WorldWideScience

Sample records for complete general secretory

  1. Secretory diarrhea.

    Science.gov (United States)

    Schiller, L R

    1999-10-01

    Diarrhea, defined as loose stools, occurs when the intestine does not complete absorption of electrolytes and water from luminal contents. This can happen when a nonabsorbable, osmotically active substance is ingested ("osmotic diarrhea") or when electrolyte absorption is impaired ("secretory diarrhea"). Most cases of acute and chronic diarrhea are due to the latter mechanism. Secretory diarrhea can result from bacterial toxins, reduced absorptive surface area caused by disease or resection, luminal secretagogues (such as bile acids or laxatives), circulating secretagogues (such as various hormones, drugs, and poisons), and medical problems that compromise regulation of intestinal function. Evaluation of patients with secretory diarrhea must be tailored to find the likely causes of this problem. Specific and nonspecific treatment can be valuable.

  2. Unsteady Stokes equations: Some complete general solutions

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    homogeneous unsteady Stokes equations are examined. A necessary and sufficient condition for a divergence-free vector to represent the velocity field of a possible unsteady Stokes flow in the absence of body forces is derived. Keywords. Complete ...

  3. Logarithmically completely monotonic functions involving the Generalized Gamma Function

    Directory of Open Access Journals (Sweden)

    Faton Merovci

    2010-12-01

    Full Text Available By a simple approach, two classes of functions involving generalization Euler's gamma function and originating from certain  problems of traffic flow are proved to be logarithmically  completely monotonic and a class of functions involving the psi function is showed to be completely monotonic.

  4. Logarithmically completely monotonic functions involving the Generalized Gamma Function

    OpenAIRE

    Faton Merovci; Valmir Krasniqi

    2010-01-01

    By a simple approach, two classes of functions involving generalization Euler's gamma function and originating from certain  problems of traffic flow are proved to be logarithmically  completely monotonic and a class of functions involving the psi function is showed to be completely monotonic.

  5. [Study of human secretory immunoglobulin A. I. Obtaining monospecific antiserum to human secretory immunoglobulin A].

    Science.gov (United States)

    German, G P; Chernokhvostova, E V; Gol'derman, S Ia

    1975-10-01

    A method of obtaining monospecific antiserum to the human secretory IgA is described. Immunochemically pure secretory IgA (isolated from human colostrum by fractionation with ammonium sulfate and gel-filtration on Sephadex G-200) was used for immunization of rabbits or sheep. Heterologous antibodies were removed by adsorption with commercial gamma globulin, normal serum, the serum of a patient suffering from A-myeloma with the IgA polymere and purified lactoferrin. Monospecific antiserum to the secretory IgA gave a reaction of complete immunological identity with the secretory IgA and a free secretory component.

  6. Differential topology and general equilibrium with complete and incomplete markets

    CERN Document Server

    Villanacci, Antonio; Benevieri, Pierluigi; Battinelli, Andrea

    2002-01-01

    General equilibrium In this book we try to cope with the challenging task of reviewing the so called general equilibrium model and of discussing one specific aspect of the approach underlying it, namely, market completeness. With the denomination "general equilibrium" (from now on in short GE) we shall mainly refer to two different things. On one hand, in particular when using the expression "GE approach", we shall refer to a long established methodolog­ ical tradition in building and developing economic models, which includes, as of today, an enormous amount of contributions, ranging in number by several 1 thousands • On the other hand, in particular when using the expression "stan­ dard differentiable GE model", we refer to a very specific version of economic model of exchange and production, to be presented in Chapters 8 and 9, and to be modified in Chapters 10 to 15. Such a version is certainly formulated within the GE approach, but it is generated by making several quite restrictive 2 assumptions •...

  7. Porosome: The Universal Secretory Portal in Cells

    Science.gov (United States)

    Jena, Bhanu

    2012-10-01

    In the past 50 years it was believed that during cell secretion, membrane-bound secretory vesicles completely merge at the cell plasma membrane resulting in the diffusion of intra-vesicular contents to the cell exterior and the compensatory retrieval of the excess membrane by endocytosis. This explanation made no sense or logic, since following cell secretion partially empty vesicles accumulate as demonstrated in electron micrographs. Furthermore, with the ``all or none'' mechanism of cell secretion by complete merger of secretory vesicle membrane at the cell plasma membrane, the cell is left with little regulation and control of the amount of content release. Moreover, it makes no sense for mammalian cells to possess such `all or none' mechanism of cell secretion, when even single-cell organisms have developed specialized and sophisticated secretory machinery, such as the secretion apparatus of Toxoplasma gondii, the contractile vacuoles in paramecium, or the various types of secretory structures in bacteria. Therefore, in 1993 in a News and Views article in Nature, E. Neher wrote ``It seems terribly wasteful that, during the release of hormones and neurotransmitters from a cell, the membrane of a vesicle should merge with the plasma membrane to be retrieved for recycling only seconds or minutes later.'' This conundrum in the molecular mechanism of cell secretion was finally resolved in 1997 following discovery of the ``Porosome,'' the universal secretory machinery in cells. Porosomes are supramolecular lipoprotein structures at the cell plasma membrane, where membrane-bound secretory vesicles transiently dock and fuse to release inravesicular contents to the outside during cell secretion. In the past decade, the composition of the porosome, its structure and dynamics at nm resolution and in real time, and its functional reconstitution into artificial lipid membrane, have all been elucidated. Since porosomes in exocrine and neuroendocrine cells measure 100-180 nm

  8. The heat flows and harmonic maps from complete manifolds into generalized regular balls

    International Nuclear Information System (INIS)

    Li Jiayu.

    1993-01-01

    Let M be a complete Riemannian manifold (compact (with or without boundary) or noncompact). Let N be a complete Riemannian manifold. We generalize the existence result for harmonic maps obtained by Hildebrandt-Kaul-Widman using the heat flow method. (author). 21 refs

  9. Generic sorting of raft lipids into secretory vesicles in yeast

    DEFF Research Database (Denmark)

    Surma, Michal A; Klose, Christian; Klemm, Robin W

    2011-01-01

    Previous work has showed that ergosterol and sphingolipids become sorted to secretory vesicles immunoisolated using a chimeric, artificial raft membrane protein as bait. In this study, we have extended this analysis to three populations of secretory vesicles isolated using natural yeast plasma...... a complete lipid overview of the yeast late secretory pathway. We could show that vesicles captured with different baits carry the same cargo and have almost identical lipid compositions; being highly enriched in ergosterol and sphingolipids. This finding indicates that lipid raft sorting is a generic...

  10. Effective description of general extensions of the Standard Model: the complete tree-level dictionary

    Science.gov (United States)

    de Blas, J.; Criado, J. C.; Pérez-Victoria, M.; Santiago, J.

    2018-03-01

    We compute all the tree-level contributions to the Wilson coefficients of the dimension-six Standard-Model effective theory in ultraviolet completions with general scalar, spinor and vector field content and arbitrary interactions. No assumption about the renormalizability of the high-energy theory is made. This provides a complete ultraviolet/infrared dictionary at the classical level, which can be used to study the low-energy implications of any model of interest, and also to look for explicit completions consistent with low-energy data.

  11. Web-Enhanced General Chemistry Increases Student Completion Rates, Success, and Satisfaction

    Science.gov (United States)

    Amaral, Katie E.; Shank, John D.; Shibley, Ivan A., Jr.; Shibley, Lisa R.

    2013-01-01

    General Chemistry I historically had one of the highest failure and withdrawal rates at Penn State Berks, a four-year college within the Penn State system. The course was completely redesigned to incorporate more group work, the use of classroom response systems, peer mentors, and a stronger online presence via the learning management system…

  12. Effect of resilient liner on masticatory efficiency and general patient satisfaction in completely edentulous patients

    DEFF Research Database (Denmark)

    Mangtani, Nidhi; Pillai, Rajath; Babu, Dinesh

    2015-01-01

    Objectives: To assess the effect of resilient lined denture on patient masticatory efficiency, general patient satisfaction and denture quality as compare to conventional complete denture over a period of one year. Material and methodology: A total of 28 completely edentulous patients (14 males...... denture liner – group 2). All patients were clinically evaluated to assess the denture quality, and administered questionnaires for masticatory efficiency and patients general satisfaction level at three intervals i.e. one month (T0), 6 months (T1) and 1 year post-insertion (T2). Results: Statistical...... masticatory efficiency improved significantly over time in controls, while in experimental group masticatory efficiency remained the same (p>.05) for almost all the questions. Patient general satisfaction score at different time intervals for each question showed no significant difference (P>.05) on inter...

  13. General individual attack on the ping-pong protocol with completely entangled pairs of qutrits

    OpenAIRE

    Vasiliu, E. V.

    2009-01-01

    The general individual (non-coherent) attack on the ping-pong protocol with completely entangled pairs of three-dimensional quantum systems (qutrits) is analyzed. The expression for amount of the eavesdropper's information as functions from probability of attack detection is derived. It is shown, that the security of the ping-pong protocol with pairs of qutrits is higher the security of the protocol with pairs of qubits. It is also shown, that with the use by legitimate users in a control mod...

  14. A complete basis for a perturbation expansion of the general N-body problem

    International Nuclear Information System (INIS)

    Laing, W Blake; Kelle, David W; Dunn, Martin; Watson, Deborah K

    2009-01-01

    We discuss a basis set developed to calculate perturbation coefficients in an expansion of the general N-body problem. This basis has two advantages. First, the basis is complete order-by-order for the perturbation series. Second, the number of independent basis tensors spanning the space for a given order does not scale with N, the number of particles, despite the generality of the problem. At first order, the number of basis tensors is 25 for all N, i.e. the problem scales as N 0 , although one would initially expect an N 6 scaling at first order. The perturbation series is expanded in inverse powers of the spatial dimension. This results in a maximally symmetric configuration at lowest order which has a point group isomorphic with the symmetric group, S N . The resulting perturbation series is order-by-order invariant under the N! operations of the S N point group which is responsible for the slower than exponential growth of the basis. In this paper, we demonstrate the completeness of the basis and perform the first test of this formalism through first order by comparing to an exactly solvable fully interacting problem of N particles with a two-body harmonic interaction potential

  15. Message from the Director General Final costs to completion of LHC

    CERN Multimedia

    Luciano Maiani

    2001-01-01

    In March this year a review of the costs for the LHC machine was started, which was completed by the end of August. This was a bottom-up review with each group concerned making a projection of the cost to completion of the project. Figures presented were worryingly high. In conjunction, the responses from industries to the calls for tender for essential machine components, especially the superconducting magnet assembly, were also higher than originally anticipated. A summary of this situation was presented to the Finance Committee last week and then to the Committee of Council. After the meetings a summary was prepared by the chairman of Committee of Council which I reprint below. CHAIRMAN'S SUMMARY In the 248th Meeting of the Committee of Council, the Director-General presented a preliminary estimate of the cost to completion of the LHC Project, approved in 1994 and scheduled for commissioning and operation in 2006. Repeating that the project is well advanced and technically sound, the figures presented, s...

  16. The Xanthomonas Ax21 protein is processed by the general secretory system and is secreted in association with outer membrane vesicles

    Directory of Open Access Journals (Sweden)

    Ofir Bahar

    2014-01-01

    Full Text Available Pattern recognition receptors (PRRs play an important role in detecting invading pathogens and mounting a robust defense response to restrict infection. In rice, one of the best characterized PRRs is XA21, a leucine rich repeat receptor-like kinase that confers broad-spectrum resistance to multiple strains of the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo. In 2009 we reported that an Xoo protein, called Ax21, is secreted by a type I-secretion system and that it serves to activate XA21-mediated immunity. This report has recently been retracted. Here we present data that corrects our previous model. We first show that Ax21 secretion does not depend on the predicted type I secretion system and that it is processed by the general secretion (Sec system. We further show that Ax21 is an outer membrane protein, secreted in association with outer membrane vesicles. Finally, we provide data showing that ax21 knockout strains do not overcome XA21-mediated immunity.

  17. Generalized index for spatial data sets as a measure of complete spatial randomness

    Science.gov (United States)

    Hackett-Jones, Emily J.; Davies, Kale J.; Binder, Benjamin J.; Landman, Kerry A.

    2012-06-01

    Spatial data sets, generated from a wide range of physical systems can be analyzed by counting the number of objects in a set of bins. Previous work has been limited to equal-sized bins, which are inappropriate for some domains (e.g., circular). We consider a nonequal size bin configuration whereby overlapping or nonoverlapping bins cover the domain. A generalized index, defined in terms of a variance between bin counts, is developed to indicate whether or not a spatial data set, generated from exclusion or nonexclusion processes, is at the complete spatial randomness (CSR) state. Limiting values of the index are determined. Using examples, we investigate trends in the generalized index as a function of density and compare the results with those using equal size bins. The smallest bin size must be much larger than the mean size of the objects. We can determine whether a spatial data set is at the CSR state or not by comparing the values of a generalized index for different bin configurations—the values will be approximately the same if the data is at the CSR state, while the values will differ if the data set is not at the CSR state. In general, the generalized index is lower than the limiting value of the index, since objects do not have access to the entire region due to blocking by other objects. These methods are applied to two applications: (i) spatial data sets generated from a cellular automata model of cell aggregation in the enteric nervous system and (ii) a known plant data distribution.

  18. General variational many-body theory with complete self-consistency for trapped bosonic systems

    International Nuclear Information System (INIS)

    Streltsov, Alexej I.; Alon, Ofir E.; Cederbaum, Lorenz S.

    2006-01-01

    In this work we develop a complete variational many-body theory for a system of N trapped bosons interacting via a general two-body potential. The many-body solution of this system is expanded over orthogonal many-body basis functions (configurations). In this theory both the many-body basis functions and the respective expansion coefficients are treated as variational parameters. The optimal variational parameters are obtained self-consistently by solving a coupled system of noneigenvalue--generally integro-differential--equations to get the one-particle functions and by diagonalizing the secular matrix problem to find the expansion coefficients. We call this theory multiconfigurational Hartree theory for bosons or MCHB(M), where M specifies explicitly the number of one-particle functions used to construct the configurations. General rules for evaluating the matrix elements of one- and two-particle operators are derived and applied to construct the secular Hamiltonian matrix. We discuss properties of the derived equations. We show that in the limiting cases of one configuration the theory boils down to the well-known Gross-Pitaevskii and the recently developed multi-orbital mean fields. The invariance of the complete solution with respect to unitary transformations of the one-particle functions is utilized to find the solution with the minimal number of contributing configurations. In the second part of our work we implement and apply the developed theory. It is demonstrated that for any practical computation where the configurational space is restricted, the description of trapped bosonic systems strongly depends on the choice of the many-body basis set used, i.e., self-consistency is of great relevance. As illustrative examples we consider bosonic systems trapped in one- and two-dimensional symmetric and asymmetric double well potentials. We demonstrate that self-consistency has great impact on the predicted physical properties of the ground and excited states

  19. Conceptual development of a complete LWR reload design methodology based on generalized perturbation theory

    International Nuclear Information System (INIS)

    White, J.R.

    1986-01-01

    A new approach for the physics design and analysis of LWR reload cores is developed and demonstrated through several practical applications. The new design philosophy uses first- and second-order response derivatives to predict the important reactor performance characteristics (power peaking, reactivity coefficients, etc.) for any number of possible material configurations (assembly shuffling and burnable poison loadings). The response derivatives are computed using generalized perturbation theory (GPT) techniques. This report describes in detail an idealized GPT-based design system. The idealized system would contain individual modules to generate the required first-order and higher-order sensitivity data. It would also contain at least two major application codes; one for core design optimization and the other for evaluation of several safety parameters of interest in off-normal situations. This ideal system would be fully automated, user-friendly, and quite flexible in its ability to provide a variety of design and analysis capabilities. Information gained form these three studies gives a good foundation for the development of a complete integrated design package

  20. The evolution of plant secretory structures and emergence of terpenoid chemical diversity.

    Science.gov (United States)

    Lange, Bernd Markus

    2015-01-01

    Secretory structures in terrestrial plants appear to have first emerged as intracellular oil bodies in liverworts. In vascular plants, internal secretory structures, such as resin ducts and laticifers, are usually found in conjunction with vascular bundles, whereas subepidermal secretory cavities and epidermal glandular trichomes generally have more complex tissue distribution patterns. The primary function of plant secretory structures is related to defense responses, both constitutive and induced, against herbivores and pathogens. The ability to sequester secondary (or specialized) metabolites and defense proteins in secretory structures was a critical adaptation that shaped plant-herbivore and plant-pathogen interactions. Although this review places particular emphasis on describing the evolution of pathways leading to terpenoids, it also assesses the emergence of other metabolite classes to outline the metabolic capabilities of different plant lineages.

  1. arXiv Effective description of general extensions of the Standard Model: the complete tree-level dictionary

    CERN Document Server

    de Blas, J.; Perez-Victoria, M.; Santiago, J.

    2018-03-19

    We compute all the tree-level contributions to the Wilson coefficients of the dimension-six Standard-Model effective theory in ultraviolet completions with general scalar, spinor and vector field content and arbitrary interactions. No assumption about the renormalizability of the high-energy theory is made. This provides a complete ultraviolet/infrared dictionary at the classical level, which can be used to study the low-energy implications of any model of interest, and also to look for explicit completions consistent with low-energy data.

  2. Quantitation of secretory protein levels by radioimmunoassay

    International Nuclear Information System (INIS)

    Klein, J.L.; Dawson, J.R.

    1978-01-01

    A radioimmunoassay was designed for the detection of secretory protein, a component of secretory immunoglobulin A, in human serum. The assay uses free secretory protein isolated from human colostrum, and antisera raised in rabbits to be purified antigen. The mean level of secretory protein in the control group was 2.34+-0.41 μg/ml (mean+-S.E.M.). The level in cord blood was slightly lower (0.74+-0.26 μg/ml), while the level in patients with ovarian carcinoma was significantly increased (12.67+-1.43 μg/ml). Pregnant women have increasingly secretory protein levels with increasing length of gestation (5.86+-2.02, 11.55+-1.30 and 17.00+-1.16 μg/ml for the first, second and third trimesters, respectively. (Auth.)

  3. Muscle as a secretory organ

    DEFF Research Database (Denmark)

    Pedersen, Bente K

    2013-01-01

    Skeletal muscle is the largest organ in the body. Skeletal muscles are primarily characterized by their mechanical activity required for posture, movement, and breathing, which depends on muscle fiber contractions. However, skeletal muscle is not just a component in our locomotor system. Recent e...... proteins produced by skeletal muscle are dependent upon contraction. Therefore, it is likely that myokines may contribute in the mediation of the health benefits of exercise.......Skeletal muscle is the largest organ in the body. Skeletal muscles are primarily characterized by their mechanical activity required for posture, movement, and breathing, which depends on muscle fiber contractions. However, skeletal muscle is not just a component in our locomotor system. Recent...... evidence has identified skeletal muscle as a secretory organ. We have suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either autocrine, paracrine, or endocrine effects should be classified as "myokines." The muscle secretome consists...

  4. Factors influencing career intentions on completion of general practice vocational training in England: a cross-sectional study.

    Science.gov (United States)

    Dale, Jeremy; Russell, Rachel; Scott, Emma; Owen, Katherine

    2017-08-17

    General practice is experiencing a growing crisis with the numbers of doctors who are training and then entering the profession in the UK failing to keep pace with workforce needs. This study investigated the immediate to medium term career intentions of those who are about to become general practitioners (GPs) and the factors that are influencing career plans. Online questionnaire survey, with quantitative answers analysed using descriptive statistics and free text data analysed using a thematic framework approach. Doctors approaching the end of 3-year GP vocational training in the West Midlands, England. 178 (57.2%) doctors completed the survey. Most participants planned to work as salaried GPs or locums rather than entering a general practice partnership for at least the first 5 years post-completion of training; others failed to express a career plan or planned to leave general practice completely or work overseas. Many were interested in developing portfolio careers.The quality of general practice experience across undergraduate, foundation and vocational training were reported as influencing personal career plans, and in particular perceptions about workload pressure and morale within the training practices in which they had been placed. Experience of a poor work-life balance as a trainee had a negative effect on career intentions, as did negative perceptions about how general practice is portrayed by politicians and the media. This study describes a number of potentially modifiable factors related to training programmes that are detrimentally influencing the career plans of newly trained GPs. In addition, there are sociodemographic factors, such as age, gender and having children, which are also influencing career plans and so need to be accommodated. With ever-increasing workload in general practice, there is an urgent need to understand and where possible address these issues at national and local level. © Article author(s) (or their employer(s) unless

  5. Quality improvement training for core medical and general practice trainees: a pilot study of project participation, completion and journal publication.

    Science.gov (United States)

    McNab, Duncan; McKay, John; Bowie, Paul

    2015-11-01

    Small-scale quality improvement projects are expected to make a significant contribution towards improving the quality of healthcare. Enabling doctors-in-training to design and lead quality improvement projects is important preparation for independent practice. Participation is mandatory in speciality training curricula. However, provision of training and ongoing support in quality improvement methods and practice is variable. We aimed to design and deliver a quality improvement training package to core medical and general practice specialty trainees and evaluate impact in terms of project participation, completion and publication in a healthcare journal. A quality improvement training package was developed and delivered to core medical trainees and general practice specialty trainees in the west of Scotland encompassing a 1-day workshop and mentoring during completion of a quality improvement project over 3 months. A mixed methods evaluation was undertaken and data collected via questionnaire surveys, knowledge assessment, and formative assessment of project proposals, completed quality improvement projects and publication success. Twenty-three participants attended the training day with 20 submitting a project proposal (87%). Ten completed quality improvement projects (43%), eight were judged as satisfactory (35%), and four were submitted and accepted for journal publication (17%). Knowledge and confidence in aspects of quality improvement improved during the pilot, while early feedback on project proposals was valued (85.7%). This small study reports modest success in training core medical trainees and general practice specialty trainees in quality improvement. Many gained knowledge of, confidence in and experience of quality improvement, while journal publication was shown to be possible. The development of educational resources to aid quality improvement project completion and mentoring support is necessary if expectations for quality improvement are to be

  6. Analysis of Membrane Protein Topology in the Plant Secretory Pathway.

    Science.gov (United States)

    Guo, Jinya; Miao, Yansong; Cai, Yi

    2017-01-01

    Topology of membrane proteins provides important information for the understanding of protein function and intermolecular associations. Integrate membrane proteins are generally transported from endoplasmic reticulum (ER) to Golgi and downstream compartments in the plant secretory pathway. Here, we describe a simple method to study membrane protein topology along the plant secretory pathway by transiently coexpressing a fluorescent protein (XFP)-tagged membrane protein and an ER export inhibitor protein, ARF1 (T31N), in tobacco BY-2 protoplast. By fractionation, microsome isolation, and trypsin digestion, membrane protein topology could be easily detected by either direct confocal microscopy imaging or western-blot analysis using specific XFP antibodies. A similar strategy in determining membrane protein topology could be widely adopted and applied to protein analysis in a broad range of eukaryotic systems, including yeast cells and mammalian cells.

  7. Secretory products of helminth parasites as immunomodulators.

    Science.gov (United States)

    Harnett, William

    2014-07-01

    Parasitic helminths release molecules into their environment, which are generally referred to as excretory-secretory products or ES. ES derived from a wide range of nematodes, trematodes and cestodes have been studied during the past 30-40 years, their characterization evolving from simple biochemical procedures such as SDS-PAGE in the early days to sophisticated proteomics in the 21st century. Study has incorporated investigation of ES structure, potential as vaccines, immunodiagnostic utility, functional activities and immunomodulatory properties. Immunomodulation by ES is increasingly the area of most intensive research with a number of defined helminth products extensively analyzed with respect to the nature of their selective effects on cells of the immune system as well as the molecular mechanisms, which underlie these immunomodulatory effects. As a consequence, we are now beginning to learn the identities of the receptors that ES employ and are increasingly acquiring detailed knowledge of the signalling pathways that they interact with and subvert. Such information is contributing to the growing idea that the anti-inflammatory properties of a number of ES products makes them suitable starting points for the development of novel drugs for treating human inflammatory disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. A General Design Methodology for Synchronous Early-Completion-Prediction Adders in Nano-CMOS DSP Architectures

    Directory of Open Access Journals (Sweden)

    Mauro Olivieri

    2013-01-01

    Full Text Available Synchronous early-completion-prediction adders (ECPAs are used for high clock rate and high-precision DSP datapaths, as they allow a dominant amount of single-cycle operations even if the worst-case carry propagation delay is longer than the clock period. Previous works have also demonstrated ECPA advantages for average leakage reduction and NBTI effects reduction in nanoscale CMOS technologies. This paper illustrates a general systematic methodology to design ECPA units, targeting nanoscale CMOS technologies, which is not available in the current literature yet. The method is fully compatible with standard VLSI macrocell design tools and standard adder structures and includes automatic definition of critical test patterns for postlayout verification. A design example is included, reporting speed and power data superior to previous works.

  9. Duplication of complete dentures using general-purpose handheld optical scanner and 3-dimensional printer: Introduction and clinical considerations.

    Science.gov (United States)

    Kurahashi, Kosuke; Matsuda, Takashi; Goto, Takaharu; Ishida, Yuichi; Ito, Teruaki; Ichikawa, Tetsuo

    2017-01-01

    To introduce a new clinical procedure for fabricating duplicates of complete dentures by bite pressure impression using digital technology, and to discuss its clinical significance. The denture is placed on a rotary table and the 3-dimensional form of the denture is digitized using a general-purpose handheld optical scanner. The duplicate denture is made of polylactic acid by a 3-dimensional printer using the 3-dimensional data. This procedure has the advantages of wasting less material, employing less human power, decreasing treatment time at the chair side, lowering the rates of contamination, and being readily fabricated at the time of the treatment visit. Copyright © 2016 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  10. Universal Dimensions of Meaning Derived from Semantic Relations among Words and Senses: Mereological Completeness vs. Ontological Generality

    Directory of Open Access Journals (Sweden)

    Alexei V. Samsonovich

    2014-07-01

    Full Text Available A key to semantic analysis is a precise and practically useful definition of meaning that is general for all domains of knowledge. We previously introduced the notion of weak semantic map: a metric space allocating concepts along their most general (universal semantic characteristics while at the same time ignoring other, domain-specific aspects of their meanings. Here we address questions of the number, quality, and mutual independence of the weak semantic dimensions. Specifically, we employ semantic relationships not previously used for weak semantic mapping, such as holonymy/meronymy (“is-part/member-of”, and we compare maps constructed from word senses to those constructed from words. We show that the “completeness” dimension derived from the holonym/meronym relation is independent of, and practically orthogonal to, the “abstractness” dimension derived from the hypernym-hyponym (“is-a” relation, while both dimensions are orthogonal to the maps derived from synonymy and antonymy. Interestingly, the choice of using relations among words vs. senses implies a non-trivial trade-off between rich and unambiguous information due to homonymy and polysemy. The practical utility of the new and prior dimensions is illustrated by the automated evaluation of different kinds of documents. Residual analysis of available linguistic resources, such as WordNet, suggests that the number of universal semantic dimensions representable in natural language may be finite. Their complete characterization, as well as the extension of results to non-linguistic materials, remains an open challenge.

  11. Synaptic Control of Secretory Trafficking in Dendrites

    Directory of Open Access Journals (Sweden)

    Cyril Hanus

    2014-06-01

    Full Text Available Localized signaling in neuronal dendrites requires tight spatial control of membrane composition. Upon initial synthesis, nascent secretory cargo in dendrites exits the endoplasmic reticulum (ER from local zones of ER complexity that are spatially coupled to post-ER compartments. Although newly synthesized membrane proteins can be processed locally, the mechanisms that control the spatial range of secretory cargo transport in dendritic segments are unknown. Here, we monitored the dynamics of nascent membrane proteins in dendritic post-ER compartments under regimes of low or increased neuronal activity. In response to activity blockade, post-ER carriers are highly mobile and are transported over long distances. Conversely, increasing synaptic activity dramatically restricts the spatial scale of post-ER trafficking along dendrites. This activity-induced confinement of secretory cargo requires site-specific phosphorylation of the kinesin motor KIF17 by Ca2+/calmodulin-dependent protein kinases (CaMK. Thus, the length scales of early secretory trafficking in dendrites are tuned by activity-dependent regulation of microtubule-dependent transport.

  12. Ursodeoxycholic acid attenuates colonic epithelial secretory function

    Science.gov (United States)

    Kelly, Orlaith B; Mroz, Magdalena S; Ward, Joseph B J; Colliva, Carolina; Scharl, Michael; Pellicciari, Roberto; Gilmer, John F; Fallon, Padraic G; Hofmann, Alan F; Roda, Aldo; Murray, Frank E; Keely, Stephen J

    2013-01-01

    Dihydroxy bile acids, such as chenodeoxycholic acid (CDCA), are well known to promote colonic fluid and electrolyte secretion, thereby causing diarrhoea associated with bile acid malabsorption. However, CDCA is rapidly metabolised by colonic bacteria to ursodeoxycholic acid (UDCA), the effects of which on epithelial transport are poorly characterised. Here, we investigated the role of UDCA in the regulation of colonic epithelial secretion. Cl− secretion was measured across voltage-clamped monolayers of T84 cells and muscle-stripped sections of mouse or human colon. Cell surface biotinylation was used to assess abundance/surface expression of transport proteins. Acute (15 min) treatment of T84 cells with bilateral UDCA attenuated Cl− secretory responses to the Ca2+ and cAMP-dependent secretagogues carbachol (CCh) and forskolin (FSK) to 14.0 ± 3.8 and 40.2 ± 7.4% of controls, respectively (n= 18, P acid (LCA). Accordingly, LCA (50–200 μm) enhanced agonist-induced secretory responses in vitro and a metabolically stable UDCA analogue, 6α-methyl-UDCA, exerted anti-secretory actions in vitro and in vivo. In conclusion, UDCA exerts direct anti-secretory actions on colonic epithelial cells and metabolically stable derivatives of the bile acid may offer a new approach for treating intestinal diseases associated with diarrhoea. PMID:23507881

  13. Predicting Secretory Proteins with SignalP

    DEFF Research Database (Denmark)

    Nielsen, Henrik

    2017-01-01

    SignalP is the currently most widely used program for prediction of signal peptides from amino acid sequences. Proteins with signal peptides are targeted to the secretory pathway, but are not necessarily secreted. After a brief introduction to the biology of signal peptides and the history...

  14. Hepatitis E Virus in Cambodia: Prevalence among the General Population and Complete Genome Sequence of Genotype 4.

    Science.gov (United States)

    Yamada, Hiroko; Takahashi, Kazuaki; Lim, Olline; Svay, Somana; Chuon, Channarena; Hok, Sirany; Do, Son Huy; Fujimoto, Mayumi; Akita, Tomoyuki; Goto, Noboru; Katayama, Keiko; Arai, Masahiro; Tanaka, Junko

    2015-01-01

    Hepatitis E virus (HEV) is a growing public health problem in many countries. In this study, we investigated HEV seroprevalence among the general population in the Siem Reap province, Cambodia, and performed HEV genetic analysis with the aim to develop an HEV prevention strategy. This seroepidemiological cross-sectional study conducted from 2010 to 2014 included 868 participants from four different locations in Siem Reap province, Cambodia. They answered questionnaires and provided blood samples for the analysis of hepatitis virus infections. Among the participants (360 men and 508 women; age range, 7-90 years), the prevalence of anti-HEV IgG was 18.4% (95% confidence interval: 15.9-21.0); HEV RNA was detected in two participants (0.23%) and was classified as genotype 3 and 4. Full-length genome of the genotype 4 isolate, CVS-Sie10, was sequenced; it contained 7,222 nucleotides and three ORFs and demonstrated high sequence identity with the swine China isolates swGX40 (95.57%), SS19 (94.37%), and swDQ (91.94%). Multivariate logistic regression analysis revealed that men, elderly people, and house workers were risk groups significantly associated with the positivity for anti-HEV IgG. This is the first report on the detection of HEV genotype 4 in humans in Cambodia and on the complete genome sequence of HEV genotype 4 from this country. Our study demonstrates that new HEV infection cases occur frequently among the general population in Cambodia, and effective preventive measures are required.

  15. Hepatitis E Virus in Cambodia: Prevalence among the General Population and Complete Genome Sequence of Genotype 4.

    Directory of Open Access Journals (Sweden)

    Hiroko Yamada

    Full Text Available Hepatitis E virus (HEV is a growing public health problem in many countries. In this study, we investigated HEV seroprevalence among the general population in the Siem Reap province, Cambodia, and performed HEV genetic analysis with the aim to develop an HEV prevention strategy. This seroepidemiological cross-sectional study conducted from 2010 to 2014 included 868 participants from four different locations in Siem Reap province, Cambodia. They answered questionnaires and provided blood samples for the analysis of hepatitis virus infections. Among the participants (360 men and 508 women; age range, 7-90 years, the prevalence of anti-HEV IgG was 18.4% (95% confidence interval: 15.9-21.0; HEV RNA was detected in two participants (0.23% and was classified as genotype 3 and 4. Full-length genome of the genotype 4 isolate, CVS-Sie10, was sequenced; it contained 7,222 nucleotides and three ORFs and demonstrated high sequence identity with the swine China isolates swGX40 (95.57%, SS19 (94.37%, and swDQ (91.94%. Multivariate logistic regression analysis revealed that men, elderly people, and house workers were risk groups significantly associated with the positivity for anti-HEV IgG. This is the first report on the detection of HEV genotype 4 in humans in Cambodia and on the complete genome sequence of HEV genotype 4 from this country. Our study demonstrates that new HEV infection cases occur frequently among the general population in Cambodia, and effective preventive measures are required.

  16. RFP tags for labeling secretory pathway proteins

    Energy Technology Data Exchange (ETDEWEB)

    Han, Liyang; Zhao, Yanhua [State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082 (China); Zhang, Xi; Peng, Jianxin [College of Life Sciences, Central China Normal University, Wuhan 430079, Hubei (China); Xu, Pingyong, E-mail: pyxu@ibp.ac.cn [Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Huan, Shuangyan, E-mail: shuangyanhuan@163.com [State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082 (China); Zhang, Mingshu, E-mail: mingshu1984@gmail.com [Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)

    2014-05-09

    Highlights: • Membrane protein Orai1 can be used to report the fusion properties of RFPs. • Artificial puncta are affected by dissociation constant as well as pKa of RFPs. • Among tested RFPs mOrange2 is the best choice for secretory protein labeling. - Abstract: Red fluorescent proteins (RFPs) are useful tools for live cell and multi-color imaging in biological studies. However, when labeling proteins in secretory pathway, many RFPs are prone to form artificial puncta, which may severely impede their further uses. Here we report a fast and easy method to evaluate RFPs fusion properties by attaching RFPs to an environment sensitive membrane protein Orai1. In addition, we revealed that intracellular artificial puncta are actually colocalized with lysosome, thus besides monomeric properties, pKa value of RFPs is also a key factor for forming intracellular artificial puncta. In summary, our current study provides a useful guide for choosing appropriate RFP for labeling secretory membrane proteins. Among RFPs tested, mOrange2 is highly recommended based on excellent monomeric property, appropriate pKa and high brightness.

  17. Secretory expression of the non-secretory-type Lentinula edodes laccase by Aspergillus oryzae.

    Science.gov (United States)

    Yano, Akira; Kikuchi, Sayaka; Nakagawa, Yuko; Sakamoto, Yuichi; Sato, Toshitsugu

    2009-01-01

    The shiitake mushroom, Lentinula edodes, has an extracelluar secretory-type laccase, Lcc1, and a fruiting-body-accumulation-type laccase, Lcc4. We previously reported the production of Lcc1 by plant cells, but had difficulty producing Lcc4. Here, we report the production of Lcc1 and Lcc4 by Aspergillus oryzae and the extracellular secretory production of Lcc4 using a modified secretion signal peptide (SP) from Lcc1. Sp-Lcc4 produced by A. oryzae had biochemical activities similar to Lcc4 produced by L. edodes. Lcc1 did not react with beta-(3,4-dihydroxyphenol) alanine (DOPA), but Lcc4 from L. edodes and A. oryzae could oxidize DOPA. K(M) values for the substrates 2,2'-azino-di-(3-ethylbenzthiazolinsulfonate), 2,6-dimethoxyphenol, guaiacol, pyrogallol, and catechol were similar for Lcc4 and Sp-Lcc4. In conclusion, a non-secretory-type fungal laccase is secreted into the culture media with its original enzymatic properties by exploiting modified secretory signal peptide. 2008 Elsevier GmbH.

  18. Secretory proteins of the pulmonary extracellular lining

    International Nuclear Information System (INIS)

    Gupta, R.P.; Patton, S.E.; Eddy, M.; Smits, H.L.; Jetten, A.M.; Nettesheim, P.; Hook, G.E.R.

    1986-01-01

    The objective of this investigation was to identify proteins in the pulmonary extracellular lining (EL) that are secreted by cells of the pulmonary epithelium. Pulmonary lavage effluents from the lungs of rabbits were centrifuged to remove all cells and particulate materials. Serum proteins were removed by repeatedly passing concentrated lavage effluent fluid through an affinity column containing IgG fraction of goat anti-rabbit (whole serum) antiserum bound to Sepharose-4B. Nonserum proteins accounted for 21.3 +/- 10.3% of the total soluble proteins in pulmonary lavage effluents. Serum free lavage effluents (SFL) contained 25 identifiable proteins as determined by using SDS-PAGE under reducing conditions. Of these proteins approximately 73% was accounted for by a single protein with MW of 66 kd. The secretory nature of the proteins present in SFL was investigated by studying the incorporation of 35 S-methionine into proteins released by lung slices and trachea followed by SDS-PAGE and autoradiography. Many, but not all proteins present in SFL were identified as proteins secreted by pulmonary tissues. The major secretory proteins appeared to have MWs of 59, 53, 48, 43, 24, 14, and 6 kd under reducing conditions. These data demonstrate the presence of several proteins in the pulmonary extracellular lining that appear to be secreted by the pulmonary epithelium

  19. Secretory pattern of canine growth hormone

    International Nuclear Information System (INIS)

    French, M.B.; Vaitkus, P.; Cukerman, E.; Sirek, A.; Sirek, O.V.

    1987-01-01

    The aim of this paper was to define the secretory pattern of growth hormone (GH) under basal conditions in fasted, conscious, male dogs accustomed to handling. Blood samples were withdrawn from a cephalic vein at 15-min intervals. In this way, any ultradian rhythms, if present, could be detected within the frequency range of 0.042-2 cycles/h. In addition, samples were drawn at either 1- or 2.5-min intervals for 2.5 or 5 h to determine whether frequency components greater than 2 cycles/h were present. GH was measured by radioimmunoassay and the raw data were submitted to time series analysis employing power spectral estimation by means of fast Fourier transformation techniques. Peak plasma levels were up to 12 times higher than the baseline concentration of ∼ 1 ng/ml. Spectral analysis revealed an endogenous frequency of 0.22 cycles/h, i.e., a periodicity of 4.5 h/cycle. The results indicate that under basal conditions the secretory bursts of canine GH are limited to one peak every 4.5 h

  20. The Role of Adenoid Mast Cells in the Pathogenesis of Secretory Otitis Media

    Directory of Open Access Journals (Sweden)

    M. Faruk Oktay

    2007-01-01

    Full Text Available To investigate the possible role of adenoid mast cells in the etiology of secretory otitis media. Between 2001-2002, 25 patients with chronic adenoitis and chronic secretory otitis media and 25 patients with isolated adenoid hypertrophy were included to the study. Adenoidectomy performed to the all patients under general anesthesia. Adenoidectomy specimens were evaluated under the light microscopy and the number of mast cells were calculated for each patient. The number of mast cells were compared between two groups. The number of mast cells were between 4-84 in the otitis media with effusion and adenoid hypertrophy group (median:52, however it was between 2-63 (median: 23 in the isolated adenoid hypertrophy group. When comparing the two groups using Mann-Withney U test, the number of mast cells found to be significantly higher in the chronic secretory otitis media group (p<0.001.Based on our findings there is a relationship between increased adenoid mast cells and otitis media with effusion and these cells may have a possible role in the etiology of chronic secretory otitis media.

  1. An inhomogeneous T-Q equation for the open XXX chain with general boundary terms: completeness and arbitrary spin

    International Nuclear Information System (INIS)

    Nepomechie, Rafael I

    2013-01-01

    An inhomogeneous T-Q equation has recently been proposed by Cao, Yang, Shi and Wang for the open spin-1/2 XXX chain with general (nondiagonal) boundary terms. We argue that a simplified version of this equation describes all the eigenvalues of the transfer matrix of this model. We also propose a generating function for the inhomogeneous T-Q equations of arbitrary spin. (fast track communication)

  2. Secretory Phospholipase A2-IIA and Cardiovascular Disease

    DEFF Research Database (Denmark)

    Holmes, Michael V; Simon, Tabassome; Exeter, Holly J

    2013-01-01

    This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease.......This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease....

  3. Mammary Analog Secretory Carcinoma of the Nasal Cavity

    DEFF Research Database (Denmark)

    Baneckova, Martina; Agaimy, Abbas; Andreasen, Simon

    2018-01-01

    Secretory carcinoma, originally described as mammary analog secretory carcinoma (MASC), is a low-grade salivary gland tumor characterized by a t(12;15)(p13;q25) translocation, resulting in an ETV6-NTRK3 gene fusion. Most MASCs are localized to the parotid gland and intraoral minor salivary glands...

  4. Lipomatous secretory meningioma: case report and review of the literature

    International Nuclear Information System (INIS)

    Liebig, T.; Hoffmann, T.; Hosten, N.; Sander, B.; Lanksch, W.R.

    1998-01-01

    Secretory meningioma is a rare entity which may be characterised by imaging features unusual for other subtypes of meningoma, such as low attenuation on CT, high (fat-tissue equivalent) signal intensity on T1-weighted MRI, marked surrounding oedema, and irregular contrast enhancement. We report a case of secretory meningioma and review the literature. (orig.) (orig.)

  5. The Effects of a Self-Monitoring Package on Homework Completion and Accuracy of Students with Disabilities in an Inclusive General Education Classroom

    Science.gov (United States)

    Falkenberg, Carol Ann; Barbetta, Patricia M.

    2013-01-01

    This study used a multiple baseline design across subjects to investigate the effects of a self-monitoring package on the math and spelling homework completion and accuracy rates of four fourth-grade students (two boys and two girls) with disabilities in an inclusive general education classroom. Throughout baseline and intervention, participants…

  6. Eustachian tube three-dimensional reconstruction of secretory otitis media

    International Nuclear Information System (INIS)

    Yu Yafeng; Zhou Weirong; Bao Xueping; Li Min; Hu Zhenmin

    2006-01-01

    Objective: To study relationship between Eustachian tube and secretory otitis media and to explore the pathogeny of secretory otitis by three-dimensional reconstruction of Eustachian tube. Methods: Thirty cases of secretory otitis media (male 19, female 11) were selected randomly. Everyone was checked by otoscope and audiometry. Their bilateral Eustachian tubes were scanning by helix CT while making Valsalva's action. All images were passed on to work station to make three-dimensional reconstruction. Results: Four patients were found have Eustachian tube diseases, while most of patients' Eustachian tubes ventilated normally. Conclusions: Three-dimensional reconstruction of Eustachian tube can open out some pathogens of some secretory otitis medias. It will be helpful to diagnosis and therapy of secretory otitis media. (authors)

  7. A Complete Design Flow of a General Purpose Wireless GPS/Inertial Platform for Motion Data Monitoring

    Directory of Open Access Journals (Sweden)

    Gianluca Borgese

    2015-07-01

    Full Text Available This work illustrates a complete design flow of an electronic system developed to support applications in which there are the need to measure motion parameters and transmit them to a remote unit for real-time teleprocessing. In order to be useful in many operative contexts, the system is flexible, compact, and lightweight. It integrates a tri-axial inertial sensor, a GPS module, a wireless transceiver and can drive a pocket camera. Data acquisition and packetization are handled in order to increase data throughput on Radio Bridge and to minimize power consumption. A trajectory reconstruction algorithm, implementing the Kalman-filter technique, allows obtaining real-time body tracking using only inertial sensors. Thanks to a graphical user interface it is possible to remotely control the system operations and to display the motion data.

  8. The patient general satisfaction of mandibular single-implant overdentures and conventional complete dentures: Study protocol for a randomized crossover trial.

    Science.gov (United States)

    Kanazawa, Manabu; Tanoue, Mariko; Miyayasu, Anna; Takeshita, Shin; Sato, Daisuke; Asami, Mari; Lam, Thuy Vo; Thu, Khaing Myat; Oda, Ken; Komagamine, Yuriko; Minakuchi, Shunsuke; Feine, Jocelyne

    2018-05-01

    Mandibular overdentures retained by a single implant placed in the midline of edentulous mandible have been reported to be more comfortable and function better than complete dentures. Although single-implant overdentures are still more costly than conventional complete dentures, there are a few studies which investigated whether mandibular single-implant overdentures are superior to complete dentures when patient general satisfaction is compared. The aim of this study is to assess patient general satisfaction with mandibular single-implant overdentures and complete dentures. This study is a randomized crossover trial to compare mandibular single-implant overdentures and complete dentures in edentulous individuals. Participant recruitment is ongoing at the time of this submission. Twenty-two participants will be recruited. New mandibular complete dentures will be fabricated. A single implant will be placed in the midline of the edentulous mandible. The mucosal surface of the complete denture around the implant will be relieved for 3 months. The participants will then be randomly allocated into 2 groups according to the order of the interventions; group 1 will receive single-implant overdentures first and will wear them for 2 months, followed by complete dentures for 2 months. Group 2 will receive the same treatments in a reverse order. After experiencing the 2 interventions, the participants will choose one of the mandibular prostheses, and yearly follow-up visits are planned for 5 years. The primary outcome of this trial is patient ratings of general satisfaction on 100 mm visual analog scales. Assessments of the prostheses and oral health-related quality of life will also be recorded as patient-reported outcomes. The secondary outcomes are cost and time for treatment. Masticatory efficiency and cognitive capacity will also be recorded. Furthermore, qualitative research will be performed to investigate the factors associated with success of these mandibular

  9. Three-dimensional ultrastructural analyses of anterior pituitary gland expose spatial relationships between endocrine cell secretory granule localization and capillary distribution.

    Science.gov (United States)

    Yoshitomi, Munetake; Ohta, Keisuke; Kanazawa, Tomonoshin; Togo, Akinobu; Hirashima, Shingo; Uemura, Kei-Ichiro; Okayama, Satoko; Morioka, Motohiro; Nakamura, Kei-Ichiro

    2016-10-31

    Endocrine and endothelial cells of the anterior pituitary gland frequently make close appositions or contacts, and the secretory granules of each endocrine cell tend to accumulate at the perivascular regions, which is generally considered to facilitate secretory functions of these cells. However, three-dimensional relationships between the localization pattern of secretory granules and blood vessels are not fully understood. To define and characterize these spatial relationships, we used scanning electron microscopy (SEM) three-dimensional reconstruction method based on focused ion-beam slicing and scanning electron microscopy (FIB/SEM). Full three-dimensional cellular architectures of the anterior pituitary tissue at ultrastructural resolution revealed that about 70% of endocrine cells were in apposition to the endothelial cells, while almost 30% of endocrine cells were entirely isolated from perivascular space in the tissue. Our three-dimensional analyses also visualized the distribution pattern of secretory granules in individual endocrine cells, showing an accumulation of secretory granules in regions in close apposition to the blood vessels in many cases. However, secretory granules in cells isolated from the perivascular region tended to distribute uniformly in the cytoplasm of these cells. These data suggest that the cellular interactions between the endocrine and endothelial cells promote an uneven cytoplasmic distribution of the secretory granules.

  10. General hybrid projective complete dislocated synchronization with non-derivative and derivative coupling based on parameter identification in several chaotic and hyperchaotic systems

    International Nuclear Information System (INIS)

    Sun Jun-Wei; Shen Yi; Zhang Guo-Dong; Wang Yan-Feng; Cui Guang-Zhao

    2013-01-01

    According to the Lyapunov stability theorem, a new general hybrid projective complete dislocated synchronization scheme with non-derivative and derivative coupling based on parameter identification is proposed under the framework of drive-response systems. Every state variable of the response system equals the summation of the hybrid drive systems in the previous hybrid synchronization. However, every state variable of the drive system equals the summation of the hybrid response systems while evolving with time in our method. Complete synchronization, hybrid dislocated synchronization, projective synchronization, non-derivative and derivative coupling, and parameter identification are included as its special item. The Lorenz chaotic system, Rössler chaotic system, memristor chaotic oscillator system, and hyperchaotic Lü system are discussed to show the effectiveness of the proposed methods. (general)

  11. Airway Secretory microRNAome Changes during Rhinovirus Infection in Early Childhood.

    Directory of Open Access Journals (Sweden)

    Maria J Gutierrez

    secretion of EVs containing miR-155, which is predicted in silico to regulate antiviral immunity. Further characterization of the airway secretory microRNAome during health and disease may lead to completely new strategies to treat and monitor respiratory conditions in all ages.

  12. Network reconstruction of the mouse secretory pathway applied on CHO cell transcriptome data

    DEFF Research Database (Denmark)

    Lund, Anne Mathilde; Kaas, Christian Schrøder; Brandl, Julian

    2017-01-01

    , counting 801 different components in mouse. By employing our mouse RECON to the CHO-K1 genome in a comparative genomic approach, we could reconstruct the protein secretory pathway of CHO cells counting 764 CHO components. This RECON furthermore facilitated the development of three alternative methods...... to study protein secretion through graphical visualizations of omics data. We have demonstrated the use of these methods to identify potential new and known targets for engineering improved growth and IgG production, as well as the general observation that CHO cells seem to have less strict transcriptional...... regulation of protein secretion than healthy mouse cells.  Conclusions: The RECON of the secretory pathway represents a strong tool for interpretation of data related to protein secretion as illustrated with transcriptomic data of Chinese Hamster Ovary (CHO) cells, the main platform for mammalian protein...

  13. Male accessory gland secretory protein polymorphism in natural ...

    Indian Academy of Sciences (India)

    [Ravi Ram K. and Ramesh S. R. 2007 Male accessory gland secretory protein polymorphism in natural ..... quence of species-specific genetic responses to variations in .... Eberhard W. G. 1996 Female control: sexual selection by cryptic.

  14. Secretory Phospholipase A(2) Activity toward Diverse Substrates

    DEFF Research Database (Denmark)

    Madsen, Jesper Jonasson; Linderoth, Lars; Subramanian, Arun Kumar

    2011-01-01

    We have studied secretory phospholipase A(2)-IIA (sPLA(2)) activity toward different phospholipid analogues by performing biophysical 1 characterizations and molecular dynamics simulations. The phospholipids were natural substrates, triple alkyl phospholipids, a prodrug anticancer etherlipid, and...

  15. Influence of continuous light and darkness on the secretory ...

    Indian Academy of Sciences (India)

    Unknown

    rent phases of the secretory process were demonstrated. (Srivastava 1999). ..... in the pineal supportive cells of deep sea fish, Nezumia liolepis (McNulty 1976) and .... factors as light and temperature. Melatonin and ... Brain Res. 52 271–296.

  16. A complete generalized adjustment criterion

    NARCIS (Netherlands)

    Perković, Emilija; Textor, Johannes; Kalisch, Markus; Maathuis, Marloes H.

    2015-01-01

    Covariate adjustment is a widely used approach to estimate total causal effects from observational data. Several graphical criteria have been developed in recent years to identify valid covariates for adjustment from graphical causal models. These criteria can handle multiple causes, latent

  17. Towards a Complete Classification of Symmetry-Protected Topological Phases for Interacting Fermions in Three Dimensions and a General Group Supercohomology Theory

    Science.gov (United States)

    Wang, Qing-Rui; Gu, Zheng-Cheng

    2018-01-01

    The classification and construction of symmetry-protected topological (SPT) phases in interacting boson and fermion systems have become a fascinating theoretical direction in recent years. It has been shown that (generalized) group cohomology theory or cobordism theory gives rise to a complete classification of SPT phases in interacting boson or spin systems. The construction and classification of SPT phases in interacting fermion systems are much more complicated, especially in three dimensions. In this work, we revisit this problem based on an equivalence class of fermionic symmetric local unitary transformations. We construct very general fixed-point SPT wave functions for interacting fermion systems. We naturally reproduce the partial classifications given by special group supercohomology theory, and we show that with an additional B ˜H2(Gb,Z2) structure [the so-called obstruction-free subgroup of H2(Gb,Z2) ], a complete classification of SPT phases for three-dimensional interacting fermion systems with a total symmetry group Gf=Gb×Z2f can be obtained for unitary symmetry group Gb. We also discuss the procedure for deriving a general group supercohomology theory in arbitrary dimensions.

  18. P-selectin targeting to secretory lysosomes of Rbl-2H3 cells

    OpenAIRE

    Kaur, J.; Cutler, D. F.

    2002-01-01

    The biogenesis of secretory lysosomes, which combine characteristics of both lysosomes and secretory granules, is currently of high interest. In particular, it is not clear whether delivery of membrane proteins to the secretory lysosome requires lysosomal, secretory granule, or some novel targeting determinants. Heterologous expression of P-selectin has established that this membrane protein contains targeting signals for both secretory granules and lysosomes. P-selectin is therefore an ideal...

  19. Progressive quality control of secretory proteins in the early secretory compartment by ERp44.

    Science.gov (United States)

    Sannino, Sara; Anelli, Tiziana; Cortini, Margherita; Masui, Shoji; Degano, Massimo; Fagioli, Claudio; Inaba, Kenji; Sitia, Roberto

    2014-10-01

    ERp44 is a pH-regulated chaperone of the secretory pathway. In the acidic milieu of the Golgi, its C-terminal tail changes conformation, simultaneously exposing the substrate-binding site for cargo capture and the RDEL motif for ER retrieval through interactions with cognate receptors. Protonation of cysteine 29 in the active site allows tail movements in vitro and in vivo. Here, we show that conserved histidine residues in the C-terminal tail also regulate ERp44 in vivo. Mutants lacking these histidine residues retain substrates more efficiently. Surprisingly, they are also O-glycosylated and partially secreted. Co-expression of client proteins prevents secretion of the histidine mutants, forcing tail opening and RDEL accessibility. Client-induced RDEL exposure allows retrieval of proteins from distinct stations along the secretory pathway, as indicated by the changes in O-glycosylation patterns upon overexpression of different partners. The ensuing gradients might help to optimize folding and assembly of different cargoes. Endogenous ERp44 is O-glycosylated and secreted by human primary endometrial cells, suggesting possible pathophysiological roles of these processes. © 2014. Published by The Company of Biologists Ltd.

  20. Secretory structure and histochemistry test of some Zingiberaceae plants

    Science.gov (United States)

    Indriyani, Serafinah

    2017-11-01

    A secretory structure is a structure that produces a plant's metabolite substances. Secretory structures are grouped into an internal and external. Zingiberaceae plants are known as traditional medicine plants and as spice plants due to secretory structures in their tissues. The objective of the research were to describe the secretory structure of Zingiberaceae plants and to discover the qualitatively primary metabolite substances in plant's tissues via histochemistry test. The research was conducted by observation descriptive design, quantitative data including the density of secretory cells per mm². The quantitative data were analyzed by ANOVA and continued by Duncan at α = 5 %. The results showed that the secretory structures in leaves, rhizome, and the root of 14 species of Zingiberaceae plants are found in the mesophyll of leaves and cortex, and also pith in rhizome and roots. The type of secretory structure is internal. Within the root of Zingiber cassumunar Roxb.(bengle), Curcuma domestica Val. (kunyit), Curcuma zedoaria (Berg.) Roscoe (kunyit putih), Zingiber zerumbet (L.) J.E. Smith (lempuyang), Alpiniapurpurata K. Schum (lengkuas merah), and Curcuma aeruginosa Val. (temu ireng) were found amylum grains, while in Kaemferia galanga L. (kencur), Boesen bergiapandurata L. (temu kunci), and Curcuma xanthorrhiza Roxb. (temulawak) there were no amylum grains in the root as well as in the leaves. The roots of bengle had the greatest density of amylum grain, it had 248.1 ± 9.8 secretory cells of amylum grains per mm². Lipids (oil droplets) were found in the root of bengle, Zingiber officinale Roxb. Var. emprit (jahe emprit), Zingiber officinale Roxb. Var. Gajah (jahe gajah), Zingiber officinale Roxb. Var. Rubrum (jahe merah), Keampferia angustifolia L. (kunci pepet), kunyit, kunyit putih, lempuyang, lengkua smerah, Curcuma aeruginosa Val. (temu ireng), and Curcuma mangga Val. and van Zijp (temu mangga); the root of lempuyang had the greatest density of oil

  1. Cellular responses to the expression of unstable secretory proteins in the filamentous fungus Aspergillus oryzae.

    Science.gov (United States)

    Yokota, Jun-Ichi; Shiro, Daisuke; Tanaka, Mizuki; Onozaki, Yasumichi; Mizutani, Osamu; Kakizono, Dararat; Ichinose, Sakurako; Shintani, Tomoko; Gomi, Katsuya; Shintani, Takahiro

    2017-03-01

    Filamentous fungi are often used as cell factories for recombinant protein production because of their ability to secrete large quantities of hydrolytic enzymes. However, even using strong transcriptional promoters, yields of nonfungal proteins are generally much lower than those of fungal proteins. Recent analyses revealed that expression of certain nonfungal secretory proteins induced the unfolded protein response (UPR), suggesting that they are recognized as proteins with folding defects in filamentous fungi. More recently, however, even highly expressed endogenous secretory proteins were found to evoke the UPR. These findings raise the question of whether the unfolded or misfolded state of proteins is selectively recognized by quality control mechanisms in filamentous fungi. In this study, a fungal secretory protein (1,2-α-D-mannosidase; MsdS) with a mutation that decreases its thermostability was expressed at different levels in Aspergillus oryzae. We found that, at moderate expression levels, wild-type MsdS was secreted to the medium, while the mutant was not. In the strain with a deletion for the hrdA gene, which is involved in the endoplasmic reticulum-associated degradation pathway, mutant MsdS had specifically increased levels in the intracellular fraction but was not secreted. When overexpressed, the mutant protein was secreted to the medium to a similar extent as the wild-type protein; however, the mutant underwent hyperglycosylation and induced the UPR. Deletion of α-amylase (the most abundant secretory protein in A. oryzae) alleviated the UPR induction by mutant MsdS overexpression. These findings suggest that misfolded MsdS and unfolded species of α-amylase might act synergistically for UPR induction.

  2. More evidence for trends in the intergenerational transmission of divorce: a completed cohort approach using data from the general social survey.

    Science.gov (United States)

    Wolfinger, Nicholas H

    2011-05-01

    Many studies have demonstrated that the children of divorce are disproportionately likely to end their own marriages. In previous work, I showed that the transmission of divorce between generations weakened substantially for General Social Survey (GSS) respondents interviewed between 1973 and 1996 (Wolfinger 1999); Li and Wu (2006, 2008) contended that my finding is a methodological artifact of the GSS's lack of marriage duration data. This article presents a completed-cohort approach to studying divorce using the GSS. The results confirm a decline in the probability of divorce transmission that cannot be explained by the right-censoring bias alleged by Li and Wu. This finding contributes to an ongoing debate about trends in the negative consequences of parental divorce, as well as demonstrating a useful approach to right-censored phenomena when event history data are not available.

  3. Remodeling of bovine oviductal epithelium by mitosis of secretory cells.

    Science.gov (United States)

    Ito, Sayaka; Kobayashi, Yoshihiko; Yamamoto, Yuki; Kimura, Koji; Okuda, Kiyoshi

    2016-11-01

    Two types of oviductal epithelial cells, secretory and ciliated, play crucial roles in the first days after fertilization in mammals. Secretory cells produce various molecules promoting embryo development, while ciliated cells facilitate transport of oocytes and zygotes by ciliary beating. The proportions of the two cell types change during the estrous cycle. The proportion of ciliated cells on the oviductal luminal surface is abundant at the follicular phase, whereas the proportion of secretory cells gradually increases with the formation of the corpus luteum. In the present study, we hypothesize that the proportions of ciliated and secretory epithelial cells are regulated by mitosis. The proportion of the cells being positive for FOXJ1 (a ciliated cell marker) or Ki67 (a mitosis marker) in epithelial cells during the estrous cycle were immunohistochemically examined. Ki67 and FOXJ1 or PAX8 (a secretory cell marker), were double-stained to clarify which types of epithelial cells undergo mitosis. In the ampulla, the percentage of FOXJ1-positive cells was highest at the day of ovulation (Day 0) and decreased by about 50 % by Days 8-12, while in the isthmus it did not change during the estrous cycle. The proportion of Ki67-positive cells was highest at around the time of ovulation in both the ampulla and isthmus. All the Ki67-positive cells were PAX8-positive and FOXJ1-negative in both the ampulla and isthmus. These findings suggest that epithelial remodeling, which is regulated by differentiation and/or proliferation of secretory cells of the oviduct, provides the optimal environment for gamete transport, fertilization and embryonic development.

  4. SPRED: A machine learning approach for the identification of classical and non-classical secretory proteins in mammalian genomes

    Energy Technology Data Exchange (ETDEWEB)

    Kandaswamy, Krishna Kumar [Institute for Neuro- and Bioinformatics, University of Luebeck, 23538 Luebeck (Germany); Graduate School for Computing in Medicine and Life Sciences, University of Luebeck, 23538 Luebeck (Germany); Pugalenthi, Ganesan [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Hartmann, Enno; Kalies, Kai-Uwe [Centre for Structural and Cell Biology in Medicine, Institute of Biology, University of Luebeck, 23538 Luebeck (Germany); Moeller, Steffen [Institute for Neuro- and Bioinformatics, University of Luebeck, 23538 Luebeck (Germany); Suganthan, P.N. [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Martinetz, Thomas, E-mail: martinetz@inb.uni-luebeck.de [Institute for Neuro- and Bioinformatics, University of Luebeck, 23538 Luebeck (Germany)

    2010-01-15

    Eukaryotic protein secretion generally occurs via the classical secretory pathway that traverses the ER and Golgi apparatus. Secreted proteins usually contain a signal sequence with all the essential information required to target them for secretion. However, some proteins like fibroblast growth factors (FGF-1, FGF-2), interleukins (IL-1 alpha, IL-1 beta), galectins and thioredoxin are exported by an alternative pathway. This is known as leaderless or non-classical secretion and works without a signal sequence. Most computational methods for the identification of secretory proteins use the signal peptide as indicator and are therefore not able to identify substrates of non-classical secretion. In this work, we report a random forest method, SPRED, to identify secretory proteins from protein sequences irrespective of N-terminal signal peptides, thus allowing also correct classification of non-classical secretory proteins. Training was performed on a dataset containing 600 extracellular proteins and 600 cytoplasmic and/or nuclear proteins. The algorithm was tested on 180 extracellular proteins and 1380 cytoplasmic and/or nuclear proteins. We obtained 85.92% accuracy from training and 82.18% accuracy from testing. Since SPRED does not use N-terminal signals, it can detect non-classical secreted proteins by filtering those secreted proteins with an N-terminal signal by using SignalP. SPRED predicted 15 out of 19 experimentally verified non-classical secretory proteins. By scanning the entire human proteome we identified 566 protein sequences potentially undergoing non-classical secretion. The dataset and standalone version of the SPRED software is available at (http://www.inb.uni-luebeck.de/tools-demos/spred/spred).

  5. SPRED: A machine learning approach for the identification of classical and non-classical secretory proteins in mammalian genomes

    International Nuclear Information System (INIS)

    Kandaswamy, Krishna Kumar; Pugalenthi, Ganesan; Hartmann, Enno; Kalies, Kai-Uwe; Moeller, Steffen; Suganthan, P.N.; Martinetz, Thomas

    2010-01-01

    Eukaryotic protein secretion generally occurs via the classical secretory pathway that traverses the ER and Golgi apparatus. Secreted proteins usually contain a signal sequence with all the essential information required to target them for secretion. However, some proteins like fibroblast growth factors (FGF-1, FGF-2), interleukins (IL-1 alpha, IL-1 beta), galectins and thioredoxin are exported by an alternative pathway. This is known as leaderless or non-classical secretion and works without a signal sequence. Most computational methods for the identification of secretory proteins use the signal peptide as indicator and are therefore not able to identify substrates of non-classical secretion. In this work, we report a random forest method, SPRED, to identify secretory proteins from protein sequences irrespective of N-terminal signal peptides, thus allowing also correct classification of non-classical secretory proteins. Training was performed on a dataset containing 600 extracellular proteins and 600 cytoplasmic and/or nuclear proteins. The algorithm was tested on 180 extracellular proteins and 1380 cytoplasmic and/or nuclear proteins. We obtained 85.92% accuracy from training and 82.18% accuracy from testing. Since SPRED does not use N-terminal signals, it can detect non-classical secreted proteins by filtering those secreted proteins with an N-terminal signal by using SignalP. SPRED predicted 15 out of 19 experimentally verified non-classical secretory proteins. By scanning the entire human proteome we identified 566 protein sequences potentially undergoing non-classical secretion. The dataset and standalone version of the SPRED software is available at (http://www.inb.uni-luebeck.de/tools-demos/spred/spred).

  6. The transcriptional corepressor MTGR1 regulates intestinal secretory lineage allocation.

    Science.gov (United States)

    Parang, Bobak; Rosenblatt, Daniel; Williams, Amanda D; Washington, Mary K; Revetta, Frank; Short, Sarah P; Reddy, Vishruth K; Hunt, Aubrey; Shroyer, Noah F; Engel, Michael E; Hiebert, Scott W; Williams, Christopher S

    2015-03-01

    Notch signaling largely determines intestinal epithelial cell fate. High Notch activity drives progenitors toward absorptive enterocytes by repressing secretory differentiation programs, whereas low Notch permits secretory cell assignment. Myeloid translocation gene-related 1 (MTGR1) is a transcriptional corepressor in the myeloid translocation gene/Eight-Twenty-One family. Given that Mtgr1(-/-) mice have a dramatic reduction of intestinal epithelial secretory cells, we hypothesized that MTGR1 is a key repressor of Notch signaling. In support of this, transcriptome analysis of laser capture microdissected Mtgr1(-/-) intestinal crypts revealed Notch activation, and secretory markers Mucin2, Chromogranin A, and Growth factor-independent 1 (Gfi1) were down-regulated in Mtgr1(-/-) whole intestines and Mtgr1(-/-) enteroids. We demonstrate that MTGR1 is in a complex with Suppressor of Hairless Homolog, a key Notch effector, and represses Notch-induced Hairy/Enhancer of Split 1 activity. Moreover, pharmacologic Notch inhibition using a γ-secretase inhibitor (GSI) rescued the hyperproliferative baseline phenotype in the Mtgr1(-/-) intestine and increased production of goblet and enteroendocrine lineages in Mtgr1(-/-) mice. GSI increased Paneth cell production in wild-type mice but failed to do so in Mtgr1(-/-) mice. We determined that MTGR1 can interact with GFI1, a transcriptional corepressor required for Paneth cell differentiation, and repress GFI1 targets. Overall, the data suggest that MTGR1, a transcriptional corepressor well characterized in hematopoiesis, plays a critical role in intestinal lineage allocation. © FASEB.

