Science.gov

Sample records for additional functional roles

  1. Functional Generalized Additive Models.

    PubMed

    McLean, Mathew W; Hooker, Giles; Staicu, Ana-Maria; Scheipl, Fabian; Ruppert, David

    2014-01-01

    We introduce the functional generalized additive model (FGAM), a novel regression model for association studies between a scalar response and a functional predictor. We model the link-transformed mean response as the integral with respect to t of F{X(t), t} where F(·,·) is an unknown regression function and X(t) is a functional covariate. Rather than having an additive model in a finite number of principal components as in Müller and Yao (2008), our model incorporates the functional predictor directly and thus our model can be viewed as the natural functional extension of generalized additive models. We estimate F(·,·) using tensor-product B-splines with roughness penalties. A pointwise quantile transformation of the functional predictor is also considered to ensure each tensor-product B-spline has observed data on its support. The methods are evaluated using simulated data and their predictive performance is compared with other competing scalar-on-function regression alternatives. We illustrate the usefulness of our approach through an application to brain tractography, where X(t) is a signal from diffusion tensor imaging at position, t, along a tract in the brain. In one example, the response is disease-status (case or control) and in a second example, it is the score on a cognitive test. R code for performing the simulations and fitting the FGAM can be found in supplemental materials available online.

  2. Role of Lewis acid additives in a palladium catalyzed directed C-H functionalization reaction of benzohydroxamic acid to isoxazolone.

    PubMed

    Athira, C; Sunoj, Raghavan B

    2016-12-20

    Metallic salts as well as protic additives are widely employed in transition metal catalyzed C-H bond functionalization reactions to improve the efficiency of catalytic protocols. In one such example, ZnCl2 and pivalic acid are used as additives in a palladium catalyzed synthesis of isoxazolone from a readily available benzohydroxamic acid under one pot conditions. In this article, we present some important mechanistic insights into the role of ZnCl2 and pivalic acid, gained by using density functional theory (M06) computations. Two interesting modes of action of ZnCl2 are identified in various catalytic steps involved in the formation of isoxazolone. The conventional Lewis acid coordination wherein zinc chloride (ZnCl2·(DMA)) binds to the carbonyl group is found to be more favored in the C-H activation step. However, the participation of a hetero-bimetallic Pd-Zn species is preferred in reductive elimination leading to Caryl-N bond formation. Pivalic acid helps in relay proton transfer in C-H bond activation through a cyclometallation deprotonation (CMD) process. The explicit inclusion of ZnCl2 and solvent N,N-dimethyl acetamide (DMA) stabilizes the transition state and also helps reduce the activation barrier for the C-H bond activation step. The electronic communication between the two metal species is playing a crucial role in stabilizing the Caryl-N bond formation transition state through a Pd-Zn hetero-bimetallic interaction.

  3. Phylogenetic analyses and characterization of RNase X25 from Drosophila melanogaster suggest a conserved housekeeping role and additional functions for RNase T2 enzymes in protostomes.

    PubMed

    Ambrosio, Linda; Morriss, Stephanie; Riaz, Ayesha; Bailey, Ryan; Ding, Jian; MacIntosh, Gustavo C

    2014-01-01

    Ribonucleases belonging to the RNase T2 family are enzymes associated with the secretory pathway that are almost absolutely conserved in all eukaryotes. Studies in plants and vertebrates suggest they have an important housekeeping function in rRNA recycling. However, little is known about this family of enzymes in protostomes. We characterized RNase X25, the only RNase T2 enzyme in Drosophila melanogaster. We found that RNase X25 is the major contributor of ribonuclease activity in flies as detected by in gel assays, and has an acidic pH preference. Gene expression analyses showed that the RNase X25 transcript is present in all adult tissues and developmental stages. RNase X25 expression is elevated in response to nutritional stresses; consistent with the hypothesis that this enzyme has a housekeeping role in recycling RNA. A correlation between induction of RNase X25 expression and autophagy was observed. Moreover, induction of gene expression was triggered by oxidative stress suggesting that RNase X25 may have additional roles in stress responses. Phylogenetic analyses of this family in protostomes showed that RNase T2 genes have undergone duplication events followed by divergence in several phyla, including the loss of catalytic residues, and suggest that RNase T2 proteins have acquired novel functions. Among those, it is likely that a role in host immunosuppression evolved independently in several groups, including parasitic Platyhelminthes and parasitoid wasps. The presence of only one RNase T2 gene in the D. melanogaster genome, without any other evident secretory RNase activity detected, makes this organism an ideal system to study the cellular functions of RNase T2 proteins associated with RNA recycling and maintenance of cellular homeostasis. On the other hand, the discovery of gene duplications in several protostome genomes also presents interesting new avenues to study additional biological functions of this ancient family of proteins.

  4. 32 CFR 2003.15 - Additional functions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... President through the National Security Advisor, the ISCAP performs such additional advisory functions as... National Defense Other Regulations Relating to National Defense INFORMATION SECURITY OVERSIGHT OFFICE, NATIONAL ARCHIVES AND RECORDS ADMINISTRATION INTERAGENCY SECURITY CLASSIFICATION APPEALS PANEL...

  5. 32 CFR 2003.15 - Additional functions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... President through the National Security Advisor, the ISCAP performs such additional advisory functions as... National Defense Other Regulations Relating to National Defense INFORMATION SECURITY OVERSIGHT OFFICE, NATIONAL ARCHIVES AND RECORDS ADMINISTRATION INTERAGENCY SECURITY CLASSIFICATION APPEALS PANEL...

  6. The diverse roles of the Nup93/Nic96 complex proteins - structural scaffolds of the nuclear pore complex with additional cellular functions.

    PubMed

    Vollmer, Benjamin; Antonin, Wolfram

    2014-05-01

    Nuclear pore complexes mediate the transport between the cell nucleoplasm and cytoplasm. These 125 MDa structures are among the largest assemblies found in eukaryotes, built from proteins organized in distinct subcomplexes that act as building blocks during nuclear pore complex biogenesis. In this review, we focus on one of these subcomplexes, the Nup93 complex in metazoa and its yeast counterpart, the Nic96 complex. We discuss its essential function in nuclear pore complex assembly as a linker between the nuclear membrane and the central part of the pore and its various roles in nuclear transport processes and beyond.

  7. Theoretical elucidation on the functional role of pyrrolidine-type ionic liquids in inducing stereoselectivity of the Michael addition of cyclohexanone with trans-β-nitrostyrene.

    PubMed

    Sun, Hui; Zhang, Dongju

    2011-03-01

    Density functional theory calculations have been carried out to elucidate the stereoselectivity of the Michael addition of cyclohexanone with trans-β-nitrostyrene, induced by a chiral ionic liquid (CIL) pyrrolidine-imidazolium bromide. By comparison of the C-C bond forming processes in the absence and presence of Br(-) anion, we found that intermolecular H-bonds between the imidazolium cation and the nitro group of trans-β-nitrostyrene and the steric hindrance of the imidazolium cation moiety on the Si-face of enamine dominate the stereoselectivity of the Michael addition. The presence of Br(-) anion obviously reduces the barrier by increasing the polarity of the C4=C5 bond of enamine. The theoretical results rationalize well the early experimental finding, and reveal a valuable clue for the further CIL design with high catalytic efficiency.

  8. Characterizing neuromorphologic alterations with additive shape functionals

    NASA Astrophysics Data System (ADS)

    Barbosa, M. S.; Costa, L. Da F.; Bernardes, E. S.; Ramakers, G.; van Pelt, J.

    2004-01-01

    The complexity of a neuronal cell shape is known to be related to its function. Specifically, among other indicators, a decreased complexity in the dendritic trees of cortical pyramidal neurons has been associated with mental retardation. In this paper we develop a procedure to address the characterization of morphological changes induced in cultured neurons by over-expressing a gene involved in mental retardation. Measures associated with the multiscale connectivity, an additive image functional, are found to give a reasonable separation criterion between two categories of cells. One category consists of a control group and two transfected groups of neurons, and the other, a class of cat ganglionary cells. The reported framework also identified a trend towards lower complexity in one of the transfected groups. Such results establish the suggested measures as an effective descriptors of cell shape.

  9. Role of edible film and coating additives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Edible films and coatings have received increasing interest because films and coatings can carry a diversity of functional ingredients. Plasticizers, such as glycerol, acetylated monoglycerides, polyethylene glycol, and sucrose are often used to modify the mechanical properties of the film or coatin...

  10. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  11. Additive Functions in Boolean Models of Gene Regulatory Network Modules

    PubMed Central

    Darabos, Christian; Di Cunto, Ferdinando; Tomassini, Marco; Moore, Jason H.; Provero, Paolo; Giacobini, Mario

    2011-01-01

    Gene-on-gene regulations are key components of every living organism. Dynamical abstract models of genetic regulatory networks help explain the genome's evolvability and robustness. These properties can be attributed to the structural topology of the graph formed by genes, as vertices, and regulatory interactions, as edges. Moreover, the actual gene interaction of each gene is believed to play a key role in the stability of the structure. With advances in biology, some effort was deployed to develop update functions in Boolean models that include recent knowledge. We combine real-life gene interaction networks with novel update functions in a Boolean model. We use two sub-networks of biological organisms, the yeast cell-cycle and the mouse embryonic stem cell, as topological support for our system. On these structures, we substitute the original random update functions by a novel threshold-based dynamic function in which the promoting and repressing effect of each interaction is considered. We use a third real-life regulatory network, along with its inferred Boolean update functions to validate the proposed update function. Results of this validation hint to increased biological plausibility of the threshold-based function. To investigate the dynamical behavior of this new model, we visualized the phase transition between order and chaos into the critical regime using Derrida plots. We complement the qualitative nature of Derrida plots with an alternative measure, the criticality distance, that also allows to discriminate between regimes in a quantitative way. Simulation on both real-life genetic regulatory networks show that there exists a set of parameters that allows the systems to operate in the critical region. This new model includes experimentally derived biological information and recent discoveries, which makes it potentially useful to guide experimental research. The update function confers additional realism to the model, while reducing the complexity

  12. Additive functions in boolean models of gene regulatory network modules.

    PubMed

    Darabos, Christian; Di Cunto, Ferdinando; Tomassini, Marco; Moore, Jason H; Provero, Paolo; Giacobini, Mario

    2011-01-01

    Gene-on-gene regulations are key components of every living organism. Dynamical abstract models of genetic regulatory networks help explain the genome's evolvability and robustness. These properties can be attributed to the structural topology of the graph formed by genes, as vertices, and regulatory interactions, as edges. Moreover, the actual gene interaction of each gene is believed to play a key role in the stability of the structure. With advances in biology, some effort was deployed to develop update functions in boolean models that include recent knowledge. We combine real-life gene interaction networks with novel update functions in a boolean model. We use two sub-networks of biological organisms, the yeast cell-cycle and the mouse embryonic stem cell, as topological support for our system. On these structures, we substitute the original random update functions by a novel threshold-based dynamic function in which the promoting and repressing effect of each interaction is considered. We use a third real-life regulatory network, along with its inferred boolean update functions to validate the proposed update function. Results of this validation hint to increased biological plausibility of the threshold-based function. To investigate the dynamical behavior of this new model, we visualized the phase transition between order and chaos into the critical regime using Derrida plots. We complement the qualitative nature of Derrida plots with an alternative measure, the criticality distance, that also allows to discriminate between regimes in a quantitative way. Simulation on both real-life genetic regulatory networks show that there exists a set of parameters that allows the systems to operate in the critical region. This new model includes experimentally derived biological information and recent discoveries, which makes it potentially useful to guide experimental research. The update function confers additional realism to the model, while reducing the complexity

  13. Roles of additives and surface control in slurry atomization

    SciTech Connect

    Tsai, S.C.

    1992-01-01

    This project studies the rheology and airblast atomization of micronized coal slurries. Its major objectives are (1) to promote further understanding of the mechanisms and the roles of additives in airblast atomization of coal water slurry (CWS), and (2) to investigate the impacts of coal particle surface properties and interparticle forces on CWS rheology. We have found that the flow behavior index (n) of a suspension (or slurry) is determined by the relative importance of the interparticle van der Waals attraction and the interparticle electrostatic repulsion. The interparticle attraction, measured by the Hamaker constant scaled to the thermal energy at 25[degrees]C (A/kT), causes particle aggregation, which breaks down at high shear rates, and thus leads to slurry pseudoplastic behavior (n< 1). At a constant particle volume fraction and surface charge density (qualitatively measured by the zeta potential in deionized water), n decreases linearly as A/kT increases. The relative viscosity of the pseudoplastic suspension with respect to that of the suspending liquid is found to be independent of particle density and correlate well with the particle Peclet number which equals the particle diffusional relaxation time multiplied by shear rate. Specifically, the relative viscosities of the pseudoplastic glycerol/water coal slurry and the ethylene glycol/glycerol sand slurry, at same volume fractions as well as similar particle size distributions and liquid viscosities, as functions of the particle Peclet number fall along the same line.

  14. Role of additional radiotherapy in advanced stages of Hodgkin's disease.

    PubMed

    Meerwaldt, J H; Coleman, C N; Fischer, R I; Lister, T A; Diehl, V

    1992-09-01

    Although radiotherapy is widely used as additional treatment following chemotherapy, its precise role has never been clearly proven. Relapses tend to occur in previously involved bulky sites. Non-randomized studies may suggest a positive effect of the addition of radiotherapy. This effect however, might also be caused by selection. Randomized studies have not resulted in a survival advantage for the patients treated with additional radiotherapy compared to no further treatment or additional chemotherapy. The SWOG study 7808 suggest a 20% benefit in remission duration for the nodular sclerosis histology subgroup. Definitive conclusions have to wait for more mature results of randomized studies including the ongoing EORTC study and the possibility to perform an overview of all studies.

  15. Some new addition formulae for Weierstrass elliptic functions

    PubMed Central

    Eilbeck, J. Chris; England, Matthew; Ônishi, Yoshihiro

    2014-01-01

    We present new addition formulae for the Weierstrass functions associated with a general elliptic curve. We prove the structure of the formulae in n-variables and give the explicit addition formulae for the 2- and 3-variable cases. These new results were inspired by new addition formulae found in the case of an equianharmonic curve, which we can now observe as a specialization of the results here. The new formulae, and the techniques used to find them, also follow the recent work for the generalization of Weierstrass functions to curves of higher genus. PMID:25383018

  16. Hyperbolic tangential function-based progressive addition lens design.

    PubMed

    Qiu, Gufeng; Cui, Xudong

    2015-12-10

    The diopter distribution is key to the successful design of a progressive addition lens. A hyperbolic tangential function is then introduced to describe well the desired diopter distribution on the lens. Simulation and fabrication show that the astigmia on the whole surface is very close to the addition, exhibiting superior performance than that of currently used high-order polynomials and cosine functions. Our investigations found that once the diopter distribution design is reasonable, both the direct and indirect methods of constructing a progressive addition lens can give consistent results. With this function we are able to effectively control the design of critical areas, the position, sizes of far-view and near-view zones, as well as the channel of the lens. This study would provide an efficient way to customize different progressive lenses not only for presbyopia, but also for anti-fatigue, office progressive usages, etc.

  17. Covalently functionalized hexagonal boron nitride nanosheets by nitrene addition.

    PubMed

    Sainsbury, Toby; Satti, Amro; May, Peter; O'Neill, Arlene; Nicolosi, Valeria; Gun'ko, Yurii K; Coleman, Jonathan N

    2012-08-27

    The covalent functionalization of exfoliated hexagonal boron nitride (h-BN) nanosheets by nitrene addition is described. Integration of functionalized h-BN nanosheets within a polycarbonate matrix is demonstrated and was found to afford significant increases in mechanical properties. This integration methodology was further extended by the covalent modification of the h-BN nanosheets with polymer chains of a polycarbonate analogue, and the integration of the polymer modified h-BN within the polymer matrix.

  18. The Role of Relational Reasoning in Children's Addition Concepts

    ERIC Educational Resources Information Center

    Farrington-Flint, Lee; Canobi, Katherine H.; Wood, Clare; Faulkner, Dorothy

    2007-01-01

    The study addresses the relational reasoning of different-aged children and how addition reasoning is related to problem-solving skills within addition and to reasoning skills outside addition. Ninety-two 5- to 8-year-olds were asked to solve a series of conceptually related and unrelated addition problems, and the speed and accuracy of all…

  19. Development of additional tasks for the executive function performance test.

    PubMed

    Hahn, Bridget; Baum, Carolyn; Moore, Jennifer; Ehrlich-Jones, Linda; Spoeri, Susan; Doherty, Meghan; Wolf, Timothy J

    2014-01-01

    OBJECTIVE. The Executive Function Performance Test (EFPT) is a reliable and valid performance-based assessment of executive function for people with stroke. The objective of this study was to enhance the clinical utility of the EFPT by developing and testing additional tasks for the EFPT in the Alternate EFPT (aEFPT). METHOD. We performed a cross-sectional study with poststroke participants (n = 25) and healthy control participants (n = 25). All participants completed a neuropsychological assessment battery and both the EFPT and the aEFPT. RESULTS. No statistically significant differences were found between the EFPT and the aEFPT when examining total scores, construct scores, and two overall task scores. Correlations between the aEFPT and the neuropsychological measures were adequate to strong (r2s = .59-.83). CONCLUSION. The aEFPT tasks are comparable to the original EFPT tasks, providing occupational therapy practitioners with additional tasks that can be used clinically to identify performance-based executive function deficits in people with stroke.

  20. Fuzzy Number Addition with the Application of Horizontal Membership Functions

    PubMed Central

    Piegat, Andrzej; Pluciński, Marcin

    2015-01-01

    The paper presents addition of fuzzy numbers realised with the application of the multidimensional RDM arithmetic and horizontal membership functions (MFs). Fuzzy arithmetic (FA) is a very difficult task because operations should be performed here on multidimensional information granules. Instead, a lot of FA methods use α-cuts in connection with 1-dimensional classical interval arithmetic that operates not on multidimensional granules but on 1-dimensional intervals. Such approach causes difficulties in calculations and is a reason for arithmetical paradoxes. The multidimensional approach allows for removing drawbacks and weaknesses of FA. It is possible thanks to the application of horizontal membership functions which considerably facilitate calculations because now uncertain values can be inserted directly into equations without using the extension principle. The paper shows how the addition operation can be realised on independent fuzzy numbers and on partly or fully dependent fuzzy numbers with taking into account the order relation and how to solve equations, which can be a difficult task for 1-dimensional FAs. PMID:26199953

  1. Nonlinear responses in salt marsh functioning to increased nitrogen addition.

    PubMed

    Vivanco, Lucía; Irvine, Irina C; Martiny, Jennifer B H

    2015-04-01

    Salt marshes provide storm protection to shorelines, sequester carbon (C), and mitigate coastal eutrophication. These valuable coastal ecosystems are confronted with increasing nitrogen (N) inputs from anthropogenic sources, such as agricultural runoff, wastewater, and atmospheric deposition. To inform predictions of salt marsh functioning and sustainability in the future, we characterized the response of a variety of plant, microbial, and sediment responses to a seven-level gradient of N addition in three Californian salt marshes after 7 and 14 months of N addition. The marshes showed variable responses to the experimental N gradient that can be grouped as neutral (root biomass, sediment respiration, potential carbon mineralization, and potential net nitrification), linear (increasing methane flux, decreasing potential net N mineralization, and increasing sediment inorganic N), and nonlinear (saturating aboveground plant biomass and leaf N content, and exponentially increasing sediment inorganic and organic N). The three salt marshes showed quantitative differences in most ecosystem properties and processes rates; however, the form of the response curves to N addition were generally consistent across the three marshes, indicating that the responses observed may be applicable to other marshes in the region. Only for sediment properties (inorganic and organic N pool) did the shape of the response differ significantly between marshes. Overall, the study suggests salt marshes are limited in their ability to sequester C and N with future increases in N, even without further losses in marsh area.

  2. The Role of Conceptual Understanding in Children's Addition Problem Solving.

    ERIC Educational Resources Information Center

    Canobi, Katherine H.; Reeve, Robert A.; Pattison, Philippa E.

    1998-01-01

    Examined the relationship between 6- to 8-year olds' conceptual understanding of additive composition, commutativity, and associativity principles and addition problem-solving procedures. Results revealed that conceptual understanding was related to using order-indifferent, decomposition, and retrieval strategies and speed and accuracy in solving…

  3. Functional role of autophagy in gastric cancer

    PubMed Central

    2016-01-01

    Autophagy is a highly regulated catabolic pathway responsible for the degradation of long-lived proteins and damaged intracellular organelles. Perturbations in autophagy are found in gastric cancer. In host gastric cells, autophagy can be induced by Helicobacter pylori (or H. pylori) infection, which is associated with the oncogenesis of gastric cancer. In gastric cancer cells, autophagy has both pro-survival and pro-death functions in determining cell fate. Besides, autophagy modulates gastric cancer metastasis by affecting a wide range of pathological events, including extracellular matrix (ECM) degradation, epithelial-to-mesenchymal transition (EMT), tumor angiogenesis, and tumor microenvironment. In addition, some of the autophagy-related proteins, such as Beclin 1, microtubule-associated protein 1 light chain 3 (MAP1-LC3), and p62/sequestosome 1 (SQSTM1) have certain prognostic values for gastric cancer. In this article, we review the recent studies regarding the functional role of autophagy in gastric cancer. PMID:26910278

  4. The role of conceptual understanding in children's addition problem solving.

    PubMed

    Canobi, K H; Reeve, R A; Pattison, P E

    1998-09-01

    The study examined the relationship between children's conceptual understanding and addition problem-solving procedures. Forty-eight 6- to 8-year-olds solved addition problems and, in a 2nd task, were prompted to judge whether a puppet could use the arithmetic properties of one problem to solve the next problem. Relational properties between consecutive problems were manipulated to reflect aspects of additive composition, commutativity, and associativity principles. Conceptual understanding was assessed by the ability to spontaneously use such relational properties in problem solving (Task 1) and to recognize and explain them when prompted (Task 2). Results revealed that conceptual understanding was related to using order-indifferent, decomposition, and retrieval strategies and speed and accuracy in solving unrelated problems. The importance of conceptual understanding for addition development is discussed.

  5. Exopolysaccharide from Lactobacillus fermentum Lf2 and its functional characterization as a yogurt additive.

    PubMed

    Ale, Elisa C; Perezlindo, Marcos J; Burns, Patricia; Tabacman, Eduardo; Reinheimer, Jorge A; Binetti, Ana G

    2016-11-01

    Lactobacillus fermentum Lf2 is a strain which is able to produce high levels (approximately 1 g/l) of crude exopolysaccharide (EPS) when it is grown in optimised conditions. The aim of this work was to characterize the functional aspects of this EPS extract, focusing on its application as a dairy food additive. Our findings are consistent with an EPS extract that acts as moderate immunomodulator, modifying s-IgA and IL-6 levels in the small intestine when added to yogurt and milk, respectively. Furthermore, this EPS extract, in a dose feasible to use as a food additive, provides protection against Salmonella infection in a murine model, thus representing a mode of action to elicit positive health benefits. Besides, it contributes to the rheological characteristics of yogurt, and could function as a food additive with both technological and functional roles, making possible the production of a new functional yogurt with improved texture.

  6. The Crucial Role of Additive Manufacturing at NASA

    NASA Technical Reports Server (NTRS)

    Vickers, John

    2016-01-01

    At NASA, the first steps of the Journey to Mars are well underway with the development of NASA's next generation launch system and investments in research and technologies that should increase the affordability, capability, and safety of exploration activities. Additive Manufacturing presents a disruptive opportunity for NASA to design and manufacture hardware with new materials at dramatically reduced cost and schedule. Opportunities to incorporate additive manufacturing align very well with NASA missions and with most NASA programs related to space, science, and aeronautics. The Agency also relies on many partnerships with other government agencies, industry and academia.

  7. Children's Additive Concepts: Promoting Understanding and the Role of Inhibition

    ERIC Educational Resources Information Center

    Robinson, Katherine M.; Dube, Adam K.

    2013-01-01

    This study investigated the promotion of children's understanding and acquisition of arithmetic concepts and the effects of inhibitory skills. Children in Grades 3, 4, and 5 solved two sets of three-term addition and subtraction problems (e.g., 3 + 24 - 24, 3 + 24 - 22) and completed an inhibition task. Half of the participants received a…

  8. The Role of Drugs, Diet, and Food Additives in Hyperactivity.

    ERIC Educational Resources Information Center

    Harshbarger, Mary E.

    A variety of causes have been suggested for hyperactivity: anoxia and other adverse birth conditions, genetic factors, delayed maturation, maternal smoking and drinking during pregnancy, interaction of temperament and environment, lead poisoning, radiation stress, allergy and food additives, and deprivation of required stimulation. Treatments…

  9. (Roles of additives and surface control in slurry atomization)

    SciTech Connect

    Not Available

    1992-01-01

    Our experimental results clearly demonstrate that the shape of particles with aspect ratio close to unity dictates the relative suspension viscosity. Suspensions of irregularly shaped particles have higher relative viscosities than suspensions of spherical particles at same volume fractions, in agreement with the reported results at high shear conditions. The relative viscosity of a Newtonian suspension is in excellent agreement with that predicted by the Krieger/Dougherty rigid sphere model using the maximum packing fraction determined from sedimentation as the sole parameter. The relative viscosity of a pseudoplastic suspension is independent of the particle density. It correlates well with the particle Peclet number. The extent of particle diffusion at high shear rates decreases considerably as the particle size increases, and less energy is dissipated as a result. The interparticle electrostatic repulsion plays no significant role in the rheology of pseudoplastic nonaqueous and aqueous glycerol suspensions of noncolloidal particles.

  10. The role of additional pulses in electropermeabilization protocols.

    PubMed

    Suárez, Cecilia; Soba, Alejandro; Maglietti, Felipe; Olaiz, Nahuel; Marshall, Guillermo

    2014-01-01

    Electropermeabilization (EP) based protocols such as those applied in medicine, food processing or environmental management, are well established and widely used. The applied voltage, as well as tissue electric conductivity, are of utmost importance for assessing final electropermeabilized area and thus EP effectiveness. Experimental results from literature report that, under certain EP protocols, consecutive pulses increase tissue electric conductivity and even the permeabilization amount. Here we introduce a theoretical model that takes into account this effect in the application of an EP-based protocol, and its validation with experimental measurements. The theoretical model describes the electric field distribution by a nonlinear Laplace equation with a variable conductivity coefficient depending on the electric field, the temperature and the quantity of pulses, and the Penne's Bioheat equation for temperature variations. In the experiments, a vegetable tissue model (potato slice) is used for measuring electric currents and tissue electropermeabilized area in different EP protocols. Experimental measurements show that, during sequential pulses and keeping constant the applied voltage, the electric current density and the blackened (electropermeabilized) area increase. This behavior can only be attributed to a rise in the electric conductivity due to a higher number of pulses. Accordingly, we present a theoretical modeling of an EP protocol that predicts correctly the increment in the electric current density observed experimentally during the addition of pulses. The model also demonstrates that the electric current increase is due to a rise in the electric conductivity, in turn induced by temperature and pulse number, with no significant changes in the electric field distribution. The EP model introduced, based on a novel formulation of the electric conductivity, leads to a more realistic description of the EP phenomenon, hopefully providing more accurate

  11. The Role of Additional Pulses in Electropermeabilization Protocols

    PubMed Central

    Suárez, Cecilia; Soba, Alejandro; Maglietti, Felipe; Olaiz, Nahuel; Marshall, Guillermo

    2014-01-01

    Electropermeabilization (EP) based protocols such as those applied in medicine, food processing or environmental management, are well established and widely used. The applied voltage, as well as tissue electric conductivity, are of utmost importance for assessing final electropermeabilized area and thus EP effectiveness. Experimental results from literature report that, under certain EP protocols, consecutive pulses increase tissue electric conductivity and even the permeabilization amount. Here we introduce a theoretical model that takes into account this effect in the application of an EP-based protocol, and its validation with experimental measurements. The theoretical model describes the electric field distribution by a nonlinear Laplace equation with a variable conductivity coefficient depending on the electric field, the temperature and the quantity of pulses, and the Penne's Bioheat equation for temperature variations. In the experiments, a vegetable tissue model (potato slice) is used for measuring electric currents and tissue electropermeabilized area in different EP protocols. Experimental measurements show that, during sequential pulses and keeping constant the applied voltage, the electric current density and the blackened (electropermeabilized) area increase. This behavior can only be attributed to a rise in the electric conductivity due to a higher number of pulses. Accordingly, we present a theoretical modeling of an EP protocol that predicts correctly the increment in the electric current density observed experimentally during the addition of pulses. The model also demonstrates that the electric current increase is due to a rise in the electric conductivity, in turn induced by temperature and pulse number, with no significant changes in the electric field distribution. The EP model introduced, based on a novel formulation of the electric conductivity, leads to a more realistic description of the EP phenomenon, hopefully providing more accurate

  12. Functions of Propolis as a natural feed additive in poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Propolis is a resinous hive product collected by honeybees from various sources of plants. Numerous scientific investigations have been focused on the biological activities of propolis and its functions as a health supplement in humans. It could have similar function in other animals, such as poultr...

  13. Additional applications of the Lambert W function in physics

    NASA Astrophysics Data System (ADS)

    Houari, Ahmed

    2013-05-01

    In this paper, using the Lambert W function, I derive closed-form analytical expressions for the decay constant of an exponentially decaying process and the time constant of a process subject to a linear resistive force. Similarly, I derive closed-form analytical formulae for the electrical resistivity of a metal and the temperature of a thermionic emitter material. Besides their theoretical importance, the results obtained will be of interest to teachers involved in undergraduate physics experiments.

  14. Mutations in RIT1 cause Noonan syndrome – additional functional evidence and expanding the clinical phenotype

    PubMed Central

    Koenighofer, Martin; Hung, Christina Y.; McCauley, Jacob L.; Dallman, Julia; Back, Emma J.; Mihalek, Ivana; Gripp, Karen W.; Sol-Church, Katia; Rusconi, Paolo; Zhang, Zhaiyi; Shi, Geng-Xian; Andres, Douglas A.; Bodamer, Olaf A.

    2015-01-01

    RASopathies are a clinically heterogeneous group of conditions caused by mutations in one of sixteen proteins in the RAS-MAPK pathway. Recently, mutations in RIT1 were identified as a novel cause for Noonan syndrome. Here we provide additional functional evidence for a causal role of RIT1 mutations and expand the associated phenotypic spectrum. We identified two de novo missense variants p.Met90Ile and, p.Ala57Gly. Both variants resulted in increased MEK-ERK signaling compared to wild-type, underscoring gain-of-function as the primary functional mechanism. Introduction of p.Met90Ile and p.Ala57Gly into zebrafish embryos reproduced not only aspects of the human phenotype but also revealed abnormalities of eye development, emphasizing the importance of RIT1 for spatial and temporal organization of the growing organism. In addition, we observed severe lymphedema of the lower extremity and genitalia in one patient. We provide additional evidence for a causal relationship between pathogenic mutations in RIT1, increased RAS-MAPK/MEK-ERK signaling and the clinical phenotype. The mutant RIT1 protein may possess reduced GTPase activity or a diminished ability to interact with cellular GTPase activating proteins, however the precise mechanism remains unknown. The phenotypic spectrum is likely to expand and includes lymphedema of the lower extremities in addition to nuchal hygroma. PMID:25959749

  15. Additive Manufacturing of Functional Elements on Sheet Metal

    NASA Astrophysics Data System (ADS)

    Schaub, Adam; Ahuja, Bhrigu; Butzhammer, Lorenz; Osterziel, Johannes; Schmidt, Michael; Merklein, Marion

    Laser Beam Melting (LBM) process with its advantages of high design flexibility and free form manufacturing methodology is often applied limitedly due to its low productivity and unsuitability for mass production compared to conventional manufacturing processes. In order to overcome these limitations, a hybrid manufacturing methodology is developed combining the additive manufacturing process of laser beam melting with sheet forming processes. With an interest towards aerospace and medical industry, the material in focus is Ti-6Al-4V. Although Ti-6Al-4V is a commercially established material and its application for LBM process has been extensively investigated, the combination of LBM of Ti-6Al-4V with sheet metal still needs to be researched. Process dynamics such as high temperature gradients and thermally induced stresses lead to complex stress states at the interaction zone between the sheet and LBM structure. Within the presented paper mechanical characterization of hybrid parts will be performed by shear testing. The association of shear strength with process parameters is further investigated by analyzing the internal structure of the hybrid geometry at varying energy inputs during the LBM process. In order to compare the hybrid manufacturing methodology with conventional fabrication, the conventional methodologies subtractive machining and state of the art Laser Beam Melting is evaluated within this work. These processes will be analyzed for their mechanical characteristics and productivity by determining the build time and raw material consumption for each case. The paper is concluded by presenting the characteristics of the hybrid manufacturing methodology compared to alternative manufacturing technologies.

  16. Sex Role Orientation and Female Sexual Functioning.

    ERIC Educational Resources Information Center

    Snow, Linda J.; Parsons, Jean L.

    1983-01-01

    Investigates the differences among 300 college women in four sex-role categories with regard to sexual behavior and attitudes. Results indicated that androgynous women did not differ significantly from feminine and masculine women with regard to sexual functioning, while undifferentiated women were more restricted. (JAC)

  17. Functional roles for noise in genetic circuits.

    PubMed

    Eldar, Avigdor; Elowitz, Michael B

    2010-09-09

    The genetic circuits that regulate cellular functions are subject to stochastic fluctuations, or 'noise', in the levels of their components. Noise, far from just a nuisance, has begun to be appreciated for its essential role in key cellular activities. Noise functions in both microbial and eukaryotic cells, in multicellular development, and in evolution. It enables coordination of gene expression across large regulons, as well as probabilistic differentiation strategies that function across cell populations. At the longest timescales, noise may facilitate evolutionary transitions. Here we review examples and emerging principles that connect noise, the architecture of the gene circuits in which it is present, and the biological functions it enables. We further indicate some of the important challenges and opportunities going forward.

  18. Hemichannels: new roles in astroglial function.

    PubMed

    Orellana, Juan A; Stehberg, Jimmy

    2014-01-01

    The role of astrocytes in brain function has evolved over the last decade, from support cells to active participants in the neuronal synapse through the release of "gliotransmitters."Astrocytes express receptors for most neurotransmitters and respond to them through Ca(2+) intracellular oscillations and propagation of intercellular Ca(2+) waves. While such waves are able to propagate among neighboring astrocytes through gap junctions, thereby activating several astrocytes simultaneously, they can also trigger the release of gliotransmitters, including glutamate, d-serine, glycine, ATP, adenosine, or GABA. There are several mechanisms by which gliotransmitter release occurs, including functional hemichannels. These gliotransmitters can activate neighboring astrocytes and participate in the propagation of intercellular Ca(2+) waves, or activate pre- and post-synaptic receptors, including NMDA, AMPA, and purinergic receptors. In consequence, hemichannels could play a pivotal role in astrocyte-to-astrocyte communication and astrocyte-to-neuron cross-talk. Recent evidence suggests that astroglial hemichannels are involved in higher brain functions including memory and glucose sensing. The present review will focus on the role of hemichannels in astrocyte-to-astrocyte and astrocyte-to neuron communication and in brain physiology.

  19. A Novel Functional Role of Collagen Glycosylation

    PubMed Central

    Jürgensen, Henrik J.; Madsen, Daniel H.; Ingvarsen, Signe; Melander, Maria C.; Gårdsvoll, Henrik; Patthy, Laszlo; Engelholm, Lars H.; Behrendt, Niels

    2011-01-01

    Collagens make up the most abundant component of interstitial extracellular matrices and basement membranes. Collagen remodeling is a crucial process in many normal physiological events and in several pathological conditions. Some collagen subtypes contain specific carbohydrate side chains, the function of which is poorly known. The endocytic collagen receptor urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180 plays an important role in matrix remodeling through its ability to internalize collagen for lysosomal degradation. uPARAP/Endo180 is a member of the mannose receptor protein family. These proteins all include a fibronectin type II domain and a series of C-type lectin-like domains, of which only a minor part possess carbohydrate recognition activity. At least two of the family members, uPARAP/Endo180 and the mannose receptor, interact with collagens. The molecular basis for this interaction is known to involve the fibronectin type II domain but nothing is known about the function of the lectin domains in this respect. In this study, we have investigated a possible role of the single active lectin domain of uPARAP/Endo180 in the interaction with collagens. By expressing truncated recombinant uPARAP/Endo180 proteins and analyzing their interaction with collagens with high and low levels of glycosylation we demonstrated that this lectin domain interacts directly with glycosylated collagens. This interaction is functionally important because it was found to modulate the endocytic efficiency of the receptor toward highly glycosylated collagens such as basement membrane collagen IV. Surprisingly, this property was not shared by the mannose receptor, which internalized glycosylated collagens independently of its lectin function. This role of modulating its uptake efficiency by a specific receptor is a previously unrecognized function of collagen glycosylation. PMID:21768090

  20. Diverse Functions of Restriction-Modification Systems in Addition to Cellular Defense

    PubMed Central

    Vasu, Kommireddy

    2013-01-01

    SUMMARY Restriction-modification (R-M) systems are ubiquitous and are often considered primitive immune systems in bacteria. Their diversity and prevalence across the prokaryotic kingdom are an indication of their success as a defense mechanism against invading genomes. However, their cellular defense function does not adequately explain the basis for their immaculate specificity in sequence recognition and nonuniform distribution, ranging from none to too many, in diverse species. The present review deals with new developments which provide insights into the roles of these enzymes in other aspects of cellular function. In this review, emphasis is placed on novel hypotheses and various findings that have not yet been dealt with in a critical review. Emerging studies indicate their role in various cellular processes other than host defense, virulence, and even controlling the rate of evolution of the organism. We also discuss how R-M systems could have successfully evolved and be involved in additional cellular portfolios, thereby increasing the relative fitness of their hosts in the population. PMID:23471617

  1. Preparation and Characterization of Nanocomposite Polymer Membranes Containing Functionalized SnO2 Additives

    PubMed Central

    Scipioni, Roberto; Gazzoli, Delia; Teocoli, Francesca; Palumbo, Oriele; Paolone, Annalisa; Ibris, Neluta; Brutti, Sergio; Navarra, Maria Assunta

    2014-01-01

    In the research of new nanocomposite proton-conducting membranes, SnO2 ceramic powders with surface functionalization have been synthesized and adopted as additives in Nafion-based polymer systems. Different synthetic routes have been explored to obtain suitable, nanometer-sized sulphated tin oxide particles. Structural and morphological characteristics, as well as surface and bulk properties of the obtained oxide powders, have been determined by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier Transform Infrared (FTIR) and Raman spectroscopies, N2 adsorption, and thermal gravimetric analysis (TGA). In addition, dynamic mechanical analysis (DMA), atomic force microscopy (AFM), thermal investigations, water uptake (WU) measurements, and ionic exchange capacity (IEC) tests have been used as characterization tools for the nanocomposite membranes. The nature of the tin oxide precursor, as well as the synthesis procedure, were found to play an important role in determining the morphology and the particle size distribution of the ceramic powder, this affecting the effective functionalization of the oxides. The incorporation of such particles, having sulphate groups on their surface, altered some peculiar properties of the resulting composite membrane, such as water content, thermo-mechanical, and morphological characteristics. PMID:24957125

  2. Role of developmental factors in hypothalamic function

    PubMed Central

    Biran, Jakob; Tahor, Maayan; Wircer, Einav; Levkowitz, Gil

    2015-01-01

    The hypothalamus is a brain region which regulates homeostasis by mediating endocrine, autonomic and behavioral functions. It is comprised of several nuclei containing distinct neuronal populations producing neuropeptides and neurotransmitters that regulate fundamental body functions including temperature and metabolic rate, thirst and hunger, sexual behavior and reproduction, circadian rhythm, and emotional responses. The identity, number and connectivity of these neuronal populations are established during the organism’s development and are of crucial importance for normal hypothalamic function. Studies have suggested that developmental abnormalities in specific hypothalamic circuits can lead to obesity, sleep disorders, anxiety, depression and autism. At the molecular level, the development of the hypothalamus is regulated by transcription factors (TF), secreted growth factors, neuropeptides and their receptors. Recent studies in zebrafish and mouse have demonstrated that some of these molecules maintain their expression in the adult brain and subsequently play a role in the physiological functions that are regulated by hypothalamic neurons. Here, we summarize the involvement of some of the key developmental factors in hypothalamic development and function by focusing on the mouse and zebrafish genetic model organisms. PMID:25954163

  3. Genetic evidence for an additional function of phage T4 gene 32 protein: interaction with ligase.

    PubMed

    Mosig, G; Breschkin, A M

    1975-04-01

    Gene 32 of bacteriophage T4 is essential for DNA replication, recombination, and repair. In an attempt to clarify the role of the corresponding gene product, we have looked for mutations that specifically inactivate one but not all of its functions and for compensating suppressor mutations in other genes. Here we describe a gene 32 ts mutant that does not produce progeny, but in contrast to an am mutant investigated by others, is capable of some primary and secondary DNA replication and of forming "joint" recombinational intermediates after infection of Escherichia coli B at the restrictive temperature. However, parental and progeny DNA strands are not ligated to covalently linked "recombinant" molecules, and single strands of vegetative DNA do not exceed unit length. Progeny production as well as capacity for covalent linkage in this gene 32 ts mutant are partially restored by additional rII mutations. Suppression by rII depends on functioning host ligase [EC 6.5.1.2; poly(deoxyribonucleotide):poly(deoxyribonucleotide) ligase (AMP-forming, NMN-forming)]. This gene 32 ts mutation (unlike some others) in turn suppresses the characteristic plaque morphology of rII mutants. We conclude that gene 32 protein, in addition to its role in DNA replication and in the formation of "joint" recombinational intermediates, interacts with T4 ligase [EC 6.5.1.1; poly(deoxyribonucleotide):poly(deoxyribonucleotide) ligase (AMP-forming)] when recombining DNA strands are covalently linked. The protein of the mutant that we describe here is mainly defective in this interaction, thus inactivating T4 ligase in recombination. Suppressing rII mutations facilitate substitution of host ligase. There is suggestive evidence that these interactions occur at the membrane.

  4. Additional role of O-acetylserine as a sulfur status-independent regulator during plant growth.

    PubMed

    Hubberten, Hans-Michael; Klie, Sebastian; Caldana, Camila; Degenkolbe, Thomas; Willmitzer, Lothar; Hoefgen, Rainer

    2012-05-01

    O-acetylserine (OAS) is one of the most prominent metabolites whose levels are altered upon sulfur starvation. However, its putative role as a signaling molecule in higher plants is controversial. This paper provides further evidence that OAS is a signaling molecule, based on computational analysis of time-series experiments and on studies of transgenic plants conditionally displaying increased OAS levels. Transcripts whose levels correlated with the transient and specific increase in OAS levels observed in leaves of Arabidopsis thaliana plants 5-10 min after transfer to darkness and with diurnal oscillation of the OAS content, showing a characteristic peak during the night, were identified. Induction of a serine-O-acetyltransferase gene (SERAT) in transgenic A. thaliana plants expressing the genes under the control of an inducible promoter resulted in a specific time-dependent increase in OAS levels. Monitoring the transcriptome response at time points at which no changes in sulfur-related metabolites except OAS were observed and correlating this with the light/dark transition and diurnal experiments resulted in identification of six genes whose expression was highly correlated with that of OAS (adenosine-5'-phosphosulfate reductase 3, sulfur-deficiency-induced 1, sulfur-deficiency-induced 2, low-sulfur-induced 1, serine hydroxymethyltransferase 7 and ChaC-like protein). These data suggest that OAS displays a signalling function leading to changes in transcript levels of a specific gene set irrespective of the sulfur status of the plant. Additionally, a role for OAS in a specific part of the sulfate response can be deduced.

  5. Brr2 plays a role in spliceosomal activation in addition to U4/U6 unwinding.

    PubMed

    Zhang, Lingdi; Li, Xueni; Hill, Ryan C; Qiu, Yan; Zhang, Wenzheng; Hansen, Kirk C; Zhao, Rui

    2015-03-31

    Brr2 is a DExD/H-box RNA helicase that is responsible for U4/U6 unwinding, a critical step in spliceosomal activation. Brr2 is a large protein (∼250 kD) that consists of an N-terminal domain (∼500 residues) with unknown function and two Hel308-like modules that are responsible for RNA unwinding. Here we demonstrate that removal of the entire N-terminal domain is lethal to Saccharomyces cerevisiae and deletion of the N-terminal 120 residues leads to splicing defects and severely impaired growth. This N-terminal truncation does not significantly affect Brr2's helicase activity. Brr2-Δ120 can be successfully assembled into the tri-snRNP (albeit at a lower level than the WT Brr2) and the spliceosomal B complex. However, the truncation significantly impairs spliceosomal activation, leading to a dramatic reduction of U5, U6 snRNAs and accumulation of U1 snRNA in the B(act) complex. The N-terminal domain of Brr2 does not seem to be directly involved in regulating U1/5'ss unwinding. Instead, the N-terminal domain seems to be critical for retaining U5 and U6 snRNPs during/after spliceosomal activation through its interaction with snRNAs and possibly other spliceosomal proteins, revealing a new role of Brr2 in spliceosomal activation in addition to U4/U6 unwinding.

  6. Roles of additives and surface control in slurry atomization. Final project report

    SciTech Connect

    Tsai, S.C.

    1992-12-31

    This project studies the rheology and airblast atomization of micronized coal slurries. Its major objectives are (1) to promote further understanding of the mechanisms and the roles of additives in airblast atomization of coal water slurry (CWS), and (2) to investigate the impacts of coal particle surface properties and interparticle forces on CWS rheology. We have found that the flow behavior index (n) of a suspension (or slurry) is determined by the relative importance of the interparticle van der Waals attraction and the interparticle electrostatic repulsion. The interparticle attraction, measured by the Hamaker constant scaled to the thermal energy at 25{degrees}C (A/kT), causes particle aggregation, which breaks down at high shear rates, and thus leads to slurry pseudoplastic behavior (n< 1). At a constant particle volume fraction and surface charge density (qualitatively measured by the zeta potential in deionized water), n decreases linearly as A/kT increases. The relative viscosity of the pseudoplastic suspension with respect to that of the suspending liquid is found to be independent of particle density and correlate well with the particle Peclet number which equals the particle diffusional relaxation time multiplied by shear rate. Specifically, the relative viscosities of the pseudoplastic glycerol/water coal slurry and the ethylene glycol/glycerol sand slurry, at same volume fractions as well as similar particle size distributions and liquid viscosities, as functions of the particle Peclet number fall along the same line.

  7. On the role of DNA in DNA-based catalytic enantioselective conjugate addition reactions.

    PubMed

    Dijk, Ewold W; Boersma, Arnold J; Feringa, Ben L; Roelfes, Gerard

    2010-09-07

    A kinetic study of DNA-based catalytic enantioselective Friedel-Crafts alkylation and Michael addition reactions showed that DNA affects the rate of these reactions significantly. Whereas in the presence of DNA, a large acceleration was found for the Friedel-Crafts alkylation and a modest acceleration in the Michael addition of dimethyl malonate, a deceleration was observed when using nitromethane as nucleophile. Also, the enantioselectivities proved to be dependent on the DNA sequence. In comparison with the previously reported Diels-Alder reaction, the results presented here suggest that DNA plays a similar role in both cycloaddition and conjugate addition reactions.

  8. Improving solubilization in microemulsions with additives. 1. The lipophilic linker role

    SciTech Connect

    Graciaa, A.; Lachaise, J.; Cucuphat, C. ); Bourrel, M. ); Salager, J.L. )

    1993-03-01

    Very lipophilic additives are able to substantially improve the solubilization in surfactant-oil-water microemulsions. The so-called lipophilic linker effect is studied, and its role is discussed. It is shown that the presence of a very lipophilic amphiphilic additive may improve substantially the solubilization in microemulsions. This substance is called a lipophilic linker because its preferential orientation in the oil layers next to the interface might provide some ordering of the oil molecules as well as an additional link with the surfactant. Both effects result in a higher interaction on the oil side of the interface. 21 refs., 5 figs., 1 tab.

  9. The Role of Number Words in Preschoolers' Addition Concepts and Problem-Solving Procedures

    ERIC Educational Resources Information Center

    Patel, Pooja; Canobi, Katherine Helen

    2010-01-01

    Preschoolers' conceptual understanding and procedural skills were examined so as to explore the role of number-words and concept-procedure interactions in their additional knowledge. Eighteen three- to four-year-olds and 24 four- to five-year-olds judged commutativity and associativity principles and solved two-term problems involving number words…

  10. Fungal endophytes: diversity and functional roles

    USGS Publications Warehouse

    Rodriguez, R.J.; White, J.F.; Arnold, A.E.; Redman, R.S.

    2009-01-01

    All plants in natural ecosystems appear to be symbiotic with fungal endophytes. This highly diverse group of fungi can have profound impacts on plant communities through increasing fitness by conferring abiotic and biotic stress tolerance, increasing biomass and decreasing water consumption, or decreasing fitness by altering resource allocation. Despite more than 100 yr of research resulting in thousands of journal articles, the ecological significance of these fungi remains poorly characterized. Historically, two endophytic groups (clavicipitaceous (C) and nonclavicipitaceous (NC)) have been discriminated based on phylogeny and life history traits. Here, we show that NC-endophytes represent three distinct functional groups based on host colonization and transmission, in planta biodiversity and fitness benefits conferred to hosts. Using this framework, we contrast the life histories, interactions with hosts and potential roles in plant ecophysiology of C- and NC-endophytes, and highlight several key questions for future work in endophyte biology.

  11. STAT6: its role in interleukin 4-mediated biological functions.

    PubMed

    Takeda, K; Kishimoto, T; Akira, S

    1997-05-01

    Interleukin (IL) 4 is known to be a cytokine which plays a central role in the regulation of immune response. Studies on cytokine signal transduction have clarified the mechanism by which IL4 exerts its functions. Two cytoplasmic proteins, signal transducer and activator of transcription (STAT) 6 and IL4-induced phosphotyrosine substrate/insulin receptor substrate 2 (4PS/IRS2), are activated in IL4 signal transduction. Recent studies from STAT6-deficient mice have revealed the essential role of STAT6 in IL4-mediated biological actions. In addition, STAT6 has also been demonstrated to be important for the functions mediated by IL13, which is related to IL4. IL4 and IL13 have been shown to induce the production of IgE, which is a major mediator in an allergic response. These findings indicate that STAT6 activation is involved in IL4- and IL13-mediated disorders such as allergy.

  12. The functional neuroanatomy of thematic role and locative relational knowledge.

    PubMed

    Wu, Denise H; Waller, Sara; Chatterjee, Anjan

    2007-09-01

    Lexical-semantic investigations in cognitive neuroscience have focused on conceptual knowledge of concrete objects. By contrast, relational concepts have been largely ignored. We examined thematic role and locative knowledge in 14 left-hemisphere-damage patients. Relational concepts shift cognitive focus away from the object to the relationship between objects, calling into question the relevance of traditional sensory-functional accounts of semantics. If extraction of a relational structure is the critical cognitive process common to both thematic and locative knowledge, then damage to neural structures involved in such an extraction would impair both kinds of knowledge. If the nature of the relationship itself is critical, then functional neuroanatomical dissociations should occur. Using a new lesion analysis method, we found that damage to the lateral temporal cortex produced deficits in thematic role knowledge and damage to inferior fronto-parietal regions produced deficits in locative knowledge. In addition, we found that conceptual knowledge of thematic roles dissociates from its mapping onto language. These relational knowledge deficits were not accounted for by deficits in processing nouns or verbs or by a general deficit in making inferences. Our results are consistent with the hypothesis that manners of visual motion serve as a point of entry for thematic role knowledge and networks dedicated to eye gaze, whereas reaching and grasping serve as a point of entry for locative knowledge. Intermediary convergence zones that are topographically guided by these sensory-motor points of entry play a critical role in the semantics of relational concepts.

  13. Pentraxins: Structure, Function, and Role in Inflammation

    PubMed Central

    Du Clos, Terry W.

    2013-01-01

    The pentraxins are an ancient family of proteins with a unique architecture found as far back in evolution as the Horseshoe crab. In humans the two members of this family are C-reactive protein and serum amyloid P. Pentraxins are defined by their sequence homology, their pentameric structure and their calcium-dependent binding to their ligands. Pentraxins function as soluble pattern recognition molecules and one of the earliest and most important roles for these proteins is host defense primarily against pathogenic bacteria. They function as opsonins for pathogens through activation of the complement pathway and through binding to Fc gamma receptors. Pentraxins also recognize membrane phospholipids and nuclear components exposed on or released by damaged cells. CRP has a specific interaction with small nuclear ribonucleoproteins whereas SAP is a major recognition molecule for DNA, two nuclear autoantigens. Studies in autoimmune and inflammatory disease models suggest that pentraxins interact with macrophage Fc receptors to regulate the inflammatory response. Because CRP is a strong acute phase reactant it is widely used as a marker of inflammation and infection. PMID:24167754

  14. Emerging Roles of Canonical TRP Channels in Neuronal Function

    PubMed Central

    Bollimuntha, Sunitha; Selvaraj, Senthil

    2011-01-01

    Ca2+ signaling in neurons is intimately associated with the regulation of vital physiological processes including growth, survival and differentiation. In neurons, Ca2+ elicits two major functions. First as a charge carrier, Ca2+ reveals an indispensable role in information relay via membrane depolarization, exocytosis, and the release of neurotransmitters. Second on a global basis, Ca2+ acts as a ubiquitous intracellular messenger to modulate neuronal function. Thus, to mediate Ca2+-dependent physiological events, neurons engage multiple mode of Ca2+ entry through a variety of Ca2+ permeable plasma membrane channels. Here we discuss a subset of specialized Ca2+-permeable non-selective TRPC channels and summarize their physiological and pathological role in the context of excitable cells. TRPC channels are predominately expressed in neuronal cells and are activated through complex mechanisms, including second messengers and store depletion. A growing body of evidence suggests a prime contribution of TRPC channels in regulating fundamental neuronal functions. TRPC channels have been shown to be associated with neuronal development, proliferation and differentiation. In addition, TRPC channels have also been suggested to have a potential role in regulating neurosecretion, long term potentiation, and synaptic plasticity. During the past years, numerous seminal discoveries relating TRPC channels to neurons have constantly emphasized on the significant contribution of this group of ion channels in regulating neuronal function. Here we review the major groundbreaking work that has uniquely placed TRPC channels in a pivotal position for governing neuronal Ca2+ signaling and associated physiological responses. PMID:21290317

  15. Aegerolysins: Structure, function, and putative biological role

    PubMed Central

    Berne, Sabina; Lah, Ljerka; Sepčić, Kristina

    2009-01-01

    Aegerolysins, discovered in fungi, bacteria and plants, are highly similar proteins with interesting biological properties. Certain aegerolysins possess antitumoral, antiproliferative, and antibacterial activities. Further possible medicinal applications include their use in the prevention of atherosclerosis, or as vaccines. Additional biotechnological value of fungal aegerolysins lies in their involvement in development, which could improve cultivation of commercially important edible mushrooms. Besides, new insights on microheterogeneity of raft-like membrane domains could be gained by using aegerolysins as specific markers in cell and molecular biology. Although the exact function of aegerolysins in their producing organisms remains to be explained, they are biochemically well characterized all-β structured proteins sharing the following common features: low isoelectric points, similar molecular weights (15–17 kDa), and stability in a wide pH range. PMID:19309687

  16. Evidence for an association between gender-role identity and a measure of executive function.

    PubMed

    Norvilitis, Jill M; Reid, Howard M

    2002-02-01

    Two studies assessed the relation between gender role and executive function. In Study One (N = 234) analyses indicated that among college students executive function, assessed by the Coolidge and Griego scale, is related to masculine gender-role classification, measured by the Bem Sex-role Inventory. This relationship remained significant when biological sex was controlled. Further, factor analysis of the Bem Sex-role Inventory identified six components, three related to executive function. Two of these scales were associated with masculine characteristics, and the third was associated with the denial of several feminine items. Study Two (N = 53) further assessed the relationship among undergraduates through additional measures of executive functions and mood, in addition to the Bem Sex-role Inventory. In this study, executive functioning, as measured by the Coolidge and Griego scale, was again generally related to masculinity. Psychological well-being was not related to gender identity or executive functioning.

  17. Functional roles of non-coding Y RNAs.

    PubMed

    Kowalski, Madzia P; Krude, Torsten

    2015-09-01

    Non-coding RNAs are involved in a multitude of cellular processes but the biochemical function of many small non-coding RNAs remains unclear. The family of small non-coding Y RNAs is conserved in vertebrates and related RNAs are present in some prokaryotic species. Y RNAs are also homologous to the newly identified family of non-coding stem-bulge RNAs (sbRNAs) in nematodes, for which potential physiological functions are only now emerging. Y RNAs are essential for the initiation of chromosomal DNA replication in vertebrates and, when bound to the Ro60 protein, they are involved in RNA stability and cellular responses to stress in several eukaryotic and prokaryotic species. Additionally, short fragments of Y RNAs have recently been identified as abundant components in the blood and tissues of humans and other mammals, with potential diagnostic value. While the number of functional roles of Y RNAs is growing, it is becoming increasingly clear that the conserved structural domains of Y RNAs are essential for distinct cellular functions. Here, we review the biochemical functions associated with these structural RNA domains, as well as the functional conservation of Y RNAs in different species. The existing biochemical and structural evidence supports a domain model for these small non-coding RNAs that has direct implications for the modular evolution of functional non-coding RNAs.

  18. Preparation and ageing-resistant properties of polyester composites modified with functional nanoscale additives

    PubMed Central

    2014-01-01

    This study investigated ageing-resistant properties of carboxyl-terminated polyester (polyethylene glycol terephthalate) composites modified with nanoscale titanium dioxide particles (nano-TiO2). The nano-TiO2 was pretreated by a dry coating method, with aluminate coupling agent as a functional grafting additive. The agglomeration resistance was evaluated, which exhibited significant improvement for the modified nanoparticles. Then, the effects of the modified nano-TiO2 on the crosslinking and ageing-resistant properties of the composites were studied. With a real-time Fourier transform infrared (FT-IR) measurement, the nano-TiO2 displayed promoting effect on the crosslinking of polyester resin with triglycidyl isocyanurate (TGIC) as crosslinking agent. Moreover, the gloss retention, colour aberration and the surface morphologies of the composites during accelerated UV ageing (1500 hours) were investigated. The results demonstrated much less degree of ageing degradation for the nanocomposites, indicating an important role of the nano-TiO2 in improving the ageing-resistant properties of synthetic polymer composites. PMID:24872802

  19. Asymmetric Catalytic Enantio- and Diastereoselective Boron Conjugate Addition Reactions of α-Functionalized α,β-Unsaturated Carbonyl Substrates.

    PubMed

    Xie, Jian-Bo; Lin, Siqi; Qiao, Shuo; Li, Guigen

    2016-08-05

    An efficient catalytic system has been established for the asymmetric boron conjugate addition of B2pin2 onto α-functionalized (involving C, N, O, and Cl) α,β-unsaturated carbonyls under mild, neutral conditions involving Cu[(S)-(R)-ppfa]Cl, AgNTf2, and alcohols. The dual additives of AgNTf2 and alcohols were found to play crucial roles for achieving high catalytic activity and enantio- and diastereoselectivity (up to 98% ee and 70:1 dr).

  20. Functionalized 3D Architected Materials via Thiol-Michael Addition and Two-Photon Lithography.

    PubMed

    Yee, Daryl W; Schulz, Michael D; Grubbs, Robert H; Greer, Julia R

    2017-02-20

    Fabrication of functionalized 3D architected materials is achieved by a facile method using functionalized acrylates synthesized via thiol-Michael addition, which are then polymerized using two-photon lithography. A wide variety of functional groups can be attached, from Boc-protected amines to fluoroalkanes. Modification of surface wetting properties and conjugation with fluorescent tags are demonstrated to highlight the potential applications of this technique.

  1. Bicyclo[3.2.1]octane synthons from cyclopropenes: functionalization of cycloadducts by nucleophilic additions.

    PubMed

    Orugunty, Ravi S; Wright, Dennis L; Battiste, Merle A; Helmich, Richard J; Abboud, Khalil

    2004-01-23

    It has been known for several decades that a highly functionalized family of tetrahalobicyclo[3.2.1]octadienes are readily available through the cycloaddition of furan or cyclopentadiene with either tetrachloro- or tetrabromocyclopropene. However, the application of these highly functionalized building blocks in synthesis has remained relatively unexplored in relation to their better-known counterparts derived through oxyallyl cation additions. As a first step toward utilizing these highly versatile intermediates in synthesis, a study of the addition of various nucleophiles to the halogenated nucleus has been conducted. It has been found that these halogenated systems are amenable to a wide range of functionalizations in high yields and with good selectivities.

  2. Ceramide biosynthesis in keratinocyte and its role in skin function.

    PubMed

    Mizutani, Yukiko; Mitsutake, Susumu; Tsuji, Kiyomi; Kihara, Akio; Igarashi, Yasuyuki

    2009-06-01

    The enucleate layer of the epidermis, i.e. the stratum corneum, is responsible for certain critical protective functions, such as epidermal permeability barrier function. Within the epidermal membrane lamella component, ceramides are the dominant lipid class by weight (over 50%) and exhibit the greatest molecular heterogeneity in terms of sphingoid base and fatty acid composition. It is now evermore important to understand how ceramide production and functions are controlled in the epidermis, since decreased epidermal ceramide content has been linked to water loss and barrier dysfunction. During the past several years, critical enzymes in ceramide biosynthesis have been identified, including ceramide synthases (CerS) and ceramide hydroxylase/desaturase. In this review, we describe the molecular heterogeneity of ceramides synthesized in the epidermis and their possible roles in epidermal permeability barrier functions. We also describe recent studies that identified the family of CerS (CerS1-CerS6) in mammals. We further focus on the roles of specific isoforms of these enzymes in synthesizing the epidermal ceramides, especially in relation to chain-length specificity. In addition, we provide experimental information, including our recent findings, as to how applying ceramide or ceramide-containing substances to skin, orally or directly, can benefit skin health.

  3. Functional neuroanatomy of developmental dyslexia: the role of orthographic depth

    PubMed Central

    Richlan, Fabio

    2014-01-01

    Orthographic depth (OD) (i.e., the complexity, consistency, or transparency of grapheme-phoneme correspondences in written alphabetic language) plays an important role in the acquisition of reading skills. Correspondingly, developmental dyslexia is characterized by different behavioral manifestations across languages varying in OD. This review focuses on the question of whether these different behavioral manifestations are associated with different functional neuroanatomical manifestations. It provides a review and critique of cross-linguistic brain imaging studies of developmental dyslexia. In addition, it includes an analysis of state-of-the-art functional neuroanatomical models of developmental dyslexia together with orthography-specific predictions derived from these models. These predictions should be tested in future brain imaging studies of typical and atypical reading in order to refine the current neurobiological understanding of developmental dyslexia, especially with respect to orthography-specific and universal aspects. PMID:24904383

  4. Probing the role of water in protein conformation and function.

    PubMed Central

    Rand, R P

    2004-01-01

    Life began in a bath of water and has never escaped it. Cellular function has forced the evolution of many mechanisms ensuring that cellular water concentration has never changed significantly. To free oneself of any conceptual distinction among all small molecules, solutes and solvents, means that experiments to probe water's specific role in molecular function can be designed like any classical chemical reaction. Such an 'osmotic stress' strategy will be described in general and for an enzyme, hexokinase. Water behaves like a reactant that competes with glucose in binding to hexokinase, and modulates its conformational change and activity. This 'osmotic stress' strategy, now applied to many very different systems, shows that water plays a significant role, energetically, in most macromolecular reactions. It can be required to fill obligatory space, it dominates nearest non-specific interactions between large surfaces, it can be a reactant modulating conformational change; all this in addition to its more commonly perceived static role as an integral part of stereospecific intramolecular structure. PMID:15306382

  5. Role of strongly interacting additives in tuning the structure and properties of polymer systems

    NASA Astrophysics Data System (ADS)

    Daga, Vikram Kumar

    Block copolymer (BCP) nanocomposites are an important class of hybrid materials in which the BCP guides the spatial location and the periodic assembly of the additives. High loadings of well-dispersed nanofillers are generally important for many applications including mechanical reinforcing of polymers. In particular the composites shown in this work might find use as etch masks in nanolithography, or for enabling various phase selective reactions for new materials development. This work explores the use of hydrogen bonding interactions between various additives (such as homopolymers and non-polymeric additives) and small, disordered BCPs to cause the formation of well-ordered morphologies with small domains. A detailed study of the organization of homopolymer chains and the evolution of structure during the process of ordering is performed. The results demonstrate that by tuning the selective interaction of the additive with the incorporating phase of the BCP, composites with significantly high loadings of additives can be formed while maintaining order in the BCP morphology. The possibility of high and selective loading of additives in one of the phases of the ordered BCP composite opens new avenues due to high degree of functionalization and the proximity of the additives within the incorporating phase. This aspect is utilized in one case for the formation of a network structure between adjoining additive cores to derive mesoporous inorganic materials with their structures templated by the BCP. The concept of additive-driven assembly is extended to formulate BCPadditive blends with an ability to undergo photo-induced ordering. Underlying this strategy is the ability to transition a weakly interacting additive to its strongly interacting form. This strategy provides an on-demand, non-intrusive route for formation of well-ordered nanostructures in arbitrarily defined regions of an otherwise disordered material. The second area explored in this dissertation deals

  6. The role of estradiol in male reproductive function

    PubMed Central

    Schulster, Michael; Bernie, Aaron M; Ramasamy, Ranjith

    2016-01-01

    Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone's effects on erectile function, spermatogenesis, and libido. PMID:26908066

  7. The role of estradiol in male reproductive function.

    PubMed

    Schulster, Michael; Bernie, Aaron M; Ramasamy, Ranjith

    2016-01-01

    Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone's effects on erectile function, spermatogenesis, and libido.

  8. Neurotrophins: Roles in Neuronal Development and Function*

    PubMed Central

    Huang, Eric J; Reichardt, Louis F

    2009-01-01

    Neurotrophins regulate development, maintenance, and function of vertebrate nervous systems. Neurotrophins activate two different classes of receptors, the Trk family of receptor tyrosine kinases and p75NTR, a member of the TNF receptor superfamily. Through these, neurotrophins activate many signaling pathways, including those mediated by ras and members of the cdc-42/ras/rho G protein families, and the MAP kinase, PI-3 kinase, and Jun kinase cascades. During development, limiting amounts of neurotrophins function as survival factors to ensure a match between the number of surviving neurons and the requirement for appropriate target innervation. They also regulate cell fate decisions, axon growth, dendrite pruning, the patterning of innervation and the expression of proteins crucial for normal neuronal function, such as neurotransmitters and ion channels. These proteins also regulate many aspects of neural function. In the mature nervous system, they control synaptic function and synaptic plasticity, while continuing to modulate neuronal survival. PMID:11520916

  9. Brief Report: Additive and Subtractive Counterfactual Reasoning of Children with High-Functioning Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Begeer, Sander; Terwogt, Mark Meerum; Lunenburg, Patty; Stegge, Hedy

    2009-01-01

    The development of additive ("If only I had done...") and subtractive ("If only I had not done....") counterfactual reasoning was examined in children with High Functioning Autism Spectrum Disorders (HFASD) (n = 72) and typically developing controls (n = 71), aged 6-12 years. Children were presented four stories where they could generate…

  10. Robust estimation of mean and dispersion functions in extended generalized additive models.

    PubMed

    Croux, Christophe; Gijbels, Irène; Prosdocimi, Ilaria

    2012-03-01

    Generalized linear models are a widely used method to obtain parametric estimates for the mean function. They have been further extended to allow the relationship between the mean function and the covariates to be more flexible via generalized additive models. However, the fixed variance structure can in many cases be too restrictive. The extended quasilikelihood (EQL) framework allows for estimation of both the mean and the dispersion/variance as functions of covariates. As for other maximum likelihood methods though, EQL estimates are not resistant to outliers: we need methods to obtain robust estimates for both the mean and the dispersion function. In this article, we obtain functional estimates for the mean and the dispersion that are both robust and smooth. The performance of the proposed method is illustrated via a simulation study and some real data examples.

  11. The Role of Cocoa as a Cigarette Additive: Opportunities for Product Regulation

    PubMed Central

    Kennedy, Ryan David; Connolly, Gregory N.

    2014-01-01

    Introduction: The 2009 Family Smoking Prevention and Tobacco Control Act prohibited the use of characterizing flavors in cigarettes; however, some of these flavors are still used in cigarettes at varying levels. We reviewed tobacco industry internal documents to investigate the role of one of these flavors, cocoa, with the objective of understanding its relationship to sensory and risk perception, promotion of dependence, and enhancement of attractiveness and acceptability. Methods: We used the Legacy Tobacco Documents Library to identify documents relevant to our research questions. Initial search terms were generated following an examination of published literature on cocoa, other cigarette additives, and sensory and risk perception. Further research questions and search terms were generated based on review of documents generated from the initial search terms. Results: Cocoa is widely applied to cigarettes and has been used by the tobacco industry as an additive since the early 20th century. Cocoa can alter the sensory properties of cigarette smoke, including by providing a more appealing taste and decreasing its harshness. The tobacco industry has experimented with manipulating cocoa levels as a means of achieving sensory properties that appeal to women and youth. Conclusions: Although cocoa is identified as a flavor on tobacco industry Web sites, it may serve other sensory purposes in cigarettes as well. Eliminating cocoa as an additive from tobacco products may affect tobacco product abuse liability by altering smokers’ perceptions of product risk, and decreasing product appeal, especially among vulnerable populations. PMID:24610479

  12. Dental indications for the instrumental functional analysis in additional consideration of health-economic aspects

    PubMed Central

    Tinnemann, Peter; Stöber, Yvonne; Roll, Stephanie; Vauth, Christoph; Willich, Stefan N.; Greiner, Wolfgang

    2010-01-01

    Background Besides clinical and radiological examination instrumental functional analyses are performed as diagnostic procedures for craniomandibular dysfunctions. Instrumental functional analyses cause substantial costs and shows a considerable variability between individual dentist practices. Objectives On the basis of published scientific evidence the validity of the instrumental functional analysis for the diagnosis of craniomandibular dysfunctions compared to clinical diagnostic procedures; the difference of the various forms of the instrumental functional analysis; the existence of a dependency on additional other factors and the need for further research are determined in this report. In addition, the cost effectiveness of the instrumental functional analysis is analysed in a health-policy context, and social, legal and ethical aspects are considered. Methods A literature search is performed in over 27 databases and by hand. Relevant companies and institutions are contacted concerning unpublished studies. The inclusion criteria for publications are (i) diagnostic studies with the indication “craniomandibular malfunction”, (ii) a comparison between clinical and instrumental functional analysis, (iii) publications since 1990, (iv) publications in English or German. The identified literature is evaluated by two scientists regarding the relevance of content and methodical quality. Results The systematic database search resulted in 962 hits. 187 medical and economic complete publications are evaluated. Since the evaluated studies are not relevant enough to answer the medical or health economic questions no study is included. Discussion The inconsistent terminology concerning craniomandibular dysfunctions and instrumental functional analyses results in a broad literature search in databases and an extensive search by hand. Since no relevant results concerning the validity of the instrumental functional analysis in comparison to the clinical functional analysis

  13. Brain and Retinal Pericytes: Origin, Function and Role

    PubMed Central

    Trost, Andrea; Lange, Simona; Schroedl, Falk; Bruckner, Daniela; Motloch, Karolina A.; Bogner, Barbara; Kaser-Eichberger, Alexandra; Strohmaier, Clemens; Runge, Christian; Aigner, Ludwig; Rivera, Francisco J.; Reitsamer, Herbert A.

