415 J023087M18 (Q64568) Plasma membrane calcium-transporting ATPase 3 (EC 3.6....3.8) (PMCA3) (Plasma membrane calcium pump isoform 3) (Plasma membrane calcium ATPase isoform 3) AT2B3_RAT 1e-179 ...

SwissProt search result: AK100483 [KOME

Lifescience Database Archive (English)

Full Text Available AK100483 J023097B04 (Q16720) Plasma membrane calcium-transporting ATPase 3 (EC 3.6....3.8) (PMCA3) (Plasma membrane calcium pump isoform 3) (Plasma membrane calcium ATPase isoform 3) AT2B3_HUMAN 9e-23 ...

SwissProt search result: AK072909 [KOME

Lifescience Database Archive (English)

Full Text Available AK072909 J023148A19 (Q16720) Plasma membrane calcium-transporting ATPase 3 (EC 3.6....3.8) (PMCA3) (Plasma membrane calcium pump isoform 3) (Plasma membrane calcium ATPase isoform 3) AT2B3_HUMAN 3e-24 ...

SwissProt search result: AK121509 [KOME

Lifescience Database Archive (English)

Full Text Available AK121509 J033023K22 (P11505) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_RAT 4e-78 ...

SwissProt search result: AK105082 [KOME

Lifescience Database Archive (English)

Full Text Available AK105082 001-046-C08 (P11505) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_RAT 3e-16 ...

SwissProt search result: AK065088 [KOME

Lifescience Database Archive (English)

Full Text Available AK065088 J013001L20 (P11505) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_RAT 1e-166 ...

SwissProt search result: AK100415 [KOME

Lifescience Database Archive (English)

Full Text Available AK100415 J023087M18 (Q01814) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) AT2B2_HUMAN 1e-146 ...

SwissProt search result: AK066259 [KOME

Lifescience Database Archive (English)

Full Text Available AK066259 J013059H11 (P11506) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) AT2B2_RAT 1e-143 ...

SwissProt search result: AK073066 [KOME

Lifescience Database Archive (English)

Full Text Available AK073066 J033023L01 (Q64542) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_RAT 5e-22 ...

SwissProt search result: AK068950 [KOME

Lifescience Database Archive (English)

Full Text Available AK068950 J023001P16 (P20020) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_HUMAN 4e-25 ...

SwissProt search result: AK110494 [KOME

Lifescience Database Archive (English)

Full Text Available AK110494 002-167-C09 (Q16720) Plasma membrane calcium-transporting ATPase 3 (EC 3.6....3.8) (PMCA3) (Plasma membrane calcium pump isoform 3) (Plasma membrane calcium ATPase isoform 3) AT2B3_HUMAN 6e-27 ...

SwissProt search result: AK109037 [KOME

Lifescience Database Archive (English)

Full Text Available AK109037 002-154-C10 (P11505) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_RAT 3e-81 ...

SwissProt search result: AK066864 [KOME

Lifescience Database Archive (English)

Full Text Available AK066864 J013085P21 (P58165) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) (Fragment) AT2B2_OREMO 4e-13 ...

SwissProt search result: AK100415 [KOME

Lifescience Database Archive (English)

Full Text Available AK100415 J023087M18 (Q64542) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_RAT 1e-178 ...

SwissProt search result: AK073220 [KOME

Lifescience Database Archive (English)

Full Text Available AK073220 J033000K23 (Q64542) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_RAT 1e-34 ...

SwissProt search result: AK067535 [KOME

Lifescience Database Archive (English)

Full Text Available AK067535 J013109J17 (P23634) Plasma membrane calcium-transporting ATPase 4 (EC 3.6....3.8) (PMCA4) (Plasma membrane calcium pump isoform 4) (Plasma membrane calcium ATPase isoform 4) AT2B4_HUMAN 2e-11 ...

SwissProt search result: AK121509 [KOME

Lifescience Database Archive (English)

Full Text Available AK121509 J033023K22 (Q16720) Plasma membrane calcium-transporting ATPase 3 (EC 3.6....3.8) (PMCA3) (Plasma membrane calcium pump isoform 3) (Plasma membrane calcium ATPase isoform 3) AT2B3_HUMAN 6e-78 ...

SwissProt search result: AK070260 [KOME

Lifescience Database Archive (English)

Full Text Available AK070260 J023045A10 (P11506) Plasma membrane calcium-transporting ATPase 2 (EC 3.6....3.8) (PMCA2) (Plasma membrane calcium pump isoform 2) (Plasma membrane calcium ATPase isoform 2) AT2B2_RAT 5e-58 ...

SwissProt search result: AK071938 [KOME

Lifescience Database Archive (English)

Full Text Available AK071938 J013083I02 (Q64568) Plasma membrane calcium-transporting ATPase 3 (EC 3.6....3.8) (PMCA3) (Plasma membrane calcium pump isoform 3) (Plasma membrane calcium ATPase isoform 3) AT2B3_RAT 1e-100 ...

SwissProt search result: AK100415 [KOME

Lifescience Database Archive (English)

Full Text Available AK100415 J023087M18 (P11505) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_RAT 1e-179 ...

SwissProt search result: AK243441 [KOME

Lifescience Database Archive (English)

Full Text Available AK243441 J100068F13 (P11505) Plasma membrane calcium-transporting ATPase 1 (EC 3.6....3.8) (PMCA1) (Plasma membrane calcium pump isoform 1) (Plasma membrane calcium ATPase isoform 1) AT2B1_RAT 4e-14 ...