  7. Secretory Phospholipase A(2)-IIA and Cardiovascular Disease

    NARCIS (Netherlands)

    Holmes, Michael V.; Simon, Tabassome; Exeter, Holly J.; Folkersen, Lasse; Asselbergs, Folkert W.; Guardiola, Montse; Cooper, Jackie A.; Palmen, Jutta; Hubacek, Jaroslav A.; Carruthers, Kathryn F.; Horne, Benjamin D.; Brunisholz, Kimberly D.; Mega, Jessica L.; Van Iperen, Erik P. A.; Li, Mingyao; Leusink, Maarten; Trompet, Stella; Verschuren, Jeffrey J. W.; Hovingh, G. Kees; Dehghan, Abbas; Nelson, Christopher P.; Kotti, Salma; Danchin, Nicolas; Scholz, Markus; Haase, Christiane L.; Rothenbacher, Dietrich; Swerdlow, Daniel I.; Kuchenbaecker, Karoline B.; Staines-Urias, Eleonora; Goel, Anuj; van 't Hooft, Ferdinand; Gertow, Karl; de Faire, Ulf; Panayiotou, Andrie G.; Tremoli, Elena; Baldassarre, Damiano; Veglia, Fabrizio; Holdt, Lesca M.; Beutner, Frank; Gansevoort, Ron T.; Navis, Gerjan J.; Mateo Leach, Irene; Breitling, Lutz P.; Brenner, Hermann; Thiery, Joachim; Dallmeier, Dhayana; Franco-Cereceda, Anders; Boer, Jolanda M. A.; Stephens, Jeffrey W.; Hofker, Marten H.; Tedgui, Alain; Hofman, Albert; Uitterlinden, Andre G.; Adamkova, Vera; Pitha, Jan; Onland-Moret, N. Charlotte; Cramer, Maarten J.; Nathoe, Hendrik M.; Spiering, Wilko; Klungel, Olaf H.; Kumari, Meena; Whincup, Peter H.; Morrow, David A.; Braund, Peter S.; Hall, Alistair S.; Olsson, Anders G.; Doevendans, Pieter A.; Trip, Mieke D.; Tobin, Martin D.; Hamsten, Anders; Watkins, Hugh; Koenig, Wolfgang; Nicolaides, Andrew N.; Teupser, Daniel; Day, Ian N. M.; Carlquist, John F.; Gaunt, Tom R.; Ford, Ian; Sattar, Naveed; Tsimikas, Sotirios; Schwartz, Gregory G.; Lawlor, Debbie A.; Morris, Richard W.; Sandhu, Manjinder S.; Poledne, Rudolf; Maitland-van der Zee, Anke H.; Khaw, Kay-Tee; Keating, Brendan J.; van der Harst, Pim; Price, Jackie F.; Mehta, Shamir R.; Yusuf, Salim; Witteman, Jaqueline C. M.; Franco, Oscar H.; Jukema, J. Wouter; de Knijff, Peter; Tybjaerg-Hansen, Anne; Rader, Daniel J.; Farrall, Martin; Samani, Nilesh J.; Kivimaki, Mika; Fox, Keith A. A.; Humphries, Steve E.; Anderson, Jeffrey L.; Boekholdt, S. Matthijs; Palmer, Tom M.; Eriksson, Per; Pare, Guillaume; Hingorani, Aroon D.; Sabatine, Marc S.; Mallat, Ziad; Casas, Juan P.; Talmud, Philippa J.

    2013-01-01

    Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. Background Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not

  8. Mammary analogue secretory carcinoma: A rare salivary gland tumour

    African Journals Online (AJOL)

    Salivary gland malignancy is rare, with a global annual incidence of. 3 per 100 000 people.[1,2] A rare salivary gland tumour, mammary analogue secretory carcinoma (MASC), has only recently been described.[3] The few reports and studies concerning MASC have been published in several pathology journals. We report ...

  9. Identification of CTLA2A, DEFB29, WFDC15B, SERPINA1F and MUP19 as Novel Tissue-Specific Secretory Factors in Mouse.

    Directory of Open Access Journals (Sweden)

    Jibin Zhang

    Full Text Available Secretory factors in animals play an important role in communication between different cells, tissues and organs. Especially, the secretory factors with specific expression in one tissue may reflect important functions and unique status of that tissue in an organism. In this study, we identified potential tissue-specific secretory factors in the fat, muscle, heart, lung, kidney and liver in the mouse by analyzing microarray data from NCBI's Gene Expression Omnibus (GEO public repository and searching and predicting their subcellular location in GeneCards and WoLF PSORT, and then confirmed tissue-specific expression of the genes using semi-quantitative PCR reactions. With this approach, we confirmed 11 lung, 7 liver, 2 heart, 1 heart and muscle, 7 kidney and 2 adipose and liver-specific secretory factors. Among these genes, 1 lung-specific gene--CTLA2A (cytotoxic T lymphocyte-associated protein 2 alpha, 3 kidney-specific genes--SERPINA1F (serpin peptidase inhibitor, Clade A, member 1F, WFDC15B (WAP four-disulfide core domain 15B and DEFB29 (defensin beta 29 and 1 liver-specific gene--MUP19 (major urinary protein 19 have not been reported as secretory factors. These genes were tagged with hemagglutinin at the 3'end and then transiently transfected to HEK293 cells. Through protein detection in cell lysate and media using Western blotting, we verified secretion of the 5 genes and predicted the potential pathways in which they may participate in the specific tissue through data analysis of GEO profiles. In addition, alternative splicing was detected in transcripts of CTLA2A and SERPINA1F and the corresponding proteins were found not to be secreted in cell culture media. Identification of novel secretory factors through the current study provides a new platform to explore novel secretory factors and a general direction for further study of these genes in the future.

  10. Letter dated 18 October 1999 from the Permanent Representative of China to the United Nations addressed to the Secretary-General. Uphold the ABM Treaty, push forward nuclear disarmament process and promote international peace and security. General Assembly. 54. session. First Committee. Agenda item 76. General and complete disarmament

    International Nuclear Information System (INIS)

    1999-01-01

    The document reproduces the text of the letter dated 18 October 1999 sent to the Secretary-General by the Permanent Representative of China to the United Nations in connection with the agenda item 76 (General and complete disarmament) of the 54th session of the General Assembly, First Committee. The letter expresses the position of the Chinese delegation concerning the proposed amendment of the Anti-Ballistic Missile Treaty (ABM Treaty)

  11. A Western Blot-based Investigation of the Yeast Secretory Pathway Designed for an Intermediate-Level Undergraduate Cell Biology Laboratory

    Science.gov (United States)

    Hood-DeGrenier, Jennifer K.

    2008-01-01

    The movement of newly synthesized proteins through the endomembrane system of eukaryotic cells, often referred to generally as the secretory pathway, is a topic covered in most intermediate-level undergraduate cell biology courses. An article previously published in this journal described a laboratory exercise in which yeast mutants defective in…

  12. Novelties in secretory structures and anatomy of Rhynchosia (Fabaceae).

    Science.gov (United States)

    De Vargas, Wanderleia; Sartori, Ângela L B; Dias, Edna S

    2015-03-01

    A comparative anatomical study was carried out on the secretory structures of leaflets from taxa belonging to the genus Rhynchosia - taxa difficult to delimit because of uncertain interspecific relations - in order to evaluate the potential diagnostic value of these anatomical traits for taxonomic assignment. A further objective was to establish consensual denomination for these secretory structures. The new anatomical features found in these taxa were sufficiently consistent to separate the species evaluated. The presence and localization of glandular-punctate structures bulbous-based trichomes, the number of layers in the palisade parenchyma and the arrangement of vascular units distinguish the taxa investigated and these characteristics can be extended to other species of Papilionoideae. The trichomes analyzed were described and classified into five types. Depicted in diagrams, photomicrographs, and by scanning electron microscopy, and listed for the first time at the genus and species levels. The information obtained served to effectively distinguish the taxa investigated among species of Papilonoideae.

  13. Giant renin secretory granules in beige mouse renal afferent arterioles

    DEFF Research Database (Denmark)

    Jensen, B L; Rasch, Ruth; Nyengaard, Jens Randel

    1997-01-01

    The mutant beige mouse (C57BL/6 bg) has a disease characterised by abnormally enlarged cytoplasmic granules in a variety of cells. With the purpose of establishing a suitable cellular model for studying renin secretion, the present study was undertaken to compare renin granule morphology in beige...... (average granular volume 0.681 microm3), whereas 1-2 large granules were present per cell in beige mice. The volume of afferent arteriole that contained secretory granules was lower in the beige mice. We conclude that the beige mouse synthesizes, stores and releases active renin. Renin secretory granules...... in beige mice are grossly enlarged with 1-2 granules per juxtaglomerular cell. Compared with control mice, a similar amount of total renin granule volume per afferent arteriole is contained in a smaller part of beige mouse afferent arteriole. Granular cells from beige mice could therefore be a valuable...

  14. Isolation of intact sub-dermal secretory cavities from Eucalyptus

    Directory of Open Access Journals (Sweden)

    Goodger Jason QD

    2010-09-01

    Full Text Available Abstract Background The biosynthesis of plant natural products in sub-dermal secretory cavities is poorly understood at the molecular level, largely due to the difficulty of physically isolating these structures for study. Our aim was to develop a protocol for isolating live and intact sub-dermal secretory cavities, and to do this, we used leaves from three species of Eucalyptus with cavities that are relatively large and rich in essential oils. Results Leaves were digested using a variety of commercially available enzymes. A pectinase from Aspergillus niger was found to allow isolation of intact cavities after a relatively short incubation (12 h, with no visible artifacts from digestion and no loss of cellular integrity or cavity contents. Several measurements indicated the potential of the isolated cavities for further functional studies. First, the cavities were found to consume oxygen at a rate that is comparable to that estimated from leaf respiratory rates. Second, mRNA was extracted from cavities, and it was used to amplify a cDNA fragment with high similarity to that of a monoterpene synthase. Third, the contents of the cavity lumen were extracted, showing an unexpectedly low abundance of volatile essential oils and a sizeable amount of non-volatile material, which is contrary to the widely accepted role of secretory cavities as predominantly essential oil repositories. Conclusions The protocol described herein is likely to be adaptable to a range of Eucalyptus species with sub-dermal secretory cavities, and should find wide application in studies of the developmental and functional biology of these structures, and the biosynthesis of the plant natural products they contain.

  15. Secretory processes involved in the formation of milk

    International Nuclear Information System (INIS)

    Knutsson, P.G.

    1976-01-01

    Current knowledge on milk formation is reviewed. Emphasis is given to sites of formation of protein, fat and lactose, and transfer of these compounds into the alveolar lumen. Further, the formation of the water phase of milk is thoroughly discussed, and evidence presented that milk formation includes both secretory and re-absorptive processes as well as diffusion. A short presentation of colostrum formation is included. Neither biochemical processes involved in synthesis of organic compounds nor mammary gland endocrinology are discussed. (author)

  16. The regulated secretory pathway and human disease: insights from gene variants and single nucleotide polymorphisms

    Directory of Open Access Journals (Sweden)

    Stephen eSalton

    2013-08-01

    Full Text Available The regulated secretory pathway provides critical control of peptide, growth factor, and hormone release from neuroendocrine and endocrine cells, and neurons, maintaining physiological homeostasis. Propeptides and prohormones are packaged into dense core granules (DCGs, where they frequently undergo tissue-specific processing as the DCG matures. Proteins of the granin family are DCG components, and although their function is not fully understood, data suggest they are involved in DCG formation and regulated protein/peptide secretion, in addition to their role as precursors of bioactive peptides. Association of gene variation, including single nucleotide polymorphisms (SNPs, with neuropsychiatric, endocrine and metabolic diseases, has implicated specific secreted proteins and peptides in disease pathogenesis. For example, a SNP at position 196 (G/A of the human brain-derived neurotrophic factor (BDNF gene dysregulates protein processing and secretion and leads to cognitive impairment. This suggests more generally that variants identified in genes encoding secreted growth factors, peptides, hormones, and proteins involved in DCG biogenesis, protein processing, and the secretory apparatus, could provide insight into the process of regulated secretion as well as disorders that result when it is impaired.

  17. A micromethod for the assay of cellular secretory physiology: Application to rabbit parietal cells

    International Nuclear Information System (INIS)

    Adrian, T.E.; Goldenring, J.R.; Oddsdottir, M.; Zdon, M.J.; Zucker, K.A.; Lewis, J.J.; Modlin, I.M.

    1989-01-01

    A micromethod for investigating secretory physiology in isolated cells was evaluated. The method utilized a specially designed polycarbonate incubation chamber to provide constant oxygenation to cells incubating in a 96-well microtiter plate. Cells were rapidly separated from media by vacuum filtration. Isolated parietal cells were utilized to demonstrate the versatility of the method for assay of intracellular accumulation of [ 14 C]-aminopyrine, secretion of intrinsic factor into the medium, and assay of intracellular cAMP. Histamine stimulated the uptake of [ 14 C]aminopyrine and intrinsic factor secretion in a sustained and linear fashion. At the end of the 2-h period uptake of aminopyrine and secretion of intrinsic factor were increased 17- and 5-fold, respectively. This response to histamine was accompanied by a rapid and sustained 3-fold rise in intracellular cyclic AMP. In contrast, carbamylcholine caused a transient increase in [ 14 C]aminopyrine accumulation and intrinsic factor secretion which was most pronounced during the first 10 min and had almost ceased by 30 min. Carbamylcholine had no effect on intracellular cAMP levels. This new method, which can handle 400 replicates using parietal cells from the fundic mucosa of a single rabbit, is suitable for studying the time course of intracellular events which accompany general secretory processes

  18. High abundance of Serine/Threonine-rich regions predicted to be hyper-O-glycosylated in the secretory proteins coded by eight fungal genomes

    Directory of Open Access Journals (Sweden)

    González Mario

    2012-09-01

    Full Text Available Abstract Background O-glycosylation of secretory proteins has been found to be an important factor in fungal biology and virulence. It consists in the addition of short glycosidic chains to Ser or Thr residues in the protein backbone via O-glycosidic bonds. Secretory proteins in fungi frequently display Ser/Thr rich regions that could be sites of extensive O-glycosylation. We have analyzed in silico the complete sets of putatively secretory proteins coded by eight fungal genomes (Botrytis cinerea, Magnaporthe grisea, Sclerotinia sclerotiorum, Ustilago maydis, Aspergillus nidulans, Neurospora crassa, Trichoderma reesei, and Saccharomyces cerevisiae in search of Ser/Thr-rich regions as well as regions predicted to be highly O-glycosylated by NetOGlyc (http://www.cbs.dtu.dk. Results By comparison with experimental data, NetOGlyc was found to overestimate the number of O-glycosylation sites in fungi by a factor of 1.5, but to be quite reliable in the prediction of highly O-glycosylated regions. About half of secretory proteins have at least one Ser/Thr-rich region, with a Ser/Thr content of at least 40% over an average length of 40 amino acids. Most secretory proteins in filamentous fungi were predicted to be O-glycosylated, sometimes in dozens or even hundreds of sites. Residues predicted to be O-glycosylated have a tendency to be grouped together forming hyper-O-glycosylated regions of varying length. Conclusions About one fourth of secretory fungal proteins were predicted to have at least one hyper-O-glycosylated region, which consists of 45 amino acids on average and displays at least one O-glycosylated Ser or Thr every four residues. These putative highly O-glycosylated regions can be found anywhere along the proteins but have a slight tendency to be at either one of the two ends.

  19. BPIFB6 Regulates Secretory Pathway Trafficking and Enterovirus Replication.

    Science.gov (United States)

    Morosky, Stefanie; Lennemann, Nicholas J; Coyne, Carolyn B

    2016-05-15

    Bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) is an endoplasmic reticulum (ER)-localized host factor that negatively regulates coxsackievirus B (CVB) replication through its control of the autophagic pathway. Here, we show that another member of the BPIFB family, BPIFB6, functions as a positive regulator of CVB, and other enterovirus, replication by controlling secretory pathway trafficking and Golgi complex morphology. We show that similar to BPIFB3, BPIFB6 localizes exclusively to the ER, where it associates with other members of the BPIFB family. However, in contrast to our findings that RNA interference (RNAi)-mediated silencing of BPIFB3 greatly enhances CVB replication, we show that silencing of BPIFB6 expression dramatically suppresses enterovirus replication in a pan-viral manner. Mechanistically, we show that loss of BPIFB6 expression induces pronounced alterations in retrograde and anterograde trafficking, which correlate with dramatic fragmentation of the Golgi complex. Taken together, these data implicate BPIFB6 as a key regulator of secretory pathway trafficking and viral replication and suggest that members of the BPIFB family participate in diverse host cell functions to regulate virus infections. Enterovirus infections are associated with a number of severe pathologies, such as aseptic meningitis, dilated cardiomyopathy, type I diabetes, paralysis, and even death. These viruses, which include coxsackievirus B (CVB), poliovirus (PV), and enterovirus 71 (EV71), co-opt the host cell secretory pathway, which controls the transport of proteins from the endoplasmic reticulum to the Golgi complex, to facilitate their replication. Here we report on the identification of a novel regulator of the secretory pathway, bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 6 (BPIFB6), whose expression is required for enterovirus replication. We show that loss of BPIFB6 expression

  20. BPIFB6 Regulates Secretory Pathway Trafficking and Enterovirus Replication

    Science.gov (United States)

    Morosky, Stefanie; Lennemann, Nicholas J.

    2016-01-01

    ABSTRACT Bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) is an endoplasmic reticulum (ER)-localized host factor that negatively regulates coxsackievirus B (CVB) replication through its control of the autophagic pathway. Here, we show that another member of the BPIFB family, BPIFB6, functions as a positive regulator of CVB, and other enterovirus, replication by controlling secretory pathway trafficking and Golgi complex morphology. We show that similar to BPIFB3, BPIFB6 localizes exclusively to the ER, where it associates with other members of the BPIFB family. However, in contrast to our findings that RNA interference (RNAi)-mediated silencing of BPIFB3 greatly enhances CVB replication, we show that silencing of BPIFB6 expression dramatically suppresses enterovirus replication in a pan-viral manner. Mechanistically, we show that loss of BPIFB6 expression induces pronounced alterations in retrograde and anterograde trafficking, which correlate with dramatic fragmentation of the Golgi complex. Taken together, these data implicate BPIFB6 as a key regulator of secretory pathway trafficking and viral replication and suggest that members of the BPIFB family participate in diverse host cell functions to regulate virus infections. IMPORTANCE Enterovirus infections are associated with a number of severe pathologies, such as aseptic meningitis, dilated cardiomyopathy, type I diabetes, paralysis, and even death. These viruses, which include coxsackievirus B (CVB), poliovirus (PV), and enterovirus 71 (EV71), co-opt the host cell secretory pathway, which controls the transport of proteins from the endoplasmic reticulum to the Golgi complex, to facilitate their replication. Here we report on the identification of a novel regulator of the secretory pathway, bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 6 (BPIFB6), whose expression is required for enterovirus replication. We show that loss of

  1. Chromatic completion

    OpenAIRE

    Barthel, Tobias

    2014-01-01

    We study the limit of the chromatic tower for not necessarily finite spectra, obtaining a generalization of the chromatic convergence theorem of Hopkins and Ravenel. Moreover, we prove that in general this limit does not coincide with harmonic localization, thereby answering a question of Ravenel's.

  2. Secretory immunity with special reference to the oral cavity

    Directory of Open Access Journals (Sweden)

    Per Brandtzaeg

    2013-03-01

    Full Text Available The two principal antibody classes present in saliva are secretory IgA (SIgA and IgG; the former is produced as dimeric IgA by local plasma cells (PCs in the stroma of salivary glands and is transported through secretory epithelia by the polymeric Ig receptor (pIgR, also named membrane secretory component (SC. Most IgG in saliva is derived from the blood circulation by passive leakage mainly via gingival crevicular epithelium, although some may be locally produced in the gingiva or salivary glands. Gut-associated lymphoid tissue (GALT and nasopharynx-associated lymphoid tissue (NALT do not contribute equally to the pool of memory/effector B cells differentiating to mucosal PCs throughout the body. Thus, enteric immunostimulation may not be the best way to activate the production of salivary IgA antibodies although the level of specific SIgA in saliva may still reflect an intestinal immune response after enteric immunization. It remains unknown whether the IgA response in submandibular/sublingual glands is better related to B-cell induction in GALT than the parotid response. Such disparity is suggested by the levels of IgA in submandibular secretions of AIDS patients, paralleling their highly upregulated intestinal IgA system, while the parotid IgA level is decreased. Parotid SIgA could more consistently be linked to immune induction in palatine tonsils/adenoids (human NALT and cervical lymph nodes, as supported by the homing molecule profile observed after immune induction at these sites. Several other variables influence the levels of antibodies in salivary secretions. These include difficulties with reproducibility and standardization of immunoassays, the impact of flow rate, acute or chronic stress, protein loss during sample handling, and uncontrolled admixture of serum-derived IgG and monomeric IgA. Despite these problems, saliva is an easily accessible biological fluid with interesting scientific and clinical potentials.

  3. Amelogenins as potential buffers during secretory-stage amelogenesis.

    Science.gov (United States)

    Guo, J; Lyaruu, D M; Takano, Y; Gibson, C W; DenBesten, P K; Bronckers, A L J J

    2015-03-01

    Amelogenins are the most abundant protein species in forming dental enamel, taken to regulate crystal shape and crystal growth. Unprotonated amelogenins can bind protons, suggesting that amelogenins could regulate the pH in enamel in situ. We hypothesized that without amelogenins the enamel would acidify unless ameloblasts were buffered by alternative ways. To investigate this, we measured the mineral and chloride content in incisor enamel of amelogenin-knockout (AmelX(-/-)) mice and determined the pH of enamel by staining with methyl-red. Ameloblasts were immunostained for anion exchanger-2 (Ae2), a transmembrane pH regulator sensitive for acid that secretes bicarbonate in exchange for chloride. The enamel of AmelX(-/-) mice was 10-fold thinner, mineralized in the secretory stage 1.8-fold more than wild-type enamel and containing less chloride (suggesting more bicarbonate secretion). Enamel of AmelX(-/-) mice stained with methyl-red contained no acidic bands in the maturation stage as seen in wild-type enamel. Secretory ameloblasts of AmelX(-/-) mice, but not wild-type mice, were immunopositive for Ae2, and stained more intensely in the maturation stage compared with wild-type mice. Exposure of AmelX(-/-) mice to fluoride enhanced the mineral content in the secretory stage, lowered chloride, and intensified Ae2 immunostaining in the enamel organ in comparison with non-fluorotic mutant teeth. The results suggest that unprotonated amelogenins may regulate the pH of forming enamel in situ. Without amelogenins, Ae2 could compensate for the pH drop associated with crystal formation. © International & American Associations for Dental Research 2014.

  4. Primary secretory otitis media in Cavalier King Charles spaniels.

    Science.gov (United States)

    Cole, Lynette K

    2012-11-01

    Primary secretory otitis media (PSOM) is a disease that has been described in the Cavalier King Charles spaniel (CKCS). A large, bulging pars flaccida identified on otoscopic examination confirms the diagnosis. However, in many CKCS with PSOM the pars flaccida is flat, and radiographic imaging is needed to confirm the diagnosis. Current treatment for PSOM includes performing a myringotomy into the caudal-ventral quadrant of the pars tensa with subsequent flushing of the mucus out of the bulla using a video otoscope. Repeat myringotomies and flushing of the middle ear are necessary to keep the middle ear free of mucus. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Genome-scale modeling of the protein secretory machinery in yeast

    DEFF Research Database (Denmark)

    Feizi, Amir; Österlund, Tobias; Petranovic, Dina

    2013-01-01

    The protein secretory machinery in Eukarya is involved in post-translational modification (PTMs) and sorting of the secretory and many transmembrane proteins. While the secretory machinery has been well-studied using classic reductionist approaches, a holistic view of its complex nature is lacking....... Here, we present the first genome-scale model for the yeast secretory machinery which captures the knowledge generated through more than 50 years of research. The model is based on the concept of a Protein Specific Information Matrix (PSIM: characterized by seven PTMs features). An algorithm...

  6. Secretory phospholipase A2 potentiates glutamate-induced rat striatal neuronal cell death in vivo

    DEFF Research Database (Denmark)

    Kolko, M; Bruhn, T; Christensen, Thomas

    1999-01-01

    The secretory phospholipases A2 (sPLA2) OS2 (10, 20 and 50 pmol) or OS1, (50 pmol) purified from taipan snake Oxyuranus scutellatus scutellatus venom, and the excitatory amino acid glutamate (Glu) (2.5 and 5.0 micromol) were injected into the right striatum of male Wistar rats. Injection of 10...... no tissue damage or neurological abnormality. After injection of 5.0 micromol Glu, the animals initially circled towards the side of injection, and gradually developed generalized clonic convulsions. These animals showed a well demarcated striatal infarct. When non-toxic concentrations of 20 pmol OS2 and 2.......5 micromol Glu were co-injected, a synergistic neurotoxicity was observed. Extensive histological damage occurred in the entire right hemisphere, and in several rats comprising part of the contralateral hemisphere. These animals were apathetic in the immediate hours following injection, with circling towards...

  7. Two-dimensional exactly and completely integrable dynamic systems (Monopoles, instantons, dual models, relativistic strings, Lund-Regge model, generalized Toda lattice, etc)

    International Nuclear Information System (INIS)

    Leznov, A.N.; Saveliev, M.V.

    1982-01-01

    An investigation of two-dimensional exactly and completely integrable dynamical systems associated with the local part of an arbitrary Lie algebra g whose grading is consistent with an arbitrary integral embedding of 3d-subalgebra in g has been carried out. The corresponding systems of nonlinear partial differential equations of the second order h been constructed in an explicit form and their genral solutions in the sense of a Goursat problem have been obtained. A method for the construction of a wide class of infinite-dimensional Lie algebras of finite growth has been proposed

  8. Optimization of Pathogenetic Treatment of Secretory Diarrhea in Infants

    Directory of Open Access Journals (Sweden)

    O.K. Koloskova

    2014-02-01

    Full Text Available The aim of the research was to access clinical efficacy of oral rehydration therapy using III generation solutions in the treatment of secretory diarrhea in infants. To achieve this aim, on the basis of infectious box unit (enteric infections of regional clinical hospital (Chernivtsi we examined 116 infants, randomly selected, with acute gastroenteritis, who admitted to the hospital with signs of exycosis due to secretory diarrhea. Among examined patients, 73 (67.5 % children with the purpose of oral rehydration therapy received rehydration solutions, and 35 (32.4 % patients received other rehydration solutions. Monitoring of the dynamics of patients’ state enabled to state that, when we used III generation mixture as a main component of oral rehydration therapy, rate of positive dynamics in terms of clinical status of patients was significantly faster, in particular, body temperature, frequency and nature of bowel movements normalized significantly earlier, vomiting disappeared. In children treated with rehydration solutions, compared with patients receiving other rehydration solutions, odds ratio to confine only oral rehydration was 3.7 (95% CI 0.4–38.9 with an absolute risk to avoid the need for infusion therapy — 11 %.

  9. Post-secretory fate of host defence components in mucus.

    Science.gov (United States)

    Salathe, Matthias; Forteza, Rosanna; Conner, Gregory E

    2002-01-01

    Airway mucus is a complex mixture of secretory products that provide a multifaceted defence against infection. Among many antimicrobial substances, mucus contains a peroxidase identical to milk lactoperoxidase (LPO) that is produced by goblet cells and submucosal glands. Airway secretions contain the substrates for LPO, namely thiocyanate and hydrogen peroxide, at concentrations sufficient for production of the biocidal compound hypothiocyanite, a fact confirmed by us in vitro. In vivo, inhibition of airway LPO in sheep significantly inhibits bacterial clearance, suggesting that the LPO system is a major contributor to host defences. Since secretory products including LPO are believed to be steadily removed by mucociliary clearance, their amount and availability on the surface is thought to be controlled solely by secretion. In contrast to this paradigm, new data suggest that LPO and other substances are retained at the ciliary border of the airway epithelium by binding to surface-associated hyaluronan, thereby providing an apical, fully active enzyme pool. Thus, hyaluronan, secreted from submucosal gland cells, plays a previously unrecognized pivotal role in mucosal host defence by retaining LPO and possibly other substances important for first line host defence at the apical surface 'ready for use' and protected from ciliary clearance.

  10. Secretory structures of Ipomoea asarifolia: anatomy and histochemistry

    Directory of Open Access Journals (Sweden)

    Fabiano M. Martins

    2012-02-01

    Full Text Available Ipomoea asarifolia (Desr. Roem. & Schult., Convolvulaceae, is a weed that infests agricultural areas and is toxic to cattle. In spite of its toxicity, the leaves of this plant are used in traditional remedies in the state of Bahia, Brazil. The present work describes the leaf anatomy of I. asarifolia and characterizes the exudates of its secretory structures. The leaves have a unistratified epidermis composed of ordinary cells with straight to slightly sinuous anticlinal walls and thin cuticles. Paracytic stomata are found on both surfaces of the leaves at the same level as the ordinary epidermal cells. Trichomes producing polysaccharide secretions occur on the petiole and leaf blade and are considered colleters. The mesophyll is dorsiventral and the vascular bundle of the central vein is bicollateral. Two opposed nectaries occur on the petiole near the leaf blade. Each nectary is composed of a small canal with internal ramifications and numerous secretory trichomes. The laticiferous glands are articulated, not anastomosed, and are composed of large diameter cells with thin cell walls. The secretions of the laticiferous glands are lipidic.

  11. Identification of Secretory Odontoblasts Using DMP1-GFP Transgenic Mice

    Science.gov (United States)

    Balic, Anamaria; Mina, Mina

    2011-01-01

    Terminal differentiation of odontoblasts from dental papilla is a long process involving several intermediate steps and changes in the transcriptional profile and expression of proteins secreted by cells in the odontoblast lineage. Transgenic mouse lines in which GFP expression is under the control of tissue-and stage specific promoters have provided powerful experimental tools for identification and isolation of cells at specific stages of differentiation along a lineage. Our previous studies showed utilization of pOBCol3.6GFP and pOBCol2.3GFP animals for identification of odontoblasts at early and late stages of polarization respectively. In the present study we used the DMP1-GFP transgenic animal as an experimental model to examine its expression during the differentiation of odontoblasts from progenitor cells in vivo and in vitro. Our observations showed that DMP1-GFP transgene is first activated in secretory/functional odontoblasts engaged in secretion of predentin and then transiently expressed at high levels in newly differentiated odontoblasts. Expression of DMP1-GFP was down-regulated in highly differentiated odontoblasts. The temporal and spatial pattern of expression of DMP1-GFP transgene closely mimics the expression of endogenous DMP1. This transgenic animal will facilitate studies of gene expression and biological functions in secretory/functional odontoblasts. PMID:21172466

  12. Increased biogenesis of glucagon-containing secretory granules and glucagon secretion in BIG3-knockout mice

    Directory of Open Access Journals (Sweden)

    Hongyu Li

    2015-03-01

    Conclusions: Together with our previous studies, the current data reveal a conserved role for BIG3 in regulating alpha- and beta-cell functions. We propose that BIG3 negatively regulates hormone production at the secretory granule biogenesis stage and that such regulatory mechanism may be used in secretory pathways of other endocrine cells.

  13. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance

    DEFF Research Database (Denmark)

    Holst, Birgitte; Madsen, Kenneth L; Jansen, Anna M

    2013-01-01

    by electron microscopy showing prominent reduction in secretory vesicle number. Evidence was also obtained for impaired insulin secretion associated with decreased glucose tolerance. PICK1 localized in cells to immature secretory vesicles, and the PICK1 BAR domain was shown by live imaging to associate...

  14. Lactadherin inhibits secretory phospholipase A2 activity on pre-apoptotic leukemia cells

    DEFF Research Database (Denmark)

    Nyegaard, Steffen; Novakovic, Valerie A.; Rasmussen, Jan Trige

    2013-01-01

    Secretory phospholipase A2 (sPLA2) is a critical component of insect and snake venoms and is secreted by mammalian leukocytes during inflammation. Elevated secretory PLA2 concentrations are associated with autoimmune diseases and septic shock. Many sPLA2’s do not bind to plasma membranes of quies...

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  18. Secretory expression of a heterologous nattokinase in Lactococcus lactis.

    Science.gov (United States)

    Liang, Xiaobo; Zhang, Lixin; Zhong, Jin; Huan, Liandong

    2007-05-01

    Nattokinase has been reported as an oral health product for the prevention of atherosclerosis. We developed a novel strategy to express a nattokinase from Bacillus subtilis in a live delivery vehicle, Lactococcus lactis. Promoter P( nisZ) and signal peptide SP(Usp) were used for inducible and secretory expression of nattokinase in L. lactis. Western blotting analysis demonstrated that nattokinase was successfully expressed, and about 94% of the enzyme was secreted to the culture. The recombinant nattokinase showed potent fibrinolytic activity, equivalent to 41.7 urokinase units per milliliter culture. Expression and delivery of such a fibrinolytic enzyme in the food-grade vehicle L. lactis would facilitate the widespread application of nattokinase in the control and prevention of thrombosis diseases.

  19. Rac1 Regulates Endometrial Secretory Function to Control Placental Development.

    Directory of Open Access Journals (Sweden)

    Juanmahel Davila

    2015-08-01

    Full Text Available During placenta development, a succession of complex molecular and cellular interactions between the maternal endometrium and the developing embryo ensures reproductive success. The precise mechanisms regulating this maternal-fetal crosstalk remain unknown. Our study revealed that the expression of Rac1, a member of the Rho family of GTPases, is markedly elevated in mouse decidua on days 7 and 8 of gestation. To investigate its function in the uterus, we created mice bearing a conditional deletion of the Rac1 gene in uterine stromal cells. Ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that Rac1 signaling regulates the expression of Rab27b, another GTPase that plays a key role in targeting vesicular trafficking. Consequently, the Rac1-null decidual cells failed to secrete vascular endothelial growth factor A, which is a critical regulator of decidual angiogenesis, and insulin-like growth factor binding protein 4, which regulates the bioavailability of insulin-like growth factors that promote proliferation and differentiation of trophoblast cell lineages in the ectoplacental cone. The lack of secretion of these key factors by Rac1-null decidua gave rise to impaired angiogenesis and dysregulated proliferation of trophoblast cells, which in turn results in overexpansion of the trophoblast giant cell lineage and disorganized placenta development. Further experiments revealed that RAC1, the human ortholog of Rac1, regulates the secretory activity of human endometrial stromal cells during decidualization, supporting the concept that this signaling G protein plays a central and conserved role in controlling endometrial secretory function. This study provides unique insights into the molecular mechanisms regulating endometrial secretions

  20. Rac1 Regulates Endometrial Secretory Function to Control Placental Development

    Science.gov (United States)

    Davila, Juanmahel; Laws, Mary J.; Kannan, Athilakshmi; Li, Quanxi; Taylor, Robert N.; Bagchi, Milan K.; Bagchi, Indrani C.

    2015-01-01

    During placenta development, a succession of complex molecular and cellular interactions between the maternal endometrium and the developing embryo ensures reproductive success. The precise mechanisms regulating this maternal-fetal crosstalk remain unknown. Our study revealed that the expression of Rac1, a member of the Rho family of GTPases, is markedly elevated in mouse decidua on days 7 and 8 of gestation. To investigate its function in the uterus, we created mice bearing a conditional deletion of the Rac1 gene in uterine stromal cells. Ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that Rac1 signaling regulates the expression of Rab27b, another GTPase that plays a key role in targeting vesicular trafficking. Consequently, the Rac1-null decidual cells failed to secrete vascular endothelial growth factor A, which is a critical regulator of decidual angiogenesis, and insulin-like growth factor binding protein 4, which regulates the bioavailability of insulin-like growth factors that promote proliferation and differentiation of trophoblast cell lineages in the ectoplacental cone. The lack of secretion of these key factors by Rac1-null decidua gave rise to impaired angiogenesis and dysregulated proliferation of trophoblast cells, which in turn results in overexpansion of the trophoblast giant cell lineage and disorganized placenta development. Further experiments revealed that RAC1, the human ortholog of Rac1, regulates the secretory activity of human endometrial stromal cells during decidualization, supporting the concept that this signaling G protein plays a central and conserved role in controlling endometrial secretory function. This study provides unique insights into the molecular mechanisms regulating endometrial secretions that mediate stromal

  1. Secretory immunoglobulin purification from whey by chromatographic techniques.

    Science.gov (United States)

    Matlschweiger, Alexander; Engelmaier, Hannah; Himmler, Gottfried; Hahn, Rainer

    2017-08-15

    Secretory immunoglobulins (SIg) are a major fraction of the mucosal immune system and represent potential drug candidates. So far, platform technologies for their purification do not exist. SIg from animal whey was used as a model to develop a simple, efficient and potentially generic chromatographic purification process. Several chromatographic stationary phases were tested. A combination of two anion-exchange steps resulted in the highest purity. The key step was the use of a small-porous anion exchanger operated in flow-through mode. Diffusion of SIg into the resin particles was significantly hindered, while the main impurities, IgG and serum albumin, were bound. In this step, initial purity was increased from 66% to 89% with a step yield of 88%. In a second anion-exchange step using giga-porous material, SIg was captured and purified by step or linear gradient elution to obtain fractions with purities >95%. For the step gradient elution step yield of highly pure SIg was 54%. Elution of SIgA and SIgM with a linear gradient resulted in a step yield of 56% and 35%, respectively. Overall yields for both anion exchange steps were 43% for the combination of flow-through and step elution mode. Combination of flow-through and linear gradient elution mode resulted in a yield of 44% for SIgA and 39% for SIgM. The proposed process allows the purification of biologically active SIg from animal whey in preparative scale. For future applications, the process can easily be adopted for purification of recombinant secretory immunoglobulin species. Copyright © 2017 Elsevier B.V. All rights reserved.

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  1. Secretory production of tetrameric native full-length streptavidin with thermostability using Streptomyces lividans as a host.

    Science.gov (United States)

    Noda, Shuhei; Matsumoto, Takuya; Tanaka, Tsutomu; Kondo, Akihiko

    2015-01-13

    Streptavidin is a tetrameric protein derived from Streptomyces avidinii, and has tight and specific biotin binding affinity. Applications of the streptavidin-biotin system have been widely studied. Streptavidin is generally produced using protein expression in Escherichia coli. In the present study, the secretory production of streptavidin was carried out using Streptomyces lividans as a host. In this study, we used the gene encoding native full-length streptavidin, whereas the core region is generally used for streptavidin production in E. coli. Tetrameric streptavidin composed of native full-length streptavidin monomers was successfully secreted in the culture supernatant of S. lividans transformants, and had specific biotin binding affinity as strong as streptavidin produced by E. coli. The amount of Sav using S. lividans was about 9 times higher than using E. coli. Surprisingly, streptavidin produced by S. lividans exhibited affinity to biotin after boiling, despite the fact that tetrameric streptavidin is known to lose its biotin binding ability after brief boiling. We successfully produced a large amount of tetrameric streptavidin as a secretory-form protein with unique thermotolerance.

  2. Construction completion report

    International Nuclear Information System (INIS)

    1990-01-01

    This Construction Completion Report documents the major construction projects at the Waste Isolation Pilot Plant (WIPP) site and related information on contracts, schedules, and other areas which affected construction. This report is not intended to be an exhaustive detailed analysis of construction, but is a general overview and summary of the WIPP construction. 10 refs., 29 figs

  3. Periodic activity of secretory glands of stomach in ulcer erosion of gastro-duodenal zone

    Directory of Open Access Journals (Sweden)

    A. I. Rudenko

    2005-12-01

    Full Text Available It was fixed, that development of atophanum-carbacholimun ulcer of the gastroduodenal zone invoked various changes of secretory activity of the stomach. The changes directly depend on a progress of pathological process. As this takes place the reaction of stomach secretory glands varies under the stimulation with histamine: the decrease of stomach secretory glands’ work capacity till 10th day and its increase after 10–15th day were observed. Disorders of the glands’ ultradian rhythms at initial stages of modeling of gastrointestinal nervous regulation disturbances testify to dependence of periodic activity of gastrointestinal tract on resistance of regulatory mechanisms correlation.

  4. The differences in RCAS1 and DFF45 endometrial expression between late proliferative, early secretory, and mid-secretory cycle phases.

    Directory of Open Access Journals (Sweden)

    Jerzy Sikora

    2008-04-01

    Full Text Available RCAS1 expression is related to the regulation of activated immune cells and to connective tissue remodeling within the endometrium. DFF45 seems to play an important role in the apoptotic process, most likely by acting through the regulation of DNA fragmentation. Its expression changes within the endometrium seem to be related to the resistance of endometrial cells to apoptosis. The aim of the present study was to evaluate RCAS1 and DFF45 endometrial expressions during ovulation and the implantation period. RCAS1 and DFF45 expression was assessed by the Western-blot method in endometrial tissue samples obtained from 20 patients. The tissue samples were classified according to the menstrual cycle phases in which they were collected, with a division into three phases: late proliferative, early secretory, and mid-secretory. The lowest level of RCAS1 and the highest level of DFF45 endometrial expression was found during the early secretory cycle phase. Statistically significantly higher RCAS1 and statistically significantly lower DFF45 endometrial expression was identified in the endometrium during the late proliferative as compared to the early secretory cycle phase. Moreover, statistically significantly higher RCAS1 and statistically significantly lower DFF45 expression was found in the endometrium during the mid-secretory as compared to the early secretory cycle phase. The preparation for implantation process in the endometrium is preceded by dynamic changes in endometrial ECM and results from the proper interaction between endometrial and immune cells. The course of this process is conditioned by the immunomodulating activity of endometrial cells and their resistance to immune-mediated apoptosis. These dynamic changes are closely related to RCAS1 and DFF45 expression alterations.

  5. Secretory NaCl and volume flow in renal tubules.

    Science.gov (United States)

    Beyenbach, K W

    1986-05-01

    This review attempts to give a retrospective survey of the available evidence concerning the secretion of NaCl and fluid in renal tubules of the vertebrate kidney. In the absence of glomerular filtration, epithelial secretory mechanisms, which to this date have not been elucidated, are responsible for the renal excretion of NaCl and water in aglomerular fish. However, proximal tubules isolated from glomerular fish kidneys of the flounder, killifish, and the shark also have the capacity to secrete NaCl and fluid. In shark proximal tubules, fluid secretion appears to be driven via secondary active transport of Cl. In another marine vertebrate, the sea snake, secretion of Na (presumably NaCl) and fluid is observed in freshwater-adapted and water-loaded animals. Proximal tubules of mammals can be made to secrete NaCl in vitro together with secretion of aryl acids. An epithelial cell line derived from dog kidney exhibits secondary active secretion of Cl when stimulated with catecholamines. Tubular secretion of NaCl and fluid may serve a variety of renal functions, all of which are considered here. The occurrence of NaCl and fluid secretion in glomerular proximal tubules of teleosts, elasmobranchs, and reptiles and in mammalian renal tissue cultures suggests that the genetic potential for NaCl secretion is present in every vertebrate kidney.

  6. Protein thiophosphorylation associated with secretory inhibition in permeabilized chromaffin cells

    International Nuclear Information System (INIS)

    Brooks, J.C.; Brooks, M.

    1985-01-01

    Permeabilized cells treated with the adenosine triphosphate analog, ( 35 S)adenosine-5'-0-3(3-thiotriphosphate) ((γ- 35 S)ATP), showed thiophosphorylation of a small number of cellular proteins. A 54 kilodalton (kDa) protein was heavily thiophosphorylated in unstimulated control cells and a 43 kilodalton protein was more heavily thiophosphorylated in calcium stimulated cells. Intact cells incorporated 35 S into a series of higher molecular weight proteins. Stimulation of prelabelled, permeabilized cells resulted in a loss of 35 S from the cells over a 20 min period. Treatment of permeabilized cells with ATPγS inhibited secretion and 35 S incorporation into the cells. Pretreatment with ATPγS resulted in subsequent inhibition of both secretion and the ability of the cells to incorporate 35 S from (γ- 35 S)ATP. These results indicate that the sites normally available for phosphorylation were inactivated by thiophosphorylation and were unavailable to participate in the secretory process. The inhibition of secretion associated with thiophosphorylation of these proteins suggests that they may play a role in the control of secretion by chromaffin cells. 15 references, 1 figure, 3 tables

  7. Correlation between CT and tympanogram in secretory otitis media

    International Nuclear Information System (INIS)

    Kobayashi, Toshimitsu; Sakurai, Tokio; Taniguchi, Kazuhiko; Takahashi, Kuniaki; Ikeda, Katsuhisa; Kawamoto, Kazutomo.

    1984-01-01

    In an attempt to evaluate the feasibility of the tympanometry in detecting the middle ear effusion (MEE) in secretory otitis media (SOM) in childhood, the findings of the computed tomography (CT) were evaluated whether they were compatible with that of tympanometry in 27 cases (51 ears) of SOM. Tympanometry (tympanogram, static compliance measurement and stapedial reflex test), pure tone audiometry and high resolution CT were performed sequentially, and the CT findings were compared with the results of the other tests. The conclusions obtained were summarized as follows. 1. Among the tests performed, tympanogram appeared to be the most reliable measure in detection of MEE. 2. Fifteen ears out of 16 with type B tympanograms and 6 ears out of 15 with type C 2 tympanograms, were diagnosed by CT as having MEE. MEE occupied the entire middile ear space in most ears with type B tympanograms. By contrast, in the ears with type C 2 tympanograms, air containing space of varying size were always observed even in the ears with MEE. (author)

  8. ERAD-dependent control of the Wnt secretory factor Evi.

    Science.gov (United States)

    Glaeser, Kathrin; Urban, Manuela; Fenech, Emma; Voloshanenko, Oksana; Kranz, Dominique; Lari, Federica; Christianson, John C; Boutros, Michael

    2018-02-15

    Active regulation of protein abundance is an essential strategy to modulate cellular signaling pathways. Within the Wnt signaling cascade, regulated degradation of β-catenin by the ubiquitin-proteasome system (UPS) affects the outcome of canonical Wnt signaling. Here, we found that abundance of the Wnt cargo receptor Evi (Wls/GPR177), which is required for Wnt protein secretion, is also regulated by the UPS through endoplasmic reticulum (ER)-associated degradation (ERAD). In the absence of Wnt ligands, Evi is ubiquitinated and targeted for ERAD in a VCP-dependent manner. Ubiquitination of Evi involves the E2-conjugating enzyme UBE2J2 and the E3-ligase CGRRF1. Furthermore, we show that a triaging complex of Porcn and VCP determines whether Evi enters the secretory or the ERAD pathway. In this way, ERAD-dependent control of Evi availability impacts the scale of Wnt protein secretion by adjusting the amount of Evi to meet the requirement of Wnt protein export. As Wnt and Evi protein levels are often dysregulated in cancer, targeting regulatory ERAD components might be a useful approach for therapeutic interventions. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

  9. Pulmonary deposition and disappearance of aerosolised secretory leucocyte protease inhibitor.

    Science.gov (United States)

    Stolk, J.; Camps, J.; Feitsma, H. I.; Hermans, J.; Dijkman, J. H.; Pauwels, E. K.

    1995-01-01

    BACKGROUND--The neutrophil elastase inhibitor, secretory leucocyte protease inhibitor (SLPI), is a potential therapeutic tool in inflammatory lung diseases such as cystic fibrosis and pulmonary emphysema. The distribution and disappearance in the lung of aerosolised recombinant SLPI (rSLPI) was investigated in healthy humans and in patients with cystic fibrosis or alpha 1-antitrypsin-associated emphysema. METHODS--To distinguish aerosolised rSLPI from endogenous SLPI the recombinant inhibitor was radiolabelled with 99m-technetium (99mTc) pertechnetate. Distribution and disappearance of aerosolised 99mTc-rSLPI in the lungs were studied by gamma radiation imaging. RESULTS--The deposition of 99mTc-rSLPI in normal volunteers was homogeneous in all lung lobes, while in patients with cystic fibrosis or emphysema only well ventilated areas showed deposition of the aerosol. The disappearance rate of 99mTc-rSLPI was biexponential. The half life of the rapid phase was 0.2-2.8 hours, while that of the slow phase was more than 24 hours. CONCLUSIONS--Future aerosol therapy with rSLPI will be most beneficial for well ventilated lung tissue that needs protection against neutrophil derived elastase. It may be more difficult to neutralise the burden of elastase in poorly ventilated, highly inflamed areas as are seen in cystic fibrosis. Images PMID:7638807

  10. Quantitative parameters of seminiferous epithelium in secretory and excretory oligoazoospermia.

    Science.gov (United States)

    Francavilla, S; Martini, M; Properzi, G; Cordeschi, G

    1990-01-01

    Testicular biopsy specimens from infertile men (sperm count, less than 10(6)/ml) were evaluated on 1-micron thick sections, and counts of stem cells and differentiated spermatogonia, primary spermatocytes, early and late spermatids, and Sertoli cells were compared to counts in six fertile men. Biopsy specimens were also compared for the appearance of seminiferous tubule wall, blood vessels, and interstitium. Infertile men were grouped according to the following diagnoses: hypospermatogenesis (n = 5), spermatocyte arrest of spermatogenesis (n = 5), and obstruction of the genital tract (n = 7). A low productivity of spermatogenesis in cases of hypospermatogenesis appeared to be due to an exaggerated degeneration of primary spermatocytes and to a yield of abnormal spermatids. A block of meiosis in spermatocyte arrest was associated with a degeneration of primary spermatocytes and with a reduced number of staminal spermatogonia. Abnormal spermiogenesis was observed in cases of obstruction of the genital tract and was associated with an increase in stem cell spermatogonia. A thickening of seminiferous tubule and blood vessel walls could be responsible for the limited functional capacity of Sertoli cells, causing altered spermiogenesis in cases of excretory azoospermia. A severe primitive failure of Sertoli cells in secretory oligoazoospermia could account for a deranged maturation and degeneration of premeiotic and postmeiotic germ cells.

  11. Mapping organelle motion reveals a vesicular conveyor belt spatially replenishing secretory vesicles in stimulated chromaffin cells.

    Science.gov (United States)

    Maucort, Guillaume; Kasula, Ravikiran; Papadopulos, Andreas; Nieminen, Timo A; Rubinsztein-Dunlop, Halina; Meunier, Frederic A

    2014-01-01

    How neurosecretory cells spatially adjust their secretory vesicle pools to replenish those that have fused and released their hormonal content is currently unknown. Here we designed a novel set of image analyses to map the probability of tracked organelles undergoing a specific type of movement (free, caged or directed). We then applied our analysis to time-lapse z-stack confocal imaging of secretory vesicles from bovine Chromaffin cells to map the global changes in vesicle motion and directionality occurring upon secretagogue stimulation. We report a defined region abutting the cortical actin network that actively transports secretory vesicles and is dissipated by actin and microtubule depolymerizing drugs. The directionality of this "conveyor belt" towards the cell surface is activated by stimulation. Actin and microtubule networks therefore cooperatively probe the microenvironment to transport secretory vesicles to the periphery, providing a mechanism whereby cells globally adjust their vesicle pools in response to secretagogue stimulation.

  12. Antigenic analyses of tissues and excretory and secretory products from Strongylus vulgaris.

    Science.gov (United States)

    Wynne, E; Slocombe, J O; Wilkie, B N

    1981-07-01

    Rabbit antisera were prepared against veronal buffered saline extracts of L4 and L5 Strongylus vulgaris, adult S. vulgaris and adult Strongylus equinus retrieved from naturally infected horses. In agar gel diffusion with these antisera, adult S vulgaris and S. equinus each appeared to have at least one unique antigen; larval S. vulgaris appeared to have two species-specific and two stage-specific antigens. There were several common antigens. Excretory and secretory products were collected also from L4 and L5 an maintained over several days in tissue culture fluid. In agar gel diffusion against the above rabbit antisera, a stage-specific antigen was found also in excretory and secretory products. In addition, excretory and secretory products had three antigens in common with adult and larval S. vulgaris, but only one of these was common to adult S. equinus. The excretory and secretory products appear, therefore, to have two species-specific and one stage-specific antigens.

  13. Chronic regulation of colonic epithelial secretory function by activation of G protein-coupled receptors.

    LENUS (Irish Health Repository)

    Toumi, F

    2011-02-01

    Enteric neurotransmitters that act at G protein-coupled receptors (GPCRs) are well known to acutely promote epithelial Cl(-) and fluid secretion. Here we examined if acute GPCR activation might have more long-term consequences for epithelial secretory function.

  14. Differential testosterone secretory capacity of the testes of aggressive and nonaggressive house mice during ontogeny

    OpenAIRE

    de Ruiter, Anne J H; Koolhaas, Jaap M; van Oortmerssen, Geert A; Bohus, Bela

    1992-01-01

    In this study, testosterone secretory capacity of testicular Leydig cells during ontogeny was determined in males of an aggressive and a nonaggressive genetic selection line of wild house mice. Neonates, 23-day-old prepubertals, and adult male mice were studied. A morphometric method was used to quantify 3-beta-hydroxy steroid dehydrogenase (3-beta-HSD)-stained Leydig cells in testicular sections to determine testosterone secretory capacity. We consider this parameter to reflect circulating t...

  15. Evaluation of beta-cell secretory capacity using glucagon-like peptide 1

    DEFF Research Database (Denmark)

    Vilsbøll, Tina; Nielsen, Mette Toft; Krarup, T

    2000-01-01

    Beta-cell secretory capacity is often evaluated with a glucagon test or a meal test. However, glucagon-like peptide 1 (GLP-1) is the most insulinotropic hormone known, and the effect is preserved in type 2 diabetic patients.......Beta-cell secretory capacity is often evaluated with a glucagon test or a meal test. However, glucagon-like peptide 1 (GLP-1) is the most insulinotropic hormone known, and the effect is preserved in type 2 diabetic patients....

  16. Understanding the Contribution of Zinc Transporters in the Function of the Early Secretory Pathway.

    Science.gov (United States)

    Kambe, Taiho; Matsunaga, Mayu; Takeda, Taka-Aki

    2017-10-19

    More than one-third of newly synthesized proteins are targeted to the early secretory pathway, which is comprised of the endoplasmic reticulum (ER), Golgi apparatus, and other intermediate compartments. The early secretory pathway plays a key role in controlling the folding, assembly, maturation, modification, trafficking, and degradation of such proteins. A considerable proportion of the secretome requires zinc as an essential factor for its structural and catalytic functions, and recent findings reveal that zinc plays a pivotal role in the function of the early secretory pathway. Hence, a disruption of zinc homeostasis and metabolism involving the early secretory pathway will lead to pathway dysregulation, resulting in various defects, including an exacerbation of homeostatic ER stress. The accumulated evidence indicates that specific members of the family of Zn transporters (ZNTs) and Zrt- and Irt-like proteins (ZIPs), which operate in the early secretory pathway, play indispensable roles in maintaining zinc homeostasis by regulating the influx and efflux of zinc. In this review, the biological functions of these transporters are discussed, focusing on recent aspects of their roles. In particular, we discuss in depth how specific ZNT transporters are employed in the activation of zinc-requiring ectoenzymes. The means by which early secretory pathway functions are controlled by zinc, mediated by specific ZNT and ZIP transporters, are also subjects of this review.

  17. Tattooing to "Toughen up": Tattoo experience and secretory immunoglobulin A.

    Science.gov (United States)

    Lynn, Christopher D; Dominguez, Johnna T; DeCaro, Jason A

    2016-09-10

    A costly signaling model suggests tattooing inoculates the immune system to heightened vigilance against stressors associated with soft tissue damage. We sought to investigate this "inoculation hypothesis" of tattooing as a costly honest signal of fitness. We hypothesized that the immune system habituates to the tattooing stressor in repeatedly tattooed individuals and that immune response to the stress of the tattooing process would correlate with lifetime tattoo experience. Participants were 24 women and 5 men (aged 18-47). We measured immune function using secretory immunoglobulin A (SIgA) and cortisol (sCORT) in saliva collected before and after tattoo sessions. We measured tattoo experience as a sum of number of tattoos, lifetime hours tattooed, years since first tattoo, percent of body covered, and number of tattoo sessions. We predicted an inverse relationship between SIgA and sCORT and less SIgA immunosuppression among those with more tattoo experience. We used hierarchical multiple regression to test for a main effect of tattoo experience on post-tattoo SIgA, controlling for pretest SIgA, tattoo session duration, body mass, and the interaction between tattoo experience and test session duration. The regression model was significant (P = 0.006) with a large effect size (r(2)  = 0.711) and significant and positive main (P = 0.03) and interaction effects (P = 0.014). Our data suggest that the body habituates over time to the tattooing stressor. It is possible that individuals with healthy immune systems heal faster, making them more likely to get multiple tattoos. Am. J. Hum. Biol. 28:603-609, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Urinary secretory IgA after nutritional rehabilitation

    Directory of Open Access Journals (Sweden)

    M.R. Teodósio

    1999-04-01

    Full Text Available We studied the secretory IgA (sIgA response of the mucosal urinary tract of malnourished children before and after nutritional rehabilitation. sIgA concentration (mg/l was determined by ELISA in 187 children aged 3 months to 5 years. The children, who frequented a day care center, were divided into four groups, according to nutritional status: 57 were eutrophic, 49 were undergrown, 57 were moderately malnourished and 24 were severely malnourished. In addition, dip slide (Urotube, Roche and dip-stick (Combur 9-Boehringer tests showed that children had no bacteriuria or any other urinary abnormalities. Plasma albumin concentration (g/dl was significantly lower (P<0.005 in the severely malnourished group (mean 3.0 ± 0.3 SD than in the eutrophic group (mean 4.0 ± 0.5 SD. When each nutritional state was analyzed, no significant differences in the sIgA were found between the 0 |-| 1 and 1 -| 5 year age range. In the moderately and severely malnourished groups, sIgA (0.36 and 0.45, respectively was significantly lower than in the eutrophic (0.69 and undergrown (0.75 groups. Ninety-five children were included in the 8-month follow-up study; 30 children were excluded from the follow-up because 4 had bacteriuria, 11 had leukocyturia, 8 had proteinuria and 7 had hematuria. Among the malnourished children, 40% showed nutritional improvement (P<0.05 and significantly increased sIgA as compared to reference values for the eutrophic and undergrown groups. These data suggest that malnourished children have a significantly lower urinary sIgA than eutrophic children. After nutritional rehabilitation, they develop local immunity with a significant increase in sIgA.

  19. Postnatal development of bile secretory physiology in the dog

    International Nuclear Information System (INIS)

    Tavoloni, N.; Jones, M.J.; Berk, P.D.

    1985-01-01

    To determine whether bile formation in the dog is an immature process at birth, several determinants of bile secretion were studied in anesthetized, bile duct-cannulated puppies of 0-42 days of age and adult dogs. Basal canalicular bile flow rate, estimated by 14 C-erythritol biliary clearance, averaged 0.182 microliter/min/g liver in 0-3 day-old puppies and increased to 0.324 and 0.461 microliter/min/g in puppies 7-21 and 28-42 days of age, respectively. Calculated ductular bile water reabsorption ( 14 C-erythritol biliary clearance-bile flow) was virtually absent in 0-3 day-old puppies, and averaged 0.017 and 0.092 microliter/min/g in puppies of 7-21 and 28-42 days of age, respectively. In adult dogs, ductular bile water reabsorption was 0.132 microliter/min/g. These functional deficiencies of the newborn dog were associated with an increased biliary permeability to 3 H-inulin which could not be accounted for solely by an increased solute diffusion due to the lower rate of canalicular bile flow. Administration of taurocholate up to 2000 nmol/min/kg produced in all animals a similar increase in canalicular bile flow and bile acid excretion, and was not associated with changes in ductular bile water reabsorption rate. These findings are interpreted to indicate that, in the dog, bile secretory function is immature at birth and develops during postnatal life

  20. Secretory pathway Ca2+/Mn2+-ATPase isoform 2 and lactation: specific localization of plasmalemmal and secretory pathway Ca2+ pump isoforms in the mammary gland

    Energy Technology Data Exchange (ETDEWEB)

    Faddy, Helen M.; Smart, Chanel E.; Xu, Ren; Lee, Genee Y.; Kenny, Paraic A.; Feng, Mingye; Rao, Rajini; Brown, Melissa A.; Bissell, Mina J.; Roberts-Thomson, Sarah J.; Monteith, Gregory R.

    2008-04-09

    The supply of calcium to the developing neonate via milk is an important physiological process. Until recently the mechanism for the enrichment of milk with calcium was thought to be almost entirely mediated via the secretory pathway. However, recent studies suggest that a specific isoform of the plasma membrane calcium ATPase, PMCA2, is the primary mechanism for calcium transport into milk, highlighting a major role for apical calcium transport. We compared the expression of the recently identified secretory calcium ATPase, SPCA2, and SPCA1, in the mouse mammary gland during different stages of development. SPCA2 levels increased over 35 fold during lactation, while SPCA1 increased only a modest two fold. The potential importance of SPCA2 in lactation was also highlighted by its localization to luminal secretory cells of the mammary gland during lactation, while SPCA1 was expressed throughout the cells of the mammary gland. We also observed major differences in the localization of PMCA2 and PMCA1 during lactation. Using the SCp2 mouse mammary epithelial cell 3D culture model, differences in the sub-cellular distribution of PMCA2 and PMCA1 were clear. These studies highlight the likely specific roles of PMCA2 and SPCA2 in lactation, and link the recently characterized SPCA2 calcium pump to the supply of calcium into milk and the regulation of Golgi resident enzymes important in lactation. They also indicate that calcium transport into milk is a complex interplay between apical and secretory pathways.

  1. A Western blot-based investigation of the yeast secretory pathway designed for an intermediate-level undergraduate cell biology laboratory.

    Science.gov (United States)

    Hood-Degrenier, Jennifer K

    2008-01-01

    The movement of newly synthesized proteins through the endomembrane system of eukaryotic cells, often referred to generally as the secretory pathway, is a topic covered in most intermediate-level undergraduate cell biology courses. An article previously published in this journal described a laboratory exercise in which yeast mutants defective in two distinct steps of protein secretion were differentiated using a genetic reporter designed specifically to identify defects in the first step of the pathway, the insertion of proteins into the endoplasmic reticulum (Vallen, 2002). We have developed two versions of a Western blotting assay that serves as a second way of distinguishing the two secretory mutants, which we pair with the genetic assay in a 3-wk laboratory module. A quiz administered before and after students participated in the lab activities revealed significant postlab gains in their understanding of the secretory pathway and experimental techniques used to study it. A second survey administered at the end of the lab module assessed student perceptions of the efficacy of the lab activities; the results of this survey indicated that the experiments were successful in meeting a set of educational goals defined by the instructor.

  2. Functional Characterization of Monomeric GTPase Rab1 in the Secretory Pathway of Leishmania*

    Science.gov (United States)

    Bahl, Surbhi; Parashar, Smriti; Malhotra, Himanshu; Raje, Manoj; Mukhopadhyay, Amitabha

    2015-01-01

    Leishmania secretes a large number of its effectors to the extracellular milieu. However, regulation of the secretory pathway in Leishmania is not well characterized. Here, we report the cloning, expression, and characterization of the Rab1 homologue from Leishmania. We have found that LdRab1 localizes in Golgi in Leishmania. To understand the role of LdRab1 in the secretory pathway of Leishmania, we have generated transgenic parasites overexpressing GFP-LdRab1:WT, GFP-LdRab1:Q67L (a GTPase-deficient dominant positive mutant of Rab1), and GFP-LdRab1:S22N (a GDP-locked dominant negative mutant of Rab1). Surprisingly, our results have shown that overexpression of GFP-LdRab1:Q67L or GFP-LdRab1:S22N does not disrupt the trafficking and localization of hemoglobin receptor in Leishmania. To determine whether the Rab1-dependent secretory pathway is conserved in parasites, we have analyzed the role of LdRab1 in the secretion of secretory acid phosphatase and Ldgp63 in Leishmania. Our results have shown that overexpression of GFP-LdRab1:Q67L or GFP-LdRab1:S22N significantly inhibits the secretion of secretory acid phosphatase by Leishmania. We have also found that overexpression of GFP-LdRab1:Q67L or GFP-LdRab1:S22N retains RFP-Ldgp63 in Golgi and blocks the secretion of Ldgp63, whereas the trafficking of RFP-Ldgp63 in GFP-LdRab1:WT-expressing cells is unaltered in comparison with control cells. Taken together, our results have shown that the Rab1-regulated secretory pathway is well conserved, and hemoglobin receptor trafficking follows an Rab1-independent secretory pathway in Leishmania. PMID:26499792

  3. Functional Characterization of Monomeric GTPase Rab1 in the Secretory Pathway of Leishmania.

    Science.gov (United States)

    Bahl, Surbhi; Parashar, Smriti; Malhotra, Himanshu; Raje, Manoj; Mukhopadhyay, Amitabha

    2015-12-11

    Leishmania secretes a large number of its effectors to the extracellular milieu. However, regulation of the secretory pathway in Leishmania is not well characterized. Here, we report the cloning, expression, and characterization of the Rab1 homologue from Leishmania. We have found that LdRab1 localizes in Golgi in Leishmania. To understand the role of LdRab1 in the secretory pathway of Leishmania, we have generated transgenic parasites overexpressing GFP-LdRab1:WT, GFP-LdRab1:Q67L (a GTPase-deficient dominant positive mutant of Rab1), and GFP-LdRab1:S22N (a GDP-locked dominant negative mutant of Rab1). Surprisingly, our results have shown that overexpression of GFP-LdRab1:Q67L or GFP-LdRab1:S22N does not disrupt the trafficking and localization of hemoglobin receptor in Leishmania. To determine whether the Rab1-dependent secretory pathway is conserved in parasites, we have analyzed the role of LdRab1 in the secretion of secretory acid phosphatase and Ldgp63 in Leishmania. Our results have shown that overexpression of GFP-LdRab1:Q67L or GFP-LdRab1:S22N significantly inhibits the secretion of secretory acid phosphatase by Leishmania. We have also found that overexpression of GFP-LdRab1:Q67L or GFP-LdRab1:S22N retains RFP-Ldgp63 in Golgi and blocks the secretion of Ldgp63, whereas the trafficking of RFP-Ldgp63 in GFP-LdRab1:WT-expressing cells is unaltered in comparison with control cells. Taken together, our results have shown that the Rab1-regulated secretory pathway is well conserved, and hemoglobin receptor trafficking follows an Rab1-independent secretory pathway in Leishmania. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Establishing human lacrimal gland cultures with secretory function.

    Directory of Open Access Journals (Sweden)

    Shubha Tiwari

    Full Text Available PURPOSE: Dry eye syndrome is a multifactorial chronic disabling disease mainly caused by the functional disruptions in the lacrimal gland. The treatment involves palliation like ocular surface lubrication and rehydration. Cell therapy involving replacement of the gland is a promising alternative for providing long-term relief to patients. This study aimed to establish functionally competent lacrimal gland cultures in-vitro and explore the presence of stem cells in the native gland and the established in-vitro cultures. METHODS: Fresh human lacrimal gland from patients undergoing exenteration was harvested for cultures after IRB approval. The freshly isolated cells were evaluated by flow cytometry for expression of stem cell markers ABCG2, high ALDH1 levels and c-kit. Cultures were established on Matrigel, collagen and HAM and the cultured cells evaluated for the presence of stem cell markers and differentiating markers of epithelial (E-cadherin, EpCAM, mesenchymal (Vimentin, CD90 and myofibroblastic (α-SMA, S-100 origin by flow cytometry and immunocytochemistry. The conditioned media was tested for secretory proteins (scIgA, lactoferrin, lysozyme post carbachol (100 µM stimulation by ELISA. RESULTS: Native human lacrimal gland expressed ABCG2 (mean±SEM: 3.1±0.61%, high ALDH1 (3.8±1.26% and c-kit (6.7±2.0%. Lacrimal gland cultures formed a monolayer, in order of preference on Matrigel, collagen and HAM within 15-20 days, containing a heterogeneous population of stem-like and differentiated cells. The epithelial cells formed 'spherules' with duct like connections, suggestive of ductal origin. The levels of scIgA (47.43 to 61.56 ng/ml, lysozyme (24.36 to 144.74 ng/ml and lactoferrin (32.45 to 40.31 ng/ml in the conditioned media were significantly higher than the negative controls (p<0.05 for all comparisons. CONCLUSION: The study reports the novel finding of establishing functionally competent human lacrimal gland cultures in-vitro. It also

  5. Effects of excretory/secretory products from Anisakis simplex (Nematoda) on immune gene expression in rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Bahlool, Qusay Zuhair Mohammad; Skovgaard, Alf; Kania, Per Walter

    2013-01-01

    Excretory/secretory (ES) products are molecules produced by parasitic nematodes, including larval Anisakis simplex, a parasite occurring in numerous marine fish hosts. The effects of these substances on host physiology have not been fully described. The present work elucidates the influence of ES...... substances on the fish immune system by measuring immune gene expression in spleen and liver of rainbow trout (Oncorhynchus mykiss) injected intraperitoneally with ES products isolated from A. simplex third stage larvae. The overall gene expression profile of exposed fish showed a generalized down....... This type of hydrolytic enzyme activity may play a role in nematode penetration of host tissue. In addition, based on the notion that A. simplex ES products may have an immune-depressive effect (by minimizing immune gene expression) it could also be suggested that worm enzymes directly target host immune...