    2016-01-01

    Pericytes are specialized mural cells located at the abluminal surface of capillary blood vessels, embedded within the basement membrane. In the vascular network these multifunctional cells fulfil diverse functions, which are indispensable for proper homoeostasis. They serve as microvascular stabilizers, are potential regulators of microvascular blood flow and have a central role in angiogenesis, as they for example regulate endothelial cell proliferation. Furthermore, pericytes, as part of the neurovascular unit, are a major component of the blood-retina/brain barrier. CNS pericytes are a heterogenic cell population derived from mesodermal and neuro-ectodermal germ layers acting as modulators of stromal and niche environmental properties. In addition, they display multipotent differentiation potential making them an intriguing target for regenerative therapies. Pericyte-deficiencies can be cause or consequence of many kinds of diseases. In diabetes, for instance, pericyte-loss is a severe pathological process in diabetic retinopathy (DR) with detrimental consequences for eye sight in millions of patients. In this review, we provide an overview of our current understanding of CNS pericyte origin and function, with a special focus on the retina in the healthy and diseased. Finally, we highlight the role of pericytes in de- and regenerative processes. PMID:26869887

  14. The role of tight junctions in mammary gland function.

    PubMed

    Stelwagen, Kerst; Singh, Kuljeet

    2014-03-01

    Tight junctions (TJ) are cellular structures that facilitate cell-cell communication and are important in maintaining the three-dimensional structure of epithelia. It is only during the last two decades that the molecular make-up of TJ is becoming unravelled, with two major transmembrane-spanning structural protein families, called occludin and claudins, being the true constituents of the TJ. These TJ proteins are linked via specific scaffolding proteins to the cell's cytoskeleton. In the mammary gland TJ between adjacent secretory epithelial cells are formed during lactogenesis and are instrumental in establishing and maintaining milk synthesis and secretion, whereas TJ integrity is compromised during mammary involution and also as result of mastitis and periods of mammary inflamation (including mastitis). They prevent the paracellular transport of ions and small molecules between the blood and milk compartments. Formation of intact TJ at the start of lactation is important for the establishment of the lactation. Conversely, loss of TJ integrity has been linked to reduced milk secretion and mammary function and increased paracellular transport of blood components into the milk and vice versa. In addition to acting as a paracellular barrier, the TJ is increasingly linked to playing an active role in intracellular signalling. This review focusses on the role of TJ in mammary function of the normal, non-malignant mammary gland, predominantly in ruminants, the major dairy producing species.

  15. The Use of Additive Manufacturing for Fabrication of Multi-Function Small Satellite Structures

    SciTech Connect

    Horais, Brian J; Love, Lonnie J; Dehoff, Ryan R

    2013-01-01

    The use of small satellites in constellations is limited only by the growing functionality of smallsats themselves. Additive manufacturing provides exciting new design opportunities for development of multifunction CubeSat structures that integrate such functions as propulsion and thermal control into the satellite structures themselves. Manufacturing of these complex multifunction structures is now possible in lightweight, high strength, materials such as titanium by using existing electron beam melting additive manufacturing processes. However, the use of today's additive manufacturing capabilities is often cost-prohibitive for small companies due to the large capital investments required. To alleviate this impediment the U.S. Department of Energy has established a Manufacturing Demonstration Facility (MDF) at their Oak Ridge National Laboratory (ORNL) in Tennessee that provides industry access to a broad range of energy-efficient additive manufacturing equipment for collaborative use by both small and large organizations. This paper presents a notional CubeSat multifunction design that integrates the propulsion system into a three-unit (3U) CubeSat structure. The full-scale structure has been designed and fabricated at the ORNL MDF. The use of additive manufacturing for spacecraft fabrication is opening up many new possibilities in design and fabrication capabilities for what had previously been impossible structures to fabricate.

  16. The Role of Attachment Functions in Psychotherapy

    PubMed Central

    Spiegel, Jeremy; Severino, Sally K.; Morrison, Nancy K.

    2000-01-01

    The authors propose to clarify concepts of emotional attunement and failures of attunement in early development derived from theoretical and clinical work (Kohut) and infant psychiatry (Stern). Early attunement failures are experienced as shameful by the infant/child, and without repair they form a nidus for later destructive adult interpersonal relationships, “social blindness,” and depression. The authors present a case illustrating these ideas. The role of empathic attunement experienced in the unique setting/structure of psychotherapy emerges as the single critical variable for a successful outcome. PMID:10608906

  17. Compositions, Functions, and Testing of Friction Brake Materials and Their Additives

    SciTech Connect

    Blau, PJ

    2001-10-22

    The purpose of this report is to present a survey of commercial brake materials and additives, and to indicate their typical properties and functions, especially as regards their use in heavy trucks. Most truck pad and shoe materials described here were designed to wear against cast iron. Brake material test methods are also briefly described. This report does not address issues associated with the fabrication and manufacturing of brake materials. Since there are literally thousands of brake material additives, and their combinations are nearly limitless, it is impractical to list them all here. Rather, an attempt has been made to capture the primary constituents and their functions. An Appendix contains thermo-physical properties of some current and potential brake materials.

  18. Radial distribution functions of non-additive hard sphere mixtures via Percus' test particle route.

    PubMed

    Hopkins, Paul; Schmidt, Matthias

    2011-08-17

    Using fundamental density functional theory we calculate the partial radial distribution functions, g(ij)(r), of a binary non-additive hard sphere mixture using either Percus' test particle approach or inversion of the analytic structure factor obtained via the Ornstein-Zernike route. We find good agreement between the theoretical results and Monte Carlo simulation data for both positive and moderate negative non-additivities. We investigate the asymptotic, [Formula: see text], decay of the g(ij)(r) and show that this agrees with the analytic analysis of the contributions to the partial structure factors in the plane of complex wavevectors. We find the test particle density profiles to be free of unphysical artefacts, contrary to earlier reports.

  19. Circulating opioids: possible physiological roles in central nervous function.

    PubMed

    Henry, J L

    1982-01-01

    Evidence is reviewed regarding the release of endorphins by such diverse conditions as stress, long distance running, acupuncture, sexual activity, suggestion and ritualistic dancing ceremonies. Additional evidence is cited regarding possible physiological roles of endorphins in antinociception, socialization, euphoria, some mental disorders, drive states and vegetative functions. The concentration of this latter type of evidence is on conditions during which endorphins seem to be exerting effects on a number of different systems together (for example, euphoria is almost always accompanied by analgesia), and the possibility is suggested that the activation of a number of functions together may be due to a global activation of opiate receptors throughout the CNS. A possible basis for this global activation arises from results from this laboratory indicating the presence of a blood-borne opioid hormone, secreted by the pituitary or by an endocrine gland under pituitary control, which is capable of passing from the blood into the CNS. This diffuse endorphinergic system, which is complementary to the well-established endorphinergic neuronal systems in the CNS, thus derives its property of global action on opiate receptors by the diffuse means by which the hormone reaches its target sites, i.e., by passing through the blood brain barrier. Thus, while each specific endorphin-mediated function can be activated by the activation of its respective neural pathway, it is proposed that the hormonal endorphinergic mechanism is activated to produce a global response provoked by conditions to which a more generalized response, including physiological and behavioural changes, is most appropriate.

  20. Risk assessment of nitrate and oxytetracycline addition on coastal ecosystem functions.

    PubMed

    Feng-Jiao, Liu; Shun-Xing, Li; Feng-Ying, Zheng; Xu-Guang, Huang; Yue-Gang, Zuo; Teng-Xiu, Tu; Xue-Qing, Wu

    2014-01-01

    Diatoms dominate phytoplankton communities in the well-mixed coastal and upwelling regions. Coastal diatoms are often exposed to both aquaculture pollution and eutrophication. But how these exposures influence on coastal ecosystem functions are unknown. To examine these influences, a coastal centric diatom, Conticribra weissflogii was maintained at different concentrations of nitrate (N) and/or oxytetracycline (OTC). Algal density, cell growth cycle, protein, chlorophyll a, superoxide dismutase (SOD) activity, and malonaldehyde (MDA) were determined for the assessment of algal biomass, lifetime, nutritional value, photosynthesis and respiration, antioxidant capacity, and lipid peroxidation, respectively. When N addition was combined with OTC pollution, the cell growth cycles were shortened by 56-73%; algal density, SOD activities, the concentrations of chlorophyll a, protein, and MDA varied between 73 and 121%, 19 and 397%, 52 and 693%, 19 and 875%, and 66 and 2733% of the values observed in N addition experiments, respectively. According to P-value analysis, the influence of OTC on algal density and SOD activity was not significant, but the effect on cell growth cycle, protein, chlorophyll a, and MDA were significant (P<0.05). The influence of N addition with simultaneous OTC pollution on the above six end points was significant. Algal biomass, lifetime, nutrition, antioxidant capacity, lipid peroxidation, photosynthesis, and respiration were all affected by the addition of OTC and N. Coastal ecosystem functions were severely affected by N and OTC additions, and the influence was increased in the order: Nfunctions.

  1. Alumina Matrix Composites with Non-Oxide Nanoparticle Addition and Enhanced Functionalities

    PubMed Central

    Galusek, Dušan; Galusková, Dagmar

    2015-01-01

    The addition of SiC or TiC nanoparticles to polycrystalline alumina matrix has long been known as an efficient way of improving the mechanical properties of alumina-based ceramics, especially strength, creep, and wear resistance. Recently, new types of nano-additives, such as carbon nanotubes (CNT), carbon nanofibers (CNF), and graphene sheets have been studied in order not only to improve the mechanical properties, but also to prepare materials with added functionalities, such as thermal and electrical conductivity. This paper provides a concise review of several types of alumina-based nanocomposites, evaluating the efficiency of various preparation methods and additives in terms of their influence on the properties of composites.

  2. A functional role for the colleters of coffee flowers

    PubMed Central

    Mayer, Juliana Lischka Sampaio; Carmello-Guerreiro, Sandra Maria; Mazzafera, Paulo

    2013-01-01

    Colleters are protuberances or trichomes that produce and release an exudate that overlays vegetative or reproductive buds. Colleters have a functional definition, as they are thought to protect young tissues against dehydration and pest attack. Decaffeinated coffee plants, named Decaffito®, have recently been obtained through chemical mutagenesis, and in addition to the absence of the alkaloid, the flowers of these plants open precociously. Decaffito mutants exhibit minimal production and secretion of the exudate by the colleters. We compared these mutants with normal coffee plants to infer the functional role of colleters and the secreted exudate covering flower buds. Decaffito mutants were obtained by sodium azide mutagenesis of Coffea arabica cv. Catuaí seeds. Wild-type plants were used as controls and are referred to as Catuaí. The flower colleters were analysed by scanning and transmission electron microscopy in addition to histochemical analysis. Histochemical analysis indicated the presence of heterogeneous exudate in the secretory cells of the colleters of both variants of coffee trees. Alkaloids were detected in Catuaí but not in Decaffito. Transmission electron microscopy revealed that the secretory cells in the Catuaí colleters possessed the normal and common characteristics found in secretory structures. In the secretory cells of the Decaffito colleters, it was not possible to identify any organelles or even the nucleus, but the cells had a darkened central cytoplasm, indicating that the secretion is produced in low amounts but not released. Our results offer a proof of concept of colleters in coffee, strongly indicating that the exudate covering the flower parts works as an adhesive to keep the petals together and the flower closed, which in part helps to avoid dehydration. Additionally, the exudate itself helps to prevent water loss from the epidermal cells of the petals.

  3. Role of Carbon-Addition and Hydrogen-Migration Reactions in Soot Surface Growth.

    PubMed

    Zhang, Hong-Bo; Hou, Dingyu; Law, Chung K; You, Xiaoqing

    2016-02-11

    Using density functional theory and master equation modeling, we have studied the kinetics of small unsaturated aliphatic molecules reacting with polycyclic aromatic hydrocarbon (PAH) molecules having a diradical character. We have found that these reactions follow the mechanism of carbon addition and hydrogen migration (CAHM) on both spin-triplet and open-shell singlet potential energy surfaces at a rate that is about ten times those of the hydrogen-abstraction-carbon-addition (HACA) reactions at 1500 K in the fuel-rich postflame region. The results also show that the most active reaction sites are in the center of the zigzag edges of the PAHs. Furthermore, the reaction products are more likely to form straight rather than branched aliphatic side chains in the case of reacting with diacetylene. The computed rate constants are also found to be independent of pressure at conditions of interest in soot formation, and the activation barriers of the CAHM reactions are linearly correlated with the diradical characters.

  4. Interactive effects between N addition and disturbance on boreal forest ecosystem structure and function

    NASA Astrophysics Data System (ADS)

    Nordin, Annika; Strengbom, Joachim; From, Fredrik

    2014-05-01

    In management of boreal forests, nitrogen (N) enrichment from atmospheric deposition or from forest fertilization can appear in combination with land-use related disturbances, i.e. tree harvesting by clear-felling. Long-term interactive effects between N enrichment and disturbance on boreal forest ecosystem structure and function are, however, poorly known. We investigated effects of N enrichment by forest fertilization done > 25 years ago on forest understory species composition in old-growth (undisturbed) forests, and in forests clear-felled 10 years ago (disturbed). In clear-felled forests we also investigated effects of the previous N addition on growth of tree saplings. The results show that the N enrichment effect on the understory species composition was strongly dependent on the disturbance caused by clear-felling. In undisturbed forests, there were small or no effects on understory species composition from N addition. In contrast, effects were large in forests first exposed to N addition and subsequently disturbed by clear-felling. Effects of N addition differed among functional groups of plants. Abundance of graminoids increased (+232%) and abundance of dwarf shrubs decreased (-44%) following disturbance in N fertilized forests. For vascular plants, the two perturbations had contrasting effects on α-(within forests) and β-diversity (among forests): in disturbed forests, N addition reduced, or had no effect on α-diversity, while β-diversity increased. For bryophytes, negative effects of disturbance on α-diversity were smaller in N fertilized forests than in forests not fertilized, while neither N addition nor disturbance had any effects on β-diversity. Moreover, sapling growth in forests clear-felled 10 years ago was significantly higher in previously N fertilized forests than in forests not fertilized. Our study show that effects of N addition on plant communities may appear small, short-lived, or even absent until exposed to a disturbance. This

  5. The role of noninnocent solvent molecules in organocatalyzed asymmetric Michael addition reactions.

    PubMed

    Patil, Mahendra P; Sunoj, Raghavan B

    2008-01-01

    A proline-catalyzed asymmetric Michael addition between ketones and trans-beta-nitrostyrene was studied by using the density-functional theory with mPW1PW91 and B3LYP functionals. Improved insight into the enantio- and diastereoselective formation of gamma-nitroketones/-aldehydes is obtained through transition-state analysis. Consideration of the activation parameters obtained from gas-phase calculations and continuum solvation models failed to reproduce the reported experimental stereoselectivities for the reaction between cyclohexanone and 3-pentanone with trans-beta-nitrostyrene. The correct diastereo- and enantioselectivites were obtained only upon explicit inclusion of solvent molecules in the diastereomeric transition states that pertain to the C--C bond formation. Among the several transition-state models that were examined, the one that exhibits cooperative hydrogen-bonding interactions with two molecules of methanol could explain the correct stereochemical outcome of the Michael reaction. The change in differential stabilization that arises as a result of electrostatic and hydrogen-bonding interactions in the key transition states is identified as the contributing factor toward obtaining the correct diastereomer. This study establishes the importance of including explicit solvent molecules in situations in which the gas-phase and continuum models are inadequate in obtaining meaningful insight regarding experimental stereoselectivities.

  6. Microplastic moves pollutants and additives to worms, reducing functions linked to health and biodiversity.

    PubMed

    Browne, Mark Anthony; Niven, Stewart J; Galloway, Tamara S; Rowland, Steve J; Thompson, Richard C

    2013-12-02

    Inadequate products, waste management, and policy are struggling to prevent plastic waste from infiltrating ecosystems [1, 2]. Disintegration into smaller pieces means that the abundance of micrometer-sized plastic (microplastic) in habitats has increased [3] and outnumbers larger debris [2, 4]. When ingested by animals, plastic provides a feasible pathway to transfer attached pollutants and additive chemicals into their tissues [5-15]. Despite positive correlations between concentrations of ingested plastic and pollutants in tissues of animals, few, if any, controlled experiments have examined whether ingested plastic transfers pollutants and additives to animals. We exposed lugworms (Arenicola marina) to sand with 5% microplastic that was presorbed with pollutants (nonylphenol and phenanthrene) and additive chemicals (Triclosan and PBDE-47). Microplastic transferred pollutants and additive chemicals into gut tissues of lugworms, causing some biological effects, although clean sand transferred larger concentrations of pollutants into their tissues. Uptake of nonylphenol from PVC or sand reduced the ability of coelomocytes to remove pathogenic bacteria by >60%. Uptake of Triclosan from PVC diminished the ability of worms to engineer sediments and caused mortality, each by >55%, while PVC alone made worms >30% more susceptible to oxidative stress. As global microplastic contamination accelerates, our findings indicate that large concentrations of microplastic and additives can harm ecophysiological functions performed by organisms.

  7. Differential activation of an identified motor neuron and neuromodulation provide Aplysia's retractor muscle an additional function.

    PubMed

    McManus, Jeffrey M; Lu, Hui; Cullins, Miranda J; Chiel, Hillel J

    2014-08-15

    To survive, animals must use the same peripheral structures to perform a variety of tasks. How does a nervous system employ one muscle to perform multiple functions? We addressed this question through work on the I3 jaw muscle of the marine mollusk Aplysia californica's feeding system. This muscle mediates retraction of Aplysia's food grasper in multiple feeding responses and is innervated by a pool of identified neurons that activate different muscle regions. One I3 motor neuron, B38, is active in the protraction phase, rather than the retraction phase, suggesting the muscle has an additional function. We used intracellular, extracellular, and muscle force recordings in several in vitro preparations as well as recordings of nerve and muscle activity from intact, behaving animals to characterize B38's activation of the muscle and its activity in different behavior types. We show that B38 specifically activates the anterior region of I3 and is specifically recruited during one behavior, swallowing. The function of this protraction-phase jaw muscle contraction is to hold food; thus the I3 muscle has an additional function beyond mediating retraction. We additionally show that B38's typical activity during in vivo swallowing is insufficient to generate force in an unmodulated muscle and that intrinsic and extrinsic modulation shift the force-frequency relationship to allow contraction. Using methods that traverse levels from individual neuron to muscle to intact animal, we show how regional muscle activation, differential motor neuron recruitment, and neuromodulation are key components in Aplysia's generation of multifunctionality.

  8. Role of endothelin in uteroplacental circulation and fetal vascular function.

    PubMed

    Paradis, Alexandra; Zhang, Lubo

    2013-09-01

    Endothelins are 21-amino acid peptides involved in vascular homeostasis. Three types of peptide have been identified, with endothelin-1 (ET-1) being the most potent vasoconstrictor currently known. Two endothelin receptor subtypes are found in various tissues, including the brain, heart, blood vessel, lung, and placenta. The ETA-receptor is associated with vasoconstriction in vascular smooth muscle. Conversely, the ETB-receptor can elicit a vasoconstrictor effect in vascular smooth muscle and a vasodilator effect via its action in endothelial cells. Both receptors play a key role in maintaining circulatory homeostasis and vascular function. Changes in ET-1 expression are found in various disease states, and overexpression of ET-1 is observed in hypertension and preeclampsia in pregnancy. Placental localization of ET-1 implies a key role in regulating the uteroplacental circulation. Additionally, ET-1 is important in the fetal circulation and is involved in the pulmonary circulation and closure of the ductus arteriosus after birth, as well as fetal growth constriction in utero. ET receptor antagonists and nitric oxide donors may provide therapeutic potential in treating conditions associated with overexpression of ET and hypertension.

  9. Functional aortic stiffness: role of CD4(+) T lymphocytes.

    PubMed

    Majeed, Beenish A; Eberson, Lance S; Tawinwung, Supannikar; Larmonier, Nicolas; Secomb, Timothy W; Larson, Douglas F

    2015-01-01

    The immune system is suggested to be essential in vascular remodeling and stiffening. To study the dependence upon lymphocytes in vascular stiffening, we compared an angiotensin II-model of vascular stiffening in normal C57BL/6J mice with lymphocyte-deficient RAG 1(-/-) mice and additionally characterized the component of vascular stiffness due to vasoconstriction vs. vascular remodeling. Chronic angiotensin II increased aortic pulse wave velocity, effective wall stiffness, and effective Young's modulus in C57BL/6J mice by three-fold but caused no change in the RAG 1(-/-) mice. These functional measurements were supported by aortic morphometric analysis. Adoptive transfer of CD4(+) T helper lymphocytes restored the angiotensin II-mediated aortic stiffening in the RAG 1(-/-) mice. In order to account for the hydraulic vs. material effects of angiotensin II on pulse wave velocity, subcutaneous osmotic pumps were removed after 21 days of angiotensin II-infusion in the WT mice to achieve normotensive values. The pulse wave velocity (PWV) decreased from three- to two-fold above baseline values up to 7 days following pump removal. This study supports the pivotal role of the CD4(+) T-lymphocytes in angiotensin II-mediated vascular stiffening and that angiotensin II-mediated aortic stiffening is due to the additive effect of active vascular smooth muscle vasoconstriction and vascular remodeling.

  10. Nitric oxide and S-nitrosoglutathione function additively during plant immunity.

    PubMed

    Yun, Byung-Wook; Skelly, Michael J; Yin, Minghui; Yu, Manda; Mun, Bong-Gyu; Lee, Sang-Uk; Hussain, Adil; Spoel, Steven H; Loake, Gary J

    2016-07-01

    Nitric oxide (NO) is emerging as a key regulator of diverse plant cellular processes. A major route for the transfer of NO bioactivity is S-nitrosylation, the addition of an NO moiety to a protein cysteine thiol forming an S-nitrosothiol (SNO). Total cellular levels of protein S-nitrosylation are controlled predominantly by S-nitrosoglutathione reductase 1 (GSNOR1) which turns over the natural NO donor, S-nitrosoglutathione (GSNO). In the absence of GSNOR1 function, GSNO accumulates, leading to dysregulation of total cellular S-nitrosylation. Here we show that endogenous NO accumulation in Arabidopsis, resulting from loss-of-function mutations in NO Overexpression 1 (NOX1), led to disabled Resistance (R) gene-mediated protection, basal resistance and defence against nonadapted pathogens. In nox1 plants both salicylic acid (SA) synthesis and signalling were suppressed, reducing SA-dependent defence gene expression. Significantly, expression of a GSNOR1 transgene complemented the SNO-dependent phenotypes of paraquat resistant 2-1 (par2-1) plants but not the NO-related characters of the nox1-1 line. Furthermore, atgsnor1-3 nox1-1 double mutants supported greater bacterial titres than either of the corresponding single mutants. Our findings imply that GSNO and NO, two pivotal redox signalling molecules, exhibit additive functions and, by extension, may have distinct or overlapping molecular targets during both immunity and development.

  11. Accessing siloxane functionalized polynorbornenes via vinyl-addition polymerization for CO2 separation membranes

    DOE PAGES

    Mahurin, Shannon Mark; Sokolov, Alexei P.; Saito, Tomonori; ...

    2016-07-06

    Here, the vinyl addition polymerization of norbornylbased monomers bearing polar functional groups is often problematic, leading to low molecular weight polymers in poor yield. Herein, we provide proof-of-principle evidence that addition-type homopolymers of siloxane substituted norbornyl-based monomers may be readily synthesized using the catalyst trans-[Ni(C6F5)2(SbPh3)2]. Polymerizations using this catalyst reached moderate to high conversion in just 5 min of polymerization and produced siloxanesubstituted polymers with molecular weights exceeding 100 kg/mol. These polymers showed excellent thermal stability (Td ≥ 362 °C) and were cast into membranes that displayed high CO2 permeability and enhanced CO2/N2 selectivity as compared to related materials.

  12. Nano- and Microgels Through Addition Reactions of Functional Oligomers and Polymers

    NASA Astrophysics Data System (ADS)

    Albrecht, Krystyna; Moeller, Martin; Groll, Juergen

    Nano- and Microgels are predominantly prepared using radical polymerization techniques. This chapter reviews alternative approaches to microgel preparation based on addition reactions of functional oligomers and polymers. This allows preparation of microgels under physiological conditions and in the presence of biologically active molecules without affecting their function. This method is therefore predominantly used to synthesize microgels for biomedical applications. Different crosslinking chemistries that have been used in this context are presented and discussed with regard to reaction conditions and stability of the reaction product. Microgels that have been prepared by these techniques are divided into two groups. Natural polymers used for the preparation of microgels are described first, followed by artificial prepolymers that are suitable for the preparation of microgels. The different preparation methods as well as the resulting microgels and their properties are presented and discussed.

  13. Evaluation of the performance of smoothing functions in generalized additive models for spatial variation in disease.

    PubMed

    Siangphoe, Umaporn; Wheeler, David C

    2015-01-01

    Generalized additive models (GAMs) with bivariate smoothing functions have been applied to estimate spatial variation in risk for many types of cancers. Only a handful of studies have evaluated the performance of smoothing functions applied in GAMs with regard to different geographical areas of elevated risk and different risk levels. This study evaluates the ability of different smoothing functions to detect overall spatial variation of risk and elevated risk in diverse geographical areas at various risk levels using a simulation study. We created five scenarios with different true risk area shapes (circle, triangle, linear) in a square study region. We applied four different smoothing functions in the GAMs, including two types of thin plate regression splines (TPRS) and two versions of locally weighted scatterplot smoothing (loess). We tested the null hypothesis of constant risk and detected areas of elevated risk using analysis of deviance with permutation methods and assessed the performance of the smoothing methods based on the spatial detection rate, sensitivity, accuracy, precision, power, and false-positive rate. The results showed that all methods had a higher sensitivity and a consistently moderate-to-high accuracy rate when the true disease risk was higher. The models generally performed better in detecting elevated risk areas than detecting overall spatial variation. One of the loess methods had the highest precision in detecting overall spatial variation across scenarios and outperformed the other methods in detecting a linear elevated risk area. The TPRS methods outperformed loess in detecting elevated risk in two circular areas.

  14. Evaluation of the Performance of Smoothing Functions in Generalized Additive Models for Spatial Variation in Disease

    PubMed Central

    Siangphoe, Umaporn; Wheeler, David C.

    2015-01-01

    Generalized additive models (GAMs) with bivariate smoothing functions have been applied to estimate spatial variation in risk for many types of cancers. Only a handful of studies have evaluated the performance of smoothing functions applied in GAMs with regard to different geographical areas of elevated risk and different risk levels. This study evaluates the ability of different smoothing functions to detect overall spatial variation of risk and elevated risk in diverse geographical areas at various risk levels using a simulation study. We created five scenarios with different true risk area shapes (circle, triangle, linear) in a square study region. We applied four different smoothing functions in the GAMs, including two types of thin plate regression splines (TPRS) and two versions of locally weighted scatterplot smoothing (loess). We tested the null hypothesis of constant risk and detected areas of elevated risk using analysis of deviance with permutation methods and assessed the performance of the smoothing methods based on the spatial detection rate, sensitivity, accuracy, precision, power, and false-positive rate. The results showed that all methods had a higher sensitivity and a consistently moderate-to-high accuracy rate when the true disease risk was higher. The models generally performed better in detecting elevated risk areas than detecting overall spatial variation. One of the loess methods had the highest precision in detecting overall spatial variation across scenarios and outperformed the other methods in detecting a linear elevated risk area. The TPRS methods outperformed loess in detecting elevated risk in two circular areas. PMID:25983545

  15. Chlorogenic Acid: Recent Advances on Its Dual Role as a Food Additive and a Nutraceutical against Metabolic Syndrome.

    PubMed

    Santana-Gálvez, Jesús; Cisneros-Zevallos, Luis; Jacobo-Velázquez, Daniel A

    2017-02-26

    Chlorogenic acid (5-O-caffeoylquinic acid) is a phenolic compound from thehydroxycinnamic acid family. This polyphenol possesses many health-promoting properties, mostof them related to the treatment of metabolic syndrome, including anti-oxidant, anti-inflammatory,antilipidemic, antidiabetic, and antihypertensive activities. The first part of this review will discussthe role of chlorogenic acid as a nutraceutical for the prevention and treatment of metabolicsyndrome and associated disorders, including in vivo studies, clinical trials, and mechanisms ofaction. The second part of the review will be dealing with the role of chlorogenic acid as a foodadditive. Chlorogenic acid has shown antimicrobial activity against a wide range of organisms,including bacteria, yeasts, molds, viruses, and amoebas. These antimicrobial properties can beuseful for the food industry in its constant search for new and natural molecules for thepreservation of food products. In addition, chlorogenic acid has antioxidant activity, particularlyagainst lipid oxidation; protective properties against degradation of other bioactive compoundspresent in food, and prebiotic activity. The combination of these properties makes chlorogenic acidan excellent candidate for the formulation of dietary supplements and functional foods.

  16. Cinchona Alkaloid Catalyzed Sulfa-Michael Addition Reactions Leading to Enantiopure β-Functionalized Cysteines.

    PubMed

    Breman, Arjen C; Telderman, Suze E M; van Santen, Roy P M; Scott, Jamie I; van Maarseveen, Jan H; Ingemann, Steen; Hiemstra, Henk

    2015-11-06

    Sulfa-Michael additions to α,β-unsaturated N-acylated oxazolidin-2-ones and related α,β-unsaturated α-amino acid derivatives have been enantioselectively catalyzed by Cinchona alkaloids functionalized with a hydrogen bond donating group at the C6' position. The series of Cinchona alkaloids includes known C6' (thio)urea and sulfonamide derivatives and several novel species with a benzimidazole, squaramide or a benzamide group at the C6' position. The sulfonamides were especially suited as bifunctional organocatalysts as they gave the products in very good diastereoselectivity and high enantioselectivity. In particular, the C6' sulfonamides catalyzed the reaction with the α,β-unsaturated α-amino acid derivatives to afford the products in a diastereomeric ratio as good as 93:7, with the major isomer being formed in an ee of up to 99%. The products of the organocatalytic sulfa-Michael addition to α,β-unsaturated α-amino acid derivatives were subsequently converted in high yields to enantiopure β-functionalized cysteines suitable for native chemical ligation.

  17. Patient advocacy in the USA: key communication role functions.

    PubMed

    Martin, Donald R; Tipton, Bryan K

    2007-09-01

    Researchers have long documented the importance of patient advocacy programs as a means of providing customer service in health-care organizations. Yet, while effective communication is often acknowledged as key to effective patient advocacy, knowledge of the specific communication role functions enacted by patient advocates remains limited, as does our understanding of the function of patient advocacy at the organizational level. This qualitative investigation not only provides a typology of communication roles enacted by patient advocates while solving problems on behalf of patients and their family members, but also integrates scholarly research on "boundary-spanning" as a means of theoretically contextualizing the advocacy role at the organizational level.

  18. How does your kidney smell? Emerging roles for olfactory receptors in renal function.

    PubMed

    Shepard, Blythe D; Pluznick, Jennifer L

    2016-05-01

    Olfactory receptors (ORs) are chemosensors that are responsible for one's sense of smell. In addition to this specialized role in the nose, recent evidence suggests that ORs are also found in a variety of additional tissues including the kidney. As this list of renal ORs continues to expand, it is becoming clear that they play important roles in renal and whole-body physiology, including a novel role in blood pressure regulation. In this review, we highlight important considerations that are crucial when studying ORs and present the current literature on renal ORs and their emerging relevance in maintaining renal function.

  19. Integrating products of Bessel functions with an additional exponential or rational factor

    NASA Astrophysics Data System (ADS)

    Van Deun, Joris; Cools, Ronald

    2008-04-01

    We provide two MATLAB programs to compute integrals of the form ex∏i=1kJν_i(ax)dxand 0∞xr+x∏i=1kJν_i(ax)dx with Jν_i(x) the Bessel function of the first kind and (real) order ν. The parameter m is a real number such that ∑ν+m>-1 (to assure integrability near zero), r is real and the numbers c and a are all strictly positive. The program can deliver accurate error estimates. Program summaryProgram title: BESSELINTR, BESSELINTC Catalogue identifier: AEAH_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEAH_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 1601 No. of bytes in distributed program, including test data, etc.: 13 161 Distribution format: tar.gz Programming language: Matlab (version ⩾6.5), Octave (version ⩾2.1.69) Computer: All supporting Matlab or Octave Operating system: All supporting Matlab or Octave RAM: For k Bessel functions our program needs approximately ( 500+140k) double precision variables Classification: 4.11 Nature of problem: The problem consists in integrating an arbitrary product of Bessel functions with an additional rational or exponential factor over a semi-infinite interval. Difficulties arise from the irregular oscillatory behaviour and the possible slow decay of the integrand, which prevents truncation at a finite point. Solution method: The interval of integration is split into a finite and infinite part. The integral over the finite part is computed using Gauss-Legendre quadrature. The integrand on the infinite part is approximated using asymptotic expansions and this approximation is integrated exactly with the aid of the upper incomplete gamma function. In the case where a rational factor is present, this factor is first expanded in a Taylor series around infinity. Restrictions: Some (and eventually all

  20. Interactions between cocoa flavanols and inorganic nitrate: additive effects on endothelial function at achievable dietary amounts.

    PubMed

    Rodriguez-Mateos, Ana; Hezel, Michael; Aydin, Hilal; Kelm, Malte; Lundberg, Jon O; Weitzberg, Eddie; Spencer, Jeremy P E; Heiss, Christian

    2015-03-01

    Dietary intervention studies have shown that flavanols and inorganic nitrate can improve vascular function, suggesting that these two bioactives may be responsible for beneficial health effects of diets rich in fruits and vegetables. We aimed to study interactions between cocoa flavanols (CF) and nitrate, focusing on absorption, bioavailability, excretion, and efficacy to increase endothelial function. In a double-blind randomized, dose-response crossover study, flow-mediated dilation (FMD) was measured in 15 healthy subjects before and at 1, 2, 3, and 4 h after consumption of CF (1.4-10.9 mg/kg bw) or nitrate (0.1-10 mg/kg bw). To study flavanol-nitrate interactions, an additional intervention trial was performed with nitrate and CF taken in sequence at low and high amounts. FMD was measured before (0 h) and at 1h after ingestion of nitrate (3 or 8.5 mg/kg bw) or water. Then subjects received a CF drink (2.7 or 10.9 mg/kg bw) or a micro- and macronutrient-matched CF-free drink. FMD was measured at 1, 2, and 4 h thereafter. Blood and urine samples were collected and assessed for CF and nitric oxide (NO) metabolites with HPLC and gas-phase reductive chemiluminescence. Finally, intragastric formation of NO after CF and nitrate consumption was investigated. Both CF and nitrate induced similar intake-dependent increases in FMD. Maximal values were achieved at 1 h postingestion and gradually decreased to reach baseline values at 4 h. These effects were additive at low intake levels, whereas CF did not further increase FMD after high nitrate intake. Nitrate did not affect flavanol absorption, bioavailability, or excretion, but CF enhanced nitrate-related gastric NO formation and attenuated the increase in plasma nitrite after nitrate intake. Both flavanols and inorganic nitrate can improve endothelial function in healthy subjects at intake amounts that are achievable with a normal diet. Even low dietary intake of these bioactives may exert relevant effects on endothelial

  1. The role of MeCP2 in CNS development and function

    PubMed Central

    Na, Elisa S.; Monteggia, Lisa M.

    2010-01-01

    Rett syndrome is a neurodevelopmental disorder that is a direct consequence of functional mutations in the methyl-CpG-binding protein-2 (MeCP2) gene, which has focused attention on epigenetic mechanisms in neurons. MeCP2 is widely believed to be a transcriptional repressor although it may have additional functions in the CNS. Genetic mouse models that compromise MeCP2 function demonstrate that homeostatic regulation of MeCP2 is necessary for normal CNS functioning. Recent work has also demonstrated that MeCP2 plays an important role in mediating synaptic transmission in the CNS in particular, spontaneous neurotransmission and short-term synaptic plasticity. This review will discuss the role of MeCP2 in CNS development and function, as well as a potential important role for MeCP2 and epigenetic processes involved in mediating transcriptional repression in Rett syndrome. PMID:20515694

  2. Phospha-Michael Addition as a New Click Reaction for Protein Functionalization.

    PubMed

    Lee, Yan-Jiun; Kurra, Yadagiri; Liu, Wenshe R

    2016-03-15

    A new type of click reaction between an alkyl phosphine and acrylamide was developed and applied for site-specific protein labeling in vitro and in live cells. Acrylamide is a small electrophilic olefin that readily undergoes phospha-Michael addition with an alkyl phosphine. Our kinetic study indicated a second-order rate constant of 0.07 m(-1)  s(-1) for the reaction between tris(2-carboxyethyl)phosphine and acrylamide at pH 7.4. To demonstrate its application in protein functionalization, we used a dansyl-phosphine conjugate to successfully label proteins that were site-specifically installed with N(ɛ) -acryloyl-l-lysine and employed a biotin-phosphine conjugate to selectively probe human proteins that were metabolically labeled with N-acryloyl-galactosamine.

  3. Enzymatic catalysis: the emerging role of conceptual density functional theory.

    PubMed

    Roos, Goedele; Geerlings, Paul; Messens, Joris

    2009-10-15

    Experimentalists and quantum chemists are living in a different world. A wealth of theoretical enzymology-related publications is hardly known by experimentalists, and vice versa. Our aim is to bring both worlds together and to show the powerful possibilities of a multidisciplinary approach to study subtle details of complicated enzymatic processes to a broad readership. MD simulations and QM/MM approaches often focus on the calculation of reaction paths based on activation energies, which is a time-consuming task. A valuable alternative is the reactivity descriptors founded in conceptual DFT like softness, electrophilicity, and the Fukui function, which describe the kinetic aspects of a reaction in terms of the response to perturbations in N and/or upsilon(r), typical for a chemical reaction, of the reagents in the ground state. As such, the relative energies at the beginning of the reaction predict a sequence of activation energies only based on the properties of the reactants (Figure 5 ). In 2003, Geerlings et al. published a key review giving a detailed description of the principles and concepts of conceptual DFT and highlighting its success to study generalized acid/base reactions including addition, substitution, and elimination reactions. Since the time that this review appeared, conceptual DFT has proven its strength in literally hundreds of papers with application to organic and inorganic reactions. Its role in unravelling enzymatic reaction mechanisms, in handling experimentally difficult accessible biochemical problems, and in the interpretation of biochemical experimental observations is emerging and very promising.

  4. Hydrogen atom addition to the surface of graphene nanoflakes: A density functional theory study

    NASA Astrophysics Data System (ADS)

    Tachikawa, Hiroto

    2017-02-01

    Polycyclic aromatic hydrocarbons (PAHs) provide a 2-dimensional (2D) reaction surface in 3-dimensional (3D) interstellar space and have been utilized as a model of graphene surfaces. In the present study, the reaction of PAHs with atomic hydrogen was investigated by means of density functional theory (DFT) to systematically elucidate the binding nature of atomic hydrogen to graphene nanoflakes. PAHs with n = 4-37 were chosen, where n indicates the number of benzene rings. Activation energies of hydrogen addition to the graphene surface were calculated to be 5.2-7.0 kcal/mol at the CAM-B3LYP/6-311G(d,p) level, which is almost constant for all PAHs. The binding energies of hydrogen atom were slightly dependent on the size (n): 14.8-28.5 kcal/mol. The absorption spectra showed that a long tail is generated at the low-energy region after hydrogen addition to the graphene surface. The electronic states of hydrogenated graphenes were discussed on the basis of theoretical results.

  5. Selectivity descriptors for the Michael addition reaction as obtained from density functional based approaches.

    PubMed

    Madjarova, G; Tadjer, A; Cholakova, Tz P; Dobrev, A A; Mineva, T

    2005-01-20

    Density functional (DF) based numerical approaches for computing orbital and atomic reactivity indices were employed in the study of selectivity descriptors for the 1,4 Michael addition reaction. To this aim, atomic and orbital Fukui indices and atomic softnesses for 2-arylmethylene-1,4-butanolides and N,N-disubstituted phenylacetamides were computed. Further on, these local selectivity descriptors have been rationalized in terms of the Pearson's hard-soft-acid-base principle to explain the observed regioselectivity. It is shown that the methods employed for local (atomic and orbital) reactivity index computations are useful and reliable for prediction of the regioselectivity upon conjugate addition of ambident nucleophiles to 2,3-unsaturated carboxylic esters. All the results reveal similar degree of localization/hardness of the 1,4-butanolides C4 and active alpha-carbon belonging to the N,N-dimethyl-phenylacetamide, while the soft alpha-carbon in LiCH2CN reacts with the soft C2 1,4-butanolide center.

  6. Development of an efficient amine-functionalized glass platform by additional silanization treatment with alkylsilane.

    PubMed

    Kamisetty, Nagendra Kumar; Pack, Seung Pil; Nonogawa, Mitsuru; Devarayapalli, Kamakshaiah Charyulu; Kodaki, Tsutomu; Makino, Keisuke

    2006-11-01

    Aminosilane-treated molecular layers on glass surfaces are frequently used as functional platforms for biosensor preparation. All the amino groups present on the surface are not available in reactive forms, because surface amino groups interact with remaining unreacted surface silanol groups. Such nonspecific interactions might reduce the efficiency of chemical immobilization of biomolecules such as DNA, enzymes, antibodies, etc., in biosensor fabrication. To improve immobilization efficiency we have used additional surface silanization with alkylsilane (capping) to convert the remaining silanol groups into Si-O-Si linkages, thereby liberating the amino groups from nonspecific interaction with the silanol groups. We prepared different types of capped amine surface and evaluated the effect of capping on immobilization efficiency by investigating the fluorescence intensity of Cy3-NHS (N-hydroxysuccinimide) dye that reacted with amino groups. The results indicate that most of the capped amine surfaces resulted in enhanced efficiency of immobilization of Cy3-NHS compared with the untreated control amine surface. We found a trend that trialkoxysilanes had greater capping effects on immobilization efficiency than monoalkoxysilanes. It was also found that the aliphatic chain of alkylsilane, which does not participate in the capping of the silanol, had an important function in enhancing immobilization efficiency. These results would be useful for preparation of an amine-modified surface platform, with enhanced immobilization efficiency, which is essential for developing many kinds of biosensors on a silica matrix.

  7. Next-generation biomedical implants using additive manufacturing of complex, cellular and functional mesh arrays.

    PubMed

    Murr, L E; Gaytan, S M; Medina, F; Lopez, H; Martinez, E; Machado, B I; Hernandez, D H; Martinez, L; Lopez, M I; Wicker, R B; Bracke, J

    2010-04-28

    In this paper, we examine prospects for the manufacture of patient-specific biomedical implants replacing hard tissues (bone), particularly knee and hip stems and large bone (femoral) intramedullary rods, using additive manufacturing (AM) by electron beam melting (EBM). Of particular interest is the fabrication of complex functional (biocompatible) mesh arrays. Mesh elements or unit cells can be divided into different regions in order to use different cell designs in different areas of the component to produce various or continually varying (functionally graded) mesh densities. Numerous design elements have been used to fabricate prototypes by AM using EBM of Ti-6Al-4V powders, where the densities have been compared with the elastic (Young) moduli determined by resonant frequency and damping analysis. Density optimization at the bone-implant interface can allow for bone ingrowth and cementless implant components. Computerized tomography (CT) scans of metal (aluminium alloy) foam have also allowed for the building of Ti-6Al-4V foams by embedding the digital-layered scans in computer-aided design or software models for EBM. Variations in mesh complexity and especially strut (or truss) dimensions alter the cooling and solidification rate, which alters the alpha-phase (hexagonal close-packed) microstructure by creating mixtures of alpha/alpha' (martensite) observed by optical and electron metallography. Microindentation hardness measurements are characteristic of these microstructures and microstructure mixtures (alpha/alpha') and sizes.

  8. Regulatory network reconstruction using an integral additive model with flexible kernel functions

    PubMed Central

    Novikov, Eugene; Barillot, Emmanuel

    2008-01-01

    Background Reconstruction of regulatory networks is one of the most challenging tasks of systems biology. A limited amount of experimental data and little prior knowledge make the problem difficult to solve. Although models that are currently used for inferring regulatory networks are sometimes able to make useful predictions about the structures and mechanisms of molecular interactions, there is still a strong demand to develop increasingly universal and accurate approaches for network reconstruction. Results The additive regulation model is represented by a set of differential equations and is frequently used for network inference from time series data. Here we generalize this model by converting differential equations into integral equations with adjustable kernel functions. These kernel functions can be selected based on prior knowledge or defined through iterative improvement in data analysis. This makes the integral model very flexible and thus capable of covering a broad range of biological systems more adequately and specifically than previous models. Conclusion We reconstructed network structures from artificial and real experimental data using differential and integral inference models. The artificial data were simulated using mathematical models implemented in JDesigner. The real data were publicly available yeast cell cycle microarray time series. The integral model outperformed the differential one for all cases. In the integral model, we tested the zero-degree polynomial and single exponential kernels. Further improvements could be expected if the kernel were selected more specifically depending on the system. PMID:18218091

  9. Cryptic biodiversity effects: importance of functional redundancy revealed through addition of food web complexity.

    PubMed

    Philpott, Stacy M; Pardee, Gabriella L; Gonthier, David J

    2012-05-01

    Interactions between predators and the degree of functional redundancy among multiple predator species may determine whether herbivores experience increased or decreased predation risk. Specialist parasites can modify predator behavior, yet rarely have cascading effects on multiple predator species and prey been evaluated. We examined influences of specialist phorid parasites (Pseudacteon spp.) on three predatory ant species and herbivores in a coffee agroecosystem. Specifically, we examined whether changes in ant richness affected fruit damage by the coffee berry borer (Hypothenemus hampei) and whether phorids altered multi-predator effects. Each ant species reduced borer damage, and without phorids, increasing predator richness did not further decrease borer damage. However, with phorids, activity of one ant species was reduced, indicating that the presence of multiple ant species was necessary to limit borer damage. In addition, phorid presence revealed synergistic effects of multiple ant species, not observed without the presence of this parasite. Thus, a trait-mediated cascade resulting from a parasite-induced predator behavioral change revealed the importance of functional redundancy, predator diversity, and food web complexity for control of this important pest.

  10. A table of integrals of the error function. II - Additions and corrections.

    NASA Technical Reports Server (NTRS)

    Geller, M.; Ng, E. W.

    1971-01-01

    Integrals of products of error functions with other functions are presented, taking into account a combination of the error function with powers, a combination of the error function with exponentials and powers, a combination of the error function with exponentials of more complicated arguments, definite integrals from Laplace transforms, and a combination of the error function with trigonometric functions. Other integrals considered include a combination of the error function with logarithms and powers, a combination of two error functions, and a combination of the error function with other special functions.

  11. Role of inorganic additives on the ballistic performance of gun propellant formulations.

    PubMed

    Damse, R S; Sikder, A K

    2008-06-15

    This paper explores the possibility of increasing the ballistic performance of gun propellant with the addition of inorganic additives viz. aluminium and ammonium perchlorate. Compositions based on propellant NQ containing additional aluminium and ammonium perchlorate in different parts were studied theoretically and experimentally. Performance in respect of ballistic parameters, sensitivity, thermal characteristics, thermal stability and mechanical properties are evaluated and compared with that of the conventional triple base propellant NQ. Experimental data on comparative study indicate that the compositions containing aluminium and ammonium perchlorate are superior to propellant NQ in respect of energy.

  12. The role of tumor necrosis factor receptor superfamily members in mammalian brain development, function and homeostasis.

    PubMed

    Twohig, Jason P; Cuff, Simone M; Yong, Audrey A; Wang, Eddie C Y

    2011-01-01

    Tumor necrosis factor receptor superfamily (TNFRSF) members were initially identified as immunological mediators, and are still commonly perceived as immunological molecules. However, our understanding of the diversity of TNFRSF members' roles in mammalian physiology has grown significantly since the first discovery of TNFRp55 (TNFRSF1) in 1975. In particular, the last decade has provided evidence for important roles in brain development, function and the emergent field of neuronal homeostasis. Recent evidence suggests that TNFRSF members are expressed in an overlapping regulated pattern during neuronal development, participating in the regulation of neuronal expansion, growth, differentiation and regional pattern development. This review examines evidence for non-immunological roles of TNFRSF members in brain development, function and maintenance under normal physiological conditions. In addition, several aspects of brain function during inflammation will also be described, when illuminating and relevant to the non-immunological role of TNFRSF members. Finally, key questions in the field will be outlined.

  13. Role of additives on tensile strength of wood-plastic composite

    NASA Astrophysics Data System (ADS)

    Khan, Mubarak A.; Ali, K. M. Idriss

    Wood-plastic composite (WPC) formation has been studied with simul+styrene system at various compositions of styrene with methanol as the swelling solvent. Effect of additives, e.g. multifunctional monomers (MFM) and oligomers used in very low quantity (1% v/v) on the polymer loading (PL) and tensile strength (TS) of the WPC has been elaborately investigated. Enhanced PL and TS values are observed. Inorganic co-additives like Lithium (Li +), Copper (Cu 2+) and acid (H +) and urea (U) used in combinations with additives (MFM or oligomers) have influenced the results of PL and TS in these systems. Li + ion has been a good replacement for H + ion; U has substantially enhanced the PL values with retention of the TS values of WPC. Co-additive Cu 2+ used in these system can act as a preservative and protective agent for WPC.

  14. The role of prop-1-ene-1,3-sultone as an additive in lithium-ion cells

    NASA Astrophysics Data System (ADS)

    Self, Julian; Hall, David S.; Madec, Lénaïc; Dahn, J. R.

    2015-12-01

    Density functional theory (DFT) is used in conjunction with experimental results to propose decomposition pathways that describe the role and ultimate fate of the PES additive in Li-ion batteries. Oxidation of PES produces carbonyl sulfide gas and ethene at the positive electrode, both experimentally observed byproducts. However, the calculated standard potential for simple PES oxidation, E0ox ∼ 6.7 V vs. Li/Li+, is quite high, suggesting this pathway is unlikely. A "reactive electrode model" is presented, in which the positive electrode material is a reagent in the pseudo-combustion of PES (and other solvents). This spontaneous process produces carbonyl sulfide, carbon dioxide, and a rock salt surface layer, all of which are experimentally observed. At the negative electrode, the reduction of PES occurs via two one-electron steps, where E0red,1 = 0.9 V and E0red,2 = 4.3 V. The reduced species, Li2PES, can react with hydrogen and methyl radicals to produce propene, methylpropene, propane and lithium sulfite. Nucleophilic Li2PES can also react with electrophilic PES, ethylene carbonate, or ethyl methyl carbonate. Eighteen possible organic sulphate 'building blocks' for the solid-electrolyte interphase (SEI) are presented. X-ray photoelectron spectroscopy (XPS) measurements demonstrate that PES reduction indeed results in both lithium sulfite and organic sulphate SEI components.

  15. Modification of Polymer Network Properties through the Addition of Functional Nanogel Particles

    NASA Astrophysics Data System (ADS)

    Liu, JianCheng

    Multifunctional acrylic and methacrylic monomers have been widely applied in many photopolymerization applications to produce crosslinked polymers with advantages such as rapid curing, broad choices of commercially available monomers and desirable physical and mechanical properties. However, there still remain critical challenges for these materials during polymerization including limited conversion and early onset of gelation as well as the generation of significant polymerization shrinkage and stress. This thesis explores the effects of network property modification through the addition of polymeric nanoparticles or nanogels. In order to understand the relationship between nanogel structure and composite material properties, nanogels with different architectures and functionalities were studied during polymerization in terms of kinetics, shrinkage and stress reduction, mechanical performance and reaction mechanisms. Nanogel composite formulations were evaluated to understand the interaction between nanogel structure with the resin matrix during polymerization through adjustment of nanogel branching densities and reactivity of polymer chain ends. It was found that both the chemical crosslinking from reactive chain ends and physical entanglements of high branching density nanogels with the resin matrix dramatically could improve final material mechanical strength. The reductions in overall volumetric shrinkage and shrinkage stress were found to follow at least proportional behavior with respect to nanogel loading concentration while maintaining similar final conversion and modulus results compared with the control resin. Nanogels containing unique functionalities were designed in order to modify reaction mechanism during secondary polymerization. A nanogel containing an integrated photoinitiator and active chain-end RAFT groups was able to initiate secondary polymerization from the nanogel phase so that localized polymerization was achieved from the beginning of

  16. Analyzing the roles of multi-functional proteins in cells: The case of arrestins and GRKs.

    PubMed

    Gurevich, Vsevolod V; Gurevich, Eugenia V

    2015-01-01

    Most proteins have multiple functions. Obviously, conventional methods of manipulating the level of the protein of interest in the cell, such as over-expression, knockout or knockdown, affect all of its functions simultaneously. The key advantage of these methods is that over-expression, knockout or knockdown does not require any knowledge of the molecular mechanisms of the function(s) of the protein of interest. The disadvantage is that these approaches are inadequate to elucidate the role of an individual function of the protein in a particular cellular process. An alternative is the use of re-engineered proteins, in which a single function is eliminated or enhanced. The use of mono-functional elements of a multi-functional protein can also yield cleaner answers. This approach requires detailed knowledge of the structural basis of each function of the protein in question. Thus, a lot of preliminary structure-function work is necessary to make it possible. However, when this information is available, replacing the protein of interest with a mutant in which individual functions are modified can shed light on the biological role of those particular functions. Here, we illustrate this point using the example of protein kinases, most of which have additional non-enzymatic functions, as well as arrestins, known multi-functional signaling regulators in the cell.

  17. Adding functionality with additive manufacturing: Fabrication of titanium-based antibiotic eluting implants.

    PubMed

    Cox, Sophie C; Jamshidi, Parastoo; Eisenstein, Neil M; Webber, Mark A; Hassanin, Hany; Attallah, Moataz M; Shepherd, Duncan E T; Addison, Owen; Grover, Liam M

    2016-07-01

    Additive manufacturing technologies have been utilised in healthcare to create patient-specific implants. This study demonstrates the potential to add new implant functionality by further exploiting the design flexibility of these technologies. Selective laser melting was used to manufacture titanium-based (Ti-6Al-4V) implants containing a reservoir. Pore channels, connecting the implant surface to the reservoir, were incorporated to facilitate antibiotic delivery. An injectable brushite, calcium phosphate cement, was formulated as a carrier vehicle for gentamicin. Incorporation of the antibiotic significantly (p=0.01) improved the compressive strength (5.8±0.7MPa) of the cement compared to non-antibiotic samples. The controlled release of gentamicin sulphate from the calcium phosphate cement injected into the implant reservoir was demonstrated in short term elution studies using ultraviolet-visible spectroscopy. Orientation of the implant pore channels were shown, using micro-computed tomography, to impact design reproducibility and the back-pressure generated during cement injection which ultimately altered porosity. The amount of antibiotic released from all implant designs over a 6hour period (<28% of the total amount) were found to exceed the minimum inhibitory concentrations of Staphylococcus aureus (16μg/mL) and Staphylococcus epidermidis (1μg/mL); two bacterial species commonly associated with periprosthetic infections. Antibacterial efficacy was confirmed against both bacterial cultures using an agar diffusion assay. Interestingly, pore channel orientation was shown to influence the directionality of inhibition zones. Promisingly, this work demonstrates the potential to additively manufacture a titanium-based antibiotic eluting implant, which is an attractive alternative to current treatment strategies of periprosthetic infections.

  18. The Human BNST: Functional Role in Anxiety and Addiction

    PubMed Central

    Avery, S N; Clauss, J A; Blackford, J U

    2016-01-01

    The consequences of chronic stress on brain structure and function are far reaching. Whereas stress can produce short-term adaptive changes in the brain, chronic stress leads to long-term maladaptive changes that increase vulnerability to psychiatric disorders, such as anxiety and addiction. These two disorders are the most prevalent psychiatric disorders in the United States, and are typically chronic, disabling, and highly comorbid. Emerging evidence implicates a tiny brain region—the bed nucleus of the stria terminalis (BNST)—in the body's stress response and in anxiety and addiction. Rodent studies provide compelling evidence that the BNST plays a central role in sustained threat monitoring, a form of adaptive anxiety, and in the withdrawal and relapse stages of addiction; however, little is known about the role of BNST in humans. Here, we review current evidence for BNST function in humans, including evidence for a role in the production of both adaptive and maladaptive anxiety. We also review preliminary evidence of the role of BNST in addiction in humans. Together, these studies provide a foundation of knowledge about the role of BNST in adaptive anxiety and stress-related disorders. Although the field is in its infancy, future investigations of human BNST function have tremendous potential to illuminate mechanisms underlying stress-related disorders and identify novel neural targets for treatment. PMID:26105138

  19. Highly Functionalized Cyclopentane Derivatives by Tandem Michael Addition/Radical Cyclization/Oxygenation Reactions.

    PubMed

    Holan, Martin; Pohl, Radek; Císařová, Ivana; Klepetářová, Blanka; Jones, Peter G; Jahn, Ullrich

    2015-06-26

    Densely functionalized cyclopentane derivatives with up to four consecutive stereocenters are assembled by a tandem Michael addition/single-electron transfer oxidation/radical cyclization/oxygenation strategy mediated by ferrocenium hexafluorophosphate, a recyclable, less toxic single-electron transfer oxidant. Ester enolates were coupled with α-benzylidene and α-alkylidene β-dicarbonyl compounds with switchable diastereoselectivity. This pivotal steering element subsequently controls the diastereoselectivity of the radical cyclization step. The substitution pattern of the radical cyclization acceptor enables a switch of the cyclization mode from a 5-exo pattern for terminally substituted olefin units to a 6-endo mode for internally substituted acceptors. The oxidative anionic/radical strategy also allows efficient termination by oxygenation with the free radical 2,2,6,6-tetramethyl-1-piperidinoxyl, and two C-C bonds and one C-O bond are thus formed in the sequence. A stereochemical model is proposed that accounts for all of the experimental results and allows the prediction of the stereochemical outcome. Further transformations of the synthesized cyclopentanes are reported.

  20. Density functional theory study of the effects of alloying additions on sulfur adsorption on nickel surfaces

    NASA Astrophysics Data System (ADS)

    Malyi, Oleksandr I.; Chen, Zhong; Kulish, Vadym V.; Bai, Kewu; Wu, Ping

    2013-01-01

    Reactions of hydrogen sulfide (H2S) with Nickel/Ytrria-doped zirconia (Ni/YDZ) anode materials might cause degradation of the performance of solid oxide fuel cells when S containing fuels are used. In this paper, we employ density functional theory to investigate S adsorption on metal (M)-doped and undoped Ni(0 0 1) and Ni(1 1 1) surfaces. Based on the performed calculations, we analyze the effects of 12 alloying additions (Ag, Au, Al, Bi, Cd, Co, Cu, Fe, Sn, Sb, V, and Zn) on the temperature of transition between clean (S atoms do not adsorb on the surfaces) and contaminated (S atoms can adsorb on the surfaces spontaneously) M-doped Ni surfaces for different concentrations of H2S in the fuel. Predicted results are consistent with many experimental studies relevant to S poisoning of both Ni/YDZ and M-doped Ni/YDZ anode materials. This study is important to understand S poisoning phenomena and to develop new S tolerant anode materials.

  1. The Roles and Functions of Vocational Education: Some Current Perspectives.

    ERIC Educational Resources Information Center

    Pratzner, Frank C.; Russell, Jill Frymier

    This report examines information from a broad base of literature and research and from three Delphi surveys of the views and opinions of small, highly select groups of knowledgeable educational leaders in order to highlight a number of key issues and arguments related to the appropriate roles and functions of public vocational education. It…

  2. Is functional hypertrophy and specific force coupled with the addition of myonuclei at the single muscle fiber level?

    PubMed

    Qaisar, Rizwan; Renaud, Guillaume; Morine, Kevin; Barton, Elisabeth R; Sweeney, H Lee; Larsson, Lars

    2012-03-01

    Muscle force is typically proportional to muscle size, resulting in constant force normalized to muscle fiber cross-sectional area (specific force). Mice overexpressing insulin-like growth factor-1 (IGF-1) exhibit a proportional gain in muscle force and size, but not the myostatin-deficient mice. In an attempt to explore the role of the cytoplasmic volume supported by individual myonuclei [myonuclear domain (MND) size] on functional capacity of skeletal muscle, we have investigated specific force in relation to MND and the content of the molecular motor protein, myosin, at the single muscle fiber level from myostatin-knockout (Mstn(-/-)) and IGF-1-overexpressing (mIgf1(+/+)) mice. We hypothesize that the addition of extra myonuclei is a prerequisite for maintenance of specific force during muscle hypertrophy. A novel algorithm was used to measure individual MNDs in 3 dimensions along the length of single muscle fibers from the fast-twitch extensor digitorum longus and the slow-twitch soleus muscle. A significant effect of the size of individual MNDs in hypertrophic muscle fibers on both specific force and myosin content was observed. This effect was muscle cell type specific and suggested there is a critical volume individual myonuclei can support efficiently. The large MNDs found in fast muscles of Mstn(-/-) mice were correlated with the decrement in specific force and myosin content in Mstn(-/-) muscles. Thus, myostatin inhibition may not be able to maintain the appropriate MND for optimal function.

  3. Updated role of nitric oxide in disorders of erythrocyte function.

    PubMed

    Kahn, Marc J; Maley, Jason H; Lasker, George F; Kadowitz, Philip J

    2013-03-01

    Nitric oxide is a potent vasodilator that plays a critical role in disorders of erythrocyte function. Sickle cell disease, paroxysmal nocturnal hemoglobinuria and banked blood preservation are three conditions where nitric oxide is intimately related to dysfunctional erythrocytes. These conditions are accompanied by hemolysis, thrombosis and vasoocclusion. Our understanding of the interaction between nitric oxide, hemoglobin, and the vasculature is constantly evolving, and by defining this role we can better direct trials aimed at improving the treatments of disorders of erythrocyte function. Here we briefly discuss nitric oxide's interaction with hemoglobin through the hypothesis regarding Snitrosohemoglobin, deoxyhemoglobin, and myoglobin as nitrite reductases. We then review the current understanding of the role of nitric oxide in sickle cell disease, paroxysmal nocturnal hemoglobinuria, and banked blood, and discuss therapeutics in development to target nitric oxide in the treatment of some of these disorders.

  4. THE ROLE OF SEROTONIN IN RESPIRATORY FUNCTION AND DYSFUNCTION

    PubMed Central

    Hilaire, Gérard; Voituron, Nicolas; Menuet, Clément; Ichiyama, Ronaldo M.; Subramanian, Hari H.; Dutschmann, Mathias

    2010-01-01

    Serotonin (5-HT) is a neuro-modulator–transmitter influencing global brain function. Past and present findings illustrate a prominent role for 5-HT in the modulation of ponto-medullary autonomic circuits. 5-HT is also involved in the control of neurotrophic processes during pre- and postnatal development of neural circuits. The functional implications of 5-HT is particularly illustrated in the alterations to the serotonergic system, as seen in a wide range of neurological disorders. This article reviews the role of 5-HT in the development and control of respiratory networks in the ponto-medullary brainstem. The review further examines the role of 5-HT in breathing disorders occurring at different stages of life, in particular, the neonatal neurodevelopmental diseases such as Rett, sudden infant death and Prader-Willi syndromes, adult diseases such as sleep apnoea and mental illness linked to neurodegeneration. PMID:20801236

  5. Latinas and Postpartum Depression: Role of Partner Relationship, Additional Children, and Breastfeeding

    ERIC Educational Resources Information Center

    Hassert, Silva; Kurpius, Sharon E. Robinson

    2011-01-01

    Breastfeeding, additional children, and partner relationship predicted postpartum depression among 59 Latinas who had an infant who was 6 months old or younger. The most powerful predictor was conflict with partner. Counselors working with Latinas experiencing postpartum depression should explore the partner relationship, particularly relationship…

  6. Testing a Gender Additive Model: The Role of Body Image in Adolescent Depression

    ERIC Educational Resources Information Center

    Bearman, Sarah Kate; Stice, Eric

    2008-01-01

    Despite consistent evidence that adolescent girls are at greater risk of developing depression than adolescent boys, risk factor models that account for this difference have been elusive. The objective of this research was to examine risk factors proposed by the "gender additive" model of depression that attempts to partially explain the increased…

  7. Functional Role of Infective Viral Particles on Metal Reduction

    SciTech Connect

    Coates, John D.

    2014-04-01

    A proposed strategy for the remediation of uranium (U) contaminated sites was based on the immobilization of U by reducing the oxidized soluble U, U(VI), to form a reduced insoluble end product, U(IV). Previous studies identified Geobacter sp., including G. sulfurreducens and G. metallireducens, as predominant U(VI)-reducing bacteria under acetate-oxidizing and U(VI)-reducing conditions. Examination of the finished genome sequence annotation of the canonical metal reducing species Geobacter sulfurreducens strain PCA and G. metallireduceans strain GS-15 as well as the draft genome sequence of G. uraniumreducens strain Rf4 identified phage related proteins. In addition, the completed genome for Anaeromyxobacter dehalogenans and the draft genome sequence of Desulfovibrio desulfuricans strain G20, two more model metal-reducing bacteria, also revealed phage related sequences. The presence of these gene sequences indicated that Geobacter spp., Anaeromyxobacter spp., and Desulfovibrio spp. are susceptible to viral infection. Furthermore, viral populations in soils and sedimentary environments in the order of 6.4×10{sup 6}–2.7×10{sup 10} VLP’s cm{sup -3} have been observed. In some cases, viral populations exceed bacterial populations in these environments suggesting that a relationship may exist between viruses and bacteria. Our preliminary screens of samples collected from the ESR FRC indicated that viral like particles were observed in significant numbers. The objective of this study was to investigate the potential functional role viruses play in metal reduction specifically Fe(III) and U(VI) reduction, the environmental parameters affecting viral infection of metal reducing bacteria, and the subsequent effects on U transport.

  8. Role of nitrogen additive and temperature on growth of diamond films from nanocrystalline to polycrystalline.

    PubMed

    Chunjiu, Tang; José, Grácio; Neves, A J; Hugo, Calisto; Fernandes, A J S; Lianshe, Fu; Sérgio, Pereira; Liping, Gu; Gil, Cabral; Carmo, M C

    2010-04-01

    In this work, the coupled effect of nitrogen addition into CH4/H2 mixtures and surface temperature on diamond growth ranging from large grained polycrystalline to fine-grained nanocrystalline were investigated. Moreover a new growth parameter window for simultaneous growth of nanocrystalline diamond (NCD) and {100} textured large-grained diamond films was developed by using a high power high pressure 5 kW microwave plasma assisted chemical vapor deposition (MPCVD) reactor. Scanning electron microscope (SEM), Raman spectroscopy, and X-ray diffraction (XRD) are employed to characterize the morphology, crystalline quality and texture of the diamond samples. Our results can be grouped by two catalogs: First, deposition run without and with 0.24% N2 addition, while keeping all the other parameters constant, resulted in a high quality transparent large-grained polycrystalline diamond film and a NCD film, respectively. This result clearly evidences nitrogen induced nanocrystallinity. Then, two different substrate surface temperatures were obtained by overlapping a small silicon slice on the top centre of a large silicon wafer of 5.08 cm in diameter in only one deposition run using 0.24% N2 addition and the same set of parameters as the previous runs. From this growth run, a NCD film of growth rate around 2.3 microm/h was obtained at low temperature, while a {100} textured large-grained diamond film of much higher growth rate about 10.4 microm/h was grown at high temperature. These results not only confirm the reproducibility of NCD by N2 addition, but also indicate that distinct growth modes were involved at different substrate temperatures with 0.24% nitrogen addition, or coupled effect of nitrogen addition and temperature on the growth of CVD diamond films happened. Finite element method (FEM) analysis was employed to simulate the temperature gradient and distribution on these two samples, and based on this simulation and other simulation results in the literature, the

  9. The role of intramolecular hydrogen bonds in nucleophilic addition reactions of ketenaminals

    NASA Astrophysics Data System (ADS)

    Isaev, A. N.

    2012-08-01

    Quantum-chemical calculations of the geometries and electronic structures of molecules of ketenaminals 3-(diaminomethylene)-2,4-pentanedione and dimethyl-2-(diaminomethylene)-malonate and calculations of the structures of intermediates in the reaction of the nucleophilic addition of the ketenaminals to the acetonitrile molecule are performed by B3LYP/6-31+G** method. Two possible scenarios of the process are shown, depending on the mutual orientation of reacting molecules. The nucleophilic addition proceeds in two stages. It is found that the rate-limiting stage of the process is the transfer of the proton of the intramolecular hydrogen bond in a ketenaminal molecule. The experimentally observed faster reaction of pyrimidine formation for the 3-(diaminomethylene)-2,4-pentanedione molecule relative to that for dimethyl-2-(diaminomethylene)-malonate is explained by the hydrogen bond being stronger and the barrier of proton transfer from the aminogroup to the ketogroup oxygen falling upon nucleophilic attack in the former molecule.

  10. Emerging role of phenolic compounds as natural food additives in fish and fish products.

    PubMed

    Maqsood, Sajid; Benjakul, Soottawat; Shahidi, Fereidoon

    2013-01-01

    Chemical and microbiological deteriorations are principal causes of quality loss of fish and fish products during handling, processing, and storage. Development of rancid odor and unpleasant flavor, changes of color and texture as well as lowering nutritional value in fish can be prevented by appropriate use of additives. Due to the potential health hazards of synthetic additives, natural products, especially antioxidants and antimicrobial agents, have been intensively examined as safe alternatives to synthetic compounds. Polyphenols (PP) are the natural antioxidants prevalent in fruits, vegetables, beverages (tea, wine, juices), plants, seaweeds, and some herbs and show antioxidative and antimicrobial activities in different fish and fish products. The use of phenolic compounds also appears to be a good alternative for sulphiting agent for retarding melanosis in crustaceans. Phenolic compounds have also been successfully employed as the processing aid for texture modification of fish mince and surimi. Thus, plant polyphenolic compounds can serve as potential additives for preventing quality deterioration or to retain the quality of fish and fish products.

  11. Functional role of bdm during flagella biogenesis in Escherichia coli.

    PubMed

    Kim, Ji-Sun; Kim, Yu Jin; Seo, Sojin; Seong, Maeng-Je; Lee, Kangseok

    2015-03-01

    The biofilm-dependent modulation gene (bdm) has recently been shown to play a role in osmotic-induced formation of biofilm in Escherichia coli. In this study, we demonstrated that deletion of bdm results in down-regulation of flagella biosynthesis genes and, consequently, a defect in E. coli motility. In addition, we employed atomic force microscopy to confirm the absence of flagella-like structures on the surface of bdm-null cells. These findings indicate that bdm plays a key role in regulatory pathway for the formation of flagella.

  12. Role of additives in wood polymer composites. Relationship to analogous radiation grafting and curing processes

    NASA Astrophysics Data System (ADS)

    Ng, Loo-Teck; Garnett, John L.; Mohajerani, Shahroo

    1999-08-01

    Wood polymer composites (WPC) were prepared by impregnating an Australian softwood, Pinus radiata with methyl methacrylate which subsequently underwent in situ polymerisation utilising either γ radiation or the catalyst-accelerator method. Novel additives including thermal initiator, crosslinking agents, an inclusion compound and oxygen scavenger were incorporated to improve the polymer loading and properties of the resulting WPC. Polymer loadings of WPC obtained utilising the accelerator-catalyst method corresponded well with those obtained using γ radiation with 20 kGy radiation dose. The mechanistic significance of the current work in analogous radiation grafting and curing processes is discussed.

  13. [Roles of additives and surface control in slurry atomization]. Quarterly report, March 1992

    SciTech Connect

    Not Available

    1992-08-01

    Our experimental results clearly demonstrate that the shape of particles with aspect ratio close to unity dictates the relative suspension viscosity. Suspensions of irregularly shaped particles have higher relative viscosities than suspensions of spherical particles at same volume fractions, in agreement with the reported results at high shear conditions. The relative viscosity of a Newtonian suspension is in excellent agreement with that predicted by the Krieger/Dougherty rigid sphere model using the maximum packing fraction determined from sedimentation as the sole parameter. The relative viscosity of a pseudoplastic suspension is independent of the particle density. It correlates well with the particle Peclet number. The extent of particle diffusion at high shear rates decreases considerably as the particle size increases, and less energy is dissipated as a result. The interparticle electrostatic repulsion plays no significant role in the rheology of pseudoplastic nonaqueous and aqueous glycerol suspensions of noncolloidal particles.

  14. The Roles and Functions of Medical Directors in Nursing Homes.

    PubMed

    Nanda, Aman

    2015-03-03

    The medical director is an important member of the healthcare team in a nursing home, and is responsible for overall coordination of care and for implementation of policies related to care of the residents in a nursing home. The residents in nursing homes are frail, medically complex, and have multiple disabilities. The medical director has an important leadership role in assisting nursing home administration in providing quality care that is consistent with current standards of care. This article provides an overview of roles and functions of the medical director, and suggests ways the medical director can be instrumental in achieving excellent care in today's nursing facilities.

  15. Role of Ag addition in L10 ordering of FePt-based nanocomposite magnets

    NASA Astrophysics Data System (ADS)

    Crisan, A. D.; Vasiliu, F.; Mercioniu, I.; Crisan, O.

    2014-01-01

    The FePt system has important perspectives as high-temperature corrosion-resistant magnets. In the form of rapidly solidified melt-spun ribbons, FePt-based magnets may exhibit in certain cases a two-phase hard-soft magnetic behaviour. The present paper deals with a microstructural and magnetic study of FePtAgB alloys with increasing Ag content. The aim is to identify and confirm the effect of Ag addition in decreasing the temperature of the FePt disorder-order structural phase transformation. A detailed high-resolution transmission electron microscopy study is employed, and the alternative disposal of hard and soft regions within the two-phase microstructure is observed and interpreted with respect to the X-ray diffraction results. In the as-cast Ag-containing samples, it is shown that there is an optimum of the Ag content for which best magnetic properties are obtained. Ag addition creates a nonlinear behaviour of the coercive field and the ordering parameter, similar to the RKKY interaction-induced interlayer exchange coupling (IEC) observed in magnetic layers separated by non-magnetic spacer layers. Direct formation of the L10 phase from the as-cast state in the FePtAgB alloys is reported with magnetic parameters compatible to other exchange spring permanent nanomagnets. These findings open novel perspectives into utilization of such alloys in applications requiring magnets operating in high-temperature industrial environments.

  16. [The role of additives in bio-mass coal briquette on sulfur retention enhancement].

    PubMed

    Lu, Yongqi; Xu, Kangfu; Ma, Yongliang; Wei, Tiejun; Hao, Jiming

    2002-01-30

    The research first conducted the sulfur-fixing experiment of bio-mass coal briquette in a tubular furnace. The impacts of three additives Al2O3, Fe2O3 and MnO2 on the sulfur retention by calcium-based sorbent in briquette were investigated, and only Al2O3 displayed the enhancement of sulfur retention. The TGA experiment was further carried out, and proved that the high-temperature decomposition of CaSO4 in the deoxidization atmosphere was effectively inhibited with the addition of Al2O3. The XPS and XRD analyses of briquette ash showed that due to the interaction among Al2O3, CaSO4 and CaO, the composite CaSO4.3CaO.3Al2O3 which has more thermal stability was formed. With its wrapping or binding onto the surface of CaSO4 crystal, the decomposition of CaSO4 was mitigated.

  17. Examining the Roles of Work Autonomous and Controlled Motivations on Satisfaction and Anxiety as a Function of Role Ambiguity.

    PubMed

    Gillet, Nicolas; Fouquereau, Evelyne; Lafrenière, Marc-André K; Huyghebaert, Tiphaine

    2016-07-03

    Past research in the self-determination theory has shown that autonomous motivation is associated with positive outcomes (e.g., work satisfaction), whereas controlled motivation is related to negative outcomes (e.g., anxiety). The purpose of the present research was to examine the moderating function of role ambiguity on the relationships between work autonomous and controlled motivations on the one hand, and work satisfaction and anxiety on the other. Six hundred and ninety-eight workers (449 men and 249 women) participated in this study. Results revealed that autonomous motivation was most strongly related to satisfaction when ambiguity was low. In addition, controlled motivation was most strongly related to anxiety when ambiguity was high. In other words, the present findings suggest that the outcomes associated with each form of motivation may vary as a function of role ambiguity. The present study thus offers meaningful insights for organizations, managers, and employees.

  18. Limited role of functional differentiation in early diversification of animals

    PubMed Central

    Knope, M.L.; Heim, N.A.; Frishkoff, L.O.; Payne, J.L.

    2015-01-01

    The origin of most animal phyla and classes during the Cambrian explosion has been hypothesized to represent an ‘early burst’ of evolutionary exploration of functional ecological possibilities. However, the ecological history of marine animals has yet to be fully quantified, preventing an assessment of the early-burst model for functional ecology. Here we use ecological assignments for 18,621 marine animal genera to assess the relative timing of functional differentiation versus taxonomic diversification from the Cambrian to the present day. We find that functional diversity increased more slowly than would be expected given the history of taxonomic diversity. Contrary to previous inferences of rapid ecological differentiation from the early appearances of all well-fossilized phyla and classes, explicit coding of functional characteristics demonstrates that Cambrian genera occupied comparatively few modes of life. Functional diversity increased in the Ordovician and, especially, during the recoveries from the end-Permian and end-Cretaceous mass extinctions. Permanent shifts in the relationship between functional and taxonomic diversity following the era-bounding extinctions indicates a critical role for these biotic crises in coupling taxonomic and functional diversity. PMID:25737406

  19. Limited role of functional differentiation in early diversification of animals.

    PubMed

    Knope, M L; Heim, N A; Frishkoff, L O; Payne, J L

    2015-03-04

    The origin of most animal phyla and classes during the Cambrian explosion has been hypothesized to represent an 'early burst' of evolutionary exploration of functional ecological possibilities. However, the ecological history of marine animals has yet to be fully quantified, preventing an assessment of the early-burst model for functional ecology. Here we use ecological assignments for 18,621 marine animal genera to assess the relative timing of functional differentiation versus taxonomic diversification from the Cambrian to the present day. We find that functional diversity increased more slowly than would be expected given the history of taxonomic diversity. Contrary to previous inferences of rapid ecological differentiation from the early appearances of all well-fossilized phyla and classes, explicit coding of functional characteristics demonstrates that Cambrian genera occupied comparatively few modes of life. Functional diversity increased in the Ordovician and, especially, during the recoveries from the end-Permian and end-Cretaceous mass extinctions. Permanent shifts in the relationship between functional and taxonomic diversity following the era-bounding extinctions indicates a critical role for these biotic crises in coupling taxonomic and functional diversity.

  20. Edge-Selectively Functionalized Graphene-Like Platelets as a Co-curing Agent and a Nanoscale Additive to Epoxy Resin

    DTIC Science & Technology

    2012-08-12

    second method is where graphene can be grown using chemical vapor deposition (CVD) on a metal substrate18–20 or from single crystal silicon carbide...1 Final Report for AOARD Grant 114042 “Edge-selectively functionalized graphene -like platelets as a co-curing agent and a nanoscale additive...the role of a molecular wedge to exfoliate the AB-graphite into individual graphene and graphene -like platelets upon dispersion in polar solvents

  1. The distinctive role of executive functions in implicit emotion regulation.

    PubMed

    Sperduti, Marco; Makowski, Dominique; Arcangeli, Margherita; Wantzen, Prany; Zalla, Tiziana; Lemaire, Stéphane; Dokic, Jérôme; Pelletier, Jérôme; Piolino, Pascale

    2017-02-01

    Several theoretical models stress the role of executive functions in emotion regulation (ER). However, most of the previous studies on ER employed explicit regulatory strategies that could have engaged executive functions, beyond regulatory processes per se. Recently, there has been renewed interest in implicit forms of ER, believed to be closer to daily-life requirements. While various studies have shown that implicit and explicit ER engage partially overlapping neurocognitive processes, the contribution of different executive functions in implicit ER has not been investigated. In the present study, we presented participants with negatively valenced pictures of varying emotional intensity preceded by short texts describing them as either fictional or real. This manipulation was meant to induce a spontaneous emotional down-regulation. We recorded electrodermal activity (EDA) and subjective reports of emotion arousal. Executive functions (updating, switching, and inhibition) were also assessed. No difference was found between the fictional and real condition on EDA. A diminished self-reported arousal was observed, however, when pictures were described as fictional for high- and mild-intensity material, but not for neutral material. The amount of down-regulation in the fictional condition was found to be predicted by interindividual variability in updating performances, but not by the other measures of executive functions, suggesting its implication even in implicit forms of ER. The relationship between down-regulation and updating was significant only for high-intensity material. We discuss the role of updating in relation to the consciousness of one's emotional state.

  2. Functional dyspepsia: the role of visceral hypersensitivity in its pathogenesis.

    PubMed

    Keohane, John; Quigley, Eamonn M M

    2006-05-07

    Functional, or non-ulcer, dyspepsia (FD) is one of the most common reasons for referral to gastroenterologists. It is associated with significant morbidity and impaired quality of life. Many authorities believe that functional dyspepsia and irritable bowel syndrome represent part of the spectrum of the same disease process. The pathophysiology of FD remains unclear but several theories have been proposed including visceral hypersensitivity, gastric motor dysfunction, Helicobacter pylori infection and psychosocial factors. In this review, we look at the evidence, to date, for the role of visceral hypersensitivity in the aetiology of FD.

  3. Structural/Functional Role of Chloride in Photosystem II

    PubMed Central

    Rivalta, Ivan; Amin, Muhamed; Luber, Sandra; Vassiliev, Serguei; Pokhrel, Ravi; Umena, Yasufumi; Kawakami, Keisuke; Shen, Jian-Ren; Kamiya, Nobuo; Bruce, Doug; Brudvig, Gary W.; Gunner, M. R.; Batista, Victor S.

    2011-01-01

    Chloride binding in photosystem II (PSII) is essential for photosynthetic water oxidation. However, the functional roles of chloride and possible binding sites, during oxygen evolution, remain controversial. This paper examines the functions of chloride based on its binding site revealed in the X-ray crystal structure of PSII at 1.9 Å resolution. We find that chloride depletion induces formation of a salt-bridge between D2-K317 and D1-D61 that could suppress proton transfer to the lumen. PMID:21678923

  4. Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses

    PubMed Central

    Yi, Young-Su; Son, Young-Jin; Ryou, Chongsuk; Sung, Gi-Ho; Kim, Jong-Hoon; Cho, Jae Youl

    2014-01-01

    Inflammation is a series of complex biological responses to protect the host from pathogen invasion. Chronic inflammation is considered a major cause of diseases, such as various types of inflammatory/autoimmune diseases and cancers. Spleen tyrosine kinase (Syk) was initially found to be highly expressed in hematopoietic cells and has been known to play crucial roles in adaptive immune responses. However, recent studies have reported that Syk is also involved in other biological functions, especially in innate immune responses. Although Syk has been extensively studied in adaptive immune responses, numerous studies have recently presented evidence that Syk has critical functions in macrophage-mediated inflammatory responses and is closely related to innate immune response. This review describes the characteristics of Syk-mediated signaling pathways, summarizes the recent findings supporting the crucial roles of Syk in macrophage-mediated inflammatory responses and diseases, and discusses Syk-targeted drug development for the therapy of inflammatory diseases. PMID:25045209

  5. The role of susceptibility weighted imaging in functional MRI.

    PubMed

    Haacke, E Mark; Ye, Yongquan

    2012-08-15

    The development of functional brain magnetic resonance imaging (fMRI) has been a boon for neuroscientists and radiologists alike. It provides for fundamental information on brain function and better diagnostic tools to study disease. In this paper, we will review some of the early concepts in high resolution gradient echo imaging with a particular emphasis on susceptibility weighted imaging (SWI) and MR angiography (MRA). We begin with the history of our own experience in this area, followed by a discussion of the role of high resolution in studying the vasculature of the brain and how this relates to the BOLD (blood oxygenation level dependent) signal. We introduce the role of SWI and susceptibility mapping (SWIM) in fMRI and close with recommendations for future high resolution experiments.

  6. Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT.

    PubMed

    Pekmezci, Melike; Rice, Terri; Molinaro, Annette M; Walsh, Kyle M; Decker, Paul A; Hansen, Helen; Sicotte, Hugues; Kollmeyer, Thomas M; McCoy, Lucie S; Sarkar, Gobinda; Perry, Arie; Giannini, Caterina; Tihan, Tarik; Berger, Mitchel S; Wiemels, Joseph L; Bracci, Paige M; Eckel-Passow, Jeanette E; Lachance, Daniel H; Clarke, Jennifer; Taylor, Jennie W; Luks, Tracy; Wiencke, John K; Jenkins, Robert B; Wrensch, Margaret R

    2017-03-02

    The "integrated diagnosis" for infiltrating gliomas in the 2016 revised World Health Organization (WHO) classification of tumors of the central nervous system requires assessment of the tumor for IDH mutations and 1p/19q codeletion. Since TERT promoter mutations and ATRX alterations have been shown to be associated with prognosis, we analyzed whether these tumor markers provide additional prognostic information within each of the five WHO 2016 categories. We used data for 1206 patients from the UCSF Adult Glioma Study, the Mayo Clinic and The Cancer Genome Atlas (TCGA) with infiltrative glioma, grades II-IV for whom tumor status for IDH, 1p/19q codeletion, ATRX, and TERT had been determined. All cases were assigned to one of 5 groups following the WHO 2016 diagnostic criteria based on their morphologic features, and IDH and 1p/19q codeletion status. These groups are: (1) Oligodendroglioma, IDH-mutant and 1p/19q-codeleted; (2) Astrocytoma, IDH-mutant; (3) Glioblastoma, IDH-mutant; (4) Glioblastoma, IDH-wildtype; and (5) Astrocytoma, IDH-wildtype. Within each group, we used univariate and multivariate Cox proportional hazards models to assess associations of overall survival with patient age at diagnosis, grade, and ATRX alteration status and/or TERT promoter mutation status. Among Group 1 IDH-mutant 1p/19q-codeleted oligodendrogliomas, the TERT-WT group had significantly worse overall survival than the TERT-MUT group (HR: 2.72, 95% CI 1.05-7.04, p = 0.04). In both Group 2, IDH-mutant astrocytomas and Group 3, IDH-mutant glioblastomas, neither TERT mutations nor ATRX alterations were significantly associated with survival. Among Group 4, IDH-wildtype glioblastomas, ATRX alterations were associated with favorable outcomes (HR: 0.36, 95% CI 0.17-0.81, p = 0.01). Among Group 5, IDH-wildtype astrocytomas, the TERT-WT group had significantly better overall survival than the TERT-MUT group (HR: 0.48, 95% CI 0.27-0.87), p = 0.02). Thus, we present evidence that in

  7. A Role-Functional Model of Design Problem Solving

    DTIC Science & Technology

    1991-12-01

    material that was in the design, (3) removing some material from the design, ( 4 ) including new information in the design space, and (5) commenting on...ITechnical Feb 1, 1988 - July 31, 1991 4 . TITLE AND SUBTITLE 5 6NIV8 MRERSos A Role-Functional Model of Design Problem Solving- PE 6115N PR RR04206...94305-3096 GK- 4 9. SPONSORING/ MONITORING AGENCY NAME(S) AND ADDRESSES) 10. SPONSORING/ MONITORING Cognitive Science Program AGENCY REPORT NUMBIR

  8. Additional approach to PDT: type III mechanism and the role of native free radicals

    NASA Astrophysics Data System (ADS)

    Gal, Dezso; Kriska, Tamas; Shutova, Tatiana G.; Nemeth, Andras

    2001-04-01

    It has been suggested by us earlier that interactions of excited triplet sensitizer (3PS) and native free radicals compete with Type I (sensitizer radical mediated) and Type II (singlet oxygen mediated) mechanisms during PDT. Evidence such as fall in the overall radical concentration in vivo ( in mice tumors) during PDT and in the life time of 3PS caused by free radicals supported this assumption In addition, following results have been obtained recently. 1.) Excited Photofrin II and m-THPC affected luminol dependent chemiluminescence (CL) generated by respiratory burst of macrophages like free radical inhibitors. 2.) Quantification of spin trapping for chemical and in vitro systems by kinetic ESR spectrometry yielded detailed knowledge of triplet-doublet interactions 3.)Measurements in open systems (tank reactor) yielded data for the interactions between 3PS and peroxy type radicals 4.)Simulation of experimental data based on mechanisms suggested gave fair agreement. Based on experimental results new PS-s called Antioxidant Carrier Sensiters (ACS-s) have been devised, synthesized and tested one of them showing enhanced activity for PDT.

  9. Number line estimation and mental addition: examining the potential roles of language and education.

    PubMed

    Laski, Elida V; Yu, Qingyi

    2014-01-01

    This study investigated the relative importance of language and education to the development of numerical knowledge. Consistent with previous research suggesting that counting systems that transparently reflect the base-10 system facilitate an understanding of numerical concepts, Chinese and Chinese American kindergartners' and second graders' number line estimation (0-100 and 0-1000) was 1 to 2 years more advanced than that of American children tested in previous studies. However, Chinese children performed better than their Chinese American peers, who were fluent in Chinese but had been educated in America, at kindergarten on 0-100 number lines, at second grade on 0-1000 number lines, and at both time points on complex addition problems. Overall, the pattern of findings suggests that educational approach may have a greater influence on numerical development than the linguistic structure of the counting system. The findings also demonstrate that, despite generating accurate estimates of numerical magnitude on 0-100 number lines earlier, it still takes Chinese children approximately 2 years to demonstrate accurate estimates on 0-1000 number lines, which raises questions about how to promote the mapping of knowledge across numerical scales.

  10. Genome-wide meta-analysis of maize heterosis reveals the potential role of additive gene expression at pericentromeric loci

    PubMed Central

    2014-01-01

    QTL, and also suggests a model for the potential role of additive expression in the formation and conservation of heterosis for GY via dominant, multigenic quantitative trait loci. Our findings contribute to a deeper understanding of the multifactorial phenomenon of heterosis, and thus to the breeding of new high yielding varieties. PMID:24693880

  11. Kinetics of the addition of olefins to Si-centered radicals: the critical role of dispersion interactions revealed by theory and experiment.

    PubMed

    Johnson, Erin R; Clarkin, Owen J; Dale, Stephen G; DiLabio, Gino A

    2015-06-04

    Solution-phase rate constants for the addition of selected olefins to the triethylsilyl and tris(trimethylsilyl)silyl radicals are measured using laser-flash photolysis and competition kinetics. The results are compared with predictions from density functional theory (DFT) calculations, both with and without dispersion corrections obtained from the exchange-hole dipole moment (XDM) model. Without a dispersion correction, the rate constants are consistently underestimated; the errors increase with system size, up to 10(6) s(-1) for the largest system considered. Dispersion interactions preferentially stabilize the transition states relative to the separated reactants and bring the DFT-calculated rate constants into excellent agreement with experiment. Thus, dispersion interactions are found to play a key role in determining the kinetics for addition reactions, particularly those involving sterically bulky functional groups.

  12. The functional architectures of addition and subtraction: Network discovery using fMRI and DCM.

    PubMed

    Yang, Yang; Zhong, Ning; Friston, Karl; Imamura, Kazuyuki; Lu, Shengfu; Li, Mi; Zhou, Haiyan; Wang, Haiyuan; Li, Kuncheng; Hu, Bin

    2017-03-27

    The neuronal mechanisms underlying arithmetic calculations are not well understood but the differences between mental addition and subtraction could be particularly revealing. Using fMRI and dynamic causal modeling (DCM), this study aimed to identify the distinct neuronal architectures engaged by the cognitive processes of simple addition and subtraction. Our results revealed significantly greater activation during subtraction in regions along the dorsal pathway, including the left inferior frontal gyrus (IFG), middle portion of dorsolateral prefrontal cortex (mDLPFC), and supplementary motor area (SMA), compared with addition. Subsequent analysis of the underlying changes in connectivity - with DCM - revealed a common circuit processing basic (numeric) attributes and the retrieval of arithmetic facts. However, DCM showed that addition was more likely to engage (numeric) retrieval-based circuits in the left hemisphere, while subtraction tended to draw on (magnitude) processing in bilateral parietal cortex, especially the right intraparietal sulcus (IPS). Our findings endorse previous hypotheses about the differences in strategic implementation, dominant hemisphere, and the neuronal circuits underlying addition and subtraction. Moreover, for simple arithmetic, our connectivity results suggest that subtraction calls on more complex processing than addition: auxiliary phonological, visual, and motor processes, for representing numbers, were engaged by subtraction, relative to addition. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  13. Manipulation of lysozyme phase behavior by additives as function of conformational stability.

    PubMed

    Galm, Lara; Morgenstern, Josefine; Hubbuch, Jürgen

    2015-10-15

    Undesired protein aggregation in general and non-native protein aggregation in particular need to be inhibited during bio-pharmaceutical processing to ensure patient safety and to maintain product activity. In this work the potency of different additives, namely glycerol, PEG 1000, and glycine, to prevent lysozyme aggregation and selectively manipulate lysozyme phase behavior was investigated. The results revealed a strong pH dependency of the additive impact on lysozyme phase behavior, lysozyme solubility, crystal size and morphology. This work aims to link this pH dependent impact to a protein-specific parameter, the conformational stability of lysozyme. At pH 3 the addition of 10% (w/v) glycerol, 10% (w/v) PEG 1000, and 1 M glycine stabilized or destabilized lysozymes' native conformation resulting in a modified size of the crystallization area without influencing lysozyme solubility, crystal size and morphology. Addition of 1 M glycine even promoted non-native aggregation at pH 3 whereas addition of PEG 1000 completely inhibited non-native aggregation. At pH 5 the addition of 10% (w/v) glycerol, 10% (w/v) PEG 1000, and 1 M glycine did not influence lysozymes' native conformation, but strongly influenced the position of the crystallization area, lysozyme solubility, crystal size and morphology. The observed pH dependent impact of the additives could be linked to a differing lysozyme conformational stability in the binary systems without additives at pH 3 and pH 5. However, in any case lysozyme phase behavior could selectively be manipulated by addition of glycerol, PEG 1000 and glycine. Furthermore, at pH 5 crystal size and morphology could selectively be manipulated.

  14. The Use of Functional Communication Training without Additional Treatment Procedures in an Inclusive School Setting

    ERIC Educational Resources Information Center

    Casey, Sean D.; Merical, Cheryl L.

    2006-01-01

    Functional communication training (FCT) is an intervention frequently used for students with developmental disabilities to reduce problematic behaviors and to increase prosocial behaviors. This intervention appears to be very effective when the communication responses trained are matched to the function of the student's problematic behaviors. In…

  15. Embedding beyond electrostatics—The role of wave function confinement

    NASA Astrophysics Data System (ADS)

    Nâbo, Lina J.; Olsen, Jógvan Magnus Haugaard; Holmgaard List, Nanna; Solanko, Lukasz M.; Wüstner, Daniel; Kongsted, Jacob

    2016-09-01

    We study excited states of cholesterol in solution and show that, in this specific case, solute wave-function confinement is the main effect of the solvent. This is rationalized on the basis of the polarizable density embedding scheme, which in addition to polarizable embedding includes non-electrostatic repulsion that effectively confines the solute wave function to its cavity. We illustrate how the inclusion of non-electrostatic repulsion results in a successful identification of the intense π → π∗ transition, which was not possible using an embedding method that only includes electrostatics. This underlines the importance of non-electrostatic repulsion in quantum-mechanical embedding-based methods.

  16. Chemical characteristic and functional properties of arenga starch-taro (Colocasia esculanta L.) flour noodle with turmeric extracts addition

    NASA Astrophysics Data System (ADS)

    Ervika Rahayu N., H.; Ariani, Dini; Miftakhussolikhah, E., Maharani P.; Yudi, P.

    2017-01-01

    Arenga starch-taro (Colocasia esculanta L.) flour noodle is an alternative carbohydrate source made from 75% arenga starch and 25% taro flour, but it has a different color with commercial noodle product. The addition of natural color from turmeric may change the consumer preference and affect chemical characteristic and functional properties of noodle. This research aims to identify chemical characteristic and functional properties of arenga starch-taro flour noodle with turmeric extract addition. Extraction was performed using 5 variances of turmeric rhizome (0.06; 0.12; 0.18; 0.24; and 0.30 g (fresh weight/ml water). Then, noodle was made and chemical characteristic (proximate analysis) as well as functional properties (amylose, resistant starch, dietary fiber, antioxidant activity) were then evaluated. The result showed that addition of turmeric extract did not change protein, fat, carbohydrate, amylose, and resistant starch content significantly, while antioxidant activity was increased (23,41%) with addition of turmeric extract.

  17. Role of Micronutrients in Skin Health and Function

    PubMed Central

    Park, Kyungho

    2015-01-01

    Skin is the first line of defense for protecting our bodies against external perturbations, including ultraviolet (UV) irradiation, mechanical/chemical stress, and bacterial infection. Nutrition is one of many factors required for the maintenance of overall skin health. An impaired nutritional status alters the structural integrity and biological function of skin, resulting in an abnormal skin barrier. In particular, the importance of micronutrients (such as certain vitamins and minerals) for skin health has been highlighted in cell culture, animal, and clinical studies. These micronutrients are employed not only as active compounds in therapeutic agents for treating certain skin diseases, but also as ingredients in cosmetic products. Here, the author describes the barrier function of the skin and the general nutritional requirements for skin health. The goal of this review is to discuss the potential roles and current knowledge of selected micronutrients in skin health and function. PMID:25995818

  18. Role of micronutrients in skin health and function.

    PubMed

    Park, Kyungho

    2015-05-01

    Skin is the first line of defense for protecting our bodies against external perturbations, including ultraviolet (UV) irradiation, mechanical/chemical stress, and bacterial infection. Nutrition is one of many factors required for the maintenance of overall skin health. An impaired nutritional status alters the structural integrity and biological function of skin, resulting in an abnormal skin barrier. In particular, the importance of micronutrients (such as certain vitamins and minerals) for skin health has been highlighted in cell culture, animal, and clinical studies. These micronutrients are employed not only as active compounds in therapeutic agents for treating certain skin diseases, but also as ingredients in cosmetic products. Here, the author describes the barrier function of the skin and the general nutritional requirements for skin health. The goal of this review is to discuss the potential roles and current knowledge of selected micronutrients in skin health and function.

  19. Functional response of osteoblasts in functionally gradient titanium alloy mesh arrays processed by 3D additive manufacturing.

    PubMed

    Nune, K C; Kumar, A; Misra, R D K; Li, S J; Hao, Y L; Yang, R

    2017-02-01

    We elucidate here the osteoblasts functions and cellular activity in 3D printed interconnected porous architecture of functionally gradient Ti-6Al-4V alloy mesh structures in terms of cell proliferation and growth, distribution of cell nuclei, synthesis of proteins (actin, vinculin, and fibronectin), and calcium deposition. Cell culture studies with pre-osteoblasts indicated that the interconnected porous architecture of functionally gradient mesh arrays was conducive to osteoblast functions. However, there were statistically significant differences in the cellular response depending on the pore size in the functionally gradient structure. The interconnected porous architecture contributed to the distribution of cells from the large pore size (G1) to the small pore size (G3), with consequent synthesis of extracellular matrix and calcium precipitation. The gradient mesh structure significantly impacted cell adhesion and influenced the proliferation stage, such that there was high distribution of cells on struts of the gradient mesh structure. Actin and vinculin showed a significant difference in normalized expression level of protein per cell, which was absent in the case of fibronectin. Osteoblasts present on mesh struts formed a confluent sheet, bridging the pores through numerous cytoplasmic extensions. The gradient mesh structure fabricated by electron beam melting was explored to obtain fundamental insights on cellular activity with respect to osteoblast functions.

  20. Roles for oestrogen receptor β in adult brain function.

    PubMed

    Handa, R J; Ogawa, S; Wang, J M; Herbison, A E

    2012-01-01

    Oestradiol exerts a profound influence upon multiple brain circuits. For the most part, these effects are mediated by oestrogen receptor (ER)α. We review here the roles of ERβ, the other ER isoform, in mediating rodent oestradiol-regulated anxiety, aggressive and sexual behaviours, the control of gonadotrophin secretion, and adult neurogenesis. Evidence exists for: (i) ERβ located in the paraventricular nucleus underpinning the suppressive influence of oestradiol on the stress axis and anxiety-like behaviour; (ii) ERβ expressed in gonadotrophin-releasing hormone neurones contributing to oestrogen negative-feedback control of gonadotrophin secretion; (iii) ERβ controlling the offset of lordosis behaviour; (iv) ERβ suppressing aggressive behaviour in males; (v) ERβ modulating responses to social stimuli; and (vi) ERβ in controlling adult neurogenesis. This review highlights two major themes; first, ERβ and ERα are usually tightly inter-related in the oestradiol-dependent control of a particular brain function. For example, even though oestradiol feedback to control reproduction occurs principally through ERα-dependent mechanisms, modulatory roles for ERβ also exist. Second, the roles of ERα and ERβ within a particular neural network may be synergistic or antagonistic. Examples of the latter include the role of ERα to enhance, and ERβ to suppress, anxiety-like and aggressive behaviours. Splice variants such as ERβ2, acting as dominant negative receptors, are of further particular interest because their expression levels may reflect preceeding oestradiol exposure of relevance to oestradiol replacement therapy. Together, this review highlights the predominant modulatory, but nonetheless important, roles of ERβ in mediating the many effects of oestradiol upon adult brain function.

  1. Learning and Recovering Additive and Multiplicative Value Functions: A Criterion Validation of Multiattribute Utility Techniques

    DTIC Science & Technology

    1982-12-01

    multiattribute value functions. Operations Research, 1979, 27, 810-822. Fishburn, P. Utility theory for decision making. New York: Wiley, 1970...Psychology, 1980, 21, 66-82. v. Winterfeldt, D. and Fischer, G.W. Multiattribute utility theory : models and assessment procedres. In D. Wendt and...plicative value functions: A criterion _____________ validation of multiattribute utility 6. 7EPPORMING ONG. RgPeR? NUgMBER techn iclues 82-1 AijWOR*JS

  2. Changes of soil bacterial activities and functions after different N additions in a temperate forest.

    PubMed

    Guo, Peng; Han, Tiwen; Zhang, Li; Li, Shushan; Ma, Dongzhu; Du, Yuhan

    2017-02-01

    It has been shown that different nitrogen (N) addition led to various influences on soil microbial activities in forest ecosystems; however, the changes of bacteria were still unclear. In this work, inorganic N (NH4NO3) and organic N (urea and glycine) were fertilized with different ratios (5:0, 1:4, 3:2, 2:3, and 1:4) on temperate forest soils, while fungicide (cycloheximide) was simultaneously added on half of each treatment to inhibit fungal activities (leaving only bacteria). After a 3-year field experiment, soil samples were harvested, then microbial enzymatic activities involved in carbon (C), and N and phosphorus (P) cycles were determined. Under laboratory conditions, four purified bacteria which were isolated from sample site had been inoculated in sterilized soils under different N types and enzymatic activities were assayed after 90-day incubation. The results showed that cellulase and polyphenol oxidase activities of non-fungicide-added treatments increased after N addition and greater organic N accelerated the increases. However, these enzymatic activities of fungicide-added treatments were not significantly influenced by N addition and N types. It may be due to the insufficient ability of bacteria to synthesize enough enzymes to decompose complex organic C (such as cellulose and lignin) into available compound, although N-limitation was alleviated. Alkaline phosphatase activities increased after N addition in both non-fungicide-added and fungicide-added treatments, and the acceleration on bacterial alkaline phosphatase activities was even greater. Furthermore, organic N showed at least 2.5 times promotion on bacteria alkaline phosphatase than those of inorganic N, which indicated greater alleviation of bacterial P-limitation after the addition of organic N. All the results indicated that soil bacteria may be seriously limited by soil available C but become the dominant decomposer of the complex P compounds after N addition, particularly greater

  3. Meaning and Function of Dummy Auxiliaries in Adult Acquisition of Dutch as an Additional Language

    ERIC Educational Resources Information Center

    Julien, Manuela; van Hout, Roeland; van de Craats, Ineke

    2016-01-01

    This article presents the results of experimental data on language production and comprehension. These show that adult learners of Dutch as an additional language, with different language backgrounds, and a L2 proficiency below level A2 (Waystage) of the Common European Framework of Reference for Languages (CEFR; Council of Europe, 2001), use…

  4. Molecular aspects of aromatic C additions to soils: Implications of biochar quality for ecosystem functionality

    EPA Science Inventory

    Solid residues of incomplete combustion (biochar or char) are continuously being added to soils due to natural vegetation fires in many ecosystems. However, new strategies for carbon sequestration in soils are likely to include the active addition of biochar to soils. Since bioc...

  5. [The roles and functions of volunteer counselors to the elderly].

    PubMed

    Chen, Chun-Yu

    2004-06-01

    In Taiwan's current counseling centers for the elderly, large numbers of volunteers are supervised by only a few social workers or nurses, so the roles and functions of these volunteers are very important. A neat summary of the services provided by the volunteers would include: (1) Direct services: telephone counseling, telephone interviewing, case handling, mail counseling, resource provision. (2) Indirect services: fundraising, supervision. (3) Administration: administrative assistance, management of institutional web sites. (4) Strategic consultancy: consultancy, provision of expertise. (5) Advocacy: service as educators and spokespersons; public relations and marketing. (6) MANAGEMENT: team leadership, plan implementation. To sum up, their functions are, by means of telephone and face-to-face contact, to provide information to the elderly about finances, medical services, housing, citizenship, the dignity of life and death, and related issues, as well as to serve as advocates for the provision of resources--such as educational courses--and to facilitate such provision. Indeed, the roles and functions of volunteer counselors become more diverse and more comprehensive by the day.

  6. Role for coronin 1 in mouse NK cell function.

    PubMed

    Tchang, Vincent Sam Yong; Stiess, Michael; Siegmund, Kerstin; Karrer, Urs; Pieters, Jean

    2017-02-01

    Coronin 1, a member of the evolutionary conserved WD repeat protein family of coronin proteins is expressed in all leukocytes, but a role for coronin 1 in natural killer (NK) cell homeostasis and function remains unclear. Here, we have analyzed the number and functionality of NK cells in the presence and absence of coronin 1. In coronin 1-deficient mice, absolute NK cell numbers and phenotype were comparable to wild type mice in blood, spleen and liver. Following in vitro stimulation of the activating NK cell receptors NK1.1, NKp46, Ly49D and NKG2D, coronin 1-deficient NK cells were functional with respect to interferon-γ production, degranulation and intracellular Ca(2+) mobilization. Also, both wild type as well as coronin 1-deficient NK cells showed comparable cytotoxic activity. Furthermore, activation and functionality of NK cells following Vesicular Stomatitis Virus (VSV) infection was similar between wild type and coronin 1-deficient mice. Taken together these data suggest that coronin 1 is dispensable for mouse NK cell homeostasis and function.

  7. Functional roles of CSPG4/NG2 in chondrosarcoma.

    PubMed

    Jamil, Nuor S M; Azfer, Asim; Worrell, Harrison; Salter, Donald M

    2016-04-01

    CSPG4/NG2 is a multifunctional transmembrane protein with limited distribution in adult tissues including articular cartilage. The purpose of this study was to investigate the possible roles of CSPG4/NG2 in chondrosarcomas and to establish whether this molecule may have potential for targeted therapy. Stable knock-down of CSPG4/NG2 in the JJ012 chondrosarcoma cell line by shRNA resulted in decreased cell proliferation and migration as well as a decrease in gene expression of the MMP (matrix metalloproteinase) 3 protease and ADAMTS4 (aggrecanase). Chondrosarcoma cells in which CSPG4/NG2 was knocked down were more sensitive to doxorubicin than wild-type cells. The results indicate that CSPG4/NG2 has roles in regulating chondrosarcoma cell function in relation to growth, spread and resistance to chemotherapy and that anti-CSPG4/NG2 therapies may have potential in the treatment of surgically unresectable chondrosarcoma.

  8. Emerging functional roles of nuclear receptors in breast cancer.

    PubMed

    Doan, Tram B; Graham, J Dinny; Clarke, Christine L

    2017-04-01

    Nuclear receptors (NRs) have been targets of intensive drug development for decades due to their roles as key regulators of multiple developmental, physiological and disease processes. In breast cancer, expression of the estrogen and progesterone receptor remains clinically important in predicting prognosis and determining therapeutic strategies. More recently, there is growing evidence supporting the involvement of multiple nuclear receptors other than the estrogen and progesterone receptors, in the regulation of various processes important to the initiation and progression of breast cancer. We review new insights into the mechanisms of action of NRs made possible by recent advances in genomic technologies and focus on the emerging functional roles of NRs in breast cancer biology, including their involvement in circadian regulation, metabolic reprogramming and breast cancer migration and metastasis.

  9. Addition of Functional Content during Core Content Instruction with Students with Moderate Disabilities

    ERIC Educational Resources Information Center

    Collins, Belva C.; Hager, Karen L.; Galloway, Carey Creech

    2011-01-01

    The purpose of this investigation was to add functional content during core content instruction of language arts, science, and math. The investigation involved three middle school students with moderate disabilities who participated in the state's alternate assessment. During instruction using a constant time delay procedure to teach required…

  10. Addition of azomethine ylides to C[sub 60]. Synthesis, characterization, and functionalization of fullerene pyrrolidines

    SciTech Connect

    Maggini, M.; Scorrano, G. ); Prato, M. )

    1993-10-20

    We report herein a new and very general fullerene functionalization, based on the 1,3-dipolar cycloaddition of azomethine ylides to C[sub 60]. Azomethine ylides, planar species of general formula (R[sup 1]R[sup 2])-C=N[sup +](R[sup 3]) - C[sup [minus

  11. Using Additional Analyses to Clarify the Functions of Problem Behavior: An Analysis of Two Cases

    ERIC Educational Resources Information Center

    Payne, Steven W.; Dozier, Claudia L.; Neidert, Pamela L.; Jowett, Erica S.; Newquist, Matthew H.

    2014-01-01

    Functional analyses (FA) have proven useful for identifying contingencies that influence problem behavior. Research has shown that some problem behavior may only occur in specific contexts or be influenced by multiple or idiosyncratic variables. When these contexts or sources of influence are not assessed in an FA, further assessment may be…

  12. Organocatalyzed cascade aza-Michael/Michael addition for the asymmetric construction of highly functionalized spiropyrazolone tetrahydroquinolines.

    PubMed

    Li, Jun-Hua; Du, Da-Ming

    2014-11-01

    An organocatalyzed diastereo- and enantioselective cascade aza-Michael/Michael addition of 2-tosylaminoenones to unsaturated pyrazolones has been developed to afford novel chiral spiropyrazolone tetrahydroquinolines containing three contiguous stereocenters. This cascade reaction proceeded well with 2 mol% chiral bifunctional tertiary amine squaramide catalyst to give the desired products in excellent yields (up to 99%) with excellent diastereoselectivity (up to >25:1 diastereomeric ratio) and high enantioselectivity (up to 91% enantiomeric excess).

  13. Metal-Catalyzed β-Functionalization of Michael Acceptors through Reductive Radical Addition Reactions.

    PubMed

    Streuff, Jan; Gansäuer, Andreas

    2015-11-23

    Transition-metal-catalyzed radical reactions are becoming increasingly important in modern organic chemistry. They offer fascinating and unconventional ways for connecting molecular fragments that are often complementary to traditional methods. In particular, reductive radical additions to α,β-unsaturated compounds have recently gained substantial attention as a result of their broad applicability in organic synthesis. This Minireview critically discusses the recent landmark achievements in this field in context with earlier reports that laid the foundation for today's developments.

  14. Oxalic acid has an additional, detoxifying function in Sclerotinia sclerotiorum pathogenesis.

    PubMed

    Heller, Annerose; Witt-Geiges, Tanja

    2013-01-01

    The mechanism of the diseases caused by the necrotroph plant pathogen Sclerotinia sclerotiorum is not well understood. To investigate the role of oxalic acid during infection high resolution, light-, scanning-, transmission electron microscopy and various histochemical staining methods were used. Our inoculation method allowed us to follow degradation of host plant tissue around single hyphae and to observe the reaction of host cells in direct contact with single invading hyphae. After penetration the outer epidermal cell wall matrix appeared degraded around subcuticular hyphae (12-24 hpi). Calcium oxalate crystals were detected in advanced (36-48 hpi) and late (72 hpi) infection stages, but not in early stages. In early infection stages, surprisingly, no toxic effect of oxalic acid eventually secreted by S. sclerotiorum was observed. As oxalic acid is a common metabolite in plants, we propose that attacked host cells are able to metabolize oxalic acid in the early infection stage and translocate it to their vacuoles where it is stored as calcium oxalate. The effects, observed on healthy tissue upon external application of oxalic acid to non-infected, living tissue and cell wall degradation of dead host cells starting at the inner side of the walls support this idea. The results indicate that oxalic acid concentrations in the early stage of infection stay below the toxic level. In plant and fungi oxalic acid/calcium oxalate plays an important role in calcium regulation. Oxalic acid likely could quench calcium ions released during cell wall breakdown to protect growing hyphae from toxic calcium concentrations in the infection area. As calcium antimonate-precipitates were found in vesicles of young hyphae, we propose that calcium is translocated to the older parts of hyphae and detoxified by building non-toxic, stable oxalate crystals. We propose an infection model where oxalic acid plays a detoxifying role in late infection stages.

  15. Effects of resource addition on recovery of production and plant functional composition in degraded semiarid grasslands.

    PubMed

    Chen, Qing; Hooper, David U; Li, Hui; Gong, Xiao Ying; Peng, Fei; Wang, Hong; Dittert, Klaus; Lin, Shan

    2017-02-28

    Degradation of semiarid ecosystems from overgrazing threatens a variety of ecosystem services. Rainfall and nitrogen commonly co-limit production in semiarid grassland ecosystems; however, few studies have reported how interactive effects of precipitation and nitrogen addition influence the recovery of grasslands degraded by overgrazing. We conducted a 6-year experiment manipulating precipitation (natural precipitation and simulated wet year precipitation) and nitrogen (0, 25 and 50 kg N ha(-1)) addition at two sites with different histories of livestock grazing (moderately and heavily grazed) in Inner Mongolian steppe. Our results suggest that recovery of plant community composition and recovery of production can be decoupled. Perennial grasses provide long-term stability of high-quality forage production in this system. Supplemental water combined with exclosures led, in the heavily grazed site, to the strongest recovery of perennial grasses, although widespread irrigation of rangeland is not a feasible management strategy in many semiarid and arid regions. N fertilization combined with exclosures, but without water addition, increased dominance of unpalatable annual species, which in turn retarded growth of perennial species and increased inter-annual variation in primary production at both sites. Alleviation of grazing pressure alone allowed recovery of desired perennial species via successional processes in the heavily grazed site. Our experiments suggest that recovery of primary production and desirable community composition are not necessarily correlated. The use of N fertilization for the management of overgrazed grassland needs careful and systematic evaluation, as it has potential to impede, rather than aid, recovery.

  16. Covariant density functional theory: The role of the pion

    SciTech Connect

    Lalazissis, G. A.; Karatzikos, S.; Serra, M.; Otsuka, T.; Ring, P.

    2009-10-15

    We investigate the role of the pion in covariant density functional theory. Starting from conventional relativistic mean field (RMF) theory with a nonlinear coupling of the {sigma} meson and without exchange terms we add pions with a pseudovector coupling to the nucleons in relativistic Hartree-Fock approximation. In order to take into account the change of the pion field in the nuclear medium the effective coupling constant of the pion is treated as a free parameter. It is found that the inclusion of the pion to this sort of density functionals does not destroy the overall description of the bulk properties by RMF. On the other hand, the noncentral contribution of the pion (tensor coupling) does have effects on single particle energies and on binding energies of certain nuclei.

  17. Role of topology in complex functional networks of beta cells

    NASA Astrophysics Data System (ADS)

    Cherubini, Christian; Filippi, Simonetta; Gizzi, Alessio; Loppini, Alessandro

    2015-10-01

    The activity of pancreatic β cells can be described by biological networks of coupled nonlinear oscillators that, via electrochemical synchronization, release insulin in response to augmented glucose levels. In this work, we analyze the emergent behavior of regular and percolated β -cells clusters through a stochastic mathematical model where "functional" networks arise. We show that the emergence and robustness of the synchronized dynamics depend both on intrinsic and extrinsic parameters. In particular, cellular noise level, glucose concentration, network spatial architecture, and cell-to-cell coupling strength are the key factors for the generation of a rhythmic and robust activity. Their role in the functional network topology associated with β -cells clusters is analyzed and discussed.

  18. Functional Gustatory Role of Chemoreceptors in Drosophila Wings.

    PubMed

    Raad, Hussein; Ferveur, Jean-François; Ledger, Neil; Capovilla, Maria; Robichon, Alain

    2016-05-17

    Neuroanatomical evidence argues for the presence of taste sensilla in Drosophila wings; however, the taste physiology of insect wings remains hypothetical, and a comprehensive link to mechanical functions, such as flight, wing flapping, and grooming, is lacking. Our data show that the sensilla of the Drosophila anterior wing margin respond to both sweet and bitter molecules through an increase in cytosolic Ca(2+) levels. Conversely, genetically modified flies presenting a wing-specific reduction in chemosensory cells show severe defects in both wing taste signaling and the exploratory guidance associated with chemodetection. In Drosophila, the chemodetection machinery includes mechanical grooming, which facilitates the contact between tastants and wing chemoreceptors, and the vibrations of flapping wings that nebulize volatile molecules as carboxylic acids. Together, these data demonstrate that the Drosophila wing chemosensory sensilla are a functional taste organ and that they may have a role in the exploration of ecological niches.

  19. Function of osteocytes in bone--their role in mechanotransduction.

    PubMed

    Burger, E H; Klein-Nulend, J; van der Plas, A; Nijweide, P J

    1995-07-01

    Although osteocytes are by far the most abundant cell type of bone, they are least understood in terms of function and regulation. Previous studies have concentrated on their possible role as mobilizers of bone calcium, via the process of osteocytic osteolysis. Currently, however, their possible involvement in mechanical adaptation, the process whereby bone tissue maintains maximal functional strength with minimal bone mass, is discussed. We have recently obtained experimental evidence that osteocytes are the mechanosensory cells of bone, involved in the transduction of mechanical loads into biochemical signals. Our results support the hypothesis that flow of fluid through the lacunar-canalicular system as a result of loading provides the physical signal that activates the cells.

  20. The Functional Role of the Periphery in Emotional Language Comprehension

    PubMed Central

    Havas, David A.; Matheson, James

    2013-01-01

    Language can impact emotion, even when it makes no reference to emotion states. For example, reading sentences with positive meanings (“The water park is refreshing on the hot summer day”) induces patterns of facial feedback congruent with the sentence emotionality (smiling), whereas sentences with negative meanings induce a frown. Moreover, blocking facial afference with botox selectively slows comprehension of emotional sentences. Therefore, theories of cognition should account for emotion-language interactions above the level of explicit emotion words, and the role of peripheral feedback in comprehension. For this special issue exploring frontiers in the role of the body and environment in cognition, we propose a theory in which facial feedback provides a context-sensitive constraint on the simulation of actions described in language. Paralleling the role of emotions in real-world behavior, our account proposes that (1) facial expressions accompany sudden shifts in wellbeing as described in language; (2) facial expressions modulate emotional action systems during reading; and (3) emotional action systems prepare the reader for an effective simulation of the ensuing language content. To inform the theory and guide future research, we outline a framework based on internal models for motor control. To support the theory, we assemble evidence from diverse areas of research. Taking a functional view of emotion, we tie the theory to behavioral and neural evidence for a role of facial feedback in cognition. Our theoretical framework provides a detailed account that can guide future research on the role of emotional feedback in language processing, and on interactions of language and emotion. It also highlights the bodily periphery as relevant to theories of embodied cognition. PMID:23750145

  1. Addition theorem of Slater type orbitals: a numerical evaluation of Barnett Coulson/Löwdin functions

    NASA Astrophysics Data System (ADS)

    Bouferguene, Ahmed

    2005-04-01

    When using the one-centre two-range expansion method to evaluate multicentre integrals over Slater type orbitals (STOs), it may become necessary to compute numerical values of the corresponding Fourier coefficients, also known as Barnett-Coulson/Löwdin Functions (BCLFs) (Bouferguene and Jones 1998 J. Chem. Phys. 109 5718). To carry out this task, it is crucial to not only have a stable numerical procedure but also a fast algorithm. In previous work (Bouferguene and Rinaldi 1994 Int. J. Quantum Chem. 50 21), BCLFs were represented by a double integral which led to a numerically stable algorithm but this turned out to be disappointingly time consuming. The present work aims at exploring another path in which BCLFs are represented either by an infinite series involving modified Bessel functions {\\bf K}_{\

  2. Functional roles affect diversity-succession relationships for boreal beetles.

    PubMed

    Gibb, Heloise; Johansson, Therese; Stenbacka, Fredrik; Hjältén, Joakim

    2013-01-01

    Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of "functional" groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species). We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists) responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies). Species associated with microhabitats that accumulate with succession (fungi and dead wood) thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience.

  3. "Hotheaded": the role OF TRPV1 in brain functions.

    PubMed

    Martins, D; Tavares, I; Morgado, C

    2014-10-01

    The TRPV1 (vanilloid 1) channel is best known for its role in sensory transmission in the nociceptive neurons of the peripheral nervous system. Although first studied in the dorsal root ganglia as the receptor for capsaicin, TRPV1 has been recently recognized to have a broader distribution in the central nervous system, where it is likely to constitute an atypical neurotransmission system involved in several functions through modulation of both neuronal and glial activities. The endovanilloid-activated brain TRPV1 channels seem to be involved in somatosensory, motor and visceral functions. Recent studies suggested that TRPV1 channels also account for more complex functions, as addiction, anxiety, mood and cognition/learning. However, more studies are needed before the relevance of TRPV1 in brain activity can be clearly stated. This review highlights the increasing importance of TRPV1 as a regulator of brain function and discusses possible bases for the future development of new therapeutic approaches that by targeting brain TRPV1 receptors might be used for the treatment of several neurological disorders.

  4. Movement dynamics reflect a functional role for weak coupling and role structure in dyadic problem solving.

    PubMed

    Abney, Drew H; Paxton, Alexandra; Dale, Rick; Kello, Christopher T

    2015-11-01

    Successful interaction requires complex coordination of body movements. Previous research has suggested a functional role for coordination and especially synchronization (i.e., time-locked movement across individuals) in different types of human interaction contexts. Although such coordination has been shown to be nearly ubiquitous in human interaction, less is known about its function. One proposal is that synchrony supports and facilitates communication (Topics Cogn Sci 1:305-319, 2009). However, questions still remain about what the properties of coordination for optimizing communication might look like. In the present study, dyads worked together to construct towers from uncooked spaghetti and marshmallows. Using cross-recurrence quantification analysis, we found that dyads with loosely coupled gross body movements performed better, supporting recent work suggesting that simple synchrony may not be the key to effective performance (Riley et al. 2011). We also found evidence that leader-follower dynamics-when sensitive to the specific role structure of the interaction-impact task performance. We discuss our results with respect to the functional role of coordination in human interaction.

  5. On the Role of Additional [4Fe-4S] Clusters with a Free Coordination Site in Radical-SAM Enzymes

    PubMed Central

    Mulliez, Etienne; Duarte, Victor; Arragain, Simon; Fontecave, Marc; Atta, Mohamed

    2017-01-01

    The canonical CysXXXCysXXCys motif is the hallmark of the Radical-SAM superfamily. This motif is responsible for the ligation of a [4Fe-4S] cluster containing a free coordination site available for SAM binding. The five enzymes MoaA, TYW1, MiaB, RimO and LipA contain in addition a second [4Fe-4S] cluster itself bound to three other cysteines and thus also displaying a potentially free coordination site. This review article summarizes recent important achievements obtained on these five enzymes with the main focus to delineate the role of this additional [4Fe-4S] cluster in catalysis. PMID:28361051

  6. The functional role of platelets in the regulation of angiogenesis.

    PubMed

    Walsh, Tony G; Metharom, Pat; Berndt, Michael C

    2015-01-01

    Functionally, platelets are primarily recognized as key regulators of thrombosis and hemostasis. Upon vessel injury, the typically quiescent platelet interacts with subendothelial matrix to regulate platelet adhesion, activation and aggregation, with subsequent induction of the coagulation cascade forming a thrombus. Recently, however, newly described roles for platelets in the regulation of angiogenesis have emerged. Platelets possess an armory of pro- and anti-angiogenic proteins, which are actively sequestered and highly organized in α-granule populations. Platelet activation facilitates their release, eliciting potent angiogenic responses through mechanisms that appear to be tightly regulated. In conjunction, the release of platelet-derived phospholipids and microparticles has also earned merit as synergistic regulators of angiogenesis. Consequently, platelets have been functionally implicated in a range of angiogenesis-dependent processes, including physiological roles in wound healing, vascular development and blood/lymphatic vessel separation, whilst facilitating aberrant angiogenesis in a range of diseases including cancer, atherosclerosis and diabetic retinopathy. Whilst the underlying mechanisms are only starting to be elucidated, significant insights have been established, suggesting that platelets represent a promising therapeutic strategy in diseases requiring angiogenic modulation. Moreover, anti-platelet therapies targeting thrombotic complications also exert protective effects in disorders characterized by persistent angiogenesis.

  7. Cytokines and macrophage function in humans - role of stress

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald (Principal Investigator)

    1996-01-01

    We have begun this study to commence the determination of the role of mild chronic stress in the effects of space flight on macrophage/monocyte function, a component of the immune response. Medical students undergoing regular periods of stress and relaxation have been shown to be an excellent model for determining the effects of stress on immune responses. We have begun using this model using the macrophage/monocyte as model leukocyte. The monocyte/macrophage plays a central role in immunoregulation. The studies to be included in this three year project are the effects of stress on: (1) interactions of monocytes with microbes, (2) monocyte production of cytokines, (3) monocyte phagocytosis and activity, and (4) monocyte expression of cell surface antigens important in immune responses. Stress hormone levels will also be carried out to determine if there is a correlation between stress effects on immune responses and hormonal levels. Psychological testing to insure subjects are actually stressed or relaxed at the time of testing will also be carried out. The results obtained from the proposed studies should be comparable with space flight studies with whole animals and isolated cell cultures. When complete this study should allow the commencement of the establishment of the role of stress as one compartment of the induction of immune alterations by space flight.

  8. Signaling mechanisms and functional roles of cofilin phosphorylation and dephosphorylation.

    PubMed

    Mizuno, Kensaku

    2013-02-01

    Cofilin and actin-depolymerizing factor (ADF) are actin-binding proteins that play an essential role in regulating actin filament dynamics and reorganization by stimulating the severance and depolymerization of actin filaments. Cofilin/ADF are inactivated by phosphorylation at the serine residue at position 3 by LIM-kinases (LIMKs) and testicular protein kinases (TESKs) and are reactivated by dephosphorylation by the slingshot (SSH) family of protein phosphatases and chronophin. This review describes recent advances in our understanding of the signaling mechanisms regulating LIMKs and SSHs and the functional roles of cofilin phospho-regulation in cell migration, tumor invasion, mitosis, neuronal development, and synaptic plasticity. Accumulating evidence demonstrates that the phospho-regulation of cofilin/ADF is a key convergence point of cell signaling networks that link extracellular stimuli to actin cytoskeletal dynamics and that spatiotemporal control of cofilin/ADF activity by LIMKs and SSHs plays a crucial role in a diverse array of cellular and physiological processes. Perturbations in the normal control of cofilin/ADF activity underlie many pathological conditions, including cancer metastasis and neurological and cardiovascular disorders.

  9. The growing family of photoactive yellow proteins and their presumed functional roles.

    PubMed

    Meyer, T E; Kyndt, J A; Memmi, S; Moser, T; Colón-Acevedo, B; Devreese, B; Van Beeumen, J J

    2012-10-01

    For several years following the discovery and characterization of the first PYP, from Halorhodospira halophila, it was thought that this photoactive protein was quite unique, notwithstanding the isolation of two additional examples in rapid succession. Mainly because of genomic and metagenomic analyses, we have now learned that more than 140 PYP genes occur in a wide variety of bacteria and metabolic niches although the protein has not been isolated in most cases. The amino acid sequences and physical properties permit their organization into at least seven groups that are also likely to be functionally distinct. Based upon action spectra and the wavelength of maximum absorbance, it was speculated nearly 20 years ago but never proven that Hr. halophila PYP was involved in phototaxis. Nevertheless, in only one instance has the functional role and interaction partner for a PYP been experimentally proven, in Rs. centenum Ppr. Genetic context is one of several types of evidence indicating that PYP is potentially involved in a number of diverse functional roles. The interaction with other sensors to modulate their activity stands out as the single most prominent role for PYP. In this review, we have attempted to summarize the evidence for the functional roles and interaction partners for some 26 of the 35 named species of PYP, which should be considered the basis for further focused molecular and biochemical research.

  10. Longitudinal functional additive model with continuous proportional outcomes for physical activity data.

    PubMed

    Li, Haocheng; Kozey-Keadle, Sarah; Kipnis, Victor; Carroll, Raymond J

    2016-01-01

    Motivated by physical activity data obtained from the BodyMedia FIT device (www.bodymedia.com), we take a functional data approach for longitudinal studies with continuous proportional outcomes. The functional structure depends on three factors. In our three-factor model, the regression structures are specified as curves measured at various factor-points with random effects that have a correlation structure. The random curve for the continuous factor is summarized using a few important principal components. The difficulties in handling the continuous proportion variables are solved by using a quasilikelihood type approximation. We develop an efficient algorithm to fit the model, which involves the selection of the number of principal components. The method is evaluated empirically by a simulation study. This approach is applied to the BodyMedia data with 935 males and 84 consecutive days of observation, for a total of 78, 540 observations. We show that sleep efficiency increases with increasing physical activity, while its variance decreases at the same time.

  11. Multivariate sequence analysis reveals additional function impacting residues in the SDR superfamily.

    PubMed

    Tiwari, Pratibha; Singh, Noopur; Dixit, Aparna; Choudhury, Devapriya

    2014-10-01

    The "extended" type of short chain dehydrogenases/reductases (SDR), share a remarkable similarity in their tertiary structures inspite of being highly divergent in their functions and sequences. We have carried out principal component analysis (PCA) on structurally equivalent residue positions of 10 SDR families using information theoretic measures like Jensen-Shannon divergence and average shannon entropy as variables. The results classify residue positions in the SDR fold into six groups, one of which is characterized by low Shannon entropies but high Jensen-Shannon divergence against the reference family SDR1E, suggesting that these positions are responsible for the specific functional identities of individual SDR families, distinguishing them from the reference family SDR1E. Site directed mutagenesis of three residues from this group in the enzyme UDP-Galactose 4-epimerase belonging to SDR1E shows that the mutants promote the formation of NADH containing abortive complexes. Finally, molecular dynamics simulations have been used to suggest a mechanism by which the mutants interfere with the re-oxidation of NADH leading to the formation of abortive complexes.

  12. Titanium-Based Hip Stems with Drug Delivery Functionality through Additive Manufacturing.

    PubMed

    Bezuidenhout, Martin B; Dimitrov, Dimitar M; van Staden, Anton D; Oosthuizen, Gert A; Dicks, Leon M T

    2015-01-01

    Postoperative infections are a major concern in patients that receive implants. These infections generally occur in areas with poor blood flow and pathogens do not always respond to antibiotic treatment. With the latest developments in nanotechnology, the incorporation of antibiotics into prosthetic implants may soon become a standard procedure. The success will, however, depend on the ability to control the release of antibiotics at concentrations high enough to prevent the development of antibiotic-resistant strains. Through additive manufacturing, antibiotics can be incorporated into cementless femoral stems to produce prosthetic devices with antimicrobial properties. With the emerging increase in resistance to antibiotics, the incorporation of antimicrobial compounds other than antibiotics, preferably drugs with a broader spectrum of antimicrobial activity, will have to be explored. This review highlights the microorganisms associated with total hip arthroplasty (THA), discusses the advantages and disadvantages of the latest materials used in hip implants, compares different antimicrobial agents that could be incorporated, and addresses novel ideas for future research.

  13. Functional Roles Affect Diversity-Succession Relationships for Boreal Beetles

    PubMed Central

    Gibb, Heloise; Johansson, Therese; Stenbacka, Fredrik; Hjältén, Joakim

    2013-01-01

    Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of “functional” groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species). We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists) responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies). Species associated with microhabitats that accumulate with succession (fungi and dead wood) thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience. PMID:23977350

  14. Organic-inorganic hybrid foams with diatomite addition: Effect on functional properties

    NASA Astrophysics Data System (ADS)

    Verdolotti, L.; D'Auria, M.; Lavorgna, M.; Vollaro, P.; Iannace, S.; Capasso, I.; Galzerano, B.; Caputo, D.; Liguori, B.

    2016-05-01

    Organic-inorganic hybrid foams were prepared by using metakaolin, diatomite as a partial (or total) replacement of metakaolin, as matrix, silicon and whipped protein as pore forming. The foamed systems were hardened at defined temperature and time and then characterized by mechanical point of view through compression tests and by functional point of view through fire reaction and acoustic tests. The experimental findings highlighted that the replacement of diatomite in the formulation affected the morphological structure of the foams and consequently their mechanical properties. In particular, the consolidation mechanism in the diatomite based-hybrid foams changed from geopolymerization to a silicate polycondensation mechanism. Therefore, mechanical performances enhanced with increasing of the diatomite content. Fire reaction tests, such as non-combustibility and cone calorimeter tests, showed positive thermal inertia of samples regardless of the content of diatomite.

  15. Synthesis of highly functionalized chiral 3,3'-disubstituted oxindoles via an organocatalytic enantioselective Michael addition of nitroalkanes to indolylidenecyanoacetates.

    PubMed

    Liu, Lu; Wu, Deyan; Zheng, Shu; Li, Tengfei; Li, Xiangmin; Wang, Sinan; Li, Jian; Li, Hao; Wang, Wei

    2012-01-06

    An efficient bifunctional cinchona alkaloid derived thiourea-promoted enantioselective conjugate addition of nitroalkanes to indolylidenecyanoacetates has been developed under neat conditions. The process leads to synthetically interesting densely functionalized 3,3'-disubstituted oxindoles with creation of up to three stereogenic centers.

  16. Catalytic asymmetric tandem Friedel-Crafts alkylation/Michael addition reaction for the synthesis of highly functionalized chromans.

    PubMed

    Peng, Jiahuan; Du, Da-Ming

    2013-01-01

    The enantioselective tandem Friedel-Crafts alkylation/Michael addition reaction of indoles with nitroolefin enoates catalyzed by a diphenylamine-linked bis(oxazoline)-Zn(OTf)2 complex was investigated. This tandem reaction afforded functionalized chiral chromans in good yields with moderate to high stereoselectivities (up to 95:5 dr, up to 99% ee).

  17. Mesoporous Titania Powders: The Role of Precursors, Ligand Addition and Calcination Rate on Their Morphology, Crystalline Structure and Photocatalytic Activity

    PubMed Central

    Masolo, Elisabetta; Meloni, Manuela; Garroni, Sebastiano; Mulas, Gabriele; Enzo, Stefano; Baró, Maria Dolors; Rossinyol, Emma; Rzeszutek, Agnieszka; Herrmann-Geppert, Iris; Pilo, Maria

    2014-01-01

    We evaluate the influence of the use of different titania precursors, calcination rate, and ligand addition on the morphology, texture and phase content of synthesized mesoporous titania samples, parameters which, in turn, can play a key role in titania photocatalytic performances. The powders, obtained through the evaporation-induced self-assembly method, are characterized by means of ex situ X-Ray Powder Diffraction (XRPD) measurements, N2 physisorption isotherms and transmission electron microscopy. The precursors are selected basing on two different approaches: the acid-base pair, using TiCl4 and Ti(OBu)4, and a more classic route with Ti(OiPr)4 and HCl. For both precursors, different specimens were prepared by resorting to different calcination rates and with and without the addition of acetylacetone, that creates coordinated species with lower hydrolysis rates, and with different calcination rates. Each sample was employed as photoanode and tested in the water splitting reaction by recording I-V curves and comparing the results with commercial P25 powders. The complex data framework suggests that a narrow pore size distribution, due to the use of acetylacetone, plays a major role in the photoactivity, leading to a current density value higher than that of P25. PMID:28344237

  18. The role of connexins in ear and skin physiology - functional insights from disease-associated mutations.

    PubMed

    Xu, Ji; Nicholson, Bruce J

    2013-01-01

    Defects in several different connexins have been associated with several different diseases. The most common of these is deafness, where a few mutations in connexin (Cx) 26 have been found to contribute to over 50% of the incidence of non-syndromic deafness in different human populations. Other mutations in Cx26 or Cx30 have also been associated with various skin phenotypes linked to deafness (palmoplanta keratoderma, Bart-Pumphrey syndrome, Vohwinkel syndrome, keratitis-ichthyosis-deafness syndrome, etc.). The large array of disease mutants offers unique opportunities to gain insights into the underlying function of gap junction proteins and their channels in the normal and pathogenic physiologies of the cochlea and epidermis. This review focuses on those mutants where the impact on channel function has been assessed, and correlated with the disease phenotype, or organ function in knock-out mouse models. These approaches have provided evidence supporting a role of gap junctions and hemichannels in K(+) removal and recycling in the ear, as well as possible roles for nutrient passage, in the cochlea. In contrast, increases in hemichannel opening leading to increased cell death, were associated with several keratitis-ichthyosis-deafness syndrome skin disease/hearing mutants. In addition to providing clues for therapeutic strategies, these findings allow us to better understand the specific functions of connexin channels that are important for normal tissue function. This article is part of a Special Issue entitled: The communicating junctions, roles and dysfunctions.

  19. Urothelial function reconsidered: A role in urinary protein secretion

    PubMed Central

    Deng, Fang-Ming; Ding, Mingxiao; Lavker, Robert M.; Sun, Tung-Tien

    2001-01-01

    Mammalian bladder epithelium functions as an effective permeability barrier. We demonstrate here that this epithelium can also function as a secretory tissue directly involved in modifying urinary protein composition. Our data indicate that normal bovine urothelium synthesizes, as its major differentiation products, two well-known proteases: tissue-type plasminogen activator and urokinase, as well as a serine protease inhibitor, PP5. Moreover, we demonstrate that the urothelium secretes these proteins in a polarized fashion into the urine via a cAMP- and calcium-regulated pathway. Urinary plasminogen activators of ruminants are therefore urothelium derived rather then kidney derived as in some other species; this heterogeneity may have evolved in response to different physiological or dietary factors. In conjunction with our recent finding that transgenic mouse urothelium can secrete ectopically expressed human growth hormone into the urine, our data establish that normal mammalian urothelium can function not only as a permeability barrier but also as a secretor of urinary proteins that can play physiological or pathological roles in the urinary tract. PMID:11136252

  20. A functional role for EGFR signaling in myelination and remyelination.

    PubMed

    Aguirre, Adan; Dupree, Jeff L; Mangin, J M; Gallo, Vittorio

    2007-08-01

    Cellular strategies for oligodendrocyte regeneration and remyelination involve characterizing endogenous neural progenitors that are capable of generating oligodendrocytes during normal development and after demyelination, and identifying the molecular signals that enhance oligodendrogenesis from these progenitors. Using both gain- and loss-of-function approaches, we explored the role of epidermal growth factor receptor (EGFR) signaling in adult myelin repair and in oligodendrogenesis. We show that 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) promoter-driven overexpression of human EGFR (hEGFR) accelerated remyelination and functional recovery following focal demyelination of mouse corpus callosum. Lesion repopulation by Cspg4+ (also known as NG2) Ascl1+ (also known as Mash1) Olig2+ progenitors and functional remyelination were accelerated in CNP-hEGFR mice compared with wild-type mice. EGFR overexpression in subventricular zone (SVZ) and corpus callosum during early postnatal development also expanded this NG2+Mash1+Olig2+ progenitor population and promoted SVZ-to-lesion migration, enhancing oligodendrocyte generation and axonal myelination. Analysis of hypomorphic EGFR-mutant mice confirmed that EGFR signaling regulates oligodendrogenesis and remyelination by NG2+Mash1+Olig2+ progenitors. EGFR targeting holds promise for enhancing oligodendrocyte regeneration and myelin repair.