  6. Regulation of vesicular traffic by a GTP-binding protein on the cytoplasmic surface of secretory vesicles in yeast

    International Nuclear Information System (INIS)

    Novick, P.J.; Goud, B.; Salminen, A.; Walworth, N.C.; Nair, J.; Potenza, M.

    1988-01-01

    Vesicular transport is an important mechanism for the intracellular traffic of proteins and lipids in eukaryotic cells. Vesicles mediate the passage of proteins between the various organelles of the secretory pathway and the exocytic release of these proteins into the extracellular environment. Vesicles also mediate the uptake of proteins and fluid from the external environment, delivering them to endosomes. Despite the generality of the vesicular transport mechanism, the process is not yet understood at a molecular level. The key questions that are addressed are (1) How are vesicles formed from the membrane of the donor organelle? (2) How are these vesicles transported? (3) How do the vesicles recognize the membrane of the target (acceptor) organelle? (4) How is membrane fusion accomplished? The genetic flexibility of yeast has been exploited to identify components of the cellular machinery required for vesicular transport

  7. Imaging Polarized Secretory Traffic at the Immune Synapse in Living T Lymphocytes.

    Science.gov (United States)

    Calvo, Víctor; Izquierdo, Manuel

    2018-01-01

    Immune synapse (IS) formation by T lymphocytes constitutes a crucial event involved in antigen-specific, cellular and humoral immune responses. After IS formation by T lymphocytes and antigen-presenting cells, the convergence of secretory vesicles toward the microtubule-organizing center (MTOC) and MTOC polarization to the IS are involved in polarized secretion at the synaptic cleft. This specialized mechanism appears to specifically provide the immune system with a fine strategy to increase the efficiency of crucial secretory effector functions of T lymphocytes, while minimizing non-specific, cytokine-mediated stimulation of bystander cells, target cell killing and activation-induced cell death. The molecular bases involved in the polarized secretory traffic toward the IS in T lymphocytes have been the focus of interest, thus different models and several imaging strategies have been developed to gain insights into the mechanisms governing directional secretory traffic. In this review, we deal with the most widely used, state-of-the-art approaches to address the molecular mechanisms underlying this crucial, immune secretory response.

  8. Effects of 5-fluorouracil on the secretory process of the rat parotid gland

    International Nuclear Information System (INIS)

    Sandborg, R.R.

    1986-01-01

    Experimental animals were injected intraperitoneally with 100 mg/kg 5-fluorouracil for three days. The total volume, amylase and protein content of cannulated parotid saliva were determined following stimulation with either 5 mg/kg pilocarpine or 5 mg/kg isoproterenol in experimental, pair-fed , and control animals. Saliva from experimental animals was significantly lower in volume, amylase and protein content than both control groups. 5-fluorouracil treatment reduced the total glandular amylase per unit DNA in both unstimulated and isoproterenol-stimulated parotid glands. Decreased protein synthesis may be the mechanism underlying depleted secretory protein stores since the contents of isolated secretory granules from experimental parotid glands contained less radiolabelled protein than either control group and whole gland homogenates showed marked reductions in the activities of three lysosomal enzymes and total RNA content. Experimental animals contained less labelled protein in their secretory granules than controls, but secreted a greater proportion of their total glandular radiolabelled secretory protein into saliva relative to amylase suggesting that newly synthesized secretory proteins are preferentially secreted

  9. Effects of 5-fluorouracil on the secretory process of the rat parotid gland

    Energy Technology Data Exchange (ETDEWEB)

    Sandborg, R.R.

    1986-01-01

    Experimental animals were injected intraperitoneally with 100 mg/kg 5-fluorouracil for three days. The total volume, amylase and protein content of cannulated parotid saliva were determined following stimulation with either 5 mg/kg pilocarpine or 5 mg/kg isoproterenol in experimental, pair-fed , and control animals. Saliva from experimental animals was significantly lower in volume, amylase and protein content than both control groups. 5-fluorouracil treatment reduced the total glandular amylase per unit DNA in both unstimulated and isoproterenol-stimulated parotid glands. Decreased protein synthesis may be the mechanism underlying depleted secretory protein stores since the contents of isolated secretory granules from experimental parotid glands contained less radiolabelled protein than either control group and whole gland homogenates showed marked reductions in the activities of three lysosomal enzymes and total RNA content. Experimental animals contained less labelled protein in their secretory granules than controls, but secreted a greater proportion of their total glandular radiolabelled secretory protein into saliva relative to amylase suggesting that newly synthesized secretory proteins are preferentially secreted.

  10. Coordinated activation of the secretory pathway during notochord formation in the Xenopus embryo.

    Science.gov (United States)

    Tanegashima, Kosuke; Zhao, Hui; Rebbert, Martha L; Dawid, Igor B

    2009-11-01

    We compared the transcriptome in the developing notochord of Xenopus laevis embryos with that of other embryonic regions. A coordinated and intense activation of a large set of secretory pathway genes was observed in the notochord, but not in notochord precursors in the axial mesoderm at early gastrula stage. The genes encoding Xbp1 and Creb3l2 were also activated in the notochord. These two transcription factors are implicated in the activation of secretory pathway genes during the unfolded protein response, where cells react to the stress of a build-up of unfolded proteins in their endoplasmic reticulum. Xbp1 and Creb3l2 are differentially expressed but not differentially activated in the notochord. Reduction of expression of Xbp1 or Creb3l2 by injection of antisense morpholinos led to strong deficits in notochord but not somitic muscle development. In addition, the expression of some, but not all, genes encoding secretory proteins was inhibited by injection of xbp1 morpholinos. Furthermore, expression of activated forms of Xbp1 or Creb3l2 in animal explants could activate a similar subset of secretory pathway genes. We conclude that coordinated activation of a battery of secretory pathway genes mediated by Xbp1 and Creb/ATF factors is a characteristic and necessary feature of notochord formation.

  11. Stage- and gender-specific proteomic analysis of Brugia malayi excretory-secretory products.

    Directory of Open Access Journals (Sweden)

    Yovany Moreno

    Full Text Available INTRODUCTION: While we lack a complete understanding of the molecular mechanisms by which parasites establish and achieve protection from host immune responses, it is accepted that many of these processes are mediated by products, primarily proteins, released from the parasite. Parasitic nematodes occur in different life stages and anatomical compartments within the host. Little is known about the composition and variability of products released at different developmental stages and their contribution to parasite survival and progression of the infection. METHODOLOGY/PRINCIPAL FINDINGS: To gain a deeper understanding on these aspects, we collected and analyzed through 1D-SDS PAGE and LC-MS/MS the Excretory-Secretory Products (ESP of adult female, adult male and microfilariae of the filarial nematode Brugia malayi, one of the etiological agents of human lymphatic filariasis. This proteomic analysis led to the identification of 228 proteins. The list includes 76 proteins with unknown function as well as also proteins with potential immunoregulatory properties, such as protease inhibitors, cytokine homologues and carbohydrate-binding proteins. Larval and adult ESP differed in composition. Only 32 proteins were shared between all three stages/genders. Consistent with this observation, different gene ontology profiles were associated with the different ESP. CONCLUSIONS/SIGNIFICANCE: A comparative analysis of the proteins released in vitro by different forms of a parasitic nematode dwelling in the same host is presented. The catalog of secreted proteins reflects different stage- and gender-specific related processes and different strategies of immune evasion, providing valuable insights on the contribution of each form of the parasite for establishing the host-parasite interaction.

  12. Effect of Semen on Vaginal Fluid Cytokines and Secretory Leukocyte Protease Inhibitor

    Directory of Open Access Journals (Sweden)

    Kathy J. Agnew

    2008-01-01

    Methods: 138 pregnant women had vaginal fluid collected for Gram stain, acid phosphatase detection by colorimetric assay, and interleukin 1-Beta, interleukin-6, interleukin-8, and secretory leukocyte protease inhibitor measurement by enzyme immunoassay. Results for women with and without acid phosphatase were compared by Mann-Whitney test. Results: of 138 subjects, 28 (20% had acid phosphatase detected; of these, only 19 (68% reported recent intercourse and 3 (11% had sperm seen on Gram stain. There were no significant differences in proinflammatory cytokine concentrations; however, secretory leukocyte protease inhibitor concentrations were significantly higher among women with acid phosphatase. Conclusions: proinflammatory cytokine measurement does not appear to be affected by the presence of semen, but secretory leukocyte protease inhibitor is significantly higher when semen is present. Detection of semen by acid phosphatase was associated with higher vaginal SLPI concentrations, however, the presence of semen did not appear to influence vaginal proinflammatory cytokine concentrations.

  13. Dipeptidyl peptidase IV is sorted to the secretory granules in pancreatic islet A-cells

    DEFF Research Database (Denmark)

    Poulsen, Mona Dam; Hansen, Gert Helge; Dabelsteen, Erik

    1993-01-01

    Dipeptidyl peptidase IV (DP IV:EC 3.4.14.5) was localized in endocrine cells of pig pancreas by immunohistochemical and enzyme histochemical methods. Immunolight microscopy with both monoclonal and polyclonal antibodies demonstrated DP IV immunoreactivity in cells located in the peripheral part...... of the islets of Langerhans. The antigen is enzymatically active, as shown by enzyme histochemical analysis with a synthetic DP IV substrate. By immunoelectron microscopy (immunogold labeling), the labeling of DP IV in the islets was associated with the secretory granules of the A-cells, as identified by double...... labeling using a monoclonal glucagon antibody as the second primary antibody. These results show that DP IV is sorted to secretory granules in the pig pancreatic islet A-cells. Furthermore, this secretory granule enzyme, as opposed to intestinal brush border DP IV, is suggested to be a soluble protein...

  14. Aspirin induces morphological transformation to the secretory state in isolated rabbit parietal cells.

    Science.gov (United States)

    Murthy, U K; Levine, R A

    1991-08-01

    The morphological response of rabbit parietal cells to aspirin was evaluated by grading several ultra-structural features including the extent of the tubulovesicular system, intracellular secretory canaliculi, and microvilli. After exposure of isolated parietal cells and gastric glands to aspirin or histamine, there was an approximately twofold increase in the ratio of secretory to nonsecretory parietal cells, and depletion of extracellular Ca2+ abolished the aspirin-induced morphological changes. Morphometry in parietal cells showed that aspirin induced a sixfold increase in secretory canalicular membrane elaboration. Aspirin potentiated histamine-induced parietal cell respiration and aminopyrine uptake ratio but did not increase basal respiration or aminopyrine uptake, suggesting an apparent dissociation from aspirin-induced morphological changes.

  15. Microbiota promote secretory cell determination in the intestinal epithelium by modulating host Notch signaling.

    Science.gov (United States)

    Troll, Joshua V; Hamilton, M Kristina; Abel, Melissa L; Ganz, Julia; Bates, Jennifer M; Stephens, W Zac; Melancon, Ellie; van der Vaart, Michiel; Meijer, Annemarie H; Distel, Martin; Eisen, Judith S; Guillemin, Karen

    2018-02-23

    Resident microbes promote many aspects of host development, although the mechanisms by which microbiota influence host tissues remain unclear. We showed previously that the microbiota is required for allocation of appropriate numbers of secretory cells in the zebrafish intestinal epithelium. Because Notch signaling is crucial for secretory fate determination, we conducted epistasis experiments to establish whether the microbiota modulates host Notch signaling. We also investigated whether innate immune signaling transduces microbiota cues via the Myd88 adaptor protein. We provide the first evidence that microbiota-induced, Myd88-dependent signaling inhibits host Notch signaling in the intestinal epithelium, thereby promoting secretory cell fate determination. These results connect microbiota activity via innate immune signaling to the Notch pathway, which also plays crucial roles in intestinal homeostasis throughout life and when impaired can result in chronic inflammation and cancer. © 2018. Published by The Company of Biologists Ltd.

  16. p-topological Cauchy completions

    Directory of Open Access Journals (Sweden)

    J. Wig

    1999-01-01

    Full Text Available The duality between “regular” and “topological” as convergence space properties extends in a natural way to the more general properties “p-regular” and “p-topological.” Since earlier papers have investigated regular, p-regular, and topological Cauchy completions, we hereby initiate a study of p-topological Cauchy completions. A p-topological Cauchy space has a p-topological completion if and only if it is “cushioned,” meaning that each equivalence class of nonconvergent Cauchy filters contains a smallest filter. For a Cauchy space allowing a p-topological completion, it is shown that a certain class of Reed completions preserve the p-topological property, including the Wyler and Kowalsky completions, which are, respectively, the finest and the coarsest p-topological completions. However, not all p-topological completions are Reed completions. Several extension theorems for p-topological completions are obtained. The most interesting of these states that any Cauchy-continuous map between Cauchy spaces allowing p-topological and p′-topological completions, respectively, can always be extended to a θ-continuous map between any p-topological completion of the first space and any p′-topological completion of the second.

  17. Distribution and structure of internal secretory reservoirs on the vegetative organs of Inula helenium L. (Asteraceae

    Directory of Open Access Journals (Sweden)

    Aneta Sulborska

    2012-12-01

    Full Text Available The aim of the study was to investigate the structure and topography of endogenous secretory tissues of Inula helenium L. By using light and electron microscopy, morphological and anatomical observations of stems, leaves and rhizomes were made. It was shown that in the stems secretory cavities were situated in the vicinity of phloem and xylem bundles. The number of the reservoirs reached its maximum value (34 at shoot flowerig termination, whereas the cavities with the largest diameter were observed at full flowering stage (44.6 µm. In the leaf petioles and midribs, the reservoirs also accompanied the vascular bundles, and their number and size increased along with the growth of the assimilation organs. Observations of the cross sections of the rhizomes revealed the presence of several rings of secretory reservoirs. The measurements of the cavities showed that as a rule the reservoirs with a larger dimension were located in the phelloderm, whereas the smallest ones in the xylem area. The secretory cavities located in the stems and leaves developed by schizogenesis, whereas the rhizome reservoirs were probably formed schizolisygenously. The cells lining the reservoirs formed a one - four-layered epithelium. Observed in TEM, the secretory cells of the mature cavities located in the rhizomes were characterised by the presence of a large central vacuole, whereas the protoplast was largely degraded. Fibrous elements of osmophilic secretion and numerous different coloured vesicles could be distinguished in it. The cell walls formed, from the side of the reservoir lumen, ingrowths into the interior of the epithelial cells. Between the cell wall and the plasmalemma of the glandular cells, a brighter periplasmatic zone with secretory vesicles was observed.

  18. Changes in mean plasma ACTH reflect changes in amplitude and frequency of secretory pulses

    International Nuclear Information System (INIS)

    Carnes, M.; Lent, S.J.; Erisman, S.; Feyzi, J.

    1988-01-01

    ACTH is secreted in an episodic manner from the anterior pituitary. Unanesthetized rats with indwelling jugular and femoral venous cannulae were continuously bled and simultaneously infused with isotonic fluid by peristaltic pump. Two-minute blood samples were collected for up to five hours in 8 male rats. ACTH was measured by radioimmunoassay. The resulting time series were analyzed for significant secretory pulses with the PULSAR program. Elevations or declines in mean plasma ACTH levels were associated with significant changes in amplitude and frequency of secretory pulses

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  7. Tailoring Escherichia coli for the L-rhamnose PBAD promoter-based production of membrane and secretory proteins

    NARCIS (Netherlands)

    Hjelm, Anna; Karyolaimos, Alexandros; Zhang, Zhe; Rujas, Edurne; Vikström, David; Slotboom, Dirk Jan; de Gier, Jan-Willem

    Membrane and secretory protein production in Escherichia coli requires precisely controlled production rates to avoid the deleterious saturation of their biogenesis pathways. Based on this requirement, the E. coli L-rhamnose PBAD promoter (PrhaBAD) is often used for membrane and secretory protein

  8. Completeness theorems in transport theory

    International Nuclear Information System (INIS)

    Zweifel, P.F.

    1984-01-01

    Ever since K. M.; Case's famous 1960 paper, transport theorists have been studying the questions of full- and half-range completeness for various transport type equations. The purpose of this note is to try to define exactly what is meant by completeness as it is needed, and used, in solving transport equations and to discuss some of the various techniques which have been, or might be, used to verify completeness. Attention is restricted to the question of full-range completeness. As a paradigm the generalized form of the transport equation first introduced by Beals is adopted

  9. Comparison of ion transport by cultured secretory and absorptive canine airway epithelia

    DEFF Research Database (Denmark)

    Boucher, R C; Larsen, Erik Hviid

    1988-01-01

    The use of primary cell culture techniques to predict the function of native respiratory epithelia was tested in studies of dog airway epithelia. Epithelial cells from Cl- secretory (tracheal) and Na+ absorptive (bronchial) airway regions were isolated by enzymatic digestion, plated on collagen...

  10. Disparate effects of p24alpha and p24delta on secretory protein transport and processing.

    Directory of Open Access Journals (Sweden)

    Jeroen R P M Strating

    Full Text Available BACKGROUND: The p24 family is thought to be somehow involved in endoplasmic reticulum (ER-to-Golgi protein transport. A subset of the p24 proteins (p24alpha(3, -beta(1, -gamma(3 and -delta(2 is upregulated when Xenopus laevis intermediate pituitary melanotrope cells are physiologically activated to produce vast amounts of their major secretory cargo, the prohormone proopiomelanocortin (POMC. METHODOLOGY/PRINCIPAL FINDINGS: Here we find that transgene expression of p24alpha(3 or p24delta(2 specifically in the Xenopus melanotrope cells in both cases causes an effective displacement of the endogenous p24 proteins, resulting in severely distorted p24 systems and disparate melanotrope cell phenotypes. Transgene expression of p24alpha(3 greatly reduces POMC transport and leads to accumulation of the prohormone in large, ER-localized electron-dense structures, whereas p24delta(2-transgenesis does not influence the overall ultrastructure of the cells nor POMC transport and cleavage, but affects the Golgi-based processes of POMC glycomaturation and sulfation. CONCLUSIONS/SIGNIFICANCE: Transgenic expression of two distinct p24 family members has disparate effects on secretory pathway functioning, illustrating the specificity and non-redundancy of our transgenic approach. We conclude that members of the p24 family furnish subcompartments of the secretory pathway with specific sets of machinery cargo to provide the proper microenvironments for efficient and correct secretory protein transport and processing.

  11. Total soluble and endogenous secretory receptor for advanced glycation endproducts (RAGE) in IBD

    NARCIS (Netherlands)

    Meijer, Berrie; Hoskin, Teagan; Ashcroft, Anna; Burgess, Laura; Keenan, Jacqueline I.; Falvey, James; Gearry, Richard B.; Day, Andrew S.

    2014-01-01

    Recruitment and activation of neutrophils, with release of specific proteins such as S100 proteins, is a feature of inflammatory bowel disease (IBD). Soluble forms of the receptor for advanced glycation endproducts (sRAGE), and variants such as endogenous secretory (esRAGE), can act as decoy

  12. Secretory expression of functional barley limit dextrinase by Pichia pastoris using high cell-density fermentation

    DEFF Research Database (Denmark)

    Vester-Christensen, Malene Bech; Abou Hachem, Maher; Næsted, Henrik

    2010-01-01

    biosynthesis by trimming of intermediate branched alpha-glucan structures. Highly active barley LD is obtained by secretory expression during high cell-density fermentation of Pichia pastoris. The LD encoding gene fragment without signal peptide was subcloned in-frame with the Saccharomyces cerevisiae alpha...

  13. Analysis of Protein Localization and Secretory Pathway Function Using the Yeast "Saccharomyces Cerevisiae"

    Science.gov (United States)

    Vallen, Elizabeth

    2002-01-01

    The isolation and characterization of mutants has been crucial in understanding a number of processes in the field of cell biology. In this exercise, students examine the effects of mutations in the secretory pathway on protein localization. Yeast strains deficient for synthesis of histidinol dehydrogenase are transformed with a plasmid encoding a…

  14. Secretory Phospholipase A2-IIA and Cardiovascular Disease: A Mendelian Randomization Study

    NARCIS (Netherlands)

    Holmes, Michael V.; Simon, Tabassome; Exeter, Holly J.; Folkersen, Lasse; Asselbergs, Folkert W.; Guardiola, Montse; Cooper, Jackie A.; Palmen, Jutta; Hubacek, Jaroslav A.; Carruthers, Kathryn F.; Horne, Benjamin D.; Brunisholz, Kimberly D.; Mega, Jessica L.; van Iperen, Erik P. A.; Li, Mingyao; Leusink, Maarten; Trompet, Stella; Verschuren, Jeffrey J. W.; Hovingh, G. Kees; Dehghan, Abbas; Nelson, Christopher P.; Kotti, Salma; Danchin, Nicolas; Scholz, Markus; Haase, Christiane L.; Rothenbacher, Dietrich; Swerdlow, Daniel I.; Kuchenbaecker, Karoline B.; Staines-Urias, Eleonora; Goel, Anuj; van 't Hooft, Ferdinand; Gertow, Karl; de Faire, Ulf; Panayiotou, Andrie G.; Tremoli, Elena; Baldassarre, Damiano; Veglia, Fabrizio; Holdt, Lesca M.; Beutner, Frank; Gansevoort, Ron T.; Navis, Gerjan J.; Mateo Leach, Irene; Breitling, Lutz P.; Brenner, Hermann; Thiery, Joachim; Dallmeier, Dhayana; Franco-Cereceda, Anders; Boer, Jolanda M. A.; Stephens, Jeffrey W.; Hofker, Marten H.; Tedgui, Alain; Hofman, Albert; Uitterlinden, André G.; Adamkova, Vera; Pitha, Jan; Onland-Moret, N. Charlotte; Cramer, Maarten J.; Nathoe, Hendrik M.; Spiering, Wilko; Klungel, Olaf H.; Kumari, Meena; Whincup, Peter H.; Morrow, David A.; Braund, Peter S.; Hall, Alistair S.; Olsson, Anders G.; Doevendans, Pieter A.; Trip, Mieke D.; Tobin, Martin D.; Hamsten, Anders; Watkins, Hugh; Koenig, Wolfgang; Nicolaides, Andrew N.; Teupser, Daniel; Day, Ian N. M.; Carlquist, John F.; Gaunt, Tom R.; Ford, Ian; Sattar, Naveed; Tsimikas, Sotirios; Schwartz, Gregory G.; Lawlor, Debbie A.; Morris, Richard W.; Sandhu, Manjinder S.; Poledne, Rudolf; Maitland-van der Zee, Anke H.; Khaw, Kay-Tee; Keating, Brendan J.; van der Harst, Pim; Price, Jackie F.; Mehta, Shamir R.; Yusuf, Salim; Witteman, Jaqueline C. M.; Franco, Oscar H.; Jukema, J. Wouter; de Knijff, Peter; Tybjaerg-Hansen, Anne; Rader, Daniel J.; Farrall, Martin; Samani, Nilesh J.; Kivimaki, Mika; Fox, Keith A. A.; Humphries, Steve E.; Anderson, Jeffrey L.; Boekholdt, S. Matthijs; Palmer, Tom M.; Eriksson, Per; Paré, Guillaume; Hingorani, Aroon D.; Sabatine, Marc S.; Mallat, Ziad; Casas, Juan P.; Talmud, Philippa J.

    2013-01-01

    This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease. Higher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is

  15. Lactadherin inhibits secretory phospholipase A2 activity on pre-apoptotic leukemia cells.

    Directory of Open Access Journals (Sweden)

    Steffen Nyegaard

    Full Text Available Secretory phospholipase A2 (sPLA2 is a critical component of insect and snake venoms and is secreted by mammalian leukocytes during inflammation. Elevated secretory PLA2 concentrations are associated with autoimmune diseases and septic shock. Many sPLA2's do not bind to plasma membranes of quiescent cells but bind and digest phospholipids on the membranes of stimulated or apoptotic cells. The capacity of these phospholipases to digest membranes of stimulated or apoptotic cells correlates to the exposure of phosphatidylserine. In the present study, the ability of the phosphatidyl-L-serine-binding protein, lactadherin to inhibit phospholipase enzyme activity has been assessed. Inhibition of human secretory phospholipase A2-V on phospholipid vesicles exceeded 90%, whereas inhibition of Naja mossambica sPLA2 plateaued at 50-60%. Lactadherin inhibited 45% of activity of Naja mossambica sPLA2 and >70% of human secretory phospholipase A2-V on the membranes of human NB4 leukemia cells treated with calcium ionophore A23187. The data indicate that lactadherin may decrease inflammation by inhibiting sPLA2.

  16. Interactions between Melanin Enzymes and Their Atypical Recruitment to the Secretory Pathway by Palmitoylation

    Directory of Open Access Journals (Sweden)

    Srijana Upadhyay

    2016-11-01

    Full Text Available Melanins are biopolymers that confer coloration and protection to the host organism against biotic or abiotic insults. The level of protection offered by melanin depends on its biosynthesis and its subcellular localization. Previously, we discovered that Aspergillus fumigatus compartmentalizes melanization in endosomes by recruiting all melanin enzymes to the secretory pathway. Surprisingly, although two laccases involved in the late steps of melanization are conventional secretory proteins, the four enzymes involved in the early steps of melanization lack a signal peptide or a transmembrane domain and are thus considered “atypical” secretory proteins. In this work, we found interactions among melanin enzymes and all melanin enzymes formed protein complexes. Surprisingly, the formation of protein complexes by melanin enzymes was not critical for their trafficking to the endosomal system. By palmitoylation profiling and biochemical analyses, we discovered that all four early melanin enzymes were strongly palmitoylated during conidiation. However, only the polyketide synthase (PKS Alb1 was strongly palmitoylated during both vegetative hyphal growth and conidiation when constitutively expressed alone. This posttranslational lipid modification correlates the endosomal localization of all early melanin enzymes. Intriguingly, bioinformatic analyses predict that palmitoylation is a common mechanism for potential membrane association of polyketide synthases (PKSs and nonribosomal peptide synthetases (NRPSs in A. fumigatus. Our findings indicate that protein-protein interactions facilitate melanization by metabolic channeling, while posttranslational lipid modifications help recruit the atypical enzymes to the secretory pathway, which is critical for compartmentalization of secondary metabolism.

  17. Glycosaminoglycan synthesis by adult rat submandibular salivary-gland secretory units.

    Science.gov (United States)

    Cutler, L S; Christian, C P; Rendell, J K

    1987-01-01

    The synthesis of glycosaminoglycans (GAG) by a preparation of purified, functional submandibular-gland secretory units (acini and intercalated ducts) was examined. Such units were isolated from Sprague-Dawley rats by digestion of minced gland with hyaluronidase and collagenase followed by gentle sieving of the digest through a graded series of Teflon screens. They incorporated amino acids into exocrine proteins which could be released by stimulation with isoproterenol as in vivo, indicating their functional integrity. Secretory units, incubated for 2 h in medium containing [35S]-sodium sulphate alone or in combination with [3H]-glucosamine, were then washed, homogenized and digested in pronase. The resulting material was then sequentially digested by specific enzymic and chemical procedures and analysed by chromatography on Sephadex G-50 columns to identify the various GAG synthesized. Secretory units synthesized a GAG mixture which was 20-25 per cent hyaluronic acid, 70-75 per cent heparan sulphate, and only 3-5 per cent chondroitin or dermatan sulphates, similar to that synthesized in vivo. No GAG was present in the secretory material, suggesting that all the GAG synthesized was destined for the basement membrane or cell surface.

  18. Loss of Sonic hedgehog leads to alterations in intestinal secretory cell maturation and autophagy.

    Directory of Open Access Journals (Sweden)

    Jessica Gagné-Sansfaçon

    Full Text Available BACKGROUND: Intestinal epithelial cells express the Sonic and Indian hedgehog ligands. Despite the strong interest in gut hedgehog signaling in GI diseases, no studies have specifically addressed the singular role of intestinal epithelial cell Sonic hedgehog signaling. The aim of this study was to investigate the specific role of Sonic hedgehog in adult ileal epithelial homeostasis. METHODOLOGY/PRINCIPAL FINDINGS: A Sonic hedgehog intestinal epithelial conditional knockout mouse model was generated. Assessment of ileal histological abnormalities, crypt epithelial cell proliferation, epithelial cell fate, junctional proteins, signaling pathways, as well as ultrastructural analysis of intracellular organelles were performed in control and mutant mice. Mice lacking intestinal epithelial Sonic Hedgehog displayed decreased ileal crypt/villus length, decreased crypt proliferation as well as a decrease in the number of ileal mucin-secreting goblet cells and antimicrobial peptide-secreting Paneth cells during adult life. These secretory cells also exhibited disruption of their secretory products in mutant mice. Ultrastructural microscopy analysis revealed a dilated ER lumen in secretory cells. This phenotype was also associated with a decrease in autophagy. CONCLUSIONS/SIGNIFICANCE: Altogether, these findings indicate that the loss of Sonic hedgehog can lead to ileal secretory cell modifications indicative of endoplasmic reticulum stress, accompanied by a significant reduction in autophagy.

  19. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance.

    Directory of Open Access Journals (Sweden)

    Birgitte Holst

    Full Text Available Secretory vesicles in endocrine cells store hormones such as growth hormone (GH and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN and their subsequent maturation remain unclear. Here, we identify the lipid binding BAR (Bin/amphiphysin/Rvs domain protein PICK1 (protein interacting with C kinase 1 as a key component early in the biogenesis of secretory vesicles in GH-producing cells. Both PICK1-deficient Drosophila and mice displayed somatic growth retardation. Growth retardation was rescued in flies by reintroducing PICK1 in neurosecretory cells producing somatotropic peptides. PICK1-deficient mice were characterized by decreased body weight and length, increased fat accumulation, impaired GH secretion, and decreased storage of GH in the pituitary. Decreased GH storage was supported by electron microscopy showing prominent reduction in secretory vesicle number. Evidence was also obtained for impaired insulin secretion associated with decreased glucose tolerance. PICK1 localized in cells to immature secretory vesicles, and the PICK1 BAR domain was shown by live imaging to associate with vesicles budding from the TGN and to possess membrane-sculpting properties in vitro. In mouse pituitary, PICK1 co-localized with the BAR domain protein ICA69, and PICK1 deficiency abolished ICA69 protein expression. In the Drosophila brain, PICK1 and ICA69 co-immunoprecipitated and showed mutually dependent expression. Finally, both in a Drosophila model of type 2 diabetes and in high-fat-diet-induced obese mice, we observed up-regulation of PICK1 mRNA expression. Our findings suggest that PICK1, together with ICA69, is critical during budding of immature secretory vesicles from the TGN and thus for vesicular storage of GH and possibly other hormones. The data link two BAR domain proteins to membrane remodeling processes in the secretory pathway of

  20. Completely continuous and weakly completely continuous abstract ...

    Indian Academy of Sciences (India)

    An algebra A is called right completely continuous (right weakly completely continuous) ... Moreover, some applications of these results in group algebras are .... A linear subspace S(G) of L1(G) is said to be a Segal algebra, if it satisfies the.

  1. Suppression of cell death by the secretory form of N-terminal ERC/mesothelin.

    Science.gov (United States)

    Wang, Tegexibaiyin; Kajino, Kazunori; Abe, Masaaki; Tan, Ke; Maruo, Masumi; Sun, Guodong; Hagiwara, Yoshiaki; Maeda, Masahiro; Hino, Okio

    2010-08-01

    ERC/mesothelin is highly expressed in malignant mesothelioma, pancreatic cancer, and ovarian cancer. It is cleaved to a 30 kDa N-terminal secretory form (N-ERC) and a 40 kDa C-terminal membranous form (C-ERC). Several functions have been reported for full-length ERC (full-ERC) and C-ERC/mesothelin, such as in cell adhesion and invasion, stimulation of cell proliferation, and the suppression of cell death. However, there have been no studies to date on the function of secretory N-ERC, despite the fact that it is abundantly secreted into the sera of mesothelioma patients. In this study, we investigated whether N-ERC could function as a secretory factor to stimulate tumor progression. Full-, N, or C-ERC was overexpressed in the human hepatocellular carcinoma cell line Huh7 that lacks endogenous expression of ERC/mesothelin. Changes in the rates of cell proliferation and cell death were determined, and the state of signal transducers was examined using various endpoints: total cell counts, trypan blue exclusion rate, BrdU incorporation rate, TUNEL assay, and the phosphorylation of ERK1/2 and Stat3. In cells overexpressing N-ERC, phosphorylation of ERK1/2 was enhanced and the rate of cell death decreased, leading to the increase of cell number. The culture medium containing the secretory N-ERC also had the activity to increase the number of cells. Our data suggested that one of the full-ERC functions reported previously was mediated by the secretory N-ERC.

  2. The neuro secretory activity in the permanent nymphs of schistocerca gregarea (Forskal) as a result of gamma irradiation of the third nymphal instar

    International Nuclear Information System (INIS)

    Elgammal, A.M.; Abdelsalam, K.A.; Mourad, A.K.

    1986-01-01

    Laboratory studies were carried out to evaluate the effect of different doses of gamma radiation on the neuro secretory activity in the permanent nymphs of schistocerca gregaria by treating them in the third nymphal instar. Treatment with 30 gray induced complete mortality for all treated nymphs. However, irradiation with a dose of 20 gray produced fourth instar nymphs which entered a state of suspended development for about 14 days. Exposure to a dose of 10 gray induced three types of response associated with the endocrine activities. Some of the treated nymphs developed to the fifth instar with soft and thin cuticle without tanning or darkening, these nymphs did not survive more than a few hours after ecdysis. Others became fifth instar with anomalous wings and normal cuticle, these survived about 18 days as permanent fifth instar nymphs before dying. The rest molted to permanent fourth instar that survived more than one month and eventually died. Corporal allata (CA) volume in the permanent nymphs were estimated by planimeter method, revealing a pronounced reduction in their size in comparison with the untreated control. This reflects a sharp inhibition in their synthetic activity of juvenile hormone (J H). It is assumed that the permanent nymphs were produced as a result of direct effect on the cerebral neuro secretory cells of the brain, the source of stimulation for J H an decdysone production. In the main time, gamma rays prevented the production of the tanning and darkening factor (Bursicon hormone) in these cells.1 fig.,3 tab

  3. Degradation of Uniquely Glycosylated Secretory Immunoglobulin A in Tears From Patients With Pseudomonas aeruginosa Keratitis

    DEFF Research Database (Denmark)

    Lomholt, Jeanet Andersen; Kilian, Mogens

    2008-01-01

    PURPOSE. To investigate the integrity of secretory IgA (S-IgA) in tear fluid during bacterial keratitis and to evaluate the significance of specific Pseudomonas aeruginosa extracellular proteases in the observed degradation of S-IgA. METHODS. The integrity of component chains of S-IgA in tear fluid...... from patients with keratitis caused by P. aeruginosa, Streptococcus group G, Moraxella catarrhalis, Staphylococcus aureus, coagulase-negative staphylococci, and the IgA1 protease-producing Streptococcus pneumoniae were compared with S-IgA in tear fluid, colostrum, and saliva from healthy individuals......, and with tear S-IgA incubated with clinical isolates and genetically engineered P. aeruginosa strains with different protease profiles. Degradation of S-IgA and the significance of its glycosylation were analyzed in Western blots developed with antibodies against individual chains of S-IgA. RESULTS. Secretory...

  4. Segregation of sphingolipids and sterols during formation of secretory vesicles at the trans-Golgi network

    DEFF Research Database (Denmark)

    Klemm, Robin W; Ejsing, Christer S.; Surma, Michal A

    2009-01-01

    The trans-Golgi network (TGN) is the major sorting station in the secretory pathway of all eukaryotic cells. How the TGN sorts proteins and lipids to generate the enrichment of sphingolipids and sterols at the plasma membrane is poorly understood. To address this fundamental question in membrane...... trafficking, we devised an immunoisolation procedure for specific recovery of post-Golgi secretory vesicles transporting a transmembrane raft protein from the TGN to the cell surface in the yeast Saccharomyces cerevisiae. Using a novel quantitative shotgun lipidomics approach, we could demonstrate that TGN...... than the late Golgi membrane, as measured by C-Laurdan spectrophotometry, strongly suggests that lipid rafts play a role in the TGN-sorting machinery....

  5. Roles of secretory leukocyte protease inhibitor amniotic membrane in oral wound healing

    Directory of Open Access Journals (Sweden)

    Elly Munadziroh

    2006-12-01

    Full Text Available Secretory Leukocyte Protease Inhibitor (SLPI is serine protease inhibitor. Secretory Leukocyte Protease Inhibitor is a protein found in secretions such as whole saliva, seminal fluid, cervical mucus, synovial fluid, breast milk, tears, and cerebral spinal fluid, as in secretions from the nose and bronchi, amniotic fluid and amniotic membrane etc. These findings demonstrate that SLPI function as a potent anti protease, anti inflammatory, bactericidal, antifungal, tissue repair, extra cellular synthesis. Impaired healing states are characterized by excessive proteolysis and often bacterial infection, leading to the hypothesis that SLPI may have a role in the process. The objectives of this article are to investigate the role of SLPI in oral inflammation and how it contributes to tissue repair in oral mucosa. The oral wound healing responses are impaired in the SLPI sufficient mice and matrix synthesis and collagen deposition are delayed. This study indicated that SLPI is a povital factor necessary for optimal wound healing.

  6. The Fas pathway is involved in pancreatic beta cell secretory function

    DEFF Research Database (Denmark)

    Schumann, Desiree M; Maedler, Kathrin; Franklin, Isobel

    2007-01-01

    Pancreatic beta cell mass and function increase in conditions of enhanced insulin demand such as obesity. Failure to adapt leads to diabetes. The molecular mechanisms controlling this adaptive process are unclear. Fas is a death receptor involved in beta cell apoptosis or proliferation, depending...... on the activity of the caspase-8 inhibitor FLIP. Here we show that the Fas pathway also regulates beta cell secretory function. We observed impaired glucose tolerance in Fas-deficient mice due to a delayed and decreased insulin secretory pattern. Expression of PDX-1, a beta cell-specific transcription factor...... regulating insulin gene expression and mitochondrial metabolism, was decreased in Fas-deficient beta cells. As a consequence, insulin and ATP production were severely reduced and only partly compensated for by increased beta cell mass. Up-regulation of FLIP enhanced NF-kappaB activity via NF...

  7. Crosstalk of Autophagy and the Secretory Pathway and Its Role in Diseases.

    Science.gov (United States)

    Zahoor, Muhammad; Farhan, Hesso

    2018-01-01

    The secretory and autophagic pathways are two fundamental, evolutionary highly conserved endomembrane processes. Typically, secretion is associated with biosynthesis and delivery of proteins. In contrast, autophagy is usually considered as a degradative pathway. Thus, an analogy to metabolic pathways is evident. Anabolic (biosynthetic) and catabolic (degradative) pathways are usually intimately linked and intertwined, and likewise, the secretory and autophagy pathways are intertwined. Investigation of this link is an emerging area of research, and we will provide an overview of some of the major advances that have been made to contribute to understanding of how secretion regulates autophagy and vice versa. Finally, we will highlight evidence that supports a potential involvement of the autophagy-secretion crosstalk in human diseases. © 2018 Elsevier Inc. All rights reserved.

  8. Comparison of Excretory-Secretory and Somatic Antigens of Ornithobilharzia turkestanicum in Agar Gel Diffusion Test

    Directory of Open Access Journals (Sweden)

    H Miranzadeh

    2008-12-01

    Full Text Available Background: Ornithobilharziosis as one of the parasitic infections may give rise to serious economic problems in animal husbandry. The Aim of the study was to prepare and compare the somatic and excretory-secretory (ES antigens of O. tur­kestanicum in gel diffusion test. Methods: Excretory-secretory (ES and somatic antigens of Ornithobilharzia turkestanicum were prepared from collected worms from mesentric blood vessels of infected sheep. The laboratory bred rabbits were immunized with antigens and then antisera were prepared. The reaction of antigens and antisera was observed in gel diffusion test. Results: ES antigens of this species showed positive reaction with antisera raised against ES and also somatic antigens. Somatic antigens also showed positive reaction with antisera raised against somatic and also ES antigens. Conclusion: The antigenicity of O. turkestanicum ES and somatic antigens is the same in gel diffusion test.

  9. The Prohormone VGF Regulates β Cell Function via Insulin Secretory Granule Biogenesis

    Directory of Open Access Journals (Sweden)

    Samuel B. Stephens

    2017-09-01

    Full Text Available The prohormone VGF is expressed in neuroendocrine and endocrine tissues and regulates nutrient and energy status both centrally and peripherally. We and others have shown that VGF-derived peptides have direct action on the islet β cell as secretagogues and cytoprotective agents; however, the endogenous function of VGF in the β cell has not been described. Here, we demonstrate that VGF regulates secretory granule formation. VGF loss-of-function studies in both isolated islets and conditional knockout mice reveal a profound decrease in stimulus-coupled insulin secretion. Moreover, VGF is necessary to facilitate efficient exit of granule cargo from the trans-Golgi network and proinsulin processing. It also functions to replenish insulin granule stores following nutrient stimulation. Our data support a model in which VGF operates at a critical node of granule biogenesis in the islet β cell to coordinate insulin biosynthesis with β cell secretory capacity.

  10. Structural Completeness in Fuzzy Logics

    Czech Academy of Sciences Publication Activity Database

    Cintula, Petr; Metcalfe, G.

    2009-01-01

    Roč. 50, č. 2 (2009), s. 153-183 ISSN 0029-4527 R&D Projects: GA MŠk(CZ) 1M0545 Institutional research plan: CEZ:AV0Z10300504 Keywords : structral logics * fuzzy logics * structural completeness * admissible rules * primitive variety * residuated lattices Subject RIV: BA - General Mathematics

  11. Completely integrable operator evolutionary equations

    International Nuclear Information System (INIS)

    Chudnovsky, D.V.

    1979-01-01

    The authors present natural generalizations of classical completely integrable equations where the functions are replaced by arbitrary operators. Among these equations are the non-linear Schroedinger, the Korteweg-de Vries, and the modified KdV equations. The Lax representation and the Baecklund transformations are presented. (Auth.)

  12. The Completeness Theorem of Godel

    Indian Academy of Sciences (India)

    GENERAL I ARTICLE. The Completeness Theorem of Godel. 2. Henkin's Proof for First Order Logic. S M Srivastava is with the. Indian Statistical,. Institute, Calcutta. He received his PhD from the Indian Statistical. Institute in 1980. His research interests are in descriptive set theory. I Part 1. An Introduction to Math- ematical ...

  13. Insulin replacement restores the vesicular secretory apparatus in the diabetic rat lacrimal gland

    Directory of Open Access Journals (Sweden)

    Ana Carolina Dias

    2015-06-01

    Full Text Available ABSTRACT Purpose: In the lacrimal gland (LG acinar cells, signaling regulates the release of secretory vesicles through specific Rab and SNARE exocytotic proteins. In diabetes mellitus (DM, the LGs are dysfunctional. The aim of this work was to determine if secretory apparatus changes were associated with any effects on the secretory vesicles (SV in diabetic rats as well as the expression levels of constituent Rab and members of the SNARE family, and if insulin supplementation reversed those changes. Methods: DM was induced in male Wistar rats with an intravenous dose of streptozotocin (60 mg/kg. One of the two diabetic groups was then treated every other day with insulin (1 IU. A third control group was injected with vehicle. After 10 weeks, Western blotting and RT-PCR were used to compared the Rab and SNARE secretory factor levels in the LGs. Transmission electron microscopy evaluated acinar cell SV density and integrity. Results: In the diabetes mellitus group, there were fewer and enlarged SV. The Rab 27b, Rab 3d, and syntaxin-1 protein expression declined in the rats with diabetes mellitus. Insulin treatment restored the SV density and the Rab 27b and syntaxin expression to their control protein levels, whereas the Vamp 2 mRNA expression increased above the control levels. Conclusions: Diabetes mellitus LG changes were associated with the declines in protein expression levels that were involved in supporting exocytosis and vesicular formation. They were partially reversed by insulin replacement therapy. These findings may help to improve therapeutic management of dry eye in diabetes mellitus.

  14. Antigenic analyses of tissues and excretory and secretory products from Strongylus vulgaris.

    OpenAIRE

    Wynne, E; Slocombe, J O; Wilkie, B N

    1981-01-01

    Rabbit antisera were prepared against veronal buffered saline extracts of L4 and L5 Strongylus vulgaris, adult S. vulgaris and adult Strongylus equinus retrieved from naturally infected horses. In agar gel diffusion with these antisera, adult S vulgaris and S. equinus each appeared to have at least one unique antigen; larval S. vulgaris appeared to have two species-specific and two stage-specific antigens. There were several common antigens. Excretory and secretory products were collected als...

  15. The secretory endometrial protein, placental protein 14, in women with ectopic gestation

    DEFF Research Database (Denmark)

    Ruge, S; Sørensen, Steen; Vejtorp, M

    1992-01-01

    OBJECTIVE: To determine the serum level of the secretory endometrial protein, placental protein 14 (PP14) and progesterone (P) in women with ectopic gestation. DESIGN: Blood samples were collected prospectively and preoperatively. Reference range was determined from a prospective population of 98......: These findings suggest that the regulation of the PP14 production involves either a control mechanism from the ovary or is mediated by paracrine secretion....

  16. Shedding light on the role of lipid flippases in the secretory pathway

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura

    that these pumps serve important functions in vesicular traffic, their activities being required to support vesicle formation in the secretory and endocytic pathways. We are now aiming at determining the mechanism by which these ATPases function in vesicle biogenesis. For this purpose, we are using novel...... biophysical approaches based on giant vesicles and several advanced bioimaging methods. The limitations and future perspectives of these techniques for the characterization of lipid translocases will be discussed in the light of our recent results....

  17. Brucella Modulates Secretory Trafficking via Multiple Type IV Secretion Effector Proteins

    Science.gov (United States)

    Myeni, Sebenzile; Child, Robert; Ng, Tony W.; Kupko, John J.; Wehrly, Tara D.; Porcella, Stephen F.; Knodler, Leigh A.; Celli, Jean

    2013-01-01

    The intracellular pathogenic bacterium Brucella generates a replicative vacuole (rBCV) derived from the endoplasmic reticulum via subversion of the host cell secretory pathway. rBCV biogenesis requires the expression of the Type IV secretion system (T4SS) VirB, which is thought to translocate effector proteins that modulate membrane trafficking along the endocytic and secretory pathways. To date, only a few T4SS substrates have been identified, whose molecular functions remain unknown. Here, we used an in silico screen to identify putative T4SS effector candidate proteins using criteria such as limited homology in other bacterial genera, the presence of features similar to known VirB T4SS effectors, GC content and presence of eukaryotic-like motifs. Using β-lactamase and CyaA adenylate cyclase reporter assays, we identified eleven proteins translocated into host cells by Brucella, five in a VirB T4SS-dependent manner, namely BAB1_0678 (BspA), BAB1_0712 (BspB), BAB1_0847 (BspC), BAB1_1671 (BspE) and BAB1_1948 (BspF). A subset of the translocated proteins targeted secretory pathway compartments when ectopically expressed in HeLa cells, and the VirB effectors BspA, BspB and BspF inhibited protein secretion. Brucella infection also impaired host protein secretion in a process requiring BspA, BspB and BspF. Single or combined deletions of bspA, bspB and bspF affected Brucella ability to replicate in macrophages and persist in the liver of infected mice. Taken together, these findings demonstrate that Brucella modulates secretory trafficking via multiple T4SS effector proteins that likely act coordinately to promote Brucella pathogenesis. PMID:23950720

  18. Labeling and exocytosis of secretory compartments in RBL mastocytes by polystyrene and mesoporous silica nanoparticles

    Directory of Open Access Journals (Sweden)

    Ekkapongpisit M

    2012-04-01

    Full Text Available Maneerat Ekkapongpisit1,*, Antonino Giovia1,*, Giuseppina Nicotra1, Matteo Ozzano1, Giuseppe Caputo2,3, Ciro Isidoro1 1Laboratory of Molecular Pathology and Nanobioimaging, Department of Health Sciences, Università del Piemonte Orientale "A. Avogadro", Novara, Italy; 2Department of Chemistry, University of Turin, Turin, 3Cyanine Technology SpA, Torino, Italy *These authors contributed equally to this workBackground: For a safe ‘in vivo’ biomedical utilization of nanoparticles, it is essential to assess not only biocompatibility, but also the potential to trigger unwanted side effects at both cellular and tissue levels. Mastocytes (cells having secretory granules containing cytokines, vasoactive amine, and proteases play a pivotal role in the immune and inflammatory responses against exogenous toxins. Mastocytes are also recruited in the tumor stroma and are involved in tumor vascularization and growth.Aim and methods: In this work, mastocyte-like rat basophilic leukemia (RBL cells were used to investigate whether carboxyl-modified 30 nm polystyrene (PS nanoparticles (NPs and naked mesoporous silica (MPS 10 nm NPs are able to label the secretory inflammatory granules, and possibly induce exocytosis of these granules. Uptake, cellular retention and localization of fluorescent NPs were analyzed by cytofluorometry and microscope imaging.Results: Our findings were that: (1 secretory granules of mastocytes are accessible by NPs via endocytosis; (2 PS and MPS silica NPs label two distinct subpopulations of inflammatory granules in RBL mastocytes; and (3 PS NPs induce calcium-dependent exocytosis of inflammatory granules.Conclusion: These findings highlight the value of NPs for live imaging of inflammatory processes, and also have important implications for the clinical use of PS-based NPs, due to their potential to trigger the unwanted activation of mastocytes.Keywords: secretory lysosomes, inflammation, nanoparticles, vesicular traffic

  19. Signaling from the secretory granule to the nucleus: Uhmk1 and PAM.

    Science.gov (United States)

    Francone, Victor P; Ifrim, Marius F; Rajagopal, Chitra; Leddy, Christopher J; Wang, Yanping; Carson, John H; Mains, Richard E; Eipper, Betty A

    2010-08-01

    Neurons and endocrine cells package peptides in secretory granules (large dense-core vesicles) for storage and stimulated release. Studies of peptidylglycine alpha-amidating monooxygenase (PAM), an essential secretory granule membrane enzyme, revealed a pathway that can relay information from secretory granules to the nucleus, resulting in alterations in gene expression. The cytosolic domain (CD) of PAM, a type 1 membrane enzyme essential for the production of amidated peptides, is basally phosphorylated by U2AF homology motif kinase 1 (Uhmk1) and other Ser/Thr kinases. Proopiomelanocortin processing in AtT-20 corticotrope tumor cells was increased when Uhmk1 expression was reduced. Uhmk1 was concentrated in the nucleus, but cycled rapidly between nucleus and cytosol. Endoproteolytic cleavage of PAM releases a soluble CD fragment that localizes to the nucleus. Localization of PAM-CD to the nucleus was decreased when PAM-CD with phosphomimetic mutations was examined and when active Uhmk1 was simultaneously overexpressed. Membrane-tethering Uhmk1 did not eliminate its ability to exclude PAM-CD from the nucleus, suggesting that cytosolic Uhmk1 could cause this response. Microarray analysis demonstrated the ability of PAM to increase expression of a small subset of genes, including aquaporin 1 (Aqp1) in AtT-20 cells. Aqp1 mRNA levels were higher in wild-type mice than in mice heterozygous for PAM, indicating that a similar relationship occurs in vivo. Expression of PAM-CD also increased Aqp1 levels whereas expression of Uhmk1 diminished Aqp1 expression. The outlines of a pathway that ties secretory granule metabolism to the transcriptome are thus apparent.

  20. Small intestine in lymphocytic and collagenous colitis: mucosal morphology, permeability, and secretory immunity to gliadin.

    OpenAIRE

    Moayyedi, P; O'Mahony, S; Jackson, P; Lynch, D A; Dixon, M F; Axon, A T

    1997-01-01

    There is a recognised association between the "microscopic" forms of colitis and coeliac disease. There are a variety of subtle small intestinal changes in patients with "latent" gluten sensitivity, namely high intraepithelial lymphocyte (IEL) counts, abnormal mucosal permeability, and high levels of secretory IgA and IgM antibody to gliadin. These changes have hitherto not been investigated in microscopic colitis. Nine patients (four collagenous, five lymphocytic colitis) with normal villous...

  1. Glucoregulation after canine islet transplantation : Contribution of insulin secretory capacity, insulin action, and the entero-insular axis

    NARCIS (Netherlands)

    vanderBurg, MPM; van Suylichem, PTR; Guicherit, OR; Frolich, M; Lemkes, HHPJ; Gooszen, HG

    1997-01-01

    The physiological glucoregulatory mechanisms after islet transplantation have been incompletely investigated, We studied the insulin secretory capacity (ISC) by intravenous arginine stimulation during 35-mM glucose clamps, insulin action during hyperinsulinemic euglycemic clamps, and mixed-meal

  2. Human protein secretory pathway genes are expressed in a tissue-specific pattern to match processing demands of the secretome

    DEFF Research Database (Denmark)

    Feizi, Amir; Gatto, Francesco; Uhlén, Mathias

    2017-01-01

    Protein secretory pathway in eukaryal cells is responsible for delivering functional secretory proteins. The dysfunction of this pathway causes a range of important human diseases from congenital disorders to cancer. Despite the piled-up knowledge on the molecular biology and biochemistry level...... in specific gene families of the secretory pathway. We also inspected the potential functional link between detected extreme genes and the corresponding tissues enriched secretome. As a result, the detected extreme genes showed correlation with the enrichment of the nature and number of specific post......-translational modifications in each tissue's secretome. Our findings conciliate both the housekeeping and tissue-specific nature of the protein secretory pathway, which we attribute to a fine-tuned regulation of defined gene families to support the diversity of secreted proteins and their modifications....

  3. Synergistic Effects of Secretory Phospholipase A2 from the Venom of Agkistrodon piscivorus piscivorus with Cancer Chemotherapeutic Agents

    Directory of Open Access Journals (Sweden)

    Jennifer Nelson

    2013-01-01

    Full Text Available Healthy cells typically resist hydrolysis catalyzed by snake venom secretory phospholipase A2. However, during various forms of programmed cell death, they become vulnerable to attack by the enzyme. This observation raises the question of whether the specificity of the enzyme for dying cells could be used as a strategy to eliminate tumor cells that have been intoxicated but not directly killed by chemotherapeutic agents. This idea was tested with S49 lymphoma cells and a broad range of antineoplastic drugs: methotrexate, daunorubicin, actinomycin D, and paclitaxel. In each case, a substantial population of treated cells was still alive yet vulnerable to attack by the enzyme. Induction of cell death by these agents also perturbed the biophysical properties of the membrane as detected by merocyanine 540 and trimethylammonium-diphenylhexatriene. These results suggest that exposure of lymphoma cells to these drugs universally causes changes to the cell membrane that render it susceptible to enzymatic attack. The data also argue that the snake venom enzyme is not only capable of clearing cell corpses but can aid in the demise of tumor cells that have initiated but not yet completed the death process.

  4. Intracellular and transcellular transport of secretory and membrane proteins in the rat hepatocyte

    International Nuclear Information System (INIS)

    Sztul, E.S.

    1984-01-01

    The intra- and transcellular transport of hepatic secretory and membrane proteins was studied in rats in vivo using [ 3 H]fucose and [ 35 S]cyteine as metabolic precursors. Incorporated radioactivity in plasma, bile, and liver subcellular fractions was measured and the labeled proteins of the Golgi complex, bile and plasma were separated by SDS-PAGE and identified by fluorography. 3 H-radioactivity in Golgi fractions peaked at 10 min post injection (p.i.) and then declined concomitantly with the appearance of labeled glycoproteins in plasma. Maximal secretion of secretory fucoproteins from the Golgi complex occurred between 10 and 20 min p.i. In contrast, the clearance of labeled proteins from Golgi membrane subfractions occurred past 30 min p.i., indicating that membrane proteins leave the Golgi complex at least 10 min later than the bulk of content proteins. A major 80K form of Secretory Component (SC) was identified in the bile by precipitation with an anti IgA antibody. A comparative study of kinetics of transport of 35 S-labeled SC and 35 S-labeled albumin showed that albumin peaked in bile at ∼45 min p.i., whereas the SC peak occurred at 80 min p.i., suggesting that the transit time differs for plasma and membrane proteins which are delivered to the bile canaliculus (BC)

  5. Snapin mediates insulin secretory granule docking, but not trans-SNARE complex formation

    Energy Technology Data Exchange (ETDEWEB)

    Somanath, Sangeeta [Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT (United Kingdom); Partridge, Christopher J. [Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Churchill Hospital, University of Oxford, Oxford, OX3 7LJ (United Kingdom); Marshall, Catriona [Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT (United Kingdom); Rowe, Tony [CSL Limited, 45 Poplar Road, Parkville, Victoria 3052 (Australia); Turner, Mark D., E-mail: mark.turner@ntu.ac.uk [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS (United Kingdom)

    2016-04-29

    Secretory granule exocytosis is a tightly regulated process requiring granule targeting, tethering, priming, and membrane fusion. At the heart of this process is the SNARE complex, which drives fusion through a coiled-coil zippering effect mediated by the granule v-SNARE protein, VAMP2, and the plasma membrane t-SNAREs, SNAP-25 and syntaxin-1A. Here we demonstrate that in pancreatic β-cells the SNAP-25 accessory protein, snapin, C-terminal H2 domain binds SNAP-25 through its N-terminal Sn-1 domain. Interestingly whilst snapin binds SNAP-25, there is only modest binding of this complex with syntaxin-1A under resting conditions. Instead synataxin-1A appears to be recruited in response to secretory stimulation. These results indicate that snapin plays a role in tethering insulin granules to the plasma membrane through coiled coil interaction of snapin with SNAP-25, with full granule fusion competency only resulting after subsequent syntaxin-1A recruitment triggered by secretory stimulation. - Highlights: • Snapin mediates granule docking. • Snapin binds SNAP-25. • SNARE complex forms downstream.

  6. Secretory proteins in the reproductive tract of the snapping turtle, Chelhydra serpentina.

    Science.gov (United States)

    Mahmoud, I Y; Paulson, J R; Dudley, M; Patzlaff, J S; Al-Kindi, A Y A

    2004-12-01

    SDS-polyacrylamide gel electrophoresis was used to separate the secretory proteins produced by the epithelial and endometrial glands of the uterine tube and uterus in the snapping turtle Chelydra serpentina. The proteins were analyzed throughout the phases of the reproductive cycle from May to August, including preovulatory, ovulatory, postovulatory or luteal, and vitellogenic phases. The pattern of secretory proteins is quite uniform along the length of the uterine tube, and the same is true of the uterus, but the patterns for uterine tube and uterus are clearly different. We identify 13 major proteins in C. serpentina egg albumen. Bands co-migrating with 11 of these are found in the uterine tube, but at most 4 are found in the uterus, suggesting that the majority of the albumen proteins are most likely secreted in the uterine tube, not in the uterus. Although some of the egg albumen proteins are present in the uterine tube only at the time of ovulation, most of the bands corresponding to albumen proteins are present throughout the breeding season even though the snapping turtle is a monoclutch species. These results suggest that the glandular secretory phase in the uterine tube is active and quite homogeneous in function regardless of location or phase of the reproductive cycle.

  7. Snapin mediates insulin secretory granule docking, but not trans-SNARE complex formation

    International Nuclear Information System (INIS)

    Somanath, Sangeeta; Partridge, Christopher J.; Marshall, Catriona; Rowe, Tony; Turner, Mark D.

    2016-01-01

    Secretory granule exocytosis is a tightly regulated process requiring granule targeting, tethering, priming, and membrane fusion. At the heart of this process is the SNARE complex, which drives fusion through a coiled-coil zippering effect mediated by the granule v-SNARE protein, VAMP2, and the plasma membrane t-SNAREs, SNAP-25 and syntaxin-1A. Here we demonstrate that in pancreatic β-cells the SNAP-25 accessory protein, snapin, C-terminal H2 domain binds SNAP-25 through its N-terminal Sn-1 domain. Interestingly whilst snapin binds SNAP-25, there is only modest binding of this complex with syntaxin-1A under resting conditions. Instead synataxin-1A appears to be recruited in response to secretory stimulation. These results indicate that snapin plays a role in tethering insulin granules to the plasma membrane through coiled coil interaction of snapin with SNAP-25, with full granule fusion competency only resulting after subsequent syntaxin-1A recruitment triggered by secretory stimulation. - Highlights: • Snapin mediates granule docking. • Snapin binds SNAP-25. • SNARE complex forms downstream.

  8. The plant secretory pathway seen through the lens of the cell wall.

    Science.gov (United States)

    van de Meene, A M L; Doblin, M S; Bacic, Antony

    2017-01-01

    Secretion in plant cells is often studied by looking at well-characterised, evolutionarily conserved membrane proteins associated with particular endomembrane compartments. Studies using live cell microscopy and fluorescent proteins have illuminated the highly dynamic nature of trafficking, and electron microscopy studies have resolved the ultrastructure of many compartments. Biochemical and molecular analyses have further informed about the function of particular proteins and endomembrane compartments. In plants, there are over 40 cell types, each with highly specialised functions, and hence potential variations in cell biological processes and cell wall structure. As the primary function of secretion in plant cells is for the biosynthesis of cell wall polysaccharides and apoplastic transport complexes, it follows that utilising our knowledge of cell wall glycosyltransferases (GTs) and their polysaccharide products will inform us about secretion. Indeed, this knowledge has led to novel insights into the secretory pathway, including previously unseen post-TGN secretory compartments. Conversely, our knowledge of trafficking routes of secretion will inform us about polarised and localised deposition of cell walls and their constituent polysaccharides/glycoproteins. In this review, we look at what is known about cell wall biosynthesis and the secretory pathway and how the different approaches can be used in a complementary manner to study secretion and provide novel insights into these processes.

  9. Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes

    OpenAIRE

    Maciejczyk, Mateusz; Kossakowska, Agnieszka; Szulimowska, Julita; Klimiuk, Anna; Knaś, Małgorzata; Car, Halina; Niklińska, Wiesława; Ładny, Jerzy Robert; Chabowski, Adrian; Zalewska, Anna

    2017-01-01

    Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands—nonstimulated and stimulated salivary flow, α-amylase, total protein—and salivary exoglycosidase activities—N...

  10. Intramuscular Priming and Intranasal Boosting Induce Strong Genital Immunity Through Secretory IgA in Minipigs Infected with Chlamydia trachomatis

    Science.gov (United States)

    Lorenzen, Emma; Follmann, Frank; Bøje, Sarah; Erneholm, Karin; Olsen, Anja Weinreich; Agerholm, Jørgen Steen; Jungersen, Gregers; Andersen, Peter

    2015-01-01

    International efforts in developing a vaccine against Chlamydia trachomatis have highlighted the need for novel immunization strategies for the induction of genital immunity. In this study, we evaluated an intramuscular (IM) prime/intranasal boost vaccination strategy in a Göttingen Minipig model with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. IM priming immunizations with CAF01 induced a significant cell-mediated interferon gamma and interleukin 17A response and a significant systemic high-titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC), we showed that the genital IgA was locally produced in the genital mucosa. The highly significant inverse correlation between the vaginal IgA SC response and the chlamydial load suggests that IgA in the minipig model is involved in protection against C. trachomatis. This is important both for our understanding of protective immunity and future vaccination strategies against C. trachomatis and genital pathogens in general. PMID:26734002

  11. 'I've put diabetes completely on the shelf till the mental stuff is in place'. How patients with doctor-assessed impaired self-care perceive disease, self-care, and support from general practitioners. A qualitative study

    DEFF Research Database (Denmark)

    Kristensen, Mads Aage Toft; Guassora, Ann Dorrit; Arreskov, Anne Beiter

    2018-01-01

    OBJECTIVE: This paper investigated patients' experiences of disease and self-care as well as perceptions of the general practitioner's role in supporting patients with impaired self-care ability. DESIGN: Qualitative interviews with 13 patients with type 2 diabetes, concurrent chronic diseases...... recommendations.   • Shifting emotional aspects were prominent in patients' considerations of disease and sustained GPs' use of a patient-centred clinical method when discussing self-care.   • Relational continuity with general practitioners was a highly valued support and should be prioritized for patients...

  12. Latino College Completion: Hawaii

    Science.gov (United States)

    Excelencia in Education (NJ1), 2012

    2012-01-01

    In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

  13. Latino College Completion: Pennsylvania

    Science.gov (United States)

    Excelencia in Education (NJ1), 2012

    2012-01-01

    In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

  14. Complete Normal Ordering 1: Foundations

    CERN Document Server

    Ellis, John; Skliros, Dimitri P.

    2016-01-01

    We introduce a new prescription for quantising scalar field theories perturbatively around a true minimum of the full quantum effective action, which is to `complete normal order' the bare action of interest. When the true vacuum of the theory is located at zero field value, the key property of this prescription is the automatic cancellation, to any finite order in perturbation theory, of all tadpole and, more generally, all `cephalopod' Feynman diagrams. The latter are connected diagrams that can be disconnected into two pieces by cutting one internal vertex, with either one or both pieces free from external lines. In addition, this procedure of `complete normal ordering' (which is an extension of the standard field theory definition of normal ordering) reduces by a substantial factor the number of Feynman diagrams to be calculated at any given loop order. We illustrate explicitly the complete normal ordering procedure and the cancellation of cephalopod diagrams in scalar field theories with non-derivative i...

  15. Completeness, supervenience and ontology

    International Nuclear Information System (INIS)

    Maudlin, Tim W E

    2007-01-01

    In 1935, Einstein, Podolsky and Rosen raised the issue of the completeness of the quantum description of a physical system. What they had in mind is whether or not the quantum description is informationally complete, in that all physical features of a system can be recovered from it. In a collapse theory such as the theory of Ghirardi, Rimini and Weber, the quantum wavefunction is informationally complete, and this has often been taken to suggest that according to that theory the wavefunction is all there is. If we distinguish the ontological completeness of a description from its informational completeness, we can see that the best interpretations of the GRW theory must postulate more physical ontology than just the wavefunction

  16. Completeness, supervenience and ontology

    Energy Technology Data Exchange (ETDEWEB)

    Maudlin, Tim W E [Department of Philosophy, Rutgers University, 26 Nichol Avenue, New Brunswick, NJ 08901-1411 (United States)

    2007-03-23

    In 1935, Einstein, Podolsky and Rosen raised the issue of the completeness of the quantum description of a physical system. What they had in mind is whether or not the quantum description is informationally complete, in that all physical features of a system can be recovered from it. In a collapse theory such as the theory of Ghirardi, Rimini and Weber, the quantum wavefunction is informationally complete, and this has often been taken to suggest that according to that theory the wavefunction is all there is. If we distinguish the ontological completeness of a description from its informational completeness, we can see that the best interpretations of the GRW theory must postulate more physical ontology than just the wavefunction.