  1. Role of cysteines in mammalian VDAC isoforms' function.

    PubMed

    De Pinto, Vito; Reina, Simona; Gupta, Ankit; Messina, Angela; Mahalakshmi, Radhakrishnan

    2016-08-01

    In this mini-review, we analyze the influence of cysteines in the structure and activity of mitochondrial outer membrane mammalian VDAC isoforms. The three VDAC isoforms show conserved sequences, similar structures and the same gene organization. The meaning of three proteins encoded in different chromosomes must thus be searched for subtle differences at the amino acid level. Among others, cysteine content is noticeable. In humans, VDAC1 has 2, VDAC2 has 9 and VDAC3 has 6 cysteines. Recent works have shown that, at variance from VDAC1, VDAC2 and VDAC3 exhibit cysteines predicted to protrude towards the intermembrane space, making them a preferred target for oxidation by ROS. Mass spectrometry in VDAC3 revealed that a disulfide bridge can be formed and other cysteine oxidations are also detectable. Both VDAC2 and VDAC3 cysteines were mutagenized to highlight their role in vitro and in complementation assays in Δporin1 yeast. Chemico-physical techniques revealed an important function of cysteines in the structural stabilization of the pore. In conclusion, the works available on VDAC cysteines support the notion that the three proteins are paralogs with a similar pore-function and slightly different, but important, ancillary biological functions. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.

  2. Titanium-Based Hip Stems with Drug Delivery Functionality through Additive Manufacturing

    PubMed Central

    Bezuidenhout, Martin B.; Dimitrov, Dimitar M.; van Staden, Anton D.; Oosthuizen, Gert A.; Dicks, Leon M. T.

    2015-01-01

    Postoperative infections are a major concern in patients that receive implants. These infections generally occur in areas with poor blood flow and pathogens do not always respond to antibiotic treatment. With the latest developments in nanotechnology, the incorporation of antibiotics into prosthetic implants may soon become a standard procedure. The success will, however, depend on the ability to control the release of antibiotics at concentrations high enough to prevent the development of antibiotic-resistant strains. Through additive manufacturing, antibiotics can be incorporated into cementless femoral stems to produce prosthetic devices with antimicrobial properties. With the emerging increase in resistance to antibiotics, the incorporation of antimicrobial compounds other than antibiotics, preferably drugs with a broader spectrum of antimicrobial activity, will have to be explored. This review highlights the microorganisms associated with total hip arthroplasty (THA), discusses the advantages and disadvantages of the latest materials used in hip implants, compares different antimicrobial agents that could be incorporated, and addresses novel ideas for future research. PMID:26504776

  3. Improvement of attenuation functions of a clayey sandstone for landfill leachate containment by bentonite addition.

    PubMed

    Ruiz, Ana I; Fernández, Raúl; Sánchez Jiménez, Nicanor; Rodríguez Rastrero, Manuel; Regadío, Mercedes; de Soto, Isabel S; Cuevas, Jaime

    2012-03-01

    Enhanced sand-clay mixtures have been prepared by using a sandstone arkosic material and have been evaluated for consideration as landfill liners. A lab-scale test was carried out under controlled conditions with different amended natural sandstones whereby leachate was passed through the compacted mixtures. The compacted samples consisted of siliceous sand (quartz-feldspar sand separated from the arkose sandstone) and clay (purified clay from arkose sandstone and two commercial bentonites) materials that were mixed in different proportions. The separation of mineral materials from a common and abundant natural source, for soil protection purposes, is proposed as an economic and environmentally efficient practice. The liner qualities were compared for their mineralogical, physicochemical and major ions transport and adsorption properties. Although all samples fulfilled hydraulic conductivity requirements, the addition of bentonite to arkose sandstone was determined to be an effective strategy to decrease the permeability of the soil and to improve the pollutants retention. The clay materials from arkose sandstone also contributed to pollutant retention by a significant improvement of the cation exchange capacity of the bulk material. However, the mixtures prepared with clay materials from the arkose, exhibited a slight increase of hydraulic conductivity. This effect has to be further evaluated.

  4. Is the structural diversity of tripeptides sufficient for developing functional food additives with satisfactory multiple bioactivities?

    NASA Astrophysics Data System (ADS)

    Wang, Jian-Hui; Liu, Yong-Le; Ning, Jing-Heng; Yu, Jian; Li, Xiang-Hong; Wang, Fa-Xiang

    2013-05-01

    Multifunctional peptides have attracted increasing attention in the food science community because of their therapeutic potential, low toxicity and rapid intestinal absorption. However, previous study demonstrated that the limited structural variations make it difficult to optimize dipeptide molecules in a good balance between desirable and undesirable properties (F. Tian, P. Zhou, F. Lv, R. Song, Z. Li, J. Pept. Sci. 13 (2007) 549-566). In the present work, we attempt to answer whether the structural diversity is sufficient for a tripeptide to have satisfactory multiple bioactivities. Statistical test, structural examination and energetic analysis confirm that peptides of three amino acids long can bind tightly to human angiotensin converting enzyme (ACE) and thus exert significant antihypertensive efficacy. Further quantitative structure-activity relationship (QSAR) modeling and prediction of all 8000 possible tripeptides reveal that their ACE-inhibitory potency exhibits a good (positive) relationship to antioxidative activity, but has only a quite modest correlation with bitterness. This means that it is possible to find certain tripeptide entities possessing the optimal combination of strong ACE-inhibitory potency, high antioxidative activity and weak bitter taste, which are the promising candidates for developing multifunctional food additives with satisfactory multiple bioactivities. The marked difference between dipeptide and tripeptide can be attributed to the fact that the structural diversity of peptides increases dramatically with a slight change in sequence length.

  5. Effects of Germinated Brown Rice Addition on the Flavor and Functionality of Yogurt.

    PubMed

    Kim, Mi-Hye; Ahn, Sung-Il; Lim, Chan-Mook; Jhoo, Jin-Woo; Kim, Gur-Yoo

    2016-01-01

    This study aimed to investigate the functional and physicochemical properties of yogurt, supplemented with germinated brown rice (GBR) containing γ-aminobutyric acid (GABA), during storage. GBR was produced by soaking brown rice at 30℃, and saccharified germinated brown rice (SGBR) was produced by treating brown rice with α- and β-amylase for 1 h, at 80℃ and 60℃, respectively. Yogurt was manufactured using a commercial starter (YC-X11, CHR. Hansen, Denmark) at 37℃ for 12 h. The fatty acids and GABA contents were analyzed using GC and HPLC, respectively. The fatty acids in the cereal samples consisted of oleic, linoleic, and palmitic acid. The portion of oleic acid was the highest, at 35.65% in GBR, and 32.16% in SGBR. During germination, the oleic acid content increased, whereas linolenic and palmitic acid contents from GBR tended to decrease. Although the portion of saturated fatty acids, such as stearic and myristic acid, decreased significantly (p<0.05), that of unsaturated fatty acids, such as oleic and linoleic acid, increased with an increase in supplementation of BR, GBR, or SGBR in the yogurt. The yogurt, supplemented with cereal samples, showed a tendency of an increase in the concentration of GABA with an increase in the supplementation of the cereal samples. However, yogurt supplemented with GBR showed the highest concentration of GABA, regardless of the supplementation of the cereal samples. These results indicated that yogurt supplemented with BR, GBR, or SGBR could be a promising dairy product.

  6. Enhancement of glycine receptor function by ethanol: role of phosphorylation

    PubMed Central

    Paola Mascia, Maria; Wick, Marilee J; Martinez, Larry D; Harris, R Adron

    1998-01-01

    The effects of several kinase inhibitors (staurosporine, GF 109203X, H89, KN62, genistein) and of the phosphatase inhibitor calyculin A were studied on the ethanol potentiation and on the function of homomeric α1 glycine receptor expressed in Xenopus oocytes using a two electrode voltage clamp recording technique.The function of the homomeric α1 glycine receptor was not modified in Xenopus oocytes pretreated with kinase inhibitors or with the phosphatase inhibitor calyculin A.The potentiation of the glycine receptor function induced by ethanol (10–200 mM) was significantly reduced in Xenopus oocytes pretreated with the PKC inhibitors staurosporine or GF 109203X.No differences in propofol (2.5 μM) or halothane (250 μM) actions were found after exposure of Xenopus oocytes to staurosporine.No differences in ethanol sensitivity were found after exposure of Xenopus oocytes expressing glycine α1 receptors to H89, KN62, genistein or to the phosphatase inhibitor calyculin A.The mutant α1 (S391A), in which the PKC phosphorylation site at serine 391 was mutated to alanine, was less sensitive to the effects of ethanol than was the α1 wild type receptor. Moreover, the ethanol potentiation of the glycine receptor function was not affected by treatment with staurosporine in oocytes expressing α1 (S391A).The splice variant of the α1 glycine receptor subunit, α1ins, containing eight additional amino acids and a potential phosphorylation site for PKA, did not differ from wild type for sensitivity to ethanol.These results indicate that phosphorylation by PKC of the homomeric α1 glycine receptor subunit modulates ethanol potentiation, but not the function of the glycine receptor. PMID:9786497

  7. Structural and functional analysis of the two haemoglobins of the antarctic seabird Catharacta maccormicki characterization of an additional phosphate binding site by molecular modelling.

    PubMed

    Tamburrini, M; Riccio, A; Romano, M; Giardina, B; di Prisco, G

    2000-10-01

    The amino-acid sequence and the oxygen-binding properties of the two haemoglobins of the Antarctic seabird south polar skua have been investigated. The two haemoglobins showed peculiar functional features, which were probably acquired to meet special needs in relation to the extreme environmental conditions. Both haemoglobins showed a weak alkaline Bohr effect which, during prolonged flight, may protect against sudden and uncontrolled stripping of oxygen in response to acidosis. We suggest that a weak Bohr effect in birds may reflect adaptation to extreme life conditions. The values of heat of oxygenation suggest different functional roles of the two haemoglobins. The experimental evidence suggests that both haemoglobins may bind phosphate at two distinct binding sites. In fact, analysis of the molecular models revealed that an additional phosphate binding site, formed by residues NA1alpha, G6alpha and HC3alpha, is located between the two alpha chains. This additional site may act as an entry/leaving site, thus increasing the probability of capturing phosphate and transferring it to the main binding site located between the two beta chains by means of a site-site migratory mechanism, thereby favouring the release of oxygen. It is suggested that most haemoglobins possess an additional phosphate binding site, having such a role in oxygen transport.

  8. Effects of Germinated Brown Rice Addition on the Flavor and Functionality of Yogurt

    PubMed Central

    2016-01-01

    This study aimed to investigate the functional and physicochemical properties of yogurt, supplemented with germinated brown rice (GBR) containing γ-aminobutyric acid (GABA), during storage. GBR was produced by soaking brown rice at 30℃, and saccharified germinated brown rice (SGBR) was produced by treating brown rice with α- and β-amylase for 1 h, at 80℃ and 60℃, respectively. Yogurt was manufactured using a commercial starter (YC-X11, CHR. Hansen, Denmark) at 37℃ for 12 h. The fatty acids and GABA contents were analyzed using GC and HPLC, respectively. The fatty acids in the cereal samples consisted of oleic, linoleic, and palmitic acid. The portion of oleic acid was the highest, at 35.65% in GBR, and 32.16% in SGBR. During germination, the oleic acid content increased, whereas linolenic and palmitic acid contents from GBR tended to decrease. Although the portion of saturated fatty acids, such as stearic and myristic acid, decreased significantly (p<0.05), that of unsaturated fatty acids, such as oleic and linoleic acid, increased with an increase in supplementation of BR, GBR, or SGBR in the yogurt. The yogurt, supplemented with cereal samples, showed a tendency of an increase in the concentration of GABA with an increase in the supplementation of the cereal samples. However, yogurt supplemented with GBR showed the highest concentration of GABA, regardless of the supplementation of the cereal samples. These results indicated that yogurt supplemented with BR, GBR, or SGBR could be a promising dairy product. PMID:27621692

  9. Role of anaerobic fungi in wheat straw degradation and effects of plant feed additives on rumen fermentation parameters in vitro.

    PubMed

    Dagar, S S; Singh, N; Goel, N; Kumar, S; Puniya, A K

    2015-01-01

    In the present study, rumen microbial groups, i.e. total rumen microbes (TRM), total anaerobic fungi (TAF), avicel enriched bacteria (AEB) and neutral detergent fibre enriched bacteria (NEB) were evaluated for wheat straw (WS) degradability and different fermentation parameters in vitro. Highest WS degradation was shown for TRM, followed by TAF, NEB and least by AEB. Similar patterns were observed with total gas production and short chain fatty acid profiles. Overall, TAF emerged as the most potent individual microbial group. In order to enhance the fibrolytic and rumen fermentation potential of TAF, we evaluated 18 plant feed additives in vitro. Among these, six plant additives namely Albizia lebbeck, Alstonia scholaris, Bacopa monnieri, Lawsonia inermis, Psidium guajava and Terminalia arjuna considerably improved WS degradation by TAF. Further evaluation showed A. lebbeck as best feed additive. The study revealed that TAF plays a significant role in WS degradation and their fibrolytic activities can be improved by inclusion of A. lebbeck in fermentation medium. Further studies are warranted to elucidate its active constituents, effect on fungal population and in vivo potential in animal system.

  10. Versatile Roles of V-ATPases Accessory Subunit Ac45 in Osteoclast Formation and Function

    PubMed Central

    Lin, Zhen; Pavlos, Nathan J.; Jiang, Qing; Xu, Jiake; Dai, Ke R.; Zheng, Ming H.

    2011-01-01

    Vacuolar-type H+-ATPases (V-ATPases) are macromolecular proton pumps that acidify intracellular cargos and deliver protons across the plasma membrane of a variety of specialized cells, including bone-resorbing osteoclasts. Extracellular acidification is crucial for osteoclastic bone resorption, a process that initiates the dissolution of mineralized bone matrix. While the importance of V-ATPases in osteoclastic resorptive function is well-defined, whether V-ATPases facilitate additional aspects of osteoclast function and/or formation remains largely obscure. Here we report that the V-ATPase accessory subunit Ac45 participates in both osteoclast formation and function. Using a siRNA-based approach, we show that targeted suppression of Ac45 impairs intracellular acidification and endocytosis, both are prerequisite for osteoclastic bone resorptive function in vitro. Interestingly, we find that knockdown of Ac45 also attenuates osteoclastogenesis owing to a reduced fusion capacity of osteoclastic precursor cells. Finally, in an effort to gain more detailed insights into the functional role of Ac45 in osteoclasts, we attempted to generate osteoclast-specific Ac45 conditional knockout mice using a Cathepsin K-Cre-LoxP system. Surprisingly, however, insertion of the neomycin cassette in the Ac45-FloxNeo mice resulted in marked disturbances in CNS development and ensuing embryonic lethality thus precluding functional assessment of Ac45 in osteoclasts and peripheral bone tissues. Based on these unexpected findings we propose that, in addition to its canonical function in V-ATPase-mediated acidification, Ac45 plays versatile roles during osteoclast formation and function. PMID:22087256

  11. Role of glutathione transport processes in kidney function

    SciTech Connect

    Lash, Lawrence H. . E-mail: l.h.lash@wayne.edu

    2005-05-01

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

  12. The Neutrophil Nucleus and Its Role in Neutrophilic Function.

    PubMed

    Carvalho, Leonardo Olivieri; Aquino, Elaine Nascimento; Neves, Anne Caroline Dias; Fontes, Wagner

    2015-09-01

    The cell nucleus plays a key role in differentiation processes in eukaryotic cells. It is not the nucleus in particular, but the organization of the genes and their remodeling that provides the data for the adjustments to be made according to the medium. The neutrophil nucleus has a different morphology. It is a multi-lobed nucleus where some researchers argue no longer function. However, studies indicate that it is very probable the occurrence of chromatin remodeling during activation steps. It may be that the human neutrophil nucleus also contributes to the mobility of neutrophils through thin tissue spaces. Questions like these will be discussed in this small review. The topics include morphology of human neutrophil nucleus, maturation process and modifications of the neutrophil nucleus, neutrophil activation and chromatin modifications, causes and consequences of multi-lobulated segmented morphology, and importance of the nucleus in the formation of neutrophil extracellular traps (NETs).

  13. The critical role of Akt in cardiovascular function.

    PubMed

    Abeyrathna, Prasanna; Su, Yunchao

    2015-11-01

    Akt kinase, a member of AGC kinases, is important in many cellular functions including proliferation, migration, cell growth and metabolism. There are three known Akt isoforms which play critical and diverse roles in the cardiovascular system. Akt activity is regulated by its upstream regulatory pathways at transcriptional and post-translational levels. Beta-catenin/Tcf-4, GLI1 and Stat-3 are some of few known transcriptional regulators of AKT gene. Threonine 308 and serine 473 are the two critical phosphorylation sites of Akt1. Translocation of Akt to the cell membrane facilitates PDK1 phosphorylation of the threonine site. The serine site is phosphorylated by mTORC2. Ack1, Src, PTK6, TBK1, IKBKE and IKKε are some of the non-canonical pathways which affect the Akt activity. Protein-protein interactions of Akt to actin and Hsp90 increase the Akt activity while Akt binding to other proteins such as CTMP and TRB3 reduces the Akt activity. The action of Akt on its downstream targets determines its function in cardiovascular processes such as cell survival, growth, proliferation, angiogenesis, vasorelaxation, and cell metabolism. Akt promotes cell survival via caspase-9, YAP, Bcl-2, and Bcl-x activities. Inhibition of FoxO proteins by Akt also increases cell survival by transcriptional mechanisms. Akt stimulates cell growth and proliferation through mTORC1. Akt also increases VEGF secretion and mediates eNOS phosphorylation, vasorelaxation and angiogenesis. Akt can increase cellular metabolism through its downstream targets GSK3 and GLUT4. The alterations of Akt signaling play an important role in many cardiovascular pathological processes such as atherosclerosis, cardiac hypertrophy, and vascular remodeling. Several Akt inhibitors have been developed and tested as anti-tumor agents. They could be potential novel therapeutics for the cardiovascular diseases.

  14. Structure and function of desmosomal proteins and their role in development and disease.

    PubMed

    Huber, O

    2003-09-01

    Desmosomes represent major intercellular adhesive junctions at basolateral membranes of epithelial cells and in other tissues. They mediate direct cell-cell contacts and provide anchorage sites for intermediate filaments important for the maintenance of tissue architecture. There is increasing evidence now that desmosomes in addition to a simple structural function have new roles in tissue morphogenesis and differentiation. Transmembrane glycoproteins of the cadherin superfamily of Ca(2+)-dependent cell-cell adhesion molecules which mediate direct intercellular interactions in desmosomes appear to be of central importance in this respect. The complex network of proteins forming the desmosomal plaque associated with the cytoplasmic domain of the desmosomal cadherins, however, is also involved in junction assembly and regulation of adhesive strength. This review summarizes the structural features of these desmosomal proteins, their function during desmosome assembly and maintenance, and their role in development and disease.

  15. Melanocortin 1 receptor variants: functional role and pigmentary associations.

    PubMed

    Dessinioti, Clio; Antoniou, Christina; Katsambas, Andreas; Stratigos, Alexander J

    2011-01-01

    The significance of human cutaneous pigmentation lies in its protective role against sun-induced DNA damage and photocarcinogenesis. Fair skin and red hair are characterized by a low eumelanin to pheomelanin ratio, and have been associated with increased risk of skin cancer. Cutaneous pigmentation is a complex genetic trait, with more than 120 genes involved in its regulation, among which the melanocortin 1 receptor gene (MC1R) plays a key role. Although a large number of single nucleotide polymorphisms (SNPs) have been identified in pigmentation genes, very few SNPs have been examined in relation to human pigmentary phenotypes and skin cancer risk. Recent GWAS have identified new candidate determinants of pigmentation traits, but MC1R remains the best characterized genetic determinant of human skin and hair pigmentation as well as the more firmly validated low-penetrance skin cancer susceptibility gene. In this review, we will address how the melanocortin system regulates pigmentation, the effect of MC1R variants on the physiologic function of the MC1 receptor, and how specific MC1R variants are associated with distinct human pigmentation phenotypes.

  16. Functional Roles of the Interaction of APP and Lipoprotein Receptors

    PubMed Central

    Pohlkamp, Theresa; Wasser, Catherine R.; Herz, Joachim

    2017-01-01

    The biological fates of the key initiator of Alzheimer’s disease (AD), the amyloid precursor protein (APP), and a family of lipoprotein receptors, the low-density lipoprotein (LDL) receptor-related proteins (LRPs) and their molecular roles in the neurodegenerative disease process are inseparably interwoven. Not only does APP bind tightly to the extracellular domains (ECDs) of several members of the LRP group, their intracellular portions are also connected through scaffolds like the one established by FE65 proteins and through interactions with adaptor proteins such as X11/Mint and Dab1. Moreover, the ECDs of APP and LRPs share common ligands, most notably Reelin, a regulator of neuronal migration during embryonic development and modulator of synaptic transmission in the adult brain, and Agrin, another signaling protein which is essential for the formation and maintenance of the neuromuscular junction (NMJ) and which likely also has critical, though at this time less well defined, roles for the regulation of central synapses. Furthermore, the major independent risk factors for AD, Apolipoprotein (Apo) E and ApoJ/Clusterin, are lipoprotein ligands for LRPs. Receptors and ligands mutually influence their intracellular trafficking and thereby the functions and abilities of neurons and the blood-brain-barrier to turn over and remove the pathological product of APP, the amyloid-β peptide. This article will review and summarize the molecular mechanisms that are shared by APP and LRPs and discuss their relative contributions to AD. PMID:28298885

  17. Role of sex hormones in the modulation of cholangiocyte function

    PubMed Central

    Mancinelli, Romina; Onori, Paolo; DeMorrow, Sharon; Francis, Heather; Glaser, Shannon; Franchitto, Antonio; Carpino, Guido; Alpini, Gianfranco; Gaudio, Eugenio

    2010-01-01

    Over the last years, cholangiocytes, the cells that line the biliary tree, have been considered an important object of study for their biological properties which involves bile formation, proliferation, injury repair, fibrosis and angiogenesis. Cholangiocyte proliferation occurs in all pathologic conditions of liver injury where it is associated with inflammation and regeneration. During these processes, biliary cells start to secrete different cytokines, growth factors, neuropeptides and hormones which represent potential mechanisms for cross talk with other liver cells. Several studies suggest that hormones, and in particular, sex hormones, play a fundamental role in the modulation of the growth of this compartment in the injured liver which functionally conditions the progression of liver disease. Understanding the mechanisms of action and the intracellular pathways of these compounds on cholangiocyte pathophysiology will provide new potential strategies for the management of chronic liver diseases. The purpose of this review is to summarize the recent findings on the role of sex hormones in cholangiocyte proliferation and biology. PMID:21607142

  18. Functional role of cannabinoid receptors in urinary bladder

    PubMed Central

    Tyagi, Pradeep; Tyagi, Vikas; Yoshimura, Naoki; Chancellor, Michael

    2010-01-01

    Cannabinoids, the active components of Cannabis sativa (maijuana), and their derivatives produce a wide spectrum of central and peripheral effects, some of which may have clinical applications. The discovery of specific cannabinoid receptors and a family of endogenous ligands of those receptors has attracted much attention to the general cannabinoid pharmacology. In recent years, studies on the functional role of cannabinoid receptors in bladder have been motivated by the therapeutic effects of cannabinoids on voiding dysfunction in multiple sclerosis patients. In this review, we shall summarize the literature on the expression of cannabinoid receptors in urinary bladder and the peripheral influence of locally and systemically administered cannabinoids in the bladder. The ongoing search for cannabinoid-based therapeutic strategies devoid of psychotropic effects can be complemented with local delivery into bladder by the intravesical route. A greater understanding of the role of the peripheral CB1 and CB2 receptor system in lower urinary tract is necessary to allow the development of new treatment for pelvic disorders. PMID:20535281

  19. Structures and Functions of Oligosaccharins: The Role of Endoglycanases

    SciTech Connect

    Bergmann, Carl W.

    2008-12-05

    The research proposed will investigate two projects that involve studies of the chemistry and biology of protein/protein and protein/carbohydrate interactions involved in host/pathogen interactions. Specifically, the projects involve (i) the interactions between fungal endopolygalacturonases and plant polygalacturonase-inhibiting proteins and (ii) the interactions between fungal endoxylanases and plant arabinoxylans. During pathogenesis fungi secrete families of endoglycanases that fragment the cell wall polysaccharides of the plant host. The result of endoglycanase action on cell wall polysaccharides can include weakening of the wall, penetration of host cells by the pathogen, solubilization of carbohydrate nutrients, and formation of oligosaccharins (oligosaccharides with regulatory function) that can stimulate plant defenses. We have made significant advances during the last funding period to support the hypothesis that the outcome of attempted pathogenesis can be influenced by protein/protein and protein/carbohydrate interactions in the extracellular matrices of the host and pathogen. We plan to expand on those successes by further exploring the mechanism of action of the endoglycanases and their plant-derived inhibitors, the expression of the various members of the endoglycanase families at various stages of infection and their role in the release of oligosaccharins and in pathogenicity, as well as the role played by the polysaccharide substrates in both pathogenicity and endoglycanase-inhibitor interactions.

  20. The Role of Control Functions in Mentalizing: Dual-Task Studies of Theory of Mind and Executive Function

    ERIC Educational Resources Information Center

    Bull, Rebecca; Phillips, Louise H.; Conway, Claire A.

    2008-01-01

    Conflicting evidence has arisen from correlational studies regarding the role of executive control functions in Theory of Mind. The current study used dual-task manipulations of executive functions (inhibition, updating and switching) to investigate the role of these control functions in mental state and non-mental state tasks. The "Eyes"…

  1. The important role of stratum corneum lipids for the cutaneous barrier function.

    PubMed

    van Smeden, J; Janssens, M; Gooris, G S; Bouwstra, J A

    2014-03-01

    The skin protects the body from unwanted influences from the environment as well as excessive water loss. The barrier function of the skin is located in the stratum corneum (SC). The SC consists of corneocytes embedded in a lipid matrix. This lipid matrix is crucial for the lipid skin barrier function. This paper provides an overview of the reported SC lipid composition and organization mainly focusing on healthy and diseased human skin. In addition, an overview is provided on the data describing the relation between lipid modulations and the impaired skin barrier function. Finally, the use of in vitro lipid models for a better understanding of the relation between the lipid composition, lipid organization and skin lipid barrier is discussed. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

  2. Role of reactive nitrogen species in blood platelet functions.

    PubMed

    Olas, Beata; Wachowicz, Barbara

    2007-12-01

    Blood platelets, in analogy to other circulating blood cells, can generate reactive oxygen/nitrogen species (ROS/RNS) that may behave as second messengers and may regulate platelet functions. Accumulating evidence suggest a role of ROS/RNS in platelet activation. On the other hand, an increased production of ROS/RNS causes oxidative stress, and thus, may contribute to the development of different diseases, including vascular complications, inflammatory and psychiatric illnesses. Oxidative stress in platelets leads to chemical changes in a wide range of their components, and platelet proteins may be initial targets of ROS/RNS action. It has been demonstrated that reaction of proteins with ROS/RNS results in the oxidation and nitration of some amino acid residues, formation of aggregates or fragmentation of proteins. In oxidized proteins new carbonyl groups and protein hydroperoxides are also formed. In platelets, low molecular weight thiols such as glutathione (GSH), cysteine and cysteinylglycine and protein thiols may be also target for ROS/RNS action. This review describes the chemical structure and biological activities of reactive nitrogen species, mainly nitric oxide ((*)NO) and peroxynitrite (ONOO(-)) and their effects on blood platelet functions, and the mechanisms involved in their action on platelets.

  3. Adult neurogenesis and its role in neuropsychiatric disease, brain repair and normal brain function.

    PubMed

    Braun, S M G; Jessberger, S

    2014-02-01

    Neural stem/progenitor cells (NSPCs) in the mammalian brain retain the ability to generate new neurones throughout life in discrete brain regions, through a process called adult neurogenesis. Adult neurogenesis, a dramatic form of adult brain circuitry plasticity, has been implicated in physiological brain function and appears to be of pivotal importance for certain forms of learning and memory. In addition, failing or altered neurogenesis has been associated with a variety of brain diseases such as major depression, epilepsy and age-related cognitive decline. Here we review recent advances in our understanding of the basic biology underlying the neurogenic process in the adult brain, focusing on mechanisms that regulate quiescence, proliferation and differentiation of NSPCs. In addition, we discuss how neurogenesis influences normal brain function, and in particular its role in memory formation, as well as its contribution to neuropsychiatric diseases. Finally, we evaluate the potential of targeting endogenous NSPCs for brain repair.

  4. Interleukin-22 and CD160 play additive roles in the host mucosal response to Clostridium difficile infection in mice.

    PubMed

    Sadighi Akha, Amir A; McDermott, Andrew J; Theriot, Casey M; Carlson, Paul E; Frank, Charles R; McDonald, Roderick A; Falkowski, Nicole R; Bergin, Ingrid L; Young, Vincent B; Huffnagle, Gary B

    2015-04-01

    Our previous work has shown the significant up-regulation of Il22 and increased phosphorylation of signal transducer and activator of transcription 3 (STAT3) as part of the mucosal inflammatory response to Clostridium difficile infection in mice. Others have shown that phosphorylation of STAT3 at mucosal surfaces includes interleukin-22 (IL-22) and CD160-mediated components. The current study sought to determine the potential role(s) of IL-22 and/or CD160 in the mucosal response to C. difficile infection. Clostridium difficile-infected mice treated with anti-IL-22, anti-CD160 or a combination of the two showed significantly reduced STAT3 phosphorylation in comparison to C. difficile-infected mice that had not received either antibody. In addition, C. difficile-infected mice treated with anti-IL-22/CD160 induced a smaller set of genes, and at significantly lower levels than the untreated C. difficile-infected mice. The affected genes included pro-inflammatory chemokines and cytokines, and anti-microbial peptides. Furthermore, histopathological and flow cytometric assessments both showed a significantly reduced influx of neutrophils in C. difficile-infected mice treated with anti-IL-22/CD160. These data demonstrate that IL-22 and CD160 are together responsible for a significant fraction of the colonic STAT3 phosphorylation in C. difficile infection. They also underscore the additive effects of IL-22 and CD160 in mediating both the pro-inflammatory and pro-survival aspects of the host mucosal response in this infection.

  5. An analytical approach to the problem of inverse optimization with additive objective functions: an application to human prehension.

    PubMed

    Terekhov, Alexander V; Pesin, Yakov B; Niu, Xun; Latash, Mark L; Zatsiorsky, Vladimir M

    2010-09-01

    We consider the problem of what is being optimized in human actions with respect to various aspects of human movements and different motor tasks. From the mathematical point of view this problem consists of finding an unknown objective function given the values at which it reaches its minimum. This problem is called the inverse optimization problem. Until now the main approach to this problems has been the cut-and-try method, which consists of introducing an objective function and checking how it reflects the experimental data. Using this approach, different objective functions have been proposed for the same motor action. In the current paper we focus on inverse optimization problems with additive objective functions and linear constraints. Such problems are typical in human movement science. The problem of muscle (or finger) force sharing is an example. For such problems we obtain sufficient conditions for uniqueness and propose a method for determining the objective functions. To illustrate our method we analyze the problem of force sharing among the fingers in a grasping task. We estimate the objective function from the experimental data and show that it can predict the force-sharing pattern for a vast range of external forces and torques applied to the grasped object. The resulting objective function is quadratic with essentially non-zero linear terms.

  6. An analytical approach to the problem of inverse optimization with additive objective functions: an application to human prehension

    PubMed Central

    Pesin, Yakov B.; Niu, Xun; Latash, Mark L.

    2010-01-01

    We consider the problem of what is being optimized in human actions with respect to various aspects of human movements and different motor tasks. From the mathematical point of view this problem consists of finding an unknown objective function given the values at which it reaches its minimum. This problem is called the inverse optimization problem. Until now the main approach to this problems has been the cut-and-try method, which consists of introducing an objective function and checking how it reflects the experimental data. Using this approach, different objective functions have been proposed for the same motor action. In the current paper we focus on inverse optimization problems with additive objective functions and linear constraints. Such problems are typical in human movement science. The problem of muscle (or finger) force sharing is an example. For such problems we obtain sufficient conditions for uniqueness and propose a method for determining the objective functions. To illustrate our method we analyze the problem of force sharing among the fingers in a grasping task. We estimate the objective function from the experimental data and show that it can predict the force-sharing pattern for a vast range of external forces and torques applied to the grasped object. The resulting objective function is quadratic with essentially non-zero linear terms. PMID:19902213

  7. Systematic Dissection of Coding Exons at Single Nucleotide Resolution Supports an Additional Role in Cell-Specific Transcriptional Regulation

    PubMed Central

    Kim, Mee J.; Findlay, Gregory M.; Martin, Beth; Zhao, Jingjing; Bell, Robert J. A.; Smith, Robin P.; Ku, Angel A.; Shendure, Jay; Ahituv, Nadav

    2014-01-01

    In addition to their protein coding function, exons can also serve as transcriptional enhancers. Mutations in these exonic-enhancers (eExons) could alter both protein function and transcription. However, the functional consequence of eExon mutations is not well known. Here, using massively parallel reporter assays, we dissect the enhancer activity of three liver eExons (SORL1 exon 17, TRAF3IP2 exon 2, PPARG exon 6) at single nucleotide resolution in the mouse liver. We find that both synonymous and non-synonymous mutations have similar effects on enhancer activity and many of the deleterious mutation clusters overlap known liver-associated transcription factor binding sites. Carrying a similar massively parallel reporter assay in HeLa cells with these three eExons found differences in their mutation profiles compared to the liver, suggesting that enhancers could have distinct operating profiles in different tissues. Our results demonstrate that eExon mutations could lead to multiple phenotypes by disrupting both the protein sequence and enhancer activity and that enhancers can have distinct mutation profiles in different cell types. PMID:25340400

  8. Selenoprotein P – Expression, Functions, and Roles in Mammals

    PubMed Central

    Burk, Raymond F.; Hill, Kristina E.

    2009-01-01

    Selenoprotein P (Sepp1) is a secreted protein that is made up of 2 domains. The larger N-terminal domain contains 1 selenocysteine residue in a redox motif and the smaller C-terminal domain contains the other 9 selenocysteines. Sepp1 isoforms of varying length occur but quantitation of them has not been achieved. Hepatic synthesis of Sepp1 affects whole-body selenium content and the liver is the source of most plasma Sepp1. ApoER2, a member of the lipoprotein receptor family, binds Sepp1 and facilitates its uptake into testis and retention of its selenium by the brain. Megalin, another lipoprotein receptor, facilitates uptake of filtered Sepp1 into proximal tubule cells of the kidney. Thus, Sepp1 serves in homeostasis and distribution of selenium. Mice with deletion of Sepp1 suffer greater morbidity and mortality from infection with Trypanosoma congolense than do wild-type mice. Mice that express only the N-terminal domain of Sepp1 have the same severity of illness as wild-type mice, indicating that the protective function of Sepp1 against the infection resides in the N-terminal (redox) domain. Thus, Sepp1 has several functions. In addition, plasma Sepp1 concentration falls in selenium deficiency and, therefore, it can be used as an index of selenium nutritional status. PMID:19345254

  9. Benchmark calculations of excess electrons in water cluster cavities: balancing the addition of atom-centered diffuse functions versus floating diffuse functions.

    PubMed

    Zhang, Changzhe; Bu, Yuxiang

    2016-09-14

    Diffuse functions have been proved to be especially crucial for the accurate characterization of excess electrons which are usually bound weakly in intermolecular zones far away from the nuclei. To examine the effects of diffuse functions on the nature of the cavity-shaped excess electrons in water cluster surroundings, both the HOMO and LUMO distributions, vertical detachment energies (VDEs) and visible absorption spectra of two selected (H2O)24(-) isomers are investigated in the present work. Two main types of diffuse functions are considered in calculations including the Pople-style atom-centered diffuse functions and the ghost-atom-based floating diffuse functions. It is found that augmentation of atom-centered diffuse functions contributes to a better description of the HOMO (corresponding to the VDE convergence), in agreement with previous studies, but also leads to unreasonable diffuse characters of the LUMO with significant red-shifts in the visible spectra, which is against the conventional point of view that the more the diffuse functions, the better the results. The issue of designing extra floating functions for excess electrons has also been systematically discussed, which indicates that the floating diffuse functions are necessary not only for reducing the computational cost but also for improving both the HOMO and LUMO accuracy. Thus, the basis sets with a combination of partial atom-centered diffuse functions and floating diffuse functions are recommended for a reliable description of the weakly bound electrons. This work presents an efficient way for characterizing the electronic properties of weakly bound electrons accurately by balancing the addition of atom-centered diffuse functions and floating diffuse functions and also by balancing the computational cost and accuracy of the calculated results, and thus is very useful in the relevant calculations of various solvated electron systems and weakly bound anionic systems.

  10. Cobalt(III)-Catalyzed Synthesis of Indazoles and Furans by C–H Bond Functionalization/Addition/Cyclization Cascades

    PubMed Central

    2015-01-01

    The development of operationally straightforward and cost-effective routes for the assembly of heterocycles from simple inputs is important for many scientific endeavors, including pharmaceutical, agrochemical, and materials research. In this article we describe the development of a new air-stable cationic Co(III) catalyst for convergent, one-step benchtop syntheses of N-aryl-2H-indazoles and furans by C–H bond additions to aldehydes followed by in situ cyclization and aromatization. Only a substoichiometric amount of AcOH is required as an additive that is both low-cost and convenient to handle. The syntheses of these heterocycles are the first examples of Co(III)-catalyzed additions to aldehydes, and reactions are demonstrated for a variety of aromatic, heteroaromatic, and aliphatic derivatives. The syntheses of both N-aryl-2H-indazoles and furans have been performed on 20 mmol scales and should be readily applicable to larger scales. The reported heterocycle syntheses also demonstrate the use of directing groups that have not previously been applied to Co(III)-catalyzed C–H bond functionalizations. Additionally, the synthesis of furans demonstrates the first example of Co(III)-catalyzed functionalization of alkenyl C–H bonds. PMID:25494296

  11. Effect of Additives on Green Sand Molding Properties using Design of Experiments and Taguchi's Quality Loss Function - An Experimental Study

    NASA Astrophysics Data System (ADS)

    Desai, Bhagyashree; Mokashi, Pavani; Anand, R. L.; Burli, S. B.; Khandal, S. V.

    2016-09-01

    The experimental study aims to underseek the effect of various additives on the green sand molding properties as a particular combination of additives could yield desired sand properties. The input parameters (factors) selected were water and powder (Fly ash, Coconut shell and Tamarind) in three levels. Experiments were planned using design of experiments (DOE). On the basis of plans, experiments were conducted to understand the behavior of sand mould properties such as compression strength, shear strength, permeability number with various additives. From the experimental results it could be concluded that the factors have significant effect on the sand properties as P-value found to be less than 0.05 for all the cases studied. The optimization based on quality loss function was also performed. The study revealed that the quality loss associated with the tamarind powder was lesser compared to other additives selected for the study. The optimization based on quality loss function and the parametric analysis using ANOVA suggested that the tamarind powder of 8 gm per Kg of molding sand and moisture content of 7% yield better properties to obtain sound castings.

  12. Cobalt(III)-catalyzed synthesis of indazoles and furans by C-H bond functionalization/addition/cyclization cascades.

    PubMed

    Hummel, Joshua R; Ellman, Jonathan A

    2015-01-14

    The development of operationally straightforward and cost-effective routes for the assembly of heterocycles from simple inputs is important for many scientific endeavors, including pharmaceutical, agrochemical, and materials research. In this article we describe the development of a new air-stable cationic Co(III) catalyst for convergent, one-step benchtop syntheses of N-aryl-2H-indazoles and furans by C-H bond additions to aldehydes followed by in situ cyclization and aromatization. Only a substoichiometric amount of AcOH is required as an additive that is both low-cost and convenient to handle. The syntheses of these heterocycles are the first examples of Co(III)-catalyzed additions to aldehydes, and reactions are demonstrated for a variety of aromatic, heteroaromatic, and aliphatic derivatives. The syntheses of both N-aryl-2H-indazoles and furans have been performed on 20 mmol scales and should be readily applicable to larger scales. The reported heterocycle syntheses also demonstrate the use of directing groups that have not previously been applied to Co(III)-catalyzed C-H bond functionalizations. Additionally, the synthesis of furans demonstrates the first example of Co(III)-catalyzed functionalization of alkenyl C-H bonds.

  13. The emerging role of Nrf2 in mitochondrial function

    PubMed Central

    Dinkova-Kostova, Albena T.; Abramov, Andrey Y.

    2015-01-01

    The transcription factor NF-E2 p45-related factor 2 (Nrf2; gene name NFE2L2) allows adaptation and survival under conditions of stress by regulating the gene expression of diverse networks of cytoprotective proteins, including antioxidant, anti-inflammatory, and detoxification enzymes as well as proteins that assist in the repair or removal of damaged macromolecules. Nrf2 has a crucial role in the maintenance of cellular redox homeostasis by regulating the biosynthesis, utilization, and regeneration of glutathione, thioredoxin, and NADPH and by controlling the production of reactive oxygen species by mitochondria and NADPH oxidase. Under homeostatic conditions, Nrf2 affects the mitochondrial membrane potential, fatty acid oxidation, availability of substrates (NADH and FADH2/succinate) for respiration, and ATP synthesis. Under conditions of stress or growth factor stimulation, activation of Nrf2 counteracts the increased reactive oxygen species production in mitochondria via transcriptional upregulation of uncoupling protein 3 and influences mitochondrial biogenesis by maintaining the levels of nuclear respiratory factor 1 and peroxisome proliferator-activated receptor γ coactivator 1α, as well as by promoting purine nucleotide biosynthesis. Pharmacological Nrf2 activators, such as the naturally occurring isothiocyanate sulforaphane, inhibit oxidant-mediated opening of the mitochondrial permeability transition pore and mitochondrial swelling. Curiously, a synthetic 1,4-diphenyl-1,2,3-triazole compound, originally designed as an Nrf2 activator, was found to promote mitophagy, thereby contributing to the overall mitochondrial homeostasis. Thus, Nrf2 is a prominent player in supporting the structural and functional integrity of the mitochondria, and this role is particularly crucial under conditions of stress. PMID:25975984

  14. Transitioning between Work and Family Roles as a Function of Boundary Flexibility and Role Salience

    ERIC Educational Resources Information Center

    Winkel, Doan E.; Clayton, Russell W.

    2010-01-01

    This study investigates the manner in which people separate their work and family roles and how they manage the boundaries of these two important roles. Specifically, we focus on how role flexibility and salience influence transitions between roles. Results indicate that the ability and willingness to flex a role boundary and role salience are…

  15. Functional neuroimaging of conversion disorder: The role of ancillary activation

    PubMed Central

    Burke, Matthew J.; Ghaffar, Omar; Staines, W. Richard; Downar, Jonathan; Feinstein, Anthony

    2014-01-01

    Background Previous functional neuroimaging studies investigating the neuroanatomy of conversion disorder have yielded inconsistent results that may be attributed to small sample sizes and disparate methodologies. The objective of this study was to better define the functional neuroanatomical correlates of conversion disorder. Methods Ten subjects meeting clinical criteria for unilateral sensory conversion disorder underwent fMRI during which a vibrotactile stimulus was applied to anesthetic and sensate areas. A block design was used with 4 s of stimulation followed by 26 s of rest, the pattern repeated 10 times. Event-related group averages of the BOLD response were compared between conditions. Results All subjects were right-handed females, with a mean age of 41. Group analyses revealed 10 areas that had significantly greater activation (p < .05) when stimulation was applied to the anesthetic body part compared to the contralateral sensate mirror region. They included right paralimbic cortices (anterior cingulate cortex and insula), right temporoparietal junction (angular gyrus and inferior parietal lobule), bilateral dorsolateral prefrontal cortex (middle frontal gyri), right orbital frontal cortex (superior frontal gyrus), right caudate, right ventral-anterior thalamus and left angular gyrus. There was a trend for activation of the somatosensory cortex contralateral to the anesthetic region to be decreased relative to the sensate side. Conclusions Sensory conversion symptoms are associated with a pattern of abnormal cerebral activation comprising neural networks implicated in emotional processing and sensory integration. Further study of the roles and potential interplay of these networks may provide a basis for an underlying psychobiological mechanism of conversion disorder. PMID:25379447

  16. Functional role of frontal alpha oscillations in creativity.

    PubMed

    Lustenberger, Caroline; Boyle, Michael R; Foulser, A Alban; Mellin, Juliann M; Fröhlich, Flavio

    2015-06-01

    Creativity, the ability to produce innovative ideas, is a key higher-order cognitive function that is poorly understood. At the level of macroscopic cortical network dynamics, recent electroencephalography (EEG) data suggests that cortical oscillations in the alpha frequency band (8-12 Hz) are correlated with creative thinking. However, whether alpha oscillations play a functional role in creativity has remained unknown. Here we show that creativity is increased by enhancing alpha power using 10 Hz transcranial alternating current stimulation (10 Hz-tACS) of the frontal cortex. In a study of 20 healthy participants with a randomized, balanced cross-over design, we found a significant improvement of 7.4% in the Creativity Index measured by the Torrance Test of Creative Thinking (TTCT), a comprehensive and most frequently used assay of creative potential and strengths. In a second similar study with 20 subjects, 40 Hz-tACS was used instead of 10 Hz-tACS to rule out a general "electrical stimulation" effect. No significant change in the Creativity Index was found for such frontal 40 Hz stimulation. Our results suggest that alpha activity in frontal brain areas is selectively involved in creativity; this enhancement represents the first demonstration of specific neuronal dynamics that drive creativity and can be modulated by non-invasive brain stimulation. Our findings agree with the model that alpha recruitment increases with internal processing demands and is involved in inhibitory top-down control, which is an important requirement for creative ideation.

  17. Functional role of aspartic proteinase cathepsin D in insect metamorphosis

    PubMed Central

    Gui, Zhong Zheng; Lee, Kwang Sik; Kim, Bo Yeon; Choi, Yong Soo; Wei, Ya Dong; Choo, Young Moo; Kang, Pil Don; Yoon, Hyung Joo; Kim, Iksoo; Je, Yeon Ho; Seo, Sook Jae; Lee, Sang Mong; Guo, Xijie; Sohn, Hung Dae; Jin, Byung Rae

    2006-01-01

    Background Metamorphosis is a complex, highly conserved and strictly regulated development process that involves the programmed cell death of obsolete larval organs. Here we show a novel functional role for the aspartic proteinase cathepsin D during insect metamorphosis. Results Cathepsin D of the silkworm Bombyx mori (BmCatD) was ecdysone-induced, differentially and spatially expressed in the larval fat body of the final instar and in the larval gut of pupal stage, and its expression led to programmed cell death. Furthermore, BmCatD was highly induced in the fat body of baculovirus-infected B. mori larvae, suggesting that this gene is involved in the induction of metamorphosis of host insects infected with baculovirus. RNA interference (RNAi)-mediated BmCatD knock-down inhibited programmed cell death of the larval fat body, resulting in the arrest of larval-pupal transformation. BmCatD RNAi also inhibited the programmed cell death of larval gut during pupal stage. Conclusion Based on these results, we concluded that BmCatD is critically involved in the programmed cell death of the larval fat body and larval gut in silkworm metamorphosis. PMID:17062167

  18. Functional roles of neuropeptides in the insect central nervous system

    NASA Astrophysics Data System (ADS)

    Nässel, D. R.

    With the completion of the Drosophila genome sequencing project we can begin to appreciate the extent of the complexity in the components involved in signal transfer and modulation in the nervous system of an animal with reasonably complex behavior. Of all the different classes of signaling substances utilized by the nervous system, the neuropeptides are the most diverse structurally and functionally. Thus peptidergic mechanisms of action in the central nervous system need to be analyzed in the context of the neuronal circuits in which they act and generalized traits cannot be established. By taking advantage of Drosophila molecular genetics and the presence of identifiable neurons, it has been possible to interfere with peptidergic signaling in small populations of central neurons and monitor the consequences on behavior. These studies and experiments on other insects with large identifiable neurons, permitting cellular analysis of signaling mechanisms, have outlined important principles for temporal and spatial action of neuropeptides in outputs of the circadian clock and in orchestrating molting behavior. Considering the large number of neuropeptides available in each insect species and their diverse distribution patterns, it is to be expected that different neuropeptides play roles in most aspects of insect physiology and behavior.

  19. Discerning the role of mechanosensors in regulating proximal tubule function.

    PubMed

    Raghavan, Venkatesan; Weisz, Ora A

    2016-01-01

    All cells in the body experience external mechanical forces such as shear stress and stretch. These forces are sensed by specialized structures in the cell known as mechanosensors. Cells lining the proximal tubule (PT) of the kidney are continuously exposed to variations in flow rates of the glomerular ultrafiltrate, which manifest as changes in axial shear stress and radial stretch. Studies suggest that these cells respond acutely to variations in flow by modulating their ion transport and endocytic functions to maintain glomerulotubular balance. Conceptually, changes in the axial shear stress in the PT could be sensed by three known structures, namely, the microvilli, the glycocalyx, and primary cilia. The orthogonal component of the force produced by flow exhibits as radial stretch and can cause expansion of the tubule. Forces of stretch are transduced by integrins, by stretch-activated channels, and by cell-cell contacts. This review summarizes our current understanding of flow sensing in PT epithelia, discusses challenges in dissecting the role of individual flow sensors in the mechanosensitive responses, and identifies potential areas of opportunity for new study.

  20. Role of motor unit structure in defining function

    NASA Technical Reports Server (NTRS)

    Monti, R. J.; Roy, R. R.; Edgerton, V. R.

    2001-01-01

    Motor units, defined as a motoneuron and all of its associated muscle fibers, are the basic functional units of skeletal muscle. Their activity represents the final output of the central nervous system, and their role in motor control has been widely studied. However, there has been relatively little work focused on the mechanical significance of recruiting variable numbers of motor units during different motor tasks. This review focuses on factors ranging from molecular to macroanatomical components that influence the mechanical output of a motor unit in the context of the whole muscle. These factors range from the mechanical properties of different muscle fiber types to the unique morphology of the muscle fibers constituting a motor unit of a given type and to the arrangement of those motor unit fibers in three dimensions within the muscle. We suggest that as a result of the integration of multiple levels of structural and physiological levels of organization, unique mechanical properties of motor units are likely to emerge. Copyright 2001 John Wiley & Sons, Inc.

  1. Bridging structure with function: structural, regulatory, and developmental role of laminins.

    PubMed

    Tzu, Julia; Marinkovich, M Peter

    2008-01-01

    The basement membrane is a highly intricate and organized portion of the extracellular matrix that interfaces with a variety of cell types including epithelial, endothelial, muscle, nerve, and fat cells. The laminin family of glycoproteins is a major constituent of the basement membrane. The 16 known laminin isoforms are formed from combinations of alpha, beta, and gamma chains, with each chain containing specific domains capable of interacting with cellular receptors such as integrins and other extracellular ligands. In addition to its role in the assembly and architectural integrity of the basement membrane, laminins interact with cells to influence proliferation, differentiation, adhesion, and migration, processes activated in normal and pathologic states. In vitro these functions are regulated by the post-translational modifications of the individual laminin chains. In vivo laminin knockout mouse studies have been particularly instructive in defining the function of specific laminins in mammalian development and have also highlighted its role as a key component of the basement membrane. In this review, we will define how laminin structure complements function and explore its role in both normal and pathologic processes.

  2. What is the functional role of the thalidomide binding protein cereblon?

    PubMed

    Chang, Xiu-Bao; Stewart, A Keith

    2011-01-01

    It has been found that nonsense mutation R419X of cereblon (CRBN) is associated with autosomal recessive non-syndromic mental retardation. Further experiments showed that CRBN binds to the cytosolic C-terminus of large-conductance Ca(++) activated potassium channel (BK(Ca)) α-subunit and the cytosolic C-terminus of a voltage-gated chloride channel-2 (ClC-2), suggesting that CRBN may play a role in memory and learning via regulating the assembly and surface expression of BK(Ca) and ClC-2 channels. In addition, it has also been found that CRBN directly interacts with the α1 subunit of AMP-activated protein kinase (AMPK) and prevents formation of a functional holoenzyme with regulatory subunits β and γ. Since AMPK is a master sensor of energy balance that inhibits ATP-consuming anabolic pathways and increases ATP-producing catabolic pathways, binding of CRBN with α1 subunit of AMPK may play a role in these pathways by regulating the function of AMPK. Furthermore, CRBN interacts with damaged DNA binding protein 1 and forms an E3 ubiquitin ligase complex with Cullin 4 where it functions as a substrate receptor in which the proteins recognized by CRBN might be ubiquitinated and degraded by proteasomes. Proteasome-mediated degradation of unneeded or damaged proteins plays a very important role in maintaining regular function of a cell, such as cell survival, dividing, proliferation and growth. Intriguingly, a new role for CRBN has been identified, i.e, the binding of immunomodulatory drugs (IMiDs), e.g. thalidomide, to CRBN has now been associated with teratogenicity and also the cytotoxicity of IMiDs, including lenalidomide, which are widely used to treat multiple myeloma patients. CRBN likely plays an important role in binding, ubiquitination and degradation of factors involved in maintaining function of myeloma cells. These new findings regarding the role of CRBN in IMiD action will stimulate intense investigation of CRBN's downstream factors involved in

  3. Hyperglycemia decreases mitochondrial function: The regulatory role of mitochondrial biogenesis

    SciTech Connect

    Palmeira, Carlos M. Rolo, Anabela P.; Berthiaume, Jessica; Bjork, James A.; Wallace, Kendall B.

    2007-12-01

    Increased generation of reactive oxygen species (ROS) is implicated in 'glucose toxicity' in diabetes. However, little is known about the action of glucose on the expression of transcription factors in hepatocytes, especially those involved in mitochondrial DNA (mtDNA) replication and transcription. Since mitochondrial functional capacity is dynamically regulated, we hypothesized that stressful conditions of hyperglycemia induce adaptations in the transcriptional control of cellular energy metabolism, including inhibition of mitochondrial biogenesis and oxidative metabolism. Cell viability, mitochondrial respiration, ROS generation and oxidized proteins were determined in HepG2 cells cultured in the presence of either 5.5 mM (control) or 30 mM glucose (high glucose) for 48 h, 96 h and 7 days. Additionally, mtDNA abundance, plasminogen activator inhibitor-1 (PAI-1), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) transcripts were evaluated by real time PCR. High glucose induced a progressive increase in ROS generation and accumulation of oxidized proteins, with no changes in cell viability. Increased expression of PAI-1 was observed as early as 96 h of exposure to high glucose. After 7 days in hyperglycemia, HepG2 cells exhibited inhibited uncoupled respiration and decreased MitoTracker Red fluorescence associated with a 25% decrease in mtDNA and 16% decrease in TFAM transcripts. These results indicate that glucose may regulate mtDNA copy number by modulating the transcriptional activity of TFAM in response to hyperglycemia-induced ROS production. The decrease of mtDNA content and inhibition of mitochondrial function may be pathogenic hallmarks in the altered metabolic status associated with diabetes.

  4. Dosage and duration effects of nitrogen additions on ectomycorrhizal sporocarp production and functioning: an example from two N-limited boreal forests

    PubMed Central

    Hasselquist, Niles J; Högberg, Peter

    2014-01-01

    Although it is well known that nitrogen (N) additions strongly affect ectomycorrhizal (EM) fungal community composition, less is known about how different N application rates and duration of N additions affect the functional role EM fungi play in the forest N cycle.We measured EM sporocarp abundance and species richness as well as determined the δ15N in EM sporocarps and tree foliage in two Pinus sylvestris forests characterized by short- and long-term N addition histories and multiple N addition treatments. After 20 and 39 years of N additions, two of the long-term N addition treatments were terminated, thereby providing a unique opportunity to examine the temporal recovery of EM sporocarps after cessation of high N loading.In general, increasing N availability significantly reduced EM sporocarp production, species richness, and the amount of N retained in EM sporocarps. However, these general responses were strongly dependent on the application rate and duration of N additions. The annual addition of 20 kg·N·ha−1 for the past 6 years resulted in a slight increase in the production and retention of N in EM sporocarps, whereas the addition of 100 kg·N·ha−1·yr−1 during the same period nearly eliminated EM sporocarps. In contrast, long-term additions of N at rates of ca. 35 or 70 kg·N·ha−1·yr−1 for the past 40 years did not eliminate tree carbon allocation to EM sporocarps, although there was a decrease in the abundance and a shift in the dominant EM sporocarp taxa. Despite no immediate recovery, EM sporocarp abundance and species richness approached those of the control 20 years after terminating N additions in the most heavily fertilized treatment, suggesting a recovery of carbon allocation to EM sporocarps after cessation of high N loading.Our results provide evidence for a tight coupling between tree carbon allocation to and N retention in EM sporocarps and moreover highlight the potential use of δ15N in EM sporocarps as a relative

  5. Separable roles of UFO during floral development revealed by conditional restoration of gene function.

    PubMed

    Laufs, Patrick; Coen, Enrico; Kronenberger, Jocelyne; Traas, Jan; Doonan, John

    2003-02-01

    The UNUSUAL FLORAL ORGANS (UFO) gene is required for several aspects of floral development in Arabidopsis including specification of organ identity in the second and third whorls and the proper pattern of primordium initiation in the inner three whorls. UFO is expressed in a dynamic pattern during the early phases of flower development. Here we dissect the role of UFO by ubiquitously expressing it in ufo loss-of-function flowers at different developmental stages and for various durations using an ethanol-inducible expression system. The previously known functions of UFO could be separated and related to its expression at specific stages of development. We show that a 24- to 48-hour period of UFO expression from floral stage 2, before any floral organs are visible, is sufficient to restore normal petal and stamen development. The earliest requirement for UFO is during stage 2, when the endogenous UFO gene is transiently expressed in the centre of the wild-type flower and is required to specify the initiation patterns of petal, stamen and carpel primordia. Petal and stamen identity is determined during stages 2 or 3, when UFO is normally expressed in the presumptive second and third whorl. Although endogenous UFO expression is absent from the stamen whorl from stage 4 onwards, stamen identity can be restored by UFO activation up to stage 6. We also observed floral phenotypes not observed in loss-of-function or constitutive gain-of-function backgrounds, revealing additional roles of UFO in outgrowth of petal primordia.

  6. The sintering of uranium carbide and of uranium-plutonium carbide, and the role of nickel as a sintering additive

    NASA Astrophysics Data System (ADS)

    Pickles, S.; Yates, G.; Bramman, J. I.; Finlayson, Moira B.

    1980-04-01

    A comparison of the experimentally determined sintering kinetics for uranium and uranium-plutonium carbides of different stoichiometries with calculations for various theoretical models has been used to indicate probable sintering mechanisms. A bulk diffusion model with activation energies approximating to those for chemical diffusion under a concentration gradient is thought to apply. Ceramography has been used to study the influence of changes in composition and sintering atmosphere on grain size and microstructure, with the conclusion that grain growth is impeded by the presence of a grain-boundary second phase. The role of nickel as a sintering aid has also been investigated using, in addition to the above techniques, electron microprobe analysis and X-ray diffraction for chemical identification of phases. It is concluded that the first stage of sintering is one of particle rearrangement in a binary metallic liquid phase (U-Ni), followed by a solution-precipitation process. On prolonged annealing ternary U-C-Ni phases are produced, dominated by the composition U 2NiC 3.

  7. Living Additive Manufacturing: Transformation of Parent Gels into Diversely Functionalized Daughter Gels Made Possible by Visible Light Photoredox Catalysis.

    PubMed

    Chen, Mao; Gu, Yuwei; Singh, Awaneesh; Zhong, Mingjiang; Jordan, Alex M; Biswas, Santidan; Korley, LaShanda T J; Balazs, Anna C; Johnson, Jeremiah A

    2017-02-22

    Light-initiated additive manufacturing techniques typically rely on layer-by-layer addition or continuous extraction of polymers formed via nonliving, free radical polymerization methods that render the final materials "dead" toward further monomer insertion; the polymer chains within the materials cannot be reactivated to induce chain extension. An alternative "living additive manufacturing" strategy would involve the use of photocontrolled living radical polymerization to spatiotemporally insert monomers into dormant "parent" materials to generate more complex and diversely functionalized "daughter" materials. Here, we demonstrate a proof-of-concept study of living additive manufacturing using end-linked polymer gels embedded with trithiocarbonate iniferters that can be activated by photoinduced single-electron transfer from an organic photoredox catalyst in solution. This system enables the synthesis of a wide range of chemically and mechanically differentiated daughter gels from a single type of parent gel via light-controlled modification of the parent's average composition, strand length, and/or cross-linking density. Daughter gels that are softer than their parent, stiffer than their parent, larger but with the same modulus as their parent, thermally responsive, polarity responsive, healable, and weldable are all realized.

  8. Additives enhancing the catalytic properties of lipase from Burkholderia cepacia immobilized on mixed-function-grafted mesoporous silica gel.

    PubMed

    Abaházi, Emese; Boros, Zoltán; Poppe, László

    2014-07-08

    Effects of various additives on the lipase from Burkholderia cepacia (BcL) immobilized on mixed-function-grafted mesoporous silica gel support by hydrophobic adsorption and covalent attachment were investigated. Catalytic properties of the immobilized biocatalysts were characterized in kinetic resolution of racemic 1-phenylethanol (rac-1a) and 1-(thiophen-2-yl)ethan-1-ol (rac-1b). Screening of more than 40 additives showed significantly enhanced productivity of immobilized BcL with several additives such as PEGs, oleic acid and polyvinyl alcohol. Effects of substrate concentration and temperature between 0-100 °C on kinetic resolution of rac-1a were studied with the best adsorbed BcLs containing PEG 20 k or PVA 18-88 additives in continuous-flow packed-bed reactor. The optimum temperature of lipase activity for BcL co-immobilized with PEG 20k found at around 30 °C determined in the continuous-flow system increased remarkably to around 80 °C for BcL co-immobilized with PVA 18-88.

  9. Living Additive Manufacturing: Transformation of Parent Gels into Diversely Functionalized Daughter Gels Made Possible by Visible Light Photoredox Catalysis

    PubMed Central

    2017-01-01

    Light-initiated additive manufacturing techniques typically rely on layer-by-layer addition or continuous extraction of polymers formed via nonliving, free radical polymerization methods that render the final materials “dead” toward further monomer insertion; the polymer chains within the materials cannot be reactivated to induce chain extension. An alternative “living additive manufacturing” strategy would involve the use of photocontrolled living radical polymerization to spatiotemporally insert monomers into dormant “parent” materials to generate more complex and diversely functionalized “daughter” materials. Here, we demonstrate a proof-of-concept study of living additive manufacturing using end-linked polymer gels embedded with trithiocarbonate iniferters that can be activated by photoinduced single-electron transfer from an organic photoredox catalyst in solution. This system enables the synthesis of a wide range of chemically and mechanically differentiated daughter gels from a single type of parent gel via light-controlled modification of the parent’s average composition, strand length, and/or cross-linking density. Daughter gels that are softer than their parent, stiffer than their parent, larger but with the same modulus as their parent, thermally responsive, polarity responsive, healable, and weldable are all realized. PMID:28280779

  10. Accessing siloxane functionalized polynorbornenes via vinyl-addition polymerization for CO2 separation membranes

    SciTech Connect

    Mahurin, Shannon Mark; Sokolov, Alexei P.; Saito, Tomonori; Long, Brian K.; Gmernicki, Kevin R.; Hong, Eunice; Maroon, Christopher R.

    2016-07-06

    Here, the vinyl addition polymerization of norbornylbased monomers bearing polar functional groups is often problematic, leading to low molecular weight polymers in poor yield. Herein, we provide proof-of-principle evidence that addition-type homopolymers of siloxane substituted norbornyl-based monomers may be readily synthesized using the catalyst trans-[Ni(C6F5)2(SbPh3)2]. Polymerizations using this catalyst reached moderate to high conversion in just 5 min of polymerization and produced siloxanesubstituted polymers with molecular weights exceeding 100 kg/mol. These polymers showed excellent thermal stability (Td ≥ 362 °C) and were cast into membranes that displayed high CO2 permeability and enhanced CO2/N2 selectivity as compared to related materials.

  11. Clinical Evaluation of Functional Vision of +1.5 Diopters near Addition, Aspheric, Rotational Asymmetric Multifocal Intraocular Lens

    PubMed Central

    Khoramnia, Rahmin; Attia, Mary Safwat; Koss, Michael Janusz; Linz, Katharina; Auffarth, Gerd Uwe

    2016-01-01

    Purpose To evaluate postoperative outcomes and visual performance in intermediate distance after implantation of a +1.5 diopters (D) addition, aspheric, rotational asymmetric multifocal intraocular lens (MIOL). Methods Patients underwent bilateral cataract surgery with implantation of an aspheric, asymmetric MIOL with +1.5 D near addition. A complete ophthalmological examination was performed preoperatively and 3 months postoperatively. The main outcome measures were monocular and binocular uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), distance corrected intermediate visual acuity (DCIVA), uncorrected near visual acuity (UNVA) and distance corrected keratometry, and manifest refraction. The Salzburg Reading Desk was used to analyze unilateral and bilateral functional vision with uncorrected and corrected reading acuity, reading distance, reading speed, and the smallest log-scaled print size that could be read effectively at near and intermediate distances. Results The study comprised 60 eyes of 30 patients (mean age, 68.30 ± 9.26 years; range, 34 to 80 years). There was significant improvement in UDVA and CDVA. Mean UIVA was 0.01 ± 0.09 logarithm of the minimum angle of resolution (logMAR) and mean DCIVA was -0.02 ± 0.11 logMAR. In Salzburg Reading Desk analysis for UIVA, the mean subjective intermediate distance was 67.58 ± 8.59 cm with mean UIVA of -0.02 ± 0.09 logMAR and mean word count of 96.38 ± 28.32 words/min. Conclusions The new aspheric, asymmetric, +1.5 D near addition MIOL offers good results for distance visual function in combination with good performance for intermediate distances and functional results for near distance. PMID:27729759

  12. Effect of additive particles on mechanical, thermal, and cell functioning properties of poly(methyl methacrylate) cement

    PubMed Central

    Khandaker, Morshed; Vaughan, Melville B; Morris, Tracy L; White, Jeremiah J; Meng, Zhaotong

    2014-01-01

    The most common bone cement material used clinically today for orthopedic surgery is poly(methyl methacrylate) (PMMA). Conventional PMMA bone cement has several mechanical, thermal, and biological disadvantages. To overcome these problems, researchers have investigated combinations of PMMA bone cement and several bioactive particles (micrometers to nanometers in size), such as magnesium oxide, hydroxyapatite, chitosan, barium sulfate, and silica. A study comparing the effect of these individual additives on the mechanical, thermal, and cell functional properties of PMMA would be important to enable selection of suitable additives and design improved PMMA cement for orthopedic applications. Therefore, the goal of this study was to determine the effect of inclusion of magnesium oxide, hydroxyapatite, chitosan, barium sulfate, and silica additives in PMMA on the mechanical, thermal, and cell functional performance of PMMA. American Society for Testing and Materials standard three-point bend flexural and fracture tests were conducted to determine the flexural strength, flexural modulus, and fracture toughness of the different PMMA samples. A custom-made temperature measurement system was used to determine maximum curing temperature and the time needed for each PMMA sample to reach its maximum curing temperature. Osteoblast adhesion and proliferation experiments were performed to determine cell viability using the different PMMA cements. We found that flexural strength and fracture toughness were significantly greater for PMMA specimens that incorporated silica than for the other specimens. All additives prolonged the time taken to reach maximum curing temperature and significantly improved cell adhesion of the PMMA samples. The results of this study could be useful for improving the union of implant-PMMA or bone-PMMA interfaces by incorporating nanoparticles into PMMA cement for orthopedic and orthodontic applications. PMID:24920906

  13. Novel real function based method to construct heterogeneous porous scaffolds and additive manufacturing for use in medical engineering.

    PubMed

    Yang, Nan; Tian, Yanling; Zhang, Dawei

    2015-11-01

    Heterogeneous porous scaffolds have important applications in biomedical engineering, as they can mimic the structures of natural tissues to achieve the corresponding properties. Here, we introduce a new and easy to implement real function based method for constructing complex, heterogeneous porous structures, including hybrid structures, stochastic structures, functionally gradient structures, and multi-scale structures, or their combinations (e.g., hybrid multi-scale structures). Based on micro-CT data, a femur-mimetic structure with gradient morphology was constructed using our method and fabricated using stereolithography. Results showed that our method could generate gradient porosity or gradient specific surfaces and be sufficiently flexible for use with micro-CT data and additive manufacturing (AM) techniques.

  14. Asymmetric Functional Organozinc Additions to Aldehydes Catalyzed by 1,1′-Bi-2-naphthols (BINOLs)†

    PubMed Central

    2015-01-01

    Conspectus Chiral alcohols are ubiquitous in organic structures. One efficient method to generate chiral alcohols is the catalytic asymmetric addition of a carbon nucleophile to a carbonyl compound since this process produces a C–C bond and a chiral center simultaneously. In comparison with the carbon nucleophiles such as an organolithium or a Grignard reagent, an organozinc reagent possesses the advantages of functional group tolerance and more mild reaction conditions. Catalytic asymmetric reactions of aldehydes with arylzincs, vinylzincs, and alkynylzincs to generate functional chiral alcohols are discussed in this Account. Our laboratory has developed a series of 1,1′-bi-2-naphthol (BINOL)-based chiral catalysts for the asymmetric organozinc addition to aldehydes. It is found that the 3,3′-dianisyl-substituted BINOLs are not only highly enantioselective for the alkylzinc addition to aldehydes, but also highly enantioselective for the diphenylzinc addition to aldehydes. A one-step synthesis has been achieved to incorporate Lewis basic amine groups into the 3,3′-positions of the partially hydrogenated H8BINOL. These H8BINOL–amine compounds have become more generally enantioselective and efficient catalysts for the diphenylzinc addition to aldehydes to produce various types of chiral benzylic alcohols. The application of the H8BINOL–amine catalysts is expanded by using in situ generated diarylzinc reagents from the reaction of aryl iodides with ZnEt2, which still gives high enantioselectivity and good catalytic activity. Such a H8BINOL–amine compound is further found to catalyze the highly enantioselective addition of vinylzincs, in situ generated from the treatment of vinyl iodides with ZnEt2, to aldehydes to give the synthetically very useful chiral allylic alcohols. We have discovered that the unfunctionalized BINOL in combination with ZnEt2 and Ti(OiPr)4 can catalyze the terminal alkyne addition to aldehydes to produce chiral propargylic alcohols

  15. [Novel role of growth factors in ovary function].

    PubMed

    Amsterdam, Abraham

    2010-12-01

    The development of the DNA microarray technique facilitated systematic studies of the modulation of gene function. Considerable attention has been focused on members of the growth factor family to elucidate the main regulators of oocyte maturation and ovarian follicle rupture. Among these growth factors, it was found, both in rodents and in humans, that amphiregulin (Ar) and epiregulin (Ep) of the epidermal growth factor (EGF) family were dramatically up-regulated by gonadotrophins in the intact ovary and in primary granulosa cells, respectively. Their role in cumulus expansion and oocyte maturation was established in rodents, and their synthesis under LH stimulation in granulosa cells was demonstrated in humans. To be activated, Ar and Ep must be cleaved by a disintegrin and metalloproteinases (ADAMs) family. However, the precise processing of Ar and Ep by the cumulus cells is still obscure. Future investigations using DNA microarray technique may reveal the repertoire of genes activated in Ar- and Ep-stimulated cumulus cells and may help elucidate the molecular basis of ovulation. EFG-like factors are also involved in triggering ovarian cancer The author hypothesized that the normal ovary maintains cyclicity in the formation of these growth factors preventing the ovary from developing ovarian cancer In ovarian cancer these growth factors are continuously formed in an autocrine manner, leading to transformation and subsequently to ovarian cancer. These growth factors are essential for both normal and neoplastic transformation of the ovary. Taking into consideration these growth factors in the treatment of ovarian malfunction may be one way of curing ovarian cancer.