  17. [Effects of secretory and osmotic diarrhea on rats intestinal function and morphology].

    Science.gov (United States)

    de Lima de Mon, Margarita; Cioccia, Anna M; González, Eduardo; Hevia, Patricio

    2002-03-01

    In order to compare intestinal morphology and function, diarrhea was produced in rats using laxatives in the diet. The 14 day study included two groups of rats with diarrhea (osmotic or secretory), two groups without diarrhea but with a degree of malnutrition which was similar to that seen in the rats with diarrhea (malnourished without diarrhea) and a well-nourished group (control). The inclusion of laxatives(lactose or bisoxatin acetate) cause a reduction in food intake, diarrhea an malnutrition. It also caused a reduction in dietary protein and fat digestibility which was proportional to the severity of diarrhea and more pronounced in secretory diarrhea. In the malnourished rats without diarrhea, malnutrition did not affect their absorptive function. Both in the rats with secretory and osmotic diarrhea an intestinal hypertrophy was observed. This hypertrophy was proportional to the severity of diarrhea and independent of its aetiology. In the intestines of the rats with both types of diarrhea there was inflammation, a greater number of mitotic figures but the flattening of the villi seen in the malnourished rats without diarrhea was not seen. In osmotic diarrhea there was, in addition, a patchy damage of the surface of the jejunal mucosa and an increment in the number of goblet cells, indicating a more severe intestinal deterioration. Since despite this greater deterioration, these rats absorbed more protein and fat we concluded that the alterations in intestinal morphology seen in this study was not predictive of intestinal function. The study also showed that diarrhea had a trophic effect on the intestine which did not occur in malnourished rats without diarrhea.

  18. Ca(2+)-calmodulin-dependent phosphorylation of islet secretory granule proteins

    International Nuclear Information System (INIS)

    Watkins, D.T.

    1991-01-01

    The effect of Ca2+ and calmodulin on phosphorylation of islet secretory granule proteins was studied. Secretory granules were incubated in a phosphorylation reaction mixture containing [32P]ATP and test reagents. The 32P-labeled proteins were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the 32P content was visualized by autoradiography, and the relative intensities of specific bands were quantitated. When the reaction mixture contained EGTA and no added Ca2+, 32P was incorporated into two proteins with molecular weights of 45,000 and 13,000. When 10(-4) M Ca2+ was added without EGTA, two additional proteins (58,000 and 48,000 Mr) were phosphorylated, and the 13,000-Mr protein was absent. The addition of 2.4 microM calmodulin markedly enhanced the phosphorylation of the 58,000- and 48,000-Mr proteins and resulted in the phosphorylation of a major protein whose molecular weight (64,000 Mr) is identical to that of one of the calmodulin binding proteins located on the granule surface. Calmodulin had no effect on phosphorylation in the absence of Ca2+ but was effective in the presence of calcium between 10 nM and 50 microM. Trifluoperazine and calmidazolium, calmodulin antagonists, produced a dose-dependent inhibition of the calmodulin effect. 12-O-tetradecanoylphorbol 13-acetate, a phorbol ester that activates protein kinase C, produced no increase in phosphorylation, and 1-(5-isoquinoline sulfonyl)-2-methyl piperazine dihydrochloride, an inhibitor of protein kinase C, had no effect. These results indicate that Ca(2+)-calmodulin-dependent protein kinases and endogenous substrates are present in islet secretory granules

  19. Heterologous Secretory Expression and Characterization of Dimerized Bone Morphogenetic Protein 2 in Bacillus subtilis

    Directory of Open Access Journals (Sweden)

    Muhammad Umair Hanif

    2017-01-01

    Full Text Available Recombinant human Bone Morphogenetic Protein 2 (rhBMP2 has important applications in the spine fusion and ortho/maxillofacial surgeries. Here we first report the secretory expression of biological active dimerized rhBMP2 from Bacillus subtilis system. The mature domain of BMP2 gene was amplified from pTz57R/BMP2 plasmid. By using pHT43 expression vector two constructs, pHT43-BMP2-M (single BMP2 gene and pHT43-BMP2-D (two BMP2 genes coupled with a linker to produce a dimer, were designed. After primary cloning (DH5α strain and sequence analysis, constructs were transformed into Bacillus subtilis for secretory expression. Expression conditions like media (2xYT and temperature (30°C were optimized. Maximum 35% and 25% secretory expression of monomer (~13 kDa and dimer (~25 kDa, respectively, were observed on SDS-PAGE in SCK6 strain. The expression and dimeric nature of rhBMP2 were confirmed by western blot and native PAGE analysis. For rhBMP2 purification, 200 ml culture supernatant was freeze dried to 10 ml and dialyzed (Tris-Cl, pH 8.5 and Fast Protein Liquid Chromatography (6 ml, Resource Q column was performed. The rhBMP2 monomer and dimer were eluted at 0.9 M and 0.6 M NaCl, respectively. The alkaline phosphatase assay of rhBMP2 (0, 50, 100, 200, and 400 ng/ml was analyzed on C2C12 cells and maximum 200 ng/ml activity was observed in dose dependent manner.

  20. Expression and secretory profile of buffalo fetal fibroblasts and Wharton's jelly feeder layers.

    Science.gov (United States)

    Parmar, Mehtab S; Mishra, Smruti Ranjan; Somal, Anjali; Pandey, Sriti; Kumar, G Sai; Sarkar, Mihir; Chandra, Vikash; Sharma, G Taru

    2017-05-01

    The present study examined the comparative expression and secretory profile of vital signaling molecules in buffalo fetal fibroblasts (BFF) and Wharton's jelly (BWJ) feeder layers at different passages. Both feeder layers were expanded up to 8th passage. Signaling molecules viz. bone morphogenetic protein 4 (BMP4), fibroblast growth factor 2 (FGF2), leukemia inhibitory factor (LIF) and transforming growth factor beta 1 (TGFB1) and pluripotency-associated transcriptional factors (POU5F1, SOX2, NANOG, KLF4, MYC and FOXD3) were immunolocalized in the both feeder types. A clear variation in the expression pattern of key signaling molecules with passaging was registered in both feeders compared to primary culture (0 passage). The conditioned media (CM) was collected from different passages (2, 4, 6, 8) of both the feeder layers and was quantified using enzyme-linked immunosorbent assay (ELISA). Concomitant to expression profile, protein quantification also revealed differences in the concentration of signaling molecules at different time points. Conjointly, expression and secretory profile revealed that 2nd passage of BFF and 6th passage of BWJ exhibit optimal levels of key signaling molecules thus may be selected as best passages for embryonic stem cells (ESCs) propagation. Further, the effect of mitomycin-C (MMC) treatment on the expression profile of signaling molecules in the selected passages of BFF and BWJ revealed that MMC modulates the expression profile of these molecules. In conclusion, the results indicate that feeder layers vary in expression and secretory pattern of vital signaling molecules with passaging. Based on these findings, the appropriate feeder passages may be selected for the quality propagation of buffalo ESCs. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Secretory IgA (SIgA: designed for antimicrobial defence

    Directory of Open Access Journals (Sweden)

    Per eBrandtzaeg

    2013-08-01

    Full Text Available Prevention of infections by vaccination remains a compelling goal to improve public health. Mucosal vaccines would make immunization procedures easier, be better suited for mass administration, and most efficiently induce immune exclusion -- a term coined for non-inflammatory antibody shielding of internal body surfaces, mediated principally by secretory immunoglobulin A (SIgA. The exported antibodies are polymeric, mainly IgA dimers (pIgA, produced by local plasma cells stimulated by antigens that target the mucosae. SIgA was early shown to be complexed with an epithelial glycoprotein -- the secretory component (SC. A common SC-dependent transport mechanism for pIgA and pentameric IgM was then proposed, implying that membrane SC acts as a receptor, now usually called the polymeric Ig receptor (pIgR. From the basolateral surface, pIg-pIgR complexes are taken up by endocytosis and then extruded into the lumen after apical cleavage of the receptor -- bound SC having stabilizing and innate functions in the secretory antibodies. Mice deficient for pIgR show that this is the only receptor responsible for epithelial export of IgA and IgM. These knockout mice show a variety of defects in their mucosal defensce and changes in their intestinal microbiota. In the gut, induction of B cells occurs in gut-associated lymphoid tissue (GALT, particularly the Peyer’s patches and isolated lymphoid follicles, but also in mesenteric lymph nodes. Plasma cell differentiation is accomplished in the lamina propria to which the activated memory/effector B cells home. The airways also receive such cells from nasopharynx-associated lymphoid tissue (NALT but by different homing receptors. This compartmentalization is a challenge for mucosal vaccination, as are the mechanisms used by the mucosal immune system to discriminate between commensal symbionts (mutualism, pathobionts and overt pathogens (elimination.

  2. Microarray profiling of progesterone-regulated endometrial genes during the rhesus monkey secretory phase

    Directory of Open Access Journals (Sweden)

    Okulicz William C

    2004-07-01

    Full Text Available Abstract Background In the endometrium the steroid hormone progesterone (P, acting through its nuclear receptors, regulates the expression of specific target genes and gene networks required for endometrial maturation. Proper endometrial maturation is considered a requirement for embryo implantation. Endometrial receptivity is a complex process that is spatially and temporally restricted and the identity of genes that regulate receptivity has been pursued by a number of investigators. Methods In this study we have used high density oligonucleotide microarrays to screen for changes in mRNA transcript levels between normal proliferative and adequate secretory phases in Rhesus monkey artificial menstrual cycles. Biotinylated cRNA was prepared from day 13 and days 21–23 of the reproductive cycle and transcript levels were compared by hybridization to Affymetrix HG-U95A arrays. Results Of ~12,000 genes profiled, we identified 108 genes that were significantly regulated during the shift from a proliferative to an adequate secretory endometrium. Of these genes, 39 were up-regulated at days 21–23 versus day 13, and 69 were down-regulated. Genes up-regulated in P-dominant tissue included: secretoglobin (uteroglobin, histone 2A, polo-like kinase (PLK, spermidine/spermine acetyltransferase 2 (SAT2, secretory leukocyte protease inhibitor (SLPI and metallothionein 1G (MT1G, all of which have been previously documented as elevated in the Rhesus monkey or human endometrium during the secretory phase. Genes down-regulated included: transforming growth factor beta-induced (TGFBI or BIGH3, matrix metalloproteinase 11 (stromelysin 3, proenkephalin (PENK, cysteine/glycine-rich protein 2 (CSRP2, collagen type VII alpha 1 (COL7A1, secreted frizzled-related protein 4 (SFRP4, progesterone receptor membrane component 1 (PGRMC1, chemokine (C-X-C ligand 12 (CXCL12 and biglycan (BGN. In addition, many novel/unknown genes were also identified. Validation of array data

  3. [Unilateral exophthalmos as the debut of a non-secretory multiple myeloma].

    Science.gov (United States)

    Castro-Rebollo, M; Cañones-Zafra, R; Vleming-Pinilla, E N; Drake-Rodríguez-Casanova, P; Pérez-Rico, C

    2009-12-01

    A 56 year-old male presented blurred vision and diplopia for 2 months, left unilateral exophthalmos, restricted ocular motility and papilledema. The imaging proofs showed osteolytic lesions in the left sphenoid bone, fourth rib and fourth dorsal vertebral body with associated masses of soft tissues. Biopsy was performed and the diagnosis of plasma cell neoplasm was established. The diagnosis of non-secretory multiple myeloma was made by analytical criteria and bone marrow biopsy. Local radiotherapy and polychemotherapy was prescribed. The ophthalmologist can play an important role in the diagnosis of systemic neoplasms that require the intervention of a multidisciplinary team.

  4. The secretory endometrial protein, placental protein 14, in women with ectopic gestation

    DEFF Research Database (Denmark)

    Ruge, S; Sørensen, Steen; Vejtorp, M

    1992-01-01

    OBJECTIVE: To determine the serum level of the secretory endometrial protein, placental protein 14 (PP14) and progesterone (P) in women with ectopic gestation. DESIGN: Blood samples were collected prospectively and preoperatively. Reference range was determined from a prospective population of 98...... observing the low serum levels of PP14 and P, a correlation analysis was made and compared with the findings in normally pregnant women. RESULTS: A significant positive correlation was found between the level of PP14 and P (P less than 0.00002), not found in normal intrauterine pregnancies. CONCLUSIONS...

  5. Reversal by EGTA of the enhanced secretory responsiveness of mast cells due to treatment with ouabain

    DEFF Research Database (Denmark)

    Johansen, Torben; Knudsen, T; Bertelsen, Niels Haldor

    1990-01-01

    The effect of EGTA on the enhancement by ouabain of compound 48/80-induced secretion from mast cells was compared with the effect on the Na(+)-K+ pump activity. The time-dependent secretory enhancement by ouabain was blocked by addition of EGTA to the cell suspension concomitantly with the addition...... of ouabain, and EGTA caused a large increase in the pump activity. Addition of 10 microM EGTA to ouabain-treated cells stopped but did not reverse the enhancement. The experiments show that the effect of ouabain was due to changes in a calcium pool utilized in compound 48/80-induced secretion following...

  6. Recognition of secretory proteins in Escherichia coli requires signals in addition to the signal sequence and slow folding

    Directory of Open Access Journals (Sweden)

    Flower Ann M

    2002-11-01

    Full Text Available Abstract Background The Sec-dependent protein export apparatus of Escherichia coli is very efficient at correctly identifying proteins to be exported from the cytoplasm. Even bacterial strains that carry prl mutations, which allow export of signal sequence-defective precursors, accurately differentiate between cytoplasmic and mutant secretory proteins. It was proposed previously that the basis for this precise discrimination is the slow folding rate of secretory proteins, resulting in binding by the secretory chaperone, SecB, and subsequent targeting to translocase. Based on this proposal, we hypothesized that a cytoplasmic protein containing a mutation that slows its rate of folding would be recognized by SecB and therefore targeted to the Sec pathway. In a Prl suppressor strain the mutant protein would be exported to the periplasm due to loss of ability to reject non-secretory proteins from the pathway. Results In the current work, we tested this hypothesis using a mutant form of λ repressor that folds slowly. No export of the mutant protein was observed, even in a prl strain. We then examined binding of the mutant λ repressor to SecB. We did not observe interaction by either of two assays, indicating that slow folding is not sufficient for SecB binding and targeting to translocase. Conclusions These results strongly suggest that to be targeted to the export pathway, secretory proteins contain signals in addition to the canonical signal sequence and the rate of folding.

  7. Overproduction of a Model Sec- and Tat-Dependent Secretory Protein Elicits Different Cellular Responses in Streptomyces lividans.

    Directory of Open Access Journals (Sweden)

    Sonia Gullón

    Full Text Available Streptomyces lividans is considered an efficient host for the secretory production of homologous and heterologous proteins. To identify possible bottlenecks in the protein production process, a comparative transcriptomic approach was adopted to study cellular responses during the overproduction of a Sec-dependent model protein (alpha-amylase and a Tat-dependent model protein (agarase in Streptomyces lividans. The overproduction of the model secretory proteins via the Sec or the Tat route in S. lividans does elicit a different major cell response in the bacterium. The stringent response is a bacterial response to nutrients' depletion, which naturally occurs at late times of the bacterial cell growth. While the induction of the stringent response at the exponential phase of growth may limit overall productivity in the case of the Tat route, the induction of that response does not take place in the case of the Sec route, which comparatively is an advantage in secretory protein production processes. Hence, this study identifies a potential major drawback in the secretory protein production process depending on the secretory route, and provides clues to improving S. lividans as a protein production host.

  8. Analysis of the effect of diabetes type 2 duration on beta cell secretory function and insulin resistance

    Directory of Open Access Journals (Sweden)

    Popović Ljiljana

    2006-01-01

    Full Text Available Diabetes type 2 is a chronic metabolic disorder. Pathogenesis of diabetes type 2 results from the impaired insulin secretion, impaired insulin action and increased endogenous glucose production. Diabetes evolves through several phases characterized by qualitative and quantitative changes of beta cell secretory function. The aim of our study was to analyze the impact of diabetes duration on beta cell secretory function and insulin resistance. The results indicated significant negative correlation of diabetes duration and fasting insulinemia, as well as beta cell secretory function assessed by HOMA β index. Our study also found significant negative correlation of diabetes duration and insulin resistance assessed by HOMA IR index. Significant positive correlation was established between beta cell secretory capacity (fasting insulinemia and HOMA β and insulin resistance assessed by HOMA IR index, independently of diabetes duration. These results indicate that: beta cell secretory capacity, assessed by HOMA β index, significantly decreases with diabetes duration. In parallel with decrease of fasting insulinemia, reduction of insulin resistance assessed by HOMA IR index was found as well.

  9. Abnormal ion content, hydration and granule expansion of the secretory granules from cystic fibrosis airway glandular cells

    International Nuclear Information System (INIS)

    Baconnais, S.; Delavoie, F.; Zahm, J.M.; Milliot, M.; Terryn, C.; Castillon, N.; Banchet, V.; Michel, J.; Danos, O.; Merten, M.; Chinet, T.; Zierold, K.; Bonnet, N.; Puchelle, E.; Balossier, G.

    2005-01-01

    The absence or decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) induces increased Na + absorption and hyperabsorption of the airway surface liquid (ASL) resulting in a dehydrated and hyperviscous ASL. Although the implication of abnormal airway submucosal gland function has been suggested, the ion and water content in the Cystic Fibrosis (CF) glandular secretory granules, before exocytosis, is unknown. We analyzed, in non-CF and CF human airway glandular cell lines (MM-39 and KM4, respectively), the ion content in the secretory granules by electron probe X-ray microanalysis and the water content by quantitative dark field imaging on freeze-dried cryosections. We demonstrated that the ion content (Na + , Mg 2+ , P, S and Cl - ) is significantly higher and the water content significantly lower in secretory granules from the CF cell line compared to the non-CF cell line. Using videomicroscopy, we observed that the secretory granule expansion was deficient in CF glandular cells. Transfection of CF cells with CFTR cDNA or inhibition of non-CF cells with CFTR inh -172, respectively restored or decreased the water content and granule expansion, in parallel with changes in ion content. We hypothesize that the decreased water and increased ion content in glandular secretory granules may contribute to the dehydration and increased viscosity of the ASL in CF

  10. The GLP-1 analogue liraglutide improves first-phase insulin secretion and maximal beta-cell secretory capacity over 14 weeks of therapy in subjects with Type 2 diabetes

    DEFF Research Database (Denmark)

    Madsbad, Sten; Vilsbøll, Tina; Brock, Birgitte

    Aims: We investigated the clinical effect of liraglutide, a long- acting GLP-1 analogue, on insulin secretion in Type 2 diabetes. Methods: Thirty-nine subjects (28 completed) from a randomised trial received a hyperglycaemic clamp (20 mM) with intravenous arginine stimulation, and an insulin...... group. Conclusion: In subjects with Type 2 diabetes, 14 weeks’ once-daily liraglutide (1.25 and 1.9 mg/day) markedly improves beta-cell function, significantly increases first-phase insulin secretion and maximal beta-cell secretory capacity....

  11. Complete Ureteral Avulsion

    Directory of Open Access Journals (Sweden)

    V. Gupta

    2005-01-01

    Full Text Available Complete avulsion of the ureter is one of the most serious complications of ureteroscopy. It requires open or laparoscopic intervention for repair. This case report emphasizes its management and presents recommendations for prevention in current urological practice.

  12. Far-infrared radiation inhibits proliferation, migration, and angiogenesis of human umbilical vein endothelial cells by suppressing secretory clusterin levels.

    Science.gov (United States)

    Hwang, Soojin; Lee, Dong-Hoon; Lee, In-Kyu; Park, Young Mi; Jo, Inho

    2014-04-28

    Far-infrared (FIR) radiation is known to lessen the risk of angiogenesis-related diseases including cancer. Because deficiency of secretory clusterin (sCLU) has been reported to inhibit angiogenesis of endothelial cells (EC), we investigated using human umbilical vein EC (HUVEC) whether sCLU mediates the inhibitory effects of FIR radiation. Although FIR radiation ranging 3-25μm wavelength at room temperature for 60min did not alter EC viability, further incubation in the culture incubator (at 37°C under 5% CO2) after radiation significantly inhibited EC proliferation, in vitro migration, and tube formation in a time-dependent manner. Under these conditions, we found decreased sCLU mRNA and protein expression in HUVEC and decreased sCLU protein secreted in culture medium. Expectedly, the replacement of control culture medium with the FIR-irradiated conditioned medium significantly decreased wound closure and tube formation of HUVEC, and vice versa. Furthermore, neutralization of sCLU with anti-sCLU antibody also mimicked all observed inhibitory effects of FIR radiation. Moreover, treatment with recombinant human sCLU protein completely reversed the inhibitory effects of FIR radiation on EC migration and angiogenesis. Lastly, vascular endothelial growth factor also increased sCLU secretion in the culture medium, and wound closure and tube formation of HUVEC, which were significantly reduced by FIR radiation. Our results demonstrate a novel mechanism by which FIR radiation inhibits the proliferation, migration, and angiogenesis of HUVEC, via decreasing sCLU. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Secretory activity and endocrine regulation of male accessory glands in the blood-sucking bug Panstrongylus megistus (Hemiptera: Reduviidae

    Directory of Open Access Journals (Sweden)

    Lêda Regis

    1987-01-01

    Full Text Available The epithelial cells of Panstrongylus megistus male accessory glands (MAG present ultrastructural characteristics of a secretory cell. Their secretory products are accumulated in the lumen of the four MAG lobes. During the first 8 days of adult life a strong secretion activity occurs, accumulating enough material to produce the first spermatophore. Cerebral neurosecretions as well as juvenile hormone are both involved in MAG secretory activity regulation. Juvenile hormone seems to be the responsible for the stimulation of most protein synthesis in male accessory glands. Cerebral neurosecretion seems to be necessary to stimulate juvenile hormone production and release by the corpus allatum. Furthermore, neurosecretion is required for some polypeptides synthesis by MAG. Although topic application of precocene II to adult males does not reproduce the same effects on MAG as does allatectomy, this compound causes strong reduction on male reproductive capacity.

  14. Molecular interpretation of ACTH-β-endorphin coaggregation: relevance to secretory granule biogenesis.

    Directory of Open Access Journals (Sweden)

    Srivastav Ranganathan

    Full Text Available Peptide/protein hormones could be stored as non-toxic amyloid-like structures in pituitary secretory granules. ACTH and β-endorphin are two of the important peptide hormones that get co-stored in the pituitary secretory granules. Here, we study molecular interactions between ACTH and β-endorphin and their colocalization in the form of amyloid aggregates. Although ACTH is known to be a part of ACTH-β-endorphin aggregate, ACTH alone cannot aggregate into amyloid under various plausible conditions. Using all atom molecular dynamics simulation we investigate the early molecular interaction events in the ACTH-β-endorphin system, β-endorphin-only system and ACTH-only system. We find that β-endorphin and ACTH formed an interacting unit, whereas negligible interactions were observed between ACTH molecules in ACTH-only system. Our data suggest that ACTH is not only involved in interaction with β-endorphin but also enhances the stability of mixed oligomers of the entire system.

  15. Sperm-storage defects and live birth in Drosophila females lacking spermathecal secretory cells.

    Directory of Open Access Journals (Sweden)

    Sandra L Schnakenberg

    2011-11-01

    Full Text Available Male Drosophila flies secrete seminal-fluid proteins that mediate proper sperm storage and fertilization, and that induce changes in female behavior. Females also produce reproductive-tract secretions, yet their contributions to postmating physiology are poorly understood. Large secretory cells line the female's spermathecae, a pair of sperm-storage organs. We identified the regulatory regions controlling transcription of two genes exclusively expressed in these spermathecal secretory cells (SSC: Spermathecal endopeptidase 1 (Send1, which is expressed in both unmated and mated females, and Spermathecal endopeptidase 2 (Send2, which is induced by mating. We used these regulatory sequences to perform precise genetic ablations of the SSC at distinct time points relative to mating. We show that the SSC are required for recruiting sperm to the spermathecae, but not for retaining sperm there. The SSC also act at a distance in the reproductive tract, in that their ablation: (1 reduces sperm motility in the female's other sperm-storage organ, the seminal receptacle; and (2 causes ovoviviparity--the retention and internal development of fertilized eggs. These results establish the reproductive functions of the SSC, shed light on the evolution of live birth, and open new avenues for studying and manipulating female fertility in insects.

  16. Secretory Vesicle Priming by CAPS Is Independent of Its SNARE-Binding MUN Domain

    Directory of Open Access Journals (Sweden)

    Cuc Quynh Nguyen Truong

    2014-11-01

    Full Text Available Priming of secretory vesicles is a prerequisite for their Ca2+-dependent fusion with the plasma membrane. The key vesicle priming proteins, Munc13s and CAPSs, are thought to mediate vesicle priming by regulating the conformation of the t-SNARE syntaxin, thereby facilitating SNARE complex assembly. Munc13s execute their priming function through their MUN domain. Given that the MUN domain of Ca2+-dependent activator protein for secretion (CAPS also binds syntaxin, it was assumed that CAPSs prime vesicles through the same mechanism as Munc13s. We studied naturally occurring splice variants of CAPS2 in CAPS1/CAPS2-deficient cells and found that CAPS2 primes vesicles independently of its MUN domain. Instead, the pleckstrin homology domain of CAPS2 seemingly is essential for its priming function. Our findings indicate a priming mode for secretory vesicles. This process apparently requires membrane phospholipids, does not involve the binding or direct conformational regulation of syntaxin by MUN domains of CAPSs, and is therefore not redundant with Munc13 action.

  17. Secretory pathway Ca2+ -ATPases promote in vitro microcalcifications in breast cancer cells.

    Science.gov (United States)

    Dang, Donna; Prasad, Hari; Rao, Rajini

    2017-11-01

    Calcification of the breast is often an outward manifestation of underlying molecular changes that drive carcinogenesis. Up to 50% of all non-palpable breast tumors and 90% of ductal carcinoma in situ present with radiographically dense mineralization in mammographic scans. However, surprisingly little is known about the molecular pathways that lead to microcalcifications in the breast. Here, we report on a rapid and quantitative in vitro assay to monitor microcalcifications in breast cancer cell lines, including MCF7, MDA-MB-231, and Hs578T. We show that the Secretory Pathway Ca 2+ -ATPases SPCA1 and SPCA2 are strongly induced under osteogenic conditions that elicit microcalcifications. SPCA gene expression is significantly elevated in breast cancer subtypes that are associated with microcalcifications. Ectopic expression of SPCA genes drives microcalcifications and is dependent on pumping activity. Conversely, knockdown of SPCA expression significantly attenuates formation of microcalcifications. We propose that high levels of SPCA pumps may initiate mineralization in the secretory pathway by elevating luminal Ca 2+ . Our new findings offer mechanistic insight and functional implications on a widely observed, yet poorly understood radiographic signature of breast cancer. © 2017 Wiley Periodicals, Inc.

  18. Secretory Overexpression of Bacillus thermocatenulatus Lipase in Saccharomyces cerevisiae Using Combinatorial Library Strategy.

    Science.gov (United States)

    Kajiwara, Shota; Yamada, Ryosuke; Ogino, Hiroyasu

    2018-04-10

    Simple and cost-effective lipase expression host microorganisms are highly desirable. A combinatorial library strategy is used to improve the secretory expression of lipase from Bacillus thermocatenulatus (BTL2) in the culture supernatant of Saccharomyces cerevisiae. A plasmid library including expression cassettes composed of sequences encoding one of each 15 promoters, 15 secretion signals, and 15 terminators derived from yeast species, S. cerevisiae, Pichia pastoris, and Hansenula polymorpha, is constructed. The S. cerevisiae transformant YPH499/D4, comprising H. polymorpha GAP promoter, S. cerevisiae SAG1 secretion signal, and P. pastoris AOX1 terminator, is selected by high-throughput screening. This transformant expresses BTL2 extra-cellularly with a 130-fold higher than the control strain, comprising S. cerevisiae PGK1 promoter, S. cerevisiae α-factor secretion signal, and S. cerevisiae PGK1 terminator, after cultivation for 72 h. This combinatorial library strategy holds promising potential for application in the optimization of the secretory expression of proteins in yeast. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Neutral sphingomyelinase (SMPD3) deficiency disrupts the Golgi secretory pathway and causes growth inhibition

    Science.gov (United States)

    Stoffel, Wilhelm; Hammels, Ina; Jenke, Bitta; Binczek, Erika; Schmidt-Soltau, Inga; Brodesser, Susanne; Schauss, Astrid; Etich, Julia; Heilig, Juliane; Zaucke, Frank

    2016-01-01

    Systemic loss of neutral sphingomyelinase (SMPD3) in mice leads to a novel form of systemic, juvenile hypoplasia (dwarfism). SMPD3 deficiency in mainly two growth regulating cell types contributes to the phenotype, in chondrocytes of skeletal growth zones to skeletal malformation and chondrodysplasia, and in hypothalamic neurosecretory neurons to systemic hypothalamus–pituitary–somatotropic hypoplasia. The unbiased smpd3−/− mouse mutant and derived smpd3−/− primary chondrocytes were instrumental in defining the enigmatic role underlying the systemic and cell autonomous role of SMPD3 in the Golgi compartment. Here we describe the unprecedented role of SMPD3. SMPD3 deficiency disrupts homeostasis of sphingomyelin (SM), ceramide (Cer) and diacylglycerol (DAG) in the Golgi SMPD3-SMS1 (SM-synthase1) cycle. Cer and DAG, two fusogenic intermediates, modify the membrane lipid bilayer for the initiation of vesicle formation and transport. Dysproteostasis, unfolded protein response, endoplasmic reticulum stress and apoptosis perturb the Golgi secretory pathway in the smpd3−/− mouse. Secretion of extracellular matrix proteins is arrested in chondrocytes and causes skeletal malformation and chondrodysplasia. Similarly, retarded secretion of proteo-hormones in hypothalamic neurosecretory neurons leads to hypothalamus induced combined pituitary hormone deficiency. SMPD3 in the regulation of the protein vesicular secretory pathway may become a diagnostic target in the etiology of unknown forms of juvenile growth and developmental inhibition. PMID:27882938

  20. Identification of Secretory Proteins in Mycobacterium tuberculosis Using Pseudo Amino Acid Composition

    Directory of Open Access Journals (Sweden)

    Huan Yang

    2016-01-01

    Full Text Available Tuberculosis is killing millions of lives every year and on the blacklist of the most appalling public health problems. Recent findings suggest that secretory protein of Mycobacterium tuberculosis may serve the purpose of developing specific vaccines and drugs due to their antigenicity. Responding to global infectious disease, we focused on the identification of secretory proteins in Mycobacterium tuberculosis. A novel method called MycoSec was designed by incorporating g-gap dipeptide compositions into pseudo amino acid composition. Analysis of variance-based technique was applied in the process of feature selection and a total of 374 optimal features were obtained and used for constructing the final predicting model. In the jackknife test, MycoSec yielded a good performance with the area under the receiver operating characteristic curve of 0.93, demonstrating that the proposed system is powerful and robust. For user’s convenience, the web server MycoSec was established and an obliging manual on how to use it was provided for getting around any trouble unnecessary.

  1. Localization and activity of multidrug resistance protein 1 in the secretory pathway of Leishmania parasites.

    Science.gov (United States)

    Dodge, Matthew A; Waller, Ross F; Chow, Larry M C; Zaman, Muhammad M; Cotton, Leanne M; McConville, Malcolm J; Wirth, Dyann F

    2004-03-01

    Upregulation of the multidrug resistance protein 1 (LeMDR1) in the protozoan parasite, Leishmania enriettii, confers resistance to hydrophobic drugs such as vinblastine, but increases the sensitivity of these parasites to the mitochondrial drug, rhodamine 123. In order to investigate the mechanism of action of LeMDR1, the subcellular localization of green fluorescent protein (GFP)-tagged versions of LeMDR1 and the fate of the traceable-fluorescent LeMDR1 substrate calcein AM were examined in both Leishmania mexicana and L. enriettii LeMDR1 -/- and overexpressing cell lines. The LeMDR1-GFP chimera was localized by fluorescence microscopy to a number of secretory and endocytic compartments, including the Golgi apparatus, endoplasmic reticulum (ER) and a multivesicular tubule (MVT)-lysosome. Pulse-chase labelling experiments with calcein AM suggested that the Golgi and ER pools, but not the MVT-lysosome pool, of LeMDR1 were active in pumping calcein AM out of the cell. Cells labelled with calcein AM under conditions that slow vesicular transport (low temperature and stationary growth) inhibited export and resulted in the accumulation of fluorescent calcein in both the Golgi and the mitochondria. We propose that LeMDR1 substrates are pumped into secretory compartments and exported from the parasite by exocytosis. Accumulation of MDR substrates in the ER can result in alternative transport to the mitochondrion, explaining the reciprocal sensitivity of drug-resistant Leishmania to vinblastine and rhodamine 123.

  2. Immunolocalization of an enterotoxic glycoprotein exoantigen on the secretory organelles of Cryptosporidium parvum sporozoites

    Directory of Open Access Journals (Sweden)

    El-Shewy K.A.

    2004-06-01

    Full Text Available In this study, the fine ultrastructures of the secretory organelles of C. parvum sporozoites were demonstrated using transmission electron microscopy (TEM. Meanwhile, a previously identified enterotoxic 18-20 kDa copro-antigen (18-20 kDa CCA, associated with cryptosporidiosis in both human and calves, was isolated and immunolocalized on C. parvum sporozoites. Using immunoelectron microscopy and anti-18-20 kDa monospecific antibody demonstrated marked existence of the 18-20 kDa CCA on the apical organelles and at the trilaminar pellicles. An anterior extrusion of this protein was demonstrated around the excysted and released sporozoites. However, non excysted sporozoites did not show this protein. Affinity blotting, with biotinylated jacalin, demonstrated the O-linked oligosaccharide moiety of this protein. The potential role of this protein in the host cell invasion and/or gliding motility remains unelucidated. However, its enterotoxicity, location and secretory nature suggest that it may be a target for neutralization or invasion inhibition of Cryptosporidium.

  3. Hydroxylase inhibition attenuates colonic epithelial secretory function and ameliorates experimental diarrhea.

    LENUS (Irish Health Repository)

    Ward, Joseph B J

    2012-02-01

    Hydroxylases are oxygen-sensing enzymes that regulate cellular responses to hypoxia. Transepithelial Cl(-) secretion, the driving force for fluid secretion, is dependent on O(2) availability for generation of cellular energy. Here, we investigated the role of hydroxylases in regulating epithelial secretion and the potential for targeting these enzymes in treatment of diarrheal disorders. Ion transport was measured as short-circuit current changes across voltage-clamped monolayers of T(84) cells and mouse colon. The antidiarrheal efficacy of dimethyloxallyl glycine (DMOG) was tested in a mouse model of allergic disease. Hydroxylase inhibition with DMOG attenuated Ca(2+)- and cAMP-dependent secretory responses in voltage-clamped T(84) cells to 20.2 +\\/- 2.6 and 38.8 +\\/- 6.7% (n=16; P<\\/=0.001) of those in control cells, respectively. Antisecretory actions of DMOG were time and concentration dependent, being maximal after 18 h of DMOG (1 mM) treatment. DMOG specifically inhibited Na(+)\\/K(+)-ATPase pump activity without altering its expression or membrane localization. In mice, DMOG inhibited agonist-induced secretory responses ex vivo and prevented allergic diarrhea in vivo. In conclusion, hydroxylases are important regulators of epithelial Cl(-) and fluid secretion and present a promising target for development of new drugs to treat transport disorders.

  4. Hydroxylase inhibition attenuates colonic epithelial secretory function and ameliorates experimental diarrhea.

    LENUS (Irish Health Repository)

    Ward, Joseph B J

    2011-02-01

    Hydroxylases are oxygen-sensing enzymes that regulate cellular responses to hypoxia. Transepithelial Cl(-) secretion, the driving force for fluid secretion, is dependent on O(2) availability for generation of cellular energy. Here, we investigated the role of hydroxylases in regulating epithelial secretion and the potential for targeting these enzymes in treatment of diarrheal disorders. Ion transport was measured as short-circuit current changes across voltage-clamped monolayers of T(84) cells and mouse colon. The antidiarrheal efficacy of dimethyloxallyl glycine (DMOG) was tested in a mouse model of allergic disease. Hydroxylase inhibition with DMOG attenuated Ca(2+)- and cAMP-dependent secretory responses in voltage-clamped T(84) cells to 20.2 ± 2.6 and 38.8 ± 6.7% (n=16; P≤0.001) of those in control cells, respectively. Antisecretory actions of DMOG were time and concentration dependent, being maximal after 18 h of DMOG (1 mM) treatment. DMOG specifically inhibited Na(+)\\/K(+)-ATPase pump activity without altering its expression or membrane localization. In mice, DMOG inhibited agonist-induced secretory responses ex vivo and prevented allergic diarrhea in vivo. In conclusion, hydroxylases are important regulators of epithelial Cl(-) and fluid secretion and present a promising target for development of new drugs to treat transport disorders.

  5. Ionic and secretory response of pancreatic islet cells to minoxidil sulfate

    International Nuclear Information System (INIS)

    Antoine, M.H.; Hermann, M.; Herchuelz, A.; Lebrun, P.

    1991-01-01

    Minoxidil sulfate is an antihypertensive agent belonging to the new class of vasodilators, the K+ channel openers. The present study was undertaken to characterize the effects of minoxidil sulfate on ionic and secretory events in rat pancreatic islets. The drug unexpectedly provoked a concentration-dependent decrease in 86Rb outflow. This inhibitory effect was reduced in a concentration-dependent manner by glucose and tolbutamide. Minoxidil sulfate did not affect 45Ca outflow from islets perfused in the presence of extracellular Ca++ and absence or presence of glucose. However, in islets exposed to a medium deprived of extracellular Ca++, the drug provoked a rise in 45Ca outflow. Whether in the absence or presence of extracellular Ca++, minoxidil sulfate increased the cytosolic free Ca++ concentration of islet cells. Lastly, minoxidil sulfate increased the release of insulin from glucose-stimulated pancreatic islets. These results suggest that minoxidil sulfate reduces the activity of the ATP-sensitive K+ channels and promotes an intracellular translocation of Ca++. The latter change might account for the effect of the drug on the insulin-releasing process. However, the secretory response to minoxidil sulfate could also be mediated, at least in part, by a modest Ca++ entry

  6. Identification and characterization of secretory proteins during ionizing radiation-induced premature senescence

    International Nuclear Information System (INIS)

    Han, Na Kyung; Hong, Mi Na; Jung, Seung Hee; Kang, Kyoung Ah; Lee, Jae Seon; Chi, Seong Gil

    2011-01-01

    Cellular senescence was first described by Hayflick and Moorhead in 1961 who observed that cultures of normal human fibroblasts had a limited replicative potential and eventually became irreversibly arrest. The majority of senescent cells assume a characteristic flattened and enlarged morphological change, senescence associated β alactosidase positivity. Recently a large number of molecular phenotypes such as changes in gene expression, protein processing and chromatin organization have been also described. In contrast to apoptosis, senescence does not destroy the cells but leaves them metabolically and synthetically active and therefore able to affect their microenvironment. In particular, senescent fibroblasts and some cancer cells were found to secrete proteins with known or putative tumor-promoting functions such as growth factors or proteolytic enzymes. However, the knowledge about secreted proteins from senescent tumor cells and their functions to surrounding cells is still lacking. In this study, changes of senescence associated secretory protein expression profile were observed in MCF7 human breast cancer cells exposed to gamma-ray radiation using two dimensional electrophoresis. Also, we identified up-regulated secretory proteins during ionizing radiation-induced cellular senescence. Here, we show that senescent human breast cancer MCF7 cells promote the proliferation, invasion and migration of neighboring cells

  7. Identification and characterization of secretory proteins during ionizing radiation-induced premature senescence

    Energy Technology Data Exchange (ETDEWEB)

    Han, Na Kyung; Hong, Mi Na; Jung, Seung Hee; Kang, Kyoung Ah; Lee, Jae Seon [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Chi, Seong Gil [Korea University, Seoul (Korea, Republic of)

    2011-05-15

    Cellular senescence was first described by Hayflick and Moorhead in 1961 who observed that cultures of normal human fibroblasts had a limited replicative potential and eventually became irreversibly arrest. The majority of senescent cells assume a characteristic flattened and enlarged morphological change, senescence associated {beta} alactosidase positivity. Recently a large number of molecular phenotypes such as changes in gene expression, protein processing and chromatin organization have been also described. In contrast to apoptosis, senescence does not destroy the cells but leaves them metabolically and synthetically active and therefore able to affect their microenvironment. In particular, senescent fibroblasts and some cancer cells were found to secrete proteins with known or putative tumor-promoting functions such as growth factors or proteolytic enzymes. However, the knowledge about secreted proteins from senescent tumor cells and their functions to surrounding cells is still lacking. In this study, changes of senescence associated secretory protein expression profile were observed in MCF7 human breast cancer cells exposed to gamma-ray radiation using two dimensional electrophoresis. Also, we identified up-regulated secretory proteins during ionizing radiation-induced cellular senescence. Here, we show that senescent human breast cancer MCF7 cells promote the proliferation, invasion and migration of neighboring cells

  8. Thyroid hormone affects secretory activity and uncoupling protein-3 expression in rat harderian gland.

    Science.gov (United States)

    Chieffi Baccari, Gabriella; Monteforte, Rossella; de Lange, Pieter; Raucci, Franca; Farina, Paola; Lanni, Antonia

    2004-07-01

    The effects of T(3) administration on the rat Harderian gland were examined at morphological, biochemical, and molecular levels. T(3) induced hypertrophy of the two cell types (A and B) present in the glandular epithelium. In type A cells, the hypertrophy was mainly due to an increase in the size of the lipid compartment. The acinar lumina were filled with lipoproteic substances, and the cells often showed an olocrine secretory pattern. In type B cells, the hypertrophy largely consisted of a marked proliferation of mitochondria endowed with tightly packed cristae, the mitochondrial number being nearly doubled (from 62 to 101/100 microm(2)). Although the average area of individual mitochondria decreased by about 50%, the total area of the mitochondrial compartment increased by about 80% (from 11 to 19/100 microm(2)). This could be ascribed to T(3)-induced mitochondrial proliferation. The morphological and morphometric data correlated well with our biochemical results, which indicated that mitochondrial respiratory activity is increased in hyperthyroid rats. T(3), by influencing the metabolic function of the mitochondrial compartment, induces lipogenesis and the release of secretory product by type A cells. Mitochondrial uncoupling proteins 2 and 3 were expressed at both mRNA and protein levels in the euthyroid rat Harderian gland. T(3) treatment increased the mRNA levels of both uncoupling protein 2 (UCP2) and UCP3, but the protein level only of UCP3. A possible role for these proteins in the Harderian gland is discussed.

  9. A pH-Regulated Quality Control Cycle for Surveillance of Secretory Protein Assembly

    Science.gov (United States)

    Vavassori, Stefano; Cortini, Margherita; Masui, Shoji; Sannino, Sara; Anelli, Tiziana; Caserta, Imma R.; Fagioli, Claudio; Mossuto, Maria F.; Fornili, Arianna; van Anken, Eelco; Degano, Massimo; Inaba, Kenji; Sitia, Roberto

    2013-01-01

    Summary To warrant the quality of the secretory proteome, stringent control systems operate at the endoplasmic reticulum (ER)-Golgi interface, preventing the release of nonnative products. Incompletely assembled oligomeric proteins that are deemed correctly folded must rely on additional quality control mechanisms dedicated to proper assembly. Here we unveil how ERp44 cycles between cisGolgi and ER in a pH-regulated manner, patrolling assembly of disulfide-linked oligomers such as IgM and adiponectin. At neutral, ER-equivalent pH, the ERp44 carboxy-terminal tail occludes the substrate-binding site. At the lower pH of the cisGolgi, conformational rearrangements of this peptide, likely involving protonation of ERp44’s active cysteine, simultaneously unmask the substrate binding site and −RDEL motif, allowing capture of orphan secretory protein subunits and ER retrieval via KDEL receptors. The ERp44 assembly control cycle couples secretion fidelity and efficiency downstream of the calnexin/calreticulin and BiP-dependent quality control cycles. PMID:23685074

  10. The effect of hepatocyte growth factor on secretory functions in human eosinophils.

    Science.gov (United States)

    Yamauchi, Yumiko; Ueki, Shigeharu; Konno, Yasunori; Ito, Wataru; Takeda, Masahide; Nakamura, Yuka; Nishikawa, Junko; Moritoki, Yuki; Omokawa, Ayumi; Saga, Tomoo; Hirokawa, Makoto

    2016-12-01

    Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is now recognized as a humoral mediator in inflammatory and immune responses. Previous studies indicated that HGF negatively regulated allergic airway inflammation. In view of eosinophils playing a role in the pathogenesis of asthma, especially in airway remodeling as a rich source of pro-fibrogenic mediators, the effects of HGF on the different types of eosinophil secretory functions were examined in this study. We found that HGF significantly inhibited IL-5-induced secretion of TGF-β and VEGF from human eosinophils. The inhibitory effect is not associated with TGF-β transcription; rather, it is associated with ultrastructural granule emptying and loss of intracellular TGF-β contents, indicating HGF inhibits the process of piecemeal degranulation. The effect of HGF on extracellular trap cell death (ETosis) that mediates cytolytic degranulation was also investigated; however, immobilized IgG- or phorbol myristate acetate-induced ETosis was only minimally attenuated by HGF. These results reveal the effect of HGF on the distinct pathways of eosinophil secretory functions and also provide novel insights into the role of HGF in the pathogenesis of allergic inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Radiation-induced secretory protein, clusterin. Its inductive mechanism and biological significance

    International Nuclear Information System (INIS)

    Suzuki, Masatoshi; Boothman, D.A.

    2007-01-01

    This paper describes biochemistry of secretory clusterin (C), its radiation-inductive mechanism and biological significance. C is a glycoprotein found to be secreted from cells given various stresses like radiation and ultraviolet (UV)-ray, and participates to red cell clustering. Human C gene locates on the chromosome 8p21-p12, C has MW of 60 kDa, its precursor undergoes the degrading processing to α- and β-chains to form their heterodimer before glycosylation, and the C is finally secreted. So many other names have been given to C due to its numerous functions which have been discovered in other fields, such as apolipoprotein J. C is abundant in plasma, milk, urine, cerebrospinal fluid, semen, etc. Within 24 hr after X-ray irradiation, extracellular insulin-like growth factor-1 (IGF-1) level is elevated, and through its binding to the receptor, Src/MAPK signaling participates to C expression. Nuclear C, also induced by radiation, is a splicing variant of C and not secreted from cells. C is induced by radiation with as low dose as 2 cGy, which is different from induction of nuclear C. Secreted C is incorporated in cells by endocytosis and promotes the intracellular survival reaction through IGF-1 receptor/MAPK/Egr-1 pathway, whereas nuclear C induces cell apoptosis via unknown mechanism. Further studies are required for elucidation of the roles of secretory and nuclear C in cellular radiation responses. (R.T.)

  12. Completeness of Lyapunov Abstraction

    DEFF Research Database (Denmark)

    Wisniewski, Rafal; Sloth, Christoffer

    2013-01-01

    the vector field, which allows the generation of a complete abstraction. To compute the functions that define the subdivision of the state space in an algorithm, we formulate a sum of squares optimization problem. This optimization problem finds the best subdivisioning functions, with respect to the ability......This paper addresses the generation of complete abstractions of polynomial dynamical systems by timed automata. For the proposed abstraction, the state space is divided into cells by sublevel sets of functions. We identify a relation between these functions and their directional derivatives along...

  13. Myringotomy versus ventilation tubes in secretory otitis media: eardrum pathology, hearing, and eustachian tube function 25 years after treatment

    DEFF Research Database (Denmark)

    Caye-Thomasen, P.; Stangerup, S.E.; Jorgensen, G.

    2008-01-01

    OBJECTIVE: This report documents the dynamics of eardrum pathology, hearing acuity, and eustachian tube function during 25 years after treatment of bilateral secretory otitis media. The included children were treated by myringotomy on the left ear and ventilation tube insertion on the right ear....... MATERIALS AND METHODS: Two hundred twenty-four children with bilateral secretory otitis media were treated by bilateral myringotomy and insertion of a ventilation tube on the right side only. The children were reexamined by otomicroscopy, tympanometry, and pure tone audiometry after 3, 7, and 25 years...

  14. Complete Rerouting Protection

    DEFF Research Database (Denmark)

    Stidsen, Thomas K.; Kjærulff, Peter

    2005-01-01

    In this paper we present a new protection method: Complete Rerouting. This is the most capacity e cient protection method for circuit switched networks and it is, to the best of our knowledge, the first time it has been described. We implement a column generation algorithm and test the performance...

  15. Complete French Teach Yourself

    CERN Document Server

    Graham, Gaelle

    2010-01-01

    The best-selling complete course for a fun and effective way to learn French. This ISBN is for the paperback book. The corresponding audio support (ISBN: 9781444100068) is also available. The book and audio support can also be purchased as a pack (ISBN: 9781444100051).

  16. Completeness of Lyapunov Abstraction

    Directory of Open Access Journals (Sweden)

    Rafael Wisniewski

    2013-08-01

    Full Text Available In this work, we continue our study on discrete abstractions of dynamical systems. To this end, we use a family of partitioning functions to generate an abstraction. The intersection of sub-level sets of the partitioning functions defines cells, which are regarded as discrete objects. The union of cells makes up the state space of the dynamical systems. Our construction gives rise to a combinatorial object - a timed automaton. We examine sound and complete abstractions. An abstraction is said to be sound when the flow of the time automata covers the flow lines of the dynamical systems. If the dynamics of the dynamical system and the time automaton are equivalent, the abstraction is complete. The commonly accepted paradigm for partitioning functions is that they ought to be transversal to the studied vector field. We show that there is no complete partitioning with transversal functions, even for particular dynamical systems whose critical sets are isolated critical points. Therefore, we allow the directional derivative along the vector field to be non-positive in this work. This considerably complicates the abstraction technique. For understanding dynamical systems, it is vital to study stable and unstable manifolds and their intersections. These objects appear naturally in this work. Indeed, we show that for an abstraction to be complete, the set of critical points of an abstraction function shall contain either the stable or unstable manifold of the dynamical system.

  17. Dual completion method

    Energy Technology Data Exchange (ETDEWEB)

    Mamedov, N Ya; Kadymova, K S; Dzhafarov, Sh T

    1963-10-28

    One type of dual completion method utilizes a single tubing string. Through the use of the proper tubing equipment, the fluid from the low-productive upper formation is lifted by utilizing the surplus energy of a submerged pump, which handles the production from the lower stratum.

  18. A complete woman

    Indian Academy of Sciences (India)

    Lawrence

    treated me like a son in the way he encouraged my education, while my mother ... cine gives me a lot of satisfaction when I see my patients getting cured. Teaching ... thing in life as a complete woman in different roles – daughter, wife, mother ...

  19. The Ca2+/H+ antiporter TMEM165 expression, localization in the developing, lactating and involuting mammary gland parallels the secretory pathway Ca2+ATPase (SPCA1)

    Science.gov (United States)

    Plasma membrane Ca2+-ATPase 2 (PMCA2) knockout mice showed that ~ 60 % of calcium in milk is transported across the mammary cells apical membrane by PMCA2. The remaining milk calcium is thought to arrive via the secretory pathway through the actions of secretory pathway Ca2+-ATPase’s 1 and/or 2 (SP...

  20. Juvenile eye growth, when completed?

    DEFF Research Database (Denmark)

    Fledelius, Hans C; Christensen, Anders S; Fledelius, Christian

    2014-01-01

    PURPOSE: To test Sorsby's classical statement of axial eye growth as completed at the age of 13 years, with a view also to differentiating between basic eye growth and juvenile elongation associated with eventual refractive change towards myopia. METHODS: (i) A total of 160 healthy eyes close...... about age 13 as general limit found support from the cross-sectional data, which suggested stable emmetropic eye size from about 11-12 years, with an average apparently outgrown male emmetropic value of 23.5 mm versus females' 22.9 mm. The longitudinal data, however, showed emmetropic growth also beyond...

  1. Projective modules and complete intersections

    CERN Document Server

    Mandal, Satya

    1997-01-01

    In these notes on "Projective Modules and Complete Intersections" an account on the recent developments in research on this subject is presented. The author's preference for the technique of Patching isotopic isomorphisms due to Quillen, formalized by Plumsted, over the techniques of elementary matrices is evident here. The treatment of Basic Element theory here incorporates Plumstead's idea of the "generalized dimension functions". These notes are highly selfcontained and should be accessible to any graduate student in commutative algebra or algebraic geometry. They include fully self-contained presentations of the theorems of Ferrand-Szpiro, Cowsik-Nori and the techniques of Lindel.

  2. The endocytic pathways of a secretory granule membrane protein in HEK293 cells: PAM and EGF traverse a dynamic multivesicular body network together.

    Science.gov (United States)

    Bäck, Nils; Kanerva, Kristiina; Kurutihalli, Vishwanatha; Yanik, Andrew; Ikonen, Elina; Mains, Richard E; Eipper, Betty A

    2017-08-01

    Peptidylglycine α-amidating monooxygenase (PAM) is highly expressed in neurons and endocrine cells, where it catalyzes one of the final steps in the biosynthesis of bioactive peptides. PAM is also expressed in unicellular organisms such as Chlamydomonas reinhardtii, which do not store peptides in secretory granules. As for other granule membrane proteins, PAM is retrieved from the cell surface and returned to the trans-Golgi network. This pathway involves regulated entry of PAM into multivesicular body intralumenal vesicles (ILVs). The aim of this study was defining the endocytic pathways utilized by PAM in cells that do not store secretory products in granules. Using stably transfected HEK293 cells, endocytic trafficking of PAM was compared to that of the mannose 6-phosphate (MPR) and EGF (EGFR) receptors, established markers for the endosome to trans-Golgi network and degradative pathways, respectively. As in neuroendocrine cells, PAM internalized by HEK293 cells accumulated in the trans-Golgi network. Based on surface biotinylation, >70% of the PAM on the cell surface was recovered intact after a 4h chase and soluble, bifunctional PAM was produced. Endosomes containing PAM generally contained both EGFR and MPR and ultrastructural analysis confirmed that all three cargos accumulated in ILVs. PAM containing multivesicular bodies made frequent dynamic tubular contacts with younger and older multivesicular bodies. Frequent dynamic contacts were observed between lysosomes and PAM containing early endosomes and multivesicular bodies. The ancient ability of PAM to localize to ciliary membranes, which release bioactive ectosomes, may be related to its ability to accumulate in ILVs and exosomes. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Secretory signal peptide modification for optimized antibody-fragment expression-secretion in Leishmania tarentolae

    Directory of Open Access Journals (Sweden)

    Klatt Stephan

    2012-07-01

    Full Text Available Abstract Background Secretory signal peptides (SPs are well-known sequence motifs targeting proteins for translocation across the endoplasmic reticulum membrane. After passing through the secretory pathway, most proteins are secreted to the environment. Here, we describe the modification of an expression vector containing the SP from secreted acid phosphatase 1 (SAP1 of Leishmania mexicana for optimized protein expression-secretion in the eukaryotic parasite Leishmania tarentolae with regard to recombinant antibody fragments. For experimental design the online tool SignalP was used, which predicts the presence and location of SPs and their cleavage sites in polypeptides. To evaluate the signal peptide cleavage site as well as changes of expression, SPs were N-terminally linked to single-chain Fragment variables (scFv’s. The ability of L. tarentolae to express complex eukaryotic proteins with highly diverse post-translational modifications and its easy bacteria-like handling, makes the parasite a promising expression system for secretory proteins. Results We generated four vectors with different SP-sequence modifications based on in-silico analyses with SignalP in respect to cleavage probability and location, named pLTEX-2 to pLTEX-5. To evaluate their functionality, we cloned four individual scFv-fragments into the vectors and transfected all 16 constructs into L. tarentolae. Independently from the expressed scFv, pLTEX-5 derived constructs showed the highest expression rate, followed by pLTEX-4 and pLTEX-2, whereas only low amounts of protein could be obtained from pLTEX-3 clones, indicating dysfunction of the SP. Next, we analysed the SP cleavage sites by Edman degradation. For pLTEX-2, -4, and -5 derived scFv’s, the results corresponded to in-silico predictions, whereas pLTEX-3 derived scFv’s contained one additional amino-acid (AA. Conclusions The obtained results demonstrate the importance of SP-sequence optimization for efficient

  4. Secretory IgM Exacerbates Tumor Progression by Inducing Accumulations of MDSCs in Mice.

    Science.gov (United States)

    Tang, Chih-Hang Anthony; Chang, Shiun; Hashimoto, Ayumi; Chen, Yi-Ju; Kang, Chang Won; Mato, Anthony R; Del Valle, Juan R; Gabrilovich, Dmitry I; Hu, Chih-Chi Andrew

    2018-06-01

    Chronic lymphocytic leukemia (CLL) cells can secrete immunoglobulin M. However, it is not clear whether secretory IgM (sIgM) plays a role in disease progression. We crossed the Eμ-TCL1 mouse model of CLL, in which the expression of human TCL1 oncogene was driven by the V(H) promoter-Ig(H)-Eμ enhancer, with MD4 mice whose B cells produced B-cell receptor (membrane-bound IgM) and sIgM with specificity for hen egg lysozyme (HEL). CLL cells that developed in these MD4/Eμ-TCL1 mice reactivated a parental Ig gene allele and secreted IgM, and did not recognize HEL. The MD4/Eμ-TCL1 mice had reduced survival, increased myeloid-derived suppressor cells (MDSC), and decreased numbers of T cells. We tested whether sIgM could contribute to the accumulation of MDSCs by crossing μS -/- mice, which could not produce sIgM, with Eμ-TCL1 mice. The μS -/- /Eμ-TCL1 mice survived longer than Eμ-TCL1 mice and developed decreased numbers of MDSCs which were less able to suppress proliferation of T cells. We targeted the synthesis of sIgM by deleting the function of XBP-1s and showed that targeting XBP-1s genetically or pharmacologically could lead to decreased sIgM, accompanied by decreased numbers and reduced functions of MDSCs in MD4/Eμ-TCL1 mice. Additionally, MDSCs from μS -/- mice grafted with Lewis lung carcinoma were inefficient suppressors of T cells, resulting in slower tumor growth. These results demonstrate that sIgM produced by B cells can upregulate the functions of MDSCs in tumor-bearing mice to aggravate cancer progression. In a mouse model of CLL, production of secretory IgM led to more MDSCs, fewer T cells, and shorter survival times for the mice. Thus, secretory IgM may aggravate the progression of this cancer. Cancer Immunol Res; 6(6); 696-710. ©2018 AACR . ©2018 American Association for Cancer Research.

  5. The complete cosmicomics

    CERN Document Server

    Calvino, Italo

    2014-01-01

    The definitive edition of Calvino’s cosmicomics, bringing together all of these enchanting stories—including some never before translated—in one volume for the first time. In Italo Calvino’s cosmicomics, primordial beings cavort on the nearby surface of the moon, play marbles with atoms, and bear ecstatic witness to Earth’s first dawn. Exploring natural phenomena and the origins of the universe, these beloved tales relate complex scientific concepts to our common sensory, emotional, human world. Now, The Complete Cosmicomics brings together all of the cosmicomic stories for the first time. Containing works previously published in Cosmicomics, t zero, and Numbers in the Dark, this single volume also includes seven previously uncollected stories, four of which have never been published in translation in the United States. This “complete and definitive collection” (Evening Standard) reconfirms the cosmicomics as a crowning literary achievement and makes them available to new generations of reader...

  6. CMS Is Finally Completed

    CERN Multimedia

    2008-01-01

    Yet another step in the completion of the Large Hadron Collider was taken yesterday morning, as the final element of the Compact Muon Solenoid was lowered nearly 100 meters bellow ground. After more than eight years of work at the world's most powerful particle accelerator, scientists hope that they will be able to start initial experiments with the LHC until the end of this year.

  7. LEAR construction completed

    CERN Multimedia

    CERN PhotoLab

    1982-01-01

    In July 1982, LEAR construction was completed, the individual systems had been dry-tested. On 16 July, the first 50 MeV (309 MeV/c) protons from Linac 1 were injected and circulated. On 11 October, the first antiprotons from the AA, decelerated in the PS to 609 MeV/c, were injected. Also in 1982, acceleration, deceleration and stochastic cooling were successfully tested. See 9007366 for a more detailed description. See also 8201061, 8204131, 8309026.

  8. SHIVA laser: nearing completion

    International Nuclear Information System (INIS)

    Glaze, J.A.; Godwin, R.O.

    1977-01-01

    Construction of the Shiva laser system is nearing completion. This laser will be operating in fall 1977 and will produce over 20 terawatts of focusable power in a subnanosecond pulse. Fusion experiments will begin early in 1978. It is anticipated that thermonuclear energy release equal to one percent that of the incident light energy will be achieved with sub-millimeter deuterium-tritium targets. From other experiments densities in excess of a thousand times that of liquid are also expected

  9. SCT Barrel Assembly Complete

    CERN Multimedia

    L. Batchelor

    As reported in the April 2005 issue of the ATLAS eNews, the first of the four Semiconductor Tracker (SCT) barrels, complete with modules and services, arrived safely at CERN in January of 2005. In the months since January, the other three completed barrels arrived as well, and integration of the four barrels into the entire barrel assembly commenced at CERN, in the SR1 building on the ATLAS experimental site, in July. Assembly was completed on schedule in September, with the addition of the innermost layer to the 4-barrel assembly. Work is now underway to seal the barrel thermal enclosure. This is necessary in order to enclose the silicon tracker in a nitrogen atmosphere and provide it with faraday-cage protection, and is a delicate and complicated task: 352 silicon module powertapes, 352 readout-fibre bundles, and over 400 Detector Control System sensors must be carefully sealed into the thermal enclosure bulkhead. The team is currently verifying the integrity of the low mass cooling system, which must be d...

  10. The Complete Problem Solver.

    Science.gov (United States)

    Hayes, John R.

    This book, designed for a college course on general problem-solving skills, focuses on skills that can be used by anyone in solving problems that occur in everyday life. Part I considers theory and practice: understanding problems, search, and protocol analysis. Part II discusses memory and knowledge acquisition: the structure of human memory,…

  11. Effect of secretory pathway gene overexpression on secretion of a fluorescent reporter protein in Aspergillus nidulans

    DEFF Research Database (Denmark)

    Schalén, Martin; Anyaogu, Diana Chinyere; Hoof, Jakob Blæsbjerg

    2016-01-01

    roles in the process have been identified through transcriptomics. The assignment of function to these genes has been enabled in combination with gene deletion studies. In this work, 14 genes known to play a role in protein secretion in filamentous fungi were overexpressed in Aspergillus nidulans....... The background strain was a fluorescent reporter secreting mRFP. The overall effect of the overexpressions could thus be easily monitored through fluorescence measurements, while the effects on physiology were determined in batch cultivations and surface growth studies. Results: Fourteen protein secretion...... pathway related genes were overexpressed with a tet-ON promoter in the RFP-secreting reporter strain and macromorphology, physiology and protein secretion were monitored when the secretory genes were induced. Overexpression of several of the chosen genes was shown to cause anomalies on growth, micro...

  12. Alpha-Synuclein Toxicity in the Early Secretory Pathway: How it Drives Neurodegeneration in Parkinsons Disease

    Directory of Open Access Journals (Sweden)

    Ting eWang

    2015-11-01

    Full Text Available Alpha-synuclein is a predominant player in the pathogenesis of Parkinson’s Disease. However, despite extensive study for two decades, its physiological and pathological mechanisms remain poorly understood. Alpha-synuclein forms a perplexing web of interactions with lipids, trafficking machinery, and other regulatory factors. One emerging consensus is that synaptic vesicles are likely the functional site for alpha-synuclein, where it appears to facilitate vesicle docking and fusion. On the other hand, the disfunctions of alpha-synuclein are more dispersed and numerous; when mutated or over-expressed, alpha-synuclein affects several membrane trafficking and stress pathways, including exocytosis, ER-to-Golgi transport, ER stress, Golgi homeostasis, endocytosis, autophagy, oxidative stress and others. Here we examine recent developments in alpha-synuclein’s toxicity in the early secretory pathway placed in the context of emerging themes from other affected pathways to help illuminate its underlying pathogenic mechanisms in neurodegeneration.

  13. Secretory leukocyte protease inhibitor protein regulates the penetrance of frontotemporal lobar degeneration in progranulin mutation carriers.

    Science.gov (United States)

    Ghidoni, Roberta; Flocco, Rosa; Paterlini, Anna; Glionna, Michela; Caruana, Loredana; Tonoli, Elisa; Binetti, Giuliano; Benussi, Luisa

    2014-01-01

    The discovery that mutations in the gene encoding for progranulin (GRN) cause frontotemporal lobar degeneration (FTLD) and other neurodegenerative diseases leading to dementia has brought renewed interest in progranulin and its functions in the central nervous system. Full length progranulin is preserved from cleavage by secretory leukocyte protease inhibitor (SLPI), one of the smallest serine protease inhibitor circulating in plasma. Herein, we investigated the relationship between circulating SLPI and progranulin in affected and unaffected subjects belonging to 26 Italian pedigrees carrying GRN null mutations. In GRN null mutation carriers, we demonstrated: i) an increase of circulating SLPI levels in affected subjects; ii) an age-related upregulation of the serine-protease inhibitor in response to lifetime progranulin shortage; and iii) a delay in the age of onset in subjects with the highest SLPI protein levels. The study of SLPI and its relation to progranulin suggests the existence of unexpected molecular players in progranulin-associated neurodegeneration.

  14. Lipopolysaccharide-binding protein: localization in secretory granules of Paneth cells in the mouse small intestine

    DEFF Research Database (Denmark)

    Hansen, Gert H; Rasmussen, Karina; Niels-Christiansen, Lise-Lotte

    2009-01-01

    Lipopolysaccharide (LPS)-binding protein (LBP) is an acute-phase protein involved in the host's response to endotoxin and mainly synthesized and secreted to the blood by the liver. But in addition, LBP is also made by extrahepatic cells, including the enterocyte-like cell line Caco-2. To study...... in closer detail the synthesis and storage of LBP in the intestinal mucosal epithelium, we performed an immunolocalization of LBP in mouse small intestine. By immunofluorescence microscopy, an antibody recognizing the 58-60 kDa protein of LBP distinctly labeled a small population of cells located deep...... into the crypts. This cell population was also positive for lysozyme and alpha-defensin 4, identifying Paneth cells as the main intestinal LBP-producing cells. By immunogold electron microscopy, intense labeling was observed in the secretory granules of these cells. We conclude that Paneth cells express LBP...

  15. Glutamate signalling and secretory phospholipase A2 modulate the release of arachidonic acid from neuronal membranes

    DEFF Research Database (Denmark)

    Rodriguez De Turco, Elena B; Jackson, Fannie R; DeCoster, Mark A

    2002-01-01

    The lipid mediators generated by phospholipases A(2) (PLA(2)), free arachidonic acid (AA), eicosanoids, and platelet-activating factor, modulate neuronal activity; when overproduced, some of them become potent neurotoxins. We have shown, using primary cortical neuron cultures, that glutamate...... and secretory PLA(2) (sPLA(2)) from bee venom (bv sPLA(2)) and Taipan snake venom (OS2) elicit synergy in inducing neuronal cell death. Low concentrations of sPLA(2) are selective ligands of cell-surface sPLA(2) receptors. We investigated which neuronal arachidonoyl phospholipids are targeted by glutamate......) and in minor changes in other phospholipids. A similar profile, although of greater magnitude, was observed 20 hr posttreatment. Glutamate (80 microM) induced much less mobilization of (3)H-AA than did sPLA(2) and resulted in a threefold greater degradation of (3)H-AA PE than of (3)H-AA PC by 20 hr...