  16. Understanding the role of multifunctional nanoengineered particulate additives on supercritical pyrolysis and combustion of hydrocarbon fuels/propellants

    NASA Astrophysics Data System (ADS)

    Sim, Hyung Sub

    This dissertation aims to understand the fundamental effects of colloidal nanostructured materials on the supercritical pyrolysis, injection, ignition, and combustion of hydrocarbon fuels/propellants. As a fuel additive, functionalized graphene sheets (FGS) without or with the decoration of metal catalysts, such as platinum (Pt) or polyoxometalates (POM) nanoparticles, were examined against conventional materials including nanometer sized fumed silica and aluminum particles. Supercritical pyrolysis experiments were performed as a function of temperature, residence time, and particle type, using a high pressure and temperature flow reactor designed to provide isothermal and isobaric flow conditions. Supercritical pyrolysis results showed that the addition of FGS-based particles at a loading concentration of 50 ppmw increased the conversion rates and reduced apparent activation energies for methylcyclohexane (MCH) and n-dodecane (n-C12H26) fuels. For example, conversion rates, and formations of C1-C5 n-alkanes and C2-C6 1-alkenes were significantly increased by 43.5 %, 59.1 %, and 50.0 % for MCH decomposition using FGS 19 (50 ppmw) at a temperature of 820 K and reduced pressure of 1.36. In addition, FGS decorated with 20 wt % Pt (20wt%Pt FGS) at a loading concentration of 50 ppmw exhibited additional enhancement in the conversion rate of n-C12H26 by up to 24.0 % compared to FGS. Especially, FGS-based particles seem to alter initiation mechanisms, which could result in higher hydrogen formation. Hydrogen selectivities for both MCH and n-C12H26 decompositions were observed to increase by nearly a factor of 2 and 10, respectively. Supercritical injection and combustion experiments were conducted using a high pressure and temperature windowed combustion chamber coupled to the flow reactor through a feed system. Supercritical injection/combustion experiments indicated that the presence of a small amount of particles (100 ppmw) in the fuel affected the injection, ignition

  17. Changes in the structure and function of microbial communities in drinking water treatment bioreactors upon addition of phosphorus.

    PubMed

    Li, Xu; Upadhyaya, Giridhar; Yuen, Wangki; Brown, Jess; Morgenroth, Eberhard; Raskin, Lutgarde

    2010-11-01

    Phosphorus was added as a nutrient to bench-scale and pilot-scale biologically active carbon (BAC) reactors operated for perchlorate and nitrate removal from contaminated groundwater. The two bioreactors responded similarly to phosphorus addition in terms of microbial community function (i.e., reactor performance), while drastically different responses in microbial community structure were detected. Improvement in reactor performance with respect to perchlorate and nitrate removal started within a few days after phosphorus addition for both reactors. Microbial community structures were evaluated using molecular techniques targeting 16S rRNA genes. Clone library results showed that the relative abundance of perchlorate-reducing bacteria (PRB) Dechloromonas and Azospira in the bench-scale reactor increased from 15.2% and 0.6% to 54.2% and 11.7% after phosphorus addition, respectively. Real-time quantitative PCR (qPCR) experiments revealed that these increases started within a few days after phosphorus addition. In contrast, after phosphorus addition, the relative abundance of Dechloromonas in the pilot-scale reactor decreased from 7.1 to 0.6%, while Zoogloea increased from 17.9 to 52.0%. The results of this study demonstrated that similar operating conditions for bench-scale and pilot-scale reactors resulted in similar contaminant removal performances, despite dramatically different responses from microbial communities. These findings suggest that it is important to evaluate the microbial community compositions inside bioreactors used for drinking water treatment, as they determine the microbial composition in the effluent and impact downstream treatment requirements for drinking water production. This information could be particularly relevant to drinking water safety, if pathogens or disinfectant-resistant bacteria are detected in the bioreactors.

  18. An additional role for the Brønsted acid-base catalysts of mandelate racemase in transition state stabilization.

    PubMed

    Nagar, Mitesh; Bearne, Stephen L

    2015-11-10

    Mandelate racemase (MR) catalyzes the interconversion of the enantiomers of mandelate and serves as a paradigm for understanding the enzyme-catalyzed abstraction of an α-proton from a carbon acid substrate with a high pKa. The enzyme utilizes a two-base mechanism with Lys 166 and His 297 acting as Brønsted acid and base catalysts, respectively, in the R → S reaction direction. In the S → R reaction direction, their roles are reversed. Using isothermal titration calorimetry (ITC), MR is shown to bind the intermediate/transition state (TS) analogue inhibitor benzohydroxamate (BzH) in an entropy-driven process with a value of ΔCp equal to -358 ± 3 cal mol(-1) K(-1), consistent with an increased number of hydrophobic interactions. However, MR binds BzH with an affinity that is ∼2 orders of magnitude greater than that predicted solely on the basis of hydrophobic interactions [St. Maurice, M., and Bearne, S. L. (2004) Biochemistry 43, 2524], suggesting that additional specific interactions contribute to binding. To test the hypothesis that cation-π/NH-π interactions between the side chains of Lys 166 and His 297 and the aromatic ring and/or the hydroxamate/hydroximate moiety of BzH contribute to the binding of BzH, site-directed mutagenesis was used to generate the MR variants K166M, K166C, H297N, and K166M/H297N and their binding affinity for various ligands determined using ITC. Comparison of the binding affinities of these MR variants with the intermediate/TS analogues BzH and cyclohexanecarbohydroxamate revealed that cation-π/NH-π interactions between His 297 and the hydroxamate/hydroximate moiety and the phenyl ring of BzH contribute approximately 0.26 and 0.91 kcal/mol to binding, respectively, while interactions with Lys 166 contribute approximately 1.74 and 1.74 kcal/mol, respectively. Similarly, comparison of the binding affinities of these mutants with substrate analogues revealed that Lys 166 contributes >2.93 kcal/mol to the binding of (R

  19. Response of Functional Structure of Soil Microbial Community to Multi-level Nitrogen Additions on the Central Tibetan Plateau

    NASA Astrophysics Data System (ADS)

    Zhang, G.; Yuan, Y.

    2015-12-01

    The use of fossil fuels and fertilizers has increased the amount of biologically reactive nitrogen in the atmosphere over the past century. Tibet is the one of the most threatened regions by nitrogen deposition, thus understanding how its microbial communities function maybe of high importance to predicting microbial responses to nitrogen deposition. Here we describe a short-time nitrogen addition conducted in an alpine steppe ecosystem to investigate the response of functional structure of soil microbial community to multi-level nitrogen addition. Using a GeoChip 4.0, we showed that functional diversities and richness of functional genes were unchanged at low level of nitrogen fertilizer inputs (<20 kg N ha-1 yr-1), but significantly decreased at higher nitrogen fertilizer inputs (>=40 kg N ha-1 yr-1). Detrended correspondence analysis indicated that the functional structure of microbial communities was markedly different across the nitrogen gradients. Most C degradation genes whose abundances significantly increased under elevated N fertilizer were those involved in the degradation of relatively labile C (starch, hemicellulose, cellulose), whereas the abundance of certain genes involved in the degradation of recalcitrant C (i.e. lignin) was largely decreased (such as manganese peroxidase, mnp). The results suggest that the elevated N fertilization rates might significantly accelerate the labile C degradation, but might not spur recalcitrant C degradation. The combined effect of gdh and ureC genes involved in N cycling appeared to shift the balance between ammonia and organic N toward organic N ammonification and hence increased the N mineralization potential. Moreover, Urease directly involved in urea mineralization significantly increased. Lastly, Canonical correspondence analysis showed that soil (TOC+NH4++NO3-+NO2-+pH) and plant (Aboveground plant productivity + Shannon Diversity) variables could explain 38.9% of the variation of soil microbial community

  20. Non-structural proteins of arthropod-borne bunyaviruses: roles and functions.

    PubMed

    Eifan, Saleh; Schnettler, Esther; Dietrich, Isabelle; Kohl, Alain; Blomström, Anne-Lie

    2013-10-04

    Viruses within the Bunyaviridae family are tri-segmented, negative-stranded RNA viruses. The family includes several emerging and re-emerging viruses of humans, animals and plants, such as Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, La Crosse virus, Schmallenberg virus and tomato spotted wilt virus. Many bunyaviruses are arthropod-borne, so-called arboviruses. Depending on the genus, bunyaviruses encode, in addition to the RNA-dependent RNA polymerase and the different structural proteins, one or several non-structural proteins. These non-structural proteins are not always essential for virus growth and replication but can play an important role in viral pathogenesis through their interaction with the host innate immune system. In this review, we will summarize current knowledge and understanding of insect-borne bunyavirus non-structural protein function(s) in vertebrate, plant and arthropod.

  1. Phosphazene additives

    DOEpatents

    Harrup, Mason K; Rollins, Harry W

    2013-11-26

    An additive comprising a phosphazene compound that has at least two reactive functional groups and at least one capping functional group bonded to phosphorus atoms of the phosphazene compound. One of the at least two reactive functional groups is configured to react with cellulose and the other of the at least two reactive functional groups is configured to react with a resin, such as an amine resin of a polycarboxylic acid resin. The at least one capping functional group is selected from the group consisting of a short chain ether group, an alkoxy group, or an aryloxy group. Also disclosed are an additive-resin admixture, a method of treating a wood product, and a wood product.

  2. Translating the basic knowledge of mitochondrial functions to metabolic therapy: role of L-carnitine.

    PubMed

    Marcovina, Santica M; Sirtori, Cesare; Peracino, Andrea; Gheorghiade, Mihai; Borum, Peggy; Remuzzi, Giuseppe; Ardehali, Hossein

    2013-02-01

    Mitochondria play important roles in human physiological processes, and therefore, their dysfunction can lead to a constellation of metabolic and nonmetabolic abnormalities such as a defect in mitochondrial gene expression, imbalance in fuel and energy homeostasis, impairment in oxidative phosphorylation, enhancement of insulin resistance, and abnormalities in fatty acid metabolism. As a consequence, mitochondrial dysfunction contributes to the pathophysiology of insulin resistance, obesity, diabetes, vascular disease, and chronic heart failure. The increased knowledge on mitochondria and their role in cellular metabolism is providing new evidence that these disorders may benefit from mitochondrial-targeted therapies. We review the current knowledge of the contribution of mitochondrial dysfunction to chronic diseases, the outcomes of experimental studies on mitochondrial-targeted therapies, and explore the potential of metabolic modulators in the treatment of selected chronic conditions. As an example of such modulators, we evaluate the efficacy of the administration of L-carnitine and its analogues acetyl and propionyl L-carnitine in several chronic diseases. L-carnitine is intrinsically involved in mitochondrial metabolism and function as it plays a key role in fatty acid oxidation and energy metabolism. In addition to the transportation of free fatty acids across the inner mitochondrial membrane, L-carnitine modulates their oxidation rate and is involved in the regulation of vital cellular functions such as apoptosis. Thus, L-carnitine and its derivatives show promise in the treatment of chronic conditions and diseases associated with mitochondrial dysfunction but further translational studies are needed to fully explore their potential.

  3. Functional relationships between leaf hydraulics and leaf economic traits in response to nutrient addition in subtropical tree species.

    PubMed

    Villagra, Mariana; Campanello, Paula I; Bucci, Sandra J; Goldstein, Guillermo

    2013-12-01

    Leaves can be both a hydraulic bottleneck and a safety valve against hydraulic catastrophic dysfunctions, and thus changes in traits related to water movement in leaves and associated costs may be critical for the success of plant growth. A 4-year fertilization experiment with nitrogen (N) and phosphorus (P) addition was done in a semideciduous Atlantic forest in northeastern Argentina. Saplings of five dominant canopy species were grown in similar gaps inside the forests (five control and five N + P addition plots). Leaf lifespan (LL), leaf mass per unit area (LMA), leaf and stem vulnerability to cavitation, leaf hydraulic conductance (K(leaf_area) and K(leaf_mass)) and leaf turgor loss point (TLP) were measured in the five species and in both treatments. Leaf lifespan tended to decrease with the addition of fertilizers, and LMA was significantly higher in plants with nutrient addition compared with individuals in control plots. The vulnerability to cavitation of leaves (P50(leaf)) either increased or decreased with the nutrient treatment depending on the species, but the average P50(leaf) did not change with nutrient addition. The P50(leaf) decreased linearly with increasing LMA and LL across species and treatments. These trade-offs have an important functional significance because more expensive (higher LMA) and less vulnerable leaves (lower P50(leaf)) are retained for a longer period of time. Osmotic potentials at TLP and at full turgor became more negative with decreasing P50(leaf) regardless of nutrient treatment. The K(leaf) on a mass basis was negatively correlated with LMA and LL, indicating that there is a carbon cost associated with increased water transport that is compensated by a longer LL. The vulnerability to cavitation of stems and leaves were similar, particularly in fertilized plants. Leaves in the species studied may not function as safety valves at low water potentials to protect the hydraulic pathway from water stress-induced cavitation

  4. The effect of tin and antimony addition on the performance of dual function cracking catalyst (DFCC) mixtures

    SciTech Connect

    Occelli, M.L. ); Naraghi, S.M.; Krishnan, V.; Suib, S.L. )

    1992-05-01

    In 1976, the Phillips Petroleum Company successfully demonstrated that the addition of certain organo-antimony compounds to a metal-contaminated heavy gas oil reduced the deleterious effects that metals such as Ni and V have on gasoline yields, coke, and hydrogen selectivities. Nickel has little effect on the activity of a fluidized cracking catalyst (FCC) but generates large amounts of gases, placing severe demands on capabilities of gas compressors. Marketed by Phillips Petroleum Company. Phil-Ad CA antimony organics have been shown to reduce by 50% gas formation due to metal contaminants, especially nickel. However, Sb, when introduced into a fluidized cracking unit, could reduce and form SbH[sub 3], stibine, that like arsine (AsH[sub 3]) is a highly toxic compound. Procedures for the safe usage of Sb in refining operations have been outlined; when used properly, Sb-containing passivating agents did not generate any detectable stibine. Recently, it has been reported that at microactivity test conditions, the additions of diluents (such as aluminas and layered magnesium silicates) capable of selectively sorbing metal contaminants from gas oils can form dual function cracking catalysts (DFCC) that retain most of their useful cracking activity even in the presence of as much as 1.0-1.5% V. It is the purpose of this paper to report the stability of Sb- and Sn-loaded alumina particles and the effects that the addition of metal passivation compounds such as Sb and Sn have on the performance of DFCC mixtures.

  5. Structural Evolution of Electrochemically Lithiated MoS2 Nanosheets and the Role of Carbon Additive in Li-Ion Batteries

    PubMed Central

    2016-01-01

    Understanding the structure and phase changes associated with conversion-type materials is key to optimizing their electrochemical performance in Li-ion batteries. For example, molybdenum disulfide (MoS2) offers a capacity up to 3-fold higher (∼1 Ah/g) than the currently used graphite anodes, but they suffer from limited Coulombic efficiency and capacity fading. The lack of insights into the structural dynamics induced by electrochemical conversion of MoS2 still hampers its implementation in high energy-density batteries. Here, by combining ab initio density-functional theory (DFT) simulation with electrochemical analysis, we found new sulfur-enriched intermediates that progressively insulate MoS2 electrodes and cause instability from the first discharge cycle. Because of this, the choice of conductive additives is critical for the battery performance. We investigate the mechanistic role of carbon additive by comparing equal loading of standard Super P carbon powder and carbon nanotubes (CNTs). The latter offer a nearly 2-fold increase in capacity and a 45% reduction in resistance along with Coulombic efficiency of over 90%. These insights into the phase changes during MoS2 conversion reactions and stabilization methods provide new solutions for implementing cost-effective metal sulfide electrodes, including Li–S systems in high energy-density batteries. PMID:27818575

  6. Structural Evolution of Electrochemically Lithiated MoS2 Nanosheets and the Role of Carbon Additive in Li-Ion Batteries.

    PubMed

    George, Chandramohan; Morris, Andrew J; Modarres, Mohammad H; De Volder, Michael

    2016-10-25

    Understanding the structure and phase changes associated with conversion-type materials is key to optimizing their electrochemical performance in Li-ion batteries. For example, molybdenum disulfide (MoS2) offers a capacity up to 3-fold higher (∼1 Ah/g) than the currently used graphite anodes, but they suffer from limited Coulombic efficiency and capacity fading. The lack of insights into the structural dynamics induced by electrochemical conversion of MoS2 still hampers its implementation in high energy-density batteries. Here, by combining ab initio density-functional theory (DFT) simulation with electrochemical analysis, we found new sulfur-enriched intermediates that progressively insulate MoS2 electrodes and cause instability from the first discharge cycle. Because of this, the choice of conductive additives is critical for the battery performance. We investigate the mechanistic role of carbon additive by comparing equal loading of standard Super P carbon powder and carbon nanotubes (CNTs). The latter offer a nearly 2-fold increase in capacity and a 45% reduction in resistance along with Coulombic efficiency of over 90%. These insights into the phase changes during MoS2 conversion reactions and stabilization methods provide new solutions for implementing cost-effective metal sulfide electrodes, including Li-S systems in high energy-density batteries.

  7. Non-parametric estimation of the odds ratios for continuous exposures using generalized additive models with an unknown link function.

    PubMed

    Cadarso-Suárez, Carmen; Roca-Pardiñas, Javier; Figueiras, Adolfo; González-Manteiga, Wenceslao

    2005-04-30

    The generalized additive, model (GAM) is a powerful and widely used tool that allows researchers to fit, non-parametrically, the effect of continuous predictors on a transformation of the mean response variable. Such a transformation is given by a so-called link function, and in GAMs this link function is assumed to be known. Nevertheless, if an incorrect choice is made for the link, the resulting GAM is misspecified and the results obtained may be misleading. In this paper, we propose a modified version of the local scoring algorithm that allows for the non-parametric estimation of the link function, by using local linear kernel smoothers. To better understand the effect that each covariate produces on the outcome, results are expressed in terms of the non-parametric odds ratio (OR) curves. Bootstrap techniques were used to correct the bias in the OR estimation and to construct point-wise confidence intervals. A simulation study was carried out to assess the behaviour of the resulting estimates. The proposed methodology was illustrated using data from the AIDS Register of Galicia (NW Spain), with a view to assessing the effect of the CD4 lymphocyte count on the probability of being AIDS-diagnosed via Tuberculosis (TB). This application shows how the link's flexibility makes it possible to obtain OR curve estimates that are less sensitive to the presence of outliers and unusual values that are often present in the extremes of the covariate distributions.

  8. Function, Role, and Clinical Application of MicroRNAs in Vascular Aging

    PubMed Central

    Zhan, Jun-Kun; Wang, Yan-Jiao; Tan, Pan; Chen, Yi-Yin; Deng, Hui-Qian

    2016-01-01

    Vascular aging, a specific type of organic aging, is related to age-dependent changes in the vasculature, including atherosclerotic plaques, arterial stiffness, fibrosis, and increased intimal thickening. Vascular aging could influence the threshold, process, and severity of various cardiovascular diseases, thus making it one of the most important risk factors in the high mortality of cardiovascular diseases. As endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are the main cell biological basis of these pathology changes of the vasculature, the structure and function of ECs and VSMCs play a key role in vascular aging. MicroRNAs (miRNAs), small noncoding RNAs, have been shown to regulate the expression of multiple messenger RNAs (mRNAs) posttranscriptionally, contributing to many crucial aspects of cell biology. Recently, miRNAs with functions associated with aging or aging-related diseases have been studied. In this review, we will summarize the reported role of miRNAs in the process of vascular aging with special emphasis on EC and VSMC functions. In addition, the potential application of miRNAs to clinical practice for the diagnosis and treatment of cardiovascular diseases will also be discussed. PMID:28097140

  9. The semidominant Mi(b) mutation identifies a role for the HLH domain in DNA binding in addition to its role in protein dimerization.

    PubMed Central

    Steingrímsson, E; Nii, A; Fisher, D E; Ferré-D'Amaré, A R; McCormick, R J; Russell, L B; Burley, S K; Ward, J M; Jenkins, N A; Copeland, N G

    1996-01-01

    The mouse microphthalmia (mi) locus encodes a basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor called MITF (microphthalmia transcription factor). Mutations at mi affect the development of several different cell types, including melanocytes, mast cells, osteoclasts and pigmented epithelial cells of the eye. Here we describe the phenotypic and molecular characterization of the semidominant Microphthalmia(brwnish) (Mi(b)) mutation. We show that this mutation primarily affects melanocytes and produces retinal degeneration. The mutation is a G to A transition leading to a Gly244Glu substitution in helix 2 of the HLH dimerization domain. This location is surprising since other semidominant mi mutations characterized to date have been shown to affect DNA binding or transcriptional activation domains of MITF and act as dominant negatives, while mutations that affect MITF dimerization are inherited recessively. Gel retardation assays showed that while the mutant MITF(Mi-b) protein retains its dimerization potential, it is defective in its ability to bind DNA. Computer modeling suggested that the Gly244Glu mutation might disrupt DNA binding by interfering with productive docking of the protein dimer onto DNA. The Mi(b) mutation therefore appears to dissociate a DNA recognition function of the HLH domain from its role in protein dimerization. Images PMID:8947051

  10. Ionic Liquids as Multi-Functional Lubricant Additives to Enhance Engine Efficiency (final report NFE-12-03876)

    SciTech Connect

    Qu, Jun; Luo, Huimin; Toops, Todd J.; West, Brian H.; Blau, Peter Julian; Dai, Sheng; Papke, Brian L.; Gao, Hong; Kheireddin, Bassem; Chen, Cheng

    2016-04-01

    This ORNL-Shell CRADA developed and investigated ionic liquids (ILs) as multifunctional additives for next-generation low-viscosity engine oils. Several groups of oil-miscible ILs were successfully designed and synthesized with high thermal stability, non-corrosiveness, excellent wettability, and most importantly effective anti-scuffing/anti-wear and friction reduction characteristics. Synergistic effects between the common anti-wear additive zinc dialkyldithiophosphate (ZDDP) and a particular group of ILs were discovered with > 30% friction reduction and 70% wear reduction compared with using ZDDP or IL alone. The IL+ZDDP tribofilm distinguishes itself from the IL or ZDDP tribofilms with substantially higher contents of metal phosphates but less metal oxides and sulfur compounds. Notably, it was revealed that the actual concentrations of functional elements on the droplet surface of the oil containing IL+ZDDP are one order magnitude higher than their nominal values. Such significantly increased concentrations of anti-wear agents are presumably expected for the oilsolid interface and believed to be responsible for the superior lubricating performance. A prototype SAE 0W-16 engine oil using a synergistic IL+ZDDP pair as the anti-wear additive has been formulated based on the compatibility between the IL and other additives. Sequence VIE full-scale engine dynamometer tests demonstrated fuel economy improvement (FEI) for this prototype oil and revealed the individual contributions from the lower oil viscosity and reduced boundary friction. The impact of IL and IL+ZDDP on exhaust emission catalyst was investigated using an accelerated small engine aging test and results were benchmarked against ZDDP.

  11. Nutritional, Health, and Technological Functionality of Lupin Flour Addition to Bread and Other Baked Products: Benefits and Challenges.

    PubMed

    Villarino, C B J; Jayasena, V; Coorey, R; Chakrabarti-Bell, S; Johnson, S K

    2016-01-01

    Lupin is an undervalued legume despite its high protein and dietary fiber content and potential health benefits. This review focuses on the nutritional value, health benefits, and technological effects of incorporating lupin flour into wheat-based bread. Results of clinical studies suggest that consuming lupin compared to wheat bread and other baked products reduce chronic disease risk markers; possibly due to increased protein and dietary fiber and bioactive compounds. However, lupin protein allergy has also been recorded. Bread quality has been improved when 10% lupin flour is substituted for refined wheat flour; possibly due to lupin-wheat protein cross-linking assisting bread volume and the high water-binding capacity (WBC) of lupin fiber delaying staling. Above 10% substitution appears to reduce bread quality due to lupin proteins low elasticity and the high WBC of its dietary fiber interrupting gluten network development. Gaps in understanding of the role of lupin flour in bread quality include the optimal formulation and processing conditions to maximize lupin incorporation, role of protein cross-linking, antistaling functionality, and bioactivity of its γ-conglutin protein.

  12. Differing Roles of Functional Movement Variability as Experience Increases in Gymnastics

    PubMed Central

    Busquets, Albert; Marina, Michel; Davids, Keith; Angulo-Barroso, Rosa

    2016-01-01

    gymnasts). Longswing assessment allowed us to evaluate inter-trial variability in representative performance context. Coordination variability presented two different configurations across experience levels depending on the variable of interest: either a U-shaped or a L- or \\-shaped graph. Increased inter-trial variability of the functional phase events offered flexibility to adapt the longswing performance in the advanced gymnasts, while decreasing variability in arm-trunk coordination modes was critical to improve longswing and to achieve the most advanced level. In addition, the relationship between variability measures and the global performance outcome (i.e. the swing amplitude) revealed different functional roles of movement variability (exploratory or restrictive) as a function of changes in experience levels. PMID:27274664

  13. The Role of Esophageal Hypersensitivity in Functional Esophageal Disorders.

    PubMed

    Farmer, Adam D; Ruffle, James K; Aziz, Qasim

    2017-02-01

    The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.

  14. Role of the ubiquitin-proteasome system in nervous system function and disease: using C. elegans as a dissecting tool.

    PubMed

    Baptista, Márcio S; Duarte, Carlos B; Maciel, Patrícia

    2012-08-01

    In addition to its central roles in protein quality control, regulation of cell cycle, intracellular signaling, DNA damage response and transcription regulation, the ubiquitin-proteasome system (UPS) plays specific roles in the nervous system, where it contributes to precise connectivity through development, and later assures functionality by regulating a wide spectrum of neuron-specific cellular processes. Aberrations in this system have been implicated in the etiology of neurodevelopmental and neurodegenerative diseases. In this review, we provide an updated view on the UPS and highlight recent findings concerning its role in normal and diseased nervous systems. We discuss the advantages of the model organism Caenorhabditis elegans as a tool to unravel the major unsolved questions concerning this biochemical pathway and its involvement in nervous system function and dysfunction, and expose the new possibilities, using state-of-the-art techniques, to assess UPS function using this model system.

  15. The Complete Mentor Role: Understanding the Six Behavioral Functions.

    ERIC Educational Resources Information Center

    Galbraith, Michael W.; Cohen, Norman H.

    1996-01-01

    Mentoring is a blend of six behavioral functions: relationship (establishing trust), information (offering advice), facilitation (introducing alternatives), confrontation (challenging), mentor model (motivating), and protege vision (encouraging initiative). (SK)

  16. Evidence for a Role of Executive Functions in Learning Biology

    ERIC Educational Resources Information Center

    Rhodes, Sinéad M.; Booth, Josephine N.; Campbell, Lorna Elise; Blythe, Richard A.; Wheate, Nial J.; Delibegovic, Mirela

    2014-01-01

    Research examining cognition and science learning has focused on working memory, but evidence implicates a broader set of executive functions. The current study examined executive functions and learning of biology in young adolescents. Fifty-six participants, aged 12-13?years, completed tasks of working memory (Spatial Working Memory), inhibition…

  17. The role of rabbit meat as functional food.

    PubMed

    Dalle Zotte, Antonella; Szendro, Zsolt

    2011-07-01

    Increasing consumer knowledge of the link between diet and health has raised the awareness and demand for functional food ingredients. Meat and its derivatives may be considered functional foods to the extent that they contain numerous compounds thought to be functional. This review will attempt to outline the excellent nutritional and dietetic properties of rabbit meat and offer an overview of the studies performed on the strategies adopted to improve the functional value of rabbit meat. Dietary manipulation has been seen to be very effective in increasing the levels of essential FA, EPA, DHA, CLA, branched chain FA, vitamin E, and selenium in rabbit meat. Dietary fortification with vitamin E or natural products such as oregano essential oil, chia seed oil, and Spirulina platensis microalga seem promising in improving the oxidative stability of rabbit meat while also adding functional ingredients.

  18. Budesonide added to modified porcine surfactant Curosurf may additionally improve the lung functions in meconium aspiration syndrome.

    PubMed

    Mikolka, P; Mokrá, D; Kopincová, J; Tomčíková-Mikušiaková, L; Calkovská, A

    2013-01-01

    Severe meconium aspiration syndrome (MAS) in newborns is often treated by exogenous surfactant. Because its efficacy is reduced by meconium-induced inflammation, glucocorticoid budesonide was added into surfactant preparation Curosurf to enhance efficacy of the surfactant therapy in experimental model of MAS. Oxygen-ventilated rabbits were intratracheally given meconium (25 mg/ml, 4 ml/kg) to induce respiratory failure. Thirty minutes later, animals were treated by intratracheal budesonide (0.25 mg/kg) or surfactant lung lavage (10 ml/kg, 5 mg phospholipids/ml) repeated twice, followed by undiluted Curosurf (100 mg phospholipids/kg) or by the above mentioned surfactant treatment with the last surfactant dose fortified with budesonide (0.25 mg/kg) or were untreated. Animals were ventilated for additional 5 hours and respiratory parameters were measured regularly. After sacrificing animals, wet-dry lung weight ratio was evaluated and plasma levels of interleukins (IL)-1beta, -6, -8, and TNF-alpha were measured by ELISA method. Efficacy of the given therapies to enhance lung functions and to diminish lung edema formation and inflammation increased from budesonide-only and surfactant-only therapy to surfactant+budesonide therapy. Combined therapy improved gas exchange from 30 min of administration, and showed a longer-lasting effect than surfactant-only therapy. In conclusions, budesonide additionally improved the effects of exogenous surfactant in experimental MAS.

  19. Resonance scattering and radiation force calculations for an elastic cylinder using the translational addition theorem for cylindrical wave functions

    SciTech Connect

    Mitri, F. G.

    2015-09-15

    The standard Resonance Scattering Theory (RST) of plane waves is extended for the case of any two-dimensional (2D) arbitrarily-shaped monochromatic beam incident upon an elastic cylinder with arbitrary location using an exact methodology based on Graf’s translational addition theorem for the cylindrical wave functions. The analysis is exact as it does not require numerical integration procedures. The formulation is valid for any cylinder of finite size and material that is immersed in a nonviscous fluid. Partial-wave series expansions (PWSEs) for the incident, internal and scattered linear pressure fields are derived, and the analysis is further extended to obtain generalized expressions for the on-axis and off-axis acoustic radiation force components. The wave-fields are expressed using generalized PWSEs involving the beam-shape coefficients (BSCs) and the scattering coefficients of the cylinder. The off-axial BSCs are expressed analytically in terms of an infinite PWSE with emphasis on the translational offset distance d. Numerical computations are considered for a zeroth-order quasi-Gaussian beam chosen as an example to illustrate the analysis. Acoustic resonance scattering directivity diagrams are calculated by subtracting an appropriate background from the expression of the scattered pressure field. In addition, computations for the radiation force exerted on an elastic cylinder centered on the axis of wave propagation of the beam, and shifted off-axially are analyzed and discussed.

  20. Composite scaffolds for osteochondral repair obtained by combination of additive manufacturing, leaching processes and hMSC-CM functionalization.

    PubMed

    Díaz Lantada, Andrés; Alarcón Iniesta, Hernán; García-Ruíz, Josefa Predestinación

    2016-02-01

    Articular repair is a relevant and challenging area for the emerging fields of tissue engineering and biofabrication. The need of significant gradients of properties, for the promotion of osteochondral repair, has led to the development of several families of composite biomaterials and scaffolds, using different effective approaches, although a perfect solution has not yet been found. In this study we present the design, modeling, rapid manufacturing and in vitro testing of a composite scaffold aimed at osteochondral repair. The presented composite scaffold stands out for having a functional gradient of density and stiffness in the bony phase, obtained in titanium by means of computer-aided design combined with additive manufacture using selective laser sintering. The chondral phase is obtained by sugar leaching, using a PDMS matrix and sugar as porogen, and is joined to the bony phase during the polymerization of PDMS, therefore avoiding the use of supporting adhesives or additional intermediate layers. The mechanical performance of the construct is biomimetic and the stiffness values of the bony and chondral phases can be tuned to the desired applications, by means of controlled modifications of different parameters. A human mesenchymal stem cell (h-MSC) conditioned medium (CM) is used for improving scaffold response. Cell culture results provide relevant information regarding the viability of the composite scaffolds used.

  1. Functional characterization of Escherichia coli GlpG and additional rhomboid proteins using an aarA mutant of Providencia stuartii.

    PubMed

    Clemmer, Katy M; Sturgill, Gwen M; Veenstra, Alexander; Rather, Philip N

    2006-05-01

    The Providencia stuartii AarA protein is a member of the rhomboid family of intramembrane serine proteases and required for the production of an extracellular signaling molecule that regulates cellular functions including peptidoglycan acetylation, methionine transport, and cysteine biosynthesis. Additional aarA-dependent phenotypes include (i) loss of an extracellular yellow pigment, (ii) inability to grow on MacConkey agar, and (iii) abnormal cell division. Since these phenotypes are easily assayed, the P. stuartii aarA mutant serves as a useful host system to investigate rhomboid function. The Escherichia coli GlpG protein was shown to be functionally similar to AarA and rescued the above aarA-dependent phenotypes in P. stuartii. GlpG proteins containing single alanine substitutions at the highly conserved catalytic triad of asparagine (N154A), serine (S201A), or histidine (H254A) residues were nonfunctional. The P. stuartii aarA mutant was also used as a biosensor to demonstrate that proteins from a variety of diverse sources exhibited rhomboid activity. In an effort to further investigate the role of a rhomboid protein in cell physiology, a glpG mutant of E. coli was constructed. In phenotype microarray experiments, the glpG mutant exhibited a slight increase in resistance to the beta-lactam antibiotic cefotaxime.

  2. Roles for text mining in protein function prediction.

    PubMed

    Verspoor, Karin M

    2014-01-01

    The Human Genome Project has provided science with a hugely valuable resource: the blueprints for life; the specification of all of the genes that make up a human. While the genes have all been identified and deciphered, it is proteins that are the workhorses of the human body: they are essential to virtually all cell functions and are the primary mechanism through which biological function is carried out. Hence in order to fully understand what happens at a molecular level in biological organisms, and eventually to enable development of treatments for diseases where some aspect of a biological system goes awry, we must understand the functions of proteins. However, experimental characterization of protein function cannot scale to the vast amount of DNA sequence data now available. Computational protein function prediction has therefore emerged as a problem at the forefront of modern biology (Radivojac et al., Nat Methods 10(13):221-227, 2013).Within the varied approaches to computational protein function prediction that have been explored, there are several that make use of biomedical literature mining. These methods take advantage of information in the published literature to associate specific proteins with specific protein functions. In this chapter, we introduce two main strategies for doing this: association of function terms, represented as Gene Ontology terms (Ashburner et al., Nat Genet 25(1):25-29, 2000), to proteins based on information in published articles, and a paradigm called LEAP-FS (Literature-Enhanced Automated Prediction of Functional Sites) in which literature mining is used to validate the predictions of an orthogonal computational protein function prediction method.

  3. Influence of silica matrix composition and functional component additives on the bioactivity and viability of encapsulated living cells

    DOE PAGES

    Savage, Travis J.; Dunphy, Darren R.; Harbaugh, Svetlana; ...

    2015-11-06

    The remarkable impact encapsulation matrix chemistry can have on the bioactivity and viability of integrated living cells is reported. Two silica chemistries (aqueous silicate and alkoxysilane), and a functional component additive (glycerol), are employed to generate three distinct silica matrices. These matrices are used to encapsulate living E. coli cells engineered with a synthetic riboswitch for cell-based biosensing. Following encapsulation, membrane integrity, reproductive capability, and riboswitch-based protein expression levels and rates are measured over a 5 week period. Striking differences in E. coli bioactivity, viability, and biosensing performance are observed for cells encapsulated within the different matrices. E. coli cellsmore » encapsulated for 35 days in aqueous silicate-based (AqS) matrices showed relatively low membrane integrity, but high reproductive capability in comparison to cells encapsulated in glycerol containing sodium silicate-based (AqS + g) and alkoxysilane-based (PGS) gels. Further, cells in sodium silicate-based matrices showed increasing fluorescence output over time, resulting in a 1.8-fold higher fluorescence level, and a faster expression rate, over cells free in solution. Furthermore, this unusual and unique combination of biological properties demonstrates that careful design of the encapsulation matrix chemistry can improve functionality of the biocomposite material, and result in new and unexpected physiological states.« less

  4. Influence of Silica Matrix Composition and Functional Component Additives on the Bioactivity and Viability of Encapsulated Living Cells

    DOE PAGES

    Savage, Travis J.; Dunphy, Darren R.; Harbaugh, Svetlana; ...

    2015-11-06

    We report the remarkable impact encapsulation matrix chemistry can have on the bioactivity and viability of integrated living cells. Two silica chemistries (aqueous silicate and alkoxysilane), and a functional component additive (glycerol), are employed to generate three distinct silica matrices. Moreover, these matrices are used to encapsulate living E. coli cells engineered with a synthetic riboswitch for cell-based biosensing. Following encapsulation, membrane integrity, reproductive capability, and riboswitch-based protein expression levels and rates are measured over a 5 week period. Striking differences in E. coli bioactivity, viability, and biosensing performance are observed for cells encapsulated within the different matrices. E. colimore » cells encapsulated for 35 days in aqueous silicate-based (AqS) matrices showed relatively low membrane integrity, but high reproductive capability in comparison to cells encapsulated in glycerol containing sodium silicate-based (AqS + g) and alkoxysilane-based (PGS) gels. Further, cells in sodium silicate-based matrices showed increasing fluorescence output over time, resulting in a 1.8-fold higher fluorescence level, and a faster expression rate, over cells free in solution. Finally, this unusual and unique combination of biological properties demonstrates that careful design of the encapsulation matrix chemistry can improve functionality of the biocomposite material, and result in new and unexpected physiological states.« less

  5. Influence of Silica Matrix Composition and Functional Component Additives on the Bioactivity and Viability of Encapsulated Living Cells

    SciTech Connect

    Savage, Travis J.; Dunphy, Darren R.; Harbaugh, Svetlana; Kelley-Loughnane, Nancy; Harper, Jason C.; Brinker, C. Jeffrey

    2015-11-06

    We report the remarkable impact encapsulation matrix chemistry can have on the bioactivity and viability of integrated living cells. Two silica chemistries (aqueous silicate and alkoxysilane), and a functional component additive (glycerol), are employed to generate three distinct silica matrices. Moreover, these matrices are used to encapsulate living E. coli cells engineered with a synthetic riboswitch for cell-based biosensing. Following encapsulation, membrane integrity, reproductive capability, and riboswitch-based protein expression levels and rates are measured over a 5 week period. Striking differences in E. coli bioactivity, viability, and biosensing performance are observed for cells encapsulated within the different matrices. E. coli cells encapsulated for 35 days in aqueous silicate-based (AqS) matrices showed relatively low membrane integrity, but high reproductive capability in comparison to cells encapsulated in glycerol containing sodium silicate-based (AqS + g) and alkoxysilane-based (PGS) gels. Further, cells in sodium silicate-based matrices showed increasing fluorescence output over time, resulting in a 1.8-fold higher fluorescence level, and a faster expression rate, over cells free in solution. Finally, this unusual and unique combination of biological properties demonstrates that careful design of the encapsulation matrix chemistry can improve functionality of the biocomposite material, and result in new and unexpected physiological states.

  6. Influence of silica matrix composition and functional component additives on the bioactivity and viability of encapsulated living cells

    SciTech Connect

    Savage, Travis J.; Dunphy, Darren R.; Harbaugh, Svetlana; Kelley-Loughnane, Nancy; Harper, Jason C.; Brinker, C. Jeffrey

    2015-11-06

    The remarkable impact encapsulation matrix chemistry can have on the bioactivity and viability of integrated living cells is reported. Two silica chemistries (aqueous silicate and alkoxysilane), and a functional component additive (glycerol), are employed to generate three distinct silica matrices. These matrices are used to encapsulate living E. coli cells engineered with a synthetic riboswitch for cell-based biosensing. Following encapsulation, membrane integrity, reproductive capability, and riboswitch-based protein expression levels and rates are measured over a 5 week period. Striking differences in E. coli bioactivity, viability, and biosensing performance are observed for cells encapsulated within the different matrices. E. coli cells encapsulated for 35 days in aqueous silicate-based (AqS) matrices showed relatively low membrane integrity, but high reproductive capability in comparison to cells encapsulated in glycerol containing sodium silicate-based (AqS + g) and alkoxysilane-based (PGS) gels. Further, cells in sodium silicate-based matrices showed increasing fluorescence output over time, resulting in a 1.8-fold higher fluorescence level, and a faster expression rate, over cells free in solution. Furthermore, this unusual and unique combination of biological properties demonstrates that careful design of the encapsulation matrix chemistry can improve functionality of the biocomposite material, and result in new and unexpected physiological states.

  7. Toward Additive-Free Small-Molecule Organic Solar Cells: Roles of the Donor Crystallization Pathway and Dynamics.

    PubMed

    Abdelsamie, Maged; Treat, Neil D; Zhao, Kui; McDowell, Caitlin; Burgers, Mark A; Li, Ruipeng; Smilgies, Detlef-M; Stingelin, Natalie; Bazan, Guillermo C; Amassian, Aram

    2015-12-02

    The ease with which small-molecule donors crystallize during solution processing is directly linked to the need for solvent additives. Donor molecules that get trapped in disordered (H1) or liquid crystalline (T1) mesophases require additive processing to promote crystallization, phase separation, and efficient light harvesting. A donor material (X2) that crystallizes directly from solution yields additive-free solar cells with an efficiency of 7.6%.

  8. Elucidating the Severity of Preclinical Traumatic Brain Injury Models: A Role for Functional Assessment?

    PubMed Central

    Turner, Ryan C.; VanGilder, Reyna L.; Naser, Zachary J.; Lucke-Wold, Brandon P.; Bailes, Julian E.; Matsumoto, Rae R.; Huber, Jason D.; Rosen, Charles L.

    2016-01-01

    Background Concussion remains a symptom-based diagnosis clinically, yet preclinical studies investigating traumatic brain injury, of which concussion is believed to represent a ‘mild’ form, emphasize histological endpoints with functional assessments often minimized or ignored all together. Recently, clinical studies have identified the importance of cognitive and neuropsychiatric symptoms, in addition to somatic complaints, following concussion. How these findings may translate to preclinical studies is unclear at present. Objective To address the contrasting endpoints utilized clinically compared to those in preclinical studies and the potential role of functional assessments in a commonly used model of diffuse axonal injury (DAI).. Methods Animals were subjected to DAI using the impact-acceleration model. Functional and behavioral assessments were conducted over 1 week following DAI prior to completion of histological assessment at 1-week post-DAI. Results We show, despite the suggestion that this model represents concussive injury, no functional impairments as determined using common measures of motor, sensorimotor, cognitive, and neuropsychiatric function following injury over the course of 1 week. The lack of functional deficits is in sharp contrast to neuropathologic findings indicating neural degeneration, astrocyte reactivity, and microglial activation. Conclusion Future studies are needed to identify functional assessments, neurophysiologic techniques, and imaging assessments more apt to distinguish differences following so-called ‘mild’ traumatic brain injury (TBI) in preclinical models and determine whether these models are truly studying concussive or subconcussive injury. These studies are needed to not only understand mechanism of injury and production of subsequent deficits, but also for rigorous evaluation of potential therapeutic agents. PMID:24448183

  9. Role of scattering distribution functions in spacecraft contamination control practices

    NASA Technical Reports Server (NTRS)

    Carosso, P. A.; Carosso, N. J. P.

    1986-01-01

    A method for spacecraft optical surface contamination monitoring based on the bidirectional reflectance distribution function (BRDF) and the bidirectional transmittance distribution function (BTDF) is described. In the experimental set up, BRDF/BTDF measurements were made at 0.6328 microns using a 35-mW He-Ne laser light source. A correlation of the second order between BRDF and cleanliness levels was observed. It is suggested that bidirectional scattering distribution functions measured on witness mirrors can give information about contamination in clean rooms or vacuum chambers, and that they can be adopted to establish contamination control criteria.

  10. The addition of functional task-oriented mental practice to conventional physical therapy improves motor skills in daily functions after stroke*

    PubMed Central

    Santos-Couto-Paz, Clarissa C.; Teixeira-Salmela, Luci F.; Tierra-Criollo, Carlos J.

    2013-01-01

    Background Mental practice (MP) is a cognitive strategy which may improve the acquisition of motor skills and functional performance of athletes and individuals with neurological injuries. Objective To determine whether an individualized, specific functional task-oriented MP, when added to conventional physical therapy (PT), promoted better learning of motor skills in daily functions in individuals with chronic stroke (13±6.5 months post-stroke). Method Nine individuals with stable mild and moderate upper limb impairments participated, by employing an A1-B-A2 single-case design. Phases A1 and A2 included one month of conventional PT, and phase B the addition of MP training to PT. The motor activity log (MAL-Brazil) was used to assess the amount of use (AOU) and quality of movement (QOM) of the paretic upper limb; the revised motor imagery questionnaire (MIQ-RS) to assess the abilities in kinesthetic and visual motor imagery; the Minnesota manual dexterity test to assess manual dexterity; and gait speed to assess mobility. Results After phase A1, no significant changes were observed for any of the outcome measures. However, after phase B, significant improvements were observed for the MAL, AOU and QOM scores (p<0.0001), and MIQ-RS kinesthetic and visual scores (p=0.003; p=0.007, respectively). The significant gains in manual dexterity (p=0.002) and gait speed (p=0.019) were maintained after phase A2. Conclusions Specific functional task-oriented MP, when added to conventional PT, led to improvements in motor imagery abilities combined with increases in the AOU and QOM in daily functions, manual dexterity, and gait speed. PMID:24271094

  11. The Role of Executive Function in Children’s Competent Adjustment to Middle School

    PubMed Central

    Jacobson, Lisa A.; Williford, Amanda P.; Pianta, Robert C.

    2012-01-01

    Executive function (EF) skills play an important role in children’s cognitive and social functioning. These skills develop throughout childhood, concurrently with a number of developmental transitions and challenges. One of these challenges is the transition from elementary into middle-level schools, which has the potential to significantly disrupt children’s academic and social trajectories. However, little is known about the role of EF in children’s adjustment during this transition. This study investigated the relation between children’s EF skills, assessed both before and during elementary school, and sixth grade academic and social competence. In addition, the influences of the type of school setting attended in sixth grade on children’s academic and behavioral outcomes were examined. EF assessed prior to and during elementary school significantly predicted sixth grade competence, as rated by teachers and parents, in both academic and social domains, after controlling for background characteristics. The interactions between type of school setting and EF skills were significant: parents tended to report more behavioral problems and less regulatory control in children with weaker EF skills who were attending middle school. In contrast, teachers reported greater academic and behavioral difficulty in students with poorer EF attending elementary school settings. In conclusion, children’s performance-based EF skills significantly affect adjustment to the academic and behavioral demands of sixth grade, with parent report suggesting greater difficulty for children with poorer EF in settings where children are provided with less external supports (e.g., middle school). PMID:21246422

  12. From structure to redox: the diverse functional roles of disulfides and implications in disease

    PubMed Central

    Bechtel, Tyler J.; Weerapana, Eranthie

    2017-01-01

    This review provides a comprehensive overview of the functional roles of disulfide bonds and their relevance to human disease. The critical roles of disulfide bonds in protein structure stabilization and redox regulation of protein activity are addressed. Disulfide bonds are essential to the structural stability of many proteins within the secretory pathway and can exist as intramolecular or inter-domain disulfides. The proper formation of these bonds often relies on folding chaperones and oxidases such as members of the protein disulfide isomerase (PDI) family. Many of the PDI family members catalyze disulfide-bond formation, reduction and isomerization through redox-active disulfides and perturbed PDI activity is characteristic of carcinomas and neurodegenerative diseases. In addition to catalytic function in oxidoreductases, redox-active disulfides are also found on a diverse array of cellular proteins and act to regulate protein activity and localization in response to oxidative changes in the local environment. These redox-active disulfides are either dynamic intramolecular protein disulfides or mixed disulfides with small-molecule thiols generating glutathionylation and cysteinylation adducts. The oxidation and reduction of redox-active disulfides are mediated by cellular reactive oxygen species and activity of reductases, such as glutaredoxin and thioredoxin. Dysregulation of cellular redox conditions and resulting changes in mixed disulfide formation are directly linked to diseases such as cardiovascular disease and Parkinson’s disease. PMID:28044432

  13. Role of CGRP-receptor component protein (RCP) in CLR/RAMP function.

    PubMed

    Dickerson, Ian M

    2013-08-01

    The receptor for calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) requires an intracellular peripheral membrane protein named CGRP-receptor component protein (RCP) for signaling. RCP is required for CGRP and AM receptor signaling, and it has recently been discovered that RCP enables signaling by binding directly to the receptor. RCP is present in most immortalized cell lines, but in vivo RCP expression is limited to specific subsets of cells, usually co-localizing with CGRP-containing neurons. RCP protein expression correlates with CGRP efficacy in vivo, suggesting that RCP regulates CGRP signaling in vivo as it does in cell culture. RCP is usually identified in cytoplasm or membranes of cells, but recently has been observed in nucleus of neurons, suggesting an additional transcriptional role for RCP in cell function. Together, these data support an essential role for RCP in CGRP and AM receptor function, in which RCP expression enhances signaling of the CGRP or AM receptor, and therefore increases the efficacy of CGRP and AM in vivo.

  14. [The current role of partial surgery as a strategy for functional preservation in laryngeal carcinoma].

    PubMed

    Rodrigo, Juan Pablo; Coca-Pelaz, Andrés; Suárez, Carlos

    2011-01-01

    With the current advances and recent organ preservation protocols for intermediate or advanced stage laryngeal cancer, based on chemotherapy, the role of surgery seemed replaced except for surgical rescue of tumours not responding to these treatments, total laryngectomy being the surgical option. This type of non-surgical treatment is offered as a strategy for organ preservation, as opposed to total laryngectomy. However, we believe that there are two organ-preservation strategies, surgical and non-surgical. A wide spectrum of surgical techniques is available and such techniques lead to excellent results, both oncological and functional (speech and swallowing). The aim of this paper is to present options for organ-preserving surgery for laryngeal cancer. A review of surgical techniques available for functional preservation in cancer of the larynx at intermediate or advanced stage is presented. In addition to classic approaches such as vertical partial laryngectomy and horizontal or supraglottic laryngectomy, options for conservative laryngeal surgery have improved significantly over the past two decades. Minimally invasive surgery, transoral laser surgery, and supracricoid partial laryngectomy have become important laryngeal preservation approaches for patients with laryngeal cancer. Surgery must define its role in the multidisciplinary treatment of advanced cancers of the larynx, which at present often favours (chemo)radiotherapy protocols.

  15. The role and functionality of Veterinary Services in food safety throughout the food chain.

    PubMed

    McKenzie, A I; Hathaway, S C

    2006-08-01

    Both national Veterinary Services and international standard-setting organisations have now embraced risk assessment as an essential tool for achieving their goals. Veterinarians have key roles in all aspects of the control of food-borne hazards of animal origin, but additional specialist skills are necessary for assessing, managing and communicating risk. Further, the deployment of Veterinary Services must reflect the multi-functional aspects of public and animal health activities. A generic risk management framework provides a systematic process whereby food safety standards and other measures are chosen and implemented on the basis of knowledge of risk and evaluation of other factors relevant to protecting human health and promoting non-discriminatory trade practices. In this context, a number of countries are exploring new administrative and structural arrangements for competent authorities. The traditional focus of veterinary involvement in food safety has been in meat hygiene at the level of the slaughterhouse. While this role continues, the emerging 'risk-based' approach to food control requires increased involvement in other segments of the meat food chain, as well as other areas such as production of milk and fish. This more extensive role requires a wider skill base and establishment of effective networks with a different range of stakeholders.

  16. The Functional Role of Neural Oscillations in Non-Verbal Emotional Communication.

    PubMed

    Symons, Ashley E; El-Deredy, Wael; Schwartze, Michael; Kotz, Sonja A

    2016-01-01

    Effective interpersonal communication depends on the ability to perceive and interpret nonverbal emotional expressions from multiple sensory modalities. Current theoretical models propose that visual and auditory emotion perception involves a network of brain regions including the primary sensory cortices, the superior temporal sulcus (STS), and orbitofrontal cortex (OFC). However, relatively little is known about how the dynamic interplay between these regions gives rise to the perception of emotions. In recent years, there has been increasing recognition of the importance of neural oscillations in mediating neural communication within and between functional neural networks. Here we review studies investigating changes in oscillatory activity during the perception of visual, auditory, and audiovisual emotional expressions, and aim to characterize the functional role of neural oscillations in nonverbal emotion perception. Findings from the reviewed literature suggest that theta band oscillations most consistently differentiate between emotional and neutral expressions. While early theta synchronization appears to reflect the initial encoding of emotionally salient sensory information, later fronto-central theta synchronization may reflect the further integration of sensory information with internal representations. Additionally, gamma synchronization reflects facilitated sensory binding of emotional expressions within regions such as the OFC, STS, and, potentially, the amygdala. However, the evidence is more ambiguous when it comes to the role of oscillations within the alpha and beta frequencies, which vary as a function of modality (or modalities), presence or absence of predictive information, and attentional or task demands. Thus, the synchronization of neural oscillations within specific frequency bands mediates the rapid detection, integration, and evaluation of emotional expressions. Moreover, the functional coupling of oscillatory activity across multiples

  17. Roles of Cbln1 in Non-Motor Functions of Mice.

    PubMed

    Otsuka, Shintaro; Konno, Kohtarou; Abe, Manabu; Motohashi, Junko; Kohda, Kazuhisa; Sakimura, Kenji; Watanabe, Masahiko; Yuzaki, Michisuke

    2016-11-16

    The cerebellum is thought to be involved in cognitive functions in addition to its well established role in motor coordination and motor learning in humans. Cerebellin 1 (Cbln1) is predominantly expressed in cerebellar granule cells and plays a crucial role in the formation and function of parallel fiber-Purkinje cell synapses. Although genes encoding Cbln1 and its postsynaptic receptor, the delta2 glutamate receptor (GluD2), are suggested to be associated with autistic-like traits and many psychiatric disorders, whether such cognitive impairments are caused by cerebellar dysfunction remains unclear. In the present study, we investigated whether and how Cbln1 signaling is involved in non-motor functions in adult mice. We show that acquisition and retention/retrieval of cued and contextual fear memory were impaired in Cbln1-null mice. In situ hybridization and immunohistochemical analyses revealed that Cbln1 is expressed in various extracerebellar regions, including the retrosplenial granular cortex and the hippocampus. In the hippocampus, Cbln1 immunoreactivity was present at the molecular layer of the dentate gyrus and the stratum lacunosum-moleculare without overt mRNA expression, suggesting that Cbln1 is provided by perforant path fibers. Retention/retrieval, but not acquisition, of cued and contextual fear memory was impaired in forebrain-predominant Cbln1-null mice. Spatial learning in the radial arm water maze was also abrogated. In contrast, acquisition of fear memory was affected in cerebellum-predominant Cbln1-null mice. These results indicate that Cbln1 in the forebrain and cerebellum mediates specific aspects of fear conditioning and spatial memory differentially and that Cbln1 signaling likely regulates motor and non-motor functions in multiple brain regions.

  18. The Functional Role of Neural Oscillations in Non-Verbal Emotional Communication

    PubMed Central

    Symons, Ashley E.; El-Deredy, Wael; Schwartze, Michael; Kotz, Sonja A.

    2016-01-01

    Effective interpersonal communication depends on the ability to perceive and interpret nonverbal emotional expressions from multiple sensory modalities. Current theoretical models propose that visual and auditory emotion perception involves a network of brain regions including the primary sensory cortices, the superior temporal sulcus (STS), and orbitofrontal cortex (OFC). However, relatively little is known about how the dynamic interplay between these regions gives rise to the perception of emotions. In recent years, there has been increasing recognition of the importance of neural oscillations in mediating neural communication within and between functional neural networks. Here we review studies investigating changes in oscillatory activity during the perception of visual, auditory, and audiovisual emotional expressions, and aim to characterize the functional role of neural oscillations in nonverbal emotion perception. Findings from the reviewed literature suggest that theta band oscillations most consistently differentiate between emotional and neutral expressions. While early theta synchronization appears to reflect the initial encoding of emotionally salient sensory information, later fronto-central theta synchronization may reflect the further integration of sensory information with internal representations. Additionally, gamma synchronization reflects facilitated sensory binding of emotional expressions within regions such as the OFC, STS, and, potentially, the amygdala. However, the evidence is more ambiguous when it comes to the role of oscillations within the alpha and beta frequencies, which vary as a function of modality (or modalities), presence or absence of predictive information, and attentional or task demands. Thus, the synchronization of neural oscillations within specific frequency bands mediates the rapid detection, integration, and evaluation of emotional expressions. Moreover, the functional coupling of oscillatory activity across multiples

  19. Thai and Korean Students' Perceptions about the Roles and Functions of School Psychologists

    ERIC Educational Resources Information Center

    Tangdhanakanond, Kamonwan; Lee, Dong Hun

    2014-01-01

    The purpose of the present study was to compare Thai and Korean college students on their perceptions of the roles and functions of school psychologists. One hundred and ninety-three Thai college students and 238 Korean counterparts participated in this study. Students rated the importance of various roles/functions of a school psychologist and…

  20. On the role of general system theory for functional neuroimaging

    PubMed Central

    Stephan, Klaas Enno

    2004-01-01

    One of the most important goals of neuroscience is to establish precise structure–function relationships in the brain. Since the 19th century, a major scientific endeavour has been to associate structurally distinct cortical regions with specific cognitive functions. This was traditionally accomplished by correlating microstructurally defined areas with lesion sites found in patients with specific neuropsychological symptoms. Modern neuroimaging techniques with high spatial resolution have promised an alternative approach, enabling non-invasive measurements of regionally specific changes of brain activity that are correlated with certain components of a cognitive process. Reviewing classic approaches towards brain structure–function relationships that are based on correlational approaches, this article argues that these approaches are not sufficient to provide an understanding of the operational principles of a dynamic system such as the brain but must be complemented by models based on general system theory. These models reflect the connectional structure of the system under investigation and emphasize context-dependent couplings between the system elements in terms of effective connectivity. The usefulness of system models whose parameters are fitted to measured functional imaging data for testing hypotheses about structure–function relationships in the brain and their potential for clinical applications is demonstrated by several empirical examples. PMID:15610393

  1. The role of chromosome domains in shaping the functional genome.

    PubMed

    Sexton, Tom; Cavalli, Giacomo

    2015-03-12

    The genome must be highly compacted to fit within eukaryotic nuclei but must be accessible to the transcriptional machinery to allow appropriate expression of genes in different cell types and throughout developmental pathways. A growing body of work has shown that the genome, analogously to proteins, forms an ordered, hierarchical structure that closely correlates and may even be causally linked with regulation of functions such as transcription. This review describes our current understanding of how these functional genomic "secondary and tertiary structures" form a blueprint for global nuclear architecture and the potential they hold for understanding and manipulating genomic regulation.

  2. Functional Roles and Therapeutic Applications of Exosomes in Hepatocellular Carcinoma.

    PubMed

    Santangelo, Laura; Battistelli, Cecilia; Montaldo, Claudia; Citarella, Franca; Strippoli, Raffaele; Cicchini, Carla

    2017-01-01

    Exosomes are important in intercellular communication. They assure the horizontal transfer of specific functional contents (i.e., proteins, lipids, RNA molecules, and circulating DNA) from donor to recipient cells. Notably, tumor-derived exosomes (TDEs) appear to be an important vehicle of specific signals in cancer, impacting on tumor growth and metastasis. Recent researches point to the characterization of exosomes in Hepatocellular Carcinoma (HCC), the major adult liver malignancy. In this review, we summarize current findings on HCC exosomes, focusing on the identification of noncoding RNAs as exosome-enriched functional regulators and new potential biomarkers. The great potential of exosomes in future HCC diagnostic and therapeutic approaches is underlined.

  3. Functional Roles and Therapeutic Applications of Exosomes in Hepatocellular Carcinoma

    PubMed Central

    Montaldo, Claudia; Strippoli, Raffaele

    2017-01-01

    Exosomes are important in intercellular communication. They assure the horizontal transfer of specific functional contents (i.e., proteins, lipids, RNA molecules, and circulating DNA) from donor to recipient cells. Notably, tumor-derived exosomes (TDEs) appear to be an important vehicle of specific signals in cancer, impacting on tumor growth and metastasis. Recent researches point to the characterization of exosomes in Hepatocellular Carcinoma (HCC), the major adult liver malignancy. In this review, we summarize current findings on HCC exosomes, focusing on the identification of noncoding RNAs as exosome-enriched functional regulators and new potential biomarkers. The great potential of exosomes in future HCC diagnostic and therapeutic approaches is underlined. PMID:28265569

  4. Role of FTO in Adipocyte Development and Function: Recent Insights

    PubMed Central

    Merkestein, Myrte; Sellayah, Dyan

    2015-01-01

    In 2007, FTO was identified as the first genome-wide association study (GWAS) gene associated with obesity in humans. Since then, various animal models have served to establish the mechanistic basis behind this association. Many earlier studies focussed on FTO's effects on food intake via central mechanisms. Emerging evidence, however, implicates adipose tissue development and function in the causal relationship between perturbations in FTO expression and obesity. The purpose of this mini review is to shed light on these new studies of FTO function in adipose tissue and present a clearer picture of its impact on obesity susceptibility. PMID:26788058

  5. Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production

    PubMed Central

    Brehm, Anja; Liu, Yin; Sheikh, Afzal; Marrero, Bernadette; Omoyinmi, Ebun; Zhou, Qing; Montealegre, Gina; Biancotto, Angelique; Reinhardt, Adam; Almeida de Jesus, Adriana; Pelletier, Martin; Tsai, Wanxia L.; Remmers, Elaine F.; Kardava, Lela; Hill, Suvimol; Kim, Hanna; Lachmann, Helen J.; Megarbane, Andre; Chae, Jae Jin; Brady, Jilian; Castillo, Rhina D.; Brown, Diane; Casano, Angel Vera; Gao, Ling; Chapelle, Dawn; Huang, Yan; Stone, Deborah; Chen, Yongqing; Sotzny, Franziska; Lee, Chyi-Chia Richard; Kastner, Daniel L.; Torrelo, Antonio; Zlotogorski, Abraham; Moir, Susan; Gadina, Massimo; McCoy, Phil; Wesley, Robert; Rother, Kristina; Hildebrand, Peter W.; Brogan, Paul; Krüger, Elke; Aksentijevich, Ivona; Goldbach-Mansky, Raphaela

    2015-01-01

    Autosomal recessive mutations in proteasome subunit β 8 (PSMB8), which encodes the inducible proteasome subunit β5i, cause the immune-dysregulatory disease chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), which is classified as a proteasome-associated autoinflammatory syndrome (PRAAS). Here, we identified 8 mutations in 4 proteasome genes, PSMA3 (encodes α7), PSMB4 (encodes β7), PSMB9 (encodes β1i), and proteasome maturation protein (POMP), that have not been previously associated with disease and 1 mutation in PSMB8 that has not been previously reported. One patient was compound heterozygous for PSMB4 mutations, 6 patients from 4 families were heterozygous for a missense mutation in 1 inducible proteasome subunit and a mutation in a constitutive proteasome subunit, and 1 patient was heterozygous for a POMP mutation, thus establishing a digenic and autosomal dominant inheritance pattern of PRAAS. Function evaluation revealed that these mutations variably affect transcription, protein expression, protein folding, proteasome assembly, and, ultimately, proteasome activity. Moreover, defects in proteasome formation and function were recapitulated by siRNA-mediated knockdown of the respective subunits in primary fibroblasts from healthy individuals. Patient-isolated hematopoietic and nonhematopoietic cells exhibited a strong IFN gene-expression signature, irrespective of genotype. Additionally, chemical proteasome inhibition or progressive depletion of proteasome subunit gene transcription with siRNA induced transcription of type I IFN genes in healthy control cells. Our results provide further insight into CANDLE genetics and link global proteasome dysfunction to increased type I IFN production. PMID:26524591

  6. Teachers’ Beliefs and Practices Regarding the Role of Executive Functions in Reading and Arithmetic

    PubMed Central

    Rapoport, Shirley; Rubinsten, Orly; Katzir, Tami

    2016-01-01

    The current study investigated early elementary school teachers’ beliefs and practices regarding the role of Executive Functions (EFs) in reading and arithmetic. A new research questionnaire was developed and judged by professionals in the academia and the field. Reponses were obtained from 144 teachers from Israel. Factor analysis divided the questionnaire into three valid and reliable subscales, reflecting (1) beliefs regarding the contribution of EFs to reading and arithmetic, (2) pedagogical practices, and (3) a connection between the cognitive mechanisms of reading and arithmetic. Findings indicate that teachers believe EFs affect students’ performance in reading and arithmetic. These beliefs were also correlated with pedagogical practices. Additionally, special education teachers’ scored higher on the different subscales compared to general education teachers. These findings shed light on the way teachers perceive the cognitive foundations of reading and arithmetic and indicate to which extent these perceptions guide their teaching practices. PMID:27799917

  7. Functional role of stromal interaction molecule 1 (STIM1) in vascular smooth muscle cells

    SciTech Connect

    Takahashi, Yoichiro; Watanabe, Hiroyuki; Murakami, Manabu; Ono, Kyoichi; Munehisa, Yoshiko; Koyama, Takashi; Nobori, Kiyoshi; Iijima, Toshihiko; Ito, Hiroshi

    2007-10-05

    We investigated the functional role of STIM1, a Ca{sup 2+} sensor in the endoplasmic reticulum (ER) that regulates store-operated Ca{sup 2+} entry (SOCE), in vascular smooth muscle cells (VSMCs). STIM1 was mainly localized at the ER and plasma membrane. The knockdown of STIM1 expression by small interfering (si) RNA drastically decreased SOCE. In contrast, an EF-hand mutant of STIM1, STIM1{sup E87A}, produced a marked increase in SOCE, which was abolished by co-transfection with siRNA to transient receptor potential canonical 1 (TRPC1). In addition, transfection with siRNA against STIM1 suppressed phosphorylation of cAMP-responsive element binding protein (CREB) and cell growth. These results suggest that STIM1 is an essential component of SOCE and that it is involved in VSMC proliferation.

  8. The role of anxiety in stuttering: Evidence from functional connectivity.

    PubMed

    Yang, Yang; Jia, Fanlu; Siok, Wai Ting; Tan, Li Hai

    2017-03-27

    Persistent developmental stuttering is a neurologically based speech disorder associated with cognitive-linguistic, motor and emotional abnormalities. Previous studies investigating the relationship between anxiety and stuttering have yielded mixed results, but it has not yet been examined whether anxiety influences brain activity underlying stuttering. Here, using functional magnetic resonance imaging (fMRI), we investigated the functional connectivity associated with state anxiety in a syllable repetition task, and trait anxiety during rest in adults who stutter (N=19) and fluent controls (N=19). During the speech task, people who stutter (PWS) showed increased functional connectivity of the right amygdala with the prefrontal gyrus (the left ventromedial frontal gyrus and right middle frontal gyrus) and the left insula compared to controls. During rest, PWS showed stronger functional connectivity between the right hippocampus and the left orbital frontal gyrus, and between the left hippocampus and left motor areas than controls. Taken together, our results suggest aberrant bottom-up and/or top-down interactions for anxiety regulation, which might be responsible for the higher level of state anxiety during speech and for the anxiety-prone trait in PWS. To our knowledge, this is the first study to examine the neural underpinnings of anxiety in PWS, thus yielding new insight into the causes of stuttering which might aid strategies for the diagnosis and treatment of stuttering.

  9. The Role of Functional Form in Causal-Based Categorization

    ERIC Educational Resources Information Center

    Rehder, Bob

    2015-01-01

    Two experiments tested how the "functional form" of the causal relations that link features of categories affects category-based inferences. Whereas "independent causes" can each bring about an effect by themselves, "conjunctive causes" all need to be present for an effect to occur. The causal model view of category…

  10. The Role of Family Functioning in Bipolar Disorder in Families

    ERIC Educational Resources Information Center

    Du Rocher Schudlich, Tina D.; Youngstrom, Eric A.; Calabrese, Joseph R.; Findling, Robert L.

    2008-01-01

    Investigated the association between family functioning and conflict and their links with mood disorder in parents and with children's risk for bipolar disorder. Participants were 272 families with a child between the ages of 5-17 years. Parents' history of psychiatric diagnoses and children's current diagnoses were obtained via semi-structured…

  11. Emotion Understanding in Preschool Children: The Role of Executive Functions

    ERIC Educational Resources Information Center

    Martins, Eva Costa; Osório, Ana; Veríssimo, Manuela; Martins, Carla

    2016-01-01

    This investigation was aimed at studying the relations between executive functions (EFs) and categorical emotion understanding while controlling for preschoolers' IQ, language ability and theory of mind (ToM). Specifically, we wanted to analyse the association between emotion understanding and set shifting, due to the lack of studies with this EF.…

  12. Parenting and Adolescent Adjustment: The Role of Parental Reflective Function

    ERIC Educational Resources Information Center

    Benbassat, Naomi; Priel, Beatriz

    2012-01-01

    Reflective function (RF) is the capacity to reflect on one's own mental experiences and those of others. This study examined the relationship between parental RF and adolescent adjustment. One hundred and five adolescents, aged 14-18, and their mothers and fathers were interviewed and completed questionnaires during home visits. We measured…

  13. Role of quantity of additional food to predators as a control in predator-prey systems with relevance to pest management and biological conservation.

    PubMed

    Srinivasu, P D N; Prasad, B S R V

    2011-10-01

    Necessity to understand the role of additional food as a tool in biological control programs is being increasingly felt, particularly due to its eco-friendly nature. A thorough mathematical analysis in this direction revealed the vital role of quality and quantity of the additional food in the controllability of the predator-prey systems. In this article controllability of the additional food--provided predator-prey system is studied from perspectives of pest eradication and biological conservation. Time optimal paths have been constructed to drive the state of the system to a desired terminal state by choosing quantity of the additional food as control variable. The theory developed in this article has been illustrated by solving problems related to pest eradication and biological conservation.

  14. Polyethylene glycol addition does not improve exogenous surfactant function in an experimental model of meconium aspiration syndrome.