  16. Subversion of the Endocytic and Secretory Pathways by Bacterial Effector Proteins

    Directory of Open Access Journals (Sweden)

    Mary M. Weber

    2018-01-01

    Full Text Available Intracellular bacteria have developed numerous strategies to hijack host vesicular trafficking pathways to form their unique replicative niches. To promote intracellular replication, the bacteria must interact with host organelles and modulate host signaling pathways to acquire nutrients and membrane for the growing parasitophorous vacuole all while suppressing activation of the immune response. To facilitate host cell subversion, bacterial pathogens use specialized secretion systems to deliver bacterial virulence factors, termed effectors, into the host cell that mimic, agonize, and/or antagonize the function of host proteins. In this review we will discuss how bacterial effector proteins from Coxiella burnetii, Brucella abortus, Salmonella enterica serovar Typhimurium, Legionella pneumophila, Chlamydia trachomatis, and Orientia tsutsugamushi manipulate the endocytic and secretory pathways. Understanding how bacterial effector proteins manipulate host processes not only gives us keen insight into bacterial pathogenesis, but also enhances our understanding of how eukaryotic membrane trafficking is regulated.

  17. Trichinella britovi human infection in Spain : antibody response to surface, excretory/secretory and somatic antigens

    Directory of Open Access Journals (Sweden)

    Rodríguez-Osorio M.

    2003-06-01

    Full Text Available A third outbreak of Trichinella britovi with 140 people involved, occurred in Granada Spain (December 1998. The source of infection was sausage made from uninspected wild boar meat. Fifty-two patients agreed to participated in this study. An elevated eosinophil level (> 5 % was detected in 59.6 % of patients, and persisted in most of these cases for two months. A moderate IgG response was observed. At the onset of symptoms, Western blot (WB test detected more positive cases than Enzyme linked immunosorbent assay (ELISA and indirect immunofluorescence (IIF. Six months from infection, ELISA revealed fewer positive cases than the other two tests. It would appear that the response to somatic antigens starts earlier than those to cuticular and excretory/secretory (ES antigens and that the response to ES antigens is the first to decrease.

  18. Phylogenetic analysis of P5 P-type ATPases, a eukaryotic lineage of secretory pathway pumps

    DEFF Research Database (Denmark)

    Møller, Annette; Asp, Torben; Holm, Preben Bach

    2008-01-01

    prokaryotic genome. Based on a protein alignment we could group the P5 ATPases into two subfamilies, P5A and P5B that, based on the number of negative charges in conserved trans-membrane segment 4, are likely to have different ion specificities. P5A ATPases are present in all eukaryotic genomes sequenced so......Eukaryotes encompass a remarkable variety of organisms and unresolved lineages. Different phylogenetic analyses have lead to conflicting conclusions as to the origin and associations between lineages and species. In this work, we investigated evolutionary relationship of a family of cation pumps...... exclusive for the secretory pathway of eukaryotes by combining the identification of lineage-specific genes with phylogenetic evolution of common genes. Sequences of P5 ATPases, which are regarded to be cation pumps in the endoplasmic reticulum (ER), were identified in all eukaryotic lineages but not in any...

  19. On psychobiology in psychoanalysis - salivary cortisol and secretory IgA as psychoanalytic process parameters

    Science.gov (United States)

    Euler, Sebastian; Schimpf, Heinrich; Hennig, Jürgen; Brosig, Burkhard

    2005-01-01

    This study investigates the psychobiological impact of psychoanalysis in its four-hour setting. During a period of five weeks, 20 subsequent hours of psychoanalysis were evaluated, involving two patients and their analysts. Before and after each session, saliva samples were taken and analysed for cortisol (sCortisol) and secretory immunoglobuline A (sIgA). Four time-series (n=80 observations) resulted and were evaluated by "Pooled Time Series Analysis" (PTSA) for significant level changes and setting-mediated rhythms. Over all sessions, sCortisol levels were reduced and sIgA secretion augmented parallel to the analytic work. In one analytic dyad a significant rhythm within the four-hour setting was observed with an increase of sCortisol in sessions 2 and 3 of the week. Psychoanalysis may, therefore, have some psychobiological impact on patients and analysts alike and may modulate immunological and endocrinological processes. PMID:19742067

  20. Dynamic Regulation of Ero1α and Peroxiredoxin 4 Localization in the Secretory Pathway*

    Science.gov (United States)

    Kakihana, Taichi; Araki, Kazutaka; Vavassori, Stefano; Iemura, Shun-ichiro; Cortini, Margherita; Fagioli, Claudio; Natsume, Tohru; Sitia, Roberto; Nagata, Kazuhiro

    2013-01-01

    In the early secretory compartment (ESC), a network of chaperones and enzymes assists oxidative folding of nascent proteins. Ero1 flavoproteins oxidize protein disulfide isomerase (PDI), generating H2O2 as a byproduct. Peroxiredoxin 4 (Prx4) can utilize luminal H2O2 to oxidize PDI, thus favoring oxidative folding while limiting oxidative stress. Interestingly, neither ER oxidase contains known ER retention signal(s), raising the question of how cells prevent their secretion. Here we show that the two proteins share similar intracellular localization mechanisms. Their secretion is prevented by sequential interactions with PDI and ERp44, two resident proteins of the ESC-bearing KDEL-like motifs. PDI binds preferentially Ero1α, whereas ERp44 equally retains Ero1α and Prx4. The different binding properties of Ero1α and Prx4 increase the robustness of ER redox homeostasis. PMID:23979138

  1. Novel binders derived from an albumin-binding domain scaffold targeting human prostate secretory protein 94 (PSP94)

    Czech Academy of Sciences Publication Activity Database

    Marečková, Lucie; Petroková, Hana; Osička, Radim; Kuchař, Milan; Malý, Petr

    2015-01-01

    Roč. 6, č. 10 (2015), s. 774-779 ISSN 1674-800X Institutional support: RVO:86652036 ; RVO:61388971 Keywords : prostate secretory protein * prostate cancer * oncomarker Subject RIV: EB - Genetics ; Molecular Biology; EB - Genetics ; Molecular Biology (MBU-M) Impact factor: 3.817, year: 2015

  2. Human milk containing specific secretory IgA inhibits binding of Giardia lamblia to nylon and glass surfaces.

    Science.gov (United States)

    Samra, H K; Ganguly, N K; Mahajan, R C

    1991-06-01

    The effects of human milk, containing specific secretory IgA, on the adherence of Giardia lamblia trophozoites in the presence and in the absence of intestinal mucus in vitro were studied. It was found that the trophozoites treated with breast milk, containing specific secretory IgA to G. lamblia, showed a significant decrease (p less than 0.01) in adherence to nylon fibre columns and glass surfaces than did trophozoites treated with milk containing no SIgA antibodies. The adherence to glass surfaces was significantly more (p less than 0.01) in the presence of intestinal mucus than when the mucus was absent. Milk that did not contain specific secretory SIgA to G. lamblia did not decrease the adherence to glass surfaces either in the presence or in the absence of mucus. The fluorescence study revealed the binding of specific secretory IgA on the trophozoite surface. The results suggest that binding of SIgA antibodies in milk to G. lamblia trophozoites inhibits parasite adherence, thus protecting against this infection in breast-fed babies.

  3. Effect of threonine on secretory immune system using a chicken intestinal ex vivo model with lipopolysaccharide challenge

    Science.gov (United States)

    Secretory IgA (sIgA) and its transcytosis receptor, polymeric immunoglobulin receptor (pIgR), along with mucus, form the first lines of intestinal defense. Threonine (Thr) is a major constituent component of intestinal mucins and IgA, which are highly secreted under lipopolysaccharide (LPS) induced ...

  4. In Candida albicans hyphae, Sec2p is physically associated with SEC2 mRNA on secretory vesicles.

    Science.gov (United States)

    Caballero-Lima, David; Hautbergue, Guillaume M; Wilson, Stuart A; Sudbery, Peter E

    2014-11-01

    Candida albicans hyphae grow in a highly polarized fashion from their tips. This polarized growth requires the continuous delivery of secretory vesicles to the tip region. Vesicle delivery depends on Sec2p, the Guanine Exchange Factor (GEF) for the Rab GTPase Sec4p. GTP bound Sec4p is required for the transit of secretory vesicles from the trans-Golgi to sites of polarized growth. We previously showed that phosphorylation of Sec2p at residue S584 was necessary for Sec2p to support hyphal, but not yeast growth. Here we show that on secretory vesicles SEC2 mRNA is physically associated with Sec2p. Moreover, we show that the phosphorylation of S584 allows SEC2 mRNA to dissociate from Sec2p and we speculate that this is necessary for Sec2p function and/or translation. During hyphal extension, the growing tip may be separated from the nucleus by up to 15 μm. Transport of SEC2 mRNA on secretory vesicles to the tip localizes SEC2 translation to tip allowing a sufficient accumulation of this key protein at the site of polarized growth. © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

  5. Cysteine-rich secretory protein 3 is a ligand of alpha1B-glycoprotein in human plasma

    DEFF Research Database (Denmark)

    Udby, Lene; Sørensen, Ole E; Pass, Jesper

    2004-01-01

    Human cysteine-rich secretory protein 3 (CRISP-3; also known as SGP28) belongs to a family of closely related proteins found in mammals and reptiles. Some mammalian CRISPs are known to be involved in the process of reproduction, whereas some of the CRISPs from reptiles are neurotoxin...

  6. Secretory Phospholipase A2 Hydrolysis Phospholipid Analogs is Dependent on Water Accessibility to the Active Site

    DEFF Research Database (Denmark)

    Peters, Günther H.J.; Møller, Martin S.; Jørgensen, Kent

    2007-01-01

    A new and unnatural type of phospholipids with the head group attached to the 2-position of the glycerol backbone has been synthesized and shown to be a good substrate for secretory phospholipase A2 (sPLA2). To investigate the unexpected sPLA2 activity, we have compared three different phospholip...

  7. Fusion of lysosomes with secretory organelles leads to uncontrolled exocytosis in the lysosomal storage disease mucolipidosis type IV.

    Science.gov (United States)

    Park, Soonhong; Ahuja, Malini; Kim, Min Seuk; Brailoiu, G Cristina; Jha, Archana; Zeng, Mei; Baydyuk, Maryna; Wu, Ling-Gang; Wassif, Christopher A; Porter, Forbes D; Zerfas, Patricia M; Eckhaus, Michael A; Brailoiu, Eugen; Shin, Dong Min; Muallem, Shmuel

    2016-02-01

    Mutations in TRPML1 cause the lysosomal storage disease mucolipidosis type IV (MLIV). The role of TRPML1 in cell function and how the mutations cause the disease are not well understood. Most studies focus on the role of TRPML1 in constitutive membrane trafficking to and from the lysosomes. However, this cannot explain impaired neuromuscular and secretory cells' functions that mediate regulated exocytosis. Here, we analyzed several forms of regulated exocytosis in a mouse model of MLIV and, opposite to expectations, we found enhanced exocytosis in secretory glands due to enlargement of secretory granules in part due to fusion with lysosomes. Preliminary exploration of synaptic vesicle size, spontaneous mEPSCs, and glutamate secretion in neurons provided further evidence for enhanced exocytosis that was rescued by re-expression of TRPML1 in neurons. These features were not observed in Niemann-Pick type C1. These findings suggest that TRPML1 may guard against pathological fusion of lysosomes with secretory organelles and suggest a new approach toward developing treatment for MLIV. © 2015 The Authors.

  8. Effects of Cichorium Intybus L. Root Extract on Secretory Activity of the Stomach in Health and Ulcer Disease.

    Science.gov (United States)

    Krylova, S G; Vymyatnina, Z K; Zueva, E P; Amosova, E N; Razina, T G; Litvinenko, V I

    2015-09-01

    Gastroprotective effect of Cichorium intybus L. root extract is demonstrated on H. Shay's model of experimental ulcer in rats. The effect is attributed to the antisecretory activity of the plant and stimulation of defense barrier function of the gastric mucosa. The regulatory effect of the phytocomplex on seasonal characteristics of the gastric secretory and defense functions in dogs with Basov's fistula is detected.

  9. Human eosinophils express, relative to other circulating leukocytes, large amounts of secretory 14-kD phospholipase A2

    NARCIS (Netherlands)

    Blom, M.; Tool, A. T.; Wever, P. C.; Wolbink, G. J.; Brouwer, M. C. [=Maria Clara; Calafat, J.; Egesten, A.; Knol, E. F.; Hack, C. E.; Roos, D.; Verhoeven, A. J.

    1998-01-01

    Human eosinophils perform several functions dependent on phospholipase A2 (PLA2) activity, most notably the synthesis of platelet-activating factor (PAF) and leukotriene C4 (LTC4). Several forms of PLA2 have been identified in mammalian cells. In the present study, the 14-kD, secretory form of PLA2

  10. Intractable secretory diarrhea in a Japanese boy with mitochondrial respiratory chain complex I deficiency.

    Science.gov (United States)

    Murayama, Kei; Nagasaka, Hironori; Tsuruoka, Tomoko; Omata, Yuko; Horie, Hiroshi; Tregoning, Simone; Thorburn, David R; Takayanagi, Masaki; Ohtake, Akira

    2009-03-01

    The etiology of secretory diarrhea in early life is often unclear. We report a Japanese boy who survived until 3 years of age, despite intractable diarrhea commencing soon after birth. The fecal sodium content was strikingly high (109 mmol/L [normal range, 27-35 mmol/L]) and the osmotic gap was decreased (15 mOsm/kg), consistent with the findings of congenital sodium diarrhea. We examined the mitochondrial respiratory chain function by blue native polyacrylamide gel electrophoresis (BN-PAGE) in-gel enzyme staining, BN-PAGE western blotting, respiratory chain enzyme activity assay, and immunohistochemistry. Liver respiratory chain complex (Co) I activity was undetectable, while other respiratory chain complex activities were increased (Co II, 138%; Co III, 153%; Co IV, 126% versus respective control activities). Liver BN-PAGE in-gel enzyme staining and western blotting showed an extremely weak complex I band, while immunohistochemistry showed extremely weak staining for the 30-kDa subunit of complex I, but normal staining for the 70-kDa subunit of complex II. The patient was, therefore, diagnosed with complex I deficiency. The overall complex I activity of the jejunum was substantially decreased (63% of the control activity). The immunohistochemistry displayed apparently decreased staining of the 30-kDa complex I subunit, together with a slightly enhanced staining of the 70-kDa complex II subunit in intestinal epithelial cells. These data imply that intestinal epithelial cells are also complex I-deficient in this patient. Complex I deficiency is a novel cause of secretory diarrhea and may act via disrupting the supply of adenosine triphosphate (ATP) needed for the maintenance of ion gradients across membranes.

  11. Human Secretory IgM Antibodies Activate Human Complement and Offer Protection at Mucosal Surface.

    Science.gov (United States)

    Michaelsen, T E; Emilsen, S; Sandin, R H; Granerud, B K; Bratlie, D; Ihle, O; Sandlie, I

    2017-01-01

    IgM molecules circulate in serum as large polymers, mainly pentamers, which can be transported by the poly-Ig receptor (pIgR) across epithelial cells to mucosal surfaces and released as secretory IgM (SIgM). The mucosal SIgM molecules have non-covalently attached secretory component (SC), which is the extracellular part of pIgR which is cleaved from the epithelial cell membrane. Serum IgM antibodies do not contain SC and have previously been shown to make a conformational change from 'a star' to a 'staple' conformation upon reaction with antigens on a cell surface, enabling them to activate complement. However, it is not clear whether SIgM similarly can induce complement activation. To clarify this issue, we constructed recombinant chimeric (mouse/human) IgM antibodies against hapten 5-iodo-4-hydroxy-3-nitro-phenacetyl (NIP) and in addition studied polyclonal IgM formed after immunization with a meningococcal group B vaccine. The monoclonal and polyclonal IgM molecules were purified by affinity chromatography on a column containing human SC in order to isolate joining-chain (J-chain) containing IgM, followed by addition of excess amounts of soluble SC to create SIgM (IgM J+ SC+). These SIgM preparations were tested for complement activation ability and shown to be nearly as active as the parental IgM J+ molecules. Thus, SIgM may offer protection against pathogens at mucosal surface by complement-mediated cell lysis or by phagocytosis mediated by complement receptors present on effector cells on mucosa. © 2016 The Foundation for the Scandinavian Journal of Immunology.

  12. Unprecedented multiplicity of Ig transmembrane and secretory mRNA forms in the cartilaginous fish.

    Science.gov (United States)

    Rumfelt, Lynn L; Diaz, Marilyn; Lohr, Rebecca L; Mochon, Evonne; Flajnik, Martin F

    2004-07-15

    In most jawed vertebrates including cartilaginous fish, membrane-bound IgM is expressed as a five Ig superfamily (Igsf)-domain H chain attached to a transmembrane (Tm) region. Heretofore, bony fish IgM was the one exception with IgM mRNA spliced to produce a four-domain Tm H chain. We now demonstrate that the Tm and secretory (Sec) mRNAs of the novel cartilaginous fish Ig isotypes, IgW and IgNAR, are present in multiple forms, most likely generated by alternative splicing. In the nurse shark, Ginglymostoma cirratum, and horn shark, Heterodontus francisci, alternative splicing of Tm exons to the second or the fourth constant (C(H)) exons produces two distinct IgW Tm cDNAs. Although the seven-domain IgW Sec cDNA form contains a canonical secretory tail shared with IgM, IgNAR, and IgA, we report a three-domain cDNA form of shark IgW (IgW(short)) having an unusual Sec tail, which is orthologous to skate IgX(short) cDNA. The IgW and IgW(short) Sec transcripts are restricted in their tissue distribution and expression levels vary among individual sharks, with all forms expressed early in ontogeny. IgNAR mRNA is alternatively spliced to produce a truncated four-domain Tm cDNA and a second Tm cDNA is expressed identical in Igsf domains as the Sec form. PBL is enriched in the Tm cDNA of these Igs. These molecular data suggest that cartilaginous fish have augmented their humoral immune repertoire by diversifying the sizes of their Ig isotypes. Furthermore, these Tm cDNAs are prototypical and the truncated variants may translate as more stable protein at the cell surface.

  13. Protein secretory patterns of rat Sertoli and peritubular cells are influenced by culture conditions

    International Nuclear Information System (INIS)

    Kierszenbaum, A.L.; Crowell, J.A.; Shabanowitz, R.B.; DePhilip, R.M.; Tres, L.L.

    1986-01-01

    An approach combining two-dimensional gel electrophoresis and autoradiography was used to correlate patterns of secretory proteins in cultures of Sertoli and peritubular cells with those observed in the incubation medium from segments of seminiferous tubules. Sertoli cells in culture and in seminiferous tubules secreted three proteins designated S70 (Mr 72,000-70,000), S45 (Mr 45,000), and S35 (Mr 35,000). Cultured Sertoli and peritubular cells and incubated seminiferous tubules secreted two proteins designated SP1 (Mr 42,000) and SP2 (Mr 50,000). SP1 and S45 have similar Mr but differ from each other in isoelectric point (pI). Cultured peritubular cells secreted a protein designated P40 (Mr 40,000) that was also seen in intact seminiferous tubules but not in seminiferous tubules lacking the peritubular cell wall. However, a large number of high-Mr proteins were observed only in the medium of cultured peritubular cells but not in the incubation medium of intact seminiferous tubules. Culture conditions influence the morphology and patterns of protein secretion of cultured peritubular cells. Peritubular cells that display a flat-stellate shape transition when placed in culture medium free of serum (with or without hormones and growth factors), accumulate various proteins in the medium that are less apparent when these cells are maintained in medium supplemented with serum. Two secretory proteins stimulated by follicle-stimulating hormone (FSH) (designated SCm1 and SCm2) previously found in the medium of cultured Sertoli cells, were also observed in the incubation medium of seminiferous tubular segments stimulated by FSH. Results of this study show that, although cultured Sertoli and peritubular cells synthesize and secrete proteins also observed in segments of incubated seminiferous tubules anther group of proteins lacks seminiferous tubular correlates

  14. Distorted secretory granule composition in mast cells with multiple protease deficiency.

    Science.gov (United States)

    Grujic, Mirjana; Calounova, Gabriela; Eriksson, Inger; Feyerabend, Thorsten; Rodewald, Hans-Reimer; Tchougounova, Elena; Kjellén, Lena; Pejler, Gunnar

    2013-10-01

    Mast cells are characterized by an abundance of secretory granules densely packed with inflammatory mediators such as bioactive amines, cytokines, serglycin proteoglycans with negatively charged glycosaminoglycan side chains of either heparin or chondroitin sulfate type, and large amounts of positively charged proteases. Despite the large biological impact of mast cell granules and their contents on various pathologies, the mechanisms that regulate granule composition are incompletely understood. In this study, we hypothesized that granule composition is dependent on a dynamic electrostatic interrelationship between different granule compounds. As a tool to evaluate this possibility, we generated mice in which mast cells are multideficient in a panel of positively charged proteases: the chymase mouse mast cell protease-4, the tryptase mouse mast cell protease-6, and carboxypeptidase A3. Through a posttranslational effect, mast cells from these mice additionally lack mouse mast cell protease-5 protein. Mast cells from mice deficient in individual proteases showed normal morphology. In contrast, mast cells with combined protease deficiency displayed a profound distortion of granule integrity, as seen both by conventional morphological criteria and by transmission electron microscopy. An assessment of granule content revealed that the distorted granule integrity in multiprotease-deficient mast cells was associated with a profound reduction of highly negatively charged heparin, whereas no reduction in chondroitin sulfate storage was observed. Taken together with previous findings showing that the storage of basic proteases conversely is regulated by anionic proteoglycans, these data suggest that secretory granule composition in mast cells is dependent on a dynamic interrelationship between granule compounds of opposite electrical charge.

  15. Virtual analysis of structurally diverse synthetic analogs as inhibitors of snake venom secretory phospholipase A2.

    Science.gov (United States)

    Sivaramakrishnan, V; Ilamathi, M; Ghosh, K S; Sathish, S; Gowda, T V; Vishwanath, B S; Rangappa, K S; Dhananjaya, B L

    2016-01-01

    Due to the toxic pathophysiological role of snake venom phospholipase A2 (PLA2 ), its compelling limitations to anti-venom therapy in humans and the need for alternative therapy foster considerable pharmacological interest towards search of PLA2 specific inhibitors. In this study, an integrated approach involving homology modeling, molecular dynamics and molecular docking studies on VRV-PL-V (Vipera russellii venom phospholipase A2 fraction-V) belonging to Group II-B secretory PLA2 from Daboia russelli pulchella is carried out in order to study the structure-based inhibitor design. The accuracy of the model was validated using multiple computational approaches. The molecular docking study of this protein was undertaken using different classes of experimentally proven, structurally diverse synthetic inhibitors of secretory PLA2 whose selection is based on IC50 value that ranges from 25 μM to 100 μM. Estimation of protein-ligand contacts by docking analysis sheds light on the importance of His 47 and Asp 48 within the VRV-PL-V binding pocket as key residue for hydrogen bond interaction with ligands. Our virtual analysis revealed that compounds with different scaffold binds to the same active site region. ADME analysis was also further performed to filter and identify the best potential specific inhibitor against VRV-PL-V. Additionally, the e-pharmacophore was generated for the best potential specific inhibitor against VRV-PL-V and reported here. The present study should therefore play a guiding role in the experimental design of VRV-PL-V inhibitors that may provide better therapeutic molecular models for PLA2 recognition and anti-ophidian activity. Copyright © 2015 John Wiley & Sons, Ltd.

  16. A two-hybrid assay to study protein interactions within the secretory pathway.

    Directory of Open Access Journals (Sweden)

    Danielle H Dube

    Full Text Available Interactions of transcriptional activators are difficult to study using transcription-based two-hybrid assays due to potent activation resulting in false positives. Here we report the development of the Golgi two-hybrid (G2H, a method that interrogates protein interactions within the Golgi, where transcriptional activators can be assayed with negligible background. The G2H relies on cell surface glycosylation to report extracellularly on protein-protein interactions occurring within the secretory pathway. In the G2H, protein pairs are fused to modular domains of the reporter glycosyltransferase, Och1p, and proper cell wall formation due to Och1p activity is observed only when a pair of proteins interacts. Cells containing interacting protein pairs are identified by selectable phenotypes associated with Och1p activity and proper cell wall formation: cells that have interacting proteins grow under selective conditions and display weak wheat germ agglutinin (WGA binding by flow cytometry, whereas cells that lack interacting proteins display stunted growth and strong WGA binding. Using this assay, we detected the interaction between transcription factor MyoD and its binding partner Id2. Interfering mutations along the MyoD:Id2 interaction interface ablated signal in the G2H assay. Furthermore, we used the G2H to detect interactions of the activation domain of Gal4p with a variety of binding partners. Finally, selective conditions were used to enrich for cells encoding interacting partners. The G2H detects protein-protein interactions that cannot be identified via traditional two-hybrid methods and should be broadly useful for probing previously inaccessible subsets of the interactome, including transcriptional activators and proteins that traffic through the secretory pathway.

  17. Diagnostic potential of low molecular weight excretory secretory proteins of Paramphistomum epiclitum for caprine amphistomosis.

    Science.gov (United States)

    Jaiswal, Amit Kumar; Shanker, Daya; Sudan, Vikrant; Singh, Amit

    2018-06-15

    In the present study, the 75% alcoholic fractionation of excretory-secretory (ES) antigen isolated from 200 to 300 live P. epiclitum was assessed for its diagnostic potential for the detection of caprine amphistomosis by using antibody detection enzyme immunoassay. Prior to enzyme immunoassay, 75% alcoholic fractionation of excretory-secretory (ES) antigen was subjected to SDS- PAGE and western blot analysis for the presence of immunoreactive polypeptides. SDS-PAGE analysis of ES antigen resolved a total 7 polypeptides bands of size 56, 27, 25, 22.5, 12, 11 and 10 kDa. Western blot analysis revealed only two immunoreactive polypeptides (11 kDa and 12 kDa) when polypeptides resolved in SDS-PAGE were probed with known positive pooled serum. None of the polypeptides showed reactions with pooled known negative serum. The working dilutions of antigen, sera and conjugates were determined by checkerboard titration for employing ELISA and cut-off O.D. was calculated 0.616 by using the mean absorbance value of 11 negative kid sera. The sensitivity and specificity of ELISA was found to be 100% and 86.76%, respectively. As per kappa value estimation, the strength of agreement was found to be good. Antibodies to 75% alcoholic fractionation of ES antigen was detected in 20% goats (n = 160) of either sex, although faecal examination detected 10.6% goats to be infected with amphistomosis. The study confirmed that 75% alcoholic fractionation of ES antigen of P. epiclitum based ELISA had good value for serodiagnosis of caprine amphistomosis. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Complete normal ordering 1: Foundations

    Directory of Open Access Journals (Sweden)

    John Ellis

    2016-08-01

    Full Text Available We introduce a new prescription for quantising scalar field theories (in generic spacetime dimension and background perturbatively around a true minimum of the full quantum effective action, which is to ‘complete normal order’ the bare action of interest. When the true vacuum of the theory is located at zero field value, the key property of this prescription is the automatic cancellation, to any finite order in perturbation theory, of all tadpole and, more generally, all ‘cephalopod’ Feynman diagrams. The latter are connected diagrams that can be disconnected into two pieces by cutting one internal vertex, with either one or both pieces free from external lines. In addition, this procedure of ‘complete normal ordering’ (which is an extension of the standard field theory definition of normal ordering reduces by a substantial factor the number of Feynman diagrams to be calculated at any given loop order. We illustrate explicitly the complete normal ordering procedure and the cancellation of cephalopod diagrams in scalar field theories with non-derivative interactions, and by using a point splitting ‘trick’ we extend this result to theories with derivative interactions, such as those appearing as non-linear σ-models in the world-sheet formulation of string theory. We focus here on theories with trivial vacua, generalising the discussion to non-trivial vacua in a follow-up paper.

  19. General topology

    CERN Document Server

    Willard, Stephen

    2004-01-01

    Among the best available reference introductions to general topology, this volume is appropriate for advanced undergraduate and beginning graduate students. Its treatment encompasses two broad areas of topology: ""continuous topology,"" represented by sections on convergence, compactness, metrization and complete metric spaces, uniform spaces, and function spaces; and ""geometric topology,"" covered by nine sections on connectivity properties, topological characterization theorems, and homotopy theory. Many standard spaces are introduced in the related problems that accompany each section (340

  20. Complete pancreas traumatic transsection

    Directory of Open Access Journals (Sweden)

    H. Hodžić

    2005-02-01

    Full Text Available This report presents a case of a twenty-year old male with complete pancreas breakdown in the middle of its corpus, which was caused by a strong abdomen compression, with injuries of the spleen, the firstjejunumcurve,mesocolon transversum, left kidney, and appereance of retroperitoneal haemathoma. Surgical treatment started 70 minutes after the injury. The treatment consisted of left pancreatectomy with previous spleenectomy, haemostasis of ruptured mesocolon transversum blood vessels, left kidney exploration, suturing of the firstjejunumcurvelession and double abdomen drainage. Posttraumatic pancreatitis which appeared on the second postoperative day and prolonged drain secretion were successfully solved by conservative treatment.

  1. Complete rerouting protection

    DEFF Research Database (Denmark)

    Stidsen, Thomas K.; Kjærulff, Peter

    2006-01-01

    Protection of communication against network failures is becoming increasingly important and in this paper we present the most capacity efficient protection method possible, the complete rerouting protection method, when requiring that all communication should be restored in case of a single link...... network failure. We present a linear programming model of the protection method and a column generation algorithm. For 6 real world networks, the minimal restoration overbuild network capacity is between 13% and 78%. We further study the importance of the density of the network, derive analytical bounds...

  2. Completion of treatment planning

    International Nuclear Information System (INIS)

    Lief, Eugene

    2008-01-01

    The outline of the lecture included the following topics: entering prescription; plan printout; print and transfer DDR; segment BEV; export to R and V; physician approval; and second check. Considerable attention, analysis and discussion. The summary is as follows: Treatment planning completion is a very responsible process which requires maximum attention; Should be independently checked by the planner, physicist, radiation oncologist and a therapist; Should not be done in a last minute rush; Proper communication between team members; Properly set procedure should prevent propagation of an error by one individual to the treatment: the error should be caught by somebody else. (P.A.)

  3. TestComplete cookbook

    CERN Document Server

    Alpaev, Gennadiy

    2013-01-01

    A practical cookbook, with a perfect package of simple, medium, and advanced recipes targeted at basic programmers as well as expert software testers, who will learn to create, manage, and run automated tests. It is packed with problem-solving recipes that are supported by simple examples.If you are a software tester or a programmer who is involved with testing automation using TestComplete, this book is ideal for you! You will be introduced to the very basics of using the tool, as well as polish any previously gained knowledge in using the tool. If you are already aware of programming basics,

  4. Complete atrioventricular canal.

    Science.gov (United States)

    Calabrò, Raffaele; Limongelli, Giuseppe

    2006-04-05

    Complete atrioventricular canal (CAVC), also referred to as complete atrioventricular septal defect, is characterised by an ostium primum atrial septal defect, a common atrioventricular valve and a variable deficiency of the ventricular septum inflow. CAVC is an uncommon congenital heart disease, accounting for about 3% of cardiac malformations. Atrioventricular canal occurs in two out of every 10,000 live births. Both sexes are equally affected and a striking association with Down syndrome was found. Depending on the morphology of the superior leaflet of the common atrioventricular valve, 3 types of CAVC have been delineated (type A, B and C, according to Rastelli's classification). CAVC results in a significant interatrial and interventricular systemic-to-pulmonary shunt, thus inducing right ventricular pressure and volume overload and pulmonary hypertension. It becomes symptomatic in infancy due to congestive heart failure and failure to thrive. Diagnosis of CAVC might be suspected from electrocardiographic and chest X-ray findings. Echocardiography confirms it and gives anatomical details. Over time, pulmonary hypertension becomes irreversible, thus precluding the surgical therapy. This is the reason why cardiac catheterisation is not mandatory in infants (less than 6 months) but is indicated in older patients if irreversible pulmonary hypertension is suspected. Medical treatment (digitalis, diuretics, vasodilators) plays a role only as a bridge toward surgery, usually performed between the 3rd and 6th month of life.

  5. Complete atrioventricular canal

    Directory of Open Access Journals (Sweden)

    Limongelli Giuseppe

    2006-04-01

    Full Text Available Abstract Complete atrioventricular canal (CAVC, also referred to as complete atrioventricular septal defect, is characterised by an ostium primum atrial septal defect, a common atrioventricular valve and a variable deficiency of the ventricular septum inflow. CAVC is an uncommon congenital heart disease, accounting for about 3% of cardiac malformations. Atrioventricular canal occurs in two out of every 10,000 live births. Both sexes are equally affected and a striking association with Down syndrome was found. Depending on the morphology of the superior leaflet of the common atrioventricular valve, 3 types of CAVC have been delineated (type A, B and C, according to Rastelli's classification. CAVC results in a significant interatrial and interventricular systemic-to-pulmonary shunt, thus inducing right ventricular pressure and volume overload and pulmonary hypertension. It becomes symptomatic in infancy due to congestive heart failure and failure to thrive. Diagnosis of CAVC might be suspected from electrocardiographic and chest X-ray findings. Echocardiography confirms it and gives anatomical details. Over time, pulmonary hypertension becomes irreversible, thus precluding the surgical therapy. This is the reason why cardiac catheterisation is not mandatory in infants (less than 6 months but is indicated in older patients if irreversible pulmonary hypertension is suspected. Medical treatment (digitalis, diuretics, vasodilators plays a role only as a bridge toward surgery, usually performed between the 3rd and 6th month of life.

  6. Barnett shale completions

    Energy Technology Data Exchange (ETDEWEB)

    Schein, G. [BJ Services, Dallas, TX (United States)

    2006-07-01

    Fractured shales yield oil and gas in various basins across the United States. A map indicating these fractured shale source-reservoir systems in the United States was presented along with the numerous similarities and differences that exist among these systems. Hydrocarbons in the organic rich black shale come from the bacterial decomposition of organic matter, primary thermogenic decomposition of organic matter or secondary thermogenic cracking of oil. The shale may be the reservoir or other horizons may be the primary or secondary reservoir. The reservoir has induced micro fractures or tectonic fractures. This paper described the well completions in the Barnett Shale in north Texas with reference to major players, reservoir properties, mineralogy, fluid sensitivity, previous treatments, design criteria and production examples. The Barnett Shale is an organic, black shale with thickness ranging from 100 to 1000 feet. The total organic carbon (TOC) averages 4.5 per cent. The unit has undergone high rate frac treatments. A review of the vertical wells in the Barnett Shale was presented along with the fracture treatment schedule and technology changes. A discussion of refracturing opportunities and proppant settling and transport revealed that additional proppant increases fluid recovery and enhances production. Compatible scale inhibitors and biocides can be beneficial. Horizontal completions in the Barnett Shale have shown better results than vertical wells, as demonstrated in a production comparison of 3 major horizontal wells in the basin. tabs., figs.

  7. On characterizations of quasi-metric completeness

    Energy Technology Data Exchange (ETDEWEB)

    Dag, H.; Romaguera, S.; Tirado, P.

    2017-07-01

    Hu proved in [4] that a metric space (X, d) is complete if and only if for any closed subspace C of (X, d), every Banach contraction on C has fixed point. Since then several authors have investigated the problem of characterizing the metric completeness by means of fixed point theorems. Recently this problem has been studied in the more general context of quasi-metric spaces for different notions of completeness. Here we present a characterization of a kind of completeness for quasi-metric spaces by means of a quasi-metric versions of Hu’s theorem. (Author)

  8. GOGOL: ACADEMIC AND COMPLETE

    Directory of Open Access Journals (Sweden)

    Yuri V. Mann

    2016-12-01

    Full Text Available The ever-increasing international interest to Gogol explains the necessity of publishing a new edition of his works. The present Complete Collection of Gogol’s Works and Letters is an academic edition prepared and published by the A. M. Gorky Institute of World Literature of the Russian Academy of Sciences. It draws on rich experience of studying and publishing Gogol’s heritage in Russia but at the same time questions and underscores Gogol’s relevance for the modern reader and his place in the world culture of our time. It intends to fill in the gaps left by the previous scholarly tradition that failed to recognize some of Gogol’s texts as part of his heritage. Such are, for example, dedicatory descriptions in books and business notes. The present edition accounts not only for the completeness of texts but also for their place within the body of Gogol’s work, as part of his life-long creative process. By counterpoising different editions, it attempts to trace down the dynamics of Gogol’s creative thought while at the same time underscores the autonomy and relevance of each period in his career. For example, this collection publishes two different versions (editions of the same work: while the most recent version has become canonical at the expense of the preceding one, the latter still preserves its meaning and historical relevance. The present edition has the advantage over its predecessors since it has an actual, physical opportunity to erase the gaps, e.g. to publish the hitherto unpublished texts. However, the editors realize that new, hitherto unknown gaps may appear and the present edition will become, in its turn, outdated. At this point, there will be a necessity in the new edition.

  9. Early events of secretory granule formation in the rat parotid acinar cell under the influence of isoproterenol. An ultrastructural and lectin cytochemical study

    Directory of Open Access Journals (Sweden)

    F D’Amico

    2009-12-01

    Full Text Available The events involved in the maturation process of acinar secretory granules of rat parotid gland were investigated ultrastructurally and cytochemically by using a battery of four lectins [Triticum vulgaris agglutinin (WGA, Ulex europaeus agglutinin I (UEA-I, Glycine max agglutinin (SBA, Arachys hypogaea agglutinin (PNA]. In order to facilitate the study, parotid glands were chronically stimulated with isoproterenol to induce secretion. Specimens were embedded in the Lowicryl K4M resin. The trans-Golgi network (TGN derived secretory granules, which we refer to as immature secretory granules, were found to be intermediate structures in the biogenesis process of the secretory granules in the rat parotid acinar cell. These early structures do not seem to be the immediate precursor of the mature secretory granules: in fact, a subsequent interaction process between these early immature granule forms and TGN elements seems to occur, leading, finally, to the mature granules. These findings could explain the origin of the polymorphic subpopulations of the secretory granules in the normal acinar cells of the rat parotid gland. The lectin staining patterns were characteristic of each lectin. Immature and mature secretory gran- ules were labelled with WGA, SBA, PNA, and lightly with UEA-I. Cis and intermediate cisternae of the Golgi apparatus were labelled with WGA, and trans cisternae with WGA and SBA.

  10. Speed Controls in Translating Secretory Proteins in Eukaryotes - an Evolutionary Perspective

    Science.gov (United States)

    Mahlab, Shelly; Linial, Michal

    2014-01-01

    Protein translation is the most expensive operation in dividing cells from bacteria to humans. Therefore, managing the speed and allocation of resources is subject to tight control. From bacteria to humans, clusters of relatively rare tRNA codons at the N′-terminal of mRNAs have been implicated in attenuating the process of ribosome allocation, and consequently the translation rate in a broad range of organisms. The current interpretation of “slow” tRNA codons does not distinguish between protein translations mediated by free- or endoplasmic reticulum (ER)-bound ribosomes. We demonstrate that proteins translated by free- or ER-bound ribosomes exhibit different overall properties in terms of their translation efficiency and speed in yeast, fly, plant, worm, bovine and human. We note that only secreted or membranous proteins with a Signal peptide (SP) are specified by segments of “slow” tRNA at the N′-terminal, followed by abundant codons that are considered “fast.” Such profiles apply to 3100 proteins of the human proteome that are composed of secreted and signal peptide (SP)-assisted membranous proteins. Remarkably, the bulks of the proteins (12,000), or membranous proteins lacking SP (3400), do not have such a pattern. Alternation of “fast” and “slow” codons was found also in proteins that translocate to mitochondria through transit peptides (TP). The differential clusters of tRNA adapted codons is not restricted to the N′-terminal of transcripts. Specifically, Glycosylphosphatidylinositol (GPI)-anchored proteins are unified by clusters of low adapted tRNAs codons at the C′-termini. Furthermore, selection of amino acids types and specific codons was shown as the driving force which establishes the translation demands for the secretory proteome. We postulate that “hard-coded” signals within the secretory proteome assist the steps of protein maturation and folding. Specifically, “speed control” signals for delaying the translation

  11. Host Immune Selection of Rumen Bacteria through Salivary Secretory IgA

    Directory of Open Access Journals (Sweden)

    Janelle M. Fouhse

    2017-05-01

    Full Text Available The rumen microbiome is integral to efficient production in cattle and shows strong host specificity, yet little is known about what host factors shape rumen microbial composition. Secretory immunoglobulin A (SIgA is produced in large amounts in the saliva, can coat both commensal and pathogenic microbes within the gut, and presents a plausible mechanism of host specificity. However, the role salivary SIgA plays in commensal bacteria selection in ruminants remains elusive. The main objectives of this study were to develop an immuno-affinity benchtop method to isolate SIgA-tagged microbiota and to determine if salivary SIgA preferentially binds selected bacteria. We hypothesized that SIgA-tagged bacteria would differ from total bacteria, thus supporting a potential host-derived mechanism in commensal bacterial selection. Whole rumen (n = 9 and oral secretion samples (n = 10 were incubated with magnetic beads conjugated with anti-secretory IgA antibodies to enrich SIgA-tagged microbiota. Microbial DNA from the oral secretion, whole rumen, SIgA-tagged oral secretion, and SIgA-tagged rumen was isolated for amplicon sequencing of V1–V3 region of 16S rDNA genes. Whole rumen and oral secretion had distinctive (P < 0.05 bacterial compositions indicated by the non-parametric multidimensional scaling plot using Euclidean distance metrics. The SIgA-tagged microbiota from rumen and oral secretion had similar abundance of Bacteroidetes, Actinobacteria, Fibrobacter, candidate phyla TM7, and Tenericutes and are clustered tightly. Composition of SIgA-tagged oral secretion microbiota was more similar to whole rumen microbiota than whole oral secretion due to enrichment of rumen bacteria (Lachnospiraceae and depletion of oral taxa (Streptococcus, Rothia, Neisseriaceae, and Lactobacillales. In conclusion, SIgA-tagged oral secretion microbiota had an increased resemblance to whole rumen microbiota, suggesting salivary SIgA-coating may be one host

  12. Interrelation secretory activity of stomach and immunes changes of peripheral blood when ulcerogenesis stomach.

    Science.gov (United States)

    Matveeva, L V; Mosina, L M

    2016-01-01

    Incidence of gastric ulcer is high in almost all countries of the world. On the development and course of the disease affect the state acid- and enzymes production stomach, immune status. The purpose was to determine the presence and power of correlative links secretory activity of the stomach and immune changes in the peripheral blood during exacerbation of ulcer disease stomach. Surveyed in obtaining informed consent 42 patients with gastric ulcer in the acute phase prior to the eradication and antisecretory therapy and 40 healthy volunteers. On the state of function acid- and enzymes production of the gastric mucosa judged by the results of a 2-hour intragastric pH-metry and serum concentration pepsinogen, gastrin before the start of active treatment. Immunophenotype lymphocytes on CD-antigens (CD3, CD4, CD8, CD16, CD19, CD45, CD56) was measured by immunofluorescence, levels immunoglobulin isotype M, G, A, E - ELISA method. When short-term intragastric pH-metry of the stomach hyperacidity patients recorded 6.7 times more likely than healthy, normacidity - 12.3 times less. Reduction of acid production was observed up to 8.6 times more, indicating the development of mucosal atrophy. Basal pH in the antrum was lower by 54.5% than in the control group, with stimulation increased by 33.6%, but remained lower than the values of healthy individuals by 48.7%. When ELISA amount pepsinogen patients showed significant increase in serum levels of PG-I relative to the control group at 33.4%, PG-II - 52%. In assessing the immune status of patients were identified changes in system phagocytes, cellular and humoral links, most pronounced for severe current peptic ulcer disease. The results indicate the presence of positive and negative correlative links mild to moderate force between indicators of secretory activity of gastric mucosal innate and adaptive immunity in patients with acute exacerbation of peptic ulcer disease. The presence and nature of these relationships should

  13. Self Completeness of Einstein Gravity

    CERN Document Server

    Dvali, Gia

    2010-01-01

    We argue, that in Einsteinian gravity the Planck length is the shortest length of nature, and any attempt of resolving trans-Planckian physics bounces back to macroscopic distances due to black hole formation. In Einstein gravity trans-Planckian propagating quantum degrees of freedom cannot exist, instead they are equivalent to the classical black holes that are fully described by lighter infra-red degrees of freedom and give exponentially-soft contribution into the virtual processes. Based on this property we argue that pure-Einstein (super)gravity and its high-dimensional generalizations are self-complete in deep-UV, but not in standard Wilsonian sense. We suggest that certain strong-coupling limit of string theory is built-in in pure Einstein gravity, whereas the role of weakly-coupled string theory limit is to consistently couple gravity to other particle species, with their number being set by the inverse string coupling. We also discuss some speculative ideas generalizing the notion of non-Wilsonian sel...

  14. Generalized Superconductivity. Generalized Levitation

    International Nuclear Information System (INIS)

    Ciobanu, B.; Agop, M.

    2004-01-01

    In the recent papers, the gravitational superconductivity is described. We introduce the concept of generalized superconductivity observing that any nongeodesic motion and, in particular, the motion in an electromagnetic field, can be transformed in a geodesic motion by a suitable choice of the connection. In the present paper, the gravitoelectromagnetic London equations have been obtained from the generalized Helmholtz vortex theorem using the generalized local equivalence principle. In this context, the gravitoelectromagnetic Meissner effect and, implicitly, the gravitoelectromagnetic levitation are given. (authors)

  15. THE PRESENCE OF ADENOID VEGETATIONS AND NASAL SPEECH, AND HEARING LOSS IN RELATION TO SECRETORY OTITIS MEDIA

    Directory of Open Access Journals (Sweden)

    Gabriela KOPACHEVA

    2004-12-01

    Full Text Available This study presents the treatment of 68 children with secretory otitis media. Children underwent adenoid vegetations, nasal speech, conductive hearing loss, ventilation disturbance in Eustachian tube. In all children adenoidectomy was indicated.38 boys and 30 girls at the age of 3-17 were divided in two main groups: * 29 children without hypertrophic (enlarged adenoids, * 39 children with enlarged (hypertrophic adenoids.The surgical treatment included insertion of ventilation tubes and adenoidectomy where there where hypertrophic adenoids.Clinical material was analyzed according to hearing threshold, hearing level, middle ear condition estimated by pure tone audiometry and tympanometry before and after treatment. Data concerning both groups were compared.The results indicated that adenoidectomy combined with the ventilation tubes facilitates secretory otitis media heeling as well as decrease of hearing impairments. That enables prompt restoration of the hearing function as an important precondition for development of the language, social, emotional and academic development of children.

  16. Deletion of glutamate dehydrogenase in beta-cells abolishes part of the insulin secretory response not required for glucose homeostasis

    DEFF Research Database (Denmark)

    Carobbio, Stefania; Frigerio, Francesca; Rubi, Blanca

    2009-01-01

    Insulin exocytosis is regulated in pancreatic ss-cells by a cascade of intracellular signals translating glucose levels into corresponding secretory responses. The mitochondrial enzyme glutamate dehydrogenase (GDH) is regarded as a major player in this process, although its abrogation has not been...... tested yet in animal models. Here, we generated transgenic mice, named betaGlud1(-/-), with ss-cell-specific GDH deletion. Our results show that GDH plays an essential role in the full development of the insulin secretory response. In situ pancreatic perfusion revealed that glucose-stimulated insulin...... secretion was reduced by 37% in betaGlud1(-/-). Furthermore, isolated islets with either constitutive or acute adenovirus-mediated knock-out of GDH showed a 49 and 38% reduction in glucose-induced insulin release, respectively. Adenovirus-mediated re-expression of GDH in betaGlud1(-/-) islets fully restored...

  17. Secretory products from thrombin-stimulated human platelets exert an inhibitory effect on NK-cytotoxic activity

    DEFF Research Database (Denmark)

    Skov Madsen, P; Hokland, P; Hokland, M

    1987-01-01

    We have investigated the interaction between human platelets and the NK-system, with special emphasis on the action of secretory products from platelets in an NK assay with 51Cr-labelled K562 as target cells. Supernatants from thrombin-stimulated platelets added to the NK assay consistently...... decreased the NK-cytotoxicity by 40% +/- 4.3%, indicating the existence of secreted products from platelets as a source of NK-inhibiting substances. In contrast, no direct cytotoxic effect of these secretory products on the target cells (K562) was seen. Thus, normal human platelets, when stimulated...... with thrombin, are capable of secreting different, yet undefined factors, which significantly inhibit NK activity in vitro. The results also suggest that the role of products from contaminating in vitro activated platelets should be borne in mind when performing conventional NK assays. Udgivelsesdato: 1986-Oct...

  18. Synthesis of sn-1 functionalized phospholipids as substrates for secretory phospholipase A2

    DEFF Research Database (Denmark)

    Linderoth, Lars; Peters, Günther H.J.; Jørgensen, K.

    2007-01-01

    Secretory phospholipase A2 (sPLA2) represents a family of small water-soluble enzymes that catalyze the hydrolysis of phospholipids in the sn-2 position liberating free fatty acids and lysophospholipids. Herein we report the synthesis of two new phospholipids (1 and 2) with bulky allyl-substituen......Secretory phospholipase A2 (sPLA2) represents a family of small water-soluble enzymes that catalyze the hydrolysis of phospholipids in the sn-2 position liberating free fatty acids and lysophospholipids. Herein we report the synthesis of two new phospholipids (1 and 2) with bulky allyl...... of the allyl-substituents by a zinc mediated allylation. Small unilamellar liposomes composed of phospholipids 1 and 2 were subjected to sPLA2 activity measurements. Our results show that only phospholipid 1 is hydrolyzed by the enzyme. Molecular dynamics simulations revealed that the lack of hydrolysis...

  19. Implicational (semilinear) logics III: completeness properties

    Czech Academy of Sciences Publication Activity Database

    Cintula, Petr; Noguera, Carles

    2018-01-01

    Roč. 57, 3-4 (2018), s. 391-420 ISSN 0933-5846 R&D Projects: GA ČR GA13-14654S EU Projects: European Commission(XE) 689176 - SYSMICS Institutional support: RVO:67985807 ; RVO:67985556 Keywords : abstract algebraic logic * protoalgebraic logics * implicational logics * disjunctional logics * semilinear logics * non-classical logics * completeness theorems * rational completeness Subject RIV: BA - General Mathematics; BA - General Mathematics (UTIA-B) OBOR OECD: Computer science s, information science , bioinformathics (hardware development to be 2.2, social aspect to be 5.8) Impact factor: 0.394, year: 2016

  20. Implicational (semilinear) logics III: completeness properties

    Czech Academy of Sciences Publication Activity Database

    Cintula, Petr; Noguera, Carles

    2018-01-01

    Roč. 57, 3-4 (2018), s. 391-420 ISSN 0933-5846 R&D Projects: GA ČR GA13-14654S EU Projects: European Commission(XE) 689176 - SYSMICS Institutional support: RVO:67985807 ; RVO:67985556 Keywords : abstract algebraic logic * protoalgebraic logics * implicational logics * disjunctional logics * semilinear logics * non-classical logics * completeness theorems * rational completeness Subject RIV: BA - General Mathematics; BA - General Mathematics (UTIA-B) OBOR OECD: Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8) Impact factor: 0.394, year: 2016

  1. Cortisol and secretory immunoglobulin A response to stress in German shepherd dogs.

    Directory of Open Access Journals (Sweden)

    Ivona Svobodová

    Full Text Available The aim of the study was to determine whether cortisol and secretory Immunoglobulin A (sIgA could be used as an indicator of acute stress in both young and adult dogs. Seventeen German shepherd puppies were exposed to the Puppy test (challenge test at the age of seven weeks. This test has been routinely used to assess the future working ability of potential police dogs. In addition, ten adult females were subjected to 4 minutes of defense training under stressful conditions. Saliva was collected from the puppies and adult females before testing and 20 minutes after the start of testing, using a cotton swab held for 1-2 minutes in each dog's mouth. Cortisol concentrations increased after the test compared to the control sample both in puppies and the adult females. However adult females showed a significant decrease in sIgA after defense training while puppies showed a tendency of increase in sIgA. We propose that salivary cortisol could be used as an indicator of stress in puppies during early ontogeny. It is not yet clear whether sIgA could be used as a useful indicator of short-term stress in dogs.

  2. Characterisation of proteolytic activity of excretory-secretory products from adult Strongylus vulgaris.

    Science.gov (United States)

    Caffrey, C R; Ryan, M F

    1994-04-01

    An excretory-secretory (ES) preparation derived from adult Strongylus vulgaris in vitro was assessed for proteolytic activity using azocasein and synthetic, fluorogenic, peptide substrates. Fractionation was by molecular sieve fast protein liquid chromatography (molecular sieve FPLC) and resolution by gelatin-substrate sodium dodecyl sulphate-polyacrylamide gel electrophoresis (gelatin-substrate SDS-PAGE). The cysteine proteinase activator, dithiothreitol (DTT), enhanced azocaseinolysis and hydrolysis of carbobenzoxy-phenylalanyl-arginine-7-amido-4-methylcoumarin (Z-Phe-Arg-NMec) by the ES preparation and was a requirement for the detection of carbobenzoxy-arginyl-arginine-7-amido-4-methylcoumarin (Z-Arg-Arg-NMec) hydrolysis. Assays of FPLC-eluted fractions, with DTT, detected a broad peak of azocaseinolytic activity (22-24 kDa) and two peaks (24 and 18 kDa) of hydrolysis using the synthetic substrates. Hydrolysis by these peaks of Z-Phe-Arg-NMec was 50-fold greater than that of Z-Arg-Arg-NMec suggesting that their specificities are more like papain or cathepsin L rather than cathepsin B. In gelatin-substrate SDS-PAGE, DTT was required to detect proteolysis by the ES preparation which was optimal at pH 6.0 and resolved into eight bands (87-29 kDa). Cysteine proteinase inhibitors were the most effective in all assays. Collectively, these data indicate that cysteine-class proteolytic activity predominates in the ES preparation of adult S. vulgaris.

  3. Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut.

    Science.gov (United States)

    Mantis, N J; Rol, N; Corthésy, B

    2011-11-01

    Secretory IgA (SIgA) serves as the first line of defense in protecting the intestinal epithelium from enteric toxins and pathogenic microorganisms. Through a process known as immune exclusion, SIgA promotes the clearance of antigens and pathogenic microorganisms from the intestinal lumen by blocking their access to epithelial receptors, entrapping them in mucus, and facilitating their removal by peristaltic and mucociliary activities. In addition, SIgA functions in mucosal immunity and intestinal homeostasis through mechanisms that have only recently been revealed. In just the past several years, SIgA has been identified as having the capacity to directly quench bacterial virulence factors, influence composition of the intestinal microbiota by Fab-dependent and Fab-independent mechanisms, promote retro-transport of antigens across the intestinal epithelium to dendritic cell subsets in gut-associated lymphoid tissue, and, finally, to downregulate proinflammatory responses normally associated with the uptake of highly pathogenic bacteria and potentially allergenic antigens. This review summarizes the intrinsic biological activities now associated with SIgA and their relationships with immunity and intestinal homeostasis.

  4. Characterization of secretory phospholipase A₂ with phospholipase A₁ activity in tobacco, Nicotiana tabacum (L.).

    Science.gov (United States)

    Fujikawa, Yukichi; Fujikawa, Ritsuko; Iijima, Noriaki; Esaka, Muneharu

    2012-03-01

    A cDNA encoding protein with homology to plant secretory phospholipase A₂ (sPLA₂), denoted as Nt1 PLA₂, was isolated from tobacco (Nicotiana tabacum). The cDNA encodes a mature protein of 118 amino acid residues with a putative signal peptide of 29 residues. The mature form of Nt1 PLA₂ has 12 cysteines, Ca²⁺ binding loop and catalytic site domain that are commonly conserved in plant sPLA₂s. The recombinant Nt1 PLA₂ was expressed as a fusion protein with thioredoxin in E. coli BL21 cells and was purified by an ion exchange chromatography after digestion of the fusion proteins by Factor Xa protease to obtain the mature form. Interestingly, Nt1 PLA₂ could hydrolyze the ester bond at the sn-1 position of glycerophospholipids as well as at the sn-2 position, when the activities were determined using mixed-micellar phospholipids with sodium cholate. Both activities for the sn-1 and -2 positions of glycerophospholipids required Ca²⁺ essentially, and maximal activities were found in an alkaline region when phosphatidylcholine, phosphatidylglycerol or phosphatidylethanolamine was used as a substrate. The level of Nt1 PLA₂ mRNA was detected at a higher level in tobacco flowers than stem, leaves and roots, and was induced by salicylic acid.

  5. Secretory carcinoma of the breast and its histopathological mimics: value of markers for differential diagnosis.

    Science.gov (United States)

    Osako, Tomo; Takeuchi, Kengo; Horii, Rie; Iwase, Takuji; Akiyama, Futoshi

    2013-10-01

    Secretory carcinoma (SC) is a rare histological type of breast cancer, and ETV6-NTRK3 gene fusion is highly specific to it. The differential diagnoses of SC include acinic cell carcinoma (ACCA) and cystic hypersecretory carcinoma (CHC), as well as invasive ductal carcinoma (IDC). For patients with these rare but distinctive histological subtypes, SC and its histopathological mimics should be differentiated from each other. However, differential markers have not yet been assessed systematically, and we aimed to identify and evaluate novel and existing markers. We reviewed 19 cases diagnosed initially as SC using integrated diagnostic techniques, including morphology, immunohistochemistry and molecular pathology, and validated promising markers in 445 breast cancers. We reclassified 19 formerly diagnosed 'SCs' into nine SCs, three ACCAs, three CHCs, three IDCs and one microglandular adenosis. We confirmed that ETV6-NTRK3 gene rearrangement and amylase positivity are good diagnostic markers for SC and ACCA, respectively. Vacuolar staining for adipophilin, positivity for α-lactalbumin and negativity for ETV6 rearrangement are diagnostic markers for CHC. In this study, we propose a panel of four markers (ETV6 rearrangement, amylase, α-lactalbumin and adipophilin) for distinguishing SC, ACCA, CHC and IDC. This simple but robust panel will serve pathologists well as a practical guide for reaching an appropriate diagnosis. © 2013 John Wiley & Sons Ltd.

  6. Absence of E protein arrests transmissible gastroenteritis coronavirus maturation in the secretory pathway

    International Nuclear Information System (INIS)

    Ortego, Javier; Ceriani, Juan E.; Patino, Cristina; Plana, Juan; Enjuanes, Luis

    2007-01-01

    A recombinant transmissible gastroenteritis coronavirus (rTGEV) in which E gene was deleted (rTGEV-ΔE) has been engineered. This deletion mutant only grows in cells expressing E protein (E + cells) indicating that E was an essential gene for TGEV replication. Electron microscopy studies of rTGEV-ΔE infected BHK-pAPN-E - cells showed that only immature intracellular virions were assembled. These virions were non-infectious and not secreted to the extracellular medium in BHK-pAPN-E - cells. RNA and protein composition analysis by RNase-gold and immunoelectron microscopy showed that rTGEV-ΔE virions contained RNA and also all the structural TGEV proteins, except the deleted E protein. Nevertheless, full virion maturation was blocked. Studies of the rTGEV-ΔE subcellular localization by confocal and immunoelectron microscopy in infected E - cells showed that in the absence of E protein virus trafficking was arrested in the intermediate compartment. Therefore, the absence of E protein in TGEV resulted in two actions, a blockade of virus trafficking in the membranes of the secretory pathway, and prevention of full virus maturation

  7. Adult Sexual Experiences as a Mediator Between Child Abuse and Current Secretory Immunoglobulin A Levels.

    Science.gov (United States)

    Waldron, Jonathan C; Scarpa, Angela; Kim-Spoon, Jungmeen; Coe, Christopher L

    2016-03-01

    The current study investigated whether a history of child abuse is a predictor of adult immune status, with unwanted adult sexual experiences as a proximal mediator. Participants included 89 young adult women (M(age) = 19.24) who were classified as having experienced no child abuse, child physical abuse, or child sexual abuse, based upon self-reported victimization history before 14 years of age. Participants also reported on unwanted sexual experiences in young adulthood and provided four saliva samples, which were collected over two consecutive days to determine secretory immunoglobulin A (sIgA). Age and negative life events were considered as covariates. The results indicated that adult sexual victimization partially mediated the relationship between child abuse (physical and sexual) and sIgA. Specifically, child abuse experiences predicted more adult sexual victimization experiences, which in turn predicted lower sIgA levels. These findings support long-term health effects of victimization, and suggest that the influence of child abuse on sIgA may be perpetuated through adult victimization. Prevention efforts should aim to empower child maltreatment survivors with skills to prevent adult re-victimization. By thwarting future unwanted sexual experiences in adulthood, individuals will be better protected from the health impairments associated with early abuse experiences. © The Author(s) 2014.

  8. Total soluble and endogenous secretory receptor for advanced glycation endproducts (RAGE) in IBD.

    Science.gov (United States)

    Meijer, Berrie; Hoskin, Teagan; Ashcroft, Anna; Burgess, Laura; Keenan, Jacqueline I; Falvey, James; Gearry, Richard B; Day, Andrew S

    2014-06-01

    Recruitment and activation of neutrophils, with release of specific proteins such as S100 proteins, is a feature of inflammatory bowel disease (IBD). Soluble forms of the receptor for advanced glycation endproducts (sRAGE), and variants such as endogenous secretory (esRAGE), can act as decoy receptors by binding ligands, including S100A12. The aims of this study were to determine total sRAGE and esRAGE concentrations in patients with IBD and correlate these with C-reactive protein (CRP), endoscopic scores and clinical disease activity scores. EDTA-plasma was collected from patients undergoing colonoscopy including those with Crohn's disease (CD: n=125), ulcerative colitis (UC: n=79) and control patients without endoscopic signs of inflammation (non-IBD: n=156). Concentrations of sRAGE and esRAGE were determined by enzyme-linked immunosorbent assay and plasma CRP concentrations measured. Standard clinical disease activity and endoscopic severity scores were defined for all subjects. Plasma sRAGE concentrations were lower in UC (but not CD) than non-IBD subjects (pdefine the significance of sRAGE and esRAGE in IBD. Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  9. Characterization and partial purification of Candida albicans Secretory IL-12 Inhibitory Factor

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    Chandra Jyotsna

    2008-02-01

    Full Text Available Abstract Background We have previously shown that supernatant from Candida albicans (CA culture contains a Secretory Interleukin (IL-12 Inhibitory Factor (CA-SIIF, which inhibits IL-12 production by human monocytes. However, the effect of CA-SIIF on secretion of other cytokines by monocytes is unknown, and detailed characterization of this factor has not been performed. Results In this study, we demonstrate that the IL-12 inhibitory activity of CA-SIIF was serum-independent, based on the reduction of IL-12 levels in monocytes stimulated under serum-independent conditions. The minimal inhibitory dose of CA-SIIF was found to be 200 μg/ml. Investigation of CA-SIIF's effect on macrophages IL-12 production in vitro and in vivo also showed that CA-SIIF inhibited IL-12 production by murine macrophages both in vitro (from 571 ± 24 pg/ml to 387 ± 87 pg/ml; P = 0.05 and in vivo (from 262 ± 6 pg/ml to 144 ± 30 pg/ml; P P P P Conclusion CA-SIIF is a glycoprotein which exhibits serum-independent inhibition of IL-12 production from monocytes in vitro and in vivo, and also modulates differentiation of monocytes into dendritic cells. These results suggest important role for CA-SIIF in interactions of C. albicans with the host immune system.

  10. Development of indirect sandwich ELISA for determination of excretory-secretory antigens of Fasciola hepatica

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    Libertad Alzamora-Gonzales

    2016-05-01

    Full Text Available Fasciolosis is a cosmopolitan parasitosis medical-veterinary importance caused by Fasciola hepatica, which affects sheep, goats and cattle; and it affects man accidentally causing an epidemic-endemic infection difficult to diagnose. The aim was to develop an indirect sandwich ELISA with 3 antibodies for detecting excretory-secretory antigens of Fasciola hepatica (ESFh. For the development of indirect sandwich ELISA were used, as capture antibody, mouse polyclonal antibodies anti ESFh and polyclonal antibodies rabbit anti-ESFh as detection antibody, at the concentrations of 10 and 5 µg/mL respectively. The conjugate used was mouse monoclonal anti- total immunoglobulins rabbit linked to peroxidase (1/1000. Were analized 31 sheep fecal samples, and the results were compared with those obtained by direct coproparasitological examination (DC and counterimmunoelectrophoresis (CIEP. The detection limit obtained for indirect sandwich ELISA was 100 ng/mL. The test had a 100% sensitivity, 96.6% specificity, positive and negative predictive values of 50% and 96.6% respectively, in relation to DC test. Comparing with CIEP the specificity obtained for indirect sandwich ELISA was 93.5% and a negative predictive value of 100%. We concluded that indirect sandwich ELISA designed is able to detect metabolic antigens in ovine feces samples and can be used for Fasciola hepatica diagnosis.

  11. Effect of Fasciola gigantica excretory secretory antigen on rat hematological indices

    Science.gov (United States)

    Ganga, G.; Sharma, R. L.

    2006-01-01

    The present study was undertaken to investigate the effect of Fasciola gigantica excretory secretory antigen (Fg-ESA) on rat hematological indices. Fg-ESA was prepared by keeping thoroughly washed 40 F. gigantica flukes in 100 ml phosphate buffer saline (PBS) for 2 h at 37℃, and centrifuging the supernatant at 12,000 g at 4℃ for 30 min. The protein content of Fg-ESA was adjusted to 1.8 mg/ml. The rats were randomly divided into two groups of six rats each. Rats in group A received 0.5 ml of Fg-ESA intraperitoneally (i.p.) for 7 days, whereas control rats in group B received 0.5 ml of PBS i.p. for 7 days. Hemograms of both groups were studied initially and on days 0, 2, 4, 14 and 21 after the final injection of Fg-ESA or PBS. Progressive and significant (p 0.05) changes in the values of mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, or mean corpuscular volume in group A. Thus, we conclude that Fg-ESA induces normocytic normochromic anemia in rats. PMID:16645335

  12. Effects of Pilates Exercise on Salivary Secretory Immunoglobulin A Levels in Older Women.

    Science.gov (United States)

    Hwang, Yoonyoung; Park, Jonghoon; Lim, Kiwon

    2016-07-01

    We examined the effects of a Pilates exercise program on the mucosal immune function in older women. The study population comprised 12 older women who were divided into a Pilates group (PG, n = 6) and a control group (CG, n = 6). Saliva samples were obtained from both groups before and after the experimental period for salivary secretory immunoglobulin A level measurement. In addition, acute high-intensity exercises were performed before and after the three-month Pilates exercise program. After three months, salivary flow was significantly higher in the PG than in the CG. After the acute high-intensity exercises were performed following the three-month Pilates exercise program, the salivary flow rate was significantly higher at all time points. The S-IgA secretion rate significantly increased 30 min after acute high-intensity exercise performed following the three-month Pilates exercise program. This study suggests that regular participation in a moderate-intensity Pilates exercise program can increase salivary flow rate and S-IgA secretion in older women.