    PubMed

    Lyra, Joao Cesar; Mascaretti, Renata Suman; Precioso, Alexander Roberto; Haddad, Luciana Branco; Mauad, Thais; Vaz, Flavio A Costa; Rebello, Celso Moura

    2009-02-01

    Meconium (MEC) is a potent inactivator of pulmonary surfactant. The authors studied the effects of polyethylene glycol addition to the exogenous surfactant over the lung mechanics and volumes. Human meconium was administrated to newborn rabbits. Animals were ventilated for 20 minutes and dynamic compliance, ventilatory pressure, and tidal volume were recorded. Animals were randomized into 3 study groups: MEC group (without surfactant therapy); S100 group (100 mg/kg surfactant); and PEG group (100 mg/kg porcine surfactant plus 5% PEG). After ventilation, a pulmonary pressure-volume curve was built. Histological analysis was carried out to calculate the mean alveolar size (Lm) and the distortion index (DI). Both groups treated with surfactant showed higher values of dynamic pulmonary compliance and lower ventilatory pressure, compared with the MEC group (P < .05). S100 group had a larger maximum lung volume, V(30), compared with the MEC group (P < .05). Lm and DI values were smaller in the groups treated with surfactant than in the MEC group (P < .05). No differences were observed between the S100 and PEG groups. Animals treated with surfactant showed significant improvement in pulmonary function as compared to nontreated animals. PEG added to exogenous surfactant did not improve lung mechanics or volumes.

  15. Toxicological features of maleilated polyflavonoids from Pinus radiata (D. Don.) as potential functional additives for biomaterials design.

    PubMed

    García, Danny E; Medina, Paulina A; Zúñiga, Valentina I

    2017-03-14

    Polyflavonoids from Pinus radiata (D. Don.) are an abundant natural oligomers highly desirable as renewable chemicals. However, structural modification of polyflavonoids is a viable strategy in order to use such polyphenols as macrobuilding-blocks for biomaterial design. Polyflavonoids were esterified with three five-member cyclic anhydrides (maleic, itaconic, and citraconic) at 20 °C during 24 h in order to diversify physicochemical-, and biological-properties for agricultural, and food-packaging applications. In addition, the influence of the chemical modification, as well as the chemical structure of the grafting on toxicological features was evaluated. Structural features of derivatives were analyzed by spectroscopy (FT-IR and (1)H-NMR), and the degree of substitution was calculated. Toxicological profile was assessed by using three target species in a wide range of concentration (0.01-100 mgL(-)(1)). Effect of polyflavonoids on the growth rate (Selenastrum capricornutum), mortality (Daphnia magna), and germination and radicle length (Lactuca sativa) was determined. Chemical modification affects the toxicological profile on the derivatives in a high extent. Results described remarkable differences in function of the target specie. The bioassays indicate differences of the polyflavonoids toxicological profile associated to the chemical structure of the grafting. Results allowed conclude that polyflavonoids from pine bark show slight toxic properties.

  16. Determining firms׳ utility functions and competitive roles from data on market shares using Lotka-Volterra models.

    PubMed

    Marasco, A; Picucci, A; Romano, A

    2016-06-01

    In this article, we include data on historical and estimated market shares of two markets. In particular, we include annual data on the market shares of the Japanese beer market (1963-2000) and biannual data on the market shares of the mobile phones market in Greece (1998-2007). In addition, we estimate monthly data on market shares for both markets. We show how this data can be used to derive firms' utility functions and their competitive roles.

  17. Morphology predicts species' functional roles and their degree of specialization in plant–frugivore interactions

    PubMed Central

    Dehling, D. Matthias; Schaefer, H. Martin; Böhning-Gaese, Katrin; Schleuning, Matthias

    2016-01-01

    Species' functional roles in key ecosystem processes such as predation, pollination or seed dispersal are determined by the resource use of consumer species. An interaction between resource and consumer species usually requires trait matching (e.g. a congruence in the morphologies of interaction partners). Species' morphology should therefore determine species' functional roles in ecological processes mediated by mutualistic or antagonistic interactions. We tested this assumption for Neotropical plant–bird mutualisms. We used a new analytical framework that assesses a species's functional role based on the analysis of the traits of its interaction partners in a multidimensional trait space. We employed this framework to test (i) whether there is correspondence between the morphology of bird species and their functional roles and (ii) whether morphologically specialized birds fulfil specialized functional roles. We found that morphological differences between bird species reflected their functional differences: (i) bird species with different morphologies foraged on distinct sets of plant species and (ii) morphologically distinct bird species fulfilled specialized functional roles. These findings encourage further assessments of species' functional roles through the analysis of their interaction partners, and the proposed analytical framework facilitates a wide range of novel analyses for network and community ecology. PMID:26817779

  18. A Key Role for Inhibins in Dendritic Cell Maturation and Function.

    PubMed

    Olguín-Alor, Roxana; de la Fuente-Granada, Marisol; Bonifaz, Laura C; Antonio-Herrera, Laura; García-Zepeda, Eduardo A; Soldevila, Gloria

    2016-01-01

    Inhibins are members of the TGFβ superfamily, which regulate many cellular processes including differentiation, proliferation, survival and apoptosis. Although initially described as hormones regulating the hypothalamus-pituitary-gonadal axis, based on their ability to antagonize Activins, our group has recently reported that they play a role in thymocyte differentiation and survival, as well as in thymic stromal cell maturation and nTreg generation. Here, we used Inhibin knock out mice (Inhα-/-) to investigate the role of Inhibins in peripheral dendritic cell maturation and function. We first demonstrated that LPS treated Inhα+/+ bone marrow derived dendritic cells (BMDC) were capable to produce significant levels of Inhibin A. Interestingly, Inhα-/- BMDC showed reduced MHCII and CD86 upregulation and increased PD-L1 expression in response to LPS compared to Inhα+/+, which correlated with reduced ability to induce proliferation of allogeneic T cells. The "semi-mature" phenotype displayed by Inhα-/- mBMDC correlated with increased levels of IL-10 and slightly decreased IL-6 production after LPS stimulation. In addition, Inhα-/- mBMDC showed impaired migration towards CCL19 and CCL21, assessed by in vitro chemotaxis and in vivo competitive homing experiments, despite their normal CCR7 expression. Furthermore, in vivo LPS-induced DC maturation was also diminished in Inhα-/- mice, specially within the LC (CD207+ CD11b+ CD103-) subpopulation. Finally, analysis of delayed type hypersensitivity responses in Inhα-/- mice, showed reduced ear swelling as a result of reduced cellular infiltration in the skin, correlating with impaired homing of CD207+ DCs to the draining lymph nodes. In summary, our data demonstrate for the first time that Inhibins play a key role in peripheral DC maturation and function, regulating the balance between immunity and tolerance.

  19. Functional analysis of centipede development supports roles for Wnt genes in posterior development and segment generation.

    PubMed

    Hayden, Luke; Schlosser, Gerhard; Arthur, Wallace

    2015-01-01

    The genes of the Wnt family play important and highly conserved roles in posterior growth and development in a wide range of animal taxa. Wnt genes also operate in arthropod segmentation, and there has been much recent debate regarding the relationship between arthropod and vertebrate segmentation mechanisms. Due to its phylogenetic position, body form, and possession of many (11) Wnt genes, the centipede Strigamia maritima is a useful system with which to examine these issues. This study takes a functional approach based on treatment with lithium chloride, which causes ubiquitous activation of canonical Wnt signalling. This is the first functional developmental study performed in any of the 15,000 species of the arthropod subphylum Myriapoda. The expression of all 11 Wnt genes in Strigamia was analyzed in relation to posterior development. Three of these genes, Wnt11, Wnt5, and WntA, were strongly expressed in the posterior region and, thus, may play important roles in posterior developmental processes. In support of this hypothesis, LiCl treatment of S. maritima embryos was observed to produce posterior developmental defects and perturbations in AbdB and Delta expression. The effects of LiCl differ depending on the developmental stage treated, with more severe effects elicited by treatment during germband formation than by treatment at later stages. These results support a role for Wnt signalling in conferring posterior identity in Strigamia. In addition, data from this study are consistent with the hypothesis of segmentation based on a "clock and wavefront" mechanism operating in this species.

  20. A Key Role for Inhibins in Dendritic Cell Maturation and Function

    PubMed Central

    Olguín-Alor, Roxana; de la Fuente-Granada, Marisol; Bonifaz, Laura C.; Antonio-Herrera, Laura; García-Zepeda, Eduardo A.; Soldevila, Gloria

    2016-01-01

    Inhibins are members of the TGFβ superfamily, which regulate many cellular processes including differentiation, proliferation, survival and apoptosis. Although initially described as hormones regulating the hypothalamus-pituitary-gonadal axis, based on their ability to antagonize Activins, our group has recently reported that they play a role in thymocyte differentiation and survival, as well as in thymic stromal cell maturation and nTreg generation. Here, we used Inhibin knock out mice (Inhα-/-) to investigate the role of Inhibins in peripheral dendritic cell maturation and function. We first demonstrated that LPS treated Inhα+/+ bone marrow derived dendritic cells (BMDC) were capable to produce significant levels of Inhibin A. Interestingly, Inhα-/- BMDC showed reduced MHCII and CD86 upregulation and increased PD-L1 expression in response to LPS compared to Inhα+/+, which correlated with reduced ability to induce proliferation of allogeneic T cells. The “semi-mature” phenotype displayed by Inhα-/- mBMDC correlated with increased levels of IL-10 and slightly decreased IL-6 production after LPS stimulation. In addition, Inhα-/- mBMDC showed impaired migration towards CCL19 and CCL21, assessed by in vitro chemotaxis and in vivo competitive homing experiments, despite their normal CCR7 expression. Furthermore, in vivo LPS-induced DC maturation was also diminished in Inhα-/- mice, specially within the LC (CD207+ CD11b+ CD103-) subpopulation. Finally, analysis of delayed type hypersensitivity responses in Inhα-/- mice, showed reduced ear swelling as a result of reduced cellular infiltration in the skin, correlating with impaired homing of CD207+ DCs to the draining lymph nodes. In summary, our data demonstrate for the first time that Inhibins play a key role in peripheral DC maturation and function, regulating the balance between immunity and tolerance. PMID:27936218

  1. The Role of Cortical Plasticity in Recovery of Function Following Allogeneic Hand Transplantation

    DTIC Science & Technology

    2015-10-01

    1 AWARD NUMBER: W81XWH-13-1-0496 TITLE: The Role of Cortical Plasticity in Recovery of Function Following Allogeneic Hand Transplantation...29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER The Role of Cortical Plasticity in Recovery of Function Following Allogeneic Hand...cortical reorganization. These persistent changes appear to diminish with recovery of hand function, suggesting that cortical reorganization is an

  2. The role of sleep in emotional brain function.

    PubMed

    Goldstein, Andrea N; Walker, Matthew P

    2014-01-01

    Rapidly emerging evidence continues to describe an intimate and causal relationship between sleep and emotional brain function. These findings are mirrored by long-standing clinical observations demonstrating that nearly all mood and anxiety disorders co-occur with one or more sleep abnormalities. This review aims to (a) provide a synthesis of recent findings describing the emotional brain and behavioral benefits triggered by sleep, and conversely, the detrimental impairments following a lack of sleep; (b) outline a proposed framework in which sleep, and specifically rapid-eye movement (REM) sleep, supports a process of affective brain homeostasis, optimally preparing the organism for next-day social and emotional functioning; and (c) describe how this hypothesized framework can explain the prevalent relationships between sleep and psychiatric disorders, with a particular focus on posttraumatic stress disorder and major depression.

  3. The Role of Sleep in Emotional Brain Function

    PubMed Central

    Goldstein, Andrea N.; Walker, Matthew P.

    2014-01-01

    Rapidly emerging evidence continues to describe an intimate and causal relationship between sleep and emotional brain function. These findings are mirrored by longstanding clinical observations demonstrating that nearly all mood and anxiety disorders co-occur with one or more sleep abnormalities. This review aims to (1) provide a synthesis of recent findings describing the emotional brain and behavioral benefits triggered by sleep, and conversely, the detrimental impairments following a lack of sleep, (2) outline a proposed framework in which sleep, and specifically rapid-eye movement (REM) sleep, supports a process of affective brain homeostasis, optimally preparing the organism for next-day social and emotional functioning, and (3) describe how this hypothesized framework can explain the prevalent relationships between sleep and psychiatric disorders, with a particular focus on post-traumatic stress disorder and major depression. PMID:24499013

  4. Dual Functional Roles of Molecular Beacon as a MicroRNA Detector and Inhibitor.

    PubMed

    Li, Wai Ming; Chan, Ching-Man; Miller, Andrew L; Lee, Chow H

    2017-03-03

    MicroRNAs are essential in many cellular processes. The ability to detect microRNAs is important for understanding its function and biogenesis. This study is aimed at using a molecular beacon to detect miR-430 in developing zebrafish embryos as a proof of principle. miR-430 is crucial for the clearance of maternal mRNA during maternal zygotic transition in embryonic development. Despite its known function, the temporal and spatial expression of miR-430 remains unclear. We used various imaging techniques, including laser scanning confocal microscopy, spinning disk, and lightsheet microscopy, to study the localization of miR-430 and any developmental defects possibly caused by the molecular beacon. Our results show that miR-430 is expressed early in development and is localized in distinct cytoplasmic granules where its target mRNA can be detected. We also show that the designed molecular beacon can inhibit the function of miR-430 and cause developmental defect in the brain, notochord, heart, and kidney, depending on the delivery site within the embryo, suggesting that miR-430 plays a diverse role in embryonic morphogenesis. When compared with morpholino, molecular beacon is 2 orders of magnitude more potent in inhibiting miR-430. Thus, our results reveal that in addition to being used as a valuable tool for the detection of microRNAs in vivo, molecular beacons can also be employed to inhibit microRNAs in a specific manner.

  5. Diverse Roles of Axonemal Dyneins in Drosophila Auditory Neuron Function and Mechanical Amplification in Hearing

    PubMed Central

    Karak, Somdatta; Jacobs, Julie S.; Kittelmann, Maike; Spalthoff, Christian; Katana, Radoslaw; Sivan-Loukianova, Elena; Schon, Michael A.; Kernan, Maurice J.; Eberl, Daniel F.; Göpfert, Martin C.

    2015-01-01

    Much like vertebrate hair cells, the chordotonal sensory neurons that mediate hearing in Drosophila are motile and amplify the mechanical input of the ear. Because the neurons bear mechanosensory primary cilia whose microtubule axonemes display dynein arms, we hypothesized that their motility is powered by dyneins. Here, we describe two axonemal dynein proteins that are required for Drosophila auditory neuron function, localize to their primary cilia, and differently contribute to mechanical amplification in hearing. Promoter fusions revealed that the two axonemal dynein genes Dmdnah3 (=CG17150) and Dmdnai2 (=CG6053) are expressed in chordotonal neurons, including the auditory ones in the fly’s ear. Null alleles of both dyneins equally abolished electrical auditory neuron responses, yet whereas mutations in Dmdnah3 facilitated mechanical amplification, amplification was abolished by mutations in Dmdnai2. Epistasis analysis revealed that Dmdnah3 acts downstream of Nan-Iav channels in controlling the amplificatory gain. Dmdnai2, in addition to being required for amplification, was essential for outer dynein arms in auditory neuron cilia. This establishes diverse roles of axonemal dyneins in Drosophila auditory neuron function and links auditory neuron motility to primary cilia and axonemal dyneins. Mutant defects in sperm competition suggest that both dyneins also function in sperm motility. PMID:26608786

  6. Gas7-Deficient Mouse Reveals Roles in Motor Function and Muscle Fiber Composition during Aging

    PubMed Central

    Huang, Bo-Tsang; Chang, Pu-Yuan; Su, Ching-Hua; Chao, Chuck C.-K.; Lin-Chao, Sue

    2012-01-01

    Background Growth arrest-specific gene 7 (Gas7) has previously been shown to be involved in neurite outgrowth in vitro; however, its actual role has yet to be determined. To investigate the physiological function of Gas7 in vivo, here we generated a Gas7-deficient mouse strain with a labile Gas7 mutant protein whose functions are similar to wild-type Gas7. Methodology/Principal Findings Our data show that aged Gas7-deficient mice have motor activity defects due to decreases in the number of spinal motor neurons and in muscle strength, of which the latter may be caused by changes in muscle fiber composition as shown in the soleus. In cross sections of the soleus of Gas7-deficient mice, gross morphological features and levels of myosin heavy chain I (MHC I) and MHC II markers revealed significantly fewer fast fibers. In addition, we found that nerve terminal sprouting, which may be associated with slow and fast muscle fiber composition, was considerably reduced at neuromuscular junctions (NMJ) during aging. Conclusions/Significance These findings indicate that Gas7 is involved in motor neuron function associated with muscle strength maintenance. PMID:22662195

  7. A role for matrix stiffness in the regulation of cardiac side population cell function.

    PubMed

    Qiu, Yiling; Bayomy, Ahmad F; Gomez, Marcus V; Bauer, Michael; Du, Ping; Yang, Yanfei; Zhang, Xin; Liao, Ronglih

    2015-05-01

    The mechanical properties of the local microenvironment may have important influence on the fate and function of adult tissue progenitor cells, altering the regenerative process. This is particularly critical following a myocardial infarction, in which the normal, compliant myocardial tissue is replaced with fibrotic, stiff scar tissue. In this study, we examined the effects of matrix stiffness on adult cardiac side population (CSP) progenitor cell behavior. Ovine and murine CSP cells were isolated and cultured on polydimethylsiloxane substrates, replicating the elastic moduli of normal and fibrotic myocardium. Proliferation capacity and cell cycling were increased in CSP cells cultured on the stiff substrate with an associated reduction in cardiomyogeneic differentiation and accelerated cell ageing. In addition, culture on stiff substrate stimulated upregulation of extracellular matrix and adhesion proteins gene expression in CSP cells. Collectively, we demonstrate that microenvironment properties, including matrix stiffness, play a critical role in regulating progenitor cell functions of endogenous resident CSP cells. Understanding the effects of the tissue microenvironment on resident cardiac progenitor cells is a critical step toward achieving functional cardiac regeneration.

  8. Aging of the Planning Process: The Role of Executive Functioning

    ERIC Educational Resources Information Center

    Sorel, Olivier; Pennequin, Valerie

    2008-01-01

    This study tested whether the aging of executive functioning is linked to the decline in planning performance. Participants were divided into three groups: group 1 composed of 15 adults with a mean age of 22.7 years, group 2 composed of 15 adults with a mean age of 68.1 years and group 3 composed of 16 adults with a mean age of 78.75 years. Each…

  9. Regulatory Roles of Fluctuation-Driven Mechanotransduction in Cell Function.

    PubMed

    Suki, Béla; Parameswaran, Harikrishnan; Imsirovic, Jasmin; Bartolák-Suki, Erzsébet

    2016-09-01

    Cells in the body are exposed to irregular mechanical stimuli. Here, we review the so-called fluctuation-driven mechanotransduction in which stresses stretching cells vary on a cycle-by-cycle basis. We argue that such mechanotransduction is an emergent network phenomenon and offer several potential mechanisms of how it regulates cell function. Several examples from the vasculature, the lung, and tissue engineering are discussed. We conclude with a list of important open questions.

  10. Multiple Roles, Multiple Lives: The Protective Effects of Role Responsibilities on the Health Functioning of African American Mothers

    PubMed Central

    Black, Angela Rose; Murry, Velma McBride; Cutrona, Carolyn E.; Chen, Yi-fu

    2009-01-01

    Using data from 747 rural African American mothers, this study incorporated Role Accumulation theory to test direct and indirect effects of stressors, coping behaviors, and role responsibilities on health functioning. Results indicated that demands emerging from financial strain were related to compromised mental health and decreases in mothers' use of effective coping strategies and role responsibility engagement. Conversely, mothers who effectively responded to stressors and fulfilled responsibilities to their children and communities experienced enhanced mental health, which in turn promoted optimal physical health. The results can inform research and intervention with African American women. PMID:19533507

  11. Role of pelvic floor in lower urinary tract function.

    PubMed

    Chermansky, Christopher J; Moalli, Pamela A

    2016-10-01

    The pelvic floor plays an integral part in lower urinary tract storage and evacuation. Normal urine storage necessitates that continence be maintained with normal urethral closure and urethral support. The endopelvic fascia of the anterior vaginal wall, its connections to the arcus tendineous fascia pelvis (ATFP), and the medial portion of the levator ani muscles must remain intact to provide normal urethral support. Thus, normal pelvic floor function is required for urine storage. Normal urine evacuation involves a series of coordinated events, the first of which involves complete relaxation of the external urethral sphincter and levator ani muscles. Acquired dysfunction of these muscles will initially result in sensory urgency and detrusor overactivity; however, with time the acquired voiding dysfunction can result in intermittent urine flow and incomplete bladder emptying, progressing to urinary retention in severe cases. This review will start with a discussion of normal pelvic floor anatomy and function. Next various injuries to the pelvic floor will be reviewed. The dysfunctional pelvic floor will be covered subsequently, with a focus on levator ani spasticity and stress urinary incontinence (SUI). Finally, future research directions of the interaction between the pelvic floor and lower urinary tract function will be discussed.

  12. Role of additional PCBM layer between ZnO and photoactive layers in inverted bulk-heterojunction solar cells.

    PubMed

    Cho, Shinuk; Kim, Kwang-Dae; Heo, Jinhee; Lee, Joo Yul; Cha, Gihoon; Seo, Bo Yeol; Kim, Young Dok; Kim, Yong Soo; Choi, Si-young; Lim, Dong Chan

    2014-03-07

    In order to induce greater light absorption, nano-patterning is often applied to the metal-oxide buffer layer in inverted bulk-heterojunction(BHJ) solar cells. However, current homogeneity was significantly disturbed at the interface, leading to an efficiency that was not fully optimized. In this work, an additional PC61BM layer was inserted between the ZnO ripple and the photoactive layer to enhance the electron extraction. The insertion of additional PC61BM layer provided substantial advantages in the operation of inverted BHJ solar cells; specifically, it enhanced current homogeneity and lowered accumulation and trapping of photogenerated charges at the ZnO interface. Inclusion of the additional PC61BM layer led to effective quenching of electron-hole recombination by a reduction in the number of accumulated charges at the surface of ZnO ripples. This resulted in a 16% increase in the efficiency of inverted BHJ solar cells to 7.7%, compared to solar cells without the additional PC61BM layer.

  13. Re(de)fining the Orthographic Neighborhood: The Role of Addition and Deletion Neighbors in Lexical Decision and Reading

    ERIC Educational Resources Information Center

    Davis, Colin J.; Perea, Manuel; Acha, Joana

    2009-01-01

    The influence of addition and deletion neighbors on visual word identification was investigated in four experiments. Experiments 1 and 2 used Spanish stimuli. In Experiment 1, lexical decision latencies were slower and less accurate for words and nonwords with higher-frequency deletion neighbors (e.g., "jugar" in "juzgar"),…

  14. Understanding the Role of Additives in Improving the Performance of Polymer:Fullerene Bulk Heterojunction Solar Cells

    NASA Astrophysics Data System (ADS)

    Chen, Wei

    2014-03-01

    Solar cells based on the polymer:fullerene bulk heterojunction (BHJ) represent one of the most promising technologies for next-generation solar energy conversion due to their low-cost and scalability. In the last fifteen years, research efforts have led to organic photovoltaic (OPV) devices with power conversion efficiencies (PCEs) ~ 12%, but these values are still insufficient for the devices to become widely marketable. To further improve solar cell performance, a thorough understanding of the complex processing-structure-performance relationships in OPV devices is required. Recently, the use of processing additives have been proved to be one of the most effective methods to tune the nanomorphology of polymer:fullerene active layer, as the incorporation of a small percentage of solvent additives results in a nearly doubling of device efficiency. However, the physics behind these improved performances by processing additives still remains unclear. In this work, by taking advantage of resonant soft x-ray scattering (RSoXS) and energy-filtered transmission electron microscopy (EFTEM), we have determined that the solvent additives induce the change in the formation mechanism of polymer:fullerene nanomorphologies in the process of film casting. Progress established in the course of these studies on structural and morphological characterizations will serve as the foundation for further improving the efficiency of polymer solar cells to realize their large-scale commercial use.

  15. Role of Irisin on the bone–muscle functional unit

    PubMed Central

    Colaianni, Graziana; Grano, Maria

    2015-01-01

    Irisin was originally recognized as a hormone-like myokine secreted as a product of fibronectin type III domain containing 5 from skeletal muscle in response to exercise both in mice and humans. The first role attributed to Irisin was its ability to induce trans-differentiation of white adipose tissue into brown, but we recently demonstrated that Irisin also has a central role in the control of bone mass, even at lower concentration than required to induce the browning response. Considering how physical exercise is important for the development of an efficient load-bearing skeleton, we can now consider this myokine as one of the molecules responsible for the positive correlation between exercise and healthy bone, linking to the well-established relationship between muscle and bone. Recombinant Irisin (r-Irisin), administered at low dose in young mice, increases cortical bone mineral density and positively modifies bone geometry. Irisin exerts its effect prevalently on osteoblast lineage by enhancing differentiation and activity of bone-forming cells, through the increase in activating transcription factor 4 expression. Low-dose r-Irisin also increases osteopontin and decreases sclerostin synthesis but did not affect Uncoupling protein 1 expression in white adipose tissue, whose upregulation is known to cause browning of fat, when Irisin is administered at a higher dose. These findings offer an explanation to the positive outcome on the skeleton triggered by skeletal muscle during physical activity and prove that the bone tissue is more sensitive than the adipose tissue to the Irisin action. PMID:26788285

  16. Role of Vitamin C in the Function of the Vascular Endothelium

    PubMed Central

    Harrison, Fiona E.

    2013-01-01

    Abstract Significance: Vitamin C, or ascorbic acid, has long been known to participate in several important functions in the vascular bed in support of endothelial cells. These functions include increasing the synthesis and deposition of type IV collagen in the basement membrane, stimulating endothelial proliferation, inhibiting apoptosis, scavenging radical species, and sparing endothelial cell-derived nitric oxide to help modulate blood flow. Although ascorbate may not be able to reverse inflammatory vascular diseases such as atherosclerosis, it may well play a role in preventing the endothelial dysfunction that is the earliest sign of many such diseases. Recent Advances: Beyond simply preventing scurvy, evidence is mounting that ascorbate is required for optimal function of many dioxygenase enzymes in addition to those involved in collagen synthesis. Several of these enzymes regulate the transcription of proteins involved in endothelial function, proliferation, and survival, including hypoxia-inducible factor-1α and histone and DNA demethylases. More recently, ascorbate has been found to acutely tighten the endothelial permeability barrier and, thus, may modulate access of ascorbate and other molecules into tissues and organs. Critical Issues: The issue of the optimal cellular content of ascorbate remains unresolved, but it appears that low millimolar ascorbate concentrations are normal in most animal tissues, in human leukocytes, and probably in the endothelium. Although there may be little benefit of increasing near maximal cellular ascorbate concentrations in normal people, many diseases and conditions have either systemic or localized cellular ascorbate deficiency as a cause for endothelial dysfunction, including early atherosclerosis, sepsis, smoking, and diabetes. Future Directions: A key focus for future studies of ascorbate and the vascular endothelium will likely be to determine the mechanisms and clinical relevance of ascorbate effects on endothelial

  17. The role of epithelium in the development, structure and function of the tissues of tooth support.

    PubMed

    Ten Cate, A R

    1996-03-01

    The roles of epithelium in the development, structure and function of the tissues of tooth support are reviewed. Epithelium is involved in initiating odontogenesis which includes the tissues of tooth support and this role is discussed. Particular attention is paid to Hertwig's epithelial root sheath and its participation in the formation of the hyaline layer on the root surface as well as its possible role in initiating the differentiation of cementoblasts. The possible functions of the epithelial cell rests are reviewed and it is concluded that as yet no function can be ascribed to them. Evidence for an increasing role for dental epithelium in tooth eruption is presented and the role of dental epithelium in establishing the dentogingival junction is discussed, with the conclusion drawn that this role temporary.

  18. Morphology and functional roles of synoviocytes in the joint.

    PubMed

    Iwanaga, T; Shikichi, M; Kitamura, H; Yanase, H; Nozawa-Inoue, K

    2000-03-01

    The joint capsule exhibits a unique cellular lining in the luminal surface of the synovial membrane. The synovial intimal cells, termed synoviocytes, are believed to be responsible for the production of synovial fluid components, for absorption from the joint cavity, and for blood/synovial fluid exchanges, but their detailed structure and function as well as pathological changes remain unclear. Two types of synoviocytes, macrophagic cells (type A cells) and fibroblast-like cells (type B cells) have been identified. Type A synoviocytes are non-fixed cells that can phagocytose actively cell debris and wastes in the joint cavity, and possess an antigen-presenting ability. These type A cells, derived from blood-borne mononuclear cells, can be considered resident macrophages (tissue macrophages) like hepatic Kupffer cells. Type B synoviocytes are characterized by the rich existence of rough endoplasmic reticulum, and dendritic processes which form a regular network in the luminal surface of the synovial membrane. Their complex three-dimensional architecture was first revealed by our recent scanning electron microscopy of macerated samples. The type B cells, which are proper synoviocytes, are involved in production of specialized matrix constituents including hyaluronan, collagens and fibronectin for the intimal interstitium and synovial fluid. The proliferative potentials of type B cells in loco are much higher than type A cells, although the transformation of subintimal fibroblasts into type B cells can not be excluded. In some mammals, type B cells show features suggesting endocrine and sensory functions, but these are not recognized in other species. The synoviocytes, which form a discontinuous cell layer, develop both fragmented basement membranes around the cells and junctional apparatus such as desmosomes and gap junctions. For an exact understanding of the mechanism of arthritis, we need to establish the morphological background of synoviocytes as well as their

  19. Diabetes and mitochondrial function: Role of hyperglycemia and oxidative stress

    SciTech Connect

    Rolo, Anabela P.; Palmeira, Carlos M. . E-mail: palmeira@ci.uc.pt

    2006-04-15

    Hyperglycemia resulting from uncontrolled glucose regulation is widely recognized as the causal link between diabetes and diabetic complications. Four major molecular mechanisms have been implicated in hyperglycemia-induced tissue damage: activation of protein kinase C (PKC) isoforms via de novo synthesis of the lipid second messenger diacylglycerol (DAG), increased hexosamine pathway flux, increased advanced glycation end product (AGE) formation, and increased polyol pathway flux. Hyperglycemia-induced overproduction of superoxide is the causal link between high glucose and the pathways responsible for hyperglycemic damage. In fact, diabetes is typically accompanied by increased production of free radicals and/or impaired antioxidant defense capabilities, indicating a central contribution for reactive oxygen species (ROS) in the onset, progression, and pathological consequences of diabetes. Besides oxidative stress, a growing body of evidence has demonstrated a link between various disturbances in mitochondrial functioning and type 2 diabetes. Mutations in mitochondrial DNA (mtDNA) and decreases in mtDNA copy number have been linked to the pathogenesis of type 2 diabetes. The study of the relationship of mtDNA to type 2 diabetes has revealed the influence of the mitochondria on nuclear-encoded glucose transporters, glucose-stimulated insulin secretion, and nuclear-encoded uncoupling proteins (UCPs) in {beta}-cell glucose toxicity. This review focuses on a range of mitochondrial factors important in the pathogenesis of diabetes. We review the published literature regarding the direct effects of hyperglycemia on mitochondrial function and suggest the possibility of regulation of mitochondrial function at a transcriptional level in response to hyperglycemia. The main goal of this review is to include a fresh consideration of pathways involved in hyperglycemia-induced diabetic complications.

  20. Functional roles of benzothiazole motif in antiepileptic drug research.

    PubMed

    Amir, Mohammad; Hassan, Mohd Zaheen

    2013-12-01

    Benzothiazoles are promising candidates for the design of novel antiepileptic drugs. The endocyclic sulphur and nitrogen functions present in this heterocyclic nucleus have been shown to be critical for the anticonvulsant activity. The present review outlines the rational design and anticonvulsant potential of promising benzothiazole lead molecules. Particular focus has been placed on the structure activity relationship of different benzothiazole derivatives giving selected examples of molecules with significant activity being that these molecules may serve as prototypes for the development of more active antiepileptic drugs.

  1. The Historical Role of the Production Function in Economics and Business

    ERIC Educational Resources Information Center

    Gordon, David; Vaughan, Richard

    2011-01-01

    The production function explains a basic technological relationship between scarce resources, or inputs, and output. This paper offers a brief overview of the historical significance and operational role of the production function in business and economics. The origin and development of this function over time is initially explored. Several…

  2. Causal role of histone acetylations in enhancer function

    PubMed Central

    Pradeepa, Madapura M.

    2017-01-01

    ABSTRACT Enhancers control development and cellular function by spatiotemporal regulation of gene expression. Co-occurrence of acetylation of histone H3 at lysine 27 (H3K27ac) and mono methylation of histone H3 at lysine 4 (H3K4me1) has been widely used for identification of active enhancers. However, increasing evidence suggests that using this combination of marks alone for enhancer identification gives an incomplete picture of the active enhancer repertoire. We have shown that the H3 globular domain acetylations, H3K64ac and H3K122ac, and an H4 tail acetylation, H4K16ac, are enriched at active enhancers together with H3K27ac, and also at a large number of enhancers without detectable H3K27ac. We propose that acetylations at these lysine residues of histones H3 and H4 might function by directly affecting chromatin structure, nucleosome–nucleosome interactions, nucleosome stability, and transcription factor accessibility. PMID:27792455

  3. Cytosolic phospholipase A2: physiological function and role in disease

    PubMed Central

    Leslie, Christina C.

    2015-01-01

    The group IV phospholipase A2 (PLA2) family is comprised of six intracellular enzymes (GIVA, -B, -C, -D, -E, and -F) commonly referred to as cytosolic PLA2 (cPLA2)α, -β, -γ, -δ, -ε, and -ζ. They contain a Ser-Asp catalytic dyad and all except cPLA2γ have a C2 domain, but differences in their catalytic activities and subcellular localization suggest unique regulation and function. With the exception of cPLA2α, the focus of this review, little is known about the in vivo function of group IV enzymes. cPLA2α catalyzes the hydrolysis of phospholipids to arachidonic acid and lysophospholipids that are precursors of numerous bioactive lipids. The regulation of cPLA2α is complex, involving transcriptional and posttranslational processes, particularly increases in calcium and phosphorylation. cPLA2α is a highly conserved widely expressed enzyme that promotes lipid mediator production in human and rodent cells from a variety of tissues. The diverse bioactive lipids produced as a result of cPLA2α activation regulate normal physiological processes and disease pathogenesis in many organ systems, as shown using cPLA2α KO mice. However, humans recently identified with cPLA2α deficiency exhibit more pronounced effects on health than observed in mice lacking cPLA2α, indicating that much remains to be learned about this interesting enzyme. PMID:25838312

  4. Muscarinic receptor family interacting proteins: role in receptor function.

    PubMed

    Borroto-Escuela, Dasiel O; Correia, Patrícia A; Romero-Fernandez, Wilber; Narvaez, Manuel; Fuxe, Kjell; Ciruela, Francisco; Garriga, Pere

    2011-02-15

    G protein-coupled receptors constitute one of the most important families of membrane receptors through which cells respond to extracellular stimuli. Receptors of this superfamily likely function as signal transduction complexes. The identification and analysis of their components provide new insights into a better understanding of these receptors' function and regulation. We used tandem-affinity purification and mass spectrometry as a systematic approach to characterize multiprotein complexes in the acetylcholine muscarinic receptor subfamily. To overcome the limitations associated with membrane protein receptor solubilization with detergents, we developed a strategy in which receptors are co-expressed with a cytoplasmic minigene construct, encoding the third intracellular loop and the C-terminal tail tagged to the tandem-affinity-cassette of each receptor subtype. Numerous protein complexes were identified, including many new interactions in various signalling pathways. Systematic identification data set together with protein interactions reported in the literature revealed a high degree of connectivity. These allow the proposal, for the first time, of an outline of the muscarinic interactome as a network of protein complexes and a context for a more reasoned and informed approach to drug discovery and muscarinic receptor subtype specificities.

  5. Cytosolic phospholipase A₂: physiological function and role in disease.

    PubMed

    Leslie, Christina C

    2015-08-01

    The group IV phospholipase A2 (PLA2) family is comprised of six intracellular enzymes (GIVA, -B, -C, -D, -E, and -F) commonly referred to as cytosolic PLA2 (cPLA2)α, -β, -γ, -δ, -ε, and -ζ. They contain a Ser-Asp catalytic dyad and all except cPLA2γ have a C2 domain, but differences in their catalytic activities and subcellular localization suggest unique regulation and function. With the exception of cPLA2α, the focus of this review, little is known about the in vivo function of group IV enzymes. cPLA2α catalyzes the hydrolysis of phospholipids to arachidonic acid and lysophospholipids that are precursors of numerous bioactive lipids. The regulation of cPLA2α is complex, involving transcriptional and posttranslational processes, particularly increases in calcium and phosphorylation. cPLA2α is a highly conserved widely expressed enzyme that promotes lipid mediator production in human and rodent cells from a variety of tissues. The diverse bioactive lipids produced as a result of cPLA2α activation regulate normal physiological processes and disease pathogenesis in many organ systems, as shown using cPLA2α KO mice. However, humans recently identified with cPLA2α deficiency exhibit more pronounced effects on health than observed in mice lacking cPLA2α, indicating that much remains to be learned about this interesting enzyme.

  6. A genetic approach for investigating vagal sensory roles in regulation of gastrointestinal function and food intake.

    PubMed

    Fox, Edward Alan

    2006-06-30

    Sensory innervation of the gastrointestinal (GI) tract by the vagus nerve plays important roles in regulation of GI function and feeding behavior. This innervation is composed of a large number of sensory pathways, each arising from a different population of sensory receptors. Progress in understanding the functions of these pathways has been impeded by their close association with vagal efferent, sympathetic, and enteric systems, which makes it difficult to selectively label or manipulate them. We suggest that a genetic approach may overcome these barriers. To illustrate the potential value of this strategy, as well as to gain insights into its application, investigations of CNS pathways and peripheral tissues involved in energy balance that benefited from the use of gene manipulations are reviewed. Next, our studies examining the feasibility of using mutations of developmental genes for manipulating individual vagal afferent pathways are reviewed. These experiments characterized mechanoreceptor morphology, density and distribution, and feeding patterns in four viable mutant mouse strains. In each strain a single population of vagal mechanoreceptors innervating the muscle wall of the GI tract was altered, and was associated with selective effects on feeding patterns, thus supporting the feasibility of this strategy. However, two limitations of this approach must be addressed for it to achieve its full potential. First, mutation effects in tissues outside the GI tract can contribute to changes in GI function or feeding. Additionally, knockouts of developmental genes are often lethal, preventing analysis of mature innervation and ingestive behavior. To address these issues, we propose to develop conditional gene knockouts restricted to specific GI tract tissues. Two genes of interest are brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), which are essential for vagal afferent development. Creating conditional knockouts of these genes requires

  7. In situ Raman and electrochemical characterization of the role of electrolyte additives in Li/SOCl2 batteries

    NASA Astrophysics Data System (ADS)

    Kovac, M.; Milicev, S.; Kovac, A.; Pejovnik, S.

    1995-05-01

    A simple glass cell has been constructed for in situ Raman characterization of discharge products in Li/SOCl2 batteries with polyvinyl chloride (PVC) and LiAl(SO3Cl4) additives. The assembly enables the characterization of catholyte-soluble discharge products in the electrolyte as well as products on the lithium and carbon electrode surfaces. The effect of the additives was also examined by scanning electron microscopy/energy dispersive spectroscopy and impedance spectroscopy and correlated to the voltage delay in batteries. The best results, as regards to the elimination of the delay effect, were obtained with a new electrolyte consisting of LiAlCl4/SOCl2 with an admixture of PVC and LiAl(SO3Cl4).

  8. [Asymmetric effects of addition versus deletion on change detection task: the role of feeling of something strange].

    PubMed

    Uchino, Yashio; Hakoda, Yuji; Shibata, Mariko

    2005-06-01

    Two experiments were conducted to examine the asymmetric effect of alterations (i.e., addition versus deletion) on recognition memory. In Experiment 1, a scale for measuring the FSS (Feeling of Something Strange) was developed (n=50) using added or deleted pictures from previous research (e.g., Uchino, Hakoda, & Yamada, 2000). Result showed that altered pictures were evaluated by "pleasant" and "odd" factors. In Experiment 2, 80 participants observed 20 pictures, and then they answered whether each test picture was altered or not. Test pictures varied in significance of the objects added or deleted on a scene. Additions were detected more easily than deletions only when added object was unexpected or unusual, while deleted object was essential to a scene (TD: typicality-disrupted condition). Then, 60 participants rated the FSS scale for test pictures. Ratings of odd factor for added pictures were higher than deleted pictures presented in the TD condition. These results suggest that superiority of addition over deletion might be due to their different effect on FSS.

  9. Hantaviral Proteins: Structure, Functions, and Role in Hantavirus Infection

    PubMed Central

    Muyangwa, Musalwa; Martynova, Ekaterina V.; Khaiboullina, Svetlana F.; Morzunov, Sergey P.; Rizvanov, Albert A.

    2015-01-01

    Hantaviruses are the members of the family Bunyaviridae that are naturally maintained in the populations of small mammals, mostly rodents. Most of these viruses can easily infect humans through contact with aerosols or dust generated by contaminated animal waste products. Depending on the particular Hantavirus involved, human infection could result in either hemorrhagic fever with renal syndrome or in Hantavirus cardiopulmonary syndrome. In the past few years, clinical cases of the Hantavirus caused diseases have been on the rise. Understanding structure of the Hantavirus genome and the functions of the key viral proteins are critical for the therapeutic agents’ research. This paper gives a brief overview of the current knowledge on the structure and properties of the Hantavirus nucleoprotein and the glycoproteins. PMID:26640463

  10. The functional roles of S1P in immunity.

    PubMed

    Hisano, Yu; Nishi, Tsuyoshi; Kawahara, Atsuo

    2012-10-01

    The lipid mediator sphingosine-1-phosphate (S1P) is generated within cells from sphingosine by two sphingosine kinases (SPHK1 and SPHK2). Intracellularly synthesized S1P is released into the extracellular fluid by S1P transporters, including SPNS2. Released S1P binds specifically to the G protein-coupled S1P receptors (S1PR1/S1P(1)-S1PR5/S1P(5)), which activate a diverse range of downstream signalling pathways. Recent studies have proposed that one of the central physiological functions of intercellular S1P signalling is in lymphocyte trafficking in vivo because genetic disruption of SPHK1/2, SPNS2 or S1PR1/S1P(1) in mice induces a lymphopenia phenotype. In this review, we discuss the current understanding of intercellular S1P signalling in the context of immunity.

  11. Biological water: Its vital role in macromolecular structure and function.

    PubMed

    Despa, Florin

    2005-12-01

    Water in tissues and cells is confined by intervening cellular components and is subject to structural effects that are not present in its bulk counterpart. The structuring effects lower the dielectric susceptibility of water molecules and induce a "red shift" of their relaxation frequency. This is also a source of polarization fields that contribute to the effective interactions between macromolecules. The behavior of water molecules at hydrophilic sites is different from that at hydrophobic sites, and this dissimilar behavior promotes the anisotropy of the hydration shell of proteins. The anisotropy of the hydration shell is essential for the enzyme function, but it is also important in detecting denaturation of the protein (i.e., proteins expose their hydrophobic parts to water during unfolding). The most significant differences between biological and ordinary water will be presented along with how this information can be used to decipher patterns in dynamical behavior of biological water and to detect possible structural changes of the cellular components.

  12. Wave functions' discernibility and the role of fluctuations

    NASA Astrophysics Data System (ADS)

    Casas, M.; Lamberti, P. W.; Plastino, A.; Plastino, A. R.; Roston, G.

    2005-05-01

    The question of distinguishability of quantum states is at the heart of quantum information processing, an issue is here addressed with reference to different distances in probability space vis-a-vis metrics in Hilbert's one. We provide further reconfirmation of Wootters' hypothesis: the possibility that statistical fluctuations in the outcomes of measurements be regarded as responsible for the Hilbert-space structure of quantum mechanics, a view that becomes here considerably strengthened. We show that distances between neighboring states, whether of statistical or Hilbert's metric origin, have as a lower bound Fisher's measure, up to second-order approximation. As a consequence, the structure of the vicinity of a given quantum state is to a large extent determined by the fluctuations of the pertinent observables. It is also shown that Tsallis' non-extensivity parameter q can be used as a tool for increasing discernibility between wave functions.

  13. The Functional Role of Reactive Stroma in Benign Prostatic Hyperplasia

    PubMed Central

    Schauer, Isaiah G.; Rowley, David R.

    2011-01-01

    The human prostate gland is one of the only internal organs that continue to enlarge throughout adulthood. The specific mechanisms that regulate this growth, as well as the pathological changes leading to the phenotype observed in the disease benign prostatic hyperplasia (BPH), are essentially unknown. Recent studies and their associated findings have made clear that many complex alterations occur, involving persistent and chronic inflammation, circulating hormonal level deregulation, and aberrant wound repair processes. BPH has been etiologically characterized as a progressive, albeit discontinuous, hyperplasia of both the glandular epithelial and stromal cell compartments coordinately yielding an expansion of the prostate gland and clinical symptoms. Interestingly, the inflammatory and repair responses observed in BPH are also key components of general wound repair in post-natal tissues. These responses include altered expression of chemokines, cytokines, matrix remodeling factors, chronic inflammatory processes, altered immune surveillance and recognition, as well as the formation of a prototypical ‘reactive’ stroma which is similar to that observed across various fibroplasias and malignancies of a variety of tissue sites. Stromal tissue, both embryonic mesenchyme, and adult reactive stroma myofibroblasts, has been shown to exert potent and functional regulatory control over epithelial proliferation and differentiation as well as immunoresponsive modulation. Thus, the functional biology of a reactive stroma, within the context of an adult disease typified by epithelial and stromal aberrant hyperplasia, is critical to understand within the context of prostate disease and beyond. The mechanisms that regulate reactive stroma biology in BPH represent targets of opportunity for new therapeutic approaches that may extend to other tissue contexts. Accordingly, this review seeks to address the dissection of important factors, signaling pathways, genes, and other

  14. The Role of Reactive Functional Groups in Adhesive Bonding at the Aramid-Epoxy Interface.

    DTIC Science & Technology

    1986-09-15

    sta end ZIP CeO . 800 North Quincy Street i-q ?AiI 3 Arlington, VA 22217 " ae’Iv o. ’to. 6 -o. !The Role of Reactive Functional . . . 1 12. onsRonfaI...Unclassified SICUMI VY’V Ct.ASSiiICATyO OP ’T-S PAGE I Cont ... 11. The Role of Reactive Functional Groups in Adhesive Bonding at the Aramid-Epoxy...T-1 ROLE OF REACTIVE FUNCTIONAL GROUPS IN ADHESIVI 3ODI;G AT THE ARA fID-EPOXY INTIFA> BY L.S. PENN, T.J. BYERLEY, AND T.K. LIAO 1IDWEST RESEARCR

  15. A γ-Secretase Independent Role for Presenilin in Calcium Homeostasis Impacts Mitochondrial Function and Morphology in Caenorhabditis elegans.

    PubMed

    Sarasija, Shaarika; Norman, Kenneth R

    2015-12-01

    Mutations in the presenilin (PSEN) encoding genes (PSEN1 and PSEN2) occur in most early onset familial Alzheimer's Disease. Despite the identification of the involvement of PSEN in Alzheimer's Disease (AD) ∼20 years ago, the underlying role of PSEN in AD is not fully understood. To gain insight into the biological function of PSEN, we investigated the role of the PSEN homolog SEL-12 in Caenorhabditis elegans. Using genetic, cell biological, and pharmacological approaches, we demonstrate that mutations in sel-12 result in defects in calcium homeostasis, leading to mitochondrial dysfunction. Moreover, consistent with mammalian PSEN, we provide evidence that SEL-12 has a critical role in mediating endoplasmic reticulum (ER) calcium release. Furthermore, we found that in SEL-12-deficient animals, calcium transfer from the ER to the mitochondria leads to fragmentation of the mitochondria and mitochondrial dysfunction. Additionally, we show that the impact that SEL-12 has on mitochondrial function is independent of its role in Notch signaling, γ-secretase proteolytic activity, and amyloid plaques. Our results reveal a critical role for PSEN in mediating mitochondrial function by regulating calcium transfer from the ER to the mitochondria.

  16. A γ-Secretase Independent Role for Presenilin in Calcium Homeostasis Impacts Mitochondrial Function and Morphology in Caenorhabditis elegans

    PubMed Central

    Sarasija, Shaarika; Norman, Kenneth R.

    2015-01-01

    Mutations in the presenilin (PSEN) encoding genes (PSEN1 and PSEN2) occur in most early onset familial Alzheimer’s Disease. Despite the identification of the involvement of PSEN in Alzheimer’s Disease (AD) ∼20 years ago, the underlying role of PSEN in AD is not fully understood. To gain insight into the biological function of PSEN, we investigated the role of the PSEN homolog SEL-12 in Caenorhabditis elegans. Using genetic, cell biological, and pharmacological approaches, we demonstrate that mutations in sel-12 result in defects in calcium homeostasis, leading to mitochondrial dysfunction. Moreover, consistent with mammalian PSEN, we provide evidence that SEL-12 has a critical role in mediating endoplasmic reticulum (ER) calcium release. Furthermore, we found that in SEL-12-deficient animals, calcium transfer from the ER to the mitochondria leads to fragmentation of the mitochondria and mitochondrial dysfunction. Additionally, we show that the impact that SEL-12 has on mitochondrial function is independent of its role in Notch signaling, γ-secretase proteolytic activity, and amyloid plaques. Our results reveal a critical role for PSEN in mediating mitochondrial function by regulating calcium transfer from the ER to the mitochondria. PMID:26500256

  17. Role of the mu opioid receptor in opioid modulation of immune function

    PubMed Central

    Ninković, Jana; Roy, Sabita

    2014-01-01

    SUMMARY Endogenous opioids are synthesized in vivo in order to modulate pain mechanisms and inflammatory pathways. Endogenous and exogenous opioids mediate analgesia in response to painful stimuli by binding to opioid receptors on neuronal cells. However, wide distribution of opioid receptors on tissues and organ systems outside the CNS, such as the cells of the immune system, indicate that opioids are capable of exerting additional effects in the periphery, such as immunomodulation. The increased prevalence of infections in opioid abusers based epidemiological studies further highlights the immunosuppressive effects of opioids. In spite of their many debilitating side effects, prescription opioids remain a gold standard for treatment of chronic pain. Therefore, given the prevalence of opioid use and abuse, opioid mediated immune suppression presents a serious concern in our society today. It is imperative to understand the mechanisms by which exogenous opioids modulate immune processes. In this review we will discuss the role of opioid receptors and their ligands in mediating immune suppressive functions. We will summarize recent studies on direct and indirect opioid modulation of the cells of the immune system as well as the role of opioids in exacerbation of certain disease states. PMID:22170499

  18. The role of Amh signaling in teleost fish--Multiple functions not restricted to the gonads.

    PubMed

    Pfennig, Frank; Standke, Andrea; Gutzeit, Herwig O

    2015-11-01

    This review summarizes the important role of Anti-Müllerian hormone (Amh) during gonad development in fishes. This Tgfβ-domain bearing hormone was named after one of its known functions, the induction of the regression of Müllerian ducts in male mammalian embryos. Later in development it is involved in male and female gonad differentiation and extragonadal expression has been reported in mammals as well. Teleosts lack Müllerian ducts, but they have amh orthologous genes. amh expression is reported from 21 fish species and possible regulatory interactions with further factors like sex steroids and gonadotropic hormones are discussed. The gonadotropin Fsh inhibits amh expression in all fish species studied. Sex steroids show no consistent influence on amh expression. Amh is produced in male Sertoli cells and female granulosa cells and inhibits germ cell proliferation and differentiation as well as steroidogenesis in both sexes. Therefore, Amh might be a central player in gonad development and a target of gonadotropic Fsh. Furthermore, there is evidence that an Amh-type II receptor is involved in germ cell regulation. Amh and its corresponding type II receptor are also present in brain and pituitary, at least in some teleosts, indicating additional roles of Amh effects in the brain-pituitary-gonadal axis. Unraveling Amh signaling is important in stem cell research and for reproduction as well as for aquaculture and in environmental science.

  19. Gli-similar proteins: their mechanisms of action, physiological functions, and roles in disease.

    PubMed

    Lichti-Kaiser, Kristin; ZeRuth, Gary; Kang, Hong Soon; Vasanth, Shivakumar; Jetten, Anton M

    2012-01-01

    Gli-similar (Glis) 1-3 proteins constitute a subfamily of Krüppel-like zinc-finger proteins that are closely related to members of the Gli family. Glis proteins have been implicated in several pathologies, including cystic kidney disease, diabetes, hypothyroidism, fibrosis, osteoporosis, psoriasis, and cancer. In humans, a mutation in the Glis2 gene has been linked to the development of nephronophthisis (NPHP), a recessive cystic kidney disease, while mutations in Glis3 lead to an extended multisystem phenotype that includes the development of neonatal diabetes, polycystic kidneys, congenital hypothyroidism, and facial dysmorphism. Glis3 has also been identified as a risk locus for type-1 and type-2 diabetes and additional studies have revealed a role for Glis3 in pancreatic endocrine development, β-cell maintenance, and insulin regulation. Similar to Gli1-3, Glis2 and 3 have been reported to localize to the primary cilium. These studies appear to suggest that Glis proteins are part of a primary cilium-associated signaling pathway(s). It has been hypothesized that Glis proteins are activated through posttranslational modifications and subsequently translocate to the nucleus where they regulate transcription by interacting with Glis-binding sites in the promoter regions of target genes. This chapter summarizes the current state of knowledge regarding mechanisms of action of the Glis family of proteins, their physiological functions, as well as their roles in disease.

  20. Gli-Similar (Glis) Proteins: Their Mechanisms of Action, Physiological Functions, and Roles in Disease

    PubMed Central

    Lichti-Kaiser, Kristin; ZeRuth, Gary; Kang, Hong Soon; Vasanth, Shivakumar; Jetten, Anton M.

    2013-01-01

    Gli-similar (Glis) 1–3 proteins constitute a sub-family of Krüppel-like zinc finger proteins that are closely related to members of the Gli family. Glis proteins have been implicated in several pathologies, including cystic kidney disease, diabetes, hypothyroidism, fibrosis, osteoporosis, psoriasis, and cancer. In humans, a mutation in the Glis2 gene has been linked to the development of nephronophthisis (NPHP), a recessive cystic kidney disease, while mutations in Glis3 lead to an extended multi-system phenotype that includes the development of neonatal diabetes, polycystic kidneys, congenital hypothyroidism, and facial dysmorphism. Glis3 has also been identified as a risk locus for type-1 and type-2 diabetes and additional studies have revealed a role for Glis3 in pancreatic endocrine development, β-cell maintenance, and insulin regulation. Similar to Gli1-3, Glis2 and 3 have been reported to localize to the primary cilium. These studies appear to suggest that Glis proteins are part of a primary cilium-associated signaling pathway(s). It has been hypothesized that Glis proteins are activated through post-translational modifications and subsequently translocate to the nucleus where they regulate transcription by interacting with Glis binding sites in the promoter regions of target genes. This chapter will summarize the current state of knowledge regarding mechanisms of action of the Glis family of proteins, their physiological functions, as well as their roles in disease. PMID:22391303

  1. Lipids in photosynthetic reaction centres: structural roles and functional holes.

    PubMed

    Jones, Michael R

    2007-01-01

    Photosynthetic proteins power the biosphere. Reaction centres, light harvesting antenna proteins and cytochrome b(6)f (or bc(1)) complexes are expressed at high levels, have been subjected to an intensive spectroscopic, biochemical and mutagenic analysis, and several have been characterised to an informatively high resolution by X-ray crystallography. In addition to revealing the structural basis for the transduction of light energy, X-ray crystallography has brought molecular insights into the relationships between these multicomponent membrane proteins and their lipid environment. Lipids resolved in the X-ray crystal structures of photosynthetic proteins bind light harvesting cofactors, fill intra-protein cavities through which quinones can diffuse, form an important part of the monomer-monomer interface in multimeric structures and may facilitate structural flexibility in complexes that undergo partial disassembly and repair. It has been proposed that individual lipids influence the biophysical properties of reaction centre cofactors, and so affect the rate of electron transfer through the complex. Lipids have also been shown to be important for successful crystallisation of photosynthetic proteins. Comparison of the three types of reaction centre that have been structurally characterised reveals interesting similarities in the position of bound lipids that may point towards a generic requirement to reinforce the structure of the core electron transfer domain. The crystallographic data are also providing new opportunities to find molecular explanations for observed effects of different types of lipid on the structure, mechanism and organisation of reaction centres and other photosynthetic proteins.

  2. A role for magnesium in neonatal parathyroid gland function

    SciTech Connect

    Loughead, J.L.; Mimouni, F.; Tsang, R.C.; Khoury, J.C. )

    1991-04-01

    Little is known of the factors regulating parathyroid function in the neonatal period. Twenty-seven term infants born after uncomplicated pregnancies, labors, and deliveries were studied to test the hypothesis that in normal newborns the amplitude of parathyroid hormone (PTH) response to decreasing serum ionized calcium (iCa) correlates with serum magnesium (Mg) concentrations. Serum iCa (ion selective electrode, Radiometer ICA 1), PTH (1-84 intact molecules, radioimmunoassay) and Mg (atomic absorption) were measured at birth (cord blood) and 24 hours of age. Repeated measures analysis of covariance showed decreasing serum iCa (p less than 0.01) and increasing serum Mg (p less than 0.01) and PTH (p less than 0.01) over time. The change in PTH over the first 24 hours was directly correlated with cord blood (r = 0.38, p less than 0.05) and 24-hr Mg concentrations (r = 0.53, p less than 0.01). We conclude that the ability of the parathyroid gland to respond to decreasing serum iCa after birth is directly related to Mg status. We speculate that neonatal hypomagnesemia may lead to a blunted PTH secretory response, thus contributing to early neonatal hypocalcemia.

  3. Indigenous perception and characterization of Yanyanku and Ikpiru: two functional additives for the fermentation of African locust bean.

    PubMed

    Agbobatinkpo, Pélagie B; Azokpota, Paulin; Akissoe, Noël; Kayodé, Polycarpe; Da Gbadji, Rachelle; Hounhouigan, D Joseph

    2011-01-01

    Indigenous perception, processing methods, and physicochemical and microbiological characteristics of Yanyanku and Ikpiru, two additives used to produce fermented African locust bean condiments, Sonru and Iru, were evaluated. According to producers, these additives accelerate the fermentation and soften the texture of the condiments. Yanyanku is produced by spontaneous fermentation with either Hibiscus sabdariffa or Gossypium hirsutum or Adansonia digitata seeds, whereas only Hibiscus sabdariffa seeds are used for Ikpiru. Both additives, with pH values ranging between 6.2 and 10 and Bacillus spores varying between 5.5 and 8.9 Log(10) (CFU/g), could be considered as softening additives or enrichment inocula to produce condiments.

  4. Aquaporins in the eye: Expression, function, and roles in ocular disease☆

    PubMed Central

    Schey, Kevin L.; Wang, Zhen; Wenke, Jamie L.; Qi, Ying

    2015-01-01

    Background All thirteen known mammalian aquaporins have been detected in the eye. Moreover, aquaporins have been identified as playing essential roles in ocular functions ranging from maintenance of lens and corneal transparency to production of aqueous humor to maintenance of cellular homeostasis and regulation of signal transduction in the retina. Scope of review This review summarizes the expression and known functions of ocular aquaporins and discusses their known and potential roles in ocular diseases. Major conclusions Aquaporins play essential roles in all ocular tissues. Remarkably, not all aquaporin function as a water permeable channel and the functions of many aquaporins in ocular tissues remain unknown. Given their vital roles in maintaining ocular function and their roles in disease, aquaporins represent potential targets for future therapeutic development. General significance Since aquaporins play key roles in ocular physiology, an understanding of these functions is important to improving ocular health and treating diseases of the eye. It is likely that future therapies for ocular diseases will rely on modulation of aquaporin expression and/or function. This article is part of a Special Issue entitled Aquaporins. PMID:24184915

  5. High quality Y3Al5O12 doped transparent ceramics for laser applications, role of sintering additives

    NASA Astrophysics Data System (ADS)

    Kaminskii, A. A.; Balashov, V. V.; Cheshev, E. A.; Kopylov, Yu L.; Koromyslov, A. L.; Krokhin, O. N.; Kravchenko, V. B.; Lopukhin, K. V.; Shemet, V. V.; Tupitsyn, I. M.

    2016-08-01

    SiO2, ZrO2, B2O3 and MgO oxides and their combinations were used as sintering aids for preparation of yttrium aluminum garnet (YAG) ceramics doped by Nd2O3, Er2O3, Ho2O3, Tm2O3 and Yb2O3. The influence of these additives on optimal sintering temperature, grain growth, volume of residual pores and optical quality of the ceramics were investigated. The best combination of the sintering additives was found and high quality samples of YAG:Nd (1 at.%) ceramics were obtained. The original method of laser optical quality characterization of ceramics was developed and tested. The main laser parameters of YAG:Nd (1 at.%) ceramics samples are measured and compared with the best well known laser ceramics. The samples of YAG:RE (RE- Er2O3, Ho2O3, Tm2O3 and Yb2O3) ceramics are obtained, and their optical transmittance spectra are measured. Composite structures of YAG:Yb (5 at.%) - YAG were obtained by the simplest method of successive joint compaction of different composition layers.

  6. Steam-on-a-chip for oil recovery: the role of alkaline additives in steam assisted gravity drainage.

    PubMed

    de Haas, Thomas W; Fadaei, Hossein; Guerrero, Uriel; Sinton, David

    2013-10-07

    We present a lab-on-a-chip approach to informing thermal oil recovery processes. Bitumen - a major global resource - is an extremely viscous oil which is extracted by injecting steam underground in a process known as Steam Assisted Gravity Drainage (SAGD). Here, a microfluidic network saturated with bitumen provides a physical model of the SAGD reservoir; steam is injected into the chip, and the oil recovery dynamics are visualized and quantified in real-time. The unique advantage of this approach is the pore-scale quantification of fluid phase dynamics under relevant reservoir conditions and pore sizes. High resolution is achieved by leveraging the inherent fluorescence of the native bitumen. The approach is applied to quantify the efficacy of an alkaline steam additive. With the additive, the mean characteristic size of oil-in-water emulsions formed during SAGD is reduced from 150 μm to 6 μm, and the corresponding recovery effectiveness is improved by ~50%. These results demonstrate that pore-scale process quantification enabled by lab-on-a-chip methods can improve the efficacy, and the associated carbon footprint, of energy intensive thermal oil recovery processes.

  7. Novel roles of the multi-functional CCR4-NOT complex in post-transcriptional regulation

    PubMed Central

    Inada, Toshifumi; Makino, Shiho

    2014-01-01

    The CCR4-NOT complex is a highly conserved specific gene silencer that also serves more general post-transcriptional functions. Specific regulatory proteins including the miRNA-induced silencing complex and its associated proteins, bind to 3’-UTR elements of mRNA and recruit the CCR4-NOT complex thereby promoting poly(A) shortening and repressing translation and/or mRNA degradation. Recent studies have shown that the CCR4-NOT complex that is tethered to mRNA by such regulator(s) represses translation and facilitates mRNA decay independent of a poly(A) tail and its shortening. In addition to deadenylase activity, the CCR4-NOT complex also has an E3 ubiquitin ligase activity and is involved in a novel protein quality control system, i.e., co-translational proteasomal-degradation of aberrant proteins. In this review, we describe recent progress in elucidation of novel roles of the multi-functional complex CCR4-NOT in post-transcriptional regulation. PMID:24904636

  8. Secondary Structure across the Bacterial Transcriptome Reveals Versatile Roles in mRNA Regulation and Function.

    PubMed

    Del Campo, Cristian; Bartholomäus, Alexander; Fedyunin, Ivan; Ignatova, Zoya

    2015-10-01

    Messenger RNA acts as an informational molecule between DNA and translating ribosomes. Emerging evidence places mRNA in central cellular processes beyond its major function as informational entity. Although individual examples show that specific structural features of mRNA regulate translation and transcript stability, their role and function throughout the bacterial transcriptome remains unknown. Combining three sequencing approaches to provide a high resolution view of global mRNA secondary structure, translation efficiency and mRNA abundance, we unraveled structural features in E. coli mRNA with implications in translation and mRNA degradation. A poorly structured site upstream of the coding sequence serves as an additional unspecific binding site of the ribosomes and the degree of its secondary structure propensity negatively correlates with gene expression. Secondary structures within coding sequences are highly dynamic and influence translation only within a very small subset of positions. A secondary structure upstream of the stop codon is enriched in genes terminated by UAA codon with likely implications in translation termination. The global analysis further substantiates a common recognition signature of RNase E to initiate endonucleolytic cleavage. This work determines for the first time the E. coli RNA structurome, highlighting the contribution of mRNA secondary structure as a direct effector of a variety of processes, including translation and mRNA degradation.

  9. Secondary Structure across the Bacterial Transcriptome Reveals Versatile Roles in mRNA Regulation and Function

    PubMed Central

    Fedyunin, Ivan; Ignatova, Zoya

    2015-01-01

    Messenger RNA acts as an informational molecule between DNA and translating ribosomes. Emerging evidence places mRNA in central cellular processes beyond its major function as informational entity. Although individual examples show that specific structural features of mRNA regulate translation and transcript stability, their role and function throughout the bacterial transcriptome remains unknown. Combining three sequencing approaches to provide a high resolution view of global mRNA secondary structure, translation efficiency and mRNA abundance, we unraveled structural features in E. coli mRNA with implications in translation and mRNA degradation. A poorly structured site upstream of the coding sequence serves as an additional unspecific binding site of the ribosomes and the degree of its secondary structure propensity negatively correlates with gene expression. Secondary structures within coding sequences are highly dynamic and influence translation only within a very small subset of positions. A secondary structure upstream of the stop codon is enriched in genes terminated by UAA codon with likely implications in translation termination. The global analysis further substantiates a common recognition signature of RNase E to initiate endonucleolytic cleavage. This work determines for the first time the E. coli RNA structurome, highlighting the contribution of mRNA secondary structure as a direct effector of a variety of processes, including translation and mRNA degradation. PMID:26495981

  10. Diverse functional roles of monosaccharide transporters and their homologs in vascular plants: a physiological perspective.

    PubMed

    Slewinski, Thomas L

    2011-07-01

    Vascular plants contain two gene families that encode monosaccharide transporter proteins. The classical monosaccharide transporter(-like) gene superfamily is large and functionally diverse, while the recently identified SWEET transporter family is smaller and, thus far, only found to transport glucose. These transporters play essential roles at many levels, ranging from organelles to the whole plant. Many family members are essential for cellular homeostasis and reproductive success. Although most transporters do not directly participate in long-distance transport, their indirect roles greatly impact carbon allocation and transport flux to the heterotrophic tissues of the plant. Functional characterization of some members from both gene families has revealed their diverse roles in carbohydrate partitioning, phloem function, resource allocation, plant defense, and sugar signaling. This review highlights the broad impacts and implications of monosaccharide transport by describing some of the functional roles of the monosaccharide transporter(-like) superfamily and the SWEET transporter family.

  11. Thyroid function. Pathogenesis of Graves ophthalmopathy--a role for TSH-R?

    PubMed

    Wall, Jack R

    2014-05-01

    A new study highlights the complexities of anti-TSH-receptor antibody function and the differences between adult and paediatric patients with Graves disease, adding to the controversy regarding the possible role of these antibodies in the development of ophthalmopathy.

  12. The Role of Laser Additive Manufacturing Methods of Metals in Repair, Refurbishment and Remanufacturing - Enabling Circular Economy

    NASA Astrophysics Data System (ADS)

    Leino, Maija; Pekkarinen, Joonas; Soukka, Risto

    Circular economy is an economy model where products, components, and materials are aimed to be kept at their highest utility and value at all times. Repair, refurbishment and remanufacturing processes are procedures aiming at returning the value of the product during its life cycle. Additive manufacturing (AM) is expected to be an enabling technology in circular economy based business models. One of AM process that enables repair, refurbishment and remanufacturing is Directed Energy Deposition. Respectively Powder Bed Fusion enables manufacturing of replacement components on demand. The aim of this study is to identify the current research findings and state of art of utilizing AM in repair, refurbishment and remanufacturing processes of metallic products. The focus is in identifying possibilities of AM in promotion of circular economy and expected environmental benefits based on the found literature. Results of the study indicate significant potential in utilizing AM in repair, refurbishment and remanufacturing activities.

  13. Role of electrolyte additives on in-vitro electrochemical behavior of micro arc oxidized titania films on Cp Ti

    NASA Astrophysics Data System (ADS)

    Venkateswarlu, K.; Rameshbabu, N.; Sreekanth, D.; Bose, A. C.; Muthupandi, V.; Babu, N. K.; Subramanian, S.

    2012-07-01

    The present work is aimed at studying the influence of electrolyte chemistry on the voltage-time (V-T) response characteristics, phase structure, surface morphology, film growth rate and corrosion properties of titania films fabricated by micro arc oxidation (MAO) on Cp Ti. The titania films were developed with a sodium phosphate based reference electrolyte comprising the additives such as sodium carbonate (Na2CO3), sodium nitrite (NaNO2) and urea (CO(NH2)2). The phase composition, surface morphology, elemental composition and thickness of the films were assessed by X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) techniques. The corrosion characteristics of the fabricated films were studied under Kokubo simulated body fluid (SBF) condition by potentiodynamic polarization, long term potential and linear polarization resistance (LPR) measurements and electrochemical impedance spectroscopy (EIS) methods. In addition, the corrosion characteristics of the grown films were analyzed by EIS curve fitting and equivalent circuit modeling. Salt spray test (SST) as per ASTM B 117 standard was also conducted to verify the corrosion resistance of the grown films. The XRD results showed that the titania films were composed of both anatase and rutile phases at different proportions. Besides, the films grown in carbonate and nitrite containing electrolyte systems showed an enhanced growth of their rutile phase in the [1 0 1] direction which could be attributed to the modifications introduced in the growth process by the abundant oxygen available during the process. The SEM-EDX and elemental mapping results showed that the respective electrolyte borne elements were incorporated and distributed uniformly in all the films. Among all the grown films under study, the film developed in carbonate containing electrolyte system exhibited considerably improved corrosion resistance due to suitable modifications in its structural and

  14. Squaramide-tertiary amine catalyzed asymmetric cascade sulfa-Michael/Michael addition via dynamic kinetic resolution: access to highly functionalized chromans with three contiguous stereocenters.