  13. Isolation and identification of java race amniotic membrane secretory leukocyte protease inhibitor gene

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    Elly Munadziroh

    2008-09-01

    Full Text Available Background: Secretory leukocyte protease inhibitor (SLPI has been found to facilitate epithelialization, maintain a normal epithelial phenotype, reduce inflammation, secrete growth factors such as IL-4, IL-6, IL-10, EGF, FGF, TGF, HGFand 2-microbulin. SLPI is serine protease inhibitor, which found in secretions such as whole saliva, seminal fluid, cervical mucus, synovial fluid, breast milk, tears, amniotic fluid and amniotic membrane. Impaired healing states are characterized by excessive proteolysis and oftenbacterial infection, leading to the hypothesis that SLPI may have a role in the healing process in oral inflammation and contributes to tissue repair in oral mucosa. The oral wound healing response is impaired in the SLPI sufficient mice since matrix synthesis and collagen deposition delayed. The objective of this research is to isolate and identify the amniotic membrane of Java Race SLPI Gene. Methods: SLPI RNA was isolated from Java Race amniotic membrane and the cDNA was amplified by polymerase chain reaction (PCR. Result: Through sequence analyses, SLPI cDNA was 530 nucleotide in length with a predicted molecular mass about 12 kDa. The nucleotide sequence showed that human SLPI from sample was 98% identical with human SLPI from gene bank. PCR analysis revealed that the mRNA of SLPI was highly expressed in the amniotic membrane from Java Race sample. Conclusion: it is demonstrated that human SLPI are highly conserved in sequence content as compared to the human SLPI from gene.

  14. Collagen can selectively trigger a platelet secretory phenotype via glycoprotein VI.

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    Véronique Ollivier

    Full Text Available Platelets are not only central actors of hemostasis and thrombosis but also of other processes including inflammation, angiogenesis, and tissue regeneration. Accumulating evidence indicates that these "non classical" functions of platelets do not necessarily rely on their well-known ability to form thrombi upon activation. This suggests the existence of non-thrombotic alternative states of platelets activation. We investigated this possibility through dose-response analysis of thrombin- and collagen-induced changes in platelet phenotype, with regards to morphological and functional markers of platelet activation including shape change, aggregation, P-selectin and phosphatidylserine surface expression, integrin activation, and release of soluble factors. We show that collagen at low dose (0.25 µg/mL selectively triggers a platelet secretory phenotype characterized by the release of dense- and alpha granule-derived soluble factors without causing any of the other major platelet changes that usually accompany thrombus formation. Using a blocking antibody to glycoprotein VI (GPVI, we further show that this response is mediated by GPVI. Taken together, our results show that platelet activation goes beyond the mechanisms leading to platelet aggregation and also includes alternative platelet phenotypes that might contribute to their thrombus-independent functions.

  15. THE EFFECT OF CURCUMIN ON SECRETORY ACTIVITY, PROLIFERATION AND APOPTOSIS OF THE PORCINE OVARIAN GRANULOSA CELLS

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    Attila Kádasi

    2012-08-01

    Full Text Available The aim of this in vitro study was to examine the effect of natural plant (Curcuma longa molecule curcumin on secretory activity, proliferation and apoptosis of porcine granulosa cells. The secretion of steroid hormones (progesterone, testosterone, accumulation of PCNA (marker of proliferation and bax (marker of apoptosis in granulosa cells of swine ovaries after curcumin treatment at the doses 0, 1, 10, 100 μg.mL-1 was determined by RIA and immunocytochemistry. It was observed that, addition of curcumin stimulated progesterone (at doses 1 and 10 μg.mL-1, but not 100 μg.mL-1 and testosterone at (100 μg.mL-1 but not 1 and 10 μg.mL-1 release. The number of cells contained PCNA was down-regulated by curcumin administration (at dose of 10 μg.mL-1, but not of 1 and 100 μg.mL-1. Bax expression was stimulated by curcumin at all doses added. Our results suggest a direct effect of curcumin on ovarian functions: steroidogenesis, proliferation and apoptosis. This could suggest antireproductive properties of curcumin in swine ovaries.

  16. Non-Cell Autonomous Effects of the Senescence-Associated Secretory Phenotype in Cancer Therapy

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    Tareq Saleh

    2018-05-01

    Full Text Available In addition to promoting various forms of cell death, most conventional anti-tumor therapies also promote senescence. There is now extensive evidence that therapy-induced senescence (TIS might be transient, raising the concern that TIS could represent an undesirable outcome of therapy by providing a mechanism for tumor dormancy and eventual disease recurrence. The senescence-associated secretory phenotype (SASP is a hallmark of TIS and may contribute to aberrant effects of cancer therapy. Here, we propose that the SASP may also serve as a major driver of escape from senescence and the re-emergence of proliferating tumor cells, wherein factors secreted from the senescent cells contribute to the restoration of tumor growth in a non-cell autonomous fashion. Accordingly, anti-SASP therapies might serve to mitigate the deleterious outcomes of TIS. In addition to providing an overview of the putative actions of the SASP, we discuss recent efforts to identify and eliminate senescent tumor cells.

  17. Filarial excretory-secretory products induce human monocytes to produce lymphangiogenic mediators.

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    Tiffany Weinkopff

    2014-07-01

    Full Text Available The nematodes Wuchereria bancrofti and Brugia spp. infect over 120 million people worldwide, causing lymphedema, elephantiasis and hydrocele, collectively known as lymphatic filariasis. Most infected individuals appear to be asymptomatic, but many exhibit sub-clinical manifestations including the lymphangiectasia that likely contributes to the development of lymphedema and elephantiasis. As adult worm excretory-secretory products (ES do not directly activate lymphatic endothelial cells (LEC, we investigated the role of monocyte/macrophage-derived soluble factors in the development of filarial lymphatic pathology. We analyzed the production of IL-8, IL-6 and VEGF-A by peripheral blood mononuclear cells (PBMC from naïve donors following stimulation with filarial ES products. ES-stimulated PBMCs produced significantly more IL-8, IL-6 and VEGF-A compared to cells cultured in medium alone; CD14(+ monocytes appear to be the primary producers of IL-8 and VEGF-A, but not IL-6. Furthermore, IL-8, IL-6 and VEGF-A induced in vitro tubule formation in LEC Matrigel cultures. Matrigel plugs supplemented with IL-8, IL-6, VEGF-A, or with supernatants from ES-stimulated PBMCs and implanted in vivo stimulated lymphangiogenesis. Collectively, these data support the hypothesis that monocytes/macrophages exposed to filarial ES products may modulate lymphatic function through the secretion of soluble factors that stimulate the vessel growth associated with the pathogenesis of filarial disease.

  18. Mechanism of inhibition of human secretory phospholipase A2 by flavonoids: rationale for lead design

    Science.gov (United States)

    Lättig, Jens; Böhl, Markus; Fischer, Petra; Tischer, Sandra; Tietböhl, Claudia; Menschikowski, Mario; Gutzeit, Herwig O.; Metz, Peter; Pisabarro, M. Teresa

    2007-08-01

    The human secretory phospholipase A2 group IIA (PLA2-IIA) is a lipolytic enzyme. Its inhibition leads to a decrease in eicosanoids levels and, thereby, to reduced inflammation. Therefore, PLA2-IIA is of high pharmacological interest in treatment of chronic diseases such as asthma and rheumatoid arthritis. Quercetin and naringenin, amongst other flavonoids, are known for their anti-inflammatory activity by modulation of enzymes of the arachidonic acid cascade. However, the mechanism by which flavonoids inhibit Phospholipase A2 (PLA2) remained unclear so far. Flavonoids are widely produced in plant tissues and, thereby, suitable targets for pharmaceutical extractions and chemical syntheses. Our work focuses on understanding the binding modes of flavonoids to PLA2, their inhibition mechanism and the rationale to modify them to obtain potent and specific inhibitors. Our computational and experimental studies focused on a set of 24 compounds including natural flavonoids and naringenin-based derivatives. Experimental results on PLA2-inhibition showed good inhibitory activity for quercetin, kaempferol, and galangin, but relatively poor for naringenin. Several naringenin derivatives were synthesized and tested for affinity and inhibitory activity improvement. 6-(1,1-dimethylallyl)naringenin revealed comparable PLA2 inhibition to quercetin-like compounds. We characterized the binding mode of these compounds and the determinants for their affinity, selectivity, and inhibitory potency. Based on our results, we suggest C(6) as the most promising position of the flavonoid scaffold to introduce chemical modifications to improve affinity, selectivity, and inhibition of PLA2-IIA by flavonoids.

  19. Influence of Modest Endotoxemia on Postoperative Antithrombin Deficiency and Circulating Secretory Immunoglobulin A Levels

    Science.gov (United States)

    Fujita, Tetsuji; Imai, Takashi; Anazawa, Sadao

    2003-01-01

    Objective: To evaluate the influence of modest endotoxemia on postoperative antithrombin deficiency and cholestasis. Summary Background Data: It has not been determined whether endotoxin translocation in small amounts is a physiological phenomenon or whether it is a potential health hazard. Methods: Blood endotoxin, antithrombin III (ATIII), secretory immunoglobulin A (sIgA), which was selected as a marker of cholestasis, C-reactive protein (CRP), and α-1-antitrypsin (AAT) concentrations were measured from the 20 patients undergoing curative gastrectomy for gastric cancer preoperatively and postoperatively. Portal and systemic blood samples were taken for the analysis of endotoxin and interleukin-6 (IL-6) concentrations during surgery in these patients. Results: Although plasma endotoxin levels showed a significant increase during surgery, we did not find a correlation with ATIII, sIgA, CRP, and IL-6 levels. Systemic blood endotoxin levels during surgery correlated with a postoperative rise of serum AAT levels. Plasma ATIII levels transiently decreased on the first and third postoperative day, and sIgA levels were shown to increase on the seventh postoperative day. There was a weak relationship between the extent of postoperative endotoxemia and a reduction in ATIII concentrations. Conclusions: The influence of modest endotoxemia on postoperative antithrombin deficiency and cholestasis was limited, and increased translocational endotoxemia during abdominal surgery may be a physiological phenomenon to trigger off an acute-phase protein response. PMID:12894020

  20. The golgin GMAP-210 is required for efficient membrane trafficking in the early secretory pathway.

    Science.gov (United States)

    Roboti, Peristera; Sato, Keisuke; Lowe, Martin

    2015-04-15

    Golgins are coiled-coil proteins that participate in membrane-tethering events at the Golgi complex. Golgin-mediated tethering is thought to be important for vesicular trafficking and Golgi organization. However, the degree to which individual golgins contribute to these processes is poorly defined, and it has been proposed that golgins act in a largely redundant manner. Previous studies on the golgin GMAP-210 (also known as TRIP11), which is mutated in the rare skeletal disorder achondrogenesis type 1A, have yielded conflicting results regarding its involvement in trafficking. Here, we re-investigated the trafficking role of GMAP-210, and found that it is indeed required for efficient trafficking in the secretory pathway. GMAP-210 acts at both the endoplasmic reticulum (ER)-to-Golgi intermediate compartment (ERGIC) and Golgi complex during anterograde trafficking, and is also required for retrograde trafficking to the ER. Using co-depletion experiments, we also found that GMAP-210 acts in a partially redundant manner with the golgin GM130 to ensure efficient anterograde cargo delivery to the cis-Golgi. In summary, our results indicate a role for GMAP-210 in several trafficking steps at the ER-Golgi interface, some of which are partially redundant with another golgin, namely GM130 (also known as GOLGA2). © 2015. Published by The Company of Biologists Ltd.

  1. Expression of ODC Antizyme Inhibitor 2 (AZIN2 in Human Secretory Cells and Tissues.

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    Tiina Rasila

    Full Text Available Ornithine decarboxylase (ODC antizyme inhibitor 2 (AZIN2, originally called ODCp, is a regulator of polyamine synthesis that we originally identified and cloned. High expression of ODCp mRNA was found in brain and testis. We reported that AZIN2 is involved in regulation of cellular vesicle transport and / or secretion, but the ultimate physiological role(s of AZIN2 is still poorly understood. In this study we used a peptide antibody (K3 to human AZIN2 and by immunohistochemistry mapped its expression in various normal tissues. We found high expression in the nervous system, in type 2 pneumocytes in the lung, in megakaryocytes, in gastric parietal cells co-localized with H,K-ATPase beta subunit, in selected enteroendocrine cells, in acinar cells of sweat glands, in podocytes, in macula densa cells and epithelium of collecting ducts in the kidney. The high expression of AZIN2 in various cells with secretory or vesicle transport activity indicates that the polyamine metabolism regulated by AZIN2 is more significantly involved in these events than previously appreciated.

  2. SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation.

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    Tomohisa Hayakawa

    Full Text Available Senescent cells develop a pro-inflammatory response termed the senescence-associated secretory phenotype (SASP. As many SASP components affect surrounding cells and alter their microenvironment, SASP may be a key phenomenon in linking cellular senesence with individual aging and age-related diseases. We herein demonstrated that the expression of Sirtuin1 (SIRT1 was decreased and the expression of SASP components was reciprocally increased during cellular senescence. The mRNAs and proteins of SASP components, such as IL-6 and IL-8, quickly accumulated in SIRT1-depleted cells, and the levels of these factors were also higher than those in control cells, indicating that SIRT1 negatively regulated the expression of SASP factors at the transcriptional level. SIRT1 bound to the promoter regions of IL-8 and IL-6, but dissociated from them during cellular senescence. The acetylation of Histone H3 (K9 and H4 (K16 of the IL-8 and IL-6 promoter regions gradually increased during cellular senescence. In SIRT1-depleted cells, the acetylation levels of these regions were already higher than those in control cells in the pre-senescent stage. Moreover, these acetylation levels in SIRT1-depleted cells were significantly higher than those in control cells during cellular senescence. These results suggest that SIRT1 repressed the expression of SASP factors through the deacetylation of histones in their promoter regions.

  3. Altered synthesis of some secretory proteins in pancreatic lobules isolated from streptozotocin-induced diabetic rats

    International Nuclear Information System (INIS)

    Duan, R.D.; Erlanson-Albertsson, C.

    1990-01-01

    The in vitro incorporation of [35S]cysteine into lipase, colipase, amylase, procarboxypeptidase A and B, and the serine proteases and total proteins was studied in pancreatic lobules isolated from normal and diabetic rats with or without insulin treatment. The incorporation of [35S]cysteine into total proteins was 65% greater in pancreatic lobules from diabetic animals than from normal rats. The increased incorporation was partly reversed by insulin treatment (2 U/100 g/day for 5 days) of diabetic rats. The relative rates of biosynthesis for amylase and the procarboxypeptidases in diabetic pancreatic lobules were decreased by 75 and 25%, respectively, after 1 h of incubation, while those for lipase, colipase, and the serine proteases were increased by 90, 85, and 35%, respectively. The absolute rates of synthesis for these enzymes changed in the same direction as the relative rates in diabetic lobules, except that for the procarboxypeptidases, which did not change. The changed rates of biosynthesis for the pancreatic enzymes were reversed by insulin treatment of the diabetic rats. Kinetic studies showed that the incorporation of [35S]cysteine into amylase, lipase, and colipase was linear until up to 2 h of incubation in normal pancreatic lobules, while in the diabetic lobules the incorporation into lipase and colipase was accelerated, reaching a plateau level already after 1 h of incubation. It is concluded that the biosynthesis of pancreatic secretory proteins in diabetic rats is greatly changed both in terms of quantity and kinetics

  4. Secretory expression of nattokinase from Bacillus subtilis YF38 in Escherichia coli.

    Science.gov (United States)

    Liang, Xiaobo; Jia, Shifang; Sun, Yufang; Chen, Meiling; Chen, Xiuzhu; Zhong, Jin; Huan, Liandong

    2007-11-01

    Nattokinase producing bacterium, B. subtilis YF38, was isolated from douchi, using the fibrin plate method. The gene encoding this enzyme was cloned by polymerase chain reaction (PCR). Cytoplasmic expression of this enzyme in E. coli resulted in inactive inclusion bodies. But with the help of two different signal peptides, the native signal peptide of nattokinase and the signal peptide of PelB, active nattokinase was successfully expressed in E. coli with periplasmic secretion, and the nattokinase in culture medium displayed high fibrinolytic activity. The fibrinolytic activity of the expressed enzyme in the culture was determined to reach 260 urokinase units per micro-liter when the recombinant strain was induced by 0.7 mmol l(-1) isopropyl-beta-D- thiogalactopyranoside (IPTG) at 20 degrees C for 20 h, resulting 49.3 mg active enzyme per liter culture. The characteristic of this recombinant nattokinase is comparable to the native nattokinase from B. subtilis YF38. Secretory expression of nattokinase in E. coli would facilitate the development of this enzyme into a therapeutic product for the control and prevention of thrombosis diseases.

  5. Prevention of secretory diarrhea by ethanol extract of Bistortae rhizoma through inhibition of chloride channel

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    Bo Yu

    2015-08-01

    Full Text Available Inhibition of cystic fibrosis transmembrane conductance regulator (CFTR and Ca2+-activated Cl- channel (CaCC represents an attractive approach for the treatment of secretory diarrhea. The aim of the study is to investigate the molecular basis of the anti-diarrheal effect of traditional Chinese herbal anti-diarrheal medicine Bistortae rhizoma. Fluorescence quenching assay indicated that the 40% methanol /water fraction (D5 dose-dependently inhibited both CFTR and CaCC function in transfected Fischer rat thyroid (FRT cells. Ex vivo studies indicated that D5 inhibited both forskolin (FSK-activated CFTR current and CCh-induced CaCC current in rat colonic mucosa. In the mouse closed-loop model, intraluminal application of D5 (200 µg/mL significantly reduced cholera toxin-stimulated fluid secretion. In the intestinal motility model, D5 significantly delayed intestinal peristalsis in mice. Our research suggests that CFTR and CaCC-mediated intestinal epithelial Cl- secretion inhibiting and gastrointestinal motility delaying may account for the anti-diarrheal activity of B. rhizoma.

  6. A dynamic study of protein secretion and aggregation in the secretory pathway.

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    Mossuto, Maria Francesca; Sannino, Sara; Mazza, Davide; Fagioli, Claudio; Vitale, Milena; Yoboue, Edgar Djaha; Sitia, Roberto; Anelli, Tiziana

    2014-01-01

    Precise coordination of protein biogenesis, traffic and homeostasis within the early secretory compartment (ESC) is key for cell physiology. As a consequence, disturbances in these processes underlie many genetic and chronic diseases. Dynamic imaging methods are needed to follow the fate of cargo proteins and their interactions with resident enzymes and folding assistants. Here we applied the Halotag labelling system to study the behavior of proteins with different fates and roles in ESC: a chaperone, an ERAD substrate and an aggregation-prone molecule. Exploiting the Halo property of binding covalently ligands labelled with different fluorochromes, we developed and performed non-radioactive pulse and chase assays to follow sequential waves of proteins in ESC, discriminating between young and old molecules at the single cell level. In this way, we could monitor secretion and degradation of ER proteins in living cells. We can also follow the biogenesis, growth, accumulation and movements of protein aggregates in the ESC. Our data show that protein deposits within ESC grow by sequential apposition of molecules up to a given size, after which novel seeds are detected. The possibility of using ligands with distinct optical and physical properties offers a novel possibility to dynamically follow the fate of proteins in the ESC.

  7. A dynamic study of protein secretion and aggregation in the secretory pathway.

    Directory of Open Access Journals (Sweden)

    Maria Francesca Mossuto

    Full Text Available Precise coordination of protein biogenesis, traffic and homeostasis within the early secretory compartment (ESC is key for cell physiology. As a consequence, disturbances in these processes underlie many genetic and chronic diseases. Dynamic imaging methods are needed to follow the fate of cargo proteins and their interactions with resident enzymes and folding assistants. Here we applied the Halotag labelling system to study the behavior of proteins with different fates and roles in ESC: a chaperone, an ERAD substrate and an aggregation-prone molecule. Exploiting the Halo property of binding covalently ligands labelled with different fluorochromes, we developed and performed non-radioactive pulse and chase assays to follow sequential waves of proteins in ESC, discriminating between young and old molecules at the single cell level. In this way, we could monitor secretion and degradation of ER proteins in living cells. We can also follow the biogenesis, growth, accumulation and movements of protein aggregates in the ESC. Our data show that protein deposits within ESC grow by sequential apposition of molecules up to a given size, after which novel seeds are detected. The possibility of using ligands with distinct optical and physical properties offers a novel possibility to dynamically follow the fate of proteins in the ESC.

  8. Lacrimal secretory IgA in active posterior uveitis induced by Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Maria Isabel Lynch

    2004-12-01

    Full Text Available It is quite difficult to diagnose active toxoplasmosis in patients with ocular toxoplasmosis. Active posterior uveitis presumably due to Toxoplasma gondii infection (APUPT is seldom produced during a prime-infection; hence most patients do not show high IgM antibodies. High levels of IgA have been described in active toxoplasmosis. The purpose of this study was to investigate possible association between APUPT and the specific anti-parasite sIgA in tears. The study was carried out as case-control. Tears of 25 clinically confirmed APUPT patients and 50 healthy control subjects were analyzed. All were IgG seropositive. Specific sIgA was determined by ELISA assay using T. gondii RH strain crude extract. Anti-T. gondii sIgA was found in 84% of the cases and in 22% of the control subjects. The intensity of the reaction was higher in APUPT cases (P = 0.007. There was strong association between APUPT patients and lacrimal sIgA (odds-ratio 18.61, P = 0.0001. ELISA test sensitivity was 84% and specificity 78% . Our data suggest that anti-T.gondii secretory IgA found in tears may become an important marker for active ocular toxoplasmosis.

  9. Lacrimal secretory IgA in active posterior uveitis induced by Toxoplasma gondii.

    Science.gov (United States)

    Lynch, Maria Isabel; Cordeiro, Francisco; Ferreira, Silvana; Ximenes, Ricardo; Oréfice, Fernando; Malagueño, Elizabeth

    2004-12-01

    It is quite difficult to diagnose active toxoplasmosis in patients with ocular toxoplasmosis. Active posterior uveitis presumably due to Toxoplasma gondii infection (APUPT) is seldom produced during a prime-infection; hence most patients do not show high IgM antibodies. High levels of IgA have been described in active toxoplasmosis. The purpose of this study was to investigate possible association between APUPT and the specific anti-parasite sIgA in tears. The study was carried out as case-control. Tears of 25 clinically confirmed APUPT patients and 50 healthy control subjects were analyzed. All were IgG seropositive. Specific sIgA was determined by ELISA assay using T. gondii RH strain crude extract. Anti-T. gondii sIgA was found in 84% of the cases and in 22% of the control subjects. The intensity of the reaction was higher in APUPT cases (P = 0.007). There was strong association between APUPT patients and lacrimal sIgA (odds-ratio 18.61, P = 0.0001). ELISA test sensitivity was 84% and specificity 78%. Our data suggest that anti-T.gondii secretory IgA found in tears may become an important marker for active ocular toxoplasmosis.

  10. Impact of infection on the secretory capacity of the male accessory glands

    Directory of Open Access Journals (Sweden)

    M. Marconi

    2009-06-01

    Full Text Available INTRODUCTION: Studies that compare the impact of different infectious entities of the male reproductive tract (MRT on the male accessory gland function are controversial. MATERIAL AND METHODS: Semen analyses of 71 patients with proven infections of the MRT were compared with the results of 40 healthy non-infected volunteers. Patients were divided into 3 groups according to their diagnosis: chronic prostatitis NIH type II (n = 38, chronic epididymitis (n = 12, and chronic urethritis (n = 21. RESULTS: The bacteriological analysis revealed 9 different types of microorganisms, considered to be the etiological agents, isolated in different secretions, including: urine, expressed prostatic secretions, semen and urethral smears: E. Coli (n = 20, Klebsiella (n = 2, Proteus spp. (n = 1, Enterococcus (n = 20, Staphylococcus spp. (n = 1, M. tuberculosis (n = 2, N. gonorrhea (n = 8, Chlamydia tr. (n = 16 and, Ureaplasma urealyticum (n = 1. The infection group had significantly (p < 0.05 lower: semen volume, alpha-glucosidase, fructose, and zinc in seminal plasma and, higher pH than the control group. None of these parameters was sufficiently accurate in the ROC analysis to discriminate between infected and non-infected men. CONCLUSION: Proven bacterial infections of the MRT impact negatively on all the accessory gland function parameters evaluated in semen, suggesting impairment of the secretory capacity of the epididymis, seminal vesicles and prostate. These findings were associated with an infectious related significant increase of semen pH. None of the semen parameters evaluated can be suggested as a diagnostic tool for infection.

  11. Ultrastructure of the surface structures and secretory glands of the rosette attachment organ of Gyrocotyle urna (Cestoda: Gyrocotylidea)

    Czech Academy of Sciences Publication Activity Database

    Poddubnaya, L. G.; Scholz, Tomáš; Kuchta, Roman; Levron, Céline; Gibson, D. I.

    2008-01-01

    Roč. 55, č. 3 (2008), s. 207-218 ISSN 0015-5683 R&D Projects: GA MŠk LC522; GA ČR GP524/07/P039; GA ČR GA524/08/0885 Institutional research plan: CEZ:AV0Z60220518 Keywords : Gyrocotyle urna * adhesive secretion * three types of secretory glands * ultrastructure Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 1.307, year: 2008

  12. DIAGNOSTIC VALUE OF A TEST FOR DETECTION OF SECRETORY IgA FOR CONFIRMATION OF ABSENCE OF FMD VIRUS CIRCULATION

    OpenAIRE

    D.N. AFONINA; N.YE. KAMALOVA; A.V. KAN’HINA; A.M. TIMINA

    2014-01-01

    In Russia the preventive vaccination dominates over other protective and preventive measures against foot and mouth disease (FMD). However, the development of the subclinical infection in immune animals should not be ruled out as these animals become virus carriers and pose a potential threat for susceptible animal population. Therefore, the design and reduction to practice of tests for identification of virus-carrier animals continues to be relevant. Secretory immunoglobulins A (sIgA) provid...

  13. Neuronal differentiation is associated with a redox-regulated increase of copper flow to the secretory pathway

    OpenAIRE

    Hatori, Yuta; Yan, Ye; Schmidt, Katharina; Furukawa, Eri; Hasan, Nesrin M.; Yang, Nan; Liu, Chin-Nung; Sockanathan, Shanthini; Lutsenko, Svetlana

    2016-01-01

    Brain development requires a fine-tuned copper homoeostasis. Copper deficiency or excess results in severe neuro-pathologies. We demonstrate that upon neuronal differentiation, cellular demand for copper increases, especially within the secretory pathway. Copper flow to this compartment is facilitated through transcriptional and metabolic regulation. Quantitative real-time imaging revealed a gradual change in the oxidation state of cytosolic glutathione upon neuronal differentiation. Transiti...

  14. Completions in sand and fractured shale

    Energy Technology Data Exchange (ETDEWEB)

    da Fonseca, C F

    1968-01-01

    The development in the Candeias-Macui area depends little on well completion. The results obtained show that the practice adopted for stimulating fractured shale is not yet defined. It is necessary to improve hole quality, to undertake the research that will prove which prospective intervals are productive, to determine the possible origin of formation damage, and then to select the most suitable stimulation technique. With this, it will be possible to study the technology of ideal completion to be used on new wells in relation to a chosen type of stimulation and future workovers. From the discussion of general completion problems in RPBA, it is concluded that there is an immediate need for training engineers in the specialties of completion, workover and well stimulation. It is also concluded that the meaning of completion must be clarified, so that sectors of responsibility may be defined in order to determine when and how each sector enters into well operations.

  15. Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes.

    Science.gov (United States)

    Maciejczyk, Mateusz; Kossakowska, Agnieszka; Szulimowska, Julita; Klimiuk, Anna; Knaś, Małgorzata; Car, Halina; Niklińska, Wiesława; Ładny, Jerzy Robert; Chabowski, Adrian; Zalewska, Anna

    2017-01-01

    Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands-nonstimulated and stimulated salivary flow, α -amylase, total protein-and salivary exoglycosidase activities-N-acetyl- β -hexosaminidase (HEX, HEX A, and HEX B), β -glucuronidase, α -fucosidase, β -galactosidase, and α -mannosidase-was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B, α -amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands.

  16. Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes

    Directory of Open Access Journals (Sweden)

    Mateusz Maciejczyk

    2017-01-01

    Full Text Available Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ- induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4 and diabetic groups (STZ2, STZ4. The secretory function of salivary glands—nonstimulated and stimulated salivary flow, α-amylase, total protein—and salivary exoglycosidase activities—N-acetyl-β-hexosaminidase (HEX, HEX A, and HEX B, β-glucuronidase, α-fucosidase, β-galactosidase, and α-mannosidase—was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B, α-amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands.

  17. MUM ENHANCERS are important for seed coat mucilage production and mucilage secretory cell differentiation in Arabidopsis thaliana.

    Science.gov (United States)

    Arsovski, Andrej A; Villota, Maria M; Rowland, Owen; Subramaniam, Rajagopal; Western, Tamara L

    2009-01-01

    Pollination triggers not only embryo development but also the differentiation of the ovule integuments to form a specialized seed coat. The mucilage secretory cells of the Arabidopsis thaliana seed coat undergo a complex differentiation process in which cell growth is followed by the synthesis and secretion of pectinaceous mucilage. A number of genes have been identified affecting mucilage secretory cell differentiation, including MUCILAGE-MODIFIED4 (MUM4). mum4 mutants produce a reduced amount of mucilage and cloning of MUM4 revealed that it encodes a UDP-L-rhamnose synthase that is developmentally up-regulated to provide rhamnose for mucilage pectin synthesis. To identify additional genes acting in mucilage synthesis and secretion, a screen for enhancers of the mum4 phenotype was performed. Eight mum enhancers (men) have been identified, two of which result from defects in known mucilage secretory cell genes (MUM2 and MYB61). Our results show that, in a mum4 background, mutations in MEN1, MEN4, and MEN5 lead to further reductions in mucilage compared to mum4 single mutants, suggesting that they are involved in mucilage synthesis or secretion. Conversely, mutations in MEN2 and MEN6 appear to affect mucilage release rather than quantity. With the exception of men4, whose single mutant exhibits reduced mucilage, none of these genes have a single mutant phenotype, suggesting that they would not have been identified outside the compromised mum4 background.

  18. Intracisternal granules in the adipokinetic cells of locusts are not degraded and apparently function as supplementary stores of secretory material.

    Science.gov (United States)

    Harthoorn, L F; Diederen, J H; Oudejans, R C; Verstegen, M M; Vullings, H G; Van der Horst, D J

    2000-01-01

    The intracisternal granules in locust adipokinetic cells appear to represent accumulations of secretory material within cisternae of the rough endoplasmic reticulum. An important question is whether these granules are destined for degradation or represent stores of (pro)hormones. Two strategies were used to answer this question. First, cytochemistry was applied to elucidate the properties of intracisternal granules. The endocytic tracers horseradish peroxidase and wheat-germ agglutinin-conjugated horseradish peroxidase were used to facilitate the identification of endocytic, autophagic, and lysosomal organelles, which may be involved in the degradation of intracisternal granules. No intracisternal granules could be found within autophagosomes, and granules fused with endocytic and lysosomal organelles were not observed, nor could tracer be found within the granules. The lysosomal enzyme acid phosphatase was absent from the granules. Second, biochemical analysis of the content of intracisternal granules revealed that these granules contain prohormones as well as hormones. Prohormones were present in relatively higher amounts compared with ordinary secretory granules. Since the intracisternal granules in locust adipokinetic cells are not degraded and contain intact (pro)hormones it is concluded that they function as supplementary stores of secretory material.

  19. General Relativity

    CERN Document Server

    Straumann, Norbert

    2013-01-01

    This book provides a completely revised and expanded version of the previous classic edition ‘General Relativity and Relativistic Astrophysics’. In Part I the foundations of general relativity are thoroughly developed, while Part II is devoted to tests of general relativity and many of its applications. Binary pulsars – our best laboratories for general relativity – are studied in considerable detail. An introduction to gravitational lensing theory is included as well, so as to make the current literature on the subject accessible to readers. Considerable attention is devoted to the study of compact objects, especially to black holes. This includes a detailed derivation of the Kerr solution, Israel’s proof of his uniqueness theorem, and a derivation of the basic laws of black hole physics. Part II ends with Witten’s proof of the positive energy theorem, which is presented in detail, together with the required tools on spin structures and spinor analysis. In Part III, all of the differential geomet...

  20. BOOK REVIEW: Complete Physics

    Science.gov (United States)

    Carson, Simon

    2000-03-01

    This book contains all the essential concepts for GCSE (or equivalent) physics courses or for general science courses at Key Stage 4. It claims to be ideal for use as a bridging resource for those intending to take physics beyond GCSE: it is no surprise, then, that the book is written at a level above that of the average Key Stage 4 student. It includes material not included in many GCSE syllabuses; this is clearly identified in the contents pages. It would be a useful resource for more able students at GCSE or for beginning A-level students. The layout of the book is attractive. It is well illustrated and colourful. Some of the illustrations are striking: each of the 12 main sections of the book begins with a title page that includes some unusual photographs illustrating physical ideas. Section 2, Forces and Motion, has a photograph of a bungee jumper leaping from the Sky Tower in New Zealand, taken at night looking along the length of the tower from its foot. Section 9, Magnets and Currents, has a computer-generated picture of the magnetic field in a fusion generator. These pictures, as well as contributing to the attractiveness of the book, could be used to initiate discussions of some of the physics. However, there are pictures that serve little useful purpose: a photograph of a recording station for seismic waves looks like any other building lit up at night. A photograph of a rock band in the middle of a section on sound carries no explanatory caption at all and is purely decorative. Other illustrations - in a variety of styles - do illustrate some physical ideas very well: the diagrams of motors and generators, for instance, are far clearer than my efforts on the blackboard! The book is divided into 14 sections with titles reflecting the traditional divisions of physics syllabuses, together with a beginning section on measurement and units and two final sections, `History of Key Ideas' and `Experimental Physics'. The first section, `Measurement and Units

  1. Secretory vesicles in live cells are not free-floating but tethered to filamentous structures: A study using photonic force microscopy

    International Nuclear Information System (INIS)

    Abu-Hamdah, Rania; Cho, Won Jin; Hoerber, J.K.H.; Jena, Bhanu P.

    2006-01-01

    It is well established that actin and microtubule cytoskeletal systems are involved in organelle transport and membrane trafficking in cells. This is also true for the transport of secretory vesicles in neuroendocrine cells and neurons. It was however unclear whether secretory vesicles remain free-floating, only to associate with such cytoskeletal systems when needing transport. This hypothesis was tested using live pancreatic acinar cells in physiological buffer solutions, using the photonic force microscope (PFM). When membrane-bound secretory vesicles (0.2-1.2 μm in diameter) in live pancreatic acinar cells were trapped at the laser focus of the PFM and pulled, they were all found tethered to filamentous structures. Mild exposure of cells to nocodazole and cytochalasin B, disrupts the tether. Immunoblot analysis of isolated secretory vesicles, further demonstrated the association of actin, myosin V, and kinesin. These studies demonstrate for the first time that secretory vesicles in live pancreatic acinar cells are tethered and not free-floating, suggesting that following vesicle biogenesis, they are placed on their own railroad track, ready to be transported to their final destination within the cell when required. This makes sense, since precision and regulation are the hallmarks of all cellular process, and therefore would hold true for the transport and localization of subcellular organelles such as secretory vesicles

  2. Secretory vesicles in live cells are not free-floating but tethered to filamentous structures: A study using photonic force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Abu-Hamdah, Rania [Department of Physiology, Wayne State University School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201 (United States); Cho, Won Jin [Department of Physiology, Wayne State University School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201 (United States); Hoerber, J.K.H. [Department of Physics, University of Bristol, Bristol BS8 1TD (United Kingdom); Jena, Bhanu P. [Department of Physiology, Wayne State University School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201 (United States)]. E-mail: bjena@med.wayne.edu

    2006-06-15

    It is well established that actin and microtubule cytoskeletal systems are involved in organelle transport and membrane trafficking in cells. This is also true for the transport of secretory vesicles in neuroendocrine cells and neurons. It was however unclear whether secretory vesicles remain free-floating, only to associate with such cytoskeletal systems when needing transport. This hypothesis was tested using live pancreatic acinar cells in physiological buffer solutions, using the photonic force microscope (PFM). When membrane-bound secretory vesicles (0.2-1.2 {mu}m in diameter) in live pancreatic acinar cells were trapped at the laser focus of the PFM and pulled, they were all found tethered to filamentous structures. Mild exposure of cells to nocodazole and cytochalasin B, disrupts the tether. Immunoblot analysis of isolated secretory vesicles, further demonstrated the association of actin, myosin V, and kinesin. These studies demonstrate for the first time that secretory vesicles in live pancreatic acinar cells are tethered and not free-floating, suggesting that following vesicle biogenesis, they are placed on their own railroad track, ready to be transported to their final destination within the cell when required. This makes sense, since precision and regulation are the hallmarks of all cellular process, and therefore would hold true for the transport and localization of subcellular organelles such as secretory vesicles.

  3. Cysteine Cathepsins in the secretory vesicle produce active peptides: Cathepsin L generates peptide neurotransmitters and cathepsin B produces beta-amyloid of Alzheimer's disease.

    Science.gov (United States)

    Hook, Vivian; Funkelstein, Lydiane; Wegrzyn, Jill; Bark, Steven; Kindy, Mark; Hook, Gregory

    2012-01-01

    Recent new findings indicate significant biological roles of cysteine cathepsin proteases in secretory vesicles for production of biologically active peptides. Notably, cathepsin L in secretory vesicles functions as a key protease for proteolytic processing of proneuropeptides (and prohormones) into active neuropeptides that are released to mediate cell-cell communication in the nervous system for neurotransmission. Moreover, cathepsin B in secretory vesicles has been recently identified as a β-secretase for production of neurotoxic β- amyloid (Aβ) peptides that accumulate in Alzheimer's disease (AD), participating as a notable factor in the severe memory loss in AD. These secretory vesicle functions of cathepsins L and B for production of biologically active peptides contrast with the well-known role of cathepsin proteases in lysosomes for the degradation of proteins to result in their inactivation. The unique secretory vesicle proteome indicates proteins of distinct functional categories that provide the intravesicular environment for support of cysteine cathepsin functions. Features of the secretory vesicle protein systems insure optimized intravesicular conditions that support the proteolytic activity of cathepsins. These new findings of recently discovered biological roles of cathepsins L and B indicate their significance in human health and disease. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Is quantum theory predictably complete?

    Energy Technology Data Exchange (ETDEWEB)

    Kupczynski, M [Department of Mathematics and Statistics, University of Ottawa, 585 King-Edward Avenue, Ottawa, Ontario K1N 6N5 (Canada); Departement de l' Informatique, UQO, Case postale 1250, succursale Hull, Gatineau, Quebec J8X 3X 7 (Canada)], E-mail: mkupczyn@uottawa.ca

    2009-07-15

    Quantum theory (QT) provides statistical predictions for various physical phenomena. To verify these predictions a considerable amount of data has been accumulated in the 'measurements' performed on the ensembles of identically prepared physical systems or in the repeated 'measurements' on some trapped 'individual physical systems'. The outcomes of these measurements are, in general, some numerical time series registered by some macroscopic instruments. The various empirical probability distributions extracted from these time series were shown to be consistent with the probabilistic predictions of QT. More than 70 years ago the claim was made that QT provided the most complete description of 'individual' physical systems and outcomes of the measurements performed on 'individual' physical systems were obtained in an intrinsically random way. Spin polarization correlation experiments (SPCEs), performed to test the validity of Bell inequalities, clearly demonstrated the existence of strong long-range correlations and confirmed that the beams hitting far away detectors somehow preserve the memory of their common source which would be destroyed if the individual counts of far away detectors were purely random. Since the probabilities describe the random experiments and are not the attributes of the 'individual' physical systems, the claim that QT provides a complete description of 'individual' physical systems seems not only unjustified but also misleading and counter productive. In this paper, we point out that we even do not know whether QT is predictably complete because it has not been tested carefully enough. Namely, it was not proven that the time series of existing experimental data did not contain some stochastic fine structures that could have been averaged out by describing them in terms of the empirical probability distributions. In this paper, we advocate various statistical tests that

  5. General general game AI

    OpenAIRE

    Togelius, Julian; Yannakakis, Georgios N.; 2016 IEEE Conference on Computational Intelligence and Games (CIG)

    2016-01-01

    Arguably the grand goal of artificial intelligence research is to produce machines with general intelligence: the capacity to solve multiple problems, not just one. Artificial intelligence (AI) has investigated the general intelligence capacity of machines within the domain of games more than any other domain given the ideal properties of games for that purpose: controlled yet interesting and computationally hard problems. This line of research, however, has so far focuse...

  6. Chinese Islam: A Complete Concert

    Directory of Open Access Journals (Sweden)

    Zvi Ben-Dor Benite

    2017-06-01

    Full Text Available Matthew S. Erie, China and Islam: The Prophet, the Party, and Law. Cambridge University Press, 2016. 472 pp. $140 (cloth/e-book. Jonathan Lipman, ed., Islamic Thought in China: Sino-Muslim Intellectual Evolution from the 17th to the 20th Century. Edinburgh University Press, 2016. 288 pp. £70 (cloth; e-book. Roberta Tontini, Muslim Sanzijing: Shifts and Continuities in the Definition of Islam in China. Brill, 2016. 238 pp. $125 (cloth. Why study a Chinese “minority” and its history? The task of scholars of Chinese Islam since the 1990s has been twofold: on the one hand, we have wanted to study Islam in China in its Chinese social and cultural context, as opposed to imagining it as a single separate entity, and to show that its history is relevant and meaningful for Chinese history in general. One could almost say that this goal was achieved a while ago. The next task has been to make the study of Chinese Islam and its history meaningful and useful for the greater community of scholars of Islam in general. It seems to me that with the books reviewed here, and with others in the making, we are getting close to reaching this target. In 1910, Marshall Broomhall’s Islam in China declared that Chinese Islam was a “neglected problem.” These books show that it is no longer neglected, and no longer a “problem”; rather, it is an exciting topic. Indeed, a complete, even if not harmonious, concert.

  7. Concatenated image completion via tensor augmentation and completion

    OpenAIRE

    Bengua, Johann A.; Tuan, Hoang D.; Phien, Ho N.; Do, Minh N.

    2016-01-01

    This paper proposes a novel framework called concatenated image completion via tensor augmentation and completion (ICTAC), which recovers missing entries of color images with high accuracy. Typical images are second- or third-order tensors (2D/3D) depending if they are grayscale or color, hence tensor completion algorithms are ideal for their recovery. The proposed framework performs image completion by concatenating copies of a single image that has missing entries into a third-order tensor,...

  8. Kurt Gödel, completeness, incompleteness

    Czech Academy of Sciences Publication Activity Database

    Hájek, Petr

    2007-01-01

    Roč. 82, č. 1 (2007), 012005_1-012005_4 E-ISSN 1742-6596. [Brno Kurt Gödel Days. Brno, 25.04.2007-28.04.2007] R&D Projects: GA AV ČR IAA100300503 Institutional research plan: CEZ:AV0Z10300504 Keywords : Kurt Gödel * completeness * incompleteness Subject RIV: BA - General Mathematics

  9. Interpolation for completely positive maps: Numerical solutions

    Czech Academy of Sciences Publication Activity Database

    Ambrozie, Calin-Grigore; Gheondea, A.

    2018-01-01

    Roč. 61, č. 1 (2018), s. 13-22 ISSN 1220-3874 Institutional support: RVO:67985840 Keywords : Choi matrix * completely positive * convex minimization Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.362, year: 2016 http://ssmr.ro/bulletin/volumes/61-1/node3.html

  10. Completeness for flat modal fixpoint logics

    NARCIS (Netherlands)

    Santocanale, L.; Venema, Y.

    2010-01-01

    This paper exhibits a general and uniform method to prove axiomatic completeness for certain modal fixpoint logics. Given a set Γ of modal formulas of the form γ(x,p1,…,pn), where x occurs only positively in γ, we obtain the flat modal fixpoint language L♯(Γ) by adding to the language of polymodal

  11. Tumor stroma with senescence-associated secretory phenotype in steatohepatitic hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Jee San Lee

    Full Text Available Senescence secretome was recently reported to promote liver cancer in an obese mouse model. Steatohepatitic hepatocellular carcinoma (SH-HCC, a new variant of HCC, has been found in metabolic syndrome patients, and pericellular fibrosis, a characteristic feature of SH-HCC, suggests that alteration of the tumor stroma might play an important role in SH-HCC development. Clinicopathological characteristics and tumor stroma showing senescence and senescence-associated secretory phenotype (SASP were investigated in 21 SH-HCCs and 34 conventional HCCs (C-HCCs. The expression of α-smooth muscle actin (α-SMA, p21Waf1/Cif1, γ-H2AX, and IL-6 was investigated by immunohistochemistry or immunofluorescence. SH-HCCs were associated with older age, higher body mass index, and a higher incidence of metabolic syndrome, compared to C-HCC (P <0.05, all. The numbers of α-SMA-positive cancer-associated fibroblasts (CAFs (P = 0.049 and α-SMA-positive CAFs co-expressing p21Waf1/Cif1 (P = 0.038, γ-H2AX (P = 0.065, and IL-6 (P = 0.048 were greater for SH-HCCs than C-HCCs. Additionally, non-tumoral liver from SH-HCCs showed a higher incidence of non-alcoholic fatty liver disease and a higher number of α-SMA-positive stellate cells expressing γ-H2AX and p21Waf1/Cif1 than that from C-HCCs (P <0.05, all. In conclusion, SH-HCCs are considered to occur more frequently in metabolic syndrome patients. Therein, senescent and damaged CAFs, as well as non-tumoral stellate cells, expressing SASP including IL-6 may contribute to the development of SH-HCC.

  12. Triclabendazole Effect on Protease Enzyme Activity in the Excretory- Secretory Products of Fasciola hepatica in Vitro.

    Directory of Open Access Journals (Sweden)

    Yosef Shrifi

    2014-03-01

    Full Text Available Fasciola hepatica is one of the most important helminthes parasites and triclabendazole (TCBZ is routinely used for treatment of infected people and animals. Secreted protease enzymes by the F. hepatica plays a critical role in the invasion, migration, nutrition and the survival of parasite and are key targets for novel drugs and vaccines. The aim of study was to determine the protease activity of excretory- secretory products (ESP of F. hepatica in the presence of TCBZ anthelmintic.F. hepatica helminthes were collected and cultured within RPMI 1640 [TCBZ treated (test and untreated (control] for 6 h at 37 °C. ESP of treated and control were collected, centrifuged and supernatants were stored at -20°C. Protein concentrations were measured according to Bradford method. Protease enzymes activities of ESP samples were estimated by using sigma's non-specific protease activity assay. ESP protein bands were detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE.Mean protein concentrations in control and treated of ESP samples were determined 196.1 ±14.52 and 376.4 ±28.20 μg/ml, respectively. Mean protease enzymes activities in control and treated were 0.37 ±0.1 and 0.089 ±0.03 U/ml, respectively. Significant difference between proteins concentrations and protease enzymes activities of two groups was observed (P<0.05. SDS-PAGE showed different patterns of protein bands between treated and control samples.The TCBZ reduced secreted protease enzymes activities and possibly effects on invasion, migration, nutrition and particularly survival of the parasite in the host tissues.

  13. Analysis of occludin trafficking, demonstrating continuous endocytosis, degradation, recycling and biosynthetic secretory trafficking.

    Directory of Open Access Journals (Sweden)

    Sarah J Fletcher

    Full Text Available Tight junctions (TJs link adjacent cells and are critical for maintenance of apical-basolateral polarity in epithelial monolayers. The TJ protein occludin functions in disparate processes, including wound healing and Hepatitis C Virus infection. Little is known about steady-state occludin trafficking into and out of the plasma membrane. Therefore, we determined the mechanisms responsible for occludin turnover in confluent Madin-Darby canine kidney (MDCK epithelial monolayers. Using various biotin-based trafficking assays we observed continuous and rapid endocytosis of plasma membrane localised occludin (the majority internalised within 30 minutes. By 120 minutes a significant reduction in internalised occludin was observed. Inhibition of lysosomal function attenuated the reduction in occludin signal post-endocytosis and promoted co-localisation with the late endocytic system. Using a similar method we demonstrated that ∼20% of internalised occludin was transported back to the cell surface. Consistent with these findings, significant co-localisation between internalised occludin and recycling endosomal compartments was observed. We then quantified the extent to which occludin synthesis and transport to the plasma membrane contributes to plasma membrane occludin homeostasis, identifying inhibition of protein synthesis led to decreased plasma membrane localised occludin. Significant co-localisation between occludin and the biosynthetic secretory pathway was demonstrated. Thus, under steady-state conditions occludin undergoes turnover via a continuous cycle of endocytosis, recycling and degradation, with degradation compensated for by biosynthetic exocytic trafficking. We developed a mathematical model to describe the endocytosis, recycling and degradation of occludin, utilising experimental data to provide quantitative estimates for the rates of these processes.

  14. Enhanced molecular aging in late-life depression: the Senescent Associated Secretory Phenotype

    Science.gov (United States)

    Diniz, Breno Satler; Reynolds, Charles F.; Sibille, Etienne; Lin, Chien-Wei; Tseng, George; Lotrich, Francis; Aizenstein, Howard J.; Butters, Meryl A.

    2016-01-01

    Objective This study aims to investigate whether a systemic molecular pattern associated with aging (senescent-associated secretory phenotype – SASP) is elevated in adults with late-life depression (LLD), compared to never-depressed elderly comparison participants. Design Cross-sectional study. Participants We included 111 older adults (80 with LLD and 31 comparison participants) in this study. Measurement A panel of 22 SASP-related proteins was extracted from a previous multiplex protein panel performed in these participants. We conducted a principal component analysis to create the SASP index based on individual weights of each of protein. Results Participants with LLD showed a significantly increased SASP index compared to comparison participants, after controlling for age, depressive symptoms, medical comorbidity (CIRS-G) scores, gender, and cognitive performance (F(1,98)=7.3, p=0.008). Correlation analyses revealed that the SASP index was positively correlated with age (r=0.2, p = 0.03) and CIRS score (r=0.27, p=0.005), and negatively correlated with information processing speed (r=−0.34, p=0.001), executive function (r=−0.27, p=0.004) and global cognitive performance (r=−0.28, p=0.007). Conclusions To the best of our knowledge, this is the first study to show that a set of proteins (i.e., SASP index) primarily associated with cellular aging, is abnormally regulated and elevated in LLD. These results suggest that individuals with LLD display enhanced aging-related molecular patterns that are associated with higher medical comorbidity and worse cognitive function. Finally, we provide a set of proteins that can serve as potential therapeutic targets and biomarkers to monitor the effects of therapeutic or preventative interventions in LLD. PMID:27856124

  15. Immunohistochemical analysis of Clara cell secretory protein expression in a transgenic model of mouse lung carcinogenesis

    International Nuclear Information System (INIS)

    Hicks, Sarah M.; Vassallo, Jeffrey D.; Dieter, Matthew Z.; Lewis, Cindy L.; Whiteley, Laurence O.; Fix, Andrew S.; Lehman-McKeeman, Lois D.

    2003-01-01

    Immunohistochemical methods have been widely used to determine the histogenesis of spontaneous and chemically-induced mouse lung tumors. Typically, antigens for either alveolar Type II cells or bronchiolar epithelial Clara cells are studied. In the present work, the morphological and immunohistochemical phenotype of a transgenic mouse designed to develop lung tumors arising from Clara cells was evaluated. In this model, Clara cell-specific transformation is accomplished by directed expression of the SV40 large T antigen (TAg) under the mouse Clara cell secretory protein (CC10) promoter. In heterozygous mice, early lesions at 1 month of age consisted of hyperplastic bronchiolar epithelial cells. These progressed to adenoma by 2 months as proliferating epithelium extended into adjacent alveolar spaces. By 4 months, a large portion of the lung parenchyma was composed of tumor masses. Expression of constitutive CC10 was diminished in transgenic animals at all time points. Only the occasional cell or segment of the bronchiolar epithelium stained positively for CC10 by immunohistochemistry, and all tumors were found to be uniformly negative for staining. These results were corroborated by Western blotting, where CC10 was readily detectable in whole lung homogenate from nontransgenic animals, but not detected in lung from transgenic animals at any time point. Tumors were also examined for expression of surfactant apoprotein C (SPC), an alveolar Type II cell-specific marker, and found to be uniformly negative for staining. These results indicate that, in this transgenic model, expression of CC10, which is widely used to determine whether lung tumors arise from Clara cells, was reduced and subsequently lost during Clara cell tumor progression

  16. Immunolocalization and immunodetection of the excretory/secretory (ES) antigens of Fasciola gigantica.

    Science.gov (United States)

    Khan, M A Hannan; Ullah, Rizwan; Rehman, Abdur; Rehman, Lubna; P A, Ahammed Shareef; Abidi, S M A

    2017-01-01

    The digenetic trematode Fasciola gigantica is a parasite of great agricultural and economic importance. Along with Fasciola hepatica, F. gigantica incurs huge economic losses to the agricultural sector. Because of unavailability of an effective and commercial vaccine, the earliest diagnosis of the disease is the only way to control the disease. The conventional coprological techniques are able to detect the disease only after the parasites get matured and starts releasing their eggs with the faeces of host, therefore prepatent infection remain undiagnosed. The alternative method is by serological tests that uses circulatory antigens. Despite high sensitivity, their reliability is quite low because of the common antigens shared between different helminth parasites. To overcome this, investigation was shifted to identify the copro-antigens which could be more sensitive and reliable. In the present study, we tried to identify some of the immunodominant proteins from the Excretory Secretory (ES) product of F. gigantica which can be further characterized and used for early detection of infection and also as drug and vaccine candidates. The ES products of F. gigantica were collected and used for raising the polyclonal antibody in rabbit. The polypeptide profile was generated as well as immunogenic polypeptides were identified. The Source of ES antigen was immunolocalized using confocal microscopy and dot blot assay was performed to diagnose field infection. The polypeptide profile of ES products revealed a total of 24 polypeptides out of which 12 immunogenic polypeptides were identified by western blotting. Confocal micrographs showed the immunolocalization of antigens in the intestinal caecae, vitalline glands, gonads as well as in the tegument of the worm. The dot blot assay confirmed the utility of ES products for the detection of field infection. Subsequently, cross reactivity was found negative with Gigantocotyle explanatum; an amphitome parasite of same habitat

  17. Immunolocalization and immunodetection of the excretory/secretory (ES antigens of Fasciola gigantica.

    Directory of Open Access Journals (Sweden)

    M A Hannan Khan

    Full Text Available The digenetic trematode Fasciola gigantica is a parasite of great agricultural and economic importance. Along with Fasciola hepatica, F. gigantica incurs huge economic losses to the agricultural sector. Because of unavailability of an effective and commercial vaccine, the earliest diagnosis of the disease is the only way to control the disease. The conventional coprological techniques are able to detect the disease only after the parasites get matured and starts releasing their eggs with the faeces of host, therefore prepatent infection remain undiagnosed. The alternative method is by serological tests that uses circulatory antigens. Despite high sensitivity, their reliability is quite low because of the common antigens shared between different helminth parasites. To overcome this, investigation was shifted to identify the copro-antigens which could be more sensitive and reliable. In the present study, we tried to identify some of the immunodominant proteins from the Excretory Secretory (ES product of F. gigantica which can be further characterized and used for early detection of infection and also as drug and vaccine candidates. The ES products of F. gigantica were collected and used for raising the polyclonal antibody in rabbit. The polypeptide profile was generated as well as immunogenic polypeptides were identified. The Source of ES antigen was immunolocalized using confocal microscopy and dot blot assay was performed to diagnose field infection. The polypeptide profile of ES products revealed a total of 24 polypeptides out of which 12 immunogenic polypeptides were identified by western blotting. Confocal micrographs showed the immunolocalization of antigens in the intestinal caecae, vitalline glands, gonads as well as in the tegument of the worm. The dot blot assay confirmed the utility of ES products for the detection of field infection. Subsequently, cross reactivity was found negative with Gigantocotyle explanatum; an amphitome parasite

  18. Efficient secretory expression of recombinant proteins in Escherichia coli with a novel actinomycete signal peptide.

    Science.gov (United States)

    Cui, Yanbing; Meng, Yiwei; Zhang, Juan; Cheng, Bin; Yin, Huijia; Gao, Chao; Xu, Ping; Yang, Chunyu

    2017-01-01

    In well-established heterologous hosts, such as Escherichia coli, recombinant proteins are usually intracellular and frequently found as inclusion bodies-especially proteins possessing high rare codon content. In this study, successful secretory expression of three hydrolases, in a constructed inducible or constitutive system, was achieved by fusion with a novel signal peptide (Kp-SP) from an actinomycete. The signal peptide efficiently enabled extracellular protein secretion and also contributed to the active expression of the intracellular recombinant proteins. The thermophilic α-amylase gene of Bacillus licheniformis was fused with Kp-SP. Both recombinants, carrying inducible and constitutive plasmids, showed remarkable increases in extracellular and intracellular amylolytic activity. Amylase activity was observed to be > 10-fold in recombinant cultures with the constitutive plasmid, pBSPPc, compared to that in recombinants lacking Kp-SP. Further, the signal peptide enabled efficient secretion of a thermophilic cellulase into the culture medium, as demonstrated by larger halo zones and increased enzymatic activities detected in both constructs from different plasmids. For heterologous proteins with a high proportion of rare codons, it is difficult to obtain high expression in E. coli owing to the codon bias. Here, the fusion of an archaeal homologue of the amylase encoding gene, FSA, with Kp-SP resulted in > 5-fold higher extracellular activity. The successful extracellular expression of the amylase indicated that the signal peptide also contributed significantly to its active expression and signified the potential value of this novel and versatile signal peptide in recombinant protein production. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Mammary analogue secretory carcinoma (MASC) of salivary gland in four Mexican patients.

    Science.gov (United States)

    Serrano-Arévalo, Mónica L; Mosqueda-Taylor, Adalberto; Domínguez-Malagón, Hugo; Michal, Michal

    2015-01-01

    The Clinco-pathological, immunohistochemical and molecular findings of four cases of Mammary Analogue Secretory Carcinoma (MASC) of salivary glands found in Mexico are described. The cases were extracted from 253 salivary gland tumors from a single institution in Mexico City. The 85 Candidates for initial selection were: low grade mucoepidermoid carcinoma (MEC) (N=70 ), Acinic cell cancinoma (AciCC) (N=14), papillary cystadenocarcinoma (N=1), and adenocarcinoma NOS (N=0). Tumors with some histological features consistent with MASC (N= 17, 6.7%) were studied by immunohistochemistry for mammaglobin, STAT5, and S-100 protein and four cases were positive (1.5%), thus the diagnosis of MASC was established, and these were submitted for molecular studies for ETV6-NTRK3. Fusion gene was demonstrated in three cases, two had been erroneously diagnosed as poorly granulated AciCC, and one as low grade MEC with microcystic pattern. Female gender predominated (3:1); one occurred in the parotid, two in minor salivary glands and one in the submaxillary gland; infiltrating borders, atypical mitosis and lymph node metastases were seen in the parotideal tumor. Two patients with major salivary gland tumors are alive and well at 10 and 20 months respectively, the two patients with minor salivary gland tumors are lost. It can be concluded that is important to think in MASC in poorly granulated AciCC and low grade MEC with microcystic pattern. Immunohistochemisty studies confirm the diagnosis, preferentially supported by molecular studies. MASC may follow aggressive behavior or transform into a high grade neoplasm.

  20. Biochemical and immunological characterization of annexin B30 from Clonorchis sinensis excretory/secretory products.

    Science.gov (United States)

    He, Lei; Ren, Mengyu; Chen, Xueqing; Wang, Xiaoyun; Li, Shan; Lin, Jinsi; Liang, Chi; Liang, Pei; Hu, Yue; Lei, Huali; Bian, Meng; Huang, Yan; Wu, Zhongdao; Li, Xuerong; Yu, Xinbing

    2014-07-01

    Clonorchis sinensis has been classified as group I biological carcinogen for cholangiocarcinoma by the World Health Organization. Biological studies on excretory/secretory products (ESPs) enabled us to understand the pathogenesis mechanism of C. sinensis and develop new strategies for the prevention of clonorchiasis. In this study, sequence analysis showed that annexin B30 from C. sinensis (CsANXB30) is composed of four annexin repeats which were characterized by type II and III Ca(2+)-binding sites or KGD motif with the capability of Ca(2+)-binding. In addition, immunoblot assay revealed that recombinant CsANXB30 (rCsANXB30) could be recognized by the sera from rats infected with C. sinensis and the sera from rats immunized by CsESPs. Real-time PCR showed that its transcriptional level was the highest at the stage of metacercaria. Immunofluorescence assay was employed to confirm that CsANXB30 was distributed in the tegument, intestine, and egg of adult worms, as well as the tegument and vitellarium of metacercaria. rCsANXB30 was able to bind phospholipid in a Ca(2+)-dependent manner and human plasminogen in a dose-dependent manner. Moreover, cytokine and antibody measurements indicated that rats subcutaneously immunized with rCsANXB30 developed a strong IL-10 production in spleen cells and a high level of IgG1 isotype, indicating that rCsANXB30 could trigger specific humoral and cellular immune response in rats. The present results implied that CsANXB30 might be involved in a host-parasite interaction and affected the immune response of the host during C. sinensis infection.

  1. The Secretory Response of Rat Peritoneal Mast Cells on Exposure to Mineral Fibers.

    Science.gov (United States)

    Borelli, Violetta; Trevisan, Elisa; Francesca, Vita; Zabucchi, Giuliano

    2018-01-10

    Exposure to mineral fibers is of substantial relevance to human health. A key event in exposure is the interaction with inflammatory cells and the subsequent generation of pro-inflammatory factors. Mast cells (MCs) have been shown to interact with titanium oxide (TiO₂) and asbestos fibers. In this study, we compared the response of rat peritoneal MCs challenged with the asbestos crocidolite and nanowires of TiO₂ to that induced by wollastonite employed as a control fiber. Rat peritoneal MCs (RPMCs), isolated from peritoneal lavage, were incubated in the presence of mineral fibers. The quantities of secreted enzymes were evaluated together with the activity of fiber-associated enzymes. The ultrastructural morphology of fiber-interacting RPMCs was analyzed with electron microscopy. Asbestos and TiO₂ stimulate MC secretion. Secreted enzymes bind to fibers and exhibit higher activity. TiO₂ and wollastonite bind and improve enzyme activity, but to a lesser degree than crocidolite. (1) Mineral fibers are able to stimulate the mast cell secretory process by both active (during membrane interaction) and/or passive (during membrane penetration) interaction; (2) fibers can be found to be associated with secreted enzymes-this process appears to create long-lasting pro-inflammatory environments and may represent the active contribution of MCs in maintaining the inflammatory process; (3) MCs and their enzymes should be considered as a therapeutic target in the pathogenesis of asbestos-induced lung inflammation; and (4) MCs can contribute to the inflammatory effect associated with selected engineered nanomaterials, such as TiO₂ nanoparticles.

  2. Deposition of lipid, protein, and secretory phospholipase A2 on hydrophilic contact lenses.

    Science.gov (United States)

    Mochizuki, Hiroshi; Yamada, Masakazu; Hatou, Shin; Kawashima, Motoko; Hata, Seiichiro

    2008-01-01

    Recent studies have shown that low tear phospholipid levels are associated with tear film instability in hydrophilic contact lens wearers. The concentration of secretory phospholipase A2 (sPLA2), the enzyme that hydrolyzes phospholipids, in tears is known to exceed the levels found in serum by four orders of magnitude. This study was performed to determine the levels of sPLA2 from the deposition on two different frequent-replacement contact lens materials. Polymacon and etafilcon A contact lenses worn for 2 weeks by 16 experienced contact lens wearers were used for the analysis. Total lipids were determined by the sulfo-phospho-vanillin reaction. Phospholipids in lipid extracts were estimated by phosphorus determination with ammonium molybdate through enzymatic digestion. Total protein was measured by bicinchoninic acid analysis. Double-antibody sandwich enzyme-linked immunosorbent assay was used to determine sPLA2 concentrations. Total lipid deposition was found to be greater in the polymacon group (66.3+/-16.3 microg/lens) than in the etafilcon A group, although phospholipids were not detected in either group. The etafilcon A group had greater deposition of protein (3.7+/-0.7 mg/lens) than the polymacon group had. The etafilcon A group deposited statistically significantly more group IIa sPLA2 (1.1+/-0.3 microg/lens) than the polymacon group (0.07+/-0.04 microg/lens) did (P<0.001). There was a significant difference in the lipid and protein deposition profiles in the two lenses tested. A significant amount of sPLA2 in the deposition on contact lenses may play a role in tear film instability in hydrophilic contact lens wearers.

  3. Regulation of membrane fusion and secretory events in the sea urchin embryo

    International Nuclear Information System (INIS)

    Roe, J.L.

    1990-01-01

    Membrane fusion and secretory events play a key role in fertilization and early development in the sea urchin embryo. To investigate the mechanism of membrane fusion, the effect of inhibitors of metalloendoprotease activity was studied on two model systems of cell fusion; fertilization and spiculogenesis by primary mesenchyme cells in the embryo. Both the zinc chelator, 1,10-phenanthroline, and peptide metalloprotease substrates were found to inhibit both fertilization and gamete fusion, while peptides that are not substrates of metalloproteases did not affect either process. Primary mesenchyme cells form the larval skeleton in the embryo by deposition of mineral and an organic matrix into a syncytial cavity formed by fusion of filopodia of these cells. Metalloprotease inhibitors were found to inhibit spiculogenesis both in vivo and in cultures of isolated primary mesenchyme cells, and the activity of a metalloprotease of the appropriate specificity was found in the primary mesenchyme cells. These two studies implicate the activity of a metalloprotease in a necessary step in membrane fusion. Following fertilization, exocytosis of the cortical granules results in the formation of the fertilization envelope and the hyaline layer, that surround the developing embryo. The hatching enzyme is secreted by the blastula stage sea urchin embryo, which proteolyzes the fertilization envelope surrounding the embryo, allowing the embryo to hatch. Using an assay that measures 125 I-fertilization envelope degradation, the hatching enzyme was identified as a 33 kDa metalloprotease, and was purified by ion-exchange and affinity chromatography from the hatching media of Strongylocentrotus purpuratus embryos. The hatching enzyme showed a substrate preference for only a minor subset of fertilization envelope proteins

  4. Herpes simplex virus downregulation of secretory leukocyte protease inhibitor enhances human papillomavirus type 16 infection.