    PubMed

    Yang, Wen; Yang, Yi; Du, Da-Ming

    2013-03-15

    An efficient asymmetric cascade sulfa-Michael/Michael addition reaction catalyzed by a chiral bifunctional squaramide-tertiary amine catalyst has been developed. This organocatalytic cascade reaction provides easy access to highly functionalized chromans with three contiguous stereocenters, including one quaternary center. In addition, a novel cascade sulfa Michael/retro-sulfa-Michael/sulfa-Michael/Michael reaction process, involving dynamic kinetic resolution, is described.

  15. The Role of Functional and Perceptual Attributes: Evidence from Picture Naming in Dementia

    ERIC Educational Resources Information Center

    Harley, Trevor A.; Grant, Fiona

    2004-01-01

    We examined the performance of a group of people with moderately severe Alzheimer's type dementia on a naming task. We found that functional information plays an important role in determining naming performance on both living and non-living things. Perceptual information may play some role in naming living things. We also found some evidence that…

  16. Representation of roles in biomedical ontologies: a case study in functional genomics.

    PubMed Central

    Burgun, Anita; Bodenreider, Olivier; Le Duff, Franck; Moussouni, Fouzia; Loreal, Olivier

    2002-01-01

    OBJECTIVE: Representing roles, i.e. functions of proteins, sequences and structures, is the cornerstone of knowledge representation in functional genomics. The objective of this study is to investigate representation of roles as functional categories or associative relations. We focus on GeneOntology (GO) and the UMLS and take examples from iron metabolism. METHODS: The terms corresponding to the main proteins involved in iron metabolism were mapped to GO (including the annotations) and the UMLS. The representation of their biological roles was then analyzed. RESULTS: Functional aspects are represented in both GO and the UMLS. However, the granularity may not be appropriate. DISCUSSION: Advantages and limits of functional categories and associative relations are discussed. PMID:12463792

  17. Tumor-promoting/progressing role of additional chromosome instability in hepatic carcinogenesis in Sgo1 (Shugoshin 1) haploinsufficient mice

    PubMed Central

    Yamada, Hiroshi Y.; Zhang, Yuting; Reddy, Arun; Mohammed, Altaf; Lightfoot, Stan; Dai, Wei

    2015-01-01

    A major etiological risk factor for hepatocellular carcinoma (HCC) is infection by Hepatitis viruses, especially hepatitis B virus and hepatitis C virus. Hepatitis B virus and hepatitis C virus do not cause aggressive activation of an oncogenic pathway, but they transactivate a broad array of genes, cause chronic inflammation, and, through interference with mitotic processes, lead to mitotic error-induced chromosome instability (ME-CIN). However, how ME-CIN is involved in the development of HCC remains unclear. Delineating the effect of ME-CIN on HCC development should help in identifying measures to combat HCC. In this study, we used ME-CIN model mice haploinsufficient in Shugoshin 1 (Sgo1−/+) to assess the role of ME-CIN in HCC development. Treatment with the carcinogen azoxymethane caused Sgo1−/+ ME-CIN model mice to develop HCCs within 6 months, whereas control mice developed no HCC (P < 0.003). The HCC development was associated with expression of early HCC markers (glutamine synthetase, glypican 3, heat shock protein 70, and the serum marker alpha fetoprotein), although without fibrosis. ME-CIN preceded the expression of HCC markers, suggesting that ME-CIN is an important early event in HCC development. In 12-month-old untreated Sgo1 mice, persistent DNA damage, altered gene expression, and spontaneous HCCs were observed. Sgo1 protein accumulated in response to DNA damage in vitro. Overall, Sgo1−/+-mediated ME-CIN strongly promoted/progressed development of HCC in the presence of an initiator carcinogen, and it had a mild initiator effect by itself. Use of the ME-CIN model mice should help in identifying drugs to counteract the effects of ME-CIN and should accelerate anti-HCC drug development. PMID:25740822

  18. A dominant role of oxygen additive on cold atmospheric-pressure He + O{sub 2} plasmas

    SciTech Connect

    Yang, Aijun; Liu, Dingxin E-mail: xhw@mail.xjtu.edu.cn; Rong, Mingzhe; Wang, Xiaohua E-mail: xhw@mail.xjtu.edu.cn; Kong, Michael G.

    2014-08-15

    We present in this paper how oxygen additive impacts on the cold atmospheric-pressure helium plasmas by means of a one-dimensional fluid model. For the oxygen concentration [O{sub 2}] > ∼0.1%, the influence of oxygen on the electron characteristics and the power dissipation becomes important, e.g., the electron density, the electron temperature in sheath, the electron-coupling power, and the sheath width decreasing by 1.6 to 16 folds with a two-log increase in [O{sub 2}] from 0.1% to 10%. Also the discharge mode evolves from the γ mode to the α mode. The reactive oxygen species are found to peak in the narrow range of [O{sub 2}] = 0.4%–0.9% in the plasmas, similar to their power-coupling values. This applies to their wall fluxes except for those of O* and O{sub 2}{sup −}. These two species have very short lifetimes, thus only when generated in boundary layers within several micrometers next to the electrode can contribute to the fluxes. The dominant reactive oxygen species and the corresponding main reactions are schematically presented, and their relations are quantified for selected applications.

  19. Role of hydration on the functionality of a proteolytic enzyme α-chymotrypsin under crowded environment.

    PubMed

    Verma, Pramod Kumar; Rakshit, Surajit; Mitra, Rajib Kumar; Pal, Samir Kumar

    2011-09-01

    Enzymes and other bio-macromolecules are not only sensitive to physical parameters such as pH, temperature and solute composition but also to water activity. A universally instructive way to vary water activity is the addition of osmotically active but otherwise inert solvents which also mimic the condition of an intercellular milieu. In the present contribution, the role of hydration on the functionality of a proteolytic enzyme α-chymotrypsin (CHT) is investigated by modulating the water activity with the addition of polyethylene glycols (PEG with an average molecular weight of 400). The addition of PEG increases the affinity of the enzyme to its substrate, however, followed by a decrease in the turnover number (k(cat)). Energetic calculations show that entrance path for the substrate is favoured, whereas the exit channel is restricted with increasing concentration of the crowding agent. This decrease is attributed to the thinning of the hydration shell of the enzyme due to the loss of critical water residues from the hydration surface of the enzyme as evidenced from volumetric and compressibility measurements. The overall secondary and tertiary structures of CHT determined from far-UV and near-UV circular dichroism (CD) measurements show no considerable change in the studied osmotic stress range. From kinetic and equilibrium data, we calculate 115 ± 30 numbers of water molecules to be altered during the enzymatic catalysis of CHT. Spectroscopic observation of water relaxation and rotational dynamics of ANS-CHT complex at various concentrations of the osmoting agent also support the dehydration of the hydration layer. Such dehydration/hydration processes during turnover imply a significant contribution of solvation to the energetics of the conformational changes.

  20. Novel expression of resistin in rat testis: functional role and regulation by nutritional status and hormonal factors.

    PubMed

    Nogueiras, Ruben; Barreiro, M Luz; Caminos, Jorge E; Gaytán, Francisco; Suominen, Janne S; Navarro, Victor M; Casanueva, Felipe F; Aguilar, Enrique; Toppari, Jorma; Diéguez, Carlos; Tena-Sempere, Manuel

    2004-07-01

    Resistin, a recently cloned adipose-secreted factor, is primarily involved in the modulation of insulin sensitivity and adipocyte differentiation. However, additional metabolic or endocrine functions of this molecule remain largely unexplored. In this study, a series of experiments were undertaken to explore the potential expression, regulation and functional role of this novel adipocytokine in rat testis. Resistin gene expression was demonstrated in rat testis throughout postnatal development, with maximum mRNA levels in adult specimens. At this age, resistin peptide was immunodetected in interstitial Leydig cells and Sertoli cells within seminiferous tubules. Testicular expression of resistin was under hormonal regulation of pituitary gonadotropins and showed stage-specificity, with peak expression values at stages II-VI of the seminiferous epithelial cycle. In addition, testicular resistin mRNA was down-regulated by the selective agonist of PPARgamma, rosiglitazone, in vivo and in vitro. Similarly, fasting and central administration of the adipocyte-derived factor, leptin, evoked a significant reduction in testicular resistin mRNA levels, whereas they remained unaltered in a model of diet-induced obesity. From a functional standpoint, resistin, in a dose-dependent manner, significantly increased both basal and choriogonadotropin-stimulated testosterone secretion in vitro. Overall, our present results provide the first evidence for the expression, regulation and functional role of resistin in rat testis. These data underscore a reproductive facet of this recently cloned molecule, which may operate as a novel endocrine integrator linking energy homeostasis and reproduction.

  1. [Functional characterization of recombinant myostatin and its inhibitory role to chicken muscle development].

    PubMed

    Yang, Wei; Wang, Kun; Chen, Yan; Zhang, Yong; Huang, Bo; Zhu, Da-Hai

    2003-11-01

    Myostatin is a recently discovered member of transforming growth factor beta (TGFbeta) superfamily and shares similar structure features with other members of TGFbeta superfamily. For a better understanding of molecular mechanism of myostatin function, the production of C-terminal truncated form of recombinant myostatin protein (rMSTN) in E. coli was previously reported. Herein, the functional role of the recombinant myostatin in regulating myogenesis in a chicken embryonic myoblasts (CEMs) system was determined. By using flow cytometric analysis, the myostatin was found to inhibit cell cycle transition from G1 to S phase and result in a cell cycle arrest at G1. In addition, myostatin blocked the multi-nucleus myotube formation and caused a decreased expression of the muscle cell differentiation markers (myogenin and MHC) in CEMs. In this study, a rabbit polyclonal antibody against myostatin was produced and high affinity and specificity of this anti-myostatin antibody to recombinant and endogenous myostatin were assayed by Western blot analysis. Further studies showed that the antibody could also recognize the tissue endogenous myostatin of human, mouse and rat. A specific 40 kD band was detected in chicken muscle, which suggested that chicken myostatin might have different splicing pattern. Immunofluorescence assay indicated that myostatin predominantly existed in the cytosol in C2C12 cells. Taken together, the results show that myostatin inhibits chicken muscle cells proliferation and differentiation and down-regulates expression of two differentiation marker gene in CEMs. Remarkably, production of functional recombinant myostatin protein and its specific antibody provides important reagents for unraveling molecular mechanisms underlying myostatin action during myogenesis.

  2. The Role of the Replacement Behavior in Function-Based Interventions

    ERIC Educational Resources Information Center

    Reeves, Linda M.

    2014-01-01

    This study examined the role of the replacement behavior when designing function-based interventions. Three students with Autism Spectrum Disorder (ASD) ages 12, 5, and 6, who displayed chronic off-task behavior participated in the three-phase study. In Phase 1, a descriptive functional behavioral assessment (FBA) was conducted for each student,…

  3. The roles of sensory function and cognitive load in age differences in inhibition: Evidence from the Stroop task.

    PubMed

    Peng, Huamao; Gao, Yue; Mao, Xiaofei

    2017-02-01

    To explore the roles of visual function and cognitive load in aging of inhibition, the present study adopted a 2 (visual perceptual stress: noise, nonnoise) × 2 (cognitive load: low, high) × 2 (age: young, old) mixed design. The Stroop task was adopted to measure inhibition. The task presentation was masked with Gaussian noise according to the visual function of each individual in order to match visual perceptual stress between age groups. The results indicated that age differences in the Stroop effect were influenced by visual function and cognitive load. When the cognitive load was low, older adults exhibited a larger Stroop effect than did younger adults in the nonnoise condition, and this age difference disappeared when the visual noise of the 2 age groups was matched. Conversely, in the high cognitive load condition, we observed significant age differences in the Stroop effect in both the nonnoise and noise conditions. The additional cognitive load made the age differences in the Stroop task reappear even when visual perceptual stress was equivalent. These results demonstrate that visual function plays an important role in the aging of inhibition and its role is moderated by cognitive load. (PsycINFO Database Record

  4. Improvement in antioxidant functionality and shelf life of yukwa (fried rice snack) by turmeric (Curcuma longa L.) powder addition.

    PubMed

    Lim, Seung-Taik; Han, Jung-Ah

    2016-05-15

    The physico-chemical, oxidative and sensory characteristics of fried rice snack, yukwa with different amounts of turmeric powder (Curcuma longa) were investigated. The moisture content of the pallet ranged from 16.47% to 19.84%. After frying the pallet, a slight decrease in the degree of expansion was obtained with increasing turmeric powder content. The textural properties of yukwa were not changed until the turmeric powder content reached 5%; however, over 8% addition induced a decrease in the hardness and an increase in the crispiness. Oxidative deterioration was effectively inhibited by turmeric powder addition, and more turmeric powder in yukwa led to higher free radical scavenging activity. Based on the sensory characteristics, a 5% addition of turmeric powder was the most acceptable for the yukwa product. In the correlation results among variables, the moisture content of the pallet proved to be the most important factor for yukwa quality.

  5. Role of APP Interactions with Heterotrimeric G Proteins: Physiological Functions and Pathological Consequences.

    PubMed

    Copenhaver, Philip F; Kögel, Donat

    2017-01-01

    Following the discovery that the amyloid precursor protein (APP) is the source of β-amyloid peptides (Aβ) that accumulate in Alzheimer's disease (AD), structural analyses suggested that the holoprotein resembles a transmembrane receptor. Initial studies using reconstituted membranes demonstrated that APP can directly interact with the heterotrimeric G protein Gαo (but not other G proteins) via an evolutionarily G protein-binding motif in its cytoplasmic domain. Subsequent investigations in cell culture showed that antibodies against the extracellular domain of APP could stimulate Gαo activity, presumably mimicking endogenous APP ligands. In addition, chronically activating wild type APP or overexpressing mutant APP isoforms linked with familial AD could provoke Go-dependent neurotoxic responses, while biochemical assays using human brain samples suggested that the endogenous APP-Go interactions are perturbed in AD patients. More recently, several G protein-dependent pathways have been implicated in the physiological roles of APP, coupled with evidence that APP interacts both physically and functionally with Gαo in a variety of contexts. Work in insect models has demonstrated that the APP ortholog APPL directly interacts with Gαo in motile neurons, whereby APPL-Gαo signaling regulates the response of migratory neurons to ligands encountered in the developing nervous system. Concurrent studies using cultured mammalian neurons and organotypic hippocampal slice preparations have shown that APP signaling transduces the neuroprotective effects of soluble sAPPα fragments via modulation of the PI3K/Akt pathway, providing a mechanism for integrating the stress and survival responses regulated by APP. Notably, this effect was also inhibited by pertussis toxin, indicating an essential role for Gαo/i proteins. Unexpectedly, C-terminal fragments (CTFs) derived from APP have also been found to interact with Gαs, whereby CTF-Gαs signaling can promote neurite outgrowth

  6. Role of APP Interactions with Heterotrimeric G Proteins: Physiological Functions and Pathological Consequences

    PubMed Central

    Copenhaver, Philip F.; Kögel, Donat

    2017-01-01

    Following the discovery that the amyloid precursor protein (APP) is the source of β-amyloid peptides (Aβ) that accumulate in Alzheimer’s disease (AD), structural analyses suggested that the holoprotein resembles a transmembrane receptor. Initial studies using reconstituted membranes demonstrated that APP can directly interact with the heterotrimeric G protein Gαo (but not other G proteins) via an evolutionarily G protein-binding motif in its cytoplasmic domain. Subsequent investigations in cell culture showed that antibodies against the extracellular domain of APP could stimulate Gαo activity, presumably mimicking endogenous APP ligands. In addition, chronically activating wild type APP or overexpressing mutant APP isoforms linked with familial AD could provoke Go-dependent neurotoxic responses, while biochemical assays using human brain samples suggested that the endogenous APP-Go interactions are perturbed in AD patients. More recently, several G protein-dependent pathways have been implicated in the physiological roles of APP, coupled with evidence that APP interacts both physically and functionally with Gαo in a variety of contexts. Work in insect models has demonstrated that the APP ortholog APPL directly interacts with Gαo in motile neurons, whereby APPL-Gαo signaling regulates the response of migratory neurons to ligands encountered in the developing nervous system. Concurrent studies using cultured mammalian neurons and organotypic hippocampal slice preparations have shown that APP signaling transduces the neuroprotective effects of soluble sAPPα fragments via modulation of the PI3K/Akt pathway, providing a mechanism for integrating the stress and survival responses regulated by APP. Notably, this effect was also inhibited by pertussis toxin, indicating an essential role for Gαo/i proteins. Unexpectedly, C-terminal fragments (CTFs) derived from APP have also been found to interact with Gαs, whereby CTF-Gαs signaling can promote neurite

  7. An essential role for IL-2 receptor in regulatory T cell function

    PubMed Central

    Levine, Andrew G; Fan, Xiying; Klein, Ulf; Zheng, Ye; Gasteiger, Georg; Feng, Yongqiang; Fontenot, Jason D.; Rudensky, Alexander Y.

    2016-01-01

    Regulatory T (Treg) cells, expressing abundant amounts of the IL-2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature implied a key role for a simple network based on IL-2 consumption by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg cell lineage specification factor Foxp3, confounding experimental efforts to understand the role of IL-2R expression and signaling in Treg suppressor function. Using genetic gain and loss of function approaches, we demonstrate that IL-2 capture is dispensable for control of CD4+ T cells, but is important for limiting CD8+ T cell activation, and that IL-2R dependent STAT5 transcription factor activation plays an essential role in Treg cell suppressor function separable from T cell receptor signaling. PMID:27595233

  8. Self-Conscious emotions’ role in functional outcomes within clinical populations

    PubMed Central

    Macaulay, Rebecca; Cohen, Alex

    2014-01-01

    Patients with severe mental illnesses (SMI) often experience dysfunction in their ability to efficiently carry out everyday roles and/or skills. These deficits are seen across many domains of daily functioning. We suggest that the “self-conscious emotions” of pride and shame play a role in these functional outcomes. Pride and shame appear to facilitate individuals’ ability to evaluate their group status, detect social threats, and to adjust their behaviors accordingly. This study utilized an objective performance measure of functional capacity and a self-report of quality of life (QoL) to examine the respective roles of pride and shame in functional outcomes within two SMI patient groups (schizophrenia and affective disorder) and a community control group. The influence of neurocognition, affect and symptomatology on functional outcomes was also assessed. The patient groups did not differ in cognitive functioning, QoL, or shame. The schizophrenia group reported significantly higher pride and displayed worse objective performance than the other groups. Within each of the groups, shame had an inverse relationship with QoL, while pride positively associated with QoL. Shame associated with worse functional capacity in the schizophrenia group. Shame associated with better functional capacity, while pride associated with worse functional capacity within the affective disorder group. PMID:24508025

  9. Tissue-specific expression and functional role of dehydrins in heat tolerance of sugarcane (Saccharum officinarum).

    PubMed

    Galani, Saddia; Wahid, Abdul; Arshad, Muhammad

    2013-04-01

    Studies on the functional roles of dehydrins (DHNs) in heat tolerance of plants are scarce. This study was conducted to immunohistolocalize DHNs in leaves of heat-tolerant (CP-4333) and heat-sensitive (HSF-240) sugarcane (Saccharum officinarum L.) clones at three phenological stages in order to elucidate their putative roles under heat stress. CP-4333 indicated greater amounts of heat-stable proteins than HSF-240 under heat stress. Western blotting revealed the expression of three DHNs in CP-4333 (13- and 15-kDa peptides at 48 h and an additional 18-kDa band at 72 h) and two (13 and 15 kDa at 48 h) in HSF-240 at formative stage; two DHNs in CP-4333 (20 and 25 kDa) and one in HSF-240 (20 kDa) at grand growth stage, while two DHNs in CP-4333 (20 and 22 kDa) and one in HSF-240 (20 kDa) at maturity stage. Tissue-specific immunohistolocalization showed that DHNs were expressed in stele particularly the phloem and the cells intervening bundle sheath and vascular bundles. Furthermore, DHNs were also found scattered along the epidermal and parenchymatous cells. Recovery of sugarcane from heat stress manifested a gradual disappearance of DHNs in both the clones, being quicker in sensitive clone (HSF-240). Results suggested specific implications for DHNs synthesis. Their synthesis in epidermis appears to protect the mesophyll tissues from heat injury. When associated to vascular tissue, they tend to ensure the normal photoassimilate loading into the sieve element-companion cell complex. DHNs diminution during recovery suggested that their expression was transitory. However, prolonged retention of DHNs by tolerant clone appears to be an adaptive advantage of sugarcane to withstand heat stress.

  10. Key Role of Amino Acid Repeat Expansions in the Functional Diversification of Duplicated Transcription Factors

    PubMed Central

    Radó-Trilla, Núria; Arató, Krisztina; Pegueroles, Cinta; Raya, Alicia; de la Luna, Susana; Albà, M. Mar

    2015-01-01

    The high regulatory complexity of vertebrates has been related to two rounds of whole genome duplication (2R-WGD) that occurred before the divergence of the major vertebrate groups. Following these events, many developmental transcription factors (TFs) were retained in multiple copies and subsequently specialized in diverse functions, whereas others reverted to their singleton state. TFs are known to be generally rich in amino acid repeats or low-complexity regions (LCRs), such as polyalanine or polyglutamine runs, which can evolve rapidly and potentially influence the transcriptional activity of the protein. Here we test the hypothesis that LCRs have played a major role in the diversification of TF gene duplicates. We find that nearly half of the TF gene families originated during the 2R-WGD contains LCRs. The number of gene duplicates with LCRs is 155 out of 550 analyzed (28%), about twice as many as the number of single copy genes with LCRs (15 out of 115, 13%). In addition, duplicated TFs preferentially accumulate certain LCR types, the most prominent of which are alanine repeats. We experimentally test the role of alanine-rich LCRs in two different TF gene families, PHOX2A/PHOX2B and LHX2/LHX9. In both cases, the presence of the alanine-rich LCR in one of the copies (PHOX2B and LHX2) significantly increases the capacity of the TF to activate transcription. Taken together, the results provide strong evidence that LCRs are important driving forces of evolutionary change in duplicated genes. PMID:25931513

  11. The role of connexins in ear and skin physiology – functional insights from disease-associated mutations

    PubMed Central

    Xu, Ji; Nicholson, Bruce J.

    2012-01-01

    Defects in several different connexins have been associated with several different diseases. The most common of these is deafness, where a few mutations in connexin (Cx) 26 have been found to contribute to over 50% of the incidence of non-syndromic deafness in different human populations. Other mutations in Cx26 or Cx30 have also been associated with various skin phenotypes linked to deafness (PPK, BPS, VS, KID, etc.). The large array of disease mutants offer unique opportunities to gain insights into the underlying function of gap junction proteins and their channels in the normal and pathogenic physiology of the cochlea and epidermis. This review focuses on those mutants where the impact on channel function has been assessed, and correlated with the disease phenotype, or organ function in knock-out mouse models. These approaches have provided evidence supporting a role of gap junctions and hemichannels in K+ removal and recycling in the ear, as well as possible roles for nutrient passage, in the cochlea. In contrast, increases in hemichannel opening leading to increased cell death, was associated with several KID skin disease/hearing mutants. In addition to providing clues for therapeutic strategies, these findings allow us to better understand the specific functions of connexin channels that are important for normal tissue function. PMID:22796187

  12. Functional role of CD95 ligand in concanavalin A-induced intestinal intraepithelial lymphocyte cytotoxicity.

    PubMed Central

    Ghoreschi, K; Muders, M; Enders, G A

    1998-01-01

    Freshly isolated murine intestinal intraepithelial lymphocytes (IEL) express CD95 ligand (CD95L), as shown by reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence-activated cell sorter (FACS) analysis. Between 15 and 25% of IEL could be stained with an antibody to CD95L. Therefore it was investigated whether the CD95L/CD95 pathway was effective in IEL cytotoxicity. Stimulation of IEL in vitro with concanavalin A (Con A) induced a strong cytotoxic response, which was much higher when using CD95-expressing target cells. This effect was most evident when comparing the specific lysis of CD95-transfected target cells of the leukaemia cell line L1210 with that of the untransfected parental cell line. In addition, an antibody to CD95 was able to dramatically reduce the specific lysis of CD95-expressing target cells. After stimulation with Con A, which is able to bind to CD95L, the effects were more obvious compared with the triggering of the T-cell receptor (TCR)-alphabeta or gamma delta. On the other hand, EGTA reduced the Con A-induced cytotoxicity. Together these findings support a role of the CD95L/CD95 pathway in IEL cytotoxicity, even though the reaction was Ca2+ sensitive. As a function, CD95L-expressing IEL should be able to contribute to the elimination of CD95-expressing target cells in the intestine. Images Figure 1 PMID:9893046

  13. Role of IGF-1 in cortical plasticity and functional deficit induced by sensorimotor restriction.

    PubMed

    Mysoet, Julien; Dupont, Erwan; Bastide, Bruno; Canu, Marie-Hélène

    2015-09-01

    In the adult rat, sensorimotor restriction by hindlimb unloading (HU) is known to induce impairments in motor behavior as well as a disorganization of somatosensory cortex (shrinkage of the cortical representation of the hindpaw, enlargement of the cutaneous receptive fields, decreased cutaneous sensibility threshold). Recently, our team has demonstrated that IGF-1 level was decreased in the somatosensory cortex of rats submitted to a 14-day period of HU. To determine whether IGF-1 is involved in these plastic mechanisms, a chronic cortical infusion of this substance was performed by means of osmotic minipump. When administered in control rats, IGF-1 affects the size of receptive fields and the cutaneous threshold, but has no effect on the somatotopic map. In addition, when injected during the whole HU period, IGF-1 is interestingly implied in cortical changes due to hypoactivity: the shrinkage of somatotopic representation of hindlimb is prevented, whereas the enlargement of receptive fields is reduced. IGF-1 has no effect on the increase in neuronal response to peripheral stimulation. We also explored the functional consequences of IGF-1 level restoration on tactile sensory discrimination. In HU rats, the percentage of paw withdrawal after a light tactile stimulation was decreased, whereas it was similar to control level in HU-IGF-1 rats. Taken together, the data clearly indicate that IGF-1 plays a key-role in cortical plastic mechanisms and in behavioral alterations induced by a decrease in sensorimotor activity.

  14. The role of functional magnetic resonance imaging in understanding reading and dyslexia.

    PubMed

    Shaywitz, Bennett A; Lyon, G Reid; Shaywitz, Sally E

    2006-01-01

    Converging evidence from a number of lines of investigation indicates that dyslexia represents a disorder within the language system and more specifically within a particular subcomponent of that system, phonological processing. Recent advances in imaging technology, particularly the development of functional magnetic resonance imaging (fMRI), provide evidence of a neurobiological signature for dyslexia, specifically a disruption of 2 left hemisphere posterior brain systems, 1 parietal-temporal, the other occipital-temporal, with compensatory engagement of anterior systems around the inferior frontal gyrus and a posterior (right occipital-temporal) system. Furthermore, good evidence indicates a computational role for the left occipital-temporal system: the development of fluent (automatic) reading. In addition, fMRI studies of young adults with reading difficulties followed prospectively and longitudinally from age 5 through their mid 20s suggests that there may be 2 types of reading difficulties, 1 primarily reflecting a genetic basis, the other, and far more common, reflecting environmental influences. The brain systems for reading are malleable and their disruption in children with dyslexia may be remediated by provision of an evidence-based, effective reading intervention. These studies offer the promise for more precise identification and effective management of dyslexia in children, adolescents, and adults.

  15. Role of fluid shear stress in regulating VWF structure, function and related blood disorders.

    PubMed

    Gogia, Shobhit; Neelamegham, Sriram

    2015-01-01

    Von Willebrand factor (VWF) is the largest glycoprotein in blood. It plays a crucial role in primary hemostasis via its binding interaction with platelet and endothelial cell surface receptors, other blood proteins and extra-cellular matrix components. This protein is found as a series of repeat units that are disulfide bonded to form multimeric structures. Once in blood, the protein multimer distribution is dynamically regulated by fluid shear stress which has two opposing effects: it promotes the aggregation or self-association of multiple VWF units, and it simultaneously reduces multimer size by facilitating the force-dependent cleavage of the protein by various proteases, most notably ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type repeats, motif 1 type 13). In addition to these effects, fluid shear also controls the solution and substrate-immobilized structure of VWF, the nature of contact between blood platelets and substrates, and the biomechanics of the GpIbα-VWF bond. These features together regulate different physiological and pathological processes including normal hemostasis, arterial and venous thrombosis, von Willebrand disease, thrombotic thrombocytopenic purpura and acquired von Willebrand syndrome. This article discusses current knowledge of VWF structure-function relationships with emphasis on the effects of hydrodynamic shear, including rapid methods to estimate the nature and magnitude of these forces in selected conditions. It shows that observations made by many investigators using solution and substrate-based shearing devices can be reconciled upon considering the physical size of VWF and the applied mechanical force in these different geometries.

  16. The ventral pallidum: Subregion-specific functional anatomy and roles in motivated behaviors

    PubMed Central

    Root, David H.; Melendez, Roberto I.; Zaborszky, Laszlo; Napier, T. Celeste

    2015-01-01

    The ventral pallidum (VP) plays a critical role in the processing and execution of motivated behaviors. Yet this brain region is often overlooked in published discussions of the neurobiology of mental health (e.g., addiction, depression). This contributes to a gap in understanding the neurobiological mechanisms of psychiatric disorders. This review is presented to help bridge the gap by providing a resource for current knowledge of VP anatomy, projection patterns and subregional circuits, and how this organization relates to the function of VP neurons and ultimately behavior. For example, ventromedial (VPvm) and dorsolateral (VPdl) VP subregions receive projections from nucleus accumbens shell and core, respectively. Inhibitory GABAergic neurons of the VPvm project to mediodorsal thalamus, lateral hypothalamus, and ventral tegmental area, and this VP subregion helps discriminate the appropriate conditions to acquire natural rewards or drugs of abuse, consume preferred foods, and perform working memory tasks. GABAergic neurons of the VPdl project to subthalamic nucleus and substantia nigra pars reticulata, and this VP subregion is modulated by, and is necessary for, drug-seeking behavior. Additional circuits arise from nonGABAergic neuronal phenotypes that are likely to excite rather than inhibit their targets. These subregional and neuronal phenotypic circuits place the VP in a unique position to process motivationally-relevant stimuli and coherent adaptive behaviors. PMID:25857550

  17. Biogeochemical hotspots within forested landscapes: quantifying the functional role of vernal pools in ecosystem processes

    NASA Astrophysics Data System (ADS)

    Capps, K. A.; Rancatti, R.; Calhoun, A.; Hunter, M.

    2013-12-01

    Biogeochemical hotspots are characterized as small areas within a landscape matrix that show comparably high chemical reaction rates relative to surrounding areas. For small, natural features to generate biogeochemical hotspots within a landscape, their contribution to nutrient dynamics must be significant relative to nutrient demand of the surrounding landscape. In northeastern forests in the US, vernal pools are abundant, small features that typically fill in spring with snow melt and precipitation and dry by the end of the summer. Ephemeral flooding alters soil moisture and the depth of the oxic/anoxic boundary in the soil, which may affect leaf-litter decomposition rates and nutrient dynamics including denitrification. Additionally, pool-breeding organisms may influence nutrient dynamics via consumer-driven nutrient remineralization. We studied the effects of vernal pools on rates of leaf-litter decomposition and denitrification in forested habitats in Maine. Our results indicate leaf-litter decomposition and denitrification rates in submerged habitats of vernal pools were greater than in upland forest habitat. Our data also suggest pool-breeding organisms, such as wood frogs, may play an important role in nutrient dynamics within vernal pools. Together, the results suggest vernal pools may function as biogeochemical hotspots within forested landscapes.

  18. Preparations of homeostatic thymus hormone consist predominantly of histones 2A and 2B and suggest additional histone functions.

    PubMed Central

    Reichhart, R; Zeppezauer, M; Jörnvall, H

    1985-01-01

    The two major constituents in preparations of the homeostatic thymus hormone (HTH) were purified. Amino acid sequence analysis showed that the components (HTH alpha and HTH beta) are identical to histones H2A and H2B, suggesting the possibility that histones might have hitherto unrecognized occurrence and functions. If the HTH activities are not ascribed to the two histones in the preparation, they could only be derived from minor constituents present in minimal amounts. Therefore, the histone structures were scrutinized for properties of relevance in relation to hormone activities and for similarities with thymic hormones. Similarities between COOH-terminal regions of histones H2A, H2B, and H3 were noticed, as well as some similarities between NH2-terminal regions of histones and parts of recognized thymus hormones and related proteins. Potential signals, resembling cleavage sites in prohormones, are present in the histone structures, and further correlations with recently discovered ubiquitin functions may explain molecular mechanisms for actions of the HTH preparations. None of the observations is significant by itself, but the combined results suggest the hypothesis of different relationships and functions, including hormone-like activities, for some histones. Images PMID:3860828

  19. Does gender play a role in functional asymmetry of ventromedial prefrontal cortex?

    PubMed

    Tranel, Daniel; Damasio, Hanna; Denburg, Natalie L; Bechara, Antoine

    2005-12-01

    We found previously in a lesion study that the right-sided sector of the ventromedial prefrontal cortices (VMPCs) was critical for social/emotional functioning and decision-making, whereas the left side appeared to be less important. It so happened that all but one of the subjects in that study were men, and the one woman did not fit the pattern very well. This prompted a follow-up investigation, in which we explored the following question: Does gender play a role in the development of defects in social conduct, emotional functioning and decision-making, following unilateral VMPC damage? We culled from our Patient Registry same-sex pairs of men or women patients who had comparable unilateral VMPC damage in either the left or right hemisphere. Two male pairs and one female pair were formed, and we included two additional women with unilateral right VMPC damage (8 patients in all). The domains of measurement covered social conduct, emotional processing and personality, and decision-making. We found a systematic effect of gender on the pattern of left-right asymmetry in VMPC. In men, there were severe defects following unilateral right VMPC damage, but not following left-sided damage. In women, there were defects following unilateral left VMPC damage; following right-sided damage, however, defects were mild or absent. The findings suggest that men and women may use different strategies to solve similar problems--e.g. men may use a more holistic, gestalt-type strategy, and women may use a more analytic, verbally-mediated strategy. Such differences could reflect asymmetric, gender-related differences in the neurobiology of left and right VMPC sectors.

  20. Unexpected Formation of Highly Functionalized Dihydropyrans via Addition-Cyclization Reactions Between Dimethyl Oxoglutaconate and α,β-Unsaturated Hydrazones.

    PubMed

    Mullins, Jason E; Etoga, Jean-Louis G; Gajewski, Mariusz; Degraw, Joseph I; Thompson, Charles M

    2009-05-20

    The condensation between dienophiles and α,β-unsaturated hydrazone azadienes was previously reported to afford piperidines. During an attempt to adapt this reaction to the preparation of piperidine-based conformationally-restricted analogs of glutamate, it was discovered that the electrophile, dimethyl oxoglutaconate (DOG) led to highly substituted dihydropyrans in 20-50% yield. The unexpected pyran product likely results from an initial 1,4-addition of the hydrazone to the oxoglutaconate followed by intramolecular cyclization of the resultant enolate oxygen to the α,β-unsaturated iminium ion. Further manipulations afford substituted tetrahydropyran 6-methamino-2,4-dicarboxylic acids.

  1. Unexpected Formation of Highly Functionalized Dihydropyrans via Addition-Cyclization Reactions Between Dimethyl Oxoglutaconate and α,β-Unsaturated Hydrazones

    PubMed Central

    Mullins, Jason E.; Etoga, Jean-Louis G.; Gajewski, Mariusz; DeGraw, Joseph I.; Thompson, Charles M.

    2009-01-01

    The condensation between dienophiles and α,β-unsaturated hydrazone azadienes was previously reported to afford piperidines. During an attempt to adapt this reaction to the preparation of piperidine-based conformationally-restricted analogs of glutamate, it was discovered that the electrophile, dimethyl oxoglutaconate (DOG) led to highly substituted dihydropyrans in 20–50% yield. The unexpected pyran product likely results from an initial 1,4-addition of the hydrazone to the oxoglutaconate followed by intramolecular cyclization of the resultant enolate oxygen to the α,β-unsaturated iminium ion. Further manipulations afford substituted tetrahydropyran 6-methamino-2,4-dicarboxylic acids. PMID:20161237

  2. Functional characterization of the Arabidopsis transcription factor bZIP29 reveals its role in leaf and root development

    PubMed Central

    Van Leene, Jelle; Blomme, Jonas; Kulkarni, Shubhada R; Cannoot, Bernard; De Winne, Nancy; Eeckhout, Dominique; Persiau, Geert; Van De Slijke, Eveline; Vercruysse, Leen; Vanden Bossche, Robin; Heyndrickx, Ken S; Vanneste, Steffen; Goossens, Alain; Gevaert, Kris; Vandepoele, Klaas; Gonzalez, Nathalie; Inzé, Dirk; De Jaeger, Geert

    2016-01-01

    Plant bZIP group I transcription factors have been reported mainly for their role during vascular development and osmosensory responses. Interestingly, bZIP29 has been identified in a cell cycle interactome, indicating additional functions of bZIP29 in plant development. Here, bZIP29 was functionally characterized to study its role during plant development. It is not present in vascular tissue but is specifically expressed in proliferative tissues. Genome-wide mapping of bZIP29 target genes confirmed its role in stress and osmosensory responses, but also identified specific binding to several core cell cycle genes and to genes involved in cell wall organization. bZIP29 protein complex analyses validated interaction with other bZIP group I members and provided insight into regulatory mechanisms acting on bZIP dimers. In agreement with bZIP29 expression in proliferative tissues and with its binding to promoters of cell cycle regulators, dominant-negative repression of bZIP29 altered the cell number in leaves and in the root meristem. A transcriptome analysis on the root meristem, however, indicated that bZIP29 might regulate cell number through control of cell wall organization. Finally, ectopic dominant-negative repression of bZIP29 and redundant factors led to a seedling-lethal phenotype, pointing to essential roles for bZIP group I factors early in plant development. PMID:27660483

  3. Structural-functional characterization of the cathodic haemoglobin of the conger eel Conger conger: molecular modelling study of an additional phosphate-binding site.

    PubMed Central

    Pellegrini, Mariagiuseppina; Giardina, Bruno; Verde, Cinzia; Carratore, Vito; Olianas, Alessandra; Sollai, Luigi; Sanna, Maria T; Castagnola, Massimo; di Prisco, Guido

    2003-01-01

    The protein sequence data for the alpha- and beta-chains have been deposited in the SWISS-PROT and TrEMBL protein knowledgebase under the accession numbers P83479 and P83478 respectively. The Conger conger (conger eel) haemoglobin (Hb) system is made of three components, one of which, the so-called cathodic Hb, representing approx. 20% of the total pigment, has been purified and characterized from both a structural and functional point of view. Stripped Hb showed a reverse Bohr effect, high oxygen affinity and slightly low cooperativity in the absence of any effector. Addition of saturating GTP strongly influences the pH dependence of the oxygen affinity, since the reverse Bohr effect, observed under stripped conditions, is converted into a small normal Bohr effect. A further investigation of the GTP effect on oxygen affinity, carried out by fitting its titration curve, demonstrated the presence of two independent binding sites. Therefore, on the basis of the amino acid sequence of the alpha- and beta-chains, which have been determined, a computer modelling study has been performed. The data suggest that C. conger cathodic Hb may bind organic phosphates at two distinct binding sites located along the central cavity of the tetramer by hydrogen bonds and/or electrostatic interactions with amino acid residues of both chains, which have been identified. Among these residues, the two Lys-alpha(G6) (where the letter refers to the haemoglobin helix and the number to the amino acid position in the helix) appear to have a key role in the GTP movement from the external binding region to the internal central cavity of the tetrameric molecule. PMID:12646043

  4. Graphite electrode thermal behavior and solid electrolyte interphase investigations: Role of state-of-the-art binders, carbonate additives and lithium bis(fluorosulfonyl)imide salt

    NASA Astrophysics Data System (ADS)

    Forestier, Coralie; Grugeon, Sylvie; Davoisne, Carine; Lecocq, Amandine; Marlair, Guy; Armand, Michel; Sannier, Lucas; Laruelle, Stephane

    2016-10-01

    The risk of thermal runaway is, for Li-ion batteries, a critical issue for large-scale applications. This results in manufacturers and researchers placing great emphasis on minimizing the heat generation and thereby mitigating safety-related risks through the search for suitable materials or additives. To this end, an in-depth stepwise investigation has been undertaken to provide a better understanding of the exothermic processes that take place at the negative electrode/electrolyte interface as well as an increased visibility of the role of the state-of-the-art electrode binders, additives and lithium salt by means of the classical DSC technique. A reliable experimental set up helped quantify the beneficial or harmful contribution of binder polymers to the exothermic behavior of the CMC/SBR containing graphite electrode film in contact with 1 M LiPF6 in EC:DMC:EMC (1:1:1 v/v/v) electrolyte. Further, the role of the VC, FEC and VEC electrolyte additives (2 wt%) in reinforcing the protective SEI layer towards thermally induced electrolyte reduction is discussed in the light of infrared spectroscopy and transmission electron microscopy analyzes results. Moreover, after a preliminary corrosion study of LiPF6/LiFSI mixtures, we showed that the 0.66/0.33 M composition can be used in commercial NMC-based LiBs with a positive effect on the thermal runaway.

  5. Lead roles for supporting actors: critical functions of inner ear supporting cells.

    PubMed

    Monzack, Elyssa L; Cunningham, Lisa L

    2013-09-01

    Many studies that aim to investigate the underlying mechanisms of hearing loss or balance disorders focus on the hair cells and spiral ganglion neurons of the inner ear. Fewer studies have examined the supporting cells that contact both of these cell types in the cochlea and vestibular end organs. While the roles of supporting cells are still being elucidated, emerging evidence indicates that they serve many functions vital to maintaining healthy populations of hair cells and spiral ganglion neurons. Here we review recent studies that highlight the critical roles supporting cells play in the development, function, survival, death, phagocytosis, and regeneration of other cell types within the inner ear. Many of these roles have also been described for glial cells in other parts of the nervous system, and lessons from these other systems continue to inform our understanding of supporting cell functions. This article is part of a Special Issue entitled "Annual Reviews 2013".

  6. From Embryonic Development to Human Diseases: The Functional Role of Caveolae/Caveolin

    PubMed Central

    Sohn, Jihee; Brick, Rachel M.; Tuan, Rocky S.

    2017-01-01

    Caveolae, an almost ubiquitous, structural component of the plasma membrane, play a critical role in many functions essential for proper cell function, including membrane trafficking, signal transduction, extracellular matrix remodeling, and tissue regeneration. Three main types of caveolin proteins have been identified from caveolae since the discovery of caveolin-1 in the early 1990s. All three (Cav-1, Cav-2, and Cav-3) play crucial roles in mammalian physiology, and can effect pathogenesis in a wide range of human diseases. While many biological activities of caveolins have been uncovered since its discovery, their role and regulation in embryonic develop remain largely poorly understood, although there is increasing evidence that caveolins may be linked to lung and brain birth defects. Further investigations are clearly needed to decipher how caveolae/caveolins mediate cellular functions and activities of normal embryogenesis and how their perturbations contribute to developmental disorders. PMID:26991990

  7. [Alteration of cognitive functions during extended wakefulness: role of the brain functional asymmetry].

    PubMed

    Volf, N V

    1996-01-01

    The study was aimed at looking into the effects of prolonged wakefulness on the activities predominantly governed by the left or right hemisphere. To this end, the subjects were requested to fulfill tests of manual/verbal interaction (1), establishment of similarity through the names of two tachistoscopic letters (2), evaluation of spatial proportions when using the right or left hand (3). The experiment was run with 16 male-subjects eight of which were tested following sleepless night whereas the other eight subjects had a normal night rest. In test 1, the deprived subjects exhibited lower tapping rate of both right and left hands than their counterparts; this fact may point to deteriorated function of anterior hemisphere compartments. The fact that under the effect of competing verbal activity both groups slowed down tapping by either hand at the same rate speaks in favor of immutability of the relative activation of anterior compartments of the right and left hemispheres, maintenance of the norm-specific basal profile of functional asymmetry after sleep deprivation. During prolonged sleep deprivation, test 2 displayed dominance of the right hemisphere in correct identification of letters which was not the case in the control. In deprived subjects test 3 showed overestimation of the left part of space when determining line lengths. Hence, results of experiments 2 and 3 suggest a relative activation of the caudal compartments of the right hemisphere during long wakefulness.

  8. Serum Basal Paraoxonase 1 Activity as an Additional Liver Function Test for the Evaluation of Patients with Chronic Hepatitis

    PubMed Central

    Halappa, Chandrakanth K; Pyati, Sudharani A; Nagaraj; Wali, Vinod

    2015-01-01

    Background The diagnostic accuracy of currently available standard panel of liver function tests is not satisfactory for the reliable diagnosis of chronic liver disorders. Earlier studies have reported that serum basal paraoxonase 1 (PON1) activity measurement may add a significant contribution to the liver function tests. Aim To assess whether the measurement of serum basal paraoxonase 1 (PON1) activity would be useful as an index of liver function status in chronic hepatitis patients. Materials and Methods The study included 50 chronic hepatitis patients and 50 apparently healthy controls based on inclusion & exclusion criteria. In all the subjects, standard liver function tests were analysed by using standard methods. Basal PON1 activity was estimated using spectrophotometric method by the hydrolysis of p-nitrophenylacetate. Student t-test, Pearson’s correlation coefficient, diagnostic validity tests and ROC curve analysis were the methods used for the statistical analysis of the data. Results The serum basal PON1 activity was significantly decreased in chronic hepatitis cases when compared to controls (p< 0.001). Also basal PON1 activity was positively correlated with serum total protein and albumin, and negatively correlated with serum total bilirubin, alanine amino transferase (ALT), and alkaline phosphatase (ALP) (p< 0.001) in chronic hepatitis cases but not in healthy controls. Diagnostic validity tests showed, basal PON1 activity was a better discriminator of chronic hepatitis than total protein, albumin and ALP with sensitivity of 68%, specificity of 100%, positive predictive value of 100% and negative predictive value of 75%. ROC curve analysis demonstrated highest diagnostic accuracy for ALT (AUC = 0.999) followed by PON1 (AUC = 0.990), total bilirubin (AUC = 0.977), ALP (AUC = 0.904), total protein (AUC = 0.790) and albumin (AUC = 0.595). Conclusion Diagnostic accuracy of serum PON1 activity is better than total bilirubin, total protein, albumin and

  9. Insights on the Application of the Retro Michael-Type Addition on Maleimide-Functionalized Gold Nanoparticles in Biology and Nanomedicine.

    PubMed

    Weissman, Max R; Winger, Kathleen T; Ghiassian, Sara; Gobbo, Pierangelo; Workentin, Mark S

    2016-03-16

    The glutathione-mediated retro Michael-type addition reaction is demonstrated to take place at the interface of small water-soluble maleimide-functionalized gold nanoparticles (Maleimide-AuNP). The retro Michael-type addition reaction can be blocked by hydrolyzing the Michael addition thioether adduct at the nanoparticle's interface under reaction conditions that do not cause AuNP decomposition. This procedure "locks" the molecule of interest onto the Maleimide-AuNP template for potential uses in medical imaging and bioconjugation, ensuring no loss of the molecular cargo from the nanocarrier. On the other hand, the glutathione-mediated retro Michael-type addition reaction can be exploited for delivering a molecular payload. As a proof of concept, a fluorogenic molecular cargo was incorporated onto a Maleimide-AuNP and delivered via the glutathione-mediated retro Michael-type addition reaction.

  10. Nickel superoxide dismutase: structural and functional roles of His1 and its H-bonding network

    SciTech Connect

    Maroney, Michael J.; Cabelli, Diane E.; Ryan, Kelly C.; Guce, Abigail I.; Johnson, Olivia E.; Brunold, Thomas C.; Garman, Scott C.

    2015-01-21

    Crystal structures of nickel-dependent superoxide dismutases (NiSODs) reveal the presence of a H-bonding network formed between the NH group of the apical imidazole ligand from His1 and the Glu17 carboxylate from a neighboring subunit in the hexameric enzyme. This interaction is supported by another intrasubunit H-bond between Glu17 and Arg47. In this study, four mutant NiSOD proteins were produced to experimentally evaluate the roles of this H-bonding network and compare the results with prior predictions from density functional theory calculations. The X-ray crystal structure of H1A-NiSOD, which lacks the apical ligand entirely, reveals that in the absence of the Glu17-His1 H-bond, the active site is disordered. Characterization of this variant using X-ray absorption spectroscopy (XAS) shows that Ni(II) is bound in the expected N₂S₂ planar coordination site. Despite these structural perturbations, the H1A-NiSOD variant retains 4% of wild-type (WT) NiSOD activity. Three other mutations were designed to preserve the apical imidazole ligand but perturb the H-bonding network: R47A-NiSOD, which lacks the intramolecular H-bonding interaction; E17R/R47A-NiSOD, which retains the intramolecular H-bond but lacks the intermolecular Glu17-His1 H-bond; and E17A/R47ANiSOD, which lacks both H-bonding interactions. These variants were characterized by a combination of techniques, including XAS to probe the nickel site structure, kinetic studies employing pulse-radiolytic production of superoxide, and electron paramagnetic resonance to assess the Ni redox activity. The results indicate that in addition to the roles in redox tuning suggested on the basis of previous computational studies, the Glu17-His1 H-bond plays an important structural role in the proper folding of the “Ni-hook” motif that is a critical feature of the active site.

  11. Nickel superoxide dismutase: structural and functional roles of His1 and its H-bonding network

    DOE PAGES

    Maroney, Michael J.; Cabelli, Diane E.; Ryan, Kelly C.; ...

    2015-01-21

    Crystal structures of nickel-dependent superoxide dismutases (NiSODs) reveal the presence of a H-bonding network formed between the NH group of the apical imidazole ligand from His1 and the Glu17 carboxylate from a neighboring subunit in the hexameric enzyme. This interaction is supported by another intrasubunit H-bond between Glu17 and Arg47. In this study, four mutant NiSOD proteins were produced to experimentally evaluate the roles of this H-bonding network and compare the results with prior predictions from density functional theory calculations. The X-ray crystal structure of H1A-NiSOD, which lacks the apical ligand entirely, reveals that in the absence of the Glu17-His1more » H-bond, the active site is disordered. Characterization of this variant using X-ray absorption spectroscopy (XAS) shows that Ni(II) is bound in the expected N₂S₂ planar coordination site. Despite these structural perturbations, the H1A-NiSOD variant retains 4% of wild-type (WT) NiSOD activity. Three other mutations were designed to preserve the apical imidazole ligand but perturb the H-bonding network: R47A-NiSOD, which lacks the intramolecular H-bonding interaction; E17R/R47A-NiSOD, which retains the intramolecular H-bond but lacks the intermolecular Glu17-His1 H-bond; and E17A/R47ANiSOD, which lacks both H-bonding interactions. These variants were characterized by a combination of techniques, including XAS to probe the nickel site structure, kinetic studies employing pulse-radiolytic production of superoxide, and electron paramagnetic resonance to assess the Ni redox activity. The results indicate that in addition to the roles in redox tuning suggested on the basis of previous computational studies, the Glu17-His1 H-bond plays an important structural role in the proper folding of the “Ni-hook” motif that is a critical feature of the active site.« less

  12. The functional O-mannose glycan on α-dystroglycan contains a phospho-ribitol primed for matriglycan addition

    PubMed Central

    Praissman, Jeremy L; Willer, Tobias; Sheikh, M Osman; Toi, Ants; Chitayat, David; Lin, Yung-Yao; Lee, Hane; Stalnaker, Stephanie H; Wang, Shuo; Prabhakar, Pradeep Kumar; Nelson, Stanley F; Stemple, Derek L; Moore, Steven A; Moremen, Kelley W; Campbell, Kevin P; Wells, Lance

    2016-01-01

    Multiple glycosyltransferases are essential for the proper modification of alpha-dystroglycan, as mutations in the encoding genes cause congenital/limb-girdle muscular dystrophies. Here we elucidate further the structure of an O-mannose-initiated glycan on alpha-dystroglycan that is required to generate its extracellular matrix-binding polysaccharide. This functional glycan contains a novel ribitol structure that links a phosphotrisaccharide to xylose. ISPD is a CDP-ribitol (ribose) pyrophosphorylase that generates the reduced sugar nucleotide for the insertion of ribitol in a phosphodiester linkage to the glycoprotein. TMEM5 is a UDP-xylosyl transferase that elaborates the structure. We demonstrate in a zebrafish model as well as in a human patient that defects in TMEM5 result in muscular dystrophy in combination with abnormal brain development. Thus, we propose a novel structure—a ribitol in a phosphodiester linkage—for the moiety on which TMEM5, B4GAT1, and LARGE act to generate the functional receptor for ECM proteins having LG domains. DOI: http://dx.doi.org/10.7554/eLife.14473.001 PMID:27130732

  13. Evidence for a functional vasodilatatory role for hydrogen sulphide in the human cutaneous microvasculature

    PubMed Central

    Kutz, Jessica L; Greaney, Jody L; Santhanam, Lakshmi; Alexander, Lacy M

    2015-01-01

    blood pressure in animal models; however, its specific mechanistic role in the human vasculature remains unclear. In the present study, we report the novel finding that the enzymes responsible for endogenous H2S production, cystathionine-γ-lyase and 3-mercaptopyruvate sulphurtransferase, are expressed in the human cutaneous circulation. Functionally, we show that H2S-induced cutaneous vasodilatation is mediated, in part, by tetraethylammonium-sensitive calcium-dependent potassium channels and not by ATP-sensitive potassium channels. In addition, nitric oxide and cyclo-oxygenase-derived byproducts are required for full expression of exogenous H2S-mediated cutaneous vasodilatation. Future investigations of the potential role for H2S with respect to modulating vascular function in humans may have important clinical implications for understanding the mechanisms underlying vascular dysfunction characteristic of multiple cardiovascular pathologies. PMID:25639684

  14. Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer

    PubMed Central

    Fang, Yiwen; Fullwood, Melissa J.

    2016-01-01

    Long non-coding RNAs (lncRNAs) play important roles in cancer. They are involved in chromatin remodeling, as well as transcriptional and post-transcriptional regulation, through a variety of chromatin-based mechanisms and via cross-talk with other RNA species. lncRNAs can function as decoys, scaffolds, and enhancer RNAs. This review summarizes the characteristics of lncRNAs, including their roles, functions, and working mechanisms, describes methods for identifying and annotating lncRNAs, and discusses future opportunities for lncRNA-based therapies using antisense oligonucleotides. PMID:26883671

  15. Possibilities of the Technology of Additive Production for Making Complex-Shape Parts and Depositing Functional Coatings from Metallic Powders

    NASA Astrophysics Data System (ADS)

    Grigor'ev, S. N.; Tarasova, T. V.

    2016-01-01

    The aspects of terminology, definitions and classification in the technology of additive production are considered. The principal possibility of fabrication of complex-shape parts from a refractory cobalt alloy by the method of selective laser melting and deposition of hard and wear-resistant coatings from Ti and SiC powders by coaxial laser surfacing is shown. The technological possibility of microlaser surfacing with lateral resolution about 100 μm in the production of parts from aluminum alloys is considered. The mechanisms of formation of structure in the studied alloys typical for selective laser melting, laser surfacing and microlaser surfacing are determined. The physical and mechanical properties of the alloys are investigated.

  16. Positive Affect in the Midst of Distress: Implications for Role Functioning

    PubMed Central

    Moskowitz, Judith Tedlie; Shmueli-Blumberg, Dikla; Acree, Michael; Folkman, Susan

    2012-01-01

    Stress has been shown to deplete the self-regulation resources hypothesized to facilitate effective role functioning. However, recent research suggests that positive affect may help to replenish these vital self-regulation resources. Based on revised Stress and Coping theory and the Broaden-and-Build theory of positive emotion, three studies provide evidence of the potential adaptive function of positive affect in the performance of roles for participants experiencing stress. Participants were students (Study 1), caregivers of ill children (Study 2), and individuals recently diagnosed with HIV (Study 3). In cross sectional analyses, using role functioning as an indicator of self-regulation performance, we found that positive affect was significantly correlated with better self regulation performance, independent of the effects of negative affect. The effects were not as strong longitudinally, however, and there was little evidence of a reciprocal association between increases in positive affect and improvements in role functioning over time. The results provide some modest support for hypotheses stemming from the Broaden and Build model of positive emotion and revised Stress and Coping theory, both of which argue for unique adaptive functions of positive affect under stressful conditions. PMID:23175617

  17. Role of Y{sub 2}O{sub 3}, CaO, MgO additives on structural and microstructural behavior of zirconia/mullite aggregates

    SciTech Connect

    Mishra, D. K.; Prusty, Sasmita; Mohapatra, B. K.; Singh, S. K.; Behera, S. N.

    2012-07-23

    Zirconia mullite (MUZ), Y{sub 2}O{sub 3}-MUZ, CaO-MUZ and MgO-MUZ composites, synthesized through plasma fusion technique, are becoming important due to their commercial scale of production within five minutes of plasma treatment from sillimanite, zircon and alumina mixture. The X-ray diffraction studies reveal the monoclinic zirconia phase in MUZ composite whereas mixed monoclinic, tetragonal and cubic phases of zirconia have been observed in Y{sub 2}O{sub 3}, CaO, MgO added MUZ composites. The Y{sub 2}O{sub 3}, CaO and MgO additives act as sintering aids to favour the transformation and stabilisation of tetragonal and cubic zirconia phases at room temperature. These additives also play a key role in the development of various forms of microstructure to achieve dense MUZ composites.

  18. NhaA antiporter functions using 10 helices, and an additional 2 contribute to assembly/stability.

    PubMed

    Padan, Etana; Danieli, Tsafi; Keren, Yael; Alkoby, Dudu; Masrati, Gal; Haliloglu, Turkan; Ben-Tal, Nir; Rimon, Abraham

    2015-10-13

    The Escherichia coli Na(+)/H(+) antiporter (Ec-NhaA) is the best-characterized of all pH-regulated Na(+)/H(+) exchangers that control cellular Na(+) and H(+) homeostasis. Ec-NhaA has 12 helices, 2 of which (VI and VII) are absent from other antiporters that share the Ec-NhaA structural fold. This α-hairpin is located in the dimer interface of the Ec-NhaA homodimer together with a β-sheet. Here we examine computationally and experimentally the role of the α-hairpin in the stability, dimerization, transport, and pH regulation of Ec-NhaA. Evolutionary analysis (ConSurf) indicates that the VI-VII helical hairpin is much less conserved than the remaining transmembrane region. Moreover, normal mode analysis also shows that intact NhaA and a variant, deleted of the α-hairpin, share similar dynamics, suggesting that the structure may be dispensable. Thus, two truncated Ec-NhaA mutants were constructed, one deleted of the α-hairpin and another also lacking the β-sheet. The mutants were studied at physiological pH in the membrane and in detergent micelles. The findings demonstrate that the truncated mutants retain significant activity and regulatory properties but are defective in the assembly/stability of the Ec-NhaA dimer.

  19. The role of functional and perceptual attributes: evidence from picture naming in dementia.

    PubMed

    Harley, Trevor A; Grant, Fiona

    2004-11-01

    We examined the performance of a group of people with moderately severe Alzheimer's type dementia on a naming task. We found that functional information plays an important role in determining naming performance on both living and non-living things. Perceptual information may play some role in naming living things. We also found some evidence that the semantic category to which an item belongs may also have some effect on naming performance. We argue that both the sensory-functional and domain-specific knowledge hypotheses may be correct: the brain is to some organized on taxonomic grounds, while the semantic representations of living and non-living things depend differentially on perceptual and functional information. These representations can be differentially disrupted by damage to modality-specific stores. At a moderate level of severity, dementia causes global damage that has the effect of disrupting both the localized taxonomic and the modality-specific stores. We discuss the nature of functional information.

  20. The role of intestinal epithelial barrier function in the development of NEC

    PubMed Central

    Halpern, Melissa D; Denning, Patricia W

    2015-01-01

    The intestinal epithelial barrier plays an important role in maintaining host health. Breakdown of intestinal barrier function is known to play a role in many diseases such as infectious enteritis, idiopathic inflammatory bowel disease, and neonatal inflammatory bowel diseases. Recently, increasing research has demonstrated the importance of understanding how intestinal epithelial barrier function develops in the premature neonate in order to develop strategies to promote its maturation. Optimizing intestinal barrier function is thought to be key to preventing neonatal inflammatory bowel diseases such as necrotizing enterocolitis. In this review, we will first summarize the key components of the intestinal epithelial barrier, what is known about its development, and how this may explain NEC pathogenesis. Finally, we will review what therapeutic strategies may be used to promote optimal development of neonatal intestinal barrier function in order to reduce the incidence and severity of NEC. PMID:25927016

  1. Semen Quality and Sperm Function Loss by Hypercholesterolemic Diet Was Recovered by Addition of Olive Oil to Diet in Rabbit

    PubMed Central

    Romero, Aida A.; Funes, Abi K.; Cid-Barria, Macarena; Cabrillana, María E.; Monclus, María A.; Simón, Layla; Vicenti, Amanda E.; Fornés, Miguel W.

    2013-01-01

    Fat increment (0.05% cholesterol, chol) in standard diet promoted a significant increase in serum and sperm membrane chol, which ultimately altered membrane-coupled sperm specific functions: osmotic resistance, acrosomal reaction, and sperm capacitation in White New Zealand rabbits. These changes were also associated with a reduction in motility percentage and appearance of abnormal sperm morphology. The present study was carried out to evaluate the effect of dietary olive oil (OO, 7% v/w) administration to several male hypercholesterolemic rabbits (hypercholesterolemic rabbits, HCR) with altered fertility parameters. These HCR males were achieved by feeding normal rabbits with a high-fat diet (0.05% chol). HCR were associated with a modest non-significant increase in body weight (standard diet, 4.08±0.17 Kg, versus high-fat diet, 4.37±0.24 Kg). Hypercholesterolemic rabbits presented a marked decrease in semen volume, sperm cell count, and percentage of sperm motility, associated with a significant increase in sperm cell abnormalities. Moreover, sperm capacitation measured by the characteristic phosphorylated protein pattern in and induced acrosomal reaction were also altered suggesting sperm dysfunction. However, the administration of OO (for 16 weeks) to rabbits that were fed with 50% of the high-fat diet normalized serum chol. Curiously, OO supply succeeded to attenuate the seminal and sperm alterations observed in HCR group. Administration of OO alone did not cause any significant changes in above mentioned parameters. These data suggest that OO administration to HCR male rabbits recovers the loss of semen quality and sperm functionality. PMID:23326331

  2. EPHB4 Regulates Human Trophoblast Cell Line HTR-8/SVneo Function: Implications for the Role of EPHB4 in Preeclampsia.

    PubMed

    Liu, Xiaoping; Hu, Ying; Zheng, Yanfang; Liu, Xiaoxia; Luo, Minglian; Liu, Weifang; Zhao, Yin; Zou, Li

    2016-09-01

    Successful pregnancy depends on well-regulated extravillous trophoblast (EVT) invasion into the uterine decidua and moderate uterine spiral artery remodeling. Ephrin receptor B4 (EPHB4) is a membrane-anchored receptor tyrosine kinase that plays an important role in various cellular functions in human normal tissue and tumors. Reportedly, EPHB4 plays important roles during placentation. Still, there is no investigation of EPHB4 modulating trophoblast function. In our study, term placentas of preeclamptic pregnancies showed a significantly increased EPHB4 expression compared to those of uncomplicated pregnancies (n = 15). Exogenous up-regulation of EPHB4 in HTR-8/SVneo cells was performed to investigate the effects of EPHB4 on cell biological behavior. The results showed that EPHB4 enhancement reduced cell proliferation and promoted trophoblast apoptosis; and inhibited cell migration, invasion, and endothelial replacement. Associated factors, such as matrix metalloproteinases, vascular endothelial growth factor, placental growth factor, and soluble Fms-like tyrosine kinase 1 were examined at transcriptional level. Furthermore, cell functional results were confirmed in a placenta-decidua coculture system, showing poor vascular remodeling. Additionally, we detected possible down-stream PI3K-Akt signal pathway involved in EPHB4-mediated function of HTR-8/SVneo cells. Our study demonstrates that EPHB4 overexpression may contribute to trophoblasts dysfunction and impair maternal artery remodeling, as is associated with the pathogenesis of preeclampsia.

  3. Is there role of additional chemotherapy after definitive local treatment for stage I/II marginal zone lymphoma?: Consortium for Improving Survival of Lymphoma (CISL) study.

    PubMed

    Koh, Myeong Seok; Kim, Won Seog; Kim, Seok Jin; Oh, Sung Yong; Yoon, Dok Hyun; Lee, Soon Il; Hong, Junshik; Song, Moo Kon; Shin, Ho-Jin; Kwon, Jung Hye; Kim, Hyo Jung; Do, Yong Rok; Suh, Cheolwon; Kim, Hyo Jin

    2015-10-01

    Even though local stage (Ann Arbor stage I/II) marginal zone lymphoma (MZL) is well controlled with local treatment-based therapy, no data exist on the role of additional chemotherapy after local treatment for stage I/II MZL. Patients with biopsy-confirmed Ann Arbor stage I/II MZL (n = 210) were included for analysis in this study. Of these, 180 patients (85.7 %) were stage I and 30 (14.3 %) were stage II. Most patients (n = 182, 86.7 %) were treated with a local modality including radiation therapy or surgery and 28 (13.3 %) received additional systemic chemotherapy after local treatment. The overall response rate was 98.3 % (95 % CI 96-100 %), with 187 complete responses and 20 partial responses. In the local treatment group, the mean progression-free survival (PFS) was 147.4 months (95 % CI 126.7-168.1 months) and the overall survival (OS) was 188.2 months (95 % CI 178.8-197.7 months). In the additional chemotherapy group, the mean PFS was 103.4 months (95 % CI 84.9-121.9 months) and the OS was 137.3 months (95 % CI 127.9-146.7 months). There was no difference between the two groups in OS (p = 0.836) and PFS (p = 0.695). Local stage MZL has a good clinical course and is well controlled with a local treatment modality without additional chemotherapy.

  4. Bilingualism and the Development of Executive Function: The Role of Attention.

    PubMed

    Bialystok, Ellen

    2015-06-01

    This paper reviews research examining the effect of bilingualism on children's cognitive development, and in particular, executive function. Studies reporting bilingual advantages in various tasks are described with the purpose of identifying the process or executive function component that might be responsible for this bilingual advantage. Several possibilities are discussed, such as inhibitory control. Finally, the role of attention is proposed as a fundamental process that initiates developmental differences in bilingual children from as early as infancy.

  5. The Role of Cortical Plasticity in Recovery of Function Following Allogeneic Hand Transplantation

    DTIC Science & Technology

    2014-10-01

    Hand   Transplantation         PRINCIPAL  INVESTIGATOR...TITLE AND SUBTITLE The Role of Cortical Plasticity in Recovery of Function Following Allogeneic Hand Transplantation 5a. CONTRACT NUMBER...W81XWH-13-1-0496 W81XWH-13-1-0496       l   l ticity  in  Recovery  of  Function  Following  Allogeneic   Hand

  6. Design and analysis of a piezoelectric material based touch screen with additional pressure and its acceleration measurement functions

    NASA Astrophysics Data System (ADS)

    Chu, Xiang-Cheng; Liu, Jia-Yi; Gao, Ren-Long; Chang, Jie; Li, Long-Tu

    2013-12-01

    Touch screens are becoming more and more prevalent in everyday environments due to their convenience and humanized operation. In this paper, a piezoelectric material based touch screen is developed and investigated. Piezoelectric ceramics arrayed under the touch panel at the edges or corners are used as tactile sensors to measure the touch positioning point similarly to conventional touch screens. However, additional touch pressure and its acceleration performance can also be obtained to obtain a higher-level human-machine interface. The piezoelectric ceramics can also be added to a traditional touch screen structure, or they can be used independently to construct a novel touch screen with a high light transmittance approach to a transparent glass. The piezoelectric ceramics were processed from PZT piezoelectric ceramic powder into a round or rectangular shape. According to the varied touch position and physical press strength of a finger, or even a gloved hand or fingernail, the piezoelectric tactile sensors will have different output voltage responses. By calculating the ratio of different piezoelectric tactile sensors’ responses and summing up all piezoelectric tactile sensors’ output voltages, the touch point position, touch pressure and touch force acceleration can be detected. A prototype of such a touch screen is manufactured and its position accuracy, touch pressure and response speed are measured in detail. The experimental results show that the prototype has many advantages such as high light transmittance, low energy cost and high durability.

  7. An Alkaline Protease from Bacillus pumilus MP 27: Functional Analysis of Its Binding Model toward Its Applications As Detergent Additive

    PubMed Central

    Baweja, Mehak; Tiwari, Rameshwar; Singh, Puneet K.; Nain, Lata; Shukla, Pratyoosh

    2016-01-01

    A proteolytic strain of Bacillus pumilus MP 27 was isolated from water samples of Southern ocean produced alkaline protease. Since protease production need expensive ingredients, an economically viable process was developed by using low cost carbon source, wheat straw, supplemented with peptone. This protease was active within temperature ranges 10–70°C at pH 9. This process was optimized by response surface methodology using a Box Bekhman design by Design Expert 7.0 software that increased the protease activity to 776.5 U/ml. Moreover, the enzyme was extremely stable at a broad range of temperature and pH retaining 69% of its activity at 50°C and 70% at pH 11. The enzyme exhibited excellent compatibility with surfactants and commercial detergents, showing 87% stability with triton X-100 and 100% stability with Tide commercial detergent. The results of the wash performance analysis demonstrated considerably good de-staining at 50 and 4°C with low supplementation (109 U/ml). Molecular modeling of the protease revealed the presence of serine proteases, subtilase family and serine active site and further docking supported the association of catalytic site with the various substrates. Certainly, such protease can be considered as a good detergent additive in detergent industry with a possibility to remove the stains effectively even in a cold wash. PMID:27536284

  8. Shyness and Vocabulary: The Roles of Executive Functioning and Home Environmental Stimulation

    PubMed Central

    Nayena Blankson, A.; O’Brien, Marion; Leerkes, Esther M.; Marcovitch, Stuart; Calkins, Susan D.

    2010-01-01

    Although shyness has often been found to be negatively related to vocabulary, few studies have examined the processes that produce or modify this relation. The present study examined executive functioning skills and home environmental stimulation as potential mediating and moderating mechanisms. A sample of 3.5-year-old children (N=254) were administered executive functioning tasks and a vocabulary test during a laboratory visit. Mothers completed questionnaires assessing child shyness and home environmental stimulation. Our primary hypothesis was that executive functioning mediates the association between shyness and vocabulary, and home environmental stimulation moderates the relation between executive functioning and vocabulary. Alternative hypotheses were also tested. Results indicated that children with better executive functioning skills developed stronger vocabularies when reared in more, versus less, stimulating environments. Implications of these results are discussed in terms of the role of shyness, executive functioning, and home environmental stimulation in early vocabulary development. PMID:22096267

  9. The extent of functional redundancy changes as species’ roles shift in different environments

    PubMed Central

    Fetzer, Ingo; Johst, Karin; Schäwe, Robert; Banitz, Thomas; Harms, Hauke; Chatzinotas, Antonis

    2015-01-01

    Assessing the ecological impacts of environmental change requires knowledge of the relationship between biodiversity and ecosystem functioning. The exact nature of this relationship can differ considerably between ecosystems, with consequences for the efficacy of species diversity as a buffer against environmental change. Using a microbial model system, we show that the relationship can vary depending on environmental conditions. Shapes suggesting functional redundancy in one environment can change, suggesting functional differences in another environment. We find that this change is due to shifting species roles and interactions. Species that are functionally redundant in one environment may become pivotal in another. Thus, caution is advised in drawing conclusions about functional redundancy based on a single environmental situation. It also implies that species richness is important because it provides a pool of species with potentially relevant traits. These species may turn out to be essential performers or partners in new interspecific interactions after environmental change. Therefore, our results challenge the generality of functional redundancy. PMID:26578806

  10. Incorporating significant amino acid pairs and protein domains to predict RNA splicing-related proteins with functional roles.

    PubMed

    Hsu, Justin Bo-Kai; Huang, Kai-Yao; Weng, Tzu-Ya; Huang, Chien-Hsun; Lee, Tzong-Yi

    2014-01-01

    Machinery of pre-mRNA splicing is carried out through the interaction of RNA sequence elements and a variety of RNA splicing-related proteins (SRPs) (e.g. spliceosome and splicing factors). Alternative splicing, which is an important post-transcriptional regulation in eukaryotes, gives rise to multiple mature mRNA isoforms, which encodes proteins with functional diversities. However, the regulation of RNA splicing is not yet fully elucidated, partly because SRPs have not yet been exhaustively identified and the experimental identification is labor-intensive. Therefore, we are motivated to design a new method for identifying SRPs with their functional roles in the regulation of RNA splicing. The experimentally verified SRPs were manually curated from research articles. According to the functional annotation of Splicing Related Gene Database, the collected SRPs were further categorized into four functional groups including small nuclear Ribonucleoprotein, Splicing Factor, Splicing Regulation Factor and Novel Spliceosome Protein. The composition of amino acid pairs indicates that there are remarkable differences among four functional groups of SRPs. Then, support vector machines (SVMs) were utilized to learn the predictive models for identifying SRPs as well as their functional roles. The cross-validation evaluation presents that the SVM models trained with significant amino acid pairs and functional domains could provide a better predictive performance. In addition, the independent testing demonstrates that the proposed method could accurately identify SRPs in mammals/plants as well as effectively distinguish between SRPs and RNA-binding proteins. This investigation provides a practical means to identifying potential SRPs and a perspective for exploring the regulation of RNA splicing.

  11. Incorporating significant amino acid pairs and protein domains to predict RNA splicing-related proteins with functional roles

    NASA Astrophysics Data System (ADS)

    Hsu, Justin Bo-Kai; Huang, Kai-Yao; Weng, Tzu-Ya; Huang, Chien-Hsun; Lee, Tzong-Yi

    2014-01-01

    Machinery of pre-mRNA splicing is carried out through the interaction of RNA sequence elements and a variety of RNA splicing-related proteins (SRPs) (e.g. spliceosome and splicing factors). Alternative splicing, which is an important post-transcriptional regulation in eukaryotes, gives rise to multiple mature mRNA isoforms, which encodes proteins with functional diversities. However, the regulation of RNA splicing is not yet fully elucidated, partly because SRPs have not yet been exhaustively identified and the experimental identification is labor-intensive. Therefore, we are motivated to design a new method for identifying SRPs with their functional roles in the regulation of RNA splicing. The experimentally verified SRPs were manually curated from research articles. According to the functional annotation of Splicing Related Gene Database, the collected SRPs were further categorized into four functional groups including small nuclear Ribonucleoprotein, Splicing Factor, Splicing Regulation Factor and Novel Spliceosome Protein. The composition of amino acid pairs indicates that there are remarkable differences among four functional groups of SRPs. Then, support vector machines (SVMs) were utilized to learn the predictive models for identifying SRPs as well as their functional roles. The cross-validation evaluation presents that the SVM models trained with significant amino acid pairs and functional domains could provide a better predictive performance. In addition, the independent testing demonstrates that the proposed method could accurately identify SRPs in mammals/plants as well as effectively distinguish between SRPs and RNA-binding proteins. This investigation provides a practical means to identifying potential SRPs and a perspective for exploring the regulation of RNA splicing.

  12. The role(s) of astrocytes and astrocyte activity in neurometabolism, neurovascular coupling, and the production of functional neuroimaging signals.

    PubMed

    Figley, Chase R; Stroman, Patrick W

    2011-02-01

    Data acquired with functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) are often interpreted in terms of the underlying neuronal activity, despite mounting evidence that these signals do not always correlate with electrophysiological recordings. Therefore, considering the increasing popularity of functional neuroimaging, it is clear that a more comprehensive theory is needed to reconcile these apparent disparities and more accurately explain the mechanisms through which various PET and fMRI signals arise. In the present article, we have turned our attention to astrocytes, which vastly outnumber neurons and are known to serve a number of functions throughout the central nervous system (CNS). For example, astrocytes are known to be critically involved in neurotransmitter uptake and recycling, and empirical data suggests that brain activation increases both oxidative and glycolytic astrocyte metabolism. Furthermore, a number of recent studies imply that astrocytes are likely to play a key role in regulating cerebral blood delivery. Therefore, we propose that, by mediating neurometabolic and neurovascular processes throughout the CNS, astrocytes could provide a common physiological basis for fMRI and PET signals. Such a theory has significant implications for the interpretation of functional neuroimaging signals, because astrocytic changes reflect subthreshold neuronal activity, simultaneous excitatory/inhibitory synaptic inputs, and other transient metabolic demands that may not elicit electrophysiological changes. It also suggests that fMRI and PET signals may have inherently less sensitivity to decreases in synaptic input (i.e. 'negative activity') and/or inhibitory (GABAergic) neurotransmission.

  13. The role of pain acceptance on function in individuals with disabilities: a longitudinal study.

    PubMed

    Jensen, Mark P; Smith, Amanda E; Alschuler, Kevin N; Gillanders, David T; Amtmann, Dagmar; Molton, Ivan R

    2016-01-01

    Having higher levels of pain acceptance has been shown to be associated positively with quality of life in patients with chronic pain, but its role in adjustment to chronic pain among individuals with physical disabilities living in the community is not known. Moreover, issues related to item overlap between measures of pain acceptance and measures of patient function have limited the conclusions that can be drawn from previous research in this area. To better understand the role that pain acceptance plays in patient function, we administered measures of pain acceptance, pain intensity, depressive symptoms, and function to 392 individuals with physical disabilities, and the pain, symptom, and function measures were readministered 3.5 years later. Analyses evaluated the main and interaction effects of initial pain acceptance on subsequent changes in pain and function. Having higher levels of pain acceptance-in particular as reflected by a willingness to engage in activities despite pain-resulted in less increase in pain intensity and more improvements in pain interference, physical function, depressive symptoms, and sleep quality. The findings indicate that previous research supporting the importance of pain acceptance to function in patients from health care settings extends to individuals with chronic pain living in the community. Moreover, they indicate that pain acceptance may have long-lasting (up to 3.5 years) beneficial effects on subsequent pain and function and on the association between change in pain and depression. Research to examine the potential benefits of community-based treatments that increase pain acceptance is warranted.

  14. Casein addition to a whey-based formula has limited effects on gut function in preterm pigs.

    PubMed

    Thymann, T; Støy, C A F; Bering, S B; Mølbak, L; Sangild, P T

    2012-12-01

    Preterm infants are susceptible to necrotizing enterocolitis (NEC). Using preterm pigs, we determined whether a whey-casein-based formula would be superior to a formula based on whey protein alone. Twenty cesarean-derived preterm pigs (92% gestation) were given total parenteral nutrition for 36 h followed by 30 h of enteral feeding with whey [protein fraction of milk formula based on whey (WHEY); n = 11] or casein and/or whey [protein fraction of milk formula based on a combination of casein and whey (CASEIN); n = 9]-based formulas. Sugar absorptive function was investigated at 6 and 30 h after initiation of enteral feeding using bolus feedings with galactose and mannitol. Pigs were killed after the last in vivo sugar absorption test and evaluated for NEC and the mid intestine was used for ex vivo measurements of hexose absorption. Microbiota profile and short chain fatty acid (SCFA) levels were studied in gut contents. Severity of NEC lesions was similar between diet groups but galactose absorption was markedly higher in CASEIN than in WHEY (P < 0.01) although only 6 h after the start of the enteral feeding period. There were no differences in ex vivo (14)C-D-glucose uptake, digestive enzymes, microbiota profile, or SCFA concentration. Casein may transiently stimulate intestinal sugar absorption but has limited effects on gut structure, microbiota, and NEC in preterm pigs.

  15. Effect of COOH-functionalized SWCNT addition on the electrical and photovoltaic characteristics of Malachite Green dye based photovoltaic cells

    NASA Astrophysics Data System (ADS)

    Chakraborty, S.; Manik, N. B.

    2014-12-01

    We report the effect of COOH-functionalized single walled carbon nanotubes (COOH-SWCNT) on the electrical and photovoltaic characteristics of Malachite Green (MG) dye based photovoltaic cells. Two different types of photovoltaic cells were prepared, one with MG dye and another by incorporating COOH-SWCNT with this dye. Cells were characterized through different electrical and photovoltaic measurements including photocurrent measurements with pulsed radiation. From the dark current—voltage (I-V) characteristic results, we observed a certain transition voltage (Vth) for both the cells beyond which the conduction mechanism of the cells change sharply. For the MG dye, Vth is 3.9 V whereas for COOH-SWCNT mixed with this dye, Vth drops to 2.7 V. The device performance improves due to the incorporation of COOH-SWCNT. The open circuit voltage and short circuit current density change from 4.2 to 97 mV and from 108 to 965 μA/cm2 respectively. Observations from photocurrent measurements show that the rate of growth and decay of the photocurrent are quite faster in the presence of COOH-SWCNT. This observation indicates a faster charge separation processes due to the incorporation of COOH-SWCNT in the MG dye cells. The high aspect ratio of COOH-SWCNT allows efficient conduction pathways for the generated charge carriers.

  16. Biological roles and functional mechanisms of arenavirus Z protein in viral replication.

    PubMed

    Wang, Jialong; Danzy, Shamika; Kumar, Naveen; Ly, Hinh; Liang, Yuying

    2012-09-01

    Arenaviruses can cause severe hemorrhagic fever diseases in humans, with limited prophylactic or therapeutic measures. A small RING-domain viral protein Z has been shown to mediate the formation of virus-like particles and to inhibit viral RNA synthesis, although its biological roles in an infectious viral life cycle have not been directly addressed. By taking advantage of the available reverse genetics system for a model arenavirus, Pichinde virus (PICV), we provide the direct evidence for the essential biological roles of the Z protein's conserved residues, including the G2 myristylation site, the conserved C and H residues of RING domain, and the poorly characterized C-terminal L79 and P80 residues. Dicodon substitutions within the late (L) domain (PSAPPYEP) of the PICV Z protein, although producing viable mutant viruses, have significantly reduced virus growth, a finding suggestive of an important role for the intact L domain in viral replication. Further structure-function analyses of both PICV and Lassa fever virus Z proteins suggest that arenavirus Z proteins have similar molecular mechanisms in mediating their multiple functions, with some interesting variations, such as the role of the G2 residue in blocking viral RNA synthesis. In summary, our studies have characterized the biological roles of the Z protein in an infectious arenavirus system and have shed important light on the distinct functions of its domains in virus budding and viral RNA regulation, the knowledge of which may lead to the development of novel antiviral drugs.

  17. Structural and surface functionality changes in reticulated vitreous carbon produced from poly(furfuryl alcohol) with sodium hydroxide additions

    NASA Astrophysics Data System (ADS)

    Oishi, Silvia Sizuka; Botelho, Edson Cocchieri; Rezende, Mirabel Cerqueira; Ferreira, Neidenêi Gomes

    2017-02-01

    The use of sodium hydroxide to neutralize the acid catalyst increases the storage life of poly(furfuryl alcohol) (PFA) resin avoiding its continuous polymerization. In this work, a concentrated sodium hydroxide solution (NaOH) was added directly to the PFA resin in order to minimize the production of wastes generated when PFA is washed with diluted basic solution. Thus, different amounts of this concentrated basic solution were added to the resin up to reaching pH values of around 3, 5, 7, and 9. From these four types of modified PFA two sample sets of reticulated vitreous carbon (RVC) were processed and heat treated at two different temperatures (1000 and 1700 °C). A correlation among cross-link density of PFA and RVC morphology, structural ordering and surface functionalities was systematically studied using Fourier transform infrared spectroscopy, scanning electron microscopy, Raman spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy techniques. The PFA neutralization (pH 7) led to its higher polymerization degree, promoting a crystallinity decrease on RVC treated at 1000 °C as well as its highest percentages of carboxylic groups on surface. A NaOH excess (pH 9) substantially increased the RVC oxygen content, but its crystallinity remained similar to those for samples from pH 3 and 5 treated at 1000 °C, probably due to the reduced presence of carboxylic group and the lower polymerization degree of its cured resin. Samples with pH 3 and 5 heat treated at 1000 and 1700 °C can be considered the most ordered which indicated that small quantities of NaOH may be advantageous to minimize continuous polymerization of PFA resin increasing its storage life and improving RVC microstructure.

  18. Game Changers: The Quest to Rethink Institutional Roles and Functions at U.S. Community Colleges

    ERIC Educational Resources Information Center

    Woods, Bob

    2014-01-01

    When the 10 members of the American Association of Community College's (AACC's) 21st-Century Implementation Team 7 (nine of whom are community college presidents) sat down in 2013 to talk about reforming institutional roles and functions at the nation's two-year career and technical colleges, everyone in the room knew the work before them would be…

  19. Teachers' Understanding of the Role of Executive Functions in Mathematics Learning

    ERIC Educational Resources Information Center

    Gilmore, Camilla; Cragg, Lucy

    2014-01-01

    Cognitive psychology research has suggested an important role for executive functions, the set of skills that monitor and control thought and action, in learning mathematics. However, there is currently little evidence about whether teachers are aware of the importance of these skills and, if so, how they come by this information. We conducted an…

  20. Minnesota School Principals' Perceptions of Minnesota School Counselors' Role and Functions

    ERIC Educational Resources Information Center

    Karch, Lisa Irene Hanson

    2010-01-01

    The purpose of the concurrent mixed methods study was to explore Minnesota principals' perceptive responses regarding the role and functions of Minnesota school counselors. A convenience sample of K-12 school principals was used for this study. Participant criteria was that each individual be a school principal in the state of Minnesota. School…

  1. A Model of School Counseling Supervision: The Goals, Functions, Roles, and Systems Model

    ERIC Educational Resources Information Center

    Wood, Chris; Rayle, Andrea Dixon

    2006-01-01

    The authors outline the Goals, Functions, Roles, and Systems Model (GFRS), a school counseling-specific model for supervising school counselors-in-training (SCITs). The GFRS was created as a guide for assisting in supervising and preparing SCITs for the multifaceted tasks they will undertake in their internships and careers. The components of this…

  2. The Role of the Verb in Grammatical Function Assignment in English and Korean

    ERIC Educational Resources Information Center

    Hwang, Heeju; Kaiser, Elsi

    2014-01-01

    One of the central questions in speech production is how speakers decide which entity to assign to which grammatical function. According to the lexical hypothesis (e.g., Bock & Levelt, 1994), verbs play a key role in this process (e.g., "send" and "receive" result in different entities being assigned to the subject…

  3. Early Childcare, Executive Functioning, and the Moderating Role of Early Stress Physiology

    ERIC Educational Resources Information Center

    Berry, Daniel; Willoughby, Michael T.; Blair, Clancy; Ursache, Alexandra; Granger, Douglas A.

    2014-01-01

    Intervention studies indicate that children's childcare experiences can be leveraged to support the development of executive functioning (EF). The role of more normative childcare experiences is less clear. Increasingly, theory and empirical work suggest that individual differences in children's physiological stress systems may be associated with…

  4. The Effects of War on Children: School Psychologists' Role and Function

    ERIC Educational Resources Information Center

    Lasser, Jon; Adams, Krysta

    2007-01-01

    War may be the most profound psychosocial stressor on child and adolescent development, for it has the potential to inflict loss, disruption of stability, deleterious health effects and family/community system disorganization. This article reviews the literature regarding the effects of war on children and explores the role and function of the…

  5. The Role and Functionality of Emotions in Feedback at University: A Qualitative Study

    ERIC Educational Resources Information Center

    Rowe, Anna D.; Fitness, Julie; Wood, Leigh N.

    2014-01-01

    This paper reports on a qualitative study exploring the role and functionality of emotions in feedback. In-depth interview data from students and lecturers at an Australian university are analysed using cognitive appraisal and prototype theory. Results suggest that students experience a range of positive and negative emotions in feedback contexts…

  6. Role of cilia in normal pancreas function and in diseased states.

    PubMed

    diIorio, Philip; Rittenhouse, Ann R; Bortell, Rita; Jurczyk, Agata

    2014-06-01

    Primary cilia play an essential role in modulating signaling cascades that shape cellular responses to environmental cues to maintain proper tissue development. Mutations in primary cilium proteins have been linked to several rare developmental disorders, collectively known as ciliopathies. Together with other disorders associated with dysfunctional cilia/centrosomes, affected individuals have increased risk of developing metabolic syndrome, neurologic disorders, and diabetes. In pancreatic tissues, cilia are found exclusively in islet and ductal cells where they play an essential role in pancreatic tissue organization. Their absence or disorganization leads to pancreatic duct abnormalities, acinar cell loss, polarity defects, and dysregulated insulin secretion. Cilia in pancreatic tissues are hubs for cellular signaling. Many signaling components, such as Hh, Notch, and Wnt, localize to pancreatic primary cilia and are necessary for proper development of pancreatic epithelium and β-cell morphogenesis. Receptors for neuroendocrine hormones, such as Somatostatin Receptor 3, also localize to the cilium and may play a more direct role in controlling insulin secretion due to somatostatin's inhibitory function. Finally, unique calcium signaling, which is at the heart of β-cell function, also occurs in primary cilia. Whereas voltage-gated calcium channels trigger insulin secretion and serve a variety of homeostatic functions in β-cells, transient receptor potential channels regulate calcium levels within the cilium that may serve as a feedback mechanism, regulating insulin secretion. This review article summarizes our current understanding of the role of primary cilia in normal pancreas function and in the diseased state.

  7. ROLE OF TYROSINE-SULFATED PROTEINS IN RETINAL STRUCTURE AND FUNCTION

    PubMed Central

    Kanan, Y.; Al-Ubaidi, M.R.

    2014-01-01

    The extracellular matrix (ECM) plays a significant role in cellular and retinal health. The study of retinal tyrosine-sulfated proteins is an important first step toward understanding the role of ECM in retinal health and diseases. These secreted proteins are members of the retinal ECM. Tyrosine sulfation was shown to be necessary for the development of proper retinal structure and function. The importance of tyrosine sulfation is further demonstrated by the evolutionary presence of tyrosylprotein sulfotransferases, enzymes that catalyze proteins’ tyrosine sulfation, and the compensatory abilities of these enzymes. Research has identified four tyrosine-sulfated retinal proteins: fibulin 2, vitronectin, complement factor H (CFH), and opticin. Vitronectin and CFH regulate the activation of the complement system and are involved in the etiology of some cases of age-related macular degeneration. Analysis of the role of tyrosine sulfation in fibulin function showed that sulfation influences the protein's ability to regulate growth and migration. Although opticin was recently shown to exhibit anti-angiogenic properties, it is not yet determined what role sulfation plays in that function. Future studies focusing on identifying all of the tyrosine-sulfated retinal proteins would be instrumental in determining the impact of sulfation on retinal protein function in retinal homeostasis and diseases. PMID:25819460

  8. Identity Diffusion as a Function of Sex-Roles in Adult Women.

    ERIC Educational Resources Information Center

    Jabury, Donald Eugene

    This study sought to demonstrate that the relative degree of adult female identity diffusion, as well as certain personality correlates, would be a function of specific sex roles and their combinations. Three groups of 32 women each were selected as married and noncareer, married and career, or unmarried and career women. They were administered a…

  9. The Role of Causal and Intentional Judgments in Moral Reasoning in Individuals with High Functioning Autism

    ERIC Educational Resources Information Center

    Buon, Marine; Dupoux, Emmanuel; Jacob, Pierre; Chaste, Pauline; Leboyer, Marion; Zalla, Tiziana

    2013-01-01

    In the present study, we investigated the ability to assign moral responsibility and punishment in adults with high functioning autism or Asperger Syndrome (HFA/AS), using non-verbal cartoons depicting an aggression, an accidental harm or a mere coincidence. Participants were asked to evaluate the agent's causal and intentional roles, his…

  10. Experiences of Habitual Physical Activity in Maintaining Roles and Functioning among Older Adults: A Qualitative Study

    PubMed Central

    Svantesson, Ulla; Willén, Carin

    2016-01-01

    Physically active older adults have reduced risk of functional restrictions and role limitations. Several aspects may interrelate and influence habitual physical activity (PA). However, older adults' own perspectives towards their PA need to be addressed. The aim of this study was to explore the experiences of habitual physical activity in maintaining roles and functioning among older adult Palestinians ≥60 years. Data were collected through in-depth interviews based on a narrative approach. Seventeen participants were recruited (aged 64–84 years). Data were analyzed using a narrative interpretative method. Findings. Three central narratives were identified, “keep moving, stay healthy,” “social connectedness, a motive to stay active,” and “adapting strategies to age-related changes.” Conclusion. Habitual physical activity was perceived as an important factor to maintain functioning and to preserve active roles in older adults. Walking was the most prominent pattern of physical activity and it was viewed as a vital tool to maintain functioning among the older adults. Social connectedness was considered as a contributing factor to the status of staying active. To adapt the process of age-related changes in a context to stay active, the participants have used different adapting strategies, including protective strategy, awareness of own capabilities, and modifying or adopting new roles. PMID:28078141

  11. The role of food in the functional gastrointestinal disorders: introduction to a manuscript series.

    PubMed

    Chey, William D

    2013-05-01

    Functional gastrointestinal disorders (FGIDs) are characterized by the presence of chronic or recurrent symptoms that are felt to originate from the gastrointestinal (GI) tract, which cannot be attributed to an identifiable structural or biochemical cause. Food is associated with symptom onset or exacerbation in a significant proportion of FGID patients. Despite this, the role of food in the pathogenesis of the FGIDs has remained poorly understood. For this reason, diet has largely played an adjunctive rather than a primary role in the management of FGID patients. In recent years, there has been a rapid expansion in our understanding of the role of food in GI function and sensation and how food relates to GI symptoms in FGID patients. In a series of evidence-based manuscripts produced by the Rome Foundation Working Group on the role of food in FGIDs, comprehensive reviews of the physiological changes associated with nutrient intake, and the respective roles of carbohydrates, fiber, protein, and fats are provided. The series concludes with a manuscript that provides guidance on proper clinical trial design when considering the role of food in FGIDs.

  12. Insights into the role of connexins in mammary gland morphogenesis and function.

    PubMed

    Stewart, Michael K G; Simek, Jamie; Laird, Dale W

    2015-06-01

    Gap junctions formed of connexin subunits link adjacent cells by direct intercellular communication that is essential for normal tissue homeostasis in the mammary gland. The mammary gland undergoes immense remodeling and requires exquisite regulation to control the proliferative, differentiating, and cell death mechanisms regulating gland development and function. The generation of novel genetically modified mice with reduced or ablated connexin function within the mammary gland has advanced our understanding of the role of gap junctions during the complex and dynamic process of mammary gland development. These studies have revealed an important stage-specific role for Cx26 (GJA1) and Cx43 (GJB2), while Cx30 (GJB6) and Cx32 (Gjb1) can be eliminated without compromising the gland. Yet, there remain gaps in our understanding of the role of mammary gland gap junctions.

  13. The role of PTEN in regulation of hepatic macrophages activation and function in progression and reversal of liver fibrosis.

    PubMed

    Cheng, Yahui; Tian, Yuanyao; Xia, Jialu; Wu, Xiaoqin; Yang, Yang; Li, Xiaofeng; Huang, Cheng; Meng, Xiaoming; Ma, Taotao; Li, Jun

    2017-02-15

    Activation of Kupffer cells (KCs) plays a pivotal role in the pathogenesis of liver fibrosis. The progression and reversal of CCl4-induced mouse liver fibrosis showed a mixed induction of hepatic classical (M1) and alternative (M2) macrophage markers. Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in modulating myeloid cell activation has recently been identified, its function in macrophage activation during hepatic fibrosis remains to be fully appreciated. In our study, PTEN expression of KCs was remarkably decreased in CCl4-induced mice but increased to a near-normal level in reversed mice. Moreover, PTEN was significantly decreased in IL4-induced RAW 264.7 cells in vitro and lower expression of PTEN was observed in M2 macrophages in vivo. In addition, loss- and gain-of-function studies suggested that PTEN regulates M2 macrophages polarization via activation of PI3K/Akt/STAT6 signaling, but had a limited effect on M1 macrophages polarization in vitro. Additionally, Ly294002, a chemical inhibitor of PI3K/Akt, could dramatically down-regulate the hallmarks of M2 macrophages. In conclusion, PTEN mediates macrophages activation by PI3K/Akt/STAT6 signaling pathway, which provides novel compelling evidences on the potential of PTEN in liver injury and opens new cellular target for the pharmacological therapy of liver fibrosis.

  14. Development of affective theory of mind across adolescence: disentangling the role of executive functions.

    PubMed

    Vetter, Nora C; Altgassen, Mareike; Phillips, Louise; Mahy, Caitlin E V; Kliegel, Matthias

    2013-01-01

    Theory of mind, the ability to understand mental states, involves inferences about others' cognitive (cognitive theory of mind) and emotional (affective theory of mind) mental states. The current study explored the role of executive functions in developing affective theory of mind across adolescence. Affective theory of mind and three subcomponents of executive functions (inhibition, updating, and shifting) were measured. Affective theory of mind was positively related to age, and all three executive functions. Specifically, inhibition explained the largest amount of variance in age-related differences in affective theory of mind.

  15. Identification of neural targets for the treatment of psychiatric disorders: the role of functional neuroimaging.

    PubMed

    Vago, David R; Epstein, Jane; Catenaccio, Eva; Stern, Emily

    2011-04-01

    Neurosurgical treatment of psychiatric disorders has been influenced by evolving neurobiological models of symptom generation. The advent of functional neuroimaging and advances in the neurosciences have revolutionized understanding of the functional neuroanatomy of psychiatric disorders. This article reviews neuroimaging studies of depression from the last 3 decades and describes an emerging neurocircuitry model of mood disorders, focusing on critical circuits of cognition and emotion, particularly those networks involved in the regulation of evaluative, expressive and experiential aspects of emotion. The relevance of this model for neurotherapeutics is discussed, as well as the role of functional neuroimaging of psychiatric disorders.

  16. The role of metabolic reprogramming in T cell fate and function

    PubMed Central

    Patsoukis, Nikolaos; Bardhan, Kankana; Weaver, Jessica; Herbel, Christoph; Seth, Pankaj; Li, Lequn; Boussiotis, Vassiliki A.

    2016-01-01

    T lymphocytes undergo extensive changes in their metabolic properties during their transition through various differentiation states, from naïve to effector to memory or regulatory roles. The cause and effect relationship between metabolism and differentiation is a field of intense investigation. Many recent studies demonstrate the dependency of T cell functional outcomes on metabolic pathways and the possibility of metabolic intervention to modify these functions. In this review, we describe the basic metabolic features of T cells and new findings on how these correlate with various differentiation fates and functions. We also highlight the latest information regarding the main factors that affect T cell metabolic reprogramming. PMID:28356677

  17. The dual roles of functional groups in the photoluminescence of graphene quantum dots.

    PubMed

    Wang, Shujun; Cole, Ivan S; Zhao, Dongyuan; Li, Qin

    2016-04-14

    The photoluminescent properties of graphene nanoparticle (named graphene quantum dots) have attracted significant research attention in recent years owing to their profound application potential. However, the photoluminescence (PL) origin of this class of nanocarbons is still unclear. In this paper, combining direct experimental evidence enabled by a facile size-tunable oxygenated graphene quantum dots (GQDs) synthesis method and theoretical calculations, the roles of the aromatic core, functional groups and disordered structures (i.e. defects and sp(3) carbon) in the PL of oxygenated GQDs are elucidated in detail. In particular, we found that the functional groups on GQDs play dual roles in the overall emission: (1) they enable π* → n and σ* → n transitions, resulting in a molecular type of PL, spectrally invariable with change of particle size or excitation energy; (2) similar to defects and sp(3) carbon, functional groups also induce structural deformation to the aromatic core, leading to mid-gap states or, in other words, energy traps, causing π* → mid-gap states → π transitions. Therefore, functional groups contribute to both the blue edge and the red shoulder of GQDs' PL spectra. The new insights on the role of functional groups in PL of fluorescent nanocarbons will enable better designs of this new class of materials.

  18. Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease

    PubMed Central

    Liao, Fan; Yoon, Hyejin; Kim, Jungsu

    2017-01-01

    Purpose of review APOE4 genotype is the strongest genetic risk factor for Alzheimer's disease. Prevailing evidence suggests that amyloid β plays a critical role in Alzheimer's disease. The objective of this article is to review the recent findings about the metabolism of apolipoprotein E (ApoE) and amyloid β and other possible mechanisms by which ApoE contributes to the pathogenesis of Alzheimer's disease. Recent findings ApoE isoforms have differential effects on amyloid β metabolism. Recent studies demonstrated that ApoE-interacting proteins, such as ATP-binding cassette A1 (ABCA1) and LDL receptor, may be promising therapeutic targets for Alzheimer's disease treatment. Activation of liver X receptor and retinoid X receptor pathway induces ABCA1 and other genes, leading to amyloid β clearance. Inhibition of the negative regulators of ABCA1, such as microRNA-33, also induces ABCA1 and decreases the levels of ApoE and amyloid β. In addition, genetic inactivation of an E3 ubiquitin ligase, myosin regulatory light chain interacting protein, increases LDL receptor levels and inhibits amyloid accumulation. Although amyloid β-dependent pathways have been extensively investigated, there have been several recent studies linking ApoE with vascular function, neuroinflammation, metabolism, synaptic plasticity, and transcriptional regulation. For example, ApoE was identified as a ligand for a microglial receptor, TREM2, and studies suggested that ApoE may affect the TREM2-mediated microglial phagocytosis. Summary Emerging data suggest that ApoE affects several amyloid β-independent pathways. These underexplored pathways may provide new insights into Alzheimer's disease pathogenesis. However, it will be important to determine to what extent each mechanism contributes to the pathogenesis of Alzheimer's disease. PMID:27922847

  19. Role of fluid shear stress in regulating VWF structure, function and related blood disorders

    PubMed Central

    Gogia, Shobhit; Neelamegham, Sriram

    2015-01-01

    Von Willebrand factor (VWF) is the largest glycoprotein in blood. It plays a crucial role in primary hemostasis via its binding interaction with platelet and endothelial cell surface receptors, other blood proteins and extra-cellular matrix components. This protein is found as a series of repeat units that are disulfide bonded to form multimeric structures. Once in blood, the protein multimer distribution is dynamically regulated by fluid shear stress which has two opposing effects: it promotes the aggregation or self-association of multiple VWF units, and it simultaneously reduces multimer size by facilitating the force-dependent cleavage of the protein by various proteases, most notably ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type repeats, motif 1 type 13). In addition to these effects, fluid shear also controls the solution and substrate-immobilized structure of VWF, the nature of contact between blood platelets and substrates, and the biomechanics of the GpIbα–VWF bond. These features together regulate different physiological and pathological processes including normal hemostasis, arterial and venous thrombosis, von Willebrand disease, thrombotic thrombocytopenic purpura and acquired von Willebrand syndrome. This article discusses current knowledge of VWF structure–function relationships with emphasis on the effects of hydrodynamic shear, including rapid methods to estimate the nature and magnitude of these forces in selected conditions. It shows that observations made by many investigators using solution and substrate-based shearing devices can be reconciled upon considering the physical size of VWF and the applied mechanical force in these different geometries. PMID:26600266

  20. The emerging role of MIR-146A in the control of hematopoiesis, immune function and cancer

    PubMed Central

    2012-01-01

    MicroRNA (miRs) represent a class of small non-coding regulatory RNAs playing a major role in the control of gene expression by repressing protein synthesis at the post-transcriptional level. Studies carried out during the last years have shown that some miRNAs plays a key role in the control of normal and malignant hgematopoiesis. In this review we focus on recent progress in analyzing the functional role of miR-146a in the control of normal and malignant hematopoiesis. On the other hand, this miRNA has shown to impact in the control of innate immune responses. Finally, many recent studies indicate a deregulation of miR-146 in many solid tumors and gene knockout studies indicate a role for this miRNA as a tumor suppressor. PMID:22453030

  1. The role of long non-coding RNAs in neurodevelopment, brain function and neurological disease.

    PubMed

    Roberts, Thomas C; Morris, Kevin V; Wood, Matthew J A

    2014-09-26

    Long non-coding RNAs (lncRNAs) are transcripts with low protein-coding potential that represent a large proportion of the transcriptional output of the cell. Many lncRNAs exhibit features indicative of functionality including tissue-restricted expression, localization to distinct subcellular structures, regulated expression and evolutionary conservation. Some lncRNAs have been shown to associate with chromatin-modifying activities and transcription factors, suggesting that a common mode of action may be to guide protein complexes to target genomic loci. However, the functions (if any) of the vast majority of lncRNA transcripts are currently unknown, and the subject of investigation. Here, we consider the putative role(s) of lncRNAs in neurodevelopment and brain function with an emphasis on the epigenetic regulation of gene expression. Associations of lncRNAs with neurodevelopmental/neuropsychiatric disorders, neurodegeneration and brain cancers are also discussed.

  2. Burst Firing in the Electrosensory System of Gymnotiform Weakly Electric Fish: Mechanisms and Functional Roles

    PubMed Central

    Metzen, Michael G.; Krahe, Rüdiger; Chacron, Maurice J.

    2016-01-01

    Neurons across sensory systems and organisms often display complex patterns of action potentials in response to sensory input. One example of such a pattern is the tendency of neurons to fire packets of action potentials (i.e., a burst) followed by quiescence. While it is well known that multiple mechanisms can generate bursts of action potentials at both the single-neuron and the network level, the functional role of burst firing in sensory processing is not so well understood to date. Here we provide a comprehensive review of the known mechanisms and functions of burst firing in processing of electrosensory stimuli in gymnotiform weakly electric fish. We also present new evidence from existing data showing that bursts and isolated spikes provide distinct information about stimulus variance. It is likely that these functional roles will be generally applicable to other systems and species. PMID:27531978

  3. Role of Gut Barrier Function in the Pathogenesis of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Dai, Xin; Wang, Bangmao

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease, and its incidence is increasing year by year. Many efforts have been made to investigate the pathogenesis of this disease. Since 1998 when Marshall proposed the conception of “gut-liver axis,” more and more researchers have paid close attention to the role of gut barrier function in the pathogenesis of NAFLD. The four aspects of gut barrier function, including physical, chemical, biological, and immunological barriers, are interrelated closely and related to NAFLD. In this paper, we present a summary of research findings on the relationship between gut barrier dysfunction and the development of NAFLD, aiming at illustrating the role of gut barrier function in the pathogenesis of this disease. PMID:25945084

  4. Marine reserves lag behind wilderness in the conservation of key functional roles

    PubMed Central

    D'agata, Stéphanie; Mouillot, David; Wantiez, Laurent; Friedlander, Alan M.; Kulbicki, Michel; Vigliola, Laurent

    2016-01-01

    Although marine reserves represent one of the most effective management responses to human impacts, their capacity to sustain the same diversity of species, functional roles and biomass of reef fishes as wilderness areas remains questionable, in particular in regions with deep and long-lasting human footprints. Here we show that fish functional diversity and biomass of top predators are significantly higher on coral reefs located at more than 20 h travel time from the main market compared with even the oldest (38 years old), largest (17,500 ha) and most restrictive (no entry) marine reserve in New Caledonia (South-Western Pacific). We further demonstrate that wilderness areas support unique ecological values with no equivalency as one gets closer to humans, even in large and well-managed marine reserves. Wilderness areas may therefore serve as benchmarks for management effectiveness and act as the last refuges for the most vulnerable functional roles. PMID:27354026

  5. The role of long non-coding RNAs in neurodevelopment, brain function and neurological disease

    PubMed Central

    Roberts, Thomas C.; Morris, Kevin V.; Wood, Matthew J. A.

    2014-01-01

    Long non-coding RNAs (lncRNAs) are transcripts with low protein-coding potential that represent a large proportion of the transcriptional output of the cell. Many lncRNAs exhibit features indicative of functionality including tissue-restricted expression, localization to distinct subcellular structures, regulated expression and evolutionary conservation. Some lncRNAs have been shown to associate with chromatin-modifying activities and transcription factors, suggesting that a common mode of action may be to guide protein complexes to target genomic loci. However, the functions (if any) of the vast majority of lncRNA transcripts are currently unknown, and the subject of investigation. Here, we consider the putative role(s) of lncRNAs in neurodevelopment and brain function with an emphasis on the epigenetic regulation of gene expression. Associations of lncRNAs with neurodevelopmental/neuropsychiatric disorders, neurodegeneration and brain cancers are also discussed. PMID:25135968

  6. ROLE OF ATP IN REGULATING RENAL MICROVASCULAR FUNCTION AND IN HYPERTENSION

    PubMed Central

    Guan, Zhengrong; Inscho, Edward W.

    2011-01-01

    Adenosine triphosphate (ATP) is an essential energy substrate for cellular metabolism but it can also influence many biological processes when released into the extracellular milieu. Research has established that extracellular ATP acts as an autocrine/paracrine factor that regulates many physiological functions. Alternatively, excessive extracellular ATP levels contribute to pathophysiological processes such as inflammation, cell proliferation and apoptosis, and atherosclerosis. Renal P2 receptors are widely distributed throughout glomeruli, vasculature and tubular segments, and participate in controlling renal vascular resistance, mediating renal autoregulation, and regulating tubular transport function. This review will focus on the role of ATP-P2 receptor signaling in regulating renal microvascular function and autoregulation, recent advances on the role of ATP-P2 signaling in hypertension-associated renal vascular injury, and emerging new directions. PMID:21768526

  7. Marine reserves lag behind wilderness in the conservation of key functional roles.

    PubMed

    D'agata, Stéphanie; Mouillot, David; Wantiez, Laurent; Friedlander, Alan M; Kulbicki, Michel; Vigliola, Laurent

    2016-06-29

    Although marine reserves represent one of the most effective management responses to human impacts, their capacity to sustain the same diversity of species, functional roles and biomass of reef fishes as wilderness areas remains questionable, in particular in regions with deep and long-lasting human footprints. Here we show that fish functional diversity and biomass of top predators are significantly higher on coral reefs located at more than 20 h travel time from the main market compared with even the oldest (38 years old), largest (17,500 ha) and most restrictive (no entry) marine reserve in New Caledonia (South-Western Pacific). We further demonstrate that wilderness areas support unique ecological values with no equivalency as one gets closer to humans, even in large and well-managed marine reserves. Wilderness areas may therefore serve as benchmarks for management effectiveness and act as the last refuges for the most vulnerable functional roles.

  8. How do Elevated CO2 and Nitrogen Addition Affect Functional Microbial Community Involved in Greenhouse Gas Flux in Salt Marsh System.

    PubMed

    Lee, Seung-Hoon; Megonigal, Patrick J; Kang, Hojeong

    2017-03-22

    Salt marshes are unique ecosystem of which a microbial community is expected to be affected by global climate change. In this study, by using T-RFLP analysis, quantitative PCR, and pyrosequencing, we comprehensively analyzed the microbial community structure responding to elevated CO2 (eCO2) and N addition in a salt marsh ecosystem subjected to CO2 manipulation and N addition for about 3 years. We focused on the genes of microbes relevant to N-cycling (denitrification and nitrification), CH4-flux (methanogens and methanotrophs), and S-cycling (sulfate reduction) considering that they are key functional groups involved in the nutrient cycle of salt marsh system. Overall, this study suggests that (1) eCO2 and N addition affect functional microbial community involved in greenhouse gas flux in salt marsh system. Specifically, the denitrification process may be facilitated, while the methanogenesis may be impeded due to the outcompeting of sulfate reduction by eCO2 and N. This implies that future global change may cause a probable change in GHGs flux and positive feedback to global climate change in salt marsh; (2) the effect of eCO2 and N on functional group seems specific and to contrast with each other, but the effect of single factor would not be compromised but complemented by combination of two factors. (3) The response of functional groups to eCO2 and/or N may be directly or indirectly related to the plant community and its response to eCO2 and/or N. This study provides new insights into our understanding of functional microbial community responses to eCO2 and/or N addition in a C3/C4 plant mixed salt marsh system.

  9. Emerging Roles of the Endolumenal Functional Lumen Imaging Probe in Gastrointestinal Motility Disorders

    PubMed Central

    Ata-Lawenko, Rona M; Lee, Yeong Yeh

    2017-01-01

    Gastrointestinal sphincters play a vital role in gut function and motility by separating the gut into functional segments. Traditionally, function of sphincters including the esophagogastric junction is studied using endoscopy and manometry. However, due to its dynamic biomechanical properties, data on distensibility and compliance may provide a more accurate representation of the sphincter function. The endolumenal functional lumen imaging probe (EndoFLIP) system uses a multi-detector impedance planimetry system to provide data on tissue distensibility and geometric changes in the sphincter as measured through resistance to volumetric distention with real-time images. With the advent of EndoFLIP studies, esophagogastric junction dysfunction and other disorders of the stomach and bowels may be better evaluated. It may be utilized as a tool in predicting effectiveness of endoscopic and surgical treatments as well as patient outcomes. PMID:28013295

  10. Role of Recbc Function in Formation of Chromosomal Rearrangements: A Two-Step Model for Recombination

    PubMed Central

    Mahan, M. J.; Roth, J. R.

    1989-01-01

    The role of recBC functions has been tested for three types of chromosomal recombination events: (1) recombination between direct repeats to generate a deletion, (2) recombination between a small circular fragment and the chromosome, and (3) recombination between inversely oriented repeats to form an inversion. Deletion formation by recombination between direct repeats, which does not require a fully reciprocal exchange, is independent of recBC function. Circle integration and inversion formation are both stimulated by the recBC function; these events require full reciprocality. The results suggest that half-reciprocal exchanges can occur without recBC, but recBC functions greatly stimulate completion of a fully reciprocal exchange. We propose that chromosomal recombination is a two-step process, and recBC functions are primarily required for the second step. PMID:2714635

  11. The Wnt Blows: On the Functional Role of Wnt Signaling in Mycobacterium tuberculosis Infection and Beyond

    PubMed Central

    Brandenburg, Julius; Reiling, Norbert

    2016-01-01

    In recent years, it has become apparent that the Wnt signaling pathway, known for its essential functions in embryonic development and tissue homeostasis, exerts immunomodulatory functions during inflammation and infection. Most functional studies indicate that Wnt5a exerts pro-inflammatory functions on its cellular targets, which include various types of immune and non-immune cells. Wnt5a expression has also been linked to the pathogenesis of chronic inflammatory diseases. Activation of beta-catenin-dependent Wnt signaling, e.g., by Wnt3a, has however been shown to limit inflammation by interfering with the nuclear factor kappa-light chain-enhancer of activated B-cells (NF-kappaB) pathway. This review focuses on the regulation of Wnt5a, Wnt3a, and the recently identified Wnt6 and their functional role in bacterial infections with a primary focus on pulmonary tuberculosis, a leading infectious cause of morbidity and mortality worldwide. PMID:28082976

  12. The Functions of Mediator in Candida albicans Support a Role in Shaping Species-Specific Gene Expression

    PubMed Central

    Jelicic, Branka; Lo, Tricia L.; Beaurepaire, Cecile; Bantun, Farkad; Quenault, Tara; Boag, Peter R.; Ramm, Georg; Callaghan, Judy; Beilharz, Traude H.; Nantel, André; Peleg, Anton Y.; Traven, Ana

    2012-01-01

    The Mediator complex is an essential co-regulator of RNA polymerase II that is conserved throughout eukaryotes. Here we present the first study of Mediator in the pathogenic fungus Candida albicans. We focused on the Middle domain subunit Med31, the Head domain subunit Med20, and Srb9/Med13 from the Kinase domain. The C. albicans Mediator shares some roles with model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, such as functions in the response to certain stresses and the role of Med31 in the expression of genes regulated by the activator Ace2. The C. albicans Mediator also has additional roles in the transcription of genes associated with virulence, for example genes related to morphogenesis and gene families enriched in pathogens, such as the ALS adhesins. Consistently, Med31, Med20, and Srb9/Med13 contribute to key virulence attributes of C. albicans, filamentation, and biofilm formation; and ALS1 is a biologically relevant target of Med31 for development of biofilms. Furthermore, Med31 affects virulence of C. albicans in the worm infection model. We present evidence that the roles of Med31 and Srb9/Med13 in the expression of the genes encoding cell wall adhesins are different between S. cerevisiae and C. albicans: they are repressors of the FLO genes in S. cerevisiae and are activators of the ALS genes in C. albicans. This suggests that Mediator subunits regulate adhesion in a distinct manner between these two distantly related fungal species. PMID:22496666

  13. Unique roles of glucagon and glucagon-like peptides: Parallels in understanding the functions of adipokinetic hormones in stress responses in insects.

    PubMed

    Bednářová, Andrea; Kodrík, Dalibor; Krishnan, Natraj

    2013-01-01

    Glucagon is conventionally regarded as a hormone, counter regulatory in function to insulin and plays a critical anti-hypoglycemic role by maintaining glucose homeostasis in both animals and humans. Glucagon performs this function by increasing hepatic glucose output to the blood by stimulating glycogenolysis and gluconeogenesis in response to starvation. Additionally it plays a homeostatic role by decreasing glycogenesis and glycolysis in tandem to try and maintain optimal glucose levels. To perform this action, it also increases energy expenditure which is contrary to what one would expect and has actions which are unique and not entirely in agreement with its role in protection from hypoglycemia. Interestingly, glucagon-like peptides (GLP-1 and GLP-2) from the major fragment of proglucagon (in non-mammalian vertebrates, as well as in mammals) may also modulate response to stress in addition to their other physiological actions. These unique modes of action occur in response to psychological, metabolic and other stress situations and mirror the role of adipokinetic hormones (AKHs) in insects which perform a similar function. The findings on the anti-stress roles of glucagon and glucagon-like peptides in mammalian and non-mammalian vertebrates may throw light on the multiple stress responsive mechanisms which operate in a concerted manner under regulation by AKH in insects thus functioning as a stress responsive hormone while also maintaining organismal homeostasis.

  14. In search for a common denominator for the diverse functions of arthropod corazonin: a role in the physiology of stress?

    PubMed

    Boerjan, Bart; Verleyen, Peter; Huybrechts, Jurgen; Schoofs, Liliane; De Loof, Arnold

    2010-04-01

    Corazonin (Crz) is an 11 amino acid C-terminally amidated neuropeptide that has been identified in most arthropods examined with the notable exception of beetles and an aphid. The Crz-receptor shares sequence similarity to the GnRH-AKH receptor family thus suggesting an ancestral function related to the control of reproduction and metabolism. In 1989, Crz was purified and identified as a potent cardioaccelerating agent in cockroaches (hence the Crz name based on "corazon", the Spanish word for "heart"). Since the initial assignment as a cardioacceleratory peptide, additional functions have been discovered, ranging from pigment migration in the integument of crustaceans and in the eye of locusts, melanization of the locust cuticle, ecdysis initiation and in various aspects of gregarization in locusts. The high degree of structural conservation of Crz, its well-conserved (immuno)-localization, mainly in specific neurosecretory cells in the pars lateralis, and its many functions, suggest that Crz is vital. Yet, Crz-deficient insects develop normally. Upon reexamining all known effects of Crz, a hypothesis was developed that the evolutionary ancient function of Crz may have been "to prepare animals for coping with the environmental stressors of the day". This function would then complement the role of pigment-dispersing factor (PDF), the prime hormonal effector of the clock, which is thought "to set a coping mechanism for the night".

  15. The roles of melanin-concentrating hormone in energy balance and reproductive function: Are they connected?

    PubMed

    Naufahu, Jane; Cunliffe, Adam D; Murray, Joanne F

    2013-01-01

    Melanin-concentrating hormone (MCH) is an anabolic neuropeptide with multiple and diverse physiological functions including a key role in energy homoeostasis. Rodent studies have shown that the ablation of functional MCH results in a lean phenotype, increased energy expenditure and resistance to diet-induced obesity. These findings have generated interest among pharmaceutical companies vigilant for potential anti-obesity agents. Nutritional status affects reproductive physiology and behaviours, thereby optimising reproductive success and the ability to meet energetic demands. This complex control system entails the integration of direct or indirect peripheral stimuli with central effector systems and involves numerous mediators. A role for MCH in the reproductive axis has emerged, giving rise to the premise that MCH may serve as an integratory mediator between those discrete systems that regulate energy balance and reproductive function. Hence, this review focuses on published evidence concerning i) the role of MCH in energy homoeostasis and ii) the regulatory role of MCH in the reproductive axis. The question as to whether the MCH system mediates the integration of energy homoeostasis with the neuroendocrine reproductive axis and, if so, by what means has received limited coverage in the literature; evidence to date and current theories are summarised herein.

  16. The emerging role of nitrite as an endogenous modulator and therapeutic agent of cardiovascular function.

    PubMed

    Tota, B; Quintieri, A M; Angelone, T

    2010-01-01

    Recently, the circulating anion nitrite (NO2-), the largest physiological reservoir of nitric oxide (NO) in the body, has revealed itself as a signalling molecule mediating numerous biological responses. Since it was estimated that as much as 70% of plasma nitrite originates from nitric oxide synthases (NOSs), mainly in the endothelium by endothelial NOS, nitrite is considered an index of NOSs activity. Exogenous sources, principally environmental pollutants and intake of vegetables, also contribute to this NO reserve. In mammalian blood, nitrite, present at nanomolar concentrations, can be reduced to bioactive NO along a physiological oxygen and pH gradient either non-enzymatically (acidic disproportionation) or by a number of enzymes including xanthine oxidoreductase, NOS, mitochondrial cytochromes and deoxygenated haemoglobin and myoglobin. The various NO-dependent nitrite-induced biological responses include hypoxic vasodilation, inhibition of mitochondrial respiration, cytoprotection following ischemia/reperfusion, and regulation of protein and gene expression. Since NO is a major paracrine-autocrine cardiovascular modulator and nitrite acts mainly as an endocrine store of NO, it is not surprising that NO2 - exerts important cardiovascular actions both under normal and physio-pathological conditions. In the interdisciplinary framework of the NO cycle concept, this review illustrates the actions exerted by nitrite on the cardiovascular system. Since the majority of the NO2 - -oriented studies focused on the systemic and regional control of blood flow both under physiological and ischemia/reperfusion conditions, we will firstly consider this issue. Secondly, the nitrite- induced effects on myocardial contractile and relaxation processes will be discussed, emphasizing the biomedical interest of nitrite as a new therapeutic agent. The importance of cardiac myoglobin as nitrite-reductase able to exert cardioprotection through a novel function, in addition to its

  17. Plant Functional Diversity Can Be Independent of Species Diversity: Observations Based on the Impact of 4-Yrs of Nitrogen and Phosphorus Additions in an Alpine Meadow.

    PubMed

    Li, Wei; Cheng, Ji-Min; Yu, Kai-Liang; Epstein, Howard E; Guo, Liang; Jing, Guang-Hua; Zhao, Jie; Du, Guo-Zhen

    2015-01-01

    Past studies have widely documented the decrease in species diversity in response to addition of nutrients, however functional diversity is often independent from species diversity. In this study, we conducted a field experiment to examine the effect of nitrogen and phosphorus fertilization ((NH4)2 HPO4) at 0, 15, 30 and 60 g m-2 yr-1 (F0, F15, F30 and F60) after 4 years of continuous fertilization on functional diversity and species diversity, and its relationship with productivity in an alpine meadow community on the Tibetan Plateau. To this purpose, three community-weighted mean trait values (specific leaf area, SLA; mature plant height, MPH; and seed size, SS) for 30 common species in each fertilization level were determined; three components of functional diversity (functional richness, FRic; functional evenness, FEve; and Rao's index of quadratic entropy, FRao) were quantified. Our results showed that: (i) species diversity sharply decreased, but functional diversity remained stable with fertilization; (ii) community-weighted mean traits (SLA and MPH) had a significant increase along the fertilization level; (iii) aboveground biomass was not correlated with functional diversity, but it was significantly correlated with species diversity and MPH. Our results suggest that decreases in species diversity due to fertilization do not result in corresponding changes in functional diversity. Functional identity of species may be more important than functional diversity in influencing aboveground productivity in this alpine meadow community, and our results also support the mass ratio hypothesis; that is, the traits of the dominant species influenced the community biomass production.

  18. Plant Functional Diversity Can Be Independent of Species Diversity: Observations Based on the Impact of 4-Yrs of Nitrogen and Phosphorus Additions in an Alpine Meadow

    PubMed Central

    Li, Wei; Cheng, Ji-Min; Yu, Kai-Liang; Epstein, Howard E.; Guo, Liang; Jing, Guang-Hua; Zhao, Jie; Du, Guo-Zhen

    2015-01-01

    Past studies have widely documented the decrease in species diversity in response to addition of nutrients, however functional diversity is often independent from species diversity. In this study, we conducted a field experiment to examine the effect of nitrogen and phosphorus fertilization ((NH4)2 HPO4) at 0, 15, 30 and 60 g m-2 yr-1 (F0, F15, F30 and F60) after 4 years of continuous fertilization on functional diversity and species diversity, and its relationship with productivity in an alpine meadow community on the Tibetan Plateau. To this purpose, three community-weighted mean trait values (specific leaf area, SLA; mature plant height, MPH; and seed size, SS) for 30 common species in each fertilization level were determined; three components of functional diversity (functional richness, FRic; functional evenness, FEve; and Rao’s index of quadratic entropy, FRao) were quantified. Our results showed that: (i) species diversity sharply decreased, but functional diversity remained stable with fertilization; (ii) community-weighted mean traits (SLA and MPH) had a significant increase along the fertilization level; (iii) aboveground biomass was not correlated with functional diversity, but it was significantly correlated with species diversity and MPH. Our results suggest that decreases in species diversity due to fertilization do not result in corresponding changes in functional diversity. Functional identity of species may be more important than functional diversity in influencing aboveground productivity in this alpine meadow community, and our results also support the mass ratio hypothesis; that is, the traits of the dominant species influenced the community biomass production. PMID:26295345

  19. A new approach to assess and predict the functional roles of proteins across all known structures.

    PubMed

    Julfayev, Elchin S; McLaughlin, Ryan J; Tao, Yi-Ping; McLaughlin, William A

    2011-03-01

    The three dimensional atomic structures of proteins provide information regarding their function; and codified relationships between structure and function enable the assessment of function from structure. In the current study, a new data mining tool was implemented that checks current gene ontology (GO) annotations and predicts new ones across all the protein structures available in the Protein Data Bank (PDB). The tool overcomes some of the challenges of utilizing large amounts of protein annotation and measurement information to form correspondences between protein structure and function. Protein attributes were extracted from the Structural Biology Knowledgebase and open source biological databases. Based on the presence or absence of a given set of attributes, a given protein's functional annotations were inferred. The results show that attributes derived from the three dimensional structures of proteins enhanced predictions over that using attributes only derived from primary amino acid sequence. Some predictions reflected known but not completely documented GO annotations. For example, predictions for the GO term for copper ion binding reflected used information a copper ion was known to interact with the protein based on information in a ligand interaction database. Other predictions were novel and require further experimental validation. These include predictions for proteins labeled as unknown function in the PDB. Two examples are a role in the regulation of transcription for the protein AF1396 from Archaeoglobus fulgidus and a role in RNA metabolism for the protein psuG from Thermotoga maritima.

  20. Addition of surfactants in ozonated water cleaning for the suppression of functional group formation and particle adhesion on the SiO2 surface

    NASA Astrophysics Data System (ADS)

    Yang, Jahyun; Im, Kyungtaek; Lim, Sangwoo

    2011-04-01

    Various kinds of surfactants were added to a cleaning solution and deionized (DI) water, and their effect on the suppression of organic function group formation and particle adhesion to a SiO2 surface was analyzed using multi-internal reflection Fourier transform infrared spectroscopy. The results implied that attached organic functional groups are affected by the chemical structure of a surfactant in DI water. Furthermore, the addition of anionic glycolic acid ethoxylate 4-tert-butylphenyl ether (GAE4E) is the most effective in terms of preventing organic group attachment and particle adhesion to the SiO2 surface, whether it was added to the cleaning solution or post-cleaning rinse water, with or without polystyrene latex particles. Moreover, it was possible to completely prevent particle adhesion to the SiO2 surface with the proper addition of GAE4E in DIO3 solution.

  1. Role of Ovarian Function Suppression in Premenopausal Women with Early Breast Cancer

    PubMed Central

    2016-01-01

    Historically, endocrine therapy for breast cancer began with ovarian ablation (OA) for the treatment of premenopausal patients. After the identification of estrogen receptors and the development of many antiestrogens, tamoxifen has been approved and used as the standard endocrine therapy for hormonal receptor (HR)-positive premenopausal patients to date. With the development of luteinizing hormone-releasing hormone agonists, the paradigm of endocrine therapy for premenopausal women with HR-positive breast cancer began to change from OA to ovarian function suppression (OFS). To date, the indication for OFS was limited to those premenopausal patients with HR-positive breast cancer who were unable to use tamoxifen as the primary adjuvant endocrine therapy. However, following the definitive demonstration of the therapeutic role of OFS added to tamoxifen or aromatase inhibitor after chemotherapy in large randomized trials, such as Tamoxifen and Exemestane Trial or Suppression of Ovarian Function Trial, the American Society of Clinical Oncology guidelines for the use of endocrine therapy in premenopausal HR-positive breast cancer were recently updated to recommend OFS in high-risk patients who required adjuvant chemotherapy. In contrast, the role of OFS to protect ovarian function during chemotherapy in premenopausal women has remained controversial, and some evidence showing the protective effect of OFS on the ovaries during chemotherapy as well as its therapeutic effect for breast cancer in premenopausal women with HR-negative breast cancer was recently published. Further evaluation is necessary to determine its exact role. In conclusion, the role of OA or OFS has been evolving, not only to improve the efficacy of breast cancer treatment, but also to preserve ovary function. OFS remains a main strategy for premenopausal women with HR-positive early breast cancer, though its exact role should be determined in further studies. PMID:28053622

  2. The functional role of the inferior parietal lobe in the dorsal and ventral stream dichotomy

    PubMed Central

    Singh-Curry, Victoria; Husain, Masud

    2009-01-01

    Current models of the visual pathways have difficulty incorporating the human inferior parietal lobe (IPL) into dorsal or ventral streams. Some recent proposals have attempted to integrate aspects of IPL function that were not hitherto dealt with well, such as differences between the left and right hemisphere and the role of the right IPL in responding to salient environmental events. However, we argue that these models also fail to capture adequately some important findings regarding the functions of the IPL. Here we critically appraise existing proposals regarding the functional architecture of the visual system, with special emphasis on the role of this region, particularly in the right hemisphere. We review evidence that shows the right IPL plays an important role in two different, but broadly complementary, aspects of attention: maintaining attentive control on current task goals as well as responding to salient new information or alerting stimuli in the environment. In our view, findings from functional imaging, electrophysiological and lesion studies are all consistent with the view that this region is part of a system that allows flexible reconfiguration of behaviour between these two alternative modes of operation. Damage to the right IPL leads to deficits in both maintaining attention and also responding to salient events, impairments that contribute to hemineglect, the classical syndrome that follows lesions of this region. PMID:19138694

  3. Molecular function and regulation of long non-coding RNAs: paradigms with potential roles in cancer.

    PubMed

    Hajjari, Mohammadreza; Khoshnevisan, Atefeh; Shin, Young Kee

    2014-11-01

    Different long non-coding RNAs (lncRNAs) are transcribed within the genome. Although initially argued to be spurious transcriptional noise, these RNAs play important roles in biological pathways, as shown by different studies. Also, there are some reports about the role of lncRNAs in different cancers. They can contribute to the development and progression of cancer by the functioning as oncogene or/and tumor suppressor molecules. In this review, we point to some important lncRNAs as examples which seem to be involved in cancer initiation/progression.

  4. Civil Society Organizations and the Functions of Global Health Governance: What Role within Intergovernmental Organizations?

    PubMed Central

    Lee, Kelley

    2016-01-01

    Amid discussion of how global health governance should and could be strengthened, the potential role of civil society organizations has been frequently raised. This paper considers the role of Civil Society Organizations (CSOs) in four health governance instruments under the auspices of the World Health Organization – the International Code on the Marketing of Breastmilk Substitutes, Framework Convention on Tobacco Control, International Health Regulations and Codex Alimentarius - and maps the functions they have contributed to. The paper draws conclusions about the opportunities and limitations CSOs represent for strengthening global health governance (GHG). PMID:27274776

  5. The human complement factor H: functional roles, genetic variations and disease associations.

    PubMed

    Rodríguez de Córdoba, Santiago; Esparza-Gordillo, Jorge; Goicoechea de Jorge, Elena; Lopez-Trascasa, Margarita; Sánchez-Corral, Pilar

    2004-06-01

    Factor H is an essential regulatory protein that plays a critical role in the homeostasis of the complement system in plasma and in the protection of bystander host cells and tissues from damage by complement activation. Genetic and structural data generated during recent years have been instrumental to delineate the functional domains responsible for these regulatory activities in factor H, which is helping to understand the molecular basis underlying the different pathologies associated to factor H. This review summarises our current knowledge of the role of factor H in health and disease.

  6. Linking Changes to Intraspecific Trait Diversity to Community Functional Diversity and Biomass in Response to Snow and Nitrogen Addition Within an Inner Mongolian Grassland

    PubMed Central

    Mao, Wei; Felton, Andrew J.; Zhang, Tonghui

    2017-01-01

    In recent years, both the intraspecific and interspecific functional diversity (FD) of plant communities have been studied with new approaches to improve an understanding about the mechanisms underlying plant species coexistence. Yet, little is known about how global change drivers will impact intraspecific FD and trait overlap among species, and in particular how this may scale to impacts on community level FD and ecosystem functioning. To address this uncertainty, we assessed the direct and indirect responses of specific leaf area (SLA) among both dominant annual and subordinate perennial species to the independent and interactive effects of nitrogen and snow addition within the Inner Mongnolian steppe. More specifically, we investigated the consequences for these responses on plant community FD, trait overlap and biomass. Nitrogen addition increased the biomass of the dominant annual species and as a result increased total community biomass. This occurred despite concurrent decreases in the biomass of subordinate perennial species. Nitrogen addition also increased intraspecific FD and trait overlap of both annual species and perennial species, and consequently increased the degree of trait overlap in SLA at the community level. However, snow addition did not significantly impact intraspecific FD and trait overlap of SLA for perennial species, but increased intraspecific FD and trait overlap of annual species, of which scaled to changes in community level FD. We found that the responses of the dominant annual species to nitrogen and snow additions were generally more sensitive than the subordinate perennial species within the inner Mongolian grassland communities of our study. As a consequence of this sensitivity, the responses of the dominant species largely drove impacts to community FD, trait overlap and community biomass. In total, our study demonstrates that the responses of dominant species in a community to environmental change may drive the initial

  7. Food additives

    PubMed Central

    Spencer, Michael

    1974-01-01

    Food additives are discussed from the food technology point of view. The reasons for their use are summarized: (1) to protect food from chemical and microbiological attack; (2) to even out seasonal supplies; (3) to improve their eating quality; (4) to improve their nutritional value. The various types of food additives are considered, e.g. colours, flavours, emulsifiers, bread and flour additives, preservatives, and nutritional additives. The paper concludes with consideration of those circumstances in which the use of additives is (a) justified and (b) unjustified. PMID:4467857

  8. Teachers' Understanding of the Role of Executive Functions in Mathematics Learning.

    PubMed

    Gilmore, Camilla; Cragg, Lucy

    2014-09-01

    Cognitive psychology research has suggested an important role for executive functions, the set of skills that monitor and control thought and action, in learning mathematics. However, there is currently little evidence about whether teachers are aware of the importance of these skills and, if so, how they come by this information. We conducted an online survey of teachers' views on the importance of a range of skills for mathematics learning. Teachers rated executive function skills, and in particular inhibition and shifting, to be important for mathematics. The value placed on executive function skills increased with increasing teaching experience. Most teachers reported that they were aware of these skills, although few knew the term "executive functions." This awareness had come about through their teaching experience rather than from formal instruction. Researchers and teacher educators could do more to highlight the importance of these skills to trainee or new teachers.

  9. The role of acculturation and family functioning in predicting HIV risk behaviors among Hispanic delinquent youth.

    PubMed

    Farrelly, Colleen; Cordova, David; Huang, Shi; Estrada, Yannine; Prado, Guillermo

    2013-06-01

    The present study examined the relationship between Berry's acculturation typology and HIV risk behaviors and whether family functioning mediated any such effects. A total of 235 high risk Hispanic adolescents were categorized into one of Berry's four acculturation typologies through the use of cut-off scores on measures of Hispanicism and Americanism. Structural equation modeling was used to examine the effects of acculturation typology on HIV risk behaviors and the indirect effects of acculturation typology on HIV risk behaviors through family functioning. Acculturation typology was related to HIV risk behaviors. Family functioning partially mediated the effects of acculturation typology on the HIV risk behavior outcomes. These findings suggest that both Americanism and Hispanicism play an important role in the etiology of HIV risk behaviors among Hispanic youth and that both, along with family functioning, are important to consider when designing preventive interventions for this population.

  10. The Role of Acculturation and Family Functioning in Predicting HIV Risk Behaviors Among Hispanic Delinquent Youth

    PubMed Central

    Farrelly, Colleen; Cordova, David; Huang, Shi; Estrada, Yannine

    2012-01-01

    The present study examined the relationship between Berry’s acculturation typology and HIV risk behaviors and whether family functioning mediated any such effects. A total of 235 high risk Hispanic adolescents were categorized into one of Berry’s four acculturation typologies through the use of cut-off scores on measures of Hispanicism and Americanism. Structural equation modeling was used to examine the effects of acculturation typology on HIV risk behaviors and the indirect effects of acculturation typology on HIV risk behaviors through family functioning. Acculturation typology was related to HIV risk behaviors. Family functioning partially mediated the effects of acculturation typology on the HIV risk behavior outcomes. These findings suggest that both Americanism and Hispanicism play an important role in the etiology of HIV risk behaviors among Hispanic youth and that both, along with family functioning, are important to consider when designing preventive interventions for this population. PMID:22532299

  11. The role of functional foods, nutraceuticals, and food supplements in intestinal health.

    PubMed

    Cencic, Avrelija; Chingwaru, Walter

    2010-06-01

    New eating habits, actual trends in production and consumption have a health, environmental and social impact. The European Union is fighting diseases characteristic of a modern age, such as obesity, osteoporosis, cancer, diabetes, allergies and dental problems. Developed countries are also faced with problems relating to aging populations, high energy foods, and unbalanced diets. The potential of nutraceuticals/functional foods/food supplements in mitigating health problems, especially in the gastrointestinal (GI) tract, is discussed. Certain members of gut microflora (e.g., probiotic/protective strains) play a role in the host health due to its involvement in nutritional, immunologic and physiological functions. The potential mechanisms by which nutraceuticals/functional foods/food supplements may alter a host's health are also highlighted in this paper. The establishment of novel functional cell models of the GI and analytical tools that allow tests in controlled experiments are highly desired for gut research.

  12. [Functional role of dragonfly legs before and after hatching: reorganization of coordinating interactions].

    PubMed

    Sviderskiĭ, V L; Plotnikova, S I; Gorelkin, V S; Severina, I Iu; Isavnina, I L

    2012-11-01

    The characteristics of a structure-functional organization of leg apparatus were examined in the dragonfly Aeshna grandis: larvae of the final stadium, which legs perform a locomotion function and adults (imago) rising on a wing, which legs lose a locomotion function and are used mainly for catching a prey in the air. It has been demonstrated that legs of the imago practically do not differ from those of the larva either in shape or in proportion of segments of the leg and all changes in the functional role of legs of the imago are implemented due to modifications of mechanisms of limb muscle control and an appropriate reorganization or coordinating interactions. As it is proved by the obtained data, this reorganization concerns mechanisms of the generation of motor commands as well as close coordination of the activity of wing and leg apparatus and some others. The abovementioned mechanisms are discussed.

  13. Kidney function assessment and its role in drug development, review and utilization.

    PubMed

    Tortorici, Michael A; Nolin, Thomas D

    2014-07-01

    A key regulatory requirement pertaining to drug development is characterization of the role of kidney function in drug disposition and response, along with provision of corresponding renal dose adjustment recommendations. Traditionally, this information has been derived from Phase I pharmacokinetic studies in which regulatory guidance exists for pharmaceutical manufacturers on the design, conduct, analysis, and interpretation of data. Categorization and stratification of subjects into kidney function groups and dosing recommendations have historically been based on creatinine clearance estimates using the Cockcroft-Gault equation. As new estimating equations have emerged, the choice of equation for assessment of kidney function has become an area of debate. This review highlights these equations and provides recent examples of the use of quantitative models, incorporating efficacy and safety to make rational dose recommendations in subjects with impaired kidney function.

  14. Teachers' Understanding of the Role of Executive Functions in Mathematics Learning

    PubMed Central

    Gilmore, Camilla; Cragg, Lucy

    2014-01-01

    Cognitive psychology research has suggested an important role for executive functions, the set of skills that monitor and control thought and action, in learning mathematics. However, there is currently little evidence about whether teachers are aware of the importance of these skills and, if so, how they come by this information. We conducted an online survey of teachers' views on the importance of a range of skills for mathematics learning. Teachers rated executive function skills, and in particular inhibition and shifting, to be important for mathematics. The value placed on executive function skills increased with increasing teaching experience. Most teachers reported that they were aware of these skills, although few knew the term “executive functions.” This awareness had come about through their teaching experience rather than from formal instruction. Researchers and teacher educators could do more to highlight the importance of these skills to trainee or new teachers. PMID:25674156

  15. Effects of C-additions on ecosystem processes in the Serengeti: The role of grazing mammals and implications for global change research

    SciTech Connect

    Wilsey, B.J.; McNaughton, S.J. )

    1994-06-01

    Increases in atmospheric CO[sub 2] are predicted to cause an increase in the C:N ratio of plant substrates entering the soil organic matter pool. We experimentally increased soil C:N ratios by adding 40 g C/m[sup 2] as sucrose (metabolic C) or cellulose (structural