    Science.gov (United States)

    Skeate, Joseph G; Porras, Tania B; Woodham, Andrew W; Jang, Julie K; Taylor, Julia R; Brand, Heike E; Kelly, Thomas J; Jung, Jae U; Da Silva, Diane M; Yuan, Weiming; Kast, W Martin

    2016-02-01

    Herpes simplex virus (HSV) was originally implicated in the aetiology of cervical cancer, and although high-risk human papillomavirus (HPV) is now the accepted causative agent, the epidemiological link between HSV and HPV-associated cancers persists. The annexin A2 heterotetramer (A2t) has been shown to mediate infectious HPV type 16 (HPV16) uptake by human keratinocytes, and secretory leukocyte protease inhibitor (SLPI), an endogenous A2t ligand, inhibits HPV16 uptake and infection. Interestingly, HSV infection induces a sustained downregulation of SLPI in epithelial cells, which we hypothesized promotes HPV16 infection through A2t. Here, we show that in vitro infection of human keratinocytes with HSV-1 or HSV-2, but not with an HSV-1 ICP4 deletion mutant that does not downregulate SLPI, leads to a >70% reduction of SLPI mRNA and a >60% decrease in secreted SLPI protein. Consequently, we observed a significant increase in the uptake of HPV16 virus-like particles and gene transduction by HPV16 pseudovirions (two- and 2.5-fold, respectively) in HSV-1- and HSV-2-infected human keratinocyte cell cultures compared with uninfected cells, whereas exogenously added SLPI reversed this effect. Using a SiMPull (single-molecule pulldown) assay, we demonstrated that endogenously secreted SLPI interacts with A2t on epithelial cells in an autocrine/paracrine manner. These results suggested that ongoing HSV infection and resultant downregulation of local levels of SLPI may impart a greater susceptibility for keratinocytes to HPV16 infection through the host cell receptor A2t, providing a mechanism that may, in part, provide an explanation for the aetiological link between HSV and HPV-associated cancers.

  5. Excretory/secretory products from Trichinella spiralis adult worms ameliorate DSS-induced colitis in mice.

    Directory of Open Access Journals (Sweden)

    Xiaodi Yang

    Full Text Available BACKGROUND: Many evidences show the inverse correlation between helminth infection and allergic or autoimmune diseases. Identification and characterization of the active helminth-derived products responsible for the beneficial effects on allergic or inflammatory diseases will provide another feasible approach to treat these diseases. METHODS AND FINDINGS: Colitis was induced in C57BL/6 mice by giving 3% DSS orally for 7 days. During this period, the mice were treated daily with the excretory/secretory products from T. spiralis adult worms (AES intraperitoneally. The severity of colitis was monitored by measuring body weight, stool consistency or bleeding, colon length and inflammation. To determine the T. spiralis AES product-induced immunological response, Th1, Th2, Th17 and regulatory cytokine profiles were measured in lymphocytes isolated from colon, mesenteric lymph nodes (MLN, and the spleen of treated mice. The CD4+ CD25+ FOXP3+ regulatory T cells (Tregs were also measured in the spleens and MLN of treated mice. Mice treated with AES significantly ameliorated the severity of the DSS-induced colitis indicated by the reduced disease manifestations, improved macroscopic and microscopic inflammation correlated with the up-regulation of Treg response (increased regulatory cytokines IL-10, TGF-beta and regulatory T cells and down-regulation of pro-inflammatory cytokines (IFN-gamma, IL-6 and IL-17 in the spleens, MLN and colon of treated mice. CONCLUSIONS: Our results provide direct evidences that T. spiralis AES have a therapeutic potential for alleviating inflammatory colitis in mice. This effect is possibly mediated by the immunomodulation of regulatory T cells to produce regulatory and anti-inflammatory cytokines and inhibit pro-inflammatory cytokines.

  6. Prematch salivary secretory immunoglobulin a in soccer players from the 2014 World Cup qualifying campaign.

    Science.gov (United States)

    Morgans, Ryland; Owen, Adam; Doran, Dominic; Drust, Barry; Morton, James P

    2015-04-01

    To monitor resting salivary secretory immunoglobulin A (SIgA) levels in international soccer players during the short-term training period that precedes international match play. In a repeated-measure design, saliva samples were obtained from 13 outfield soccer players who participated in the training camps preceding 7 games (5 home and 2 away) of the 2014 FIFA World Cup qualifying campaign. Samples were obtained daily for 4 d preceding each game (and analyzed for SIgA using the IPRO oral-fluid-collection system) at match day minus 1 (MD-1), minus 2 (MD-2), minus 3 (MD-3), and minus 4 (MD-4). SIgA displayed a progressive decline (P = .01) during the 4-d training period (MD-4, 365 ± 127 μg/mL; MD-3, 348 ± 154 μg/mL; MD-2, 290 ± 138 μg/mL; MD-1, 256 ± 90 μg/mL) such that MD-1 values were significantly lower (P = .01) than both MD-4 and MD-3. The 95% confidence intervals for the differences between MD-1 and MD-4 were -191 to -26 and between MD-1 and MD-3 were -155 to -28. Data demonstrate that a short-term soccer-training camp in preparation for international competition induces detectable perturbations to mucosal immunity. Future studies should monitor SIgA (as a practical and noninvasive measure of immunity) alongside internal and external measures of training load in an attempt to strategically individualize training and nutritional strategies that may support optimal preparation for high-level competition.

  7. Potential role of recombinant secretory leucoprotease inhibitor in the prevention of neutrophil mediated matrix degradation.

    Science.gov (United States)

    Llewellyn-Jones, C G; Lomas, D A; Stockley, R A

    1994-06-01

    Neutrophil elastase is able to degrade connective tissue matrices and is thought to be involved in the pathogenesis of destructive lung diseases. The ability of recombinant secretory leucoprotease inhibitor (rSLPI) to inhibit neutrophil mediated degradation of fibronectin in vitro is demonstrated and its efficacy compared with native alpha-1-proteinase inhibitor (n alpha 1-PI), recombinant alpha-1-proteinase inhibitor (r alpha 1-PI), and the chemical elastase inhibitor ICI 200,355. When preincubated with neutrophils both rSLPI and r alpha 1-PI were effective inhibitors of fibronectin degradation although n alpha 1-PI and ICI 200,355 were less effective. Recombinant SLPI was the most effective inhibitor when the cells were allowed to adhere to fibronectin before the addition of the inhibitors. Preincubation of rSLPI (0.1 mumol/l) with the fibronectin plate resulted in almost total inhibition of fibronectin degradation (reduced to 3.3 (SE 0.9)% of control). Pretreating the fibronectin plate with 1 mumol/l rSLPI, r alpha 1-PI and ICI 200,355 followed by thorough washing before the addition of cells resulted in no inhibition of fibronectin degradation with r alpha 1-PI and the ICI inhibitor, but rSLPI retained its inhibitory effect. This effect could be reduced by adding rSLPI in high pH buffer or 2 mol/1 NaCl. It is postulated that rSLPI binds to fibronectin to form a protective layer which prevents its degradation by neutrophil elastase. It may prove to be the most useful therapeutic agent in the prevention of neutrophil mediated lung damage.

  8. Structure completion for facade layouts

    KAUST Repository

    Fan, Lubin; Musialski, Przemyslaw; Liu, Ligang; Wonka, Peter

    2014-01-01

    completion with large missing parts is an ill-posed problem. Therefore, we combine two sources of information to derive our solution: the observed shapes and a database of complete layouts. The problem is also very difficult, because shape positions

  9. Non-completion and informed consent.

    Science.gov (United States)

    Wertheimer, Alan

    2014-02-01

    There is a good deal of biomedical research that does not produce scientifically useful data because it fails to recruit a sufficient number of subjects. This fact is typically not disclosed to prospective subjects. In general, the guidance about consent concerns the information required to make intelligent self-interested decisions and ignores some of the information required for intelligent altruistic decisions. Bioethics has worried about the 'therapeutic misconception', but has ignored the 'completion misconception'. This article argues that, other things being equal, prospective subjects should be informed about the possibility of non-completion as part of the standard consent process if (1) it is or should be anticipatable that there is a non-trivial possibility of non-completion and (2) that information is likely to be relevant to a prospective subject's decision to consent. The article then considers several objections to the argument, including the objection that disclosing non-completion information would make recruitment even more difficult.

  10. Wolfram syndrome 1 gene (WFS1) product localizes to secretory granules and determines granule acidification in pancreatic beta-cells.

    Science.gov (United States)

    Hatanaka, Masayuki; Tanabe, Katsuya; Yanai, Akie; Ohta, Yasuharu; Kondo, Manabu; Akiyama, Masaru; Shinoda, Koh; Oka, Yoshitomo; Tanizawa, Yukio

    2011-04-01

    Wolfram syndrome is an autosomal recessive disorder characterized by juvenile-onset insulin-dependent diabetes mellitus and optic atrophy. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER) resident transmembrane protein. The Wfs1-null mouse exhibits progressive insulin deficiency causing diabetes. Previous work suggested that the function of the WFS1 protein is connected to unfolded protein response and to intracellular Ca(2+) homeostasis. However, its precise molecular function in pancreatic β-cells remains elusive. In our present study, immunofluorescent and electron-microscopic analyses revealed that WFS1 localizes not only to ER but also to secretory granules in pancreatic β-cells. Intragranular acidification was assessed by measuring intracellular fluorescence intensity raised by the acidotrophic agent, 3-[2,4-dinitroanilino]-3'-amino-N-methyldipropyramine. Compared with wild-type β-cells, there was a 32% reduction in the intensity in WFS1-deficient β-cells, indicating the impairment of granular acidification. This phenotype may, at least partly, account for the evidence that Wfs1-null islets have impaired proinsulin processing, resulting in an increased circulating proinsulin level. Morphometric analysis using electron microscopy evidenced that the density of secretory granules attached to the plasma membrane was significantly reduced in Wfs1-null β-cells relative to that in wild-type β-cells. This may be relevant to the recent finding that granular acidification is required for the priming of secretory granules preceding exocytosis and may partly explain the fact that glucose-induced insulin secretion is profoundly impaired in young prediabetic Wfs1-null mice. These results thus provide new insights into the molecular mechanisms of β-cell dysfunction in patients with Wolfram syndrome.

  11. Magic informationally complete POVMs with permutations

    Science.gov (United States)

    Planat, Michel; Gedik, Zafer

    2017-09-01

    Eigenstates of permutation gates are either stabilizer states (for gates in the Pauli group) or magic states, thus allowing universal quantum computation (Planat, Rukhsan-Ul-Haq 2017 Adv. Math. Phys. 2017, 5287862 (doi:10.1155/2017/5287862)). We show in this paper that a subset of such magic states, when acting on the generalized Pauli group, define (asymmetric) informationally complete POVMs. Such informationally complete POVMs, investigated in dimensions 2-12, exhibit simple finite geometries in their projector products and, for dimensions 4 and 8 and 9, relate to two-qubit, three-qubit and two-qutrit contextuality.

  12. Report of a complete second branchial fistula.

    LENUS (Irish Health Repository)

    Khan, Mohammad Habibullah

    2010-08-01

    We report a case of complete congenital branchial fistula with an internal opening near the tonsillar fossa. Cysts, fistulas, and sinuses of the second branchial cleft are the most common developmental anomalies arising from the branchial apparatus. In our case, a 43-year-old man presented with a several-year history of a discharging sinus from the right side of his neck, consistent with a branchial fistula. He underwent various investigations and finally was treated with a one-stage complete surgical excision of the fistula tract. We describe the general clinical presentation, investigations, and surgical outcome of this case.

  13. Effects of sexually dimorphic growth hormone secretory patterns on arachidonic acid metabolizing enzymes in rodent heart

    International Nuclear Information System (INIS)

    Zhang, Furong; Yu, Xuming; He, Chunyan; Ouyang, Xiufang; Wu, Jinhua; Li, Jie; Zhang, Junjie; Duan, Xuejiao; Wan, Yu; Yue, Jiang

    2015-01-01

    The arachidonic acid (AA) metabolizing enzymes are the potential therapeutic targets of cardiovascular diseases (CVDs). As sex differences have been shown in the risk and outcome of CVDs, we investigated the regulation of heart AA metabolizing enzymes (COXs, LOXs, and CYPs) by sex-dependent growth hormone (GH) secretory patterns. The pulsatile (masculine) GH secretion at a physiological concentration decreased CYP1A1 and CYP2J3 mRNA levels more efficiently in the H9c2 cells compared with the constant (feminine) GH secretion; however, CYP1B1 mRNA levels were higher following the pulsatile GH secretion. Sex differences in CYP1A1, CYP1B1, and CYP2J11 mRNA levels were observed in both the wild-type and GHR deficient mice. No sex differences in the mRNA levels of COXs, LOXs, or CYP2E1 were observed in the wild-type mice. The constant GH infusion induced heart CYP1A1 and CYP2J11, and decreased CYP1B1 in the male C57/B6 mice constantly infused with GH (0.4 μg/h, 7 days). The activity of rat Cyp2j3 promoter was inhibited by the STAT5B protein, but was activated by C/EBPα (CEBPA). Compared with the constant GH administration, the levels of the nuclear phosphorylated STAT5B protein and its binding to the rat Cyp2j3 promoter were higher following the pulsatile GH administration. The constant GH infusion decreased the binding of the nuclear phosphorylated STAT5B protein to the mouse Cyp2j11 promoter. The data suggest the sexually dimorphic transcription of heart AA metabolizing enzymes, which might alter the risk and outcome of CVDs. GHR-STAT5B signal transduction pathway may be involved in the sex difference in heart CYP2J levels. - Highlights: • The transcription of heart Cyp1a1, Cyp1b1 and Cyp2j genes is sexually dimorphic. • There are no sex differences in the mRNA levels of heart COXs, LOXs, or CYP2E1. • GHR-STAT5B pathway is involved in sexually dimorphic transcription of heart Cpy2j genes. • Heart CYPs-mediated metabolism pathway of arachidonic acid may be sex

  14. Identification of colonic fibroblast secretomes reveals secretory factors regulating colon cancer cell proliferation.

    Science.gov (United States)

    Chen, Sun-Xia; Xu, Xiao-En; Wang, Xiao-Qing; Cui, Shu-Jian; Xu, Lei-Lei; Jiang, Ying-Hua; Zhang, Yang; Yan, Hai-Bo; Zhang, Qian; Qiao, Jie; Yang, Peng-Yuan; Liu, Feng

    2014-10-14

    Stromal microenvironment influences tumor cell proliferation and migration. Fibroblasts represent the most abundant stromal constituents. Here, we established two pairs of normal fibroblast (NF) and cancer-associated fibroblast (CAF) cultures from colorectal adenocarcinoma tissues and the normal counterparts. The NFs and CAFs were stained positive for typical fibroblast markers and inhibited colon cancer (CC) cell proliferation in in vitro cocultures and in xenograft mouse models. The fibroblast conditioned media were analyzed using LC-MS and 227 proteins were identified at a false discovery rate of 1.3%, including 131 putative secretory and 20 plasma membrane proteins. These proteins were enriched for functional categories of extracellular matrix, adhesion, cell motion, inflammatory response, redox homeostasis and peptidase inhibitor. Secreted protein acidic and rich in cysteine, transgelin, follistatin-related protein 1 (FSTL1) and decorin was abundant in the fibroblast secretome as confirmed by Western blot. Silencing of FSTL1 and transgelin in colonic fibroblast cell line CCD-18Co induced an accelerated proliferation of CC cells in cocultures. Exogenous FSTL1 attenuates CC cell proliferation in a negative fashion. FSTL1 was upregulated in CC patient plasma and cancerous tissues but had no implication in prognosis. Our results provided novel insights into the molecular signatures and modulatory role of CC associated fibroblasts. In this study, a label-free LC-MS was performed to analyze the secretomes of two paired primary fibroblasts, which were isolated from fresh surgical specimen of colorectal adenocarcinoma and adjacent normal colonic tissues and exhibited negative modulatory activity for colon cancer cell growth in in vitro cocultures and in vivo xenograph mouse models. Follistatin-related protein 1 was further revealed to be one of the stroma-derived factors of potential suppression role for colon cancer cell proliferation. Our results provide novel

  15. Effects of sexually dimorphic growth hormone secretory patterns on arachidonic acid metabolizing enzymes in rodent heart

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Furong; Yu, Xuming [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); He, Chunyan [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Ouyang, Xiufang; Wu, Jinhua; Li, Jie; Zhang, Junjie; Duan, Xuejiao [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Wan, Yu [Department of Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Yue, Jiang, E-mail: yuejiang@whu.edu.cn [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China)

    2015-12-15

    The arachidonic acid (AA) metabolizing enzymes are the potential therapeutic targets of cardiovascular diseases (CVDs). As sex differences have been shown in the risk and outcome of CVDs, we investigated the regulation of heart AA metabolizing enzymes (COXs, LOXs, and CYPs) by sex-dependent growth hormone (GH) secretory patterns. The pulsatile (masculine) GH secretion at a physiological concentration decreased CYP1A1 and CYP2J3 mRNA levels more efficiently in the H9c2 cells compared with the constant (feminine) GH secretion; however, CYP1B1 mRNA levels were higher following the pulsatile GH secretion. Sex differences in CYP1A1, CYP1B1, and CYP2J11 mRNA levels were observed in both the wild-type and GHR deficient mice. No sex differences in the mRNA levels of COXs, LOXs, or CYP2E1 were observed in the wild-type mice. The constant GH infusion induced heart CYP1A1 and CYP2J11, and decreased CYP1B1 in the male C57/B6 mice constantly infused with GH (0.4 μg/h, 7 days). The activity of rat Cyp2j3 promoter was inhibited by the STAT5B protein, but was activated by C/EBPα (CEBPA). Compared with the constant GH administration, the levels of the nuclear phosphorylated STAT5B protein and its binding to the rat Cyp2j3 promoter were higher following the pulsatile GH administration. The constant GH infusion decreased the binding of the nuclear phosphorylated STAT5B protein to the mouse Cyp2j11 promoter. The data suggest the sexually dimorphic transcription of heart AA metabolizing enzymes, which might alter the risk and outcome of CVDs. GHR-STAT5B signal transduction pathway may be involved in the sex difference in heart CYP2J levels. - Highlights: • The transcription of heart Cyp1a1, Cyp1b1 and Cyp2j genes is sexually dimorphic. • There are no sex differences in the mRNA levels of heart COXs, LOXs, or CYP2E1. • GHR-STAT5B pathway is involved in sexually dimorphic transcription of heart Cpy2j genes. • Heart CYPs-mediated metabolism pathway of arachidonic acid may be sex

  16. Molecular characterization of Clonorchis sinensis secretory myoglobin: Delineating its role in anti-oxidative survival

    Science.gov (United States)

    2014-01-01

    Background Clonorchiasis is a globally important, neglected food-borne disease caused by Clonorchis sinensis (C. sinensis), and it is highly related to cholangiocarcinoma and hepatocellular carcinoma. Increased molecular evidence has strongly suggested that the adult worm of C. sinensis continuously releases excretory-secretory proteins (ESPs), which play important roles in the parasite-host interactions, to establish successful infection and ensure its own survival. Myoglobin, a hemoprotein, is present in high concentrations in trematodes and ESPs. To further understand the biological function of CsMb and its putative roles in the interactions of C. sinensis with its host, we explored the molecular characterization of CsMb in this paper. Methods We expressed CsMb and its mutants in E. coli BL21 and identified its molecular characteristics using bioinformatics analysis and experimental approaches. Reverse transcription PCR analysis was used to measure myoglobin transcripts of C. sinensis with different culture conditions. The peroxidase activity of CsMb was confirmed by spectrophotometry. We co-cultured RAW264.7 cells with recombinant CsMb (rCsMb), and we then measured the production of hydrogen peroxide (H2O2) and nitric oxide (NO) in addition to the mRNA levels of inducible nitric oxide synthase (iNOS), Cu-Zn superoxide dismutase (SOD1) and Mn superoxide dismutase (SOD2) in activated RAW264.7 cells. Results In the in vitro culture of adult worms, the transcripts of CsMb increased with the increase of oxygen content. Oxidative stress conditions induced by H2O2 increased the levels of CsMb transcripts in a dose-dependent manner. Furthermore, CsMb catalyzed oxidation reactions in the presence of H2O2, and amino acid 34 of CsMb played an essential role in its reaction with H2O2. In addition, CsMb significantly reduced H2O2 and NO levels in LPS-activated macrophages, and CsMb downregulated iNOS and SOD expression in activated macrophages. Conclusion The present study

  17. Ex vivo effect of varespladib on secretory phospholipase A2 alveolar activity in infants with ARDS.

    Directory of Open Access Journals (Sweden)

    Daniele De Luca

    Full Text Available Secretory phospholipase A2 (sPLA2 plays a pivotal role in acute respiratory distress syndrome (ARDS. This enzyme seems an interesting target to reduce surfactant catabolism and lung tissue inflammation. Varespladib is a specifically designed indolic sPLA2 inhibitor, which has shown promising results in animals and adults. No specific data in pediatric ARDS patients are yet available.We studied varespladib in broncho-alveolar lavage (BAL fluids obtained ex vivo from pediatric ARDS patients. Clinical data and worst gas exchange values during the ARDS course were recorded. Samples were treated with saline or 10-40-100 µM varespladib and incubated at 37°C. Total sPLA2 activity was measured by non-radioactive method. BAL samples were subjected to western blotting to identify the main sPLA isotypes with different sensitivity to varespladib. Results was corrected for lavage dilution using the serum-to-BAL urea ratio and for varespladib absorbance.Varespladib reduces sPLA2 activity (p<0.0001 at 10,40 and 100 µM; both sPLA2 activity reduction and its ratio to total proteins significantly raise with increasing varespladib concentrations (p<0.001. IC(50 was 80 µM. Western blotting revealed the presence of sPLA2-IIA and -IB isotypes in BAL samples. Significant correlations exist between the sPLA2 activity reduction/proteins ratio and PaO(2 (rho = 0.63;p<0.001, PaO(2/FiO(2 (rho = 0.7; p<0.001, oxygenation (rho = -0.6; p<0.001 and ventilation (rho = -0.4;p = 0.038 indexes.Varespladib significantly inhibits sPLA2 in BAL of infants affected by post-neonatal ARDS. Inhibition seems to be inversely related to the severity of gas exchange impairment.

  18. Quantitative proteomic study of Aspergillus Fumigatus secretome revealed deamidation of secretory enzymes.

    Science.gov (United States)

    Adav, Sunil S; Ravindran, Anita; Sze, Siu Kwan

    2015-04-24

    Aspergillus sp. plays an essential role in lignocellulosic biomass recycling and is also exploited as cell factories for the production of industrial enzymes. This study profiled the secretome of Aspergillus fumigatus when grown with cellulose, xylan and starch by high throughput quantitative proteomics using isobaric tags for relative and absolute quantification (iTRAQ). Post translational modifications (PTMs) of proteins play a critical role in protein functions. However, our understanding of the PTMs in secretory proteins is limited. Here, we present the identification of PTMs such as deamidation of secreted proteins of A. fumigatus. This study quantified diverse groups of extracellular secreted enzymes and their functional classification revealed cellulases and glycoside hydrolases (32.9%), amylases (0.9%), hemicellulases (16.2%), lignin degrading enzymes (8.1%), peptidases and proteases (11.7%), chitinases, lipases and phosphatases (7.6%), and proteins with unknown function (22.5%). The comparison of quantitative iTRAQ results revealed that cellulose and xylan stimulates expression of specific cellulases and hemicellulases, and their abundance level as a function of substrate. In-depth data analysis revealed deamidation as a major PTM of key cellulose hydrolyzing enzymes like endoglucanases, cellobiohydrolases and glucosidases. Hemicellulose degrading endo-1,4-beta-xylanase, monosidases, xylosidases, lignin degrading laccase, isoamyl alcohol oxidase and oxidoreductases were also found to be deamidated. The filamentous fungi play an essential role in lignocellulosic biomass recycling and fungal strains belonging to Aspergillus were also exploited as cell factories for the production of organic acids, pharmaceuticals, and industrially important enzymes. In this study, extracellular proteins secreted by thermophilic A. fumigatus when grown with cellulose, xylan and starch were profiled using isobaric tags for relative and absolute quantification (iTRAQ) by

  19. Effect of salivary secretory IgA on the adhesion of Candida albicans to polystyrene.

    Science.gov (United States)

    San Millán, R; Elguezabal, N; Regúlez, P; Moragues, M D; Quindós, G; Pontón, J

    2000-09-01

    Attachment of Candida albicans to plastic materials of dental prostheses or to salivary macromolecules adsorbed on their surface is believed to be a critical event in the development of denture stomatitis. In an earlier study, it was shown that adhesion of C. albicans to polystyrene, a model system to study the adhesion of C. albicans to plastic materials, can be partially inhibited with an mAb directed against cell wall polysaccharides of C. albicans. In the present study, the role of whole saliva in the adhesion of C. albicans to polystyrene has been investigated, and three mAbs directed against epitopes of cell wall mannoproteins have been used to mimic the inhibitory effect observed with salivary secretory IgA (sIgA) on the adhesion of C. albicans to polystyrene. In the absence of whole saliva, adherence of C. albicans 3153 increased with germination. However, the presence of whole saliva enhanced the adhesion to polystyrene of C. albicans 3153 yeast cells but decreased the adhesion of germinated cells. The enhancement of adhesion of yeast cells to polystyrene mediated by saliva was confirmed with an agerminative mutant of C. albicans 3153. The inhibition of the adhesion of C. albicans 3153 germ tubes to polystyrene was due to the salivary sIgA since sIgA-depleted saliva enhanced the adhesion of C. albicans 3153 to polystyrene. The inhibitory effect mediated by sIgA was not related to the inhibition of germination but to the blockage of adhesins expressed on the cell wall surface of the germ tubes. The three mAbs studied reduced the adhesion of C. albicans 3153 to polystyrene at levels equivalent to those for purified sIgA. The highest reduction in the adhesion was obtained with the IgA mAb N3B. The best results were obtained when the three mAbs were combined. The results suggest that whole saliva plays a different role in the adhesion of C. albicans to polystyrene depending on the morphological phase of C. albicans. These results may give new insights into the

  20. Restoring the secretory function of irradiation-damaged salivary gland by administrating deferoxamine in mice.

    Directory of Open Access Journals (Sweden)

    Junye Zhang

    Full Text Available One of the major side effects of radiotherapy for treatments of the head and neck cancer is the radiation-induced dysfunction of salivary glands. The aim of the present study is to investigate the efficacy of deferoxamine (DFO to restore the secretory function of radiation-damaged salivary glands in mice.DFO (50 mg/kg/d was administered intraperitoneally in C57BL/6 mice for 3 days before and/or after point-fixed irradiation (18 Gy of submandibular glands. The total 55 mice were randomly divided into: (1 Normal group: mice received no treatment (n = 5; (2 Irradiation group (IR: mice only received irradiation (n = 5; (3 Pre-DFO group (D+IR (n = 10; (4 Pre+Post DFO group (D+IR+D (n = 10; (5 Post-DFO group (IR+D (n = 10; (6 For each DFO-treated group, the mice were intraperitoneally injected with 0.1 ml sterilized water alone (by which DFO was dissolved for 3 days before and/or after irradiation, and served as control. Sham1: Pre-sterilized water group (n = 5; sham2: Pre+Post sterilized water group (n = 5; sham3: Post-sterilized water group (n = 5. The salivary flow rate (SFR was assessed at 30th, 60th and 90th day after irradiation, respectively. After 90 days, all mice were sacrificed and their submandibular glands were removed for further examinations.The salivary glands showed remarkable dysfunction and tissue damage after irradiation. DFO restored SFR in the irradiated glands to a level comparable to that in normal glands and angiogenesis in damaged tissue was greatly increased. DFO also increased the expression levels of HIF-1α and VEGF while reduced apoptotic cells. Furthermore, Sca-1+cells were preserved in the salivary glands treated with DFO before IR.Our results indicate DFO could prevent the radiation-induced dysfunction of salivary glands in mice. The mechanism of this protective effect may involve increased angiogenesis, reduced apoptosis of acinar cells and more preserved stem cells.

  1. Effects of Pregnancy and Bacterial Vaginosis on Proinflammatory Cytokine and Secretory Leukocyte Protease Inhibitor Concentrations in Vaginal Secretions

    Directory of Open Access Journals (Sweden)

    Jennifer Balkus

    2010-01-01

    Full Text Available We compared vaginal proinflammatory cytokine and secretory leukocyte protease inhibitor (SLPI concentrations among pregnant and nonpregnant women according to bacterial vaginosis (BV status. One-hundred and twenty-two women at 12–20 weeks' gestation and 133 nonpregnant controls had vaginal concentrations of interleukin (IL-1β, IL-6, IL-8, and SLPI measured by enzyme immunoassay. Multivariable linear regression was used to evaluate factors independently associated with vaginal cytokine and SLPI response. Pregnancy and BV were both independently associated with increased vaginal concentrations of IL-1β and IL-8; pregnant women had increased concentrations of SLPI, while women with BV had decreased SLPI concentrations.

  2. Intramuscular Priming and Intranasal Boosting Induce Strong Genital Immunity Through Secretory IgA in Minipigs Infected with Chlamydia trachomatis

    DEFF Research Database (Denmark)

    Lorenzen, Emma; Follmann, Frank; Bøje, Sarah

    2015-01-01

    with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. IM priming immunizations with CAF01 induced a significant cell-mediated interferon gamma and interleukin 17A response and a significant systemic high......-titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC), we showed that the genital Ig...

  3. Osh4p is needed to reduce the level of phosphatidylinositol-4-phosphate on secretory vesicles as they mature

    OpenAIRE

    Ling, Yading; Hayano, Scott; Novick, Peter

    2014-01-01

    Phosphatidylinositol-4-phosphate (PI4P) is produced on both the Golgi and the plasma membrane. Despite extensive vesicular traffic between these compartments, genetic analysis suggests that the two pools of PI4P do not efficiently mix with one another. Several lines of evidence indicate that the PI4P produced on the Golgi is normally incorporated into secretory vesicles, but the fate of that pool has been unclear. We show here that in yeast the oxysterol-binding proteins Osh1?Osh7 are collect...

  4. Anti-Toxoplasma gondii secretory IgA in tears of patients with ocular toxoplasmosis: immunodiagnostic validation by ELISA

    OpenAIRE

    Lynch,Maria Isabel; Malagueño,Elizabeth; Lynch,Luiz Felipe; Ferreira,Silvana; Stheling,Raphael; Oréfice,Fernando

    2009-01-01

    Toxoplasma gondii causes posterior uveitis and the specific diagnosis is based on clinical criteria. The presence of anti-T. gondii secretory IgA (sIgA) antibodies in patients' tears has been reported and an association was found between ocular toxoplasmosis and the anti-T. gondii sIgA isotype in Brazilian patients. The purpose of this study was to provide an objective validation of the published ELISA test for determining the presence of anti-T. gondii sIgA in the tears of individuals with o...

  5. Structural evolution and tissue-specific expression of tetrapod-specific second isoform of secretory pathway Ca2+-ATPase

    International Nuclear Information System (INIS)

    Pestov, Nikolay B.; Dmitriev, Ruslan I.; Kostina, Maria B.; Korneenko, Tatyana V.; Shakhparonov, Mikhail I.; Modyanov, Nikolai N.

    2012-01-01

    Highlights: ► Full-length secretory pathway Ca-ATPase (SPCA2) cloned from rat duodenum. ► ATP2C2 gene (encoding SPCA2) exists only in genomes of Tetrapoda. ► Rat and pig SPCA2 are expressed in intestines, lung and some secretory glands. ► Subcellular localization of SPCA2 may depend on tissue type. ► In rat duodenum, SPCA2 is localized in plasma membrane-associated compartments. -- Abstract: Secretory pathway Ca-ATPases are less characterized mammalian calcium pumps than plasma membrane Ca-ATPases and sarco-endoplasmic reticulum Ca-ATPases. Here we report analysis of molecular evolution, alternative splicing, tissue-specific expression and subcellular localization of the second isoform of the secretory pathway Ca-ATPase (SPCA2), the product of the ATP2C2 gene. The primary structure of SPCA2 from rat duodenum deduced from full-length transcript contains 944 amino acid residues, and exhibits 65% sequence identity with known SPCA1. The rat SPCA2 sequence is also highly homologous to putative human protein KIAA0703, however, the latter seems to have an aberrant N-terminus originating from intron 2. The tissue-specificity of SPCA2 expression is different from ubiquitous SPCA1. Rat SPCA2 transcripts were detected predominantly in gastrointestinal tract, lung, trachea, lactating mammary gland, skin and preputial gland. In the newborn pig, the expression profile is very similar with one remarkable exception: porcine bulbourethral gland gave the strongest signal. Upon overexpression in cultured cells, SPCA2 shows an intracellular distribution with remarkable enrichment in Golgi. However, in vivo SPCA2 may be localized in compartments that differ among various tissues: it is intracellular in epidermis, but enriched in plasma membranes of the intestinal epithelium. Analysis of SPCA2 sequences from various vertebrate species argue that ATP2C2 gene radiated from ATP2C1 (encoding SPCA1) during adaptation of tetrapod ancestors to terrestrial habitats.

  6. Sialotranscriptomics of Rhipicephalus zambeziensis reveals intricate expression profiles of secretory proteins and suggests tight temporal transcriptional regulation during blood-feeding.

    Science.gov (United States)

    de Castro, Minique Hilda; de Klerk, Daniel; Pienaar, Ronel; Rees, D Jasper G; Mans, Ben J

    2017-08-10

    Ticks secrete a diverse mixture of secretory proteins into the host to evade its immune response and facilitate blood-feeding, making secretory proteins attractive targets for the production of recombinant anti-tick vaccines. The largely neglected tick species, Rhipicephalus zambeziensis, is an efficient vector of Theileria parva in southern Africa but its available sequence information is limited. Next generation sequencing has advanced sequence availability for ticks in recent years and has assisted the characterisation of secretory proteins. This study focused on the de novo assembly and annotation of the salivary gland transcriptome of R. zambeziensis and the temporal expression of secretory protein transcripts in female and male ticks, before the onset of feeding and during early and late feeding. The sialotranscriptome of R. zambeziensis yielded 23,631 transcripts from which 13,584 non-redundant proteins were predicted. Eighty-six percent of these contained a predicted start and stop codon and were estimated to be putatively full-length proteins. A fifth (2569) of the predicted proteins were annotated as putative secretory proteins and explained 52% of the expression in the transcriptome. Expression analyses revealed that 2832 transcripts were differentially expressed among feeding time points and 1209 between the tick sexes. The expression analyses further indicated that 57% of the annotated secretory protein transcripts were differentially expressed. Dynamic expression profiles of secretory protein transcripts were observed during feeding of female ticks. Whereby a number of transcripts were upregulated during early feeding, presumably for feeding site establishment and then during late feeding, 52% of these were downregulated, indicating that transcripts were required at specific feeding stages. This suggested that secretory proteins are under stringent transcriptional regulation that fine-tunes their expression in salivary glands during feeding. No open

  7. Secretory granule formation and membrane recycling by the trans-Golgi network in adipokinetic cells of Locusta migratoria in relation to flight and rest.

    Science.gov (United States)

    Diederen, J H; Vullings, H G

    1995-03-01

    The influence of flight activity on the formation of secretory granules and the concomitant membrane recycling by the trans-Golgi network in the peptidergic neurosecretory adipokinetic cells of Locusta migratoria was investigated by means of ultrastructural morphometric methods. The patterns of labelling of the trans-Golgi network by the exogenous adsorptive endocytotic tracer wheat-germ agglutinin-conjugated horse-radish peroxidase and by the endogenous marker enzyme acid phosphatase were used as parameters and were measured by an automatic image analysis system. The results show that endocytosed fragments of plasma membrane with bound peroxidase label were transported to the trans-Golgi network and used to build new secretory granules. The amounts of peroxidase and especially of acid phosphatase within the trans-Golgi network showed a strong tendency to be smaller in flight-stimulated cells than in non-stimulated cells. The amounts of acid phosphatase in the immature secretory granules originating from the trans-Golgi network were significantly smaller in stimulated cells. The number of immature secretory granules positive for acid phosphatase tended to be higher in stimulated cells. Thus, flight stimulation of adipokinetic cells for 1 h influences the functioning of the trans-Golgi network; this most probably results in a slight enhancement of the production of secretory granules by the trans-Golgi network.

  8. Evaluation of the secretory immunoglobulin A levels in the colostrum and milk of mothers of term and pre-trerm newborns

    Directory of Open Access Journals (Sweden)

    Edílson D. Araújo

    Full Text Available OBJECTIVE: To determine and to compare the levels of secretory immunoglobulin A in samples of colostrum and milk of mothers of term and preterm neonates. MATERIAL AND METHODS: The levels of secretory immunoglobulin A of 10 mothers of term neonates and 10 mothers of preterm neonates were determined from 5mL of colostrum or milk collected on the 1st, 4th, 10th and 15th days of the puerperal period, using the radial immunodifusion technique. We employed anamnesis, as well as physical and gynecological exams in women in the puerperal period. All the patients were attended at the Januário Cicco Maternity College. RESULTS: The secretory immunoglobulin A levels were significantly higher in the colostrum and milk of mothers of preterm neonates when compared with the levels found in colostrum and milk of mothers of term neonates (Mann-Whitney test, p<0.0001. There was a significant decline in the secretory immunoglobulin A levels of the colostrum and milk of the mothers of term and preterm neonates during the four periods (Kruskal-Wallis test, p<00001. CONCLUSIONS: The secretory immunoglobulin A levels in colostrum and milk of mothers of preterm neonates were significantly higher than in the mothers of term neonates, demonstrating immunological adaptation in preterm neonate breast-feeding.

  9. Distribution Profile of Inositol 1,4,5-Trisphosphate Receptor/Ca2+ Channels in α and β Cells of Pancreas: Dominant Localization in Secretory Granules and Common Error in Identification of Secretory Granule Membranes.

    Science.gov (United States)

    Hur, Yong Suk; Yoo, Seung Hyun

    2015-01-01

    The α and β cells of pancreatic islet release important hormones in response to intracellular Ca increases that result from Ca releases through the inositol 1,4,5-trisphoshate receptor (IP3R)/Ca channels. Yet no systematic studies on distribution of IP3R/Ca channels have been done, prompting us to investigate the distribution of all 3 IP3R isoforms. Immunogold electron microscopy was performed to determine the presence and the relative concentrations of all 3 IP3R isoforms in 2 major organelles secretory granules (SGs) and the endoplasmic reticulum of α and β cells of rat pancreas. All 3 IP3R isoforms were present in SG membranes of both cells, and the IP3R concentrations in SGs were ∼2-fold higher than those in the endoplasmic reticulum. Moreover, large halos shown in the electron microscope images of insulin-containing SGs of β cells were gap spaces that resulted from separation of granule membranes from the surrounding cytoplasm. These results strongly suggest the important roles of SGs in IP3-induced, Ca-dependent regulatory secretory pathway in pancreas. Moreover, the accurate location of SG membranes of β cells was further confirmed by the location of another integral membrane protein synaptotagmin V and of membrane phospholipid PI(4,5)P2.

  10. Latino College Completion: New York

    Science.gov (United States)

    Excelencia in Education (NJ1), 2012

    2012-01-01

    In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

  11. Latino College Completion: United States

    Science.gov (United States)

    Excelencia in Education (NJ1), 2012

    2012-01-01

    In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

  12. Latino College Completion: South Dakota

    Science.gov (United States)

    Excelencia in Education (NJ1), 2012

    2012-01-01

    In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

  13. Latino College Completion: North Dakota

    Science.gov (United States)

    Excelencia in Education (NJ1), 2012

    2012-01-01

    In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

  14. Latino College Completion: New Mexico

    Science.gov (United States)

    Excelencia in Education (NJ1), 2012

    2012-01-01

    In 2009, Excelencia in Education launched the Ensuring America's Future initiative to inform, organize, and engage leaders in a tactical plan to increase Latino college completion. An executive summary of Latino College Completion in 50 states synthesizes information on 50 state factsheets and builds on the national benchmarking guide. Each…

  15. Structure completion for facade layouts

    KAUST Repository

    Fan, Lubin

    2014-11-18

    (Figure Presented) We present a method to complete missing structures in facade layouts. Starting from an abstraction of the partially observed layout as a set of shapes, we can propose one or multiple possible completed layouts. Structure completion with large missing parts is an ill-posed problem. Therefore, we combine two sources of information to derive our solution: the observed shapes and a database of complete layouts. The problem is also very difficult, because shape positions and attributes have to be estimated jointly. Our proposed solution is to break the problem into two components: a statistical model to evaluate layouts and a planning algorithm to generate candidate layouts. This ensures that the completed result is consistent with the observation and the layouts in the database.

  16. Clinical significance of determination of changes of serum IL-6, hs-CRP and saliva secretory IgA levels after treatment in patients with periodontitis

    International Nuclear Information System (INIS)

    Wang Tongwu

    2009-01-01

    Objective: To explore the clinical significance of changes of serum IL-6, hs-CRP and saliva secretory IgA levels after treatment in patients with periodontitis. Methods: Serum IL-6, saliva secretory IgA (with RIA) and serum hs-CRP (with immuno-tarbility method) levels were measured in 42 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment serum IL-6, hs-CRP and saliva secretory IgA levels in the patients wree significantly higher than those in controls (P 0.05). However, the saliva secreatory IgA levels were still significantly higher than those in controls (P<0.05). Conclusion: There was disturbance of immunomodulation in patients with periodontitis as expressed by the changes of cytokines levels in the course of the diseases. (authors)

  17. Characterization of Phospholipids in Insulin Secretory Granules and Mitochondria in Pancreatic Beta Cells and Their Changes with Glucose Stimulation*

    Science.gov (United States)

    MacDonald, Michael J.; Ade, Lacmbouh; Ntambi, James M.; Ansari, Israr-Ul H.; Stoker, Scott W.

    2015-01-01

    The lipid composition of insulin secretory granules (ISG) has never previously been thoroughly characterized. We characterized the phospholipid composition of ISG and mitochondria in pancreatic beta cells without and with glucose stimulation. The phospholipid/protein ratios of most phospholipids containing unsaturated fatty acids were higher in ISG than in whole cells and in mitochondria. The concentrations of negatively charged phospholipids, phosphatidylserine, and phosphatidylinositol in ISG were 5-fold higher than in the whole cell. In ISG phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin, fatty acids 12:0 and 14:0 were high, as were phosphatidylserine and phosphatidylinositol containing 18-carbon unsaturated FA. With glucose stimulation, the concentration of many ISG phosphatidylserines and phosphatidylinositols increased; unsaturated fatty acids in phosphatidylserine increased; and most phosphatidylethanolamines, phosphatidylcholines, sphingomyelins, and lysophosphatidylcholines were unchanged. Unsaturation and shorter fatty acid length in phospholipids facilitate curvature and fluidity of membranes, which favors fusion of membranes. Recent evidence suggests that negatively charged phospholipids, such as phosphatidylserine, act as coupling factors enhancing the interaction of positively charged regions in SNARE proteins in synaptic or secretory vesicle membrane lipid bilayers with positively charged regions in SNARE proteins in the plasma membrane lipid bilayer to facilitate docking of vesicles to the plasma membrane during exocytosis. The results indicate that ISG phospholipids are in a dynamic state and are consistent with the idea that changes in ISG phospholipids facilitate fusion of ISG with the plasma membrane-enhancing glucose-stimulated insulin exocytosis. PMID:25762724

  18. Characterization of phospholipids in insulin secretory granules and mitochondria in pancreatic beta cells and their changes with glucose stimulation.

    Science.gov (United States)

    MacDonald, Michael J; Ade, Lacmbouh; Ntambi, James M; Ansari, Israr-Ul H; Stoker, Scott W

    2015-04-24

    The lipid composition of insulin secretory granules (ISG) has never previously been thoroughly characterized. We characterized the phospholipid composition of ISG and mitochondria in pancreatic beta cells without and with glucose stimulation. The phospholipid/protein ratios of most phospholipids containing unsaturated fatty acids were higher in ISG than in whole cells and in mitochondria. The concentrations of negatively charged phospholipids, phosphatidylserine, and phosphatidylinositol in ISG were 5-fold higher than in the whole cell. In ISG phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin, fatty acids 12:0 and 14:0 were high, as were phosphatidylserine and phosphatidylinositol containing 18-carbon unsaturated FA. With glucose stimulation, the concentration of many ISG phosphatidylserines and phosphatidylinositols increased; unsaturated fatty acids in phosphatidylserine increased; and most phosphatidylethanolamines, phosphatidylcholines, sphingomyelins, and lysophosphatidylcholines were unchanged. Unsaturation and shorter fatty acid length in phospholipids facilitate curvature and fluidity of membranes, which favors fusion of membranes. Recent evidence suggests that negatively charged phospholipids, such as phosphatidylserine, act as coupling factors enhancing the interaction of positively charged regions in SNARE proteins in synaptic or secretory vesicle membrane lipid bilayers with positively charged regions in SNARE proteins in the plasma membrane lipid bilayer to facilitate docking of vesicles to the plasma membrane during exocytosis. The results indicate that ISG phospholipids are in a dynamic state and are consistent with the idea that changes in ISG phospholipids facilitate fusion of ISG with the plasma membrane-enhancing glucose-stimulated insulin exocytosis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Phosphopeptidomics Reveals Differential Phosphorylation States and Novel SxE Phosphosite Motifs of Neuropeptides in Dense Core Secretory Vesicles

    Science.gov (United States)

    Lietz, Christopher B.; Toneff, Thomas; Mosier, Charles; Podvin, Sonia; O'Donoghue, Anthony J.; Hook, Vivian

    2018-03-01

    Neuropeptides are vital for cell-cell communication and function in the regulation of the nervous and endocrine systems. They are generated by post-translational modification (PTM) steps resulting in small active peptides generated from prohormone precursors. Phosphorylation is a significant PTM for the bioactivity of neuropeptides. From the known diversity of distinct neuropeptide functions, it is hypothesized that the extent of phosphorylation varies among different neuropeptides. To assess this hypothesis, neuropeptide-containing dense core secretory vesicles from bovine adrenal medullary chromaffin cells were subjected to global phosphopeptidomics analyses by liquid chromatography (LC)-mass spectrometry (MS/MS). Phosphopeptides were identified directly by LC-MS/MS and indirectly by phosphatase treatment followed by LC-MS/MS. The data identified numerous phosphorylated peptides derived from neuropeptide precursors such as chromogranins, secretogranins, proenkephalin and pro-NPY. Phosphosite occupancies were observed at high and low levels among identified peptides and many of the high occupancy phosphopeptides represent prohormone-derived peptides with currently unknown bioactivities. Peptide sequence analyses demonstrated SxE as the most prevalent phosphorylation site motif, corresponding to phosphorylation sites of the Fam20C protein kinase known to be present in the secretory pathway. The range of high to low phosphosite occupancies for neuropeptides demonstrates cellular regulation of neuropeptide phosphorylation. [Figure not available: see fulltext.

  20. Primary structure of bovine pituitary secretory protein I (chromogranin A) deduced from the cDNA sequence

    International Nuclear Information System (INIS)

    Ahn, T.G.; Cohn, D.V.; Gorr, S.U.; Ornstein, D.L.; Kashdan, M.A.; Levine, M.A.

    1987-01-01

    Secretory protein I (SP-I), also referred to as chromogranin A, is an acidic glycoprotein that has been found in every tissue of endocrine and neuroendocrine origin examined but never in exocrine or epithelial cells. Its co-storage and co-secretion with peptide hormones and neurotransmitters suggest that it has an important endocrine or secretory function. The authors have isolated cDNA clones from a bovine pituitary λgt11 expression library using an antiserum to parathyroid SP-I. The largest clone (SP4B) hybridized to a transcript of 2.1 kilobases in RNA from parathyroid, pituitary, and adrenal medulla. Immunoblots of bacterial lysates derived from SP4B lysognes demonstrated specific antibody binding to an SP4B/β-galactosidase fusion protein (160 kDa) with a cDNA-derived component of 46 kDa. Radioimmunoassay of the bacterial lystates with SP-I antiserum yielded parallel displacement curves of 125 I-labeled SP-I by the SP4B lysate and authentic SP-I. SP4B contains a cDNA of 1614 nucleotides that encodes a 449-amino acid protein (calculated mass, 50 kDa). The nucleotide sequences of the pituitary SP-I cDNA and adrenal medullary SP-I cDNAs are nearly identical. Analysis of genomic DNA suggests that pituitary, adrenal, and parathyroid SP-I are products of the same gene

  1. Absence of an increase in the duration of the circadian melatonin secretory episode in totally blind human subjects

    Science.gov (United States)

    Klerman, E. B.; Zeitzer, J. M.; Duffy, J. F.; Khalsa, S. B.; Czeisler, C. A.

    2001-01-01

    The daily rhythm of melatonin influences multiple physiological measures, including sleep tendency, circadian rhythms, and reproductive function in seasonally breeding mammals. The biological signal for photoperiodic changes in seasonally breeding mammals is a change in the duration of melatonin secretion, which in a natural environment reflects the different durations of daylight across the year, with longer nights leading to a longer duration of melatonin secretion. These seasonal changes in the duration of melatonin secretion do not simply reflect the known acute suppression of melatonin secretion by ocular light exposure, but also represent long-term changes in the endogenous nocturnal melatonin episode that persist in constant conditions. As the eyes of totally blind individuals do not transmit ocular light information, we hypothesized that the duration of the melatonin secretory episode in blind subjects would be longer than those in sighted individuals, who are exposed to light for all their waking hours in an urban environment. We assessed the melatonin secretory profile during constant posture, dim light conditions in 17 blind and 157 sighted adults, all of whom were healthy and using no prescription or nonprescription medications. The duration of melatonin secretion was not significantly different between blind and sighted individuals. Healthy blind individuals after years without ocular light exposure do not have a longer duration of melatonin secretion than healthy sighted individuals.

  2. Comparative innate immune interactions of human and bovine secretory IgA with pathogenic and non-pathogenic bacteria.

    Science.gov (United States)

    Hodgkinson, Alison J; Cakebread, Julie; Callaghan, Megan; Harris, Paul; Brunt, Rachel; Anderson, Rachel C; Armstrong, Kelly M; Haigh, Brendan

    2017-03-01

    Secretory IgA (SIgA) from milk contributes to early colonization and maintenance of commensal/symbiotic bacteria in the gut, as well as providing defence against pathogens. SIgA binds bacteria using specific antigenic sites or non-specifically via its glycans attached to α-heavy-chain and secretory component. In our study, we tested the hypothesis that human and bovine SIgA have similar innate-binding activity for bacteria. SIgAs, isolated from human and bovine milk, were incubated with a selection of commensal, pathogenic and probiotic bacteria. Using flow cytometry, we measured numbers of bacteria binding SIgA and their level of SIgA binding. The percentage of bacteria bound by human and bovine SIgA varied from 30 to 90% depending on bacterial species and strains, but was remarkably consistent between human and bovine SIgA. The level of SIgA binding per bacterial cell was lower for those bacteria that had a higher percentage of SIgA-bound bacteria, and higher for those bacteria that had lower percentage of SIgA-bound bacteria. Overall, human and bovine SIgA interacted with bacteria in a comparable way. This contributes to longer term research about the potential benefits of bovine SIgA for human consumers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. A Role for Serglycin Proteoglycan in Mast Cell Apoptosis Induced by a Secretory Granule-mediated Pathway*

    Science.gov (United States)

    Melo, Fabio Rabelo; Waern, Ida; Rönnberg, Elin; Åbrink, Magnus; Lee, David M.; Schlenner, Susan M.; Feyerabend, Thorsten B.; Rodewald, Hans-Reimer; Turk, Boris; Wernersson, Sara; Pejler, Gunnar

    2011-01-01

    Mast cell secretory granules (secretory lysosomes) contain large amounts of fully active proteases bound to serglycin proteoglycan. Damage to the granule membrane will thus lead to the release of serglycin and serglycin-bound proteases into the cytosol, which potentially could lead to proteolytic activation of cytosolic pro-apoptotic compounds. We therefore hypothesized that mast cells are susceptible to apoptosis induced by permeabilization of the granule membrane and that this process is serglycin-dependent. Indeed, we show that wild-type mast cells are highly sensitive to apoptosis induced by granule permeabilization, whereas serglycin-deficient cells are largely resistant. The reduced sensitivity of serglycin−/− cells to apoptosis was accompanied by reduced granule damage, reduced release of proteases into the cytosol, and defective caspase-3 activation. Mechanistically, the apoptosis-promoting effect of serglycin involved serglycin-dependent proteases, as indicated by reduced sensitivity to apoptosis and reduced caspase-3 activation in cells lacking individual mast cell-specific proteases. Together, these findings implicate serglycin proteoglycan as a novel player in mast cell apoptosis. PMID:21123167

  4. Secretory IgA, albumin level, and bone density as markers of biostimulatory effects of laser radiation

    Science.gov (United States)

    Kucerova, Hana; Dostalova, Tatjana; Himmlova, Lucia; Bartova, Jirina; Mazanek, Jiri

    1998-12-01

    The aim of contribution is to evaluate the effects of low- level laser radiation on healing process after human molars extraction in lower jaw using frequency 5 Hz, 292 Hz and 9000 Hz. Changes in bone density and monitoring of secretory IgA and albumin levels in saliva were used as a marker of biostimulatory effect. Bone density after extraction and 6 month after surgical treatment was examined using the dental digital radiography. Bone healing was followed by osseointegration of bone structure in extraction wound. Changes of bone density, secretory IgA and albumin levels were compared in groups of patients with laser therapy and control group without laser therapy. Differences in levels of the saliva markers (sIgA and albumin) were found to be significant comparing irradiated and non-irradiated groups, as well as comparing groups irradiated by various modulatory frequencies. Density of alveolar bone (histogram) was examined on five slices acquired from every RVG image. Histograms were evaluated with computer program for microscopic image analysis. Differences of density were verified in area of the whole slice. There were no significant differences found between the bone density in irradiated and non irradiated groups perhaps due to our used therapeutical diagram.

  5. Excavating the surface-associated and secretory proteome of Mycobacterium leprae for identifying vaccines and diagnostic markers relevant immunodominant epitopes.

    Science.gov (United States)

    Rana, Aarti; Thakur, Shweta; Bhardwaj, Nupur; Kumar, Devender; Akhter, Yusuf

    2016-12-01

    For centuries, Mycobacterium leprae, etiological agent of leprosy, has been afflicting mankind regardless of extensive use of live-attenuated vaccines and antibiotics. Surface-associated and secretory proteins (SASPs) are attractive targets against bacteria. We have integrated biological knowledge with computational approaches and present a proteome-wide identification of SASPs. We also performed computational assignment of immunodominant epitopes as coordinates of prospective antigenic candidates in most important class of SASPs, the outer membrane proteins (OMPs). Exploiting the known protein sequence and structural characteristics shared by the SASPs from bacteria, 17 lipoproteins, 11 secretory and 19 novel OMPs (including 4 essential proteins) were identified in M. leprae As OMPs represent the most exposed antigens on the cell surface, their immunoinformatics analysis showed that the identified 19 OMPs harbor T-cell MHC class I epitopes and class II epitopes against HLA-DR alleles (54), while 15 OMPs present potential T-cell class II epitopes against HLA-DQ alleles (6) and 7 OMPs possess T-cell class II epitopes against HLA-DP alleles (5) of humans. Additionally, 11 M. leprae OMPs were found to have B-cell epitopes and these may be considered as prime candidates for the development of new immunotherapeutics against M. leprae. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Phosphopeptidomics Reveals Differential Phosphorylation States and Novel SxE Phosphosite Motifs of Neuropeptides in Dense Core Secretory Vesicles

    Science.gov (United States)

    Lietz, Christopher B.; Toneff, Thomas; Mosier, Charles; Podvin, Sonia; O'Donoghue, Anthony J.; Hook, Vivian

    2018-05-01

    Neuropeptides are vital for cell-cell communication and function in the regulation of the nervous and endocrine systems. They are generated by post-translational modification (PTM) steps resulting in small active peptides generated from prohormone precursors. Phosphorylation is a significant PTM for the bioactivity of neuropeptides. From the known diversity of distinct neuropeptide functions, it is hypothesized that the extent of phosphorylation varies among different neuropeptides. To assess this hypothesis, neuropeptide-containing dense core secretory vesicles from bovine adrenal medullary chromaffin cells were subjected to global phosphopeptidomics analyses by liquid chromatography (LC)-mass spectrometry (MS/MS). Phosphopeptides were identified directly by LC-MS/MS and indirectly by phosphatase treatment followed by LC-MS/MS. The data identified numerous phosphorylated peptides derived from neuropeptide precursors such as chromogranins, secretogranins, proenkephalin and pro-NPY. Phosphosite occupancies were observed at high and low levels among identified peptides and many of the high occupancy phosphopeptides represent prohormone-derived peptides with currently unknown bioactivities. Peptide sequence analyses demonstrated SxE as the most prevalent phosphorylation site motif, corresponding to phosphorylation sites of the Fam20C protein kinase known to be present in the secretory pathway. The range of high to low phosphosite occupancies for neuropeptides demonstrates cellular regulation of neuropeptide phosphorylation. [Figure not available: see fulltext.

  7. Neuronal differentiation is associated with a redox-regulated increase of copper flow to the secretory pathway.

    Science.gov (United States)

    Hatori, Yuta; Yan, Ye; Schmidt, Katharina; Furukawa, Eri; Hasan, Nesrin M; Yang, Nan; Liu, Chin-Nung; Sockanathan, Shanthini; Lutsenko, Svetlana

    2016-02-16

    Brain development requires a fine-tuned copper homoeostasis. Copper deficiency or excess results in severe neuro-pathologies. We demonstrate that upon neuronal differentiation, cellular demand for copper increases, especially within the secretory pathway. Copper flow to this compartment is facilitated through transcriptional and metabolic regulation. Quantitative real-time imaging revealed a gradual change in the oxidation state of cytosolic glutathione upon neuronal differentiation. Transition from a broad range of redox states to a uniformly reducing cytosol facilitates reduction of the copper chaperone Atox1, liberating its metal-binding site. Concomitantly, expression of Atox1 and its partner, a copper transporter ATP7A, is upregulated. These events produce a higher flux of copper through the secretory pathway that balances copper in the cytosol and increases supply of the cofactor to copper-dependent enzymes, expression of which is elevated in differentiated neurons. Direct link between glutathione oxidation and copper compartmentalization allows for rapid metabolic adjustments essential for normal neuronal function.

  8. Different redox sensitivity of endoplasmic reticulum associated degradation clients suggests a novel role for disulphide bonds in secretory proteins.

    Science.gov (United States)

    Medraño-Fernandez, Iria; Fagioli, Claudio; Mezghrani, Alexandre; Otsu, Mieko; Sitia, Roberto

    2014-04-01

    To maintain proteostasis in the endoplasmic reticulum (ER), terminally misfolded secretory proteins must be recognized, partially unfolded, and dislocated to the cytosol for proteasomal destruction, in a complex process called ER-associated degradation (ERAD). Dislocation implies reduction of inter-chain disulphide bonds. When in its reduced form, protein disulphide isomerase (PDI) can act not only as a reductase but also as an unfoldase, preparing substrates for dislocation. PDI oxidation by Ero1 favours substrate release and transport across the ER membrane. Here we addressed the redox dependency of ERAD and found that DTT stimulates the dislocation of proteins with DTT-resistant disulphide bonds (i.e., orphan Ig-μ chains) but stabilizes a ribophorin mutant (Ri332) devoid of them. DTT promotes the association of Ri332, but not of Ig-µ, with PDI. This discrepancy may suggest that disulphide bonds in cargo proteins can be utilized to oxidize PDI, hence facilitating substrate detachment and degradation also in the absence of Ero1. Accordingly, Ero1 silencing retards Ri332 degradation, but has little if any effect on Ig-µ. Thus, some disulphides can increase the stability and simultaneously favour quality control of secretory proteins.

  9. Elevation of susceptibility to ozone-induced acute tracheobronchial injury in transgenic mice deficient in Clara cell secretory protein

    International Nuclear Information System (INIS)

    Plopper, C.G.; Mango, G.W.; Hatch, G.E.; Wong, V.J.; Toskala, E.; Reynolds, S.D.; Tarkington, B.K.; Stripp, B.R.

    2006-01-01

    Increases in Clara cell abundance or cellular expression of Clara cell secretory protein (CCSP) may cause increased tolerance of the lung to acute oxidant injury by repeated exposure to ozone (O 3 ). This study defines how disruption of the gene for CCSP synthesis affects the susceptibility of tracheobronchial epithelium to acute oxidant injury. Mice homozygous for a null allele of the CCSP gene (CCSP-/-) and wild type (CCSP+/+) littermates were exposed to ozone (0.2 ppm, 8 h; 1 ppm, 8 h) or filtered air. Injury was evaluated by light and scanning electron microscopy, and the abundance of necrotic, ciliated, and nonciliated cells was estimated by morphometry. Proximal and midlevel intrapulmonary airways and terminal bronchioles were evaluated. There was no difference in airway epithelial composition between CCSP+/+ and CCSP-/- mice exposed to filtered air, and exposure to 0.2 ppm ozone caused little injury to the epithelium of both CCSP+/+ and CCSP-/- mice. After exposure to 1.0 ppm ozone, CCSP-/- mice suffered from a greater degree of epithelial injury throughout the airways compared to CCSP+/+ mice. CCSP-/- mice had both ciliated and nonciliated cell injury. Furthermore, lack of CCSP was associated with a shift in airway injury to include proximal airway generations. Therefore, we conclude that CCSP modulates the susceptibility of the epithelium to oxidant-induced injury. Whether this is due to the presence of CCSP on the acellular lining layer surface and/or its intracellular distribution in the secretory cell population needs to be defined

  10. Primary structure of bovine pituitary secretory protein I (chromogranin A) deduced from the cDNA sequence

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, T.G.; Cohn, D.V.; Gorr, S.U.; Ornstein, D.L.; Kashdan, M.A.; Levine, M.A.

    1987-07-01

    Secretory protein I (SP-I), also referred to as chromogranin A, is an acidic glycoprotein that has been found in every tissue of endocrine and neuroendocrine origin examined but never in exocrine or epithelial cells. Its co-storage and co-secretion with peptide hormones and neurotransmitters suggest that it has an important endocrine or secretory function. The authors have isolated cDNA clones from a bovine pituitary lambdagt11 expression library using an antiserum to parathyroid SP-I. The largest clone (SP4B) hybridized to a transcript of 2.1 kilobases in RNA from parathyroid, pituitary, and adrenal medulla. Immunoblots of bacterial lysates derived from SP4B lysognes demonstrated specific antibody binding to an SP4B/..beta..-galactosidase fusion protein (160 kDa) with a cDNA-derived component of 46 kDa. Radioimmunoassay of the bacterial lystates with SP-I antiserum yielded parallel displacement curves of /sup 125/I-labeled SP-I by the SP4B lysate and authentic SP-I. SP4B contains a cDNA of 1614 nucleotides that encodes a 449-amino acid protein (calculated mass, 50 kDa). The nucleotide sequences of the pituitary SP-I cDNA and adrenal medullary SP-I cDNAs are nearly identical. Analysis of genomic DNA suggests that pituitary, adrenal, and parathyroid SP-I are products of the same gene.

  11. The effect of metformin on monocyte secretory function in simvastatin-treated patients with impaired fasting glucose.

    Science.gov (United States)

    Krysiak, Robert; Okopien, Bogusław

    2013-01-01

    This study was designed to investigate whether metformin affects monocyte secretory function in patients with impaired fasting glucose receiving chronic statin therapy. The study included 48 patients with impaired fasting glucose treated for at least three months with simvastatin (40 mg daily). These patients were randomized to either metformin (3 g daily) or placebo, which was administered together with simvastatin for 90 days. Plasma lipids, glucose homeostasis markers, monocyte cytokine release and plasma C-reactive protein levels were determined before randomization and at the end of the treatment. Compared to placebo, metformin reduced monocyte release of tumor necrosis factor-α, interleukin-1β, interleukin-6, monocyte chemoattractant protein-1 and interleukin-8, as well as decreased plasma C-reactive protein levels, which were accompanied by an improvement in insulin sensitivity. The obtained results suggest that metformin may inhibit monocyte secretory function and reduce systemic inflammation in statin-treated patients with prediabetes. Impaired fasting glucose patients with high cardiovascular risk may receive the greatest benefits from concomitant treatment with a statin and metformin. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Complexity of Products of Some Complete and Complete Bipartite Graphs

    Directory of Open Access Journals (Sweden)

    S. N. Daoud

    2013-01-01

    Full Text Available The number of spanning trees in graphs (networks is an important invariant; it is also an important measure of reliability of a network. In this paper, we derive simple formulas of the complexity, number of spanning trees, of products of some complete and complete bipartite graphs such as cartesian product, normal product, composition product, tensor product, and symmetric product, using linear algebra and matrix analysis techniques.

  13. [Expansion of secretory cells in the fallopian tubal epithelium in the early stages of the pathogenesis of ovarian serous carcinomas].

    Science.gov (United States)

    Asaturova, A V; Ezhova, L S; Faizullina, N M; Adamyan, L V; Khabas, G N; Sannikova, M V

    to investigate the frequency of the types of fallopian tubal secretory cell expansion (SCE) in diseases of the reproductive organs and to determine the immunophenotype and biological role of the cells in the early stages of the pathogenesis of high-grade ovarian serous carcinomas (HGOSC). The investigation enrolled 287 patients with extraovarian diseases and ovarian serous tumors varying in grade, whose fallopian tubes were morphologically and immunohistochemically examined using p53, Ki-67, PAX2, Bcl-2, beta-catenin, and ALDH1 markers. The material was statistically processed applying the Mann-Whitney test and χ2 test. The rate of secretory cell proliferation (SCP) (more than 10 consecutive secretory cells) and that of secretory cell overgrowth (SCO) (more than 30 consecutive secretory cells) increase with age in all investigated reproductive system diseases. The rate of SCP in the corpus fimbriatum of the patients with HGOSC was 5.9 times higher than that in those with extraovarian disease (pepithelium (2.8), in SCP (1.3), in SCO (1.2), in serous tubal intraepithelial carcinoma (STIC) (1.0), and in HGOSC (0.9); Bcl-2 was in the intact epithelium (2.2), in SCP (2.1), STIC (0.9), and in HGOSC (0.6), β-catenin was in the intact epithelium (0.5), in SCP (2.85), in SCO (2.95), in STIC (0.6), and in HGOSC (0.5); ALDH1 was in the intact epithelium (0.5), in SCP (2.91), in SCO (2.92), in STIC (1.2), and in HGOSC (0.6). There were statistically significant differences with a 95% confidence interval (pepithelium and pathology (fallopian tube lesions and HGOSC); 2) Bcl-2 between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 3) beta-catenin between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 4) ALDH1 between the intact epithelium and SCE, between and SCE and STIC, and between STIC and HGOSC. SCE was shown to be an independent intraepithelial lesion. The incidence of this abnormality increased with age and significantly

  14. Trend of Complete Hydatidiform Mole

    Directory of Open Access Journals (Sweden)

    K Thapa

    2010-03-01

    Full Text Available INTRODUCTION: Complete Hydatidiform mole is one of the most frequent abnormal pregnancies. This review studies the trend of complete mole in Paropakar Maternity and Women's hospital and clinical ability to detect it. METHODS: This is a retrospective study of 504 cases of complete hydatidiform mole recorded at Paropakar maternity and women's hospital, Kathmandu, during 2058-2065 B.S. Medical records were reviewed and incidence, clinical presentation and method of diagnosis were studied. RESULTS: During the study period, there were 13,9117 births and 504 complete moles, 12 partial moles, 48 persistent gestational tumours, six choriocarcinoma and four invasive moles recorded in the hospital. The incidence of complete mole was one per 276 births. It was prevalent among women younger than 29 years (80% and among the primigravidae (36.7%. More than 90% women presented in the first half of their pregnancy and vaginal bleeding was the main complaint (68.3%. Suction evacuation, dilation and evacuation followed by sharp curettage and abdominal hysterectomy were performed in 80.6%, 17.6% and 1.2% of the women respectively. Persistent mole and choriocarcinoma developed in 9.5% and 0.4% respectively. CONCLUSIONS: Complete mole has the highest incidence. It affects mostly younger women and presents with vaginal bleeding most of the time, usually in the first half of their pregnancy. Keywords: complete hydatidiform mole, gestational trophoblastic disease, persistent gestational tumours.

  15. Sorting of a HaloTag protein that has only a signal peptide sequence into exocrine secretory granules without protein aggregation.

    Science.gov (United States)

    Fujita-Yoshigaki, Junko; Matsuki-Fukushima, Miwako; Yokoyama, Megumi; Katsumata-Kato, Osamu

    2013-11-15

    The mechanism involved in the sorting and accumulation of secretory cargo proteins, such as amylase, into secretory granules of exocrine cells remains to be solved. To clarify that sorting mechanism, we expressed a reporter protein HaloTag fused with partial sequences of salivary amylase protein in primary cultured parotid acinar cells. We found that a HaloTag protein fused with only the signal peptide sequence (Met(1)-Ala(25)) of amylase, termed SS25H, colocalized well with endogenous amylase, which was confirmed by immunofluorescence microscopy. Percoll-density gradient centrifugation of secretory granule fractions shows that the distributions of amylase and SS25H were similar. These results suggest that SS25H is transported to secretory granules and is not discriminated from endogenous amylase by the machinery that functions to remove proteins other than granule cargo from immature granules. Another reporter protein, DsRed2, that has the same signal peptide sequence also colocalized with amylase, suggesting that the sorting to secretory granules is not dependent on a characteristic of the HaloTag protein. Whereas Blue Native PAGE demonstrates that endogenous amylase forms a high-molecular-weight complex, SS25H does not participate in the complex and does not form self-aggregates. Nevertheless, SS25H was released from cells by the addition of a β-adrenergic agonist, isoproterenol, which also induces amylase secretion. These results indicate that addition of the signal peptide sequence, which is necessary for the translocation in the endoplasmic reticulum, is sufficient for the transportation and storage of cargo proteins in secretory granules of exocrine cells.

  16. Secretory cavities and volatiles of Myrrhinium atropurpureum Schott var. atropurpureum (Myrtaceae): an endemic species collected in the restingas of Rio de Janeiro, Brazil.

    Science.gov (United States)

    Victório, Cristiane Pimentel; Moreira, Claudio B; Souza, Marcelo da Costa; Sato, Alice; Arruda, Rosani do Carmo de Oliveira

    2011-07-01

    In this study, we investigated the leaf anatomy and the composition of volatiles in Myrrhinium atropurpureum var. atropurpureum endemic to Rio de Janeiro restingas. Particularly, leaf secretory structures were described using light microscopy, and histochemical tests were performed from fresh leaves to localize the secondary metabolites. To observe secretory cavities, fixed leaf samples were free-hand sectioned. To evaluate lipophilic compounds and terpenoids the following reagents were employed: Sudans III and IV, Red oil O and Nile blue. Leaf volatiles were characterized by gas chromatography after hydrodistillation (HD) or simultaneous distillation-extraction (SDE). Leaf analysis showed several cavities in mesophyll that are the main sites of lipophilic and terpenoid production. Monoterpenes, which represented more than 80% of the major volatiles, were characterized mainly by alpha- and beta-pinene and 1,8-cineole. In order to provide tools for M. atropurpureum identification, the following distinguishing characteristics were revealed by the following data: 1) adaxial face clear and densely punctuated by the presence of round or ellipsoidal secretory cavities randomly distributed in the mesophyll; 2) the presence of cells overlying the upper neck cells of secretory cavities; 3) the presence of numerous paracytic stomata distributed on the abaxial leaf surface, but absent in vein regions and leaf margin; and 4) non-glandular trichomes on both leaf surfaces. Our study of the compounds produced by the secretory cavities of M. atropurpureum led us to conclude that volatile terpenoid class are the main secretory compounds and that they consist of a high concentration of monoterpenes, which may indicate the phytotherapeutic importance of this plant.

  17. Impact of simulated microgravity on the secretory and adhesive activity of cultured human vascular endothelial cells.

    Science.gov (United States)

    Rudimov, Evgeny; Buravkova, Ludmila; Pogodina, Margarita; Andrianova, Irina

    The layer of vascular endothelial cells (ECs) is a dynamic,disseminated organ that perform the function of an interface between the blood and vascular wall. The endothelial monolayer is able to quickly respond to changes in the microenvironment due to its synthesis of vasoactive substances, chemokines, adhesion molecules expression, etc. ECs are highly sensitive to gravitational changes and capable of short-term and long-term responses (Sangha et al., 2001; Buravkova et al., 2005; Infanger et al., 2006, 2007. However, the question remains how to reflect the impact of microgravity on endothelium under the inflammatory process. Therefore, the aim of this study was to investigate secretory and adhesive activity of human umbilical vein endothelial cells (HUVECs) during simulated microgravity and TNF-a activation. HUVECs were isolated according to Gimbrone et al. (1978) in modification A. Antonov (1981) and used for experiments at 2-4 passages. HUVECs were activated by low level of TNF-a (2 ng/ml). Microgravity was generated by Random Positioning Machine (RPM, Dutch Space, Leiden) placed into the thermostat at 37°C. After 24 hours of clinorotation we measured adhesion molecules expression on the cell surface (ICAM-1, VCAM-1, PECAM-1, E-selectin, CD144, endoglin (CD105)) and cell viability using a flow cytometry. To evaluate the level of target gene expression was used the real time RT-PCR. IL-6 and IL-8 concentration was measured in the conditioned medium of HUVECs by using the ELISA test. We found that simulated microgravity within 24 hours caused a decrease of ICAM-1, CD144, and E-selectin expression, at the same time not affect the cell viability, endoglin and PECAM-1 expression on the surface HUVEC. Furthermore, there were no changes of the level of IL-6 and IL-8 gene expression and their products in the culture medium. TNF-activated HUVECs showed an increase in gene expression of interleukins and molecules involved in the adhesion process, which also was confirmed

  18. Subcellular localization of SV2 and other secretory vesicle components in PC12 cells by an efficient method of preembedding EM immunocytochemistry for cell cultures

    DEFF Research Database (Denmark)

    Tanner, V A; Ploug, Thorkil; Tao-Cheng, J H

    1996-01-01

    substantially improved the efficiency of the preembedding EM ICC procedures for cell cultures. The advantages and related caveats of this method are discussed. SV2 was distinctly localized on dusters of synaptic vesicles and large dense-cored vesicles (LDCV). The distribution of SV2 on these two types...... of secretory vesicles was compared quantitatively to that of another secretory vesicle-associated transmembrane protein, synaptophysin. In cultures under similar experimental conditions, the ratio of SV2 vs synaptophysin ICC staining on synaptic vesicle dusters was about 1:1, whereas it was about 9:1 on LDCV...

  19. Exactly and completely integrable nonlinear dynamical systems

    International Nuclear Information System (INIS)

    Leznov, A.N.; Savel'ev, M.V.

    1987-01-01

    The survey is devoted to a consitent exposition of the group-algebraic methods for the integration of systems of nonlinear partial differential equations possessing a nontrivial internal symmetry algebra. Samples of exactly and completely integrable wave and evolution equations are considered in detail, including generalized (periodic and finite nonperiodic Toda lattice, nonlinear Schroedinger, Korteweg-de Vries, Lotka-Volterra equations, etc.) For exactly integrable systems the general solutions of the Cauchy and Goursat problems are given in an explicit form, while for completely integrable systems an effective method for the construction of their soliton solutions is developed. Application of the developed methods to a differential geometry problem of classification of the integrable manifolds embeddings is discussed. For exactly integrable systems the supersymmetric extensions are constructed. By the example of the generalized Toda lattice a quantization scheme is developed. It includes an explicit derivation of the corresponding Heisenberg operators and their desription in terms of the quantum algebras of the Hopf type. Among multidimensional systems the four-dimensional self-dual Yang-Mills equations are investigated most attentively with a goal of constructing their general solutions

  20. Large Hadron Collider nears completion

    CERN Multimedia

    2008-01-01

    Installation of the final component of the Large Hadron Collider particle accelerator is under way along the Franco-Swiss border near Geneva, Switzerland. When completed this summer, the LHC will be the world's largest and most complex scientific instrument.

  1. Complete Blood Count (For Parents)

    Science.gov (United States)

    ... Kids Deal With Injections and Blood Tests Blood Culture Anemia Blood Test: Basic Metabolic Panel (BMP) Blood Test: Hemoglobin Basic Blood Chemistry Tests Word! Complete Blood Count (CBC) Medical Tests and Procedures ( ...

  2. Monitoring Completed Navigation Projects Program

    National Research Council Canada - National Science Library

    Bottin, Jr., Robert R

    2001-01-01

    ... (MCNP) Program. The program was formerly known as the Monitoring Completed Coastal Projects Program, but was modified in the late 1990s to include all navigation projects, inland as well as coastal...

  3. Complete colonic duplication in children.

    Science.gov (United States)

    Khaleghnejad Tabari, Ahmad; Mirshemirani, Alireza; Khaleghnejad Tabari, Nasibeh

    2012-01-01

    Complete colonic duplication is a very rare congenital anomaly that may have different presentations according to its location and size. Complete colonic duplication can occur in 15% of gastrointestinal duplication. We report two cases of complete colonic duplications, and their characteristics. We present two patients with complete colonic duplication with different types and presentations. Case 1: A 2- year old boy presented to the clinic with abdominal protrusion, difficulty to defecate, chronic constipation and mucosal prolaps covered bulging (rectocele) since he was 6 months old. The patient had palpable pelvic mass with doughy consistency. Rectal exam confirmed perirectal mass with soft consistency. The patient underwent a surgical operation that had total tubular colorectal duplication with one blind end and was treated with simple fenestration of distal end, and was discharged without complication. After two years follow up, he had normal defecation and good weight gain. Case 2: A 2 -day old infant was referred with imperforate anus and complete duplication of recto-sigmoid colon, diphallus, double bladder, and hypospadiasis. After clinical and paraclinical investigations, he underwent operations in several stages in different periods, and was discharged without complications. After four years follow up, he led a normal life. The patients with complete duplication have to be examined carefully because of the high incidence of other systemic anomalies. Treatment includes simple resection of distal common wall, fenestration, and repair other associated anomalies.

  4. Effects of growth hormone administration on bone mineral metabolism, PTH sensitivity and PTH secretory rhythm in postmenopausal women with established osteoporosis.

    Science.gov (United States)

    Joseph, Franklin; Ahmad, Aftab M; Ul-Haq, Mazhar; Durham, Brian H; Whittingham, Pauline; Fraser, William D; Vora, Jiten P

    2008-05-01

    Growth hormone (GH) replacement improves target organ sensitivity to PTH, PTH circadian rhythm, calcium and phosphate metabolism, bone turnover, and BMD in adult GH-deficient (AGHD) patients. In postmenopausal women with established osteoporosis, GH and insulin like growth factor-1 (IGF-1) concentrations are low, and administration of GH has been shown to increase bone turnover and BMD, but the mechanisms remain unclear. We studied the effects of GH administration on PTH sensitivity, PTH circadian rhythm, and bone mineral metabolism in postmenopausal women with established osteoporosis. Fourteen postmenopausal women with osteoporosis were compared with 14 healthy premenopausal controls at baseline that then received GH for a period of 12 mo. Patients were hospitalized for 24 h before and 1, 3, 6, and 12 mo after GH administration and half-hourly blood and 3-h urine samples were collected. PTH, calcium (Ca), phosphate (PO(4)), nephrogenous cyclic AMP (NcAMP), beta C-telopeptide of type 1 collagen (betaCTX), procollagen type I amino-terminal propeptide (PINP), and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured. Circadian rhythm analysis was performed using Chronolab 3.0 and Student's t-test and general linear model ANOVAs for repeated measures were used where appropriate. IGF-1 concentration was significantly lower in the women with established osteoporosis compared with controls (101.5 +/- 8.9 versus 140.9 +/- 10.8 mug/liter; p bone mineral metabolism. GH administration to postmenopausal osteoporotic women improves target organ sensitivity to PTH and bone mineral metabolism and alters PTH secretory pattern with greater increases in bone formation than resorption. These changes, resulting in a net positive bone balance, may partly explain the mechanism causing the increase in BMD after long-term administration of GH in postmenopausal women with osteoporosis shown in previous studies and proposes a further component in the development of age

  5. Regulation of HIV-Gag Expression and Targeting to the Endolysosomal/Secretory Pathway by the Luminal Domain of Lysosomal-Associated Membrane Protein (LAMP-1) Enhance Gag-Specific Immune Response

    Science.gov (United States)

    Lucas, Carolina Gonçalves de Oliveira; Rigato, Paula Ordonhez; Gonçalves, Jorge Luiz Santos; Sato, Maria Notomi; Maciel, Milton; Peçanha, Ligia Maria Torres; August, J. Thomas; de Azevedo Marques, Ernesto Torres; de Arruda, Luciana Barros

    2014-01-01

    We have previously demonstrated that a DNA vaccine encoding HIV-p55gag in association with the lysosomal associated membrane protein-1 (LAMP-1) elicited a greater Gag-specific immune response, in comparison to a DNA encoding the native gag. In vitro studies have also demonstrated that LAMP/Gag was highly expressed and was present in MHCII containing compartments in transfected cells. In this study, the mechanisms involved in these processes and the relative contributions of the increased expression and altered traffic for the enhanced immune response were addressed. Cells transfected with plasmid DNA constructs containing p55gag attached to truncated sequences of LAMP-1 showed that the increased expression of gag mRNA required p55gag in frame with at least 741 bp of the LAMP-1 luminal domain. LAMP luminal domain also showed to be essential for Gag traffic through lysosomes and, in this case, the whole sequence was required. Further analysis of the trafficking pathway of the intact LAMP/Gag chimera demonstrated that it was secreted, at least in part, associated with exosome-like vesicles. Immunization of mice with LAMP/gag chimeric plasmids demonstrated that high expression level alone can induce a substantial transient antibody response, but targeting of the antigen to the endolysosomal/secretory pathways was required for establishment of cellular and memory response. The intact LAMP/gag construct induced polyfunctional CD4+ T cell response, which presence at the time of immunization was required for CD8+ T cell priming. LAMP-mediated targeting to endolysosomal/secretory pathway is an important new mechanistic element in LAMP-mediated enhanced immunity with applications to the development of novel anti-HIV vaccines and to general vaccinology field. PMID:24932692

  6. Secretory activity and cell cycle alteration of alveolar type II cells in the early and late phase after irradiation

    International Nuclear Information System (INIS)

    Willner, Jochen; Vordermark, Dirk; Schmidt, Michael; Gassel, Andreamaria; Flentje, Michael; Wirtz, Hubert

    2003-01-01

    Purpose: Type II cells and the surfactant system have been proposed to play a central role in pathogenesis of radiation pneumonitis. We analyzed the secretory function and proliferation parameters of alveolar type II cells in the early (until 24 h) and late phase (1-5 weeks) after irradiation (RT) in vitro and in vivo. Methods and Materials: Type II cells were isolated from rats according to the method of Dobbs. Stimulation of secretion was induced with terbutaline, adenosine triphosphate (ATP), and 12-O-tetradecanoylphorbol-13-acetate (TPA) for a 2-h period. Determination of secretion was performed using 3 H-labeled phosphatidylcholine. For the early-phase analysis, freshly isolated and adherent type II cells were irradiated in vitro with 9-21 Gy (stepwise increase of 3 Gy). Secretion stimulation was initiated 1, 6, 24, and 48 h after RT. For late-phase analysis, type II cells were isolated 1-5 weeks after 18 Gy whole lung or sham RT. Each experiment was repeated at least fivefold. Flow cytometry was used to determine cell cycle distribution and proliferating cell nuclear antigen index. Results: During the early-phase (in vitro) analysis, we found a normal stimulation of surfactant secretion in irradiated, as well as unirradiated, cells. No change in basal secretion and no dose effect were seen. During the late phase, 1-5 weeks after whole lung RT, we observed enhanced secretory activity for all secretagogues and a small increase in basal secretion in Weeks 3 and 4 (pneumonitis phase) compared with controls. The total number of isolated type II cells, as well as the rate of viable cells, decreased after the second post-RT week. Cell cycle alterations suggesting an irreversible G 2 /M block occurred in the second post-RT week and did not resolve during the observation period. The proliferating cell nuclear antigen index of type II cells from irradiated rats did not differ from that of controls. Conclusion: In contrast to literature data, we observed no direct

  7. The fate of completed intentions.

    Science.gov (United States)

    Anderson, Francis T; Einstein, Gilles O

    2017-04-01

    The goal of this research was to determine whether and how people deactivate prospective memory (PM) intentions after they have been completed. One view proposes that PM intentions can be deactivated after completion, such that they no longer come to mind and interfere with current tasks. Another view is that now irrelevant completed PM intentions exhibit persisting activation, and continue to be retrieved. In Experiment 1, participants were given a PM intention embedded within the ongoing task during Phase 1, after which participants were told either that the PM task had been completed or suspended until later. During Phase 2, participants were instructed to perform only the ongoing task and were periodically prompted to report their thoughts. Critically, the PM targets from Phase 1 reappeared in Phase 2. All of our measures, including thoughts reported about the PM task, supported the existence of persisting activation. In Experiment 2, we varied conditions that were expected to mitigate persisting activation. Despite our best attempts to promote deactivation, we found evidence for the persistence of spontaneous retrieval in all groups after intentions were completed. The theoretical and practical implications of this potential dark side to spontaneous retrieval are discussed.

  8. Completeness in quantum mechanics and the Weyl-Titchmarsh-Kodaira theorem

    Energy Technology Data Exchange (ETDEWEB)

    Palma, G [Departamento de Fisica, Universidad de Santiago de Chile, Casilla 307, Santiago 2 (Chile); Prado, H; Reyes, E G, E-mail: guillermo.palma@usach.c, E-mail: humberto.prado@usach.c, E-mail: ereyes@fermat.usach.c [Departamento de Matematica y Ciencia de la Computacion, Universidad de Santiago de Chile, Casilla 307 Correo 2, Santiago (Chile)

    2010-06-25

    We discuss the completeness of (generalized) eigenfunctions in quantum mechanics using the classical theory developed by Weyl, Titchmarsh, and Kodaira. As applications, we rigorously prove the completeness of generalized eigenfunctions for the step and well potentials.

  9. Reactor plant for Belene NPP completion

    International Nuclear Information System (INIS)

    Dragunov, Yu. G.; Ryzhov, S. B.; Ermakov, D. N.; Repin, A. I.

    2004-01-01

    Construction of 'Belene' NPP was started at the end of 80-ties using project U-87 with V-320 reactor plant, general designer of this plant is OKB 'Gidropress'. At the beginning of 90-ties, on completing the considerable number of deliveries and performance of civil engineering work at the site the NPP construction was suspended. Nowadays, considering the state of affairs at the site and the work performed by Bulgarian Party on preservation of the equipment delivered, the most perspective is supposed to be implementation of the following versions in completing 'Belene' NPP: for completion of Unit 1 - reactor plant VVER-1000 on the basis of V-320 reactor with the maximum use of the delivered equipment (V-320M) having the extended service life and safety improvement; for Unit 2 - advanced reactor plant VVER-1000. For the upgraded reactor plant V-230M the basic solutions and characteristics are presented, as well as the calculated justification of strength and safety analyses, design of the reactor core and fuel cycle, instrumentation and control systems, application of the 'leak-before break' in the project and implementation of safety measures. For the modernised reactor plant V-392M the main characteristics and basic changes are presented, concerning reactor pressure vessel, steam generator, reactor coolant pump set. Design of NPP with the modernized reactor plant V-320M meets the up-to-date requirements and can be licensed for completion and operation. In the design of NPP with the advanced reactor plant the basic solutions and the equipment are used that are similar to those used in standard reactor plant V-320 and new one with VVER-1000 under construction and completion in Russia, and abroad. Compliance of reactor design with the up-to-date international requirements, considering the extended service life of the main equipment, shows its rather high potential for implementation during completion of 'Belene' NPP

  10. Delineation of glutamate pathways and secretory responses in pancreatic islets with ß-cell-specific abrogation of the glutamate dehydrogenase

    DEFF Research Database (Denmark)

    Vetterli, Laurene; Carobbio, Stefania; Pournourmohammadi, Shirin

    2012-01-01

    isolated from βGlud1(-/-) mice exhibited half of the response measured in control islets. The amplifying pathway, tested at stimulatory glucose concentrations in the presence of KCl and diazoxide, was markedly inhibited in βGlud1(-/-) islets. On glucose stimulation, net synthesis of glutamate from α......-ketoglutarate was impaired in GDH-deficient islets. Accordingly, glucose-induced elevation of glutamate levels observed in control islets was absent in βGlud1(-/-) islets. Parallel biochemical pathways, namely alanine and aspartate aminotransferases, could not compensate for the lack of GDH. However, the secretory response...... to glucose was fully restored by the provision of cellular glutamate when βGlud1(-/-) islets were exposed to dimethyl glutamate. This shows that permissive levels of glutamate are required for the full development of glucose-stimulated insulin secretion and that GDH plays an indispensable role...

  11. Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel Nonconventional Secretory Pathway

    DEFF Research Database (Denmark)

    Jensen, Camilla Stampe; Watanabe, Shoji; Stas, Jeroen Ingrid

    2017-01-01

    the localization of Kv2.1 in these two different membrane compartments in cultured rat hippocampal neurons of mixed sex. Our data uncover a unique ability of Kv2.1 channels to use two molecularly distinct trafficking pathways to accomplish this. Somatodendritic Kv2.1 channels are targeted by the conventional...... secretory pathway, whereas axonal Kv2.1 channels are targeted by a nonconventional trafficking pathway independent of the Golgi apparatus. We further identified a new AIS trafficking motif in the C-terminus of Kv2.1, and show that putative phosphorylation sites in this region are critical for the restricted.......SIGNIFICANCE STATEMENT Our study uncovered a novel mechanism that targets the Kv2.1 voltage-gated potassium channel to two distinct trafficking pathways and two distinct subcellular destinations: the somatodendritic plasma membrane and that of the axon initial segment. We also identified a distinct motif, including...

  12. Rotavirus specific plasma secretory immunoglobulin in children with acute gastroenteritis and children vaccinated with an attenuated human rotavirus vaccine

    Science.gov (United States)

    Herrera, Daniel; Vásquez, Camilo; Corthésy, Blaise; Franco, Manuel A; Angel, Juana

    2013-01-01

    Rotavirus (RV)–specific secretory immunoglobulin (RV-SIg) has been previously detected in serum of naturally RV infected children and shown to reflect the intestinal Ig immune response. Total plasma SIgA and plasma RV-SIg were evaluated by ELISA in children with gastroenteritis due or not due to RV infection and in 50 children vaccinated with the attenuated RIX4414 human RV vaccine and 62 placebo recipients. RV-SIg was only detected in children with evidence of previous RV infection or with acute RV gastroenteritis. Vaccinees had higher RV-SIg titers than placebo recipients and RV-SIg titers increased after the second vaccine dose. RV-SIg measured after the second dose correlated with protection when vaccinees and placebo recipients were analyzed jointly. RV-SIg may serve as a valuable correlate of protection for RV vaccines. PMID:23839157

  13. Correlative scanning-transmission electron microscopy reveals that a chimeric flavivirus is released as individual particles in secretory vesicles.

    Directory of Open Access Journals (Sweden)

    Julien Burlaud-Gaillard

    Full Text Available The intracellular morphogenesis of flaviviruses has been well described, but flavivirus release from the host cell remains poorly documented. We took advantage of the optimized production of an attenuated chimeric yellow fever/dengue virus for vaccine purposes to study this phenomenon by microscopic approaches. Scanning electron microscopy (SEM showed the release of numerous viral particles at the cell surface through a short-lived process. For transmission electron microscopy (TEM studies of the intracellular ultrastructure of the small number of cells releasing viral particles at a given time, we developed a new correlative microscopy method: CSEMTEM (for correlative scanning electron microscopy - transmission electron microscopy. CSEMTEM analysis suggested that chimeric flavivirus particles were released as individual particles, in small exocytosis vesicles, via a regulated secretory pathway. Our morphological findings provide new insight into interactions between flaviviruses and cells and demonstrate that CSEMTEM is a useful new method, complementary to SEM observations of biological events by intracellular TEM investigations.

  14. In vitro conditions modify immunoassayability of bovine pituitary prolactin and growth hormone: insights into their secretory granule storage forms

    International Nuclear Information System (INIS)

    Lorenson, M.Y.

    1985-01-01

    The amount of immunoassayable intracellular bovine (b) PRL and GH varies depending on treatment conditions. The present studies were designed to characterize the mechanisms involved and to compare immunoassayability of both hormones under similar conditions. Pituitary homogenate and secretory granule hormones displayed both time- and temperature-dependent increases when incubated at pH 10.5 with reduced glutathione. Changes in immunoassayability seem to reflect conversion from poorly immunoactive tissue hormone oligomers to monomeric hormone. The data indicate that oligomeric bPRL is stabilized primarily by intermolecular disulfide bonds, although it is also susceptible to urea, SDS, and EDTA; granule thiols may also influence the conversion to monomer. The storage form of bGH appears to be stabilized differently. Maneuvers demonstrated in these studies to influence immunoassayability correlate very well with their previously established effects on hormone release and secretion, strengthening the likelihood that a functional link exists between assayability and secretion

  15. Increased expression and activity of group IIA and X secretory phospholipase A2 in peritumoral versus central colon carcinoma tissue

    DEFF Research Database (Denmark)

    Tribler, Line; Jensen, Lotte T.; Jørgensen, Kent

    2007-01-01

    Secretory phospholipase A2 (sPLA2) type IIA and X was analyzed in tumors from 22 patients with colon adenocarcinomas in order to determine the involvement and activity of sPLA2 in colon cancer. Evaluation of immunoreactive sPLA2 IIA by Western blotting showed a significantly higher level...... in the periphery of the tumors, compared to central tumor regions. Increased levels of sPLA2 IIA protein correlated with a two-fold increase in sPLA2 enzymatic activity in the peripheral regions compared to central regions. Nineteen out of 22 tumors showed high levels of sPLA2 IIA, whereas 7 out of the 22 tumors...... showed sPLA2 type X. These data demonstrate that both sPLA2 type IIA and X are present in human colon cancer and suggest a role for sPLA2 in colon cancer tumor immunology and tumorigenesis....

  16. The Relationship between the Ionic Composition of the Environment and the Secretory Activity of the Endocrine Cell Types of Stannius Corpuscles in the Teleost Gasterosteus aculeatus

    NARCIS (Netherlands)

    Wendelaar Bonga, S.E.; Greven, J.A.A.; Veenhuis, M.

    1976-01-01

    The corpuscles of Stannius of threespined sticklebacks contain two glandular cell types of presumed endocrine nature. To elucidate the function of both cell types the secretory activity of the cells was studied in fully adapted seawater and freshwater fishes and in specimens transferred from sea

  17. INDUCTION OF A SECRETORY IGA RESPONSE IN THE MURINE FEMALE UROGENITAL TRACT BY IMMUNIZATION OF THE LUNGS WITH LIPOSOME-SUPPLEMENTED VIRAL SUBUNIT ANTIGEN

    NARCIS (Netherlands)

    DEHAAN, A; RENEGAR, KB; SMALL, PA; WILSCHUT, J

    This study demonstrates that liposomes administered to the lower respiratory tract of mice have the capacity to stimulate secretory IgA (s-IgA) antibody production in the female urogenital system. Total respiratory tract immunization of mice with influenza virus subunit antigen simply mixed with

  18. Secretory phospholipase A2 responsive liposomes exhibit a potent anti-neoplastic effect in vitro, but induce unforeseen severe toxicity in vivo

    DEFF Research Database (Denmark)

    Østrem, Ragnhild Garborg; Parhamifar, Ladan; Pourhassan, Houman

    2017-01-01

    The clinical use of liposomal drug delivery vehicles is often hindered by insufficient drug release. Here we present the rational design of liposomes optimized for secretory phospholipase A2 (sPLA2) triggered drug release, and test their utility in vitro and in vivo. We hypothesized...

  19. [The observation and analysis the function and morphology of the eustachian tube in secretory otitis media and chronic rhinosinusitis in children].

    Science.gov (United States)

    Xia, Zhongfang; Wang, Zhinan; Xu, Zhongxiang; Cui, Long; Wei, Cuifen; Liu, Yan; Huang, Fang

    2014-07-01

    To observe and analyze the function and morphology of pharyngeal ostium of the eustachian tubes in secretory otitis media and chronic rhinosinusitis in children under direct vision,in order to provide an objective basis for clinical treatments. Fifty cases of secretory otitis media,50 cases of chronic rhinosinusitis and a control group of 50 cases with hoarseness were examined under video laryngoscope to observe the pharyngeal ostium morphological changes of the eustachian tubes, and their functional statuses were tested by using acoustic impedance instrument. All the data were analyzed by statistical methods. (1) In the secretory otitis group, the abnomal rate of the pharyngeal ostium of the eustachian tubes was 94% while the chronic rhinosinusitis group was 80%,and between them there was no significant differences (P > 0.05). But both of them had significant differences with the control group (P otitis group, the rate of the eustachian tube dysfunction was 70% while the chronic rhinosinusitis group was 26%, and between them there was significant differences (P otitis media and chronic rhinosinusitis in children. Eustachian tube dysfunction played a dominant role in the pathogenesis of secretory otitis media in children rather than the morphological change did compared to the chronic rhinosinusitis in children.

  20. The roles of supernatant of macrophage treated by excretory-secretory products from muscle larvae of Trichinella spiralis on the differentiation of C2C12 myoblasts

    Science.gov (United States)

    The excretory-secretory products (ESPs) released by the muscle-larvae (ML) stage of Trichinella spiralis have been suggested to be involved in nurse cell formation. However, the molecular mechanisms by which ML-ESPs modulate nurse cell formation remain unclear. Macrophages exert either beneficial or...

  1. Characterization of an endoprotease from rat small intestinal mucosal secretory granules which generates somatostatin-28 from prosomatostatin by cleavage after a single arginine residue

    NARCIS (Netherlands)

    Beinfeld, M. C.; Bourdais, J.; Kuks, P.; Morel, A.; Cohen, P.

    1989-01-01

    We have extracted, characterized, and partially purified an enzyme from secretory granules from rat small intestinal mucosa which cleaves a synthetic prosomatostatin substrate on the carboxyl side of a single arginine residue. This substrate Leu-Gln-Arg-Ser-Ala-Asn-Ser-NH2 contains the monobasic

  2. NPP Cernavoda Unit 2 Financing Completion Works

    International Nuclear Information System (INIS)

    Chirica, T.; Stefanescu, A.; Constantin, C.; Dobrin, M.

    2002-01-01

    NPP Cernavoda Unit 2 completion is the highest priority of the Romanian power sector strategy. The nuclear energy represents, through its technological features of adopted solution (a CANDU nuclear power plant) and also through technological and economical performance indicators, the best solution to fulfill the demands concerning the sustainable development and the electricity request. The guidelines of energy strategy regarding the nuclear sector development in Romania are framing in the general policy for energy system development at least costs and they are responding to requests concerning the environment and people protection. The paper presents the financing alternatives for Unit 2 completion works taking into consideration the financing market conditions. The paper presents the impact of the financing conditions on the project efficiency, as well as the facilities offered by the Romanian Government in order to support this project. (author)

  3. Quantum space and quantum completeness

    Science.gov (United States)

    Jurić, Tajron

    2018-05-01

    Motivated by the question whether quantum gravity can "smear out" the classical singularity we analyze a certain quantum space and its quantum-mechanical completeness. Classical singularity is understood as a geodesic incompleteness, while quantum completeness requires a unique unitary time evolution for test fields propagating on an underlying background. Here the crucial point is that quantum completeness renders the Hamiltonian (or spatial part of the wave operator) to be essentially self-adjoint in order to generate a unique time evolution. We examine a model of quantum space which consists of a noncommutative BTZ black hole probed by a test scalar field. We show that the quantum gravity (noncommutative) effect is to enlarge the domain of BTZ parameters for which the relevant wave operator is essentially self-adjoint. This means that the corresponding quantum space is quantum complete for a larger range of BTZ parameters rendering the conclusion that in the quantum space one observes the effect of "smearing out" the singularity.

  4. Program Costs and Student Completion

    Science.gov (United States)

    Manning, Terri M.; Crosta, Peter M.

    2014-01-01

    Community colleges are under pressure to increase completion rates, prepare students for the workplace, and contain costs. Colleges need to know the financial implications of what are often perceived as routine decisions: course scheduling, program offerings, and the provision of support services. This chapter presents a methodology for estimating…

  5. Globals of Completely Regular Monoids

    Institute of Scientific and Technical Information of China (English)

    Wu Qian-qian; Gan Ai-ping; Du Xian-kun

    2015-01-01

    An element of a semigroup S is called irreducible if it cannot be expressed as a product of two elements in S both distinct from itself. In this paper we show that the class C of all completely regular monoids with irreducible identity elements satisfies the strong isomorphism property and so it is globally determined.

  6. Complete nitrification by Nitrospira bacteria

    DEFF Research Database (Denmark)

    Daims, Holger; Lebedeva, Elena V.; Pjevac, Petra

    2015-01-01

    Nitrification, the oxidation of ammonia via nitrite to nitrate, has always been considered to be a two-step process catalysed by chemolithoautotrophic microorganisms oxidizing either ammonia or nitrite. No known nitrifier carries out both steps, although complete nitrification should be energetic...

  7. Spring valve for well completion

    Energy Technology Data Exchange (ETDEWEB)

    Gorbatov, P T

    1966-07-22

    A spring-loaded valve for well completion consists of a housing with a spring-loaded closing element. In order to protect the closing element from corrosion which might lower the pressure drop, the closing element is made in the form of a piston. It is tightly connected with sealing elements. The housing has orifices, overlapping the piston in the initial position.

  8. Largest particle detector nearing completion

    CERN Multimedia

    2006-01-01

    "Construction of another part of the Large Hadron Collider (LHC), the worl's largest particle accelerator at CERN in Switzerland, is nearing completion. The Compact Muon Solenoid (CMS) is oner of the LHC project's four large particle detectors. (1/2 page)

  9. YB0 SERVICES INSTALLATION COMPLETED

    CERN Document Server

    The beauty of the completed YB0 was briefly visible at P5 as preparations continue for Tracker installation. A tremendous effort, lasting 7 months and involving more than 100 workers on the busiest days, resulted in 5700 electrical cables, 780 optical cables with 65k fibre channels, and 550 pipes laid on YB0 for HB, EB and Tracker.

  10. Adrenergic regulation of cytoplasmic structures related to secretory processes in pig pinealocytes-an ultrastructural, quantitative study.

    Science.gov (United States)

    Przybylska-Gornowicz, Barbara; Lewczuk, Bogdan; Ziółkowska, Natalia; Prusik, Magdalena

    2017-10-01

    Two structures, considered as secretory in nature, are present in the pinealocytes in of the domestic pig show the presence of two structures, which are considered as secretory in nature - the dense core vesicles (DCV) and the membrane bounded (dense) bodies (MBB). The latter are extremely numerous in pig pinealocytes (they occupy 6-20% of the cytoplasm), and the number of MBB changes under different physiological and experimental conditions. Norepinephrine is the main neurotransmitter that regulates the secretion of pineal melatonin. The present study was carried out to 1) clarify whether the DCV and their source - the Golgi apparatus (GA) - as well as the MBB are controlled by norepinephrine, 2) determine the effect of adrenergic stimulation on these structures, and 3) identify the receptors involved in the regulation of these structures. The studies were performed using a static organ culture of pig pineal explants. The explants were incubated in a control medium between 08:00 and 20:00 and in a medium with 10μM norepinephrine or alpha- or beta-adrenoceptor agonists between 20:00 and 08:00 on five consecutive days. The tissues were subsequently prepared for ultrastructural analysis. The results distinctly showed that the DCV, GA and MBB in pig pinealocytes are under adrenergic control. The stimulation of the beta-adrenoceptors resulted in an increase in the numerical density of the DCV and a decrease in the relative volume of the GA in the perikarya, while the incubation with agonists of the alpha1-adrenoceptors was ineffective. The relative volume of the MBB in the perikarya significantly decreased after treatment with both beta-agonists and alpha1-agonists, which suggested the involvement of two types of adrenoceptors in the regulation of these structures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Novel method for isolation of murine clara cell secretory protein-expressing cells with traces of stemness.

    Directory of Open Access Journals (Sweden)

    Xiao-Yang Wang

    Full Text Available Clara cells are non-ciliated, secretory bronchiolar epithelial cells that serve to detoxify harmful inhaled substances. Clara cells also function as stem/progenitor cells for repair in the bronchioles. Clara cell secretory protein (CCSP is specifically expressed in pulmonary Clara cells and is widely used as a Clara cell marker. In addition CCSP promoter is commonly used to direct gene expression into the lung in transgenic models. The discovery of CCSP immunoreactivity in plasma membranes of airway lining cells prompted us to explore the possibility of enriching Clara cells by flow cytometry. We established a novel and simple method for the isolation of CCSP-expressing cell Clara cells using a combination of mechanical and enzymatic dissociation followed by flow cytometry sorting technology. We showed that ∼25% of dissociated cells from whole lung expressed CCSP. In the resulting preparation, up to 98% of cells expressed CCSP. Notably, we found that several common stem cell markers including CD44, CD133, Sca-1 and Sox2 were expressed in CCSP(+ cells. Moreover, CCSP(+ cells were able to form spheroid colonies in vitro with 0.97‰ efficiency. Parallel studies in vivo confirmed that a small population of CCSP(-expressing cells in mouse airways also demonstrates stem cell-like properties such as label retention and harboring rare bronchioalveolar stem cells (BASCs in terminal bronchioles (TBs. We conclude that CCSP(+ cells exhibit a number of stem cell-like features including stem cell marker expression, bronchosphere colony formation and self-renewal ability. Clara cell isolation by flow cytometry sorting is a useful method for investigating the function of primary Clara cells in stem cell research and mouse models.

  12. Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal.

    Science.gov (United States)

    Goldfine, A B; Mun, E C; Devine, E; Bernier, R; Baz-Hecht, M; Jones, D B; Schneider, B E; Holst, J J; Patti, M E

    2007-12-01

    Hyperinsulinemic hypoglycemia is newly recognized as a rare but important complication after Roux-en-Y gastric bypass (GB). The etiology of the syndrome and metabolic characteristics remain incompletely understood. Recent studies suggest that levels of incretin hormones are increased after GB and may promote excessive beta-cell function and/or growth. We performed a cross-sectional analysis of metabolic variables, in both the fasting state and after a liquid mixed-meal challenge, in four subject groups: 1) with clinically significant hypoglycemia [neuroglycopenia (NG)] after GB surgery, 2) with no symptoms of hypoglycemia at similar duration after GB surgery, 3) without GB similar to preoperative body mass index of the surgical cohorts, and 4) without GB similar to current body mass index of the surgical cohorts. Insulin and C-peptide after the liquid mixed meal were both higher relative to the glucose level achieved in persons after GB with NG compared with asymptomatic individuals. Glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic peptide levels were higher in both post-GB surgical groups compared with both overweight and morbidly obese persons, and glucagon-like peptide 1 was markedly higher in the group with NG. Insulin resistance, assessed by homeostasis model assessment of insulin resistance, the composite insulin sensitivity index, or adiponectin, was similar in both post-GB groups. Dumping score was also higher in both GB groups but did not discriminate between asymptomatic and symptomatic patients. Notably, the frequency of asymptomatic hypoglycemia after a liquid mixed meal was high in post-GB patients. A robust insulin secretory response was associated with postprandial hypoglycemia in patients after GB presenting with NG. Increased incretin levels may contribute to the increased insulin secretory response.

  13. The secretory phospholipase A2 group IIA: a missing link between inflammation, activated renin-angiotensin system, and atherogenesis?

    Directory of Open Access Journals (Sweden)

    Dimitar Divchev

    2008-06-01

    Full Text Available Dimitar Divchev, Bernhard SchiefferDepartment of Cardiology and Angiology, Medizinische Hochschule Hannover, GermanyAbstract: Inflammation, lipid peroxidation and chronic activation of the renin–angiotensin system (RAS are hallmarks of the development of atherosclerosis. Recent studies have suggested the involvement of the pro-inflammatory secretory phospholipase A2 (sPLA2-IIA in atherogenesis. This enzyme is produced by different cell types through stimulation by proinflammatory cytokines. It is detectable in the intima and in media smooth muscle cells, not only in atherosclerotic lesions but also in the very early stages of atherogenesis. sPLA2-IIA can hydrolyse the phospholipid monolayers of low density lipoproteins (LDL. Such modified LDL show increased affinity to proteoglycans. The modified particles have a greater tendency to aggregate and an enhanced ability to insert cholesterol into cells. This modification may promote macrophage LDL uptake leading to the formation of foam cells. Furthermore, sPLA2-IIA is not only a mediator for localized inflammation but may be also used as an independent predictor of adverse outcomes in patients with stable coronary artery disease or acute coronary syndromes. An interaction between activated RAS and phospholipases has been indicated by observations showing that inhibitors of sPLA2 decrease angiotensin (Ang II-induced macrophage lipid peroxidation. Meanwhile, various interactions between Ang II and oxLDL have been demonstrated suggesting a central role of sPLA2-IIA in these processes and offering a possible target for treatment. The role of sPLA2-IIA in the perpetuation of atherosclerosis appears to be the missing link between inflammation, activated RAS and lipidperoxidation.Keywords: secretory phospholipase A2, lipoproteins, renin-angiotensin system, inflammation, atherosclerosis

  14. Secretory structures on the leaf rachis of Caesalpinieae and Mimosoideae (Leguminosae): implications for the evolution of nectary glands.

    Science.gov (United States)

    Pascal, L M; Motte-Florac, E F; McKey, D B

    2000-03-01

    Cup- or sometimes slit-shaped nectary glands on the rachis are a widespread trait in the legume subfamily Mimosoideae, especially in derived tribes. Their spotty occurrence in genera that appear to be basal has led to uncertainty about when in the mimosoid radiation this character evolved. Until now, specialized rachis glands were unknown in caesalpinioids thought to be related to ancestral mimosoids. We report here the occurrence of rachis glands in seven of the ten species of the Paleotropical genus Erythrophleum, a member of the Dimorphandra group of caesalpinioids thought to include the sister group(s) of mimosoids. The histological structure and location of Erythrophleum glands suggest homology with those of mimosoids; these glands are simpler structurally than rachis glands of any known mimosoid. The Erythrophleum glands differ from those of most mimosoids in the following respects: (1) they are smaller than glands of mimosoids; (2) the secretory surface is sunken in a pit capped by a small round pore rather than exposed on a broad concave or flat surface; (3) a smaller number of cells are involved in production and secretion of nectar; (4) vascular supply to the nectary is less extensive; and (5) mechanical support tissue (sclerenchyma) is less extensive and less organized. Rachis glands appear to be absent in the nine other genera included in the Dimorphandra group. We also report the occurrence of other secretory structures (patches of glandular trichomes) on the rachis of some Caesalpinieae and Mimoseae that lack specialized nectary glands and suggest that these patches of trichomes are primitive homologues of more organized glands. We discuss the significance of these glands and of the patches of trichomes for understanding relationships among primitive mimosoids and related caesalpinioids, and for understanding the origin of ant-guard defenses typical of many mimosoids.

  15. Comparative Assay of Glutathione S- Transferase (GSTs Activity of Excretory-Secretory Materials and Somatic Extract of Fasciola spp Parasites

    Directory of Open Access Journals (Sweden)

    Heshmatollah Alirahmi

    2010-12-01

    Full Text Available Fascioliasis is a worldwide parasitic disease in human and domestic animals. The causative agents of fascioliasis are Fasciola hepatica and Fasciola gigantica. In the recent years, fasciola resistance to drugs has been reported in the many of publications. Fasciola spp has detoxification system including GST enzyme which may be responsible for its resistance. Therefore , the aim of the study was to assay of GST enzyme activity in fasciola parasites. Fasciola gigantica and Fasciola hepatica helminths were collected from abattoir as a live and cultured in buffer media for 4 h at 37 °C. Excretory-Secretory products were collected and stored in -80◦C. F. gigantica and Fasciola hepatica were homogenized with homogenizing buffer in a glass homogenizer to prepare of somatic extract. Suspension was then centrifuged and supernatant was stored at -80°C. In order to assay the enzyme activity, excretory-secretory and somatic extracts in the form of cocktails (potassium phosphate buffer, reduced glutathione and 1-chloro-2,4-dinitrobenzene substrates were prepared and their absorbance recorded for 5 minutes at 340 nm. The total and specific GST activity of F. gigantica somatic and ES products were obtained as 2916.00, 272.01 micromole/minute and 1.33, 1.70 micromole/minute/mg protein, respectively. Fasciola hepatica also showed 2705.00, 276.86 micromole/minute and 1.33, 1.52 micromole/minute/mg protein, respectively. These results are important for analysis of parasite survival / resistance to drugs which use for treatment of fascioliasis.

  16. Comparative Assay of Glutathione S- Transferase (GSTs Activity of Excretory-Secretory Materials and Somatic Extract of Fasciola spp Parasites

    Directory of Open Access Journals (Sweden)

    Taghi Golmohamadi

    2010-11-01

    Full Text Available Fascioliasis is a worldwide parasitic disease in human and domestic animals. The causative agents of fascioliasis are Fasciola hepatica and Fasciola gigantica. In the recent years, fasciola resistance to drugs has been reported in the many of publications. Fasciola spp has detoxification system including GST enzyme which may be responsible for its resistance. Therefore , the aim of the study was to assay of GST enzyme activity in fasciola parasites. Fasciola gigantica and Fasciola hepatica helminths were collected from abattoir as a live and cultured in buffer media for 4 h at 37 °C. Excretory-Secretory products were collected and stored in -80◦C. F. gigantica and Fasciola hepatica were homogenized with homogenizing buffer in a glass homogenizer to prepare of somatic extract. Suspension was then centrifuged and supernatant was stored at -80°C. In order to assay the enzyme activity, excretory-secretory and somatic extracts in the form of cocktails (potassium phosphate buffer, reduced glutathione and 1-chloro-2,4-dinitrobenzene substrates were prepared and their absorbance recorded for 5 minutes at 340 nm. The total and specific GST activity of F. gigantica somatic and ES products were obtained as 2916.00, 272.01 micromole/minute and 1.33, 1.70 micromole/minute/mg protein, respectively. Fasciola hepatica also showed 2705.00, 276.86 micromole/minute and 1.33, 1.52 micromole/minute/mg protein, respectively. These results are important for analysis of parasite survival / resistance to drugs which use for treatment of fascioliasis.

  17. Multisoliton formula for completely integrable two-dimensional systems

    International Nuclear Information System (INIS)

    Chudnovsky, D.V.; Chudnovsky, G.V.

    1979-01-01

    For general two-dimensional completely integrable systems, the exact formulae for multisoliton type solutions are given. The formulae are obtained algebrically from solutions of two linear partial differential equations

  18. PROBABILISTIC RELATIONAL MODELS OF COMPLETE IL-SEMIRINGS

    OpenAIRE

    Tsumagari, Norihiro

    2012-01-01

    This paper studies basic properties of probabilistic multirelations which are generalized the semantic domain of probabilistic systems and then provides two probabilistic models of complete IL-semirings using probabilistic multirelations. Also it is shown that these models need not be models of complete idempotentsemirings.

  19. EIA completes corrections to drilling estimates series

    International Nuclear Information System (INIS)

    Trapmann, W.; Shambaugh, P.

    1998-01-01

    The Energy Information Administration (EIA) has published monthly and annual estimates of US oil and gas drilling activity since 1978. These data are key information for many industry analysts, serving as a leading indicator of trends in the industry and a barometer of general industry status. They are assessed directly for trends, as well as in combination with other measures to assess the productivity and profitability of upstream industry operations. They are major reference points for federal and state policymakers. EIA does not itself collect drilling activity data. Instead, it relies on an external source for data on oil, bas, and dry well completions. These data are provided to EIA monthly on an as reported basis. During a recent effort to enhance EIA's well completion data system, the detection of unusual patterns in the well completion data as received led to an expanded examination of these data. Substantial discrepancies between the data as received by EIA and correct record counts since 1987 were identified. For total wells by year, the errors ranged up to more than 2,300 wells, 11% of the 1995 total, and the impact of these errors extended backward in time to at least the early 1980s. When the magnitude and extent of the as reported well completion data problem were confirmed, EIA suspended its publication and distribution of updated drilling data. EIA staff proceeded to acquire replacement files with the as reported records and then revise the statistical portion of its drilling data system to reflect the new information. The replacement files unfortunately also included erroneous data based on the improper allocation of wells between exploration and development. EIA has now resolved the two data problems and generated revised time series estimates for well completions and footage drilled. The paper describes the problems in the data, differences between the series, and maintaining future data quality

  20. Pathologic features of suicidal complete decapitations.

    Science.gov (United States)

    Tsokos, M; Türk, E E; Uchigasaki, S; Püschel, K

    2004-01-28

    Despite high suicide rates all over the world, complete decapitation as a consequence of violent suicide methods is exceptionally rare and there is always a potential for confusion with homicide as well as with body dismemberment or mutilation. We analyzed the phenomenology and morphology of 10 cases (six male, four female; individual age 18-60 years) of suicidal complete decapitation that were subjected to medico-legal autopsies at the Institute of Legal Medicine, University of Hamburg, Germany, between 1995 and 2002. All decapitations occurred while the person was alive as proven by signs of vitality. Blood alcohol levels were positive in five cases and ranged between 28 and 202 mg/dl. The applied methods of suicide were running over by a train in eight cases and hanging in two cases. In suicidal hanging resulting in complete decapitation the wound margins were clear-cut with an adjacent sharply demarcated circumferential band-like abrasion zone showing a homogenous width, the latter determined by the thickness of the rope. In decapitations due to railway interference a broad spectrum of pathologic alterations such as the co-existence of irregular, ragged and sharp-edged wound margins, vascular and nervous pathways forming bridges in the depth of the wound and bruising could be observed. In such cases skin abrasion zones were generally not circumferential and showed a heterogenous width. Concerning hanging-related complete decapitations, our findings are well in line with those of other authors, namely that heavy body weight of the suicidal, fall from a great height and in some cases inelastic and/or thin rope material used for the noose are the determining factors decisive for complete decapitation.

  1. Complete spacelike immersions with topology

    International Nuclear Information System (INIS)

    Harris, S.G.

    1988-01-01

    A fairly large class of Lorentz manifolds is defined, called WH normal manifolds, which are approximately those for which timelike infinity is a single point. It is shown that, in such a space, an immersed spacelike hypersurface which is complete must, if it is self-intersecting, not achronal or proper, satisfy strong topological conditions; in particular, if the immersion is injective in the fundamental group, then the hypersurface must be closed, embedded and achronal (i.e. a partial Cauchy surface). WH normal spaces include products of any Riemannian manifold with Minkowski 1-space; in such space, a complete immersed spacelike hypersurface must be immersed as a covering space for the Riemannian factor. (author)

  2. Generalized functions

    CERN Document Server

    Gelfand, I M; Graev, M I; Vilenkin, N Y; Pyatetskii-Shapiro, I I

    Volume 1 is devoted to basics of the theory of generalized functions. The first chapter contains main definitions and most important properties of generalized functions as functional on the space of smooth functions with compact support. The second chapter talks about the Fourier transform of generalized functions. In Chapter 3, definitions and properties of some important classes of generalized functions are discussed; in particular, generalized functions supported on submanifolds of lower dimension, generalized functions associated with quadratic forms, and homogeneous generalized functions are studied in detail. Many simple basic examples make this book an excellent place for a novice to get acquainted with the theory of generalized functions. A long appendix presents basics of generalized functions of complex variables.

  3. Completeness in Hybrid Type Theory

    DEFF Research Database (Denmark)

    Areces, Carlos; Blackburn, Patrick Rowan; Huertas, Antonia

    2014-01-01

    We show that basic hybridization (adding nominals and @ operators) makes it possible to give straightforward Henkin-style completeness proofs even when the modal logic being hybridized is higher-order. The key ideas are to add nominals as expressions of type t, and to extend to arbitrary types th......-style intensional models; we build, as simply as we can, hybrid logicover Henkin’s logic...

  4. [Anterior guidance in complete dentures].

    Science.gov (United States)

    Dubreuil, J; Trevelo, A

    1990-01-01

    Although the anterior guidance in complete dentures is not really a guide, the arrangement of the anterior maxillary and mandibular prosthetic teeth, defines a propulsive line called the virtual anterior guidance, a part from the cinematic criterias. The influence of this guide on cuspal movement is superior, in all mandibular points, to the influence of the condylar pathway. If this line is not respected, the practitioner may have to do excessive grindings during occlusal adjustments.

  5. Efficient Completion of Weighted Automata

    Directory of Open Access Journals (Sweden)

    Johannes Waldmann

    2016-09-01

    Full Text Available We consider directed graphs with edge labels from a semiring. We present an algorithm that allows efficient execution of queries for existence and weights of paths, and allows updates of the graph: adding nodes and edges, and changing weights of existing edges. We apply this method in the construction of matchbound certificates for automatically proving termination of string rewriting. We re-implement the decomposition/completion algorithm of Endrullis et al. (2006 in our framework, and achieve comparable performance.

  6. Complete experiments in electron-atom collisions

    International Nuclear Information System (INIS)

    Anderson, N.; Bartschat, K.

    1996-01-01

    This paper addresses the advances up to the present in complete electron-atom collision experiments. The aim is to present a series of key examples for fundamental scattering processes, together with the experimental techniques that have been used. The purpose is not a full presentation of all processes studied, nor of all data that have been accumulated; rather, it is to select examples of the most recent theoretical and experimental results that will enable the reader to assess the present level of achievement. We hope that the power of this approach will become evident along the way, in the sense that it provides an efficient framework for a systematic, and complete test of the current theoretical understanding. In addition, it may produce specific recipes for ways to select experimental geometries that most efficiently test theoretical predictions, and it may reveal connections between apparently unrelated observables from often very different and highly sophisticated experiments, thus providing valuable consistency checks. The presentation is structured in the following way. To begin with, a general analysis of scattering amplitude properties concludes in a recipe for determination of the number of independent parameters necessary to define a complete experiment for a given process. We then proceed to analyze in a systematic way a string of specific cases of elastic and inelastic collisions, with gradually increasing levels of sophistication. Finally, we comment on directions in which future studies could fruitfully be pursued. 77 refs., 53 figs

  7. Matter in general relativity

    Science.gov (United States)

    Ray, J. R.

    1982-01-01

    Two theories of matter in general relativity, the fluid theory and the kinetic theory, were studied. Results include: (1) a discussion of various methods of completing the fluid equations; (2) a method of constructing charged general relativistic solutions in kinetic theory; and (3) a proof and discussion of the incompatibility of perfect fluid solutions in anisotropic cosmologies. Interpretations of NASA gravitational experiments using the above mentioned results were started. Two papers were prepared for publications based on this work.

  8. General Editorial

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. General Editorial. Articles in Resonance – Journal of Science Education. Volume 19 Issue 1 January 2014 pp 1-2 General Editorial. General Editorial on Publication Ethics · R Ramaswamy · More Details Fulltext PDF. Volume 19 Issue 1 January 2014 pp 3-3 ...

  9. Restoration of the cellular secretory milieu overrides androgen dependence of in vivo generated castration resistant prostate cancer cells overexpressing the androgen receptor.

    Science.gov (United States)

    Patki, Mugdha; Huang, Yanfang; Ratnam, Manohar

    2016-07-22

    It is believed that growth of castration resistant prostate cancer (CRPC) cells is enabled by sensitization to minimal residual post-castrate androgen due to overexpression of the androgen receptor (AR). Evidence is derived from androgen-induced colony formation in the absence of cell-secreted factors or from studies involving forced AR overexpression in hormone-dependent cells. On the other hand, standard cell line models established from CRPC patient tumors (e.g., LNCaP and VCaP) are hormone-dependent and require selection pressure in castrated mice to re-emerge as CRPC cells and the resulting tumors then tend to be insensitive to the androgen antagonist enzalutamide. Therefore, we examined established CRPC model cells produced by castration of mice bearing hormone-dependent cell line xenografts including CRPC cells overexpressing full-length AR (C4-2) or co-expressing wtAR and splice-variant AR-V7 that is incapable of ligand binding (22Rv1). In standard colony formation assays, C4-2 cells were shown to be androgen-dependent and sensitive to enzalutamide whereas 22Rv1 cells were incapable of colony formation under identical conditions. However, both C4-2 and 22Rv1 cells formed colonies in conditioned media derived from the same cells or from HEK293 fibroblasts that were proven to lack androgenic activity. This effect was (i) not enhanced by androgen, (ii) insensitive to enzalutamide, (iii) dependent on AR (in C4-2) and on AR-V7 and wtAR (in 22Rv1) and (iv) sensitive to inhibitors of several signaling pathways, similar to androgen-stimulation. Therefore, during progression to CRPC in vivo, coordinate cellular changes accompanying overexpression of AR may enable cooperation between hormone-independent activity of AR and actions of cellular secretory factors to completely override androgen-dependence and sensitivity to drugs targeting hormonal factors. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Completion of the TRT Barrel

    CERN Multimedia

    Gagnon, P

    On February 3, the US-TRT team proudly completed the installation of the 96th barrel TRT module on its support structure in the SR building at CERN. This happy event came after many years of R&D initiated in the nineties by the TA1 team at CERN, followed by the construction of the modules in three American institutes (Duke, Hampton and Indiana Universities) from 1996 to 2003. In total, the 96 barrel modules contain 52544 kapton straws, each 4 mm in diameter and strung with a 30 micron gold-plated tungsten wire. Each wire was manually inserted, a feat in itself! The inner layer modules contain 329 straws, the middle layer modules have 520 straws and the outer layer, 793 straws. Thirty- two modules of each type form a full layer. Their special geometry was designed such as to leave no dead region. On average, a particle will cross 36 straws. Kirill Egorov, Chuck Mahlon and John Callahan inserted the last module in the Barrel Support Structure. After completion in the US, all modules were transferred...

  11. LHCf completes its first run

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    LHCf, one of the three smaller experiments at the LHC, has completed its first run. The detectors were removed last week and the analysis of data is continuing. The first results will be ready by the end of the year.   One of the two LHCf detectors during the removal operations inside the LHC tunnel. LHCf is made up of two independent detectors located in the tunnel 140 m either side of the ATLAS collision point. The experiment studies the secondary particles created during the head-on collisions in the LHC because they are similar to those created in a cosmic ray shower produced when a cosmic particle hits the Earth’s atmosphere. The focus of the experiment is to compare the various shower models used to estimate the primary energy of ultra-high-energy cosmic rays. The energy of proton-proton collisions at the LHC will be equivalent to a cosmic ray of 1017eV hitting the atmosphere, very close to the highest energies observed in the sky. “We have now completed the fir...

  12. Complete family of separability criteria

    International Nuclear Information System (INIS)

    Doherty, Andrew C.; Spedalieri, Federico M.; Parrilo, Pablo A.

    2004-01-01

    We introduce a family of separability criteria that are based on the existence of extensions of a bipartite quantum state ρ to a larger number of parties satisfying certain symmetry properties. It can be easily shown that all separable states have the required extensions, so the nonexistence of such an extension for a particular state implies that the state is entangled. One of the main advantages of this approach is that searching for the extension can be cast as a convex optimization problem known as a semidefinite program. Whenever an extension does not exist, the dual optimization constructs an explicit entanglement witness for the particular state. These separability tests can be ordered in a hierarchical structure whose first step corresponds to the well-known positive partial transpose (Peres-Horodecki) criterion, and each test in the hierarchy is at least as powerful as the preceding one. This hierarchy is complete, in the sense that any entangled state is guaranteed to fail a test at some finite point in the hierarchy, thus showing it is entangled. The entanglement witnesses corresponding to each step of the hierarchy have well-defined and very interesting algebraic properties that, in turn, allow for a characterization of the interior of the set of positive maps. Coupled with some recent results on the computational complexity of the separability problem, which has been shown to be NP hard, this hierarchy of tests gives a complete and also computationally and theoretically appealing characterization of mixed bipartite entangled states

  13. SPS completes LS1 activities

    CERN Multimedia

    Katarina Anthony

    2014-01-01

    On 27 June, the SPS closed its doors to the LS1 engineers, bringing to an end almost 17 months of activities. The machine now enters the hardware-testing phase in preparation for an October restart.   Photo 1: The SPS transfer tunnel, TT10, reinforced with steal beams. Having completed their LS1 activities right on schedule (to the day!), the SPS team is now preparing the machine for its restart. Over the next eight weeks, hardware tests of the SPS dipole and quadrupole power converters will be underway, led by the TE-EPC (Electrical Power Converters) team. "OP start-up test activities will also be running in parallel, utilising the off hours when EPC is not using the machine," says David McFarlane, the SPS technical coordinator from the Engineering Department. "The primary beam testing phase will start at the beginning of September, once hardware tests and DSO safety tests have been completed." It has been a long journey to this point, with several major...

  14. AEgIS installation completed

    CERN Multimedia

    Katarina Anthony

    2012-01-01

    Gravity. Despite first being described over three centuries ago, it remains one of the least understood of the fundamental forces explored by physicists. At CERN’s recently completed AEgIS experiment, a team has set out to examine the effect of gravity on an as-yet-uncharted realm: antimatter.   The complete AEgIS set-up. Located in the AD hall, the AEgIS experiment plans to  make the first direct measurement of Earth’s gravitation effect on antimatter. By sending a beam of antihydrogen atoms through very thin gratings, the experiment will be able to measure how far the antihydrogen atoms fall and in how much time – giving the AEgIS team a measurement of the gravitational coupling. “By the end of 2012, we had finished by putting all the elements of the experiment together,” explains Michael Doser, AEgIS Spokesperson. “Now we have to show that they can all work together and, unfortunately, we will have no antiproton beams fo...

  15. New complete noncompact Spin(7) manifolds

    International Nuclear Information System (INIS)

    Cvetic, M.; Gibbons, G.W.; Lue, H.; Pope, C.N.

    2002-01-01

    We construct new explicit metrics on complete noncompact Riemannian 8-manifolds with holonomy Spin(7). One manifold, which we denote by (A 8 , is topologically R 8 and another, which we denote by B 8 , is the bundle of chiral spinors over S 4 . Unlike the previously-known complete noncompact metric of Spin(7) holonomy, which was also defined on the bundle of chiral spinors over S 4 , our new metrics are asymptotically locally conical (ALC): near infinity they approach a circle bundle with fibres of constant length over a cone whose base is the squashed Einstein metric on CP 3 . We construct the covariantly-constant spinor and calibrating 4-form. We also obtain an L 2 -normalisable harmonic 4-form for the (A)) 8 manifold, and two such 4-forms (of opposite dualities) for the B 8 manifold. We use the metrics to construct new supersymmetric brane solutions in M-theory and string theory. In particular, we construct resolved fractional M2-branes involving the use of the L 2 harmonic 4-forms, and show that for each manifold there is a supersymmetric example. An intriguing feature of the new A 8 and B 8 Spin(7) metrics is that they are actually the same local solution, with the two different complete manifolds corresponding to taking the radial coordinate to be either positive or negative. We make a comparison with the Taub-NUT and Taub-BOLT metrics, which by contrast do not have special holonomy. In we construct the general solution of our first-order equations for Spin(7) holonomy, and obtain further regular metrics that are complete on manifolds B 8 + and B 8 - similar to B 8

  16. DAQ INSTALLATION IN USC COMPLETED

    CERN Multimedia

    A. Racz

    After one year of work at P5 in the underground control rooms (USC55-S1&S2), the DAQ installation in USC55 is completed. The first half of 2006 was dedicated to the DAQ infrastructures installation (private cable trays, rack equipment for a very dense cabling, connection to services i.e. water, power, network). The second half has been spent to install the custom made electronics (FRLs and FMMs) and place all the inter-rack cables/fibers connecting all sub-systems to central DAQ (more details are given in the internal pages). The installation has been carried out by DAQ group members, coming from the hardware and software side as well. The pictures show the very nice team spirit !

  17. Generalized estimating equations

    CERN Document Server

    Hardin, James W

    2002-01-01

    Although powerful and flexible, the method of generalized linear models (GLM) is limited in its ability to accurately deal with longitudinal and clustered data. Developed specifically to accommodate these data types, the method of Generalized Estimating Equations (GEE) extends the GLM algorithm to accommodate the correlated data encountered in health research, social science, biology, and other related fields.Generalized Estimating Equations provides the first complete treatment of GEE methodology in all of its variations. After introducing the subject and reviewing GLM, the authors examine th

  18. Listeria-vectored vaccine expressing the Mycobacterium tuberculosis 30 kDa major secretory protein via the constitutively active prfA* regulon boosts BCG efficacy against tuberculosis.

    Science.gov (United States)

    Jia, Qingmei; Dillon, Barbara Jane; Masleša-Galić, Saša; Horwitz, Marcus A

    2017-06-19

    A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective BCG vaccine. Here we investigate novel live attenuated recombinant Listeria monocytogenes (rLm) vaccines expressing the Mycobacterium tuberculosis (Mtb) 30 kDa major secretory protein (r30/Ag85B) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated Lm vectors, rLm Δ actA (LmI), rLm Δ actA Δ inlB (LmII), and rLm Δ actA Δ inlB prfA * (LmIII), we constructed five rLm30 vaccine candidates expressing the r30 linked in-frame to the Lm Listeriolycin O signal sequence and driven by the hly promoter (h30) or linked in-frame to the ActA N-terminus and driven by the actA promoter (a30). All five rLm30 vaccines secreted r30 in broth and macrophages; while rLm expressing r30 via a constitutively active prfA * regulon (rLmIII/a30) expressed the greatest amount of r30 in broth culture, all five rLm vaccines expressed equivalent amounts of r30 in infected macrophages. In comparative studies, boosting BCG-immunized mice with rLmIII/a30 induced the strongest antigen-specific T-cell responses, including splenic and lung polyfunctional CD4+ T-cells expressing the three cytokines of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) ( P vaccines were generally more potent booster vaccines than r30 in adjuvant and a recombinant adenovirus vaccine expressing r30. In a setting in which BCG alone was highly immunoprotective, boosting mice with rLmIII/a30, the most potent of the vaccines, significantly enhanced protection against aerosolized Mtb ( P <0.01). Copyright © 2017 American Society for Microbiology.

  19. Generalized product

    OpenAIRE

    Greco, Salvatore; Mesiar, Radko; Rindone, Fabio

    2014-01-01

    Aggregation functions on [0,1] with annihilator 0 can be seen as a generalized product on [0,1]. We study the generalized product on the bipolar scale [–1,1], stressing the axiomatic point of view. Based on newly introduced bipolar properties, such as the bipolar increasingness, bipolar unit element, bipolar idempotent element, several kinds of generalized bipolar product are introduced and studied. A special stress is put on bipolar semicopulas, bipolar quasi-copulas and bipolar copulas.

  20. In vivo secretory potential and the effect of combination therapy with octreotide and cabergoline in patients with clinically non-functioning pituitary adenomas

    DEFF Research Database (Denmark)

    Andersen, M; Bjerre, P; Schrøder, H D

    2001-01-01

    The secretory capacity, in vivo, of clinically non-functioning pituitary adenomas may possibly predict tumour volume reduction during intensive medical therapy. Ten patients (mean (range) 53 years (26-73)) with clinically non-functioning macroadenomas, > or = 10 mm were studied. The secretory...... capacity of the adenomas was examined using basal, NaCl and TRH-stimulated LH, FSH and alpha-subunit levels. The effect on tumour volume of 6 months' therapy with the combination of a somatostatin analogue, octreotide 200 microg x 3/day and a dopamine-D2-agonist, cabergoline 0.5 mg x 1/day was studied...... therapy in all of our patients with non-functioning pituitary adenomas....